CN114456134B - Alpha-fluoroalkyl substituted cyclopropyl alcohol compound, and preparation method and application thereof - Google Patents
Alpha-fluoroalkyl substituted cyclopropyl alcohol compound, and preparation method and application thereof Download PDFInfo
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- CN114456134B CN114456134B CN202111160158.1A CN202111160158A CN114456134B CN 114456134 B CN114456134 B CN 114456134B CN 202111160158 A CN202111160158 A CN 202111160158A CN 114456134 B CN114456134 B CN 114456134B
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- pyridine
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- -1 cyclopropyl alcohol compound Chemical class 0.000 title claims abstract description 87
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 75
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 44
- 229910052741 iridium Inorganic materials 0.000 claims description 34
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 32
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 10
- 150000001336 alkenes Chemical class 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000007983 Tris buffer Substances 0.000 claims description 9
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 9
- 239000010703 silicon Substances 0.000 claims description 9
- 229910052710 silicon Inorganic materials 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- RHXQSMVSBYAGQV-UHFFFAOYSA-N 2-(4-tert-butylphenyl)pyridine Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=CC=N1 RHXQSMVSBYAGQV-UHFFFAOYSA-N 0.000 claims description 5
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 4
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 claims description 4
- FMKQPMDFNYNYAG-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine Chemical compound FC1=CC(F)=CC=C1C1=CC=C(C(F)(F)F)C=N1 FMKQPMDFNYNYAG-UHFFFAOYSA-N 0.000 claims description 4
- YSHMQTRICHYLGF-UHFFFAOYSA-N 4-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=NC=C1 YSHMQTRICHYLGF-UHFFFAOYSA-N 0.000 claims description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
- 238000005286 illumination Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 3
- WHELTKFSBJNBMQ-UHFFFAOYSA-L dichlororuthenium;2-pyridin-2-ylpyridine;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ru+2].N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1 WHELTKFSBJNBMQ-UHFFFAOYSA-L 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- OYNJAUIAADXAOW-UHFFFAOYSA-N 2,3,5,6-tetra(carbazol-9-yl)benzene-1,4-dicarbonitrile Chemical compound C1=CC=CC=2C3=CC=CC=C3N(C1=2)C1=C(C(=C(C(=C1C#N)N1C2=CC=CC=C2C=2C=CC=CC1=2)N1C2=CC=CC=C2C=2C=CC=CC1=2)C#N)N1C2=CC=CC=C2C=2C=CC=CC1=2 OYNJAUIAADXAOW-UHFFFAOYSA-N 0.000 claims description 2
- COHVUSHFIAMZSW-UHFFFAOYSA-N 2-(2,4-difluorophenyl)-5-methylpyridine Chemical compound N1=CC(C)=CC=C1C1=CC=C(F)C=C1F COHVUSHFIAMZSW-UHFFFAOYSA-N 0.000 claims description 2
- IHMXVSZXHFTOFN-UHFFFAOYSA-N 2-ethyloxolane Chemical compound CCC1CCCO1 IHMXVSZXHFTOFN-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- KJPUWZVESPGSAG-UHFFFAOYSA-N 2-propyloxetane Chemical compound CCCC1CCO1 KJPUWZVESPGSAG-UHFFFAOYSA-N 0.000 claims description 2
- VEEMVPAUPIJPLA-UHFFFAOYSA-N 2-pyrazin-2-ylpyrazine ruthenium Chemical compound [Ru].c1cnc(cn1)-c1cnccn1.c1cnc(cn1)-c1cnccn1.c1cnc(cn1)-c1cnccn1 VEEMVPAUPIJPLA-UHFFFAOYSA-N 0.000 claims description 2
- BXKPAPTYLLPPEO-UHFFFAOYSA-L 2-pyridin-2-ylpyridine;ruthenium(2+);diperchlorate Chemical compound [Ru+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O.N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1.N1=CC=CC=C1C1=CC=CC=N1 BXKPAPTYLLPPEO-UHFFFAOYSA-L 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- DBZJJPROPLPMSN-UHFFFAOYSA-N bromoeosin Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C(O)C(Br)=C1OC1=C(Br)C(O)=C(Br)C=C21 DBZJJPROPLPMSN-UHFFFAOYSA-N 0.000 claims description 2
- BTVWZWFKMIUSGS-UHFFFAOYSA-N dimethylethyleneglycol Natural products CC(C)(O)CO BTVWZWFKMIUSGS-UHFFFAOYSA-N 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000011941 photocatalyst Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims 2
- 229910052707 ruthenium Inorganic materials 0.000 claims 2
- FXBMDTJNJYRHOY-UHFFFAOYSA-N 1-butyl-2-fluorobenzene Chemical compound CCCCC1=CC=CC=C1F FXBMDTJNJYRHOY-UHFFFAOYSA-N 0.000 claims 1
- ZFUHNOCBMAPCPI-UHFFFAOYSA-N 2-(3-tert-butylphenyl)pyridine Chemical compound CC(C)(C)C1=CC=CC(C=2N=CC=CC=2)=C1 ZFUHNOCBMAPCPI-UHFFFAOYSA-N 0.000 claims 1
- KGZSSIFFYUBVOX-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]pyridine Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=N1 KGZSSIFFYUBVOX-UHFFFAOYSA-N 0.000 claims 1
- AZFHXIBNMPIGOD-UHFFFAOYSA-N 4-hydroxypent-3-en-2-one iridium Chemical compound [Ir].CC(O)=CC(C)=O.CC(O)=CC(C)=O.CC(O)=CC(C)=O AZFHXIBNMPIGOD-UHFFFAOYSA-N 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- SOGYDYRLWDFJTE-UHFFFAOYSA-K iridium(3+);phosphate Chemical compound [Ir+3].[O-]P([O-])([O-])=O SOGYDYRLWDFJTE-UHFFFAOYSA-K 0.000 claims 1
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical group 0.000 abstract description 33
- 125000000217 alkyl group Chemical group 0.000 abstract description 13
- 125000005842 heteroatom Chemical group 0.000 abstract description 12
- 125000003118 aryl group Chemical group 0.000 abstract description 11
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 abstract description 10
- 125000000304 alkynyl group Chemical group 0.000 abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 10
- 125000004185 ester group Chemical group 0.000 abstract description 6
- 150000002148 esters Chemical class 0.000 abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 4
- 229910052736 halogen Inorganic materials 0.000 abstract description 4
- 150000002367 halogens Chemical class 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 120
- 239000011541 reaction mixture Substances 0.000 description 43
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 32
- 238000004293 19F NMR spectroscopy Methods 0.000 description 27
- 238000005160 1H NMR spectroscopy Methods 0.000 description 27
- 239000011734 sodium Substances 0.000 description 26
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 23
- 239000012043 crude product Substances 0.000 description 22
- 238000010898 silica gel chromatography Methods 0.000 description 22
- 239000000203 mixture Substances 0.000 description 21
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 20
- 239000007788 liquid Substances 0.000 description 19
- 229910052786 argon Inorganic materials 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000012267 brine Substances 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 7
- 239000003480 eluent Substances 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YOXHCYXIAVIFCZ-UHFFFAOYSA-N cyclopropanol Chemical class OC1CC1 YOXHCYXIAVIFCZ-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000008049 diazo compounds Chemical class 0.000 description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- HLYTZTFNIRBLNA-LNTINUHCSA-K iridium(3+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ir+3].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O HLYTZTFNIRBLNA-LNTINUHCSA-K 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 2
- 150000001420 substituted heterocyclic compounds Chemical class 0.000 description 2
- IRJQVGFFSLLUHN-UHFFFAOYSA-N 1-(cyclopropen-1-yloxy)cyclopropene Chemical class C1C=C1OC1=CC1 IRJQVGFFSLLUHN-UHFFFAOYSA-N 0.000 description 1
- MHWIDTQQBWGUCD-UHFFFAOYSA-N 2-(4-fluorophenyl)pyridine Chemical compound C1=CC(F)=CC=C1C1=CC=CC=N1 MHWIDTQQBWGUCD-UHFFFAOYSA-N 0.000 description 1
- OUPMUGIXWNVDSN-UHFFFAOYSA-N 2-[hydroxy-(1-oxido-4-oxoquinoxalin-4-ium-2-yl)methyl]-4-methoxyphenol Chemical compound COC1=CC=C(O)C(C(O)C=2N(C3=CC=CC=C3[N+](=O)C=2)[O-])=C1 OUPMUGIXWNVDSN-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- XCHARIIIZLLEBL-UHFFFAOYSA-N Medicagenic acid 3-O-beta-D-glucoside Chemical compound C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C(O)=O)C)(C)C1=CCC2C3(C)CC(O)C4OC1OC(CO)C(O)C(O)C1O XCHARIIIZLLEBL-UHFFFAOYSA-N 0.000 description 1
- UNLXTLJKCRZIOW-UHFFFAOYSA-N O.O.O.O.O.O.[Ru+2].N1=C(C=CC=C1)C1=NC=CC=C1.N1=C(C=CC=C1)C1=NC=CC=C1.N1=C(C=CC=C1)C1=NC=CC=C1 Chemical compound O.O.O.O.O.O.[Ru+2].N1=C(C=CC=C1)C1=NC=CC=C1.N1=C(C=CC=C1)C1=NC=CC=C1.N1=C(C=CC=C1)C1=NC=CC=C1 UNLXTLJKCRZIOW-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- VYXSBFYARXAAKO-WTKGSRSZSA-N chembl402140 Chemical compound Cl.C1=2C=C(C)C(NCC)=CC=2OC2=C\C(=N/CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-WTKGSRSZSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000005888 cyclopropanation reaction Methods 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- ACGUYXCXAPNIKK-UHFFFAOYSA-N hexachlorophene Chemical compound OC1=C(Cl)C=C(Cl)C(Cl)=C1CC1=C(O)C(Cl)=CC(Cl)=C1Cl ACGUYXCXAPNIKK-UHFFFAOYSA-N 0.000 description 1
- MILUBEOXRNEUHS-UHFFFAOYSA-N iridium(3+) Chemical compound [Ir+3] MILUBEOXRNEUHS-UHFFFAOYSA-N 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C35/02—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic
- C07C35/04—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring monocyclic containing a three or four-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
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Abstract
The invention relates to the technical field of organic synthesis, in particular to an alpha-fluoroalkyl substituted cyclopropyl alcohol compound, a preparation method and application thereof, and the molecular structural formula is as follows: Wherein R 1、R2、R3、R4 is any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester, cyano, nitro, sulfonyl, heteroatom and hydrogen atom, rf is CF 3、CF2R5 or CFR 6R7,R5 is any one of halogen, aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester, cyano, nitro, sulfonyl, carboxyl, heteroatom and hydrogen atom; r 6、R7 is any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitro, sulfonyl, heteroatom and hydrogen atom, and can be the same or different. The alpha-fluoroalkyl substituted cyclopropyl alcohol compound is a novel compound structure and has high diastereoselectivity.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to an alpha-fluoroalkyl substituted cyclopropyl alcohol compound, a preparation method and application thereof.
Background
Alpha-fluoroalkyl alcohol dicing is widely found in many bioactive compounds, and thus has attracted close attention by organic synthetic chemists. However, the method for directly synthesizing alpha-fluoroalkyl alcohol is limited, 2012, reissig et al report the synthesis of fluoroalkyl-substituted cyclopropenyl ether compounds [ H.— U.Reissig, helvetica Chimica Acta,2012,95 (10), 1818-1830], and the cyclization reaction of fluorine-containing enol silyl ether with diazo compounds [ 2+1 ] under the catalysis of transition metal rhodium acetate to obtain alpha-fluoroalkyl cyclopropyl silyl ether, which can not well control dr, and the low-content compounds are limited to diazo compounds containing ester groups, so that the substrate universality is poor. Conventional methods generally result from nucleophilic addition of an aldehyde or ketone. However, these methods do not control the regioselectivity of the substrate and require multi-step synthesis for a particular aldehyde or ketone, and thus there is an urgent need to develop a method capable of directly introducing a-fluoroalkyl alcohol cut blocks. The invention mainly researches a method for directly synthesizing alpha-fluoroalkyl substituted cyclopropyl alcohol and application thereof.
Disclosure of Invention
It is an object of the present invention to provide an α -fluoroalkyl substituted cyclopropyl alcohol compound having high diastereoselectivity.
The second purpose of the invention is to provide a preparation method of the alpha-fluoroalkyl substituted cyclopropyl alcohol compound, which has simple operation and simple reaction conditions.
The invention further aims to provide an application of the alpha-fluoroalkyl substituted cyclopropyl alcohol compound.
The scheme adopted by the invention for achieving one of the purposes is as follows: an alpha-fluoroalkyl substituted cyclopropyl alcohol compound, which has the following molecular structural formula:
Wherein R 1、R2、R3、R4 is any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester, cyano, nitro, sulfonyl, heteroatom and hydrogen atom, which may be the same or different, and Rf is any one of halogen, aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester, cyano, nitro, sulfonyl, carboxyl, heteroatom and hydrogen atom; r 6、R7 is any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitro, sulfonyl, heteroatom and hydrogen atom, and can be the same or different.
The hetero atoms are silicon, oxygen, sulfur, nitrogen and other hetero atoms.
Preferably, the aryl group bears one or more substituents; when there are a plurality of substituents, the substituents may be the same or different.
Preferably, the alkyl group has 1 to 20 carbon atoms and is of a linear structure, a cyclic structure or a branched structure.
Preferably, the alkyl group has one or more substituents, and when having a plurality of substituents, the substituents may be the same or different and the positions may be the same or different.
The scheme adopted by the invention for achieving the second purpose is as follows: under the protection of inert gas, firstly, olefin A and fluorine-containing acyl silicon B are dissolved in an organic solvent, then, stirring reaction is carried out under the illumination, desilication is carried out after the reaction, and purification is carried out, thus obtaining the alpha-fluoroalkyl substituted cyclopropyl alcohol compound.
Preferably, the olefin A has the molecular structural formula
The molecular structural formula of the fluorine-containing acyl silicon B is
Wherein R 1、R2、R3、R4 is any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester, cyano, nitro, sulfonyl, heteroatom and hydrogen atom, which may be the same or different, and Rf is any one of halogen, aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester, cyano, nitro, sulfonyl, carboxyl, heteroatom and hydrogen atom; r 6、R7 is any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitro, sulfonyl, heteroatom and hydrogen atom, and can be the same or different, and R 8、R9、R10 is any one of aryl, heteroaryl, alkyl, alkenyl, alkynyl, ester group, cyano, nitro, sulfonyl, heteroatom and hydrogen atom, and can be the same or different.
Preferably, the organic solvent is at least one of methanol, ethanol, isopropanol, tert-butanol, tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, dimethylethylene glycol, methyl tert-butyl ether, 1, 4-epoxyhexaane, 1, 3-epoxyhexaane, methylene chloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, saturated alkanes of C 4-12, fluorinated or chlorinated alkanes of C 3-12, benzene, toluene, xylene, trimethylbenzene, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, acetone, N-methylpyrrolidone, acetonitrile, saturated alkylnitriles of C 3-12.
Preferably, the molar ratio between the olefin A and the fluorine-containing acyl silicon B is 1:1-6; the concentration of olefin A in the mixed solution is between 0.1M and 1M.
Preferably, the raw materials also comprise a catalyst, wherein the photocatalyst is tris [ 2-phenylpyridine-C2, N ] iridium (III), bis [2- (2, 4-difluorophenyl) -5-trifluoromethyl pyridine ] [2-2 '-bis (4-tert-butylpyridine) ] iridium bis (hexafluorophosphate), bis [2- (2, 4-difluorophenyl) -5-methylpyridine ] [2,2' -bis (tetra-tert-butylpyridine) ] iridium bis (hexafluorophosphate), bis [2- (2, 4-difluorophenyl) -5-trifluoromethylpyridine ] [2-2 '-bipyridine ] iridium bis (hexafluorophosphate), bis [2,2' -bis (4-tert-butylpyridine) ] bis [2- (2, 4-difluorophenyl) pyridine ] iridium (III) hexafluorophosphate, (4, 4 '-di-tert-butyl-2, 2' -bipyridine) bis [ (2-pyridyl) phenyl ] iridium (III) hexafluorophosphate, acetyl bis (2-methyl-3-phenylpyrazine-C2, N) iridium, bis (2, 3-diphenylpyrazine-C2, N) iridium acetylacetonate, bis (2, 3-diphenylquinoxaline) iridium acetylacetonate, bis (2-phenylpyrimidine-C2, N) iridium acetylacetonate, and, (2, 2' -bipyridine) bis [2- (4-fluorophenyl) pyridine ] iridium (III) hexafluorophosphate, (2, 2' -bipyridine) bis [2- (2, 4-difluorophenyl) pyridine ] iridium (III) hexafluorophosphate, (2, 2' -bipyridine) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, (2-2 ' -bis (4-tert-butylphenyl) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, (1, 10-phenanthroline) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, tris (2- (4-fluorophenyl) pyridine) iridium, tris [2- (4, 6-difluorophenyl) pyridine-C2, N ] iridium (III), bis [2- (3-tert-butylphenyl) -4-tert-butylphenyl) pyridine ] [2,2' -bis (4-tert-butylphenyl) pyridine) ] hexafluorophosphate, bis [2- (2-chlorophenyl) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, tris (2, 10-phenanthroline) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, tris (2- (4-fluorophenyl) pyridine) iridium (III) tris (III) iridium (III) fluoride, tris [2- (4-difluorophenyl) pyridine ] 2, N ] iridium (III) Rhodamine 6G, tris (1, 10-phenanthroline) ruthenium (II) bis (hexafluorophosphate), tris (4, 4 '-dimethyl-2, 2' -bipyridine) ruthenium (III) (hexafluorophosphate) salt, tris (2, 2 '-bipyrazine) ruthenium bis (hexafluorophosphonic acid) salt, tris (2, 2' -bipyridine) ruthenium bis (hexafluorophosphate) salt, tris (2, 2 '-bipyridine) ruthenium bis (perchloric acid) salt, tris (2, 2' -bipyridine) ruthenium bis (tetrafluoroborate) salt, tris (2, 2 '-bipyridine) ruthenium (II) hexahydrate, 9-mesityl-10-tetrafluoroborate, 2,3,5, 6-tetrakis (9-carbazolyl) -terephthalonitrile, 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN), derivatives of 4CzIPN, tris (2, 2' -bipyridine) ruthenium (II) chloride hexahydrate, solvent red 43. The catalyst is used as raw material, the reaction can be carried out without catalyst, and after the catalyst is added, the yield is partially improved without influencing the reactivity.
The temperature of the reaction is between-78 ℃ and 180 ℃ and the reaction time is within 3-24 hours. The illumination process can adopt any one of visible light such as white light, blue light, purple light, green light, sunlight and the like or other illumination modes. The invention carries out post-treatment on the reaction product after the reaction is finished, and comprises purification methods such as suction filtration, concentration, recrystallization, column chromatography and the like.
The reaction scheme of the method of the invention can be represented as follows:
Wherein the compound of formula A represents an alkene, the compound of formula B represents a fluorine-containing acyl silicon, and the compound of formula G represents an alpha-fluoroalkyl substituted cyclopropyl alcohol.
The scheme adopted by the invention for achieving the third purpose is as follows: the application of the alpha-fluoroalkyl substituted cyclopropyl alcohol compound in synthesizing alpha-fluoroalkyl ketone and fluorine-containing substituted heterocyclic compound.
The invention has the following advantages and beneficial effects:
(1) The alpha-fluoroalkyl substituted cyclopropyl alcohol compound is a novel compound structure and has high diastereoselectivity.
(2) The preparation method of the invention realizes the cyclopropanation of fluorine-containing acyl silicon and olefin induced by visible light, directly and efficiently synthesizes the alpha-fluoroalkyl substituted cyclopropyl alcohol, and shows excellent diastereoselectivity.
(3) The preparation method of the invention does not need to be promoted by a catalyst or other additives, and has simple reaction conditions.
(4) The reaction conditions related to the preparation method have good functional group tolerance and substrate universality, and the substituent groups can be alkyl, alkoxy, ester group and the like, heteroaromatic ring and halogen.
(5) The product of the invention can also be applied to the synthesis of various alpha-fluoroalkyl ketones and fluorine-containing substituted heterocyclic compounds.
Detailed Description
For a better understanding of the present invention, the following examples are further illustrative of the present invention, but the contents of the present invention are not limited to the following examples only.
Example 1:
In a glove box, A (38.8 mg,0.2 mmol), dried DCE (0.5 mL) and B (92.8 mg,0.4mmol,2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a blue LED lamp of 6W, and the reaction mixture was stirred at room temperature for 24 hours. The blue lamp was then turned off, TBAF (0.24mL,1.0M in THF,1.2equiv) was added and the mixture was stirred under ice for 10min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give the title compound G1 (52.6 mg as a colorless oily liquid, yield) 90％).1H NMR(400MHz,CDCl3,25℃)δ7.57(dd,J＝1.8,0.9Hz,1H),7.18(dd,J＝3.5,0.9Hz,1H),6.51(dd,J＝3.5,1.7Hz,1H),4.49–4.21(m,2H),2.97(s,1H),1.88–1.77(m,2H),1.61–1.48(m,4H),1.26–1.15(m,2H),0.69–0.58(m,1H).13C NMR(151MHz,CDCl3,25℃)δ159.1,146.5,144.8,125.3(q,J＝274.5Hz),118.1,112.0,64.9,57.0(q,J＝37.7Hz),28.3,25.8,25.7,21.2(q,J＝1.6Hz),16.0(q,J＝2.0Hz).19F NMR(375MHz,CDCl3,25℃)δ–77.2(s,3F).IR(ATR):3440,2945,2866,1711,1580,1476,1405,1301,1141,1081,1014,910,764,734cm-1.HRMS(ESI,m/z):calcd for C13H16F3O4 +(M+H)+:293.0995;Found:293.0998.
Example 2:
In a glove box, A (20.8 mg,0.2 mmol), dried DCM (0.5 mL) and B (92.8 mg,0.4mmol,2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a blue LED lamp of 6W, and the reaction mixture was stirred at room temperature for 24 hours. The blue lamp was then turned off, TBAF (0.24mL,1.0M in THF,1.2equiv) was added and the mixture was stirred under ice for 10min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (50/1 to 10/1, v/v) to give the title compound G2 (28.3 mg as a colorless oily liquid, yield) 70％).1H NMR(600MHz,CDCl3,25℃)δ7.38-7.31(m,2H),7.31-7.27(m,1H),7.25-7.21(m,2H),2.58(dd,J＝10.4,7.8Hz,1H),2.46(s,1H),1.57(dd,J＝10.5,6.9Hz,1H),1.48-1.39(m,1H).19F NMR(375MHz,CDCl3,25℃)δ77.1.(s,3F).
Example 3:
In a glove box, A (20.8 mg,0.2 mmol), dried DCM (0.5 mL) and B (92.8 mg,0.4mmol,2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6W white LED lamp, and the reaction mixture was stirred at room temperature for 24 hours. The blue lamp was then turned off, TBAF (0.24mL,1.0M in THF,1.2equiv) was added and the mixture was stirred under ice for 10min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (50/1 to 10/1, v/v) to give the title compound G3 (colorless oily liquid 27.2mg, yield) 67％).1H NMR(600MHz,CDCl3,25℃)δ7.38-7.31(m,2H),7.31-7.27(m,1H),7.25-7.21(m,2H),2.58(dd,J＝10.4,7.8Hz,1H),2.46(s,1H),1.57(dd,J＝10.5,6.9Hz,1H),1.48-1.39(m,1H).19F NMR(375MHz,CDCl3,25℃)δ77.1.(s,3F).
Example 4:
In a glove box, A (20.8 mg,0.2 mmol), dried DCM (0.5 mL) and B (92.8 mg,0.4mmol,2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6W green LED lamp, and the reaction mixture was stirred at room temperature for 24 hours. The blue lamp was then turned off, TBAF (0.24mL,1.0M in THF,1.2equiv) was added and the mixture was stirred under ice for 10min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (50/1 to 10/1, v/v) to give the title compound G4 (26.3 mg as a colorless oily liquid, yield) 64％).1H NMR(600MHz,CDCl3,25℃)δ7.38-7.31(m,2H),7.31-7.27(m,1H),7.25-7.21(m,2H),2.58(dd,J＝10.4,7.8Hz,1H),2.46(s,1H),1.57(dd,J＝10.5,6.9Hz,1H),1.48-1.39(m,1H).19F NMR(375MHz,CDCl3,25℃)δ77.1.(s,3F).
Example 5:
In a glove box, A (26.4 mg,0.2 mmol), dried DCM (0.5 mL) and B (92.8 mg,0.4mmol,2 equiv.) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a 6W violet LED lamp, and the reaction mixture was stirred at room temperature for 24 hours. The blue lamp was then turned off, TBAF (0.24mL,1.0M in THF,1.2equiv) was added and the mixture was stirred under ice for 10min. The reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give the title compound G5 (colorless oily liquid 32.7mg, yield) 71％).1H NMR(400MHz,CDCl3,25℃)δ7.34–7.25(m,2H),7.24–7.18(m,3H),2.84–2.59(m,2H),2.07(s,1H),2.02–1.94(m,1H),1.76–1.67(m,1H),1.30–1.23(m,1H),1.15–1.10(m,1H),0.62–0.55(m,1H).19F NMR(565MHz,CDCl3,25℃)δ–77.1(s,3F).
Example 6:
In a glove box, A (20.4 mg,0.1 mmol), dried DCM (1 mL) and B (74.4 mg,0.3mmol,3 equiv.) were added to a dry photoreaction tube equipped with a magnetic stirrer. The photoreaction tube was sealed, taken out of the glove box, and then irradiated with a blue LED lamp of 6W, and the reaction mixture was stirred at room temperature for 12 hours. The blue lamp was then turned off and the reaction mixture was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give the title compound G6 (84.0 mg as a colorless oily liquid, yield) 92％).1H NMR(400MHz,CDCl3,25℃)δ8.08–8.00(m,2H),7.62–7.52(m,3H),7.46–7.33(m,5H),4.35–4.20(m,2H),1.82–1.69(m,2H),1.56–1.13(m,6H),0.64(td,J＝6.6,2.3Hz,1H),0.48(dd,J＝5.6,1.0Hz,6H).13C NMR(151MHz,CDCl3,25℃)δ166.8,137.6,133.2(d,J＝77.4Hz),130.6,129.9,129.7,128.5,128.0,65.0,63.7(dd,J＝32.5,29.9Hz),28.5,26.5,25.6,21.1(d,J＝3.8Hz),17.9(d,J＝2.6Hz),0.4(dd,J＝59.2,2.3Hz).129.2(t,J＝289.5Hz).19F NMR(375MHz,CDCl3,25℃)δ-60.7(dd,J＝2537.3,165.5Hz,2F).IR(ATR):3071,2952,2862,1718,1454,1316,1274,1118,1028,962,835,712cm-1.
Example 7:
In an argon filled glove box, A (26.4 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred under ambient sunlight for 6 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 37.1mg of the title compound G7 (colorless oil, yield) 88％).1H NMR(600MHz,CDCl3)δ7.35–7.28(m,2H),7.23–7.21(m),5.55(t,J＝57.0Hz,1H),2.82–2.66(m,2H),2.00–1.97(m,1H),1.81–1.69(m,2H),1.11–1.06(m,1H),0.98(dd,J＝10.0,5.9Hz,1H),0.53(ddt,J＝6.7,4.1,2.4Hz,1H);13C NMR(100MHz,CDCl3)δ141.8,128.7,128.7,116.0(t,J＝241.1Hz),57.8(t,J＝27.0Hz),35.8,28.7,20.3(t,J＝3.2Hz),15.1(t,J＝3.5Hz);19F NMR(375MHz,CDCl3)δ–125.7(d,J＝56.9Hz).IR(ATR):3418,3027,2930,1603,1495,1454,1305,1256,1107,749cm1.HRMS(ESI,m/z):calcd for C12H14F2NaO+(M+Na)+:235.0905;Found:235.0901.
Example 8:
In an argon-filled glove box, A (23.6 mg,0.2 mmol) and dry EA (1.0 mL) were added to a reaction tube equipped with a magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 30.2mg of the title compound G8 (colorless oil, yield) 76％).1H NMR(400MHz,CDCl3)δ7.36–7.27(m,4H),7.27–7.20(m,1H),5.74(t,J＝56.9Hz,1H),2.94–2.83(m),2.41(s,1H),1.44(dq,J＝9.9,7.2Hz,1H),1.13(dd,J＝9.9,6.2Hz,1H),0.76(td,J＝6.6,3.3Hz,1H);13CNMR(100MHz,CDCl3)δ140.9,128.7,128.2,126.4,116.0(t,J＝240.9Hz),58.1(t,J＝27.0Hz),32.5,21.1(t,J＝2.8Hz),15.4(t,J＝3.1Hz);19F NMR(375MHz,CDCl3)δ–125.8(dd,J＝56.9,4.4Hz).IR(ATR):3384,3027,2922,1063,1494,1267,1103,1040,910,731cm1.HRMS(ESI,m/z):calcd for C11H12F2NaO+(M+Na)+:221.0748;Found:221.0746.
Example 9:
in an argon-filled glove box, A (26.8 mg,0.2 mmol) and dried Toluene (1.0 mL) were added to a reaction tube equipped with a magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and PE/EA (20/1 to 10/1, v/v) as eluent to give 28.9mg of the title compound G9 (colorless oil, yield) 68％).1H NMR(400MHz,CDCl3)δ7.35-7.27(m,2H),7.03-6.87(m,3H),5.83(t,J＝56.9Hz,1H),4.34(dd,J＝10.3,5.6Hz,1H),4.05-3.92(m,1H),2.75(s,1H),1.78-1.66(m,1H),1.20(dd,J＝10.0,6.5Hz,1H),0.94(ddt,J＝6.7,4.8,2.5Hz,1H);13C NMR(100MHz,CDCl3)δ158.5,129.7,121.4,115.2(t,J＝240.0Hz),114.9,66.4,57.9(t,J＝27.5Hz),19.3(t,J＝3.4Hz),14.2(t,J＝3.4Hz);19F NMR(375MHz,CDCl3)δ-125.2--128.5(m).IR(ATR)：3407,3402,1599,1495,1390,1301,1241,1107,1040,828,757cm1.HRMS(ESI,m/z)：calcd for C11H12F2NaO2 +(M+Na)+：237.0698;Found：237.0697.
Example 10:
In an argon-filled glove box, A (32.6 mg,0.2 mmol) and dry n-hexane 1.0 mL) were added to a reaction tube equipped with a magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and PE/EA (20/1 to 10/1, v/v) as eluent to give 28.9mg of the title compound G10 (colorless oil, yield) 68％).1H NMR(400MHz,CDCl3)δ5.68(t,J＝56.9Hz,1H),3.43(t,J＝6.7Hz,2H),2.27(s,1H),1.98-1.84(m,2H),1.60-1.51(m,4H),1.13-0.98(m,2H),0.59-0.52(m,1H);13C NMR(100MHz,CDCl3)δ116.1(t,J＝239.5Hz),57.9(t,J＝26.7Hz),33.9,32.4,28.2,25.6,20.3(t,J＝2.9Hz),15.2(t,J＝3.3Hz);19F NMR(375MHz,CDCl3)δ125.7(d,J＝56.8Hz).IR(ATR)：3374,2941,2859,1662,1454,1417,1290,1260,1107,1055,913,738cm1.
Example 11:
In an argon-filled glove box, A (20.8 mg,0.2 mmol) and dry chloroform (1.0 mL) were added to a reaction tube equipped with a magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and PE/EA (20/1 to 10/1, v/v) as eluent to give 32.1mg of the title compound G11 (colorless oil, yield) 81％).1H NMR(400MHz,CDCl3)δ5.68(t,J＝56.9Hz,1H),3.56(t,J＝6.6Hz,2H),2.24(s,1H),1.89-1.78(m,2H),1.63-1.53(m,4H),1.12-0.98(m,2H),0.56(ddt,J＝8.1,5.6,2.5Hz);13C NMR(100MHz,CDCl3)δ116.1(t,J＝240.6Hz),57.9(t,J＝27.2Hz),45.1,32.3,26.9,25.8,20.4(t,J＝3.0Hz),15.2(t,J＝3.4Hz);19F NMR(375MHz,CDCl3)δ125.7(d,J＝57.4Hz).IR(ATR)：3067,2960,2859,1662,1603,1498,1402,1320,1107,701cm1.
Example 12:
In an argon-filled glove box, A (20.8 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 23.1mg of the title compound G12 (pale yellow liquid, yield) 60％).1H NMR(400MHz,CDCl3)δ5.74(dd,J＝58.2,56.8Hz,1H),5.05(s,1H),2.73-2.62(m,2H),2.19(s,3H),1.94-1.81(m,1H),1.71-1.60(m,1H),1.02-0.85(m,2H),0.54(ddt,J＝7.9,5.4,2.7Hz,1H);13C NMR(100MHz,CDCl3)δ211.4,115.9(t,J＝241.4Hz),57.1(t,27.4Hz),43.5,30.4,20.0(t,J＝3.1Hz),19.7,15.0(t,J＝3.6Hz);19F NMR(375MHz,CDCl3)δ111.7-140.7(m).IR(ATR)：3362,2963,2933,1707,1409,1371,1308,1170,1111,1047,910,842cm1.HRMS(ESI,m/z)：calcd for C8H12F2NaO2 +(M+Na)+：201.0698;Found：201.0694.
Example 13:
In an argon-filled glove box, A (28.4 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 36.8mg of the title compound G13 (pale yellow liquid, yield) 83％).1H NMR(400MHz,CDCl3)δ5.68(t,J＝57.0Hz,1H),4.20-3.94(m,2H),2.77(s,1H),2.05(s,3H),1.72-1.62(m,2H),1.58-1.41(m,4H),1.11-0.95(m,2H),0.53(ddd,J＝5.6,4.5,2.6Hz,1H);13C NMR(100MHz,CDCl3)δ171.7,116.2(t,J＝240.6Hz),64.6,57.8(t,J＝27.1Hz),28.2,25.9,25.9,21.1,20.3(t,J＝3.1Hz),15.1(t,J＝3.5Hz);19F NMR(375MHz,CDCl3)δ125.7(dd,J＝56.6,21.6Hz).IR(ATR)：3414,2948,2862,1718,1461,1367,1252,1103,1036,917,738cm1.HRMS(ESI,m/z)：calcd for C10H17F2O3 +(M+H)+：223.1140;Found：223.1135.
Example 14:
in an argon-filled glove box, A (40.8 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 45.2mg of the title compound G14 (colorless liquid, yield) 80％).1H NMR(400MHz,CDCl3)δ8.16-7.89(m,1H),7.06-6.82(m,1H),5.69(t,J＝57.0Hz,0H),4.30(ddt,J＝30.9,10.8,6.7Hz,1H),3.85(s,2H),2.91(s,1H),1.90-1.71(m,3H),1.66-1.46(m,3H),1.11-0.93(m,1H),0.55(ddt,J＝6.7,5.6,2.5Hz,1H);13C NMR(150MHz,CDCl3)δ166.8,163.5,131.7,122.9,116.2(t,J＝240.6Hz),113.7,64.7,57.8(t,J＝27.0Hz),55.5,28.4,26.0,25.9,20.4(t,J＝3.0Hz),15.1(t,J＝3.4Hz);19F NMR(375MHz,CDCl3)δ125.7(dd,J＝56.9,19.3Hz).IR(ATR)：3444,2945,2863,1700,1454,1387,1279,1111,1051,716cm1.HRMS(ESI,m/z)：calcd for C15H18F2NaO3 +(M+Na)+：307.1116;Found：307.1112.
Example 15:
In an argon-filled glove box, A (46.8 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 51.5mg of the title compound G15 (pale yellow liquid, yield) 82％).1H NMR (400MHz,CDCl3)δ8.14-7.97(m,2H),7.60-7.52(m,1H),7.48-7.40(m,2H),5.69(t,J＝57.0Hz,1H),4.49-4.26(m,2H),2.68(s,1H),1.91-1.75(m,2H),1.66-1.53(m,4H),1.14-0.93(m,2H),0.56(ddt,J＝6.6,5.5,2.5Hz,1H);13C NMR(150MHz,CDCl3)δ167.0,133.1,130.5,129.7,128.5,116.2(t,J＝240.6Hz),65.0,57.9(t,J＝27.1Hz),28.4,26.1,25.9,20.4(t,J＝3.0Hz),15.1(t,J＝3.4Hz);19F NMR(375MHz,CDCl3)δ125.6(dd,J＝56.9,19.8Hz).IR(ATR)：3418,2937,2863,2251,1692,1607,1513,1260,1170,1103cm1.HRMS(ESI,m/z)：calcd for C16H20F2NaO4 +(M+Na)+：337.1222;Found：337.1219.
Example 16:
In an argon-filled glove box, A (50.8 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 43.8mg of the title compound G16 (pale yellow liquid, yield) 66％).1H NMR(400MHz,CDCl3)δ8.61(d,J＝1.6Hz,1H),8.06(dd,J＝8.6,1.7Hz,1H),7.96(dd,J＝8.2,1.4Hz,1H),7.88(dd,J＝8.2,1.5Hz,2H),7.57(dddd,J＝19.1,8.1,6.8,1.4Hz,2H),5.71(t,J＝57.0Hz,1H),4.56-4.25(m,2H),2.65(s,1H),1.99-1.81(m,2H),1.73-1.55(m,4H),1.20-0.93(m,2H),0.58(ddt,J＝6.7,5.5,2.6Hz,1H);13C NMR(150MHz,CDCl3)δ167.1,135.7,132.6,131.2,129.5,128.4,128.3,127.9,127.7,126.8,125.4,116.2(t,J＝240.8Hz),65.1,57.9(t,J＝27.0Hz),28.5,26.1,26.0,20.4(t,J＝3.1Hz),15.1(t,J＝3.3Hz);19F NMR(375MHz,CDCl3)δ125.7(dd,J＝56.5,20.9Hz(dd,J＝56.9,19.8Hz).IR(ATR)：3459,3064,2945,2866,1715,1469,1290,1230,1103,1051cm1.HRMS(ESI,m/z)：calcd for C19H20F2NaO3 +(M+Na)+：357.1273;Found：357.1270.
Example 17:
In an argon-filled glove box, A (44.4 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 47.4mg of the title compound G17 (pale yellow liquid, yield) 78％).1H NMR (400MHz,CDCl3)δ8.14-8.00(m,2H),7.21-7.03(m,2H),5.69(t,J＝57.0Hz,1H),4.49-4.14(m,2H),2.62(s,1H),1.89-1.76(m),1.65-1.48(m,4H),1.14-0.95(m,2H),0.56(ddd,J＝6.0,4.6,2.7Hz,1H);13C NMR(150MHz,CDCl3)δ166.0,165.9(d,J＝253.8Hz),132.2(d,J＝9.3Hz),126.7(d,J＝3.2Hz),116.2(t,J＝240.8Hz),115.6(d,J＝21.9Hz),65.1,57.9(t,J＝27.1Hz),28.4,26.0,25.9,20.4(t,J＝3.0Hz),15.1(t,J＝3.5Hz);19F NMR(375MHz,CDCl2)δ125.7(dd,J＝57.2,20.1Hz).IR(ATR)：3452,2945,2863,2255,1707,1602,1510,1279,1111,910cm1.HRMS(ESI,m/z)：calcd for C15H17F3NaO3 +(M+Na)+：325.1022;Found：325.1016.
Example 18:
In an argon-filled glove box, A (47.6 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and PE/EA (20/1 to 10/1, v/v) as eluent to give 49.2mg of the title compound G18 (pale yellow liquid, yield) 77％).1H NMR (400MHz,CDCl3)δ8.01-7.90(m,1H),7.47-7.38(m,1H),5.69(t,J＝57.0Hz,1H),4.46-4.20(m,1H),2.56(s,1H),1.88-1.74(m,1H),1.61-1.51(m,2H),1.14-0.96(m,1H),0.56(ddt,J＝6.5,5.5,2.6Hz,1H);13C NMR(150MHz,CDCl3)δ166.1,139.5,131.1,128.9,128.8,116.2(t,J＝240.8Hz),65.2,57.9(t,J＝27.0Hz),28.4,26.0,25.9,20.4(t,J＝3.0Hz),15.2(t,J＝3.4Hz);19F NMR(375MHz,CDCl3)δ105.2-106.0(m,1F),125.7(dd,J＝57.2,21.4Hz,1F).IR(ATR)：3437,2945,2900,1722,1491,1401,1275,1096,1051,973cm1.HRMS(ESI,m/z)：calcd for C15H17ClF2NaO3 +(M+Na)+：341.0726;Found：341.0727.
Example 19:
In an argon-filled glove box, A (45.8 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 40.5mg of the title compound G19 (pale yellow liquid, yield) 66％).1H NMR(400MHz,CDCl3)δ8.27-8.07(m,2H),7.92-7.65(m,2H),5.69(t,J＝56.9Hz,1H),4.38(qt,J＝10.9,6.7Hz,2H),2.53(s,1H),1.891.78(m,2H),1.611.54(m,4H),1.14-0.97(m,2H),0.56(ddt,J＝8.5,5.4,2.6Hz,1H);13C NMR(150MHz,CDCl3)δ165.2,134.3,132.4,130.2,118.1,116.5,116.2(t,J＝240.7Hz),65.8,57.8(t,J＝27.2Hz),28.3,26.0(d,J＝7.8Hz),20.3(t,J＝3.1Hz),15.2(t,J＝3.5Hz);19F NMR(375MHz,CDCl3)δ125.7(dd,J＝55.8,14.2Hz).IR(ATR)：3470,2933,2863,2233,1722,1282,1111,1051,865,768cm1.HRMS(ESI,m/z)：calcd for C16H17F2NNaO3 +(M+Na)+：332.1069;Found：332.1061.
Example 20:
In an argon filled glove box, A (42.0 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 50.9mg of the title compound G20 (pale yellow liquid, yield) 88％).1H NMR(400MHz,CDCl3)δ7.80(dd,J＝3.8,1.3Hz,1H),7.55(dd,J＝5.0,1.3Hz,1H),7.10(dd,J＝5.0,3.7Hz,1H),5.69(t,J＝57.0Hz,1H),4.49-4.26(m,2H),2.55(s,1H),1.91-1.74(m,2H),1.62-1.50(m,4H),1.17-0.93(m,2H),0.56(ddt,J＝8.6,5.4,2.6Hz,1H);13C NMR 162.6,134.0,133.5,132.5,127.9,116.2(t,J＝240.8Hz),65.1,57.9(t,J＝27.1Hz),28.4,26.0,25.9,20.4(t,J＝3.0Hz),15.1(t,J＝3.5Hz);19F NMR(375MHz,CDCl3)δ125.7(dd,J＝57.4,18.6Hz).IR(ATR)：3444,2945,2863,2255,1711,1416,1275,1103,906cm1.HRMS(ESI,m/z)：calcd for C13H16F2NaO3S+(M+Na)+：313.0680;Found：313.0677.
Example 21:
in an argon-filled glove box, 4CzIPN (2.4 mg,1.5 mmol%), A (20.8 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stirring bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. TBAF (1.0M in THF, 0.72mL,0.72mmol,3.6 eq.) was then added and the mixture was stirred at room temperature for 10 min. The reaction mixture was quenched with water (5 mL) and extracted with DCM (3X 20 mL). The organic phases were combined and washed with brine, dried over innumerable Na 2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (20/1 to 10/1, v/v) to give 26.2mg of the target compound G21 (major) (colorless liquid, yield 71%) and 5.0mg of the target compound G21' (minor) (white solid, yield 14％).G21(major)1H NMR(400MHz,CDCl3)δ7.37-7.3l(m,2H),7.29-7.22(m,3H),5.91(dd,J＝57.9,56.5Hz,1H),2.45(dd,J＝10.2,7.7Hz,1H),2.16(s,1H),1.46-1.33(m,2H);13C NMR(150MHz,CDCl3)134.6,128.9,128.6,127.1,115.3(t,J＝241.5Hz),58.5(t,J＝27.8Hz),25.1(t,J＝3.4Hz),15.2(t,J＝3.6Hz);19F NMR(375MHz,CDCl3)δ123.6-129.4(m,2F).IR(ATR)：3354,3090,2967,1603,1498,1409,1260,1088,1055,973cm1.HRMS(APCI-,m/z)：calcd fbr C10H9F2O-(M-H)-：183.0627;Found：183.0627.G21'(minor)1H NMR(400MHz,CDCl3)δ7.35-7.28(m,2H),7.27-7.22(m,3H),5.10(dd,J＝54.5,53.1Hz,1H),2.89-2.55(m,2H),1.51-1.39(m,2H).13C NMR(151MHz,CDCl3)δ135.1,128.9,128.8,127.3,116.0(t,J＝238.2Hz),58.8(t,J＝25.9Hz),29.5(d,J＝6.4Hz),15.2(d,J＝5.6Hz).19F NMR(376MHz,CDCl3)δ-120.9--134.6(m,2F).IR(ATR)：3411,3064,1710,1603,1290,1238,1096,1044,939,cm1.HRMS(APCI-,m/z)：calcd for C10H9F2O-(M-H)-：183.0627;Found：183.0627.
Example 22:
In an argon filled glove box, A (23.6 mg,0.2 mmol) and dry DCM (1.0 mL) were added to the reaction tube with the magnetic stir bar. Then B (128.4 mg,0.6mmol,3 eq.) was added. The tube was sealed with a septum-fitted screw cap and removed from the glove box. The reaction mixture was stirred at room temperature under blue light (6W) for 12 hours. MeOH (1 mL) was then added, TMSCl (5 ul,5 mol%) and the mixture was stirred at room temperature for 5 min. The reaction solution was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (200 to 300 mesh) and eluted with PE/EA (40/1 to 10/1, v/v) to give 19.8mg of the title compound G22 (colorless liquid, yield 946%) and 21.2mg of the title compound G22' (white solid, yield) 49％).G221H NMR(400MHz,CDCl3)δ7.34-7.19(m,5H),2.87(s,1H),1.71(d,J＝3.2Hz,1H),1.57(s,3H),1.11-1.05(m,1H);13C NMR(400MHz,CDCl3)140.4,129.3,128.6,127.6,125.4(q,J＝276.2Hz),59.4(q,J＝37.0Hz),32.3,23.3(d,J＝2.2Hz),21.9(d,J＝2.7Hz);19F NMR(375MHz,CDCl3)δ71.7(s,3F)IR(ATR)：3526,3466,1379,1141,1081,928,871,768,701cm1.G22,1H NMR(400MHz,CDCl3)δ7.42-7.36(m,2H),7.34-7.27(m,3H),2.07(s,1H),1.54(q,J＝1.4Hz,3H),1.52-1.48(m,1H),1.43(d,J＝6.6Hz,1H).13C NMR(151MHz,CDCl3δ140.91,128.50,128.35,127.02,125.03(q,J＝276.2Hz),61.04(d,J＝36.0Hz),32.57,23.03,21.64.19F NMR(375MHz,CDCl3)δ70.2(s,3F)IR(ATR)：3284,1498,1446,1386,1260,1179,1141,1081,935,772,705cm1.
Application examples for the preparation of ketones
The reaction formula is shown as follows:
Wherein the compound of formula G represents an alpha-fluoroalkyl substituted cyclopropylalcohol compound and formula H represents an alpha-fluoroalkyl substituted ketone compound.
The specific implementation cases are as follows:
Example 23:
To a 25mL reaction tube was added NaOH (0.6 mmol,40.4 mg), meOH (2 mL), G4 (0.2 mmol,40. Mg), and the reaction was left at room temperature for 12 hours, then 4 equivalents of trifluoroacetic acid were added and reacted at room temperature for 10 minutes. 2mL of water was added, extracted with DCM, washed with saturated brine, dried over anhydrous sodium sulfate and eluted with PE/EA (40/1-10/1, v/v) to give 33.2mg of the title compound H1 (colorless liquid, yield) 82％).1H NMR(400MHz,CDCl3)δ7.35-7.27(m,2H),7.26-7.16(m,3H),3.12-2.93(m,4H).13C NMR(151MHz,CDCl3δ90.8(q,J＝35.3Hz),139.4,128.9,128.4,126.8,115.7(q,J＝292.0Hz),38.2,28.4.19F NMR(375MHz,CDCl3)δ79.1(s,3F).
Application examples for preparing fluorine-containing heterocyclic Compounds
The reaction formula is shown as follows:
wherein the compound of formula G represents an alpha-fluoroalkyl substituted cyclopropyl alcohol compound, formula I represents an aryl diazonium salt compound, and formula J represents a fluorine-containing heterocyclic compound
The specific implementation cases are as follows:
Example 24:
in a glove box, I1 (0.1 mmol,19.2 mg), cu (OAc) 2 (0.1 mmol,18 mg), acetonitrile (0.5 mL), G5 (0.15 mmol,34.5 mg) were added and reacted at room temperature for 12 hours. By passing a plug, DCM as eluent, spin-drying and using PE/EA (10/1-5/1, v/v) as eluent, 31.1mg of the target compound M1 (pale yellow solid, yield) 93％).1H NMR(400MHz,CDCl3)δ7.37-7.28(m,4H),7.28-7.20(m,6H),3.25(d,J＝18.1Hz,1H),3.04-2.89(m,3H),2.77(s,1H),2.72(t,J＝7.6Hz,2H).13C NMR(151MHz,CDCl3)δ152.6,140.9,140.8,129.0,128.7,128.5,126.5,126.5,125.4,123.5(q),93.3(q,J＝31.2Hz),46.5,32.9,31.6.19F NMR(375MHz,CDCl3)δ77.8(s,3F).
To a 4mL vial was added M1 (0.093 mmol,31.1 mg), DCM (0.5 mL), and finally CF 3 COOH (0.0186 mmol,21.2 mg), reacted at room temperature for 5 minutes, the reaction was directly dried by spin and with PE/EA (40/1-10/1, v/v) to give 23.8mg of the title compound J1. (pale yellow liquid, yield) 81％).1H NMR(400MHz,CDCl3)δ7.50-7.43(m,5H),7.34-7.28(m,2H),7.26-7.20(m,3H),6.58(s,1H),3.02(s,4H).13C NMR(151MHz,CDCl3)δ152.8,141.3,139.3,133.1(q,J＝78.1,39.0Hz),129.2,128.6,128.6,126.3,125.8,120.0(q,J＝268.9Hz),108.0(q,J＝2.5Hz),35.7,30.0.19F NMR(375MHz,CDCl3)δ57.3(s,3F).
While the invention has been described with respect to the preferred embodiments, it will be understood that the invention is not limited thereto, but is capable of modification and variation without departing from the spirit of the invention, as will be apparent to those skilled in the art.
Claims (4)
1. The preparation method of the alpha-fluoroalkyl substituted cyclopropyl alcohol compound is characterized in that under the protection of inert gas, olefin A and fluorine-containing acyl silicon B are dissolved in an organic solvent, stirred and reacted under illumination, and desilicated and purified after the reaction, so that the alpha-fluoroalkyl substituted cyclopropyl alcohol compound is obtained;
the molecular structural formula of the olefin A is 、/>、/>、、/>、/>、/>、/>、、/>、/>、/>、、/>、/>、/>、、/>、/>、/>At least one of (a) and (b);
correspondingly, the molecular structural formula of the fluorine-containing acyl silicon B is 、/>、At least one of (a) and (b);
The molecular structural formula of the alpha-fluoroalkyl substituted cyclopropyl alcohol compound is at least one of the following:
、/>、/>、/>、、/>、/>、/>、、/>、/>、、/>、/>、、/>、/>、/>、。
2. The method for preparing the alpha-fluoroalkyl substituted cyclopropyl alcohol compound according to claim 1, wherein the method comprises the following steps: the organic solvent is at least one of methanol, ethanol, isopropanol, tertiary butanol, tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, dimethylethylene glycol ether, methyl tertiary butyl ether, 1, 4-epoxyhexaane, 1, 3-epoxyhexaane, methylene dichloride, 1, 2-dichloroethane, chloroform, carbon tetrachloride, saturated alkane of C 4-12, fluorinated or chlorinated alkane of C 3-12, benzene, toluene, xylene, trimethylbenzene, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, acetone, N-methylpyrrolidone, acetonitrile and saturated alkyl nitrile of C 3-12.
3. The method for preparing the alpha-fluoroalkyl substituted cyclopropyl alcohol compound according to claim 1, wherein the method comprises the following steps: the mol ratio between the olefin A and the fluorine-containing acyl silicon B is 1:1-6; the concentration of olefin A in the mixed solution is between 0.1M and 1M.
4. The method for preparing the alpha-fluoroalkyl substituted cyclopropyl alcohol compound according to claim 1, wherein the method comprises the following steps: the raw materials also comprise a catalyst, wherein the photocatalyst is tris [ 2-phenylpyridine-C2, N ] iridium (III), bis [2- (2, 4-difluorophenyl) -5-trifluoromethylpyridine ] [2-2 '-bis (4-tert-butylpyridine) ] iridium bis (hexafluorophosphate), bis [2- (2, 4-difluorophenyl) -5-methylpyridine ] [2,2' -bis (tetra-tert-butylpyridine) ] iridium bis (hexafluorophosphate), bis [2- (2, 4-difluorophenyl) -5-trifluoromethylpyridine ] [2-2 '-bipyridine ] iridium bis (hexafluorophosphate), [2,2' -bis (4-tert-butylpyridine) ] bis [2- (2, 4-difluorophenyl) pyridine ] iridium (III) hexafluorophosphate, (4, 4 '-di-tert-butyl-2, 2' -bipyridine) bis [ (2-pyridyl) phenyl ] iridium (III) hexafluorophosphate, bis (2-methyl-3-phenylpyrazine-C2, N) acetyl pyruvic 2, N-difluorophenyl) -5-trifluoromethylpyridine ] [2-2 '-bipyridine ] iridium bis (hexafluorophosphate, [2,2' -bis (4-difluorophenyl) pyridine ] iridium (III) hexafluorophosphate, bis [ 4,4 '-di-tert-butyl-phenyl ] iridium (III) acetylacetonate, bis (2-diphenyl) dipyr-2, 2' -bipyridine ] iridium (III) hexafluorophosphate, acetyl pyruvic 2, N-dipyr-2-dipyr-3-dipyr-C (2, 2 '-bipyridine) bis [2- (2, 4-difluorophenyl) pyridine ] iridium (III) hexafluorophosphate, (2, 2' -bipyridine) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, (2-2 '-bis (4-tert-butylphenyl) pyridine) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, (1, 10-phenanthroline) bis [2- (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, tris (2- (4-fluorophenyl) pyridine) iridium, tris [2- (4, 6-difluorophenyl) pyridine-C2, N ] iridium (III), bis [2- (3-tert-butylphenyl) -4-tert-butylphenyl ] [2,2' -bis (4-tert-butylphenyl) pyridine) ] iridium (III) hexafluorophosphate, tetra (2- (2-pyridyl) phenyl) bis (III) dichloro tetrakis [2- (4-trifluoromethylphenyl) pyridine ], [2,2 '-bis [ 2-tert-butylphenyl ] pyridine ] ruthenium (III) bis [2, 6-fluorophenyl ] bis (6-phenanthridine ] iridium (III) hexafluorophosphate, tris [2- (3-tert-butylphenyl) pyridine ] bis [ 2-tert-butylphenyl) pyridine ] ruthenium (III) bis [2,2' -bis (4-tert-butylphenyl) pyridine ] iridium (III) hexafluorophosphate, bis [ 2-4-butylphenyl ] bis (4-tert-butylphenyl) pyridine ] iridium (III) phosphate, bis (2-4-butylphenyl) fluoride Any one of tris (4, 4 '-dimethyl-2, 2' -bipyridine) ruthenium (III) (hexafluorophosphoric acid) salt, tris (2, 2 '-bipyrazine) ruthenium bis (hexafluorophosphonic acid) salt, tris (2, 2' -bipyridine) ruthenium bis (hexafluorophosphoric acid) salt, tris (2, 2 '-bipyridine) ruthenium bis (perchloric acid) salt, tris (2, 2' -bipyridine) ruthenium bis (tetrafluoroboric acid) salt, tris (2, 2 '-bipyridine) ruthenium (II) chloride hexahydrate, 9-mesityl-10-phenylacridine-10-tetrafluoroborate, 2,3,5, 6-tetrakis (9-carbazolyl) -terephthalonitrile, 2,4,5, 6-tetrakis (9-carbazolyl) -isophthalonitrile (4 CzIPN), tris (2, 2' -bipyridine) ruthenium (II) chloride hexahydrate, and solvent red 43.
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