CN115260096A - 一种基于一氧化碳气体或一氧化碳替代源合成二氢异喹啉酮类化合物的方法 - Google Patents
一种基于一氧化碳气体或一氧化碳替代源合成二氢异喹啉酮类化合物的方法 Download PDFInfo
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- CN115260096A CN115260096A CN202210996828.1A CN202210996828A CN115260096A CN 115260096 A CN115260096 A CN 115260096A CN 202210996828 A CN202210996828 A CN 202210996828A CN 115260096 A CN115260096 A CN 115260096A
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- carbon monoxide
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- phosphine
- tert
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- 238000000034 method Methods 0.000 title claims abstract description 56
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229910002091 carbon monoxide Inorganic materials 0.000 title claims abstract description 35
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 4
- -1 dihydroisoquinolinone compound Chemical class 0.000 title claims description 21
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 27
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000003446 ligand Substances 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 125000003518 norbornenyl group Chemical class C12(C=CC(CC1)C2)* 0.000 claims abstract description 7
- 150000001503 aryl iodides Chemical class 0.000 claims abstract description 6
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 4
- 230000009471 action Effects 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000007789 gas Substances 0.000 claims description 17
- 125000001424 substituent group Chemical group 0.000 claims description 17
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-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 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 5
- 230000000996 additive effect Effects 0.000 claims description 5
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
- 125000004185 ester group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 235000011181 potassium carbonates Nutrition 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- 239000001632 sodium acetate Substances 0.000 claims description 4
- 235000017281 sodium acetate Nutrition 0.000 claims description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- 230000001681 protective effect Effects 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 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 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 claims description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 claims description 2
- 101150003085 Pdcl gene Proteins 0.000 claims description 2
- 150000001348 alkyl chlorides Chemical class 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- DLIJPAHLBJIQHE-UHFFFAOYSA-N butylphosphane Chemical compound CCCCP DLIJPAHLBJIQHE-UHFFFAOYSA-N 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 229940071870 hydroiodic acid Drugs 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 claims description 2
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 claims description 2
- IAQRGUVFOMOMEM-ONEGZZNKSA-N trans-but-2-ene Chemical group C\C=C\C IAQRGUVFOMOMEM-ONEGZZNKSA-N 0.000 claims 2
- KRZJRNZICWNMOA-GXSJLCMTSA-N (3s,4r)-4,8-dihydroxy-3-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=CC=C2[C@@H](O)[C@@H](OC)CC(=O)C2=C1O KRZJRNZICWNMOA-GXSJLCMTSA-N 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000004442 acylamino group Chemical group 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 30
- WGLUNLJVYNJMBU-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-[(3-methyl-1-oxo-2,4-dihydroisoquinolin-3-yl)methyl]decanamide Chemical class C1=CC=C2C(=O)NC(CN(CCN(C)C)C(=O)CCCCCCCCC)(C)CC2=C1 WGLUNLJVYNJMBU-UHFFFAOYSA-N 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 230000003321 amplification Effects 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 238000003199 nucleic acid amplification method Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 57
- 239000007787 solid Substances 0.000 description 23
- 239000011734 sodium Substances 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- SORQIYFSJAWBNQ-UHFFFAOYSA-N 1-iodo-2-propan-2-ylbenzene Chemical compound CC(C)C1=CC=CC=C1I SORQIYFSJAWBNQ-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000010276 construction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- RINOYHWVBUKAQE-UHFFFAOYSA-N 1-iodo-2-methylbenzene Chemical compound CC1=CC=CC=C1I RINOYHWVBUKAQE-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 2
- BTVWZWFKMIUSGS-UHFFFAOYSA-N dimethylethyleneglycol Natural products CC(C)(O)CO BTVWZWFKMIUSGS-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
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- 238000000967 suction filtration Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical group C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 1
- MPEOPBCQHNWNFB-UHFFFAOYSA-N 1-chloro-2-iodobenzene Chemical compound ClC1=CC=CC=C1I MPEOPBCQHNWNFB-UHFFFAOYSA-N 0.000 description 1
- OEHHXVIJMCMYGM-UHFFFAOYSA-N 1-chloro-3-iodo-2-methylbenzene Chemical compound CC1=C(Cl)C=CC=C1I OEHHXVIJMCMYGM-UHFFFAOYSA-N 0.000 description 1
- IGZGUYVVBABKOY-UHFFFAOYSA-N 1-iodo-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1I IGZGUYVVBABKOY-UHFFFAOYSA-N 0.000 description 1
- NHPPIJMARIVBGU-UHFFFAOYSA-N 1-iodonaphthalene Chemical compound C1=CC=C2C(I)=CC=CC2=C1 NHPPIJMARIVBGU-UHFFFAOYSA-N 0.000 description 1
- VWBMDRDQJLUMMS-UHFFFAOYSA-N 4-fluoro-1-iodo-2-methylbenzene Chemical compound CC1=CC(F)=CC=C1I VWBMDRDQJLUMMS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 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
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000012300 argon atmosphere Substances 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
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 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
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
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Abstract
本发明公开了一种基于一氧化碳气体或一氧化碳替代源合成二氢异喹啉酮类化合物的方法。该方法以简单易得的芳基碘化物、氮杂环丙烷和一氧化碳分子为起始原料，在钯催化剂、膦配体、降冰片烯衍生物以及碱的作用下，在60℃‑70℃下于有机溶剂中搅拌反应，即可得到二氢异喹啉酮类化合物。该方法具有原料廉价易得，反应条件温和，制备过程简单，化学选择性好，底物适用范围广，易于放大等优点，具有较大的应用潜力，为工业化生产奠定了良好的基础。
Description
技术领域
本发明属于有机合成领域，具体涉及一种基于一氧化碳气体或一氧化碳替代源，构建二氢异喹啉酮类化合物的方法。
背景技术
二氢异喹啉骨架是一类重要的杂环化合物和药效结构单元，广泛存在于天然产物及生物活性分子中。含有这类骨架的分子通常具有多种药理特性，如抗HIV([1]J.Med.Chem.2011, 54,1812)、抗抑郁([2]Phytochem.Lett.2011,4,407)、抗肿瘤([3]ACSMed.Chem.Lett.2013, 4,606)、治疗神经性疼痛等([4]J.Med.Chem.2012,55,2452)。由于其广泛的生物活性，关于此类骨架的合成方法已被广泛报道，主要包括五种类型：(1)氨基甲酸酯/尿素/硫脲/异氰酸酯/叠氮酰胺的分子内环化([5]J.Org.Chem.2012,77,9313；[6]Chem.Eur.J.2014,20,8682； [7]Tetrahedron Lett.2015,56,3410；[8]Synthesis.2009,16,2809；[9]Chem.Commun.2012,48, 8141；[10]Org.Lett.2002,4,3079；[11]Bull.KoreanChem.Soc.2012,33,333；[12]Bull. Korean Chem.Soc.2012,33,739)、(2)一氧化碳参与的羰基化反应([13]J.Org.Chem.2016,81, 5256；[14]Organometallics,2013,32,649；[15]Adv.Synth.Catal.2017,359,3707；[16]J.Org. Chem.2009,74,8332；[17]J.Org.Chem.2010,75,8410；[18]Org.Lett.2015,17,2848；[19]J. Am.Chem.Soc.2004,126,14342；[20]Eur.J.Org.Chem.2014,6418；[21]Tetrahedron Lett. 2012,53,4816)、(3)导向基参与的C-H活化策略([22]Org.Lett.2014,16,4684；[23]J.Org. Chem.2018,83,13587；[24]J.Am.Chem.Soc.2011,133,2350；[25]J.Am.Chem.Soc.2017,139, 3537；[26]ACS Catal.2015,5,210；[27]Chem.Commun.2016,52,164.)、(4)无金属催化的 Domino反应、([28]Org.Lett.2015,17,2724；[29]J.Org.Chem.2016,12,301；[30]TetrahedronLett.2019,61,151499；[31]J.Org.Chem.2018,83,9718.)(5)异喹啉衍生物的氧化反应等。([32]Synlett 2011,8,1121；[33]J.Org.Chem.2018,83,260.[34]ChemCatChem 2015,7,2313； [35]Angew.Chem.2016,128,7328；[36]Green Chem.2014,16,4524)。
尽管已经取得了显著的发展，但在反应效率、底物普适性和产物多样性等方面仍有很大的改进空间，现存方法大多需要预先连接特殊官能团，存在原料复杂不易得，步骤经济性较差的问题。因此发展高效、简洁的合成新方法，利用简单易得的原料合成二氢异喹啉酮类化合物合物仍是化学领域的研究热点及难点。
发明内容
为了解决现有技术中存在的不足，本发明提供一种基于一氧化碳气体或一氧化碳替代源，构建二氢异喹啉酮类化合物的方法。该方法所用的原料廉价易得，反应条件温和，制备过程简单，化学选择性好，底物适用范围广。
本发明提供的技术方案具体如下：
一种基于一氧化碳气体或一氧化碳替代源，构建二氢异喹啉酮类化合物的方法，包括以下步骤：
在保护气体氛围下，以芳基碘化物A、氮杂环丙烷B和一氧化碳气体C或一氧化碳替代源K为起始原料，在钯催化剂D、膦配体E、降冰片烯衍生物F和碱G的作用下，加入添加剂H，于有机溶剂I中搅拌反应至完全，反应结束后将反应物分离即可得到式J所示的二氢异喹啉酮类化合物；其中，当一氧化碳替代源K为起始原料时，将其溶于溶剂M中并加入碱L以产生一氧化碳；
反应方程式如下：
其中，R1为烷基、芳基、酯基、酰胺基、烷氧基、卤素、全氟烷基中的一种或几种，位于芳环2-4位；R2为氢、烷基、芳基、苄基、烷氧基、苄氧基、叔丁基二甲基硅氧基中的一种或几种；R3为磺酰基、苯甲酰基、苄氧羰基、叔丁氧羰基、苄基中的一种或几种，x表示 R1的个数，0≤x≤3；y表示R2的个数，y＝1；z表示R3的个数，z＝1。
进一步，所述烷基为具有1～6个碳原子的烷基，包括甲基、乙基、异丙基等；所述芳基为苯基、苄基等；所述酯基为-COOR，其中R为具有1～2个碳原子的烷基；所述酰胺基为-CONHR，其中R为具有1～2个碳原子的烷基；所述烷氧基是指具有1～6个碳原子的烷氧基，包括甲氧基、苄氧基等；卤素是指氟、氯、溴、碘；所述磺酰基为甲磺酰基、对甲苯磺酰基、对硝基苯磺酰基、对溴苯磺酰基等。
进一步，所述一氧化碳气体C为一氧化碳与惰性气体的混合气，混合比例为1:1至1:20 中任意一种比例。所述惰性气体包括氩气、氮气，优选的为氩气。
更进一步，所述混合气比例为一氧化碳：氩气＝1：7。
进一步，所述钯催化剂D为Pd(PPh3)4、Pd(dba)2、Pd2(dba)3、Pd(OAc)2、Pd(PhCN)2Cl2、 Pd(MeCN)2Cl2、PdCl2、PdI2、[Pd(allyl)Cl]2中的任意一种或几种。优选的钯催化剂D为Pd(OAc)2。
进一步，所述膦配体E为三芳基膦、三烷基膦、二环己基(2',4',6'-三异丙基-[1,1'-二苯基]-2- 基)膦、二环己基(2',4',6'-三异丙基-3,6-二甲氧基-[1,1'-二苯基]-2-基)膦、二环己基(2',6'-二甲氧基-[1,1'-二苯基]-2-基)膦、2'-(二环己基膦基)-N,N-二甲基-[1,1'-二苯基]-2-胺、二环己基(2',6'- 二异丙氧基-[1,1'-二苯基]-2-基)膦、三(2-呋喃基)膦、(3S,5S,7S)-金刚烷-1-基((1R,5S)-金刚烷-2- 基)(丁基)膦中的任意一种或几种。优选的，E为2-双环己基膦-2'-(N,N-二甲胺)联苯。
进一步，所有降冰片烯衍生物F的结构式为：
其中：
i)R4为左边五元环上的取代基，p代表取代基个数，0≤p≤8；R5为双键上的取代基，q代表取代基个数，0≤q≤2；
ii)左边五元环上取代基数目为2个及2个以上时，可以相同，也可以不相同；双键上的取代基数目为2个时，可以相同，也可以不相同；
iii)R4和R5取代基的种类可以相同，也可以不相同；
iii)每个R4和R5独立地为酯基、羧基、氰基、硝基、酰胺基、磺酰基、羟基、巯基、烷氧基、芳基、杂环芳基、烷基或卤素。优选的，2-降冰片烯-5,6-乙二酰胺喹啉、2-降冰片烯-5-甲酰苯胺或2-降冰片烯-5,6-乙二酰胺联苯作为共催化剂。
进一步，所述碱G为碳酸锂、碳酸钠、碳酸钾、碳酸铯、醋酸钠、醋酸钾、醋酸铯、磷酸三钾、甲酸钾、碳酸氢钠、碳酸氢钾、氢氧化钠、氢氧化钾、叔丁醇钠、叔丁醇钾中的任意一种或几种。优选碱G为碳酸钾。
进一步，所述添加剂H为甲醇、乙醇、异丙醇、叔丁醇、三氟乙醇、六氟异丙醇、甲酸、乙酸、三氟乙酸、对甲苯磺酸、苯酚、间氯苯酚、对三氟甲基苯酚、对硝基苯酚、盐酸、氢溴酸、氢碘酸中的任意一种或几种。优选添加剂H为三氟乙醇。
进一步，所述溶剂I为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、乙醚、二甲基乙二醚、甲基叔丁基醚、1,4-二氧六烷、1,3-二氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的任意一种或几种。优选溶剂I为N-甲基吡咯烷酮。
进一步，所述碱L为碳酸氢钠、醋酸钠、碳酸铯、磷酸钾、三乙胺、三乙烯二胺、吡啶、4-二甲氨基吡啶中的任意一种或几种。优选碱L为三乙胺。
进一步，所述溶剂M为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、乙醚、二甲基乙二醚、甲基叔丁基醚、1,4-二氧六烷、1,3-二氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的任意一种或几种。优选溶剂M为1,4-二氧六环。
进一步，各原料的投料摩尔比为：
条件一，芳基碘化物A:氮杂环丙烷B:催化剂D:膦配体E:降冰片烯衍生物F:碱 G＝1.0:1.0-3.0:0.05-0.2:0.1-0.4:0.2-1.0:1.0-3.0。优选的，上述各组分的比例依次为1.0:1.2:0.1:0.2:0.5:1.0。
条件二，芳基碘化物A :氮杂环丙烷B:对三氟甲基甲酸芳酯C：催化剂D:膦配体E:降冰片烯衍生物F:碱G＝1.0:1.0-3.0:1.2-3.0:0.05-0.2:0.1-0.4:0.2-1.0:1.0-3.0。优选的，上述各组分的比例依次为：1.0:1.2:2.0:0.1:0.2:0.5:1.0。
进一步，所述保护气体选自氩气或氮气。优选为氩气。
进一步，所述反应温度为40-100℃。优选反应温度为60℃-70℃。
进一步，所述反应时间为1-72h。优选反应时间为16h。
进一步，所述反应物分离的方法为将反应混合物过滤、浓缩和柱层析纯化。所述过滤采用抽滤的方式，抽滤过程可使用砂芯漏斗在减压的条件下过滤。所述浓缩过程可采用减压蒸馏等方法，例如用旋转蒸发仪减压浓缩。所述纯化方法可采用柱层析分离纯化。
本发明的方法可以高效地制备二氢异喹啉酮类化合物，和现有技术相比，本发明具有以下有益效果：
i)本发明所涉及的主要原料芳基碘代物绝大部分为商品化试剂、且价格低廉，种类繁多，多组分一步完成二氢异喹啉酮骨架的构建；
ii)本发明方法使用一氧化碳气体或简单易制备的对三氟甲基甲酸芳酯作为羰基源均可实现二氢异喹啉酮类化合物的高效构建，原料廉价易得，减少工艺步骤，可大幅降低生产成本；
iii)反应条件温和，避免一般构建该类骨架所需要的高温高压；
iv)本发明方法具有很好的底物适用范围和官能团兼容性。
具体实施方式
下面通过实例对本发明给予进一步说明，值得注意的是，本发明不仅限于下述的实施例。
实施例1：化合物J-1的制备
使用一氧化碳气体，条件1：
在手套箱中，向干燥并装有磁力搅拌子的10ml支口反应管中加入醋酸钯(4.5mg,0.02 mmol)、2-双环己基膦-2'-(N,N-二甲胺)联苯(15.6mg,0.04mmol)和干燥的N-甲基吡咯烷酮 (0.5mL)，催化剂和配体预搅半小时后加入碳酸钾(27.6mg,0.2mmol)和2-降冰片烯-5,6- 乙二酰胺喹啉(29.4mg,0.1mmol)。加入2-甲基碘苯(43.6mg,0.2mmol)，反应管支口连接CO：Ar＝1:7的混合气气球，放置在60℃反应盘中加热搅拌，J-1结构式所示氮杂环丙烷 (79mg,0.4mmol)溶于干燥的N-甲基吡咯烷酮(1.0mL)用注射泵设置参数5h慢慢滴加入反应管中，总计反应16小时。反应液用乙酸乙酯与水萃取，水相反萃三次，集中有机相用饱和氯化钠冲洗三次，有机相用无水硫酸钠干燥，减压蒸馏除去溶剂，柱层析分离纯化得化合物J-1(淡黄色固体，73％产率)
使用4-三氟甲基甲酸苯酯作为一氧化碳替代源，条件2：
在手套箱中，向干燥并装有磁力搅拌子的双室反应管的一氧化碳消耗室分别加入醋酸钯 (4.5mg,0.02mmol)、2-双环己基膦-2'-(N,N-二甲胺)联苯。(15.6mg,0.04mmol)和干燥的N- 甲基吡咯烷酮(0.5mL)，催化剂和配体预搅半小时后加入碳酸钾(27.6mg,0.2mmol)和2- 降冰片烯-5,6-乙二酰胺喹啉(29.4mg,0.1mmol)、2-甲基碘苯(43.6mg,0.2mmol)；在一氧化碳生成室分别加入4-三氟甲基甲酸苯酯(76mg,0.4mmol)、三乙胺(24.3mg,0.24mmol) 和干燥的1,4-二氧六环(1.0mL)，最后将氮杂环丙烷(47mg,0.24mmol)溶于干燥的N-甲基吡咯烷酮(1.0mL)用注射泵设置参数5h慢慢加入一氧化碳消耗室中，置于60℃在氩气保护氛围下反应16小时。一氧化碳消耗室的混合物用乙酸乙酯和饱和氯化钠溶液萃取，无水硫酸钠干燥，减压蒸馏除去溶剂，柱层析分离纯化得化合物J-1(淡黄色固体，72％产率)。1H NMR(400MHz,CDCl3)δ7.97(d,J＝8.1Hz,2H),7.30(m,3H),7.10(d,J＝7.6Hz,1H), 7.03(d,J＝7.5Hz,1H),4.22–4.14(m,2H),3.04(t,J＝6.1Hz,2H),2.55(s,3H),2.42(s,3H)；13C NMR(100MHz,CDCl3)δ164.0,144.7,142.8,140.5,136.9,132.5,131.4,129.6,128.6, 127.0,125.4,44.8,30.4,22.6,21.8；HRMS(ESI-TOF):calc’d forC17H17NaNO3S[M+Na+] 338.0821,Found 338.0817.
实施例2：化合物J-2的制备
操作步骤同实例1条件1，区别在于使用碘化物为4-氟-2-甲基碘苯(47.2mg,0.2mmol)、反应温度为65℃，得化合物J-2(淡黄色固体，79％产率)。1H NMR(400MHz,CDCl3):δ 7.95(d,J＝8.4Hz,2H),7.32(d,J＝8.0Hz,2H),6.80(dd,J＝9.6,2.6Hz,1H),6.74(dd,J＝8.3, 2.6Hz,1H),4.17(t,J＝6.1Hz,2H),3.03(t,J＝6.1Hz,2H),2.54(s,3H),2.42(s,3H).13C NMR (100MHz,CDCl3):δ164.16(d,J＝255.3Hz),163.13,146.60(d,J＝9.4Hz),144.71,143.56(d, J＝9.4Hz),136.69,129.52,128.52,123.25(d,J＝2.9Hz),118.17(d,J＝21.1Hz),112.23(d,J＝ 21.7Hz),44.42,30.46,22.86,21.76.HRMS(ESI-TOF):calc’dfor C17H17F1NO3S[M+H+] 334.0908,found 334.0906.
实施例3：化合物J-3的制备
操作步骤同实例1条件1，区别在于使用碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，得化合物J-3(淡黄色固体，82％产率)。1H NMR(400MHz,CDCl3):δ7.97(d,J＝8.3Hz,2H), 7.34(m,4H),7.00(dd,J＝7.1,1.5Hz,1H),4.13(t,J＝6.0Hz,2H),3.95(p,J＝6.8Hz,1H),2.99 (t,J＝6.0Hz,2H),2.42(s,3H),1.14(d,J＝6.8Hz,6H).13C NMR(100MHz,CDCl3):δ163.76, 153.11,144.55,140.11,136.96,132.56,129.47,128.45,126.58,126.02,124.81,44.88,30.70, 28.81,24.10,21.74.HRMS(ESI-TOF):calc’d forC19H22NO3S[M+H+]334.1315,found 334.1312.
实施例4：化合物J-4的制备
操作步骤同实例1条件1，区别在于使用碘化物为2-氯碘苯(47.6mg,0.2mmol)、滴加时间为8h，得化合物J-4(淡黄色固体，50％产率)。1H NMR(400MHz,CDCl3):δ7.98(d, J＝8.2Hz,2H),7.37–7.27(m,4H),7.11(dd,J＝6.1,2.7Hz,1H),4.20(t,J＝6.0Hz,2H),3.04(t,J＝6.0Hz,2H),2.42(s,3H).13C NMR(100MHz,CDCl3):δ161.02,144.93,142.27,136.45,136.11,133.12,131.25,129.59,128.74,126.11,126.06,44.48,30.43,21.79.HRMS(ESI-TOF): calc’d for C16H15Cl1NO3S[M+H+]336.0456,found 336.0454.
实施例5：化合物J-5的制备
操作步骤同实例1条件1，区别在于使用碘化物为2-三氟甲基碘苯(49.2mg,0.2mmol)、反应温度为65℃，得化合物J-5(淡黄色固体，52％产率)。1H NMR(400MHz,CDCl3):δ 7.97(d,J＝8.4Hz,2H),7.69(d,J＝7.8Hz,1H),7.54(t,J＝7.8Hz,1H),7.42(d,J＝7.7Hz,1H), 7.31(d,J＝8.1Hz,2H),4.20(t,J＝6.0Hz,2H),3.08(t,J＝6.0Hz,2H),2.42(s,3H).13C NMR δ160.82,145.04,141.79,136.15,132.43,131.20,130.98(q,J＝33.0Hz),129.56,128.66,127.94, 127.09(q,J＝6.3Hz),123.13(q,J＝273.8Hz),44.53,30.48,21.77.HRMS(ESI-TOF):calc’d for C17H15F3NO3S[M+H+]370.0719,found 370.0718.
实施例6：化合物J-6的制备
操作步骤同实例1条件1，区别在于使用碘化物为4-甲酸甲酯-2甲基碘苯(55.2mg,0.2 mmol)，得化合物J-6(淡黄色固体，71％产率)。1H NMR(400MHz,CDCl3):δ7.97(d,J＝8.4Hz,2H),7.75(d,J＝1.7Hz,1H),7.69(s,1H),7.33(d,J＝8.1Hz,2H),4.20(t,J＝6.1Hz,2H),3.91(s,3H),3.08(t,J＝6.1Hz,2H),2.59(s,3H),2.43(s,3H).13C NMR(100MHz,CDCl3): δ166.04,163.18,144.77,142.83,140.48,136.46,132.86,131.92,130.39,129.46,128.51,126.12, 52.50,44.56,30.14,22.39,21.69.HRMS(ESI-TOF):calc’d forC19H19NaNO5S[M+Na+] 396.0876,found 396.0881.
实施例7：化合物J-7的制备
操作步骤同实例1条件1，区别在于使用碘化物为3-甲酸甲酯-2甲基碘苯(55.2mg,0.2 mmol)、反应温度为65℃，得化合物J-7(淡黄色固体，80％产率)。1H NMR(400MHz,CDCl3):δ7.95(d,J＝8.4Hz,2H),7.73(d,J＝7.9Hz,1H),7.32(d,J＝8.1Hz,2H),7.08(d,J＝ 7.9Hz,1H),4.18(t,J＝6.1Hz,2H),3.86(s,2H),3.02(t,J＝6.1Hz,2H),2.64(s,3H),2.41(s, 3H).13C NMR(100MHz,CDCl3):δ168.24,163.30,144.84,143.53,142.86,136.64,133.40, 132.87,129.54,128.89,128.53,124.88,52.39,44.49,30.67,21.76,18.78.HRMS(ESI-TOF): calc’d for C19H19NaNO5S[M+Na+]396.0876,found 396.0881.
实施例8：化合物J-8的制备
操作步骤同实例1条件1，区别在于使用碘化物为3-氯-2甲基碘苯(50.4mg,0.2mmol)、滴加时间为8h，得化合物J-8(淡黄色固体，70％产率)。1H NMR(400MHz,CDCl3):δ7.96 (d,J＝8.3Hz,2H),7.42(d,J＝8.1Hz,1H),7.32(d,J＝8.1Hz,2H),6.98(d,J＝8.1Hz,1H), 4.18(t,J＝6.0Hz,2H),2.98(t,J＝6.0Hz,2H),2.58(s,3H),2.42(s,3H).13C NMR(100MHz, CDCl3):δ163.27,144.87,139.87,138.99,136.66,135.56,133.24,129.57,129.23,128.58,44.71, 30.18,21.80,18.14.HRMS(ESI-TOF):calc’d for C17H16Cl1NO3S[M+H+]350.0612,found 350.0607.
实施例9：化合物J-9的制备
操作步骤同实例1条件1，区别在于使用碘化物为1-碘萘(50.8mg,0.2mmol)、反应温度为65℃，得化合物J-9(白色固体，57％产率)。1H NMR(400MHz,CDCl3):δ9.06(d,J＝8.7Hz,1H),8.02(d,J＝8.4Hz,2H),7.93(d,J＝8.3Hz,1H),7.79(dd,J＝8.1,1.5Hz,1H),7.56 (ddd,J＝8.6,6.9,1.5Hz,1H),7.47(ddd,J＝8.0,6.8,1.2Hz,1H),7.33(d,J＝8.1Hz,2H),7.28 (d,J＝8.4Hz,1zH),4.29(t,J＝6.2Hz,2H),3.20(t,J＝6.2Hz,2H),2.42(s,3H).13C NMR(100 MHz,CDCl3):δ163.88,144.70,141.03,136.88,134.58,133.28,131.79,129.56,128.77,128.67, 128.59,126.49,126.33,125.08,123.37,44.17,30.77,21.78.HRMS(ESI-TOF):calc’d for C20H18NO3S[M+H+]352.1002,found 352.1007.
实施例10：化合物J-10的制备
操作步骤同实例1条件1，区别在于使用碘化物为2，3环己基碘萘(51.6mg,0.2mmol)，得化合物J-10(淡黄色固体，58％产率)。1H NMR(400MHz,CDCl3):δ7.95(d,J＝8.4Hz, 2H),7.31(d,J＝8.1Hz,2H),7.13(d,J＝7.7Hz,1H),6.93(d,J＝7.7Hz,1H),4.17(dd,J＝6.8, 5.4Hz,2H),3.04(t,J＝5.8Hz,2H),2.97(t,J＝6.0Hz,2H),2.74(t,J＝5.9Hz,2H),2.42(s,3H), 1.70(pd,J＝5.2,4.4,2.4Hz,4H).13C NMR(100MHz,CDCl3):δ164.01,144.39,141.45,137.98, 137.65,136.97,133.94,129.37,128.36,126.79,124.40,44.81,30.22,28.55,23.05,22.24,21.66. HRMS(ESI-TOF):calc’d for C20H21NO3S[M+H+]356.1315,found 356.1316.
实施例11：化合物J-11的制备
操作步骤同实例1条件1，区别在于使用碘化物为3，4二甲氧基-2-氯碘萘(59.6mg,0.2 mmol)、滴加时间为8h，得化合物J-11(淡黄色固体，60％产率)。1H NMR(400MHz,CDCl3):δ7.97(d,J＝8.4Hz,1H),7.31(d,J＝8.1Hz,1H),6.61(s,1H),4.18(dd,J＝6.7,5.4Hz,1H),3.90(s,2H),3.79(s,2H),2.99(t,J＝6.0Hz,1H),2.41(s,2H).13C NMR(100MHz,CDCl3):δ159.93,155.83,144.98,143.75,137.54,135.66,130.22,128.56,127.69,118.00,107.85,59.68, 55.33,43.38,29.76,20.79.HRMS(ESI-TOF):calc’d for C18H18ClNaNO5S[M+Na+]418.0492, found 418.0486.
实施例12：化合物J-12的制备
操作步骤同实例1条件1，区别在于所使用的碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，氮杂环丙烷如结构式J-12所示(70.8mg)，得化合物J-12(无色液体，61％产率)。1H NMR (400MHz,CDCl3):δ7.50–7.46(m,2H),7.37(dq,J＝8.6,7.0Hz,5H),7.01(dd,J＝5.4,3.3Hz, 1H),5.36(s,2zH),4.10–3.95(m,3H),2.93(t,J＝6.0Hz,2H),1.27(d,J＝6.8Hz,6H).13C NMR(100MHz,CDCl3):δ164.10,154.09,152.93,140.07,135.78,132.09,128.70,128.44, 128.37,128.02,126.02,124.48,68.60,44.64,29.74,29.23,24.35.HRMS(ESI-TOF):calc’d for C20H22NO3[M+H+]324.1594,found 324.1594.
实施例13：化合物J-13的制备
操作步骤同实例1条件1，区别在于所使用的碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，氮杂环丙烷如结构式J-13所示(48.4mg)，得化合物J-13(淡黄色固体，76％产率)。1H NMR (400MHz,CDCl3):δ7.50–7.46(m,2H),7.37(dq,J＝8.6,7.0Hz,5H),7.01(dd,J＝5.4,3.3Hz, 1H),5.36(s,2zH),4.10–3.95(m,3H),2.93(t,J＝6.0Hz,2H),1.27(d,J＝6.8Hz,6H).13C NMR(100MHz,CDCl3):δ164.10,154.09,152.93,140.07,135.78,132.09,128.70,128.44, 128.37,128.02,126.02,124.48,68.60,44.64,29.74,29.23,24.35.HRMS(ESI-TOF):calc’d for C13H18NO3S1[M+H+]268.1002,found 268.1006.
实施例14：化合物J-14的制备
操作步骤同实例1条件1，区别在于所使用的碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，氮杂环丙烷如结构式J-14所示(91.2mg)，得化合物J-14(淡黄色固体，46％产率)。1H NMR (400MHz,CDCl3):δ7.50–7.46(m,2H),7.37(dq,J＝8.6,7.0Hz,5H),7.01(dd,J＝5.4,3.3Hz, 1H),5.36(s,2zH),4.10–3.95(m,3H),2.93(t,J＝6.0Hz,2H),1.27(d,J＝6.8Hz,6H).13C NMR(100MHz,CDCl3):δ164.10,154.09,152.93,140.07,135.78,132.09,128.70,128.44, 128.37,128.02,126.02,124.48,68.60,44.64,29.74,29.23,24.35.HRMS(ESI-TOF):calc’d for C18H18NaN2O5S[M+Na+]397.0829,found 397.0833.
实施例15：化合物J-15的制备
操作步骤同实例1条件1，区别在于所使用的碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，氮杂环丙烷如结构式J-15所示(57.2mg)，得化合物J-15(无色液体，23％产率)。1H NMR (400MHz,CDCl3):δ7.36(d,J＝5.0Hz,2H),7.00(p,J＝4.5Hz,1H),4.03(hept,J＝6.9Hz, 1H),3.93–3.86(m,2H),2.91(t,J＝6.0Hz,2H),1.57(s,9H),1.26(d,J＝6.8Hz,6H).13C NMR (100MHz,CDCl3):δ164.42,152.74,152.45,140.01,131.78,128.38,125.89,124.37,82.97, 44.43,29.85,29.18,28.24,24.34HRMS(ESI-TOF):calc’d for C17H24N1O3[M+H+]290.1751, found 290.1750.
实施例16：化合物J-16的制备
操作步骤同实例1条件1，区别在于所使用的碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，氮杂环丙烷如结构式J-16所示并直接加入(31.9mg，0.24mmol)，加入三氟乙醇(80mg， 4.0equiv)，得化合物J-16(无色液体，20％产率)。1H NMR(400MHz,CDCl3):δ7.39–7.30 (m,7H),6.97(dd,J＝7.0,1.7Hz,1H),4.80(s,2H),4.38(hept,J＝6.9Hz,1H),3.42(dd,J＝7.0, 5.7Hz,2H),2.84(t,J＝6.3Hz,2H),1.29(d,J＝6.9Hz,6H).13C NMR(100MHz,CDCl3):δ 164.98,151.85,139.39,137.94,130.89,128.63,127.99,127.37,125.62,124.44,50.29,45.19, 30.13,28.85,24.31HRMS(ESI-TOF):calc’d for C19H22N1O1[M+H+]280.1696,found 280.1697
实施例17：化合物J-17的制备
操作步骤同实例1条件1，区别在于所使用的碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，氮杂环丙烷如结构式J-17所示并直接加入(50.6mg，0.24mmol)，加入三氟乙醇(80mg， 4.0equiv)，得化合物J-17(淡黄色固体，63％产率)。1H NMR(400MHz,CDCl3):δ7.98(d, J＝8.4Hz,2H),7.37(t,J＝7.6Hz,1H),7.31(d,J＝8.3Hz,3H),6.99(dt,J＝7.3,1.3Hz,1H), 5.08–4.97(m,1H),3.99(p,J＝6.8Hz,1H),3.33(dd,J＝15.6,5.5Hz,1H),2.73(dd,J＝15.7, 2.1Hz,1H),2.42(s,3H),1.30(d,J＝6.6Hz,3H),1.22(d,J＝6.8Hz,3H),1.07(d,J＝6.9Hz, 3H).13C NMR(100MHz,CDCl3):δ163.30,152.67,144.41,137.57,137.34,132.69,129.43, 128.56,126.24,125.95,125.90,51.46,36.76,28.61,24.19,23.96,21.76,20.01.HRMS (ESI-TOF):calc’d for C20H24N1O3S[M+H+]358.1471,found358.1476.
实施例18：化合物J-18的制备
操作步骤同实例1条件1，区别在于所使用的碘化物为2-异丙基碘苯(49.2mg,0.2mmol)，氮杂环丙烷如结构式J-18所示并直接加入(32.4mg，0.24mmol)，加入三氟乙醇(80mg， 4.0equiv)，得化合物J-18(淡黄色固体，70％产率)。1H NMR(400MHz,CDCl3):δ7.43(dt, J＝14.6,7.8Hz,2H),7.04(d,J＝7.1Hz,1H),4.83(td,J＝6.2,2.0Hz,1H),4.12(p,J＝6.8Hz, 1H),3.47(s,3H),3.39(dd,J＝15.8,5.6Hz,1H),2.75(dd,J＝15.9,2.1Hz,1H),1.31(d,J＝6.7 Hz,3H),1.22(dd,J＝6.8,4.8Hz,6H).13C NMR(100MHz,CDCl3):δ164.67,153.22,137.79, 133.17,126.22,126.16,125.63,50.49,43.30,36.57,29.05,24.49,23.90,19.64.HRMS (ESI-TOF):calc’d for C14H20N1O3S[M+H+]282.1158,found 282.1159.
实施例19：化合物J-19的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如结构式J-19所示(50.7mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)得化合物J-19(淡黄色固体，52％产率)。1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.3Hz,2H),7.30(t,J＝7.3Hz,3H),7.10(d,J＝7.6Hz,1H),7.02(d,J＝7.5Hz,1H),5.06(tt,J＝7.5,3.8Hz,1H),3.39(dd,J＝15.7,5.6Hz,1H), 2.76(dd,J＝15.8,2.1Hz,1H),2.55(s,3H),2.42(s,3H),1.31(d,J＝6.6Hz,3H)；13CNMR(100 MHz,CDCl3)δ163.3,144.5,142.3,138.0,137.3,132.6,131.4,129.5,128.7,126.5,51.4,36.4, 22.5,21.8,20.1；HRMS(ESI-TOF):calc’d for C18H19NaNO3S[M+Na+]352.0977,found 352.0979.
实施例20：化合物J-20的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如结构式J-20所示(324mg0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-20(白色固体，50％产率)。1H NMR(400MHz,CDCl3)δ7.37(t,J＝7.6Hz,1H),7.18(d,J＝7.7Hz,1H),7.07(d,J＝7.5Hz, 1H),4.86(pd,J＝6.3,1.7Hz,1H),3.46(s,3H),3.44–3.36(m,1H),2.76(dd,J＝15.9,2.0Hz,1H),2.69(s,3H),1.24(d,J＝6.7Hz,3H)；13C NMR(100MHz,CDCl3)δ164.7,142.7,138.2,133.1,131.6,126.8,125.9,50.5,43.3,36.2,22.8,19.7；HRMS(ESI-TOF):calc’d forC12H15NaNO3S[M+Na+]276.0664,found 276.0669.
实施例21：化合物J-21的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如结构式J-21所示(54.1mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-21(白色固体，53％产率)。1H NMR(400MHz,CDCl3)δ7.97(d,J＝8.3Hz,2H),7.30(dd,J＝9.8,7.9Hz,3H),7.09(d,J＝7.7 Hz,1H),7.01(d,J＝7.5Hz,1H),4.78(dtd,J＝8.0,5.6,2.0Hz,1H),3.27(dd,J＝15.9,5.4Hz, 1H),2.92(dd,J＝15.9,2.1Hz,1H),2.56(s,3H),2.41(s,3H),1.79(ddd,J＝13.8,7.8,6.2Hz, 1H),1.50(ddq,J＝14.4,8.9,7.3Hz,1H),0.95(t,J＝7.4Hz,3H)；13C NMR(100MHz,CDCl3)δ 163.4,144.5,142.2,137.9,137.4,132.6,131.4,129.5,128.8,126.8,126.3,57.0,33.2,26.5,22.4, 21.8,11.1；HRMS(ESI-TOF):calc’d for C19H21NaNO3S[M+Na+]366.1134,found 366.1133.
实施例22：化合物J-22的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如如结构式J-22所示(68.9mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-22(白色固体，59％产率)。1H NMR(400MHz,CDCl3)δ8.03(d,J＝8.4Hz,2H),7.36(dt,J＝15.0,7.5Hz,5H),7.29(m,1H), 7.16(t,J＝7.7Hz,3H),6.99(d,J＝7.5Hz,1H),5.07(dddd,J＝11.4,5.9,3.9,1.9Hz,1H),3.22 (dd,J＝13.1,4.0Hz,1H),3.13(dd,J＝15.9,5.6Hz,1H),2.80–2.68(m,2H),2.62(s,3H),2.45 (s,3H)；13C NMR(100MHz,CDCl3)δ163.4,144.6,142.4,137.8,137.6,137.3,132.8,131.5, 129.5,129.4,128.9,128.8,127.1,126.9,126.5,56.9,39.6,31.9,22.4,21.8；HRMS(ESI-TOF): calc’d for C24H23NaNO3S[M+Na+]428.1290,found 428.1292.
实施例23：化合物J-23的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如如结构式J-23所示(68.0mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-23(淡黄色油状液体，41％产率)。1H NMR(400MHz,CDCl3)δ7.96(d,J＝8.1Hz,2H),7.31(m,3H),7.10(d,J＝7.7Hz,1H),7.00(d,J＝7.5Hz,1H),4.98–4.89(m,1H),3.67(s,3H),3.32(dd,J＝16.0,5.4Hz,1H),2.86(dd,J＝16.0,2.1Hz,1H),2.57(s,3H),2.53–2.45(m,2H),2.41(s,3H),1.98(td,J＝14.4, 8.1Hz,1H),1.81(dq,J＝14.5,7.4Hz,1H)；13C NMR(100MHz,CDCl3)δ173.3,163.2,144.7, 142.4,137.6,137.0,132.8,131.6,129.5,128.8,126.6,126.3,54.9,51.9,34.6,31.0,28.7,22.3, 21.8；HRMS(ESI-TOF):calc’d for C21H23NNaO5S[M+Na+]424.1189,found424.1191.
实施例24：化合物J-24的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如如结构式J-24所示(57.9mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-24(白色固体，46％产率)。1H NMR(400MHz,CDCl3)δ8.00(d,J＝8.2Hz,2H),7.31(t,J＝8.4Hz,3H),7.10(d,J＝7.6Hz, 1H),7.03(d,J＝7.5Hz,1H),5.01(tdd,J＝7.5,6.2,5.5,3.4Hz,1H),3.54(dd,J＝9.4,5.4Hz, 1H),3.30(s,3H),3.29–3.20(m,2H),3.12(dd,J＝16.1,2.1Hz,1H),2.55(s,3H),2.42(s,3H)；13C NMR(100MHz,CDCl3)δ163.3,144.6,142.2,137.7,137.2,132.8,131.4,129.5,128.9, 126.5,126.5,71.9,59.2,53.7,31.0,22.5,21.8；HRMS(ESI-TOF):calc’d for C19H21NaNO4S [M+Na+]382.1083,found 382.1081.
实施例25：化合物J-25的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如如结构式J-25所示(76.0mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-25(无色油状液体，48％产率)。1H NMR(400MHz,CDCl3)δ7.67(d,J＝8.1Hz,2H),7.24(m,4H),7.19(m,4H),7.07(d,J＝ 7.6Hz,1H),6.89(d,J＝7.5Hz,1H),4.39–4.26(m,3H),3.40(dd,J＝14.8,6.8Hz,1H),3.25(dd, J＝14.8,5.7Hz,1H),2.76(dd,J＝16.2,3.1Hz,1H),2.61(dd,J＝16.2,11.4Hz,1H),2.53(s,3H), 2.38(s,3H)；13C NMR(100MHz,CDCl3)δ164.1,144.0,143.0,139.7,136.1,135.8,133.0,131.2, 130.1,129.1,128.9,128.3,127.5,125.6,123.4,76.4,54.0,51.0,32.1,22.3,21.7；HRMS (ESI-TOF):calc’d for C25H25NNaO4S[M+Na+]458.1396,found458.1395.
实施例26：化合物J-26的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如如结构式J-26所示(81.9mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-26(白色固体，54％产率)。1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.1Hz,2H),7.35–7.27(m,3H),7.08(d,J＝7.6Hz,1H), 7.01(d,J＝7.5Hz,1H),4.86(dq,J＝8.7,4.2Hz,1H),3.81(dd,J＝9.8,4.7Hz,1H),3.45(t,J＝ 9.5Hz,1H),3.20(d,J＝3.8Hz,2H),2.55(s,3H),2.42(s,3H),0.82(s,9H),-0.06(d,J＝25.6Hz, 6H)；13C NMR(100MHz,CDCl3)δ163.6,144.6,142.0,137.8,137.3,132.6,131.3,129.5,128.7, 126.7,126.4,62.8,55.8,30.6,25.9,22.5,21.8,18.3,-5.4,-5.6；HRMS(ESI-TOF):calc’d for C24H33NaNO4SSi[M+Na+]482.1791,found 482.1793.
实施例27：化合物J-27的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷如如结构式J-27所示(65.1mg, 0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-27(无色油状液体，49％产率)。1H NMR(400MHz,CDCl3)δ8.02(d,J＝8.2Hz,2H),7.30(m,3H),7.09(d,J＝7.6Hz,1H),7.03(d,J＝7.5Hz,1H),4.92(ddd,J＝7.4,5.6,2.1Hz,1H),4.17(d,J＝7.1Hz,1H),3.33(s,3H), 3.28(m,4H),3.15(dd,J＝16.3,2.1Hz,1H),2.57(s,3H),2.41(s,3H)；13C NMR(100MHz, CDCl3)δ163.3,144.3,142.4,138.5,137.3,132.8,131.3,129.3,129.2,126.5,126.0,104.1,56.1, 55.7,54.9,30.9,22.6,21.8；HRMS(ESI-TOF):calc’d forC20H23NaNO5S[M+Na+]412.1189, found 412.1183.
实施例28：化合物J-28和J-29的制备
操作步骤同实例1条件2，区别在于所使用的氮杂环丙烷为如所示(65.5mg,0.24mmol)、加入三氟乙醇(60mg,0.6mmol)，得化合物J-28(白色固体，24％产率)。1H NMR(400MHz,CDCl3)δ7.84(d,J＝8.3Hz,2H),7.28(d,J＝2.7Hz,2H),7.25–7.19(m,4H),7.09(dd,J＝9.5,7.6Hz,3H),6.87(d,J＝7.5Hz,1H),6.12(dd,J＝6.0,2.1Hz,1H),3.77(dd,J＝15.8, 6.1Hz,1H),3.21(dd,J＝15.8,2.2Hz,1H),2.62(s,3H),2.44(s,3H)；13C NMR(100MHz, CDCl3)δ163.9,144.6,142.1,139.4,137.3,136.7,132.8,131.5,129.2,128.7,127.7,126.9,126.4, 126.3,58.1,37.4,22.6,21.8；HRMS(ESI-TOF):calc’d forC23H21NaNO3S[M+Na+]414.1134, found 414.1136.
以上所述，仅为本发明较佳的具体实施方式，但本发明保护的范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内所做的任何修改，等同替换和改进等，均应包含在发明的保护范围之内。
Claims (10)
1.一种基于一氧化碳气体或一氧化碳替代源合成二氢异喹啉酮类化合物的方法，其特征在于，包括以下步骤：
在保护气体氛围下，以芳基碘化物A、氮杂环丙烷B和一氧化碳气体C或一氧化碳替代源K为起始原料，在钯催化剂D、膦配体E、降冰片烯衍生物F和碱G的作用下，加入添加剂H，于有机溶剂I中搅拌反应至完全，反应结束后将反应物分离即可得到式J所示的二氢异喹啉酮类化合物；其中，当一氧化碳替代源K为起始原料时，将其溶于溶剂M中并加入碱L以产生一氧化碳；
反应方程式如下：
其中，R1为烷基、芳基、酯基、酰胺基、烷氧基、卤素、全氟烷基中的一种或几种，位于芳环2-4位；R2为氢、烷基、芳基、烷氧基、苄氧基、叔丁基二甲基硅氧基中的一种或几种，R3为磺酰基、酰基、烷氧羰基、烷基中的一种或几种，x表示R1的个数，0≤x≤3；y表示R2的个数，y＝1；z表示R3的个数，z＝1。
2.根据权利要求1所述的方法，其特征在于：所述所述一氧化碳气体C为一氧化碳与惰性气体的混合气，混合比例为1:1至1:20中任意一种比例。
3.根据权利要求1所述的方法，其特征在于：所述钯催化剂D为Pd(PPh3)4、Pd(dba)2、Pd2(dba)3、Pd(OAc)2、Pd(PhCN)2Cl2、Pd(MeCN)2Cl2、PdCl2、PdI2、[Pd(allyl)Cl]2中的任意一种或几种。
4.根据权利要求1所述的方法，其特征在于：所述膦配体E为三芳基膦、三烷基膦、二环己基(2',4',6'-三异丙基-[1,1'-二苯基]-2-基)膦、二环己基(2',4',6'-三异丙基-3,6-二甲氧基-[1,1'-二苯基]-2-基)膦、二环己基(2',6'-二甲氧基-[1,1'-二苯基]-2-基)膦、2'-(二环己基膦基)-N,N-二甲基-[1,1'-二苯基]-2-胺、二环己基(2',6'-二异丙氧基-[1,1'-二苯基]-2-基)膦、三(2-呋喃基)膦、(3S,5S,7S)-金刚烷-1-基((1R,5S)-金刚烷-2-基)(丁基)膦中的任意一种或几种。
5.根据权利要求1所述的方法，其特征在于：所述降冰片烯衍生物F的结构式为：
其中：
i)R4为左边五元环上的取代基，p代表取代基个数，0≤p≤8；R5为双键上的取代基，q代表取代基个数，0≤q≤2；
ii)左边五元环上取代基数目为2个及2个以上时，可以相同，也可以不相同；双键上的取代基数目为2个时，可以相同，也可以不相同；
iii)R4和R5取代基的种类可以相同，也可以不相同；
iii)每个R4和R5独立地为酯基、羧基、氰基、硝基、酰胺基、磺酰基、羟基、巯基、烷氧基、芳基、杂环芳基、烷基或卤素。
6.根据权利要求1所述的方法，其特征在于：所述碱G为碳酸锂、碳酸钠、碳酸钾、碳酸铯、醋酸钠、醋酸钾、醋酸铯、磷酸三钾、甲酸钾、碳酸氢钠、碳酸氢钾、氢氧化钠、氢氧化钾、叔丁醇钠、叔丁醇钾中的任意一种或几种；所述碱L为碳酸氢钠、醋酸钠、碳酸铯、磷酸钾、三乙胺、三乙烯二胺、吡啶、4-二甲氨基吡啶中的任意一种或几种。
7.根据权利要求1所述的方法，其特征在于：所述添加剂H为甲醇、乙醇、异丙醇、叔丁醇、三氟乙醇、六氟异丙醇、甲酸、乙酸、三氟乙酸、对甲苯磺酸、苯酚、间氯苯酚、对三氟甲基苯酚、对硝基苯酚、盐酸、氢溴酸、氢碘酸中的任意一种或几种。
8.根据权利要求1所述的方法，其特征在于：所述溶剂I为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、乙醚、二甲基乙二醚、甲基叔丁基醚、1,4-二氧六烷、1,3-二氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的任意一种或几种。
9.根据权利要求1所述的方法，其特征在于：所述溶剂M为甲醇、乙醇、异丙醇、叔丁醇、四氢呋喃、2-甲基四氢呋喃、乙醚、二甲基乙二醚、甲基叔丁基醚、1,4-二氧六烷、1,3-二氧六烷、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、C4-12的饱和烷烃、C3-12的氟代或者氯代烷烃、苯、甲苯、二甲苯、三甲苯、二甲亚砜、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、丙酮、N-甲基吡咯烷酮、乙腈、C3-12的饱和烷基腈中的任意一种或几种。
10.根据权利要求1所述的方法，其特征在于：所述反应温度为40-100℃。
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