CN114456134B - 一种α-氟烷基取代的环丙基醇类化合物、其制备方法及应用 - Google Patents
一种α-氟烷基取代的环丙基醇类化合物、其制备方法及应用 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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- -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
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Abstract
本发明涉及有机合成的技术领域,具体涉及一种α‑氟烷基取代的环丙基醇类化合物、其制备方法及应用,其分子结构式如下:其中,R1、R2、R3、R4分别为芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、杂原子、氢原子中的任意一种,Rf为CF3、CF2R5或CFR6R7,R5为卤素、芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、羧基、杂原子、氢原子中的任意一种;R6、R7分别为芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、杂原子、氢原子中的任意一种,可以相同也可以不同。本发明的α‑氟烷基取代的环丙基醇类化合物是一种新型化合物结构,具有高的非对映选择性。
Description
技术领域
本发明涉及有机合成的技术领域,具体涉及一种α-氟烷基取代的环丙基醇类化合物、其制备方法及应用。
背景技术
α-氟烷基醇切块在许多生物活性化合物中广泛存在,从而引起了有机合成化学家们的密切关注。然而直接合成α-氟烷基醇的方法有限,2012年,Reissig等人报道了氟烷基取代的环丙烯基醚类化合物的合成[H.-U.Reissig,Helvetica Chimica Acta,2012,95(10),1818-1830],在过渡金属醋酸铑的催化下,含氟烯醇硅醚与重氮化合物【2+1】环化反应得到了α-氟烷基环丙基硅醚,该反应并不能很好的控制dr,并且低物局限于含有酯基的重氮类化合物,底物普适性差。传统的方法一般是对醛或酮的亲核加成产生。但是这些方法无法控制底物的区域选择性,并且对于特定的醛或酮需要多步合成,因此急需发展一种能直接引入α-氟烷基醇切块的方法。本发明主要研究了直接合成α-氟烷基取代的环丙基醇的方法及应用。
发明内容
本发明的目的之一在于提供一种α-氟烷基取代的环丙基醇类化合物,具有高的非对映选择性。
本发明的目的之二在于提供一种α-氟烷基取代的环丙基醇类化合物的制备方法,操作简单,反应条件简单。
本发明的目的之三在于提供一种α-氟烷基取代的环丙基醇类化合物的应用。
本发明实现目的之一所采用的方案是:一种α-氟烷基取代的环丙基醇类化合物,其分子结构式如下:
其中,R1、R2、R3、R4分别为芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、杂原子、氢原子中的任意一种,可以相同也可以不同,Rf为CF3、CF2R5或CFR6R7,R5为卤素、芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、羧基、杂原子、氢原子中的任意一种;R6、R7分别为芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、杂原子、氢原子中的任意一种,可以相同也可以不同。
杂原子为硅、氧、硫、氮等杂原子。
优选地,所述芳基带有一个或者多个取代基;当具有多个取代基时,取代基可以相同或不同。
优选地,所述烷基具有1-20个碳原子,为直链结构、环状结构或者支链结构。
优选地,所述烷基带有一个或多个取代基,当具有多个取代基时,取代基可以相同也可以不同,位置可以相同也可以不相同。
本发明实现目的之二所采用的方案是:一种所述的α-氟烷基取代的环丙基醇类化合物的制备方法,在惰性气体保护下,先将烯烃A和含氟酰基硅B溶于有机溶剂中,然后在光照下搅拌反应,反应后脱硅提纯,即得到α-氟烷基取代的环丙基醇化合物。
优选地,所述烯烃A的分子结构式为
所述含氟酰基硅B的分子结构式为
其中,R1、R2、R3、R4分别为芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、杂原子、氢原子中的任意一种,可以相同也可以不同,Rf为CF3、CF2R5或CFR6R7,R5为卤素、芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、羧基、杂原子、氢原子中的任意一种;R6、R7为芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、杂原子、氢原子中的任意一种,可以相同也可以不同,R8、R9、R10分别为芳基、杂芳基、烷基、烯基、炔基、酯基、氰基、硝基、磺酰基、杂原子、氢原子中的任意一种,可以相同也可以不同。
优选地,所述有机溶剂为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、***、二甲基乙二醚、甲基叔丁基醚、1,4-环氧六烷、1,3-环氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的至少一种。
优选地,所述烯烃A和含氟酰基硅B之间的摩尔比为1:1-6;混合溶液中烯烃A的浓度在0.1M到1M之间。
优选地,原料还包括催化剂,所述光催化剂为三[2-苯基吡啶-C2,N]铱(III)、二[2-(2,4-二氟苯基)-5-三氟甲基吡啶][2-2'-联(4-叔丁基吡啶)]铱二(六氟磷酸)盐、二[2-(2,4-二氟苯基)-5-甲基吡啶][2,2'-联(四叔丁基吡啶)]铱二(六氟磷酸)盐、二[2-(2,4-二氟苯基)-5-三氟甲基吡啶][2-2'-联吡啶]铱二(六氟磷酸)盐、[2,2'-联(4-叔丁基吡啶)]双[2-(2,4-二氟苯基)吡啶]铱(III)六氟磷酸盐、(4,4'-二叔丁基-2,2'-联吡啶)双[(2-吡啶基)苯基]铱(III)六氟磷酸盐、乙酰丙酮酸二(2-甲基-3-苯基吡嗪-C2,N)合铱、乙酰丙酮酸二(2,3-二苯基吡嗪-C2,N)合铱、乙酰丙酮酸二(2,3-二苯基喹喔啉)合铱、乙酰丙酮酸二(2-苯基嘧啶-C2,N)合铱、(2,2'-联吡啶)双[2-(4-氟苯基)吡啶]铱(III)六氟磷酸盐、(2,2'-联吡啶)双[2-(2,4-二氟苯基)吡啶]铱(III)六氟磷酸盐、(2,2'-联吡啶)双[2-(4-叔丁基苯基)吡啶]铱(III)六氟磷酸盐、(2-2'-联(4-叔丁基吡啶)双[2-(4-叔丁基苯基)吡啶]铱(III)六氟磷酸盐、(1,10-菲罗啉)双[2-(4-叔丁基苯基)吡啶]铱(III)六氟磷酸盐、三(2-(4-氟苯基)吡啶)合铱、三[2-(4,6-二氟苯基)吡啶-C2,N]铱(III)、二[2-(3-叔丁基苯基)-4-叔丁基吡啶][2,2`-联(4-叔丁基吡啶)]合铱(III)六氟磷酸盐、二氯四(2-(2-吡啶基)苯基)二铱(III)、三(2-(4-三氟甲基苯基)吡啶)合铱、[2,2'-联(4-叔丁基吡啶)]双[2-(4-氟苯基)吡啶]铱(III)六氟磷酸盐、罗丹明6G、三(1,10-菲咯啉)钌(II)双(六氟磷酸盐)、三(4,4'-二甲基-2,2'-联吡啶)钌(III)(六氟磷酸)盐、三(2,2'-联吡嗪)钌二(六氟膦酸)盐、三(2,2'-联吡啶)钌二(六氟磷酸)盐、三(2,2'-联吡啶)钌二(高氯酸)盐、三(2,2'-联吡啶)钌二(四氟硼酸)盐、三(2,2'-联吡啶)氯化钌(II)六水合物、9-均三甲苯基-10-苯基吖啶-10-四氟硼酸盐、2,3,5,6-四(9-咔唑基)-对苯二腈、2,4,5,6-四(9-咔唑基)-间苯二腈(4CzIPN)、4CzIPN的衍生物、三(2,2'-联吡啶)氯化钌(II)六水合物、溶剂红43中的任意一种。催化剂作为选用原料,本反应在没有催化剂的作用下也能进行,加入催化剂之后对产率有部分提高,并不影响反应性。
所述反应的温度为-78℃到180℃,反应时间在3-24小时以内。光照过程可采用白光、蓝光、紫光、绿光、太阳光等可见光中的任意一种或者其它光照方式。本发明在反应完成后对反应产物进行后处理,包括抽滤、浓缩、重结晶和柱层析等纯化方法。
本发明方法的反应式可表示如下:
其中,式A化合物代表烯烃,式B化合物代表含氟酰基硅,式G代表α-氟烷基取代的环丙基醇。
本发明实现目的之三所采用的方案是:一种所述的α-氟烷基取代的环丙基醇类化合物在合成α-氟烷基酮及含氟取代杂环化合物中的应用。
本发明具有以下优点和有益效果:
(1)本发明的α-氟烷基取代的环丙基醇类化合物是一种新型化合物结构,具有高的非对映选择性。
(2)本发明的制备方法实现了可见光诱导的含氟酰基硅与烯烃的环丙烷化,直接高效地合成α-氟烷基取代的环丙基醇,并且表现出极好的非对映选择性。
(3)本发明的制备方法不需要用催化剂来促进,也不需要其他添加剂,反应条件简单。
(4)本发明的制备方法所涉及的反应条件具有良好的官能团容忍性和底物普适性,取代基可以为烷基、烷氧基、酯基等、杂芳环、卤素。
(5)本发明的产物还可以应用于合成各种α-氟烷基酮及含氟取代杂环化合物。
具体实施方式
为更好的理解本发明,下面的实施例是对本发明的进一步说明,但本发明的内容不仅仅局限于下面的实施例。
实施例1:
在手套箱中,向干燥并装有磁力搅拌子的光反应管中加入A(38.8mg,0.2mmol),干燥的DCE(0.5mL)和B(92.8mg,0.4mmol,2equiv.)。将光反应管密封,从手套箱中取出,然后用6W的蓝色LED灯照射,反应混合物在室温下搅拌24小时。然后关闭蓝灯,加入TBAF(0.24mL,1.0M in THF,1.2equiv.),并将混合物在冰浴下搅拌10min。将反应混合物在减压下浓缩。粗产物用硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)洗脱,得到目标化合物G1(无色油状液体52.6mg,产率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 forC13H16F3O4 +(M+H)+:293.0995;Found:293.0998。
实施例2:
在手套箱中,向干燥并装有磁力搅拌子的光反应管中加入A(20.8mg,0.2mmol),干燥的DCM(0.5mL)和B(92.8mg,0.4mmol,2equiv.)。将光反应管密封,从手套箱中取出,然后用6W的蓝色LED灯照射,反应混合物在室温下搅拌24小时。然后关闭蓝灯,加入TBAF(0.24mL,1.0M in THF,1.2equiv.),并将混合物在冰浴下搅拌10min。将反应混合物在减压下浓缩。粗产物用硅胶柱色谱纯化(200~300目),并用PE/EA(50/1~10/1,v/v)洗脱,得到目标化合物G2(无色油状液体28.3mg,产率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)。
实施例3:
在手套箱中,向干燥并装有磁力搅拌子的光反应管中加入A(20.8mg,0.2mmol),干燥的DCM(0.5mL)和B(92.8mg,0.4mmol,2equiv.)。将光反应管密封,从手套箱中取出,然后用6W的白色LED灯照射,反应混合物在室温下搅拌24小时。然后关闭蓝灯,加入TBAF(0.24mL,1.0M in THF,1.2equiv.),并将混合物在冰浴下搅拌10min。将反应混合物在减压下浓缩。粗产物用硅胶柱色谱纯化(200~300目),并用PE/EA(50/1~10/1,v/v)洗脱,得到目标化合物G3(无色油状液体27.2mg,产率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)。
实施例4:
在手套箱中,向干燥并装有磁力搅拌子的光反应管中加入A(20.8mg,0.2mmol),干燥的DCM(0.5mL)和B(92.8mg,0.4mmol,2equiv.)。将光反应管密封,从手套箱中取出,然后用6W的绿色LED灯照射,反应混合物在室温下搅拌24小时。然后关闭蓝灯,加入TBAF(0.24mL,1.0M in THF,1.2equiv.),并将混合物在冰浴下搅拌10min。将反应混合物在减压下浓缩。粗产物用硅胶柱色谱纯化(200~300目),并用PE/EA(50/1~10/1,v/v)洗脱,得到目标化合物G4(无色油状液体26.3mg,产率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)。
实施例5:
在手套箱中,向干燥并装有磁力搅拌子的光反应管中加入A(26.4mg,0.2mmol),干燥的DCM(0.5mL)和B(92.8mg,0.4mmol,2equiv.)。将光反应管密封,从手套箱中取出,然后用6W的紫色LED灯照射,反应混合物在室温下搅拌24小时。然后关闭蓝灯,加入TBAF(0.24mL,1.0M in THF,1.2equiv.),并将混合物在冰浴下搅拌10min。将反应混合物在减压下浓缩。粗产物用硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)洗脱,得到目标化合物G5(无色油状液体32.7mg,产率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)。
实施例6:
在手套箱中,向干燥并装有磁力搅拌子的光反应管中加入A(20.4mg,0.1mmol),干燥的DCM(1mL)和B(74.4mg,0.3mmol,3equiv.)。将光反应管密封,从手套箱中取出,然后用6W的蓝色LED灯照射,反应混合物在室温下搅拌12小时。然后关闭蓝灯,将反应混合物在减压下浓缩。粗产物用硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)洗脱,得到目标化合物G6(无色油状液体84.0mg,产率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。
实施例7:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(26.4mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温太阳光下搅拌6小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到37.1mg目标化合物G7(无色油状物,产率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。
实施例8:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(23.6mg,0.2mmol)和干燥的EA(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到30.2mg目标化合物G8(无色油状物,产率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。
实施例9:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(26.8mg,0.2mmol)和干燥的Toluene(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到28.9mg目标化合物G9(无色油状物,产率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。
实施例10:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(32.6mg,0.2mmol)和干燥的正己烷1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到28.9mg目标化合物G10(无色油状物,产率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。
实施例11:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(20.8mg,0.2mmol)和干燥的氯仿(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到32.1mg目标化合物G11(无色油状物,产率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。
实施例12:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(20.8mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到23.1mg目标化合物G12(淡黄色液体,产率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。
实施例13:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(28.4mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到36.8mg目标化合物G13(淡黄色液体,产率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。
实施例14:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(40.8mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到45.2mg目标化合物G14(无色液体,产率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 forC15H18F2NaO3 +(M+Na)+:307.1116;Found:307.1112。
实施例15:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(46.8mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到51.5mg目标化合物G15(淡黄色液体,产率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。
实施例16:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(50.8mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到43.8mg目标化合物G16(淡黄色液体,产率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。
实施例17:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(44.4mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到47.4mg目标化合物G17(淡黄色液体,产率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。
实施例18:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(47.6mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到49.2mg目标化合物G18(淡黄色液体,产率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。
实施例19:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(45.8mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到40.5mg目标化合物G19(淡黄色液体,产率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。
实施例20:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(42.0mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到50.9mg目标化合物G20(淡黄色液体,产率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。
实施例21:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入4CzIPN(2.4mg,1.5mmol%),A(20.8mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入TBAF(1.0M的THF溶液,0.72mL,0.72mmol,3.6当量),并将混合物在室温搅拌10分钟。用水(5mL)淬灭反应混合物,并用DCM(3×20mL)萃取。合并有机相并用盐水洗涤,无数Na2SO4干燥,减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(20/1~10/1,v/v)作为洗脱剂,得到26.2mg目标化合物G21(major)(无色液体,产率71%)和5.0mg目标化合物G21’(minor)(白色固体,产率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):calcdfor C10H9F2O-(M-H)-:183.0627;Found:183.0627。
实施例22:
在充满氩气的手套箱中,在装有磁力搅拌棒的反应管中加入A(23.6mg,0.2mmol)和干燥的DCM(1.0mL)。然后加入B(128.4mg,0.6mmol,3当量)。用装有隔膜的螺帽将管密封,将其从手套箱中取出。将反应混合物在室温蓝光下(6W)搅拌12小时。然后加入MeOH(1mL),TMSCl(5ul,5mol%),将混合物在室温搅拌5分钟。反应液减压下浓缩。粗产物经硅胶柱色谱纯化(200~300目),并用PE/EA(40/1~10/1,v/v)作为洗脱剂,得到19.8mg目标化合物G22(无色液体,产946%)和21.2mg目标化合物G22’(白色固体,产率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。
制备酮的应用实施例
反应通式如下所示:
其中,式G化合物代表α-氟烷基取代环丙基醇化合物,式H代表α-氟烷基取代酮化合物。
具体实施案例如下:
实施例23:
向25mL的反应管中加入NaOH(0.6mmol,40.4mg),MeOH(2ml),G4(0.2mmol,40.mg),反应置于室温反应12小时,然后加入4当量的三氟乙酸,室温反应10分钟。加入2mL水,DCM萃取,饱和食盐水洗涤,无水硫酸钠干燥,并用PE/EA(40/1~10/1,v/v)作为洗脱剂,得到33.2mg的目标化合物H1(无色液体,产率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).
制备含氟杂环化合物的应用实施例
反应通式如下所示:
其中,式G化合物代表α-氟烷基取代环丙基醇化合物,式I代表芳基重氮盐化合物,式J代表含氟杂环化合物
具体实施案例如下:
实例24:
在手套箱中加入I1(0.1mmol,19.2mg),Cu(OAc)2(0.1mmol,18mg),乙腈(0.5mL),G5(0.15mmol,34.5mg),室温反应12小时。过一个plug,DCM作为洗脱剂,旋干、并用PE/EA(10/1~5/1,v/v)作为洗脱剂,得到31.1mg的目标化合物M1(淡黄色固体,产率93%)。1HNMR(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).
向4mL的小瓶子中加入M1(0.093mmol,31.1mg),DCM(0.5mL),最后加入CF3COOH(0.0186mmol,21.2mg),室温反应5分钟,反应液直接旋干,并用PE/EA(40/1~10/1,v/v),得到23.8mg的目标化合物J1。(淡黄色液体,产率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).
以上所述是本发明的优选实施方式而已,当然不能以此来限定本发明之权利范围,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和变动,这些改进和变动也视为本发明的保护范围。
Claims (4)
1.一种α-氟烷基取代的环丙基醇类化合物的制备方法,其特征在于,在惰性气体保护下,先将烯烃A和含氟酰基硅B溶于有机溶剂中,光照下搅拌反应,反应后脱硅提纯,即得到α-氟烷基取代的环丙基醇化合物;
所述烯烃A的分子结构式为、/>、/>、、/>、/>、/>、/>、、/>、/>、/>、、/>、/>、/>、、/>、/>、/>中的至少一种;
对应的,所述含氟酰基硅B的分子结构式为、/>、中的至少一种;
所述α-氟烷基取代的环丙基醇类化合物分子结构式为如下所示中的至少一种:
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2.根据权利要求1所述的α-氟烷基取代的环丙基醇类化合物的制备方法,其特征在于:所述有机溶剂为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、***、二甲基乙二醚、甲基叔丁基醚、1,4-环氧六烷、1,3-环氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的至少一种。
3.根据权利要求1所述的α-氟烷基取代的环丙基醇类化合物的制备方法,其特征在于:所述烯烃A和含氟酰基硅B之间的摩尔比为1:1-6;混合溶液中烯烃A的浓度在0.1M到1M之间。
4. 根据权利要求1所述的α-氟烷基取代的环丙基醇类化合物的制备方法,其特征在于:原料还包括催化剂,所述光催化剂为三[2-苯基吡啶-C2,N]铱(III)、二[2-(2,4-二氟苯基)-5-三氟甲基吡啶][2-2'-联(4-叔丁基吡啶)]铱二(六氟磷酸)盐、二[2-(2,4-二氟苯基)-5-甲基吡啶][2,2'-联(四叔丁基吡啶)]铱二(六氟磷酸)盐、二[2-(2,4-二氟苯基)-5-三氟甲基吡啶][2-2'-联吡啶]铱二(六氟磷酸)盐、[2,2'-联(4-叔丁基吡啶)]双[2-(2,4-二氟苯基)吡啶]铱(III) 六氟磷酸盐、(4,4'-二叔丁基-2,2'-联吡啶)双[(2-吡啶基)苯基]铱(III)六氟磷酸盐、乙酰丙酮酸二(2-甲基-3-苯基吡嗪-C2,N)合铱、乙酰丙酮酸二(2,3-二苯基吡嗪-C2,N)合铱、乙酰丙酮酸二(2,3-二苯基喹喔啉)合铱、乙酰丙酮酸二(2-苯基嘧啶-C2,N)合铱、(2,2'-联吡啶)双[2-(4-氟苯基)吡啶]铱(III) 六氟磷酸盐、(2,2'-联吡啶)双[2-(2,4-二氟苯基)吡啶]铱(III) 六氟磷酸盐、(2,2'-联吡啶)双[2-(4-叔丁基苯基)吡啶]铱(III)六氟磷酸盐、(2-2'-联(4-叔丁基吡啶)双[2-(4-叔丁基苯基)吡啶]铱(III) 六氟磷酸盐、(1,10-菲罗啉)双[2-(4-叔丁基苯基)吡啶]铱(III) 六氟磷酸盐、三(2-(4-氟苯基)吡啶)合铱、三[2-(4,6-二氟苯基)吡啶-C2,N]铱(III)、二[2-(3-叔丁基苯基)-4-叔丁基吡啶][2,2`-联(4-叔丁基吡啶)]合铱(III)六氟磷酸盐、二氯四(2-(2-吡啶基)苯基)二铱(III)、三(2-(4-三氟甲基苯基)吡啶)合铱、[2,2'-联(4-叔丁基吡啶)]双[2-(4-氟苯基)吡啶]铱(III) 六氟磷酸盐、罗丹明 6G、三(1,10-菲咯啉)钌(II)双(六氟磷酸盐)、三(4,4'-二甲基-2,2'-联吡啶)钌(III)(六氟磷酸)盐、三(2,2'-联吡嗪)钌二(六氟膦酸)盐、三(2,2'-联吡啶)钌二(六氟磷酸)盐、三(2,2'-联吡啶)钌二(高氯酸)盐、三(2,2'-联吡啶)钌二(四氟硼酸)盐、三(2,2'-联吡啶)氯化钌(II) 六水合物、9-均三甲苯基-10-苯基吖啶-10-四氟硼酸盐、2,3,5,6-四(9-咔唑基)-对苯二腈、2,4,5,6-四(9-咔唑基)-间苯二腈(4CzIPN)、三(2,2'-联吡啶)氯化钌(II) 六水合物、溶剂红43中的任意一种。
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