CN100344376C - 可回收的手性易位反应催化剂 - Google Patents
可回收的手性易位反应催化剂 Download PDFInfo
- Publication number
- CN100344376C CN100344376C CNB038135841A CN03813584A CN100344376C CN 100344376 C CN100344376 C CN 100344376C CN B038135841 A CNB038135841 A CN B038135841A CN 03813584 A CN03813584 A CN 03813584A CN 100344376 C CN100344376 C CN 100344376C
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- China
- Prior art keywords
- metal catalyst
- chiral metal
- reaction
- alkyl
- chiral
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003054 catalyst Substances 0.000 title claims abstract description 90
- 238000005649 metathesis reaction Methods 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 43
- 229910052751 metal Inorganic materials 0.000 claims abstract description 41
- 239000002184 metal Substances 0.000 claims abstract description 39
- 150000001336 alkenes Chemical class 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 239000000126 substance Substances 0.000 claims description 25
- 239000000460 chlorine Substances 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 238000005686 cross metathesis reaction Methods 0.000 claims description 15
- 229910052723 transition metal Inorganic materials 0.000 claims description 15
- 150000003624 transition metals Chemical group 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 229910052707 ruthenium Inorganic materials 0.000 claims description 12
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 11
- 125000001931 aliphatic group Chemical group 0.000 claims description 10
- 239000010948 rhodium Substances 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- -1 alkyl sulfide Chemical compound 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 8
- 229910052701 rubidium Chemical group 0.000 claims description 8
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 7
- 229910052750 molybdenum Inorganic materials 0.000 claims description 7
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical group [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 claims description 7
- 229910052721 tungsten Inorganic materials 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 229910052703 rhodium Inorganic materials 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 239000005864 Sulphur Substances 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 239000011733 molybdenum Substances 0.000 claims description 5
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims description 5
- 239000010937 tungsten Substances 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 4
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 150000001768 cations Chemical class 0.000 claims description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
- 238000007152 ring opening metathesis polymerisation reaction Methods 0.000 claims 6
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 230000017105 transposition Effects 0.000 claims 3
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Chemical group 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 11
- 238000005865 alkene metathesis reaction Methods 0.000 abstract description 9
- 125000002524 organometallic group Chemical group 0.000 abstract description 3
- 150000002739 metals Chemical class 0.000 abstract description 2
- 230000009257 reactivity Effects 0.000 abstract description 2
- 239000003446 ligand Substances 0.000 abstract 2
- 238000006798 ring closing metathesis reaction Methods 0.000 abstract 2
- 230000000707 stereoselective effect Effects 0.000 abstract 2
- 238000007142 ring opening reaction Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 41
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 35
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- 239000007787 solid Substances 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 238000004364 calculation method Methods 0.000 description 19
- 239000000376 reactant Substances 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- 239000011780 sodium chloride Substances 0.000 description 16
- 239000003205 fragrance Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000000463 material Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000006555 catalytic reaction Methods 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 11
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 238000010586 diagram Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- HIXQCPGXQVQHJP-UHFFFAOYSA-N nobin Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3N)=C(O)C=CC2=C1 HIXQCPGXQVQHJP-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 7
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 150000004985 diamines Chemical class 0.000 description 6
- WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 4
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical compound CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000013507 mapping Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910001958 silver carbonate Inorganic materials 0.000 description 4
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000001414 amino alcohols Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- HAXUFHXMBCWDPM-UHFFFAOYSA-N fluoromethoxybenzene Chemical compound FCOC1=CC=CC=C1 HAXUFHXMBCWDPM-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
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- 150000003839 salts Chemical class 0.000 description 3
- 239000011949 solid catalyst Substances 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- XNIGURFWNPLWJM-UHFFFAOYSA-N 1-bromo-2-methoxynaphthalene Chemical compound C1=CC=CC2=C(Br)C(OC)=CC=C21 XNIGURFWNPLWJM-UHFFFAOYSA-N 0.000 description 2
- LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 2
- UQRONKZLYKUEMO-UHFFFAOYSA-N 4-methyl-1-(2,4,6-trimethylphenyl)pent-4-en-2-one Chemical group CC(=C)CC(=O)Cc1c(C)cc(C)cc1C UQRONKZLYKUEMO-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 125000004067 aliphatic alkene group Chemical group 0.000 description 2
- 150000008378 aryl ethers Chemical class 0.000 description 2
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- LDLDYFCCDKENPD-UHFFFAOYSA-N ethenylcyclohexane Chemical compound C=CC1CCCCC1 LDLDYFCCDKENPD-UHFFFAOYSA-N 0.000 description 2
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- 125000005843 halogen group Chemical group 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003863 metallic catalyst Substances 0.000 description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- CBDLNOVOFXJEOB-UHFFFAOYSA-N 1-methoxy-4-(4-methoxyphenoxy)benzene Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(OC)C=C1 CBDLNOVOFXJEOB-UHFFFAOYSA-N 0.000 description 1
- KWVPRPSXBZNOHS-UHFFFAOYSA-N 2,4,6-Trimethylaniline Chemical compound CC1=CC(C)=C(N)C(C)=C1 KWVPRPSXBZNOHS-UHFFFAOYSA-N 0.000 description 1
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 1
- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
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- 229910001369 Brass Inorganic materials 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 230000010777 Disulfide Reduction Effects 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000012327 Ruthenium complex Substances 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 150000005347 biaryls Chemical group 0.000 description 1
- 230000002902 bimodal effect Effects 0.000 description 1
- 239000010951 brass Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
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- 238000003776 cleavage reaction Methods 0.000 description 1
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- 210000001787 dendrite Anatomy 0.000 description 1
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- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
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- 239000012046 mixed solvent Substances 0.000 description 1
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- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
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Abstract
本发明涉及用于立体选择性烯烃易位反应的手性金属催化剂,在此易位反应中该催化剂可回收和重复使用。本发明的手性金属基易位催化剂包括多齿光活性或外消旋手性配位基,以使其能够用于不对称合成过程,例如烯类的开环和闭环易位反应(分别为ROM和RCM)。本发明的催化剂是包含一个或多个手性二齿配位基的有机多价金属配位化合物,其表现出超强的反应性和立体选择性。本发明还提供制备该催化剂的方法和将其用于催化立体选择性烯烃易位反应以得到相对高过量的对映异构体或立体异构体的不对称产物的方法。
Description
技术背景
金属催化烯烃易位反应作为出发点用来开发一些区域选择和立体选择方法。在化学合成复杂有机化合物和聚合物中这些方法是重要步骤。特别地,这些反应在小分子合成的医药化学中常常是决定性的步骤。有机金属催化剂,特别是基于锇、钌或钨的过渡金属配位化合物,用于许多这种有机转化反应。用于涉及末端烯烃闭环易位反应(RCM)的不对称合成的钼基手性催化剂的催化活性已有报导,例如见La etal.J.Am.Chem.Soc.,(1998)120,9720。然而,这些催化剂对空气和水分极为敏感,因而限制了它们对一系列含末端烯烃的底物的应用性。此外,由于产物在用色谱方法纯化时的不稳定性,因此从反应产物中分离已有技术的手性易位反应催化剂常常是有问题的。
发明内容
本发明涉及能够催化含末端烯烃和/或中间烯烃的底物的立体选择性合成的烯烃易位反应催化剂。本发明的催化剂既稳定又可回收。更特别的是,本发明涉及用于立体选择烯烃易位反应的手性过渡金属催化剂。本发明还涉及在此易位反应中可回收和可重复使用的手性过渡金属催化剂。本发明的手性过渡金属基易位催化剂包括多齿的光活性或外消旋的手性配位基(以下称为“手性配位基”),这使其能够应用在不对称合成过程中,例如,在烯烃的开环和闭环易位反应中(分别为ROM和RCM)。本发明的催化剂是包含一个或多个手性二齿配位基的有机过渡金属配位化合物,其表现出超强的反应性和立体选择性质。本发明的催化剂可以是单体的、聚合的或枝状的形态,并且能够以立体选择的方式促进不同形式的烯烃易位反应。本催化剂可以有效地从反应混合物中回收并重复使用,因此是可回收的。本发明还提供了制备该催化剂的方法和将其用于催化立体选择烯烃易位反应的方法。
除了形成末端烯烃的能力之外,本发明的催化剂通过催化易位反应来有效形成多取代烯烃,其中以对映体选择的方式提供相对高的对映异构体或立体异构体过量(分别为ee和de)的不对称产物。多取代烯烃可以是二取代、三取代和四取代烯烃。本发明的手性催化剂的聚合和枝状形态提供了可更容易分离的附加优点。因为其对非末端烯烃具有活性,因而可用来合成三和四取代烯烃。本发明的手性催化剂能够被回收(如标准过滤或色谱方法),在产物中没有或仅有痕量有毒金属污染物,并且能够在后续反应中重复使用。
一方面,本发明包括包含具有以下化学式(1)的金属催化剂的组合物:
其中:
M为多价金属。在一个优选实施方案中,M为包括如钌(Ru)、铷(Rb)、铑(Rh)、钼(Mo)或钨(W)的过渡金属。
X包括氧(O)或硫(S);
R包括烷基、烯基、炔基、芳基、芳烷基、烷氧基、烯氧基、炔氧基、芳氧基、烷氧羰基、烷基氨基、烷基硫、烷基磺酰基、烷基亚硫酰基;每个基团可任选以烷基、卤素、烷氧基、芳基或杂芳基基团取代;
R1和R2分别包括吸电子配位基;
a、b、c和d各自包括氢(H)、卤素原子或烷基、烯基、炔基、芳基、芳烷基、烷氧基、烯氧基、炔氧基、芳氧基、烷氧羰基、烷基氨基、烷基硫、烷基磺酰基、烷基亚硫酰基;每个基团可任选以烷基、卤素、芳基或杂芳基基团取代;和
Y包括给电子配位基。在一个实施方案中,Y包括杂环基团或碳烯基团。在一个优选实施方案中,Y为杂脂肪族或杂芳香族配位基、碳烯配位基、膦配位基或化学式(2)的杂环:
其中:R3包括芳香环且Z包括芳香环或杂芳环取代基。
Z包括芳香环或杂芳环取代基。Z键合至Y以及R1或R2。在一个实施方案中,Z是手性的。当Z为联芳基,如1,1’-联二萘基时,Z可以具有结构异构体(旋转对映异构现象),其中手性决定于绕两芳环间单键的空间位阻旋转。
在一个实施方案中,R1或R2是各自分别不相同的阳离子吸电子单价或二价配位基。在另一个实施方案中R1或R2是杂原子。优选R1或R2是氧(O)或硫(S)。在另一个实施方案中R1或R2是卤素。R1和R2优选为氯(Cl)。
在一个实施方案中,M为钌;X为O;R为低级烷基(如,C1-C12直链或支链烷基);R1为杂原子,优选为氧或硫;R2为卤素原子;a、b、c和d各自包括氢或低级烷基(如,C1-C12);Y包括4,5-二氢咪唑-2-叉环或膦基团;以及Z包括1,1’-联二萘基。
在一个优选实施方案中,M为钌;X和R1为O;R为异丙基;R2为氯原子(Cl);a、b、c和d各自包含氢;以及Y包括具有下式(2)的杂环结构:
其中R3包括芳环基团,Z则如上所述。在当前优选实施方案中,R3包括2,4,6-三甲基苯基(mesityl)基团,以及Z如上所述。
附图说明
图1是说明本发明的手性易位催化剂9的x-射线晶体结构的示意图。
具体实施方式
本发明涉及用于立体选择合成的既有效又可重复使用的手性易位催化剂。更具体地,本发明涉及包含具有光活性或外消旋的手性配位基的过渡金属催化剂。一方面,本发明的手性配位基是多齿的,并且包括芳香基和含碳烯的基团。根据本发明的手性配位基可以是含有一个或多个手性中心的纯对映异构体或非对映异构体。根据本发明的手性配位基可以是对映异构体或非对映异构体的外消旋或非外消旋的混合物。优选地,根据本发明的配位基具有至少约85%ee的光纯度。
本发明的手性催化剂是有机金属配位化合物,其包括通过金属配位键与一个或多个本发明的多齿手性配位基相连接的过渡金属。本发明还提供制备该手性催化剂的方法,以及它们在催化从烯烃出发的不对称的、立体选择的烯烃合成上的用途。
本发明的手性催化剂可以是对金属中心、配位基或既对金属又对配位基成手性。
在一个实施方案中,本发明提供过渡金属基配位化合物,包括与本发明的多齿手性配位基配位的过渡金属,如Mo、W、Rh、Rb或Ru(化学式(1))。本发明的手性配位基可以为纯对映异构体、外消旋体或优选具有约85%ee的对映异构体混合物。在一个优选实施方案中,本发明的手性配位基是包括碳烯基和芳基的双齿手性配位基(化学式(2))。
在一个实施方案中,本发明的手性催化剂可由化学式(3)表示,其中M为Ru、Rb、Rh、Mo或W,R4、R5和R6分别为H、烷基、烷氧基、芳基或杂芳基。
本发明的手性催化剂3带有固相金属中心,且能够被制备成高纯度的非对映或对映异构体而无需进一步的光学拆分,并且是在空气中稳定的和可回收的。手性催化剂3有效地促进烯烃底物的不对称开环/交叉易位(cross metathesis)反应,而且能够通过以标准分离技术方法分离产物从而从反应混合物中回收。
本发明的手性易位催化剂3能够通过列于图解1的一般反应顺序合成。在三乙酰硼氢化钠(NaBH(OAc)3)存在下光学纯1,1’-二萘基-氨基酚4和醛5的还原胺化反应得到相应的氨基醇6。氨基醇6到咪唑鎓盐7的转化由两步完成。通过标准过滤在纯化体中得到光学纯的7。光学纯咪唑鎓盐7到催化剂3的转化通过在碳酸银存在下将7与催化失活过渡金属配位化合物8(由本领域公知方法制备)反应来完成。
图解1
Boc=叔丁氧基羰基,i-Pr=异丙基
在一个优选实施方案中,本发明的手性催化剂包括一个与手性配位基配位的Ru金属中心,其中手性配位基包括碳烯基团和含联萘环的芳香基团。该优选实施方案催化剂的化学结构如下式(9)所示。
手性催化剂9带有固相Ru中心,并能够制备成>98%的非对映和对映异构体纯度而无需进一步的光学拆分,并且是在空气中稳定的和可回收的。手性催化剂9有效促进各种底物(包括一般不被目前已知的金属基易位催化剂催化的底物)在空气中的不对称开环/交叉易位反应(AROM/CM),且易于回收和重复使用。
合成非对映异构光学纯的9的代表性实施例如图解2所示。在三乙酰硼氢化钠(NaBH(OAc)3)存在下包括光学纯的4和醛11的还原胺化反应得到分离产率>98%的氨基醇12。12到咪唑鎓盐13的转化包括两步,得到约83%的总产率。通过标准过滤在纯化体中得到光学纯的13。咪唑鎓盐13到催化剂9的转化通过在碳酸银存在下将13与催化失活的Ru配位化合物14反应来完成。经过硅胶色谱后配位化合物9以52%的分离产率生成。
图解2
Boc=叔丁氧基羰基,i-Pr=异丙基
催化剂9是空气稳定的,可通过使用未蒸馏溶剂的硅胶色谱进行纯化,且其非对映和对映异构体纯度由HPLC分析得到(分离为分别>98%的de和ee)。手性配位化合物9通过x-射线晶体结构分析来确定结构特征(图1)。
本发明的手性易位催化剂的典型催化活性示于在烯烃易位反应中的代表性实施例催化剂9的情况(图解3)。手性Ru催化剂9促进底物二烯15和二烯炔酸(dienyne)17的RCM反应,得到环化不饱和产物16和18,分别生成二或三取代烯烃。催化剂9可以通过硅胶色谱高产率回收。其分离之后,9能够被重新使用并不会有明显的活性损失。例如,从16的合成中回收并重复使用的催化剂以相当灵敏的方式影响15的RCM反应(48小时约93%的转化率)并且以约90%的分离收率提供目标产物(约78%的催化剂被回收)。
图解3
本发明的催化剂对于对映体选择易位反应是有效和实用的手性催化剂。由本发明的手性催化剂催化的AROM/CM反应的实施例示于表1。如实施例1所示,在THF中存在10mol%的催化剂9(50℃)下,将19用5倍当量的苯乙烯处理,导致80%ee和71%的分离收率(>98%的反式)的20a生成。Ru催化AROM/CM反应对脂肪族烯烃具有高选择性。对于如1-庚烯的脂肪族烯烃和大空间体积的乙烯基环己烷(2-3项),以>98%ee、>98%的反式和57-60%产率得到20b-c。
本手性催化剂提供的优点包括:(i)高反应后催化剂色谱回收率(约88-96%的收率),(ii)无可观测的来自末端烯烃的均二聚反应或内消旋二烯烃的加成交叉易位反应(CM)的副产物,(iii)可以重复使用回收催化剂,且没有任何明显的对映体选择性和催化活性的损失;和(iv)能够完成采用手性Mo基催化剂一般不能进行的转化(如表1所示)。
表1Ru催化三环降冰片烯的AROM/CM
条目 | R | 温度(℃);时间(h) | 转化率(%);b收率(%)c | 回收率(%)c | 反式∶顺式b | ee(%)d |
123 | Ph an-C5H11 bCy c | 50;1.050;1.550;1.0 | >98;71>98;57>98;60 | 969288 | >98∶2>98∶2>98∶2 | 80>98>98 |
a条件:条目1中5当量末端烯烃;条目2-3中2当量;THF,氮气下。b 1H NMR分析。c色谱后的分离收率。d手性HPLC。
在对映体选择性催化AROM/CM反应中本发明手性催化剂的立体选择性能力示于图解4。例如,用5mol%的手性催化剂9催化21a的转变,在室温、空气中以及使用试剂级(不蒸馏、不脱气)或纯化THF的条件下,得到约95%ee和~66%分离收率(>98%的反式)的22a。当使用0.5mol%的9时,21b反应75分钟得到~96%ee和~76%收率(>98%的反式)的22b。
图解4
实验方法和材料
一般方法
所有涉及手性配位基合成的结晶中间体,包括杂环和二胺的盐酸盐,优选在真空干燥器或含P2O5的干燥枪(Abderhalden pistol)中干燥约12小时以上。反应通常采用蒸馏或脱气的溶剂、在干燥氮气氛下、在烘箱(135℃)和火焰干燥玻璃器皿中,以标准Schlenk或真空线技术(vacuum-line technology)进行。红外(IR)光谱在Perkin-Elmer 781分光光度计上记录,以cm-1记录νmax。峰的特征分为宽(br)、强(s)、中等(m)和弱(w)。1H NMR谱在Varian Gemini 2000(400MHz)光谱仪上记录。相对于四甲基硅烷的化学位移以ppm表示,并以溶剂共振作为内标(CDCl3:δ7.26ppm,(CD3)2SO:δ2.50ppm)。数据报告格式如下:化学位移、多重性(s=单峰,d=双峰,t=三峰,q=四峰,br=宽峰,m=多重峰),耦合常数(Hz)、积分和分配。13C NMR谱在Varian Gemini 2000(100MHz)光谱仪上采用完全质子去耦来记录。相对于四甲基硅烷的化学位移以ppm表示,并以溶剂共振作为内标(CDCl3:δ77.16ppm,(CD3)2SO:δ39.52ppm)。对映异构体比例通过手性HPLC分析(手性技术公司Chiralpak AS,Chiralpak AD,和Chiralpak OD(0.46cm×25cm))与真正外消旋物质对比来确定。见以下进一步的详述。
材料:Cl2Ru(=CH-o-OiPrC6H4)PPh3(14)按已有的报道制备(Kingsbury et al.,J.Am.Chem.Soc.(1999),121,791)。所有其它材料均由商业来源得到并在使用前纯化。四氢呋喃和甲苯从金属钠/苯甲酮羰游基中蒸馏。CH2Cl2、1,2-二氯乙烷、CDCl3、(CD3)2SO、戊烷、己烷、环己烷、三乙基胺、乙醇、异丙醇、苯乙烯、1-庚烯和乙烯基环己烷均从氢化钙中蒸馏。甲醇在氮气下经过Mg蒸馏。丙酮从碳酸钾中蒸馏。二甲基甲酰胺经活化的4分子筛处理储存在氮气中。2,4,6-三甲基苯胺(Aldrich)真空蒸馏。4-溴-2-甲基-2-丁烯(Aldrich)在使用前真空蒸馏至无色油状。氢化钾(Aldrich)以戊烷洗涤,真空干燥并储存于手套箱中。三溴化硼(Aldrich)用冷阱真空蒸馏。甲基碘(Aldrich)和氯甲酸乙酯(Aldrich)从氯化钙中蒸馏。原甲酸三乙酯(Aldrich)从金属钠中蒸馏。cis-5-降冰片烯-endo-2,3-二羧酸酐(Aldrich)从环己烷中重结晶。下列材料从商业来源购买并以得到的状态使用:Mg粉(Strem)、二碳酸二叔丁酯(Advanced Chemtech)、二甲基硫(Aldrich)、碳酸银(I)(Strem)、2-甲氧基萘(Aldrich)、48%HBr(Fisher)、(CH3)2SO(Aldrich)、乙酸(Fisher)、1-羟基-2-萘酸(Aldrich)、(1R,2S,5R)-(-)-薄荷醇(Aldrich)、油中的60%氢化钠(Aldrich)、氢氧化钾(Fisher)、三乙酰基硼氢化钠(Aldrich)和氯化氢气体(AGA)。
硅胶色谱柱由压缩空气驱动并使用得自TSI化学公司(剑桥,美国马萨诸塞州)的硅胶60(230-400目;pH(10%悬浮液)6.5-7.0;表面积500m2/g;孔隙体积0.75ml/g)进行操作。手性催化剂9在有机溶剂中形成暗褐色溶液。在视觉观察上,色谱如同柱上的褐色条带一样行进,并且通过简单的视觉观测就可明显发现洗脱液级分中催化剂的存在。在烯烃易位反应之后的纯化和回收使用试剂级溶剂于空气中进行。用于催化剂洗提的合适的混合溶剂包括:4∶1己烷∶EtOAc、3∶1己烷∶Et2O、和100%CH2Cl2(Rf值~0.15-0.30)。对极性反应产物而言,反应混合物在CH2Cl2中穿过硅胶短塞以从反应产物中分离催化剂,并借助第二色谱柱来分离有机物质。
通过采用(1R,2S,5R)-(-)-薄荷醇作为手性辅助剂的非对映选择二芳基偶合反应来实施外消旋的4的合成方法。
本发明通过以下实施例进行说明,但这不意味着受到任何限制。
实施例
实施例1
1-溴-2-甲氧基萘。根据文献方法制备。Majetich,G.;Hicks,R.;Reister,S.,J.Org.Chem.(1997),62,4321-4326。
IR(NaCl):3047(w),2972(m),2943(m),2843(m),1622(s),1596(m),1501(s),1467(m),1454(m),14.40(w),1353(m),1335(m),1271(s),1247(w),1219(m),1187(m),1173(w),1153(w),1064(s),1023(m),892(m),840(m),813(m),803(s),763(m),743(s),518(m).
1H NMR(400MHz,CDCl3):δ8.19(d,J=8.6Hz,1H),7.75(t,J=8.5Hz,2H),7.53(t,J=8.2Hz,1H),7.36(t,J=7.9Hz,1H),7.22(d,J=9.0Hz,1H),3.98(s,3H)。
13C NMR(100MHz,CDCl3):δ153.88,133.25,130.94,129.09,128.16,127.86,126.24,124.43,113.74,108.78,57.17。
HRMS计算值C11H9BrO:235.9837.实测值:235.9838。
分析计算值C11H9BrO:C,55.72;H,3.83.实测值:C,55.66;H,3.82。
实施例2
1-甲氧基萘甲酸甲酯。根据描述于文献Hattori,T.;Hotta,H.;Miyano,S.Bull.Chem.Soc.Jpn.(1993),66,613-622的方法制备。
IR(NaCl):3058(w),2997(w),2948(m),2846(w),1725(s),1628(m),1597(m),1570(m),1504(m),1466(m),1445(m),1434(m),1373(s),1343(s),1279(s),1239(s),1214(m),1191(m),1153(m),1133(s),1084(s),1001(m),829(m),802(m),787(m),768(s),715(w)。
1H NMR(400MHz,CDCl3):δ8.30-8.26(m,1H),7.87-7.84(m,2H),7.62(d,J=8.6Hz,1H),7.61-7.54(m,2H),4.07(s,3H),3.99(s,3H)。
13C NMR(100MHz,CDCl3):δ166.85,158.44,136.93,128.47,128.02,126.83,126.68,123.78,123.77,119.34,63.56,52.41.
HRMS计算值C13H12O3:216.0786.实测值:216.0787.
分析计算值C13H12O3:C,72.21;H,5.59.实测值:C,72.50;H,5.52。
实施例3
1-(-)-薄荷氧基-2-萘甲酸-(-)-薄荷酯根据描述于文献Hattori,T.;Hotta,H.;Miyano,S.Bull.Chem.Soc.Jpn.(1993),66,613-622的方法制备。
IR(NaCl):3058(w),2954(s),2956(s),2869(m),1719(s),1625(w),1598(w),1568(w),1502(w),1457(m),1387(m),1371(m),1342(m),1319(m),1277(s),1235(s),1215(m),1203(m),1181(w),1148(s),1137(s),1098(m),1081(s),1038(w),1007(w),983(m),962(m),920(w),823(w),801(w),766(m),741(w).
1H NMR(400MHz,CDCl3):δ8.32(d,J=8.5Hz,1H),7.81(d,J=7.7Hz,1H),7.67(d,J=8.6Hz,1H),7.56-7.48(m,3H),5.04(td,J=10.9,4.4Hz,1H),4.34(td,J=10.9,4.2Hz,1H),2.67(quintetd,J=6.8,2.2Hz,1H),2.21-2.16(m,1H),2.05(quintetd,J=7.2,2.7Hz,1H),1.79-1.52(m,7H),1.28-0.83(m,23H),0.74(d,J=6.6Hz,3H).
13C NMR(100MHz,CDCl3):δ166.77,154.10,136.24,130.12,127.86,127.74,126.22,126.00,124.56,122.40,121.15,82.11,74.59,49.64,47.27,41.17,39.97,34.59,34.46,31.67,31.61,26.38,25.82,23.50,23.42,22.24,22.22,21.60,21.04,16.77,16.56.
HRMS计算值C31H44O3:464.3290.实测值:464.3290.
分析计算值C31H44O3:C,80.13;H,9.54.实测值:C,80.22;H,9.63.
实施例4
(S)-2’-甲氧基-1,1’-联二萘-2-羧酸-(-)-薄荷酯。在100ml圆底烧瓶中将Mg粉(1.30g,58.2mmol)悬浮于5ml THF中并用套管以1-溴-2-甲氧基萘溶液(4.60g,19.4mmol于20ml THF中)处理。回流搅拌该混合物1.5小时。加入苯(25ml)并且将该混合物在0℃下用套管转移到1-(-)-薄荷氧基-2-萘甲酸-(-)-薄荷酯溶液中(7.64g,16.4mmol于15ml苯中)。移除冰浴并在22℃搅拌得到的溶液3天。然后加入50ml饱和氯化铵溶液结束混合物的反应。以100ml水和100ml苯稀释该混合物并将其转移到分液漏斗。各以一倍体积的水和饱和氯化钠溶液洗涤有机层。然后将溶液经MgSO4干燥、过滤并浓缩成黄色的稠油。在直径10cm长20cm的硅胶色谱柱上以20∶1的己烷∶Et2O(Rf=0.15)纯化,得到亮白固体(5.95g,12.8mmol,78%)。
IR(NaCI):3059(m),3003(w),2954(s),2933(s),2868(s),1721(s),1697(s),1622(m),1294(s),1510(s),1461(s),1433(m),1367(m),1336(s),1321(s),1271(s),1250(s),1213(w),1180(m),1147(s),1136(s),1127(s),1084(s),1054(m),1038(w),1021(m),1008(w),982(m),963(m),907(w),869(w),832(m),808(s),788(w),768(s),738(s),704(w).
1H NMR(400MHz,CDCl3):δ8.14(d,J=8.6Hz,1H),7.99(m,2H),7.94(d,J=8.1Hz,1H),7.85(d,J=8.2Hz,1H),7.53(t,J=7.5Hz,1H),7.42(d,J=9.0Hz,1H),7.36(d,J=8.4Hz,1H),7.29(t,J=7.8Hz,2H),7.17(dd,J=8.4,7.2Hz,1H),6.97(d,J=8.4Hz,1H),4.49(td,J=10.8,4.4Hz,1H),3.75(s,3H),1.55-1.15(m,5H),0.91-0.48(m,11H),-0.21(q,J=12.3Hz,1H).
13C NMR(100MHz,CDCl3):δ167.60,154.32,136.60,135.19,134.31,133.07,129.94,129.38,129.14,128.10,127.98,127.83,127.63,126.66,126.62,126.62,126.52,124.97,123.58,122.40,113.29,74.41,56.51,46.68,39.67,34.19,31.11,25.65,22.90,21.98,21.06,15.82.
HRMS计算值C32H34O3:466.2508.实测值:466.2508.
分析计算值C32H34O3:C,82.37;H,7.34.实测值:C,82.13;H,7.30.
实施例5
(S)-2’-甲氧基-1,1’-联二萘-2-羧酸。将KOH(18.7g,333mmol,20倍当量)的纯乙醇(167ml)溶液通过漏斗倒入含有(S)-2’-甲氧基-1,1’-联二萘-2-羧酸-(-)-薄荷酯(7.8g,16.7mmol)的500ml圆底烧瓶中。该烧瓶装有回流冷凝器并通入氮气。用加热套加热使不溶的酯逐渐溶解,形成亮黄色溶液。回流搅拌该溶液24小时,直至混合物的TLC(薄层色谱)分析指出没有起始物质存在。将反应混合物冷却到22℃并浓缩到体积<15ml。该溶液以250ml水稀释并用三份200ml Et2O洗涤(弃去有机层)。然后,用浓盐酸将水层酸化至pH<2,得到大量沉积的絮状白色沉淀。以三份200ml Et2O从所述的水层萃取出该固体。合并这些有机层,经MgSO4干燥并过滤。浓缩所得的溶液得到亮黄色结晶固体状纯度>98%的酸(5.43g,>98%收率)。
IR(NaCl):3059(br),3013(br),2935(w),2898(w),2838(m),2635(br),2564(br),1691(s),1621(m),1593(m),1566(w),1508(m),1464(m),1432(w),1408(w),1360(w),1332(w),1288(m),1263(s),1249(s),1178(w),1145(m),1130(w),1084(m),1054(w),1020(w),956(w),908(w),835(w),806(m),772(m),752(m),735(m).
1H NMR(400MHz,CDCl3):δ9.60(br,1H,COOH),8.15(d,J=8.8Hz,1H,芳香H),8.01-7.97(m,2H,芳香H),7.94(d,J=8.4Hz,1H,芳香H),7.89(d,J=8.2Hz,1H,芳香H),7.54(m,1H,芳香H),7.37(d,J=9.2Hz,1H,芳香H),7.33-7.21(m,3H,芳香H),7.17(dd,J=7.5,7.5Hz,1H,芳香H),6.89(d,J=8.6Hz,1H,芳香H),3.68(s,3H,ArOCH3).
13C NMR(100MHz,CDCl3):δ154.30,138.21,135.65,133.89,133.07,129.72,129.07,128.14,128.09,128.04,127.88,126.85,126.61,124.94,123.61,121.59,113.74,56.72.
HRMS计算值C22H16O3:328.1099.实测值:328.1098.
分析计算值C22H16O3:C,80.47;H,4.91.实测值:C,80.24;H,4.96.
实施例6
(S)-2-氨基-2’-甲氧基-1,1’-联二萘。将(S)-2’-甲氧基-1,1’-联二萘-2-羧酸(5.43g,16.5mmol)、83ml丙酮和Et3N(2.53ml,18.2mmol,1.10当量)装入250ml圆底烧瓶中,并将得到的溶液冷却到-15℃(CO2/乙二醇浴)。随后逐滴滴加氯甲酸乙酯(1.89ml,19.8mmol,1.20当量)导致形成絮状白色沉淀。该悬浮液在-15℃搅拌30分钟,直到加入溶于16ml水中的NaN3(3.22g,49.5mmol,3.0当量)溶液时。在-15℃再搅拌90分钟后,以150ml水稀释该反应混合物并用125ml冷苯分三次洗涤。用400ml冷的饱和氯化钠溶液洗涤合并的有机层,经MgSO4干燥,并直接过滤到含1.0g活化4分子筛的500ml圆底烧瓶中。给该烧瓶装上回流冷凝器和加热套并且回流加热该黄铜色溶液2小时。冷却到22℃后,溶液被过滤到另一含有溶于85ml水中的KOH(46.3g,825mmol,50当量)溶液的500ml圆底烧瓶中。将得到的两相混合物剧烈搅拌16小时并转移至分液漏斗中。分离出有机层并用100ml苯洗涤水层两次。将该溶液干燥(MgSO4)、过滤、浓缩得到由1H NMR分析判断的纯度>95%的亮黄色固体。该物质在使用前通常要进一步纯化。将该固体溶解在20-25mlCH2Cl2之后,加入8-10g硅胶并在减压下从该泥浆状液体中移除溶剂。负载产物的硅胶被装在广口硅胶塞上并用1∶1己烷∶Et2O(Rf=0.30)洗提。以极好的收率得到作为亮白固体的题头所述产物(4.74g,96%)。作为选择,未纯化的产物从纯乙醇中重结晶为白色固体(3.95g,80%)。
IR(NaCl):3483(br),3384(m),3056(w),3004(w),2964(w),2939(w),2838(w),1619(s),1591(m),1506(s),1474(w),1463(m),1431(m),1381(m),1352(w),1330(w),1261(s),1246(s),1213(w),1178(w),1146(m),1132(w),1111(w),1076(m),1048(w),1019(w),903(w),811(s),781(w),775(w),749(m),736(m),707(w).
1H NMR(400MHz,CDCl3):δ8.00(d,J=9.0Hz,1H,芳香H),7.89(d,J=8.2Hz,1H,芳香H),7.81-7.77(m,2H,芳香H),7.48(d,J=9.0Hz,1H,芳香H),7.35(m,1H,芳香H),7.28-7.13(m,4H,芳香H),7.14(d,J=8.6Hz,1H,芳香H),6.99-6.96(m,1H,芳香H),3.79(s,3H,ArOCH3),3.57(s,2H,ArNH2).
13C NMR(100MHz,CDCl3):δ155.59,142.03,134.30,133.76,130.13,129.72,129.14,128.38,128.19,128.14,127.04,126.42,125.15,124.43,124.06,122.29,119.00,118.35,114.49,114.05,57.01.
HRMS计算值C21H17NO:299.1310.实测值:299.13l0.
分析计算值C21H17NO:C,84.25;H,5.72;N,4.68.实测值:C,84.07;H,5.77;N,4.68.[a]D 25-67.11°(c=1.041,CHCl3).
实施例7
(S)-2-氨基-2’-羟基-1,1’-联二萘(NOBIN)(10)。在250ml圆底烧瓶中溶解(S)-2-氨基-2’-甲氧基-1,1’-联二萘(4.30g,14.4mmol)于144ml CH2Cl2中并将该无色溶液冷却到0℃。然后用注射器逐滴加入三溴化硼(BBr3)(5.44ml,57.5mmol,4.0当量),此时溶液轻微变黄。该反应混合物加热至22℃并搅拌12小时,此时以如下所述方法测试少量试样以证实不存在起始物(1H NMR分析)。将该反应混合物冷却到0℃并小心地倾入含100ml 5M NaOH的1L分液漏斗中。在消耗掉过量BBr3后,将该混合物以200ml水和200ml乙酸乙酯稀释。移除有机层,并用100ml乙酸乙酯洗涤水层两次。混合的有机层用MgSO4干燥,过滤并浓缩成以1H NMR分析鉴定纯度>95%的白色固体。该物质在还原胺化之前进一步纯化。在将该固体溶解于最小1∶1EtOAc∶CH2Cl2后(大约50~60ml),加入25g硅胶,随后从该浆状液体中减压移除溶剂。将该负载产物的硅胶装在广口硅胶塞上并以3∶1己烷∶EtOAc(Rf=0.29)洗提。该过程得到白色固体产物(3.34g,96%)。作为选择,未纯化产物也可以从纯乙醇中重结晶为白色固体(3.07g,75%)。
IR(NaCI):3396(m),3323(m),3300(br),3057(w),1616(s),1594(s),1508(m),1471(w),1461(w),1381(s),1344(w),1273(w),1214(m),1168(m),1142(m),1128(m),910(w),820(s),775(w),752(w),727(s)。
1H NMR(400MHz,CDCl3):δ7.93(d,J=9.0Hz,1H,芳香H),7.90-7.84(m,2H,芳香H),7.82-7.79(m,1H,芳香H),7.38(d,J=9.0Hz,1H,芳香H),7.35(ddd,J=8.0,6.8,1.5Hz,1H,芳香H),7.30-7.16(m,4H,芳香H),7.15(d,J=8.8Hz,1H,芳香H),7.07-7.03(m,1H,芳香H),5.13(s,1H,ArOH),3.74(s,2H,ArNH2)。
13C NMR(100MHz,CDCl3):δ151.97,143.90,134.27,133.34,130.78,130.51,129.67,128.52,128.46,128.40,127.47,127.11,124.69,123.88,123.80,122.91,118.31,117.84,114.42,108.62。
HRMS计算值C20H15NO:285.1154,实测值:285.1154。
分析计算值C20H15NO:C,84.19;H,5.30;N,4.91.实测值:C,83.97;H,5.18;N,4.84。[α]D 25-56.38°(c=1.002,CHCl3).
实施例8
N-(叔-丁氧基羰基)-2,4,6-三甲基苯基胺。在100ml圆底烧瓶中装入2,4,6-三甲基苯胺(3.59g,26.6mmol)和20ml THF。将二碳酸二叔丁酯(5.81g,26.6mmol,1.0当量)称重后加入25ml梨形烧瓶并溶解于30ml THF中。通过移液管将酐转移到芳基胺溶液中。用3ml部分THF来完成转移(最终浓度0.5M)。该反应烧瓶装有回流冷凝器和加热套,并将得到的无色溶液回流加热7天。此时,取得该反应混合物的1H NMR谱以最终证实不存在起始的苯胺。真空移除溶剂得到最优纯度>98%的白色结晶固体产物(6.25g,>98%),该产物以8∶1己烷∶EtOAc(Rf=0.20)通过硅胶色谱进行额外纯化。尽管有UV活性,但该产物可用茚三酮TLC染色来检测。
IR(NaCI):3303(br),3004(w),2978(m),2922(m),2862(w),1698(s),1611(w),1507(s),1458(m),1391(m),1366(s),1308(w),1248(s),1171(s),1055(m),1022(m),904(w),849(m),777(w),707(w)。
1H NMR(400MHz,CDCl3):δ6.88(s,2H,芳香H),5.89(br,1H,ArNH),2.27(s,3H,p-CH3),2.23(s,6H,o-CH3),1.52(br,9H,OC(CH3)3)。
13C NMR(100MHz,CDCl3):δ153.95,136.45,135.63,131.48,128.85,79.69,28.40,20.95,18.31。
HRMS计算值C14H21NO2:235.1572.实测值:235.1567。
分析计算值C14H21NO2:C,71.46;H,8.99.实测值:C,71.56;H,8.76。
实施例9
N-(叔-丁氧基羰基)-N-(3-甲基-2-丁烯基)-2,4,6-三甲基苯基胺。在100ml圆底烧瓶内加入20ml DMF的KH(1.27g,31.7mmol,1.10当量)悬浮液并冷却至0℃。将芳基碳酸酯(6.67g,28.7mmol,1.0当量)溶解于DMF(40ml)中并通过套管逐滴加入反应混合物中,导致剧烈的气体放出。将得到的混合物加热至22℃并搅拌1小时。接着用注射器逐滴加入4-溴-2-甲基-2-丁烯(3.98ml,34.5mmol,1.20当量),快速产生白色KBr盐的沉淀。在22℃下1小时额外搅拌后,转移该混合物至分液漏斗并以100ml饱和碳酸氢钠、100ml水和200ml Et2O稀释。移除有机层并用150mlEt2O分两次洗涤水层。合并有机层并以一倍体积的饱和氯化钠溶液洗涤。得到的混合物以MgSO4干燥、过滤并浓缩成青铜色的油,由1H NMR分析判定其纯度>95%。该物质在氧化***前可进一步纯化。通过用10∶1己烷∶Et2O(Rf=0.32)的硅胶色谱完成,获得无色油状烯烃(7.85g,90%收率)。在22℃的CDCl3中,该物质以2.4∶1的酰胺旋转异构体的混合物存在。以下1H NMR和13C NMR数据证明该混合物中存在每一种异构体。
IR(NaCl):2975(m),2925(m),2861(w),1698(s),1483(m),1452(m),1390(s),1365(m),1329(w),1305(m),1290(m),1255(m),1239(w),1172(s),1136(m),1043(w),1000(w),870(w),851(w),770(w).
1H NMR(400MHz,CDCl3):δ6.84(s,2H,芳香H),6.81(s,2H,芳香H),5.30(m,1H,烯H),4.04(d,J=7.2Hz,2H,NCH2),3.97(d,J=7.2Hz,2H,NCH2),2.25(s,6H,o-CH3),2.23(s,3H,p-CH3),2.16(s,3H,p-CH3),2.13(s,6H,o-CH3),1.66(s,3H,CHC(CH3)2),1.63(s,3H,CHC(CH3)2),1.51(s,9H,OC(CH3)3),1.46(s,3H,CHC(CH3)2),1.42(s,3H,CHC(CH3)2),1.32(s,9H,OC(CH3)3).
13C NMR(100MHz,CDCl3):δ155.07,154.31,137.91,137.57,136.64,136.27,136.01,135.69,135.22,134.48,129.21,128.78,120.96,120.22,79.68,79.13,47.67,46.50,28.61,28.45,25.81,25.76,21.06,18.33,18.25,17.71,17.59.
HRMS计算值C19H29NO2:303.2198.实测值:303.2201.
分析计算值C19H29NO2:C,75.21;H,9.63;N,4.62.实测值:C,75.50;H,9.76;N,4.55.
实施例10
N-(叔丁氧基羰基)-N-(甲酰甲基)-2,4,6-三甲基苯基胺。将得自实施例10的烯烃(6.07g,20.0mmol,1.0当量)溶解于150ml CH2Cl2和50ml甲醇中(3∶1比例,0.1M)。将固体碳酸氢钠直接加入该溶液中,形成白色悬浮液。在烧瓶装上塑料盖,并在盖上刺入(12英寸)16号和较小号注射器针头以释放气体。冷却烧瓶至-78℃并将臭氧通过注射器针头鼓泡入反应混合物,直到TLC分析指出没有起始物质残留(通常10-15分钟)。将该反应混合物加热至22℃,并用二甲基硫还原(2.90ml,39.5mmol,2.0当量)。在高真空下移除溶剂和过量的二甲基硫。将得到的油状残余物以5∶1己烷∶EtOAc(Rf=0.35)在短(产物夹层)、广口柱(12cm高;10cm直径)上进行硅胶色谱,以良好的收率得到预期的无色、粘滞油状的醛(4.55g,82%)。在TLC板上对该物质进行UV检测很困难,但其很容易用茚三酮染色。在22℃的CDCl3中,该物质以1.6∶1的酰胺旋转异构体的混合物存在。以下1H NMR和13C NMR数据报告该混合物中的每一个共振。
IR(NaCl):3450(br),3369(br),2977(s),2923(s),2863(m),2820(m),2720(w),1737(s),1693(s),1610(w),1486(s),1455(s),1423(s),1368(s),1342(m),1319(s),1302(s),1277(m),1255(s),1224(s),1168(s),1151(s),1068(m),1038(m),988(m),951(w),913(w),874(w),854(m),816(w),773(m),733(w),675(w),625(w),601(w),585(w).
1H NMR(400MHz,CDCl3):69.81(m,1H,CHO),6.89(d,J=0.4Hz,2H,芳香H),6.87(d,J=0.6Hz,2H,芳香H),3.96(d,J=1.6Hz,2H,NCH2),3.95(d,J=1.4Hz,2H,NCH2),2.27(s,6H,o-CH3),2.25(s,3H,p-CH3),2.23(s,3H,p-CH3),2.21(s,6H,o-CH3),1.49(s,9H,OC(CH3)3),1.36(s,9H,OC(CH3)3).
13C NMR(100MHz,CDCl3):8198.87,198.83,155.54,153.67,137.83,137.68,137.64,137.33,135.66,135.25,129.58,129.26,81.59,80.75,59.79,59.22,28.28,28.23,20.99,18.32,18.25.
HRMS计算值C16H23NO3:277.1678.实测值:277.1679.
分析计算值C16H23NO3:C,69.29;H,8.36;N,5.05.实测值:C,69.44;H,8.31;N,5.01.
实施例11
二胺(12)。将(S)-2-氨基-2’-羟基-1,1’-联二萘(NOBIN)(10)(1.004g,3.519mmol,1.0当量)和三乙酰基硼氢化钠(1.492g,7.038mmol,2.0当量)以固体形态加入到100ml圆底烧瓶中并悬浮于30ml的1,2-二氯乙烷中。将所述的醛(976mg,3.25mmol,1.0当量)的10ml 1,2-二氯乙烷溶液用气密注射器逐滴加入1小时。当反应进行时,该固体逐渐溶解。30分钟额外搅拌后,该反应混合物几乎为匀相且TLC分析显示仅有微量的未反应NOBIN(10)。反应可以通过在该混合物中缓慢加入额外的醛来完成(一般过量0.5当量)。当通过TLC分析发现NOBIN(10)完全消耗时,以100ml碳酸氢钠和50ml CH2Cl2稀释该反应混合物。移除有机层,并将水层用100ml CH2Cl2洗涤两次。将合并的有机层经MgSO4干燥、过滤和浓缩。用7∶3的己烷∶Et2O(Rf=0.25)进行硅胶色谱纯化得到高收率的白色泡沫状的受保护二胺(1.85g,96%)。在22℃的CDCl3中,该物质以2.7∶1的酰胺旋转异构体的混合物存在。以下1H NMR和13C NMR数据报告该混合物中的每一个共振。
IR(NaCl):3508(m),3470(m),3394(br),3055(m),2977(s),2927(s),2861(m),1737(m),1693(s),1619(s),1598(s),1573(w),1513(s),1494(s),1464(m),1455(m),1428(m),1393(s),1378(s),1367(s),1344(m),1311(m),1294(m),1268(m),1251(m),1217(m),1203(m),1174(s),1150(s),1080(w),1037(w),1026(w),1008(w),985(w),974(w),855(m),816(m),773(m),747(m),703(w).
1H NMR(400MHz,CDCl3):δ7.94-7.89(m,2H,芳香H),7.87-7.84(m,1H,芳香H),7.82-7.77(m,1H,芳香H),7.35(d,J=9.2Hz,1H,芳香H),7.35-7.29(m,1H,芳香H),7.30(d,J=8.8Hz,1H,芳香H),7.25-7.15(m,3H,芳香H),7.11-7.07(m,1H,芳香H),6.96-6.92(m,1H,芳香H),6.83-6.77(m,1H,芳香H),5.12(s,1H,ArOH),5.06(s,1H,ArOH),4.09(br,1H,ArNH),3.78(br,1H,ArNH),3.61-3.50(m,1H,ArNHCH2),3.45-3.33(m,3H,ArNHCH2),2.24(s,3H,p-CH3),2.22(s,3H,p-CH3),2.09(s,3H,o-CH3),2.07(s,3H,o-CH3),2.05(s,3H,o-CH3),2.03(s,3H,o-CH3),1.51(s,9H,OC(CH3)3),1.23(s,9H,OC(CH3)3).
13C NMR(100MHz,CDCl3):δ155.39,154.15,152.13,144.99,144.78,137.48,137.39,137.06,136.60,135.70,135.60,135.34,135.20,134.33,134.30,133.54,133.40,131.01,130.82,130.59,130.40,129.69,129.50,129.10,129.08,128.46,128.41,128.29,127.73,127.59,127.44,127.21,127.06,126.88,124.65,124.51,123.80,123.64,123.61,122.50,122.16,117.83,117.78,114.16,113.95,113.62,113.56,108.32,107.98,80.55,79.68,49.75,49.04,42.40,42.37,28.58,28.28,20.99,18.13,18.09,18.02,17.99,15.39.
HRMS计算值C36H38N2O3:546.2882.实测值:546.2882.
分析计算值C36H38N2O3:C,79.09;H,7.01;N,5.12.实测值:C,78.90;H,7.26;N,4.94.
实施例12
氯化咪唑鎓(13)。将单保护二胺12(225mg,0.412mmol)在10ml的圆底烧瓶中溶解于4.5ml无水甲醇中并且将得到的无色溶液冷却至-78℃。将无水HCl温和地鼓泡通过该溶液5分钟。然后将反应物加热至22℃并在减压下移除溶剂。得到>98%纯度(1H NMR分析)的白色结晶固体产物(214mg,>98%),将其在真空下在含P2O5的干燥枪中经过回流的异丙醇进行严格干燥(12小时)。
IR(KBr):3396(s),3054(s),2956(s),2731(s),2363(w),1690(w),1619(s),1597(s),1511(s),1484(m),1431(s),1342(m),1272(m),1210(m),1148(m),1025(w),975(w),857(w),877(s),749(s),576(w),424(w).
1H NMR(400MHz,(CD3)2SO):δ9.41(br,1H,ArOH),7.94-7.85(m,3H,芳香H),7.80(d,J=8.1Hz,1H,芳香H),7.39(d,J=9.0Hz,2H,芳香H),7.26(dd,J=7.6,7.5Hz,1H,芳香H),7.19-7.07(m,3H,芳香H),6.93(s,2H,mesityl芳香H),6.88(d,J=8.4Hz,1H,芳香H),6.72(d,J=8.4Hz,1H,芳香H),4.07(br,4H,ArNH2R),3.78-3.70(m,1H,ArNH2CH2),3.66-3.57(m,1H,ArNH2CH2),3.25-3.37(m,2H,ArNH2CH2),2.31(s,6H,o-CH3),2.20(s,3H,p-CH3).
13C NMR(100MHz,(CD3)2SO):δ153.56,143.12,138.32,133.90,133.73,131.71,130.71,130.31,129.38,128.78,128.49,128.06,127.86,127.21,126.18,125.98,124.03,123.73,122.55,121.42,118.96,114.14,114.07,113.69,49.85,20.21,17.61.
HRMS计算值C31H31N2O:447.2346.实测值:447.2346.[α]D 25-27.92°(c=1.018,MeOH).
在25ml圆底烧瓶中,将二胺盐酸盐(725mg,1.40mmol)悬浮于14ml原甲酸三乙酯(0.1M)中。该容器装配有短颈蒸馏头并浸入预热至125℃的油浴中。当反应进行时,有粘性的、树胶状的固体沉积在烧瓶壁上,并在反应混合物中结块。在125℃下搅拌反应混合物并周期性加热蒸馏头(约每30分钟一次)以保证彻底移除乙醇(通常4小时),随后得到白色沉积物。将烧瓶冷却至22℃,用30ml Et2O稀释该混合物并过滤。该沉积物以另外的Et2O(2×10ml)洗涤并在真空下在含P2O5的干燥枪中用回流的异丙醇干燥(573mg白色固体,83%)。
IR(KBr):3422(br),2950(m),2839(m),2677(w),2590(w),1618(s),1590(m),1503(m),1478(w),1434(w),1344(m),1302(w),1276(m),1256(s),1225(w),1213(w),978(w),825(w),755(w),515(w),494(w).
1H NMR(400MHz,(CD3)2SO):δ10.56(br,1H,ArOH),8.67(s,1H,NCHN),8.28(d,J=8.6Hz,1H,芳香H),8.14(d,J=8.2Hz,1H,芳香H),8.04(d,J=9.0Hz,1H,芳香H),7.98(d,J=8.8Hz,1H,芳香H),7.95(d,J=8.2Hz,1H,芳香H),7.64-7.57(m,2H,芳香H),7.41(ddd,J=8.4,7.1,1.1Hz,1H,芳香H),7.32(ddd,J=8.0,6.9,1.1Hz,1H,芳香H),7.26(ddd,J=8.2,6.8,1.3Hz,1H,芳香H),7.14(d,J=8.4Hz,1H,芳香H),6.93(br,2H,mesityl芳香H),6.87(d,J=8.2Hz,1H,芳香H),4.34(dd,J=21.6,10.4Hz,1H,ArNH2CH2),4.20(dd,J=21.6,10.4Hz,1H,ArNH2CH2),4.01(dd,J=11.2,10.4Hz,2H,ArNH2CH2),2.20(s,3H,p-CH3),1.98(br,3H,o-CH3),1.71(br,3H,o-CH3).
13C NMR(100MHz,(CD3)2SO):δ158.24,153.40,139.54,135.25,133.34,133.23,132.93,132.40,130.84,130.75,130.48,129.73,129.16,128.39,128.36,127.97,127.47,127.31,127.26,126.21,123.62,123.37,123.12,118.51,113.01,51.28,50.62,20.46,16.67.
HRMS计算值C32H29ClN2O(M-Cl):457.2280.实测值(FAB on C32H29ClN20):457.2281.
分析计算值C32H29ClN2O:C,77.95;H,5.93;N,5.68.实测值:C,77.68;H,5.82;N,5.59.[α]D 25-15.82°(c=0.9818,DMSO).
实施例13
钌配位化合物(9)。在手套箱中将Cl2Ru(=CH-o-OiPrC6H4)PPH3(14)(288mg,0.495mmol)、碳酸银(I)(136mg,0.495mmol)和配位基盐(7)(244mg,0.495mmol)加入到10ml的圆底烧瓶中。将该容器从手套箱中移出并将该固体悬浮在2.5mlTHF和2.5ml苯(0.10M)中。该烧瓶装有回流冷凝器并浸入预热至75℃的油浴中。搅拌该反应物30分钟,在搅拌期间,该混合物保持为多相体系但是逐渐从亮粉红色变为暗绿/褐色。然后将反应混合物冷却至22℃并通过温和吹入N2浓缩。1H NMR分析发现91%的原始反应混合物转化为在15.98ppm处的新单峰,其对应于9的碳烯质子。该金属碳烯配位化合物通过以CH2Cl2为洗提液(Rf=0.10)的硅胶柱色谱(直径3cm,长10cm)得到分离。减压下移除溶剂得到褐色固体残留物(191mg,52%)。作为选择,将浓缩的CH2Cl2溶液以己烷或戊烷研磨以沉淀出亮褐色粉末状催化剂。
IR(NaCl):3049(w),2974(w),2917(w),1615(w),1588(m),1575(w),1559(w),1506(w),1490(w),1475(s),1455(m),1424(s),1404(w),1384(w),1374(w),1355(m),1342(m),1312(w),1296(m),1275(s),1239(m),1211(w),1155(w),1112(m),1097(w),981(w),937(w),839(w),825(w),784(w),746(s),684(w).
1H NMR(400MHz,CDCl3):δ15.96(s,1H,RuCH),8.22(d,J=8.7Hz,1H,芳香H),8.07(d,J=8.6Hz,1H,芳香H),8.01(d,J=8.4Hz,1H,芳香H),7.74(d,J=7.6Hz,1H,芳香H),7.58(d,J=90Hz,1H,芳香H),7.52(ddd,J=8.1,6.0,2.1Hz,1H,芳香H),7.36(ddd,J=8.2,4.5,4.1Hz,1H,芳香H),7.31-7.10(m,4H,芳香H),7.06(br,1H,芳香H),6.98(br,1H,芳香H),6.90(s,2H,2,4,6三甲苯基芳香H),6.89(s,1H,芳香H),6.67(d,J=8.6Hz,1H,芳香H),6.66(d,J=8.9Hz,1H,芳香H),4.77(septet,J=6.1Hz,1H,ArOCH(CH3)2),4.28-4.22(m,1H,ArNH2CH2),3.92-3.85(m,1H,ArNH2CH2),3.61-3.48(m,2H,ArNH2CH2),2.43(s,3H,o-CH3),2.22(s,3H,o-CH3),1.74(s,3H,p-CH3),1.05(d,J=6.1Hz,3H,ArOCH(CH3)2),0.56(d,J=6.1Hz,3H,ArOCH(CH3)2).
13C NMR(100MHz,CDCl3):5281.62,214.54,169.96,152.32,144.30,138.62,138.36,137.93,137.40,137.34,137.12,134.48,134.41,133.64,129.79,129.29,128.89,128.57,128.49,128.12,127.98,127.91,127.84,127.78,126.81,126.58,125.88,124.45,122.44,121.77,121.63,119.32,112.98,74.83,52.88,51.48,21.27,20.41,20.39,18.49,18.00.
HRMS计算值C42H39ClN2O2Ru:740.1744.实测值:740.1746.
分析计算值C42H39ClN2O2Ru:C,68.14;H,5.31;N,3.78.实测值:C,67.89;H,5.58;N,3.55.[α]D 25-980.2°(c=0.1752,CHCl3).
实施例14
用催化剂(9)进行闭环易位反应的代表性方法。在手套箱中将N-烯丙基-N-甲苯磺酰基甲基丙烯酰胺(15)(26.7mg,0.0956mmol)和6.8mg(0.0092mmol,9.6%)的外消旋的9加入5ml圆底烧瓶中。从箱中移出该烧瓶并将该固体溶解于0.96ml的甲苯中(0.1M)。该烧瓶装有回流冷凝器,并浸入油浴中,在80℃加热48小时。此时,由TLC分析指示所有初始物质被消耗。温和吹入N2浓缩该暗褐色溶液,得到暗褐色结晶固体。通过直接以CH2Cl2为洗提液的柱色谱(直径3cm,长10cm)分别得到白色预期固体产物(23.2mg,97%)和回收的褐色固体催化剂(6.2mg,91%)。将该催化剂残余物直接转移至5ml干净的圆底烧瓶中用来进行后继反应。再次用N2气流来浓缩该溶液为褐色固体。在烧瓶中载入新鲜底物(27.9mg,0.100mmol)并重复上述反应。80℃48小时后对反应混合物的1HNMR分析发现93%转化为产物(16)。再次进行上述纯化过程得到产物(22.6mg,90%)和以高收率回收催化剂(5.8mg,78%).
实施例15
顺式-5-降冰片烯-endo-2,3-二羧酸酐的AROM/CM反应的代表性方法。在手套箱中将顺式-5-降冰片烯-endo-2,3-二羧酸酐19(12.2mg,0.0743mmol)、苯乙烯(43μL,0.375mmol,5.0当量)和9(5.5mg,0.0074mmol,10mol%)一起加入5ml圆底烧瓶中。从箱中移出该烧瓶并将该固体溶解于0.40ml的THF中(0.2M)。在容器顶部装上回流冷凝器并在50℃油浴中搅拌该褐色溶液1.5小时。此时,TCL分析已检测不到初始物质。将干燥硅胶(750mg)加入反应混合物中,并吸收掉烧瓶中所有溶剂。减压下移除该浆料中的残余溶剂。把该负载产物的硅胶直接装入直径3cm、长15cm的柱中并用5∶1的己烷∶EtOAc洗提,得到无色油状产物(20a)(Rf=0.16,14.2mg,71%)和褐色固体催化剂(Rf=0.20,5.3mg,96%)。
4-苯乙烯基-6-乙烯基-四氢-环戊[c]呋喃-1,3-二酮(20a)。
IR(NaCl):3081(w),3024(w),2960(w),2923(m),2853(w),1854(s),1776(s),1640(w),1602(w),1494(w),1449(w),1324(w),1257(m),1205(s),1089(m),1004(s),968(s),921(s),794(m),752(m),695(m).
1H NMR(400MHz,CDCl3):87.39(d,J=7.0Hz,2H),7.32(t,J=7.3Hz,2H),7.24(t,J=7.3Hz,1H),6.53(d,J=15.8Hz,1H),6.30(dd,J=15.8,7.9Hz,1H),6.03-5.93(m,1H),5.24(d,J=1.0Hz,1H),5.21(dt,J=6.8,1.0Hz,1H),3.59-5.51(m,2H),3.22-3.12(m,1H),3.11-3.01(m,1H),2.14(dt,J=12.8,5.4Hz,1H),1.57(quartet,J=12.8Hz,1H).
13C NMR(100MHz,CDCl3):8170.71,170.69,136.78,134.92,132.44,128.75,127.90,126.62,126.50,117.57,49.98,49.56,46.94,46.37,36.72.
分析计算值C17H16O3:C,76.10;H,6.01.实测值:C,76.16;H,6.28.
4-庚-1-烯基-6-乙烯基-四氢-环戊[c]呋喃-1,3-二酮(20b)。
IR(NaCl):3055(w),2959(s),2927(s),2855(s),1855(s),1778(s),1642(w),1456(m),1378(w),1325(m),1264(s),1205(s),1092(s),1004(s),972(s),920(s),797(s),739(s),704(s),574(m).
1H NMR(400MHz,CDCl3):δ5.96(ddd,J=16.7,10.6,7.3Hz,1H),5.60(dt,J=15.4,6.4Hz,1H),5.50(dd,J=15.2,7.5Hz,1H),5.18(s,1H),5.15(dt,J=8.1,1.1Hz,1H),3.4(quartet,J=8.4Hz,2H),3.00-2.90(m,2H),2.06-1.97(m,3H),1.47-1.23(m,7H),0.87(t,J=6.9Hz,3H).
13C NMR(100MHz,CDCl3):δ170.96,170.71,135.17,133.92,126.34,117.26,49.71,49.67,46.80,46.11,36.72,32.50,31.45,28.98,22.62,14.17.
HRMS计算值C16H22O3:262.1569.实测值:262.1569.
4-(2-环己基-乙烯基)-6-乙烯基-四氢-环戊[c]呋喃-1,3-二酮(20c)。
IR(NaCl):2933(s),2848(m),1848(m),1785(s),1643(w),1445(w),1259(w),1199(m),1093(s),1004(w),969(w),960(w),929(m),792(w).
1H NMR(400MHz,CDCl3):δ5.96(ddd,J=17.4,10.8,6.6Hz,1H),5.55-5.41(m,2H),5.18(d,J=1.2Hz,1H),5.15(dt,J=7.9,1.3Hz,1H),3.44(q,J=8.2Hz,2H),3.00-2.89(m,2H),2.04-1.91(m,2H),1.76-1.58(m,4H),1.42(q,J=13.0Hz,1H),1.32-0.98(m,6H).
13C NMR(100MHz,CDCl3):δ170.97,170.63,139.58,135.19,124.02,117.30,49.80,46.89,46.10,40.67,36.69,33.01,32.98,26.28,26.13.
HRMS计算值C17H22O3:274.1569.实测值:274.1571.
分析计算值C17H22O3:C,74.42;H,8.08.实测值:C,74.29;H,7.95.
此处报道的7-反式-降冰片基芳基醚是在标准Mitsunobu醚化条件下由适当的酚和7-反式-降冰片醇制备的。该取代反应以结构保持方式进行。
7-反式-降冰片基p-三氟代苯基醚(21a)。
IR(NaCl):3064(w),2979(m),2945(m),2871(w),1617(m),1590(w),1518(m),1458(w),1423(w),1329(s),1311(m),1277(w),1256(s),1244(m),1161(m),1120(s),1109(s),1072(m),1048(s),1010(w),858(w),835(m),713(m),631(m).
1H NMR(400MHz,CDCl3):δ7.52(d,J=9.1Hz,2H,芳香H),6.97(d,J=9.1Hz,2H,芳香H),6.07(t,J=2.2Hz,2H,烯类H),4.01(s,1H,ArOCH),2.88-2.84(m,2H,ArOCH(CHR1R2)2),1.90-1.8(m,2H,脂肪族H),1.07(ddd,J=11.4,3.8,0.8Hz,2H,脂肪族H).
13C NMR(100MHz,CDCl3):δ160.12,133.97,126.88(q,JCF=3.8Hz),115.27,85.95,43.69,21.88.
HRMS计算值C14H13F3O:254.0918.实测值:254.0918.
分析计算值C14H13F3O:C,66.14;H,5.15.实测值:C,66.36;H,5.06.
7-反式-降冰片基p-甲氧基苯基醚(21b)。
IR(NaCl):3060(w),2975(m),2944(m),2868(w),2833(w),1506(s),1464(w),1456(w),1442(w),1350(w),1335(w),1305(w),1258(w),1228(s),1181(w),1127(w),1106(w),1092(w),1065(m),1039(m),825(m),749(m),712(m).
1H NMR(400MHz,CDCl3):δ6.83(ddt,J=18.3,9.1,2.8Hz,4H,芳香H),6.04(t,J=2.2Hz,2H,烯H),3.89(br,1H,ArOCH),3.77(s,3H,ArOCH3),2.82-2.79(m,2H,ArOCH(CHR1R2)2),1.92-1.87(m,2H,脂肪族H),1.04(dd,J=10.5,3.8Hz,2H,脂肪族H).
13C NMR(100MHz,CDCl3):δ154.08,151.77,134.17,116.77,114.70,86.97,55.85,43.82,21.88.
HRMS计算值C14H16O2:216.1150.实测值:216.1150.
分析计算值C14H16O2:C,77.75;H,7.46.实测值:C,77.48;H,7.21.
实施例16
7-反式-降冰片基芳基醚的室温AROM/CM反应的代表性方法。将7-反式-降冰片基p-三氟代甲基苯基醚(21a)(67.2mg,0.264mmol)和苯乙烯(55.8mg,0.536mmol,2.0当量)以纯油形式在空气中称重后加入5ml的圆底烧瓶中并溶解于2.6ml THF中(0.1M)。然后直接将配位化合物9(9.9mg,0.0134mmol,5mol%)以固体形式一次性加入到该无色溶液中。该烧瓶在22℃下敞口搅拌1小时,此时TLC分析指示反应完成。将干燥硅胶(1.25g)一次性加入该混合物中。在减压下将残余溶剂从得到的浆料中移除。然后将该含有产物的干燥硅胶直接装上色谱柱(直径2.5cm,长10cm)并在CH2Cl2中压紧;用100%的CH2Cl2洗提得到褐色固体催化剂(Rf~0.10,8.5mg,86%)和非极性有机产物的粗混物。而后,用100∶1己烷∶Et2O通过硅胶重新进行色谱分级,得到预期无色油状产物(Rf=0.25,62.4mg,66%)。
2-苯乙烯基-5-乙烯基-环戊基-p-三氟代甲基苯基醚(22a)。
IR(NaCl):2956(w),2929(w),2872(w),1615(m),1589(w),1517(m),1493(w),1449(w),1422(w),1327(s),1311(m),1253(s),1178(m),1161(m),1112(s),1068(m),1009(m),965(w),917(w),836(m),747(m),693(m).
1H NMR(400MHz,CDCl3):δ7.48(d,J=8.4Hz,2H,芳香H),7.34-7.27(m,4H,芳香H),7.24-7.19(m,1H,芳香H),6.97(d,J=8.4Hz,2H,芳香H),6.44(dd,J=15.8,1.0Hz,1H,PhCHCHR),6.21(dd,J=15.8,8.0Hz,1H,PhCHCHR),5.90(ddd,J=18.2,10.4,7.8Hz,1H,RCHCH2),5.12(ddd,J=17.2,1.6,1.4Hz,1H,RCHCH2),5.07(ddd,J=10.2,1.4,1.0Hz,1H,RCHCH2),4.38(t,J=5.1Hz,1H,ArOCH),2.99-2.90(m,1H,ArOCH(CHR1R2)2),2.87-2.79(m,1H,ArOCH(CHR1R2)2),2.16-2.04(m,2H,脂肪族H),1.79-1.67(m,2H,脂肪族H).
13C NMR(100MHz,CDCl3):δ161.29,139.69,137.34,131.41,130.79,128.72,127.48,126.90(q,Yep=3.9Hz),126.25,116.29,115.53,89.23,50.06,49.71,29.83,29.41.
HRMS计算值C22H21F3O:358.1544.实测值:358.1544.
分析计算值C22H21F3O:C,73.73;H,5.91.实测值:C,74.00;H,6.20.
2-苯乙烯基-5-乙烯基-环戊基-p-甲氧基苯基醚(22b)。
IR(NaCl):2951(m),2931(m),2871(w),1506(s),1464(w),1448(w),1228(s),1180(w),1039(m),965(w),914(w),825(m),749(m),693(m).
1H NMR(400MHz,CDCl3):δ7.34-7.26(m,4H,芳香H),7.23-7.18(m,1H,芳香H),6.86(d,J=9.2Hz,1H,芳香H),6.86(dd,J=10.4,6.1Hz,1H,芳香H),6.77(d,J=9.2Hz,1H,芳香H),6.77(dd,J=10.4,6.1Hz,1H,芳香H),6.43(dd,J=15.8,0.8Hz,1H,PhCHCHR),6.21(dd,J=15.8,8.2Hz,1H,PhCHCHR),5.89(ddd,J=18.0,10.4,7.6Hz,1H,RCHCH2),5.11(dt,J=17.2,1.6Hz,1H,RCHCH2),5.04(ddd,J=10.4,1.8,1.2Hz,1H,RCHCH2),4.20(t,J=5.7Hz,1H,ArOCH),3.74(s,3H,ArOCH3),2.97-2.88(m,1H,ArOCH(CHR1R2)2),2.85-2.77(m,1H,ArOCH(CHR1R2)2),2.12-2.00(m,2H,脂肪族H),1.74-1.62(m,2H,脂肪族H).
13C NMR(100MHz,CDCl3):δ154.19,152.96,140.30,137.65,132.22,130.31,128.64,127.25,126.24,118.19,115.03,114.61,90.52,55.82,50.05,49.67,29.54,29.09.
HRMS计算值C22H24O2:320.1776.实测值:320.1776.
分析计算值C22H24O2:C,82.46;H,7.55.实测值:C,82.34;H,7.80.
在此引用的所有专利、专利申请和发表的参考文献兹通过完整引用而引入。在本发明已由参考其优选实施方案来具体说明和描述的同时,应该理解到在不违背包括于所附权利要求中的本发明范围的情况下,本领域的技术人员可以对形式和细节进行各种修改。
Claims (45)
1.一种具有化学式(1)的手性金属催化剂:
其中:
M为过渡金属或铷(Rb);
X为氧(O)或硫(S);
R选自包括烷基、烯基、炔基、芳基、芳烷基、烷氧基、烯氧基、炔氧基、芳氧基、烷氧羰基、烷基氨基、烷基硫、烷基磺酰基和烷基亚硫酰基的基团;其中每个基团可任选以烷基、卤素、烷氧基、芳基或杂芳基基团取代;
R1和R2各自分别为吸电子的单价或二价配位基,条件是至少其中之一为二价配位基;
a、b、c和d各自分别地选自包括氢、卤素、烷基、烯基、炔基、芳基、芳烷基、烷氧基、烯氧基、炔氧基、芳氧基、烷氧羰基、烷基氨基、烷基硫、烷基磺酰基和烷基亚硫酰基的基团;其中每个基团可任选以烷基、卤素、芳基或杂芳基基团取代;
Y为给电子配位基;和
Z为键合至Y以及R1或R2的芳香环或杂芳香环取代基,条件是R1或R2为二价配位基。
2.权利要求1的手性金属催化剂,其中M选自钌(Ru)、铷(Rb)、铑(Rh)、钼(Mo)或钨(W)。
3.权利要求1的手性金属催化剂,其中M为钌(Ru)。
4.权利要求1的手性金属催化剂,其中R为C1~C12的直链或支链烷基。
5.权利要求4的手性金属催化剂,其中R为异丙基。
6.权利要求1的手性金属催化剂,其中R1或R2各自分别为不相同的阳离子吸电子单价或二价配位基。
7.权利要求1的手性金属催化剂,其中R1或R2为杂原子。
8.权利要求7的手性金属催化剂,其中R1或R2为氧(O)或硫(S)。
9.权利要求1的手性金属催化剂,其中R1或R2为卤素。
10.权利要求9的手性金属催化剂,其中R1或R2为氯(Cl)。
11.权利要求1的手性金属催化剂,其中a、b、c和d各自分别为氢或C1~C12的直链或支链烷基。
12.权利要求11的手性金属催化剂,其中a、b、c和d均为氢。
13.权利要求1的手性金属催化剂,其中X为氧(O)。
15.权利要求14的手性金属催化剂,其中R3为2,4,6-三甲基苯基。
16.权利要求14的手性金属催化剂,其中Z为1,1’-联二萘基。
17.权利要求1的手性金属催化剂,其中Z为手性的。
18.权利要求1的手性金属催化剂,其中Z为1,1’-联二萘基。
20.权利要求19的手性金属催化剂,其中M选自钌(Ru)、铷(Rb)、铑(Rh)、钼(Mo)或钨(W)。
21.权利要求19的手性金属催化剂,其中M为钌(Ru)。
22.权利要求19的手性金属催化剂,其中R4、R5和R6各自分别为C1~C12的直链或支链烷基。
23.权利要求22的手性金属催化剂,其中R4、R5和R6均为甲基。
24.权利要求19的手性金属催化剂,其中M为钌(Ru)且R4、R5和R6均为甲基。
25.一种制备具有化学式(3)的手性金属催化剂的方法:
其中:M为过渡金属或铷(Rb);和
R4、R5和R6各自分别选自包括氢、烷基、烷氧基、芳基或杂芳基的基团;
其步骤包括:
a)1,1’-联二萘基-氨基酚(化学式(4)):
与醛(5)反应:
其中R4、R5和R6如上所定义,Boc为叔丁氧羰基,
形成具有化学式(6)的化合物:
其中R4、R5和R6和Boc如上所定义;
b)酸存在下具有化学式(6)的化合物反应生成具有化学式(7)的化合物:
其中w为反离子,R4、R5和R6如上所定义;
c)具有化学式(7)的化合物与具有化学式(8)的化合物反应:
其中M如上所定义,
生成具有化学式(3)的手性过渡金属催化剂。
26.权利要求25的方法,其中M选自钌(Ru)、铷(Rb)、铑(Rh)、钼(Mo)或钨(W)。
27.权利要求25的方法,其中M为钌(Ru)。
28.权利要求25的方法,其中w为卤素、磷酸盐或硫酸盐基团。
29.权利要求28的方法,其中w为氯(Cl)。
30.权利要求25的方法,其中R4、R5和R6各自分别为C1~C12的直链或支链烷基。
31.权利要求30的方法,其中R4、R5和R6均为甲基。
32.一种通过使用权利要求1的手性金属催化剂进行对映异构体选择性易位反应得到多取代烯烃的方法。
33.权利要求32的方法,其中所述的对映异构体选择性易位反应为开环易位(ROM)反应。
34.权利要求32的方法,其中所述的对映异构体选择性易位反应为闭环易位(RCM)反应。
35.权利要求32的方法,其中所述的对映异构体选择性易位反应为不对称开环/交叉易位(AROM/CM)反应。
36.一种通过使用权利要求1的手性金属催化剂进行对映异构体选择性易位反应得到多取代烯烃的方法,其中所述的手性金属催化剂被回收并重复使用多次。
37.权利要求36的方法,其中所述的对映异构体选择性易位反应为开环易位(ROM)反应。
38.权利要求36的方法,其中所述的对映异构体选择性易位反应为闭环易位(RCM)反应。
39.权利要求36的方法,其中所述的对映异构体选择性易位反应为不对称开环/交叉易位(AROM/CM)反应。
40.权利要求36的方法,其中所述手性金属催化剂在对映异构体选择性易位反应中被回收并重复使用多次。
41.一种通过使用权利要求19的手性金属催化剂进行对映异构体选择性易位反应得到多取代烯烃的方法。
42.权利要求41的方法,其中所述的对映异构体选择性易位反应为开环易位(ROM)反应。
43.权利要求41的方法,其中所述的对映异构体选择性易位反应为闭环易位(RCM)反应。
44.权利要求41的方法,其中所述的对映异构体选择性易位反应为不对称开环/交叉易位(AROM/CM)反应。
45.权利要求41的方法,其中所述催化剂在对映异构体选择性易位反应中被回收并重复使用多次。
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WO2010083881A1 (en) | 2009-01-21 | 2010-07-29 | Henkel Ag & Co. Kgaa | Olefin metathesis polymerisation |
US8362311B2 (en) | 2009-09-30 | 2013-01-29 | Massachusetts Institute Of Technology | Highly Z-selective olefins metathesis |
US9024034B2 (en) | 2009-11-09 | 2015-05-05 | Exxonmobil Chemical Patents Inc. | Metathesis catalysts and processes for use thereof |
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CN102153483B (zh) * | 2011-01-28 | 2013-10-30 | 华南理工大学 | 轴手性邻二胺化合物及其制备方法 |
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WO1997042151A1 (en) * | 1996-05-03 | 1997-11-13 | Dsm N.V. | Cyclopentadiene compound substituted by chiral groups |
US6207868B1 (en) * | 1997-06-13 | 2001-03-27 | The Penn State Research Foundation | Asymmetric synthesis catalyzed by transition metal complexes with chiral ligands |
US6121473A (en) * | 1998-02-19 | 2000-09-19 | Massachusetts Institute Of Technology | Asymmetric ring-closing metathesis reactions |
EP1105400A1 (en) * | 1998-08-21 | 2001-06-13 | The Penn State Research Foundation | Asymmetric catalysis based on chiral phospholanes |
US6380392B1 (en) * | 1999-06-30 | 2002-04-30 | The Penn State Research Foundation | Ligands based on chiral 2-amino-2′-hydroxy-1,1′-binaphthyl and related frameworks for asymmetric catalysis |
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