CN108586284A - 一种轴手性芳基烯烃化合物及其合成方法 - Google Patents
一种轴手性芳基烯烃化合物及其合成方法 Download PDFInfo
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- CN108586284A CN108586284A CN201810375860.1A CN201810375860A CN108586284A CN 108586284 A CN108586284 A CN 108586284A CN 201810375860 A CN201810375860 A CN 201810375860A CN 108586284 A CN108586284 A CN 108586284A
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- China
- Prior art keywords
- aryl
- olefin compound
- axial chirality
- synthetic method
- added
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- -1 aryl olefin compound Chemical class 0.000 title claims abstract description 56
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 238000010189 synthetic method Methods 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 100
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 49
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 23
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 75
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 20
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 18
- 229940071536 silver acetate Drugs 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 150000002923 oximes Chemical class 0.000 claims description 11
- 150000001336 alkenes Chemical class 0.000 claims description 10
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000004054 benzoquinones Chemical class 0.000 claims description 6
- 239000003446 ligand Substances 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000007800 oxidant agent Substances 0.000 claims description 5
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- 150000002940 palladium Chemical class 0.000 claims description 4
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 claims description 4
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 4
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 4
- 229910001923 silver oxide Inorganic materials 0.000 claims description 4
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000012429 reaction media Substances 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 230000002950 deficient Effects 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 49
- 230000004888 barrier function Effects 0.000 abstract description 3
- 230000006340 racemization Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 139
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 124
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 31
- 239000000203 mixture Substances 0.000 description 31
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 23
- 238000004440 column chromatography Methods 0.000 description 22
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- 239000003921 oil Substances 0.000 description 22
- 238000002360 preparation method Methods 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 238000010828 elution Methods 0.000 description 20
- KTHDTJVBEPMMGL-VKHMYHEASA-N N-acetyl-L-alanine Chemical compound OC(=O)[C@H](C)NC(C)=O KTHDTJVBEPMMGL-VKHMYHEASA-N 0.000 description 19
- KTHDTJVBEPMMGL-UHFFFAOYSA-N N-acetyl-L-alanine Natural products OC(=O)C(C)NC(C)=O KTHDTJVBEPMMGL-UHFFFAOYSA-N 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 238000010898 silica gel chromatography Methods 0.000 description 18
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 12
- 229940048053 acrylate Drugs 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 9
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000004575 stone Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 235000010338 boric acid Nutrition 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- 229920002554 vinyl polymer Polymers 0.000 description 3
- JLIDVCMBCGBIEY-UHFFFAOYSA-N 1-penten-3-one Chemical compound CCC(=O)C=C JLIDVCMBCGBIEY-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- STNJBCKSHOAVAJ-UHFFFAOYSA-N Methacrolein Chemical compound CC(=C)C=O STNJBCKSHOAVAJ-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 2
- 150000005347 biaryls Chemical group 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000006880 cross-coupling reaction Methods 0.000 description 2
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical class C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 2
- 238000006772 olefination reaction Methods 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical compound C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 description 1
- RRCMGJCFMJBHQC-UHFFFAOYSA-N (2-chlorophenyl)boronic acid Chemical class OB(O)C1=CC=CC=C1Cl RRCMGJCFMJBHQC-UHFFFAOYSA-N 0.000 description 1
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical class CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 1
- JXJFPLFPNPIVPE-UHFFFAOYSA-N (2-phenylphenoxy)boronic acid Chemical compound OB(O)OC1=CC=CC=C1C1=CC=CC=C1 JXJFPLFPNPIVPE-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KKUKTXOBAWVSHC-UHFFFAOYSA-N Dimethylphosphate Chemical compound COP(O)(=O)OC KKUKTXOBAWVSHC-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- WXNXCEHXYPACJF-ZETCQYMHSA-M N-acetyl-L-leucinate Chemical compound CC(C)C[C@@H](C([O-])=O)NC(C)=O WXNXCEHXYPACJF-ZETCQYMHSA-M 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000035217 Ring chromosome 1 syndrome Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001344 alkene derivatives Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 238000009412 basement excavation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 125000005619 boric acid group Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- AVHITTXOFHLCBC-UHFFFAOYSA-N bromobenzene ethene Chemical group C=C.BrC1=CC=CC=C1 AVHITTXOFHLCBC-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- ROLKQUDZUWUVJB-UHFFFAOYSA-N chlorobenzene;ethene Chemical group C=C.ClC1=CC=CC=C1 ROLKQUDZUWUVJB-UHFFFAOYSA-N 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- UCQFCFPECQILOL-UHFFFAOYSA-N diethyl hydrogen phosphate Chemical compound CCOP(O)(=O)OCC UCQFCFPECQILOL-UHFFFAOYSA-N 0.000 description 1
- KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical compound C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- URCAYJXJXYLGTI-UHFFFAOYSA-N ethene fluorobenzene Chemical group C=C.FC1=CC=CC=C1 URCAYJXJXYLGTI-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002561 ketenes Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/12—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reactions not involving the formation of oxyimino groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
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Abstract
本发明涉及化学合成技术领域,为解决手性轴的芳基烯烃化合物合成过程中存在旋转能垒较低,易于消旋且难以控制反应的问题,本发明提出了一种轴手性芳基烯烃化合物及其合成方法,在手性钯络合物催化下对芳基碳‑氢键直接进行不对称烯基化,从而得到轴手性芳基烯烃化合物。该反应可在空气氛下完成,操作简单,后处理方便。
Description
技术领域
本发明涉及化学合成技术领域,具体涉及一种利用钯催化的分子间不对称碳-氢键烯基化反应合成轴手性芳基烯烃的制备方法。
背景技术
轴手性化合物广泛存在于生物活性分子中,作为手性配体和催化剂己在多种类型的不对称催化反应中发挥了重要作用。轴手性常见于旋转受限的联芳环类化合物,鉴于此类分子骨架的重要性,化学家发展了诸多催化构建轴手性联芳环化合物的合成方法,包括芳基化合物间的氧化/交叉偶联、芳环的不对称构筑、联芳环化合物的动力学拆分和去对称化等。与此形成鲜明对照的是,在芳环和烯烃之间具有一个手性轴的芳基烯烃化合物无论是在合成还是应用方面的研究相对滞后,究其原因主要是这类化合物旋转能垒较低易于消旋且难以控制反应的立体选择性。2016年,Gu等报道了利用钯催化的芳基溴化物与腙反应合成轴手性芳基烯烃化合物的研究(Angew.Chem.Int.Ed.2016,55,2286)。使用腙作为卡宾前体使得偶联反应可以在温和的条件下进行,获得了高ee值的目标化合物。随后该小组还发展了钯催化的2-碘代环己烯酮与芳基硼酸的不对称偶联反应合成轴手性芳基烯烃的方法(Angew.Chem.Int.Ed.2017,56,4777)。除了上述过渡金属催化的不对称合成路线外,有机催化也可用于轴手性芳基烯烃的合成。如Tan等利用脯胺醇硅醚催化的1,3-二酮、β-酮酯、丙二腈对炔烃的迈克尔加成反应以高产率、高区域和立体选择性制备了系列芳基烯烃化合物。尽管人们在催化合成轴手性芳基烯烃方面己取得一定的进展,但还有很大的研究空间值得合成化学家去挖掘。比如说,为了得到稳定结构的目标轴手性化合物,通常需要冗长的合成路线以制备多取代和大位阻的芳基卤化物和有机金属试剂,这在一定程度上阻碍了不对称交叉偶联方法学在轴手性芳基烯烃合成领域中的应用。另外,这些催化反应或多或少存在着一些问题,如反应底物范围受限,低转换率和较低的立体选择性。
众所周知,C-H键是一种广泛存在于各类有机化合物的化学键。C-H键活化策略被公认为是一种最直接、快捷构建C-C键和C-杂原子键的有效方法,在提高反应原子经济性的同时还大大缩短了合成路线,减少了废物的排放,属于绿色化学过程。近年来随着化学家在此领域的持续深入研究,已经有开发出几例高效的催化体系,对特定结构的芳基或烯基底物实现了区域选择性和立体选择性的功能化。如Gu等人利用不对称烯基C-H键芳化反应在轴手性磷-烯化合物的催化合成中取得了较高的收率和对映选择性(Chin.J.Chem.2018,36,11),但遗憾的是所用底物为手性化合物。
发明内容
为解决手性轴的芳基烯烃化合物合成过程中存在旋转能垒较低,易于消旋且难以控制反应的问题,本发明提出了一种轴手性芳基烯烃化合物及其合成方法,该反应可在空气氛下完成,操作简单,后处理方便。
本发明是通过以下技术方案实现的:一种轴手性芳基烯烃化合物的结构式如(1)表示:
其中,R1选自烷基,芳基中一种,R2选自烷基,芳基中一种;R3选自烷基,芳基,卤素中一种;R4选自酯基,芳基,醛基,羰基,磺酰基,磷酸酯中一种。
作为优选,R1选自甲基、叔丁基、苯基中一种;R2选自甲基、苯基中一种;R3选自甲基、甲氧基、羟基、苯基、氟、氯、溴中一种;R4选自甲酯、乙酯、丁酯、叔丁酯、对甲氧基苯基、对硝基苯基、对氟苯基、对氯苯基、对溴苯基、苯基砜、磷酸二甲酯、磷酸二乙酯中一种。
所述的轴手性芳基烯烃化合物的合成方法为:在手性钯络合物催化下对芳基碳-氢键直接进行不对称烯基化,从而得到轴手性芳基烯烃化合物。
作为优选,合成方法为:以3-烷基-2-芳基1-环己烯基肟和烯烃衍生物为反应物,以钯盐与配体形成的络合物为催化剂前体,在氧化剂存在下,在反应介质中,在空气中于40-80℃下反应10-48h,反应结束后用常规分离方法分离出产物,得到轴手性芳基烯烃。
反应式如下所示:
作为优选,3-烷基-2-芳基-1-环己烯基肟选自摩尔浓度为0.1-1mol/L的溶液。
烯烃的使用量与3-烷基-2-芳基-1-环己烯基肟的摩尔比为1.1-3∶1,所述的烯烃为选自共轭或缺电子烯烃。
反应介质选自甲醇、四氢呋喃、特戊醇、甲苯、六氟异丙醇、乙二醇二甲醚中一种或几种。使用量为使反应充分进行的量。
钯盐选自醋酸钯、二(乙酰丙酮)钯、三氟乙酸钯、四乙腈四氟硼酸钯、氯化钯中一种,使用量为3-烷基-2-芳基-1-环己烯基肟摩尔量的1~10%。
配体选自单保护手性氨基酸,使用量为3-烷基-2-芳基-1-环己烯基肟摩尔量的1~20%。作为优选,配体选自具有以下结构式的化合物中一种:
氧化剂选自醋酸银、苯醌、氧气、氧化银、碳酸银中一种,氧化剂与3-烷基-2-芳基-1-环己烯基肟的摩尔比大于1.1∶1。作为优选,醋酸银、苯醌、氧化银、碳酸银与3-烷基-2-芳基-1-环己烯基肟的摩尔比为1.1-3∶1
本发明以易于制备的3-烷基-2-芳基-1-环己烯基肟为原料,经分子间的烯化反应即可高效合成系列轴手性芳基烯烃。催化前体为商品化试剂或原位形成,在空气中于一定温度搅拌即可完成反应,操作简单。粗产品经过快速柱层析除杂后减压浓缩可得纯品,后处理方便。
与现有技术相比,本发明的有益效果是:
(1)本方法可在常温下完成,操作简单,后处理方便。
(2)本方法对含有不同类种取代基的芳基和烯烃均具有较好的适应性,可以较高产率、对映选择性获得系列轴手性芳基烯烃化合物。
具体实施方式
下面通过实施例对本发明作进一步详细说明,实施例中所用原料均可市购或采用常规方法制备。
制备例1:3-甲基-2-碘-1-环己烯酮的合成
向500mL圆底烧瓶中加入碘单质(25.38g,120mmol),吡啶(19.2mL,240mmol,),200mL二氯甲烷。置于搅拌器上搅拌,室温下加入【双(三氟乙酰氧基)碘】苯(51.60g,120mmol)。该溶液在室温下搅拌1小时,直至碘颜色消失。再加入3-甲基-1-环己烯酮(22.02g,200mmol),室温反应过夜。混合物用饱和的过硫酸钠溶液和二氯甲烷萃取三次。有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=10∶1洗脱,抽干得黄色液体(46.1314g,195.5mmol),产率97.7%。
制备例2:3-苯基-2-碘-1-环己烯酮的合成
向250mL圆底烧瓶中加入碘单质(6.34g,30mmol),吡啶(4.8mL,60mmol,),50mL二氯甲烷。置于搅拌器上搅拌,室温下加入【双(三氟乙酰氧基)碘】苯(12.90g,30mmol)。该溶液在室温下搅拌1小时,直至碘颜色消失。再加入3-苯基-1-环己烯酮(8.7g,50mmol),室温反应过夜。混合物用饱和的过硫酸钠溶液和二氯甲烷萃取三次。有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=10∶1洗脱,抽干得黄色液体(6.5g,21.8mmol),产率44%。
制备例3:3-甲基-2-萘基-1-环己烯酮的合成
1-萘基硼酸(1.72g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,untilPH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=10∶1洗脱,抽干,产率83%。
制备例4:3-甲基-2-(2-甲基苯基)-1-环己烯酮的合成
2-甲基苯硼酸(1.35g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,untilPH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚:乙酸乙酯=10:1洗脱,抽干,产率53%。
制备例5:3-甲基-2-(2-氯苯基)-1-环己烯酮的合成
2-氯苯硼酸(1.56g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,untilPH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=10∶1洗脱,抽干产率28%。
制备例6:3-甲基-2-(2-羟基苯基)-1-环己烯酮的合成
2-羟基苯硼酸(1.38g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,untilPH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚∶乙酸乙酯=5∶1洗脱,抽干,产率58%。
制备例7:3-甲基-2-(2-甲氧基苯基)-1-环己烯酮的合成
2-羟基苯硼酸(1.52g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,untilPH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=5∶1洗脱,抽干产率46%。
制备例8:3-甲基-2-联苯-1-环己烯酮的合成
2-苯基苯硼酸(1.98g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,untilPH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=10∶1洗脱,抽干,产率64%。
制备例9:3-甲基-2-(2-甲基-5-氟苯基)-1-环己烯酮的合成
2-甲基-5-氟苯硼酸(1.54g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,until PH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=10∶1洗脱,抽干,产率70%。
制备例10:3-甲基-2-萘己环基-1-环己烯酮的合成
2-萘己环-1-硼酸(2.8g,10mmol),3-甲基-2-碘-1-环己烯酮(2.596g,11mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(0.58g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,until PH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚∶乙酸乙酯=10∶1洗脱,抽干,产率72.3%。
制备例11:3-苯基-2-萘基-1-环己烯酮的合成
1-萘基硼酸(3.44g,20mmol),3-苯基-2-碘-1-环己烯酮(5.96g,20mmol)在氮气保护下溶解于1,4-二氧六环中。加入四(三苯基膦)钯(1.16g,5mol%)。该反应在氮气中置换三次,室温搅拌10分钟后,加入2mol/L的碳酸钠溶液(15mL).将反应移至100℃下反应过夜。冷却至室温,加入15mL乙酸乙酯和20mL水进行稀释,加入2mol/L HCl(ca 13mL,until PH=7)进行中和。该混合液用15mL乙酸乙酯萃取4次,混合物经饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=10∶1洗脱,抽干,产率22%。
制备例12:3-甲基-2-萘基-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-萘基-1-环己烯酮(1.95g,8.3mmol),加入20mL甲醇充分溶解,加入甲氧基胺盐酸盐(2.08g,24mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(2.09g,24mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(30mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=30∶1洗脱,抽干得白色固体,产率87%。
1H NMR(400MHz,CDCl3)δ7.86-7.81(m,1H),7.77(d,J=8.2Hz,1H),7.66(d,J=8.0Hz,1H),7.49-7.35(m,3H),7.19(dd,J=7.0,1.0Hz,1H),3.53(s,3H),2.77-2.67(m,2H),2.36(dd,J=11.1,5.4Hz,2H),1.99-1.88(m,2H),1.46(s,3H).
13C NMR(101MHz,CDCl3)δ156.88(s),143.35(s),136.51(s),133.49(s),132.37(s),129.82(s),128.12(s),127.37(s),126.78(s),125.88(s),125.45(s),125.32(s),125.25(s),61.45(s),31.79(s),22.99(s),21.75(s),21.21(s).
HRMS(ESI)m/z:[M+Na]+calculated for C18H19NaNO:288.1359,found:288.1361
制备例13:3-甲基-2-(2-甲基苯基)-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-(2-甲基苯基)-1-环己烯酮(0.53g,2.65mmol),加入5mL甲醇充分溶解,加入甲氧基胺盐酸盐(0.66g,8mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(0.67g,8mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(10mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=30∶1洗脱,抽干得白色固体,产率50%。
1H NMR(400MHz,CDCl3)δ7.15(dt,J=9.2,4.0Hz,3H),6.95(d,J=6.3Hz,1H),3.67(s,3H),2.73-2.49(m,2H),2.25(t,J=5.8Hz,2H),2.10(s,3H),1.89-1.74(m,2H),1.50(d,J=0.5Hz,3H).
13c NMR(101MHz,CDCl3)δ141.72(s),136.51(s),129.93(s),129.31(s),126.53(s),125.17(s),61.54(s),31.55(s),22.87(s),21.38(s),21.11(s),19.42(s).
HRMS(ESI)m/z:[M+Na]+calculated for C15H19NNaO:252.1359,found:252.1370
制备例14:3-甲基-2-(2-氯苯基)-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-(2-氯苯基)-1-环己烯酮(0.32g,1.4mmol),加入5mL甲醇充分溶解,加入甲氧基胺盐酸盐(0.36g,4.2mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(0.36g,4.2mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(10mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=30∶1洗脱,抽干得白色固体,产率80.7%。
1H NMR(400MHz,CDCl3)δ7.39-7.33(m,1H),7.26-7.16(m,2H),7.11-7.04(m,1H),3.67(s,3H),2.71-2.53(m,2H),2.35-2.17(m,2H),1.90-1.75(m,2H),1.55(s,3H).
13C NMR(101MHz,CDCl3)δ155.81(s),142.85(s),137.46(s),133.93(s),131.74(s),129.39(s),128.99(s),127.88(s),126.12(s),61.58(s),31.53(s),22.74(s),21.35(s),20.91(s).
HRMS(ESI)m/z:[M+H]+calculated for C14H17ClNO:250.0993,found:250.0994
制备例15:3-甲基-2-(2-羟基苯基)-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-(2-羟基苯基)-1-环己烯酮(1.25g,6.2mmol),加入15mL甲醇充分溶解,加入甲氧基胺盐酸盐(1.55g,18.6mmol)。
该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(1.56g,18.6mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(30mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=15∶1洗脱,抽干得白色固体,产率53%。
1H NMR(400MHz,CDCl3)δ7.25-7.18(m,1H),7.01-6.94(m,2H),6.90(t,J=7.3Hz,1H),3.78(s,3H),2.77-2.54(m,2H),2.38-2.19(m,2H),1.92-1.71(m,2H),1.67(s,3H).
13C NMR(101MHz,CDCl3)δ157.44(s),153.57(s),147.22(s),131.64(s),128.77(s),127.52(s),125.80(s),120.25(s),117.37(s),61.93(s),31.97(s),23.41(s),22.53(s),20.57(s).
HRMS(ESI)m/z:[M+H]+calculated for C14H18NO2:232.1332,found:232.1336
制备例16:3-甲基-2-(2-甲氧基苯基)-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-(2-甲氧基苯基)-1-环己烯酮(0.40g,1.9mmol),加入5mL甲醇充分溶解,加入甲氧基胺盐酸盐(0.48g,5.7mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(0.48g,5.7mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(10mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=15∶1洗脱,抽干得白色固体,产率99%。
1H NMR(400MHz,CDCl3)δ7.28-7.22(m,1H),7.01-6.87(m,3H),3.76(d,J=6.4Hz,3H),3.67(s,3H),2.73-2.52(m,2H),2.34-2.17(m,2H),1.90-1.72(m,2H),1.57(s,3H).
13C NMR(101MHz,CDCl3)δ157.21(s),156.46(s),142.11(s),131.61(s),128.05(s),127.85(s),127.71(s),120.19(s),111.32(s),61.40(s),55.93(s),31.61(s),22.84(s),21.63(s),21.03(s).
HRMS(ESI)m/z:[M+Na]+calculated for C15H19NNaO2:268.1308,found:268.1321
制备例17:3-甲基-2-联苯-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-联苯-1-环己烯酮(1.68g,6.4mmol),加入20mL甲醇充分溶解,加入甲氧基胺盐酸盐(1.61g,19.2mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(1.61g,19.2mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(20mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=30∶1洗脱,抽干得白色固体,产率51%。
1H NMR(400MHz,CDCl3)δ7.39-7.26(m,7H),7.23(dd,J=6.1,3.4Hz,1H),7.12(d,J=6.3Hz,1H),3.69(s,3H),2.55-2.34(m,2H),2.16-1.89(m,2H),1.77-1.54(m,2H),1.40(s,3H).
13C NMR(101MHz,CDCl3)δ157.15(s),142.37(s),142.02(s),141.85(s),136.90(s),131.03(s),129.28(s),128.69(s),127.38(s),126.84(s),126.60(s),126.47(s),61.53(s),31.50(s),22.72(s),21.74(s),20.73(s).
HRMS(ESI)m/z:[M+H]+calculated for C20H22NO:292.1696,found:292.1685
制备例18:3-甲基-2-(2-甲基-5-氟苯基)-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-(2-甲基-5-氟苯基)-1-环己烯酮(1.53g,7mmol),加入15mL甲醇充分溶解,加入甲氧基胺盐酸盐(1.75g,21mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(1.76g,21mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(30mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=30∶1洗脱,抽干得白色固体,产率68%。
1H NMR(400MHz,CDCl3)δ7.14-7.07(m,1H),6.85(td,J=8.5,2.6Hz,1H),6.69(dd,J=9.5,2.5Hz,1H),3.68(s,3H),2.71-2.53(m,2H),2.25(t,J=5.9Hz,2H),2.05(s,3H),1.81(p,J=6.4Hz,2H),1.52(s,3H).
13c NMR(101MHz,CDCl3)δ162.02(s),159.61(s),155.79(s),142.05(s),139.93(d,J=7.8Hz),132.10(d,J=3.0Hz),130.36(d,J=7.8Hz),116.57(d,J=20.6Hz),113.15(d,J=20.7Hz),61.60(s),31.49(s),22.77(s),21.31(s),21.00(s),18.62(s).
HRMS(ESI)m/z:[M+H]+calculated for C15H19FNO:248.1445,found:248.1448
制备例19:3-甲基-2-萘己环基-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-甲基-2-萘己环基-1-环己烯酮(0.52g,2mmol),加入5mL甲醇充分溶解,加入甲氧基胺盐酸盐(0.50g,6mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(0.51g,6mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(10mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=30∶1洗脱,抽干得白色固体,产率66%。
1H NMR(400MHz,CDCl3)δ7.38-7.30(m,2H),7.28(d,J=6.4Hz,1H),7.22(d,J=6.1Hz,1H),7.14(d,J=7.0Hz,1H),3.56(s,3H),3.45-3.35(m,4H),2.72(td,J=6.3,2.8Hz,2H),2.42-2.28(m,2H),1.96-1.87(m,2H),1.48(s,3H).
13c NMR(101MHz,CDCl3)δ156.97(s),145.95(s),144.47(s),143.20(s),139.33(s),131.65(s),130.82(s),129.19(d,J=15.8Hz),127.19(s),121.10(s),118.73(d,J=17.0Hz),61.46(s),31.87(s),30.55(s),30.12(s),23.08(s),21.86(s),21.28(s).
HRMS(ESI)m/z:[M+Na]+calculated for C20H21NNaO:314.1515,found:314.1528
制备例20:3-苯基-2-萘基-1-环己烯基肟的合成
向100mL圆底烧瓶加入3-苯基-2-萘基-1-环己烯酮(1.31g,4.4mmol),加入10mL甲醇充分溶解,加入甲氧基胺盐酸盐(1.10g,13.2mmol)。该溶液在室温下搅拌10分钟,然后分批次加入碳酸氢钠(1.11g,13.2mmol),在此反应温度下反应6小时以上。混合液用乙酸乙酯(20mL)稀释,饱和氯化钠水溶液洗涤,有机相用无水硫酸钠干燥,混合物经硅胶柱层析,石油醚/乙酸乙酯=30∶1洗脱,抽干得白色固体,产率86%。
1H NMR(400MHz,CDCl3)δ7.84-7.76(m,1H),7.73(dd,J=6.2,2.9Hz,1H),7.60(d,J=8.2Hz,1H),7.45-7.32(m,2H),7.21(dd,J=12.4,4.9Hz,1H),7.00(d,J=6.9Hz,1H),6.97-6.87(m,3H),6.87-6.73(m,2H),3.53(s,3H),2.95-2.72(m,3H),2.66(dt,J=17.4,5.7Hz,1H),2.17-1.96(m,2H).
13C NMR(101MHz,CDCl3)δ156.78(s),146.16(s),142.33(s),136.23(s),133.16(d,J=19.4Hz),131.91(s),128.49(s),128.06(s),127.37(d,J=11.0Hz),126.82(s),126.49(d,J=3.9Hz),125.38-124.88(m),61.74(s),32.31(s),23.28(s),21.57(s).
HRMS(ESI)m/z:[M+H]+calculated for C23H22NO:328.1696,found:328.1696
实施例1:
Ethyl(E)-3-(1-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)naphthalen-2-yl)acry late的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.13g,0.5mmol),丙烯酸乙酯(0.16mL,1.5mmol),醋酸钯(0.01g,0.05mmol),N-乙酰-L-丙氨酸(0.013g,0.1mmol),醋酸银(0.25g,1.5mmol),再加入5mL甲醇。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为70%.
1H NMR(400MHz,CDCl3)δ7.75(d,J=13.0Hz,1H),7.72(d,J=4.5Hz,1H),7.70-7.65(m,2H),7.63(d,J=8.9Hz,1H),7.42-7.16(m,2H),6.38(d,J=16.0Hz,1H),4.17(q,J=7.1Hz,2H),3.43(d,J=17.2Hz,3H),2.80-2.56(m,2H),2.34(t,J=5.9Hz,2H),1.98-1.87(m,2H),1.29(s,3H),1.26(t,J=7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ167.36(s),156.20(s),144.93(s),143.71(s),138.54(s),134.11(s),132.39(s),130.02(s),127.99(s),127.43(s),127.21(s),126.73(s),126.57(s),126.31(s),122.63(s),118.32(s),61.55(s),60.28(s),31.84(s),22.90(s),21.49(s),21.18(s),14.33(s).
HRMS(ESI)m/z:[M+Na]+calculated for C23H25NNa03:386.1727,found:386.1739Enantiomeric excess was determined by HPLC with a Chiralpak AD-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,97%ee);major enantiomer tr=5.97min,minor enantiomer tr=6.82min.
实施例2:
Ethyl(E)-3-((E)-2′-(methoxyimino)-6,6′-dimethyl-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-2-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-(2-甲基苯基)-1-环己烯基肟(0.023g,0.1mmol),丙烯酸乙酯(32μL,0.3mmol),三氟乙酸钯(0.0017g,0.005mmol),N-乙酰-L-丙氨酸(0.0026g,0.02mmol),醋酸银(0.05g,0.3mmol),再加入1mL甲苯。将反应管移至40℃油浴反应14小时。快速柱层析后减压浓缩得产物,产率为43%.
1H NMR(400MHz,CDCl3)δ7.62(d,J=16.0Hz,1H),7.47(dt,J=7.8,3.9Hz,1H),7.24-7.14(m,2H),6.31(d,J=16.0Hz,1H),4.22(tt,J=7.2,3.6Hz,2H),3.64(d,J=7.1Hz,3H),2.74(ddd,J=16.9,7.3,5.5Hz,1H),2.58(ddd,J=16.9,8.1,5.7Hz,1H),2.39-2.21(m,2H),2.10(s,3H),1.96-1.79(m,2H),1.40(s,3H),1.31(t,J=7.1Hz,3H).
1aC NMR(101MHz,CDCl3)δ167.32(s),155.57(s),144.14(s),143.30(s),139.25(s),137.23(s),133.23(s),131.13(s),128.38(s),126.81(s),123.14(s),118.11(s),61.60(s),60.19(s),31.60(s),22.81(s),21.07(s),19.60(s),14.30(s).
HRMS(ESI)m/z:[M+H]+calculated for C20H26NO3:328.1907,found:328.1915Enantiomeric excess was determined by HPLC with a Chiralpak OJ-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,99.9%ee);major enantiomer tr=4.95min,minor enantiomer tr=6.55min.
实施例3:
Ethyl(E)-3-((E)-6-chloro-2′-(methoxyimino)-6′-methyl-2′,3′,4′,5′-tetrahydro-[1,1′-biphe nyl]-2-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-(2-氯苯基)-1-环己烯基肟(0.0747g,0.3mmol),丙烯酸乙酯(96μL,0.9mmol),氯化钯(0.0053g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),苯醌(0.0973g,0.9mmol),再加入3mL甲苯。
将反应管移至50℃油浴反应36小时。快速柱层析后减压浓缩得产物,产率为35%.
1H NMR(400MHz,CDCl3)δ7.57(d,J=16.1Hz,1H),7.53(d,J=8.2Hz,1H),7.41(d,J=7.9Hz,1H),7.23(t,J=7.9Hz,1H),6.34(d,J=16.0Hz,1H),4.23(q,J=7.1Hz,2H),3.63(s,3H),2.73(dt,J=16.8,6.3Hz,1H),2.58(ddd,J=16.8,7.8,6.0Hz,1H),2.32(t,J=6.0Hz,2H),1.93-1.82(m,2H),1.46(s,3H),1.31(t,J=7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ166.87(s),155.19(s),144.40(s),142.95(s),138.22(s),135.57(s),134.80(s),130.33(s),127.95(s),126.99(s),124.01(s),119.61(s),61.64(s),60.41(s),31.59(s),22.66(s),21.09(s),20.86(s),14.27(s).
HRMS(ESI)m/z:[M+H]+calculated for C19H23ClNO3:348.1361,found:348.1357Enantiomeric excess was determined by HPLC with a Chiralpak OJ-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,99.9%ee);major enantiomer tr=5.53min,minor enantiomer tr=6.68min.
实施例4:
ethyl(E)-3-((E)-6-hydroxy-2′-(methoxyimino)-6′-methyl-2′,3′,4′,5′-tetrahydro-[1,1′-bip henyl]-2-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-(2-羟基苯基)-1-环己烯基肟(0.0693g,0.3mmol),丙烯酸乙酯(96μL,0.9mmol),醋酸钯(0.0034g,0.015mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至70℃油浴反应20小时。快速柱层析后减压浓缩得产物,产率为69%.
1H NMR(400MHz,CDCl3)δ7.55(d,J=15.9Hz,1H),7.26-7.18(m,2H),6.98(dd,J=7.0,2.0Hz,1H),6.34(d,J=15.9Hz,1H),5.45(d,J=82.7Hz,1H),4.22(dt,J=13.4,6.7Hz,2H),3.71(s,3H),2.87-2.56(m,2H),2.42-2.24(m,2H),1.89(dd,J=11.8,5.8Hz,2H),1.51(s,3H),1.31(t,J=7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ167.18(s),156.15(s),153.41(s),148.92(s),143.30(s),134.46(s),128.52(s),126.21(s),123.85(s),118.78(s),118.44(s),117.59(s),61.93(s),60.35(s),31.86(s),23.16(s),21.80(s),20.77(s),14.30(s).
HRMS(ESI)m/z:[M+H]+calculated for C19H24NO4:330.1700,found:330.1690Enantiomeric excess was determined by HPLC with a Chiralpak OX-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,95.5%ee);major enantiomer tr=8.93min,minor enantiomer tr=10.41min.
实施例5:
ethyl(E)-3-((E)-6-methoxy-2′-(methoxyimino)-6′-methyl-2′,3′,4′,5′-tetrahydro-[1,1′-bip henyl]-2-yl)acrylate)的合成
向25mL反应管中加入3-甲基-2-(2-甲氧基苯基)-1-环己烯基肟(0.0735g,0.3mmol),丙烯酸乙酯(96μL,0.9mmol),醋酸钯(0.0067g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至70℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为72%.
1H NMR(400MHz,CDCl3)δ7.59(d,J=16.0Hz,1H),7.28-7.24(m,2H),6.96-6.84(m,1H),6.33(d,J=16.0Hz,1H),4.22(q,J=7.1Hz,2H),3.75(s,3H),3.62(s,3H),2.75(dt,J=16.7,6.1Hz,1H),2.55(ddd,J=16.7,8.3,5.9Hz,1H),2.29(d,J=5.7Hz,2H),1.91-1.81(m,2H),1.45(s,3H),1.31(t,J=7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ167.22(s),157.35(s),156.00(s),143.71(d,J=4.6Hz),134.58(s),129.09(s),127.84(s),125.33(s),118.58(s),118.04(s),112.39(s),61.46(s),60.23(s),56.19(s),31.62(s),22.78(s),21.38(s),21.04(s),14.29(s).
HRMS(ESI)m/z:[M+H]+calculated for C20H26NO4:344.1856,found:344.1852Enantiomeric excess was determined by HPLC witha Chiralpak IC column(hexanes:2-propanol=90∶10,0.8mL/min,254nm,99.9%ee);major enantiomer tr=5.86min,minor enantiomer tr=7.30min.
实施例6:
ethyl(E)-3-((E)-2″-(methoxyimino)-6″-methyl-2″,3″,4″,5″-tetrahydro-[1,1′:2′,1″-terph enyl]-3′-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-联苯-1-环己烯基肟(0.0873g,0.3mmol),丙烯酸乙酯(96μL,0.9mmol),醋酸钯(0.0067g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),苯醌(0.0973g,0.9mmol),再加入3mL四氢呋喃。将反应管移至60℃油浴反应40小时。快速柱层析后减压浓缩得产物,产率为38%.
1H NMR(400MHz,CDCl3)δ7.69-7.65(m,1H),7.64-7.62(m,1H),7.36(t,J=7.6Hz,1H),7.34-7.30(m,1H),7.29-7.25(m,3H),7.25-7.22(m,2H),6.37(d,J=15.9Hz,1H),4.23(q,J=7.1Hz,2H),3.67(s,3H),2.53(ddd,J=16.7,8.6,4.8Hz,1H),2.31(ddd,J=16.7,8.2,4.8Hz,1H),2.23-2.07(m,1H),1.99-1.84(m,1H),1.78-1.63(m,1H),1.52-1.41(m,1H),1.32(dd,J=8.9,5.3Hz,6H).
13C NMR(101MHz,CDCl3)δ167.24(s),156.84(s),144.26(s),143.79(s),142.69(s),141.92(s),138.07(s),133.87(s),131.13(s),128.62(s),128.28(s),127.33(s),127.09(s),126.74(s),124.70(s),118.52(s),61.61(s),60.26(s),31.44(s),22.53(s),21.65(s),20.60(s),14.31(s).
HRMS(ESI)m/z:[M+H]+calculated for C25H28No3:390.2064,found:390.2061Enantiomeric excess was determined by HPLC with a Chiralpak IC column(hexanes:2-propanol=96∶4,0.8mL/min,254nm,99.9%ee);major enantiomer tr=6.20min,minor enantiomer tr=7.11min.
实施例7:
ethyl(E)-3-((E)-3-fluoro-2′-(methoxyimino)-6,6′-dimethyl-2′,3′,4′,5′-tetrahydro-[1,1′-biphenyl]-2-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-(2-甲基-5-氟苯基)-1-环己烯基肟(0.0741g,0.3mmol),丙烯酸乙酯(96μL,0.9mmol),二(乙酰丙酮)钯(0.0091g,0.03mmol),N-乙酰-L-亮氨酸(0.0105g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为56%.
1H NMR(400MHz,CDCl3)δ7.45(d,J=16.3Hz,1H),7.13(dd,J=8.2,5.5Hz,1H),6.93(dd,J=11.1,8.5Hz,1H),6.56(d,J=16.3Hz,1H),4.22(q,J=7.0Hz,2H),3.65(d,J=10.1Hz,3H),2.78-2.68(m,1H),2.57(ddd,J=16.9,8.0,5.8Hz,1H),2.37-2.23(m,2H),2.05(s,3H),1.93-1.80(m,2H),1.43(s,3H),1.31(t,J=7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ167.63(s),161.58(s),159.08(s),155.23(s),143.50(s),141.12(d,J=2.9Hz),138.29(s),132.63(d,J=3.4Hz),131.43(d,J=9.4Hz),128.18(s),122.52(s),122.37(s),121.17(s),121.07(s),114.20(s),113.98(s),61.67(s),60.28(s),31.56(s),22.76(s),21.00(d,J=7.3Hz),19.17(s),14.30(s).
HRMS(ESI)m/z:[M+H]+calculated for C20H25FNO3:346.1813,found:346.1806Enantiomeric excess was determined by HPLC with a Chiralpak IC column(hexanes:2-propanol=96∶4,0.8mL/min,254nm,97.7%ee);major enantiomer tr=6.00min,minor enantiomer tr=7.70min.
实施例8:
ethyl(E)-3-(5-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)-1,2-dihydroacenaph thylen-4-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-萘己环基-1-环己烯基肟(0.0981g,0.3mmol),丙烯酸乙酯(96μL,0.9mmol),四乙腈四氟硼酸钯(0.0067g,0.015mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),氧气,再加入3mL甲醇。将反应管移至40℃油浴反应32小时。快速柱层析后减压浓缩,得产物产率为26%.
1H NMR(400MHz,CDCl3)δ7.77(d,J=16.0Hz,1H),7.48(s,1H),7.31(d,J=8.3Hz,1H),7.19(d,J=6.8Hz,2H),6.37(d,J=15.9Hz,1H),4.17(q,J=7.1Hz,2H),3.48-3.40(m,3H),3.38-3.28(m,4H),2.78-2.57(m,2H),2.33(t,J=5.9Hz,2H),1.98-1.85(m,2H),1.31(s,3H),1.26(t,J=7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ167.51(s),156.35(s),145.71(s),144.96(d,J=11.6Hz),144.63(s),140.11(s),134.64(s),131.77(s),130.69(s),128.04(s),126.84(s),121.96(s),120.30(s),117.74(s),115.94(s),61.51(s),60.19(s),31.88(s),30.50(s),30.02(s),22.96(s),21.52(s),21.24(s),14.33(s).
HRMS(ESI)m/z:[M+H]+calculated for C25H28NO3:390.2064,found:390.2061Enantiomeric excess was determined by HPLC with a Chiralpak OX-Hcolumn(hexanes:2-propanol=98∶2,0.5mL/min,254nm,98%ee);major enantiomer tr=15.91min,minor enantiomer tr=19.29min.
实施例9:
ethyl(E)-3-(1-((E)-3-(methoxyimino)-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)naphthale n-2-yl)acrylate的合成
向25mL反应管中加入3-苯基-2-萘基-1-环己烯基肟(0.0981g,0.3mmol),丙烯酸乙酯(96μL,0.9mmol),醋酸钯(0.0067g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入2mL甲醇。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为62%.
1H NMR(400MHz,CDCl3)δ7.89(d,J=16.0Hz,1H),7.85(d,J=9.3Hz,1H),7.74-7.67(m,1H),7.61(d,J=8.6Hz,1H),7.49(d,J=8.7Hz,1H),7.41(p,J=6.3Hz,2H),6.87(q,J=6.0Hz,3H),6.77(d,J=6.4Hz,2H),6.24(d,J=15.9Hz,1H),4.35-4.17(m,2H),3.49(d,J=13.9Hz,3H),3.03-2.77(m,3H),2.71(dt,J=11.7,5.6Hz,1H),2.14(d,J=4.2Hz,2H),1.35(t,J=7.1Hz,3H).
13C NMR(101MHz,CDCl3)δ167.34(s),156.32(s),147.92(s),144.06(s),141.78(s),138.13(s),133.62(s),133.24(s),130.15(s),128.81(s),127.89(s),127.46(s),127.39(s),127.26(s),126.73(s),126.65(s),126.29(s),126.13(s),122.38(s),118.13(s),61.79(s),60.25(s),32.39(s),23.18(s),21.51(s),14.39(s).
HRMS(ESI)m/z:[M+H]+calculated for C28H28NO3:426.2064,found:426.2066Enantiomeric excess was determined by HPLC with a Chiralpak IC column(hexanes:2-propanol=95∶5,0.8mL/min,254nm,95.5%ee);major enantiomer tr=6.84min,minor enantiomer tr=8.52min.
实施例10:
methyl
(E)-3-(1-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)naphthalen-2-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),丙烯酸甲酯(0.0775g,0.9mmol),醋酸钯(0.0034g,0.015mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至50℃油浴反应36小时。快速柱层析后减压浓缩得产物,产率为67%.
1H NMR(400MHz,CDCl3)δ7.83(d,J=5.7Hz,1H),7.81-7.65(m,4H),7.44(dt,J=15.0,7.2Hz,2H),6.46(d,J=16.0Hz,1H),3.79(s,3H),3.49(s,3H),2.85-2.65(m,2H),2.43(t,J=6.1Hz,2H),2.04-1.95(m,2H),1.37(s,3H)
13C NMR(101MHz,CDCl3)δ167.78(s),156.18(s),144.94(s),143.95(s),138.59(s),134.14(s),132.37(s),129.98(s),127.98(s),127.44(s),127.20(s),126.65(d,J=11.8Hz),126.33(s),122.63(s),117.92(s),61.55(s),51.55(s),31.83(s),22.88(s),21.46(s),21.17(s).
HRMS(ESI)m/z:[M+Na]+calculated for C22H23NNaO3:372.1570,found:372.1579Enantiomeric excess was determined by HPLC with a Chiralpak AD-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,96%ee);major enantiomer tr=6.21min.minor enantiomer tr=7.31min.
实施例11:
butyl
(E)-3-(1-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)naphthalen-2-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),丙烯酸丁酯(0.0385g,0.3mmol),氯化钯(0.0053g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为34%.
1H NMR(400MHz,CDCl3)δ7.82(d,J=6.7Hz,1H),7.77(dd,J=14.1,5.2Hz,3H),7.73-7.67(m,1H),7.43(dt,J=21.7,6.9Hz,2H),6.46(d,J=16.0Hz,1H),4.20(t,J=6.5Hz,2H),3.49(s,3H),2.88-2.61(m,2H),2.42(t,J=6.0Hz,2H),1.99(p,J=6.4Hz,2H),1.75-1.63(m,2H),1.52-1.39(m,2H),1.37(s,3H),0.97(t,J=7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ167.40(s),156.18(s),144.91(s),143.62(s),138.50(s),134.11(s),132.39(s),130.02(s),127.98(s),127.42(s),127.22(s),126.64(d,J=15.6Hz),126.30(s),122.59(s),118.35(s),64.19(s),61.53(s),31.83(s),30.81(s),22.88(s),21.47(s),21.16(s),19.26(s),13.73(s).
HRMS(ESI)m/z:[M+Na]+calculated for C25H29NNaO3:414.2040,found:414.2052Enantiomeric excess was determined by HPLC with a Chiralpak AD-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,96%ee);major enantiomer tr=5.77min,minor enantiomer tr=6.74min.
实施例12:
tert-butyl
(E)-3-(1-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)naphthalen-2-yl)acrylate的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),丙烯酸叔丁酯(0.1154g,0.9mmol),二(乙酰丙酮)钯(0.0091g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至40℃油浴反应32小时。快速柱层析后减压浓缩得产物,产率为56%.
1H NMR(400MHz,CDCl3)δ7.80(d,J=7.8Hz,1H),7.77-7.73(m,2H),7.70(dd,J=8.8,5.4Hz,2H),7.42(ddd,J=15.1,13.7,6.8Hz,2H),6.40(d,J=16.0Hz,1H),3.49(s,3H),2.84-2.65(m,2H),2.42(t,J=6.0Hz,2H),2.08-1.90(m,2H),1.53(s,9H),1.37(s,3H).
13C NMR(101MHz,CDCl3)δ166.63(s),156.23(s),144.89(s),142.48(s),138.25(s),134.00(s),132.42(s),130.13(s),127.96(s),127.35(s),127.20(s),126.72(s),126.45(s),126.25(s),122.65(s),120.26(s),80.12(s),61.54(s),31.83(s),28.29(s),22.90(s),21.52(s),21.19(s).
HRMS(ESI)m/z:[M+Na]+calculated for C25H29NNaO3:414.2040,found:414.2050Enantiomeric excess was determined by HPLC with a Chiralpak AD-Hcolumn(hexanes:2-propanol=97∶3,0.8mL/min,254nm,99.9%ee);major enantiomer tr=5.29min,minor enantiomer tr=6.52min.
实施例13:
diethyl((E)-2-(1-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)naphthalen-2-yl)vinyl)phosphonate的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),乙烯基膦酸二乙酯(0.1477g,0.9mmol),醋酸钯(0.0067g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。
将反应管移至45℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为88%.
1H NMR(400MHz,CDCl3)δ7.82(d,J=7.9Hz,1H),7.78(d,J=8.8Hz,1H),7.71(d,J=8.8Hz,2H),7.65-7.53(m,1H),7.52-7.39(m,2H),6.27(t,J=18.2Hz,1H),4.12(dd,J=13.7,6.8Hz,4H),3.48(s,3H),2.73(d,J=3.3Hz,2H),2.41(d,J=5.4Hz,2H),2.03-1.95(m,2H),1.42-1.31(m,9H).
13C NMR(101MHz,CDCl3)δ155.06(s),143.97(s),133.03(s),131.20(s),127.00(s),126.43(s),126.01(s),125.57(d,J=2.7Hz),125.36(s),121.30(s),60.83(d,J=4.2Hz),60.51(s),30.79(s),21.84(s),20.53(s),20.10(s),15.37(d,J=6.1Hz).
HRMS(ESI)m/z:[M+Na]+calculated for C24H30NNaO4P:450.1805,found:450.1819Enantiomeric excess was determined by HPLC with a Chiralpak AD-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,99.9%ee);major enantiomer tr=11.03min,minor enantiomer tr=12.43min.
实施例14:
(E)-1-(1-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)naphthalen-2-yl)pent-1-en-3-one的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),乙基乙烯酮(0.0757g,0.9mmol),四乙腈四氟硼酸钯(0.0067g,0.015mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL六氟异丙醇∶乙二醇二甲醚=1∶1。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为27%.
1H NMR(400MHz,CDCl3)δ7.81(d,J=8.0Hz,1H),7.80-7.75(m,2H),7.73(t,J=4.9Hz,1H),7.69(d,J=3.3Hz,1H),7.51-7.37(m,2H),6.76(d,J=16.2Hz,1H),3.49(s,3H),2.89-2.61(m,4H),2.43(t,J=6.0Hz,2H),2.05-1.93(m,2H),1.37(s,3H),1.17(t,J=7.3Hz,3H).
13C NMR(101MHz,CDCl3)δ201.26(s),145.09(s),141.54(s),138.96(s),134.18(s),132.37(s),130.11(s),128.05(s),127.51(s),127.20(s),126.68(s),126.40(s),126.29(s),122.50(s),61.61(s),33.92(s),31.85(s),22.91(s),21.54(s),21.25(s),8.44(s).
HRMS(ESI)m/z:[M+Na]+calculated for C23H25NNaO2:370.1778,found:370.1789Enantiomeric excess was determined by HPLC with a Chiralpak AS-Hcolumn(hexanes:2-propanol=94∶6,0.8mL/min,254nm,99.9%ee);major enantiomer tr=8.22min,minor enantiomer tr=10.65min.
实施例15:
(E)-2-(2-((E)-4-chlorostyryl)naphthalen-1-yl)-3-methylcyclohex-2-en-1-one O-methyl oxime的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0265g,0.1mmol),对氯苯乙烯(0.0416g,0.3mmol),醋酸钯(0.0023g,0.01mmol),N-苄氧羰基-L-缬氨酸(0.0050g,0.02mmol),醋酸银(0.05g,0.3mmol),再加入1mL甲醇。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为74%.
1H NMR(400MHz,CDCl3)δ7.83(d,J=8.7Hz,1H),7.79(dd,J=14.4,5.5Hz,2H),7.70-7.63(m,1H),7.46-7.35(m,4H),7.31(d,J=8.5Hz,2H),7.18(d,J=16.3Hz,1H),7.07(d,J=16.3Hz,1H),3.51(s,3H),2.89-2.70(m,2H),2.42(d,J=5.6Hz,2H),2.00(qt,J=14.3,7.3Hz,2H),1.38(s,3H).
13C NMR(101MHz,CDCl3)δ155.97(s),144.61(s),136.60(s),135.34(s),133.07(s),132.89(s),132.59(s),132.19(s),128.83(s),128.39(s),127.93(s),127.74(s),127.59(d,J=4.0Hz),127.21(s),126.24(s),126.05(s),125.51(s),122.49(s),61.59(s),31.89(s),29.71(s),23.00(s),21.45(d,J=5.9Hz).
HRMS(ESI)m/z:[M+H]+calculated for C26H25ClNO:402.1619,found:402.1616Enantiomeric excess was determined by HPLC with a Chiralpak OX-Hcolumn(hexanes:2-propanol=98∶2,0.5mL/min,254nm,97%ee);major enantiomer tr=9.04min,minor enantiomer tr=9.94min.
实施例16:
(E)-2-(2-((E)-4-fluorostyryl)naphthalen-1-yl)-3-methylcyclohex-2-en-1-one O-methyl oxime的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0265g,0.1mmol),对氟苯乙烯(0.0366g,0.3mmol),醋酸钯(0.0023g,0.01mmol),N-乙酰-L-丙氨酸(0.0026g,0.02mmol),氧化银(0.0372g,0.3mmol),再加入1mL甲醇。将反应管移至40℃油浴反应28小时。快速柱层析后减压浓缩得产物,产率为71%.
1H NMR(400MHz,CDCl3)δ7.83(d,J=8.7Hz,1H),7.81-7.74(m,2H),7.66(dd,J=6.8,2.8Hz,1H),7.47-7.34(m,4H),7.10(d,J=2.6Hz,2H),7.05(dd,J=12.1,5.3Hz,2H),3.51(s,3H),2.91-2.68(m,2H),2.43(t,J=5.7Hz,2H),2.07-1.94(m,2H),1.38(s,3H).
13C NMR(101MHz,CDCl3)δ163.43(s),160.98(s),155.97(s),144.54(s),135.09(s),134.28(s),132.99(s),132.61(s),132.35(s),127.99-127.83(m),127.79(s),127.67(s),127.52(s),127.17(s),126.20(s),126.02(s),125.41(s),122.50(s),115.70(s),115.49(s),61.58(s),31.89(s),23.00(s),21.45(d,J=4.5Hz).
HRMS(ESI)m/z:[M+H]+calculated for C26H25FNO:386.1915,found:386.1910Enantiomeric excess was determined by HPLC with a Chiralpak OX-Hcolumn(hexanes:2-propanol=98∶2,0.8mL/min,254nm,96%ee);major enantiomer tr=8.89min,minor enantiomer tr=9.78min.
实施例17:
(E)-2-(2-((E)-4-bromostyryl)naphthalen-1-yl)-3-methylcyclohex-2-en-1-one O-methyl oxime的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0265g,0.1mmol),对溴苯乙烯(0.0549g,0.3mmol),二(乙酰丙酮)钯(0.0091g,0.01mmol),Boc-L-叔亮氨酸(0.0046g,0.02mmol),醋酸银(0.05g,0.3mmol),再加入1mL甲醇。
将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为64%.
1H NMR(400MHz,CDCl3)δ7.83(d,J=8.7Hz,1H),7.81-7.74(m,2H),7.71-7.61(m,1H),7.47(d,J=8.5Hz,2H),7.44-7.36(m,2H),7.31(d,J=8.4Hz,2H),7.19(d,J=16.3Hz,1H),7.05(d,J=16.3Hz,1H),3.52(d,J=9.9Hz,3H),2.88-2.68(m,2H),2.42(d,J=5.2Hz,2H),2.07-1.91(m,2H),1.38(s,3H)
13C NMR(101MHz,CDCl3)δ155.97(s),144.61(s),137.05(s),135.38(s),133.08(s),132.59(s),132.17(s),131.77(s),128.52(s),127.94(s),127.74(s),127.62(s),127.23(s),126.24(s),126.06(s),125.53(s),122.48(s),121.00(s),61.59(s),31.89(s),23.00(s),21.45(d,J=6.2Hz).
HRMS(ESI)m/z:[M+H]+calculated for C26H24BrNO:446.1114,found:446.1115Enantiomeric excess was determined by HPLC with a Chiralpak OX-Hcolumn(hexanes:2-propanol=98∶2,0.5mL/min,254nm,95%ee);major enantiomer tr=9.49min,minor enantiomer tr=10.37min.
实施例18:
(E)-2-(2-((E)-4-methoxystyryl)naphthalen-1-yl)-3-methylcyclohex-2-en-1-oneO-methyl oxime的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),对甲氧基苯乙烯(0.1208g,0.9mmol),三氟乙酸钯(0.0100g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL四氢呋喃。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为50%.
1H NMR(400MHz,CDCl3)67.85(d,J=8.7Hz,1H),7.78(dd,J=14.8,5.8Hz,2H),7.70-7.62(m,1H),7.43-7.35(m,4H),7.08(s,2H),6.90(d,J=8.5Hz,2H),3.83(s,3H),3.51(s,3H),2.86-2.71(m,2H),2.42(t,J=5.8Hz,2H),2.07-1.96(m,2H),1.38(s,3H).
13C NMR(101MHz,CDCl3)δ159.14(s),155.98(s),144.45(s),134.59(s),132.78(d,J=3.3Hz),132.67(s),130.91(s),128.38(s),127.89(s),127.67(s),127.07(s),126.15(s),125.92(s),125.70(s),125.17(s),122.56(s),114.15(s),61.58(s),55.37(s),31.90(s),23.02(s),21.47(d,J=3.7Hz).
HRMS(ESI)m/z:[M+H]+calculated for C27H28NO2:398.2115,found:398.2104Enantiomeric excess was determined by HPLC with a Chiralpak OX-Hcolumn(hexanes:2-propanol=95∶5,0.8mL/min,254nm,96%ee);major enantiomer tr=6.70min,minor enantiomer tr=8.03min.
实施例19:
(E)-3-methyl-2-(2-((E)-2-(phenylsulfonyl)vinyl)naphthalen-1-yl)cyclohex-2-en-1-oneO-methyl oxime的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),苯基乙烯基砜(0.1514g,0.9mmol),醋酸钯(0.0067g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至80℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为87%.
1H NMR(400MHz,CDCl3)δ7.92(s,1H),7.90(s,1H),7.85-7.68(m,4H),7.66-7.38(m,6H),6.83(d,J=15.5Hz,1H),3.43(s,3H),2.86-2.65(m,2H),2.43(t,J=5.9Hz,2H),2.02(dt,J=12.8,6.3Hz,2H),1.35(s,3H).
13C NMR(101MHz,CDCl3)δ156.24(s),145.55(s),142.30(s),141.06(s),139.35(s),134.39(s),133.15(s),129.25(s),128.27(s),128.12(s),127.69(d,J=5.0Hz),127.37(s),127.13(s),126.71(d,J=8.7Hz),122.63(s),61.59(s),31.82(s),22.86(s),21.63(s),21.11(s).
HRMS(ESI)m/z:[M+H]+calculated for C26H26NO3S:432.1628,found:432.1618Enantiomeric excess was determined by HPLC with a Chiralpak AD-Hcolumn(hexanes:2-propanol=75∶25,0.8mL/min,254nm,99%ee);major enantiomer tr=8.03min,minor enantiomer tr=9.24min.
实施例20:
(E)-3-(1-((E)-6-(methoxyimino)-2-methylcyclohex-1-en-1-yl)naphthalen-2-yl)acrylalde hyde的合成
向25mL反应管中加入3-甲基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),丙烯醛(0.0158g,0.3mmol),四乙腈四氟硼酸钯(0.0067g,0.015mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),苯醌(0.0324g,0.9mmol),再加入3mL甲醇。
将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为16%.
1H NMR(400MHz,CDCl3)δ9.66(d,J=7.7Hz,1H),7.89-7.78(m,2H),7.78-7.69(m,2H),7.59(d,J=15.9Hz,1H),7.51(t,J=7.1Hz,1H),7.44(t,J=7.4Hz,1H),6.76(dd,J=15.9,7.7Hz,1H),3.50(s,3H),2.88-2.64(m,2H),2.45(t,J=5.8Hz,2H),2.00(dt,J=12.9,6.2Hz,2H),1.39(s,3H).
13C NMR(101MHz,CDCl3)δ194.18(s),156.08(s),151.96(s),145.39(s),139.37(s),134.58(s),132.24(s),129.68(s),128.90(s),128.16(s),127.74(s),127.20(s),127.00(s),126.79(s),126.63(s),122.61(s),61.68(s),31.85(s),22.87(s),21.52(s),21.18(s).
HRMS(ESI)m/z:[M+H]+calculated for C21H22NO2:320.1645,found:320.1647Enantiomeric excess was determined by HPLC with a Chiralpak IB column(hexanes:2-propanol=98∶2,0.8mL/min,254nm,99.9%ee);major enantiomer tr=12.03min,minor enantiomer tr=13.66min.
实施例21:
Diethyl((E)-2-(1-((E)-3-(methoxyimino)-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)naphth alen-2-yl)vinyl)phosphonate的合成
向25mL反应管中加入3-苯基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),乙烯基膦酸二乙酯(0.1477g,0.9mmol),醋酸钯(0.0067g,0.03mmol),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),醋酸银(0.1502g,0.9mmol),再加入3mL甲醇。将反应管移至70℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为72%.
1H NMR(400MHz,CDCl3)δ7.88-7.82(m,1H),7.73-7.69(m,1H),7.63(dd,J=15.9,7.0Hz,2H),7.49(d,J=8.7Hz,1H),7.45-7.38(m,2H),6.92-6.83(m,3H),6.79(d,J=6.7Hz,2H),6.07(t,J=18.2Hz,1H),4.18-4.02(m,4H),3.51(s,3H),2.89-2.78(m,3H),2.71(dt,J=17.4,5.5Hz,1H),2.13(td,J=12.6,6.5Hz,2H),1.36(t,J=7.0Hz,6H).
13C NMR(101MHz,CDCl3)δ155.25(s),146.85(s),140.70(s),136.57(s),132.57(s),126.88(s),126.44(s),126.35(s),126.17(s),125.71(s),125.29(s),125.17(s),121.05(s),60.73(s),31.33(s),22.14(s),20.45(s),15.42(d,J=6.5Hz).
HRMS(ESI)m/z:[M+H]+calculated for C29H33NO4P:490.2142,found:490.2157Enantiomeric excess was determined by HPLC with a Chiralpak IC column(hexanes:2-propanol=85∶15,0.8mL/min,254nm,97.5%ee);major enantiomer tr=13.11min,minor enantiomer tr=16.16min.
实施例22:
(E)-2-(2-((E)-2-(phenylsulfonyl)vinyl)naphthalen-1-yl)-5,6-dihydro-[1,1′-biphenyl]-3(4H)-one O-methyl oxime的合成
向25mL反应管中加入3-苯基-2-萘基-1-环己烯基肟(0.0795g,0.3mmol),苯基乙烯基砜(0.1514g,0.9mmol),四乙腈四氟硼酸钯(0.0134g,0.03mmol)),N-乙酰-L-丙氨酸(0.0079g,0.06mmol),碳酸银(0.2482g,0.9mmol),再加入3mL甲醇。将反应管移至40℃油浴反应48小时。快速柱层析后减压浓缩得产物,产率为30%.
1H NMR(400MHz,CDCl3)δ7.92(s,1H),7.90(s,1H),7.87(d,J=9.3Hz,1H),7.82(d,J=15.4Hz,1H),7.72-7.67(m,1H),7.64-7.52(m,4H),7.44(p,J=6.8Hz,2H),7.31(d,J=8.7Hz,1H),6.85(dt,J=24.1,7.1Hz,3H),6.73(d,J=7.2Hz,2H),6.62(d,J=15.4Hz,1H),3.47(s,3H),2.86(ddd,J=14.4,8.1,5.3Hz,3H),2.71(dt,J=11.6,5.5Hz,1H),2.25-2.07(m,2H).
13C NMR(101MHz,CDCl3)δ156.35(s),148.53(s),142.14(s),141.50(s),141.10(s),139.29(s),133.21(d,J=6.1Hz),129.25(s),128.45(s),128.16(s),128.02(s),127.73(s),127.66(s),127.52(s),127.41(s),126.99-126.84(m),126.67(s),126.49(s),122.45(s),61.83(s),32.39(s),23.16(s),21.48(s).
HRMS(ESI)m/z:[M+H]+calculated for C31H28NO3S:494.1784,found:494.1780Enantiomeric excess was determined by HPLC with a Chiralpak AD-Hcolumn(hexanes:2-propanol=80∶20,0.8mL/min,254nm,99.9%ee);major enantiomertr=8.28min,minor enantiomer tr=10.78min.
Claims (10)
1.一种轴手性芳基烯烃化合物,其特征在于,所述轴手性芳基烯烃化合物的结构式如(1)表示:
其中,R1选自烷基,芳基中一种,R2选自烷基,芳基中一种;R3选自烷基,芳基,卤素中一种;R4选自酯基,芳基,醛基,羰基,磺酰基,磷酸酯中一种。
2.一种根据权利要求1所述的轴手性芳基烯烃化合物的合成方法,其特征在于,所述的合成方法为:在手性钯络合物催化下对芳基碳-氢键直接进行不对称烯基化,从而得到轴手性芳基烯烃化合物。
3.根据权利要求2所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,以3-烷基-2-芳基-1-环己烯基肟和烯烃为反应物,以钯盐与配体形成的络合物为催化剂前体,在氧化剂存在下,在反应介质中,在空气中于40-80℃下反应10-48h后分离出产物,得到轴手性芳基烯烃。
4.根据权利要求3所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,3-烷基-2-芳基-1-环己烯基肟选自摩尔浓度为0.1-1mol/L的溶液。
5.根据权利要求3所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,烯烃选自共轭或缺电子烯烃,烯烃的使用量与3-烷基-2-芳基-1-环己烯基肟的摩尔比为1.1-3∶1。
6.根据权利要求3所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,反应介质选自甲醇、四氢呋喃、特戊醇、甲苯、六氟异丙醇、乙二醇二甲醚中一种或几种。
7.根据权利要求2或3所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,钯盐选自醋酸钯、二(乙酰丙酮)钯、三氟乙酸钯、四乙腈四氟硼酸钯、氯化钯中一种,使用量为3-烷基-2-芳基-1-环己烯基肟摩尔量的1~10%。
8.根据权利要求2或3所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,配体选自单保护手性氨基酸,使用量为3-烷基-2-芳基-1-环己烯基肟摩尔量的1~20%。
9.根据权利要求8所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,配体选自具有以下结构式的化合物中一种:
10.根据权利要求3所述的一种轴手性芳基烯烃化合物的合成方法,其特征在于,氧化剂选自醋酸银、苯醌、氧气、氧化银、碳酸银中一种,氧化剂与3-烷基-2-芳基-1-环己烯基肟的摩尔比大于1.1∶1。
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110698507A (zh) * | 2019-01-10 | 2020-01-17 | 杭州师范大学 | 一种芳乙烯基硅烷化合物的制备方法 |
CN111848322A (zh) * | 2020-08-05 | 2020-10-30 | 江苏师范大学 | 一种轴手性氧化吲哚取代的苯乙烯类化合物及其拆分方法与应用 |
CN115043729A (zh) * | 2022-07-04 | 2022-09-13 | 青岛大学 | 一种2,2’-二氟联芳基化合物的不对称合成方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2249152A1 (es) * | 2004-07-08 | 2006-03-16 | Consejo Superior Investig. Cientificas | Catalizador para reacciones de hidrogenacion enantioselectivas, procedimiento de preparacion y utilizacion. |
CN101391970A (zh) * | 2008-11-06 | 2009-03-25 | 上海交通大学 | 轴手性含双席夫碱配体 |
-
2018
- 2018-04-24 CN CN201810375860.1A patent/CN108586284B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2249152A1 (es) * | 2004-07-08 | 2006-03-16 | Consejo Superior Investig. Cientificas | Catalizador para reacciones de hidrogenacion enantioselectivas, procedimiento de preparacion y utilizacion. |
CN101391970A (zh) * | 2008-11-06 | 2009-03-25 | 上海交通大学 | 轴手性含双席夫碱配体 |
Non-Patent Citations (2)
Title |
---|
CHONGQING PAN,等: "Palladium‐Catalyzed Enantioselective Synthesis of 2‐Aryl Cyclohex‐2‐enone Atropisomers: Platform Molecules for the Divergent Synthesis of Axially Chiral Biaryl Compounds", 《ANGEW. CHEM., INT. ED.》 * |
杨志翔,等: "双功能轴手性联二萘酚酰胺催化蒽酮和硝基烯烃的不对称Michael加成反应", 《福建师范大学学报(自然科学版)》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110698507A (zh) * | 2019-01-10 | 2020-01-17 | 杭州师范大学 | 一种芳乙烯基硅烷化合物的制备方法 |
CN110698507B (zh) * | 2019-01-10 | 2022-09-23 | 杭州师范大学 | 一种芳乙烯基硅烷化合物的制备方法 |
CN111848322A (zh) * | 2020-08-05 | 2020-10-30 | 江苏师范大学 | 一种轴手性氧化吲哚取代的苯乙烯类化合物及其拆分方法与应用 |
CN111848322B (zh) * | 2020-08-05 | 2022-12-16 | 江苏师范大学 | 一种轴手性氧化吲哚取代的苯乙烯类化合物及其拆分方法与应用 |
CN115043729A (zh) * | 2022-07-04 | 2022-09-13 | 青岛大学 | 一种2,2’-二氟联芳基化合物的不对称合成方法 |
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