CN114716289B - 一种手性苄醇类衍生物的制备方法 - Google Patents
一种手性苄醇类衍生物的制备方法 Download PDFInfo
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- CN114716289B CN114716289B CN202210328201.9A CN202210328201A CN114716289B CN 114716289 B CN114716289 B CN 114716289B CN 202210328201 A CN202210328201 A CN 202210328201A CN 114716289 B CN114716289 B CN 114716289B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 65
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 title claims abstract description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 174
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims abstract description 120
- 239000003446 ligand Substances 0.000 claims abstract description 80
- 150000001875 compounds Chemical class 0.000 claims abstract description 69
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 claims abstract description 63
- AVWLPUQJODERGA-UHFFFAOYSA-L cobalt(2+);diiodide Chemical compound [Co+2].[I-].[I-] AVWLPUQJODERGA-UHFFFAOYSA-L 0.000 claims abstract description 63
- 239000011541 reaction mixture Substances 0.000 claims abstract description 63
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims abstract description 62
- -1 aromatic iodo compound Chemical class 0.000 claims abstract description 23
- 229910017052 cobalt Inorganic materials 0.000 claims abstract description 18
- 239000010941 cobalt Substances 0.000 claims abstract description 18
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 12
- 235000019445 benzyl alcohol Nutrition 0.000 claims abstract description 11
- 239000011941 photocatalyst Substances 0.000 claims abstract description 10
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 6
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims abstract description 3
- 238000004440 column chromatography Methods 0.000 claims description 57
- 239000003480 eluent Substances 0.000 claims description 56
- 239000003208 petroleum Substances 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910000085 borane Inorganic materials 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical class 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical class 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 1
- 125000005544 phthalimido group Chemical group 0.000 claims 1
- 230000003287 optical effect Effects 0.000 abstract description 56
- 229910021584 Cobalt(II) iodide Inorganic materials 0.000 abstract description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 110
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 110
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 107
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 106
- 238000004458 analytical method Methods 0.000 description 55
- 229910052786 argon Inorganic materials 0.000 description 55
- 238000001514 detection method Methods 0.000 description 55
- 238000010828 elution Methods 0.000 description 55
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 55
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
- 238000012512 characterization method Methods 0.000 description 54
- 239000000741 silica gel Substances 0.000 description 54
- 229910002027 silica gel Inorganic materials 0.000 description 54
- 230000014759 maintenance of location Effects 0.000 description 52
- NXYICUMSYKIABQ-UHFFFAOYSA-N 1-iodo-4-phenylbenzene Chemical compound C1=CC(I)=CC=C1C1=CC=CC=C1 NXYICUMSYKIABQ-UHFFFAOYSA-N 0.000 description 35
- PJKVFARRVXDXAD-UHFFFAOYSA-N 2-naphthaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CC=C21 PJKVFARRVXDXAD-UHFFFAOYSA-N 0.000 description 18
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 6
- 150000001503 aryl iodides Chemical class 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 3
- 229950011260 betanaphthol Drugs 0.000 description 3
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 2
- DVQWNQBEUKXONL-UHFFFAOYSA-N 1-iodo-2-methoxybenzene Chemical compound COC1=CC=CC=C1I DVQWNQBEUKXONL-UHFFFAOYSA-N 0.000 description 2
- FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 description 2
- OYIGWMXXIFYAGD-UHFFFAOYSA-N 3-iodo-9h-carbazole Chemical compound C1=CC=C2C3=CC(I)=CC=C3NC2=C1 OYIGWMXXIFYAGD-UHFFFAOYSA-N 0.000 description 2
- HRNNNYZRMMSALR-UHFFFAOYSA-N 4-(sulfanylmethyl)benzaldehyde Chemical compound SCC1=CC=C(C=O)C=C1 HRNNNYZRMMSALR-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- 150000003938 benzyl alcohols Chemical class 0.000 description 2
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 2
- RUMOYJJNUMEFDD-JTQLQIEISA-N (4r)-4-prop-1-en-2-ylcyclohexene-1-carbaldehyde Chemical compound CC(=C)[C@@H]1CCC(C=O)=CC1 RUMOYJJNUMEFDD-JTQLQIEISA-N 0.000 description 1
- VLUMOWNVWOXZAU-VQHVLOKHSA-N (e)-2-methyl-3-phenylprop-2-enal Chemical compound O=CC(/C)=C/C1=CC=CC=C1 VLUMOWNVWOXZAU-VQHVLOKHSA-N 0.000 description 1
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- WQRWNOKNRHCLHV-TWGQIWQCSA-N (z)-2-bromo-3-phenylprop-2-enal Chemical compound O=CC(/Br)=C/C1=CC=CC=C1 WQRWNOKNRHCLHV-TWGQIWQCSA-N 0.000 description 1
- KSASJELKLBIMSG-UHFFFAOYSA-N 1,2-difluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1F KSASJELKLBIMSG-UHFFFAOYSA-N 0.000 description 1
- OIPHRFQIBIQGJF-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylindole-3-carbaldehyde Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=CC=CC=C2C(C=O)=C1 OIPHRFQIBIQGJF-UHFFFAOYSA-N 0.000 description 1
- UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 description 1
- GWQSENYKCGJTRI-UHFFFAOYSA-N 1-chloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1 GWQSENYKCGJTRI-UHFFFAOYSA-N 0.000 description 1
- KGNQDBQYEBMPFZ-UHFFFAOYSA-N 1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1 KGNQDBQYEBMPFZ-UHFFFAOYSA-N 0.000 description 1
- RTUDBROGOZBBIC-UHFFFAOYSA-N 1-iodo-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(I)C=C1 RTUDBROGOZBBIC-UHFFFAOYSA-N 0.000 description 1
- SKGRFPGOGCHDPC-UHFFFAOYSA-N 1-iodo-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(I)C=C1 SKGRFPGOGCHDPC-UHFFFAOYSA-N 0.000 description 1
- UCTUXUGXIFRVGX-UHFFFAOYSA-N 2,3,4-trimethoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(OC)=C1OC UCTUXUGXIFRVGX-UHFFFAOYSA-N 0.000 description 1
- WEBVDBDZSOJGPB-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-carbaldehyde Chemical compound O=CC1=CC=C2OCCC2=C1 WEBVDBDZSOJGPB-UHFFFAOYSA-N 0.000 description 1
- TWFSYIOOAAYYAL-UHFFFAOYSA-N 2,4,6-trichlorobenzaldehyde Chemical compound ClC1=CC(Cl)=C(C=O)C(Cl)=C1 TWFSYIOOAAYYAL-UHFFFAOYSA-N 0.000 description 1
- DRCPJRZHAJMWOU-UHFFFAOYSA-N 2-diphenylphosphinobenzaldehyde Chemical compound O=CC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 DRCPJRZHAJMWOU-UHFFFAOYSA-N 0.000 description 1
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 1
- YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical compound O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 description 1
- DMBMXJJGPXADPO-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C=O)C=C1 DMBMXJJGPXADPO-UHFFFAOYSA-N 0.000 description 1
- XQNVDQZWOBPLQZ-UHFFFAOYSA-N 4-(trifluoromethoxy)benzaldehyde Chemical compound FC(F)(F)OC1=CC=C(C=O)C=C1 XQNVDQZWOBPLQZ-UHFFFAOYSA-N 0.000 description 1
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 1
- OTXINXDGSUFPNU-UHFFFAOYSA-N 4-tert-butylbenzaldehyde Chemical compound CC(C)(C)C1=CC=C(C=O)C=C1 OTXINXDGSUFPNU-UHFFFAOYSA-N 0.000 description 1
- ULMSEXZJAKWUQX-UHFFFAOYSA-N 5-iodo-1-(4-methylphenyl)sulfonylindole Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=CC=C(I)C=C2C=C1 ULMSEXZJAKWUQX-UHFFFAOYSA-N 0.000 description 1
- KMRMUZKLFIEVAO-UHFFFAOYSA-N 7,7-dimethylbicyclo[3.1.1]hept-3-ene-4-carbaldehyde Chemical compound C1C2C(C)(C)C1CC=C2C=O KMRMUZKLFIEVAO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KMRMUZKLFIEVAO-RKDXNWHRSA-N Myrtenal Natural products C1[C@H]2C(C)(C)[C@@H]1CC=C2C=O KMRMUZKLFIEVAO-RKDXNWHRSA-N 0.000 description 1
- CTYPJIUQROQJBG-JWQCQUIFSA-N [(2r,4r)-4-diphenylphosphanylpentan-2-yl]-diphenylphosphane Chemical compound C=1C=CC=CC=1P([C@H](C)C[C@@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 CTYPJIUQROQJBG-JWQCQUIFSA-N 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- IWJMQXOBCQTQCF-UHFFFAOYSA-N but-3-enal Chemical compound C=CCC=O IWJMQXOBCQTQCF-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- INVYSLWXPIEDIQ-UHFFFAOYSA-N cyclobutanecarbaldehyde Chemical compound O=CC1CCC1 INVYSLWXPIEDIQ-UHFFFAOYSA-N 0.000 description 1
- KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- RUMOYJJNUMEFDD-UHFFFAOYSA-N perillaldehyde Natural products CC(=C)C1CCC(C=O)=CC1 RUMOYJJNUMEFDD-UHFFFAOYSA-N 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N phenyl propionaldehyde Natural products CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
- B01J31/0248—Nitriles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/19—Catalysts containing parts with different compositions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J35/00—Catalysts, in general, characterised by their form or physical properties
- B01J35/30—Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
- B01J35/39—Photocatalytic properties
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B41/00—Formation or introduction of functional groups containing oxygen
- C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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Abstract
本发明提供了一种手性苄醇类衍生物的制备方法,手性苄醇类衍生物的制备方法包括如下步骤:S1、在惰性气体保护下,在二氯甲烷溶剂中加入配体以及碘化钴(II),配体与Co(II)配位生成二价钴配体化合物,得到二价钴配体化合物溶液;S2、在所述二价钴配体化合物溶液中加入光催化剂2,4,5,6‑四(9‑咔唑基)‑间苯二腈、二异丙基乙基胺、还原剂二氢吡啶、芳香碘代物和醛类化合物得到反应混合物,所述反应混合物在蓝光照射下反应得到手性苄醇类化合物。基于本发明的方法,安全、简单、高效、且高选择性地合成具有光学活性的苄醇,解决了现有技术中存在安全性低以及适用范围窄的问题。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种手性苄醇类衍生物的制备方法。
背景技术
手性苄醇及其衍生物作为重要的结构单元,广泛分布于天然产物、药物以及各种材料分子中,寻找一种高效、直接的途径来合成这些化合物一直吸引着化学家们的关注。以往,化学家们通过过渡金属或者酶催化的不对称氢化来构建手性苄醇,但是这些策略普遍存在一定的底物限制。现有技术中通过简单芳基卤代物和醛类化合物制备手性苄醇的报道较少,且这些方法都使用了当量的锌粉,存在易燃易爆的危险性。因此,发展手性苄醇的安全、高效、简单、适用范围广的合成方法具有重要意义。
发明内容
本发明解决的技术问题为:提供一种手性苄醇类衍生物的制备方法,提供一种安全、简单、高效、高选择性地合成具有光学活性的苄醇的方法,用以解决现有技术中存在安全性低以及适用范围窄的问题。
本发明提供的具体解决方案如下:
本发明提供了一种手性苄醇类衍生物的制备方法,手性苄醇类衍生物具有通式I所示的结构,通式I所示的手性苄醇类衍生物的制备方法包括如下步骤:
S1、在惰性气体保护下,在二氯甲烷溶剂中加入配体VI(R,R)-BDPP以及碘化钴(II),配体与碘化钴(II)配位生成二价钴配体化合物,得到二价钴配体化合物溶液;
S2、在所述二价钴配体化合物溶液中加入光催化剂2,4,5,6-四(9-咔唑基)-间苯二腈4CzIPN、二异丙基乙基胺i-Pr2NEt、还原剂二氢吡啶HE、式所示的II芳香碘代物以及式III所示的醛类化合物得到反应混合物,将所述反应混合物在蓝光照射下反应得到式I所示的手性苄醇类化合物;
配体VI的结构如下式所示:
上述反应式中,
R选自芳基、杂芳基、烯基、烷基,或选自被相同或不同的取代基单取代或多取代的芳基、杂芳基、烯基、烷基,所述杂芳基中杂原子选自N、S或O中的一种或多种;
环A选自芳基或苯并杂芳基;
各所述R1分别独立地选自H、酯基、氰基、卤素、氨基磺酰基、烷基磺酰基、取代或未取代烷基、取代或未取代烷氧基、取代或未取代的炔基中的一种。
基于本发明的技术方案具有如下有益效果:
(1)基于本发明的方法,以碘化钴(II)和(2R,4R)-(+)-2,4-双(二苯基磷)戊烷配体生成的二价钴配体化合物作为手性催化剂,以4CzIPN为光催化剂,以二氢吡啶为还原剂,制备得到了手性苄醇类衍生物,无需使用锌粉,制备方法简单,安全。
(2)基于本发明的方法从简单的芳基碘代物和醛类化合物出发,高效、高选择性地合成了一系列具有光学活性的苄醇,原料简单易得,底物适用范围广。
(3)基于本发明的方法,在蓝光照射下或者可见光照射下,光催化剂2,4,5,6-四(9-咔唑基)-间苯二腈达到激发态,随后被二氢吡啶单电子还原成低价态的光催化剂,低价态的光催化剂将二价钴配体化合物还原成一价钴配体化合物,一价钴(L*Co(I))可与芳基碘代物(Ar-I)发成氧化加成生成三价的芳基钴物种(Ar-L*Co(III)-I),随后被低价态光催化剂还原成二价的芳基钴物种(Ar-L*Co(II)-I),二价的芳基钴物种与醛基(R-CHO)通过醛基O上的孤对电子先与Co(II)发生配位,随后迁移插入,生成苄基醇阴离子,最后质子化得到产物,反应过程中,在配体VI的作用下,醛基O配位以及芳基迁移插入具有高度选择性,最终生成了具有特定手性的苄基醇阴离子。
优选地,所述环A选自苯基、联苯基、萘基、苯并呋喃、苯并噻吩、吲哚、咔唑或喹啉中的一种。
优选地,R为被相同或不同的取代基单取代或多取代的芳基、杂芳基、烯基、烷基时,R上的各所述取代基独立地选自卤素、氰基、烷基、烯基、芳香基、硼烷基、取代硼烷基、烷氧基、取代烷氧基、巯基、烷基巯基、烷基膦氧基、苯基膦氧基或邻苯二甲酰亚胺基中的一种。
优选地,所述手性苄醇类衍生物选自以下结构中的一种:
通过本发明的方法制备的上述结构,产率较高且对映体选择性高。
优选地,S1中配体VI与所述碘化钴(II)的摩尔比为1:(1~3)。
进一步,所述混合反应液二价钴配体化合物、光催化剂2,4,5,6-四(9-咔唑基)-间苯二腈、二异丙基乙基胺、还原剂二氢吡啶、式所示的II芳香碘代物以及式III所示的醛类化合物的摩尔比为(5%~15%):(0.5%~4%):(1.5~3):(1~2):(1~2):1。该条件下,产物的产率高。
优选地,S2中通过TLC监测反应进程,待反应完成后,以石油醚和乙酸乙酯为淋洗液进行柱层析得到式I所述的手性苄醇类衍生物。
优选地,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱,得到式VII所示的吲哚化合物产物。
本发明的附加方面和优点将在下面的描述中部分给出,部分将从下面的描述中变得明显,或通过本发明的实践了解到。
具体实施方式
下面详细描述本发明的实施例,下面描述的实施例是示例性的,旨在用于解释本发明,而不能理解为对本发明的限制。
若无特别说明,实施例所用试剂和原料均为市购得到。
实施例1
化合物I-1的制备
如反应式A所示,在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-碘苯甲酸甲酯II-1(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol,1.0equiv.),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-1目标产物55.9mg,产率96%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.99(d,J=7.9Hz,2H),7.91–7.69(m,4H),7.56–7.43(m,4H),7.39(d,J=8.5Hz,1H),6.02(s,1H),3.89(s,3H),2.66–2.43(m,1H)
13C NMR(100MHz,CDCl3)δ167.05,148.60,140.63,133.31,133.10,129.95,129.41,128.77,128.18,127.84,126.59,126.50,126.36,125.52,124.70,76.14
高分辨:计算值:[M-OH]+:275.1067,实测值:275.1065.
[α]D 25=-53.53(c=1.11 in CHCl3)
光学纯度分析:产物的对映体过量96%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,230nm,25℃,保留时间为t1=21.36分钟,t2=25.23分钟。
化合物I-2的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-甲氧基碘苯II-2(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-2目标产物54.7mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.90–7.83(m,2H),7.83–7.73(m,4H),7.52–7.42(m,4H),7.37(d,J=8.5Hz,1H),5.98(s,1H),2.91(s,1H),2.52(d,J=1.5Hz,3H)
13C NMR(100MHz,CDCl3)δ198.12,148.91,140.65,136.31,133.31,133.09,128.73,128.68,128.15,127.81,126.73,126.47,126.32,125.50,124.67,76.03,26.71
高分辨:计算值:[M-OH]+:259.1117,实测值:259.1114.
[α]D 25=-61.87(c=1.09 in CHCl3)
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,230nm,25℃,保留时间为t1=17.55分钟,t2=20.76分钟。
实施例3
化合物I-3的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-氰基碘苯II-3(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,以V石油醚/V乙酸乙酯=10:1-5:1柱层接得到式I-3目标产物51.1mg,产率98%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.82(m,4H),7.60(d,J=8.4Hz,2H),7.57–7.45(m,4H),7.36(d,J=8.6Hz,1H),6.01(d,J=3.3Hz,1H),2.57(d,J=3.4Hz,1H).
13C NMR(100MHz,CDCl3)δ148.74,140.15,133.30,133.22,132.42,129.04,128.16,127.88,127.25,126.69,126.58,125.73,124.47,118.93,111.34,75.89.高分辨:计算值:[M-OH]+:242.0964,实测值:242.0965.
[α]D 25=(c=1.00in CHCl3)
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,230nm,25℃,保留时间为t1=16.00分钟,t2=19.27分钟。
实施例4
化合物I-4的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-三氟甲基基碘苯II-4(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-4目标产物59.1mg,产率98%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.95–7.74(m,3H),7.65–7.43(m,7H),7.38(d,J=8.6,1H),6.02(s,1H),2.47(s,1H).
13C NMR(100MHz,CDCl3)δ147.45,140.52,133.33,133.17,130.01,129.69,128.88,128.19,127.87,126.94,126.59,126.45,125.63,125.59,125.56,125.52,124.60,122.89,75.99.
19F NMR(376MHz,CDCl3)δ-62.46.
高分辨:计算值:[M]+:302.0913,实测值:302.0914.
[α]D 25=64.47(c=1.19in CHCl3)
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=13.97分钟,t2=15.43分钟。
实施例5
化合物I-5的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-((二丙基氨基)磺酰基)碘苯II-5(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-5目标产物73mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.82(m,4H),7.77–7.64(m,2H),7.60–7.42(m,4H),7.38(dd,J=8.5,2.7Hz,1H),6.01(d,J=3.6Hz,1H),3.19(qd,J=7.3,3.0Hz,4H),2.78(d,J=3.4Hz,1H),1.10(td,J=7.0,6.1,3.2Hz,6H).
13C NMR(100MHz,CDCl3)δ148.16,140.43,139.29,133.29,133.13,128.82,128.16,127.84,127.24,127.19,126.56,126.43,125.60,124.62,75.81,42.22.
高分辨:计算值:[M+H]+:370.1471,实测值:370.1468.
[α]D 25=-73.30(c=1.60in CHCl3)
光学纯度分析:产物的对映体过量98%,手性OD-H柱(异丙醇:正己烷为30:70,v:v),1.0mL/min,254nm,25℃,保留时间为t1=15.67分钟,t2=21.78分钟。
实施例6
化合物I-6的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),对氟碘苯II-6(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-6目标产物37.6mg,产率75%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.89–7.69(m,4H),7.51–7.41(m,2H),7.36(m,3H),7.07–6.91(m,2H),5.95(d,J=3.1Hz,1H),2.44(d,J=3.5Hz,1H).
13C NMR(100MHz,CDCl3)δ163.55,161.11,141.05,139.52,139.48,133.34,133.03,128.59,128.56,128.48,128.18,127.82,126.44,126.23,125.13,124.72,115.58,115.37,75.83.
19F NMR(376MHz,CDCl3)δ-114.85.
高分辨:计算值:[M-OH]+:235.0918,实测值:235.0918.
[α]D 25=2.97(c=0.74in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,230nm,25℃,保留时间为t1=11.40分钟,t2=13.26分钟。
实施例7
化合物I-7的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),对氯碘苯II-7(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-7目标产物43.0mg,产率80%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.89–7.69(m,4H),7.54–7.41(m,2H),7.39–7.26(m,5H),5.93(s,1H),2.46(s,1H).
13C NMR(100MHz,CDCl3)δ142.14,140.81,133.49,133.32,133.07,128.76,128.68,128.17,128.15,127.83,126.48,126.30,125.28,124.68,75.83
高分辨:计算值:[M-OH]+:251.0622,实测值:251.0625
[α]D 25=13.50(c=0.86in CHCl3).
光学纯度分析:产物的对映体过量98%,手性OD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,220nm,25℃,保留时间为t1=18.18分钟,t2=20.58分钟。
实施例8
化合物I-8的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),对溴碘苯II-8(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-8目标产物57.6mg,产率92%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.80–7.63(m,4H),7.45–7.31(m,4H),7.28(dd,J=8.6,1.7Hz,1H),7.23–7.14(m,2H),5.83(s,1H),2.39(s,1H).
13C NMR(100MHz,CDCl3)δ142.66,140.75,133.32,133.08,131.71,128.69,128.49,128.18,127.83,126.48,126.31,125.31,124.67,121.64,75.87.
高分辨:计算值:[M-OH]+:295.0117,实测值:295.0116.
[α]D 25=-20.90(c=1.13in CHCl3)
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,230nm,25℃,保留时间为t1=12.95分钟,t2=14.36分钟。
实施例9
化合物I-9的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),对甲基碘苯II-9(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-9目标产物37.2mg,产率75%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.88(d,J=1.6Hz,1H),7.84–7.72(m,3H),7.50–7.36(m,3H),7.28(d,J=8.0Hz,2H),7.14(d,J=7.9Hz,2H),5.95(d,J=3.3Hz,1H),2.35(d,J=3.5Hz,1H),2.32(s,3H)
13C NMR(100MHz,CDCl3)δ141.39,140.90,137.54,133.37,132.95,129.36,128.39,128.19,127.78,126.83,126.27,126.02,124.97,124.89,76.32,21.26.
高分辨:计算值:[M-OH]+:231.1168,,实测值:231.1162.
[α]D 25=20.20(c=0.73in CHCl3)
光学纯度分析:产物的对映体过量98%,手性OD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,220nm,25℃,保留时间为t1=14.86分钟,t2=16.57分钟。
化合物I-10的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-10目标产物60.4mg,产率97%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.94(s,1H),7.88–7.78(m,3H),7.58(m,4H),7.52–7.41(m,7H),7.38–7.31(m,1H),6.06(s,1H),2.45(s,1H)
13C NMR(100MHz,CDCl3)δ142.79,141.19,140.88,140.73,133.41,133.06,128.90,128.55,128.22,127.83,127.44,127.28,127.23,126.37,126.15,125.18,124.89,76.29
高分辨:计算值:[M-OH]+:293.1325,实测值:293.1316.
[α]D 25=2.67(c=1.21in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,230nm,25℃,保留时间为t1=18.13分钟,t2=22.45分钟。
实施例11
化合物I-11的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),对甲氧基碘苯II-11(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-11目标产物40.8mg,产率77%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.90(d,J=1.6Hz,1H),7.87–7.76(m,3H),7.54–7.44(m,2H),7.41(dd,J=8.5,1.7Hz,1H),7.36–7.28(m,2H),6.93–6.82(m,2H),5.96(s,1H),3.79(s,3H),2.41(d,J=2.4Hz,1H).
13C NMR(100MHz,CDCl3)δ159.22,141.46,136.11,133.37,132.93,128.35,128.22,128.19,127.78,126.27,126.01,124.90,124.87,114.03,76.01,55.40
高分辨:计算值:[M-OH]+:247.1117,实测值:247.1114.
[α]D 25=22.40(c=0.85in CHCl3)
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=15.92分钟,t2=18.92分钟。
化合物I-12的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),对三氟甲氧基碘苯II-12(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-12目标产物46.1mg,产率72%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.93–7.77(m,4H),7.57–7.36(m,5H),7.19(d,J=8.3Hz,2H),6.01(s,1H),2.43(s,1H).
13C NMR(100MHz,CDCl3)δ142.34,140.78,133.35,133.12,128.76,128.20,127.86,126.53,126.36,125.32,124.65,121.12,75.82.
19F NMR(376MHz,CDCl3)δ-57.80,-57.81
高分辨:计算值:[M-OH]+:301.0835,实测值:301.0834.
[α]D 25=-19.40(c=0.92in CHCl3)
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=11.06分钟,t2=12.73分钟。
实施例13
化合物I-13的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),(4-碘苯基乙炔)三甲基硅烷II-13(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-13目标产物65.2mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.88–7.73(m,4H),7.57–7.41(m,4H),7.37(m,3H),5.97(d,J=3.1Hz,1H),2.39(d,J=3.3Hz,1H),0.25(s,9H)
13C NMR(100MHz,CDCl3)δ143.96,140.83,133.33,133.06,132.26,128.62,128.19,127.82,126.63,126.43,126.26,125.40,124.84,122.50,104.99,94.49,76.16,0.11
高分辨:计算值:[M-OH]+:313.1407,实测值:313.1406.
[α]D 25=30.37(c=1.32in CHCl3
光学纯度分析:产物的对映体过量98%,手性AD-H柱(异丙醇:正己烷为5:95,v:v),1.0mL/min,254nm,25℃,保留时间为t1=24.68分钟,t2=22.09分钟。
实施例14
化合物I-14的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),(4-碘苯基乙炔)三甲基硅烷II-13(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-13目标产物65.2mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.88–7.73(m,4H),7.57–7.41(m,4H),7.37(m,3H),5.97(d,J=3.1Hz,1H),2.39(d,J=3.3Hz,1H),0.25(s,9H)
13C NMR(100MHz,CDCl3)δ143.96,140.83,133.33,133.06,132.26,128.62,128.19,127.82,126.63,126.43,126.26,125.40,124.84,122.50,104.99,94.49,76.16,0.11
高分辨:计算值:[M-OH]+:313.1407,实测值:313.1406.
[α]D 25=30.37(c=1.32in CHCl3
光学纯度分析:产物的对映体过量98%,手性AD-H柱(异丙醇:正己烷为5:95,v:v),1.0mL/min,254nm,25℃,保留时间为t1=24.68分钟,t2=22.09分钟。
实施例15
化合物I-15的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),邻甲氧基碘苯II-13(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-13目标产物35.2mg,产率67%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.87(s,1H),7.84–7.73(m,3H),7.54–7.37(m,3H),7.30–7.20(m,2H),7.02–6.83(m,2H),6.22(d,J=4.5Hz,1H),3.81(s,3H),3.16(d,J=5.0Hz,1H)
13C NMR(100MHz,CDCl3)δ156.93,140.72,133.37,132.86,131.89,128.99,128.21,128.19,127.94,127.73,126.06,125.82,125.18,125.08,120.94,110.86,72.39,55.56
高分辨:计算值:[M-OH]+:247.1117,实测值:247.1115.
[α]D 25=52.00(c=0.71in CHCl3)
光学纯度分析:产物的对映体过量98%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=14.96分钟,t2=22.02分钟。
实施例16
化合物I-16的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),2-甲氧基碘苯II-16(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-16目标产物51.3mg,产率97%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.89(s,1H),7.87–7.77(m,3H),7.53–7.40(m,3H),7.27(d,J=7.8Hz,1H),7.00(m,2H),6.87–6.78(m,1H),5.94(s,1H),3.78(s,3H),2.58(s,1H).
13C NMR(100MHz,CDCl3)159.82,145.38,141.09,133.32,132.97,129.67,128.43,128.19,127.77,126.27,126.07,125.12,124.83,119.15,113.14,112.31,76.32,55.32高
分辨:计算值:[M-OH]+:247.1117,实测值:247.1115.
[α]D 25=-9.97(c=1.02in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=18.38分钟,t2=21.12分钟。
实施例17
化合物I-17的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),3-甲基碘苯II-17(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-17目标产物37.8mg,产率76%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.91(d,J=1.7Hz,1H),7.89–7.75(m,3H),7.54–7.39(m,3H),7.28–7.19(m,3H),7.14–7.07(m,1H),5.97(s,1H),2.38(s,1H),2.34(s,3H).
13C NMR(100MHz,CDCl3)δ143.73,141.31,138.38,133.38,132.98,128.59,128.58,128.41,128.21,127.79,127.50,126.28,126.05,125.05,124.92,123.93,76.52,21.61
高分辨:计算值:[M-OH]+:231.1168,实测值:231.1166.
[α]D 25=9.37(c=0.76in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=10.56分钟,t2=12.37分钟。
实施例18
化合物I-18的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),3,4-二氟碘苯II-18(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-18目标产物47.6mg,产率88%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.82(m,4H),7.57–7.42(m,2H),7.37(dd,J=8.5,1.7Hz,1H),7.25(td,J=8.5,1.8Hz,1H),7.17–7.01(m,2H),5.93(s,1H),2.40(s,1H)
13C NMR(100MHz,CDCl3)δ167.58,151.64,151.11,149.30,148.65,140.53,133.33,133.18,128.86,128.19,127.88,126.60,126.45,125.40,124.53,122.73,122.70,117.39,117.22,115.87,115.70,75.46.
19F NMR(376MHz,CDCl3)δ-137.23,-137.29,-139.50,-139.55
高分辨:计算值:[M-OH]+:253.0823,实测值:253.0822.
[α]D 25=-36.20(c=0.96in CHCl3).
光学纯度分析:产物的对映体过量95%,手性AD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=13.42分钟,t2=16.22分钟。
实施例19
化合物I-19的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),3-碘咔唑II-19(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-19目标产物51.7mg,产率66%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ8.21(s,1H),8.11(d,J=7.7Hz,1H),7.99(s,1H),7.89–7.76(m,3H),7.64–7.33(m,12H),7.31–7.22(m,1H),6.22(s,1H),2.43(s,1H)
13C NMR(100MHz,CDCl3)δ141.79,141.38,140.59,137.71,135.72,133.43,132.94,130.01,128.36,128.25,127.80,127.63,127.17,126.27,126.20,126.01,125.29,125.12,124.96,123.52,123.37,120.56,120.14,118.84,110.06,109.98,76.84
高分辨:计算值:[M-OH]+:382.1590,实测值:382.1590.
[α]D 25=31.10(c=1.02in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,254nm,25℃,保留时间为t1=55.82分钟,t2=61.15分钟。
实施例20
化合物I-20的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),3-碘咔唑II-20(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-19目标产物55.4mg,产率97%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ1H NMR(400MHz,Chloroform-d)δ8.75(dd,J=4.3,1.7Hz,1H),8.08(dd,J=8.4,1.6Hz,1H),7.97(d,J=8.8Hz,1H),7.94–7.86(m,2H),7.79(m,3H),7.65(dd,J=8.8,2.0Hz,1H),7.53–7.41(m,3H),7.31(dd,J=8.3,4.2Hz,1H),6.15(s,1H),3.91(s,1H)
13C NMR(100MHz,CDCl3)δ150.30,147.67,142.30,142.23,141.02,136.48,133.35,133.06,129.53,128.85,128.63,128.18,128.16,127.81,126.40,126.23,125.53,124.94,121.38,76.0
高分辨:计算值:[M+H]+:286.1226,实测值:286.1226.
[α]D 25=-27.17(c=1.11in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为30:70,v:v),1.0mL/min,220nm,25℃,保留时间为t1=16.44分钟,t2=19.09分钟。
实施例21
化合物I-21的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),5-碘-1-(4-甲苯磺酰基)-1H-吲哚II-21(0.3mmol,1.5equiv)和2-萘醛III-1(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-21目标产物72.8mg,产率85%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ8.21(s,1H),8.11(d,J=7.7Hz,1H),7.99(s,1H),7.89–7.76(m,3H),7.64–7.33(m,12H),7.31–7.22(m,1H),6.22(s,1H),2.43(s,1H)
13C NMR(100MHz,CDCl3)δ145.10,141.32,139.06,135.34,134.36,133.34,132.97,130.99,130.03,128.43,128.19,127.80,126.94,126.37,126.14,125.00,124.86,123.81,119.67,113.73,109.22,76.48,21.69
高分辨:计算值:[M-OH]+:410.1209,实测值:410.1209.
[α]D 25=11.85(c=1.45in CHCl3).
光学纯度分析:产物的对映体过量99%,手性OD-H柱(异丙醇:正己烷为30:70,v:v),1.0mL/min,254nm,25℃,保留时间为t1=23.53分钟,t2=26.82分钟。
实施例22
化合物I-22的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-氟苯甲醛III-2(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-22目标产物54.6mg,产率98%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.47(m,4H),7.38–7.19(m,7H),6.93(m,2H),5.73(s,1H),2.40(s,1H)
13C NMR(100MHz,CDCl3)δ163.51,161.07,142.74,140.74,139.57,128.91,128.39,128.31,127.50,127.43,127.19,127.01,115.57,115.36,75.46
19F NMR(376MHz,CDCl3)δ-114.90.
高分辨:计算值:[M-OH]+:261.1074,实测值:261.1076.
[α]D 25=1.15(c=1.09in CHCl3).
光学纯度分析:产物的对映体过量96%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=11.64分钟,t2=13.56分钟。
实施例23
化合物I-23的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-氯苯甲醛III-3(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-233目标产物56.5mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.60–7.53(m,4H),7.47–7.39(m,4H),7.34(m,5H),5.87(d,J=3.3Hz,1H),2.26(d,J=3.4Hz,1H)
13C NMR(100MHz,CDCl3)δ142.55,142.27,140.94,140.75,133.49,128.94,128.81,128.01,127.54,127.23,127.09,75.54
高分辨:计算值:[M-OH]+:277.0779,实测值:277.0779.
[α]D 25=14.20(c=1.13in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=13.29分钟,t2=14.68分钟。
实施例24
化合物I-24的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-溴苯甲醛III-4(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-24目标产物61.1mg,产率90%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.61–7.51(m,4H),7.50–7.30(m,7H),7.30–7.25(m,2H),5.80(d,J=3.1Hz,1H),2.37(d,J=3.3Hz,1H).
13C NMR(100MHz,CDCl3)δ142.76,142.44,140.91,140.71,131.73,128.92,128.34,127.54,127.51,127.20,127.09,121.62,75.54
高分辨:计算值:[M-OH]+:321.0273,实测值:321.0271.
[α]D 25=15.33(c=1.23in CHCl3).
光学纯度分析:产物的对映体过量96%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=13.71分钟,t2=16.26分钟。
实施例25
化合物I-25的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-氰基苯甲醛III-5(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-22目标产物48.7mg,产率85%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.65(d,J=8.4Hz,2H),7.61–7.52(m,6H),7.48–7.38(m,4H),7.38–7.32(m,1H),5.92(s,1H),2.49–2.29(m,1H)
13C NMR(100MHz,CDCl3)δ148.83,141.86,141.44,140.55,132.48,128.98,127.77,127.69,127.27,127.22,127.16,118.95,111.42,75.59.
高分辨:计算值:[M-OH]+:268.1121,实测值:268.1122
[α]D 25=47.00(c=0.98in CHCl3).
光学纯度分析:产物的对映体过量95%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,254nm,25℃,保留时间为t1=15.97分钟,t2=61.1519.40分钟。
实施例26
化合物I-26的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-三氟甲基苯甲醛III-6(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-26目标产物57.5mg,产率88%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.64–7.50(m,8H),7.42(m,4H),7.37–7.31(m,1H),5.90(s,1H),2.43(s,1H))
13C NMR(100MHz,CDCl3)δ147.58,142.23,141.17,140.66,130.01,129.69,128.95,127.63,127.61,127.21,126.81,125.65,125.62,125.58,125.54,122.91,75.65.
19F NMR(376MHz,CDCl3)δ-62.43.
高分辨:计算值:[M-OH]+:311.1042,实测值:311.1044.
[α]D 25=18.80(c=1.15in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,254nm,25℃,保留时间为t1=11.84分钟,t2=14.88分钟。
实施例27
化合物I-27的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-叔丁基苯甲醛III-7(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-27目标产物47.9mg,产率76%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.61–7.51(m,4H),7.48–7.27(m,9H),5.83(s,1H),2.33(s,1H),1.30(s,9H)
13C NMR(100MHz,CDCl3)3C NMR(101MHz,CDCl3)δ150.71,143.06,140.97,140.47,128.87,127.37,127.31,127.20,127.03,126.44,125.61,75.98,34.65,31.47
高分辨:计算值:[M-OH]+:299.1794,实测值:299.1794.
[α]D 25=-14.60(c=0.96in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=9.36分钟,t2=0.69分钟。
实施例28
化合物I-28的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-甲酰基苯硼酸频哪醇酯III-8(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-28目标产物55.3mg,产率72%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.80(d,J=7.6Hz,2H),7.53(m,4H),7.40(m,6H),7.35–7.27(m,1H),5.83(s,1H),2.59(s,1H),1.31(s,12H).
13C NMR(100MHz,CDCl3)δ146.92,142.82,140.86,140.58,135.15,128.84,127.37,127.35,127.18,127.15,125.87,83.91,76.07,24.95
1B NMR(128MHz,CDCl3)δ30.39.
高分辨:计算值:[M-OH]+:368.2020,实测值:368.2020.
[α]D 25=3.8(c=1.10in CHCl3)..
光学纯度分析:产物的对映体过量98%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=20.48分钟,t2=22.18分钟。
实施例29
化合物I-29的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-甲氧基苯甲醛III-9(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-29目标产物55.1mg,产率95%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.60(m,4H),7.51–7.41(m,4H),7.36(m,3H),6.96–6.85(m,2H),5.84(s,1H),3.81(s,3H),2.50(s,1H)
13C NMR(100MHz,CDCl3)δ159.14,143.18,140.90,140.36,136.22,128.85,128.01,127.36,127.26,127.16,126.93,114.00,75.64,55.3
高分辨:计算值:[M-OH]+:273.1274,实测值:273.1275.
[α]D 25=24.70(c=1.10in CHCl3).
光学纯度分析:产物的对映体过量95%,手性OD-H柱(异丙醇:正己烷为5:955,v:v),1.0mL/min,254nm,25℃,保留时间为t1=55.82分钟,t2=61.15分钟。
实施例30
化合物I-30的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-三氟甲氧基苯甲醛III-10(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-30目标产物60.2mg,产率87%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.48(d,J=8.1Hz,5H),7.34(m,7H),7.25(m,1H),7.10(d,J=8.3Hz,2H),5.77(s,1H),2.35(s,1H).
13C NMR(100MHz,CDCl3)δ148.64,148.62,142.45,142.41,140.96,140.69,128.93,128.04,127.56,127.53,127.20,127.10,121.12,75.44
高分辨:计算值:[M-OH]+:327.0991,实测值:327.0993.
[α]D 25=17.30(c=1.20in CHCl3).
光学纯度分析:产物的对映体过量96%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,254nm,25℃,保留时间为t1=8.42分钟,t2=10.20分钟。
实施例31
化合物I-31的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-硫甲基苯甲醛III-11(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-31目标产物58.7mg,产率96%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.54–7.45(m,4H),7.35(m,4H),7.30–7.22(m,3H),7.20–7.13(m,2H),5.76(s,1H),2.38(s,3H).
13C NMR(100MHz,CDCl3)δ142.82,140.84,140.76,140.65,137.91,128.89,127.44,127.40,127.20,127.03,126.78,75.75,15.96
高分辨:计算值:[M-OH]+:289.1045,实测值:289.1044.
[α]D 25=-3.40(c=1.16in CHCl3).
光学纯度分析:产物的对映体过量99%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,254nm,25℃,保留时间为t1=13.32分钟,t2=14.40分钟。
实施例32
化合物I-32的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2-氧苄基苯甲醛III-12(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-32目标产物65.4mg,产率89%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.65–7.48(m,4H),7.41(m,5H),7.36–7.14(m,6H),7.04–6.91(m,2H),6.09(d,J=5.7Hz,1H),5.03(d,J=2.7Hz,2H),3.02(d,J=5.9Hz,1H).
13C NMR(100MHz,CDCl3)δ155.85,142.68,141.10,140.15,136.59,132.27,128.89,128.87,128.67,128.17,128.05,127.59,127.30,127.19,127.14,127.03,121.22,112.10,72.52,70.26
高分辨:计算值:[M-OH]+:349.1587,实测值:349.1586.
[α]D 25=c=1.28in CHCl3)
光学纯度分析:产物的对映体过量93%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,254nm,25℃,保留时间为t1=18.26分钟,t2=16.97分钟。
实施例33
化合物I-33的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和邻溴甲醛III-13(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-33目标产物40.6mg,产率60%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.62(dd,J=7.9,1.6Hz,1H),7.60–7.50(m,5H),7.43(m,4H),7.38–7.29(m,2H),7.15(d,J=7.7,1H),6.22(d,J=3.4Hz,1H),2.52(d,J=3.6Hz,1H)
13C NMR(100MHz,CDCl3)δ142.56,141.24,140.81,140.75,132.98,129.30,128.88,128.55,127.92,127.59,127.46,127.34,127.20,122.88,74.66
高分辨:计算值:[M-OH]+:321.0273,实测值:321.0272.
[α]D 25=-54.50(c=0.81in CHCl3).
光学纯度分析:产物的对映体过量89%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=10.40分钟,t2=16.80分钟。
实施例34
化合物I-34的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2-二苯基膦氧苯甲醛III-14(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-34目标产物85.1mg,产率92%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.72–7.58(m,3H),7.53(m,6H),7.42(m,6H),7.33(m,1H),7.27–7.18(m,6H),7.07(dd,J=14.3,7.6Hz,1H),6.19(s,1H)
13C NMR(100MHz,CDCl3)δ150.41,150.34,141.05,140.85,139.74,134.22,134.09,133.27,132.75,132.73,132.53,132.50,132.28,132.23,132.18,132.16,132.06,131.96,131.84,131.40,130.77,130.67,130.41,128.97,128.85,128.81,128.73,128.61,127.22,127.15,127.13,127.02,126.65,73.49,73.44.
31P NMR(162MHz,CDCl3)δ35.40
高分辨:计算值:[M+H]+:461.1665,实测值:461.1664.
[α]D 25=-269.80(c=1.66in CHCl3).
光学纯度分析:产物的对映体过量89%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=40.05分钟,t2=47.06分钟。
实施例35
化合物I-35的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2,3,4-三甲氧基苯甲醛III-15(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-35目标产物61.3mg,产率87%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.65–7.53(m,4H),7.50–7.38(m,4H),7.39–7.29(m,1H),7.01(d,J=8.6Hz,1H),6.67(d,J=8.6Hz,1H),5.98(s,1H),3.86(s,6H),3.70(s,3H),2.93(s,1H).
13C NMR(100MHz,CDCl3)δ153.63,151.46,143.24,142.33,140.98,140.14,129.95,128.88,127.36,127.17,127.08,126.90,122.45,107.11,72.44,60.97,60.86,56.13
高分辨:计算值:[M-OH]+:333.1485,实测值:333.1487.
[α]D 25=-42.50(c=1.23in CHCl3.
光学纯度分析:产物的对映体过量91%,手性OD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,254nm,25℃,保留时间为t1=13.32分钟,t2=14.40分钟。
实施例36
化合物I-36的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2,4,6-三氯苯甲醛III-6(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-36目标产物61.5mg,产率84%。
1H NMR(400MHz,CDCl3)δ7.56(m,4H),7.46–7.29(m,7H),6.62(d,J=10.2Hz,1H),3.35(d,J=10.8Hz,1H)..
13C NMR(100MHz,CDCl3)δ140.70,140.44,140.04,136.56,135.83,134.58,129.40,128.90,127.48,127.22,127.17,125.93,72.02
高分辨:计算值:[M-OH]+:344.9999,实测值:344.9994.
[α]D 25=-131.40(c=1.24in CHCl3).
光学纯度分析:产物的对映体过量99%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=6.17分钟,t2=8.00分钟。
实施例37
化合物I-37的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和4-硫甲基苯甲醛III-17(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-36目标产物47.0mg,产率69%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ8.07(d,J=8.6Hz,1H),7.88–7.76(m,2H),7.58–7.24(m,12H),6.78(d,J=8.8Hz,1H),4.16(d,J=8.9Hz,1H),3.83(s,3H).
13C NMR(100MHz,CDCl3)δ154.96,143.54,141.02,139.61,132.20,130.12,129.60,128.80,128.72,127.20,127.13,127.09,127.05,126.93,126.39,124.10,123.91,123.68,113.74,69.75,56.67
高分辨:计算值:[M-OH]+:323.1430,实测值:323.1433..
[α]D 25=-168.30(c=0.94in CHCl3)
光学纯度分析:产物的对映体过量98%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,254nm,25℃,保留时间为t1=14.24分钟,t2=18.97分钟。
实施例38
化合物I-38的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2,3-二氢苯并呋喃-5-甲醛III-18(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-31目标产物47.8mg,产率79%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.57(m,4H),7.50–7.38(m,4H),7.34(m,1H),7.30–7.20(m,2H),7.15(d,J=8.2Hz,1H),6.75(d,J=8.2Hz,1H),5.84(s,1H),4.56(d,J=8.7Hz,2H),3.18(t,J=8.7Hz,2H),2.17(s,1H).
13C NMR(100MHz,CDCl3)δ159.82,143.31,140.94,140.38,136.31,128.88,127.59,127.39,127.31,127.20,126.90,126.84,123.54,109.19,75.99,71.52,29.81.
高分辨:计算值:[M-OH]+:285.1274,实测值:285.1273.
[α]D 25=-8.80(c=0.96in CHCl3).
光学纯度分析:产物的对映体过量96%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,254nm,25℃,保留时间为t1=15.74分钟,t2=18.77分钟。
实施例39
化合物I-39的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和1,3-二苯甲醛III-19(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-39目标产物35.8mg,产率81%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.66–7.56(m,9H),7.50(m,4H),7.43(m,4H),7.38–7.24(m,5H),5.87(s,2H).
13C NMR(100MHz,CDCl3)δ146.30,145.66,141.64,140.39,129.66,128.84,128.02,127.88,127.86,127.63,127.46,125.94,125.48,75.91
高分辨:计算值:[M-OH]+:425.1900,实测值:425.1896.
光学纯度分析:产物的对映体过量99%,dr>19:1,手性AD-H柱(异丙醇:正己烷为30:770,v:v),1.0mL/min,254nm,25℃,保留时间为t1=11.40分钟,t2=13.26分钟。
实施例40
化合物I-40的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2-呋喃甲醛III-20(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-40目标产物35.8mg,产率72%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.63–7.56(m,4H),7.50(d,J=7.9Hz,2H),7.47–7.39(m,3H),7.35(m,1H),6.33(m,1H),6.18(d,J=3.2Hz,1H),5.87(s,1H),2.46(s,1H)
13C NMR(100MHz,CDCl3)δ155.93,142.77,141.12,140.84,139.89,128.92,127.51,127.37,127.25,127.17,110.41,107.66,70.05
高分辨:计算值:[M-OH]+:233.0961,实测值:233.0963.
[α]D 25=-5.85(c=0.72in CHCl3).
光学纯度分析:产物的对映体过量95%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=10.67分钟,t2=11.59分钟。
实施例41
化合物I-41的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2-醛基吡咯-1-甲酸叔丁酯III-21(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-41目标产物55.3mg,产率79%。
产物表征数据:
1H NMR(400MHz,CDCl3)7.60(m,4H),7.45(m,4H),7.39–7.29(m,1H),7.25–7.15(m,1H),6.06(m,2H),5.86–5.74(d,J=5.6Hz,1H),4.60(d,J=5.7Hz,1H),1.57(s,9H)
13C NMR(100MHz,CDCl3)δ182.49,150.41,141.08,140.70,140.27,137.88,128.86,127.47,127.29,127.18,126.86,122.53,121.34,114.88,111.84,110.42,84.95,68.90,28.04
高分辨:计算值:[M-OH]+:332.1645,实测值:332.1644.
[α]D 25=-17.90(c=1.10in CHCl3).
光学纯度分析:产物的对映体过量89%,手性OD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,254nm,25℃,保留时间为t1=6.33分钟,t2=6.85分钟。
实施例42
化合物I-42的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和1-[(4-甲基苯基)磺酰基]-1H-吲哚-3-甲醛III-22(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-42目标产物81.6mg,产率90%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.97(d,J=8.3Hz,1H),7.79–7.72(m,2H),7.62–7.54(m,4H),7.53–7.40(m,6H),7.38–7.08(m,6H),6.06(d,J=3.4Hz,1H),2.34(s,3H),2.29(d,J=3.8Hz,1H)
13C NMR(100MHz,CDCl3)δ145.13,141.15,141.08,140.72,135.77,135.28,130.03,129.01,128.92,127.55,127.51,127.28,127.22,126.99,125.55,125.01,124.03,123.39,120.72,113.85,70.24,21.69
高分辨:计算值:[M-OH]+:289.1045,实测值:289.1044.
[α]D 25=3.00(c=1.62in CHCl3).
光学纯度分析:产物的对映体过量90%,手性OD-H柱(异丙醇:正己烷为30:70,v:v),1.0mL/min,254nm,25℃,保留时间为t1=14.15分钟,t2=23.53分钟。
实施例43
化合物I-43的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和3-噻吩甲醛III-23(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-43目标产物52.8mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)7.55(m,4H),7.40(m,4H),7.36–7.28(m,1H),7.24(dd,J=5.1,3.0Hz,1H),7.16(d,J=2.9Hz,1H),6.99(dd,J=4.9,1.3Hz,1H),5.84(s,1H),2.59(s,1H)
13C NMR(100MHz,CDCl3)δ145.29,142.44,140.80,140.70,128.88,127.43,127.33,127.17,127.02,126.50,126.36,121.80,72.64
高分辨:计算值:[M-OH]+:249.0732,实测值:249.0733.
[α]D 25=10.20(c=1.06in CHCl3).
光学纯度分析:产物的对映体过量93%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=12.61分钟,t2=15.05分钟。
实施例44
化合物I-44的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和2-苯并噻吩甲醛III-24(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-44目标产物62.6mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.77(d,J=7.6Hz,1H),7.68(d,J=7.6Hz,1H),7.64–7.49(m,6H),7.43(t,J=7.5Hz,2H),7.31(m,3H),7.15(s,1H),6.13(s,1H),2.56(s,1H).
13C NMR(100MHz,CDCl3)δ148.65,141.62,141.28,140.74,140.01,139.53,128.93,127.56,127.51,127.25,127.02,124.46,124.43,123.77,122.59,121.43,72.92.
高分辨:计算值:[M-OH]+:299.0889,实测值:299.0888.
[α]D 25=-4.15(c=1.42in CHCl3).
光学纯度分析:产物的对映体过量99%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=14.15分钟,t2=23.53分钟。
实施例45
化合物I-45的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和(E)-2-甲基-3-苯基丙烯醛III-25(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-45目标产物54.8mg,产率91%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.65–7.54(m,4H),7.53–7.38(m,4H),7.38–7.27(m,5H),7.23(m,1H),6.80(s,1H),5.32(d,J=2.5Hz,1H),2.12(d,J=2.9Hz,1H),1.78(s,3H)
13C NMR(100MHz,CDCl3)δ141.20,140.93,140.63,139.62,137.57,129.19,128.90,128.29,127.42,127.30,127.22,127.17,127.05,126.72,126.22,79.43,14.23
高分辨:计算值:[M-OH]+:283.1481,实测值:283.1483.
[α]D 25=-49.50(c=1.09in CHCl3).
光学纯度分析:产物的对映体过量98%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=14.00分钟,t2=14.00分钟。
实施例46
化合物I-46的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和α-溴代肉桂醛III-26(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-46目标产物66.5mg,产率91%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.74–7.48(m,8H),7.48–7.26(m,7H),5.50(d,J=5.4Hz,1H),2.66–2.55(m,1H).
13C NMR(100MHz,CDCl3)δ141.28,140.74,139.51,135.02,129.32,128.93,128.90,128.57,128.48,128.35,127.56,127.42,127.29,127.26,79.09.
高分辨:计算值:[M-OH]+:347.0430,实测值:347.0434.
[α]D 25=-18.60(c=1.25in CHCl3).
光学纯度分析:产物的对映体过量97%,手性OD-H柱(异丙醇:正己烷为15:85,v:v),1.0mL/min,254nm,25℃,保留时间为t1=19.47分钟,t2=21.50分钟。
实施例47
化合物I-47的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和顺-2-甲基-2-丁醛III-27(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-47目标产物36.7mg,产率77%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.58(m,4H),7.43(m,4H),7.33(m,1H),5.75(q,J=6.8Hz,1H),5.18(s,1H),1.89(s,1H),1.68(d,J=6.7Hz,3H),1.53(s,3H)
13C NMR(100MHz,CDCl3)δ141.67,141.06,140.26,137.67,128.88,127.33,127.21,127.10,126.76,121.61,79.32,13.37,11.86
高分辨:计算值:[M-OH]+:221.1325,实测值:221.1322
[α]D 25=-45.50(c=0.74in CHCl3).
光学纯度分析:产物的对映体过量90%,手性OD-H柱(异丙醇:正己烷为110:90,v:v),1.0mL/min,254nm,25℃,保留时间为t1=8.93分钟,t2=12.59分钟。
实施例48
化合物I-48的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和桃金娘烯醛III-28(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-48目标产物51.1mg,产率84%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.58(m,4H),7.46–7.38(m,4H),7.33(m,1H),5.64(s,1H),5.19(s,1H),2.44–2.21(m,3H),2.18–2.02(m,2H),1.21(s,3H),1.12(d,J=8.6Hz,1H),0.77(s,3H)
13C NMR(100MHz,CDCl3)δ149.49,141.04,140.85,140.11,128.87,127.31,127.18,126.96,126.90,119.40,76.55,42.35,40.78,37.84,32.11,31.42,26.11,21.43.
高分辨:计算值:[M-OH]+:287.1794,实测值:287.1795.
[α]D 25=-33.10(c=1.02in CHCl3).
光学纯度分析:dr>19:1.
实施例49
化合物I-49的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和(+)-紫苏醛III-29(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-49目标产物42.3mg,产率70%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.58(m,4H),7.51–7.39(m,4H),7.34(m,1H),5.93(d,J=4.6Hz,1H),5.15(s,1H),4.71(d,J=4.4Hz,2H),2.35–2.11(m,2H),1.98(m,3H),1.86–1.74(m,1H),1.73(s,3H),1.43(qd,J=11.3,5.9Hz,1H)
13C NMR(100MHz,CDCl3)δ149.90,141.68,140.99,140.40,139.21,128.89,127.37,127.21,127.18,126.89,122.99,108.81,77.95,41.28,30.62,27.55,24.88,20.92.
高分辨:计算值:[M-OH]+:287.1794,实测值:287.1794..
[α]D 25=-54.50(c=0.86in CHCl3)
光学纯度分析:dr>19:1.。
实施例50
化合物I-50的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和苯丙醛III-30(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-42目标产物39.2mg,产率68%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.59(m,4H),7.48–7.39(m,4H),7.36(d,J=7.3Hz,1H),7.33–7.10(m,5H),4.81–4.68(m,1H),2.91–2.64(m,2H),2.28–2.00(m,2H),1.90(s,1H)
13C NMR(100MHz,CDCl3)δ143.69,141.86,140.92,140.72,128.92,128.60,128.55,127.44,127.41,127.22,126.52,126.03,73.76,40.56,32.21
高分辨:计算值:[M-OH]+:271.1481,实测值:271.1482
[α]D 25=3.93(c=0.78in CHCl3).
光学纯度分析:产物的对映体过量91%,手性OD-H柱(异丙醇:正己烷为15:75,v:v),1.0mL/min,254nm,25℃,保留时间为t1=40.78分钟,t2=43.14分钟。
实施例51
化合物I-51的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和N-(2-乙醛基)邻苯二甲酰亚胺III-31(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-51目标产物35.4mg,产率52%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.86(m,2H),7.73(dd,J=5.5,3.1Hz,2H),7.64–7.49(m,6H),7.44(m,2H),7.35(m,1H),5.12(d,J=8.5Hz,1H),4.14–3.91(m,2H),2.95(d,J=8.4Hz,1H)
13C NMR(100MHz,CDCl3)δ168.95,141.12,140.76,140.16,134.33,131.99,128.92,127.52,127.47,127.23,126.48,123.65,72.62,45.86
高分辨:计算值:[M-OH]+:326.1176,实测值:326.1177.
[α]D 25=12.30(c=0.71in CHCl3).
光学纯度分析:产物的对映体过量81%,手性OD-H柱(异丙醇:正己烷为20:80,v:v),1.0mL/min,254nm,25℃,保留时间为t1=23.63分钟,t2=27.15分钟。
实施例52
化合物I-52的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和3-丁烯醛III-32(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-52目标产物27.8mg,产率58%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.59(m,4H),7.48–7.39(m,4H),7.35(m,1H),5.86(ddt,J=17.1,10.4,6.7Hz,1H),5.15–4.93(m,2H),4.75(dd,J=7.7,5.6Hz,1H),2.50–2.33(m,1H),2.19(m,2H),2.02–1.78(m,2H)
13C NMR(100MHz,CDCl3)δ143.74,140.94,140.65,138.29,128.91,127.42,127.37,127.21,126.48,115.20,73.92,38.16,30.24.
高分辨:计算值:[M-OH]+:221.1325,实测值:221.1321.
[α]D 25=14.30(c=0.57in CHCl3).
光学纯度分析:产物的对映体过量90%,手性AD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,254nm,25℃,保留时间为t1=8.99分钟,t2=10.35分钟。
实施例53
化合物I-53的制备
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在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和环己基甲醛III-33(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-53目标产物52.7mg,产率99%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.63–7.53(m,4H),7.43(dd,J=8.4,6.9Hz,2H),7.39–7.31(m,3H),4.42(d,J=7.2Hz,1H),2.10–1.96(m,1H),1.87(s,1H),1.78(dt,J=12.3,3.5Hz,1H),1.66(ddt,J=11.7,7.8,3.7Hz,2H),1.44(d,J=12.5Hz,1H),1.35–0.81(m,6H)
13C NMR(100MHz,CDCl3)δ142.80,141.02,140.45,128.89,127.36,127.21,127.19,127.06,79.28,45.11,29.48,28.97,26.57,26.26,26.17
高分辨:计算值:[M-OH]+:249.1638,实测值:249.1638.
[α]D 25=27.70(c=1.05in CHCl3).
光学纯度分析:产物的对映体过量95%,手性OD-H柱(异丙醇:正己烷为5:95,v:v),1.0mL/min,254nm,25℃,保留时间为t1=21.20分钟,t2=24.40分钟。
实施例54
化合物I-54的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和环丁基甲醛III-34(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-54目标产物35.2mg,产率74%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.57(m,4H),7.51–7.29(m,5H),4.63(d,J=8.0Hz,1H),2.67(q,J=7.8Hz,1H),2.06(m,2H),1.84(d,J=7.3Hz,5H).
13C NMR(100MHz,CDCl3)δ142.24,141.00,140.56,128.89,127.37,127.22,127.20,126.76,78.33,42.53,24.99,24.56,17.9
高分辨:计算值:[M-OH]+:221.1325,实测值:221.1326.
[α]D 25=14.50(c=0.71in CHCl3).
光学纯度分析:产物的对映体过量90%,手性AD-H柱(异丙醇:正己烷为10:90,v:v),1.0mL/min,254nm,25℃,保留时间为t1=10.31分钟,t2=10.93分钟。
实施例55
化合物I-55的制备
在室温下,碘化钴(0.02mmol,10mol%)与配体IV(0.024mmol,12mol%)溶于2mL毫升二氯甲烷中,在氩气保护下搅拌2小时。随后加入2,4,5,6-四(9-咔唑基)-间苯二腈(0.004mmol,2mol%.),N,N-二异丙基乙胺(0.4mmol,2.0equiv.),二氢吡啶(0.28mmol,1.4equiv.),4-苯基碘苯II-10(0.3mmol,1.5equiv)和特戊醛III-35(0.2mmol),反应混合物在5W蓝灯照射下反应直到TLC检测反应完全,柱层析(采用硅胶柱,采用体积比从10:1到5:1的石油醚-乙酸乙酯作为洗脱剂进行梯度洗脱)得到式I-55目标产物25.4mg,产率53%。
产物表征数据:
1H NMR(400MHz,CDCl3)δ7.60(dd,J=7.7,1.6Hz,2H),7.58–7.52(m,2H),7.44(m,2H),7.41–7.32(m,3H),4.46(d,J=2.5Hz,1H),1.88(d,J=2.8Hz,1H),0.96(s,9H)
13C NMR(100MHz,CDCl3)δ141.38,141.00,140.26,128.90,128.18,127.36,127.18,126.42,82.32,35.88,26.09.
高分辨:计算值:[M-OH]+:223.1481,实测值:223.1485.
[α]D 25=13.30(c=0.50in CHCl3).
光学纯度分析:产物的对映体过量99%,手性OD-H柱(异丙醇:正己烷为5:955,v:v),1.0mL/min,254nm,25℃,保留时间为t1=21.05分钟,t2=26.64分钟。
基于本发明的方法,从简单的芳基碘代物和醛类化合物出发制备得到了一系列手性苄醇类化合物,制备方法简单、适用范围广、产率高(产率高于50%)且对映体选择性高(高于85%)。
尽管上面已经详细描述了本发明的实施例,本领域的普通技术人员可以理解:在不脱离本发明的原理和宗旨的情况下可以对这些实施例进行多种变化、修改、替换和变型,本发明的范围由权利要求及其等同物限定。
Claims (6)
1.一种手性苄醇类衍生物的制备方法,其特征在于,手性苄醇类衍生物具有通式I所示的结构,通式I所示的手性苄醇类衍生物的制备方法包括如下步骤:
S1、在惰性气体保护下,在二氯甲烷溶剂中加入配体VI以及碘化钴,配体与碘化钴配位生成二价钴配体化合物,得到二价钴配体化合物溶液;
S2、在所述二价钴配体化合物溶液中加入光催化剂2,4,5,6-四(9-咔唑基)-间苯二腈、二异丙基乙基胺、还原剂二氢吡啶、式II所示的芳香碘代物以及式III所示的醛类化合物得到反应混合物,将所述反应混合物在蓝光照射下反应得到式I所示的手性苄醇类化合物;
配体VI的结构如下式所示:
上述反应式中,
R选自芳基、杂芳基、烯基、烷基,或选自被相同或不同的取代基单取代或多取代的芳基、杂芳基、烯基、烷基,所述杂芳基中杂原子选自N、S或O中的一种或多种;
环A选自芳基或苯并杂芳基;
各所述R1分别独立地选自H、酯基、氰基、卤素、氨基磺酰基、烷基磺酰基、取代或未取代烷基、取代或未取代烷氧基、取代或未取代的炔基中的一种;
所述手性苄醇类衍生物选自以下结构中的一种:
2.根据权利要求1所述的手性苄醇类衍生物的制备方法,其特征在于,所述环A选自苯基、联苯基、萘基、苯并呋喃、苯并噻吩、吲哚、咔唑或喹啉中的一种。
3.根据权利要求1所述手性苄醇类衍生物的制备方法,其特征在于,R为被相同或不同的取代基单取代或多取代的芳基、杂芳基、烯基、烷基时,R上的各所述取代基独立地选自卤素、氰基、烷基、烯基、芳香基、硼烷基、取代硼烷基、烷氧基、取代烷氧基、巯基、烷基巯基、烷基膦氧基、苯基膦氧基或邻苯二甲酰亚胺基中的一种。
4.根据权利要求1所述的手性苄醇类衍生物的制备方法,其特征在于,S1中配体VI与所述碘化钴的摩尔比为1:(1~3)。
5.根据权利要求1所述的手性苄醇类衍生物的制备方法,其特征在于,所述混合反应液二价钴配体化合物、光催化剂2,4,5,6-四(9-咔唑基)-间苯二腈、二异丙基乙基胺、还原剂二氢吡啶、式II所示的芳香碘代物以及式III所示的醛类化合物的摩尔比为(5%~15%):(0.5%~4%):(1.5~3):(1~2):(1~2):1。
6.根据权利要求1所述的手性苄醇类衍生物的制备方法,其特征在于,S2中通过TLC监测反应进程,待反应完成后,以石油醚和乙酸乙酯为淋洗液进行柱层析得到式I所述的手性苄醇类衍生物。
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