CN114105822B - 伪c2对称性的手性双烯丙基取代化合物及其制备方法和应用 - Google Patents
伪c2对称性的手性双烯丙基取代化合物及其制备方法和应用 Download PDFInfo
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- CN114105822B CN114105822B CN202111353383.7A CN202111353383A CN114105822B CN 114105822 B CN114105822 B CN 114105822B CN 202111353383 A CN202111353383 A CN 202111353383A CN 114105822 B CN114105822 B CN 114105822B
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- diallyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 105
- PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical group C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 title claims abstract description 87
- 238000002360 preparation method Methods 0.000 title claims abstract description 56
- 238000006243 chemical reaction Methods 0.000 claims abstract description 114
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 80
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 21
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical class O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims abstract description 17
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims abstract description 16
- 150000001639 boron compounds Chemical class 0.000 claims abstract description 6
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical class C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 96
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 71
- 239000002904 solvent Substances 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 40
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 40
- -1 T-butoxycarbonyl Chemical group 0.000 claims description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- 229910052741 iridium Inorganic materials 0.000 claims description 30
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 30
- 239000003054 catalyst Substances 0.000 claims description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 27
- 239000003446 ligand Substances 0.000 claims description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 21
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 21
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 21
- 239000011734 sodium Substances 0.000 claims description 20
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- 239000003960 organic solvent Substances 0.000 claims description 17
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 16
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 16
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 11
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 11
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 11
- 229960001701 chloroform Drugs 0.000 claims description 11
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 9
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 8
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 8
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 8
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 8
- 229940011051 isopropyl acetate Drugs 0.000 claims description 8
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 8
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 5
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 150000002503 iridium Chemical class 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 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 claims description 4
- 238000010791 quenching Methods 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- VGQWCQNHAMVTJY-RKUAQPHYSA-N (5z,11z)-dibenzo[2,1-a:2',1'-f][8]annulene Chemical compound C/1=C/C2=CC=CC=C2\C=C/C2=CC=CC=C2\1 VGQWCQNHAMVTJY-RKUAQPHYSA-N 0.000 claims description 3
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 claims description 3
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 3
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- BUYVJWVYKPKZEX-DWVXZKBMSA-N (1z,5z)-cycloocta-1,5-diene;(z)-4-hydroxypent-3-en-2-one;rhodium Chemical compound [Rh].C\C(O)=C\C(C)=O.C\1C\C=C/CC\C=C/1 BUYVJWVYKPKZEX-DWVXZKBMSA-N 0.000 claims description 2
- LEJWHNWXNMGGKE-MIXQCLKLSA-N (1z,5z)-cycloocta-1,5-diene;methanol;rhodium Chemical compound [Rh].[Rh].OC.OC.C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 LEJWHNWXNMGGKE-MIXQCLKLSA-N 0.000 claims description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 2
- ZRXHLJNBNWVNIM-UHFFFAOYSA-N 3-methyl-1-benzofuran Chemical compound C1=CC=C2C(C)=COC2=C1 ZRXHLJNBNWVNIM-UHFFFAOYSA-N 0.000 claims description 2
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 claims description 2
- FWCKTRBZOUCGTM-UHFFFAOYSA-N B.C(C(C)O)O Chemical compound B.C(C(C)O)O FWCKTRBZOUCGTM-UHFFFAOYSA-N 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 claims description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
- 238000004440 column chromatography Methods 0.000 claims description 2
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical group [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- INHCSSUBVCNVSK-UHFFFAOYSA-L lithium sulfate Inorganic materials [Li+].[Li+].[O-]S([O-])(=O)=O INHCSSUBVCNVSK-UHFFFAOYSA-L 0.000 claims description 2
- JEQLMQDIGPQFJR-UHFFFAOYSA-N methanesulfonic acid;sulfuric acid Chemical compound CS(O)(=O)=O.OS(O)(=O)=O JEQLMQDIGPQFJR-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- 150000008300 phosphoramidites Chemical class 0.000 claims description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 2
- 235000011152 sodium sulphate Nutrition 0.000 claims description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 2
- RBTVSNLYYIMMKS-UHFFFAOYSA-N tert-butyl 3-aminoazetidine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CC(N)C1 RBTVSNLYYIMMKS-UHFFFAOYSA-N 0.000 claims description 2
- 244000052769 pathogen Species 0.000 claims 5
- 230000001717 pathogenic effect Effects 0.000 claims 5
- 229920000742 Cotton Polymers 0.000 claims 2
- 241000223218 Fusarium Species 0.000 claims 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 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 claims 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 claims 1
- 240000008067 Cucumis sativus Species 0.000 claims 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- 241000209140 Triticum Species 0.000 claims 1
- 235000021307 Triticum Nutrition 0.000 claims 1
- 239000000022 bacteriostatic agent Substances 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 claims 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 230000003287 optical effect Effects 0.000 abstract description 2
- 239000000460 chlorine Substances 0.000 description 56
- 238000004128 high performance liquid chromatography Methods 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 29
- 125000000217 alkyl group Chemical group 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 23
- 238000004809 thin layer chromatography Methods 0.000 description 22
- 238000012544 monitoring process Methods 0.000 description 20
- 229910052757 nitrogen Inorganic materials 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical class COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 13
- DJACTCNGCHPGOI-UHFFFAOYSA-N butyl 2-cyanoacetate Chemical group CCCCOC(=O)CC#N DJACTCNGCHPGOI-UHFFFAOYSA-N 0.000 description 13
- 125000003118 aryl group Chemical group 0.000 description 11
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- BFNYNEMRWHFIMR-UHFFFAOYSA-N tert-butyl 2-cyanoacetate Chemical compound CC(C)(C)OC(=O)CC#N BFNYNEMRWHFIMR-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000010948 rhodium Substances 0.000 description 3
- XGCDBGRZEKYHNV-UHFFFAOYSA-N 1,1-bis(diphenylphosphino)methane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CP(C=1C=CC=CC=1)C1=CC=CC=C1 XGCDBGRZEKYHNV-UHFFFAOYSA-N 0.000 description 2
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical group [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- NXPVXGMVVNYCGZ-VMPITWQZSA-N methyl [(e)-3-phenylprop-2-enyl] carbonate Chemical compound COC(=O)OC\C=C\C1=CC=CC=C1 NXPVXGMVVNYCGZ-VMPITWQZSA-N 0.000 description 2
- YHLVIDQQTOMBGN-UHFFFAOYSA-N methyl prop-2-enyl carbonate Chemical compound COC(=O)OCC=C YHLVIDQQTOMBGN-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- FRYRJNHMRVINIZ-UHFFFAOYSA-N B1CCOO1 Chemical compound B1CCOO1 FRYRJNHMRVINIZ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- WKMCMBLFYZYNDU-UHFFFAOYSA-N C[Si](C)(C)N([Na])[Si](C)(C)C.[Li] Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C.[Li] WKMCMBLFYZYNDU-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Natural products CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910010277 boron hydride Inorganic materials 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
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- XNYOSXARXANYPB-UHFFFAOYSA-N dicyclohexylborane Chemical compound C1CCCCC1BC1CCCCC1 XNYOSXARXANYPB-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 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
- 150000002815 nickel Chemical class 0.000 description 1
- 125000005245 nitryl group Chemical group [N+](=O)([O-])* 0.000 description 1
- 150000002940 palladium Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003283 rhodium Chemical class 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/41—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/34—Nitriles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/06—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms of an acyclic and unsaturated carbon skeleton
- C07C255/07—Mononitriles
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/10—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and halogen atoms, or nitro or nitroso groups, bound to the same acyclic carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/23—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same unsaturated acyclic carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
本发明提供一种伪C2对称性的手性双烯丙基取代化合物,所述伪C2对称性的手性双烯丙基取代化合物的结构如下式I所示,本发明还提供该化合物在制备伪C2对称性的手性双烯丙基取代化合物II、具有手性取代四氢呋喃类化合物III、伪C2对称性的手性双烯丙基取代化合物IV、伪C2对称性的手性双烷基硼类化合物V中的应用。本发明还提供一种伪C2对称性的手性双烯丙基取代化合物的制备方法,该制备方法操作简单,成本低,产率高,所得反应目标化合物对映选择性好,产率55~98%,对映选择性过量>95%,得到的化合物光学纯度极高。
Description
技术领域
本发明专利涉及化学医药和农药领域,尤其是指一种伪C2对称性的手性双烯丙基取代化合物及其制备方法和应用。
背景技术
手性烯丙基结构单元因其具有烯基等极易转化修饰的官能团和烯丙位较为稳定的手性位点使其成为被广泛合成与研究的热门结构单元。因此高效,普适,容易使用的烯丙基结构单元的合成方法一直是合成化学中的热点研究领域。而目前具有双手性烯丙基的结构单元因其两个手性烯丙基在反应中会有明显的相互干扰作用,而导致其反应活性较低和立体选择性控制困难,所以目前鲜有高效催化不对称合成的报道。
发明内容
本发明旨在至少在一定程度上解决现有技术中存在的技术问题之一,由此,在本发明的第一方面,本发明提供一种伪C2对称性的手性双烯丙基取代化合物,所述伪C2对称性的手性双烯丙基取代化合物的结构如下式I所示,
其中,R1、R2分别独立地选自-H、-CF3、羧基、氰基、酯基、硝基、羰基、取代的酰胺基、磺酰基、取代的磺酰胺基、亚磺酰基、取代的亚磺酰胺基、取代或未取代的芳基、取代或未取代的杂芳基、取代或未取代的茂金属基,且R1、R2不相同和R1、R2其中一个为苯甲酰基时另一个不为-H;所述取代芳基、取代杂芳基和取代茂金属基的取代基为卤素、硝基、酚羟基、取代的磺酰胺、取代的硅基、烷基、烷氧基、氧羰基、氮羰基、-CF3、-CN或取代的氨基,所述羰基包括烷基取代酰基、取代或未取代的芳甲酰基、取代或未取代的杂芳甲酰基、取代或未取代的茂金属甲酰基;
R3、R4独立地为-H、烷基、苯基、萘基、吡啶基、噻吩基、卤代烷基、C2~C20链烯基、取代或未取代的芳基、C5~C25芳基取代的烷基、C5~C25芳基取代的烯基、-OCOR7、-(C0~C8烷基)-OR8、-(C0~C8烷基)-SR9、或-(C1~C8烷基)-NR10R11、取代或不取代的5~20元不饱和杂环基;所述取代芳基的取代基为卤素、C1~C20烷基、C1~C20烷氧基、C1~C20羰基、-OCOR12、-CF3、-CN或取代的氨基;所述取代氨基的取代基为C1~C20烷基、C4~C24芳基或C2~C20链烯基;所述取代或不取代的不饱和杂环基含有1~5个杂原子,所述的杂原子为N、0或S;所述取代不饱和杂环基取代基为对甲苯磺酰基、C1~C20烷基、C1~C20烷氧基、C4~C24芳基、C5~C25芳基取代的C1~C20烷基、卤素或C2~C20链烯基;
或,R3和R4组合成环,所述的环为C4~C24饱和或不饱和的环烷基、5~20元不饱和或不饱和的杂环基;所述的杂环基含有1~3个杂原子,所述的杂原子为N、0或S;
R1、R2其中一个为-COOMe时,R3和R4不为甲基。
R5、R6独立地为-H、C1~C20烷基、C1~C20卤代烷基、C2~C20链烯基、C4~C24芳基、C5~C25芳基取代的C1~C20烷基、-OCOR13、-(C0~C8烷基)-OR14、-(C0~C8烷基)-SR15、或-(C0~C8烷基)-NR16R17,且R5、R6至少有一个为-H;
R7~R17独立地选自C1~C8烷基、C5~C14芳基取代的C1~C8烷基或C4~C15芳基。
优选地,R1、R2分别独立地选自-H、-COOtBu、羧基、氰基;
R3、R4独立地为-H、烷基、苯基、萘基、吡啶基、噻吩基或取代苯基,所述取代苯基的取代基选自卤素、烷基、烷氧基;或,R3和R4组合成环,所述的环为C4~C24饱和或不饱和的环烷基、5~20元不饱和或不饱和的杂环基;所述的杂环基含有1~3个杂原子,所述的杂原子为N、0或S;
R5、R6独立地为-H、C1~C20烷基。
在本发明的第二方面,本发明提供一种在本发明的第一方面所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,反应式如下所示,
其中,LG为OCO2R18、OP(O)2OR19、卤素、-OR20、氧磺酰基中的一种,R18、R19分别独立地为C1~C8烷基、C5~C14芳基取代的C1~C8烷基或C4~C15芳基,R20为C1~C8烷基、C5~C14芳基取代的C1~C8烷基或C4~C15芳基;
所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,包括如下步骤:以铱络合物作为催化剂,底物-1与底物-2进行催化反应,得到式I所示的伪C2对称性的手性双烯丙基取代化合物。
在本发明的一个或多个实施例中,伪C2对称性的手性双烯丙基取代化合物的制备方法,反应体系中,还加入碱,所述碱选自醇的碱金属盐、胺的碱金属盐、碱金属碳酸盐、碱金属氢氧化物或第一有机碱中的一种或多种;
优选地,所述醇的碱金属盐为叔丁醇钾、叔丁醇钠、异丙醇钾或异丙醇钠,所述胺的碱金属盐为二异丙基胺基锂、双三甲基硅基胺基锂、双三甲基硅基胺基钠或双三甲基硅基胺基钾,所述碱金属碳酸盐为碳酸钾、碳酸钠或碳酸铯;所述碱金属氢氧化物为氢氧化钾或氢氧化钠,所述第一有机碱为三乙胺、四甲基乙二胺、1,5-二氮杂二环[4.3.0]壬-5-烯、1,8-二氮杂二环十一碳-7-烯、1,4-二氮杂二环[2.2.2]辛烷、吡啶、4-二甲氨基吡啶、N-甲基吗啉、三乙烯二胺、四甲基胍、2-叔丁基-1,1,3,3-四甲基胍;
更优选地,所述碱选自第一有机碱或碱金属碳酸盐中的一种或两种;
任选地,所述碱与底物-1的摩尔比为(0.01~10)∶1。
在本发明的一个或多个实施例中,伪C2对称性的手性双烯丙基取代化合物的制备方法,反应在溶剂中进行,所述溶剂选自甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、乙酸乙酯、乙酸异丁酯、乙酸异丙酯、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种。
在本发明的一个或多个实施例中,伪C2对称性的手性双烯丙基取代化合物的制备方法,所述铱络合物与底物-1的摩尔比为(0.0001~10)∶1;
所述铱络合物的制备方法包括如下步骤:将金属铱盐和手性配体L以1:2摩尔比溶于有机溶剂中,加入第二有机碱经反应,得到所述铱络合物,控制反应温度为30~70℃,优选地,控制反应温度为40~60℃;
优选地,所述金属铱盐选自[Ir(COD)Cl]2、[Ir(DBCOT)Cl]2、[Ir(COD)OMe]2中一种或多种;
优选地,所述第二有机碱选自三乙胺、四甲基乙二胺、1,5-二氮杂二环[4.3.0]壬-5-烯、1,8-二氮杂二环十一碳-7-烯、1,4-二氮杂二环[2.2.2]辛烷、吡啶、4-二甲氨基吡啶、N-甲基吗啉、三乙烯二胺、四甲基胍、2-叔丁基-1,1,3,3-四甲基胍中的一种或多种。
在本发明的一个或多个实施例中,伪C2对称性的手性双烯丙基取代化合物的制备方法,反应体系中,还加入手性配体,所述手性配体的结构式选自如下结构中一种或多种:
在本发明的一个或多个实施例中,伪C2对称性的手性双烯丙基取代化合物的制备方法,所述底物-1与底物-2的摩尔比为1:(2~10);
优选地,控制反应体系中所述底物-1的浓度范围为0.001~3.0M。
在本发明的一个或多个实施例中,伪C2对称性的手性双烯丙基取代化合物的制备方法,控制反应温度为-20~110℃;
优选地,控制反应温度为0~30℃;
任选地,控制反应时间为0.1~96h。
在本发明的第三方面,本发明提供一种在本发明第一方面所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物II和/或具有手性取代四氢呋喃类化合物III中的应用,
所述伪C2对称性的手性双烯丙基取代化合物II的结构式为
所述具有手性取代四氢呋喃类化合物III的结构式为
优选地,所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物II的化学式如下所示:
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物II,包括:将所述伪C2对称性的手性双烯丙基取代化合物I在酸中进行水解,得到所述的伪C2对称性的手性双烯丙基取代化合物II:
优选地,所述酸为三氟乙酸、盐酸或硫酸甲磺酸;
优选地,所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物II在溶剂中进行,所述溶剂选自甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、甲苯和二氧六环中的一种或多种。
进一步地,伪C2对称性的手性双烯丙基取代化合物II制备具有手性取代四氢呋喃类化合物III的化学式如下所示:
伪C2对称性的手性双烯丙基取代化合物II制备具有手性取代四氢呋喃类化合物III,包括:将伪C2对称性的手性双烯丙基取代化合物II溶于有机溶剂中,加入碳酸盐或碳酸氢盐、碘,在-40~30℃下反应,反应完成后加入硫代硫酸钠饱和水溶液淬灭,再经柱层析得到所述具有手性取代四氢呋喃类化合物III:
优选地,所述碳酸盐或碳酸氢盐为碱金属的碳酸盐或碳酸氢盐;所述有机溶剂选自乙酸乙酯、乙酸异丁酯、乙酸异丙酯、甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种;
优选地,反应温度控制为-40~0℃。
在本发明的第四方面,本发明提供一种在本发明第一方面所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物IV中的应用,所述伪C2对称性的手性双烯丙基取代化合物IV的结构式为
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物IV的化学式如下所示:
伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物IV,包括:在有机溶剂中加入伪C2对称性的手性双烯丙基取代化合物I和水,在碱金属盐的存在下通过加热或者微波反应,得到所述伪C2对称性的手性双烯丙基取代化合物IV;
优选地,在惰性气体保护下,在溶剂中加入伪C2对称性的手性双烯丙基取代化合物I、水和碱金属盐,在50~180℃反应0.1~24小时;
优选地,控制所述反应体系中伪C2对称性的手性双烯丙基取代化合物I的浓度范围为0.001~3.0M;
优选地,所述水与伪C2对称性的手性双烯丙基取代化合物I的摩尔比为1:(1~100);
优选地,所述有机溶剂选自乙酸乙酯、乙酸异丁酯、乙酸异丙酯、甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种;所述碱金属盐为卤化锂、卤化钠、卤化钾、硫酸锂、硫酸钠、硫酸钾、氰化钾、氰化钠和氰化锂中的一种或多种;
更优选地,所述有机溶剂为二甲亚砜、N,N-二甲基甲酰胺或N,N-二甲基乙酰胺;
任选地,控制反应温度为130~160℃。
在本发明的第五方面,本发明提供一种在本发明第一方面所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烷基硼类化合物V中的应用,所述伪C2对称性的手性双烷基硼类化合物V的结构式为:其中,R21为 中的任意一种;
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烷基硼类化合物V的反应式如下所示:
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烷基硼类化合物V,包括:在惰性气体保护下,在有机溶剂中加入伪C2对称性的手性双烯丙基取代化合物I、氢硼化合物、金属催化剂和配体,在0~100℃反应0.5~24小时;
其中,所述反应体系中,伪C2对称性的手性双烯丙基取代化合物I的浓度范围为0.001~3.0M;
优选地,所述氢硼化合物与所述伪C2对称性的手性双烯丙基取代化合物I的摩尔比为1:(2~20);
优选地,所述有机溶剂选自乙酸乙酯、乙酸异丁酯、乙酸异丙酯、甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种;优选地,所述有机溶剂为二氯甲烷、三氯甲烷、1,2-二氯乙烷、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、甲苯或二氧六环;
优选地,所述金属催化剂为铜盐、镍盐、钯盐、铱盐或铑盐;所述金属催化剂的阴离子选自氯、溴、碘、醋酸根、硫酸根、硫酸氢根、磷酸根、磷酸氢根、磷酸二氢根、氢氧根、甲氧负离子、乙酰丙酮负离子、六氟乙酰丙酮负离子和四氟硼酸根中的一种或多种;
优选地,所述金属催化剂为醋酸亚铜、碘化亚铜、氯化亚铜、Ni(COD)2、醋酸钯、四(三苯基膦)钯、[Ir(COD)Cl]2、[Ir(DBCOT)Cl]2、[Ir(COD)OMe]2、Rh(COD)2BF4、Rh(acac)(COD)、[Rh(COE)2Cl]2、[Rh(C2H4)2Cl]2、[Rh(OMe)(1,5-cod)]2。
优选地,所述配体为有机膦配体、氮杂卡宾配体、亚磷酰胺配体和噁唑啉类配体;优选地,所述配体为三苯基膦、三环己基膦、三叔丁基膦、双(二苯基膦基)甲烷、1,2-双(二苯基膦基)乙烷、1,3-双(二苯基膦基)丙烷或1,4-双(二苯基膦基)丁烷有机磷配体。
优选地,所述氢硼化合物为儿茶酚硼烷、频那醇硼烷、丙二醇硼烷、(+)-二异松蒎烯基硼烷、(-)-二异松蒎烯基硼烷、二环己基硼烷。优选地,控制反应温度为20~40℃。
在本发明的第六方面,本发明提供一种在本发明第一方面所述的伪C2对称性的手性双烯丙基取代化合物和/或本发明第三方面制备得到的伪C2对称性的手性双烯丙基取代化合物II、具有手性取代四氢呋喃类化合物III和/或本发明第四方面制备得到的伪C2对称性的手性双烯丙基取代化合物IV和/或本发明第五方面制备得到的伪C2对称性的手性双烷基硼类化合物V在制备农药和/或抑菌剂中的应用。
本发明还提供在本发明第一方面所述的伪C2对称性的手性双烯丙基取代化合物和/或本发明第三方面制备得到的伪C2对称性的手性双烯丙基取代化合物II、具有手性取代四氢呋喃类化合物III和/或本发明第四方面制备得到的伪C2对称性的手性双烯丙基取代化合物IV和/或本发明第五方面制备得到的伪C2对称性的手性双烷基硼类化合物V在制备手性非天然氨基酸及其衍生物中的用途。
本发明还提供在本发明第一方面所述的伪C2对称性的手性双烯丙基取代化合物和/或本发明第三方面制备得到的伪C2对称性的手性双烯丙基取代化合物II、具有手性取代四氢呋喃类化合物III和/或本发明第四方面制备得到的伪C2对称性的手性双烯丙基取代化合物IV和/或本发明第五方面制备得到的伪C2对称性的手性双烷基硼类化合物V在制备具有手性氨基酸结构单元、手性烷基羧酸和羧酸酯结构单元和手性胺结构单元的化合物中的用途。
相比于现有技术,本发明的有益效果在于:
1、本发明提供一种伪C2对称性的手性双烯丙基取代化合物,并提供了其在制备伪C2对称性的手性双烯丙基取代化合物II、具有手性取代四氢呋喃类化合物III、伪C2对称性的手性双烯丙基取代化合物IV、伪C2对称性的手性双烷基硼类化合物V中的应用;
2、本发明提供一种伪C2对称性的手性双烯丙基取代化合物的制备方法,该制备方法操作简单,成本低,产率高,所得反应目标化合物对映选择性好,产率55~98%,对映选择性过量>95%,得到的化合物光学纯度极高;
3、本发明方法合成简单,成本低,产率高,所得反应目标化合物对映选择性好,产率55~98%,对映选择性过量>95%;
4、本发明方法采用铱络合物作为催化剂,在反应中表现出催化反应速度快和催化剂用量低的优点;
5、本发明提供的方法只需要使用商业可得的配体,方法整体简便易行;
6、本发明提供的方法制备的化合物里,有多个重要官能团,可以轻易转化成其他有用基团,能作为原料合成大量的有效化合物,比如用于合成含手性胺结构的化合物,而很多具有重要生物活性的化合物都具有手性胺结构单元;
7、本发明提供的方法能够容忍非常多类型的底物,包括药物化学中重要的杂环类底物;
8、本发明的提供的方法可以制备手性非天然氨基酸及其衍生物;
9、本发明的方法得到的化合物可以用于制备具有手性氨基酸结构单元的抗抑郁类药物、抗肿瘤类药物或天然产物。
10、本发明的方法得到的化合物可以用于制备农药和抑菌剂。
具体实施方式
下面将结合实施例对本发明的方案进行解释。本领域技术人员将会理解,下面的实施例仅用于说明本发明,而不应视为限定本发明的范围。实施例中未注明具体技术或条件的,按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。以下实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行,使用的方法如无特别说明,均为本领域公知的常规方法,使用的耗材和试剂如无特别说明,均为市场购得。除非另有说明,本文中所用的专业与科学术语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法或材料也可应用于本发明中。
以下实施例中,采用的手性配体(S,S,S)-L1的结构式为采用的配体(R,R,R)-L1的结构式为/>采用的手性配体(S,Sa)-L1的结构式为
实施例1
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol肉桂基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率97%,熔点92-94℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate1.0mL/min,λ=220nm);tr=5.78 and 6.61min.[α]25 D=-108.66(c 1.64,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.44–7.40(m,2H),7.35–7.26(m,7H),7.25–7.21(m,1H),6.64(ddd,J=17.0,10.1Hz,9.9Hz,1H),6.20(ddd,J=16.9,10.2,9.3Hz,1H),5.31(dd,J=10.2,1.6Hz,1H),5.22(dd,J=17.0,1.4Hz,1H),5.20(dd,J=10.1,1.6Hz,1H),5.13(dd,J=16.9,1.4Hz,1H),3.91(d,J=9.3Hz,1H),3.83(d,J=9.9Hz,1H),0.99(s,9H).13C NMR(101MHz,Chloroform-d)δ165.4,138.8,138.4,134.6,134.3,129.09,129.06,128.49,128.45,127.9,127.6,119.7,119.6,118.5,84.0,58.6,55.3,53.4,27.2.;HRMS(ESI+)计算值C25H27NNaO2 +([M+Na]+):396.1934,测量值:396.1923。
实施例2
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol对氟苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率97%,熔点54-56℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate 1.0mL/min,λ=220nm);tr=5.28and 5.72min.[α]25 D=-87.68(c 1.25,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.42–7.36(m,2H),7.32–7.27(m,2H),7.04–6.94(m,4H),6.59(ddd,J=17.2,10.0,10.0Hz,1H),6.17(ddd,J=17.2,10.2,9.2Hz,1H),5.32(dd,J=10.0,1.2Hz,1H),5.23(dd,J=10.4,1.2Hz,1H),5.20(dd,J=17.2,1.0Hz,1H),5.13(dd,J=17.2,1.0Hz,1H),3.90(d,J=9.2Hz,1H),3.81(d,J=10.0Hz,1H),1.03(s,9H).13C NMR(101MHz,Chloroform-d)δ165.3,162.3(d,J=246Hz),162.2(d,J=245Hz),134.5(d,J=3Hz),134.14,134.10(d,J=3Hz),133.8,130.7(d,J=7Hz),130.6(d,J=8Hz),120.0,119.9,118.2,115.4(d,J=21Hz),115.3(d,J=22Hz),84.3,58.7,54.3,52.5,27.2.;19F NMR(376MHz,Chloroform-d)δ-114.16–-114.39(m),-114.46–-114.71(m).HRMS(ESI+)计算值C25H26F2NO2 +([M+H]+):410.1926,测量值:410.1922。
实施例3
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol对氯苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率96%,熔点58-60℃,手性高效液相色谱测定产物的对映选择性过量98%,HPLC(Chiralpak ID,i-propanol/hexane=2/98,flowrate 1.0mL/min,λ=220nm);tr=4.95 and 5.94min.[α]25 D=-120.96(c 1.46,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.37–7.33(m,2H),7.32–7.26(m,5H),7.26–7.24(m,1H),6.56(ddd,J=17.0,10.0Hz,10.0Hz,1H),6.15(ddd,J=16.9,10.2,9.4Hz,1H),5.33(dd,J=10.2,1.5Hz,1H),5.24(dd,J=10.2,1.5Hz,1H),5.21(dd,J=16.9,1.2Hz,1H),5.14(dd,J=16.9,1.2Hz,1H),3.88(d,J=9.4Hz,1H),3.79(d,J=10.0Hz,1H),1.04(s,9H).13C NMR(101MHz,Chloroform-d)δ165.1,137.1,136.7,133.9,133.7,133.5,130.4,130.4,128.7,128.6,120.28,120.25,118.1,84.6,58.3,54.5,52.6,27.2.;HRMS(ESI+)计算值C25H25NNaO2 +([M+Na]+):464.1155,测量值:464.1133。
实施例4
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol对溴苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率99%,熔点98-100℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate 1.0mL/min,λ=220nm);tr=6.021 and 7.65min.[α]25 D=-114.83(c 1.51,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.46–7.40(m,4H),7.31–7.26(m,2H),7.22–7.17(m,2H),6.56(ddd,J=17.0,10.0Hz,10.0Hz,1H),6.15(ddd,J=16.9,10.2,9.3Hz,1H),5.32(dd,J=10.1,1.5Hz,1H),5.24(dd,J=10.1,1.2Hz,1H),5.20(dd,J=16.9,1.0Hz,1H),5.14(dd,J=16.9,1.0Hz,1H),3.87(d,J=9.3Hz,1H),3.77(d,J=10.0Hz,1H),1.04(s,9H).13C NMR(101MHz,Chloroform-d)δ165.1,137.6,137.2,133.8,133.5,131.7,131.6,130.8,130.7,122.0,121.8,120.4,120.3,118.1,84.6,58.2,54.6,52.7,27.3.;HRMS(APCI+)计算值C25H26Br2NO2 +([M+H]+):530.0325,测量值:530.0337。
实施例5
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol对三氟甲基苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率91%,熔点59-61℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate 1.0mL/min,λ=220nm);tr=4.14 and 4.71min.[α]25 D=-88.82(c 0.93,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.61–7.54(m,6H),7.46(d,J=8.2Hz,2H),6.61(ddd,J=17.0,10.0Hz,10.0Hz,1H),6.19(ddd,J=16.9,10.2,9.4Hz,1H),5.38(dd,J=10.2,1.4Hz,1H),5.262(dd,J=10.2,1.4Hz,1H),5.257(dd,J=16.9,1.0Hz,1H),5.17(dd,J=16.9,1.0Hz,1H),3.99(d,J=9.4Hz,1H),3.90(d,J=10.0Hz,1H),0.99(s,9H).13C NMR(101MHz,Chloroform-d)δ164.9,142.5,142.1,133.3,133.1,130.3(q,J=32Hz),130.1(q,J=34Hz),129.51,129.49,125.5(q,J=4Hz),125.4(q,J=4Hz),123.93(q,J=271Hz),123.90(q,J=271Hz),121.0,120.8,117.9,84.9,58.0,54.9,53.1,27.1.;19F NMR(376MHz,Chloroform-d)δ-62.67,-62.77.HRMS(APCI+)计算值C27H26F6NO2 +([M+H]+):510.1862,测量值:510.1875。
实施例6
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol对甲基苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率99%,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate1.0mL/min,λ=220nm);tr=6.59 and 12.39min.[α]25 D=-118.70(c 0.58,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.31–7.27(m,2H),7.22–7.18(m,2H),7.13–7.06(m,4H),6.60(ddd,J=17.0,10.0Hz,10.0Hz,1H),6.19(ddd,J=16.9,10.2,9.4Hz,1H),5.28(dd,J=10.2,1.6Hz,1H),5.19(dd,J=17.0,1.5Hz,1H),5.18(dd,J=10.0,1.6Hz,1H),5.12(dd,J=16.9,1.5,1H),3.87(d,J=9.4Hz,1H),3.77(d,J=10.0Hz,1H),2.32(s,3H),2.29(s,3H),1.02(s,9H).13C NMR(101MHz,Chloroform-d)δ165.5,137.5,137.2,135.8,135.5,134.9,134.6,129.2,129.0,128.92,128.85,119.33,119.28,118.6,83.8,58.7,55.0,53.0,27.2,21.1,21.0.;HRMS(ESI+)计算值C27H31NNaO2 +([M+Na]+):424.2247,测量值:424.2238。
实施例7
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol对甲氧基苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率81%,手性高效液相色谱测定产物的对映选择性过量99%,HPLC(Chiralpak IE,i-propanol/hexane=10/90,flow rate1.0mL/min,λ=238nm);tr=7.48 and 10.19min.[α]25 D=-126.00(c 0.55,CH2Cl2);核磁测定非对映选择性18:1,1H NMR(400MHz,Chloroform-d)δ7.36–7.29(m,2H),7.26–7.21(m,2H),6.86–6.80(m,4H),6.59(ddd,J=17.0,10.1,10.0Hz,1H),6.18(ddd,J=16.9,10.2,9.3Hz,1H),5.28(dd,J=10.2,1.7Hz,1H),5.19(dd,J=10.1,1.5Hz,1H),5.18(dd,J=17.0,1.7Hz,1H),5.11(d,J=16.9,1.7Hz,1H),3.86(d,J=9.3Hz,1H),3.79(s,3H),3.78(d,J=10.0Hz,1H),3.76(s,3H),1.04(s,9H).13C NMR(101MHz,Chloroform-d)δ165.6,159.1,159.0,134.8,134.5,131.0,130.6,130.1,130.0,119.19,119.16,118.7,113.83,113.77,83.8,59.1,55.3,55.2,54.4,52.6,27.3.;HRMS(ESI+)计算值C27H31NNaO4 +([M+Na]+):456.2145,测量值:456.2135。
实施例8
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol间氟苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率95%,手性高效液相色谱测定产物的对映选择性过量99%,HPLC(Chiralpak IE,i-propanol/hexane=1/99,flow rate 1.0mL/min,λ=238nm);tr=6.60 and 8.11min.[α]25 D=-94.44(c 0.72,CH2Cl2);核磁测定非对映选择性20:1,1H NMR(400MHz,Chloroform-d)δ7.33–7.28(m,1H),7.26–7.24(m,1H),7.21(dt,J=7.7,1.5Hz,1H),7.16–7.11(m,2H),7.04–6.92(m,3H),6.57(ddd,J=17.0,10.0,9.9Hz,1H),6.17(ddd,J=16.9,10.2,9.4Hz,1H),5.35(dd,J=10.0,1.5Hz,1H),5.25(dd,J=10.2,1.5Hz,1H),5.23(dd,J=17.0,1.5Hz,1H),5.16(dd,J=16.9,1.5Hz,1H),3.90(d,J=9.4Hz,1H),3.81(d,J=9.9Hz,1H),1.05(s,9H).13C NMR(101MHz,Chloroform-d)δ165.1,162.62(d,J=245Hz),162.55(d,J=245Hz),140.9(d,J=7Hz),140.5(d,J=7Hz),133.7,133.4,130.1(d,J=9Hz),130.0(d,J=8Hz),125.0(d,J=3Hz),124.7(d,J=3Hz),120.4,120.3,118.0,116.2(d,J=34Hz),115.9(d,J=34Hz),114.9(d,J=21Hz),114.(d,J=29Hz),114.6(d,J=29Hz),84.6,58.2,54.8(d,J=2Hz),52.9(d,J=2Hz),27.2.;19F NMR(376MHz,Chloroform-d)δ-112.48–-112.59(m),-112.59–-112.68(m).HRMS(ESI+)计算值C25H25F2NNaO2 +([M+Na]+):432.1746,测量值:432.1740。
实施例9
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol间氯苯基烯丙碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率86%,熔点78-80℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=1/99,flow rate 1.0mL/min,λ=220nm);tr=5.98 and 7.84min.[α]25 D=-90.81(c 0.74,CH2Cl2);核磁测定非对映选择性17:1,1H NMR(400MHz,Chloroform-d)δ7.36(dt,J=5.4,2.1Hz,2H),7.29–7.26(m,3H),7.26–7.22(m,3H),6.57(ddd,J=17.0,10.3,10.0Hz,1H),6.17(ddd,J=16.9,10.2,9.5Hz,1H),5.35(dd,J=10.2,1.5Hz,1H),5.27(dd,J=10.3,1.3Hz,1H),5.22(dd,J=17.0,1.5Hz,1H),5.17(dd,J=16.9,1.3Hz,1H),3.88(d,J=9.5Hz,1H),3.78(d,J=10.0Hz,1H),1.07(s,9H).13C NMR(101MHz,Chloroform-d)δ165.0,140.5,140.1,134.3,134.2,133.7,133.4,129.9,129.8,129.5,128.8,128.1,127.8,127.6,127.0,120.5,117.8,84.8,58.2,54.8,52.9,27.3.;HRMS(ESI+)计算值C25H25Cl2NNaO2 +([M+Na]+):464.1155,测量值:464.1156。
实施例10
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol间溴苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率88%,熔点108-110℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=1/99,flow rate 1.0mL/min,λ=220nm);tr=6.99 and 8.55min.[α]25 D=-82.36(c 1.27,CH2Cl2);核磁测定非对映选择性18:1,1H NMR(400MHz,Chloroform-d)δ7.50(t,J=1.9Hz,1H),7.44–7.37(m,4H),7.30(dt,J=7.8,1.4Hz,1H),7.19(dt,J=11.0,7.8Hz,2H),6.56(ddd,J=17.0,10.2,10.0Hz,1H),6.17(ddd,J=16.8,10.1,9.5Hz,1H),5.34(dd,J=10.2,1.5Hz,1H),5.27(dd,J=10.1,1.4Hz,1H),5.22(dd,J=16.9,1.4Hz,1H),5.17(dd,J=16.9,1.0Hz,1H),3.86(d,J=9.5Hz,1H),3.76(d,J=10.0Hz,1H),1.08(s,9H).13C NMR(101MHz,Chloroform-d)δ165.0,140.8,140.4,133.6,133.3,132.3,131.7,131.1,130.8,130.1,130.1,128.0,127.4,122.6,122.4,120.6,120.5,117.8,84.9,58.2,54.8,52.8,27.3.;HRMS(ESI+)计算值C25H26Br2NO2 +([M+H]+):530.0325,测量值:530.0313。
实施例11
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol间甲基苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率93%,熔点82-84℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=1/99,flow rate 1.0mL/min,λ=220nm);tr=6.58 and 8.90min.[α]25 D=-96.06(c 0.66,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.26(d,J=8.1Hz,1H),7.22–7.16(m,3H),7.15–7.10(m,2H),7.08(dd,J=7.5,1.3Hz,1H),7.05–7.01(m,1H),6.63(ddd,J=16.9,10.1,9.9Hz,1H),6.21(ddd,J=16.9,10.2,9.4Hz,1H),5.29(dd,J=10.1,1.7Hz,1H),5.201(dd,J=10.1,1.5Hz,1H),5.198(dd,J=16.9,1.7Hz,1H),5.13(dd,J=16.9,1.5Hz,1H),3.87(d,J=9.4Hz,1H),3.77(d,J=9.9Hz,1H),2.32(s,3H),2.30(s,3H),1.01(s,9H).13C NMR(101MHz,Chloroform-d)δ165.5,138.7,138.3,138.0,137.9,134.8,134.5,129.9,129.6,128.6,128.38,128.36,128.2,126.1,125.9,119.44,119.39,118.4,83.8,58.5,55.3,53.4,27.2,21.4,21.3.;HRMS(ESI+)计算值C27H31NNaO2 +([M+Na]+):424.2247,测量值:424.2238。
实施例12
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol间甲氧基苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率92%,熔点103-105℃,手性高效液相色谱测定产物的对映选择性过量96%,HPLC(Chiralpak IE,i-propanol/hexane=10/90,flow rate 1.0mL/min,λ=220nm);tr=6.72 and 9.24min.[α]25 D=-99.07(c 0.75,CH2Cl2);核磁测定非对映选择性10:1,1H NMR(400MHz,Chloroform-d)δ7.24–7.20(m,1H),7.20–7.16(m,1H),7.03–6.99(m,1H),6.97–6.92(m,2H),6.88(t,J=2.1Hz,1H),6.83–6.76(m,2H),6.60(ddd,J=17.0,10.0,10.0Hz,1H),6.18(ddd,J=16.9,10.2,9.3Hz,1H),5.30(dd,J=10.0,1.7Hz,1H),5.21(dd,J=16.9,1.2Hz,1H),5.19(dd,J=10.2,1.2Hz,1H),5.12(dd,J=17.0,1.7Hz,1H),3.87(d,J=9.3Hz,1H),3.81(d,J=10.0Hz,1H),3.80(s,3H),3.78(s,3H),1.04(s,9H).13C NMR(101MHz,Chloroform-d)δ165.4,159.52,159.48,140.2,139.7,134.5,134.3,129.44,129.42,121.34,121.29,119.6,119.5,115.0,114.3,113.6,113.2,84.0,58.4,55.3,55.21,55.19,53.5,27.2.;HRMS(ESI+)计算值C27H31NNaO4 +([M+Na]+):456.2145,测量值:456.2138。
实施例13
的制备/>
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol 3,4-二氯苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率98%,熔点64-66℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate 1.0mL/min,λ=220nm);tr=5.07 and 6.66min.[α]25 D=-118.04(c 0.56,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.45(d,J=2.1Hz,1H),7.43–7.38(m,2H),7.36–7.29(m,2H),7.20(dd,J=8.4,2.2Hz,1H),6.52(ddd,J=17.0,10.0.9.9Hz,1H),6.14(ddd,J=16.8,10.2,9.5Hz,1H),5.36(dd,J=10.0,1.4Hz,1H),5.30(dd,J=10.2,1.2Hz,1H),5.22(dd,J=17.0,1.4Hz,1H),5.30(dd,J=16.8,1.2Hz,1H),3.86(d,J=9.5Hz,1H),3.75(d,J=9.9Hz,1H),1.10(s,9H).13C NMR(101MHz,Chloroform-d)δ164.8,138.5,138.3,133.1,132.8,132.7,132.5,132.2,132.0,131.3,130.6,130.54,130.46,128.6,128.1,121.1,121.0,117.6,85.3,58.0,54.1,52.3,27.3.;HRMS(ESI+)计算值C25H23Cl4NNaO2 +([M+Na]+):532.0375,测量值:532.0360。
实施例14
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol 3,5-二氯苯基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率97%,熔点88-90℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate 1.0mL/min,λ=210nm);tr=5.00 and 5.86min.[α]25 D=-86.52(c 0.69,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.30(d,J=2.0Hz,3H),7.27(t,J=1.9Hz,1H),7.19(d,J=1.8Hz,2H),6.50(ddd,J=16.9,10.1,9.9Hz,1H),6.13(ddd,J=16.9,10.1,9.6Hz,1H),5.37(dd,J=10.1,1.3Hz,1H),5.33(dd,J=10.1,1.1Hz,1H),5.23(dd,J=16.9,1.3Hz,1H),5.21(dd,J=16.9,1.1Hz,1H),3.85(d,J=9.6Hz,1H),3.72(d,J=9.9Hz,1H),1.14(s,9H).13C NMR(101MHz,Chloroform-d)δ164.7,141.5,141.2,135.1,135.0,132.9,132.5,128.3,128.0,127.51,127.49,121.4,121.3,117.2,85.5,57.6,54.5,52.5,27.3.;HRMS(ESI+)计算值C25H23Cl4NNaO2 +([M+Na]+):532.0375,测量值:532.0368。
实施例15
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol 2-萘基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率97%,熔点116-118℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flow rate 1.0mL/min,λ=232nm);tr=10.70 and 21.76min.[α]25 D=-155.41(c 0.85,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.85–7.76(m,8H),7.61(dd,J=8.6,1.8Hz,1H),7.51–7.43(m,5H),6.79(ddd,J=17.0,10.0Hz,10.0Hz,1H),6.35(ddd,J=16.9,10.0Hz,9.8Hz,1H),5.37(dd,J=10.2,1.5Hz,1H),5.29(dd,J=17.0,1.5Hz,1H),5.23(dd,J=10.0,1.2Hz,1H),5.20(dd,J=16.9,1.2Hz,1H),4.17(d,J=10.0Hz,1H),4.06(d,J=10.0Hz,1H),0.84(s,9H).13C NMR(101MHz,Chloroform-d)δ165.6,136.1,135.9,134.5,134.4,133.3,133.2,132.9,132.7,128.3,128.23,128.20,128.1,128.0,127.9,127.6,127.5,126.9,126.7,126.2,126.12,126.05,126.0,120.0,119.8,118.5,84.1,58.6,55.5,53.6,27.1.;HRMS(ESI+)计算值C33H31NNaO2 +([M+Na]+):496.2247,测量值:496.2242。
实施例16
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(S,Sa)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol 1-萘基烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率77%,熔点80-82℃,手性高效液相色谱测定产物的对映选择性过量96%,HPLC(Chiralpak IE,i-propanol/hexane=2/98,flowrate 1.0mL/min,λ=220nm);tr=11.46 and 17.56min.[α]25 D=-123.58(c 0.95,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ8.41(d,J=8.7Hz,1H),8.09(d,J=8.7Hz,1H),7.88(dt,J=7.9,1.9Hz,2H),7.85–7.76(m,2H),7.75–7.64(m,2H),7.62–7.51(m,3H),7.49–7.37(m,4H),6.64(ddd,J=16.7,9.8.9.5Hz,1H),6.06(ddd,J=16.9,10.2,9.2Hz,1H),5.37(dd,J=16.7,1.2Hz,1H),5.36(dd,J=9.8,1.2Hz,1H),5.21(d,J=9.5Hz,1H),5.03(d,J=9.2Hz,1H),4.83(dd,J=10.2,1.2Hz,1H),4.65(dd,J=16.9,1.2Hz,1H),3.15(s,3H).13C NMR(101MHz,Chloroform-d)δ167.5,135.5,135.4,134.8,134.3,134.1,133.9,132.3,130.7,129.2,128.9,128.6,128.1,126.6,126.3,125.9,125.8,125.6,125.3,125.2,125.1,122.6,122.4,119.4,118.2,118.1,59.3,52.7,48.5,46.0.;HRMS(ESI+)计算值C30H25NNaO2 +([M+Na]+):454.1778,测量值:454.1771。
实施例17
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol 3-吡啶烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率56%,熔点106-108℃,手性高效液相色谱测定产物的对映选择性过量>99%,HPLC(Chiralpak IE,i-propanol/hexane=20/80,flow rate 1.0mL/min,λ=220nm);tr=27.78 and 36.47min.[α]25 D=-112.50(c 0.84,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ8.54(ddt,J=14.3,4.8,2.5Hz,4H),7.88(ddd,J=8.0,2.4,1.6Hz,1H),7.74–7.66(m,1H),7.30–7.24(m,2H),6.60(ddd,J=17.0,10.0,9.9Hz,1H),6.17(ddd,J=16.9,10.2,9.4Hz,1H),5.40(dd,J=10.2,1.4Hz,1H),5.28(dd,J=17.0,1.0Hz,1H),5.27(dd,J=10.0,1.4Hz,1H),5.18(dd,J=16.9,1.0Hz,1H),3.97(d,J=9.4Hz,1H),3.89(d,J=9.9Hz,1H),1.04(s,9H).13C NMR(101MHz,Chloroform-d)δ164.8,150.5,150.2,149.3,149.1,136.4,135.9,134.3,133.9,133.1,132.7,123.4,123.3,121.1,121.0,117.7,85.2,58.3,52.8,50.7,27.2.;HRMS(APCI+)计算值C23H26N3O2 +([M+H]+):376.2020,测量值:376.2031。
实施例18
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol 2-噻吩烯丙基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率55%,熔点96-98℃,手性高效液相色谱测定产物的对映选择性过量96%,HPLC(Chiralpak IE,i-propanol/hexane=1/99,flowrate 1.0mL/min,λ=220nm);tr=9.26 and 10.42min.[α]25 D=-97.75(c 0.71,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.22(dd,J=5.1,1.2Hz,1H),7.19(dd,J=5.1,1.2Hz,1H),7.14–7.10(m,2H),6.97(dd,J=5.1,3.6Hz,1H),6.93(dd,J=5.1,3.6Hz,1H),6.46(ddd,J=16.9,10.0,9.8Hz,1H),6.15(ddd,J=16.8,10.2,9.2Hz,1H),5.34(dd,J=10.2,1.4Hz,1H),5.251(dd,J=10.0,1.2Hz,1H),5.246(dd,J=16.8,1.4Hz,1H),5.34(dd,J=16.9,1.2Hz,1H),4.23(d,J=9.2Hz,1H),4.16(d,J=9.8Hz,1H),1.13(s,9H).13C NMR(101MHz,Chloroform-d)δ165.0,140.32,140.25,133.9,133.8,126.8,126.6,126.5,126.4,124.9,124.8,120.1,119.7,118.4,84.3,59.6,50.3,48.7,27.3.;HRMS(ESI+)计算值C21H23NNaO2S2 +([M+Na]+):408.1062,测量值:408.1056。
实施例19
的制备
在25mL反应管中加入0.005mmol[Ir(COD)Cl]2、0.010mmol(R,R,R)-L1、0.5mL除氧THF和0.5mL除氧正丙胺,50℃下反应30分钟后在减压条件下蒸去溶剂得到铱催化剂。在25℃氮气保护下,依次加入0.20mmol氰基乙酸叔丁酯、0.44mmol肉桂基碳酸甲酯和0.40mmol碳酸铯和2mL二氯甲烷,在25℃下反应。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率87%,通过转化成酰胺后经手性高效液相色谱测定产物的对映选择性过量95%,[α]25 D=-9.03(c 1.03,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ5.84(ddd,J=17.2,11.6,8.7Hz,1H),5.82(ddd,J=17.2,10.4,9.0Hz,1H),5.203(dd,J=11.6,1.6Hz,1H),5.196(dd,J=17.2,1.2Hz,1H),5.12(dd,J=17.2,1.6Hz,1H),5.10(dd,J=10.4,1.2Hz,1H),2.75(dq,J=9.0,6.9Hz,1H),2.75(dq,J=8.7,6.8Hz,1H),1.51(s,9H),1.23(d,J=6.9Hz,3H),1.15(d,J=6.8Hz,3H).13C NMR(101MHz,Chloroform-d)δ166.0,136.7,136.4,118.3,118.2,117.8,84.1,58.4,42.7,41.6,27.9,17.2,16.5.;HRMS(ESI+)计算值C15H23NNaO2 +([M+Na]+):272.1621,测量值:272.1615。
实施例20
的制备
将0.2mmol实例14所得产物溶于2mL二氯乙烷中,加入1mL三氟乙酸,在氩气保护下反应2小时。通过薄层色谱监测反应,反应结束后,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率81%,熔点86-88℃,[α]25 D=115.71(c 0.91,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.30(dt,J=16.8,1.7Hz,2H),7.22(dd,J=19.6,1.9Hz,4H),6.79(bs,1H),6.35(ddd,J=16.9,10.1,9.6Hz,1H),6.10(ddd,J=16.8,10.0,9.8Hz,1H),5.38(dd,J=10.1,1.1Hz,1H),5.32(dd,J=10.0,1.2Hz,1H),5.25(d,J=16.8,1.1Hz,1H),5.20(d,J=16.9,1.2Hz,1H),3.85(d,J=9.6Hz,1H),3.80(d,J=9.8Hz,1H).13C NMR(101MHz,Chloroform-d)δ169.2,141.1,140.6,135.3,135.2,132.4,132.0,128.6,128.4,127.5,127.3,127.2,121.8,121.7,58.0,54.3,52.2.;HRMS(ESI+)计算值C21H14Cl4NNa2O2([M+2Na-H]+):497.9569,测量值:497.9573。
实施例21
的制备
将0.1mmol实例20所得产物溶于1mL乙腈中,在0℃下加入0.2mmol NaHCO3和0.2mmol I2,在氩气保护下反应5小时。通过薄层色谱监测反应,反应结束后,用10%Na2S2O3淬灭,用二氯甲烷你萃取三次,合并有机相再用10%NaHCO3和饱和食盐水洗。干燥后减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率57%,熔点232-234℃,手性高效液相色谱测定产物的对映选择性过量99%,HPLC(Chiralpak ID,i-propanol/hexane=20/80,flow rate 1.0mL/min,λ=210nm);tr=6.00 and 8.41min;[α]25 D=-50.14(c 0.74,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.45(t,J=1.8Hz,1H),7.38(t,J=1.8Hz,1H),7.24(d,J=1.8Hz,2H),7.10(d,J=1.8Hz,2H),6.30(ddd,J=16.8,10.0,9.3Hz,1H),5.61(d,J=10.0Hz,1H),5.50(d,J=16.8Hz,1H),4.96(ddd,J=9.4,5.7,5.5Hz,1H),3.95(d,J=5.5Hz,1H),3.72(d,J=9.3Hz,1H),3.36(dd,J=10.3,5.7Hz,1H),2.76(dd,J=10.3,9.4Hz,1H).13C NMR(101MHz,Chloroform-d)δ167.2,138.5,136.2,135.7,134.9,132.5,130.1,129.3,126.9,122.9,114.0,80.1,57.1,52.9,52.7,-1.3.;HRMS(ESI+)计算值C21H14Cl4INNaO2 +([M+Na]+):601.8716,测量值:601.8692。
实施例22
的制备
将0.2mmol实例14所得产物、29.2mg氯化锂、1.5mL DMF和13μL水加入到氩气保护的反应管中,回流反应2小时。反应结束后,加入2.5mL饱和氯化铵溶液,用2.5mL乙醚萃取三次,合并有机相用无水硫酸镁干燥。减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率69%,手性高效液相色谱测定产物的对映选择性过量99%,HPLC(Chiralpak IE,i-propanol/hexane=5/95,flow rate 1.0mL/min,λ=220nm);tr=6.13 and 6.45min.[α]25 D=-62.25(c 0.89,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.31(q,J=1.9Hz,2H),7.12(dd,J=8.4,1.8Hz,4H),6.11(ddd,J=16.9,10.2,9.0Hz,1H),5.90(ddd,J=16.9,10.2,8.6Hz,1H),5.42(dd,J=10.2,1.3Hz,1H),5.33(dd,J=10.2,1.5Hz,1H),5.25(dd,J=16.9,1.5Hz,1H),5.24(dd,J=16.9,1.3Hz,1H),3.54(dd,J=9.2,5.4Hz,1H),3.41(dd,J=9.3,8.6Hz,1H),3.12(dd,J=9.3,5.4Hz,1H).13C NMR(101MHz,Chloroform-d)δ143.2,142.4,135.9,135.64,135.55,133.8,128.2,128.0,126.5,126.2,121.0,119.8,117.9,49.5,48.0,42.8.;HRMS(ESI+)计算值C20H15Cl4NNa+([M+Na]+):431.9851,测量值:431.9860。
实施例23
的制备
在25mL反应管中加入0.01mmol[Ir(COD)Cl]2、0.02mmol DPPM和2mL二氯甲烷,在氩气保护下室温搅拌0.5小时。后加入0.20mmol实例15所得产物和1.0mmol 4,4,5,5-四甲基-1,3,2-二氧杂环戊硼烷,在室温下反应过夜。通过薄层色谱监测反应,反应结束后,用1mL甲醇淬灭,减压下除去溶剂之后通过硅胶柱层析纯化得到产物,产率71%,手性高效液相色谱测定产物的对映选择性过量99%,熔点92-95℃,HPLC(Chiralpak IE,i-propanol/hexane=5/95,flow rate 1.0mL/min,λ=220nm);tr=13.08 and 18.84min.[α]25 D=30.13(c 0.76,CH2Cl2);核磁测定非对映选择性>20:1,1H NMR(400MHz,Chloroform-d)δ7.84–7.79(m,4H),7.77–7.68(m,4H),7.60–7.50(m,2H),7.46–7.40(m,4H),3.49(dd,J=12.1,3.2Hz,1H),3.33(dd,J=12.0,2.9Hz,1H),2.48–2.32(m,1H),2.11–2.03(m,1H),1.91–1.70(m,1H),1.59–1.44(m,1H),1.18(s,6H),1.18(s,6H),1.02(s,6H),1.00(s,6H),0.89(s,9H),0.67–0.58(m,1H),0.53–0.45(m,1H),0.42–0.33(m,1H),0.28–0.18(m,1H).13CNMR(101MHz,Chloroform-d)δ166.7,136.7,135.7,133.3,133.04,133.03,132.7,129.0,128.2,128.0,127.8,127.6,127.5,127.3,127.21,127.19,125.9,125.8,125.74,125.71,125.6,119.1,83.3,82.9,82.7,60.4,53.6,52.0,27.0,25.7,24.82,24.77,24.6,24.5,9.0.;HRMS(ESI+)计算值C45H57B2NNaO6 +([M+Na]+):752.4264,测量值:752.4269。
实施例24
杀菌活性检测
药液浓度50ppm,用5mm打空器取所制的琼脂片,分挑入各培养皿,设空白对照,将其在恒温培养箱27℃培养48-72小时,检查菌斑直径,抑制率=(对照菌斑直径-样品菌斑直径)/对照菌斑直径×100%,同时做一重复。测定结果见表1。
助溶剂:二甲基甲酞胺;乳化剂:吐温-80;配制溶液:无菌水。其中,二甲基甲酞胺/H2O=1/1000;乳化剂/H2O=5/1000(重量百分比)。
表1本发明化合物的抑菌率
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尽管上面已经示出和描述了本发明的实施例,可以理解的是,上述实施例是示例性的,不能理解为对本发明的限制,本领域的普通技术人员在本发明的范围内可以对上述实施例进行变化、修改、替换和变型,均应包含在本发明的保护范围之内。
Claims (21)
1.一种伪C2对称性的手性双烯丙基取代化合物,其特征在于,所述伪C2对称性的手性双烯丙基取代化合物的结构如下式I所示,
其中,R1为叔丁氧羰基;R2为氰基;R3、R5、R6为氢;R4选自苯基、1-萘基、2-萘基、3-吡啶基、2-噻吩基、甲基、 中的至少一种。
2.一种权利要求1所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,反应式如下所示,
其中,LG为OCO2CH3;
所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,包括如下步骤:以铱络合物作为催化剂,底物-1与底物-2进行催化反应,得到式I所示的伪C2对称性的手性双烯丙基取代化合物;
反应体系中添加碱,所述碱为碳酸铯;
所述铱络合物为金属铱盐[Ir(COD)Cl]2与手性配体(R,R,R)-L1、(S,Sa)-L1在正丙胺存在下制备所得的铱络合物;
其中,手性配体(R,R,R)-L1的结构式为手性配体(S,Sa)-L1的结构式为
3.根据权利要求2所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,反应体系中,所述碱与底物-1的摩尔比为(0.01~10)∶1。
4.根据权利要求2所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,所述反应在溶剂中进行,所述溶剂选自甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、乙酸乙酯、乙酸异丁酯、乙酸异丙酯、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种。
5.根据权利要求2所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,所述铱络合物与底物-1的摩尔比为(0.0001~10)∶1;
所述铱络合物的制备方法包括如下步骤:将金属铱盐和手性配体以1:2摩尔比溶于有机溶剂中,加入第二有机碱经反应,得到所述铱络合物,控制反应温度为30~70℃。
6.根据权利要求5所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,控制反应温度为40~60℃。
7.根据权利要求5所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,所述第二有机碱选自三乙胺、四甲基乙二胺、1,5-二氮杂二环[4.3.0]壬-5-烯、1,8-二氮杂二环十一碳-7-烯、1,4-二氮杂二环[2.2.2]辛烷、吡啶、4-二甲氨基吡啶、N-甲基吗啉、三乙烯二胺、四甲基胍、2-叔丁基-1,1,3,3-四甲基胍中的一种或多种。
8.根据权利要求2所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,所述底物-1与底物-2的摩尔比为1:(2~10)。
9.根据权利要求2所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,控制反应体系中所述底物-1的浓度范围为0.001~3.0M。
10.根据权利要求2所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,控制反应温度为-20~110℃。
11.根据权利要求10所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,控制反应温度为0~30℃。
12.根据权利要求2所述的伪C2对称性的手性双烯丙基取代化合物的制备方法,其特征在于,控制反应时间为0.1~96h。
13.一种权利要求1所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物II和/或具有手性取代四氢呋喃类化合物III中的应用,其特征在于,
所述伪C2对称性的手性双烯丙基取代化合物II的结构式为
所述具有手性取代四氢呋喃类化合物III的结构式为
其中,R1、R2、R3、R4、R5、R6的定义与权利要求1中R1、R2、R3、R4、R5、R6的定义相同。
14.根据权利要求13所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物II和/或具有手性取代四氢呋喃类化合物III中的应用,其特征在于,所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物II的化学式如下所示:
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物II,包括:将所述伪C2对称性的手性双烯丙基取代化合物I在酸中进行水解,得到所述的伪C2对称性的手性双烯丙基取代化合物II:
所述酸为三氟乙酸、盐酸或硫酸甲磺酸;
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物II在溶剂中进行,所述溶剂选自甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、甲苯和二氧六环中的一种或多种;
伪C2对称性的手性双烯丙基取代化合物II制备具有手性取代四氢呋喃类化合物III的化学式如下所示:
伪C2对称性的手性双烯丙基取代化合物II制备具有手性取代四氢呋喃类化合物III,包括:将伪C2对称性的手性双烯丙基取代化合物II溶于有机溶剂中,加入碳酸盐或碳酸氢盐、碘,在-40~30℃下反应,反应完成后加入硫代硫酸钠饱和水溶液淬灭,再经柱层析得到所述具有手性取代四氢呋喃类化合物III;
所述碳酸盐或碳酸氢盐为碱金属的碳酸盐或碳酸氢盐;所述有机溶剂选自乙酸乙酯、乙酸异丁酯、乙酸异丙酯、甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种。
15.一种权利要求1所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物IV中的应用,其特征在于,所述伪C2对称性的手性双烯丙基取代化合物IV的结构式为
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物IV的化学式如下所示:
伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烯丙基取代化合物IV,包括:在有机溶剂中加入伪C2对称性的手性双烯丙基取代化合物I和水,在碱金属盐的存在下通过加热或者微波反应,得到所述伪C2对称性的手性双烯丙基取代化合物IV;
其中,R1、R2、R3、R4、R5、R6的定义与权利要求1中R1、R2、R3、R4、R5、R6的定义相同。
16.根据权利要求15所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物IV中的应用,其特征在于,在惰性气体保护下,在溶剂中加入伪C2对称性的手性双烯丙基取代化合物I、水和碱金属盐,在50~180℃反应0.1~24小时;
控制所述反应体系中伪C2对称性的手性双烯丙基取代化合物I的浓度范围为0.001~3.0M;
所述水与伪C2对称性的手性双烯丙基取代化合物I的摩尔比为1:(1~100);
所述有机溶剂选自乙酸乙酯、乙酸异丁酯、乙酸异丙酯、甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种;所述碱金属盐为卤化锂、卤化钠、卤化钾、硫酸锂、硫酸钠、硫酸钾、氰化钾、氰化钠和氰化锂中的一种或多种。
17.根据权利要求16所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物IV中的应用,其特征在于,所述有机溶剂为二甲亚砜、N,N-二甲基甲酰胺或N,N-二甲基乙酰胺。
18.根据权利要求16所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烯丙基取代化合物IV中的应用,其特征在于,控制反应温度为130~160℃。
19.一种权利要求1所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烷基硼类化合物V中的应用,其特征在于,所述伪C2对称性的手性双烷基硼类化合物V的结构式为:其中,R21为/>中的任意一种;
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烷基硼类化合物V的反应式如下所示:
所述伪C2对称性的手性双烯丙基取代化合物制备伪C2对称性的手性双烷基硼类化合物V,包括:在惰性气体保护下,在有机溶剂中加入伪C2对称性的手性双烯丙基取代化合物I、氢硼化合物、金属催化剂和配体,在0~100℃反应0.5~24小时;
其中,所述反应体系中,伪C2对称性的手性双烯丙基取代化合物I的浓度范围为0.001~3.0M;
其中,R1、R2、R3、R4、R5、R6的定义与权利要求1中R1、R2、R3、R4、R5、R6的定义相同。
20.根据权利要求19所述的伪C2对称性的手性双烯丙基取代化合物在制备伪C2对称性的手性双烷基硼类化合物V中的应用,其特征在于,所述氢硼化合物与所述伪C2对称性的手性双烯丙基取代化合物I的摩尔比为1:(2~20);
所述有机溶剂选自乙酸乙酯、乙酸异丁酯、乙酸异丙酯、甲醇、乙醇、异丙醇、叔丁醇、仲丁醇、正己烷、环己烷、正庚烷、丙酮、丁酮、乙醚、甲基叔丁基醚、甲基环戊基醚、甲基四氢呋喃、四氢呋喃、乙腈、二氯甲烷、三氯甲烷、1,2-二氯乙烷、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、甲苯和二氧六环中的至少一种;
所述金属催化剂为醋酸亚铜、碘化亚铜、氯化亚铜、Ni(COD)2、醋酸钯、四(三苯基膦)钯、[Ir(COD)Cl]2、[Ir(DBCOT)Cl]2、[Ir(COD)OMe]2、Rh(COD)2BF4、Rh(acac)(COD)、[Rh(COE)2Cl]2、[Rh(C2H4)2Cl]2、[Rh(OMe)(1,5-cod)]2;
所述配体为有机膦配体、氮杂卡宾配体、亚磷酰胺配体或噁唑啉类配体;
所述氢硼化合物为儿茶酚硼烷、频那醇硼烷、丙二醇硼烷;
控制反应温度为20~40℃。
21.一种权利要求1所述的伪C2对称性的手性双烯丙基取代化合物在制备棉花炭疽病菌、小麦赤霉病菌、棉花枯萎病菌、黄瓜灰霉病菌、水稻纹枯病菌和/或苹果轮纹病菌抑菌剂中的应用。
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