CN117486740A - 过渡金属催化亚胺的不对称还原加成反应高效合成手性α-氨基酸衍生物的新方法 - Google Patents
过渡金属催化亚胺的不对称还原加成反应高效合成手性α-氨基酸衍生物的新方法 Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 287
- 150000002466 imines Chemical class 0.000 title claims abstract description 34
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 title claims abstract description 12
- 229910052723 transition metal Inorganic materials 0.000 title claims abstract description 8
- 150000003624 transition metals Chemical class 0.000 title claims abstract description 8
- 238000007259 addition reaction Methods 0.000 title claims abstract description 7
- 230000002194 synthesizing effect Effects 0.000 title claims description 5
- 230000003197 catalytic effect Effects 0.000 title abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 164
- 239000003446 ligand Substances 0.000 claims abstract description 33
- 239000000654 additive Substances 0.000 claims abstract description 12
- 230000000996 additive effect Effects 0.000 claims abstract description 12
- 239000012039 electrophile Substances 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 221
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 85
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 70
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 66
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 52
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 30
- -1 sulfonyloxy Chemical group 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 21
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 238000006467 substitution reaction Methods 0.000 claims description 16
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims description 14
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 235000009518 sodium iodide Nutrition 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 9
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 7
- 239000007789 gas Substances 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- AVWLPUQJODERGA-UHFFFAOYSA-L cobalt(2+);diiodide Chemical group [Co+2].[I-].[I-] AVWLPUQJODERGA-UHFFFAOYSA-L 0.000 claims description 4
- BZRRQSJJPUGBAA-UHFFFAOYSA-L cobalt(ii) bromide Chemical compound Br[Co]Br BZRRQSJJPUGBAA-UHFFFAOYSA-L 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 claims description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 4
- JAAGVIUFBAHDMA-UHFFFAOYSA-M rubidium bromide Chemical compound [Br-].[Rb+] JAAGVIUFBAHDMA-UHFFFAOYSA-M 0.000 claims description 4
- FGDZQCVHDSGLHJ-UHFFFAOYSA-M rubidium chloride Chemical compound [Cl-].[Rb+] FGDZQCVHDSGLHJ-UHFFFAOYSA-M 0.000 claims description 4
- WFUBYPSJBBQSOU-UHFFFAOYSA-M rubidium iodide Chemical compound [Rb+].[I-] WFUBYPSJBBQSOU-UHFFFAOYSA-M 0.000 claims description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 229910017052 cobalt Inorganic materials 0.000 claims description 3
- 239000010941 cobalt Substances 0.000 claims description 3
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 3
- 229940125782 compound 2 Drugs 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000011592 zinc chloride Substances 0.000 claims description 3
- 235000005074 zinc chloride Nutrition 0.000 claims description 3
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 2
- VHSVJTYBTJCDFL-UHFFFAOYSA-L 1,2-dimethoxyethane;nickel(2+);dibromide Chemical compound Br[Ni]Br.COCCOC VHSVJTYBTJCDFL-UHFFFAOYSA-L 0.000 claims description 2
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 2
- CBXRMKZFYQISIV-UHFFFAOYSA-N 1-n,1-n,1-n',1-n',2-n,2-n,2-n',2-n'-octamethylethene-1,1,2,2-tetramine Chemical group CN(C)C(N(C)C)=C(N(C)C)N(C)C CBXRMKZFYQISIV-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- LJANIJWBPMOASO-UHFFFAOYSA-N C(CC(=O)C)(=O)[Co] Chemical compound C(CC(=O)C)(=O)[Co] LJANIJWBPMOASO-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 229910021555 Chromium Chloride Inorganic materials 0.000 claims description 2
- 229910021580 Cobalt(II) chloride Inorganic materials 0.000 claims description 2
- 229910021584 Cobalt(II) iodide Inorganic materials 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- 229910021575 Iron(II) bromide Inorganic materials 0.000 claims description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 claims description 2
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 claims description 2
- LYQFWZFBNBDLEO-UHFFFAOYSA-M caesium bromide Chemical compound [Br-].[Cs+] LYQFWZFBNBDLEO-UHFFFAOYSA-M 0.000 claims description 2
- XQPRBTXUXXVTKB-UHFFFAOYSA-M caesium iodide Chemical compound [I-].[Cs+] XQPRBTXUXXVTKB-UHFFFAOYSA-M 0.000 claims description 2
- QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 claims description 2
- XZQOHYZUWTWZBL-UHFFFAOYSA-L chromium(ii) bromide Chemical compound [Cr+2].[Br-].[Br-] XZQOHYZUWTWZBL-UHFFFAOYSA-L 0.000 claims description 2
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 claims description 2
- BSUSEPIPTZNHMN-UHFFFAOYSA-L cobalt(2+);diperchlorate Chemical compound [Co+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O BSUSEPIPTZNHMN-UHFFFAOYSA-L 0.000 claims description 2
- QAHREYKOYSIQPH-UHFFFAOYSA-L cobalt(II) acetate Chemical compound [Co+2].CC([O-])=O.CC([O-])=O QAHREYKOYSIQPH-UHFFFAOYSA-L 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- 229960003280 cupric chloride Drugs 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- JAGHDVYKBYUAFD-UHFFFAOYSA-L cyclopenta-1,3-diene;titanium(4+);dichloride Chemical compound [Cl-].[Cl-].[Ti+4].C1C=CC=[C-]1.C1C=CC=[C-]1 JAGHDVYKBYUAFD-UHFFFAOYSA-L 0.000 claims description 2
- OCMNCWNTDDVHFK-UHFFFAOYSA-L dichloronickel;1,2-dimethoxyethane Chemical compound Cl[Ni]Cl.COCCOC OCMNCWNTDDVHFK-UHFFFAOYSA-L 0.000 claims description 2
- MMVQMUXBBRNGMA-UHFFFAOYSA-L diiodocobalt;triphenylphosphane Chemical compound I[Co]I.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MMVQMUXBBRNGMA-UHFFFAOYSA-L 0.000 claims description 2
- 229940032296 ferric chloride Drugs 0.000 claims description 2
- 229940046149 ferrous bromide Drugs 0.000 claims description 2
- 229960002089 ferrous chloride Drugs 0.000 claims description 2
- ALDOUWLIYKWJTN-UHFFFAOYSA-N fluoro(dioxido)borane;nickel(2+) Chemical compound [Ni+2].[O-]B([O-])F ALDOUWLIYKWJTN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052734 helium Inorganic materials 0.000 claims description 2
- 239000001307 helium Substances 0.000 claims description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- GYCHYNMREWYSKH-UHFFFAOYSA-L iron(ii) bromide Chemical compound [Fe+2].[Br-].[Br-] GYCHYNMREWYSKH-UHFFFAOYSA-L 0.000 claims description 2
- 229910052743 krypton Inorganic materials 0.000 claims description 2
- DNNSSWSSYDEUBZ-UHFFFAOYSA-N krypton atom Chemical compound [Kr] DNNSSWSSYDEUBZ-UHFFFAOYSA-N 0.000 claims description 2
- WGJJZRVGLPOKQT-UHFFFAOYSA-K lanthanum(3+);trifluoromethanesulfonate Chemical compound [La+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F WGJJZRVGLPOKQT-UHFFFAOYSA-K 0.000 claims description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 claims description 2
- 229910001641 magnesium iodide Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 2
- WYRSPTDNOIZOGA-UHFFFAOYSA-K neodymium(3+);trifluoromethanesulfonate Chemical compound [Nd+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F WYRSPTDNOIZOGA-UHFFFAOYSA-K 0.000 claims description 2
- 229910052754 neon Inorganic materials 0.000 claims description 2
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 claims description 2
- 150000002815 nickel Chemical class 0.000 claims description 2
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 claims description 2
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 claims description 2
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 claims description 2
- ZLQBNKOPBDZKDP-UHFFFAOYSA-L nickel(2+);diperchlorate Chemical compound [Ni+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O ZLQBNKOPBDZKDP-UHFFFAOYSA-L 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- CLSUSRZJUQMOHH-UHFFFAOYSA-L platinum dichloride Chemical compound Cl[Pt]Cl CLSUSRZJUQMOHH-UHFFFAOYSA-L 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 2
- 229940102127 rubidium chloride Drugs 0.000 claims description 2
- HZXJVDYQRYYYOR-UHFFFAOYSA-K scandium(iii) trifluoromethanesulfonate Chemical compound [Sc+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HZXJVDYQRYYYOR-UHFFFAOYSA-K 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 125000003375 sulfoxide group Chemical group 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 claims description 2
- JPJIEXKLJOWQQK-UHFFFAOYSA-K trifluoromethanesulfonate;yttrium(3+) Chemical compound [Y+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F JPJIEXKLJOWQQK-UHFFFAOYSA-K 0.000 claims description 2
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- PYFSLJVSCGXYAJ-UHFFFAOYSA-N methyl 2-hydroxy-4-[[3-(2-hydroxyphenyl)phenyl]sulfonylamino]benzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=CC=CC(C=2C(=CC=CC=2)O)=C1 PYFSLJVSCGXYAJ-UHFFFAOYSA-N 0.000 description 1
- QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 1
- YGDGZDGRCWHDOU-UHFFFAOYSA-N methyl 4-[[5-chloro-4-(2-hydroxyphenyl)thiophen-2-yl]sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=CC(C=2C(=CC=CC=2)O)=C(Cl)S1 YGDGZDGRCWHDOU-UHFFFAOYSA-N 0.000 description 1
- ZUVVLBGWTRIOFH-UHFFFAOYSA-N methyl 4-methyl-2-[(4-methylphenyl)sulfonylamino]pentanoate Chemical compound COC(=O)C(CC(C)C)NS(=O)(=O)C1=CC=C(C)C=C1 ZUVVLBGWTRIOFH-UHFFFAOYSA-N 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- SBUAYSSKTAGAGF-UHFFFAOYSA-N prop-2-ynyl dihydrogen phosphate Chemical compound OP(O)(=O)OCC#C SBUAYSSKTAGAGF-UHFFFAOYSA-N 0.000 description 1
- 238000006702 propargylation reaction Methods 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- RKSOPLXZQNSWAS-UHFFFAOYSA-N tert-butyl bromide Chemical compound CC(C)(C)Br RKSOPLXZQNSWAS-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
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Abstract
本发明公开了一种过渡金属催化亚胺与有机亲电试剂的不对称还原性加成反应，为不同种类手性α‑氨基酸类衍生物的高效合成提供了一类便捷的新方法。该方法的合成过程为：在反应管中按比例加入催化剂、手性配体、亚胺、有机亲电试剂、添加剂及溶剂，于室温下搅拌一定的时间后，粗产品经柱层析分离纯化即可得到相应的对映选择性富集的α‑氨基酸类衍生物。与传统的方法相比，本发明方法避免了有机金属试剂的使用，具有操作简便、步骤经济、条件温和及官能团容忍性出色等优点，能以高收率及出色的对映选择性制备多样化的手性α‑氨基酸类衍生物。本发明公开的合成方法将在药学、化学及生物学等领域具有广阔的应用前景。
Description
技术领域
本发明属于有机合成化学领域，具体涉及一种过渡金属催化有机亲电试剂对亚胺的不对称还原性加成反应高效合成手性α-氨基酸衍生物的新方法。
背景技术
手性α-氨基酸作为一类常见的有机小分子骨架，广泛存在于天然产物及药物活性分子中，同时也是生命体中的多肽和蛋白质的基本砌块。人体所必需的20种手性氨基酸即蛋白源氨基酸，是生命体进行各种代谢及生理活动的重要基础。近年来，手性蛋白源氨基酸衍生物的合成有所报道，主要包括不对称氢化[Nájera,C.；Sansano,J.M.Chem.Rev.2018,107(11),4584-4671；Xie,J.-H.；Zhu,S.-F.；Zhou,Q.-L.Chem.Rev.2011,111(3),1713-1760；Wang,H.；Wen,J.；Zhang,X.Chem.Rev.2021,121(13),7530-7567.]及卡宾前体对N-H键的对映选择性***[Li,M.-L.；Yu,J.-H.；Li,Y.-H.；Zhu,S.-F.；Zhou,Q.-L.Science2019,366(6468),990-994；Ren,Y.-Y.；Zhu,S.-F.；Zhou,Q.-L.Org.Biomol.Chem.2018,16,3087-3094.]等方法。然而目前已发展的合成方法仍然存在一定的局限性，例如手性α-三级碳氨基酸产物仅限于一级烷基取代的底物，对于α位含位阻较大的二级、三级烷基以及其他非烷基取代的氨基酸产物目前仍然鲜有报道。因此，为了建立多样化的手性α-三级碳氨基酸衍生物的化合物库，发展一类更为普适的合成新方法具有重要的科学意义及应用价值。
非蛋白源手性α-季碳氨基酸衍生物具有良好的结构刚性及多样性，并被认为能使新形成的多肽折叠可控、增强其化学及酶降解抵抗性[Kaul R.；Balaram,P.Bioorg.Med.Chem.1999,7(1),105-117；Schiller,P.W.；Weltrowska,G.；Dung,N.T.M.；Lemieux,C.；Chung,N.N.；Marsden,B.J.；Wilkes,B.C.J.Med.Chem.1991,34(10),3125-3132.]。然而，该类化合物难以通过自然界获取。目前已发展的α-季碳氨基酸衍生物的不对称合成方法主要有酮亚胺的不对称亲核加成反应[Eftekhari-Sis,B.；Zirak,M.Chem.Rev.2017,117,8326.]、Strecker反应[Wang,J.；Liu,X.；Feng,X.Chem.Rev.2011,111(11),6947–6983]、席夫碱衍生的α-氨基酯的不对称烷基化反应[Wright,T.B.；Evans,P.A.Chem.Rev.2021,121(15),9196–9242]和羰基化合物的不对称α-亲电胺化反应[Zhou,F.；Liao,F.-M.；Yu,J.-S.；Zhou,J.Synthesis 2014,46(22),2983-3003；]。但以上的策略存在适用性窄、官能团容忍性差、需要使用手性辅基等局限。因此，目前手性α-季碳氨基酸衍生物通用性的合成方法仍然处于相对匮乏的阶段，非天然氨基酸产物的多样性合成也受到限制。因此，如何高效及高选择性地构建非天然的手性α-季碳氨基酸一直是合成化学家面临的挑战之一。在药物合成化学中，对映体富集的α-季碳氨基酸衍生物很多情况下仍然是通过手性拆分来完成。亲核性的有机金属试剂对α-酮亚胺酯的不对称加成反应是构筑手性α-季碳氨基酸衍生物的最为直接和有效的方式之一。但有机金属试剂制备繁琐，稳定性差、不易储存，同时官能团容忍性差。综上所述，发展一类全新、高效普适的合成方法构建多样化的手性α-氨基酸衍生物具有相当重要的意义。
发明内容
针对现有技术存在的问题，本发明的目的在于通过廉价过渡金属催化的还原性加成策略，实现不同亲电试剂对亚胺的不对称加成反应，为α-氨基酸衍生物的模块化合成提供一类高效绿色的合成新方法，解决传统合成方法存在的步骤繁琐、原料需预制备且稳定性差、普适性窄、成本较高等问题。本发明原料易得，操作简便，条件温和，官能团耐受性好，适用性广泛，提供了一种快速有效构筑α-氨基酸衍生物的分子平台。
[1]为实现上述目的，本发明的技术方案如下：
一种过渡金属催化亲电试剂与亚胺的不对称还原性加成反应高效合成α-氨基酸衍生物的新方法，包含以下操作步骤：以亚胺及有机亲电试剂为起始原料，在保护气体下，加入催化剂、手性配体、还原剂、添加剂和有机溶剂，其化学反应式如下所示：
其中，R1为氢、任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、烯基、炔基；
R2为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、任选取代C1～C20的烷基-氧基，任选取代的C3～C20的环烷基-氧基、任选取代的C6～C20的苄基-氧基、任选取代C6～C20的(杂)芳基-氧基、C1～C20的胺基、氨基、C1～C20的烷基-硫基；
R3为氢、任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基或任选取代C3～C20的杂芳基；C2～C16的酯基、C1～C16的肼基、任选取代C1～C20的硅基、任选取代C1～C20的砜基、任选取代C1～C20的亚砜基；
R为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C3～C20的烯丙基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、任选取代C2～C20的烯基、任选取代C2～C20的炔基；
X为卤素、任选取代C1～C20的醚、任选取代C1～C20的酯基、任选取代C1～C20的酰氧基、任选取代C1～C20的碳酸酯基、任选取代C2～C20的磷酸酯、任选取代C1～C20的磺酰氧基；
其中，R1和R3可以相连成碳环，如下式所述，其中n为0-10；其中，R4为一个或多个独立选自下组的取代基：氢、任选取代的C1～C20的烷基、任选取代的C3～C20的环烷基、任选取代的C6～C20的苄基、任选取代的C5～C20的芳基、任选取代的C3～C20的杂芳基、硝基、C2～C20的酯基、C1～C20的酰胺基、C2～C16的硼酯基、C1～C20的酰基、醛基、氰基、C1～C20的胺基、氨基、C1～C20的烷基-氧基、C1～C20的烷基-硫基、卤素，R4中的任意两个可以相连成碳环或包含一个或多个选自O、N和S的杂原子的杂环；
R1和R2可以相连成包含N原子的杂环；如下式所述，其中，R5为一个或多个个独立选自下组的取代基：氢、任选取代的C1～C20的烷基、任选取代的C3～C20的环烷基、任选取代的C6～C20的苄基、任选取代的C5～C20的芳基、任选取代的C3～C20的杂芳基、硝基、C2～C20的酯基、C1～C20的酰胺基、C2～C16的硼酯基、C1～C20的酰基、醛基、氰基、C1～C20的胺基、氨基、C1～C20的烷基-氧基、C1～C20的烷基-硫基、卤素，R5中的任意两个可以相连成碳环或包含一个或多个选自O、N和S的杂原子的杂环；R6为氢、任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基或任选取代C3～C20的杂芳基；C2～C16的酯基、C1～C16的肼基、任选取代C1～C20的磺酰基；
所述“任选取代”为未被取代、或被如下基团取代：任选取代的C1～C20的烷基、任选取代的C1～C20的烷基-氧基、任选取代的C1～C20的烷基-硫基、卤素、硝基、任选取代的C2～C20的酯基、任选取代的C1～C20的酰基、任选取代的C1～C20的氰基、任选取代的C1～C20的醛基、任选取代的C2～C20的硼酯基、任选取代的C1～C20的酰胺基、任选取代的C1～C20的胺基、氨基，或任选取代的C6～C20的芳基、任选取代的C3～C20的杂芳基、任选取代的C5～C20的苄基；所述“取代”的个数可不做限定；
用*标注的碳为S构型手性碳或R构型手性碳。
2、根据权利要求1所述的制备方法，其特征在于：
所述催化剂为碘化钴(II)、溴化钴(II)、氯化钴(II)、高氯酸钴(II)、乙酰乙酰钴(II)、醋酸钴(II)、二(三苯基膦)碘化钴、碘化镍(II)、溴化镍(II)、氯化镍(II)、高氯酸镍、四氟硼酸镍、六氟磷酸镍、溴化镍(II)乙二醇二甲基醚络合物、氯化镍(II)乙二醇二甲基醚络合物、乙酰丙酮镍及以上钴或镍盐所对应的水合物、氯化亚铜、氯化铜、氯化钯、乙酸钯、氯化铂、溴化铬、氯化铬、双(环戊二烯基)二氯化钛、溴化铁、溴化亚铁、氯化铁、氯化亚铁；优选碘化钴或溴化钴；
和/或，所述配体为以下NPN及PHOX配体中的一种，如下式所述，其中，R7为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基、C2～C20的酯基；R8为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基；R9为一个或多个独立选自下组的取代基：氢、任选取代的C1～C20的烷基、任选取代的C3～C20的环烷基、任选取代的C6～C20的苄基、任选取代的C5～C20的芳基、任选取代的C3～C20的杂芳基、硝基、C1～C20的酰胺基、C2～C16的硼酯基、氰基、C1～C20的胺基、氨基、C1～C20的烷基-氧基、C1～C20的烷基-硫基、卤素；R10为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基；R11为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基；用*标注的碳为S构型手性碳或R构型手性碳；优选NPN配体；
在本发明中，所述还原剂为锌粉、锰粉、铟粉、镁粉、四(二甲氨基)乙烯中的一种或一种以上；优选锌粉、锰粉或铟粉；
在本发明中，所述添加剂为甲醇、乙醇、异丙醇、六氟异丙醇、三氟甲磺酸锌、三氟甲磺酸钪、三氟甲磺酸镧、三氟甲磺酸钕、三氟甲磺酸钇、三氟乙酸、碘化锌、溴化锌、氯化锌、碘化锂、溴化锂、氯化锂、碘化钠、溴化钠、氯化钠、碘化钾、溴化钾、氯化钾、碘化铷、溴化铷、氯化铷、碘化铯、溴化铯、碘化镁、溴化镁、氯化镁、四丁基碘化铵、四丁基溴化铵中的一种或一种以上；优选甲醇、乙醇、异丙醇、碘化钠、碘化锂、四丁基碘化铵中的一种或几种；
在本发明中，所述有机溶剂可以为乙腈、丙腈、丁腈、苯甲腈、四氢呋喃、2-甲基四氢呋喃、***、甲基叔丁基醚、环戊基甲基醚、二氧六环、乙二醇二甲醚、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲亚砜、N-甲基吡咯烷酮、1,3-二甲基-2-咪唑啉酮、二氯甲烷、氯仿、四氯化碳、1,2-二氯乙烷、苯、甲苯、二甲苯、甲醇、乙醇、丙醇、异丙醇、丁醇、中的一种或一种以上；优选乙腈、四氢呋喃、二氧六环、乙二醇二甲醚、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲醇、乙醇、异丙醇中的一种或几种；
在本发明中，所述保护气体可以为本领域该类反应常规的保护气体，如所述的保护气体包括氮气、氩气、氦气、氖气、或氪气；
在本发明中，所述的有机溶剂中的摩尔浓度为0.01～2.0M，优选0.02-0.5M；
在本发明中，所述的化合物1与化合物2的摩尔比为5:1～1:5，优选1:1-1:4；
在本发明中，所述的化合物1与所述催化剂的摩尔比为1:0.001～1:0.3，优选1:0.01-1:0.2；
在本发明中，所述的化合物1与所述添加剂的摩尔比为1:0.5～1:5，优选1:1-1:3；
在本发明中，所述反应温度可以为本领域该类反应常规的反应温度，如所述的反应温度为0～120℃，优选10-80℃；
在本发明中，所述反应时间可以为本领域该类反应常规的反应时间，如所述的反应时间为1-60h，优选3-48h。
与现有技术相比，本发明具有如下优点及有益效果：
本发明从廉价易得的原料出发，通过廉价过渡金属催化的不对称还原加成策略，实现了有机亲电试剂对亚胺的对映选择性加成反应。本发明操作简便，原子经济性高，底物普适性广泛，官能团容忍性出色，立体选择性专一，合成效率高。为手性氨基酸衍生物的模块化合成提供了一类通用性平台，将在制药、生命科学及生物化学领域产生重要的应用价值。
附图说明
图1是实施例1制得化合物的核磁共振氢谱图。
图2是实施例1制得化合物的核磁共振碳谱图。
图3是实施例24制得化合物的核磁共振氢谱图。
图4是实施例24制得化合物的核磁共振碳谱图。
图5是实施例81制得化合物的核磁共振氢谱图。
图6是实施例81制得化合物的核磁共振碳谱图。
图7是实施例93制得化合物的核磁共振氢谱图。
图8是实施例93制得化合物的核磁共振碳谱图。
图9是实施例130制得化合物的核磁共振氢谱图。
图10是实施例130制得化合物的核磁共振碳谱图。
具体实施方式
下面将结合本发明中的实施例，对本发明中的技术方案进行清楚、完整地描述。显然，所描述的实施例仅仅只是本发明的一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
(一)钴催化亚胺的不对称还原烷基化反应
通用步骤1：
向预先烘干的反应管中加入手性配体(6mol％)，Mn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、乙腈(0.2M)、烷基碘代物或溴代物2(1.5equiv)和相应的醇(1.0equiv)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中剧烈搅拌一定的时间。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3。
通用步骤2：
向预先烘干的反应管中加入手性配体(12mol％)，In(3.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoBr2(5mol％)、NaI(3.5equiv)、乙腈(0.4M)和烷基氯代物2(1.5equiv)。将反应管从手套箱内移出，封口膜密封，置于80℃油浴中剧烈搅拌一定的时间。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3
通用步骤3：
向预先烘干的反应管中加入手性配体(6mol％)，Mn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、乙腈(0.2M)、烷基溴代物2(1.5equiv)和异丙醇(1.0equiv)。将反应管从手套箱内移出，封口膜密封，置于30℃油浴中剧烈搅拌一定的时间。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3。反应对映选择性通过N-Bz保护的产物测试得到。
通用步骤4：
向预先烘干的反应管中加入手性配体(6mol％)，随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、乙腈(0.2M)。所得反应液预搅10分钟后，依次加入酮亚胺1(1.0equiv)、Mn(2.0equiv)、烷基碘代物2(1.5equiv)和异丙醇(1.0equiv)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中剧烈搅拌一定的时间。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3。
通用步骤5：
向预先烘干的反应管中加入手性配体(6mol％)，Zn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、碘化锂、MeCN/DMA＝9/1(0.2M)、α-氯代羰基化合物2(1.5equiv)和相应的醇(1.0equiv)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中剧烈搅拌一定的时间。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3。
通用步骤6：
向预先烘干的反应管中加入手性配体(6.0mo1％),Mn(2.5equiv)、和亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5.0mo1％)、NaI(3.0equiv)、MeCN/DME(9/1,0.05M)、烷基碘代物或溴代物2(2.0equiv)和相应的醇(1.0equiv)。随后将反应管从手套箱内移出，封口膜密封，置于35℃油中剧烈搅拌一定的时间。待反应完毕，将反应液旋干，所得粗产品使用快速柱层析纯化得到产物3。(PMP定义为对甲氧基苯基)
通用步骤7：
向一合适大小的茄形瓶中加入乙醛酸酯(1.2equiv)、PMPNH2(1.0equiv)、MgSO4(500mg/mmol)与DCM(0.5M)，反应液于室温下搅拌至原料消耗完成。随后将反应液使用硅藻土过滤，DCM洗涤滤饼，滤液旋干并于真空泵上将残余少量溶剂抽干，直接使用。
向预先烘干的反应管中加入手性配体(6.0mo1％),Mn(2.5equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5.0mo1％)、NaI(3.0equiv)、上述亚胺(1.0equiv)的乙腈溶液(0.1M)、MeCN/DME(9/1,0.1M)(总浓度为0.05M)、烷基碘代物或溴代物2(2.0equiv)和相应的醇(1.0equiv)。随后将反应管从手套箱内移出，封口膜密封，置于35℃油中剧烈搅拌一定的时间。待反应完毕，将反应液旋干，所得粗产品使用快速柱层析纯化得到产物3。
实施例1：
操作过程如通用步骤1，得无色油状液体70.6mg,89％收率，反应放大至克级规模得1.67g,84％收率；Rf＝0.56(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.60(d,J＝7.2Hz,2H),7.33(t,J＝7.6Hz,2H),7.28–7.24(m,1H),6.61(d,J＝8.8Hz,2H),6.34(d,J＝8.8Hz,2H),5.03(s,1H),4.96(sept,J＝6.4Hz,1H),3.68(s,3H),2.50–2.34(m,2H),1.36–1.13(m,13H),1.00(d,J＝6.0Hz,3H),0.85(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.6,151.9,141.6,138.7,128.4,127.3,127.2,116.5,114.4,69.4,66.6,55.6,33.2,31.7,29.6,29.1,23.8,22.7,21.7,21.3,14.2；HRMS(ESI):[M+H]+Calcd for C25H36NO3 +:398.2690；found:398.2694.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.228min(major),tR2＝9.105min(minor)；98％e.e.；[α]D 25＝31.3(c＝7.00,CHCl3).
操作过程如通用步骤1，以1-溴庚烷为亲电试剂，2.0当量LiI作为添加剂，得无色油状液体69.9mg,88％收率，97％ee；1H NMR(400MHz,CDCl3):δ7.60(d,J＝7.2Hz,2H),7.33(t,J＝7.6Hz,2H),7.27–7.24(m,1H),6.61(d,J＝8.8Hz,2H),6.34(d,J＝8.8Hz,2H),5.03(s,1H),4.96(sept,J＝6.4Hz,1H),3.67(s,3H),2.49–2.34(m,2H),1.33–1.08(m,13H),1.00(d,J＝6.0Hz,3H),0.85(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.6,152.0,141.6,138.7,128.4,127.3,127.2,116.5,114.5,69.4,66.7,55.7,33.3,31.8,29.6,29.1,23.9,22.7,21.7,21.4,14.2.
操作过程如通用步骤2，得无色油状液体66.8mg,84％收率，99％ee；1H NMR(400MHz,CDCl3):δ7.61(d,J＝7.2Hz,2H),7.33(t,J＝7.6Hz,2H),7.28–7.24(m,1H),6.61(d,J＝8.8Hz,2H),6.35(d,J＝8.8Hz,2H),5.05(s,1H),4.97(sept,J＝6.4Hz,1H),3.68(s,3H),2.50–2.35(m,2H),1.33–1.08(m,13H),1.01(d,J＝6.0Hz,3H),0.85(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.5,152.0,141.6,138.7,128.4,127.3,127.2,116.5,114.4,69.4,66.7,55.7,33.3,31.7,29.6,29.1,23.8,22.7,21.7,21.3,14.2.
实施例2：
操作过程如通用步骤1，得无色油状液体83.9mg,96％收率；Rf＝0.67(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.61(d,J＝7.2Hz,2H),7.34(t,J＝7.6Hz,2H),7.28–7.24(m,1H),6.60(d,J＝8.8Hz,2H),6.34(d,J＝8.8Hz,2H),5.04–4.93(m,3H),3.67(s,3H),2.51(td,J＝12.8,3.6Hz,1H),2.35(td,J＝12.4,4.0Hz,1H),1.89–1.79(m,2H),1.66(s,3H),1.53(s,3H),1.40–1.27(m,2H),1.25–1.16(m,4H),1.10–1.03(m,1H),1.00(d,J＝6.0Hz,3H),0.94–0.88(m,1H),0.83(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.5,152.0,141.7,138.6,131.2,128.4,127.3,127.2,124.9,116.6,114.4,69.4,66.6,55.7,36.9,32.4,30.8,30.6,25.8,25.4,21.7,21.3,19.8,17.7；HRMS(ESI):[M+H]+Calcd forCalcd for C28H40NO3 +:438.3003；found:438.2994.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝6.457min(major),tR2＝10.361min(minor)；99:1d.r.；[α]D 25＝124.6(c＝1.34,CHCl3).
实施例3：
操作过程如通用步骤1，得无色油状液体59.9mg,67％收率；Rf＝0.53(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.87(d,J＝7.6Hz,2H),7.60(d,J＝7.6Hz,2H),7.53(t,J＝7.2Hz,1H),7.42(t,J＝7.6Hz,2H),7.34(t,J＝7.6Hz,2H),7.28–7.25(m,1H),6.61(d,J＝8.8Hz,2H),6.36(d,J＝8.8Hz,2H),5.12(s,1H),4.96(sept,J＝6.4Hz,1H),3.67(s,3H),2.91(t,J＝7.6Hz,2H),2.65(ddd,J＝13.6,11.2,5.2Hz,1H),2.46(ddd,J＝13.6,11.2,5.2Hz,1H),1.79–1.61(m,2H),1.18(d,J＝6.4Hz,3H),1.01(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ199.7,173.2,151.9,141.2,138.4,136.7,133.0,128.6,128.5,128.1,127.4,127.1,116.4,114.5,69.7,66.5,55.6,38.5,32.9,21.5,21.3,18.9；HRMS(ESI):[M+H]+Calcd for Calcd for C28H32NO4 +:446.2326；found:446.2332.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝16.418min(major),tR2＝26.463min(minor)；99％e.e.；[α]D 25＝30.6(c＝5.32,CHCl3).
实施例4：
操作过程如通用步骤1，得白色固体35.6mg,50％收率；Rf＝0.79(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.57(d,J＝7.2Hz,2H),7.35(t,J＝6.8Hz,2H),7.30–7.26(m,1H),6.61(d,J＝8.8Hz,2H),6.35(d,J＝8.8Hz,2H),5.04(s,1H),3.67(s,3H),3.66(s,3H),3.59(s,3H),2.91(ddd,J＝14.0,10.4,5.2Hz,1H),2.77(ddd,J＝14.0,10.4,5.6Hz,1H),2.36(ddd,J＝16.4,10.4,5.6Hz,1H),2.19(ddd,J＝16.4,10.4,5.2Hz,1H)；13C NMR(100MHz,CDCl3):δ174.1,173.5,152.4,140.3,137.7,128.8,127.8,127.0,116.7,114.6,66.0,55.6,53.3,51.8,29.2,28.9；HRMS(ESI):[M+H]+Calcd for Calcd for C20H24NO5 +:358.1649；found:358.1640.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝22.457min(major),tR2＝25.116min(minor)；97％e.e.；[α]D 25＝52.5(c＝2.57,CHCl3).
实施例5：
操作过程如通用步骤1，得淡黄色油状液体63.1mg,79％收率；Rf＝0.23(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.58(d,J＝7.6Hz,2H),7.32(t,J＝7.2Hz,2H),7.27–7.23(m,1H),6.60(d,J＝9.2Hz,2H),6.35(d,J＝8.8Hz,2H),5.02(bs,1H),4.95(sept,J＝6.0Hz,1H),4.79(t,J＝4.8Hz,1H),3.96–3.86(m,2H),3.84–3.76(m,2H),3.66(s,3H),2.65(ddd,J＝13.6,12.0,4.0Hz,1H),2.50(ddd,J＝13.6,12.4,4.8Hz,1H),1.74–1.65(m,1H),1.50–1.42(m,1H),1.18(d,J＝6.4Hz,3H),1.01(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,152.0,141.0,138.4,128.4,127.4,127.1,116.6,114.4,104.2,69.6,66.2,64.87,64.85,55.6,28.6,28.1,21.6,21.3；HRMS(ESI):[M+H]+Calcd for Calcd for C23H30NO5 +:400.2118；found:400.2110.HPLC(Chiralpak AD-H):n-Hexane/EtOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝22.513min(major),tR2＝25.526min(minor)；94％e.e.；[α]D 25＝44.3(c＝5.22,CHCl3).
实施例6：
操作过程如通用步骤1，得无色粘稠油状液30.0mg,61％收率；Rf＝0.50(PE/Et2O/acetone＝6/1/1)；1H NMR(400MHz,CDCl3):δ7.56(d,J＝8.0Hz,2H),7.35–7.25(m,8H),6.60(d,J＝8.8Hz,2H),6.33(d,J＝8.8Hz,2H),5.09–5.04(m,3H),4.95(sept,J＝6.4Hz,1H),4.57(t,J＝5.6Hz,1H),3.64(s,3H),3.21–3.09(m,2H),2.53(td,J＝13.6,4.8Hz,1H),2.42(td,J＝12.0,4.8Hz,1H)1.54–1.43(m,1H),1.41–1.32(m,1H),1.18(d,J＝6.0Hz,3H),0.98(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,156.4,152.1,141.0,138.2,136.7,128.62,128.56,128.2,128.17,127.6,127.0,116.6,114.6,69.8,66.7,66.3,55.6,40.9,30.4,24.7,21.7,21.3；HRMS(ESI):[M+H]+Calcd for Calcd for C29H35N2O5 +:491.2540；found:491.2550.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝32.088min(major),tR2＝33.474min(minor)；99％e.e.；[α]D 25＝35.7(c＝2.71,CHCl3).
实施例7：
操作过程如通用步骤1，得无色油状液体57.4mg,73％收率；Rf＝0.47(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.55(d,J＝7.2Hz,2H),7.29(t,J＝7.6Hz,2H),7.22(t,J＝7.2Hz,1H),6.59(d,J＝9.2Hz,2H),6.30(d,J＝9.2Hz,2H),5.21(s,1H),4.93(sept,J＝6.0Hz,1H),3.67(s,3H),2.48(dd,J＝14.0,7.2Hz,1H),2.39(dd,J＝14.4,4.0Hz,1H),1.69–1.53(m,5H),1.47–1.34(m,2H),1.19(d,J＝6.0Hz,3H),1.15–1.06(m,2H),0.99–0.86(m,5H)；13C NMR(100MHz,CDCl3):δ174.1,151.5,141.9,139.0,128.4,127.3,127.2,115.8,114.4,69.6,65.7,55.6,40.9,34.6,33.9,33.7,26.5,26.43,26.38,21.6,21.2；HRMS(ESI):[M+H]+Calcd for Calcd for C25H34NO3 +:396.2533；found:396.2524.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝9.269min(major),tR2＝13.763min(minor)；99％e.e.；[α]D 25＝6.58(c＝2.19,CHCl3).
实施例8：
操作过程如通用步骤1，得淡黄色粘稠油状液44.1mg,83％收率；Rf＝0.28(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.49(d,J＝7.2Hz,2H),7.35–7.19(m,8H),6.58(d,J＝9.2Hz,2H),6.30(d,J＝8.8Hz,2H),5.24(s,1H),5.08(s,2H),4.91(sept,J＝6.4Hz,1H),4.13–3.94(m,2H),3.64(s,3H),2.68–2.64(m,2H),2.53(dd,J＝14.4,7.2Hz,1H),2.45(dd,J＝14.4,4.8Hz,1H),1.64–1.54(m,2H),1.43–1.39(m,1H),1.25–1.07(m,5H),0.90(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.9,155.3,151.7,141.3,138.5,137.0,128.5,128.5,128.0,127.9,127.5 126.9,115.8,114.5,69.9,67.0,65.4,55.6,44.3,44.1,39.7,33.1,32.32,32.28,21.6,21.1；HRMS(ESI):[M+H]+Calcd for Calcd for C32H39N2O5 +:531.2853；found:531.2863.HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate1.0mL/min,T＝25℃,λ＝210nm,tR1＝7.029min(major),tR2＝8.826min(minor)；98％e.e.；[α]D 25＝11.2(c＝5.12,CHCl3).
在反应管中依次加入酮酸酯(0.2mmol,1.0equiv.)、对甲氧基苯胺(0.4mmol,2.0equiv.)无水苯(0.4M,0.5mL)、TsOH·H2O(0.02mmol,10mol％)和分子筛。所得反应液加热回流24h后，冷却至室温，随后用硅藻土过滤，DCM洗涤。滤液旋干得到亚胺粗产品。加入L1(0.024mmol,12mol％),Mn(0.4mmol,2.0equiv.)。反应管转移至手套箱，依次加入CoI2(0.02mmol,10mol％)、MeCN(0.2M)、碘代物(0.4mmol,2.0equiv.)和异丙醇(0.2mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌24h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到黄色油状液86.3mg,81％收率,97％ee。
实施例9：
操作过程如通用步骤1，得无色油状液51.7mg,70％收率；Rf＝0.40(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.52–7.50(m,2H),7.27(t,J＝7.2Hz,2H),7.20(tt,J＝7.6,1.6Hz,1H),6.58(d,J＝8.8Hz,2H),6.25(d,J＝9.2Hz,2H),5.39(s,1H),4.93(sept,J＝6.4Hz,1H),3.65(s,3H),2.71(d,J＝14.4Hz,1H),2.50(d,J＝14.8Hz,1H),1.21(d,J＝6.4Hz,3H),0.95(s,9H),0.86(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ174.5,151.0,142.3,139.3,128.4,127.2,126.9,115.5,114.4,69.7,65.2,55.6,44.0,31.8,30.7,21.5,21.0；HRMS(ESI):[M+H]+Calcd for Calcd for C23H32NO3 +:370.2377；found:370.2368.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝80/20,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝3.753min(major),tR2＝5.540min(minor)；98％e.e.；[α]D 25＝39.4(c＝2.46,CHCl3).
实施例10：
操作过程如通用步骤1，得淡黄色油状液70.5mg,68％收率；Rf＝0.71(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.50(d,J＝7.6Hz,2H),7.28(t,J＝7.2Hz,2H),7.21(t,J＝7.2Hz,1H),7.01(d,J＝7.2Hz,1H),6.67(d,J＝7.2Hz,1H),6.59–6.55(m,3H),6.26(d,J＝8.8Hz,2H),5.42(s,1H),4.93(sept,J＝6.4Hz,1H),3.74(t,J＝6.4Hz,2H),3.61(s,3H),2.75(d,J＝14.8Hz,1H),2.56(d,J＝14.4Hz,1H),2.32(s,3H),2.19(s,3H),1.83–1.67(m,2H),1.50–1.36(m,2H),1.22(d,J＝6.4Hz,3H),0.99(s,3H),0.96(s,3H),0.86(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ174.5,157.2,151.2,142.2,139.1,136.5,130.3,128.5,127.2,126.9,123.6,120.6,115.5,114.4,112.1,69.8,68.5,65.0,55.6,41.9,40.8,34.1,28.0,26.8,24.5,21.6,21.5,21.0,15.9；HRMS(ESI):[M+H]+Calcd for Calcdfor C33H44NO4 +:518.3265；found:518.3256.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.330min(major),tR2＝12.729min(minor)；98％e.e.；[α]D 25＝30.6(c＝4.26,CHCl3).
实施例11：
操作过程如通用步骤1，得淡黄色固体108.8mg,87％收率；Rf＝0.36(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.64(d,J＝8.8Hz,4H),7.46(d,J＝8.4Hz,2H),7.35(t,J＝7.6Hz,2H),7.29(d,J＝7.2Hz,1H),6.87(d,J＝8.8Hz,1H),6.68(d,J＝8.4Hz,2H),6.62(dd,J＝9.2,2.4Hz,1H),6.47(d,J＝8.4Hz,2H),6.40(d,J＝2.4Hz,1H),5.34(s,1H),5.07(sept,J＝6.4Hz,1H),3.69(s,3H),3.64(s,3H),2.87–2.71(m,3H),2.47–2.40(m,1H),2.16(s,3H),1.33(d,J＝6.4Hz,3H),1.03(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,168.2,155.9,152.1,141.2,139.0,138.2,134.2,133.9,131.1,130.9,130.8,129.1,128.6,127.6,126.9,119.0,116.4,115.0,114.6,111.5,100.7,69.9,66.2,55.7,55.5,32.2,21.8,21.2,18.7,12.9；HRMS(ESI):[M+H]+Calcd for Calcd for C37H38ClN2O5 +:625.2464；found:625.2455.HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.388min(major),tR2＝9.053min(minor)；97％e.e.；[α]D 25＝74.3(c＝0.84,CHCl3).
实施例12：
操作过程如通用步骤1，得无色粘稠油状液108.5mg,79％收率；Rf＝0.17(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.59(d,J＝7.6Hz,2H),7.32(t,J＝7.6Hz,2H),7.27–7.23(m,1H),6.60(d,J＝8.8Hz,2H),6.33(d,J＝8.8Hz,2H),5.03(bs,1H),4.95(sept,J＝6.4Hz,1H),3.67(s,3H),3.51(dt,J＝12.0,4.4Hz,1H),3.36(s,3H),3.30(s,3H),3.18–3.10(m,1H),2.44(td,J＝11.6,4.0Hz,1H),2.26(td,J＝11.6,4.0Hz,1H),1.91(tt,J＝12.0,3.2Hz,2H),1.82–1.51(m,8H),1.38–1.26(m,8H),1.18(d,J＝6.0Hz,3H),1.15–0.92(m,11H),0.89(s,3H),0.80(d,J＝6.4Hz,3H),0.59(s,3H)；13C NMR(100MHz,CDCl3):δ173.6,152.0,141.7,138.7,128.4,127.3,127.2,116.7,114.4,80.3,77.3,69.4,66.8,56.2,56.0,55.8,55.71,55.70,45.0,42.9,40.1,40.0,36.1,35.82,35.78,35.5,34.8,33.7,31.8,28.2,27.1,25.6,24.3,23.8,21.7,21.4,20.9,20.2,18.7,12.1；HRMS(ESI):[M+H]+Calcd for Calcd for C44H66NO5 +:688.4936；found:688.4932.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝10.576min(minor),tR2＝11.844min(major)；98:2d.r.；[α]D 25＝39.4(c＝8.42,CHCl3).
实施例13：
操作过程如通用步骤1，得淡黄色粘稠油状液68.3mg,66％收率；Rf＝0.29(PE/EtOAc＝4/1)；1H NMR(400MHz,CDCl3):δ7.65(dd,J＝8.4,1.2Hz,2H),7.32(t,J＝7.2Hz,2H),7.24(tt,J＝7.2,2.0Hz,1H),6.58(d,J＝8.8Hz,2H),6.24(d,J＝8.8Hz,2H),5.59(s,1H),5.00(sept,J＝6.4Hz,1H),4.68(d,J＝3.6Hz,1H),3.75(ddd,J＝9.6,8.0,2.4Hz,1H),3.65(s,3H),3.60(s,3H),3.55(s,3H),3.51–3.43(m,4H),3.23(s,3H),3.13(dd,J＝9.6,3.6Hz,1H),2.79(t,J＝9.2Hz,1H),2.73(dd,J＝14.4,2.0Hz,1H),2.27(dd,J＝14.8,7.6Hz,1H),1.13(d,J＝6.0Hz,3H),1.03(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ172.8,151.6,141.0,140.2,128.2,127.7,127.3,115.8,114.1,97.6,83.7,83.4,81.8,69.3,67.9,67.1,60.8,60.8,59.0,55.9,55.6,42.4,21.7,21.4；HRMS(ESI):[M+H]+Calcdfor Calcd for C28H40NO8 +:518.2748；found:518.2741.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝40℃,λ＝220nm,tR1＝5.709min(minor),tR2＝6.317min(major)；>99:1d.r.；[α]D 25＝82.3(c＝6.83,CHCl3).
实施例14：
操作过程如通用步骤1，得黄色油状液96.1mg,68％收率；Rf＝0.43(PE/acetone＝3/1)；1H NMR(400MHz,CDCl3):δ7.54(d,J＝7.2Hz,2H),7.31–7.27(m,3H),7.23(t,J＝7.2Hz,1H),6.56(d,J＝9.2Hz,2H),6.30(d,J＝8.8Hz,2H),5.94(d,J＝4.0Hz,1H),5.68(d,J＝8.4Hz,1H),5.35–5.28(m,2H),4.99(bs,1H)4.92(sept,J＝6.4Hz,1H),4.36–4.30(m,3H),3.86(td,J＝6.8,2.8Hz,2H),3.64(s,3H),2.54–2.38(m,2H),2.12(s,3H),2.10(s,3H),2.08(s,3H),1.70–1.59(m,1H),1.54–1.43(m,1H),1.15(d,J＝6.0Hz,3H),0.97(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.1,170.2,169.64,169.58,162.1,152.0,150.8,141.0,138.2,137.0,128.4,127.4,127.1,116.7,114.4,102.8,88.7,79.6,73.1,69.9,69.6,66.4,63.0,55.6,41.0,30.5,22.5,21.5,21.3,20.8,20.6,20.5；HRMS(ESI):[M+H]+Calcd for Calcd for C36H44N3O12 +:710.2920；found:710.2919.HPLC(Chiralpak IBN-5):n-Hexane/EtOH＝80/20,flow rate 1.0mL/min,T＝40℃,λ＝220nm,tR1＝15.456min(major),tR2＝17.359min(minor)；98.5:1.5d.r.；[α]D 25＝14.8(c＝6.86,CHCl3).
实施例15：
操作过程如通用步骤1，得无色油状液67.3mg,99％收率；Rf＝0.42(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.69(d,J＝7.2Hz,2H),7.34–7.26(m,3H),6.59(d,J＝8.8Hz,2H),6.36(d,J＝8.8Hz,2H),4.93(sept,J＝6.4Hz,1H),4.11(bs,1H),3.66(s,3H),2.47(sept,J＝6.8Hz,1H),1.15(d,J＝6.4Hz,3H),0.91(d,J＝6.4Hz,3H),0.87(d,J＝6.4Hz,3H),0.81(d,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ172.9,152.4,140.5,136.6,129.5,127.4,127.1,116.8,114.1,71.1,68.5,55.7,38.6,21.8,21.5,18.4,17.4；HRMS(ESI):[M+H]+Calcd for Calcd for C21H28NO3 +:342.2064；found:342.2066.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.233min(minor),tR2＝11.813min(major)；99％e.e.；[α]D 25＝112.3(c＝3.70,CHCl3).
操作过程如通用步骤2，得无色油状液13.8mg,40％收率,97％ee；1H NMR(400MHz,CDCl3):δ7.69(d,J＝6.8Hz,2H),7.34–7.27(m,3H),6.59(d,J＝9.2Hz,2H),6.36(d,J＝9.2Hz,2H),4.93(sept,J＝6.4Hz,1H),4.13(bs,1H),3.67(s,3H),2.48(sept,J＝6.8Hz,1H),1.15(d,J＝6.0Hz,3H),0.91(d,J＝6.8Hz,3H),0.87(d,J＝6.4Hz,3H),0.81(d,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ173.0,152.5,140.6,136.8,129.6,127.5,127.2,117.0,114.3,71.2,68.7,55.8,38.7,21.9,21.6,18.5,17.5；
实施例16：
操作过程如通用步骤1，得无色油状液70.2mg,96％收率；Rf＝0.40(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.71(d,J＝7.2Hz,2H),7.32–7.22(m,3H),6.58(d,J＝8.8Hz,2H),6.32(d,J＝8.8Hz,2H),4.94(sept,J＝6.4Hz,1H),4.35(s,1H),3.65(s,3H),2.70(quint,J＝8.4Hz,1H),1.74–1.68(m,1H),1.58–1.40(m,7H),1.12(d,J＝6.0Hz,3H),0.91(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.3,152.2,140.4,139.1,128.9,127.7,127.0,116.7,114.1,69.2,68.7,55.6,50.2,27.8,27.4,25.05,25.03,21.7,21.4；HRMS(ESI):[M+H]+Calcd for Calcd for C23H30NO3 +:368.2220；found:368.2214.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝11.210min(minor),tR2＝12.566min(major)；98％e.e.；[α]D 25＝75.5(c＝5.28,CHCl3).
操作过程如通用步骤1，得无色油状液72.7mg,99％收率,98％ee；Rf＝0.40(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.73(d,J＝7.2Hz,2H),7.34–7.24(m,3H),6.60(d,J＝8.8Hz,2H),6.34(d,J＝8.0Hz,2H),4.96(sept,J＝6.4Hz,1H),4.36(s,1H),3.65(s,3H),2.72(quint,J＝8.4Hz,1H),1.76–1.70(m,1H),1.59–1.44(m,7H),1.14(d,J＝6.4Hz,3H),0.93(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.3,152.3,140.4,139.2,128.9,127.7,127.0,116.8,114.1,69.2,68.7,55.7,50.2,27.8,27.5,25.1,25.1,21.8,21.5.
实施例17：
操作过程如通用步骤1，得无色油状液68.9mg,90％收率；1H NMR(400MHz,CDCl3):δ7.69(d,J＝6.8Hz,2H),7.34–7.26(m,3H),6.60(d,J＝9.2Hz,2H),6.35(d,J＝8.8Hz,2H),4.93(sept,J＝6.4Hz,1H),4.15(s,1H),3.67(s,3H),2.11(tt,J＝12.0,2.8Hz,1H),1.91(d,J＝12.8Hz,1H),1.76–1.66(m,3H),1.60(d,J＝12.8Hz,1H),1.33–1.19(m,2H),1.15(d,J＝6.4Hz,3H),1.11–0.94(m,2H),0.88(d,J＝6.4Hz,3H),0.58(qd,J＝12.8,3.2Hz,1H)；13CNMR(100MHz,CDCl3):δ172.8,152.3,140.5,137.2,129.4,127.3,127.0,116.6,114.1,71.1,68.4,55.6,49.4,28.8,27.8,26.8,26.6,26.4,21.8,21.5；HRMS(ESI):[M+H]+Calcdfor Calcd for C24H32NO3 +:382.2377；found:382.2369.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝235nm,tR1＝5.986min(minor),tR2＝7.055min(major)；98％e.e.；[α]D 25＝107.6(c＝6.00,CHCl3).
实施例18：
操作过程如通用步骤1，得无色油状液62.6mg,79％收率；Rf＝0.60(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.67(d,J＝6.8Hz,2H),7.34–7.26(m,3H),6.60(d,J＝8.8Hz,2H),6.37(d,J＝8.8Hz,2H),4.95(sept,J＝6.4Hz,1H),4.08(bs,1H),3.67(s,3H),2.23(tt,J＝10.4,2.8Hz,1H),2.02–1.97(m,1H),1.83–1.77(m,1H),1.73–1.65(m,1H),1.63–1.49(m,3H),1.45–1.34(m,4H),1.29–1.20(m,1H),1.16(d,J＝6.4Hz,3H),0.88(d,J＝6.4Hz,3H),0.85–0.76(m,1H)；13C NMR(100MHz,CDCl3):δ172.9,152.4,140.4,137.1,129.4,127.3,127.0,116.9,114.1,71.9,68.4,55.6,49.8,30.8,29.4,27.51,27.46,21.8,21.5；HRMS(ESI):[M+H]+Calcd for Calcd for C25H34NO3 +:396.2533；found:396.2525.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝9.630min(minor),tR2＝11.379min(major)；99％e.e.；[α]D 25＝122.7(c＝6.10,CHCl3).
实施例19：
操作过程如通用步骤1，得无色油状液69.4mg,85％收率；1H NMR(400MHz,CDCl3):δ7.69(d,J＝7.2Hz,2H),7.34–7.26(m,3H),6.60(d,J＝8.8Hz,2H),6.36(d,J＝9.2Hz,2H),4.95(sept,J＝6.4Hz,1H),4.06(s,1H),3.67(s,3H),2.38(tt,J＝9.2,2.4Hz,1H),1.91(dt,J＝14.8,4.0Hz,1H),1.73–1.40(m,11H),1.35–1.27(m,1H),1.18(d,J＝6.4Hz,3H),1.03–0.92(m,1H),0.88(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.0,152.4,140.4,137.3,129.4,127.3,127.0,116.9,114.0,72.3,68.5,55.6,48.0,29.8,28.7,27.1,26.54,26.46,26.3,25.9,21.8,21.5；HRMS(ESI):[M+H]+Calcd for Calcd for C26H36NO3 +:410.2690；found:410.2678.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝9.325min(minor),tR2＝10.813min(major)；97％e.e.；[α]D 25＝30.4(c＝6.11,CHCl3).
实施例20：
操作过程如通用步骤1，得白色固体65.8mg,68％收率；Rf＝0.28(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.63(d,J＝7.2Hz,2H),7.34–7.28(m,3H),6.60(d,J＝8.8Hz,2H),6.37(d,J＝8.8Hz,2H),4.94(sept,J＝6.4Hz,1H),4.17–4.10(m,3H),3.66(s,3H),2.70–2.63(m,2H),2.31–2.25(m,1H),1.87–1.82(m,1H),1.63–1.59(m,1H),1.39(s,9H),1.26–1.21(m,1H),1.10(d,J＝6.0Hz,3H),0.90(d,J＝6.4Hz,3H),0.88–0.83(m,1H)；13CNMR(100MHz,CDCl3):δ172.4,154.7,152.6,140.0,136.9,129.0,127.6,127.3,117.0,114.1,79.5,70.4,68.8,55.6,47.1,44.2,28.4,28.0,26.9,21.7,21.4；HRMS(ESI):[M+H]+Calcd for Calcd for C28H39N2O5 +:483.2853；found:483.2861.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.302min(minor),tR2＝7.508min(major)；96％e.e.；[α]D 25＝58.1(c＝4.56,CHCl3).
实施例21：
操作过程如通用步骤1，得无色油状液70.9mg,93％收率；Rf＝0.2(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.66(d,J＝6.8Hz,2H),7.35–7.28(m,3H),6.61(d,J＝8.8Hz,2H),6.38(d,J＝9.2Hz,2H),4.95(sept,J＝6.4Hz,1H),4.17(s,1H),3.96–3.93(m,2H),3.67(s,3H),3.43–3.33(m,2H),2.45–2.37(m,1H),1.76–1.70(m,1H),1.51–1.45(m,2H),1.19(td,J＝12.4,4.4Hz,1H),1.12(d,J＝6.0Hz,3H),0.91(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ172.4,152.6,140.0,137.0,129.0,127.7,127.4,117.0,114.1,70.4,68.8,68.1,55.6,46.1,28.7,27.8,21.8,21.5；HRMS(ESI):[M+H]+Calcd for Calcd forC23H30NO4 +:384.2169；found:384.2173.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝210nm,T＝25℃,tR1＝6.702min(minor),tR2＝10.645min(major)；97％e.e.；[α]D 25＝81.0(c＝5.45,CHCl3).
实施例22：
操作过程如通用步骤1，得无色油状液49.4mg,54％收率；Rf＝0.16(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.42–7.28(m,5H),6.62(d,J＝8.8Hz,2H),6.42(d,J＝8.8Hz,2H),5.05(sept,J＝6.4Hz,1H),4.67(bs,1H),4.17(t,J＝7.2Hz,1H),4.07(t,J＝8.8Hz,1H),3.79(d,J＝7.2Hz,2H),3.68(s,3H),3.50(quint,J＝7.6Hz,1H),1.38(s,9H),1.11(d,J＝6.4Hz,6H)；13C NMR(100MHz,CDCl3):δ172.3,156.1,153.5,139.2,138.3,128.5,127.9,127.5,119.1,114.3,79.6,70.0,68.1,55.6,50.5,35.1,28.4,21.6,21.5；HRMS(ESI):[M+H]+Calcd for Calcd for C26H35N2O5 +:455.2540；found:455.2547.HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.783min(minor),tR2＝8.713min(major)；89％e.e.；[α]D 25＝36.1(c＝1.55,CHCl3).
实施例23：
操作过程如通用步骤1，得无色油状液51.4mg,72％收率；Rf＝0.47(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.43–7.41(m,2H),7.38–7.29(m,3H),6.64(d,J＝9.2Hz,2H),6.44(d,J＝8.8Hz,2H),5.05(sept,J＝6.4Hz,1H),4.92–4.83(m,3H),4.59–4.53(m,2H),3.96(quint,J＝7.6Hz,1H),3.69(s,3H),1.11(d,J＝6.0Hz,3H),1.10(d,J＝6.4Hz,3H)；13CNMR(100MHz,CDCl3):δ172.4,153.3,139.1,138.5,128.5,127.9,127.5,118.7,114.3,72.89,72.85,69.9,67.8,55.6,41.8,21.6,21.5；HRMS(ESI):[M+H]+Calcd for Calcd forC21H26NO4 +:356.1856；found:356.1858.HPLC(Chiralpak AD-H):n-Hexane/EtOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝21.598min(minor),tR2＝27.599min(major)；95％e.e.；[α]D 25＝46.0(c＝4.30,CHCl3).
实施例24：
操作过程如通用步骤1，得淡黄色油状液33.2mg,67％收率；Rf＝0.15(PE/EtOAc＝10/1)；1H NMR(400MHz,DMSO-d6)δ7.52(d,J＝7.2Hz,2H),7.31(t,J＝7.2Hz,2H),7.24(t,J＝7.2Hz,1H),6.56(d,J＝8.8Hz,2H),6.35(d,J＝9.2Hz,2H),5.59(s,1H),4.84(sept,J＝6.0Hz,1H),3.82–3.76(m,2H),3.56(s,3H),3.50(bs,2H),2.87(quint,J＝8.8Hz,1H),2.21–2.15(m,1H),2.11–2.03(m,2H),1.88–1.82(m,1H),1.33(s,9H),1.09(d,J＝6.4Hz,3H),0.87(d,J＝6.0Hz,3H)；13C NMR(100MHz,DMSO-d6)δ172.4,155.8,151.7,140.7,139.5,128.4,128.1,127.4,116.5,114.1,78.8,68.5,68.1,55.5,39.1,34.6,34.0,32.7,28.5,22.0,21.6；HRMS(ESI):[M+H]+Calcd for Calcd for C29H39N2O5 +:495.2853；found:495.2844.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝14.433min(major),tR2＝16.946min(minor)；95％e.e.；[α]D 25＝23.2(c＝1.75,CHCl3).
实施例25：
操作过程如通用步骤1，得淡黄色油状液41.2mg,79％收率；Rf＝0.20(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.55(d,J＝7.6Hz,2H),7.33–7.24(m,3H),6.58(d,J＝8.8Hz,2H),6.35(d,J＝8.8Hz,2H),4.97(sept,J＝6.0Hz,1H),4.51(s,1H),3.66(s,3H),3.35–3.13(m,5H),1.95–1.85(m,2H),1.81–1.67(m,3H),1.53(t,J＝5.6Hz,2H),1.43(s,9H),1.28–1.25(m,1H),1.09(d,J＝6.0Hz,3H),1.00(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.8,155.0,152.5,139.8,139.7,128.1,128.0,127.3,117.4,114.2,79.4,69.2,68.7,55.6,40.8,38.8,37.4,35.9,34.9,34.0,33.1,32.7,28.5,21.8,21.6；HRMS(ESI):[M+H]+Calcd for Calcd for C31H43N2O5 +:523.3166；found:523.3157.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝11.562min(major),tR2＝15.997min(minor)；97％e.e.；[α]D 25＝30.1(c＝4.16,CHCl3).
在反应管中依次加入酮酸酯(0.2mmol,1.0equiv.)、对甲氧基苯胺(0.4mmol,2.0equiv.)无水苯(0.4M,0.5mL)、TsOH·H2O(0.02mmol,10mol％)和分子筛。所得反应液加热回流24h后，冷却至室温，随后用硅藻土过滤，DCM洗涤。滤液旋干得到亚胺粗产品。加入L1(0.024mmol,12mol％),Mn(0.4mmol,2.0equiv.)。反应管转移至手套箱，依次加入CoI2(0.02mmol,10mol％)、MeCN(0.2M)、碘代物(0.4mmol,2.0equiv.)和异丙醇(0.2mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌22h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到黄色油状液87.3mg,84％收率,97％ee。
实施例26：
操作过程如通用步骤1，得淡黄色粘稠油状液65.1mg,74％收率；Rf＝0.44(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.66(d,J＝6.8Hz,2H),7.33–7.26(m,3H),6.59(d,J＝9.2Hz,2H),6.35(d,J＝8.8Hz,2H),4.94(sept,J＝6.4Hz,1H),4.15(s,1H),3.89–3.79(m,4H),3.66(s,3H),2.18–2.11(m,1H),1.89(dt,J＝13.2,3.2Hz,1H),1.76–1.70(m,2H),1.65–1.62(m,1H),1.54(qd,J＝13.6,4.0Hz,2H),1.38(qd,J＝13.2,3.2Hz,1H),1.12(d,J＝6.0Hz,3H),1.00(qd,J＝13.2,3.2Hz,1H),0.88(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.7,152.4,140.3,137.1,129.1,127.6,127.2,116.8,114.1,108.3,70.5,68.7,64.34,64.31,55.6,48.0,35.1,35.0,25.8,24.9,21.8,21.5；HRMS(ESI):[M+H]+Calcd for Calcd for C26H34NO5 +:440.2431；found:440.2438.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝6.494min(major),tR2＝7.152min(minor)；98％e.e.；[α]D 25＝175.4(c＝0.39,CHCl3).
在反应管中依次加入酮酸酯(0.2mmol,1.0equiv.)、对甲氧基苯胺(0.4mmol,2.0equiv.)无水苯(0.4M,0.5mL)、TsOH·H2O(0.02mmol,10mol％)和分子筛。所得反应液加热回流24h后，冷却至室温，随后用硅藻土过滤，DCM洗涤。滤液旋干得到亚胺粗产品。加入L1(0.024mmol,12mol％),Mn(0.4mmol,2.0equiv.)。反应管转移至手套箱，依次加入CoI2(0.02mmol,10mol％)、MeCN(0.2M)、碘代物(0.4mmol,2.0equiv.)和异丙醇(0.2mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌17h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到黄色油状液67.9mg,77％收率,98％ee。
实施例27：
操作过程如通用步骤1，得白色固体65.5mg,64％收率；Rf＝0.39(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.65(d,J＝7.2Hz,2H),7.31–7.28(m,2H),7.26–7.23(m,1H),6.59(d,J＝8.8Hz,2H),6.32(d,J＝8.4Hz,2H),4.95–4.91(m,1H),4.23–4.07(m,3H),3.66(s,3H),2.70(bs,1H),1.95–1.88(m,2H),1.71–1.44(m,6H),1.35–1.29(m,9H),1.13–1.10(m,3H),0.89–0.87(m,3H)；13C NMR(100MHz,CDCl3,rotamers):δ172.6,172.2,153.6,152.4,140.13,140.06,137.3,136.8,129.1,128.8,127.62,127.59,127.2,116.7,114.0,79.2,69.9,69.8,68.7,55.6,53.7,53.1,39.9,39.6,32.4,31.9,31.6,31.3,28.4,27.7,27.5,21.7,21.4；HRMS(ESI):[M+H]+Calcd for Calcd for C30H41N2O5 +:509.3010；found:509.3019.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.509min(minor),tR2＝9.289min(major)；94.5:5.5d.r.；[α]D 25＝73.6(c＝3.91,CHCl3).
实施例28：
操作过程如通用步骤1，得无色油状液43.4mg,61％收率；Rf＝0.42(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ8.02(s,2H),7.30–7.23(m,3H),6.56(d,J＝9.2Hz,2H),6.20(d,J＝9.2Hz,2H),4.91(sept,J＝6.4Hz,1H),4.33(s,1H),3.65(s,3H),1.18(d,J＝6.4Hz,3H),1.03(s,9H),0.73(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.6,152.0,141.3,137.5,130.4,127.2,126.9,116.3,114.1,71.9,68.5,55.8,39.1,26.6,22.0,21.2；HRMS(ESI):[M+H]+Calcd for Calcd for C22H30NO3 +:356.2220；found:356.2215.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝4.819min(major),tR2＝10.347min(minor)；95％e.e.；[α]D 25＝122.9(c＝3.12,CHCl3).
操作过程如通用步骤2，得无色油状液27.2mg,77％收率，98％ee；1H NMR(400MHz,CDCl3):δ8.03(s,2H),7.30–7.23(m,3H),6.57(d,J＝8.8Hz,2H),6.20(d,J＝9.2Hz,2H),4.92(sept,J＝6.4Hz,1H),4.34(bs,1H),3.65(s,3H),1.18(d,J＝6.4Hz,3H),1.03(s,9H),0.73(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ172.6,152.0,141.3,137.5,130.4,127.2,127.0,116.3,114.1,72.0,68.5,55.8,39.1,26.6,22.0,21.2.
在反应管中依次加入酮酸酯(0.2mmol,1.0equiv.)、对甲氧基苯胺(0.4mmol,2.0equiv.)无水苯(0.4M,0.5mL)、TsOH·H2O(0.02mmol,10mol％)和分子筛。所得反应液加热回流24h后，冷却至室温，随后用硅藻土过滤，DCM洗涤。滤液旋干得到亚胺粗产品。加入L1(0.024mmol,12mol％),Mn(0.4mmol,2.0equiv.)。反应管转移至手套箱，依次加入CoI2(0.02mmol,10mol％)、MeCN(0.2M)、叔丁基溴代物(0.4mmol,2.0equiv.)和异丙醇(0.2mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌17h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到黄色油状液67.9mg,77％收率,98％ee。
实施例29：
操作过程如通用步骤1，得无色油状液24.3mg,55％收率；1H NMR(400MHz,CDCl3):δ8.03(bs,2H),7.30–7.24(m,5H),7.19–7.15(m,1H),7.12–7.10(m,2H),6.55(d,J＝9.2Hz,2H),6.18(d,J＝8.8Hz,2H),4.91(sept,J＝6.4Hz,1H),4.36(s,1H),3.65(s,3H),2.58(td,J＝13.2,5.2Hz,1H),2.49(td,J＝13.2,5.2Hz,1H),1.76(td,J＝13.2,5.2Hz,1H),1.64(td,J＝12.8,5.2Hz,1H),1.15(d,J＝6.4Hz,3H),1.13(s,3H),1.12(s,3H),0.72(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ172.5,152.0,142.8,141.1,137,1,130.6,128.5,128.4,127.3,127.1,125.9,116.4,114.0,72.8,68.6,55.7,42.0,39.4,31.2,22.83,22.79,22.0,21.2；HRMS(ESI):[M+H]+Calcd for Calcd for C29H36NO3 +:446.2690；found:446.2691.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝6.973min(minor),tR2＝13.752min(major)；92％e.e.；[α]D 25＝78.3(c＝2.53,CHCl3).
实施例30：
操作过程如通用步骤1，得无色油状液10.3mg,26％收率；1H NMR(400MHz,CDCl3):δ8.08–7.86(m,2H),7.28–7.23(m,3H),6.55(d,J＝9.2Hz,2H),6.17(d,J＝8.8Hz,2H),4.90(sept,J＝6.4Hz,1H),4.38(s,1H),3.65(s,3H),1.64–1.55(m,5H),1.50–1.47(m,2H),1.42–1.34(m,3H),1.17(d,J＝6.4Hz,3H),1.02(s,3H),0.72(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.6,151.9,141.4,137.1,130.8,127.1,126.9,116.2,114.0,73.3,68.5,55.8,42.2,32.2,31.9,25.9,22.34,22.32,22.0,21.2,18.1；HRMS(ESI):[M+H]+Calcd for Calcd for C25H34NO3 +:396.2533；found:396.2526.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.319min(minor),tR2＝10.974min(major)；95％e.e.；[α]D 25＝86.8(c＝1.27,CHCl3).
实施例31：
操作过程如通用步骤2，得无色油状液63.6mg,76％收率；Rf＝0.37(PE/EA＝20/1)；1H NMR(400MHz,CDCl3):δ7.57(d,J＝7.6Hz,2H),7.33(t,J＝7.2Hz,2H),7.27–7.21(m,3H),7.18–7.14(m,1H),7.06(d,J＝7.2Hz,2H),6.61(d,J＝9.2Hz,2H),6.33(d,J＝8.8Hz,2H),5.05(s,1H),4.94(sept,J＝6.4Hz,1H),3.70(s,3H),2.58(t,J＝7.6Hz,2H),2.55–2.39(m,2H),1.77–1.66(m,1H),1.50–1.39(m,1H),1.14(d,J＝6.4Hz,3H),0.98(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.4,152.1,141.9,141.5,138.6,128.5,128.4,128.4,127.4,127.1,125.8,116.6,114.5,69.5,66.6,55.7,35.7,32.8,25.4,21.6,21.3；HRMS(ESI):[M+H]+Calcd for Calcd for C27H32NO3 +:418.2377；found:418.2368.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝8.839min(major),tR2＝12.155min(minor)；98％e.e.；[α]D 25＝33.9(c＝6.15,CHCl3).
实施例32：
操作过程如通用步骤2，得无色油状液21mg,44％收率；1H NMR(400MHz,CDCl3):δ7.59(d,J＝7.2Hz,2H),7.32(t,J＝7.2Hz,2H),7.27–7.23(m,1H),6.60(d,J＝8.8Hz,2H),6.33(d,J＝9.2Hz,2H),5.02(s,1H),4.95(sept,J＝6.4Hz,1H),3.67(s,3H),3.52(t,J＝6.8Hz,2H),2.48–2.33(m,2H),1.78–1.71(m,2H),1.43–1.35(m,2H),1.32–1.17(m,15H),1.00(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.5,152.0,141.5,138.7,128.5,127.4,127.2,116.6,114.5,69.4,66.7,55.7,45.3,33.3,32.8,29.6,29.5,29.4,29.4,29.0,27.0,23.8,21.7,21.4；HRMS(ESI):[M+H]+Calcd for Calcd for C28H41ClNO3 +:474.2770；found:474.2760.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝254nm,tR1＝11.254min(major),tR2＝14.969min(minor)；97％e.e.；[α]D 25＝25.2(c＝1.59,CHCl3).
实施例33：
操作过程如通用步骤2，得黄色油状液52.5mg,68％收率；1H NMR(400MHz,CDCl3):δ7.58(d,J＝7.2Hz,2H),7.35(t,J＝6.8Hz,2H),7.29–7.26(m,1H),6.61(d,J＝8.8Hz,2H),6.32(d,J＝9.2Hz,2H),5.01(s,1H),3.67(s,3H),3.66(s,3H),3.61(s,3H),2.54–2.38(m,2H),2.22(ddd,J＝8.4,7.2,2.8Hz,2H),1.67–1.50(m,2H),1.40–1.27(m,1H),1.18–1.07(m,1H)；13C NMR(100MHz,CDCl3):δ174.5,173.9,152.2,141.2,138.7,128.7,127.6,127.1,116.7,114.5,66.6,55.6,53.1,51.5,33.8,33.0,24.8,23.6；HRMS(ESI):[M+H]+Calcd forCalcd for C22H28NO5 +:386.1962；found:386.1953.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝9.626min(major),tR2＝12.279min(minor)；98％e.e.；[α]D 25＝36.1(c＝3.76,CHCl3).
实施例34：
操作过程如通用步骤2，得无色油状液49.2mg,56％收率；Rf＝0.29(PE/EA＝1/2)；1H NMR(400MHz,CDCl3):δ7.58(d,J＝7.2Hz,2H),7.30(t,J＝7.2Hz,2H),7.23(d,J＝7.2Hz,1H),6.58(d,J＝9.2Hz,2H),6.33(d,J＝8.8Hz,2H),5.08(s,1H),4.93(sept,J＝6.4Hz,1H),3.64(s,3H),3.37(t,J＝6.8Hz,2H),3.17(t,J＝6.4Hz,2H),2.64–2.56(m,1H),2.42–2.34(m,1H),2.22–2.13(m,2H),1.85–1.75(m,4H),1.61–1.53(m,2H),1.17(d,J＝6.0Hz,3H),0.99(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,171.0,151.9,141.2,138.6,128.4,127.3,127.1,116.4,114.4,69.6,66.5,55.6,46.4,45.6,34.9,33.2,26.1,24.4,21.6,21.3,19.4；HRMS(ESI):[M+H]+Calcd for Calcd for C26H35N2O4 +:439.2592；found:439.2584.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝20.967min(minor),tR2＝26.688min(major)；98％e.e.；[α]D 25＝35.0(c＝1.64,CHCl3).
实施例35：
操作过程如通用步骤2，得无色油状液41.8mg,42％收率；Rf＝0.13(PE/EA＝10/1)；1H NMR(400MHz,CDCl3):δ7.58(d,J＝7.2Hz,2H),7.32(t,J＝7.2Hz,2H),7.26–7.23(m,1H),6.60(d,J＝9.2Hz,2H),6.33(d,J＝9.2Hz,2H),5.02(s,1H),4.95(sept,J＝6.4Hz,1H),4.46(s,1H),3.67(s,3H),3.02(d,J＝6.0Hz,2H),2.47–2.33(m,2H),1.43(s,9H),1.37–1.21(m,8H),1.17(d,J＝6.4Hz,3H),0.99(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.5,156.1,152.0,141.5,138.7,128.4,127.4,127.1,116.5,114.5,79.1,69.5,66.6,55.7,40.6,33.1,29.9,29.2,28.5,26.5,23.7,21.7,21.3；HRMS(ESI):[M+H]+Calcd forCalcd for C29H43N2O5 +:499.3167；found:499.3157.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝12.781min(major),tR2＝19.600min(minor)；99％e.e.；[α]D 25＝32.9(c＝3.26,CHCl3).
实施例36：
操作过程如通用步骤2，得黄色油状液70.5mg,72％收率；Rf＝0.30(PE/EA＝10/1)；1H NMR(400MHz,CDCl3):δ7.63(d,J＝7.2Hz,2H),7.36(t,J＝7.2Hz,2H),7.30–7.26(m,1H),7.19(dd,J＝8.8,7.6Hz,2H),6.71(t,J＝7.2Hz,1H),6.64(d,J＝8.8Hz,2H),6.60(d,J＝8.0Hz,2H),6.38(d,J＝8.8Hz,2H),5.09(s,1H),4.99(sept,J＝6.4Hz,1H),3.68(s,3H),3.58(s,1H),3.04(t,J＝7.2Hz,2H),2.52–2.39(m,2H),1.53–1.48(m,2H),1.42–1.30(m,6H),1.21(d,J＝6.0Hz,3H),1.03(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.4,152.0,148.6,141.5,138.6,129.3,128.4,127.4,127.1,117.1,116.5,114.5,112.7,69.5,66.6,55.6,43.9,33.1,29.34,29.31,26.8,23.9,21.7,21.3；HRMS(ESI):[M+H]+Calcd forCalcd for C30H39N2O3 +:475.2956；found:475.2946.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,T＝25℃,λ＝254nm,tR1＝15.764min(major),tR2＝26.182min(minor)；99％e.e.；[α]D 25＝28.5(c＝4.65,CHCl3).
实施例37：
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操作过程如通用步骤2，得黄色油状液64.5mg,63％收率；Rf＝0.43(PE/EA＝20/1)；1H NMR(400MHz,CDCl3):δ7.60(d,J＝7.2Hz,2H),7.33(t,J＝7.2Hz,2H),7.26(t,J＝7.2Hz,1H),6.61(d,J＝9.2Hz,2H),6.34(d,J＝8.8Hz,2H),5.03(s,1H),4.96(sept,J＝6.4Hz,1H),3.67(s,3H),3.55(t,J＝6.8Hz,2H),2.51–2.35(m,2H),1.47–1.40(m,2H),1.37–1.26(m,5H),1.18(d,J＝6.4Hz,3H),1.15–1.07(m,1H),1.00(d,J＝6.4Hz,3H),0.90(s,9H),0.04(s,6H)；13C NMR(100MHz,CDCl3):δ173.5,152.0,141.6,138.7,128.4,127.3,127.2,116.5,114.5,69.4,66.6,63.2,55.6,33.3,32.8,29.5,26.1,25.7,23.9,21.7,21.3,18.5,-5.2；；HRMS(ESI):[M+H]+Calcd for Calcd for C30H48NO4Si+:514.3348；found:514.3338.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝4.740min(major),tR2＝6.467min(minor)；95％e.e.；[α]D 25＝30.8(c＝5.82,CHCl3).
实施例38：
操作过程如通用步骤2，得黄色油状液48mg,50％收率；Rf＝0.19(PE/EA＝20/1)；1HNMR(400MHz,CDCl3):δ7.60(d,J＝7.2Hz,2H),7.34(t,J＝7.2Hz,2H),7.29–7.25(m,2H),7.20(d,J＝8.8Hz,2H),6.72(d,J＝8.8Hz,2H),6.60(d,J＝8.8Hz,2H),6.35(d,J＝9.2Hz,2H),5.05(s,1H),4.97(sept,J＝6.4Hz,1H),3.84–3.73(m,2H),3.67(s,3H),2.60–2.42(m,2H),1.81–1.66(m,2H),1.52–1.44(m,1H),1.39–1.31(m,1H),1.18(d,J＝6.4Hz,3H),1.00(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,157.5,152.0,141.3,138.4,129.2,128.4,127.4,127.0,125.3,116.6,115.7,114.4,69.5,67.7,66.5,55.5,32.7,29.0,21.6,21.2,20.4；HRMS(ESI):[M+H]+Calcd for Calcd for C28H33ClNO4 +:482.2093；found:482.2084.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝48.088min(minor),tR2＝57.380min(major)；98％e.e.；[α]D 25＝19.4(c＝2.41,CHCl3).
实施例39：
操作过程如通用步骤1，得淡黄色油状液56.6mg,75％收率；Rf＝0.37(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ8.13(s,1H),7.89–7.83(m,3H),7.76(d,J＝8.8Hz,1H),7.52–7.48(m,2H),6.61(d,J＝8.8Hz,2H),6.42(d,J＝8.8Hz,2H),5.19(bs,1H),5.00(sept,J＝6.4Hz,1H),3.67(s,3H),2.70(dq,J＝13.6,7.2Hz,1H),2.57(dq,J＝13.6,7.2Hz,1H),1.22(d,J＝6.4Hz,3H),0.99(d,J＝6.0Hz,3H),0.91(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.3,152.0,139.3,138.6,133.4,132.7,128.5,128.2,127.6,126.2,126.1,126.0,125.3,116.7,114.5,69.6,67.3,55.6,26.1,21.7,21.4,8.4；HRMS(ESI):[M+H]+Calcd for Calcd for C24H28NO3 +:378.2064；found:378.2055.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝9.960min(major),tR2＝15.950min(minor)；98％e.e.；[α]D 25＝77.0(c＝5.05,CHCl3).
实施例40：
操作过程如通用步骤1，得黄色油状液30.2mg,73％收率；1H NMR(400MHz,CDCl3):δ7.51(d,J＝8.0Hz,1H),7.28–7.24(m,1H),6.96(t,J＝7.6Hz,1H),6.81(d,J＝8.0Hz,1H),6.61(d,J＝8.8Hz,2H),6.53(d,J＝8.8Hz,2H),4.96(sept,J＝6.4Hz,1H),4.30(bs,1H),3.98(td,J＝12.4,2.8Hz,2H),3.69(s,3H),3.68(s,3H),3.51–3.42(m,2H),2.77(tt,J＝12.0,2.8Hz,1H),2.02(dt,J＝13.2,2.4Hz,1H),1.91(dt,J＝13.6,2.4Hz,1H),1.44(qd,J＝12.4,4.0Hz,1H),1.28–1.17(m,1H),1.13(d,J＝6.4Hz,3H),1.02(d,J＝6.4Hz,3H)；13CNMR(100MHz,CDCl3):δ172.1,157.0,153.5,139.2,128.9,127.8,120.0,114.0,111.1,68.8,68.6,68.5,68.1,55.6,55.0,41.1,29.1,28.8,21.9,21.7；HRMS(ESI):[M+H]+Calcdfor Calcd for C24H35NO5 +:414.2275；found:414.2268.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝24.129min(minor),tR2＝26.298min(major)；96％e.e.；[α]D 25＝20.1(c＝2.67,CHCl3).
实施例41：
操作过程如通用步骤1，得无色油状液26.5mg,67％收率；1H NMR(400MHz,CDCl3):δ7.90(s,1H),7.81(d,J＝8.0Hz,2H),7.54(d,J＝7.6Hz,2H),7.45(t,J＝8.0Hz,2H),6.63(d,J＝9.2Hz,2H),6.32(d,J＝8.8Hz,2H),5.01(bs,1H),4.96(sept,J＝6.4Hz,1H),3.68(s,3H),2.51(dq,J＝14.0,6.4Hz,1H),2.42(dq,J＝14.0,7.2Hz,1H),1.19(d,J＝6.4Hz,3H),1.01(d,J＝6.4Hz,3H),0.82(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ172.7,152.3,142.7,138.2,130.9,130.8(q,JC-F＝31.9Hz),128.9,124.37(quint,JC-F＝3.8Hz),124.36(q,JC-F＝270.8Hz),124.35(q,JC-F＝3.8Hz),116.7,114.6,69.9,67.1,55.7,26.8,21.6,21.3,8.3；19F NMR(376MHz,CDCl3):δ-62.4；HRMS(ESI):[M+H]+Calcd for Calcd forC21H25F3NO3 +:396.1781；found:396.1772.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.788min(major),tR2＝8.238min(minor)；95％e.e.；[α]D 25＝64.2(c＝2.65,CHCl3).
实施例42：
操作过程如通用步骤1，得淡黄色油状液69.4mg,86％收率；Rf＝0.31(PE/EtOAc＝50/1)；1H NMR(400MHz,CDCl3):δ7.84(s,1H),7.65–7.62(m,1H),7.26–7.21(m,2H),6.61(d,J＝8.4Hz,2H),6.31(d,J＝9.2Hz,2H),4.94(sept,J＝6.4Hz,1H),4.30(s,1H),3.67(s,3H),2.63(quint,J＝8.0Hz,1H),1.76–1.69(m,1H),1.56–1.35(m,7H),1.15(d,J＝6.0Hz,3H),0.88(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.8,152.4,141.4,140.0,133.7,129.1,128.9,127.24,127.23,116.6,114.2,68.95,68.89,55.6,50.7,27.6,27.4,25.0,24.9,21.8,21.4；HRMS(ESI):[M+H]+Calcd for Calcd for C23H29ClNO3 +:402.1830；found:402.1823.HPLC(Chiralcel OJ-H):n-Hexane/i-PrOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝10.010min(major),tR2＝15.810min(minor)；98％e.e.；[α]D 25＝57.6(c＝5.64,CHCl3).
实施例43：
操作过程如通用步骤1，得淡黄色油状液46.3mg,53％收率；Rf＝0.29(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.55(d,J＝8.8Hz,2H),7.45(d,J＝8.8Hz,2H),6.62(d,J＝9.2Hz,2H),6.33(d,J＝9.2Hz,2H),4.15(bs,1H),3.97–3.93(m,2H),3.68(s,3H),3.60(s,3H),3.41–3.31(m,2H),2.39–2.31(m,1H),1.69–1.65(m,1H),1.51–1.37(m,2H),1.15(qd,J＝12.4,4.4Hz,1H)；13C NMR(100MHz,CDCl3):δ173.3,152.8,139.2,135.9,131.0,130.9,121.8,116.9,114.3,70.3,68.0,55.6,52.5,46.3,29.8,28.4,27.9；HRMS(ESI):[M+H]+Calcd for Calcd for C21H25BrNO4 +:434.0961；found:434.0953.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝10.684min(minor),tR2＝15.128min(major)；93％e.e.；[α]D 25＝87.5(c＝1.70,CHCl3).
实施例44：
操作过程如通用步骤1，得淡黄色油状液71.1mg,98％收率；Rf＝0.31(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.90(d,J＝2.0Hz,1H),7.56(dd,J＝8.4,2.4Hz,1H),7.39(d,J＝8.8Hz,1H),6.62(d,J＝8.8Hz,2H),6.32(d,J＝9.2Hz,2H),4.92(sept,J＝6.4Hz,1H),4.10(s,1H),3.95(dd,J＝11.2,3.6Hz,2H),3.67(s,3H),3.38(td,J＝12.0,2.0Hz,1H),3.33(td,J＝11.2,3.2Hz,1H),2.30(tt,J＝12.0,3.2Hz,1H),1.74–1.70(m,1H),1.52–1.40(m,2H),1.15(d,J＝6.4Hz,3H),1.08(qd,J＝12.4,4.4Hz,1H),0.84(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ171.7,153.0,139.4,137.4,131.9,131.6,131.4,129.5,129.0,116.8,114.3,69.8,69.3,68.0,67.9,55.7,46.7,28.3,27.7,21.8,21.4；HRMS(ESI):[M+H]+Calcd for Calcd for C23H28Cl2NO4 +:452.1390；found:452.1382.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.013min(minor),tR2＝13.339min(major)；90％e.e.；[α]D 25＝90.2(c＝1.31,CHCl3).
实施例45：
操作过程如通用步骤1，得白色固体36.3mg,87％收率；Rf＝0.24(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.37–7.31(m,2H),6.76(tt,J＝8.4,2.4Hz,1H),6.62(d,J＝9.2Hz,2H),6.33(d,J＝8.8Hz,2H),4.92(sept,J＝6.4Hz,1H),4.11(s,1H),3.96(dd,J＝11.2,3.6Hz,2H),3.68(s,3H),3.38(td,J＝12.0,1.6Hz,1H),3.34(td,J＝12.0,2.0Hz,1H),2.29(tt,J＝12.0,3.2Hz,1H),1.73–1.68(m,1H),1.56–1.41(m,2H),1.15(d,J＝6.4Hz,3H),1.10(td,J＝12.4,4.4Hz,1H),0.85(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ171.6,162.6(d,JC-F＝244.7Hz),162.5(d,JC-F＝244.7Hz),153.0,141.4(t,JC-F＝8.7Hz),139.5,116.7,114.3,112.5(d,JC-F＝26.6Hz),112.5(d,JC-F＝12.2Hz),103.0(t,JC-F＝25.3Hz),70.1(t,JC-F＝2.2Hz),69.3,68.0,68.0,55.7,46.8,28.4,27.8,21.8,21.4；19FNMR(376MHz,CDCl3):δ-110.3；HRMS(ESI):[M+H]+Calcd for Calcd for C23H28F2NO4 +:420.1981；found:420.1972.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝210nm,tR1＝7.031min(minor),tR2＝7.493min(major)；89％e.e.；[α]D 25＝94.1(c＝3.63,CHCl3).
实施例46：
操作过程如通用步骤1，得白色固体31.1mg,66％收率；Rf＝0.35(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.43(d,J＝8.8Hz,2H),6.79(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),6.33(d,J＝9.2Hz,2H),5.06(sept,J＝6.4Hz,1H),4.99(bs,1H),4.94(sept,J＝6.4Hz,1H),3.67(s,3H),2.47(dq,J＝14.0,6.8Hz,1H),2.35(dq,J＝14.0,7.2Hz,1H),1.584(s,3H),1.581(s,3H),1.19–1.16(m,9H),0.98(d,J＝6.4Hz,3H),0.78(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.9,173.5,154.8,151.9,138.7,134.7,128.0,118.5,116.6,114.4,79.1,69.3,69.0,66.6,55.7,26.0,25.5,25.5,21.7,21.3,8.4；HRMS(ESI):[M+H]+Calcd for Calcd for C27H38NO6 +:472.2694；found:472.2686.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.331min(major),tR2＝15.669min(minor)；97％e.e.；[α]D 25＝57.4(c＝3.14,CHCl3).
实施例47：
操作过程如通用步骤1，得黄色油状液35.7mg,57％收率；Rf＝0.32(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.74(bs,4H),6.58(d,J＝8.8Hz,2H),6.57(s,1H),6.23(d,J＝9.2Hz,2H),4.95(bs,1H),4.92(sept,J＝6.4Hz,1H),3.91(s,3H),3.81(s,3H),3.67(s,3H),3.45(s,3H),2.39–2.28(m,2H),1.24–1.12(m,13H),0.94(d,J＝6.4Hz,3H),0.82(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ172.6,172.3,164.3,161.4,152.4,147.7,137.9,137.5,128.3,127.2,116.5,114.5,89.9,70.0,66.7,55.6,54.8,54.2,34.6,34.1,31.7,29.4,29.0,23.6,22.7,21.5,21.2,14.1；HRMS(ESI):[M+H]+Calcd for Calcd forC32H45N4O7S+:629.3003；found:629.2994.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,tR1＝18.908min(major),tR2＝25.950min(minor)；94％ee；[α]D 25＝42.0(c＝3.4,CHCl3).HPLC(Chiralpak AD-H):n-Hexane/EtOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝18.908min(major),tR2＝25.950min(minor)；94％e.e.；[α]D 25＝42.0(c＝3.40,CHCl3).
实施例48：
操作过程如通用步骤1，得无色油状液36.6mg,86％收率；Rf＝0.55(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.49(d,J＝9.2Hz,2H),6.85(d,J＝8.8Hz,2H),6.61(d,J＝8.8Hz,2H),6.34(d,J＝8.8Hz,2H),4.99(bs,1H),4.95(sept,J＝6.4Hz,1H),3.80(s,3H),3.67(s,3H),2.45–2.30(m,2H),1.34–1.17(m,13H),1.01(d,J＝6.0Hz,3H),0.84(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.8,158.8,151.9,138.8,133.6,128.4,116.5,114.4,113.7,69.3,66.2,55.7,55.3,33.4,31.8,29.6,29.1,23.9,22.7,21.7,21.4,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C26H38NO4 +:428.2795；found:428.2786.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝12.241min(major),tR2＝14.361min(minor)；99％e.e.；[α]D 25＝123.3(c＝0.55,CHCl3).
实施例49：
操作过程如通用步骤1，得黄色油状液40.0mg,86％收率；Rf＝0.69(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.75(d,J＝8.4Hz,2H),7.59(d,J＝8.4Hz,2H),6.62(d,J＝9.2Hz,2H),6.30(d,J＝8.8Hz,2H),5.00(bs,1H),4.96(sept,J＝6.4Hz,1H),3.68(s,3H),2.46–2.33(m,2H),1.29–1.16(m,13H),1.02(d,J＝6.4Hz,3H),0.84(t,J＝6.8Hz,3H)；13CNMR(100MHz,CDCl3):δ172.8,152.3,145.7,138.3,129.6(q,JC-F＝32.1Hz),127.8,125.4(q,JC-F＝3.9Hz),124.3(q,JC-F＝270.3Hz),116.5,114.6,69.9,66.7,55.7,34.0,31.7,29.5,29.1,23.7,22.7,21.6,21.4,14.2；19F NMR(376MHz,CDCl3):δ-62.4；HRMS(ESI):[M+H]+Calcd for Calcd for C26H35F3NO3 +:466.2564；found:466.2555.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝40℃,λ＝254nm,tR1＝5.967min(minor),tR2＝7.056min(major)；98％e.e.；[α]D 25＝102.6(c＝1.22,CHCl3).
实施例50：
操作过程如通用步骤1，得黄色油状液38.1mg,88％收率；Rf＝0.58(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.54(d,J＝8.4Hz,2H),7.30(d,J＝8.8Hz,2H),6.61(d,J＝8.8Hz,2H),6.31(d,J＝8.8Hz,2H),4.98(bs,1H),4.95(sept,J＝6.4Hz,1H),3.68(s,3H),2.44–2.29(m,2H),1.34–1.17(m,13H),1.02(d,J＝6.4Hz,3H),0.84(t,J＝7.2Hz,3H)；13CNMR(100MHz,CDCl3):δ173.1,152.1,140.2,138.4,133.3,128.8,128.6,116.5,114.5,69.7,66.3,55.7,33.7,31.7,29.5,29.1,23.8,22.7,21.7,21.4,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C25H35ClNO3 +:432.2300；found:432.2293.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝40℃,λ＝220nm,tR1＝7.204min(major),tR2＝8.746min(minor)；93％e.e.；[α]D 25＝58.3(c＝3.25,CHCl3).
实施例51：
操作过程如通用步骤1，得白色固体22mg,61％收率；Rf＝0.24(PE/EtOAc＝4/1)；1HNMR(400MHz,CDCl3):δ7.27–7.25(m,2H),6.98(dd,J＝5.2,4.0Hz,1H),6.63(d,J＝8.8Hz,2H),6.38(d,J＝8.8Hz,2H),4.33(bs,1H),3.98(dd,J＝11.2,3.6Hz,2H),3.68(s,3H),3.66(s,3H),3.36(td,J＝12.0,1.6Hz,1H),3.35(td,J＝12.0,2.0Hz,1H),2.22(tt,J＝12.0,3.2Hz,1H),1.70(dt,J＝14.0,2.8Hz,1H),1.59(qd,J＝12.0,4.4Hz,1H),1.45(dt,J＝13.6,3.2Hz,1H),1.35(qd,J＝12.8,4.4Hz,1H)；13C NMR(100MHz,CDCl3):δ173.4,152.7,141.4,139.5,127.6,126.5,125.9,116.3,114.3,69.4,68.0,67.9,55.6,52.6,47.5,28.0,27.9；HRMS(ESI):[M+H]+Calcd for Calcd for C19H24NO4S+:362.1421；found:362.1415.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝17.239min(minor),tR2＝18.998min(major)；94％e.e.；[α]D 25＝138.9(c＝0.19,CHCl3).
实施例52：
操作过程如通用步骤1，得黄色固体26.5mg,65％收率；Rf＝0.35(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.90(d,J＝1.2Hz,1H),7.42(dd,J＝8.8,1.6Hz,1H),7.26(d,J＝8.8Hz,1H),7.05(d,J＝3.2Hz,1H),6.60(d,J＝9.2Hz,2H),6.48(d,J＝2.8Hz,1H),6.42(d,J＝9.2Hz,2H),4.36(bs,1H),3.93(td,J＝11.2,3.2Hz,2H),3.79(s,3H),3.67(s,3H),3.62(s,3H),3.45–3.35(m,2H),2.55(tt,J＝12.0,2.8Hz,1H),1.69(dt,J＝13.6,2.8Hz,1H),1.60(dt,J＝12.8,2.8Hz,1H),1.45(qd,J＝12.0,4.0Hz,1H),1.34(qd,J＝12.4,4.4Hz,1H)；13C NMR(100MHz,CDCl3):δ174.5,152.5,140.0,136.1,129.2,128.1,128.0,122.5,121.0,117.3,114.2,108.5,101.5,71.0,68.3,55.6,52.3,45.6,33.0,29.0,28.1；HRMS(ESI):[M+K]+Calcd for Calcd for C24H28KN2O4 +:447.1681；found:447.1684.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝13.033min(minor),tR2＝24.717min(major)；97％e.e.；[α]D 25＝37.4(c＝2.94,CHCl3).
实施例53：
操作过程如通用步骤1，得无色油状液198.4mg,71％收率；Rf＝0.58(PE/EtOAc＝10/1)；1HNMR(400MHz,CDCl3):δ6.74(d,J＝8.8Hz,2H),6.65(d,J＝8.8Hz,2H),4.16(qd,J＝7.2,0.8Hz,2H),3.74(s,3H),1.88–1.76(m,3H),1.46(s,3H),1.23(t,J＝7.2Hz,3H),0.90(d,J＝6.4Hz,3H),0.89(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ176.5,153.5,139.2,119.3,114.5,61.5,61.3,55.7,48.4,24.5,24.1,23.9,23.5,14.3；HRMS(ESI):[M+H]+Calcd for Calcd for C16H26NO3 +:280.1907；found:280.1904.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝99/1,flow rate 0.5mL/min,T＝25℃,λ＝220nm,tR1＝17.134min(minor),tR2＝17.818min(major)；93％e.e.；[α]D 25＝-6.7(c＝5.34,CHCl3).
实施例54：
向预先烘干的反应管中加入手性配体(6mol％)，Mn(2.0equiv)和酮亚胺1(3.5mmol,1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、乙腈(0.2M)、烷基碘代物(1.5equiv)和异丙醇(1.0equiv)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌20h。随后向反应液中加入HCl(1.0M in H2O,3.0equiv)，室温下反应6h。待反应完毕，加入饱和碳酸氢钠水溶液，分离有机相后，水相用乙酸乙酯萃取三次。合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到淡棕色油状液782.6mg,84％收率；Rf＝0.44(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ6.82(d,J＝8.8Hz,2H),6.75(d,J＝9.2Hz,2H),4.18(q,J＝7.2Hz,2H),3.93–3.87(m,1H),3.81–3.75(m,1H),3.74(s,3H),2.19(ddd,J＝14.4,7.2,4.4Hz,1H),2.05(ddd,J＝14.8,6.8,4.0Hz,1H),1.40(s,3H),1.23(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ175.9,155.0,137.9,122.2,114.4,62.4,61.6,59.9,55.6,40.1,23.0,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C14H22NO4 +:268.1543；found:268.1540.HPLC(Chiralpak IBN-5):n-Hexane/EtOH＝90/10,flow rate1.0mL/min,T＝25℃,λ＝210nm,tR1＝9.323min(minor),tR2＝9.805min(major)；90％e.e.；[α]D 25＝17.1(c＝0.34,CHCl3).
实施例55：
在反应管中依次加入酮酸酯(0.2mmol,1.0equiv.)、对甲氧基苯胺(0.4mmol,2.0equiv.)无水苯(0.4M,0.5mL)、TsOH·H2O(0.02mmol,10mol％)和分子筛。所得反应液加热回流24h后，冷却至室温，随后用硅藻土过滤，DCM洗涤。滤液旋干得到的亚胺粗产品经抽真空干燥后加入L3(0.024mmol,12mol％),In(0.4mmol,2.0equiv.)。反应管转移至手套箱，依次加入CoI2(0.02mmol,10mol％)、MeCN(0.2M)、1-碘庚烷(0.4mmol,2.0equiv.)和乙醇(0.2mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌24h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到黄色油状液18.4mg,45％收率；Rf＝0.38(PE/EA＝10/1)；1HNMR(400MHz,CDCl3):δ7.24(t,J＝7.6Hz,2H),7.15(t,J＝7.2Hz,1H),7.05(d,J＝6.8Hz,2H),6.76(d,J＝8.8Hz,2H),6.69(d,J＝9.2Hz,2H),4.33(bs,1H),4.20(q,J＝7.2Hz,2H),3.76(s,3H),3.61(s,3H),2.65(ddd,J＝13.6,12.0,5.2Hz,2H),2.40(ddd,J＝13.2,11.6,5.6Hz,2H),2.30–2.14(m,2H),1.97(ddd,J＝13.6,11.6,4.4Hz,2H),1.82(ddd,J＝14.0,12.0,4.8Hz,2H),1.37–1.09(m,13H),0.85(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ175.5,152.9,142.0,139.2,128.50,128.47,126.0,118.1,114.8,65.1,61.5,55.8,38.0,36.3,31.8,30.4,29.6,29.1,23.8,22.7,14.5,14.2；HRMS(ESI):[M+Na]+Calcd for Calcdfor C26H37NNaO3 +:434.2666；found:434.2675.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝6.179min(minor),tR2＝6.699min(major)；92％e.e.；[α]D 2＝7.41(c＝0.54,CHCl3).
实施例56：
操作过程如通用步骤1，得无色油状液23.5mg,63％收率；Rf＝0.48(PE/EA＝20/1)；1H NMR(400MHz,CDCl3):δ6.73(d,J＝8.8Hz,2H),6.62(d,J＝8.8Hz,2H),4.36(bs,1H),3.75(s,3H),3.74(s,3H),2.03–1.99(m,2H),1.92–1.89(m,1H),1.85–1.71(m,4H),1.63–1.61(m,1H),1.32–1.00(m,14H),0.88–0.75(m,4H)；13C NMR(100MHz,CDCl3):δ175.5,152.6,139.4,118.1,114.6,68.5,55.7,52.1,44.3,32.5,31.8,29.8,29.1,28.2,27.0,26.8,26.5,24.0,22.7,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C23H38NO3 +:376.2847；found:376.2840.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝254nm,tR1＝7.321min(minor),tR2＝10.534min(major)；99％e.e.；[α]D 25＝14.8(c＝2.13,CHCl3).
实施例57：
操作过程如通用步骤1，得无色油状液43.4mg,59％收率；Rf＝0.57(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ6.84(d,J＝8.8Hz,2H),6.77(d,J＝9.2Hz,2H),4.57(bs,1H),4.35(qd,J＝7.2,0.8Hz,2H),3.76(s,3H),3.41(dt,J＝10.8,6.4Hz,1H),3.36(dt,J＝10.8,6.4Hz,1H),2.24–2.09(m,2H),1.70–1.56(m,2H),1.37–1.23(m,5H)；13C NMR(100MHz,CDCl3):δ168.7,154.9,136.5,124.8(q,JC-F＝286.7Hz),121.8,114.5,68.5(q,JC-F＝26.6Hz),63.4,55.6,44.3,32.2,28.1,20.5,14.1；19F NMR(376MHz,CDCl3):δ-73.3；HRMS(ESI):[M+H]+Calcd for Calcd for C16H22ClF3NO3 +:368.1235；found:368.1232.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝10.673min(minor),tR2＝17.175min(major)；97％e.e.；[α]D 25＝17.3(c＝0.98,CHCl3).
实施例58：
操作过程如通用步骤1，得黄色油状液45.9mg,72％收率；Rf＝0.40(PE/EtOAc＝10/1)；1HNMR(400MHz,CDCl3):δ6.80(d,J＝9.2Hz,2H),6.75(d,J＝9.2Hz,2H),4.30(qd,J＝7.2,2.4Hz,2H),3.90(bs,1H),3.75(s,3H),2.57(sept,J＝7.2Hz,1H),1.29(t,J＝7.2Hz,3H),1.15(dd,J＝6.8,0.8Hz,3H),1.09(d,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ168.5,154.5,137.3,125.3(q,JC-F＝288.4Hz),120.9,114.3,71.4(q,JC-F＝24.7Hz),62.4,55.6,32.9,17.8,14.1；19F NMR(376MHz,CDCl3):δ-65.6；HRMS(ESI):[M+H]+Calcd for Calcdfor C15H21F3NO3 +:320.1468；found:320.1463.HPLC(Chiralpak IBN-5):n-Hexane/EtOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.777min(minor),tR2＝8.752min(major)；98％e.e.；[α]D 25＝29.5(c＝2.33,CHCl3).
实施例59：
操作过程如通用步骤1，得淡黄色油状液43.5mg,60％收率；Rf＝0.25(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ6.81(d,J＝9.2Hz,2H),6.75(d,J＝9.2Hz,2H),4.38–4.26(m,2H),4.05–3.98(m,3H),3.75(s,3H),3.36(td,J＝11.6,2.0Hz,1H),3.32(td,J＝11.6,2.0Hz,1H),2.48(tt,J＝12.0,3.2Hz,1H),1.88(qd,J＝12.4,4.4Hz,1H),1.72–1.55(m,3H),1.31(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ168.0,154.8,136.7,125.0(q,JC-F＝288.4Hz),121.5(q,JC-F＝1.3Hz),114.3,71.0(q,JC-F＝24.7Hz),68.1,68.0,62.8,55.6,39.7,28.0,27.7,14.1；19F NMR(376MHz,CDCl3):δ-65.6；HRMS(ESI):[M+H]+Calcd forCalcd for C17H23F3NO4 +:362.1574；found:362.1570.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.179min(major),tR2＝10.618min(minor)；99％e.e.；[α]D 25＝20.0(c＝0.94,CHCl3).
实施例60：
操作过程如通用步骤1，得黄色固体24.2mg,74％收率；Rf＝0.75(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.60(d,J＝7.2Hz,2H),7.32(t,J＝7.6Hz,2H),7.27–7.23(m,1H),6.78(dd,J＝8.0,1.6Hz,1H),6.58(td,J＝7.6,1.6Hz,1H),6.52(td,J＝8.0,1.2Hz,1H),6.00(dd,J＝7.6,1.6Hz,1H),5.94(s,1H),4.96(sept,J＝6.4Hz,1H),3.92(s,3H),2.56(dq,J＝13.6,7.2Hz,1H),2.48(dq,J＝14.0,7.2Hz,1H),1.19(d,J＝6.4Hz,3H),1.01(d,J＝6.4Hz,3H),0.79(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.3,147.5,141.1,134.5,128.5,127.4,127.2,120.5,116.4,112.9,109.6,69.5,66.8,55.8,25.9,21.7,21.4,8.4；HRMS(ESI):[M+H]+Calcd for Calcd for C20H26NO3 +:328.1907；found:328.1902.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝210nm,tR1＝5.319min(minor),tR2＝5.732min(major)；81％e.e.；[α]D 25＝53.7(c＝0.63,CHCl3).
实施例61：
操作过程如通用步骤1，得无色油状液20.4mg,62％收率；Rf＝0.44(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.60–7.23(m,2H),7.35–7.31(m,2H),7.27–7.23(m,1H),6.91(t,J＝8.0Hz,1H),6.18(ddd,J＝8.0,2.4,0.8Hz,1H),6.02(ddd,J＝8.0,2.4,0.8Hz,1H),5.91(t,J＝2.4Hz,1H),5.41(s,1H),4.96(sept,J＝6.4Hz,1H),3.61(s,3H),2.59(qd,J＝14.0,7.2Hz,1H),2.53(qd,J＝13.6,7.2Hz,1H),1.21(d,J＝6.0Hz,3H),0.99(d,J＝6.4Hz,3H),0.84(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.3,160.3,145.9,141.0,129.6,128.6,127.5,127.0,108.2,102.6,100.9,69.7,66.8,55.0,25.6,21.7,21.3,8.5；HRMS(ESI):[M+H]+Calcd for Calcd for C20H26NO3 +:328.1907；found:328.1900.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.259min(major),tR2＝11.368min(minor)；94％e.e.；[α]D 25＝77.6(c＝1.58,CHCl3).
实施例62：
操作过程如通用步骤1，得黄色油状液21.4mg,68％收率；Rf＝0.28(PE/EtOAc＝50/1)；1H NMR(400MHz,CDCl3):δ7.59–7.56(m,2H),7.36–7.31(m,2H),7.29–7.24(m,1H),6.71(t,J＝8.8Hz,2H),6.33–6.28(m,2H),5.23(s,1H),4.96(sept,J＝6.4Hz,1H),2.56(dq,J＝14.0,7.2Hz,1H),2.42(dq,J＝14.4,7.2Hz,1H),1.20(d,J＝6.0Hz,3H),0.99(d,J＝6.0Hz,3H),0.82(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,155.7(d,JC-F＝233.5Hz),141.0,140.9(d,JC-F＝1.8Hz),128.6,127.5,127.1,115.9(d,JC-F＝7.3Hz),115.4(d,JC-F＝22.0Hz),69.7,67.0,25.8,21.7,21.3,8.4.19F NMR(376MHz,CDCl3):δ-128.2；HRMS(ESI):[M+H]+Calcd for Calcd for C19H23FNO2 +:316.1707；found:316.1701.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.821min(major),tR2＝8.373min(minor)；93％e.e.；[α]D 25＝57.9(c＝1.23,CHCl3).
实施例63：
在氮气氛围下，向含有α-酮酸酯(0.2mmol,1.0equiv.)、NMe(TMS)2(0.24mmol,1.2equiv.)的DCM溶液中加入TMSOTf(0.01mmol,5mol％)。所得反应液加热至60℃反应16h后，冷却至室温，旋干得到的亚胺粗产品。随后在手套箱中依次向该反应管中加入L3(0.024mmol,12mol％),Mn(0.4mmol,2.0equiv.)、CoI2(0.02mmol,10mol％)、MeCN(0.2M)、1-碘庚烷(0.4mmol,2.0equiv.)和异丙醇(0.2mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌40h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到无色油状液50.4mg,83％收率；Rf＝0.33(PE/EtOAc＝5/1)；1H NMR(400MHz,DMSO-d6):δ7.37–7.36(m,2H),7.32(t,J＝7.2Hz,2H),7.23(t,J＝7.2Hz,1H),4.92(sept,J＝6.4Hz,1H),2.07(s,3H),1.99(ddd,J＝13.6,11.6,4.4Hz,1H),1.84(ddd,J＝14.0,11.6,4.8Hz,1H),1.24–1.18(m,9H),1.11(d,J＝6.4Hz,6H),1.04–0.94(m,1H),0.82(t,J＝7.2Hz,3H)；13C NMR(100MHz,DMSO-d6):δ173.6,141.9,127.9,126.8,126.1,67.8,67.6,34.1,31.1,29.3,29.2,28.6,22.7,22.0,21.4,21.3,13.9；HRMS(ESI):[M+H]+Calcd for Calcd for C19H32NO2 +:306.2428；found:306.2418.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝99/9,flow rate 0.5mL/min,T＝25℃,λ＝220nm,tR1＝15.725min(minor),tR2＝18.586min(major)；96％e.e.；[α]D 23＝23.9(c＝0.36,CHCl3).
实施例64：
在氮气氛围下，向含有α-酮酸酯(0.1mmol,1.0equiv.)、NCH2CH2Ph(TMS)2(0.12mmol,1.2equiv.)的DCM(0.2M,0.5mL)溶液中加入TMSOTf(0.005mmol,5mol％)。所得反应液加热至60℃反应15h后，冷却至室温，旋干得到的亚胺粗产品。随后在手套箱中依次向该反应管中加入L3(0.012mmol,12mol％)、Mn(0.2mmol,2.0equiv.)、CoI2(0.01mmol,10mol％)、MeCN(0.2M)、1-碘庚烷(0.2mmol,2.0equiv.)和异丙醇(0.1mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌24h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到无色油状液27.8mg,70％收率；Rf＝0.55(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.38–7.35(m,2H),7.30–7.28(m,3H),7.24–7.18(m,5H),4.98(sept,J＝6.4Hz,1H),2.86–2.74(m,2H),2.65–2.54(m,2H),2.09(ddd,J＝14.0,11.2,5.2Hz,1H),2.01(bs,1H),1.93(ddd,J＝13.6,11.2,4.8Hz,1H),1.31–1.21(m,10H),1.11(d,J＝6.4Hz,3H),1.09(d,J＝6.0Hz,3H),0.86(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ174.5,142.2,140.2,128.9,128.5,128.2,127.1,126.4,126.3,68.4,68.0,44.5,37.1,34.9,31.9,30.0,29.3,23.3,22.8,21.7,21.7,14.2.HRMS(ESI):[M+H]+Calcd for Calcd for C26H38NO2 +:396.2898；found:396.2888.HPLC(Chiralpak AD-H):n-Hexane/EtOH＝99.5/0.5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.943min(minor),tR2＝6.882min(major)；97％e.e.；[α]D 23＝32.1(c＝0.52,CHCl3).
实施例65：
在氮气氛围下，向含有α-酮酸酯(0.1mmol,1.0equiv.)、NPMB(TMS)2(0.12mmol,1.2equiv.)的DCE(0.2M,0.5mL)溶液中加入TMSOTf(0.01mmol,10mol％)。所得反应液加热至60℃反应直至原料消耗完。冷却至室温，旋干得到的亚胺粗产品。随后在手套箱中依次向该反应管中加入L3(0.012mmol,12mol％)、Mn(0.2mmol,2.0equiv.)、CoI2(0.01mmol,10mol％)、MeCN(0.2M)、1-碘庚烷(0.2mmol,2.0equiv.)和异丙醇(0.1mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌21h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到无色油状液27.6mg,67％收率；Rf＝0.52(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.50(d,J＝7.2Hz,2H),7.34–7.30(m,3H),7.27–7.23(m,2H),6.87(d,J＝8.4Hz,2H),5.09(sept,J＝6.4Hz,1H),3.80(s,3H),3.50(1/2abq,J＝12.0Hz,1H),3.41(1/2abq,J＝12.0Hz,1H),2.22–2.14(m,1H),2.05–1.99(m,1H),1.74(bs,1H),1.25–1.17(m,16H),0.86(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ174.6,158.8,142.1,132.8,129.6,128.2,127.2,126.5,113.9,68.6,68.3,55.4,47.2,35.3,32.0,30.0,29.3,23.4,22.8,21.9,21.8,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C26H38NO3 +:412.2847；found:412.2840.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝8.659min(major),tR2＝10.905min(minor)；97％e.e.；[α]D 23＝37.5(c＝1.66,CHCl3).
实施例66：
在氮气氛围下，向含有α-酮酸酯(0.2mmol,1.0equiv.)、NBn(TMS)2(0.24mmol,1.2equiv.)的DCE(0.2M,1.0mL)溶液中加入TMSOTf(0.02mmol,10mol％)。所得反应液加热至60℃直至原料消耗完。冷却至室温，减压浓缩得到的亚胺粗产品。随后在手套箱中依次向该反应管中加入L3(0.024mmol,12mol％),Mn(0.4mmol,2.0equiv.)、CoI2(0.02mmol,10mol％)、MeCN(0.2M)、1-碘庚烷(0.4mmol,2.0equiv.)和异丙醇(0.2mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中搅拌23h.待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到无色油状液46.5mg,61％收率；Rf＝0.69(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.50(d,J＝7.2Hz,2H),7.38–7.31(m,6H),7.26–7.24(m,2H),5.08(sept,J＝6.4Hz,1H),3.56(1/2abq,J＝12.0Hz,1H),3.47(1/2abq,J＝12.0Hz,1H),2.21–2.16(m,2H),2.05–1.99(m,1H),1.24–1.17(m,16H),0.85(t,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ174.6,142.1,140.8,128.5,128.4,128.2,127.2,127.1,126.5,68.6,68.3,47.8,35.3,32.0,30.0,29.3,23.4,22.8,21.9,21.8,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C18H30NO2 +:292.2272；found:292.2263.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.515min(major),tR2＝6.283min(minor)；97％e.e.；[α]D 23＝21.4(c＝0.89,CHCl3).
实施例67：
操作过程如通用步骤1，得无色油状液54.9mg,74％收率；Rf＝0.58(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.62(d,J＝7.6Hz,2H),7.36(t,J＝7.2Hz,2H),7.30–7.27(m,1H),6.62(d,J＝9.2Hz,2H),6.34(d,J＝8.8Hz,2H),5.05(s,1H),3.68(s,3H),3.66(s,3H),2.51–2.37(m,2H),1.32–1.19(m,9H),1.10–1.03(m,1H),0.85(t,J＝7.2Hz,3H)；13CNMR(100MHz,CDCl3):δ174.7,152.1,141.4,138.4,128.6,127.5,127.2,116.6,114.4,66.7,55.6,53.1,33.2,31.7,29.5,29.0,23.8,22.7,14.2；HRMS(ESI):[M+H]+Calcd forCalcd for C23H32NO3 +:370.2377；found:370.2370.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.276min(major),tR2＝9.535min(minor)；98％e.e.；[α]D 25＝30.7(c＝1.77,CHCl3).
实施例68：
操作过程如通用步骤1，得黄色油状液57.4mg,75％收率；Rf＝0.64(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.61(d,J＝7.6Hz,2H),7.34(t,J＝8.0Hz,2H),7.29–7.25(m,1H),6.61(d,J＝9.2Hz,2H),6.33(d,J＝9.2Hz,2H),5.03(s,1H),4.19(dq,J＝10.8,7.2Hz,1H),4.05(dq,J＝10.8,7.2Hz,1H),3.67(s,3H),2.51–2.36(m,2H),1.35–1.04(m,13H),0.84(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ174.1,152.0,141.5,138.6,128.6,127.5,127.2,116.6,114.4,66.7,61.9,55.7,33.3,31.7,29.6,29.1,23.8,22.7,14.2,14.1；HRMS(ESI):[M+H]+Calcd for Calcd for C24H34NO3 +:384.2533；found:384.2528.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.377min(major),tR2＝10.428min(minor)；97％e.e.；[α]D 25＝31.0(c＝3.79,CHCl3).
实施例69：
向预先烘干的反应管中加入L1(0.03mmol,6mol％),Mn(1.0mmol,2.0equiv.)和酮亚胺1(0.5mmol,1.0equiv.)。随后将该反应管移至手套箱中，依次加入CoI2(0.025mmol5mol％),MeCN(0.2M),、烷基碘代物(0.75mmol,1.5equiv.)和异丙醇(0.5mmol,1.0equiv.)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中剧烈搅拌20h。随后向反应液中加入HCl(1.0M in H2O,3.0equiv)，室温下反应6h。待反应完毕，加入饱和碳酸氢钠水溶液，分离有机相后，水相用乙酸乙酯萃取三次。合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到无色油状液138.7mg,81％收率；Rf＝0.31(PE/EtOAc＝3/1)；1HNMR(400MHz,CDCl3):δ7.50–7.47(m,2H),7.33–7.29(m,2H),7.27–7.22(m,1H),6.61(d,J＝8.8Hz,2H),6.43(d,J＝8.8Hz,2H),5.23(bs,1H),4.96(setp,J＝6.4Hz,1H),3.72(t,J＝6.0Hz,2H),3.67(s,3H),2.88(dt,J＝14.4,6.4Hz,1H),2.67(dt,J＝14.0,5.6Hz,1H),2.23(bs,1H),1.19(d,J＝6.4Hz,3H),0.99(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.6,152.6,140.6,138.1,128.6,127.6,126.8,117.5,114.5,70.0,65.9,59.7,55.7,36.2,21.6,21.3；HRMS(ESI):[M+H]+Calcd for Calcd for C20H26NO4 +:344.1856；found:344.1850.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝80/20,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝5.709min(major),tR2＝6.659min(minor)；98％e.e.；[α]D 25＝60.7(c＝3.32,CHCl3).
在0℃下，向含有PPh3(0.15mmol,1.5equiv.)和咪唑(0.15mmol,1.5equiv.)的DCM(0.2M)溶液中加入上述产物(0.1mmol,1.0equiv.)，随后分批加入I2(0.15mmol,1.5equiv.)，所得反应液缓慢恢复至室温继续搅拌24h。待反应完成后，加入饱和Na2S2O3水溶液淬灭，分液后水相经DCM萃取三次，合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到淡黄色油状液27.3mg,84％收率；Rf＝0.60(PE/EtOAc＝10/1)；1H NMR(400MHz,DMSO-d6):δ7.39–7.35(m,2H),7.31–7.26(m,3H),6.73(d,J＝8.8Hz,2H),6.36(d,J＝9.2Hz,2H),4.88(setp,J＝6.4Hz,1H),3.96–3.87(m,2H),3.62(s,3H),2.94(ddd,J＝10.8,8.4,4.4Hz,1H),2.38(ddd,J＝10.8,8.4,7.2Hz,1H),1.12(d,J＝6.4Hz,3H),0.90(d,J＝6.0Hz,3H)；13C NMR(100MHz,DMSO-d6):δ170.1,152.0,142.4,141.4,128.1,127.2,126.0,114.1,113.2,75.5,68.4,55.3,48.0,31.3,21.4,21.2；HRMS(ESI):[M+H]+Calcd forCalcd for C20H24NO3 +:326.1751；found:326.1745.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝9.960min(minor),tR2＝11.678min(major)；96％e.e.；[α]D 25＝-34.7(c＝0.98,CHCl3).
实施例70：
操作过程如通用步骤1，得无色油状液57.2mg,84％收率；Rf＝0.58(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.49(d,J＝7.6Hz,2H),7.31(t,J＝8.0Hz,2H),7.26–7.22(m,1H),6.70(d,J＝9.2Hz,2H),6.42(d,J＝9.2Hz,2H),4.87(sept,J＝6.4Hz,1H),3.69–3.66(m,4H),3.57(td,J＝9.2,6.4Hz,1H),2.75(td,J＝11.6,6.8Hz,1H),2.25(ddd,J＝12.0,6.8,2.8Hz,1H),2.04–1.97(m,1H),1.93–1.81(m,1H),1.16(d,J＝6.4Hz,3H),0.75(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ174.1,151.4,141.5,141.1,128.2,127.6,126.9,114.4,114.3,74.0,68.7,55.8,50.8,44.9,23.3,21.7,21.3；HRMS(ESI):[M+H]+Calcd for Calcd for C21H26NO3 +:340.1907；found:340.1900.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.455min(minor),tR2＝13.416min(major)；97％e.e.；[α]D 25＝-12.8(c＝5.19,CHCl3).
实施例71：
操作过程如通用步骤1，得无色油状液55.1mg,78％收率；Rf＝0.30(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.32(dd,J＝8.0,2.0Hz,2H),7.22–7.14(m,3H),6.77(d,J＝9.2Hz,2H),6.53(d,J＝8.8Hz,2H),5.14(sept,J＝6.4Hz,1H),3.67(s,3H),3.62–3.55(m,1H),3.41(dt,J＝12.0,4.0Hz,1H),2.52(dt,J＝13.2,5.2Hz,1H),2.21(td,J＝12.4,4.0Hz,1H),1.82–1.72(m,3H),1.58–1.50(m,1H),1.21(d,J＝6.4Hz,3H),1.20(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.0,154.1,144.2,141.7,128.0,127.9,127.2,126.1,112.7,71.5,68.4,55.3,51.5,37.6,25.7,22.3,21.8；HRMS(ESI):[M+H]+Calcd forCalcd for C22H28NO3 +:354.2064；found:354.2066.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝210nm,tR1＝6.230min(minor),tR2＝6.967min(major)；97％e.e.；[α]D 25＝38.8(c＝4.24,CHCl3).
实施例72：
操作过程如通用步骤1，得无色油状液128.6mg,52％收率；Rf＝0.61(PE/EtOAc＝20/1)；1HNMR(400MHz,CDCl3):δ7.58(d,J＝6.8Hz,2H),7.33(t,J＝6.8Hz,2H),7.28–7.24(m,1H),6.61(d,J＝9.2Hz,2H),6.34(d,J＝8.8Hz,2H),5.04(s,1H),4.96(sept,J＝6.4Hz,1H),3.68(s,3H),3.07(t,J＝7.2Hz,2H),2.52–2.37(m,2H),1.71(dt,J＝13.6,6.8Hz,2H),1.43–1.26(m,3H),1.20(d,J＝6.4Hz,3H),1.18–1.11(m,1H),1.00(d,J＝6.4Hz,3H)；13CNMR(100MHz,CDCl3):δ173.4,152.0,141.3,138.5,128.5,127.4,127.1,116.5,114.5,69.6,66.5,55.7,33.1,32.9,30.4,22.8,21.7,21.3,7.0；HRMS(ESI):[M+H]+Calcd forCalcd for C23H31INO3 +:496.1343；found:496.1352.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝13.020min(major),tR2＝18.762min(minor)；98％e.e.；[α]D 25＝35.4(c＝1.75,CHCl3).
在干燥的反应管中加入上述产物(0.05mmol,1.0equiv.)、K2CO3(0.15mmol,3.0equiv.)和MeCN(1.0mL)所得反应液在95℃下反应18h.待反应完成后，加水淬灭，分液后水相经DCM萃取三次，合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到无色油状液12.6mg,68％收率；Rf＝0.41(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.49–7.46(m,2H),7.29(t,J＝7.2Hz,2H),7.25–7.20(m,1H),6.64(d,J＝9.2Hz,2H),6.55(d,J＝9.2Hz,2H),4.90(sept,J＝6.4Hz,1H),3.76–3.68(m,4H),3.52(ddd,J＝16.0,9.6,1.6Hz,1H),2.61(dd,J＝14.8,8.8Hz,1H),2.04(dd,J＝14.8,6.4Hz,1H),1.99–1.90(m,2H),1.88–1.81(m,1H),1.79–1.71(m,1H),1.65–1.62(m,1H),1.46–1.37(m,1H),1.18(d,J＝6.0Hz,3H),0.85(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ174.0,151.8,145.5,141.5,128.8,127.8,126.8,117.0,113.7,72.2,68.9,55.8,51.4,45.0,31.0,29.8,23.8,21.8,21.2；HRMS(ESI):[M+H]+Calcd for Calcd for C23H30NO3 +:368.2220；found:368.2213.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝6.857min(minor),tR2＝10.790min(major)；98％ee；[α]D 25＝-41.5(c＝1.23,CHCl3).
实施例73：
操作过程如通用步骤1，得无色油状液47.8mg,63％收率；Rf＝0.11(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.44–7.41(m,2H),7.33–7.25(m,3H),6.72(d,J＝9.2Hz,2H),6.45(d,J＝8.8Hz,2H),4.85(sept,J＝6.4Hz,1H),4.75(d,J＝6.4Hz,1H),4.66(d,J＝6.4Hz,1H),4.44(d,J＝6.4Hz,1H),4.06(d,J＝8.8Hz,1H),4.00(d,J＝6.4Hz,1H),3.79(d,J＝9.2Hz,1H),3.71(s,3H),2.93(d,J＝12.4Hz,1H),2.68(d,J＝12.4Hz,1H),1.15(d,J＝6.0Hz,3H),0.74(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.1,152.0,140.8,140.5,127.9,127.8,127.3,114.7,114.4,83.5,78.4,74.1,69.2,60.1,55.8,53.2,44.2,21.7,21.3；HRMS(ESI):[M+H]+Calcd for Calcd for C23H28NO4 +:382.2013；found:382.2006.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝6.622min(minor),tR2＝10.892min(major)；92％e.e.；[α]D 25＝5.6(c＝4.11,CHCl3).
实施例74：
操作过程如通用步骤1，反应20h后，向反应液中加入HCl(1.0M in H2O,6.0equiv)，室温下反应6h。待反应完毕，加入饱和碳酸氢钠水溶液，分离有机相后，水相用二氯甲烷萃取三次。合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到无色油状液19.6mg,69％收率；Rf＝0.22(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.55–7.52(m,2H),7.40–7.30(m,3H),6.68(d,J＝9.2Hz,2H),6.56(d,J＝9.2Hz,2H),4.49(td,J＝9.2,2.4Hz,2H),4.34(ddd,J＝10.0,9.2,6.4Hz,1H),3.70(s,3H),3.07(ddd,J＝13.6,6.4,2.4Hz,1H),2.84(ddd,J＝13.2,10.0,8.8Hz,1H)；13C NMR(100MHz,CDCl3):δ177.2,153.7,137.9,137.6,129.1,128.7,126.4,118.7,114.7,65.6,64.2,55.7,35.9；HRMS(ESI):[M+H]+Calcd for Calcd for C17H18NO3 +:284.1281；found:284.1275.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝80/20,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝12.777min(minor),tR2＝18.421min(major)；98％e.e.；[α]D 25＝31.0(c＝4.53,CHCl3).
实施例75：
在0℃下，向含有α-季碳氨基酸酯(0.14mmol,1.0equiv.)的THF(1.0mL)溶液中加入LiAlH4(0.28mmol,2.0equiv.),所得反应液缓慢恢复至室温搅拌至原料完全消耗完。待反应完毕，加水淬灭，硅藻土过滤，乙酸乙酯洗涤滤饼。分离有机相后，水相用乙酸乙酯萃取三次。合并有机相，Na2SO4干燥，过滤，旋干，以当量收率得到手性氨基醇产物；Rf＝0.39(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.39–7.32(m,4H),7.27–7.24(m,1H),6.62(d,J＝8.8Hz,2H),6.38(d,J＝8.4Hz,2H),4.02(1/2ABq,J＝7.2Hz,1H),3.92(1/2ABq,J＝9.3Hz,1H),3.68(s,3H),2.02–1.96(m,1H),1.85–1.80(m,1H),1.25–1.18(m,10H),0.84(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ152.5,143.3,139.2,128.7,127.0,126.7,117.5,114.6,65.4,62.7,55.7,38.4,31.9,30.0,29.2,23.5,22.7,14.2；HRMS(ESI):[M+H]+Calcdfor Calcd for C22H32NO2 +:342.2428；found:342.2421.[α]D 25＝29.8(c＝0.84,CHCl3).
在0℃下，向上述氨基醇(0.1mmol,1.0equiv.)的DCM(0.1M)溶液中加入NEt3(0.2mmol,2.0equiv.)搅拌5min后,加入MsCl(0.15mmol,1.5equiv.)。所得反应液在室温下搅拌3h。待反应完毕，向反应液中加入饱和碳酸氢钠水溶液，分离有机相后，水相用二氯甲烷萃取三次。合并有机相，Na2SO4干燥，过滤，旋干，所得粗产品溶于DMF中，随后加入K2CO3(0.42mmol,3.0equiv.)，室温下搅拌12h.待反应完毕，加水淬灭，分离有机相后，水相用乙酸乙酯萃取三次。合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到氮杂三元环产物18.8mg,58％收率；Rf＝0.36(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.44(d,J＝6.8Hz,2H),7.34(t,J＝7.6Hz,2H),7.27–7.23(m,1H),6.94(d,J＝8.8Hz,2H),6.81(d,J＝8.8Hz,2H),3.78(s,3H),2.63(s,1H),2.24(s,1H),1.88–1.81(m,1H),1.69–1.68(m,1H),1.36–1.13(m,10H),0.83(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ155.0,143.0,141.6,128.3,128.2,127.1,122.0,114.2,55.6,49.1,38.5,34.9,31.8,29.8,29.2,26.8,22.7,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C22H30NO+:324.2322；found:324.2314.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.934min(major),tR2＝9.325min(minor)；92％e.e.；[α]D 25＝31.0(c＝4.53,CHCl3).
实施例76：
在-78℃下，向含有α-季碳氨基醇(0.025mmol,1.0equiv.)和2,6-二甲基吡啶(4.5equiv.)的DCM(0.1M)溶液中加入三光气(0.018mmol,0.7equiv.)，所得反应液在室温下搅拌19h。待反应结束后，加入1.0M HCl淬灭并用饱和NaHCO3中和.分液后水相经DCM萃取三次，合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到淡黄色油状液8.9mg,97％收率；Rf＝0.42(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.39–7.33(m,5H),6.81(d,J＝9.2Hz,2H),6.73(d,J＝8.8Hz,2H),4.56(1/2ABq,J＝8.8Hz,1H),4.49(1/2ABq,J＝9.3Hz,1H),3.74(s,3H),2.20–2.12(m,1H),2.07–2.00(m,1H),1.37–1.20(m,10H),0.86(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ158.3,157.3,142.3,129.1,128.5,128.2,127.9,126.3,114.2,74.4,67.0,55.5,35.2,31.8,29.9,29.1,23.2,22.7,14.2；HRMS(ESI):[M+H]+Calcd for Calcd for C23H30NO3 +:368.2220；found:368.2215.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝20.793min(major),tR2＝24.298min(minor)；99％e.e.；[α]D 25＝51.5(c＝0.66,CHCl3).
实施例77：
操作过程如通用步骤1，得淡黄色油状液24.1mg,45％收率；Rf＝0.26(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.71(d,J＝7.2Hz,2H),7.30(t,J＝7.2Hz,2H),7.23(t,J＝7.2Hz,1H),6.53(d,J＝8.8Hz,2H),6.17(d,J＝8.8Hz,2H),5.84(s,1H),4.90(sept,J＝6.4Hz,1H),4.51(dd,J＝7.6,2.8Hz,1H),4.17(dd,J＝7.6,2.0Hz,1H),4.05(d,J＝2.8Hz,1H),3.82(dd,J＝12.8,2.4Hz,1H),3.68(d,J＝12.8Hz,1H),3.64(s,3H),2.80(ABq,J＝14.4Hz,2H),1.47(s,3H),1.42(s,3H),1.31(s,3H),1.29(s,3H),1.07(d,J＝6.4Hz,3H),1.05(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.5,151.3,142.4,140.6,128.6,127.2,127.0,116.3,114.0,109.3,108.3,103.9,74.7,70.8,70.6,69.0,65.4,61.3,55.8,48.4,26.4,25.8,24.8,24.4,21.5,21.4；HRMS(ESI):[M+H]+Calcd for Calcd forC30H40NO8 +:542.2748；found:542.2740.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,λ＝220nm,T＝40℃,tR1＝5.264min(major),tR2＝6.266min(minor)；>99:1d.r.；[α]D 25＝77.4(c＝0.31,CHCl3).
实施例78：
操作过程如通用步骤1，得无色油状液35.6mg,66％收率；Rf＝0.27(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.61(d,J＝7.2Hz,2H),7.31(t,J＝7.6Hz,2H),7.23(t,J＝7.2Hz,1H),6.55(d,J＝8.8Hz,2H),6.18(d,J＝8.8Hz,2H),5.29(s,1H),4.81(sept,J＝6.4Hz,1H),4.54(dd,J＝8.0,2.4Hz,1H),4.17(d,J＝8.4Hz,1H),4.00(d,J＝2.4Hz,1H),3.76(dd,J＝12.8,1.6Hz,1H),3.66–3.62(m,4H),3.25(d,J＝14.0Hz,1H),2.70(d,J＝13.6Hz,1H),1.61(s,3H),1.34(s,3H),1.33(s,3H),1.23(d,J＝6.4Hz,3H),0.99(d,J＝6.4Hz,3H),0.57(s,3H)；13C NMR(100MHz,CDCl3):δ172.8,151.3,142.3,140.4,128.7,127.3,126.7,116.0,114.3,108.9,108.3,102.7,74.6,70.5,70.4,69.9,64.1,60.3,55.9,41.6,26.4,26.1,23.9,23.3,21.4；HRMS(ESI):[M+H]+Calcd for Calcd for C30H40NO8 +:542.2748；found:542.2739.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,λ＝254nm,T＝40℃,tR1＝5.252min(minor),tR2＝6.224min(major)；>99:1d.r.；[α]D 25＝-4.76(c＝2.94,CHCl3).
实施例79：
0℃下，向含有α-季碳氨基酸酯(0.2mmol,1.0equiv.)的MeCN(2.0mL)溶液中缓慢加入硝酸铈铵水溶液(1.0mol/L,5.0equiv.)，所得反应液继续在0℃下搅拌0.5h。待反应结束后，反应液用水稀释，***萃取三次。水相用饱和碳酸钠调至pH＝9，20％aq.Na2SO3淬灭，DCM萃取4次，合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到氮上脱保护的产物21.5mg,62％收率；1H NMR(400MHz,CDCl3):δ4.15(qd,J＝7.2,2.0Hz,2H),2.09(bs,2H),1.75–1.68(m,2H),1.59–1.53(m,1H),1.33(s,3H),1.28(t,J＝7.2Hz,3H),0.92(d,J＝6.4Hz,3H),0.85(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ178.2,61.2,57.6,49.4,27.8,24.6,24.5,23.2,14.3.HRMS(ESI):[M+H]+Calcd for Calcd for C9H20NO2 +:174.1489；found:174.1488.
0℃下，向上述产物(0.07mmol,1.0equiv.)的THF(1.0mL)溶液中加入LiAlH4(0.14mmol,2.0equiv.)，所得反应液缓慢恢复至室温搅拌过夜。加水淬灭后，用硅藻土过滤，乙酸乙酯润洗滤饼，分离有机相后，水相用乙酸乙酯萃取三次。合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到手性氨基醇产物8.6mg,94％收率；1H NMR(400MHz,CDCl3):1H NMR(400MHz,CDCl3):δ3.30(ABq,J＝10.8Hz,2H),1.74(sept,J＝6.4Hz,1H),1.32(qd,J＝6.4,1.2Hz,1H),1.10(s,3H),0.96(t,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ70.7,53.6,49.0,29.8,25.3,25.3,24.2.HRMS(ESI):[M+H]+Calcd for Calcd forC7H18NO+:132.1383；found:132.1384.[α]D 25＝13.3(c＝1.38,CHCl3).
实施例80：
在0℃下，向含有PPh3(0.75mmol,1.5equiv.)和咪唑(0.75mmol,1.5equiv.)的DCM(0.2M)溶液中加入起始原料(0.5mmol,1.0equiv.)，随后分批加入I2(0.75mmol,1.5equiv.)，所得反应液缓慢恢复至室温继续搅拌11h。待反应完成后，加入饱和Na2S2O3水溶液淬灭，分液后水相经DCM萃取三次，合并有机相，Na2SO4干燥，过滤，旋干，使用快速柱层析纯化得到亮黄色油状液104mg,83％收率；Rf＝0.35(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ6.78(d,J＝9.2Hz,2H),6.51(d,J＝8.8Hz,2H),4.25–4.12(m,2H),3.79(ddd,J＝8.8,6.4,4.8Hz,1H),3.74(s,3H),3.70(dt,J＝8.4,6.4Hz,1H),2.66(ddd,J＝10.8,8.4,6.4Hz,1H),2.15(ddd,J＝10.8,8.4,4.8Hz,1H),1.20(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ174.4,152.7,142.5,114.6,114.2,69.6,61.1,55.8,46.7,29.0,20.8,14.3.HRMS(ESI):[M+H]+Calcd for Calcd for C14H20NO3 +:250.1438；found:250.1435.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝230nm,tR1＝18.259min(major),tR2＝20.799min(minor)；90％e.e.；[α]D 25＝67(c＝1.06,CHCl3).
向含有上述产物(0.1mmol,1.0equiv.)的MeCN/H2O(1/1mL)溶液中加入H5IO4(0.15mmol,1.5equiv.)和H2SO4(1.0M in H2O,0.15mmol,1.5equiv.)，所得反应液在室温下搅拌3h。待反应结束后，反应液用水稀释，***萃取三次。水相用饱和碳酸钠调至pH＝9，DCM萃取4次，合并有机相，Na2SO4干燥，过滤，加入HCl(4M in 1,4-dioxane)搅拌10min后旋干，得到盐酸盐产物11.6mg,64％收率；1H NMR(400MHz,CD3OD):δ4.35(q,J＝7.2Hz,2H),4.06(td,J＝10.0,7.6Hz,1H),3.92(td,J＝10.0,6.4Hz,1H),2.83(ddd,J＝12.4,9.6,7.6Hz,1H),2.56(ddd,J＝12.4,9.2,6.4Hz,1H),1.84(s,3H),1.34(t,J＝7.2Hz,3H)；13C NMR(100MHz,CD3OD):δ170.1,67.6,63.0,40.4,29.1,20.9,12.8.HRMS(ESI):[M+H]+Calcd forCalcd for C7H15ClNO2 +:180.0786；found:180.0784；[α]D 25＝37.1(c＝0.82,CHCl3).
实施例81：
操作过程如通用步骤3，得无色油状液36.6mg,72％收率；Rf＝0.25(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):5.00(sept,6.4Hz,1H),2.93(t,J＝6.4Hz,2H),2.50(bs,1H),2.16–2.08(m,1H),1.83–1.71(m,2H),1.69–1.59(m,2H),1.48(td,J＝12.4,4.0Hz,1H),1.29–1.21(m,15H),1.11–1.03(m,1H),0.84(t,J＝6.8Hz,3H)；13CNMR(100MHz,CDCl3):δ176.8,69.4,68.3,46.5,40.2,36.1,31.9,30.0,29.2,25.3,24.9,22.7,21.90,21.88,14.2；HRMS(ESI):[M+H]+Calcd for C15H30NO2 +:256.2271；found:256.2264.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,tR1＝7.572min(major),tR2＝11.532min(minor)；99％e.e.；[α]D 23＝-26.0(c＝0.1,CHCl3).
实施例82：
操作过程如通用步骤3，得无色油状液27.2mg,64％收率；Rf＝0.3(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):5.00(sept,6.0Hz,1H),2.95(t,J＝6.8Hz,2H),2.37(bs,1H),2.16–2.09(m,1H),1.81–1.72(m,2H),1.70–1.59(m,3H),1.49(dd,J＝13.6,5.6Hz,1H),1.23(d,J＝6.4Hz,3H),1.22(d,J＝6.4Hz,3H),0.90(d,J＝6.8Hz,3H),0.82(d,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ177.2,69.1,68.4,48.6,46.3,37.4,25.6,24.4,24.3,23.2,21.9,21.8；HRMS(ESI):[M+H]+Calcd for C12H24NO2 +:214.1802；found:214.2795.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0 mL/min, λ ＝ 220 nm, tR1＝ 7.012 min (major), tR2 ＝ 10.344 min (minor)；99％e.e.；[α]D 23＝-26.5(c＝0.4,CHCl3).
实施例83：
操作过程如通用步骤3，得无色油状液47.3mg,61％收率；Rf＝0.34(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):δ4.99(sept,J＝6.4Hz,1H),3.89–3.79(m,3H),3.68(dd,J＝8.8,6.4Hz,1H),3.08–3.03(m,1H),2.96–2.88(m,2H),2.40(bs,1H),2.13–2.06(m,1H),1.81–1.60(m,3H),1.41(s,9H),1.22(d,J＝6.0Hz,3H),1.21(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ175.9,156.4,79.3,69.11,69.07,51.2,50.1,47.4,35.4,32.7,28.5,25.7,21.8；HRMS(ESI):[M+H]+Calcd for C16H29N2O4 +:313.2122；HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,tR1＝11.456min(major),tR2＝14.260min(minor)；90％e.e.；[α]D 23＝-52.9(c＝0.14,CHCl3).
实施例84：
操作过程如通用步骤3，得无色油状液19.4mg,49％收率；Rf＝0.29(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):5.02(sept,6.4Hz,1H),2.90(t,J＝6.4Hz,2H),2.37(bs,1H),2.13–2.06(m,1H),1.95(sept,J＝6.8Hz,1H),1.78–1.68(m,2H),1.67–1.55(m,1H),1.24(d,J＝6.0Hz,6H),0.89(d,J＝6.8Hz,3H),0.87(d,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ176.8,72.9,68.4,46.8,35.8,33.4,25.3,22.0,18.6,17.5；HRMS(ESI):[M+H]+Calcd forC11H22NO2 +:200.1645；found:200.1639；HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,tR1＝8.111min(major),tR2＝10.205min(minor)；99％e.e.；[α]D 23＝-112.2(c＝0.06,CHCl3).
实施例85：
操作过程如通用步骤3，得无色油状液31.4mg,70％收率；Rf＝0.29(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):5.01(sept,J＝6.4Hz,1H),2.98–2.87(m,2H),2.40(bs,1H),2.31–2.23(m,1H),2.15–2.08(m,1H),1.79–1.71(m,2H),1.68–1.56(m,4H),1.54–1.46(m,3H),1.44–1.37(m,1H),1.33–1.27(m,1H),1.24(d,J＝6.4Hz,6H)；13C NMR(100MHz,CDCl3):δ177.3,71.4,68.4,47.3,47.0,34.2,28.1,27.2,25.8,25.6,25.4,21.94,21.91；HRMS(ESI):[M+H]+Calcd for C13H24NO2 +:226.1802；found:226.1795；HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,tR1＝9.577min(major),tR2＝19.402min(minor)；99％e.e.；[α]D 23＝-37.9(c＝0.19,CHCl3).
实施例86：
操作过程如通用步骤3，得无色油状液41.0mg,75％收率；Rf＝0.47(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):7.17–7.08(m,4H),5.02(sept,J＝6.4Hz,1H),3.05–2.94(m,5H),2.90–2.78(m,2H),2.50(bs,1H),2.25–2.17(m,1H),1.90–1.76(m,2H),1.73–1.61(m,1H),1.25(d,J＝6.4Hz,3H),1.22(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ176.9,142.95,142.85,126.23,126.18,124.5,124.4,71.1,68.7,47.05,47.02,35.0,34.3,34.0,25.6,21.9,21.8；HRMS(ESI):[M+H]+Calcd for C17H24NO2 +:274.1802；found:274.1794.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,λ＝220nm,tR1＝11.803min(major),tR2＝14.518min(minor)；98％e.e.；[α]D 23＝-45.2(c＝0.22,CHCl3).
实施例87：
操作过程如通用步骤3，得无色油状液34.0mg,71％收率；Rf＝0.29(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):5.01(sept,J＝6.4Hz,1H),3.96(td,J＝10.4,4.0Hz,2H),3.37–3.27(m,2H),2.90(t,J＝6.8Hz,2H),2.39(bs,1H),2.15–2.07(m,1H),1.85–1.38(m,8H),1.24(d,J＝6.4Hz,6H)；13C NMR(100MHz,CDCl3):δ176.1,72.0,68.8,68.28,68.27,46.5,43.8,32.7,28.8,27.8,25.1,21.98,21.94；HRMS(ESI):[M+H]+Calcd for C13H24NO3 +:242.1751；found:242.1744.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,λ＝254nm,tR1＝11.950min(major),tR2＝17.941min(minor)；99％e.e.；[α]D 23＝-14.8(c＝0.18,CHCl3).
实施例88：
操作过程如通用步骤3，得无色油状液37.8mg,75％收率；Rf＝0.32(PE/EtOAc＝10/1+NEt3)；1H NMR(400MHz,CDCl3):5.00(sept,J＝6.0Hz,1H),2.93–2.84(m,2H),2.40(bs,1H),2.17–2.07(m,1H),1.76–1.60(m,8H),1.56–1.36(m,6H),1.33–1.17(m,8H)；13CNMR(100MHz,CDCl3):δ176.9,73.6,68.3,47.5,46.6,33.2,30.3,29.5,28.1,27.9,27.8,27.6,25.2,21.9；HRMS(ESI):[M+H]+Calcd for C15H28NO2 +:254.2115；found:254.2107.HPLC(Chiralcel OD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,λ＝254nm,tR1＝7.786min(major),tR2＝9.035min(minor)；99％e.e.；[α]D 23＝-70.3(c＝0.11,CHCl3).
实施例89：
操作过程如通用步骤3，得无色油状液35.9mg,63％收率；Rf＝0.44(DCM/CH3OH＝20/1)；1HNMR(400MHz,CDCl3):δ5.02(sept,J＝6.4Hz,1H),2.89–2.75(m,4H),2.39–2.34(m,2H),2.29(bs,1H),2.12(ddd,J＝12.4,8.0,4.0Hz,1H),2.02–1.90(m,3H),1.81(td,J＝13.6,4.0Hz,1H),1.72–1.54(m,3H),1.50–1.33(m,2H),1.26(d,J＝6.4Hz,3H),1.24(d,J＝6.4Hz,3H),0.86(t,J＝7.6Hz,3H)；13C NMR(100MHz,CDCl3):δ176.6,68.8,46.3,40.4,31.8,31.3,30.4,25.0,24.3,23.9,23.9,21.9,21.9,8.8；HRMS(ESI):[M+H]+Calcd forC15H28NO2S+:286.1757；found:286.1826.HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝254nm,tR1＝9.559min(major),tR2＝15.609min(minor)；97％e.e.；[α]D 23＝-39.2(c＝0.08,CHCl3).
实施例90：
操作过程如通用步骤3，得无色油状液47.3mg,61％收率；Rf＝0.19(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):4.99(sept,J＝6.4Hz,1H),4.22(quint,J＝9.2Hz,1H),3.02(dd,J＝10.8,5.6Hz,1H),2.78(dd,J＝11.2,4.0Hz,1H),2.38–2.33(m,2H),1.79(td,J＝13.2,4.4Hz,1H),1.70–1.63(m,2H),1.40–1.21(m,15H),1.12–1.05(m,1H),0.88–0.82(m,12H),0.013(s,3H),0.007(s,3H)；13C NMR(100MHz,CDCl3):δ176.2,72.5,68.9,68.4,55.1,45.5,40.1,31.8,29.9,29.2,25.9,25.0,22.7,21.9,21.8,18.2,14.2,-4.7；HRMS(ESI):[M+H]+Calcd for C21H44NO3Si+:386.3085；found:386.3073.HPLC(Chiralcel OD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝220nm,tR1＝6.476min(minor),tR2＝7.052min(major)；>99:1d.r.；[α]D 23＝52.8(c＝0.13,CHCl3).
实施例91：
操作过程如通用步骤3，得无色油状液42.8mg,56％收率；Rf＝0.19(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):1H NMR(400MHz,CDCl3)δ4.99(sept,J＝6.4Hz,1H),4.23(tt,J＝5.2,2.8Hz,1H),2.95–2.86(m,2H),2.72(bs,1H),2.19(dt,J＝13.6,2.0Hz,1H),1.80–1.73(m,2H),1.43–1.32(m,2H),1.24–1.21(m,14H),1.07–1.00(m,1H),0.85–0.80(m,12H),-0.01(s,6H)；13C NMR(100MHz,CDCl3):δ13C NMR(100MHz,CDCl3)δ176.2,72.7,68.45,68.42,55.8,46.4,41.1,31.9,29.9,29.3,25.8,25.0,22.7,21.9,21.9,18.1,14.2,-4.7,-4.8；HRMS(ESI):[M+H]+Calcd for C21H44NO3Si+:386.3085；found:386.3073.HPLC(Chiralcel OD-H):n-Hexane/i-PrOH＝98/2,flow rate1.0mL/min,λ＝220nm,tR1＝6.517min(major),tR2＝7.092min(minor)；>99:1d.r.；[α]D 23＝52.8(c＝0.13,CHCl3).
实施例92：
操作过程如通用步骤3，得无色油状液29.9mg,55％收率；Rf＝0.43(DCM/CH3OH＝10/1)；1H NMR(400MHz,CDCl3):δ5.06(sept,J＝6.4Hz,1H),2.86(dt,J＝12.0,4.0Hz,1H),2.66(td,J＝11.6,2.8Hz,1H),2.16–2.12(m,2H),1.66–1.62(m,1H),1.57–1.38(m,5H),1.31–1.22(m,16H),0.85(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ175.5,67.9,62.6,43.7,41.9,33.3,31.8,30.0,29.2,25.6,23.3,22.7,22.3,22.1,22.0,14.2；HRMS(ESI):[M+H]+Calcd for C16H32NO2 +:270.2428；found:270.2421；HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝11.317min(major),tR2＝13.499min(minor)；98％e.e.；[α]D 23＝79.2(c＝0.08,CHCl3).
实施例93：
操作过程如通用步骤4，得黄色油状液85.6mg,96％收率；Rf＝0.56(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.43(d,J＝7.2Hz,1H),7.23–7.17(m,4H),7.08(t,J＝7.6Hz,1H),6.99–6.97(m,2H),6.67(d,J＝7.6Hz,1H),6.53(d,J＝8.8Hz,2H),6.37(d,J＝8.8Hz,2H),5.08(1/2abq,J＝15.6Hz,1H),4.63(1/2abq,J＝16.0Hz,1H),3.79(bs,1H),3.67(s,3H),2.12–1.96(m,2H),1.29–1.18(m,9H),1.08–0.99(m,1H),0.86(t,J＝7.2Hz,3H).13CNMR(100MHz,CDCl3):δ178.3,154.5,142.7,138.6,135.5,130.1,128.9,128.6,127.5,127.4,124.3,123.0,120.5,114.3,109.5,66.9,55.4,43.8,40.0,31.8,29.6,29.0,23.1,22.6,14.1；HRMS(ESI):[M+H]+Calcd for C29H35N2O2 +:443.2693；found:443.2685；HPLC(Chiralpcel OJ-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.692min(major),tR2＝13.277min(minor)；93％e.e.；[α]D 23＝-133.0(c＝0.19,CHCl3).
实施例94：
操作过程如通用步骤4，得黄色固体71.2mg,92％收率；Rf＝0.38(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.46(d,J＝7.2Hz,1H),7.22–7.18(m,4H),7.07(t,J＝7.6Hz,1H),6.96–6.94(m,2H),6.67(d,J＝7.6Hz,1H),6.53(d,J＝8.8Hz,2H),6.37(d,J＝9.2Hz,2H),5.11(1/2abq,J＝15.6Hz,1H),4.58(1/2abq,J＝16.4Hz,1H),3.98(bs,1H),3.67(s,3H),2.34(sept,J＝6.8Hz,1H),1.23(d,J＝6.8Hz,3H),0.76(d,J＝6.8Hz,3H).13C NMR(100MHz,CDCl3):δ178.5,154.4,143.3,139.2,135.5,129.0,128.6,128.4,127.5,127.4,125.4,122.5,120.8,114.2,109.4,70.1,55.4,43.7,37.0,16.8,16.6.HRMS(ESI):[M+H]+Calcd for C25H27N2O2 +:387.2067；found:387.2060；HPLC(Chiralpak AD-H):n-Hexane/EtOH＝90/10,flow rate 1.0mL/min,T＝40℃,λ＝220nm,tR1＝15.107min(major),tR2＝20.125min(minor)；95％e.e.；[α]D 23＝-224.4(c＝0.33,CHCl3).
实施例95：
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操作过程如通用步骤4，得黄色粘稠油状液88.3mg,97％收率；Rf＝0.52(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.23–7.20(m,4H),7.01–6.98(m,3H),6.57(d,J＝8.0Hz,1H),6.53(d,J＝9.2Hz,2H),6.34(d,J＝9.2Hz,2H),5.06(1/2abq,J＝15.6Hz,1H),4.62(1/2abq,J＝15.6Hz,1H),4.01(bs,1H),3.67(s,3H),2.33(s,3H),2.08–1.94(m,2H),1.28–1.15(m,9H),1.06–0.99(m,1H),0.86(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3):δ178.3,154.2,140.3,139.0,135.7,132.5,130.3,129.2,128.6,127.52,127.48,124.9,119.9,114.3,109.3,66.7,55.4,43.9,40.3,31.8,29.7,29.1,23.1,22.7,21.3,14.2.HRMS(ESI):[M+H]+Calcd for C30H37N2O2 +:457.2850；found:457.2843；HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝6.788min(minor),tR2＝7.609min(major)；90％e.e.；[α]D 23＝-122.5(c＝0.66,CHCl3).
实施例96：
操作过程如通用步骤4，得红色油状液90.2mg,87％收率；Rf＝0.56(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.50(t,J＝7.2Hz,3H),7.43(t,J＝7.2Hz,2H),7.35(t,J＝7.2Hz,2H),7.26–7.24(m,3H),7.06–7.04(m,2H),6.92(d,J＝1.6Hz,1H),6.57(d,J＝8.8Hz,2H),6.42(d,J＝8.8Hz,2H),5.13(1/2abq,J＝15.6Hz,1H),4.73(1/2abq,J＝15.6Hz,1H),4.02(bs,1H),3.69(s,3H),2.16–1.99(m,2H),1.33–1.19(m,9H),1.17–1.08(m,1H),0.88(t,J＝6.8Hz,3H).13C NMR(100MHz,CDCl3):δ178.6,154.4,143.3,142.1,140.7,138.8,135.5,129.3,128.9,128.7,127.7,127.6,127.4,127.1,124.5,121.9,120.3,114.3,108.2,66.7,55.4,43.9,40.2,31.8,29.7,29.1,23.2,22.7,14.1.HRMS(ESI):[M+H]+Calcd for C35H39N2O2 +:519.3006；found:519.2998.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝8.318min(minor),tR2＝10.217min(major)；91％e.e.；[α]D 23＝-62.6(c＝0.74,CHCl3).
实施例97：
操作过程如通用步骤4，得黄色油状液88.6mg,94％收率；Rf＝0.39(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.30(d,J＝8.0Hz,1H),7.21–7.19(m,3H),6.97–6.94(m,2H),6.58(dd,J＝8.4,2.4Hz,1H),6.54(d,J＝8.8Hz,2H),6.37(d,J＝8.8Hz,2H),6.26(d,J＝2.4Hz,1H),5.04(1/2abq,J＝15.6Hz,1H),4.58(1/2abq,J＝15.6Hz,1H),3.99(bs,1H),3.73(s,3H),3.67(s,3H),2.08–1.92(m,2H),1.28–1.14(m,9H),1.08–1.01(m,1H),0.86(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3):δ178.9,160.5,154.4,144.0,138.8,135.5,128.6,127.5,127.4,124.9,121.9,120.6,114.2,106.5,97.7,66.5,55.40,55.38,43.8,40.2,31.8,29.6,29.1,23.2,22.7,14.1.HRMS(ESI):[M+H]+Calcd for C30H37N2O3 +:473.2799；found:473.2794.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝8.121min(minor),tR2＝9.360min(major)；89％e.e.；[α]D 23＝-78.8(c＝0.98,CHCl3).
实施例98：
操作过程如通用步骤4，得黄色固体86.4mg,91％收率；Rf＝0.44(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.22–7.19(m,3H),7.04(d,J＝2.8Hz,1H),6.99–6.97(m,2H),6.71(dd,J＝8.4,2.8Hz,1H),6.57(d,J＝8.4Hz,1H),6.54(d,J＝8.8Hz,2H),6.37(d,J＝9.2Hz,2H),5.06(1/2abq,J＝15.6Hz,1H),4.60(1/2abq,J＝15.6Hz,1H),4.06(bs,1H),3.77(s,3H),3.67(s,3H),2.08–1.95(m,2H),1.30–1.14(m,9H),1.07–0.98(m,1H),0.86(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3):δ178.0,156.3,154.3,138.8,136.1,135.6,131.7,128.6,127.5,127.4,120.2,114.3,113.4,111.2,110.0,67.1,55.8,55.4,43.9,40.2,31.8,29.6,29.0,23.1,22.6,14.1.HRMS(ESI):[M+H]+Calcd for C30H37N2O3 +:473.2799；found:437.2791.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝8.952min(minor),tR2＝10.308min(major)；90％e.e.；[α]D 23＝-103.0(c＝0.18,CHCl3).
实施例99：
操作过程如通用步骤4，得黄色固体64.6mg,68％收率；Rf＝0.56(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.40(d,J＝2.4Hz,1H),7.23–7.20(m,3H),7.16(dd,J＝8.4,2.0Hz,1H),6.97–6.94(m,2H),6.58(d,J＝8.4Hz,1H),6.55(d,J＝8.8Hz,2H),6.36(d,J＝9.2Hz,2H),5.08(1/2abq,J＝15.6Hz,1H),4.59(1/2abq,J＝15.6Hz,1H),3.94(bs,1H),3.68(s,3H),2.08–1.95(m,2H),1.28–1.14(m,9H),1.06–0.98(m,1H),0.87(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3):δ178.0,154.6,141.2,138.4,135.1,132.2,128.9,128.7,128.5,127.8,127.4,124.6,120.4,114.4,110.5,67.0,55.4,43.9,40.1,31.8,29.6,29.0,23.1,22.7,14.1.HRMS(ESI):[M+H]+Calcd for C29H34ClN2O2 +:477.2303；found:477.2297.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝7.668min(minor),tR2＝8.943min(major)；91％e.e.；[α]D 23＝-155.8(c＝0.41,CHCl3).
实施例100：
操作过程如通用步骤4，得黄色固体67.4mg,73％收率；Rf＝0.48(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.36(dd,J＝8.0,5.2Hz,1H),7.24–7.18(m,3H),6.95–6.92(m,2H),6.76(ddd,J＝9.2,8.0,2.0Hz,1H),6.55(d,J＝8.8Hz,2H),6.40(dd,J＝8.8,2.4Hz,1H),6.36(d,J＝8.8Hz,2H),5.06(1/2abq,J＝15.6Hz,1H),4.57(1/2abq,J＝15.6Hz,1H),3.93(bs,1H),3.68(s,3H),2.09–1.94(m,2H),1.28–1.15(m,9H),1.05–0.99(m,1H),0.86(t,J＝6.8Hz,3H).13C NMR(100MHz,CDCl3):δ178.7,163.3(d,J＝244.3Hz),154.7,144.3(d,J＝11.5Hz),138.5,135.0,128.8,127.8,127.4,125.5(d,J＝3.0Hz),125.3(d,J＝9.7Hz),120.9,114.3,109.2(d,J＝22.3Hz),98.4(d,J＝27.4Hz),66.7,55.4,43.9,40.0,31.8,29.6,29.1,23.1,22.7,14.1.19F NMR(376MHz,CDCl3)δ-110.8.HRMS(ESI):[M+H]+Calcd for C29H34FN2O2 +:461.2599；found:461.2592.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,T＝40℃,λ＝254nm,tR1＝7.280min(minor),tR2＝8.767min(major)；93％e.e.；[α]D 23＝-106.1(c＝1.34,CHCl3).
实施例101：
操作过程如通用步骤4，得红色粘稠油状液90mg,85％收率；Rf＝0.63(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.34(d,J＝2.0Hz,1H),7.24–7.19(m,3H),7.05(dd,J＝8.4,1.6Hz,1H),6.93–6.91(m,2H),6.62(d,J＝8.4Hz,1H),6.55(d,J＝8.8Hz,2H),6.39(d,J＝8.8Hz,2H),5.08(1/2abq,J＝16.0Hz,1H),4.59(1/2abq,J＝15.6Hz,1H),4.02(bs,1H),3.69(s,3H),2.11–1.96(m,2H),1.30–1.16(m,9H),1.07–1.00(m,1H),0.86(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3):δ178.3,154.9,145.1(q,J＝2.1Hz),141.4,138.2,135.0,132.0,128.8,127.8,127.3,122.0,121.4,120.6(q,J＝255.0Hz),118.3,114.3,110.0,67.4,55.4,43.9,39.9,31.7,29.5,29.0,23.1,22.6,14.1.19F NMR(376MHz,CDCl3)δ-58.3.HRMS(ESI):[M+H]+Calcdfor C30H34F3N2O3 +:527.2516；found:527.2507.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝6.768min(minor),tR2＝7.788min(major)；86％e.e.；[α]D 25＝-72.1(c＝0.42,CHCl3).
实施例102：
操作过程如通用步骤4，得黄色固体52.4mg,84％收率；Rf＝0.32(PE/EA＝3/1)；1HNMR(400MHz,CDCl3):δ7.34–7.30(m,2H),7.09(t,J＝7.6Hz,1H),6.84(d,J＝8.0Hz,1H),6.52(d,J＝8.8Hz,2H),6.24(d,J＝8.8Hz,2H),3.73(bs,1H),3.62(s,3H),3.17(s,3H),2.00–1.86(m,2H),1.21–1.09(m,1H),1.08–0.95(m,1H),0.82(t,J＝7.6Hz,3H).13C NMR(100MHz,CDCl3):δ178.5,153.6,143.4,139.0,130.3,129.0,124.0,123.0,118.2,114.4,108.4,66.1,55.5,42.5,26.2,16.4,14.0.HRMS(ESI):[M+H]+Calcd for C19H23N2O2 +:311.1754；found:311.1749.HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝17.957min(minor),tR2＝19.337min(major)；90％e.e.；[α]D 23＝-64.9(c＝0.22,CHCl3).
实施例103：
操作过程如通用步骤5，得无色油状液体59.4mg,80％收率；Rf＝0.44(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.67(d,J＝7.2Hz,2H),7.37(t,J＝7.2Hz,2H),7.33–7.29(m,1H),6.58(d,J＝8.8Hz,2H),6.30(d,J＝9.2Hz,2H),5.29(bs,1H),4.24–4.11(m,2H),3.67(s,3H),3.58(1/2ABq,J＝15.6Hz,1H),3.43(1/2ABq,J＝15.2Hz,1H),2.82(s,3H),2.66(s,3H),1.16(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.3,169.9,152.6,140.8,139.0,128.8,127.9,127.1,117.9,114.3,65.8,61.9,55.6,37.2,37.0,35.5,14.0.HRMS(ESI):[M+H]+Calcd for C21H27N2O4 +:371.1965；found:371.1960.HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝210nm,tR1＝7.429min(minor),tR2＝9.586min(major)；98％ee；[α]D 19.0＝-26.48(c＝1.05,CH2Cl2).
实施例104：
操作过程如通用步骤5，得无色油状液体51.0mg,72％收率；Rf＝0.41(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.66(d,J＝7.6Hz,2H),7.37(t,J＝7.2Hz,2H),7.33–7.29(m,1H),6.58(d,J＝8.8Hz,2H),6.30(d,J＝9.2Hz,2H),5.26(bs,1H),3.71(s,3H),3.67(s,3H),3.58(1/2ABq,J＝15.6Hz,1H),3.45(1/2ABq,J＝15.6Hz,1H),2.82(s,3H),2.65(s,3H)；13C NMR(100MHz,CDCl3):δ173.9,169.9,152.8,140.7,138.9,128.9,128.0,127.1,118.0,114.4,65.8,55.7,53.1,37.2,35.5,29.8；HRMS(ESI):[M+H]+Calcd for C20H25N2O4 +:357.1809；found:357.1803；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate1.0mL/min,T＝25℃,λ＝210nm,tR1＝8.552min(minor),tR2＝10.975min(major)；98％ee；[α]D 19.0＝31.82(c＝0.07,CH2Cl2).
实施例105：
操作过程如通用步骤5，得无色油状液体69.3mg,90％收率；Rf＝0.50(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.65(d,J＝7.6Hz,2H),7.35(t,J＝6.8Hz,2H),7.30–7.27(m,1H),6.57(d,J＝8.8Hz,2H),6.30(d,J＝8.2Hz,2H),5.32(bs,1H),4.99(sept,J＝6.0Hz,1H),3.65(s,3H),3.54(1/2ABq,J＝15.6Hz,1H),3.37(1/2ABq,J＝15.6Hz,1H),2.81(s,3H),2.67(s,3H),1.18(d,J＝6.4Hz,3H),1.07(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.6,169.9,152.6,141.0,139.2,128.7,127.7,127.0,117.9,114.3,69.3,65.8,55.6,37.2,37.1,35.4,21.5,21.4；HRMS(ESI):[M+H]+Calcd for C22H29N2O4 +:385.2122；found:385.2117；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate1.0mL/min,T＝25℃,λ＝210nm,tR1＝7.256min(minor),tR2＝9.285min(major)；98％ee；[α]D 25.5＝-39.82(c＝0.85,CH2Cl2).
实施例106：
操作过程如通用步骤5，得无色油状液体43.0mg，61％收率；Rf＝0.60(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.66(d,J＝7.6Hz,2H),7.37(t,J＝7.2Hz,2H),7.32–7.28(m,1H),7.04(d,J＝7.6Hz,1H),6.76(t,J＝7.2Hz,1H),6.56(t,J＝7.2Hz,1H),5.99(d,J＝8.0Hz,1H),5.60(bs,1H),4.26–4.13(m,2H),3.65(ABq,J＝15.2Hz,2H),2.79(s,3H),2.59(s,3H),2.27(s,3H),1.16(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ173.3,169.6,143.0,140.4,130.4,128.8,127.8,126.9,126.1,124.4,117.4,113.5,65.3,62.0,37.0,36.7,35.3,17.7,13.9；HRMS(ESI):[M+H]+Calcd for C21H27N2O3 +:355.2016；found:355.2016；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝210nm,tR1＝5.825min(minor),tR2＝8.902min(major)；98％ee；[α]D 26.0＝-85.76
实施例107：
操作过程如通用步骤5，得无色油状液体32.0mg,86％；收率；Rf＝0.63(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.62(d,J＝7.6Hz,2H),7.36(t,J＝7.2Hz,2H),7.31–7.27(m,1H),6.68(t,J＝8.8Hz,2H),6.30–6.26(m,2H),5.53(bs,1H),5.00(sept,J＝6.0Hz,1H),3.55(1/2ABq,J＝15.2Hz,1H),3.36(1/2ABq,J＝15.6Hz,1H),2.82(s,3H),2.71(s,3H),1.17(d,J＝6.4Hz,3H),1.06(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.4,169.7,156.2(d,JC-F＝234.6Hz),141.6(d,JC-F＝2.0Hz),140.4,128.8,127.9,126.9,117.2(d,JC-F＝7.2Hz),115.2(d,JC-F＝21.9Hz),69.5,65.7,37.3,37.2,35.4,21.5,21.4；19F NMR(376MHz,CDCl3):δ-127.0；HRMS(ESI):[M+H]+Calcd for C21H26FN2O3 +:373.1922；found:373.1922；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝5.586min(minor),tR2＝6.848min(major)；98％ee；[α]D 19.0＝73.48(c＝0.75,CH2Cl2).
实施例108：
操作过程如通用步骤5，得无色油状液体27.6mg,69％收率；Rf＝0.53(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.56(d,J＝8.8Hz,2H),6.88(d,J＝8.8Hz,2H),6.58(d,J＝9.2Hz,2H),6.31(d,J＝8.8Hz,2H),5.25(bs,1H),4.23–4.09(m,2H),3.80(s,3H),3.66(s,3H),3.53(1/2ABq,J＝15.2Hz,1H),3.38(1/2ABq,J＝15.6Hz,1H),2.81(s,3H),2.66(s,3H),1.16(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.5,170.0,159.2,152.7,139.2,132.8,128.3,118.0,114.3,114.1,65.3,61.8,55.6,55.3,37.2,37.1,35.4,14.0；HRMS(ESI):[M+H]+Calcd for C22H29N2O5+:401.2071；found:401.2077；HPLC(ChiralpakIBN):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝11.058min(minor),tR2＝17.051min(minor)；98％ee；[α]D 25.5＝-67.42(c＝0.45,CH2Cl2).
实施例109：
操作过程如通用步骤5，得无色油状液体71.6mg,85％收率；Rf＝0.50(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.63(s,1H),7.56–7.51(m,1H),7.28–7.23(m,2H),6.56(d,J＝8.8Hz,2H),6.27(d,J＝8.8Hz,2H),5.23(bs,1H),4.97(sept,J＝6.0Hz,1H),3.63(s,3H),3.45(1/2ABq,J＝15.6Hz,1H),3.32(1/2ABq,J＝15.2Hz,1H),2.77(s,3H),2.62(s,3H),1.15(d,J＝6.0Hz,3H),1.06(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.0,169.4,152.9,143.4,138.8,134.7,129.9,128.0,127.3,125.4,118.0,114.3,69.6,65.6,55.6,37.1,36.9,35.4,21.5,21.4；HRMS(ESI):[M+H]+Calcd for C22H28ClN2O4 +:419.1732；found:419.1730；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝210nm,tR1＝6.882min(minor),tR2＝8.352min(major)；97％ee；[α]D 19.0＝65.00(c＝0.05,CH2Cl2).
实施例110：
操作过程如通用步骤5，得黄色油状液体26.7mg,65％收率；Rf＝0.42(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.97(d,J＝1.2Hz,1H),7.59(dd,J＝8.8,2.0Hz,1H),7.29(d,J＝8.8Hz,1H),7.07(d,J＝2.8Hz,1H),6.54(d,J＝9.2Hz,2H),6.49(d,J＝3.6Hz,1H),6.32(d,J＝8.8Hz,2H),5.32(bs,1H),3.79(s,3H),3.71–3.67(m,4H),3.64(s,3H),3.54(1/2ABq,J＝15.6Hz,1H),2.84(s,3H),2.68(s,3H)；13C NMR(100MHz,CDCl3):δ174.6,170.3,152.6,139.4,136.4,131.7,129.5,128.7,121.0,119.2,117.9,114.3,109.7,101.5,65.8,55.7,53.0,37.3,37.2,35.5,33.0；HRMS(ESI):[M+H]+Calcd for C23H28N3O4 +:410.2074；found:410.2076；HPLC(Chiralpak IBN):n-Hexane/EtOH＝80/20,flow rate 1.0mL/min,T＝40℃,λ＝210nm,tR1＝8.149min(minor),tR2＝9.021min(major)；98％ee；[α]D 19.0＝-166.57(c＝0.23,CH2Cl2).
实施例111：
操作过程如通用步骤5，得白色固体31.2mg,51％收率；Rf＝0.39(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ6.77–6.71(m,4H),4.75(bs,1H),4.22(qd,J＝7.2,2.0Hz,2H),3.73(s,3H),2.89–2.85(m,7H),2.70(1/2ABq,J＝16.0Hz,1H),1.53(s,3H),1.25(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ175.9,170.3,154.7,138.6,122.8,114.2,61.4,61.0,55.6,40.4,37.3,35.4,24.9,14.2.HRMS(ESI):[M+H]+Calcd for C16H25N2O4 +:309.1809；found:309.1808；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate1.0mL/min,T＝25℃,λ＝210nm,tR1＝12.854min(major),tR2＝13.576min(minor)；91％ee；[α]D 26.0＝-37.33(c＝1.01,CH2Cl2).
实施例112：
操作过程如通用步骤5，得白色固体22.0mg,61％收率；Rf＝0.63(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ6.91(d,J＝8.8Hz,2H),6.73(d,J＝8.8Hz,2H),4.99(bs,1H),4.44–4.27(m,2H),3.74(s,3H),3.11(1/2ABq,J＝16.0Hz,1H),3.03(1/2ABq,J＝16.4Hz,1H),2.62(s,3H),2.57(s,3H),1.31(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ168.6,167.2,155.8,136.3,125.7,124.6(q,JC-F＝284.2Hz),113.9,66.8(q,JC-F＝26.5Hz),63.2,55.6,37.0,35.4,32.1,14.0；19F NMR(376MHz,CDCl3):δ-74.8；HRMS(ESI):[M+H]+Calcdfor C16H22F3N2O4 +:363.1526；found:363.1529；
HPLC(Chiralpak IBN):n-Hexane/EtOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝15.269min(major),tR2＝17.630min(minor)；97％ee；[α]D 26.0＝-13.76(c＝0.67,CH2Cl2).
实施例113：
操作过程如通用步骤5，得无色油状液体57.4mg,67％收率；Rf＝0.32(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.70(d,J＝7.2Hz,2H),7.37(t,J＝6.8Hz,2H),7.32–7.28(m,1H),6.56(d,J＝8.8Hz,2H),6.30(d,J＝9.2Hz,2H),5.29(bs,1H),4.27–4.05(m,2H),3.79(sept,J＝6.4Hz,1H),3.64(s,3H),3.55(1/2ABq,J＝16.0Hz,1H),3.41–3.23(m,2H),1.33(d,J＝6.8Hz,3H),1.26(d,J＝6.8Hz,3H),1.14(t,J＝7.2Hz,3H),1.10(d,J＝6.8Hz,3H),0.70(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.4,168.3,153.0,141.2,139.4,128.7,127.8,127.3,118.6,114.3,65.8,61.6,55.8,48.4,45.8,38.5,20.9,20.7,20.3,14.0.HRMS(ESI):[M+H]+Calcd for C25H35N2O4 +:427.2591；found:427.2587；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝15.537min(minor),tR2＝17.948min(major)；98％ee；[α]D 19.0＝-188.75(c＝1.1,CH2Cl2).
实施例114：
操作过程如通用步骤5，得白色固体64.3mg,65％收率；Rf＝0.39(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.55(d,J＝7.2Hz,2H),7.33–7.26(m,5H),7.26–7.14(m,3H),7.19–7.09(m,3H),6.72(bs,2H),6.63(d,J＝9.2Hz,2H),6.30(d,J＝8.8Hz,2H),5.35(bs,1H),4.24–4.11(m,2H),3.73(s,3H),3.68(1/2ABq,J＝15.6Hz,1H),3.31(1/2ABq,J＝15.6Hz,1H),1.17(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.0,169.9,152.8,142.3,140.6,139.0,129.6,129.0,128.7,127.8,127.0,126.5,117.6,114.8,65.9,62.1,55.8,39.4,14.0.HRMS(ESI):[M+H]+Calcd for C31H31N2O4 +:495.2278；found:495.2271；HPLC(Chiralpak AD-H):n-Hexane/EtOH＝85/15,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝16.845min(major),tR2＝19.683min(minor)；97％ee；[α]D 26.0＝-237.90(c＝1.38,CH2Cl2).
实施例115：
操作过程如通用步骤5，得无色油状液体69.9mg,72％收率；Rf＝0.68(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.47(d,J＝6.8Hz,2H),7.32–7.20(m,6H),6.81–6.41(m,4H),6.20(d,J＝8.4Hz,2H),5.19(bs,1H),5.02(sept,J＝6.4Hz,1H),3.85–3.78(m,2H),3.76(s,3H),3.43(1/2ABq,J＝16.4Hz,1H),3.08(1/2ABq,J＝16.0Hz,1H),2.65(ddd,J＝16.8,7.6,6.8Hz,1H),2.48(ddd,J＝16.4,7.2,6.4Hz,1H),1.25(d,J＝6.0Hz,3H),1.06(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ172.4,170.2,152.9,141.0,140.5,138.9,130.0,128.7,128.6,128.0,127.8,126.9,117.7,117.6,114.7,69.6,65.6,55.8,45.5,38.3,21.6,21.4,16.3；HRMS(ESI):[M+H]+Calcdfor C29H31N3O4 +:486.2387；found:486.2386；HPLC(Chiralpak IBN):n-Hexane/EtOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝39.008min(minor),tR2＝41.074min(major)；98％ee；[α]D 26.0＝-8.18(c＝0.51,CH2Cl2).
实施例116：
操作过程如通用步骤5，得淡黄色固体82.7mg,77％收率；Rf＝0.41(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.48(d,J＝7.2Hz,2H),7.30–7.21(m,4H),6.79–6.65(m,3H),6.58(d,J＝9.2Hz,2H),6.20(d,J＝8.8Hz,2H),5.23(bs,1H),4.46(1/2ABq,J＝16.8Hz,1H),4.21(dq,J＝10.4,7.2Hz,1H),4.17–4.09(m,3H),3.92(1/2ABq,J＝17.2Hz,1H),3.78(s,3H),3.72(s,3H),3.47(1/2ABq,J＝16.0Hz,1H),3.17(1/2ABq,J＝16.0Hz,1H),1.22(t,J＝7.2Hz,3H),1.16(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,170.6,168.9,159.2,152.7,140.5,138.9,134.7,129.3,128.7,127.7,127.0,117.8,114.6,114.6,65.5,62.0,61.2,55.8,55.5,51.2,37.8,14.2,13.9.HRMS(ESI):[M+H]+Calcd for C30H35N2O7 +:535.2439；found:535.2436；HPLC(Chiralpak IBN):n-Hexane/EtOH＝85/15,flow rate1.0mL/min,T＝40℃,λ＝210nm,tR1＝5.785min(minor),tR2＝6.467min(major)；95％ee；[α]D 26.0＝-7.25(c＝1.87,CH2Cl2).
实施例117：
操作过程如通用步骤5，得无色油状液体25.4mg,66％收率；Rf＝0.21(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.67(d,J＝7.2Hz,2H),7.37(t,J＝7.2Hz,2H),7.32–7.29(m,1H),6.58(d,J＝8.8Hz,2H),6.32(d,J＝8.8Hz,2H),5.27(bs,1H),4.23–4.09(m,2H),3.65(bs,5H),3.26(s,3H),3.07(s,3H),1.15(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,171.0,152.7,140.7,138.9,128.8,127.9,127.1,117.9,114.4,65.1,62.0,61.0,55.7,35.9,29.8,14.0.HRMS(ESI):[M+H]+Calcd for C21H27N2O5 +:387.1914；found:387.1917；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate1.0mL/min,T＝25℃,λ＝210nm,tR1＝7.393min(minor),tR2＝9.011min(major)；98％ee；[α]D 26.0＝-40.18(c＝0.73,CH2Cl2).
实施例118：
操作过程如通用步骤5，得无色油状液体67.7mg,85％收率；Rf＝0.42(PE/EtOAc＝1/1)；1H NMR(400MHz,CDCl3):δ7.66(d,J＝7.2Hz,2H),7.37(t,J＝6.8Hz,2H),7.32–7.28(m,1H),6.58(d,J＝8.8Hz,2H),6.32(d,J＝9.2Hz,2H),5.32(bs,1H),4.24–4.11(m,2H),3.66(s,3H),3.60(1/2ABq,J＝15.2Hz,1H),3.39–3.29(m,3H),3.24–3.19(m,1H),2.70–2.65(m,1H),1.77–1.65(m,4H),1.63(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.2,168.3,152.8,141.1,139.2,128.8,127.8,127.1,118.0,114.4,65.8,62.0,55.8,46.5,45.6,38.9,26.0,24.3,14.0.HRMS(ESI):[M+H]+Calcd for C23H29N2O4 +:397.2122；found:397.2120；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝25℃,λ＝210nm,tR1＝10.024min(minor),tR2＝13.829min(major)；98％ee；[α]D 26.0＝-28.99(c＝2.64,CH2Cl2).
实施例119：
操作过程如通用步骤5，得白色固体78.9mg,92％收率；Rf＝0.19(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.64(d,J＝7.2Hz,2H),7.36(t,J＝7.2Hz,2H),7.31–7.28(m,1H),6.59(d,J＝9.2Hz,2H),6.31(d,J＝8.8Hz,2H),5.29(bs,1H),5.01(sept,J＝6.4Hz,1H),3.66(s,3H),3.64–3.57(m,2H),3.55(1/2ABq,J＝15.2Hz,1H),3.48(1/2ABq,J＝15.2Hz,1H),3.44–3.34(m,3H),3.23(ddd,J＝13.2,7.6,3.2Hz,1H),3.06(ddd,J＝13.2,4.8,2.4Hz,1H),2.96(ddd,J＝14.0,7.6,2.8Hz,1H),1.21(d,J＝6.4Hz,3H),1.06(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ172.5,168.4,152.8,140.8,139.0,128.8,127.9,127.0,117.6,114.5,69.6,66.7,66.2,65.6,55.8,46.2,42.0,36.3,21.6,21.4；HRMS(ESI):[M+H]+Calcd for C24H31N2O5 +:427.2227；found:427.2224；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝95/5,flow rate1.0mL/min,T＝40℃,λ＝220nm,tR1＝16.720min(minor),tR2＝17.717min(major)；98％ee；[α]D 26.0＝-26.07(c＝2.00,CH2Cl2).
实施例120：
操作过程如通用步骤5，得白色固体32.9mg,67％收率；Rf＝0.24(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.49(d,J＝7.2Hz,2H),7.32(t,J＝6.8Hz,2H),7.29–7.26(m,1H),6.62(d,J＝8.8Hz,2H),6.37(d,J＝8.8Hz,2H),5.47(bs,1H),5.28(bs,1H),5.02(sept,J＝6.4Hz,1H),3.68(s,3H),3.40(1/2ABq,J＝14.4Hz,1H),3.12(1/2ABq,J＝14.8Hz,1H),2.01–1.99(m,3H),1.86–1.79(m,6H),1.62–1.61(m,6H),1.22(d,J＝6.4Hz,3H),1.00(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ172.4,168.3,152.9,140.4,138.2,128.7,127.8,126.8,118.2,114.6,69.9,65.2,55.8,51.9,41.5,41.4,36.4,29.5,21.7,21.4.HRMS(ESI):[M+H]+Calcd for C30H39N2O5 +:491.2904；found:491.2899；HPLC(Chiralcel OJ-H):n-Hexane/EtOH＝97/3,flow rate0.25mL/min,T＝40℃,λ＝220nm,tR1＝31.145min(major),tR2＝33.551min(minor)；98％ee；[α]D 26.0＝2.56(c＝1.25,CH2Cl2).
实施例121：
操作过程如通用步骤5，得白色固体48.1mg,65％收率；Rf＝0.41(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.58(d,J＝6.8Hz,2H),7.36(t,J＝7.2Hz,2H),7.32–7.28(m,1H),6.59(d,J＝8.8Hz,2H),6.30(d,J＝8.8Hz,2H),5.20(bs,1H),4.21(dq,J＝10.8,7.2Hz,1H),4.10(dq,J＝10.8,6.8Hz,1H),4.05(q,J＝7.2Hz,2H),3.70(1/2ABq,J＝16.4Hz,1H),3.67(s,3H),3.40(1/2ABq,J＝16.0Hz,1H),1.16(t,J＝7.2Hz,3H),1.14(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ172.8,170.7,152.7,139.9,138.2,128.9,128.0,126.9,117.5,114.5,64.9,62.3,60.8,55.7,38.6,14.2,14.0.HRMS(ESI):[M+H]+Calcdfor C21H26NO5 +:372.1805；found:372.1803；HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝13.003min(minor),tR2＝18.044min(major)；96％ee；[α]D 26.0＝-71.43(c＝0.84,CH2Cl2).
实施例122：
操作过程如通用步骤5，得白色固体62.3mg,72％收率；Rf＝0.43(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.63(d,J＝7.2Hz,2H),7.39(t,J＝6.4Hz,2H),7.35–7.31(m,3H),7.20(t,J＝7.2Hz,1H),6.92(d,J＝7.6Hz,2H),6.65(d,J＝9.2Hz,2H),6.40(d,J＝8.8Hz,2H),6.53(d,J＝8.8Hz,2H),5.27(bs,1H),5.01(sept,J＝6.4Hz,1H),3.97(1/2ABq,J＝16.0Hz,1H),3.70–3.66(m,4H),1.22(d,J＝6.0Hz,3H),1.07(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ171.9,169.3,152.9,150.4,139.9,138.1,129.5,128.9,128.1,126.9,126.1,121.6,117.7,114.6,70.2,65.2,55.7,38.8,21.6,21.4；HRMS(ESI):[M+H]+Calcdfor C26H28NO5 +:434.1962；found:434.1958；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.735min(major),tR2＝9.223min(minor)；95％ee；[α]D 26.0＝-38.93(c＝0.38,CH2Cl2).
实施例123：
操作过程如通用步骤5，得无色油状液体11.6mg,26％收率；Rf＝0.60(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.62(d,J＝8.0Hz,2H),7.36(t,J＝7.2Hz,2H),7.30(t,J＝6.8Hz,1H),6.58(d,J＝8.8Hz,2H),6.28(d,J＝8.4Hz,2H),5.16(bs,1H),4.98(sept,J＝6.8Hz,1H),3.67–3.55(m,5H),2.23(dt,J＝16.8,7.2Hz,1H),2.06(dt,J＝16.0,7.6Hz,1H)；1.40–1.33(m,2H),1.28–1.12(m,11H),1.07(d,J＝6.4Hz,3H),0.86(d,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ208.8,172.4,152.9,140.7,138.6,128.8,127.9,126.9,118.0,114.5,69.6,65.1,55.7,45.7,43.4,31.7,29.1,29.1,23.8,22.7,21.6,21.4,14.2；HRMS(ESI):[M+H]+Calcd for C27H38NO4 +:440.2795；found:440.2798；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝10.242min(major),tR2＝11.241min(minor)；98％ee；[α]D 26.0＝-105.25(c＝0.39,CH2Cl2).
实施例124：
操作过程如通用步骤5，得无色油状液体57.4mg,68％收率；Rf＝0.36(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.46(d,J＝7.2Hz,2H),7.33(t,J＝7.2Hz,2H),7.29–7.26(m,1H),6.61(d,J＝9.2Hz,2H),6.29(d,J＝8.8Hz,2H),5.44(bs,1H),5.02(sept,J＝6.4Hz,1H),4.34(1/2ABq,J＝14.4Hz,1H),4.19(1/2ABq,J＝14.4Hz,1H),3.66(s,3H),2.63(s,6H),1.27(d,J＝6.4Hz,3H),1.00(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ170.8,152.1,138.7,137.6,129.0,128.2,126.5,115.9,114.6,70.9,63.8,55.6,51.1,36.9,21.5,21.2；HRMS(ESI):[M+H]+Calcd for C21H29N2O5S+:421.1792；found:421.1788；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝12.590min(minor),tR2＝13.633min(major)；98％ee；[α]D 26.0＝26.59(c＝1.23,CH2Cl2).
实施例125：
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操作过程如通用步骤5，得淡黄色油状液体57.4mg,68％收率；Rf＝0.36(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.46(d,J＝7.2Hz,2H),7.33(t,J＝7.2Hz,2H),7.29–7.26(m,1H),6.61(d,J＝9.2Hz,2H),6.29(d,J＝8.8Hz,2H),5.44(bs,1H),5.02(sept,J＝6.4Hz,1H),4.34(1/2ABq,J＝14.4Hz,1H),4.19(1/2ABq,J＝14.4Hz,1H),3.66(s,3H),2.63(s,6H),1.27(d,J＝6.4Hz,3H),1.00(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ170.8,152.1,138.7,137.6,129.0,128.2,126.5,115.9,114.6,70.9,63.8,55.6,51.1,36.9,21.5,21.2；HRMS(ESI):[M+H]+Calcd for C21H29N2O5S+:421.1792；found:421.1788；HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝90/10,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝12.590min(minor),tR2＝13.633min(major)；98％ee；[α]D 26.0＝26.59(c＝1.23,CH2Cl2).
实施例126：
操作过程如通用步骤5，得无色油状液体28.7mg,52％收率；Rf＝0.48(PE/EtOA＝1/1)；1HNMR(400MHz,CDCl3):δ7.66(d,J＝7.2Hz,2H),7.39(t,J＝7.2Hz,2H),7.32(t,J＝7.2Hz,1H),7.24(bs,1H),6.59(d,J＝8.8Hz,2H),6.32(d,J＝8.8Hz,2H),5.26(bs,1H),4.48–4.42(m,2H),3.71(s,3H),3.69(s,3H),3.66–3.61(m,4H),3.39(1/2ABq,J＝15.6Hz,1H),3.35(td,J＝11.2,2.4Hz,1H),2.62(td,J＝9.6,7.2Hz,1H),2.27–2.22(m,1H),1.99–1.87(m,1H),1.64–1.48(m,5H),0.93(d,J＝6.0Hz,3H),0.90(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ173.8,173.2,170.9,170.2,153.1,140.6,138.8,129.0,128.1,127.0,118.2,114.5,65.6,59.7,55.8,53.1,52.3,51.2,47.4,41.2,38.7,27.1,25.0,24.9,23.0,22.0；HRMS(ESI):[M+H]+Calcd for C30H40N3O7 +:554.2861；found:554.2864；[α]D 19.0＝239.76(c＝0.28,CH2Cl2).
实施例127：
操作过程如通用步骤5，得无色油状液体97.5mg,62％收率；Rf＝0.32(PE/EtOA＝1/1)；1HNMR(400MHz,CDCl3):δ7.78–7.72(m,4H),7.59(dd,J＝8.8,1.6Hz,1H),7.47–7.42(m,2H),7.33–7.31(m,2H),7.16–7.10(m,3H),7.06(dd,J＝8.8,2.4Hz,1H),6.74–6.67(m,2H),6.60–6.55(m,3H),6.28(d,J＝8.0Hz,2H),5.14(sept,J＝6.4Hz,1H),3.74(s,3H),3.69(s,3H),3.63(s,3H),3.59–3.45(m,6H),3.38(ABq,J＝16.4Hz,2H),3.33–3.23(m,2H),3.17–3.11(m,2H),1.30(d,J＝6.0Hz,3H),1.29(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ173.6,171.0,170.2,167.9,159.2,137.7,133.3,132.9,132.5,132.4,131.4,128.6,128.5,128.5,127.7,127.6,127.5,126.4,126.2,126.1,124.8,118.1,114.4,114.1,113.9,71.1,69.8,66.8,66.5,65.9,55.8,55.4,53.0,46.5,42.0,40.7,39.6,21.9,21.7.HRMS(ESI):[M+H]+Calcd for C46H50N3O9 +:788.3542；found:788.3547；[α]D 26.0＝44.06(c＝0.53,CH2Cl2).
实施例128：
操作过程如通用步骤5，得无色油状液体53.6mg,68％收率；Rf＝0.48(PE/EtOA＝3/1)；1HNMR(400MHz,CDCl3):δ7.87(d,J＝7.2Hz,2H),7.54(t,J＝7.2Hz,1H),7.43(t,J＝7.6Hz,4H),7.38(d,J＝8.0Hz,2H),7.26–7.11(m,6H),6.81(dd,J＝8.8,2.8Hz,1H),6.66(dd,J＝8.8,2.8Hz,1H),6.57(d,J＝8.8Hz,3H),6.32(d,J＝7.6Hz,1H),6.19(d,J＝8.8Hz,2H),5.26(bs,1H),5.12(sept,J＝6.4Hz,1H),4.89(sept,J＝6.4Hz,1H),3.74(s,3H),3.71(s,3H),3.15(1/2ABq,J＝16.8Hz,1H),2.95(1/2ABq,J＝16.4Hz,1H),2.81(t,J＝6.8Hz,2H),2.30(td,J＝13.6,4.4Hz,1H),1.99(td,J＝13.6,4.4Hz,1H),1.71–1.60(m,1H),1.47–1.36(m,1H),1.31(d,J＝6.4Hz,3H),1.29(d,J＝6.4Hz,3H),1.09(d,J＝6.4Hz,3H),0.97(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ199.7,172.4,171.0,170.1,159.1,152.5,137.6,137.0,133.0,132.2,132.1,131.3,129.3,128.7,128.5,128.1,127.6,127.5,127.4,126.9,117.7,114.4,114.0,113.9,70.9,69.3,69.2,65.4,55.8,55.4,39.7,38.7,36.5,21.9,21.9,21.4,21.3,20.1.HRMS(ESI):[M+H]+Calcd for C48H53N2O8 +:785.3796；found:785.3792；[α]D 25.5＝178.82(c＝0.52,CH2Cl2).
实施例129：
操作过程如通用步骤5，使用(R)-L3，得无色油状液体58.4mg,74％收率；Rf＝0.56(PE/EtOA＝1/1)；1H NMR(400MHz,CDCl3):δ7.73(d,J＝7.2Hz,2H),7.55(d,J＝6.8Hz,2H),7.50(t,J＝7.2Hz,1H),7.41–7.31(m,8H),7.26–7.15(m,3H),6.89(dd,J＝8.8,3.2Hz,1H),6.51(dd,J＝8.8,3.2Hz,1H),6.39(d,J＝8.4Hz,2H),5.83–5.78(m,3H),5.08(sept,J＝6.4Hz,1H),4.97–4.88(m,2H),3.78(s,3H),3.69(s,3H),3.29(1/2ABq,J＝16.4Hz,1H),2.85(1/2ABq,J＝16.4Hz,1H),2.57(t,J＝7.2Hz,2H),1.86–1.71(m,2H),1.35(d,J＝5.6Hz,3H),1.34(d,J＝5.6Hz,3H),1.30–1.22(m,2H),1.19(d,J＝6.4Hz,3H),1.03(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ199.3,172.2,170.9,169.8,159.4,152.4,137.7,136.7,133.0,132.0,131.8,131.5,129.2,128.6,128.6,128.0,127.7,127.6,127.2,126.9,117.5,114.4,114.2,114.1,69.7,69.4,69.1,65.7,55.8,55.5,39.3,38.4,37.6,22.1,21.9,21.5,21.3,19.4.HRMS(ESI):[M+H]+Calcd for C48H53N2O8 +:785.3796；found:785.3802；[α]D 25.5＝-42.52(c＝0.51,CH2Cl2).
实施例130：
操作过程如通用步骤7，得黄色油状液体47.4mg，74％收率；Rf＝0.68(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.74(d,J＝8.8Hz,2H),6.58(d,J＝8.8Hz,2H),5.01(sept,J＝6.4Hz,1H),3.91(t,J＝6.8Hz,1H),3.83(bs,1H),3.72(s,3H),1.81–1.66(m,2H),1.44–1.37(m,2H),1.34–1.23(m,8H),1.21(d,J＝6.0Hz,3H),1.17(d,J＝6.4Hz,3H),0.86(t,J＝7.2Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.3,152.7,141.3,115.2,114.9,68.5,58.0,55.8,33.3,31.9,29.4,29.2,25.7,22.7,22.0,21.9,14.2；
HRMS(ESI):[M+H]+Calcd for C19H32NO3 +:322.2377；found:322.2372；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝9.941min(major),tR2＝16.202min(minor)；95％ee。
实施例131：
操作过程如通用步骤7，得黄色油状液体32.8mg，62％收率；Rf＝0.59(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.76(d,J＝8.8Hz,2H),6.60(d,J＝9.2Hz,2H),5.02(sept,J＝6.4Hz,1H),3.93(t,J＝6.8Hz,1H),3.73(s,3H),3.63(bs,1H),1.82–1.66(m,2H),1.46(ddt,J＝6.8,3.6,3.6Hz,2H),1.22(d,J＝6.0Hz,3H),1.18(d,J＝6.0Hz,3H),0.95(t,J＝7.6Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.2,152.8,141.3,115.2,114.9,68.4,57.9,55.8,35.4,22.0,21.8,19.0,14.0；
HRMS(ESI):[M+H]+Calcd for C15H24NO3 +:266.1751；found:266.1747；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝12.070min(major),tR2＝19.098min(minor)；96％ee。
实施例132：
操作过程如通用步骤7，得黄色油状液体46.6mg,73％收率；Rf＝0.57(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.76(d,J＝8.9Hz,2H),6.59(d,J＝8.9Hz,2H),5.80(ddt,J＝16.8,10.0,6.4Hz,1H),5.05–4.92(m,3H),3.92(t,J＝6.8Hz,1H),3.81(bs,1H),3.73(s,3H),2.04(q,J＝7.2Hz,2H),1.84–1.67(m,2H),1.48–1.32(m,6H),1.22(d,J＝6.4Hz,3H),1.18(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.1,152.8,141.3,139.0,115.2,114.9,114.5,68.5,58.0,55.8,33.7,33.2,28.9,28.8,25.5,22.0,21.9；
HRMS(ESI):[M+H]+Calcd for C19H30NO3 +:320.2220；found:320.2216；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝12.258min(major),tR2＝21.007min(minor)；95％ee。
实施例133：
操作过程如通用步骤6，得淡黄色油状液体43.4mg，71％收率；Rf＝0.72(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.76(d,J＝8.8Hz,2H),6.60(d,J＝8.8Hz,2H),5.49–5.39(m,1H),5.36–5.30(m,1H),5.03(sept,J＝6.4Hz,1H),3.94(t,J＝6.4Hz,1H),3.87(bs,1H),3.73(s,3H),2.26–2.11(m,2H),2.03(quint,J＝7.6Hz,1H),1.85(ddt,J＝13.6,8.4,6.0Hz,1H),1.75(ddt,J＝13.6,8.8,6.8Hz,1H),1.22(d,J＝6.0Hz,3H),1.19(d,J＝6.4Hz,3H),0.94(t,J＝7.6Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.1,152.7,141.2,133.2,127.5,115.3,114.9,68.6,57.6,55.8,33.2,23.4,21.9,21.8,20.6,14.4；
HRMS(ESI):[M+H]+Calcd for C18H28NO3 +:306.2064；found:306.2063；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝6.908min(major),tR2＝10.640min(minor)；91％ee.
实施例134：
操作过程如通用步骤7，得无色油状液体39.1mg,64％收率；Rf＝0.42(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.68(d,J＝8.8Hz,2H),6.52(d,J＝8.8Hz,2H),4.95(sept,J＝6.4Hz,1H),3.86(t,J＝6.4Hz,1H),3.75(bs,1H),3.66(s,3H),2.13(ddt,J＝6.8,3.2,3.2Hz,2H),1.78–1.62(m,2H),1.53–1.45(m,4H),1.15(d,J＝6.4Hz,3H),1.12(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.0,152.8,141.2,115.3,114.9,84.2,68.64,68.59,57.9,55.8,32.7,28.3,24.8,21.95,21.85,18.4；
HRMS(ESI):[M+H]+Calcd for C18H26NO3 +:304.1907；found:304.1903；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝25.461min(major),tR2＝40.857min(minor)；92％ee.
实施例135：
操作过程如通用步骤6，得淡黄色油状液体55.1mg,84％收率；Rf＝0.38(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.76(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),5.02(sept,J＝6.3Hz,1H),3.92(t,J＝6.4Hz,1H),3.85(bs,1H),3.73(s,3H),3.52(t,J＝6.4Hz,2H),1.85–1.70(m,4H),1.53–1.42(m,4H),1.22(d,J＝6.0Hz,3H),1.18(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.0,152.8,141.2,115.3,114.9,68.6,57.9,55.8,45.0,33.0,32.5,26.7,25.0,21.9,21.8；
HRMS(ESI):[M+H]+Calcd for C17H27ClNO3 +:328.1674；found:328.1676；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝11.238min(major),tR2＝17.719min(minor)；94％ee.
实施例136：
操作过程如通用步骤6，并添加TBAI(1.0equiv)代替NaI，得淡黄色油状液体47.7mg,78％收率；Rf＝0.25(PE/EtOAc＝5/2)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),5.02(sept,J＝6.4Hz,1H),3.92(t,J＝6.4Hz,1H),3.88(bs,1H),3.72(s,3H),2.33(t,J＝7.2Hz,2H),1.87–1.55(m,6H),1.21(d,J＝6.4Hz,3H),1.19(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ173.6,152.9,140.9,119.5,115.3,114.9,68.8,57.7,55.8,32.3,25.2,24.9,21.9,21.8,17.1；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝16.923min(major),tR2＝23.560min(minor)；91％ee.
实施例137：
操作过程如通用步骤7，得淡黄色粘稠油状液体56.5mg,76％收率；Rf＝0.39(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ7.08(d,J＝8.4Hz,2H),6.82(d,J＝8.4Hz,2H),6.76(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,1H),5.01(sept,J＝6.4Hz,1H),3.94(t,J＝5.6Hz,1H),3.79(s,3H),3.74(s,3H),2.66–2.55(m,2H),1.87–1.70(m,4H),1.21(d,J＝6.4Hz,3H),1.17(d,J＝6.0Hz,3H),N–H was invisible；
13C NMR(100MHz,CDCl3):δ174.0,157.9,152.8,141.2,134.0,129.4,115.3,114.9,113.9,68.5,57.9,55.8,55.3,34.7,32.6,27.6,21.9,21.8；
HRMS(ESI):[M+H]+Calcd for C22H30NO4 +:372.2169；found:372.2170；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝16.070min(major),tR2＝25.110min(minor)；90％ee.
实施例138：
操作过程如通用步骤6，得淡黄色油状液体50.8mg,62％；Rf＝0.38(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),5.01(sept,J＝6.0Hz,1H),4.03(t,J＝6.8Hz,2H),3.91(t,J＝6.4Hz,1H),3.72(s,3H),1.83–1.66(m,2H),1.60(quin,J＝6.8Hz,2H),1.47–1.33(m,6H),1.21(d,J＝6.4Hz,3H),1.19(s+d,J＝6.8Hz,9H+3H)；
13C NMR(100MHz,CDCl3):δ178.7,174.1,152.8,141.2,115.2,114.9,68.5,64.4,58.0,55.8,38.8,33.1,29.1,28.6,27.3,25.8,25.6,21.9,21.8；
HRMS(ESI):[M+H]+Calcd for C23H39NO5 +:408.2744；found:408.2747；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝10.237min(major),tR2＝15.275min(minor)；91％ee.
实施例139：
操作过程如通用步骤6，得淡黄色油状液体59.7mg,73％收率；Rf＝0.54(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝9.2Hz,2H),6.59(d,J＝8.8Hz,2H),5.02(sept,J＝6.4Hz,1H),3.92(t,J＝6.4Hz,1H),3.73(s,3H),3.61(t,J＝6.4Hz,2H),1.86–1.69(m,2H),1.59–1.43(m,4H),1.21(d,J＝6.4Hz,3H),1.18(d,J＝6.4Hz,3H),0.89(s,9H),0.04(s,6H)；
13C NMR(100MHz,CDCl3):δ174.1,152.8,141.2,115.3,114.9,68.5,63.0,58.1,55.8,33.1,32.6,26.1,22.2,21.9,21.8,18.4,-5.2；
HRMS(ESI):[M+H]+Calcd for C22H40NO4Si+:410.2721；found:410.2726；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝4.608min(major),tR2＝5.775min(minor)；90％ee.
实施例140：
操作过程如通用步骤7，得黄色油状液体59.4mg,71％收率；Rf＝0.63(PE/EtOAc＝3/1)；
1H NMR(400MHz,CDCl3):δ6.74(d,J＝8.8Hz,2H),6.57(d,J＝8.8Hz,2H),5.00(sept,J＝6.4Hz,1H),3.90(t,J＝6.8Hz,1H),3.81(bs,1H),3.71(s,3H),1.81–1.65(m,2H),1.45–1.29(m,6H),1.22(s,12H),1.20(d,J＝6.0Hz,3H),1.17(d,J＝6.0Hz,3H),0.76(t,J＝7.6Hz,2H)；
13C NMR(100MHz,CDCl3):δ174.2,152.7,141.3,115.2,114.9,83.0,68.4,58.0,55.8,33.2,32.2,25.5,24.9,23.9,21.9,21.8(one alkyl carbon was overlapped)；
HRMS(ESI):[M+H]+Calcd for C23H39BNO5 +:420.2916；found:420.2909；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.231min(major),tR2＝7.298min(minor)；90％ee.
实施例141：
操作过程如通用步骤6，得淡黄色油状液体34.4mg,53％收率；Rf＝0.55(PE/EtOAc＝3/1)；
1H NMR(400MHz,CDCl3):δ6.76(d,J＝8.8Hz,2H),6.58(d,J＝8.8Hz,2H),3.96(t,J＝6.4Hz,1H),3.82(bs,1H),3.73(s,3H),3.69(s,3H),3.66(s,3H),2.30(t,J＝7.6Hz,2H),1.85–1.69(m,2H),1.62(quint,J＝7.6Hz,2H),1.48–1.31(m,4H)；
13C NMR(100MHz,CDCl3):δ175.1,174.2,152.9,141.1,115.2,115.0,57.8,55.8,52.1,51.6,34.0,33.2,28.9,25.5,24.8；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝13.240min(major),tR2＝20.103min(minor)；90％ee.
实施例142：
操作过程如通用步骤6，并添加TBAI(1.0equiv)代替NaI，得黄色固体50.8mg,79％收率；Rf＝0.33(PE/EtOAc＝3/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),5.01(sept,J＝6.4Hz,1H),4.90(t,J＝4.0Hz,1H),3.99–3.91(m,3H),3.89–3.81(m,2H),3.72(s,3H),1.98–1.78(m,4H),1.21(d,J＝6.0Hz,3H),1.18(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ173.8,152.8,141.2,115.3,114.9,104.0,68.6,65.1,65.0,57.9,55.8,30.0,27.3,21.9,21.8；
HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝12.717min(major),tR2＝18.924min(minor)；89％ee.
实施例143：
操作过程如通用步骤6，并添加TBAI(1.0equiv)代替NaI，得黄色固体62.0mg,76％收率；Rf＝0.52(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ7.53(d,J＝7.6Hz,1H),7.24–7.19(m,2H),7.07(ddd,J＝8.0,5.2,4.0Hz,1H),6.78(d,J＝8.8Hz,2H),6.62(d,J＝9.2Hz,2H),5.05(sept,J＝6.4Hz,1H),4.00(dd,J＝7.2,6.0Hz,1H),3.74(s,3H),2.97–2.83(m,2H),2.17–1.98(m,2H),1.24(d,J＝6.4Hz,3H),1.22(d,J＝6.0Hz,3H)；
13C NMR(100MHz,CDCl3):δ173.7,152.7,141.0,140.5,132.9,130.6,128.0,127.6,124.4,115.3,114.8,68.7,57.6,55.7,33.0,32.4,21.9,21.8；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝9.079min(major),tR2＝16.023min(minor)；91％ee.
实施例144：
操作过程如通用步骤6，并添加TBAI(1.0equiv)代替NaI，得棕色粘稠液体40.1mg,57％收率；Rf＝0.51(PE/EtOAc＝3/1)；
1H NMR(400MHz,CDCl3):δ6.74(d,J＝8.8Hz,2H),6.58(d,J＝8.8Hz,2H),5.00(sept,J＝6.4Hz,1H),3.90(t,J＝6.4Hz,1H),3.72(s,3H),2.42–2.36(m,4H),1.82–1.65(m,2H),1.57(quint,J＝7.6Hz,2H),1.47–1.39(m,2H),1.35–1.27(m,2H),1.20(d,J＝6.0Hz,3H),1.17(d,J＝6.4Hz,3H),1.03(t,J＝7.6Hz,3H)；
13C NMR(100MHz,CDCl3):δ211.8,174.1,152.8,141.2,115.2,114.9,68.5,58.0,55.8,42.2,36.0,33.0,29.0,25.5,23.7,21.9,21.8,7.9；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝85/15,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝8.483min(major),tR2＝13.259min(minor)；91％ee.
实施例145：
操作过程如通用步骤6，并添加TBAI(1.0equiv)代替NaI，得黄色粘稠液体24.9mg,56％收率；Rf＝0.57(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ7.43(t,J＝8.0Hz,1H),6.75(d,J＝8.8Hz,2H),6.69(d,J＝7.2Hz,1H),6.59(d,J＝8.8Hz,2H),6.50(d,J＝8.0Hz,1H),5.02(sept,J＝6.4Hz,1H),4.23(t,J＝6.8Hz,2H),3.92(t,J＝6.8Hz,1H),3.84(bs,1H),3.73(s,3H),2.43(s,3H),1.83–1.67(m,4H),1.47–1.30(m,10H),1.21(d,J＝6.0Hz,3H),1.18(d,J＝6.0Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.2,163.7,156.4,152.8,141.3,138.8,115.6,115.3,114.9,107.1,68.5,66.0,58.1,55.8,33.3,29.5,29.4,29.2,26.2,25.7,24.3,22.0,21.9(one alkyl carbon was overlapped)；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝6.904min(major),tR2＝9.616min(minor)；90％ee.
实施例146：
操作过程如通用步骤6，得淡黄色液体71.5mg,79％收率；Rf＝0.41(PE/acetone＝3/1)；
1H NMR(400MHz,CDCl3):δ7.38–7.28(m,5H),6.76(d,J＝8.8Hz,2H),6.60(d,J＝8.8Hz,2H),5.13(s,2H),5.01(sept,J＝6.4Hz,1H),4.18(bs,2H),3.99(t,J＝6.8Hz,1H),3.73(s,3H),2.76(bs,2H),1.80–1.63(m,5H),1.21–1.16(m,2H,overlapped withtwodoublet peaks),1.20(d,J＝6.0Hz,3H),1.17(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.3,155.3,152.9,141.0,137.0,128.5,128.0,127.9,115.4,114.9,68.6,67.1,55.75,55.70,44.14,44.09,39.9,32.7,32.3,31.8,21.9,21.8；
HRMS(ESI):[M+H]+Calcd for C26H35N2O5 +:455.2540；found:455.2544；
HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝19.412min(major),tR2＝20.759min(minor)；90％ee.
实施例147：
操作过程如通用步骤7，得黄色固体51.1mg,83％收率；Rf＝0.61(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),4.96(sept,J＝6.4Hz,1H),3.94(dd,J＝9.6,6.0Hz,1H),3.73(s,3H),3.48(bs,1H),1.19(d,J＝6.4Hz,3H),1.15(d,J＝6.4Hz,3H),1.11(1/2abqd,J＝22.8,6.0Hz,1H),1.01(1/2abqd,J＝22.8,9.6Hz,1H),0.08(s,9H)；
13C NMR(100MHz,CDCl3):δ175.3,152.9,141.2,115.4,114.9,68.3,55.8,55.4,21.9,21.7,21.6,-0.9；
HRMS(ESI):[M+H]+Calcd for C16H28NO3Si+:310.1833；found:310.1828；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.133min(major),tR2＝14.771min(minor)；98％ee.
实施例148：
操作过程如通用步骤6，得淡黄色粘稠液体55.6mg,75％收率；Rf＝0.59(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),4.97(sept,J＝6.4Hz,1H),4.00(dd,J＝7.2,4.8Hz,1H),3.73(s,3H),3.63(bs,1H),1.96(bs,3H),1.71–1.56(m,13H),1.43(dd,J＝14.4,7.2Hz,1H),1.19(d,J＝6.4Hz,3H),1.15(d,J＝6.0Hz,3H)；
13C NMR(100MHz,CDCl3):δ175.0,152.7,141.1,115.3,114.9,68.2,55.8,54.2,48.0,42.7,37.0,32.7,28.7,21.9,21.7；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝6.369min(major),tR2＝12.466min(minor)；99％ee.
实施例149：
操作过程如通用步骤6，得淡黄色粘稠液体41.3mg,71％收率；Rf＝0.55(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝9.2Hz,2H),6.61(d,J＝8.8Hz,2H),5.01(sept,J＝6.4Hz,1H),3.74(s,1H),3.73(s,3H),2.20(sext,J＝8.0Hz,1H),1.87–1.79(m,1H),1.74–1.54(m,5H),1.51–1.40(m,2H),1.20(d,J＝6.4Hz,3H),1.17(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.1,152.7,141.7,115.3,114.9,68.3,62.4,55.8,43.3,29.6,29.2,25.5,25.3,22.0,21.9；
HRMS(ESI):[M+H]+Calcd for C17H26NO3 +:292.1907；found:292.1907；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝11.212min(major),tR2＝19.608min(minor)；96％ee.
实施例150：
操作过程如通用步骤6，得黄色粘稠液体34.7mg,54％收率；Rf＝0.69(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,2H),6.60(d,J＝9.2Hz,2H),5.02(sept,J＝6.4Hz,1H),3.89(bs,1H),3.76(d,J＝5.6Hz,1H),3.73(s,3H),1.96–1.88(m,1H),1.86–1.80(m,1H),1.77–1.67(m,3H),1.62–1.37(m,8H),1.21(d,J＝6.4Hz,3H),1.19(d,J＝6.0Hz,3H)；
13C NMR(100MHz,CDCl3):δ173.7,152.6,141.7,115.3,114.9,68.4,63.8,55.8,42.7,31.2,30.1,28.6,28.0,26.9,26.7,22.0,21.9；
HRMS(ESI):[M+H]+Calcd for C19H30NO3 +:320.2220；found:320.2221；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝11.437min(major),tR2＝21.929min(minor)；97％ee.
实施例151：
操作过程如通用步骤6，得黄色粘稠液体48.7mg,73％收率；Rf＝0.74(PE/EtOAc＝5/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝9.2Hz,2H),6.60(d,J＝9.2Hz,2H),5.02(sept,J＝6.4Hz,1H),3.87(bs,1H),3.73(s+d,4H,doublet peak was overlapped),2.03–1.95(m,1H),1.83–1.41(m,14H),1.21(d,J＝6.4Hz,3H),1.19(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ173.8,152.6,141.7,115.3,114.9,68.3,64.3,55.8,40.7,30.3,28.5,27.0,26.7,26.6,26.4,25.2,22.0,21.9；
HRMS(ESI):[M+H]+Calcd for C20H32NO3 +:334.2377；found:334.2377；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝7.101min(major),tR2＝13.499min(minor)；95％ee.
实施例152：
操作过程如通用步骤6，得淡黄色粘稠液体42.6mg,52％收率；Rf＝0.43(PE/EtOAc＝3/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,2H),6.59(d,J＝9.2Hz,2H),5.01(sept,J＝6.4Hz,1H),4.14(bs,2H),3.87(bs,1H),3.75(d,J＝6.8Hz,1H),3.72(s,3H),2.68(t,J＝12.4Hz,2H),1.88–1.77(m,3H),1.61(d,J＝12.0Hz,1H),1.44(s,9H),1.20(d,J＝6.0Hz,3H),1.19(d,J＝6.4Hz,3H)；
13C NMR(100MHz,CDCl3):δ173.1,154.8,152.9,141.4,115.5,114.9,79.6,68.8,62.8,55.8,43.7,39.9,29.8,28.5,21.99,21.96；
HRMS(ESI):[M+H]+Calcd for C22H35N2O5 +:407.2545；found:407.2545；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝6.980min(major),tR2＝12.524min(minor)；90％ee.
实施例153：
操作过程如通用步骤6，得黄色固体46.4mg,50％收率；Rf＝0.33(PE/acetone＝6/1)；
1H NMR(400MHz,CDCl3):δ7.62(d,J＝8.4Hz,2H),7.31(d,J＝8.0Hz,2H),6.73(d,J＝9.2Hz,2H),6.55(d,J＝8.8Hz,2H),4.98(sept,J＝6.4Hz,1H),3.89–3.78(m,3H),3.71(s+d,4H,doublet peak was overlapped),2.42(s,3H),2.20(td,J＝11.6,2.8Hz,2H),1.89(d,J＝13.2Hz,1H),1.69–1.49(m,4H),1.17(d,J＝6.4Hz,3H),1.17(d,J＝6.0Hz,3H)；
13C NMR(100MHz,CDCl3):δ172.7,152.9,143.6,141.0,133.0,129.7,127.8,115.5,114.9,69.0,62.2,55.8,46.4,46.2,38.8,28.03,27.99,21.9,21.6(one alkylcarbon was overlapped)；
HRMS(ESI):[M+H]+Calcd for C24H33N2O5S+:461.2105；found:461.2106；
HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝80/20,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝21.938min(major),tR2＝26.216min(minor)；90％ee.
实施例154：
操作过程如通用步骤6，得黄色液体27.2mg,44％收率；Rf＝0.31(PE/EA＝3/1)；
1H NMR(400MHz,CDCl3):δ6.69(d,J＝9.2Hz,2H),6.54(d,J＝8.8Hz,2H),4.95(sept,J＝6.4Hz,1H),3.96–3.90(m,2H),3.79(bs,1H),3.79–3.66(s+m,3H+1H),3.34–3.28(m,2H),1.93–1.83(m,1H),1.73–1.68(m,1H),1.57–1.40(m,3H),1.13(dd,J＝6.4,4.8Hz,6H)；
13C NMR(100MHz,CDCl3):δ173.1,152.9,141.4,115.5,114.9,68.8,68.0,67.7,63.0,55.8,38.8,29.55,29.54,22.01,21.99；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝11.959min(major),tR2＝17.071min(minor)；93％ee.
实施例155：
操作过程如通用步骤6，得淡黄色液体32.2mg,58％收率；Rf＝0.31(PE/EA＝3/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝9.2Hz,2H),6.63(d,J＝9.2Hz,2H),5.01(sept,J＝6.3Hz,1H),3.90(bs,1H),3.73(s,3H),3.63(s,1H),1.18(t,J＝5.6Hz,6H),1.07(s,9H)；
13C NMR(100MHz,CDCl3):δ173.2,152.8,142.0,115.7,114.9,68.3,67.2,55.8,34.4,27.0,22.1,22.0；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝6.162min(major),tR2＝7.892min(minor)；92％ee.
实施例156：
操作过程如通用步骤6，得黄色液体51.2mg,65％收率；Rf＝0.47(PE/EA＝4/1)；
1H NMR(400MHz,CDCl3):δ6.75(d,J＝8.8Hz,1H),6.66(d,J＝8.8Hz,1H),4.99(sept,J＝6.4Hz,1H,twolines were overlapped),5.01(s,1H),4.64(d,J＝6.0Hz,1H),4.58(d,J＝6.0Hz,1H),4.50(dd,J＝11.6,3.2Hz,1H),4.13(dd,J＝10.0,2.8Hz,1H),3.90(bs,1H),3.72(s,3H),3.43(s,3H),2.09(ddd,J＝14.0,11.6,2.8Hz,1H),1.72(ddd,J＝13.6,10.0,3.6Hz,1H),1.46(s,3H),1.31(s,3H),1.19(t,J＝6.8Hz,6H)；
13C NMR(100MHz,CDCl3):δ174.2,153.0,141.7,115.9,114.8,112.5,109.8,85.6,84.4,83.8,68.8,56.1,55.8,55.3,39.3,26.6,25.1,21.9,21.8；
HRMS(ESI):[M+H]+Calcd for C21H32NO7 +:410.2173；found:410.2177；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝12.012min(major),tR2＝14.274min(minor)；98:2dr.
实施例157：
操作过程如通用步骤6，得灰色粘稠液体21.6mg,55％收率；Rf＝0.45(PE/EA＝2/1)；
1H NMR(400MHz,CDCl3):δ6.78(d,J＝9.2Hz,2H),6.67(d,J＝9.2Hz,1.91H,major),6.61(d,J＝8.2Hz,0.09H,minor),5.01(sept,J＝6.4Hz,1H),4.89(dd,J＝8.0,5.2Hz,1H),4.76(d,J＝5.6Hz,1H),4.64(d,J＝6.0Hz,0.04H,minor),4.60(d,J＝6.0Hz,0.96H,major),4.09(t,J＝6.0Hz,1H),3.87(bs,1H),3.74(s,3H),2.05–2.01(m,2H),1.47(s,3H),1.37(s,3H),1.20(d,J＝6.0Hz,6H)；
13C NMR(100MHz,CDCl3):δ173.7,173.0,153.7,140.7,116.4,115.0,114.2,80.1,79.5,75.1,69.6,55.8,55.5,37.1,26.9,25.8,21.9,21.8；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝35.503min(major),tR2＝50.553min(minor)；96:4dr.
实施例158：
操作过程如通用步骤6，得淡黄色液体63.0mg,68％收率；Rf＝0.24(PE/EA＝4/1)；
1H NMR(400MHz,CDCl3):δ6.73(d,J＝8.8Hz,2H),6.58(d,J＝8.8Hz,2H),5.01(sept,J＝6.4Hz,1H),4.58(dd,J＝8.0,2.8Hz,1H),4.29(dd,J＝8.0,4.8Hz,1H),4.23(d,J＝2.4Hz,1H),4.19(dd,J＝8.0,1.6Hz,1H),3.81(dd,J＝13.2,2.0Hz,1H),3.71(s,3H),3.66(d,J＝12.8Hz,1H),2.47(dd,J＝14.0,4.8Hz,1H),2.06(dd,J＝14.0,8.0Hz,1H),1.51(s,3H),1.48(s,3H),1.34(s,3H),1.33(s,3H),1.21(d,J＝6.0Hz,3H),1.17(d,J＝6.0Hz,3H)；
13C NMR(100MHz,CDCl3):δ173.7,152.7,141.0,115.3,114.7,109.3,108.5,102.7,73.6,70.9,70.5,68.4,61.3,55.7,54.3,42.5,26.5,25.9,25.2,24.3,21.8,21.7；
HRMS(ESI):[M+H]+Calcd for C24H36NO8 +:466.2435；found:466.2440；
HPLC(Chiralpak IBN-5):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝6.993min(major),tR2＝9.562min(minor)；95:5dr.
实施例159：
操作过程如通用步骤6，得淡黄色液体55.2mg,76％收率；Rf＝0.51(PE/Et2O＝10/3)；
1H NMR(400MHz,CDCl3):δ6.76(d,J＝8.8Hz,2H),6.60(d,J＝9.2Hz,2H),5.11–4.98(m,2H),3.90(t,J＝6.4Hz,1H),3.86(bs,1H),3.73(s,3H),1.95(non,J＝7.6Hz,2H),1.76(dd,J＝15.2,6.8Hz,2H),1.68(d,J＝0.8Hz,3H),1.59(s,3H),1.48–1.39(m,2H),1.37–1.11(m,10H),0.89(d,J＝6.0Hz,3H)；
13C NMR(100MHz,CDCl3):δ174.2,152.7,141.3,131.3,124.8,115.2,114.9,68.4,58.3,55.8,37.0,32.7,32.3,30.8,25.8,25.5,21.94,21.86,19.5,17.7；
HRMS(ESI):[M+H]+Calcd for C22H36NO3 +:362.2690；found:362.2690；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝5.489min(major),tR2＝9.738min(minor)；96:4dr.
实施例160：
操作过程如通用步骤6，得淡黄色液体63.6mg,72％收率；Rf＝0.55(PE/EA＝5/1)；
1H NMR(400MHz,CDCl3):δ7.03(d,J＝7.6Hz,1H),6.77(d,J＝8.8Hz,2H),6.68(d,J＝6.8Hz,1H),6.64–6.62(m,3H),4.99(sept,J＝6.4Hz,1H),4.00(dd,J＝7.2,5.2Hz,1H),3.94(t,J＝6.4Hz,2H),3.75(s,3H),3.68(bs,1H),2.33(s,3H),2.20(s,3H),1.85–1.77(m,3H),1.63(dd,J＝14.0,7.2Hz,1H),1.54–1.47(m,2H),1.20(d,J＝6.0Hz,3H),1.17(d,J＝6.4Hz,3H),1.05(s,3H),1.04(s,3H)；
13C NMR(100MHz,CDCl3):δ174.9,157.1,152.9,141.0,136.5,130.4,123.7,120.7,115.5,114.9,112.1,68.5,68.4,55.8,55.6,45.1,38.7,33.0,27.6,24.4,21.9,21.7,21.5,15.9；
HRMS(ESI):[M+H]+Calcd for C27H40NO4 +:442.2952；found:442.2953；
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝7.423min(major),tR2＝15.200min(minor)；98％ee.
(二)钴催化亚胺的不对称还原烯丙基化反应
通用步骤8：
向预先烘干的8mL小反应管中加入手性配体(6mol％)，Mn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、碘化锂(20mol％)、乙腈(0.2M)、烯丙基亲电试剂2(1.5equiv)和对应的醇(1.0equiv)。将反应管从手套箱内移出，封口膜密封，置于35℃油浴中剧烈搅拌48h。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗反应液使用快速柱层析纯化得到产物3。
通用步骤9：
向预先烘干的8mL小反应管中加入手性配体(6mol％)，Mn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、氯化锌(20mol％)、乙腈(0.2M)、双烯丙基亲电试剂4(1.5equiv)。将反应管从手套箱内移出，封口膜密封，置于50℃油浴中剧烈搅拌48h。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗反应液使用快速柱层析纯化得到产物5。
实施例161：
操作过程如通用步骤8，得黄色油状液体68.4mg,87％收率；Rf＝0.38(PE/EA＝10/1)
1H NMR(400MHz,CDCl3):δ7.55(d,J＝7.2Hz,2H),7.28(t,J＝6.8Hz,2H),7.22–7.15(m,5H),7.13–7.09(m,1H),6.55(d,J＝9.2Hz,2H),6.28(d,J＝9.2Hz,2H),6.23(d,J＝16.0Hz,1H),5.95(td,J＝14.4,6.8Hz,1H),4.94(s,1H),4.16-4.07(m，1H)，4.01-3.93(m，1H)，3.59(s，3H)，3.27(d，J＝7.2Hz，2H)，1.06(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ173.3,152.3,140.9,138.5,137.2,134.4,128.7,128.6,127.7,127.5,127.2,126.3,123.9,117.0,114.5,66.9,62.1,55.7,37.5,14.2.
HRMS(ESI):[M+H]+Calcd for C30H30NO3 +:452.2220；found:452.2209.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝254nm,t＝8.509min,t＝12.924min；95％ee.
实施例162：
操作过程如通用步骤8，得白色固体85.1mg,94％收率；Rf＝0.39(PE/EA＝10/1)；
1H NMR(400MHz,CDCl3):δ7.67–7.62(m,3H),7.56(d,J＝7.2Hz,2H),7.48(s,1H),7.39–7.26(m,4H),7.22–7.19(m,1H),7.11(s,1H),6.55(d,J＝8.8Hz,2H),6.38(d,J＝15.6Hz,1H),6.30(d,J＝8.8Hz,1H),6.08(td,J＝15.6,7.2Hz,1H),4.98(s,1H),4.16–4.08(m,1H),4.02–3.94(m,1H),3.59(s,3H),3.32(d,J＝7.2Hz,2H),1.06(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3):δ173.4,152.3,140.9,138.6,134.7,134.5,133.7,133.0,128.7,128.2,128.0,127.7,127.7,127.2,126.3,126.0,125.8,124.3,123.6,117.1,114.6,67.0,62.1,55.7,37.6,14.2.
HRMS(ESI):[M+H]+Calcd for C30H30NO3 +:452.2220；found:452.2209.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝12.888min(maJor)),t＝22.199min(minor)；95％ee.
实施例163：
操作过程如通用步骤8，得无色油状液体78.4mg,82％收率；Rf＝0.48(PE/EA＝10/1)；
1H NMR(400MHz,CDCl3):δ7.65(d,J＝7.6Hz,2H),7.42–7.38(m,4H),7.34–7.30(m,1H),7.12(d,J＝8.4Hz,2H),6.66(d,J＝9.2Hz,2H),6.39(d,J＝8.8Hz,2H),6.27(d,J＝16.0Hz,1H),6.06(td,J＝15.6,7.2Hz,1H),5.05(s,1H),4.27–4.19(m,1H),4.13–4.05(m,1H),3.71(s,3H),3.38(d,J＝7.2Hz,2H),1.17(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ173.3,152.4,140.8,138.4,136.1,133.1,131.7,128.7,127.8,127.7,127.1,124.9,121.2,117.0,114.5,66.8,62.1,55.7,37.4,14.2.
HRMS(ESI):[M+H]+Calcd for C26H27BrNO3 +:480.1169；found:480.1159.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝10.185min(major),t＝15.894min(minor)；93％ee.
实施例164：
操作过程如通用步骤8，得白色固体78.9mg,95％收率；Rf＝0.53(PE/EA＝10/1)；
1H NMR(400MHz,CDCl3):δ7.66(d,J＝7.6Hz,2H),7.34(t,J＝7.2Hz,2H),7.33–7.30(m,2H),7.15–7.09(m,3H),6.64(d,J＝8.8Hz,2H),6.53(d,J＝15.6Hz,1H),6.38(d,J＝8.8Hz,2H),5.91(dt,J＝15.6,6.8Hz,1H),5.04(s,1H),4.25–4.17(m,1H),4.14–4.06(m,1H),3.69(s,3H),3.44–3.35(m,2H),2.21(s,3H),1.17(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3):δ173.4,152.3,141.0,138.6,136.5,135.2,132.3,130.2,128.7,127.7,127.4,127.2,126.2,126.0,125.4,117.0 114.6,67.0,62.1,55.8,37.7,19.8,14.2.
HRMS(ESI):[M+H]+Calcd for C27H30NO3 +:416.2220；found:416.2219.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝6.652min(major)),t＝12.503min(minor)；96％ee.
实施例165：
操作过程如通用步骤8，得淡黄色油状液体74.7mg,90％收率，E/Z＝2.5:1；Rf＝0.54(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.69(d,J＝7.2Hz,2H),7.56(d,J＝7.2Hz,0.8H),7.40(t,J＝7.2Hz,2H),7.30(t,J＝6.4Hz,4H),7.28–7.26(m,0.8H),7.21(t,J＝7.6Hz,1.6H),7.15(d,J＝7.2Hz,2H),7.09(d,J＝7.2Hz,0.8H),6.65(d,J＝8.8Hz,2H),6.49(d,J＝8.8Hz,0.8H),6.43(s,0.4H),6.36(d,J＝9.2Hz,2H),6.19(s,1H),6.16(d,J＝9.2Hz,0.8H),5.21(s,1H),4.91(s,0.4H),4.22–4.11(m,2H),4.08–3.98(m,0.8H),3.73–3.67(m,4.6H),3.48–3.39(m,2.4H),1.82(d,J＝1.6Hz,1.2H),1.77(d,J＝1.2Hz,3H),1.16(t,J＝6.8Hz,3H),1.04(t,J＝7.2Hz,1.2H).
13C NMR(100MHz,CDCl3):δ174.1,173.7,151.7,151.7,141.2,141.0,138.8,138.7,138.1,137.9,134.2,133.9,130.8,130.5,129.0,128.9,128.7,128.6,128.4,128.1,128.1,127.5,127.4,127.2,126.3,126.2,116.1,115.9,114.5,114.2,66.6,66.2,62.0,61.9,55.7,55.6,44.4,38.2,24.4,19.1,14.0,13.8.
HRMS(ESI):[M+H]+Calcd for C27H30NO3 +:416.2220；found:416.2219.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,λ＝254nm,t＝7.211min,t＝10.931min,t＝13.021min,t＝21.236min；96％ee.
实施例166：
操作过程如通用步骤8，得黄色油状液54.8mg,66％收率；Rf＝0.52(PE/EA＝10/1)；
1H NMR(400MHz,CDCl3):δ7.71–7.69(m,2H),7.40(t,J＝7.2Hz,2H),7.34–7.28(m,5H),7.26–7.22(m,1H),6.65–6.61(m,2H),6.41–6.37(m,2H),5.64(dt,J＝1.2,7.2Hz,1H),5.02(s,1H),4.23–4.15(m,1H),4.14–4.07(m,1H),3.43(1/2abqd,J＝14.4,7.2Hz,1H),3.32(1/2abqd,J＝14.4,7.2Hz,1H),1.82(s,3H),1.15(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ173.7,152.4,144.0,141.3,138.9,138.6,128.7,128.3,127.7,127.2,127.0,125.9,121.7,117.3,114.5,66.9,62.1,55.7,33.2,16.2,14.1.
HRMS(ESI):[M+H]+Calcd for C27H30NO3 +:416.2220；found:416.2219.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝9.981min(major),t＝21.951min(minor)；92％ee.
实施例167：
操作过程如通用步骤8，得无色油状液体66.4mg,81％收率；Rf＝0.41(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.59(d,J＝7.6Hz,2H),7.33(t,J＝7.2Hz,2H),7.28–7.24(m,1H),6.60(d,J＝8.8Hz,2H),6.31(d,J＝8.8Hz,2H),5.40(dt,J＝15.2,6.8Hz,1H),5.24(dt,J＝15.2,7.2Hz,1H),4.98(s,1H),4.20–4.12(m,1H),4.07–3.99(m,1H),3.66(s,3H),3.11(d,J＝7.2Hz,2H),1.91(dt,J＝7.2,7.2Hz,2H),1.30–1.25(m,2H),1.13(t,J＝6.8Hz,3H),0.84(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ173.5,152.1,141.1,138.7,135.6,128.6,128.6,127.5,127.3,123.6,116.8,114.4,66.8,61.9,55.7,37.2,34.9,22.6,14.1,13.7.
HRMS(ESI):[M+H]+Calcd for C23H28NO5 +:398.1962；found:398.1961.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝254nm,t＝9.704min,t＝16.317min；90％ee..
实施例168：
操作过程如通用步骤8，得淡黄色油状液65.6mg,85％收率；Rf＝0.59(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.59(d,J＝7.6Hz,2H),7.33(t,J＝7.2Hz,2H),7.28–7.24(m,1H),6.59(d,J＝8.8Hz,2H),6.30(d,J＝8.8Hz,2H),5.33(dd,J＝15.6,6.8Hz,1H),5.21(dd,J＝14.4,7.2Hz,1H),4.95(s,1H),4.19–4.10(m,1H),4.06–3.98(m,1H),3.66(s,3H),3.08(d,J＝7.2Hz,2H),1.90–1.81(m,1H),1.68–1.59(m,5H),1.27–1.09(m,6H),1.01–0.92(m,2H).
13C NMR(100MHz,CDCl3):δ173.5,152.1,141.8,141.2,138.7,128.6,127.5,127.3,120.9,116.9,114.5,66.9,61.9,55.7,41.0,37.1,33.1,33.1,26.2,26.1,14.2.
HRMS(ESI):[M+H]+Calcd for C23H28NO5 +:398.1962；found:398.1961.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝220nm,t＝11.379min,t＝19.672min；97％ee.
实施例169：
操作过程如通用步骤8，得黄色油状液29.5mg,39％收率；Rf＝0.62(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.63–7.60(m,2H),7.37–7.34(m,2H),7.30–7.28(m,1H),6.63–6.59(m,2H),6.34–6.30(m,2H),5.43(d,J＝15.6Hz,1H),5.17(td,J＝15.6,7.2Hz,1H),4.97(s,1H),4.18–4.12(m,1H),4.08–4.00(m,1H),3.68(s,3H),3.10(d,J＝7.2Hz,2H),1.16(t,J＝7.2Hz,3H),0.94(s,9H).
13C NMR(100MHz,CDCl3):δ173.5,152.2,146.8,141.2,138.8,128.6,127.5,127.3,118.1,116.9,114.5,67.0,61.8,55.7,37.2,33.2,29.6,14.2.
HRMS(ESI):[M+H]+Calcd for C23H28NO5 +:398.1962；found:398.1961.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,λ＝220nm,t＝5.832min,t＝10.365min；97％ee..
实施例170：
操作过程如通用步骤8，得淡黄色油状液44.1mg,48％收率；Rf＝0.59(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.61(d,J＝7.2Hz,2H),7.47–7.45(m,2H),7.38–7.35(m,5H),7.31–7.26(m,1H),6.62–6.58(m,2H),6.30–6.27(m,2H),5.94(td,J＝18.4,6.8Hz,1H),5.78(d,J＝18.4Hz,1H),4.97(s,1H),4.18–4.10(m,1H),4.06–3.98(m,1H),3.69(s,3H),3.29(d,J＝6.4Hz,1H),1.11(t,J＝7.2Hz,3H),0.29(s,6H).
13C NMR(100MHz,CDCl3):δ173.3,152.3,142.2,141.0,138.7,138.6,134.0,129.1,128.7,127.9,127.6,127.2,117.1,114.5,66.6,62.0,55.7,41.2,14.1,-2.6,-2.6
HRMS(ESI):[M+H]+Calcd for C28H34NO3Si+:460.2302；found:460.2302.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,λ＝254nm,t＝5.969min,t＝12.803min；92％ee.
实施例171：
操作过程如通用步骤8，得黄色油状液体34.8mg,44％收率；Rf＝0.26(PE/EA＝10/1)；
1H NMR(400MHz,CDCl3):δ7.57(d,J＝7.2Hz,2H),7.36(t,J＝7.2Hz,2H),7.32–7.28(m,1H),6.79(td,J＝15.6,7.2Hz,1H),6.65–6.61(m,2H),6.38–6.34(m,2H),5.76(d,J＝15.6Hz,1H),4.97(s,1H),4.24–4.04(m,4H),3.68(s,3H),3.42–3.32(m,2H),1.26(t,J＝6.8Hz,3H),1.15(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3):δ172.9,166.0,152.6,142.6,140.4,137.9,128.8,127.9,126.9,125.3,117.2,114.6,66.4,62.4,60.4,55.7,36.3,14.3,14.1.
HRMS(ESI):[M+H]+Calcd for C24H32NO3 +:382.2377；found:382.2374.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝12.063min,t＝14.443min；93％ee.
实施例172：
操作过程如通用步骤8，得黄色油状液体52.7mg,56％收率；Rf＝0.52(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.61(d,J＝7.6Hz,2H),7.36(t,J＝7.2Hz,2H),7.29(d,J＝7.2Hz,1H),6.61(d,J＝9.2Hz,2H),6.32(d,J＝8.8Hz,2H),5.56–5.46(m,2H),4.96(s,1H),4.23–4.15(m,1H),4.09–4.01(m,3H),3.68(s,3H),3.24–3.15(m,2H),1.15(t,J＝6.8Hz,3H),0.90(s,9H).
13C NMR(100MHz,CDCl3):δ173.4,152.2,141.0,138.6,134.3,128.6,127.6,127.2,123.9,116.9,114.5,66.7,63.6,62.0,55.7,36.7,26.0,18.5,14.2,-5.1.
HRMS(ESI):[M+H]+Calcd for C27H40NO4Si+:470.2721；found:470.2720.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝220nm,t＝7.219min,t＝11.056min；81％ee.
实施例173：
操作过程如通用步骤8，得淡黄色粘稠油状液59.5mg,78％收率；Rf＝0.59(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.63–7.61(m,2H),7.34(t,J＝6.8Hz,2H),7.28–7.24(m,1H),6.62–6.58(m,2H),6.30–6.26(m,2H),5.32–5.29(m,1H),5.03(s,1H),4.17–4.03(m,2H),3.67(s,3H),3.13(abq,J＝13.6Hz,2H),1.92–1.82(m,3H),1.73–1.65(m,1H),1.51–1.49(m,4H),1.13(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ173.9,151.7,141.4,139.1,133.0,128.5,127.4,127.3,127.1,116.1,114.4,66.4,61.8,55.7,42.8,29.5,25.6,23.2,22.2,14.0.
HRMS(ESI):[M+H]+Calcd for C24H30NO3 +:380.2220；found:380.2219.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝5.685min(maJor),t＝10.994min(minor)；94％ee.
实施例174：
操作过程如通用步骤8，得黄色油状液45.6mg,93％收率；Rf＝0.68(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.66–7.64(m,2H),7.33–7.29(m,2H),7.27–7.23(m,1H),6.63–6.59(m,2H),6.32–6.28(m,2H),5.27(s,1H),4.18–4.03(m,2H),3.72(d,J＝13.2Hz,1H),3.68(s,3H),3.05(d,J＝13.2Hz,1H),2.42–2.30(m,2H),1.83(ddd,J＝14.8,8.4,2.4Hz,1H),1.70(ddd,J＝14.4,8.4,2.4Hz,1H),1.65–1.57(m,2H),1.51–1.46(m,2H),1.30–1.18(m,2H),1.05(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ173.9,151.7,149.4,140.1,139.9,128.4,128.0,127.3,126.2,115.9,114.3,107.9,97.5,67.9,61.6,55.7,47.5,34.8,33.8,32.3,26.4,25.5,14.1,0.4.
HRMS(ESI):[M+H]+Calcd for C30H40NO3Si+:490.2772；found:490.2770.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝220nm,t＝5.570min(major),t＝6.538min(minor)；93％ee.
实施例175：
操作过程如通用步骤8，得黄色油状液66.4mg,81％收率；Rf＝0.41(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.32–7.28(m,5H),7.23–7.22(m,2H),7.03(dd,J＝5.2,3.6Hz,1H),6.73–6.69(m,2H),6.53–6.49(m,2H),6.36(d,J＝16.0Hz,1H),6.01(td,J＝15.6,7.6Hz,1H),5.06(s,1H),4.30–4.22(m,1H),4.20–4.12(m,1H),3.73(s,3H),3.38(1/2abqd,J＝14.0,8.0Hz,1H),3.24(1/2abqd,J＝13.6,8.0Hz,1H),1.22(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ172.4,152.7,146.5,138.4,137.0,134.9,128.6,127.62,127.1,126.3,126.1,125.5,123.0,117.4,114.5,65.6,62.3,55.6,40.4,14.2.
HRMS(ESI):[M+H]+Calcd for C24H26NO3S+:408.1628；found:408.1618.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝9.731min,t＝19.739min；93％ee.
实施例176：
操作过程如通用步骤8，得白色固体81.5mg,94％收率；Rf＝0.41(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.58(d,J＝8.8Hz,2H),7.32–7.27(m,4H),7.25–7.20(m,1H),6.93(d,J＝8.8Hz,2H),6.68(d,J＝9.2Hz,2H),6.41(d,J＝9.2Hz,2H),6.35(d,J＝15.6Hz,1H),6.06(dt,J＝16.0,7.2Hz,1H),5.03(s,1H),4.28–4.20(m,1H),4.14–4.05(m,1H),3.84(s,3H),3.72(s,3H),3.36(d,J＝7.2Hz,2H),1.19(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3):δ173.5,159.0,152.3,138.7,137.3,134.3,132.9,128.6,128.4,127.4,126.3,124.0,117.0,114.5,114.0,66.5,62.0,55.7,55.3,37.5,14.2.
HRMS(ESI):[M+H]+Calcd for C27H30NO4 +:432.2169；found:432.2159.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝254nm,t＝14.201min,t＝24.412min；96％ee.
实施例177：
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操作过程如通用步骤8，得无色油状液77.7mg,81％收率。
1H NMR(400MHz,CDCl3):δ7.36–7.12(m,8H),6.91(t,J＝7.2Hz,1H),6.56(d,J＝8.4Hz,1H),6.28(d,J＝8.4Hz,2H),6.23(d,J＝16.0Hz,1H),5.91(td,J＝15.6,7.6Hz,1H),4.92(s,1H),4.16–4.08(m,1H),4.03–3.95(m,1H),3.60(s,3H),3.27–3.18(m,2H),1.07(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ172.8,163.2(d,JC–F＝244.1Hz),152.5,143.8(d,JC–F＝6.6Hz),138.2,137.1,134.6,130.1(d,JC–F＝8.0Hz),128.6,127.6,126.3,123.4,122.9(d,JC–F＝2.9Hz),117.0,114.7(d,JC–F＝21.1Hz),114.61,114.56(d,JC–F＝23.0Hz),66.7(d,JC–F＝1.9Hz),62.3,55.7,37.7,14.2.
19F NMR(376MHz,CDCl3):-112.5.
HRMS(ESI):[M+H]+Calcd for C26H27FNO3 +:420.1969；found:420.1958.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝9.546min(minor),t＝12.838min(maJor)；95％ee.
实施例178：
操作过程如通用步骤8，得无色油状液，75％收率；Rf＝0.48(PE/EA＝5/1)。
1H NMR(400MHz,CDCl3):δ7.59(d,J＝8.8Hz,2H),7.34(d,J＝8.8Hz,2H),7.30–7.19(m,5H),6.65(d,J＝8.8Hz,2H),6.35(d,J＝9.2Hz,2H),6.31(d,J＝16.0Hz,1H),5.99(td,J＝15.6,7.2Hz,1H),4.98(s,1H),4.24–4.16(m,1H),4.11–4.03(m,1H),3.70(s,3H),3.30(d,J＝7.2Hz,2H),1.16(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3):δ172.9,152.5,139.5,138.3,137.1,134.7,133.7,128.9,128.8,128.6,127.6,126.3,123.4,117.0,114.6,66.6,62.3,55.7,37.9,14.2.
实施例179：
操作过程如通用步骤6，得白色固体76.8mg,80％收率；Rf＝0.48(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.35–7.28(m,4H),7.24–7.20(m,1H),6.78–6.74(m,2H),6.70–6.66(m,2H),6.46(d,J＝16.0Hz,1H),6.17(td,J＝16.0,7.6Hz,1H),4.19(q,J＝7.2Hz,2H),3.75(s,3H),2.81–2.68(m,2H),1.52(s,3H),1.23(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.6,153.8,138.9,137.2,134.4,128.7,127.5,126.3,124.2,119.8,114.5,61.6,61.3,55.7,42.7,23.4,14.4.
HRMS(ESI):[M+H]+Calcd for C26H27BrNO3 +:480.1169；found:480.1158.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝254nm,t＝10.184min,t＝15.900min；93％ee.
实施例180：
操作过程如通用步骤8，得无色油状液33.7mg,99％收率；Rf＝0.54(PE/EA＝5/1).
1H NMR(400MHz,CDCl3):δ7.35–7.28(m,4H),7.24–7.20(m,1H),6.78–6.74(m,2H),6.70–6.66(m,2H),6.46(d,J＝16.0Hz,1H),6.17(td,J＝16.0,7.6Hz,1H),4.19(q,J＝7.2Hz,2H),3.75(s,3H),2.81–2.68(m,2H),1.52(s,3H),1.23(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ175.6,153.8,138.9,137.2,134.4,128.7,127.5,126.3,124.2,119.8,114.5,61.6,61.3,55.7,42.7,23.4,14.4.
HRMS(ESI):[M+H]+Calcd for C21H26NO3 +:340.1907；found:340.1898.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝220nm,t＝11.230min,t＝12.385min；93％ee..
实施例181：
操作过程如通用步骤8，得白色固体24.3mg,62％收率；Rf＝0.50(PE/EA＝20/1).
1H NMR(400MHz,CDCl3):δ7.30–7.26(m,2H),7.24–7.21(m,1H),6.91–6.87(m,2H),6.81–6.77(m,2H),6.36(d,J＝15.6Hz,1H),5.88(td,J＝15.6,8.0Hz,1H),4.50(s,1H),4.32(q,J＝7.2Hz,2H),3.77(s,3H),3.16(m,1H),2.99(1/2abqd,J＝14.4,8.0Hz,1H),1.30(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ168.5,155.0,136.8,136.7,135.4,128.7,127.8,126.4,124.7(q,JC–F＝286.3Hz),122.1(q,JC–F＝1.9Hz),121.4,114.5,68.4(q,JC–F＝26.1Hz),63.2,55.6,33.8,29.8,14.2.
19F NMR(376MHz,CDCl3):-72.5.
HRMS(ESI):[M+H]+Calcd for C21H23F3NO3 +:394.1625；found:394.1623.
HPLC(Chiralpak IBN):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,λ＝254nm,t＝6.042min,t＝6.836min；90％ee.
实施例182：
操作过程如通用步骤8，得无色油状液40.2mg,47％收率；Rf＝0.48(PE/EA＝20/1).
1H NMR(400MHz,CDCl3):δ7.26–7.12(m,8H),7.06(d,J＝7.6Hz,2H),6.77(d,J＝8.8Hz,2H),6.72(d,J＝8.8Hz,2H),6.34(d,J＝16.0Hz,1H),6.08(dt,J＝16.0,7.2Hz,1H),4.24–4.12(m,2H),3.74(s,3H),2.90(dd,J＝14.4,7.2Hz,1H),2.78–2.65(m,2H),2.54–2.45(m,1H),2.32–2.19(m,2H),1.25(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3):δ174.7,153.3,141.7,138.9,137.3,133.8,128.6,128.5,127.4,126.3,126.1,124.3,118.6,114.8,65.2,61.6,55.8,39.3,38.3,30.4,14.5.
HRMS(ESI):[M+H]+Calcd for C21H23F3NO3 +:394.1625；found:394.1623.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝254nm,t＝13.807min,t＝16.227min；93％ee.
实施例183：
操作过程如通用步骤8，得无色油状液79.1mg,99％收率；Rf＝0.40(PE/EA＝20/1).
1H NMR(400MHz,CDCl3):δ7.66(d,J＝7.6Hz,2H),7.41(J＝7.2Hz,2H),7.36–7.22(m,6H),6.80–6.74(m,2H),6.39–6.33(m,3H),6.04(td,J＝16.0,7.2Hz,1H),5.24(s,1H),4.29–4.21(m,1H),4.14–4.06(m,1H),3.46–3.35(m,2H),1.19(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3):δ173.1,156.0(d,JC–F＝234.3Hz),140.9(d,JC–F＝2.0Hz),140.4,137.2,134.6,128.8,128.6,127.9,127.6,127.1,126.3,123.6,116.4(d,JC–F＝7.2Hz),115.4(d,JC–F＝22.0Hz),66.7,62.2,37.3,14.2.
19F NMR(376MHz,CDCl3):-127.5.
HRMS(ESI):[M+H]+Calcd for C25H25FNO2 +:390.1864；found:390.1860.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝90/10,flow rate 1.0mL/min,λ＝254nm,t＝5.707min,t＝8.609min；95％ee.
实施例184：
操作过程如通用步骤8，得无色油状液16.2mg,52％收率；Rf＝0.43(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.36–7.33(m,2H),7.21–7.12(m,3H),6.93(d,J＝8.8Hz,2H),6.56(d,J＝9.2Hz,2H),5.95–5.89(m,1H),5.83–5.80(m,1H),5.09(sept,J＝6.0Hz,1H),4.17–4.10(m,1H),3.91–3.83(m,1H),3.67(s,3H),3.05–2.99(m,1H),2.93–2.86(m,1H),1.19(d,J＝6.4Hz,3H),1.17(d,J＝6.4Hz,3H).
13C NMR(100MHz,CDCl3):δ172.7,155.2,143.3,140.5,128.0,128.0,127.4,127.3,127.2,124.6,113.1,69.4,68.7,55.4,52.7,35.4,21.8,21.7.
HRMS(ESI):[M+H]+Calcd for C21H23F3NO3 +:394.1625；found:394.1623.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝220nm,t＝11.869min,t＝14.759min；80％ee.
实施例185：
操作过程如通用步骤9，得黄色油状液50％收率；Rf0.41(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.36–7.33(m,2H),7.21–7.12(m,3H),6.93(d,J＝8.8Hz,2H),6.56(d,J＝9.2Hz,2H),5.95–5.89(m,1H),5.83–5.80(m,1H),5.09(sept,J＝6.0Hz,1H),4.17–4.10(m,1H),3.91–3.83(m,1H),3.67(s,3H),3.05–2.99(m,1H),2.93–2.86(m,1H),1.19(d,J＝6.4Hz,3H),1.17(d,J＝6.4Hz,3H).
13C NMR(100MHz,CDCl3):δ172.7,155.2,143.3,140.5,128.0,128.0,127.4,127.3,127.2,124.6,113.1,69.4,68.7,55.4,52.7,35.4,21.8,21.7.
HRMS(ESI):[M+H]+Calcd for C21H23F3NO3 +:394.1625；found:394.1623.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝95/5,flow rate 1.0mL/min,λ＝254nm,t＝9.800min(minor),t＝10.315min(maJor)；94％ee.
实施例186：
操作过程如通用步骤9，得淡黄色油状液33.9mg,84％收率；Rf＝0.57(PE/EA＝10/1).
1H NMR(400MHz,C6D6):δ7.43(d,J＝7.2Hz,2H),7.04(d,J＝8.8Hz,2H),6.92(t,J＝7.2Hz,2H),6.82–6.78(m,1H),6.47(d,J＝8.8Hz,2H),4.97(sept,J＝6.0Hz,1H),4.00(d,J＝16.8Hz,1H),3.68(d,J＝16.4Hz,1H),3.06(s,3H),2.80–2.71(m,2H),1.76(s,2H),1.57(s,2H),1.47–1.28(m,4H),0.84(d,J＝6.4Hz,6H).
13C NMR(100MHz,C6D6):δ172.4,155.7,143.7,141.5,128.2,128.0,127.6,127.4,126.9,113.6,70.6,68.1,57.1,54.8,42.1,30.4,27.0,23.4,23.2,21.8,21.7.
HRMS(ESI):[M+H]+Calcd for C26H32NO3 +:406.2377；found:406.2381.
HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝220nm,t＝7.795min,t＝8.630min；95％ee.
实施例187：
操作过程如通用步骤9，得淡黄色粘稠油状液20.3mg,55％收率；Rf＝0.59(PE/EA＝10/1).
1H NMR(400MHz,CDCl3):δ7.37(d,J＝8.8Hz,2H),6.800(d,J＝9.2Hz,2H),4.28–4.14(m,2H),3.78–3.75(m,4H),3.44(d,J＝16.4Hz,1H),2.69–2.57(m,2H),2.00–1.94(m,2H),1.89–1.84(m,2H),1.72–1.56(m,4H),1.23(t,J＝6.8Hz,3H).
13C NMR(100MHz,CDCl3):δ168.6,157.8,141.5,130.1,127.4,123.2,113.8,69.5(d,JC–F＝24.9Hz),61.9,55.5,55.4,35.2,29.9,29.5,26.7,22.9,22.7,14.1.
19F NMR(376MHz,CDCl3):-69.0.
HRMS(ESI):[M+H]+Calcd for C21H23F3NO3+:394.1625；found:394.1623.
HPLC(Chiralpak OJ-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,λ＝220nm,t＝8.543min,t＝23.574min；97％ee.
(三)钴催化亚胺的不对称还原炔丙基化反应
通用步骤10：
向预先烘干的反应管中加入手性配体(6mol％)，Mn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mol％)、乙腈(0.2M)、炔丙基磷酸酯(2.0equiv)。将反应管从手套箱内移出，封口膜密封，置于40℃油浴中剧烈搅拌48小时。待反应完毕，反应液使用硅藻土过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3。
实施例188：
操作过程如通用步骤10，得无色油状液体76.8mg,83％收率，反应放大到3mmol规模得989.1mg,71％收率；Rf＝0.43(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.59-7.57(m,2H),7.39–7.31(m,3H),6.61(d,J＝8.8Hz,2H),6.36(d,J＝8.8Hz,2H),4.98(br s,1H),3.69(s,3H),3.68(s,3H),3.44(1/2abq,J＝16.4,1H),3.23(1/2abq,J＝16.4,1H),1.04-1.02(m,21H)；13C NMR(100MHz,CDCl3):δ173.1,153.2,140.0,138.1,128.9,128.1,127.1,118.6,114.4,10.1,84.4,67.2,55.7,53.2,26.5,18.7,11.3；HPLC(Chiralpak AD-H):n-Hexane/i-PrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝7.011min(major),tR2＝8.175min(minor)；95％e.e.；
实施例189：
操作过程如通用步骤10，得无色油状液体77.2mg,78％收率；Rf＝0.35(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.49(d,J＝8.8Hz,2H),6.89(d,J＝8.8Hz,2H),6.62(d,J＝8.8Hz,2H),6.37(d,J＝8.8Hz,2H),3.81(s,3H),3.70(s,3H),3.69(s,3H),3.42(1/2abq,J＝16.4,1H),3.20(1/2abq,J＝16.4,1H),1.05-1.03(m,21H)；13C NMR(100MHz,CDCl3):δ173.2,159.4,153.1,138.2,131.9,128.3,118.6,114.4,114.2,103.2,84.3,66.7,55.6,55.4,53.1,26.5,18.7,11.3；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99/1,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝16.333min(major),tR2＝17.522min(minor)；94％e.e.；
实施例190：
操作过程如通用步骤10，得无色油状液体83.1mg,81％收率；Rf＝0.42(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ8.05(s,1H),7.87-7.84(m,3H),7.76(dd,J＝2.0,8.8Hz,1H),7.54-7.49(m,2H),6.60(d,J＝8.8Hz,2H),6.42(d,J＝8.8Hz,2H),5.10(br s,1H),3.71(s,3H),3.67(s,3H),3.61(1/2abq,J＝16.4,1H),3.36(1/2abq,J＝16.4,1H),1.08-1.06(m,21H)；13C NMR(100MHz,CDCl3):δ173.0,153.2,138.1,137.7,133.4,133.0,128.7,128.6,127.7,126.6,126.4,126.1,125.0,118.7,114.4,103.0,84.5,67.3,55.6,53.2,26.5,18.7,11.3；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝10.436min(major),tR2＝15.953min(minor)；96％e.e.；
实施例191：
操作过程如通用步骤10，得无色油状液体66.1mg,62％收率；Rf＝0.39(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.75(d,J＝7.6,2H),7.63(d,J＝7.6,2H),6.64(d,J＝8.8,2H),6.57(d,J＝8.8,2H),4.96(br s,1H),3.71(s,3H),3.70(s,3H),3.42(1/2abq,J＝16.4,1H),3.24(1/2abq,J＝16.4,1H),1.05-1.02(m,21H)；13C NMR(100MHz,CDCl3):δ172.4,153.5,144.0,137.6,130.3(q,JC-F＝32.4Hz),127.8,125.8(q,JC-F＝3.5Hz),124.2(q,JC-F＝270.3Hz),118.7,114.5,102.3,85.1,67.1,55.6,53.4,27.2,18.7,11.3；19F NMR(376MHz,CDCl3):δ-62.6.HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝99/1,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝18.001min(major),tR2＝25.006min(minor)；99％e.e.；
实施例192：
操作过程如通用步骤10，得无色油状液体76.2mg,73％收率；Rf＝0.47(PE/EtOAc＝20/1)；
1H NMR(400MHz,CDCl3):δ7.50-7.45(m,4H),6.64-6.61(m,2H),6.38-6.34(m,2H),4.99(septet,J＝6.4Hz,1H),4.94(br s,1H),3.69(s,3H),3.38(1/2abq,J＝16.4,1H),3.21(1/2abq,J＝16.4,1H),1.20(d,J＝6.4,3H),1.06(d,J＝6.4,3H),1.04-1.01(m,21H)；
13C NMR(100MHz,CDCl3):δ171.3,153.0,139.3,137.9,131.7,128.9,122.0,118.2,114.3,102.4,84.5,69.9,66.4,55.6,26.6,21.5,21.3,18.6,11.2；
HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝13.757min(major),tR2＝23.466min(minor)；88％e.e.；
实施例193：
操作过程如通用步骤10，得无色油状液体88.5mg,85％收率；Rf＝0.24(PE/EtOAc＝20/1)；
1H NMR(400MHz,CDCl3):δ7.45(d,J＝7.6,1H),7.29(t,J＝7.6,1H),6.94(t,J＝7.6,1H),6.86(d,J＝7.6,1H),6.68-6.62(m,4H),5.02(septet,J＝6.4Hz,1H),4.50(br s,1H),3.76(s,3H),3.71(s,3H),3.20(1/2abq,J＝16.8,1H),3.10(1/2abq,J＝16.8,1H),1.12(dd,J＝2.4,6.4Hz,6H),1.06-1.03(m,21H)；
13C NMR(100MHz,CDCl3):δ172.0,156.7,154.6,138.0,129.3,129.1,128.3,122.9,120.3,113.9,111.0,103.8,84.6,68.7,65.3,55.5,55.3,27.6,21.7,18.7,11.4；
HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝95/5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝4.591min(minor),tR2＝5.560min(major)；87％e.e.；
实施例194：
操作过程如通用步骤10，得无色油状液体73.4mg,71％收率；Rf＝0.16(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.81(s,1H),7.49(dd,J＝1.2,8.8Hz,1H),7.31(d,J＝8.4Hz,1H),7.07(d,J＝2.8Hz,1H),6.57(d,J＝8.8Hz,2H),7.49(d,J＝3.2Hz,1H),6.37(d,J＝8.8Hz,2H),5.11(br s,1H),3.79(s,3H),3.68(s,3H),3.66(s,3H),3.59(1/2abq,J＝16.4,1H),3.59(1/2abq,J＝16.4,1H),3.32(1/2abq,J＝16.4,1H),1.08-1.05(m,21H)；13CNMR(100MHz,CDCl3):δ173.7,152.9,138.5,136.4,130.9,129.5,128.7,120.9,119.3,118.5,114.3,109.7,103.7,101.6,84.0,67.3,55.6,53.1,33.0,26.4,18.7,11.3；
HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝20.947min(major),tR2＝25.247min(minor)；97％e.e.；
实施例195：
操作过程如通用步骤10，得无色油状液体60.3mg,64％收率；Rf＝0.45(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.30(d,J＝4.8Hz,2H),7.13(d,J＝3.6Hz,1H),6.99(t,J＝4.0Hz,1H),6.66(d,J＝8.8Hz,2H),6.48(d,J＝8.8Hz,2H),5.10(br s,1H),3.75,(s,3H),3.70(s,3H),3.35(1/2abq,J＝16.4,1H),3.28(1/2abq,J＝16.4,1H),1.05-1.03(m,21H)；13C NMR(100MHz,CDCl3):δ172.2,153.4,145.5,137.8,127.2,126.6,125.5,118.7,114.4,102.2,84.8,65.6,55.6,53.4,28.6,18.7,11.3；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.454min(major),tR2＝13.118min(minor)；93％e.e.；
实施例196：
操作过程如通用步骤10，得无色油状液体81.9mg,90％收率；Rf＝0.71(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.57(d,J＝7.6Hz,2H),7.40-7.31(m,3H),6.72(t,J＝8.8Hz,2H),6.31(dd,J＝4.4,8.8Hz,2H),5.22(br s,1H),3.70(s,3H),3.50(1/2abq,J＝16.4,1H),3.27(1/2abq,J＝16.4,1H),1.05-1.03(m,21H)；13C NMR(100MHz,CDCl3):δ172.8,156.6(d,JC-F＝230.0Hz),140.6(d,JC-F＝2.0Hz),139.4,129.0,128.2,127.0,117.5(d,JC-F＝7.3Hz),115.4(d,JC-F＝21.9Hz),102.7,84.5,66.8,53.3,26.3,18.7,11.3；19FNMR(376MHz,CDCl3):δ-126.5.HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate1.0mL/min,T＝25℃,λ＝220nm,tR1＝4.440min(major),tR2＝5.898min(minor)；92％e.e.；
实施例197：
操作过程如通用步骤10，得无色油状液体57.6mg,58％收率；Rf＝0.26(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.70(d,J＝8.8Hz,2H),7.52(d,J＝7.6Hz,2H),7.39-7.30(m,3H),6.31(d,J＝8.8Hz,2H),5.89(br s,5.88),3.80(s,3H),3.72(s,3H),3.59(1/2abq,J＝16.4,1H),3.39(1/2abq,J＝16.4,1H),1.03-1.01(m,21H)；13C NMR(100MHz,CDCl3):δ172.5,167.3,148.3,138.2,131.1,129.3,128.5,126.7,119.3,114.4,102.2,84.8,66.3,53.6,51.6,26.2,18.7,11.2；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝9.749min(major),tR2＝12.225min(minor)；93％e.e.；
实施例198：
操作过程如通用步骤10，得无色油状液体65.6mg,65％收率；Rf＝0.31(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.59(d,J＝7.6Hz,2H),7.38-7.26(m,3H),6.60(d,J＝8.4Hz,2H),6.36(d,J＝8.8Hz,2H),5.02(br s,1H),3.82(t,J＝4.4Hz,4H),3.69(s,3H),3.46(1/2abq,J＝16.4,1H),3.25(1/2abq,J＝16.4,1H),2.98(t,J＝4.4Hz,4H),1.05-1.02(m,21H)；13C NMR(100MHz,CDCl3):δ173.0,139.9,128.9,128.1,127.1,118.1,117.5,103.1,84.3,67.1,67.0,53.2,50.9,26.5,18.7,11.3；HPLC(Chiralpak AD-H):n-Hexane/EtOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝4.844min(minor),tR2＝12.656min(major)；92％e.e.；
实施例199：
操作过程如通用步骤10，得无色油状液体67.6mg,73％收率；Rf＝0.53(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.60-7.57(m,2H),7.40-7.29(m,3H),6.92(t,J＝8.0Hz,1H),6.24(dd,J＝0.4,2.4Hz,1H),5.99(dd,J＝0.4,2.4Hz,1H),5.90(t,J＝2.0Hz,1H),5.39(br s,1H),3.71(s,3H),3,60(s,3H),3.54(1/2abq,J＝16.4,1H),3.40(1/2abq,J＝16.4,1H),1.06-1.03(m,21H)；13C NMR(100MHz,CDCl3):δ172.8,160.3,145.6,139.4,129.6,129.0,128.1,126.9,109.0,103.9,102.9,101.8,84.3,66.5,54.9,53.3,26.1,18.7,11.3；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝99/1,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.222min(major),tR2＝9.870min(minor)；94％e.e.；
实施例200：
操作过程如通用步骤10，得白色固体81.6mg,84％收率；Rf＝0.53(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ8.11-8.09(m,1H),7.77-7.75(m,1H),7.64(d,J＝8.0Hz,2H),7.49-7.44(m,2H),7.39-7.30(m,3H),7.16(d,J＝8.0Hz,2H),7.02(t,J＝8.0Hz,2H),6.36(d,J＝7.6Hz,2H),3.76(s,3H),3.64(s,2H),0.94-0.90(m,21H)；13C NMR(100MHz,CDCl3):δ173.3,139.0,138.9,134.6,129.0,128.7,128.2,127.0,125.8,125.7,124.9,124.4,120.6,117.7,107.7,102.7,84.5,66.5,53.5,26.1,18.6(d,J＝2.1Hz),11.2；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.288min(major),tR2＝6.357min(minor)；87％e.e.；
实施例201：
操作过程如通用步骤10，得无色油状液体64.7mg,67％收率；Rf＝0.41(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.58-7.55(m,2H),7.40-7.29(m,3H),6.50(d,J＝8.4Hz,2H),5.98(d,J＝2.0Hz,1H),5.88(dd,J＝1.2,8.4Hz,1H),5.79(dd,J＝1.6,10.0Hz,1H),5.07(br s,1H),3.70(s,3H),3.46(1/2abq,J＝16.4,1H),3.27(1/2abq,J＝16.4,1H),1.05-1.03(m,21H)；13C NMR(100MHz,CDCl3):172.9,147.8,140.7,139.8,139.5,129.0,128.2,127.0,109.5,108.3,103.0,100.7,99.8,84.5,67.1,53.3,26.3,18.7,11.3；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝13.291min(major),tR2＝18.778min(minor)；99％e.e.；
实施例202：
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操作过程如通用步骤10，得无色油状液体38.9mg,51％收率；Rf＝0.39(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.59-7.56(m,2H),7.40-7.30(m,3H),6.64-6.61(m,2H),6.39-6.35(m,2H),4.97(br s,1H),3.71(s,3H),3.69(s,3H),3.37(1/2abq,J＝16.4,1H),3.17(1/2abq,J＝16.4,1H),0.14(s,9H)；13C NMR(100MHz,CDCl3):δ173.1,153.3,139.9,138.1,128.8,128.1,127.1,118.9,114.4,101.9,88.8,67.2,55.6,53.2,26.6,-0.1；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.826min(major),tR2＝6.224min(minor)；97％e.e.；
实施例203：
操作过程如通用步骤10，得无色油状液体39.6mg,47％收率；Rf＝0.42(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.59(d,J＝7.2Hz,2H),7.40-7.32(m,3H),6.63(d,J＝8.8Hz,2H),6.37(d,J＝8.8Hz,2H),4.98(br s,1H),3.71(s,3H),3.69(s,3H),3.41(1/2abq,J＝16.4,1H),3.21(1/2abq,J＝16.4,1H),0.93(s,9H),0.08(s,6H)；13C NMR(100MHz,CDCl3):δ173.0,153.2,139.9,138.1,128.9,128.2,127.1,118.7,114.4,102.3,86.8,67.2,55.6,53.2,29.8,26.5,26.2,16.5,-4.4,-4.5；
实施例204：
操作过程如通用步骤10在50℃下反应，得无色油状液体26.8mg,37％收率；Rf＝0.30(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ7.58(d,J＝7.2Hz,2H),7.38-7.31(m,3H),6.62(d,J＝9.2Hz,2H),6.37(d,J＝9.2Hz,2H),3.70(s,3H),3.68(s,3H),3.34-3.29(m,1H),3.15-3.10(m,1H),2.14-2.11(m,2H),1.47-1.32(m,1H),0.90(t,J＝7.2Hz,4H)；13CNMR(100MHz,CDCl3):δ173.4,153.2 140.0,138.1,128.8,128.1,127.2,118.7,114.4,84.2,74.7,67.4,55.6,53.2,31.1,25.7,21.9,18.5,13.7；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝18.690min(minor),tR2＝24.302min(major)；84％e.e.；
实施例205：
操作过程如通用步骤10，得白色固体52.2mg,71％收率；Rf＝0.41(PE/EtOAc＝20/1)；1H NMR(400MHz,CDCl3):δ5.59(d,J＝7.6Hz,2H),7.39-7.30(m,3H),6.62(d,J＝9.2Hz,2H),6.36(d,J＝9.2Hz,2H),3.70(s,3H),3.69(s,3H),3.28(1/2abq,J＝16.0,1H),3.07(1/2abq,J＝16.0,1H),1.18(s,9H),0.08(s,6H)；13C NMR(100MHz,CDCl3):δ173.3,153.1,140.2,138.4,128.8,128.0,127.2,118.7,114.3,92.9,73.4,67.4,55.6,53.1,31.2,27.5,25.5；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝5.779min(major),tR2＝6.255min(minor)；92％e.e.
(四)钴催化亚胺的不对称还原烯基化反应
通用步骤11：
向预先烘干的反应管中加入手性配体(12mmol％)，Mn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mmol％)、乙腈与相应的醇(4/1，0.2M)、烯基碘代物。将反应管从手套箱内移出，封口膜密封，置于油浴中剧烈搅拌一定时间。待反应完毕，反应液使用硅胶过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3。
通用步骤12：
向预先烘干的反应管中加入手性配体(12mmol％)，Mn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mmol％)、乙腈(0.2M)、烯基碘代物和相应的醇(1.0equiv)。将反应管从手套箱内移出，封口膜密封，置于油浴中剧烈搅拌一定时间。待反应完毕，反应液使用硅胶过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到产物3。
实施例206：
操作过程如通用步骤11，得白色固体79.5mg，84％收率，Rf＝0.69(PE/EtOAc＝10/1)；M.P.:114-115℃；1H NMR(400MHz,CDCl3):δ7.68(d,J＝7.2Hz,2H),7.58(s,1H),7.36(t,J＝6.8Hz,2H),7.31–7.28(m,2H),7.26–7.21(m,2H),7.16(d,J＝7.2Hz,2H),6.74(d,J＝9.2Hz,2H),6.63(d,J＝8.8Hz,2H),5.08(sept,J＝6.4Hz,1H),4.93(bs,1H),3.75(s,3H),1.31(d,J＝6.4Hz,3H),1.13(d,J＝6.4Hz,3H),-0.26(s,9H)；13C NMR(100MHz,CDCl3):δ173.0,152.3,146.5,142.2,140.0,139.5,139.1,129.5,128.6,128.0,127.8,127.8,127.0,117.5,114.1,74.7,70.1,55.9,21.9,21.4,2.0；HRMS(ESI):[M+Na]+Calcd forC29H35NO3SiNa+:496.2278；found:496.2271；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝25℃,λ＝220nm,tR1＝8.881min(minor),tR2＝9.687min(major)；>99％ee；[α]D 25.2＝-46.4(c＝0.59,CH2Cl2).
实施例207：
操作过程如通用步骤11，得白色固体74.2mg，81％收率，Rf＝0.67(PE/EtOAc＝10/1)；M.P.:85-86℃；1H NMR(400MHz,CDCl3):δ7.68(d,J＝8.0Hz,2H),7.54(s,1H),7.35(t,J＝6.8Hz,2H),7.31–7.27(m,2H),7.26–7.20(m,2H),7.15(d,J＝7.6Hz,2H),6.74(d,J＝8.4Hz,2H),6.63(d,J＝8.4Hz,2H),4.95(bs,1H),4.31–4.18(m,2H),3.75(s,3H),1.26(t,J＝7.2Hz,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ173.6,152.4,146.8,142.1,139.9,139.3,139.1,129.4,128.5,128.1,127.8,127.8,127.1,117.7,114.1,74.7,62.2,55.8,14.0,1.8；HRMS(ESI):[M+Na]+Calcd for C28H33NO3SiNa+:482.2122；found:482.2119；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝28℃,λ＝254nm,tR1＝9.585min(minor),tR2＝9.819min(major)；99％ee；[α]D 25.2＝-44.8(c＝0.53,CH2Cl2).
实施例208：
操作过程如通用步骤11，得无色油状物73.2mg，82％收率，Rf＝0.53(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.68(d,J＝7.6Hz,2H),7.53(s,1H),7.36(t,J＝7.2Hz,2H),7.32–7.28(m,2H),7.26–7.21(m,2H),7.16(d,J＝7.2Hz,2H),6.75(d,J＝8.8Hz,2H),6.63(d,J＝8.8Hz,2H),4.93(bs,1H),3.79(s,3H),3.76(s,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ174.1,152.4,146.9,142.0,139.8,139.2,139.1,129.3,128.5,128.2,127.9,127.8,127.1,117.7,114.1,74.7,55.8,52.9,1.7；HRMS(ESI):[M+Na]+Calcd forC27H31NO3SiNa+:468.1965；found:468.1960；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 0.5mL/min,T＝25℃,λ＝254nm,tR1＝18.738min(minor),tR2＝22.869min(major)；99％ee；[α]D 25.2＝-36.8(c＝0.42,CH2Cl2).
实施例209：
操作过程如通用步骤12，得黄色油状物10.4mg，22％收率，Rf＝0.59(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.66–7.63(m,1H),7.40(s,1H),7.28–7.12(m,8H),6.67(d,J＝9.2Hz,2H),6.54(d,J＝8.8Hz,2H),4.69(bs,1H),4.30–4.16(m,2H),3.72(s,3H),2.45(s,3H),1.23(t,J＝6.8Hz,3H),-0.21(s,9H)；13C NMR(100MHz,CDCl3):δ173.3,152.6,147.2,140.6,140.1,139.1,137.9,137.8,132.8,130.6,128.4,128.0,127.9,127.1,125.8,118.4,113.9,76.3,62.0,55.8,22.6,14.1,2.4；HRMS(ESI):[M+Na]+Calcd forC29H35NO3SiNa+:496.2278；found:496.2279；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝10.155min(minor),tR2＝14.861min(major)；98％ee；[α]D 25.2＝13.3(c＝0.99,CH2Cl2).
实施例210：
操作过程如通用步骤11，得黄色油状物23.1mg，47％收率，Rf＝0.30(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.87(s,1H),7.47(dd,J＝7.6Hz,1.2Hz,1H),7.32–7.29(m,2H),7.26–7.18(m,4H),6.90(t,J＝7.6Hz,1H),6.75(d,J＝8.0Hz,1H),6.60–6.55(m,4H),5.07(bs,1H),4.36–4.12(m,2H),3.69(s,3H),3.68(s,3H),1.23(t,J＝7.2Hz,3H),-0.17(s,9H)；13C NMR(100MHz,CDCl3):δ173.9,156.9,152.6,147.3,143.4,140.6,139.6,131.7,129.2,128.8,128.6,127.8,126.9,119.7,119.2,113.6,111.3,73.6,61.6,55.7,55.3,14.2,3.2；HRMS(ESI):[M+Na]+Calcd for C29H35NO4SiNa+:512.2228；found:512.2225；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99/1,flow rate 1.0mL/min,T＝27℃,λ＝220nm,tR1＝9.506min(major),tR2＝10.329min(minor)；98％ee；[α]D 25.2＝-54.6(c＝0.43,CH2Cl2).
实施例211：
操作过程如通用步骤11，得淡黄色固体66.2mg，65％收率，Rf＝0.77(PE/EtOAc＝10/1)；M.P.:107-109℃；1H NMR(400MHz,CDCl3):δ7.70(s,1H),7.59–7.56(m,1H),7.49(s,1H),7.29–7.21(m,5H),7.14(d,J＝7.2Hz,2H),6.74(d,J＝8.8Hz,2H),6.61(d,J＝8.8Hz,2H),5.08(sept,J＝6.4Hz,1H),4.94(bs,1H),3.76(s,3H),1.31(d,J＝6.4Hz,3H),1.16(d,J＝6.4Hz,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ172.6,152.6,147.0,142.0,141.4,139.6,138.9,134.0,129.9,129.3,128.5,128.0,127.8,127.8,127.2,117.8,114.2,74.6,70.5,55.9,21.8,21.4,1.9；HRMS(ESI):[M+Na]+Calcd for C29H34ClNO3SiNa+:530.1889；found:530.1890；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate1.0mL/min,T＝28℃,λ＝254nm,tR1＝8.160min(minor),tR2＝9.559min(major)；>99％ee；[α]D 25.2＝39.1(c＝0.77CH2Cl2)；
实施例212：
操作过程如通用步骤11，得到白色固体71.4mg，71％收率，Rf＝0.57(PE/EtOAc＝10/1)；M.P.:153-155℃；1H NMR(400MHz,CDCl3):δ7.58(d,J＝8.4Hz,3H),7.29–7.20(m,3H),7.15(d,J＝7.6Hz,2H),6.87(d,J＝8.8Hz,2H),6.73(d,J＝8.8Hz,2H),6.61(d,J＝8.8Hz,2H),5.06(sept,J＝6.4Hz,1H),4.91(bs,1H),3.81(s,3H),3.75(s,3H),1.30(d,J＝6.4Hz,3H),1.12(d,J＝6.4Hz,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ173.1,159.1,152.3,146.2,142.2,140.0,139.5,130.9,130.8,128.6,127.8,127.0,117.4,114.1,113.3,74.2,70.0,55.9,55.4,21.9,21.4,2.0；HRMS(ESI):[M+Na]+Calcd forC30H37NO4SiNa+:526.2384；found:526.2386；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝90/10,flow rate 1.0mL/min,T＝28℃,λ＝254nm,tR1＝5.004min(major),tR2＝13.524min(minor)；>99％ee；[α]D 25.1＝-37.3(c＝0.56,CH2Cl2).
实施例213：
操作过程如通用步骤11，得到白色固体87.4mg，85％收率，Rf＝0.68(PE/EtOAc＝10/1)；M.P.:121-122℃；1H NMR(400MHz,CDCl3):δ7.84(d,J＝8.0Hz,2H),7.61(d,J＝8.4Hz,2H),7.39(s,1H),7.30–7.21(m,3H),7.12(d,J＝7.2Hz,2H),6.76(d,J＝9.2Hz,2H),6.60(d,J＝8.8Hz,2H),4.99(bs,1H),3.81(s,3H),3.76(s,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ173.6,152.7,147.4,143.2,142.0,139.3,138.6,130.1(q,JC-F＝31.9Hz),130.0,128.4,127.9,127.3,125.1(q,JC-F＝3.5Hz),124.2(q,JC-F＝270.5Hz),118.0,114.2,74.7,55.8,53.2,1.6；19F NMR(376MHz,CDCl3):δ-62.5；HRMS(ESI):[M+Na]+Calcd for C28H30F3NO3SiNa+:536.1839；found:536.1841；HPLC(Chiralpak IBN-5):n-Hexane/EtOH＝99.5/0.5,flow rate 1.0mL/min,T＝28℃,λ＝254nm,tR1＝8.860min(minor),tR2＝9.327min(major)；>99％ee；[α]D 24.8＝13.2(c＝0.71,CH2Cl2).
实施例214：
操作过程如通用步骤11，得黄色油状物33.8mg，59％收率，Rf＝0.53(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.67(d,J＝8.4Hz,2H),7.43–7.41(m,3H),7.28–7.20(m,3H),7.11(d,J＝7.2Hz,2H),6.74(d,J＝8.8Hz,2H),6.58(d,J＝8.8Hz,2H),4.92(bs,1H),3.78(s,3H),3.75(s,3H),-0.29(s,9H)；13C NMR(100MHz,CDCl3):δ173.7,152.6,147.2,141.8,139.5,138.9,138.7,137.3,131.6,128.4,127.9,127.3,117.9,114.2,94.0,74.5,55.8,53.1,1.6；HRMS(ESI):[M+H]+Calcd for C27H31INO3Si+:572.1112；found:572.1105.HPLC(Chiralpak IBN-5):n-Hexane/EtOH＝99.5/0.5,flow rate1.0mL/min,T＝40℃,λ＝254nm,tR1＝11.348min(minor),tR2＝11.706min(major)；>99％ee；[α]D 25.2＝17.2(c＝0.61,CH2Cl2).
实施例215：
操作过程如通用步骤11，得到白色固体74.3mg，74％收率，Rf＝0.69(PE/EtOAc＝10/1)；M.P.:116-118℃；1H NMR(400MHz,CDCl3):δ8.19(s,1H),7.84–7.81(m,4H),7.56(s,1H),7.51–7.45(m,2H),7.29–7.22(m,3H),7.16(d,J＝7.2Hz,2H),6.75(d,J＝8.8Hz,2H),6.68(d,J＝9.2Hz,2H),5.10(sept,J＝6.4Hz,1H),5.07(bs,1H),3.76(s,3H),1.34(d,J＝6.4Hz,3H),1.16(d,J＝6.4Hz,3H),-0.24(s,9H)；13C NMR(100MHz,CDCl3):δ173.0,152.4,147.2,142.0,139.9,139.3,136.8,133.2132.9,129.0,128.7,128.6,127.8,127.5,127.5,127.1,127.1,126.5,126.1,118.0,114.1,75.0,70.4,55.9,21.9,21.5,2.0；HRMS(ESI):[M+Na]+Calcd for C33H37NO3SiNa+:546.2435；found:546.2429；HPLC(Chiralpak IBN-5):n-Hexane/EtOH＝99.5/0.5,flowrate1.0mL/min,T＝25℃,λ＝254nm,tR1＝8.373min(minor),tR2＝9.275min(major)；>99％ee；[α]D 25.2＝46.9(c＝0.68,CH2Cl2).
实施例216：
操作过程如通用步骤11，得到白色固体54.6mg，55％收率，Rf＝0.35(PE/EtOAc＝10/1)；M.P.:159-161℃；1H NMR(400MHz,CDCl3):δ7.92(d,J＝1.2Hz,1H),7.60(s,1H),7.52(dd,J＝8.8,1.6Hz,1H),7.29-7.15(m,6H),7.04(d,J＝2.8Hz,1H),6.73(d,J＝9.2Hz,2H),6.65(d,J＝8.8Hz,2H),6.47(d,J＝2.8Hz,1H),4.96(bs,1H),3.79(s,3H),3.78(s,3H),3.75(s,3H),-0.28(s,9H)；13C NMR(100MHz,CDCl3):δ174.5,152.2,146.8,142.2,140.2,139.5,136.3,129.9,129.4,128.6,128.4,127.7,126.9,123.0,122.0,117.8,114.1,108.7,101.8,74.8,55.8,52.7,33.0,1.8；HRMS(ESI):[M+Na]+Calcd for C30H34N2O3SiNa+:521.2231；found:521.2230；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝95/5,flow rate1.0mL/min,T＝28℃,λ＝254nm,tR1＝10.580min(minor),tR2＝18.277min(major)；>99％ee；[α]D 25.0＝-13.5(c＝0.33,CH2Cl2).
实施例217：
操作过程如通用步骤11，得黄色油状物64.9mg，72％收率，Rf＝0.60(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.85(s,1H),7.32–7.28(m,3H),7.26–7.18(m,4H),7.00(dd,J＝4.8,3.6Hz,1H),6.72(q,J＝9.2Hz,4H),4.92(bs,1H),3.79(s,3H),3.75(s,3H),-0.26(s,9H)；13C NMR(100MHz,CDCl3):δ173.1,152.9,146.2,145.5,142.3,139.9,138.9,128.4,128.0,127.9,127.2,127.1,126.6,118.1,114.2,72.1,55.8,52.9,1.6；HRMS(ESI):[M+H]+Calcd for C25H30NO3SSi+:452.1710；found:452.1701.HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝25℃,λ＝254nm,tR1＝14.136min(minor),tR2＝15.893min(major)；>99％ee；[α]D 24.9＝-66.2(c＝0.15,CH2Cl2)；
实施例218：
操作过程如通用步骤12，得无色油状物51.1mg，57％收率，Rf＝0.72(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.82(s,1H),7.37–7.28(m,3H),7.26–7.23(m,2H),6.91(d,J＝9.2Hz,2H),6.78(d,J＝8.8Hz,2H),4.95(bs,1H),4.43-4.35(m,1H),4.32-4.24(m,1H),3.77(s,3H),1.36(t,J＝6.8Hz,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ168.7,153.6,147.2,139.4,137.7,137.4,129.2,128.4,128.1,127.7,124.8(q,JC-F＝292.6Hz),119.1,114.2,72.8(q,JC-F＝24.6Hz),63.5,55.8,13.9,1.7；19F NMR(376MHz,CDCl3):δ-66.4；HRMS(ESI):[M+H]+Calcd for C23H29F3NO3Si+:452.1863；found:452.1859；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝28℃,λ＝254nm,tR1＝6.594min(minor),tR2＝7.150min(major)；98％ee；[α]D 25.2＝-172.7(c＝1.01,CH2Cl2).
实施例219：
操作过程如通用步骤12，得黄色油状物55.0mg，57％收率，Rf＝0.62(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.51(s,1H),7.34(t,J＝6.8Hz,2H),7.30–7.25(m,3H),6.82(d,J＝9.2Hz,2H),6.74(d,J＝8.8Hz,2H),4.78(bs,1H),4.22(q,J＝6.8Hz,2H),3.75(s,3H),1.70(s,3H),1.30(t,J＝7.2Hz,3H),-0.17(s,9H)；13C NMR(100MHz,CDCl3):δ176.0,152.8,147.3,142.9,140.5,139.7,128.5,128.0,127.2,117.9,114.4,66.3,61.9,55.7,24.0,14.2,1.7；HRMS(ESI):[M+Na]+Calcd for C23H31NO3SiNa+:420.1965；found:420.1967；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝5.858min(major),tR2＝7.838min(minor)；>99％ee；[α]D 25.1＝-349.1(c＝0.38,CH2Cl2).
实施例220：
室温下向反应管中加入对茴香胺(4.0mmol,2.0e quiv)、2-氧代-4-苯基丁酸乙酯(2.0mmol,1.0equiv)和DCM(0.5M)。将所得反应混合物在50℃搅拌40min。完成后，将反应混合物在真空中浓缩。粗产品经快速柱层析(PE/EtOAc/NEt3＝10/1/0.2)纯化，得到黄色油状物(353.2mg,57％)，并通过GC确认。之后的操作过程如通用步骤1，得黄色油状物45.9mg，47％收率，Rf＝0.69(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.57(s,1H),7.34–7.32(m,2H),7.31–7.27(m,1H),7.23–7.18(m,4H),7.15–7.11(m,1H),6.90(d,J＝6.8Hz,2H),6.86(d,J＝9.2Hz,2H),6.79(d,J＝9.2Hz,2H),5.05(bs,1H),4.32–4.23(m,2H),3.78(s,3H),2.71–2.56(m,2H),2.43–2.25(m,2H),1.35(t,J＝7.2Hz,3H),-0.18(s,9H)；13C NMR(100MHz,CDCl3):δ174.5,152.5,147.5,143.1,141.9,140.5,139.5,128.5,128.4,128.4,128.0,127.2,126.0,117.0,114.6,68.2,62.0,55.8,36.4,30.1,14.4.1.9；HRMS(ESI):[M+H]+Calcd for C30H38NO3Si+:488.2615；found:488.2615；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝7.760min(major),tR2＝10.718min(minor)；>99％ee；[α]D 25.0＝-287.6(c＝0.76,CH2Cl2).
实施例221：
操作过程如通用步骤11，得黄色油状物69.3mg，80％收率，Rf＝0.67(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.63(d,J＝7.2Hz,2H),7.50(s,1H),7.35(t,J＝6.8Hz,2H),7.31–7.28(m,1H),7.26–7.19(m,3H),7.12(d,J＝7.2Hz,2H),6.84(t,J＝8.8Hz,2H),6.61–6.56(m,2H),5.09(bs,1H),3.78(s,3H),-0.29(s,9H)；13C NMR(100MHz,CDCl3):δ173.9,156.2(d,JC-F＝234.2Hz),147.2,141.6,141.4(d,JC-F＝1.5Hz),139.6,138.4,129.3,128.4,128.3,128.1,127.9,127.2,117.3(d,JC-F＝7.7Hz),115.0(d,JC-F＝21,9Hz),74.5,53.0,1.6；19F NMR(376MHz,CDCl3):δ-127.4；HRMS(ESI):[M+H]+Calcd for C26H29FNO2Si+:434.1946；found:434.1947；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flowrate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝8.196min(minor),tR2＝8.857min(major)；>99％ee；[α]D 25.3＝-16.0(c＝0.53,CH2Cl2).
实施例222：
操作过程如通用步骤11，得黄色油状物72.8mg，71％收率，Rf＝0.72(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.63(d,J＝6.8Hz,2H),7.58(s,1H),7.38(t,J＝7.2Hz,2H),7.35–7.29(m,3H),7.26–7.22(m,1H),7.17(d,J＝7.2Hz,2H),7.13(t,J＝8.0Hz,1H),6.60(d,J＝8.4Hz,2H),6.56(s,1H),5.39(bs,1H),4.35–4.21(m,2H),1.29(t,J＝7.2Hz,3H),-0.25(s,9H)；13C NMR(100MHz,CDCl3):δ173.1,149.9(q,JC-F＝2.3Hz),147.4,146.8,141.5,139.5,137.8,129.5,129.2,128.5,128.4,128.2,127.9,127.2,120.6(q,JC-F＝254.7Hz),114.7,109.6,108.6,74.3,62.6,14.0,1.7；19F NMR(376MHz,CDCl3):δ-57.4；HRMS(ESI):[M+H]+Calcd for C28H31F3NO3Si+:514.2020；found:514.2021；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate0.5mL/min,T＝30℃,λ＝254nm,tR1＝11.745min(minor),tR2＝12.263min(major)；99％ee；[α]D 25.3＝18.8(c＝0.34,CH2Cl2).
实施例223：
在室温氮气氛围下，向预先烘干的反应管中依次加入酮酸酯(0.2mmol,1.0equiv)、无水DCM(0.2M,1.0mL)、NMe(TMS)2(0.24mmol,1.2equiv)和TMSOTf(0.01mmol,5mol％)，在60℃下将混合物搅拌12h。待反应完毕，在减压下浓缩反应混合物获得粗亚胺。移入手套箱，向反应管中依次加入手性配体(12mmol％)、Mn(2.0equiv)、CoI2(10mol％)、MeCN(0.8ml)、iPrOH(0.2ml)和烯基碘代物(2.0equiv)。将反应管从手套箱内移出，封口膜密封，置于油浴中剧烈搅拌一定时间。待反应完毕，反应液使用硅胶过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，所得粗产品使用快速柱层析纯化得到无色油状产物30.0mg,39％收率。Rf＝0.67(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.54(d,J＝7.6Hz,2H),7.41(s,1H),7.32(t,J＝7.6Hz,3H),7.28–7.26(m,2H),7.24–7.21(m,3H),5.07(sept,J＝6.0Hz,1H),2.35(s,3H),1.94(bs,1H),1.26(d,J＝6.4Hz,3H),1.19(d,J＝6.4Hz,3H),-0.17(s,9H)；13C NMR(100MHz,CDCl3):δ173.4,146.3,143.9,140.6,140.5,129.1 128.7,127.9,127.8,127.3,127.0,75.2,69.1,30.7,21.9,21.7,2.4；HRMS(ESI):[M+H]+Calcdfor C23H32NO2Si+:382.2197；found:382.2197；HPLC(ChiralpakAD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝4.800min(minor),tR2＝6.040min(major)；99％ee；[α]D 25.3＝-11.9(c＝0.54,CH2Cl2).
实施例224：
操作过程如通用步骤11，得黄色油状物70.2mg，68％收率，Rf＝0.66(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.68(s,1H),7.62(d,J＝7.2Hz,2H),7.34–7.27(m,5H),7.26–7.20(m,3H),6.70(d,J＝8.8Hz,2H),6.57(d,J＝8.8Hz,2H),4.98(sept,J＝6.4Hz,1H),4.80(bs,1H),3.73(s,3H),1.17(d,J＝6.4Hz,3H),1.04(d,J＝6.0Hz,3H),0.65(t,J＝8.0Hz,9H),0.30(q,J＝7.6Hz,6H)；13C NMR(100MHz,CDCl3):δ173.1,152.4,145.7,141.5,140.1,139.9,138.9,130.0,128.1,127.8,127.7,127.7,127.1,117.1,114.2,75.2,70.0,55.9,21.7,21.4,7.8,5.4；HRMS(ESI):[M+H]+Calcd for C32H42NO3Si+:516.2928；found:516.2928；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝28℃,λ＝254nm,tR1＝7.490min(minor),tR2＝8.220min(major)；99％ee；[α]D 24.6＝22.5(c＝0.45,CH2Cl2).
实施例225：
操作过程如通用步骤11，得无色油状物51.8mg，50％收率，Rf＝0.66(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.70(s,1H),7.66(d,J＝7.6Hz,2H),7.32(d,J＝6.8Hz,2H),7.29–7.26(m,2H),7.25–7.20(m,2H),7.16(d,J＝7.2Hz,2H),6.70(d,J＝9.2Hz,2H),6.58(d,J＝9.2Hz,2H),5.00(sept,J＝6.4Hz,1H),4.97(bs,1H),3.74(s,3H),1.16(d,J＝6.4Hz,3H),1.14(d,J＝6.0Hz,3H),0.60(s,9H),0.04(s,3H),-0.21(s,3H)；13C NMR(100MHz,CDCl3):δ173.2,152.4,147.5,141.4,140.3,139.7,139.1,130.3,128.8,127.8,127.7,127.5,127.2,117.5,114.2,75.9,70.0,55.8,28.7,21.7,21.4,18.4,0.5,0.2；HRMS(ESI):[M+H]+Calcd for C32H42NO3Si+:516.2928；found:516.2925；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate0.5mL/min,T＝30℃,λ＝254nm,tR1＝14.987min(minor),tR2＝15.627min(major)；>99％ee；[α]D 24.8＝93.1(c＝0.53,CH2Cl2).
实施例226：
操作过程如通用步骤11，得淡黄色固体84.9mg，79％收率，Rf＝0.67(PE/EtOAc＝10/1)；M.P.:41-43℃；1H NMR(400MHz,CDCl3):δ7.67–7.65(m,3H),7.36–7.28(m,3H),7.21–7.15(m,1H),7.10–7.08(m,4H),7.06–7.00(m,3H),6.88(d,J＝7.2Hz,2H),6.75(d,J＝8.8Hz,2H),6.59(d,J＝9.2Hz,2H),4.98(sept,J＝6.4Hz,1H),4.90(bs,1H),3.76(s,3H),1.20(d,J＝6.0Hz,3H),1.06(d,J＝6.0Hz,3H),0.12(s,3H),-0.01(s,3H)；13C NMR(100MHz,CDCl3):δ172.8,152.3,147.6,140.7,140.5,139.5,139.2,138.8,134.1,129.7,128.5,128.2,127.9,127.8,127.5,127.1,126.7,117.2,114.2,74.9,70.2,55.9,21.7,21.3,1.1,0.4；HRMS(ESI):[M+H]+Calcd for C34H38NO3Si+:536.2615；found:536.2619；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝9.000min(minor),tR2＝10.514min(major)；>99％ee；[α]D 24.9＝-39.1(c＝0.52,CH2Cl2).
实施例227：
操作过程如通用步骤11，得到白色固体80.5mg，83％收率，Rf＝0.67(PE/EtOAc＝10/1)；M.P.:85-86℃；1H NMR(400MHz,CDCl3):7.67(d,J＝7.2Hz,2H),7.53(s,1H),7.34(t,J＝7.2Hz,2H),7.30–7.26(m,1H),7.09–7.03(m,4H),6.73(d,J＝8.8Hz,2H),6.61(d,J＝8.8Hz,2H),5.07(sept,J＝6.4Hz,1H),4.91(bs,1H),3.75(s,3H),2.33(s,3H),1.30(d,J＝6.0Hz,3H),1.12(d,J＝6.0Hz,3H),-0.26(s,9H)；13C NMR(100MHz,CDCl3):δ173.1,152.2,146.6,141.8,139.5,139.1,136.9,136.6,129.5,128.5,128.0,127.8,117.5,114.1,74.7,70.1,55.8,21.9,21.4,21.3,2.0；HRMS(ESI):[M+Na]+Calcd for C30H37NO3SiNa+:510.2435；found:510.2435；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flowrate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝7.719min(minor),tR2＝8.116min(major)；98％ee；[α]D 24.8＝-30.1(c＝0.84,CH2Cl2)；
实施例228：
操作过程如通用步骤11，得无色油状物67.3mg，67％收率，Rf＝0.66(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.65(d,J＝7.2Hz,2H),7.49(s,1H),7.33(t,J＝6.8Hz,2H),7.30–7.27(m,1H),7.06(d,J＝8.0Hz,2H),6.80(d,J＝8.8Hz,2H),6.71(d,J＝8.8Hz,2H),6.60(d,J＝8.8Hz,2H),5.05(sept,J＝6.4Hz,1H),4.90(bs,1H),3.79(s,3H),3.74(s,3H),1.28(d,J＝6.0Hz,3H),1.11(d,J＝6.0Hz,3H),-0.26(s,9H)；13C NMR(100MHz,CDCl3):δ173.0,158.7,152.2,146.2,141.7,139.5,139.1,132.2,129.7,129.4,127.9,127.7,117.4,114.0,113.1,74.7,70.0,55.8,55.2,21.8,21.3,1.9；HRMS(ESI):[M+Na]+Calcdfor C30H37NO4SiNa+:526.2384；found:526.2386；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝12.122min(major),tR2＝22.891min(minor)；>99％ee；[α]D 25.2＝-43.2(c＝0.63,CH2Cl2).
实施例229：
操作过程如通用步骤11，得到白色固体76.6mg，75％收率，Rf＝0.63(PE/EtOAc＝10/1)；M.P.:106-107℃；1H NMR(400MHz,CDCl3):7.64(d,J＝7.2Hz,2H),7.48(s,1H),7.35(t,J＝6.8Hz,2H),7.32–7.27(m,1H),7.24(d,J＝8.4Hz,2H),7.08(d,J＝8.0Hz,2H),6.72(d,J＝8.8Hz,2H),6.59(d,J＝8.8Hz,2H),5.07(sept,J＝6.4Hz,1H),4.89(bs,1H),3.74(s,3H),1.30(d,J＝6.4Hz,3H),1.10(d,J＝6.4Hz,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ172.8,152.4,145.1,143.2,139.4,138.9,138.4,132.9,130.0,129.4,128.1,128.0,127.9,117.5,114.1,74.7,70.2,55.8,21.9,21.4,2.0；HRMS(ESI):[M+H]+Calcdfor C29H35ClNO3Si+:508.2069；found:508.2069；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝10.243min(major),tR2＝13.198min(minor)；>99％ee；[α]D 25.2＝-34.2(c＝0.61,CH2Cl2).
实施例230：
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操作过程如通用步骤11，得黄色油状物72.4mg，67％收率，Rf＝0.67(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.66(d,J＝8.0Hz,2H),7.56(s,1H),7.54(d,J＝8.0Hz,2H),7.37(t,J＝6.8Hz,2H),7.33–7.27(m,3H),6.74(d,J＝8.8Hz,2H),6.61(d,J＝8.8Hz,2H),5.08(sept,J＝6.4Hz,1H),4.89(bs,1H),3.75(s,3H),1.32(d,J＝6.0Hz,3H),1.10(d,J＝6.0Hz,3H),-0.27(s,9H)；13C NMR(100MHz,CDCl3):δ172.7,152.5,144.7,143.9,143.9,139.3,138.9,129.4,129.2(q,JC-F＝34.8Hz),129.0,128.2,128.0,124.8(q,JC-F＝3.7Hz),124.3(q,JC-F＝270.1Hz),117.5,114.1,74.7,70.3,55.8,21.9,21.4,2.0；19F NMR(376MHz,CDCl3):δ-62.4；HRMS(ESI):[M+H]+Calcd for C30H35F3NO3Si+:542.2333；found:542.2335；HPLC(Chiralpak IBN-5):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝7.740min(minor),tR2＝9.597min(major)；99％ee；[α]D 24.8＝-19.8(c＝0.64,CH2Cl2).
实施例231：
操作过程如通用步骤11，得无色油状物77.6mg，77％收率，Rf＝0.66(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.66(d,J＝7.2Hz,2H),7.52(s,1H),7.34(t,J＝6.8Hz,2H),7.31–7.28(m,1H),7.18(t,J＝8.0Hz,1H),6.78–6.68(m,5H),6.61(d,J＝8.8Hz,2H),5.06(sept,J＝6.4Hz,1H),4.90(bs,1H),3.78(s,3H),3.74(s,3H),1.30(d,J＝6.4Hz,3H),1.11(d,J＝6.0Hz,3H),-0.25(s,9H)；13C NMR(100MHz,CDCl3):δ173.0,159.1,152.3,146.3,142.1,141.3,139.5,139.0,129.5,128.8,128.0,127.8,121.1,117.6,114.1,114.1,112.5,74.7,70.2,55.8,55.3,21.9,21.4,2.0；HRMS(ESI):[M+H]+Calcd forC30H38NO4Si+:504.2565；found:504.2568；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝5.646min(major),tR2＝11.691min(minor)；>99％ee；[α]D 24.7＝-60.8(c＝0.55,CH2Cl2).
实施例232：
操作过程如通用步骤11，得无色油状物55.1mg，53％收率，Rf＝0.58(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.97(d,J＝8.0Hz,1H),7.84–7.74(m,5H),7.54–7.47(m,2H),7.40–7.36(m,3H),7.30(t,J＝7.2Hz,1H),7.23(d,J＝6.8Hz,1H),6.79(d,J＝8.8Hz,2H),6.72(d,J＝8.8Hz,2H),5.11(sept,J＝6.4Hz,1H),5.06(bs,1H),3.78(s,3H),1.33(d,J＝6.4Hz,3H),1.23(d,J＝6.0Hz,3H),-0.42(s,9H)；13C NMR(100MHz,CDCl3):δ172.9,152.4,144.8,144.1,139.6,138.8,137.5,133.3,132.2,129.6,128.4,128.2,127.9,127.8,126.4,126.2,126.0,125.8,125.1,117.4,114.3,74.6,70.3,55.9,22.0,21.5,1.7；HRMS(ESI):[M+H]+Calcd for C33H38NO3Si+:524.2615；found:524.2613；HPLC(ChiralpakAD-H):n-Hexane/iPrOH＝98/2,flow rate1.0mL/min,T＝30℃,λ＝220nm,tR1＝8.690min(major),tR2＝21.213min(minor)；>99％ee；[α]D 24.7＝-64.5(c＝0.56,CH2Cl2).
实施例233：
操作过程如通用步骤12，得淡黄色固体70.2mg，77％收率，Rf＝0.66(PE/EtOAc＝10/1)；M.P.:69-70℃；1H NMR(400MHz,CDCl3):7.54(dd,J＝8.4,1.6Hz,2H),7.32–7.23(m,3H),6.65(d,J＝8.8Hz,2H),6.48(d,J＝9.2Hz,2H),6.33(s,1H),5.01(sept,J＝6.4Hz,1H),4.84(bs,1H),3.71(s,3H),1.27(d,J＝6.0Hz,3H),1.09(d,J＝5.2Hz,3H),1.09(m,9H),0.04(s,9H)；
13C NMR(100MHz,CDCl3):δ173.5,159.0,152.0,140.0,139.2,132.6,129.7,127.8,127.5,117.7,113.9,76.7,70.0,55.8,35.0,31.2,21.8,21.3,3.8；
HRMS(ESI):[M+H]+Calcd for C27H40NO3Si+:454.2772；found:454.2773；
HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝4.215min(major),tR2＝8.576min(minor)；99％ee；[α]D 24.9＝34.4(c＝0.65,CH2Cl2).
实施例234：
操作过程如通用步骤12，得淡黄色固体60.6mg，67％收率,Z/E＝17/1,Rf＝0.68(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.54(d,J＝6.8Hz,2H),7.33–7.24(m,3H),6.65(d,J＝8.8Hz,2H),6.46(d,J＝8.8Hz,2H),6.20(t,J＝8.0Hz,1H),5.03(sept,J＝6.4Hz,1H),4.88(bs,1H),3.72(s,3H),2.25–2.16(m,2H),1.35–1.30(m,4H),1.28(d,J＝6.0Hz,3H),1.10(d,J＝6.4Hz,3H),0.89(t,J＝6.8Hz,3H),-0.06(s,9H)；13C NMR(100MHz,CDCl3):δ173.4,152.0,147.4,139.4,139.2,136.9,129.5,127.8,127.5,117.5,113.9,74.3,70.0,55.8,31.8,31.6,22.8,21.9,21.4,14.2,1.0；HRMS(ESI):[M+H]+Calcd for C27H40NO3Si+:454.2772；found:454.2774；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝99/1,flow rate1.0mL/min,T＝30℃,λ＝254nm,tR1＝5.747min(major),tR2＝16.611min(minor)；99％ee；[α]D 25.0＝30.4(c＝0.63,CH2Cl2).
实施例235：
操作过程如通用步骤11，得到黄色固体67.5mg，71％收率，Rf＝0.50(PE/EtOAc＝10/1)；M.P.:142-143℃；1H NMR(400MHz,CDCl3):7.89(d,J＝6.8Hz,2H),7.42–7.35(m,3H),7.25–7.20(m,3H),7.05–7.00(m,5H),6.95(s,1H),6.74–6.72(m,2H),6.68(d,J＝9.2Hz,2H),6.57(d,J＝8.8Hz,2H),5.23(bs,1H),4.80(sept,J＝6.4Hz,1H),3.69(s,3H),1.02(d,J＝6.4Hz,3H),0.99(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ171.8,152.2,138.9,138.8,138.0,137.6,136.2,132.5,130.6,130.5,129.5,128.2,127.9,127.9,127.8,127.7,127.1,117.2,114.4,73.8,70.3,55.7,21.4；HRMS(ESI):[M+H]+Calcd forC32H32NO3Si+:478.2377；found:478.2377；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝11.666min(major),tR2＝18.178min(minor)；98％ee；[α]D 25.0＝-134.5(c＝0.74,CH2Cl2).
实施例236：
操作过程如通用步骤11，得无色油状物33.9mg，67％收率，Rf＝0.45(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):7.87(d,J＝6.8Hz,2H),7.41–7.32(m,3H),7.06–7.02(m,3H),6.93(d,J＝8.8Hz,2H),6.91(s,1H),6.75(d,J＝8.8Hz,4H),6.67(d,J＝9.2Hz,2H),6.55(d,J＝8.8Hz,2H),5.20(bs,1H),4.81(sept,J＝6.4Hz,1H),3.78(s,3H),3.69(s,3H),1.03(d,J＝6.4Hz,3H),1.01(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ171.9,159.0,152.1,139.0,138.5,137.6,136.3,132.4,131.7,130.5,130.0,129.5,127.9,127.8,127.7,127.0,117.1,114.3,113.7,73.9,70.2,55.7,55.2,21.4；HRMS(ESI):[M+H]+Calcdfor C33H34NO3Si+:508.2482；found:508.2484；HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝98/2,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝20.944min(major),tR2＝26.127min(minor)；97％ee；[α]D 25.1＝-136.0(c＝0.42,CH2Cl2).
实施例237：
向预先烘干的反应管中加入手性配体(12mmol％)，Mn(2.0equiv)和酮亚胺(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(5mmol％)、乙腈与相应的醇(4/1，0.2M)、烯基碘代物。将反应管从手套箱内移出，封口膜密封，置于油浴中剧烈搅拌一定时间。待反应完毕，反应液使用硅胶过滤，滤渣使用乙酸乙酯洗涤三次，将滤液旋干，在0℃条件下向所得粗产品中加入1ml THF和3.0equiv TBAF(1M in THF)，然后在室温下反应2h。待反应完毕，使用饱和NH4Cl溶液淬灭，乙酸乙酯萃取，并用盐水洗涤三次，所得粗产品使用快速柱层析纯化得到无色油状产物64.4mg,80％收率，Rf＝0.56(PE/EtOAc＝10/1)。
1H NMR(400MHz,CDCl3):7.46(d,J＝7.6Hz,2H),7.33(d,J＝7.6Hz,2H),7.26–7.13(m,6H),6.91(d,J＝15.6Hz,1H),6.73(d,J＝15.6Hz,1H),6.53(d,J＝8.8Hz,2H),6.41(d,J＝8.8Hz,2H),5.02(bs,1H),4.93(sept,J＝6.4Hz,1H),3.57(s,3H),1.11(d,J＝6.4Hz,3H),0.89(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ172.5,152.1,140.9,139.1,137.0,131.8,128.7,127.8,127.7,127.1,126.9,116.7,114.3,70.0,68.7,55.6,21.7,21.3；HRMS(ESI):[M+Na]+Calcd for C26H27NO3SiNa+:424.1883；found:424.1881；HPLC(ChiralpakIBN-5):n-Hexane/iPrOH＝99.5/0.5,flowrate 1.0 mL/min,T＝30℃,λ＝254 nm,tR1＝18.179 min(major),tR2＝20.934 min(minor)；>99％ee；[α]D 25.2＝-23.9(c＝0.66,CH2Cl2).
实施例238：
操作过程如通用步骤12，得黄色油状物29.0mg，73％收率，Rf＝0.57(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.49(s,1H),7.31–7.24(m,3H),7.16(d,J＝6.8Hz,2H),6.79(d,J＝8.8Hz,2H),6.61(d,J＝8.8Hz,2H),5.11(sept,J＝6.4Hz,1H),4.68(s,1H),4.34(bs,1H),3.76(s,3H),1.30(d,J＝6.4Hz,3H),1.26(d,J＝6.0Hz,3H),0.01(s,9H).13CNMR(100MHz,CDCl3):δ172.6,152.6,144.3,141.2,141.0,139.6,128.5,128.0,127.4,115.1,114.9,69.0,62.5,55.9,22.1,21.9,0.7.HPLC(Chiralpak AD-H):n-Hexane/iPrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝6.787min(major),tR2＝15.127min(minor)；95％ee。
(五)钴催化亚胺的不对称还原氨甲酰基化反应
通用步骤13：
向预先烘干的反应管中加入手性配体(12mol％)，Zn(2.0equiv)和酮亚胺1(1.0equiv)。随后将该反应管移至手套箱中，依次加入CoI2(10mol％)、碘化钠(1.0equiv)、DMF(0.2M)、胺甲酰氯2(2.0equiv)。将反应管从手套箱内移出，封口膜密封，置于30℃油浴中剧烈搅拌一定的时间。待反应完毕，向反应液中加水和乙酸乙酯淬灭，用水洗涤有机相三次，再用EA萃取水相三次。有机层合并，用饱和食盐水洗涤，再使用硫酸钠干燥，旋干所得粗产品使用快速柱层析纯化得到产物3。
实施例239：
操作过程如通用步骤13，得白色固体398.5mg,77％收率；Rf＝0.45(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.73(d,J＝7.2Hz,2H),7.31–7.22(m,3H),6.63(d,J＝8.8Hz,2H),6.59(d,J＝9.2Hz,2H),5.57(bs,1H),5.04(sept,J＝6.0Hz,1H),3.67(s,3H),3.45–3.26(m,4H),1.17(ABq,J＝6.4Hz,6H),1.05(t,J＝7.2Hz,3H),0.73(t,J＝7.2Hz,3H)；13CNMR(100MHz,CDCl3):δ169.5,167.0,152.4,138.3,136.9,129.3,127.8,116.3,114.5,70.3,70.3,55.7,41.6,41.1,21.7,21.4,12.8,12.0；HRMS(ESI):[M+H]+Calcd forC23H31N2O4 +:399.2278；found:399.2278.HPLC(Chiralpak AD-H):n-Hexane/EtOH＝95/5,flow rate 1.0mL/min,T＝40℃,λ＝220nm,tR1＝10.103min(major)tR2＝12.791min(minor)；99％e.e.
实施例240：
操作过程如通用步骤13，得白色固体45.9mg,60％收率；Rf＝0.41(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.73(d,J＝7.2Hz,2H),7.31–7.22(m,3H),6.63(d,J＝9.2Hz,2H),6.54(d,J＝8.8Hz,2H),5.59(bs,1H),4.21(q,J＝6.8Hz,2H),3.67(s,3H),3.49–3.21(m,4H),1.19(t,J＝7.2Hz,3H),1.02(t,J＝7.2Hz,3H),0.72(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ170.0,167.0,152.6,138.2,136.9,129.2,127.9,127.9,116.5,114.5,70.4,62.4,55.7,41.5,41.3,14.0,12.7,12.0；HRMS(ESI):[M+H]+Calcd for C22H29N2O4 +:385.2122；found:385.2122.HPLC(Chiralpak AD):n-Hexane/EtOH＝80/20,flow rate1.0mL/min,λ＝220nm,tR1＝7.964min(major),tR2＝9.433min(minor)；97％e.e.
实施例241：
操作过程如通用步骤13，得黄色固体41.6mg,56％收率；Rf＝0.40(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.71(d,J＝8.0Hz,2H),7.32–7.23(m,3H),6.62(d,J＝8.8Hz,2H),6.53(d,J＝8.8Hz,2H),5.59(bs,1H),3.75(s,1H),3.67(s,3H),3.49–3.20(m,4H),1.01(t,J＝6.8Hz,3H),0.72(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ170.5,166.9,152.7,138.1,136.8,129.0,128.0,127.9,116.6,114.5,70.5,55.6,53.2,41.4,12.7,12.0；HRMS(ESI):[M+H]+Calcd for C21H27N2O4 +:371.1965；found:371.1969.HPLC(Chiralpak AD):n-Hexane/iPrOH＝95/5,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝26.926min(major),tR2＝30.267min(minor)；95％e.e.
实施例242：
操作过程如通用步骤13，得白色固体39.9mg,49％收率；Rf＝0.34(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.28(dd,J＝5.2,0.8Hz,1H),7.18(d,J＝3.2Hz,1H),6.88(dd,J＝4.8,3.6Hz,1H),6.64(d,J＝8.8Hz,2H),6.56(d,J＝8.8Hz,2H),5.72(bs,1H),5.03(sept,J＝6.4Hz,1H),3.67(s,3H),3.45–3.25(m,4H),1.15(dd,J＝18.4,6.4Hz,6H),1.09(t,J＝6.4Hz,3H),0.82(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ169.4,166.4,152.8,140.7,137.8,127.9,127.7,125.7,116.6,114.5,70.9,68.6,55.6,41.6,41.5,21.6,21.2,12.9,12.0；HRMS(ESI):[M+H]+Calcd for C21H29N2O4S+:521.2202；found:521.2208.HPLC(Chiralpak IBN):n-Hexane/iPrOH＝99.5/0.5,flow rate 1.0mL/min,T＝30℃,λ＝220nm,tR1＝35.500min(major),tR2＝41.007min(minor)；92％e.e.
实施例243：
操作过程如通用步骤13，得无色液体27.2mg,42％收率；Rf＝0.67(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ6.73(d,J＝9.2Hz,2H),6.60(d,J＝9.2Hz,2H),4.62(s,1H),4.33–4.25(m,2H),3.72(s,3H),3.47(sept,J＝7.2Hz,2H),3.27(sept,J＝6.8Hz,2H),1.65(s,3H),1.28(t,J＝6.8Hz,3H),1.12(t,J＝7.2Hz,3H),0.97(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ173.5,168.6,152.8,138.3,116.7,114.9,64.7,62.5,55.7,41.7,41.1,22.7,14.2,13.4,12.2；HRMS(ESI):[M+H]+Calcdfor C17H27N2O4 +:322.1963；found:322.1965.HPLC(Chiralpak AD):n-Hexane/EtOH＝95/5,flow rate1.0mL/min,λ＝220nm,tR1＝10.727min(major),tR2＝11.896min(minor)；94％e.e.
实施例244：
操作过程如通用步骤13，得白色固体67.6mg,79％收率；Rf＝0.50(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.62(d,J＝8.8Hz,2H),6.81(d,J＝8.8Hz,2H),6.62(d,J＝8.8Hz,2H),6.52(d,J＝8.8Hz,2H),5.51(s,1H),5.03(sept,J＝6.4Hz,1H),3.76(s,3H),3.66(s,3H),3.41–3.22(m,4H),1.17(dd,J＝11.2,6.4Hz,6H),1.03(t,J＝7.2Hz,3H),0.76(t,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ169.7,167.1,159.1,152.4,138.4,130.6,128.7,116.2,114.5,113.2,70.3,69.8,55.7,55.3,41.6,41.1,21.7,21.4,13.0,12.1；HRMS(ESI):[M+H]+Calcd for C24H33N2O5 +:429.2386；found:429.2384.HPLC(ChiralpakAD):n-Hexane/EtOH＝80/20,flow rate 1.0mL/min,λ＝220nm,tR1＝9.454min(major),tR2＝16.076min(minor)；97％e.e.
实施例245:
操作过程如通用步骤13，得白色固体43.5mg,53％收率；Rf＝0.35(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.67(d,J＝8.8Hz,2H),7.28–7.24(m,2H),6.64(d,J＝9.2Hz,2H),6.50(d,J＝8.8Hz,2H),5.49(s,1H),4.22(q,J＝7.2Hz,2H),3.68(s,3H),3.42–3.24(m,4H),1.20(t,J＝7.2Hz,3H),1.00(t,J＝7.6Hz,3H),0.81(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ169.9,166.4,152.7,137.7,135.4,134.0,130.8,128.0,116.3,114.6,70.1,62.7,55.7,41.4,14.0,12.9,12.0；HPLC(Chiralpak AD):n-Hexane/EtOH＝85/15,flow rate 1.0mL/min,T＝40℃,λ＝220nm,tR1＝7.628min(major),tR2＝10.408min(minor)；88％e.e.
实施例246:
操作过程如通用步骤13，得到无色油状液体47.1mg,46％收率；Rf＝0.35(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ7.73and 7.62(2d,J＝8.4or 7.2Hz,2H),7.47(d,J＝8.4Hz,1H),7.31–7.23(m,1H),6.64and 6.62(2d,J＝5.2Hz,2H),6.53and 6.50(2d,J＝9.2Hz,2H),5.58and 5.47(2s,1H),4.21(q,J＝7.2Hz,2H),3.68and 3.67(2s,3H),3.42–3.23(m,4H),1.20(td,J＝7.2,2.8Hz,3H),1.01(ABq,J＝7.6Hz,3H),0.81and 0.72(2t,J＝6.8or 7.6Hz,3H)；13C NMR(100MHz,CDCl3):δ170.0,169.8,166.9,166.3,152.7,152.5,138.2,137.7,136.9,136.8,136.7,131.4,129.1,127.9,127.8,116.4,116.2,114.6,114.5,94.2,70.3,70.2,62.7,62.4,55.6,41.5,41.3,14.0,14.0,12.9,12.7,12.0；HRMS(ESI):[M+H]+Calcd for C22H29IN2O4 +:511.1097；found:511.1088；HPLC(Chiralpak AD):n-Hexane/iPrOH＝80/20,flow rate 1.0mL/min,λ＝254nm,tR1＝7.312min(major),tR2＝15.833min(minor)；96％e.e.
实施例247:
操作过程如通用步骤13，得到黄色固体51.8mg,59％收率；Rf＝0.47(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.61(d,J＝8.4Hz,2H),7.29(d,J＝8.8Hz,2H),6.63(d,J＝8.8Hz,2H),6.50(d,J＝9.2Hz,2H),5.52(s,1H),4.20(q,J＝7.2Hz,2H),3.68(s,3H),3.49–3.19(m,4H),1.28(s,9H),1.20(t,J＝7.2Hz,3H),1.02(t,J＝7.2Hz,3H),0.72(t,J＝6.8Hz,3H)；13C NMR(100MHz,CDCl3):δ170.2,167.1,152.4,150.6,138.4,133.6,128.7,124.8,116.3,114.5,70.3,62.4,55.6,41.6,41.3,34.5,31.4,14.0,12.7,12.0；HPLC(Chiralpak AD):n-Hexane/iPrOH＝85/15,flowrate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝5.682min(major),tR2＝10.679min(minor)；94％e.e.
实施例248:
操作过程如通用步骤13，得到白色固体66.7mg,74％收率；Rf＝0.43(PE/EtOAc＝10/1)；1H NMR(400MHz,CDCl3):δ8.33(s,1H),7.82–7.75(m,4H),7.48–7.41(m,2H),6.61(ABq,J＝9.2Hz,4H),5.70(s,1H),5.06(sept,J＝6.4Hz,1H),3.66(s,3H),3.48–3.26(m,4H),1.19(dd,J＝8.8,6.0Hz,6H),1.06(t,J＝7.2Hz,3H),0.70(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ169.4,166.9,152.5,138.3,134.7,133.0,132.9,128.8,128.5,127.5,127.3,127.2,126.4,125.9,116.4,114.5,70.4,55.6,41.6,41.1,21.7,21.5,12.8,12.0；HRMS(ESI):[M+H]+Calcd for C27H33N2O4 +:449.2432；found:449.2435.HPLC(ChiralpakAD):n-Hexane/iPrOH＝80/20,flow rate 1.0mL/min,λ＝220nm,tR1＝9.849min(major),tR2＝21.517min(minor)；96％e.e.
实施例249:
操作过程如通用步骤13，得到白色固体62.9mg,76％收率；Rf＝0.58(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.73(d,J＝7.2Hz,2H),7.31–7.23(m,3H),6.50(d,J＝8.4Hz,1H),6.23(d,J＝2.4Hz,1H),6.01(dd,J＝8.4,2.0Hz,1H),5.78(s,1H),5.67(bs,1H),5.05(sept,J＝6.0Hz,1H),3.41–3.27(m,4H),1.18(dd,J＝13.2,6.0Hz,6H),1.06(t,J＝7.2Hz,3H),0.72(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ169.3,166.8,148.0,140.0,139.7,136.8,129.3,127.9,108.4,107.1,100.6,98.0,70.4,70.1,41.6,41.2,21.7,21.4,12.8,12.0；HRMS(ESI):[M+H]+Calcd for C23H29N2O5 +:413.2067；found:413.2071.HPLC(Chiralpak AD):n-Hexane/EtOH＝80/20,flow rate 1.0mL/min,λ＝220nm,tR1＝7.664min(major),tR2＝9.483min(minor)；93％e.e.
实施例250:
操作过程如通用步骤13，得到黄色固体65.1mg,72％收率；Rf＝0.14(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.72(d,J＝6.8Hz,2H),7.30–7.21(m,3H),6.69–5.01(m,4H),5.60(bs,1H),5.03(sept,J＝6.4Hz,1H),3.81(t,J＝4.8Hz,4H),3.40–3.26(m,4H),2.96(bs,4H),1.16(dd,J＝7.6,6.4Hz,6H),1.04(t,J＝7.2Hz,3H),0.72(t,J＝7.2Hz,3H)；13C NMR(100MHz,CDCl3):δ169.5,166.9,143.5,138.6,136.6,129.3,127.7,117.7,115.9,70.3,67.1,51.0,41.6,41.1,21.6,21.3,12.8,11.9；HRMS(ESI):[M+H]+Calcd forC26H36N3O4 +:454.2706；found:454.2720.HPLC(Chiralpak AD):n-Hexane/EtOH＝90/10,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝11.679min(major),tR2＝14.579min(minor)；93％e.e.
实施例251:
操作过程如通用步骤13，得到白色固体48.9mg,65％收率；Rf＝0.49(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.69(dd,J＝8.4,2.0Hz,2H),7.37–7.27(m,3H),6.66(d,J＝9.2Hz,2H),6.53(d,J＝8.8Hz,2H),5.39(bs,1H),5.06(sept,J＝6.4Hz,1H),3.69(s,3H),2.94(s,6H),1.24(d,J＝6.4Hz,3H),1.18(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ169.5,167.7,152.5,138.0,136.4,129.3,127.9,127.7,115.9,114.6,70.7,55.7,37.8,37.3,21.7,21.3；HRMS(ESI):[M+H]+Calcd for C21H27N2O4 +:371.1964；found:371.1965.HPLC(Chiralpak AD):n-Hexane/iPrOH＝90/10,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝13.367min(major),tR2＝16.525min(minor)；91％e.e.
实施例252:
操作过程如通用步骤13，得到白色固体63.0mg,60％收率；Rf＝0.45(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.78(d,J＝6.8Hz,2H),7.31–7.28(m,6H),7.19–7.11(m,5H),6.68–6.65(m,4H),6.52(d,J＝8.8Hz,2H),5.61(bs,1H),4.95(sept,J＝6.4Hz,1H),4.73(d,J＝14.4Hz,2H),4.25(dd,J＝38.0,15.2Hz,2H),3.72(s,3H),1.09(dd,J＝12.4,6.4Hz,6H)；13C NMR(100MHz,CDCl3):δ169.3,168.5,152.5,138.1,136.8,136.2,135.5,129.6,128.8,128.7,128.6,128.5,128.1,128.0,127.9,127.7,127.5,127.5,116.3,114.7,71.0,70.4,55.7,49.9,48.2,21.6,21.3；HRMS(ESI):[M+H]+Calcd for C33H35N2O4 +:523.2591；found:523.2597.HPLC(Chiralpak AD):n-Hexane/iPrOH＝95/5,flow rate1.0mL/min,T＝40℃,λ＝254nm,tR1＝38.959min(major),tR2＝46.500min(minor)；99％e.e.
实施例253:
操作过程如通用步骤13，得到白色固体43.2mg,54％收率；Rf＝0.17(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.72(dd,J＝8.0,2.0Hz,2H),7.32–7.27(m,3H),6.65(d,J＝9.2Hz,2H),6.52(d,J＝8.8Hz,2H),5.07(sept,J＝6.0Hz,1H),3.68(s,3H),3.58–3.39(m,3H),3.16–3.10(m,1H),1.79–1.69(m,3H),1.64–1.58(m,1H),1.23(d,J＝6.0Hz,3H),1.17(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ169.3,166.0,152.3,137.9,136.0,129.4,127.9,127.7,115.7,114.6,71.1,70.6,55.7,47.9,46.5,26.8,23.3,21.7,21.3；HPLC(Chiralpak AD):n-Hexane/iPrOH＝85/15,flow rate1.0mL/min,T＝40℃,λ＝254nm,tR1＝10.574min(major),tR2＝15.637min(minor)；93％e.e.
实施例254:
操作过程如通用步骤13，得到白色固体36.5mg,46％收率；Rf＝0.67(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.75(d,J＝6.8Hz,2H),7.32–7.27(m,3H),6.64(d,J＝8.8Hz,2H),6.51(d,J＝8.8Hz,2H),5.37(bs,1H),5.07(sept,J＝6.4Hz,1H),4.26(sext,J＝6.0Hz,1H),3.68(s,3H),3.48–3.42(m,1H),3.23–3.17(m,1H),1.88(sept,J＝7.2Hz,1H),1.80(sept,J＝6.4Hz,1H),5.67(sept,J＝6.4Hz,1H),1.38(sept,J＝7.2Hz,1H),1.21(dd,J＝19.2,6.4Hz,6H),0.93(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ169.4,165.6,152.4,137.8,136.2,129.5,128.0,127.6,115.8,114.6,71.2,70.7,55.8,55.3,46.5,31.5,24.8,21.7,21.3,18.8；HRMS(ESI):[M+H]+Calcd for C24H31N2O4 +:411.2276；found:411.2278.
实施例255:
操作过程如通用步骤13，得到白色固体60.1mg,73％收率；Rf＝0.32(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.69(dd,J＝8.4,2.0Hz,2H),7.32–7.25(m,3H),6.65(d,J＝9.2Hz,2H),6.55(d,J＝8.8Hz,2H),5.06(sept,J＝6.0Hz,1H),3.86–3.06(m,4H),3.69(s,3H),1.47–1.25(m,6H),1.20(dd,J＝11.2,6.4Hz,6H)；13C NMR(100MHz,CDCl3):δ169.6,166.2,152.4,138.3,136.7,129.2,127.7,116.0,114.5,70.5,55.6,46.8,45.0,25.5,24.4,21.7,21.4；HPLC(Chiralpak AD):n-Hexane/iPrOH＝85/15,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝9.951min(major),tR2＝11.909min(minor)；93％e.e.
实施例256:
操作过程如通用步骤13，得到白色固体38.1mg,44％收率；Rf＝0.48(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.73(d,J＝7.2Hz,2H),7.31–7.24(m,3H),6.65(d,J＝8.8Hz,2H),6.50(d,J＝8.8Hz,2H),5.39(bs,1H),5.05(sept,J＝6.4Hz,1H),3.68(s,3H),3.63(dd,J＝12.0,8.0Hz,1H),3.45–3.06(m,3H),2.47(bs,2H),1.79–1.71(m,1H),1.53–0.87(m,5H),1.81(dd,J＝32.0,6.4Hz,6H)；13C NMR(100MHz,CDCl3):δ169.4,165.8,152.4,137.9,136.2,129.4,127.9,127.6,115.6,114.6,71.1,70.8,55.8,53.9,52.1,44.0,40.8,32.3,31.9,25.4,21.8,21.3；HRMS(ESI):[M+H]+Calcd for C26H33N2O4 +:437.2435；found:437.2438.HPLC(Chiralpak AD):n-Hexane/iPrOH＝85/15,flow rate 1.0mL/min,T＝40℃,λ＝254nm,tR1＝11.218min(major),tR2＝19.265min(minor)；90％e.e.
实施例257:
操作过程如通用步骤13，得到白色固体43.9mg,50％收率；Rf＝0.48(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.69(d,J＝7.2Hz,2H),7.33–7.27(m,3H),6.66(d,J＝8.4Hz,2H),6.45(d,J＝8.8Hz,2H),5.29(bs,1H),5.07(sept,J＝6.4Hz,1H),4.33–4.15(m,2H),4.18–4.08(m,2H),3.69(s,6H),3.22(bs,1H),1.32–1.25(m,3H),1.28(d,J＝5.6Hz,3H)；13C NMR(100MHz,CDCl3):δ172.8,168.6,167.0,152.5,137.7,134.7,129.2,128.2,127.8,115.6,114.7,71.3,69.9,55.7,54.6,52.4,51.6,32.6,21.6,21.3；HPLC(ChiralpakAD):n-Hexane/iPrOH＝80/20,flow rate 1.0mL/min,λ＝220nm,tR1＝18.096min(major),tR2＝33.916min(minor)；89％e.e.
实施例258:
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操作过程如通用步骤13，得到白色固体67.0mg,79％收率；Rf＝0.61(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.73(dd,J＝8.4,5.6Hz,2H),7.31–7.27(m,2H),7.26–7.22(m,1H),6.64(d,J＝8.8Hz,2H),6.53(d,J＝9.2Hz,2H),5.52(bs,1H),5.03(sept,J＝6.0Hz,1H),3.67(s,3H),3.61(bs,2H),3.29(bs,2H),1.59–1.24(m,8H),1.17(dd,J＝11.2,6.4Hz,6H)；13C NMR(100MHz,CDCl3):δ169.6,167.2,152.4,138.3,136.8,129.4,127.8,127.7,116.1,114.6,70.6,70.5,55.7,47.7,28.8,28.1,26.8,25.1,21.7,21.4；HRMS(ESI):[M+H]+Calcd for C25H33N2O4 +:425.2430；found:425.2435.HPLC(Chiralpak AD):n-Hexane/iPrOH＝80/20,flow rate 1.0mL/min,λ＝220nm,tR1＝10.754min(major),tR2＝12.359min(minor)；96％e.e.
实施例259:
操作过程如通用步骤13，得到白色固体60.5mg,65％收率；Rf＝0.41(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.70(d,J＝6.8Hz,2H),7.32–7.29(m,3H),7.07(d,J＝5.2Hz,2H),6.72(bs,1H),6.63(d,J＝8.8Hz,2H),6.53(d,J＝8.4Hz,2H),5.41(bs,1H),4.96(d,J＝54Hz,1H),4.64(d,J＝14.4Hz,1H),4.53(bs,1H),4.19–3.84(m,2H),3.67(s,3H),3.62–3.49(m,1H),2.87–2.46(m,2H),1.12–0.87(m,6H)；13C NMR(100MHz,CDCl3):δ169.5,166.9,152.6,137.9,136.3,131.5,129.2,128.0,127.8,124.7,123.5,116.2,114.6,71.1,70.9,55.6,46.1,42.4,24.8,21.2；HPLC(Chiralpak AD):n-Hexane/iPrOH＝85/15,flow rate 1.0mL/min,T＝40℃,λ＝220nm,tR1＝17.312min(major),tR2＝28.859min(minor)；94％e.e.
实施例260:
操作过程如通用步骤13，得到白色固体60.4mg,57％收率；Rf＝0.35(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.75(d,J＝6.4Hz,2H),7.50–7.48(m,1H),7.32–7.31(m,3H),7.07(d,J＝3.2Hz,2H),6.86(d,J＝5.2Hz,1H),6.69(d,J＝8.0Hz,2H),6.67(d,J＝7.6Hz,2H),5.43(bs,1H),5.10(sept,J＝6.0Hz,1H),4.66(s,2H),3.71(s,3H),2.97(s,3H),1.29(d,J＝5.6Hz,3H),1.21(d,J＝6.4Hz,3H)；13C NMR(100MHz,CDCl3):δ169.4,167.9,152.7,137.6,136.1,135.8,132.7,129.4,128.7,128.3,128.1,127.7,127.6,123.4,116.2,114.7,71.2,70.9,55.7,53.1,35.5,21.8,21.4；HPLC(Chiralpak AD):n-Hexane/iPrOH＝80/20,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝8.219min(major),tR2＝11.675min(minor)；92％e.e.
实施例261:
操作过程如通用步骤13，得到白色固体50.9mg,57％收率；Rf＝0.44(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ8.25(d,J＝8.0Hz,1H),7.76(d,J＝7.2Hz,2H),7.35–7.29(m,3H),7.19(t,J＝8.0Hz,1H),7.14(d,J＝7.2Hz,1H),7.02(t,J＝7.2Hz,1H),6.63(d,J＝8.8Hz,2H),6.57(d,J＝9.2Hz,2H),5.45(bs,1H),5.11(sept,J＝6.0Hz,1H),4.18(q,J＝9.6Hz,1H),3.90–3.83(m,1H),3.65(s,3H),3.09–2.94(m,2H),1.24(d,J＝6.4Hz,3H),1.18(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ169.2,165.9,152.6,143.9,137.3,135.4,131.3,129.6,128.3,127.8,127.6,124.5,124.4,118.3,115.9,114.8,72.2,71.4,55.6,48.3,29.0,21.7,21.3；HPLC(Chiralpak AD):n-Hexane/iPrOH＝80/20,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝7.098min(major)，tR2＝12.389min(minor)；94％e.e.
实施例262:
操作过程如通用步骤13，得到白色固体55.5mg,60％收率；Rf＝0.38(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.68(s,2H),7.24(bs,3H),6.83(d,J＝14.4Hz,4H),6.70(d,J＝8.4Hz,2H),6.35(bs,2H),4.85(bs,1H),3.81(s,3H),3.71(s,3H),3.18(s,3H),1.33(d,J＝6.0Hz,3H),1.00(bs,3H)；13C NMR(100MHz,CDCl3):δ168.5,167.8,159.3,151.9,137.6,136.0 134.9,129.8,127.8,127.3,115.3,114.6,114.1,70.8,55.6,55.5,40.9,21.7,21.0；HPLC(Chiralpak AD):n-Hexane/iPrOH＝95/5,flowrate1.0mL/min,T＝30℃,λ＝254nm,tR1＝31.061min(major),tR2＝35.125min(minor)；94％e.e.
实施例263:
操作过程如通用步骤13，得到白色固体66.0mg,74％收率；Rf＝0.67(PE/EtOAc＝3/1)；1H NMR(400MHz,CDCl3):δ7.68(s,2H),7.35–7.23(m,6H),6.99–6.81(m,2H),6.69(d,J＝8.8Hz,2H),6.32(s,2H),4.90(s,1H),4.60(bs,1H),3.71(s,3H),3.63(q,J＝6.8Hz,2H),1.35(d,J＝6.4Hz,3H),1.03(s,6H)；13C NMR(100MHz,CDCl3):δ168.6,166.6,151.9,140.9,137.5,135.9,129.8,128.8,128.3,127.8,127.3,115.4,114.5,70.8,70.8,55.6,47.8,21.6,21.0,12.6；HPLC(Chiralpak IBN):n-Hexane/iPrOH＝99/1,flow rate 1.0mL/min,T＝30℃,λ＝254nm,tR1＝13.974min(major),tR2＝16.532min(minor)；90％e.e.
实施例264:
操作过程如通用步骤13，得到白色固体40.6mg,45％收率；Rf＝0.23(PE/EtOAc＝5/1)；1H NMR(400MHz,CDCl3):δ7.72(s,2H),7.33–7.28(m,2H),6.64(d,J＝8.8Hz,2H),6.60(d,J＝9.2Hz,2H),5.48(bs,1H),3.67(s,3H),2.19–1.86(m,6H),1.61(d,J＝8.8Hz,2H),1.18(d,J＝6.0Hz,3H),1.14(d,J＝6.0Hz,3H)；13C NMR(100MHz,CDCl3):δ207.8,169.4,164.2,152.8,138.0,129.3,128.3,128.0,115.9,114.8,71.2,60.5,55.6,53.0,48.6,29.8,27.2,21.7,21.3；HRMS(ESI):[M+H]+Calcd for C26H31N2O5 +:451.2227；found:451.2228.HPLC(Chiralpak AD):n-Hexane/iPrOH＝80/20,flow rate 1.0mL/min,λ＝220nm,tR1＝12.533min(major),tR2＝19.079min(minor)；88％e.e.实施例265：PHOX类配体应用于钴催化亚胺的不对称还原烷基化反应
操作过程如通用步骤1，使用L11代替L1，以52％收率，75％ee得到氨基酸酯产物。
对比例1：喹啉-咪唑啉配体应用于钴催化亚胺的不对称还原烷基化反应的对比。
操作过程如通用步骤1，使用L6代替L1及La(OTf)3代替异丙醇作为添加剂，以36％收率，4％ee得到氨基酸酯产物。
对比例2：喹啉-噁唑啉配体应用于钴催化亚胺的不对称还原烷基化反应的对比。
操作过程如通用步骤1，使用L7代替L1及La(OTf)3代替异丙醇作为添加剂，以48％收率，5％ee得到氨基酸酯产物。
对比例3：吡啶-噁唑啉配体应用于钴催化亚胺的不对称还原烷基化反应的对比。
操作过程如通用步骤1，使用L8代替L1及La(OTf)3代替异丙醇作为添加剂，以40％收率，20％ee得到氨基酸酯产物。
对比例4：双噁唑啉配体应用于钴催化亚胺的不对称还原烷基化反应的对比。
操作过程如通用步骤1，使用L9代替L1及La(OTf)3代替异丙醇作为添加剂，以36％收率，15％ee得到氨基酸酯产物。
对比例5：吡啶-双噁唑啉配体应用于钴催化亚胺的不对称还原烷基化反应的对比。
操作过程如通用步骤1，使用L10代替L1及La(OTf)3代替异丙醇作为添加剂，以29％收率，0％ee得到氨基酸酯产物。
Claims (2)
1.一种基于过渡金属催化有机亲电试剂与亚胺的不对称还原加成反应高效合成手性α-氨基酸衍生物的新方法，包含以下操作步骤：以亚胺及有机亲电试剂为起始原料，在保护气体下，加入催化剂、手性配体、还原剂、添加剂和有机溶剂，其化学反应式如下所示：
其中，R1为氢、任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、烯基、炔基；
R2为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、任选取代C1～C20的烷基-氧基，任选取代的C3～C20的环烷基-氧基、任选取代的C6～C20的苄基-氧基、任选取代C6～C20的(杂)芳基-氧基、C1～C20的胺基、氨基、C1～C20的烷基-硫基；
R3为氢、任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基或任选取代C3～C20的杂芳基；C2～C16的酯基、C1～C16的肼基、任选取代C1～C20的硅基、任选取代C1～C20的砜基、任选取代C1～C20的亚砜基；
R为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C3～C20的烯丙基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、任选取代C2～C20的烯基、任选取代C2～C20的炔基；
X为卤素、任选取代C1～C20的醚、任选取代C1～C20的酯基、任选取代C1～C20的酰氧基、任选取代C1～C20的碳酸酯基、任选取代C2～C20的磷酸酯、任选取代C1～C20的磺酰氧基；
其中，R1和R3可以相连成碳环，如下式所述，其中n为0-10；其中，R4为一个或多个独立选自下组的取代基：氢、任选取代的C1～C20的烷基、任选取代的C3～C20的环烷基、任选取代的C6～C20的苄基、任选取代的C5～C20的芳基、任选取代的C3～C20的杂芳基、硝基、C2～C20的酯基、C1～C20的酰胺基、C2～C16的硼酯基、C1～C20的酰基、醛基、氰基、C1～C20的胺基、氨基、C1～C20的烷基-氧基、C1～C20的烷基-硫基、卤素，R4中的任意两个可以相连成碳环或包含一个或多个选自O、N和S的杂原子的杂环；
R1和R2可以相连成包含N原子的杂环；如下式所述，其中，R5为一个或多个个独立选自下组的取代基：氢、任选取代的C1～C20的烷基、任选取代的C3～C20的环烷基、任选取代的C6～C20的苄基、任选取代的C5～C20的芳基、任选取代的C3～C20的杂芳基、硝基、C2～C20的酯基、C1～C20的酰胺基、C2～C16的硼酯基、C1～C20的酰基、醛基、氰基、C1～C20的胺基、氨基、C1～C20的烷基-氧基、C1～C20的烷基-硫基、卤素，R5中的任意两个可以相连成碳环或包含一个或多个选自O、N和S的杂原子的杂环；R6为氢、任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基或任选取代C3～C20的杂芳基；C2～C16的酯基、C1～C16的肼基、任选取代C1～C20的磺酰基；
所述“任选取代”为未被取代、或被如下基团取代：任选取代的C1～C20的烷基、任选取代的C1～C20的烷基-氧基、任选取代的C1～C20的烷基-硫基、卤素、硝基、任选取代的C2～C20的酯基、任选取代的C1～C20的酰基、任选取代的C1～C20的氰基、任选取代的C1～C20的醛基、任选取代的C2～C20的硼酯基、任选取代的C1～C20的酰胺基、任选取代的C1～C20的胺基、氨基，或任选取代的C6～C20的芳基、任选取代的C3～C20的杂芳基、任选取代的C5～C20的苄基；所述“取代”的个数可不做限定；
用*标注的碳为S构型手性碳或R构型手性碳。
2.根据权利要求1所述的制备方法，其特征在于：
所述催化剂为碘化钴(II)、溴化钴(II)、氯化钴(II)、高氯酸钴(II)、乙酰乙酰钴(II)、醋酸钴(II)、二(三苯基膦)碘化钴、碘化镍(II)、溴化镍(II)、氯化镍(II)、高氯酸镍、四氟硼酸镍、六氟磷酸镍、溴化镍(II)乙二醇二甲基醚络合物、氯化镍(II)乙二醇二甲基醚络合物、乙酰丙酮镍及以上钴或镍盐所对应的水合物、氯化亚铜、氯化铜、氯化钯、乙酸钯、氯化铂、溴化铬、氯化铬、双(环戊二烯基)二氯化钛、溴化铁、溴化亚铁、氯化铁、氯化亚铁；优选碘化钴或溴化钴；
和/或，所述配体为以下NPN及PHOX配体中的一种，如下式所述，其中，R7为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基、C2～C20的酯基；R8为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基；R9为一个或多个独立选自下组的取代基：氢、任选取代的C1～C20的烷基、任选取代的C3～C20的环烷基、任选取代的C6～C20的苄基、任选取代的C5～C20的芳基、任选取代的C3～C20的杂芳基、硝基、C1～C20的酰胺基、C2～C16的硼酯基、氰基、C1～C20的胺基、氨基、C1～C20的烷基-氧基、C1～C20的烷基-硫基、卤素；R10为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基；R11为任选取代C1～C20的烷基、任选取代C3～C20的环烷基、任选取代C6～C20的苄基、任选取代C6～C20的芳基、任选取代C3～C20的杂芳基、C2～C20的烯基、C2～C20的炔基；用*标注的碳为S构型手性碳或R构型手性碳；优选NPN配体；
NPN配体
PHOX配体
和/或，所述还原剂为锌粉、锰粉、铟粉、镁粉、四(二甲氨基)乙烯中的一种或一种以上；优选锌粉、锰粉或铟粉；
和/或，所述添加剂为甲醇、乙醇、异丙醇、六氟异丙醇、三氟甲磺酸锌、三氟甲磺酸钪、三氟甲磺酸镧、三氟甲磺酸钕、三氟甲磺酸钇、三氟乙酸、碘化锌、溴化锌、氯化锌、碘化锂、溴化锂、氯化锂、碘化钠、溴化钠、氯化钠、碘化钾、溴化钾、氯化钾、碘化铷、溴化铷、氯化铷、碘化铯、溴化铯、碘化镁、溴化镁、氯化镁、四丁基碘化铵、四丁基溴化铵中的一种或一种以上；优选甲醇、乙醇、异丙醇、碘化钠、碘化锂、四丁基碘化铵中的一种或几种；
和/或，所述有机溶剂可以为乙腈、丙腈、丁腈、苯甲腈、四氢呋喃、2-甲基四氢呋喃、***、甲基叔丁基醚、环戊基甲基醚、二氧六环、乙二醇二甲醚、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲亚砜、N-甲基吡咯烷酮、1,3-二甲基-2-咪唑啉酮、二氯甲烷、氯仿、四氯化碳、1,2-二氯乙烷、苯、甲苯、二甲苯、甲醇、乙醇、丙醇、异丙醇、丁醇、中的一种或一种以上；优选乙腈、四氢呋喃、二氧六环、乙二醇二甲醚、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲醇、乙醇、异丙醇中的一种或几种；
和/或，所述保护气体可以为本领域该类反应常规的保护气体，如所述的保护气体包括氮气、氩气、氦气、氖气、或氪气；
和/或，所述的有机溶剂中的摩尔浓度为0.01～2.0M，优选0.02-0.5M；
和/或，所述的化合物1与化合物2的摩尔比为5:1～1:5，优选1:1-1:4；
和/或，所述的化合物1与所述催化剂的摩尔比为1:0.001～1:0.2，优选1:0.01-1:0.2；
和/或，所述的化合物1与所述添加剂的摩尔比为1:0.5～1:5，优选1:1-1:3；
和/或，所述反应温度可以为本领域该类反应常规的反应温度，如所述的反应温度为0～120℃，优选10-80℃；
和/或，所述反应时间可以为本领域该类反应常规的反应时间，如所述的反应时间为1-48h，优选3-48h。
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