CN113773227B - Method for preparing epsilon-, zeta-, eta-cyano carboxylic acid from carbon dioxide - Google Patents
Method for preparing epsilon-, zeta-, eta-cyano carboxylic acid from carbon dioxide Download PDFInfo
- Publication number
- CN113773227B CN113773227B CN202111000883.2A CN202111000883A CN113773227B CN 113773227 B CN113773227 B CN 113773227B CN 202111000883 A CN202111000883 A CN 202111000883A CN 113773227 B CN113773227 B CN 113773227B
- Authority
- CN
- China
- Prior art keywords
- methyl
- mmol
- reaction mixture
- cyano
- stirred
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 title claims abstract description 90
- 229910002092 carbon dioxide Inorganic materials 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 16
- 239000001569 carbon dioxide Substances 0.000 title claims abstract description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 117
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims abstract description 40
- 150000001336 alkenes Chemical class 0.000 claims abstract description 20
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 11
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052707 ruthenium Inorganic materials 0.000 claims abstract description 8
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 7
- 229910052741 iridium Inorganic materials 0.000 claims abstract description 7
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000001424 substituent group Chemical group 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000003054 catalyst Substances 0.000 claims abstract description 3
- -1 cyclic ketone oxime Chemical class 0.000 claims description 86
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 73
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Chemical group 0.000 claims description 6
- 229910052739 hydrogen Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- 239000011941 photocatalyst Substances 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- CHEANNSDVJOIBS-MHZLTWQESA-N (3s)-3-cyclopropyl-3-[3-[[3-(5,5-dimethylcyclopenten-1-yl)-4-(2-fluoro-5-methoxyphenyl)phenyl]methoxy]phenyl]propanoic acid Chemical compound COC1=CC=C(F)C(C=2C(=CC(COC=3C=C(C=CC=3)[C@@H](CC(O)=O)C3CC3)=CC=2)C=2C(CCC=2)(C)C)=C1 CHEANNSDVJOIBS-MHZLTWQESA-N 0.000 claims description 2
- 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 2
- YSHMQTRICHYLGF-UHFFFAOYSA-N 4-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=NC=C1 YSHMQTRICHYLGF-UHFFFAOYSA-N 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 150000007513 acids Chemical class 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 235000021286 stilbenes Nutrition 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 150000001629 stilbenes Chemical class 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- 239000011541 reaction mixture Substances 0.000 description 105
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- 239000004809 Teflon Substances 0.000 description 35
- 229920006362 Teflon® Polymers 0.000 description 35
- 239000012267 brine Substances 0.000 description 35
- 238000003818 flash chromatography Methods 0.000 description 35
- 238000005286 illumination Methods 0.000 description 35
- 239000012044 organic layer Substances 0.000 description 35
- 239000000741 silica gel Substances 0.000 description 35
- 229910002027 silica gel Inorganic materials 0.000 description 35
- 239000011734 sodium Substances 0.000 description 35
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 description 33
- WOEYXRRXUBAVOU-UHFFFAOYSA-N (cyclobutylideneamino) 4-(trifluoromethyl)benzoate Chemical compound FC(C1=CC=C(C(=O)ON=C2CCC2)C=C1)(F)F WOEYXRRXUBAVOU-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
- JTMIBKLFJRXBDR-UHFFFAOYSA-N methyl 6-cyano-2,2-diphenylhexanoate Chemical compound COC(C(CCCCC#N)(C1=CC=CC=C1)C1=CC=CC=C1)=O JTMIBKLFJRXBDR-UHFFFAOYSA-N 0.000 description 8
- HJMZMZRCABDKKV-UHFFFAOYSA-N carbonocyanidic acid Chemical class OC(=O)C#N HJMZMZRCABDKKV-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical class N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 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 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 238000006473 carboxylation reaction Methods 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical class N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- VEZUQRBDRNJBJY-UHFFFAOYSA-N cyclohexanone oxime Chemical class ON=C1CCCCC1 VEZUQRBDRNJBJY-UHFFFAOYSA-N 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- GAOPEAYFZYECSK-UHFFFAOYSA-N 1-(1-phenylethenyl)-4-(trifluoromethyl)benzene Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=C)C1=CC=CC=C1 GAOPEAYFZYECSK-UHFFFAOYSA-N 0.000 description 1
- RFBNEESZDICKQI-UHFFFAOYSA-N 1-bromo-4-(1-phenylethenyl)benzene Chemical compound C1=CC(Br)=CC=C1C(=C)C1=CC=CC=C1 RFBNEESZDICKQI-UHFFFAOYSA-N 0.000 description 1
- QUAWDTPUQBNQER-UHFFFAOYSA-N 1-chloro-2-(1-phenylethenyl)benzene Chemical compound ClC1=CC=CC=C1C(=C)C1=CC=CC=C1 QUAWDTPUQBNQER-UHFFFAOYSA-N 0.000 description 1
- QRSXZQQKWIHIHY-UHFFFAOYSA-N 1-chloro-4-(1-phenylethenyl)benzene Chemical compound C1=CC(Cl)=CC=C1C(=C)C1=CC=CC=C1 QRSXZQQKWIHIHY-UHFFFAOYSA-N 0.000 description 1
- JKCDDOONAYOQEY-UHFFFAOYSA-N 1-fluoro-4-(1-phenylethenyl)benzene Chemical compound C1=CC(F)=CC=C1C(=C)C1=CC=CC=C1 JKCDDOONAYOQEY-UHFFFAOYSA-N 0.000 description 1
- DOLKMMRRGVRVFW-UHFFFAOYSA-N 1-methoxy-4-(1-phenylethenyl)benzene Chemical compound C1=CC(OC)=CC=C1C(=C)C1=CC=CC=C1 DOLKMMRRGVRVFW-UHFFFAOYSA-N 0.000 description 1
- FDQSYHPHYBJTFT-UHFFFAOYSA-N 1-methyl-3-(1-phenylethenyl)benzene Chemical compound CC1=CC=CC(C(=C)C=2C=CC=CC=2)=C1 FDQSYHPHYBJTFT-UHFFFAOYSA-N 0.000 description 1
- QGMAPACCTPTCOS-UHFFFAOYSA-N 1-methyl-4-(1-phenylethenyl)benzene Chemical compound C1=CC(C)=CC=C1C(=C)C1=CC=CC=C1 QGMAPACCTPTCOS-UHFFFAOYSA-N 0.000 description 1
- 125000004806 1-methylethylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- KYVBUUNCHXRYOS-UHFFFAOYSA-N 1-phenylprop-1-enylbenzene Chemical group C=1C=CC=CC=1C(=CC)C1=CC=CC=C1 KYVBUUNCHXRYOS-UHFFFAOYSA-N 0.000 description 1
- XGMSJGYRVWSIKN-UHFFFAOYSA-N 2,4-dichloro-1-(1-phenylethenyl)benzene Chemical compound ClC1=CC(Cl)=CC=C1C(=C)C1=CC=CC=C1 XGMSJGYRVWSIKN-UHFFFAOYSA-N 0.000 description 1
- AEROPCOJVBDWCE-UHFFFAOYSA-N 2-(1-phenylethenyl)thiophene Chemical compound C=1C=CC=CC=1C(=C)C1=CC=CS1 AEROPCOJVBDWCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- HWXLJSSJNXFROM-UHFFFAOYSA-N [(3-phenylcyclobutylidene)amino] 4-(trifluoromethyl)benzoate Chemical compound FC(C1=CC=C(C(=O)ON=C2CC(C2)C2=CC=CC=C2)C=C1)(F)F HWXLJSSJNXFROM-UHFFFAOYSA-N 0.000 description 1
- WRQJHJGSIKYHII-UHFFFAOYSA-N [(3-phenylmethoxycyclobutylidene)amino] 4-(trifluoromethyl)benzoate Chemical compound O=C(C1=CC=C(C(F)(F)F)C=C1)ON=C(C1)CC1OCC1=CC=CC=C1 WRQJHJGSIKYHII-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000002210 biocatalytic effect Effects 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- NUMHUJZXKZKUBN-UHFFFAOYSA-N methyl 4-ethenylbenzoate Chemical compound COC(=O)C1=CC=C(C=C)C=C1 NUMHUJZXKZKUBN-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- YDYCXDWUKJSHMI-UHFFFAOYSA-N n-cyclobutylidenehydroxylamine Chemical class ON=C1CCC1 YDYCXDWUKJSHMI-UHFFFAOYSA-N 0.000 description 1
- YGNXYFLJZILPEK-UHFFFAOYSA-N n-cyclopentylidenehydroxylamine Chemical class ON=C1CCCC1 YGNXYFLJZILPEK-UHFFFAOYSA-N 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 238000007342 radical addition reaction Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及医药、有机化工及精细化工领域,具体涉及一种由二氧化碳制备ε‑,ζ‑,η‑氰基羧酸的方法。以烯烃和环酮肟为原料,铱、4CZIPN或钌为催化剂,在还原剂存在下,二甲亚砜做溶剂,2x3W蓝色LED,室温反应12~24小时,然后加入碘甲烷在50℃油浴锅中再进行合成反应1小时得到产物。反应后的产物经过简单后处理即可以高产率得到一系列ε‑,ζ‑,η‑氰基羧酸化合物。各类取代基的二苯乙烯,以及各类取代基的环酮肟都可作为反应底物,得到相应ε‑,ζ‑,η‑氰基羧酸化合物。The invention relates to the fields of medicine, organic chemical industry and fine chemical industry, in particular to a method for preparing ε-, ζ-, η-cyanocarboxylic acids from carbon dioxide. Using olefins and cyclic ketoxime as raw materials, iridium, 4CZIPN or ruthenium as catalysts, in the presence of a reducing agent, dimethyl sulfoxide as a solvent, 2x3W blue LEDs, react at room temperature for 12 to 24 hours, then add methyl iodide and carry out a synthesis reaction in an oil bath at 50°C for 1 hour to obtain the product. After the reaction, a series of ε-, ζ-, η-cyanocarboxylic acid compounds can be obtained in high yield after simple post-treatment. Stilbenes with various substituents and cyclic ketoximes with various substituents can be used as reaction substrates to obtain the corresponding ε-, ζ-, η-cyanocarboxylic acid compounds.
Description
技术领域technical field
本发明涉及医药、有机化工及精细化工领域,特别涉及一种铱、4CzIPN或钌催化的,以二氧化碳、烯烃、环酮肟为原料,以DIPEA或者三乙胺为还原剂,DMSO为溶剂,简单高效的合成ε-,ζ-,η-氰基羧酸化合物的方法。The present invention relates to the fields of medicine, organic chemical industry and fine chemical industry, in particular to a simple and efficient method for synthesizing ε-, ζ-, η-cyanocarboxylic acid compounds catalyzed by iridium, 4CzIPN or ruthenium, using carbon dioxide, olefins and cyclic ketone oxime as raw materials, using DIPEA or triethylamine as reducing agent, and DMSO as solvent.
背景技术Background technique
氰基羧酸是一类重要的具有生物活性的化合物,也是构建维生素B6、咖啡因、叶酸等药物分子的重要中间体(参见:(a)Oliver,L.;Jens-Uwe,R.;Hilke-Marie,L.;Paul,H.;Constanze,M.Preparation cyano carboxylic acid esters,EP 2455365A1,20120523;(b)Michael Paul,B.;John Wing,W.Biocatalytic preparation of 1-cyanocyclohexaneacetic,WO 2004111256A1,20041223.)。此外,其结构中的氰基可以水解成羧基,所得的脂肪族二羧酸化合物,在高分子聚合反应中有着广泛的应用,是合成聚酰胺、聚酯的重要单体,因此,该类化合物的有效合成具有较强的应用价值(参见:Ren,W.;Chu,J.;Sun,F.;Shi,Y.Org.Lett.2019,21,5967-5970;(b)Yang,J.;Liu,J.;Ge,Y.;Huang,W.;Neumann,H.;Jackstell,R.;Beller,M.Angew.Chem.Int.Ed.2020,59,20394–20398.)。该类化合物的经典合成方法是利用卤代羧酸与氰化钠或者氢氰酸的亲核取代反应制备得到,然而该法中需要用到剧毒的氰化钠或者氢氰酸,给实际操作带来了极大的麻烦;此外,通过二腈类化合物的单氰基水解反应,也是制备氰基羧酸的一类重要方法,然而化合物中两个氰基具有相似的反应活性,如何控制反应条件,保证只有一个氰基被水解,是一项具有挑战性的工作(参见:Zhu,D.;MukherJee,C.;Biehl,E.R.;Hua,L.Adv.Synth.Catal.2007,349,1667–1670.)。Cyanocarboxylic acids are a class of important biologically active compounds, and are also important intermediates for the construction of vitamin B6, caffeine, folic acid and other drug molecules (see: (a) Oliver, L.; Jens-Uwe, R.; Hilke-Marie, L.; Paul, H.; Constanze, M. Preparation cyano carboxylic acid esters, EP 2455365A1, 20120523; (b) Michael Paul , B.; John Wing, W. Biocatalytic preparation of 1-cyanocyclohexaneacetic, WO 2004111256A1, 20041223.). In addition, the cyano group in its structure can be hydrolyzed into a carboxyl group, and the resulting aliphatic dicarboxylic acid compound is widely used in polymer polymerization reactions and is an important monomer for the synthesis of polyamides and polyesters. Therefore, the effective synthesis of such compounds has strong application value (see: Ren, W.; Chu, J.; Sun, F.; Shi, Y. Org. Lett. 2019, 21, 5967-5970; (b) Yang, J.; Liu, J.; Ge, Y.; Huang, W.; Neumann, H.; Jackstell, R.; Beller, M. Angew. Chem. Int. Ed. 2020, 59, 20394–20398.). The classic synthetic method of this kind of compound is to utilize the nucleophilic substitution reaction of halogenated carboxylic acid and sodium cyanide or hydrocyanic acid to prepare, yet need to use highly toxic sodium cyanide or hydrocyanic acid in this method, has brought great trouble to practical operation; In addition, through the single cyano group hydrolysis reaction of dinitrile compound, also is a class of important method of preparing cyano carboxylic acid, but two cyano groups have similar reactivity in the compound, how to control reaction conditions, guarantees that only one cyano group is hydrolyzed, is a challenging work (see: Zhu, D .; MukherJee, C.; Biehl, E.R.; Hua, L. Adv. Synth. Catal. 2007, 349, 1667–1670.).
近期,于达刚教授报道了通过环酮肟酯与二氧化碳的开环羧基化反应,可以得到一系列的氰基羧酸,然而该反应只限于2-芳基取代的环酮肟酯,底物适用范围较窄,且底物的合成难度较大(参见:Jiang,Y.-X.;Chen,L.;Ran,C.-K.;Song,L.;Zhang,W.;Liao,L.-L.;Yu,D.-G.ChemSusChem 2020,13,6312–6317.)。进一步发展通过简单易得的原料,反应条件温和的方法,实现不同碳链长度的氰基羧酸类化合物的快速构建,具有较高的研究价值。Recently, Professor Yu Dagang reported that a series of cyanocarboxylic acids can be obtained through the ring-opening carboxylation of cyclic ketoxime esters with carbon dioxide. However, this reaction is limited to 2-aryl substituted cyclic ketoxime esters, and the scope of substrate application is narrow, and the synthesis of substrates is difficult (see: Jiang, Y.-X.; Chen, L.; Ran, C.-K.; Song, L.; Zhang, W.; Liao, L.-L.; Yu, D.-G. ChemSus Chem 2020, 13, 6312–6317.). It is of high research value to further develop the method of using simple and easy-to-obtain raw materials and mild reaction conditions to realize the rapid construction of cyanocarboxylic acid compounds with different carbon chain lengths.
发明内容Contents of the invention
鉴于背景技术中的不足,本发明以廉价易得的二氧化碳、烯烃、环酮肟(2-位,3-位,3,3,-位取代的环丁酮肟、环戊酮肟、环己酮肟等)为起始原料,在可见光促进,铱、4CZIPN或钌的催化作用下,通过连续的自由基加成/单电子还原/羧基化反应,合成了一系列的ε-,ζ-,η-氰基羧酸。本发明方法原料来源广泛,操作方法简便,易于分离纯化,产率较高。In view of the deficiencies in the background technology, the present invention uses cheap and readily available carbon dioxide, olefins, and cyclic ketone oximes (2-, 3-, and 3,3,-substituted cyclobutanone oxime, cyclopentanone oxime, cyclohexanone oxime, etc.) as starting materials, and under the promotion of visible light, under the catalysis of iridium, 4CZIPN or ruthenium, a series of ε-, ζ-, η-cyanocarboxylic acids are synthesized through continuous free radical addition/one-electron reduction/carboxylation reactions. The method of the invention has wide sources of raw materials, simple operation method, easy separation and purification, and high yield.
本发明ε-,ζ-,η-氰基羧酸化合物的合成方法为:以烯烃和环酮肟为原料,铱、4CZIPN或钌为光催化剂,在还原剂的参与下,二甲亚砜作溶剂,所有参与反应的原料加完之后充入二氧化碳气体,进行反应,得到一系列的氰基羧酸化合物。The synthesis method of the ε-, ζ-, η-cyanocarboxylic acid compound of the present invention is as follows: olefins and cyclic ketoxime are used as raw materials, iridium, 4CZIPN or ruthenium are used as photocatalysts, with the participation of a reducing agent, dimethyl sulfoxide is used as a solvent, and after all the raw materials participating in the reaction are added, carbon dioxide gas is charged to carry out the reaction to obtain a series of cyanocarboxylic acid compounds.
该反应的具体工艺过程如下所示:The specific technological process of this reaction is as follows:
烯烃上的R’,R为苯基、甲基、萘基、 噻吩基或者氢;R’,R为苯基时,其取代基为氟、氯、溴、甲氧基、酯基和对三氟甲基;R1为甲基或者氢。R' on the olefin, R is phenyl, methyl, naphthyl, thienyl or hydrogen; R', when R is phenyl, its substituents are fluorine, chlorine, bromine, methoxy, ester group and p-trifluoromethyl; R1 is methyl or hydrogen.
所使用原料烯烃的结构式为:烯烃上的R’,R为苯基、甲基、萘基、噻吩基或者氢;R’,R为苯基时,其取代基为氟、氯、溴、甲氧基、酯基和对三氟甲基;R1为甲基或者氢。The structural formula of the raw material olefin used is: R' on the olefin, R is phenyl, methyl, naphthyl, thienyl or hydrogen; R', when R is phenyl, its substituents are fluorine, chlorine, bromine, methoxy, ester and p-trifluoromethyl; R1 is methyl or hydrogen.
环酮肟选自四元环、六元环、杂环以及他们带有的不同取代基产物。The cyclic ketoxime is selected from four-membered rings, six-membered rings, heterocyclic rings and their different substituent products.
所使用的原料环酮肟的结构式为:环酮肟上R3、R4、R5选自芳基、甲基、氰基、苄基、酯中的一种;X为C、O、N;R2=p-CF3C6H4CO,n=1,2,3。The structural formula of the raw material cyclic ketoxime used is: R 3 , R 4 , and R 5 on the cyclic ketoxime are selected from one of aryl, methyl, cyano, benzyl, and ester; X is C, O, N; R 2 =p-CF 3 C 6 H 4 CO, n=1,2,3.
本发明具体的反应条件为:2x 3W蓝色LED,室温12~24小时,然后加入碘甲烷50℃油浴锅中再反应1小时。The specific reaction conditions of the present invention are: 2x 3W blue LEDs, room temperature for 12 to 24 hours, then add methyl iodide in a 50°C oil bath and react for another hour.
上述反应所使用的光催化剂为二[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,三(2,2'-联吡啶)钌二(六氟磷酸)盐,2,4,5,6-四(9-咔唑基)-间苯二腈,催化剂的用量为烯烃摩尔数的2mol%;The photocatalyst used in the above reaction is bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium bis(hexafluorophosphate) salt, three(2,2'-bipyridyl)ruthenium bis(hexafluorophosphate)salt, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile, and the consumption of the catalyst is 2mol% of the olefin moles;
所使用的烯烃与环酮肟摩尔比为1:1.5,二氧化碳的压力为0.1MPa;The molar ratio of olefin to cyclic ketoxime used is 1:1.5, and the pressure of carbon dioxide is 0.1MPa;
所使用的还原剂为N,N-二异丙基乙胺(DIPEA)、或三乙胺(Et3N);其与烯烃的摩尔比为3.0:1。The reducing agent used is N,N-diisopropylethylamine (DIPEA) or triethylamine (Et 3 N); the molar ratio of it to olefin is 3.0:1.
碘甲烷与烯烃摩尔比为4:1。The molar ratio of iodomethane to olefin is 4:1.
所述的反应后处理简便,只需要简单的柱色谱分离方法,以石油醚与乙酸乙酯的混合溶剂为洗脱剂就可以得到纯净的ε-,ζ-,η-氰基羧酸化合物。The post-reaction treatment is simple and simple, and pure ε-, ζ-, η-cyanocarboxylic acid compounds can be obtained only by a simple column chromatography separation method using a mixed solvent of petroleum ether and ethyl acetate as an eluent.
本发明采用的原料烯烃和环酮肟根据文献合成得到(Cheng,Z.;Jin,W.;Liu,C.B2pin2-catalyzed oxidative cleavage of a C=C double bond with molecularoxygen,Org.Chem.Front.2019,6,841-845;Zhao,B.;Shi,Z.Angew.Chem.Int.Ed.2017,56,12727–12731.)。The raw material olefin and cyclic ketoxime used in the present invention were synthesized according to the literature (Cheng, Z.; Jin, W.; Liu, CB 2 pin 2 -catalyzed oxidative cleavage of a C=C double bond with molecular oxygen, Org. Chem. Front. 2019, 6, 841-845; Zhao, B.; Shi, Z. Angew. Chem. Int. Ed.2 017, 56, 12727–12731.).
有益效果:Beneficial effect:
本发明首次使用烯烃与环酮肟合成一系列ε-,ζ-,η-氰基羧酸化合物的合成提供了一条更加简洁可行的途径,具有重要的应用价值。The invention provides a more concise and feasible way to synthesize a series of ε-, ζ-, η-cyanocarboxylic acid compounds by using olefin and cyclic ketone oxime for the first time, and has important application value.
具体实施方式Detailed ways
下面结合实施例对本发明进行详细的说明,本发明各实施例反应如下:Below in conjunction with embodiment the present invention is described in detail, each embodiment of the present invention reacts as follows:
实施例1 6-氰基-2,2-二苯基己酸甲酯Example 1 6-cyano-2,2-diphenylhexanoic acid methyl ester
Methyl 6-cyano-2,2-diphenylhexanoateMethyl 6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mLSchlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,产率为76%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H).13C NMR(101MHz,CDCl3)δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M+)。1,1-Stilbene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube fitted with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 76% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M + )。
实施例2 6-氰基-2-苯基-2-(对甲苯基)己酸甲酯Example 2 Methyl 6-cyano-2-phenyl-2-(p-tolyl)hexanoate
Methyl 6-cyano-2-phenyl-2-(p-tolyl)hexanoateMethyl 6-cyano-2-phenyl-2-(p-tolyl)hexanoate
将1-甲基-4-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为60%。核磁数据:1H NMR(400MHz,CDCl3)δ7.28–7.19(m,6H),7.11–7.06(m,4H),3.64(s,3H),2.35-2.32(m,2H),2.30(s,3H),2.22(t,J=7.3Hz,2H),1.62–1.55(m,2H),1.20–1.14(m,2H).13C NMR(101MHz,CDCl3))δ174.64,142.61,139.38,136.53,128.66,128.63,128.56,127.88,126.79,119.53,59.78,52.35,37.33,25.78,24.56,20.89,16.87.质谱数据:MS(EI):321.2(M+)。1-Methyl-4-(1-phenylethenyl)benzene (0.2mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to a 20mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 60% yield.核磁数据: 1 H NMR(400MHz,CDCl3)δ7.28–7.19(m,6H),7.11–7.06(m,4H),3.64(s,3H),2.35-2.32(m,2H),2.30(s,3H),2.22(t,J=7.3Hz,2H),1.62–1.55(m,2H),1.20–1.14(m,2H). 13 C NMR(101MHz,CDCl3))δ174.64,142.61,139.38,136.53,128.66,128.63,128.56,127.88,126.79,119.53,59.78,52.35,37.33,25.78,24.56,20.89,16.87.质谱数据:MS(EI):321.2(M + )。
实施例3:6-氰基-2-(4-甲氧基苯基)-2-苯基己酸甲酯Example 3: Methyl 6-cyano-2-(4-methoxyphenyl)-2-phenylhexanoate
Methyl 6-cyano-2-(4-methoxyphenyl)-2-phenylhexanoateMethyl 6-cyano-2-(4-methoxyphenyl)-2-phenylhexanoate
将1-甲氧基-4-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为68%。核磁数据:1H NMR(400MH z,CDCl3)δ7.36–7.26(m,5H),7.24–7.21(m,2H),6.90–6.86(m,2H),3.84(s,3H),3.73(s,3H),2.42–2.37(m,2H),2.30(t,J=7.3Hz,2H),1.70–1.63(m,2H),1.27–1.20(m,2H).13C NMR(101MHz,CDCl3)δ174.7,158.3,142.8,134.3,129.8,128.6,127.9,126.8,119.5,113.2,59.4,55.1,52.3,37.4,25.8,24.6,16.9.质谱数据:MS(EI):337.2(M+)。1-Methoxy-4-(1-phenylethenyl)benzene (0.2mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to a 20mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 68% yield.核磁数据: 1 H NMR(400MH z,CDCl 3 )δ7.36–7.26(m,5H),7.24–7.21(m,2H),6.90–6.86(m,2H),3.84(s,3H),3.73(s,3H),2.42–2.37(m,2H),2.30(t,J=7.3Hz,2H),1.70–1.63(m,2H),1.27–1.20(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.7,158.3,142.8,134.3,129.8,128.6,127.9,126.8,119.5,113.2,59.4,55.1,52.3,37.4,25.8,24.6,16.9.质谱数据:MS(EI):337.2(M + )。
实施例4:6-氰基-2-(4-氟苯基)-2-苯基己酸甲酯Example 4: Methyl 6-cyano-2-(4-fluorophenyl)-2-phenylhexanoate
Methyl 6-cyano-2-(4-fluorophenyl)-2-phenylhexanoateMethyl 6-cyano-2-(4-fluorophenyl)-2-phenylhexanoate
将1-氟-4-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率56%。核磁数据:1H NMR(400MHz,CDCl3)δ7.33–7.26(m,3H),7.24–7.20(m,4H),6.98(t,J=8.7Hz,2H),3.67(s,3H),2.38–2.34(m,2H),2.27(t,J=7.2Hz,2H),1.66–1.59(m,2H),1.26–1.16(m,2H).13C NMR(101MHz,CDCl3)δ174.3,142.3,130.4,130.4,128.5,128.1,127.0,114.9,114.6,59.6,52.5,37.4,25.7,24.5,16.9.质谱数据:MS(EI):325.2(M+)。1-Fluoro-4-(1-phenylethenyl)benzene (0.2mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to a 20mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 56% yield.核磁数据: 1 H NMR(400MHz,CDCl3)δ7.33–7.26(m,3H),7.24–7.20(m,4H),6.98(t,J=8.7Hz,2H),3.67(s,3H),2.38–2.34(m,2H),2.27(t,J=7.2Hz,2H),1.66–1.59(m,2H),1.26–1.16(m,2H). 13 C NMR(101MHz,CDCl3)δ174.3,142.3,130.4,130.4,128.5,128.1,127.0,114.9,114.6,59.6,52.5,37.4,25.7,24.5,16.9.质谱数据:MS(EI):325.2(M + )。
实施例5:2-(4-氯苯基)-6-氰基-2-苯基己酸甲酯Example 5: Methyl 2-(4-chlorophenyl)-6-cyano-2-phenylhexanoate
Methyl 2-(4-chlorophenyl)-6-cyano-2-phenylhexanoateMethyl 2-(4-chlorophenyl)-6-cyano-2-phenylhexanoate
将1-氯-4-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为59%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.27(m,5H),7.24–7.19(m,4H),3.70(s,3H),2.37(t,J=8.1Hz,2H),2.28(t,J=7.2Hz,2H),1.68–1.61(m,2H),1.27–1.18(m,2H).13C NMR(101MHz,CDCl3)δ174.1,142.1,141.1,132.8,130.2,128.5,128.1,128.1,127.1,119.4,59.7,52.5,37.2,25.7,24.5,16.9.质谱数据:MS(EI):341.1(M+)。1-Chloro-4-(1-phenylvinyl)benzene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to a 20 mL Schlenk tube equipped with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 59% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.27(m,5H),7.24–7.19(m,4H),3.70(s,3H),2.37(t,J=8.1Hz,2H),2.28(t,J=7.2Hz,2H),1.68–1.61(m,2H),1.27–1.18(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.1,142.1,141.1,132.8,130.2,128.5,128.1,128.1,127.1,119.4,59.7,52.5,37.2,25.7,24.5,16.9.质谱数据:MS(EI):341.1(M + )。
实施例6:2-(4-溴苯基)-6-氰基-2-苯基己酸甲酯Example 6: Methyl 2-(4-bromophenyl)-6-cyano-2-phenylhexanoate
Methyl 2-(4-bromophenyl)-6-cyano-2-phenylhexanoateMethyl 2-(4-bromophenyl)-6-cyano-2-phenylhexanoate
将1-溴-4-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为83%。核磁数据:1H NMR(400MHz,CDCl3)δ7.44(d,J=8.6Hz,2H),7.35–7.28(m,4H),7.23(d,J=7.0Hz,3H),7.15(d,J=8.6,2H),3.71(s,3H),2.37(t,J=8.1Hz,2H),2.29(t,J=7.2Hz,2H),1.68–1.61(m,2H),1.24–1.15(m,2H).13C NMR(101MHz,CDCl3)δ173.9,141.9,141.6,131.0,130.5,128.4,128.1,127.1,121.0,119.4,59.7,52.5,37.1,25.6,24.5,16.8.质谱数据:MS(EI):385.1(M+)。1-Bromo-4-(1-phenylvinyl)benzene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to a 20 mL Schlenk tube equipped with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 83% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.44(d,J=8.6Hz,2H),7.35–7.28(m,4H),7.23(d,J=7.0Hz,3H),7.15(d,J=8.6,2H),3.71(s,3H),2.37(t,J=8.1Hz,2H),2.29(t,J=7.2Hz,2H),1.68–1.61(m,2H),1.24–1.15(m,2H). 13 C NMR(101MHz,CDCl 3 )δ173.9,141.9,141.6,131.0,130.5,128.4,128.1,127.1,121.0,119.4,59.7,52.5,37.1,25.6,24.5,16.8.质谱数据:MS(EI):385.1(M + )。
实施例7:6-氰基-2-苯基-2-(4-(三氟甲基)苯基)己酸甲酯Example 7: Methyl 6-cyano-2-phenyl-2-(4-(trifluoromethyl)phenyl)hexanoate
Methyl 6-cyano-2-phenyl-2-(4-(trifluoromethyl)phenyl)hexanoateMethyl 6-cyano-2-phenyl-2-(4-(trifluoromethyl)phenyl)hexanoate
将1-(1-苯基乙烯基)-4-(三氟甲基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为44%。核磁数据:1H NMR(400MHz,CDCl3)δ7.52(d,J=8.4Hz,2H),7.34(d,J=8.2Hz,2H),7.31–7.27(m,2H),7.26–7.22(m,1H),7.20–7.17(m,2H),3.67(s,3H),2.39–2.34(m,2H),2.24(t,J=7.2Hz,2H),1.65–1.57(m,2H),1.19–1.12(m,2H).13C NMR(101MHz,CDCl3)δ173.8,141.7,129.2,128.5,128.2,127.3,124.9,124.8,119.4,60.1,52.6,37.2,25.7,24.5,16.9.质谱数据:MS(EI):375.1(M+)。1-(1-Phenylvinyl)-4-(trifluoromethyl)benzene (0.2mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to 20mL Schlenk Tubes, fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 44% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.52(d,J=8.4Hz,2H),7.34(d,J=8.2Hz,2H),7.31–7.27(m,2H),7.26–7.22(m,1H),7.20–7.17(m,2H),3.67(s,3H),2.39–2.34(m,2H),2.24(t,J=7.2Hz,2H),1.65–1.57(m,2H),1.19–1.12(m,2H). 13 C NMR(101MHz,CDCl 3 )δ173.8,141.7,129.2,128.5,128.2,127.3,124.9,124.8,119.4,60.1,52.6,37.2,25.7,24.5,16.9.质谱数据:MS(EI):375.1(M + )。
实施例8:6-氰基-2-苯基-2-(间甲苯基)己酸甲酯Example 8: Methyl 6-cyano-2-phenyl-2-(m-tolyl)hexanoate
Methyl 6-cyano-2-phenyl-2-(m-tolyl)hexanoateMethyl 6-cyano-2-phenyl-2-(m-tolyl)hexanoate
将1-甲基-3-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为59%。核磁数据:1H NMR(400MHz,CDCl3)δ7.33–7.18(m,6H),7.07(t,J=10.4Hz,3H),3.70(s,3H),2.40–2.34(m,2H),2.33(s,3H),2.27(t,J=7.3Hz,2H),1.67–1.59(m,2H),1.27–1.17(m,2H).13C NMR(101MHz,CDCl3)δ174.6,142.5,142.4,137.5,129.2,128.7,127.9,127.8,127.6,126.9,125.8,119.5,60.0,52.3,37.3,25.8,24.6,21.6,16.8.质谱数据:MS(EI):321.2(M+)。1-Methyl-3-(1-phenylethenyl)benzene (0.2mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to a 20mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 59% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.33–7.18(m,6H),7.07(t,J=10.4Hz,3H),3.70(s,3H),2.40–2.34(m,2H),2.33(s,3H),2.27(t,J=7.3Hz,2H),1.67–1.59(m,2H),1.27–1.17(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.6,142.5,142.4,137.5,129.2,128.7,127.9,127.8,127.6,126.9,125.8,119.5,60.0,52.3,37.3,25.8,24.6,21.6,16.8.质谱数据:MS(EI):321.2(M + )。
实施例9:2-(2-氯苯基)-6-氰基-2-苯基己酸甲酯Example 9: Methyl 2-(2-chlorophenyl)-6-cyano-2-phenylhexanoate
Methyl 2-(2-chlorophenyl)-6-cyano-2-phenylhexanoateMethyl 2-(2-chlorophenyl)-6-cyano-2-phenylhexanoate
将1-氯-2-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为66%。核磁数据:1H NMR(400MHz,CDCl3)δ7.3–7.30(m,3H),7.26–7.22(m,5H),7.17–7.13(m,1H),3.71(s,3H),2.39–2.35(m,2H),2.28(t,J=7.2Hz,2H),1.68–1.61(m,2H),1.23–1.14(m,2H).13C NMR(101MHz,CDCl3)δ174.1,140.2,134.1,131.0,130.9,128.9,128.3,128.1,127.3,126.1,59.2,52.5,33.1,25.6,24.2,16.9.质谱数据:MS(EI):282.1(M+)。1-Chloro-2-(1-phenylvinyl)benzene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to a 20 mL Schlenk tube equipped with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 66% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.3–7.30(m,3H),7.26–7.22(m,5H),7.17–7.13(m,1H),3.71(s,3H),2.39–2.35(m,2H),2.28(t,J=7.2Hz,2H),1.68–1.61(m,2H),1.23–1.14(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.1,140.2,134.1,131.0,130.9,128.9,128.3,128.1,127.3,126.1,59.2,52.5,33.1,25.6,24.2,16.9.质谱数据:MS(EI):282.1(M + )。
实施例10:6-氰基-2-(2,4-二氯苯基)-2-苯基己酸甲酯Example 10: Methyl 6-cyano-2-(2,4-dichlorophenyl)-2-phenylhexanoate
Methyl 6-cyano-2-(2,4-dichlorophenyl)-2-phenylhexanoateMethyl 6-cyano-2-(2,4-dichlorophenyl)-2-phenylhexanoate
将2,4-二氯-1-(1-苯基乙烯基)苯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为67%。核磁数据:1H NMR(400MHz,CDCl3)δ7.44(d,J=7.4Hz,2H),7.40(d,J=2.2Hz,1H),7.38–7.28(m,3H),7.16(dd,J=8.6,2.2Hz,1H),7.00(d,J=8.6Hz,1H),3.66(s,3H),2.69–2.61(m,1H),2.54–2.46(m,1H),2.35–2.21(m,2H),1.75–1.56(m,2H),1.43–1.33(m,1H),0.96–0.86(m,1H).13CNMR(101MHz,CDCl3)δ173.7,139.0,138.9,134.8,133.4,131.9,130.6,128.8,128.3,127.5,126.4,119.3,58.9,52.6,33.1,25.6,24.2,16.9.质谱数据:MS(EI):375.1(M+)。2,4-Dichloro-1-(1-phenylethenyl)benzene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to a 20mL Schlenk tube , with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 67% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.44(d,J=7.4Hz,2H),7.40(d,J=2.2Hz,1H),7.38–7.28(m,3H),7.16(dd,J=8.6,2.2Hz,1H),7.00(d,J=8.6Hz,1H),3.66(s,3H),2.69–2.61(m,1H),2.54–2.46(m,1H),2.35–2.21(m,2H),1.75–1.56(m,2H),1.43–1.33(m,1H),0.96–0.86(m,1H). 13 CNMR(101MHz,CDCl 3 )δ173.7,139.0,138.9,134.8,133.4,131.9,130.6,128.8,128.3,127.5,126.4,119.3,58.9,52.6,33.1,25.6,24.2,16.9.质谱数据:MS(EI):375.1(M + )。
实施例11:6-氰基-2,2-二对甲苯基己酸甲酯Example 11: Methyl 6-cyano-2,2-di-p-tolylhexanoate
Methyl 6-cyano-2,2-di-p-tolylhexanoateMethyl 6-cyano-2,2-di-p-tolylhexanoate
将4,4'-(乙烯-1,1-二基)双(甲苯)(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为62%。核磁数据:1H NMR(400MH z,CDCl3)δ7.15-7.13(m,2H),7.12-7.13(d,J=2.9Hz,6H),7.10(s,1H),3.68(s,3H),2.37(s,1H),2.34(s,6H),2.32(s,1H),2.28(s,2H),1.63(t,J=7.6Hz,2H),1.25–1.20(m,2H).13C NMR(101MHz,CDCl3)δ174.8,139.5,136.4,128.6,128.5,119.6,77.3,77.00,76.7,59.5,52.3,37.4,25.8,24.6,20.9,16.9.质谱数据:MS(EI):335.2(M+)。4,4′-(ethylene-1,1-diyl)bis(toluene) (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to 20 mL of Sch Lenk tubes, fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 62% yield.核磁数据: 1 H NMR(400MH z,CDCl3)δ7.15-7.13(m,2H),7.12-7.13(d,J=2.9Hz,6H),7.10(s,1H),3.68(s,3H),2.37(s,1H),2.34(s,6H),2.32(s,1H),2.28(s,2H),1.63(t,J=7.6Hz,2H),1.25–1.20(m,2H). 13 C NMR(101MHz,CDCl3)δ174.8,139.5,136.4,128.6,128.5,119.6,77.3,77.00,76.7,59.5,52.3,37.4,25.8,24.6,20.9,16.9.质谱数据:MS(EI):335.2(M+)。
实施例12:2,2-双(4-氯苯基)-6-氰基己酸甲酯Example 12: Methyl 2,2-bis(4-chlorophenyl)-6-cyanohexanoate
Methyl 2,2-bis(4-chlorophenyl)-6-cyanohexanoateMethyl 2,2-bis(4-chlorophenyl)-6-cyanohexanoate
将4,4'-(乙烯-1,1-二基)双(氯苯)(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为33%。核磁数据:1H NMR(400MH z,CDCl3)δ7.30–7.26(m,4H),7.17–7.14(m,4H),3.69(s,3H),2.34–2.26(m,4H),1.64(t,J=7.5Hz,2H),1.25–1.17(m,2H).13C NMR(101MHz,CDCl3)δ173.7,140.7,133.1,130.0,128.3,119.4,59.3,52.7,37.2,25.7,24.5,16.9.质谱数据:MS(EI):375.1(M+)。4,4′-(ethylene-1,1-diyl)bis(chlorobenzene) (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to 20 mL of Sch Lenk tubes, fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 33% yield.核磁数据: 1 H NMR(400MH z,CDCl 3 )δ7.30–7.26(m,4H),7.17–7.14(m,4H),3.69(s,3H),2.34–2.26(m,4H),1.64(t,J=7.5Hz,2H),1.25–1.17(m,2H). 13 C NMR(101MHz,CDCl 3 )δ173.7,140.7,133.1,130.0,128.3,119.4,59.3,52.7,37.2,25.7,24.5,16.9.质谱数据:MS(EI):375.1(M + )。
实施例13:6-氰基-2-(萘-2-基)-2-苯基己酸甲酯Example 13: Methyl 6-cyano-2-(naphthalen-2-yl)-2-phenylhexanoate
Methyl 6-cyano-2-(naphthalen-2-yl)-2-phenylhexanoateMethyl 6-cyano-2-(naphthalen-2-yl)-2-phenylhexanoate
将2-(1-苯基乙烯基)萘(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为82%。核磁数据:1H NMR(400MHz,CDCl3)δ7.71–7.68(m,3H),7.64(d,J=8.8Hz,1H),7.36(d,J=9.8Hz,2H),7.22–7.16(m,6H),3.60(s,3H),2.44–2.32(m,2H),2.13(t,J=7.3Hz,2H),1.57–1.49(m,2H),1.18–1.12(m,2H).13C NMR(101MHz,CDCl3)δ174.3,142.4,139.7,132.7,132.1,128.7,128.1,128.0,127.5,127.3,127.2,127.1,126.9,126.1,126.1,119.5,60.1,52.4,37.20,25.7,24.6,16.8.质谱数据:MS(EI):357.2(M+)。2- (1-phenyl ethylene) 萘 (0.2 mmol), cytotosor O- (4- (trifluorophyl) benzol) 肟 (0.3 mmol), IR [(DF (CF 3 ) PPY)] 2 (DTBBPY) PF 6 (2mol %, 3.4 mg), DIPEA (0.3 mmol), and DMSO, and DMSO (2.0ml) Add to the 20ml SCHLENK tube with Teflon hat. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 82% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.71–7.68(m,3H),7.64(d,J=8.8Hz,1H),7.36(d,J=9.8Hz,2H),7.22–7.16(m,6H),3.60(s,3H),2.44–2.32(m,2H),2.13(t,J=7.3Hz,2H),1.57–1.49(m,2H),1.18–1.12(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.3,142.4,139.7,132.7,132.1,128.7,128.1,128.0,127.5,127.3,127.2,127.1,126.9,126.1,126.1,119.5,60.1,52.4,37.20,25.7,24.6,16.8.质谱数据:MS(EI):357.2(M + )。
实施例14:6-氰基-2-苯基-2-(噻吩-2-基)己酸甲酯Example 14: Methyl 6-cyano-2-phenyl-2-(thiophen-2-yl)hexanoate
Methyl 6-cyano-2-phenyl-2-(thiophen-2-yl)hexanoateMethyl 6-cyano-2-phenyl-2-(thiophen-2-yl)hexanoate
将2-(1-苯基乙烯基)噻吩(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为56%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.27(m,4H),7.25(d,J=6.7Hz,2H),6.98(t,J=4.7Hz,2H),3.75(s,3H),2.51–2.36(m,2H),2.29(t,J=7.2Hz,2H),1.70–1.62(m,2H),1.40–1.30(m,2H).13C NMR(101MHz,CDCl3)δ173.6,145.8,142.8,128.1,127.4,127.2,127.0,126.2,125.1,119.4,57.8,52.6,39.1,25.6,24.6,16.9.质谱数据:MS(EI):313.1(M+)。2-(1-Phenylvinyl)thiophene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube fitted with a Teflon cap . The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 56% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.27(m,4H),7.25(d,J=6.7Hz,2H),6.98(t,J=4.7Hz,2H),3.75(s,3H),2.51–2.36(m,2H),2.29(t,J=7.2Hz,2H),1.70–1.62(m,2H),1.40–1.30(m,2H). 13 C NMR(101MHz,CDCl 3 )δ173.6,145.8,142.8,128.1,127.4,127.2,127.0,126.2,125.1,119.4,57.8,52.6,39.1,25.6,24.6,16.9.质谱数据:MS(EI):313.1(M + )。
实施例15:(R)-6-氰基-3-甲基-2,2-二苯基己酸甲酯Example 15: Methyl (R)-6-cyano-3-methyl-2,2-diphenylhexanoate
Methyl(R)-6-cyano-3-methyl-2,2-diphenylhexanoateMethyl(R)-6-cyano-3-methyl-2,2-diphenylhexanoate
将1-甲基-2,2-二苯基乙烯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为14%。核磁数据:1H NMR(400MHz,CDCl3)δ7.31–7.24(m,11H,overlappedwith CDCl3),3.62(s,3H),3.14–3.06(m,1H),2.34–2.29(m,2H),1.77–1.66(m,4H),0.85(d,J=6.6Hz,3H).13C NMR(101MHz,CDCl3)δ174.6,127.5,126.9,126.9,119.6,65.6,52.3,35.5,29.7,24.0,17.3.质谱数据:MS(EI):321.2(M+)。1-Methyl-2,2-diphenylethylene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube fitted with a Teflon cap . The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 14% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.31–7.24(m,11H,overlappedwith CDCl 3 ),3.62(s,3H),3.14–3.06(m,1H),2.34–2.29(m,2H),1.77–1.66(m,4H),0.85(d,J=6.6Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ174.6,127.5,126.9,126.9,119.6,65.6,52.3,35.5,29.7,24.0,17.3.质谱数据:MS(EI):321.2(M + )。
实施例16:6-氰基-2-甲基-2-(萘-2-基)己酸甲酯Example 16: Methyl 6-cyano-2-methyl-2-(naphthalen-2-yl)hexanoate
Methyl 6-cyano-2-methyl-2-(naphthalen-2-yl)hexanoateMethyl 6-cyano-2-methyl-2-(naphthalen-2-yl)hexanoate
将2-(1-甲基乙烯基)萘(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Sch lenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为25%。核磁数据:1H NMR(400MHz,CDCl3)δ7.84–7.79(m,3H),7.72(d,J=2.0Hz,1H),7.50–7.45(m,2H),7.40(dd,J=8.8,2.0Hz,1H),3.67(s,3H),2.33–2.29(m,2H),2.17–2.00(m,2H),1.69(s,3H),1.67–1.63(m,2H),1.40–1.30(m,2H).13C NMR(101MHz,CDCl3)δ176.5,140.5,133.2,132.2,128.2,128.0,127.4,126.2,126.0,124.4,124.3,119.5,52.3,50.1,38.4,25.8,23.9,22.4,17.0.质谱数据:MS(EI):295.2(M+)。2- (1-methyl ethylene) 萘 (0.2 mmol), cytotosor O- (4- (trifluorophyl) benzol) 肟 (0.3 mmol), IR [(DF (CF 3 ) PPY)] 2 (DTBBPY) PF 6 (2mol %, 3.4 mg), DIPEA (0.3mmol), and DMSO ( 2.0ml) Add to the 20ml SCHLENK tube with Teflon hat. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 25% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.84–7.79(m,3H),7.72(d,J=2.0Hz,1H),7.50–7.45(m,2H),7.40(dd,J=8.8,2.0Hz,1H),3.67(s,3H),2.33–2.29(m,2H),2.17–2.00(m,2H),1.69(s,3H),1.67–1.63(m,2H),1.40–1.30(m,2H). 13 C NMR(101MHz,CDCl 3 )δ176.5,140.5,133.2,132.2,128.2,128.0,127.4,126.2,126.0,124.4,124.3,119.5,52.3,50.1,38.4,25.8,23.9,22.4,17.0.质谱数据:MS(EI):295.2(M + )。
实施例17:(S)-4-(6-氰基-1-甲氧基-1-氧代己-2-基)苯甲酸甲酯Example 17: (S)-methyl 4-(6-cyano-1-methoxy-1-oxohex-2-yl)benzoate
Methyl(S)-4-(6-cyano-1-methoxy-1-oxohexan-2-yl)benzoateMethyl(S)-4-(6-cyano-1-methoxy-1-oxohexan-2-yl)benzoate
将4-乙烯基苯甲酸甲酯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为72%。核磁数据:1H NMR(400MHz,CDCl3)δ7.98(d,J=8.4Hz,2H),7.34(d,J=8.4Hz,2H),3.89(s,3H),3.65(s,3H),3.59(t,J=7.6Hz,1H),2.30(t,J=7.1Hz,2H),2.16–2.07(m,1H),1.82–1.76(m,1H),1.69–1.63(m,2H),1.44–1.33(m,2H).13C NMR(101MHz,CDCl3)δ173.4,166.7,143.6,130.0,129.3,127.8,119.3,52.2,52.1,51.2,32.4,26.5,25.0,16.9.质谱数据:MS(EI):289.1(M+)。Methyl 4-vinylbenzoate (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube fitted with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 72% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.98(d,J=8.4Hz,2H),7.34(d,J=8.4Hz,2H),3.89(s,3H),3.65(s,3H),3.59(t,J=7.6Hz,1H),2.30(t,J=7.1Hz,2H),2.16–2.07(m,1H),1.82–1.76(m,1H),1.69–1.63(m,2H),1.44–1.33(m,2H). 13 C NMR(101MHz,CDCl 3 )δ173.4,166.7,143.6,130.0,129.3,127.8,119.3,52.2,52.1,51.2,32.4,26.5,25.0,16.9.质谱数据:MS(EI):289.1(M + )。
实施例18:5-(氰甲基)-2,2-二苯基己二酸二甲酯Example 18: Dimethyl 5-(cyanomethyl)-2,2-diphenyladipate
Dimethyl 5-(cyanomethyl)-2,2-diphenylhexanedioateDimethyl 5-(cyanomethyl)-2,2-diphenylhexanedioate
将1,1-二苯乙烯(0.2mmol)、3-(((4-(三氟甲基)苯甲酰基)氧基)亚氨基)环丁烷-1-羧酸甲酯(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为60%。核磁数据:1H NMR(400MHz,CDCl3)δ7.30(dd,J=14.2,6.6Hz,6H),7.25–7.21(m,4H),3.71(s,3H),3.69(s,3H),2.70–2.57(m,2H),2.51–2.40(m,2H),2.37–2.29(m,1H),1.59–1.40(m,2H).13C NMR(101MHz,CDCl3)δ172.7,142.1,142.0,128.6,128.6,128.0,127.0,59.9,52.5,52.3,41.6,34.9,27.2,19.1.质谱数据:MS(EI):365.2(M+)。1,1-Stilbene (0.2mmol), methyl 3-(((4-(trifluoromethyl)benzoyl)oxy)imino)cyclobutane-1-carboxylate (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to 20mL Sch Lenk tubes, fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 60% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.30(dd,J=14.2,6.6Hz,6H),7.25–7.21(m,4H),3.71(s,3H),3.69(s,3H),2.70–2.57(m,2H),2.51–2.40(m,2H),2.37–2.29(m,1H),1.59–1.40(m,2H). 13 C NMR(101MHz,CDCl 3 )δ172.7,142.1,142.0,128.6,128.6,128.0,127.0,59.9,52.5,52.3,41.6,34.9,27.2,19.1.质谱数据:MS(EI):365.2(M + )。
实施例19:6-氰基-2,2,5-三苯基己酸甲酯Example 19: Methyl 6-cyano-2,2,5-triphenylhexanoate
Methyl 6-cyano-2,2,5-triphenylhexanoateMethyl 6-cyano-2,2,5-triphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、3-苯基环丁烷-1-酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为77%。核磁数据:1H NMR(400MHz,CDCl3)δ7.35–7.28(m,9H),7.20(d,J=7.4Hz,4H),7.10(d,J=7.0Hz,2H),3.67(s,3H),2.89–2.81(m,1H),2.49(d,J=7.0Hz,2H),2.40–2.33(m,1H),2.24–2.17(m,1H),1.68–1.52(m,2H).13C NMR(101MHz,CDCl3)δ174.4,142.3,142.2,141.0,128.7,128.6,127.9,127.9,127.4,127.2,126.9,126.8,118.2,60.0,52.3,42.4,35.7,30.2,25.3.质谱数据:MS(EI):383.2(M+)。1,1-Stilbene (0.2 mmol), 3-phenylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to a 20 mL Schlenk tube equipped with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 77% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.35–7.28(m,9H),7.20(d,J=7.4Hz,4H),7.10(d,J=7.0Hz,2H),3.67(s,3H),2.89–2.81(m,1H),2.49(d,J=7.0Hz,2H),2.40–2.33(m,1H),2.24–2.17(m,1H),1.68–1.52(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.4,142.3,142.2,141.0,128.7,128.6,127.9,127.9,127.4,127.2,126.9,126.8,118.2,60.0,52.3,42.4,35.7,30.2,25.3.质谱数据:MS(EI):383.2(M + )。
实施例20:5-苄基-6-氰基-2,2-二苯基己酸甲酯Example 20: Methyl 5-benzyl-6-cyano-2,2-diphenylhexanoate
Methyl 5-benzyl-6-cyano-2,2-diphenylhexanoateMethyl 5-benzyl-6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、3-苄基环丁烷-1-酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA5/1)纯化,得到所需产物,收率为71%。核磁数据:1H NMR(400MHz,CDC l3)δ7.28(t,J=7.1Hz,4H),7.25–7.18(m,9H),7.06(d,J=6.7Hz,2H),3.67(s,3H),2.73(dd,J=13.8,5.6Hz,1H),2.52–2.39(m,3H),2.23(dd,J=16.8,5.4Hz,1H),2.13(dd,J=16.9,5.6Hz,1H),1.90–1.86(m,1H),1.29–1.25(m,2H).13C NMR(101MHz,CDCl3)δ174.4,142.4,142.3,138.6,128.9,128.7,128.6,128.5,127.9,127.9,126.9,126.9,126.4,118.3,60.1,52.4,39.4,37.7,35.5,29.0,20.9.质谱数据:MS(EI):397.2(M+)。1,1-Stilbene (0.2mmol), 3-benzylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol), and DMSO (2.0mL) were added to a 20mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 71% yield.核磁数据: 1 H NMR(400MHz,CDC l 3 )δ7.28(t,J=7.1Hz,4H),7.25–7.18(m,9H),7.06(d,J=6.7Hz,2H),3.67(s,3H),2.73(dd,J=13.8,5.6Hz,1H),2.52–2.39(m,3H),2.23(dd,J=16.8,5.4Hz,1H),2.13(dd,J=16.9,5.6Hz,1H),1.90–1.86(m,1H),1.29–1.25(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.4,142.4,142.3,138.6,128.9,128.7,128.6,128.5,127.9,127.9,126.9,126.9,126.4,118.3,60.1,52.4,39.4,37.7,35.5,29.0,20.9.质谱数据:MS(EI):397.2(M + )。
实施例21:5-(苄氧基)-6-氰基-2,2-二苯基己酸甲酯Example 21: Methyl 5-(Benzyloxy)-6-cyano-2,2-diphenylhexanoate
Methyl 5-(benzyloxy)-6-cyano-2,2-diphenylhexanoateMethyl 5-(benzyloxy)-6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、3-苄氧基环丁烷-1-酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为50%。核磁数据:1H NMR(400MHz,CDCl3)δ7.24–7.10(m,15H),4.38(q,J=11.6Hz,2H),3.57(s,3H),3.52–3.45(m,1H),2.36(d,J=5.9Hz,2H),2.25–2.17(m,1H),1.39–1.23(m,2H),1.15–1.08(m,1H).13C NMR(101MHz,CDCl3)δ174.4,142.4,142.1,137.4,128.8,128.7,128.4,128.0,127.9,127.8,127.0,126.9,117.5,74.4,71.6,59.9,52.4,33.1,29.5,22.8.质谱数据:MS(EI):413.2(M+)。1,1-Stilbene (0.2mmol), 3-benzyloxycyclobutan-1-one O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol), and DMSO (2.0mL) were added to a 20mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 50% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.24–7.10(m,15H),4.38(q,J=11.6Hz,2H),3.57(s,3H),3.52–3.45(m,1H),2.36(d,J=5.9Hz,2H),2.25–2.17(m,1H),1.39–1.23(m,2H),1.15–1.08(m,1H). 13 C NMR(101MHz,CDCl 3 )δ174.4,142.4,142.1,137.4,128.8,128.7,128.4,128.0,127.9,127.8,127.0,126.9,117.5,74.4,71.6,59.9,52.4,33.1,29.5,22.8.质谱数据:MS(EI):413.2(M + )。
实施例22:5-(((苄氧基)羰基)氨基)-6-氰基-2,2-二苯基己酸甲酯Example 22: Methyl 5-(((Benzyloxy)carbonyl)amino)-6-cyano-2,2-diphenylhexanoate
Methyl 5-(((benzyloxy)carbonyl)amino)-6-cyano-2,2-diphenylhexanoateMethyl 5-(((benzyloxy)carbonyl)amino)-6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、(3-(((4-(三氟甲基)苯甲酰基)氧基)亚氨基)环丁基)氨基甲酸苄酯(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)·PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA5/1)纯化,得到所需产物,收率为39%。核磁数据:1H NMR(400MHz,CDCl3)δ7.36–7.27(m,12H),7.24–7.18(m,3H),5.14–5.08(m,4H),3.70(s,3H),2.78–2.64(m,1H),2.56–2.44(m,2H),2.37–2.31(m,1H),1.33(d,J=6.9Hz,2H).13C NMR(101MHz,CDCl3)δ174.4,155.8,142.3,142.1,136.0,128.6,128.6,128.5,128.5,128.2,128.2,128.1,128.1,128.1,128.0,127.1,127.1,117.0,66.9,59.9,52.6,48.2,43.6,34.6,29.5,25.0,23.8,19.4.质谱数据:MS(EI):456.2(M+)。1,1-Stilbene (0.2mmol), benzyl (3-(((4-(trifluoromethyl)benzoyl)oxy)imino)cyclobutyl)carbamate (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy)· PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to 20mL Schlenk tubes, fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 39% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.36–7.27(m,12H),7.24–7.18(m,3H),5.14–5.08(m,4H),3.70(s,3H),2.78–2.64(m,1H),2.56–2.44(m,2H),2.37–2.31(m,1H),1.33(d,J=6.9Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ174.4,155.8,142.3,142.1,136.0,128.6,128.6,128.5,128.5,128.2,128.2,128.1,128.1,128.1,128.0,127.1,127.1,117.0,66.9,59.9,52.6,48.2,43.6,34.6,29.5,25.0,23.8,19.4.质谱数据:MS(EI):456.2(M + )。
实施例23:5,6-二氰基-2,2-二苯基己酸甲酯Example 23: Methyl 5,6-dicyano-2,2-diphenylhexanoate
Methyl 5-(((benzyloxy)carbonyl)amino)-6-cyano-2,2-diphenylhexanoateMethyl 5-(((benzyloxy)carbonyl)amino)-6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、3-氰基环丁烷-1-酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为80%。核磁数据:1H NMR(400MHz,CDCl3)δ7.33–7.28(m,6H),7.23(d,J=1.8Hz,1H),7.22–7.19(m,3H),3.68(s,3H),2.77–2.73(m,1H),2.59(dd,J=6.8,4.0Hz,2H),2.49–2.42(m,1H),1.54–1.48(m,3H).13C NMR(101MHz,CDCl3)δ174.0,141.7,141.7,128.5,128.5,128.2,128.2,127.3,118.7,115.4,59.7,52.6,35.3,28.6,27.7,20.7.质谱数据:MS(EI):332.2(M+)。1,1-Stilbene (0.2 mmol), 3-cyanocyclobutan-1-one O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 80% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.33–7.28(m,6H),7.23(d,J=1.8Hz,1H),7.22–7.19(m,3H),3.68(s,3H),2.77–2.73(m,1H),2.59(dd,J=6.8,4.0Hz,2H),2.49–2.42(m,1H),1.54–1.48(m,3H). 13 C NMR(101MHz,CDCl 3 )δ174.0,141.7,141.7,128.5,128.5,128.2,128.2,127.3,118.7,115.4,59.7,52.6,35.3,28.6,27.7,20.7.质谱数据:MS(EI):332.2(M + )。
实施例24:6-氰基-5-甲基-2,2,5-三苯基己酸甲酯Example 24: Methyl 6-cyano-5-methyl-2,2,5-triphenylhexanoate
Methyl 6-cyano-5-methyl-2,2,5-triphenylhexanoateMethyl 6-cyano-5-methyl-2,2,5-triphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、3-甲基3-苯基环丁烷-1-酮O-(4-(三氟甲基)苯甲基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为70%。核磁数据:1H NMR(400MHz,CDCl3)δ7.35–7.28(m,9H),7.19–7.16(m,4H),7.13(d,J=7.4Hz,2H),3.67(s,3H),2.62–2.51(m,2H),2.30–2.22(m,1H),2.10–2.01(m,1H),1.73–1.65(m,1H),1.56(dd,J=12.7,4.2Hz,1H),1.51(s,3H).13C NMR(101MHz,CDCl3)δ174.3,143.4,142.3,142.2,128.7,128.7,128.5,127.9,127.9,126.8,126.7,125.7,117.8,59.8,52.3,40.0,36.4,32.7,31.7,24.8.质谱数据:MS(EI):397.2(M+)。1,1-Stilbene (0.2 mmol), 3-methyl 3-phenylcyclobutan-1-one O-(4-(trifluoromethyl)benzyl)oxime (0.3 mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to a 20mL Schlenk tube equipped with Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 70% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.35–7.28(m,9H),7.19–7.16(m,4H),7.13(d,J=7.4Hz,2H),3.67(s,3H),2.62–2.51(m,2H),2.30–2.22(m,1H),2.10–2.01(m,1H),1.73–1.65(m,1H),1.56(dd,J=12.7,4.2Hz,1H),1.51(s,3H). 13 C NMR(101MHz,CDCl 3 )δ174.3,143.4,142.3,142.2,128.7,128.7,128.5,127.9,127.9,126.8,126.7,125.7,117.8,59.8,52.3,40.0,36.4,32.7,31.7,24.8.质谱数据:MS(EI):397.2(M + )。
实施例25:4-(氰甲基)-4-(4-甲氧基-4-氧代-3,3-二苯基丁基)哌啶-1-羧酸叔丁酯Example 25: tert-butyl 4-(cyanomethyl)-4-(4-methoxy-4-oxo-3,3-diphenylbutyl)piperidine-1-carboxylate
tert-Butyl4-(cyanomethyl)-4-(4-methoxy-4-oxo-3,3-diphenylbutyl)piperidine-1-carboxylatetert-Butyl4-(cyanomethyl)-4-(4-methoxy-4-oxo-3,3-diphenylbutyl)piperidine-1-carboxylate
将二苯乙烯(0.2mmol)、2-(((4-(三氟甲基)苯甲酰基)氧基)亚氨基)-7-氮杂螺[3.5]壬烷-7-羧酸叔丁酯(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为76%。核磁数据:1H NM R(400MHz,CDCl3)δ7.29(d,J=8.8Hz,3H),7.24–7.21(m,7H),3.66(s,3H),3.38–3.35(m,2H),3.06–2.99(m,2H),2.32–2.26(m,4H),1.43–1.41(m,4H),1.39(s,9H),1.25–1.21(m,2H).13C NMR(101MHz,CDCl3)δ174.2,154.5,142.2,128.6,128.0,127.0,117.3,79.6,59.9,52.4,34.1,31.7,30.9,28.3,26.3.质谱数据:MS(EI):476.3(M+)。Stilbene (0.2 mmol), 2-(((4-(trifluoromethyl)benzoyl)oxy)imino)-7-azaspiro[3.5]nonane-7-carboxylic acid tert-butyl ester (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) Add to 20mL Schlenk tubes fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 76% yield.核磁数据: 1 H NM R(400MHz,CDCl 3 )δ7.29(d,J=8.8Hz,3H),7.24–7.21(m,7H),3.66(s,3H),3.38–3.35(m,2H),3.06–2.99(m,2H),2.32–2.26(m,4H),1.43–1.41(m,4H),1.39(s,9H),1.25–1.21(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.2,154.5,142.2,128.6,128.0,127.0,117.3,79.6,59.9,52.4,34.1,31.7,30.9,28.3,26.3.质谱数据:MS(EI):476.3(M + )。
实施例26:6-氰基-4-甲基-2,2-二苯基己酸甲酯Example 26: Methyl 6-cyano-4-methyl-2,2-diphenylhexanoate
Methyl 6-cyano-2,2,4-triphenylhexanoateMethyl 6-cyano-2,2,4-triphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、2-甲基环丁烷-1-酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为78%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.26(m,10H),3.68(s,3H),2.35(t,J=5.1Hz,2H),2.26–2.08(m,2H),1.45–1.38(m,1H),1.28(dd,J=7.5Hz,2H),0.63(d,J=6.7Hz,3H).13C NMR(101MHz,CDCl3)δ174.5,143.1,142.9,128.9,128.8,128.0,127.9,127.0,126.9,119.7,60.0,52.3,44.7,33.2,29.4,20.2,14.7.质谱数据:MS(EI):321.2(M+)。1,1-Stilbene (0.2 mmol), 2-methylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to a 20 mL Schlenk tube equipped with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 78% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.26(m,10H),3.68(s,3H),2.35(t,J=5.1Hz,2H),2.26–2.08(m,2H),1.45–1.38(m,1H),1.28(dd,J=7.5Hz,2H),0.63(d,J=6.7Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ174.5,143.1,142.9,128.9,128.8,128.0,127.9,127.0,126.9,119.7,60.0,52.3,44.7,33.2,29.4,20.2,14.7.质谱数据:MS(EI):321.2(M + )。
实施例27:6-氰基-2,2,4-三苯基己酸甲酯Example 27: Methyl 6-cyano-2,2,4-triphenylhexanoate
Methyl 6-cyano-2,2,4-triphenylhexanoateMethyl 6-cyano-2,2,4-triphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、2-苯基环丁烷-1-酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为19%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.26(m,10H),3.68(s,3H),2.35(t,J=5.1Hz,2H),2.26–2.08(m,2H),1.45–1.38(m,1H),1.28(dd,J=7.5Hz,2H),0.63(d,J=6.7Hz,3H).13C NMR(101MHz,CDCl3)δ174.5,143.1,142.9,128.9,128.8,128.0,127.9,127.0,126.9,119.7,60.0,52.3,44.7,33.2,29.4,20.2,14.7.质谱数据:MS(EI):378(M+);1,1-Stilbene (0.2 mmol), 2-phenylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol) and DMSO (2.0 mL) were added to a 20 mL Schlenk tube equipped with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 19% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.26(m,10H),3.68(s,3H),2.35(t,J=5.1Hz,2H),2.26–2.08(m,2H),1.45–1.38(m,1H),1.28(dd,J=7.5Hz,2H),0.63(d,J=6.7Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ174.5,143.1,142.9,128.9,128.8,128.0,127.9,127.0,126.9,119.7,60.0,52.3,44.7,33.2,29.4,20.2,14.7.质谱数据:MS(EI):378(M+);
实施例28:4-(氰基甲氧基)-2,2-二苯基丁酸甲酯Example 28: Methyl 4-(cyanomethoxy)-2,2-diphenylbutyrate
Methyl 4-(cyanomethoxy)-2,2-diphenylbutanoateMethyl 4-(cyanomethoxy)-2,2-diphenylbutanoate
将1,1-二苯乙烯(0.2mmol)、3-氧代环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为66%。核磁数据:1H NMR(400MHz,CDCl3)δ7.32–7.28(m,6H),7.25–7.23(m,4H),4.07(s,2H),3.69(s,3H),3.36(t,J=7.1Hz,2H),2.73(t,J=7.2Hz,2H).13C NMR(101MHz,CDCl3)δ174.1,142.1,128.5,128.1,127.1,115.8,69.0,58.2,56.1,52.5,37.3.质谱数据:MS(EI):309.1(M+)。Add 1,1-stilbene (0.2 mmol), 3-oxocyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) to a 20 mL Schlenk tube fitted with a Teflon cap . The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 66% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.32–7.28(m,6H),7.25–7.23(m,4H),4.07(s,2H),3.69(s,3H),3.36(t,J=7.1Hz,2H),2.73(t,J=7.2Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ174.1,142.1,128.5,128.1,127.1,115.8,69.0,58.2,56.1,52.5,37.3.质谱数据:MS(EI):309.1(M + )。
实施例29:4-((叔丁氧羰基)(氰甲基)氨基)-2,2-二苯基丁酸甲酯Example 29: Methyl 4-((tert-butoxycarbonyl)(cyanomethyl)amino)-2,2-diphenylbutyrate
Methyl 4-((tert-butoxycarbonyl)(cyanomethyl)amino)-2,2-diphenylbutanoateMethyl 4-((tert-butoxycarbonyl)(cyanomethyl)amino)-2,2-diphenylbutanoate
将1,1-二苯乙烯(0.2mmol)、3-(((4-(三氟甲基)苯甲酰基)氧基)亚氨基)氮杂环丁烷-1-羧酸叔丁酯(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)·PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA5/1)纯化,得到所需产物,收率为74%。核磁数据:1H NM R(400MHz,CDCl3)δ7.33–7.28(m,6H),7.25–7.23(m,4H),4.03(d,J=50.8Hz,2H),3.71(s,3H),3.07–3.03(m,2H),2.62(s,2H),1.46(s,3H),1.37(s,6H).13C NMR(101MHz,CDCl3)δ174.1,154.4,141.9,128.5,128.2,127.2,116.2,81.5,58.7,52.6,45.4,36.1,35.2,28.1.质谱数据:MS(EI):408.2(M+)。1,1-Stilbene (0.2mmol), 3-(((4-(trifluoromethyl)benzoyl)oxy)imino)azetidine-1-carboxylate tert-butyl ester (0.3mmol), Ir[(dF(CF3)ppy)]2(dtbbpy)·PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to 20mL Sch Lenk tubes, fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 74% yield.核磁数据: 1 H NM R(400MHz,CDCl3)δ7.33–7.28(m,6H),7.25–7.23(m,4H),4.03(d,J=50.8Hz,2H),3.71(s,3H),3.07–3.03(m,2H),2.62(s,2H),1.46(s,3H),1.37(s,6H). 13 C NMR(101MHz,CDCl3)δ174.1,154.4,141.9,128.5,128.2,127.2,116.2,81.5,58.7,52.6,45.4,36.1,35.2,28.1.质谱数据:MS(EI):408.2(M + )。
实施例30:4-(氰基甲氧基)-2,2-二苯基丁酸甲酯Example 30: Methyl 4-(cyanomethoxy)-2,2-diphenylbutyrate
Methyl 4-(2-cyanoethoxy)-2,2-diphenylpentanoateMethyl 4-(2-cyanoethoxy)-2,2-diphenylpentanoate
将1,1-二苯乙烯(0.2mmol)、2-甲基二氢呋喃-3(2H)-酮-O--(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为59%。核磁数据1H NMR(400MHz,CDCl3)δ7.36(d,J=7.6Hz,2H),7.31–7.28(m,6H),7.24–7.20(m,2H),3.65(s,3H),3.57–3.51(m,1H),3.10–3.05(m,2H),2.99–2.93(m,1H),2.43–2.37(m,2H),2.29(dd,J=13.9,3.1Hz,1H),1.09(d,J=6.0Hz,3H).13CNMR(101MHz,CDCl3)δ174.5,143.6,142.9,129.2,128.3,128.0,127.6,126.8,126.5,117.9,73.1,62.6,57.9,52.1,45.6,19.5,18.7.质谱数据:MS(EI):337.2(M+)。1,1-Stilbene (0.2mmol), 2-methyldihydrofuran-3(2H)-one-O--(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to 20mL Sch Lenk tubes, fitted with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (PE/EA 5/1) to give the desired product in 59% yield.核磁数据1 H NMR(400MHz,CDCl 3 )δ7.36(d,J=7.6Hz,2H),7.31–7.28(m,6H),7.24–7.20(m,2H),3.65(s,3H),3.57–3.51(m,1H),3.10–3.05(m,2H),2.99–2.93(m,1H),2.43–2.37(m,2H),2.29(dd,J=13.9,3.1Hz,1H),1.09(d,J=6.0Hz,3H). 13 CNMR(101MHz,CDCl 3 )δ174.5,143.6,142.9,129.2,128.3,128.0,127.6,126.8,126.5,117.9,73.1,62.6,57.9,52.1,45.6,19.5,18.7.质谱数据:MS(EI):337.2(M + )。
实施例31:3-((3-氰甲基)-1,2,2-三甲基环戊基)-2,2-二苯基丙酸甲酯Example 31: Methyl 3-((3-cyanomethyl)-1,2,2-trimethylcyclopentyl)-2,2-diphenylpropionate
Methyl 3-(3-(cyanomethyl)-1,2,2-trimethylcyclopentyl)-2,2-diphenylpropanoateMethyl 3-(3-(cyanomethyl)-1,2,2-trimethylcyclopentyl)-2,2-diphenylpropanoate
将1,1-二苯乙烯(0.2mmol)、1,7,7-三甲基二环[2.2.0]庚烷-O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为21%。核磁数据:1H NMR(400MHz,CDCl3)δ7.44(d,J=7.0Hz,2H),7.38(d,J=7.0Hz,2H),7.27–7.25(m,3H),7.23–7.20(m,4H,overlapped with CDCl3),3.64(s,3H),2.65(d,J=13.8Hz,1H),2.52(d,J=13.8Hz,1H),2.39–2.34(m,1H),2.25–2.19(m,1H),2.17–2.11(m,1H),1.82–1.77(m,1H),1.25–1.11(m,2H),1.04(s,3H),0.82–0.77(m,1H),0.72(s,3H),0.46(s,3H).13C NMR(101MHz,CDCl3)δ174.5,145.2,144.6,129.1,128.9,127.8,127.8,126.6,126.6,120.0,57.1,52.1,47.6,46.8,44.1,44.0,32.7,28.7,23.5,20.3,19.7,18.7.质谱数据:MS(EI):389.2(M+)。1,1-Stilbene (0.2mmol), 1,7,7-Trimethylbicyclo[2.2.0]heptane-O-(4-(trifluoromethyl)benzoyl)oxime (0.3mmol), Ir[(dF( CF3 )ppy)] 2 (dtbbpy) PF6 (2mol%, 3.4mg), DIPEA (0.3mmol) and DMSO (2.0mL) were added to 2 0 mL Schlenk tubes with Teflon caps. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 21% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.44(d,J=7.0Hz,2H),7.38(d,J=7.0Hz,2H),7.27–7.25(m,3H),7.23–7.20(m,4H,overlapped with CDCl 3 ),3.64(s,3H),2.65(d,J=13.8Hz,1H),2.52(d,J=13.8Hz,1H),2.39–2.34(m,1H),2.25–2.19(m,1H),2.17–2.11(m,1H),1.82–1.77(m,1H),1.25–1.11(m,2H),1.04(s,3H),0.82–0.77(m,1H),0.72(s,3H),0.46(s,3H). 13 C NMR(101MHz,CDCl 3 )δ174.5,145.2,144.6,129.1,128.9,127.8,127.8,126.6,126.6,120.0,57.1,52.1,47.6,46.8,44.1,44.0,32.7,28.7,23.5,20.3,19.7,18.7.质谱数据:MS(EI):389.2(M + )。
实施例32:8-氰基-2,2,4-三苯基辛酸甲酯Example 32: Methyl 8-cyano-2,2,4-triphenyloctanoate
Methyl 8-cyano-2,2,4-triphenyloctanoateMethyl 8-cyano-2,2,4-triphenyloctanoate
将1,1-二苯乙烯(0.2mmol)、2-苯基环己酮-O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,收率为21%。核磁数据:1H NMR(400MHz,CDCl3)δ7.44(d,J=7.0Hz,2H),7.38(d,J=7.0Hz,2H),7.27–7.25(m,3H),7.23–7.20(m,4H,overlapped with CDCl3),3.64(s,3H),2.65(d,J=13.8Hz,1H),2.52(d,J=13.8Hz,1H),2.39–2.34(m,1H),2.25–2.19(m,1H),2.17–2.11(m,1H),1.82–1.77(m,1H),1.25–1.11(m,2H),1.04(s,3H),0.82–0.77(m,1H),0.72(s,3H),0.46(s,3H).13C NMR(101MHz,CDCl3)δ174.5,145.2,144.6,129.1,128.9,127.8,127.8,126.6,126.6,120.0,57.1,52.1,47.6,46.8,44.1,44.0,32.7,28.7,23.5,20.3,19.7,18.7.质谱数据:MS(EI):389.2(M+)。Add 1,1-stilbene (0.2 mmol), 2-phenylcyclohexanone-O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) to a 20 mL Schlenk tube fitted with a Teflon cap . The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 21% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.44(d,J=7.0Hz,2H),7.38(d,J=7.0Hz,2H),7.27–7.25(m,3H),7.23–7.20(m,4H,overlapped with CDCl 3 ),3.64(s,3H),2.65(d,J=13.8Hz,1H),2.52(d,J=13.8Hz,1H),2.39–2.34(m,1H),2.25–2.19(m,1H),2.17–2.11(m,1H),1.82–1.77(m,1H),1.25–1.11(m,2H),1.04(s,3H),0.82–0.77(m,1H),0.72(s,3H),0.46(s,3H). 13 C NMR(101MHz,CDCl 3 )δ174.5,145.2,144.6,129.1,128.9,127.8,127.8,126.6,126.6,120.0,57.1,52.1,47.6,46.8,44.1,44.0,32.7,28.7,23.5,20.3,19.7,18.7.质谱数据:MS(EI):389.2(M + )。
实施例33:6-氰基-2,2-二苯基己酸甲酯Example 33: Methyl 6-cyano-2,2-diphenylhexanoate
Methyl 6-cyano-2,2-diphenylhexanoateMethyl 6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、Ir[(dF(CF3)ppy)]2(dtbbpy)PF6(2mol%,3.4mg)、Et3N(0.3mmol)和DMSO(2.0mL)加入到20mLSchlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,产率为66%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H).13C NMR(101MHz,CDCl3)δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M+)。1,1-Stilbene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), Ir[(dF(CF 3 )ppy)] 2 (dtbbpy)PF 6 (2 mol%, 3.4 mg), Et 3 N (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube fitted with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 66% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M + )。
实施例34:6-氰基-2,2-二苯基己酸甲酯Example 34: Methyl 6-cyano-2,2-diphenylhexanoate
Methyl 6-cyano-2,2-diphenylhexanoateMethyl 6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、2,4,5,6-四(9-咔唑基)-间苯二腈(2mol%,3.1mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA5/1)纯化,得到所需产物,产率为53%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H).13C NMR(101MHz,CDCl3)δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M+)。1,1-Stilbene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (2 mol%, 3.1 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube fitted with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 53% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M + )。
实施例35:6-氰基-2,2-二苯基己酸甲酯Example 35: Methyl 6-cyano-2,2-diphenylhexanoate
Methyl 6-cyano-2,2-diphenylhexanoateMethyl 6-cyano-2,2-diphenylhexanoate
将1,1-二苯乙烯(0.2mmol)、环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.3mmol)、三(2,2'-联吡啶)钌二(六氟磷酸)盐(2mol%,3.4mg)、DIPEA(0.3mmol)和DMSO(2.0mL)加入到20mL Schlenk管,配有特氟龙帽。将反应容器抽真空至约-0.1MPa(每次最后30秒)并分三次回填CO2(1个大气压)。然后,将Schlenk管在室温下在2×3W蓝光LED照射下搅拌12小时。之后,向反应混合物中加MeI(0.8mmol),将反应混合物在50℃下搅拌约1小时,然后将反应混合物盐水稀释并用乙酸乙酯萃取(EA)至少6次(2mL×6)。随后,合并的有机层经无水Na2SO4干燥并在减压下浓缩。残余物通过硅胶快速色谱法(PE/EA 5/1)纯化,得到所需产物,产率为51%。核磁数据:1H NMR(400MHz,CDCl3)δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H).13C NMR(101MHz,CDCl3)δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M+)。1,1-Stilbene (0.2 mmol), cyclobutanone O-(4-(trifluoromethyl)benzoyl)oxime (0.3 mmol), tris(2,2'-bipyridyl)ruthenium bis(hexafluorophosphate) salt (2 mol%, 3.4 mg), DIPEA (0.3 mmol), and DMSO (2.0 mL) were added to a 20 mL Schlenk tube fitted with a Teflon cap. The reaction vessel was evacuated to about -0.1 MPa (last 30 seconds each) and backfilled with CO2 (1 atm) in three installments. Then, the Schlenk tube was stirred at room temperature under 2 × 3W blue LED illumination for 12 h. After that, MeI (0.8 mmol) was added to the reaction mixture, the reaction mixture was stirred at 50 °C for about 1 hour, then the reaction mixture was diluted with brine and extracted (EA) with ethyl acetate at least 6 times (2 mL×6). Then, the combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (PE/EA 5/1) to give the desired product in 51% yield.核磁数据: 1 H NMR(400MHz,CDCl 3 )δ7.34–7.28(m,10H),3.71(s,3H),2.43–2.38(m,2H),2.27(t,J=7.2Hz,2H),1.68-1.60(m,2H),1.26-1.19(m,2H). 13 C NMR(101MHz,CDCl 3 )δ174.5,142.4,128.7,127.9,126.9,119.5,60.1,52.4,37.3,29.6,25.7,24.5,16.8.质谱数据:MS(EI):307.2(M + )。
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111000883.2A CN113773227B (en) | 2021-08-30 | 2021-08-30 | Method for preparing epsilon-, zeta-, eta-cyano carboxylic acid from carbon dioxide |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111000883.2A CN113773227B (en) | 2021-08-30 | 2021-08-30 | Method for preparing epsilon-, zeta-, eta-cyano carboxylic acid from carbon dioxide |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113773227A CN113773227A (en) | 2021-12-10 |
CN113773227B true CN113773227B (en) | 2023-07-25 |
Family
ID=78839790
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111000883.2A Active CN113773227B (en) | 2021-08-30 | 2021-08-30 | Method for preparing epsilon-, zeta-, eta-cyano carboxylic acid from carbon dioxide |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113773227B (en) |
-
2021
- 2021-08-30 CN CN202111000883.2A patent/CN113773227B/en active Active
Non-Patent Citations (4)
Title |
---|
A dual photoredox-nickel strategy for remote functionalization via iminyl radicals: radical ring-opening-arylation, -vinylation and -alkylation cascades;Elizabeth M Dauncey 等;《Chemical science》;第10卷(第33期);第7728-7733页 * |
Iron‐Catalyzed Ring‐Opening/Allylation of Cyclobutanone Oxime Esters with Allylic Sulfones;Zhao, JF 等;《Advanced Synthesis & Catalysis》;第360卷(第9期);第1775-1779页 * |
Synthesis of Functionalized Nitriles by Microwave-Promoted Fragmentations of Cyclic Iminyl Radicals;Mary M. Jackman 等;《Chemistry - A European Journal》;第24卷(第3期);第594-598页 * |
Visible-Light Photoredox-Catalyzed Ring-Opening Carboxylation of Cyclic Oxime Esters with CO2;Yuan-Xu Jiang 等;《ChemSusChem》;第13卷(第23期);第6312-6317页 * |
Also Published As
Publication number | Publication date |
---|---|
CN113773227A (en) | 2021-12-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107674044A (en) | A kind of method using carbon dioxide, amine and aryldiazonium acetic acid esters synthesis of carbamates | |
CN108834409B (en) | Process for producing fluorine-containing compound | |
CN108864147A (en) | Eight yuan of nitrogen oxa- ring spiral shell oxindole compounds of one kind and preparation method | |
WO2009136646A1 (en) | Method for producing unsaturated organic compound | |
CN113773227B (en) | Method for preparing epsilon-, zeta-, eta-cyano carboxylic acid from carbon dioxide | |
CN118373738A (en) | Method for preparing gamma-aldehyde carboxylic ester by carbon dioxide | |
CN115490613B (en) | A kind of preparation method of aromatic nitrile compound | |
CN117736104A (en) | Method for synthesizing butanedicarboxylate derivative by visible light catalysis | |
CN113668004B (en) | Method for electrochemical synthesis of non-natural amino acid derivatives | |
CN113480485B (en) | 1,2, 4-triaryl-1, 2, 4-triazoles compound and synthetic method thereof | |
CN112239432B (en) | Preparation method of chiral 3,4-dihydrobenzothiadiazines | |
CN115286635A (en) | Synthesis method of chiral cyclo-pyrazolone compound | |
CN112574108B (en) | Preparation method of polysubstituted benzo [ b ] azepine compound | |
CN106748964B (en) | 2-Alkylthio(oxy)yl-3-azabicyclo[3,1,0]-2-cyclohexene derivatives and their synthesis | |
CN104262283A (en) | 1,2-oxa-cyclic compound derivative and preparation method thereof | |
CN102731386B (en) | Preparation method of para-diimide derivative | |
CN114507177B (en) | Method for preparing functionalized methyl 2-(3-oxoisoindoline-1-ylidene)acetate from carbon dioxide | |
CN115572269B (en) | N-trifluoroisopropylazole and indole compound and preparation method thereof | |
CN110668940A (en) | Synthesis of α,β-Unsaturated Carboxylate Derivatives Catalyzed by Visible Light | |
CN114907266B (en) | A kind of preparation method of dihydropyrazole compounds | |
CN112028756B (en) | A kind of synthetic method of 2-benzylbenzaldehyde derivative | |
CN108409630A (en) | A kind of preparation method of 3-hydroxyl-2-indolinone derivative in water phase | |
CN110615729B (en) | Method for selectively generating cis-olefin by deamination coupling of secondary carbon primary amine and aryl terminal alkyne | |
CN102775392B (en) | N-protected-3,5-disubstituted indole derivative and its preparation method and application | |
CN117682982A (en) | A method for preparing α-carbonyldifluoride-modified glutarimide compounds |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |