CN113372184A - 一种基于手性转移策略合成c–n轴手性菲啶酮类化合物的方法 - Google Patents
一种基于手性转移策略合成c–n轴手性菲啶酮类化合物的方法 Download PDFInfo
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- CN113372184A CN113372184A CN202110327590.9A CN202110327590A CN113372184A CN 113372184 A CN113372184 A CN 113372184A CN 202110327590 A CN202110327590 A CN 202110327590A CN 113372184 A CN113372184 A CN 113372184A
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- 238000000034 method Methods 0.000 title claims abstract description 73
- -1 phenanthridinone compound Chemical class 0.000 title claims abstract description 12
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 7
- 238000012546 transfer Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 239000003446 ligand Substances 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 6
- RZFVLEJOHSLEFR-UHFFFAOYSA-N phenanthridone Chemical class C1=CC=C2C(O)=NC3=CC=CC=C3C2=C1 RZFVLEJOHSLEFR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 125000003368 amide group Chemical group 0.000 claims abstract description 5
- 150000001499 aryl bromides Chemical class 0.000 claims abstract description 4
- 150000001503 aryl iodides Chemical class 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
- 238000003756 stirring Methods 0.000 claims abstract description 3
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 94
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- 125000001424 substituent group Chemical group 0.000 claims description 18
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-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
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 229910052786 argon Inorganic materials 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 235000011181 potassium carbonates Nutrition 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 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 5
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- 230000001681 protective effect Effects 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 4
- 230000035484 reaction time Effects 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
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910021606 Palladium(II) iodide Inorganic materials 0.000 claims description 2
- 229910002666 PdCl2 Inorganic materials 0.000 claims description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- RBYGDVHOECIAFC-UHFFFAOYSA-L acetonitrile;palladium(2+);dichloride Chemical compound [Cl-].[Cl-].[Pd+2].CC#N.CC#N RBYGDVHOECIAFC-UHFFFAOYSA-L 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 150000001348 alkyl chlorides Chemical class 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 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
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 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
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- HNNUTDROYPGBMR-UHFFFAOYSA-L palladium(ii) iodide Chemical compound [Pd+2].[I-].[I-] HNNUTDROYPGBMR-UHFFFAOYSA-L 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
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 229910052710 silicon Inorganic materials 0.000 claims description 2
- 239000010703 silicon Substances 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 claims description 2
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- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000003396 thiol group Chemical group [H]S* 0.000 claims 1
- IAQRGUVFOMOMEM-ONEGZZNKSA-N trans-but-2-ene Chemical group C\C=C\C IAQRGUVFOMOMEM-ONEGZZNKSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 48
- 239000000758 substrate Substances 0.000 abstract description 4
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- 150000001875 compounds Chemical class 0.000 description 95
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 45
- 238000005160 1H NMR spectroscopy Methods 0.000 description 45
- 238000004128 high performance liquid chromatography Methods 0.000 description 45
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 43
- 239000007788 liquid Substances 0.000 description 28
- 239000007787 solid Substances 0.000 description 18
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 16
- NHPPIJMARIVBGU-UHFFFAOYSA-N 1-iodonaphthalene Chemical compound C1=CC=C2C(I)=CC=CC2=C1 NHPPIJMARIVBGU-UHFFFAOYSA-N 0.000 description 13
- IGISPMBUGPHLBY-UHFFFAOYSA-N 1-iodo-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(I)=C1 IGISPMBUGPHLBY-UHFFFAOYSA-N 0.000 description 6
- 238000004293 19F NMR spectroscopy Methods 0.000 description 6
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- 239000000203 mixture Substances 0.000 description 4
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
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- UWLLADJDESDEJQ-SFYZADRCSA-N ethyl (1S,4R)-bicyclo[2.2.1]hept-2-ene-2-carboxylate Chemical compound CCOC(=O)C1=C[C@@H]2CC[C@H]1C2 UWLLADJDESDEJQ-SFYZADRCSA-N 0.000 description 2
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- OEHHXVIJMCMYGM-UHFFFAOYSA-N 1-chloro-3-iodo-2-methylbenzene Chemical compound CC1=C(Cl)C=CC=C1I OEHHXVIJMCMYGM-UHFFFAOYSA-N 0.000 description 1
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- FBCNACVFOFCZHW-UHFFFAOYSA-N 5-iodo-1,2,3,4-tetrahydronaphthalene Chemical compound C1CCCC2=C1C=CC=C2I FBCNACVFOFCZHW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910014263 BrF3 Inorganic materials 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
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
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Abstract
本发明公开了一种基于手性转移策略合成C‑N轴手性菲啶酮类化合物的方法。该方法以简单易得的芳基碘化物和带有酰胺基团侧链的芳基溴化物为起始原料，在钯催化剂、膦配体、手性降冰片烯衍生物以及碱的作用下，在40‑100℃下于有机溶剂中搅拌反应，即可得到C–N轴手性菲啶酮类化合物。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，对映选择性高，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，具体涉及一种基于手性转移策略合成C-N轴手性菲啶酮类化合物的方法。
背景技术
轴手性骨架是一类非常重要的结构单元，广泛存在于具有生物活性的天然产物、药物分子、手性材料以及手性配体和催化剂中。其中，联芳基轴手性化合物的合成研究已经得到了长足的发展([1]Chem.Commun.2019,55,8514；[2]Acc.Chem.Res.2018,51,534；[3]Chem. Rev.2015,115,11239；[4]Chem.Soc.Rev.2015,44,3418)，而C–N轴手性化合物的不对称合成研究则相对较少([5]Acc.Chem.Res.2021,54,719；[6]Sci Sin Chim 2020,50,509；[7]Org.Prep. Proced.Int.2014,46,1)，其原因主要是C–N轴具有较高的旋转自由度和较低的旋转能垒，从而导致该类化合物的不对称合成具有很大的挑战。
自2002年Taguchi和Curran小组分别报道了第一例通过钯催化的氮烯丙基化反应不对称合成C–N轴手性苯胺类化合物以来([8]J.Org.Chem.2002,67,8682；[9]Tetrahedron: Asymmetry 2002,14,587)，一些有效的合成C–N轴手性骨架的方法相继被开发出来。已报道的不对称合成方法主要包括以下5种类型：(1)直接不对称构建C–N键([10]Angew.Chem.Int. Ed.2020,59,6775；[11]Angew.Chem.Int.Ed.2020,59,8844；[12]Nat.Commun.2019,10,3063； [13]Angew.Chem.Int.Ed.2006,45,1147)；(2)苯胺化合物的不对称N–H官能团化反应([14] J.Am.Chem.Soc.2005,127,3676；[15]J.Am.Chem.Soc.2006,128,12923；[16]ACS.Catal. 2019,9,2286；[17]J.Am.Chem.Soc.2012,134,916；[18]ACS Catal.2020,10,2324；[19]Nat. Commun.2019,10,3061；[20]J.Am.Chem.Soc.2018,140,12836)；(3)C–N键邻位C–H键的不对称官能团化反应([21]J.Am.Chem.Soc.2020,142,18266；[22]Angew.Chem.Int.Ed.2020, 59,13552；[23]Angew.Chem.Int.Ed.2019,58,6732；[24]J.Am.Chem.Soc.2015,137,12369； [25]J.Am.Chem.Soc.2018,140,868)；(4)不对称从头构建其中的一个芳环([26]Angew.Chem.Int.Ed.2019,58,15824；[27]J.Am.Chem.Soc.2017,139,1714；[28]Nat.Commun.2017,8,15489；[29]J.Am.Chem.Soc.2006,128,4586)；(5)对称苯胺化合物的去对称化反应([30]Nat. Commun.2020,11,2904；[31]Nat.Commun.2016,7,10677；[32]J.Am.Chem.Soc.2014,136, 10250)。
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。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C–N轴手性化合物仍然是轴手性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手性转移策略合成C–N轴手性菲啶酮类化合物的方法。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，对映选择性高，底物适用范围广，可放大到克级。
本发明提供的技术方案具体如下：
一种基于手性转移策略合成C-N轴手性菲啶酮类化合物的方法，包括以下步骤：
在保护气体氛围下，以芳基碘化物A和芳基溴化物B为起始原料，在钯催化剂C、膦配体D、手性降冰片烯衍生物E和碱F的作用下，于有机溶剂G中搅拌反应至完全，反应结束后将反应物分离即可得到式I所示的C–N轴手性菲啶酮类化合物；
反应方程式如下：
其中，R1-R5为芳基、杂环芳基、烷基、酯基、醛基、羧基、羟基、巯基、硅基、氨基、氰基、硝基、酰胺基、磺酰基、烷氧基、烯基、炔基、卤素中的一种或几种；x表示R1的个数，0≤x≤4；y表示R4的个数，0≤y≤4；z表示R5的个数，0≤z≤3；Ar1、Ar2和Ar3为芳烃或杂环芳烃。优选的，烷基为具有1～20个碳原子的烷基，例如甲基、乙基、异丙基、癸基、十六烷基等；烷氧基是指具有1～10个碳原子的烷氧基，例如甲氧基等；卤素是指氟、氯、溴、碘。
进一步，所述钯催化剂C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C为Pd(OAc)2。
进一步，所述膦配体D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。优选的膦配体D为三(2-呋喃基)膦。
进一步，所述手性降冰片烯衍生物E的结构式为：
其中：
i)R6为左边五元环上的取代基，p代表取代基个数，0≤p≤8；R7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)R6和R7取代基的种类可以相同，也可以不相同；
iii)每个R6和R7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、烷基或卤素等。优选(1S,4R)-2-降冰片烯乙酯作为手性共催化剂。
进一步，所述碱F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F为碳酸钾。
进一步，所述溶剂G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G为乙腈。
进一步，各原料的投料摩尔比为芳基碘化物A:芳基溴化物B:催化剂C:膦配体D:降冰片烯衍生物E:碱F＝1.5:1:0.1:0.22:0.5:2.5。
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70℃。
进一步，所述反应时间为1-72h。优选反应时间为36h。
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C–N轴手性菲啶酮化合物，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；另一反应组分芳基溴化物制备简单，只需一步反应即可得到；
ii)本发明方法仅需简单的手性降冰片烯衍生物作为手性源即可实现高效的手性诱导(ee 值高达99％)，是现有不对称催化策略的重要补充；
iii)本发明方法具有很好的底物适用范围和官能团兼容性；
iv)本发明方法可以大量(克级)制备C–N轴手性菲啶酮化合物，具有较大的应用潜力，为工业化生产奠定了良好的基础。
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I-1的制备
在氩气保护下，向干燥并装有磁力搅拌子的反应管中加入醋酸钯(2.3mg，0.01mmol)、三(2-呋喃基)膦(5.1mg，0.022mmol)、碳酸钾(34.6mg,0.25mmol)和干燥的乙腈(1.0 mL)，然后加入(1S,4R)-2-降冰片烯-2-甲酸乙酯(8.3mg，0.05mmol)、2-甲基碘苯(32.7mg， 0.15mmol)和2-溴-3-甲基-N-(2-叔丁基苯基)苯甲酰胺(34.6mg，0.1mmol)。所得混合物于 70℃在氩气保护氛围下反应36小时。反应结束后冷却至室温，混合物用硅藻土过滤，乙酸乙酯洗涤，减压蒸馏除去溶剂，柱层析分离纯化得化合物I-1(黄色固体，91％产率，92％ee)。1H NMR(400MHz,CDCl3):δ8.42(d,J＝7.9Hz,1H),8.21(dd,J＝7.1,2.6Hz,1H),7.62(t,J＝8.6Hz,2H),7.47(t,J＝7.6Hz,1H),7.41(t,J＝7.6Hz,1H),7.25(t,J＝7.4Hz,1H),7.16–7.11 (m,3H),2.93(s,3H),1.71(s,3H),1.19(s,9H)；13C NMR(100MHz,CDCl3):δ164.26,147.75, 139.12,138.27,137.22,134.66,134.40,134.36,132.95,129.41,128.84,127.42,127.35,127.13, 127.02,126.48,125.44,121.65,121.29,36.40,31.57,25.82,23.78；HRMS(ESI-TOF):calc’d for C25H25NNaO[M+Na+]378.1828,found 378.1830；HPLC:Daicel Chiralpak AD-H column,10％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝7.22min,tR(minor)＝6.72min；
-86.2 (c 1.00,CHCl3).
实施例2：化合物I-2的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-乙基碘苯(34.8mg)，60℃反应45 小时，得化合物I-2(白色固体，64％产率，91％ee)。1H NMR(400MHz,CDCl3):δ8.41(d, J＝7.7Hz,1H),8.17(dd,J＝8.0,1.7Hz,1H),7.63–7.60(m,2H),7.46(t,J＝7.6Hz,1H),7.41(td,J＝8.1,7.7,1.5Hz,1H),7.26(t,J＝6.9Hz,2H),7.21(t,J＝7.7Hz,1H),7.12–7.10(m,1H), 2.92(s,3H),2.16–2.07(m,1H),1.87–1.78(m,1H),1.17(s,9H),0.86(t,J＝7.4Hz,3H)；13C NMR(100MHz,CDCl3):δ164.38,147.22,139.70,137.97,137.22,134.77,134.33,132.12, 131.85,131.72,129.53,128.71,127.38,127.31,127.11,126.90,126.52,121.84,121.50,36.37, 31.53,26.75,25.75,16.53；HRMS(ESI-TOF):calc’d forC26H27NNaO[M+Na+]392.1985,found 392.1976；HPLC:Daicel Chiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝254nm, tR(major)＝5.21min,tR(minor)＝4.79min；
-51.7(c 1.00,CHCl3).
实施例3：化合物I-3的制备
操作步骤同实施例1，区别在于所使用的碘化物为邻位TBS保护的羟甲基碘苯(52.2mg), 得化合物I-3(棕色油状液体，73％产率，96％ee)。1H NMR(400MHz,CDCl3):δ8.41(d,J＝ 7.7Hz,1H),8.25(d,J＝8.0Hz,1H),7.90(d,J＝7.5Hz,1H),7.66–7.62(m,2H),7.50–7.44(m, 2H),7.32–7.28(m,2H),7.19(dd,J＝7.8,1.6Hz,1H),3.87(s,2H),2.94(s,3H),1.17(s,9H), 0.85(s,9H),-0.10(s,3H),-0.11(s,3H)；13C NMR(100MHz,CDCl3):δ164.29,148.07,139.04, 137.27,136.52,134.86,134.44,133.22,129.41,129.39,128.82,127.89,127.36,127.34,127.26, 127.06,126.52,121.37,120.92,62.04,36.41,31.59,26.08,25.73,18.34,-5.15,-5.21；HRMS (ESI-TOF):calc’d for C31H39NNaO2Si[M+Na+]508.2642,found 508.2634；HPLC:Daicel Chiralpak IA column,5％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝7.52min,tR (minor)＝8.08min；
-67.5(c2.00,CHCl3).
实施例4：化合物I-4的制备
操作步骤同实施例1，区别在于所使用的碘化物为邻碘苯乙酸甲酯(41.4mg)，得化合物 I-4(黄色油状液体，81％产率，91％ee)。1H NMR(400MHz,CDCl3):δ8.39(d,J＝7.8Hz,1H), 8.28(dd,J＝8.1,1.6Hz,1H),7.65(dt,J＝7.8,1.7Hz,2H),7.52–7.45(m,1H),7.43(dd,J＝8.0, 1.5Hz,1H),7.26–7.21(m,2H),7.15(dd,J＝7.5,1.6Hz,1H),7.04(dd,J＝7.9,1.5Hz,1H),3.52 (s,3H),3.18(d,J＝18.1Hz,1H),3.02(d,J＝18.1Hz,1H),2.93(s,3H),1.16(s,9H)；13C NMR (100MHz,CDCl3):δ171.95,164.18,147.36,138.79,138.46,137.36,134.86,134.52,134.41, 132.06,129.81,129.15,128.31,127.54,127.34,127.31,127.10,122.15,121.38,121.22,51.85, 39.95,36.29,31.47,25.69；HRMS(ESI-TOF):calc’d for C27H27NNaO3[M+Na+]436.1883,found 436.1883；HPLC:Daicel ChiralpakIA column,10％iPrOH in nhexane,1mL/min,λ＝254nm,tR (major)＝11.42min,tR(minor)＝12.92min；
-1.3(c 1.00,CHCl3).
实施例5：化合物I-5的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-碘联苯(42.0mg)，60℃反应45小时，得化合物I-5(无色油状液体，66％产率，93％ee)。1H NMR(400MHz,CDCl3):δ8.46 (d,J＝7.8Hz,1H),8.40(d,J＝8.0Hz,1H),7.66(d,J＝7.4Hz,1H),7.49(t,J＝7.6Hz,1H),7.28–7.21(m,2H),7.05–6.97(m,3H),6.96–6.92(m,1H),6.90–6.86(m,1H),6.84–6.81(m,1H),6.67(dd,J＝7.9,1.5Hz,1H),6.62–6.56(m,2H),3.01(s,3H),0.94(s,9H)；13C NMR(100MHz,CDCl3):δ164.02,145.34,142.48,138.35,137.41,136.68,135.69,134.57,134.03,133.78,132.21, 130.54,128.80,128.24,128.04,127.98,127.82,127.56,127.21,126.71,125.81,122.48,120.78, 35.76,31.57,26.07；HRMS(ESI-TOF):calc’d forC30H27NNaO[M+Na+]440.1985,found 440.1988；HPLC:Daicel Chiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝254nm, tR(major)＝7.52min,tR(minor)＝4.94min；
-125.8(c 1.00,CHCl3).
实施例6：化合物I-6的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-氟碘苯(33.3mg)，得化合物I-6(白色固体，63％产率，98％ee)。1H NMR(400MHz,CDCl3):δ8.49(dd,J＝7.9,1.5Hz,1H),8.23 (d,J＝8.3Hz,1H),7.67(d,J＝6.9Hz,1H),7.63(dd,J＝8.2,1.5Hz,1H),7.53(t,J＝7.7Hz,1H), 7.44–7.40(m,1H),7.28(td,J＝7.6,1.6Hz,1H),7.21(td,J＝8.2,4.8Hz,1H),7.12–7.05(m, 2H),2.98(s,3H),1.24(s,9H)；13C NMR(100MHz,CDCl3):δ163.27,150.39(d,J＝247.8Hz), 146.57(d,J＝4.6Hz),139.27(d,J＝4.5Hz),137.67,134.80,133.36(d,J＝2.5Hz),130.28(d,J＝ 5.3Hz),129.09,128.52(d,J＝3.9Hz),128.44,128.11,127.75,127.72,126.83,123.78(d,J＝3.8 Hz),123.23,121.95(d,J＝8.4Hz),116.87(d,J＝22.8Hz),36.26,31.71,26.15；HRMS (ESI-TOF):calc’d for C24H22FNNaO[M+Na+]382.1578,found 382.1571；HPLC:Daicel Chiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝6.76min,tR (minor)＝6.25min；
-70.2(c 1.00,CHCl3).
实施例7：化合物I-7的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-苄氧基碘苯(46.5mg)，得化合物 I-7(黄色固体，70％产率，94％ee)。1H NMR(400MHz,CDCl3):δ8.45(dd,J＝7.9,1.5Hz,1H), 8.02(d,J＝8.2Hz,1H),7.62(d,J＝7.3Hz,1H),7.47(t,J＝7.6Hz,1H),7.39–7.37(m,1H),7.27 –7.23(m,3H),7.17–7.11(m,3H),6.98–6.94(m,4H),4.60(d,J＝12.2Hz,1H),4.44(d,J＝ 12.3Hz,1H),2.95(s,3H),1.18(s,9H)；13C NMR(100MHz,CDCl3):δ163.79,147.69,146.01, 141.14,137.26,136.58,134.56,134.00,129.90,129.29,128.82,128.36,127.89,127.82,127.59, 127.58,127.49,127.45,126.08,122.67,121.88,121.10,114.76,72.12,36.34,31.75,26.04；HRMS (ESI-TOF):calc’d for C31H29NNaO2[M+Na+]470.2091,found 470.2075；HPLC:Daicel Chiralpak AD-H column,15％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝7.61min,tR(minor)＝ 6.51min；
16.2(c1.00,CHCl3).
实施例8：化合物I-8的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲氧基碘苯(35.1mg)，得化合物 I-8(白色固体，78％产率，93％ee)。1H NMR(400MHz,CDCl3):δ8.47(d,J＝7.9Hz,1H),8.05 (d,J＝8.3Hz,1H),7.63(d,J＝7.3Hz,1H),7.59(d,J＝8.1Hz,1H),7.48(t,J＝7.6Hz,1H),7.31 (t,J＝7.6Hz,1H),7.22(t,J＝8.2Hz,1H),7.17(td,J＝7.4,1.4Hz,1H),6.96(d,J＝8.0Hz,1H), 6.88(d,J＝7.8Hz,1H),3.24(s,3H),2.97(s,3H),1.25(s,9H)；13C NMR(100MHz,CDCl3):δ 163.72,148.26,146.33,141.33,137.29,134.62,133.98,130.04,129.09,128.79,127.91,127.59, 127.53,127.27,126.02,122.65,121.98,120.86,113.71,56.29,36.53,31.80,26.15；HRMS (ESI-TOF):calc’d for C25H25NNaO2[M+Na+]394.1778,found 394.1775；HPLC:Daicel Chiralpak AD-H column,15％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝6.00min,tR(minor)＝ 5.66min；
-31.5(c1.00,CHCl3).
实施例9：化合物I-9的制备
操作步骤同实施例1，区别在于所使用的碘化物为2，3-二甲基碘苯(34.8mg)，60℃反应45小时，得化合物I-9(黄色油状液体，76％产率，87％ee)。1H NMR(400MHz,CDCl3): δ8.41(d,J＝5.6Hz,1H),8.07(d,J＝8.3Hz,1H),7.62(t,J＝6.8Hz,2H),7.45(t,J＝7.6Hz,1H), 7.39(t,J＝7.7Hz,1H),7.23(t,J＝7.5Hz,1H),7.10(d,J＝8.3Hz,1H),6.97(d,J＝7.8Hz,1H), 2.91(s,3H),2.29(s,3H),1.65(s,3H),1.26(s,9H)；13C NMR(100MHz,CDCl3):δ164.66,147.43, 140.12,139.67,139.08,137.11,134.52,134.06,131.67,129.73,128.32,127.10,126.99,126.90, 126.67,125.59,123.89,123.75,120.03,36.59,31.60,25.63,22.03,17.96；HRMS(ESI-TOF): calc’d for C26H28NO[M+H+]370.2165,found370.2157；HPLC:Daicel Chiralpak AD-H column, 10％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝6.39min,tR(minor)＝7.26min；
-72.8(c 1.00,CHCl3).
实施例10：化合物I-10的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基-3-氯碘苯(37.9mg)，60℃反应45小时，得化合物I-10(黄色油状液体，70％产率，94％ee)。1H NMR(400MHz,CDCl3):δ8.39(d,J＝7.8Hz,1H),8.07(d,J＝8.8Hz,1H),7.65–7.61(m,2H),7.49(d,J＝7.7Hz,1H),7.43–7.39(m,1H),7.30(d,J＝8.8Hz,1H),7.23(dd,J＝7.5,1.4Hz,1H),6.95(dd,J＝7.8,1.4 Hz,1H),2.89(s,3H),1.81(s,3H),1.24(s,9H)；13C NMR(100MHz,CDCl3):δ164.44,147.45, 140.23,139.41,137.49,137.41,134.25,133.85,131.62,129.87,128.75,127.70,127.23,127.02, 126.88,126.52,123.42,122.55,120.38,36.60,31.63,25.49,19.09；HRMS(ESI-TOF):calc’d for C25H24ClNNaO[M+Na+]412.1439,found 412.1431；HPLC:Daicel Chiralpak AD-H column,10％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝8.07min,tR(minor)＝7.37min；
-66.3 (c 1.00,CHCl3).
实施例11：化合物I-11的制备
操作步骤同实施例1，区别在于所使用的碘化物为2，4-二甲基碘苯(34.8mg)，60℃反应45小时，得化合物I-11(黄色固体，80％产率，93％ee)。1H NMR(400MHz,CDCl3):δ8.42(dd,J＝7.9,1.5Hz,1H),8.02(s,1H),7.64–7.60(m,2H),7.46(t,J＝7.6Hz,1H),7.43–7.39(m, 1H),7.28–7.23(m,1H),7.13(dd,J＝7.8,1.6Hz,1H),7.00(s,1H),2.95(s,3H),2.41(s,3H), 1.69(s,3H),1.20(s,9H)；13C NMR(100MHz,CDCl3):δ164.16,147.73,139.23,137.13,136.09, 135.42,134.66,134.31,132.95,130.37,129.37,128.78,127.51,127.31,127.22,127.13,126.47, 125.23,121.66,36.38,31.56,25.84,23.62,20.92；HRMS(ESI-TOF):calc’d for C26H27NNaO [M+Na+]392.1985,found 392.1988；HPLC:DaicelChiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝4.85min,tR(minor)＝5.22min；
-79.8(c 1.00, CHCl3).
实施例12：化合物I-12的制备
操作步骤同实施例1，区别在于所使用的碘化物为2，4-二甲基碘苯(35.4mg)，得化合物I-12(无色油状液体，72％产率，92％ee)。1H NMR(400MHz,CDCl3):δ8.43(d,J＝7.8Hz,1H),7.96(dd,J＝10.5,3.0Hz,1H),7.65–7.60(m,2H),7.50(t,J＝7.6Hz,1H),7.44–7.40(m, 1H),7.28–7.24(m,1H),7.12(dd,J＝7.8,1.6Hz,1H),6.92(dd,J＝8.6,3.0Hz,1H),2.94(s,3H), 1.70(s,3H),1.19(s,9H)；13C NMR(100MHz,CDCl3):δ163.93,156.67(d,J＝239.5Hz),147.76, 138.88,137.43,134.76(d,J＝2.3Hz),134.51,133.78(d,J＝2.5Hz),132.89,129.50,128.98, 128.01,127.80(d,J＝7.4Hz),127.61,127.41,126.56,122.93(d,J＝8.2Hz),120.98(d,J＝22.3 Hz),112.69(d,J＝23.8Hz),36.39,31.54,25.79,24.02；HRMS(ESI-TOF):calc’d for C25H24FNNaO[M+Na+]396.1734,found 396.1739；HPLC:Daicel Chiralpak AD-H column,10％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝7.01min,tR(minor)＝5.58min；
-73.8 (c 1.00,CHCl3).
实施例13：化合物I-13的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-甲基-4-溴碘苯(44.5mg)，得化合物I-13(黄色固体，67％产率，96％ee)。1H NMR(400MHz,CDCl3):δ8.41(d,J＝7.7Hz,1H), 8.33(d,J＝2.3Hz,1H),7.65(d,J＝7.3Hz,1H),7.61(dd,J＝8.2,1.4Hz,1H),7.50(t,J＝7.6Hz, 1H),7.43(td,J＝7.8,1.5Hz,1H),7.29–7.24(m,2H),7.10(dd,J＝7.7,1.5Hz,1H),2.93(s,3H), 1.68(s,3H),1.19(s,9H)；13C NMR(100MHz,CDCl3):δ163.98,147.76,138.66,137.49,137.39, 136.34,134.46,133.43,132.81,129.52,129.31,129.09,128.04,127.66,127.53,127.29,126.60, 123.21,114.06,36.41,31.58,25.57,23.61；HRMS(ESI-TOF):calc’d for C25H24BrNNaO[M+Na+] 456.0933,found 456.0931；HPLC:Daicel Chiralpak IA column,10％iPrOH in nhexane,1mL/min, λ＝254nm,tR(major)＝7.22min,tR(minor)＝6.88min；
-75.0(c 1.00,CHCl3).
实施例14：化合物I-14的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-甲基-4-碘苯甲酸甲酯(41.4mg),得化合物I-14(无色油状液体，91％产率，96％ee)。1H NMR(400MHz,CDCl3):δ8.96(d,J＝ 2.1Hz,1H),8.41(dd,J＝8.0,1.6Hz,1H),7.83–7.82(m,1H),7.68(d,J＝6.8Hz,1H),7.62(dd, J＝8.2,1.5Hz,1H),7.51(t,J＝7.6Hz,1H),7.46–7.42(m,1H),7.29–7.25(m,1H),7.10(dd,J ＝7.8,1.6Hz,1H),3.95(s,3H),2.99(s,3H),1.75(s,3H),1.19(s,9H)；13C NMR(100MHz, CDCl3):δ166.87,164.37,147.75,141.73,138.50,137.63,134.83,134.75,134.10,132.74,129.58, 129.18,128.80,127.94,127.24,127.22,126.59,125.52,122.52,121.27,52.34,36.44,31.60,25.64, 23.84；HRMS(ESI-TOF):calc’d forC27H27NNaO3[M+Na+]436.1883,found 436.1882；HPLC: Daicel Chiralpak AD-H column,20％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝6.69 min,tR(minor)＝7.53min；
-88.9(c 1.00,CHCl3).
实施例15：化合物I-15的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-甲基-4-碘苯甲酰胺(41.3mg)，得化合物I-15(白色固体，68％产率，97％ee)。1H NMR(400MHz,CDCl3):δ8.51(d,J＝2.1Hz, 1H),8.35(dd,J＝7.9,1.6Hz,1H),7.58–7.50(m,3H),7.43–7.36(m,2H),7.14–7.10(m,1H), 6.68(q,J＝4.7Hz,1H),6.55(dd,J＝7.9,1.5Hz,1H),2.92–2.81(m,6H),1.66(s,3H),1.17(s, 9H)；13C NMR(100MHz,CDCl3):δ168.03,164.51,147.65,140.16,138.32,137.61,134.68, 133.88,132.12,132.07,129.60,128.98,127.86,127.62,126.86,126.73,126.59,126.08,125.29, 121.13,36.46,31.58,26.93,25.61,23.56；HRMS(ESI-TOF):calc’d for C27H28N2NaO2[M+Na+] 435.2043,found 435.2038；HPLC:DaicelChiralpak AD-H column,15％iPrOH in nhexane,1 mL/min,λ＝300nm,tR(major)＝8.26min,tR(minor)＝7.58min；
-78.0(c 1.00,CHCl3).
实施例16：化合物I-16的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-碘苯甲酸甲酯(39.3mg)，60℃反应60小时，得化合物I-16(白色固体，61％产率，95％ee)。1H NMR(400MHz,CDCl3):δ8.54(t,J＝9.0Hz,2H),7.88(d,J＝8.6Hz,1H),7.74(d,J＝8.1Hz,1H),7.69(d,J＝7.4Hz,1H),7.57 (t,J＝7.6Hz,1H),7.51(t,J＝7.7Hz,1H),7.41(t,J＝7.5Hz,1H),7.31(s,1H),7.02(d,J＝7.7 Hz,1H),3.84(s,3H),3.03(s,3H),1.15(s,9H)；13C NMR(100MHz,CDCl3):δ166.48,162.83, 147.53,140.42,137.64,135.61,135.41,132.67,131.55,130.14,129.48,129.44,128.64,128.49, 128.36,127.87,127.77,124.32,122.33,118.96,52.46,36.15,31.69,26.18；HRMS(ESI-TOF): calc’d for C26H25NNaO3[M+Na+]422.1727,found422.1722；HPLC:Daicel Chiralpak IA column, 10％iPrOH in nhexane,1mL/min,λ＝230nm,tR(major)＝10.66min,tR(minor)＝12.80min；
-39.4(c 1.00,CHCl3).
实施例17：化合物I-17的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-三氟甲基碘苯(40.8mg)，75℃反应30小时，得化合物I-17(无色油状液体，54％产率，92％ee)。1H NMR(400MHz,CDCl3): δ8.59–8.55(m,2H),7.74(dd,J＝8.2,1.5Hz,1H),7.72–7.70(m,1H),7.58(t,J＝7.7Hz,1H),7.52–7.48(m,2H),7.42(td,J＝7.5,1.5Hz,1H),7.03(dd,J＝7.8,1.5Hz,1H),6.85(d,J＝1.3 Hz,1H),3.03(s,3H),1.15(s,9H)；13C NMR(100MHz,CDCl3):δ162.78,147.52,140.59,137.78, 135.31,135.29,132.38,131.48,130.26,129.87(q,J＝32.7Hz),129.67,128.72,128.47,128.36, 128.30,127.93,125.12,123.76(q,J＝270.6Hz),123.37,118.05(q,J＝3.7Hz),114.69(q,J＝4.1 Hz),36.16,31.66,26.12；19F NMR(376MHz,CDCl3):δ-62.9；HRMS(ESI-TOF):calc’d for C25H22F3NNaO[M+Na+]432.1546,found 432.1543；HPLC:DaicelChiralpak IA column,10％iPrOH in nhexane,1mL/min,λ＝230nm,tR(major)＝7.17min,tR(minor)＝8.83min；
-56.4 (c 1.00,CHCl3).
实施例18：化合物I-18的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-乙酰基碘苯(36.9mg)，70℃反应 48小时，得化合物I-18(无色油状液体，42％产率，93％ee)。1H NMR(400MHz,CDCl3): δ8.56(dd,J＝8.1,1.9Hz,2H),7.81(dd,J＝8.6,1.9Hz,1H),7.75(dd,J＝8.2,1.5Hz,1H),7.71 –7.69(m,1H),7.58(t,J＝7.7Hz,1H),7.53–7.49(m,1H),7.41(td,J＝7.5,1.5Hz,1H),7.18(d, J＝1.9Hz,1H),7.03(dd,J＝7.8,1.5Hz,1H),3.03(s,3H),2.43(s,3H),1.16(s,9H)；13C NMR (100MHz,CDCl3):δ197.19,162.84,147.58,140.55,137.68,136.01,135.59,135.48,132.59, 131.55,130.18,129.57,128.74,128.53,128.39,127.98,127.91,124.45,121.09,117.81,36.19, 31.72,26.59,26.19；HRMS(ESI-TOF):calc’d forC26H25NNaO2[M+Na+]406.1778,found 406.1774；HPLC:Daicel Chiralpak IA column,15％iPrOH in nhexane,1mL/min,λ＝254nm,tR (major)＝9.13min,tR(minor)＝13.28min；
-52.7(c 1.00,CHCl3).
实施例19：化合物I-19的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，70℃反应24小时，得化合物I-19(无色油状液体，96％产率，95％ee)。1H NMR(400MHz,CDCl3):δ8.45(d,J＝7.8Hz,1H),8.30(d,J＝8.9Hz,1H),7.81(d,J＝8.0Hz,1H),7.74(d,J＝8.2Hz,1H),7.67(t,J ＝7.9Hz,2H),7.54–7.47(m,2H),7.35(t,J＝7.4Hz,1H),7.28–7.24(m,1H),7.17(d,J＝9.1 Hz,1H),6.99–6.92(m,2H),2.95(s,3H),1.19(s,9H)；13C NMR(100MHz,CDCl3):δ164.71, 147.18,140.37,137.13,135.77,134.94,134.83,134.31,131.50,130.25,128.99,128.34,127.76, 127.52,127.37,126.90,126.13,126.06,125.45,124.55,123.74,122.25,117.18,36.54,31.63, 25.09；HRMS(ESI-TOF):calc’d for C28H25NNaO[M+Na+]414.1828,found 414.1824；HPLC: Daicel Chiralpak AD-H column,20％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝6.68 min,tR(minor)＝6.07min；
-69.9(c2.00,CHCl3).
实施例20：化合物I-20的制备
操作步骤同实施例1，区别在于所使用的碘化物为4-溴-1-碘萘(50mg)，得化合物I-20 (黄色固体，65％产率，96％ee)。1H NMR(400MHz,CDCl3):δ8.65(s,1H),8.45(d,J＝7.8Hz, 1H),8.28(d,J＝8.4Hz,1H),7.75(d,J＝7.9Hz,1H),7.70(d,J＝7.3Hz,1H),7.55(t,J＝7.6Hz, 1H),7.48(q,J＝7.9Hz,2H),7.36(d,J＝9.0Hz,1H),7.25(t,J＝7.5Hz,1H),7.03(t,J＝7.9Hz, 1H),6.87(d,J＝7.3Hz,1H),2.96(s,3H),1.22(s,9H)；13C NMR(100MHz,CDCl3):δ164.58, 147.16,140.11,137.37,135.63,134.21,133.72,132.47,131.17,130.41,129.15,129.10,128.05, 127.86,127.62,127.34,127.32,127.05,126.41,125.13,124.86,117.65,115.68,36.61,31.65, 24.75；HRMS(ESI-TOF):calc’d forC28H24BrNNaO[M+Na+]492.0933,found 492.0923；HPLC: Daicel Chiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝6.25 min,tR(minor)＝5.55min；
-34.5(c 1.00,CHCl3).
实施例21：化合物I-21的制备
操作步骤同实施例1，区别在于所使用的碘化物为5-碘四氢化萘(38.7mg)，70℃反应 24小时，得化合物I-21(黄色油状液体，91％产率，94％ee)。1H NMR(400MHz,CDCl3):δ8.42(dd,J＝7.9,1.5Hz,1H),8.09(d,J＝8.4Hz,1H),7.61(dd,J＝8.1,1.5Hz,2H),7.44(t,J＝ 7.6Hz,1H),7.41–7.37(m,1H),7.22(td,J＝7.5,1.5Hz,1H),7.04–7.01(m,2H),2.92(s,3H), 2.85(t,J＝6.7Hz,2H),2.08(dt,J＝16.5,5.5Hz,1H),1.85–1.78(m,1H),1.66–1.44(m,3H), 1.39–1.26(m,1H),1.23(s,9H)；13C NMR(100MHz,CDCl3):δ164.75,147.37,140.24,140.11, 138.73,137.13,134.72,134.02,132.02,129.58,128.36,127.13,126.91,126.45,126.29,125.51, 123.14,119.41,36.54,31.58,30.59,28.56,25.70,23.32,21.60；HRMS(ESI-TOF):calc’d for C28H29NNaO[M+Na+]418.2141,found 418.2137；HPLC:Daicel Chiralpak AD-H column,10％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝6.12min,tR(minor)＝6.81min；
-69.5 (c 2.00,CHCl3).
实施例22：化合物I-22的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘芘(49.2mg)，得化合物I-22(黄色油状液体，55％产率，94％ee)。1H NMR(400MHz,CDCl3):δ9.01(s,1H),8.53(dd,J＝7.9, 1.5Hz,1H),8.10(dd,J＝7.1,1.6Hz,1H),8.06(d,J＝8.9Hz,1H),8.01–7.90(m,3H),7.82(dd, J＝8.2,1.5Hz,1H),7.79–7.74(m,1H),7.60(t,J＝7.6Hz,1H),7.58–7.45(m,3H),7.29–7.24 (m,1H),6.91(dd,J＝7.9,1.5Hz,1H),3.11(s,3H),1.30(s,9H)；13C NMR(100MHz,CDCl3):δ 164.85,147.46,140.83,137.35,134.78,134.59,134.05,132.11,131.36,130.58,130.37,129.03, 127.93,127.73,127.68,127.13,126.73,126.64,126.19,125.72,125.40,125.24,124.99,124.89, 124.45,124.22,119.00,118.80,36.68,31.71,25.22；HRMS(ESI-TOF):calc’d for C34H27NNaO [M+Na+]488.1985,found 488.1978；HPLC:Daicel Chiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝290nm,tR(major)＝8.93min,tR(minor)＝9.99min；
-54.3(c 1.00, CHCl3).
实施例23：化合物I-23的制备
操作步骤同实施例1，区别在于所使用的碘化物为2,6-二苄氧基-3-碘苯甲酸甲酯(71.1mg), 得化合物I-23(无色油状液体，58％产率，90％ee)。1H NMR(400MHz,CDCl3):δ8.44(dd, J＝7.9,1.5Hz,1H),7.67(s,1H),7.60(d,J＝6.7Hz,1H),7.49(t,J＝7.6Hz,1H),7.46–7.33(m, 7H),7.25–7.19(m,2H),7.16–7.11(m,2H),7.08–7.05(m,1H),6.91–6.89(m,2H),5.25(s, 2H),4.56(d,J＝12.2Hz,1H),4.10(d,J＝12.1Hz,1H),3.48(s,3H),2.73(s,3H),1.18(s,9H)；13C NMR(100MHz,CDCl3):δ166.16,163.27,150.00,146.87,145.47,139.58,137.41,137.19, 136.60,134.40,133.35,129.64,129.56,128.80,128.66,128.54,128.27,128.11,127.99,127.79, 127.71,127.28,126.73,126.37,126.31,123.66,121.37,108.43,71.10,65.47,52.64,36.49,31.85, 25.50；HRMS(ESI-TOF):calc’d for C40H37NNaO5[M+Na+]634.2564,found 634.2560；HPLC: Daicel Chiralpak AD-Hcolumn,20％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝12.98 min,tR(minor)＝10.10min；
3.0(c 1.00,CHCl3).
实施例24：化合物I-24的制备
操作步骤同实施例1，区别在于所使用的碘化物如产物结构式所示(61.5mg)，得化合物 I-24(黄色固体，45％产率，89％ee)。1H NMR(400MHz,CDCl3):δ8.46(dd,J＝7.9,1.5Hz, 1H),7.77(s,1H),7.67(dd,J＝7.6,1.5Hz,1H),7.57(t,J＝7.6Hz,1H),7.30(d,J＝7.8Hz,1H), 7.21–7.12(m,3H),7.09–6.94(m,5H),4.74(d,J＝10.7Hz,1H),4.34(d,J＝10.7Hz,1H),2.98 (s,3H),1.76(s,3H),1.64(s,3H),1.11(s,9H)；13C NMR(100MHz,CDCl3):δ163.13,157.85, 150.67,148.77,145.99,139.77,137.63,136.09,135.50,132.33,129.73,129.50,129.40,129.26, 129.13,129.02,127.85,127.81,127.60,127.55,127.50,126.23,110.76,108.19,105.48,77.02, 36.26,31.73,27.00,25.87,24.38；HRMS(ESI-TOF):calc’d for C35H34NO5[M+H+]548.2432, found 548.2420；HPLC:DaicelChiralpak AD-H column,20％iPrOH in nhexane,1mL/min,λ＝ 254nm,tR(major)＝11.04min,tR(minor)＝6.78min；
-3.4(c 1.00,CHCl3).
实施例25：化合物I-25的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-碘-2-甲氧基吡啶(35.3mg)，得化合物I-25(黄色油状液体，50％产率，96％ee)。1H NMR(400MHz,CDCl3):δ8.51(d,J＝7.7Hz,1H),7.99(d,J＝5.7Hz,1H),7.92(d,J＝5.8Hz,1H),7.67(d,J＝7.3Hz,1H),7.61–7.56(m, 2H),7.35(td,J＝7.7,1.5Hz,1H),7.19(td,J＝7.5,1.5Hz,1H),6.89(dd,J＝7.9,1.5Hz,1H), 3.48(s,3H),2.99(s,3H),1.22(s,9H)；13C NMR(100MHz,CDCl3):δ163.43,153.20,146.19, 140.13,138.30,137.55,135.71,131.90,129.60,129.33,129.23,128.85,128.08,127.80,126.15, 124.04,114.84,53.48,36.45,31.81,25.93；HRMS(ESI-TOF):calc’d for C24H24N2NaO2[M+Na+] 395.1730,found 395.1727；HPLC:DaicelChiralpak AD-H column,15％iPrOH in nhexane,1 mL/min,λ＝254nm,tR(major)＝6.94min,tR(minor)＝5.74min；
-71.9(c 1.00,CHCl3).
实施例26：化合物I-26的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为2-溴-3- 氯-N-(2-叔丁基苯基)苯甲酰胺(36.7mg)，70℃反应24小时，得化合物I-26(棕色油状液体， 97％产率，93％ee)。1H NMR(400MHz,CDCl3):δ9.11(d,J＝8.9Hz,1H),8.53(dq,J＝7.9,1.4 Hz,1H),7.90(dd,J＝7.8,1.5Hz,1H),7.82(d,J＝7.9Hz,1H),7.76(d,J＝8.2Hz,1H),7.69(d,J ＝9.0Hz,1H),7.55–7.50(m,2H),7.38(t,J＝7.4Hz,1H),7.30–7.26(m,1H),7.19(d,J＝9.1 Hz,1H),7.00–6.96(m,1H),6.92(dd,J＝7.8,1.4Hz,1H),1.21(s,9H)；13CNMR(100MHz, CDCl3):δ163.66,147.10,140.02,136.54,136.18,135.49,132.66,131.29,130.40,130.38,129.19, 128.74,128.42,128.16,128.05,127.85,126.52,126.18,124.71,124.66,123.55,122.46,115.10, 36.57,31.62；HRMS(ESI-TOF):calc’d forC27H22ClNNaO[M+Na+]434.1282,found 434.1276； HPLC:Daicel Chiralpak AD-H column,20％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major) ＝5.83min,tR(minor)＝5.39min；
-80.7(c 2.00,CHCl3).
实施例27：化合物I-27的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为2-溴-3- 硝基-N-(2-叔丁基苯基)苯甲酰胺(37.7mg)，70℃反应24小时，得化合物I-27(棕色油状液体，90％产率，98％ee)。1H NMR(400MHz,CDCl3):δ8.75(dd,J＝8.0,1.4Hz,1H),8.09(dd, J＝7.8,1.4Hz,1H),7.82–7.76(m,2H),7.68(t,J＝7.8Hz,1H),7.64–7.61(m,2H),7.57–7.53 (m,1H),7.43–7.39(m,1H),7.31(td,J＝7.6,1.5Hz,1H),7.15(d,J＝9.1Hz,1H),7.04–7.00(m, 1H),6.96(dd,J＝7.8,1.5Hz,1H),1.21(s,9H)；13C NMR(100MHz,CDCl3):δ162.59,148.05, 147.16,139.46,136.80,135.88,132.74,131.11,130.61,129.50,129.18,128.87,128.27,128.02, 127.92,127.40,127.28,126.27,125.40,124.34,123.92,123.01,111.96,36.62,31.64；HRMS (ESI-TOF):calc’d for C27H23N2O3[M+H+]423.1703,found 423.1702；HPLC:Daicel Chiralpak AD-H column,15％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝8.20min,tR(minor)＝ 7.73min；
-211.3(c2.00,CHCl3).
实施例28：化合物I-28的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为1-溴-N-(2- 叔丁基苯基)-2-萘甲酰胺(38.2mg)，70℃反应24小时，得化合物I-28(棕色油状液体，83％产率，98％ee)。1H NMR(400MHz,CDCl3):δ8.85(d,J＝8.0Hz,1H),8.57(d,J＝8.8Hz,1H), 8.50–8.47(m,1H),8.06(dd,J＝7.4,2.0Hz,1H),8.00(d,J＝8.6Hz,1H),7.87(d,J＝8.0Hz, 1H),7.80–7.77(m,1H),7.75–7.67(m,3H),7.58–7.53(m,1H),7.41(t,J＝7.4Hz,1H),7.33(t, J＝7.5Hz,1H),7.14(d,J＝9.1Hz,1H),7.03(t,J＝7.7Hz,2H),1.21(t,J＝1.5Hz,9H)；13C NMR(100MHz,CDCl3):δ164.41,147.18,140.07,136.68,136.16,135.11,134.60,131.72, 130.24,129.28,129.06,128.86,128.74,128.49,128.47,128.20,128.00,126.67,126.59,126.42, 126.19,124.89,124.50,123.83,123.78,122.81,116.18,36.50,31.62；HRMS(ESI-TOF):calc’d for C31H26NO[M+H+]428.2009,found428.2011；HPLC:Daicel Chiralpak AD-H column,20％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝8.89min,tR(minor)＝7.56min；
-152.3(c 2.00,CHCl3).
实施例29：化合物I-29的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为2-溴-3- 甲基-N-(2-叔丁基-4-溴苯基)苯甲酰胺(42.5mg)，70℃反应24小时，得化合物I-29(白色固体，83％产率，95％ee)。1H NMR(400MHz,CDCl3):δ8.44(dd,J＝7.9,1.5Hz,1H),8.31(d, J＝8.9Hz,1H),7.87(d,J＝2.3Hz,1H),7.84(dd,J＝8.2,1.4Hz,1H),7.71–7.68(m,2H),7.54(t, J＝7.6Hz,1H),7.44–7.35(m,2H),7.28(d,J＝9.1Hz,1H),7.10–7.06(m,1H),6.79(d,J＝8.4 Hz,1H),2.96(s,3H),1.21(s,9H)；13C NMR(100MHz,CDCl3):δ164.66,149.71,139.73,137.35, 135.31,134.89,134.84,134.42,133.49,133.09,130.96,128.53,127.67,127.19,126.93,126.19, 125.82,125.44,124.84,123.51,122.95,122.51,117.37,36.80,31.45,25.05；HRMS(ESI-TOF): calc’d for C28H24BrNNaO[M+Na+]492.0933,found 492.0927；HPLC:Daicel Chiralpak AD-H column,10％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝13.61min,tR(minor)＝11.16 min；
-29.9(c2.00,CHCl3).
实施例30：化合物I-30的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为2-溴-3- 甲基-N-(2-叔丁基-4-苯基苯基)苯甲酰胺(42.2mg)，60℃反应36小时，得化合物I-30(白色固体，79％产率，98％ee)。1H NMR(400MHz,CDCl3):δ8.49(d,J＝7.9Hz,1H),8.34(d,J ＝8.9Hz,1H),7.98–7.97(m,1H),7.84(dd,J＝8.1,1.4Hz,1H),7.73–7.68(m,4H),7.57–7.49 (m,4H),7.45–7.31(m,3H),7.07–6.95(m,2H),2.98(s,3H),1.27(s,9H)；13C NMR(100MHz, CDCl3):δ164.79,147.46,141.67,141.03,139.70,137.21,135.77,134.98,134.87,134.35,131.90, 129.22,128.96,128.39,127.66,127.57,127.48,127.38,126.97,126.55,126.18,126.12,125.48, 124.65,123.79,122.34,117.29,36.74,31.68,25.09；HRMS(ESI-TOF):calc’d for C34H30NO [M+H+]468.2322,found 468.2315；HPLC:Daicel Chiralpak AD-H column,10％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝15.26min,tR(minor)＝14.32min；
-7.4(c 2.00, CHCl3).
实施例31：化合物I-31的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为2-溴-3- 甲基-N-(2-叔丁基-4-醛基苯基)苯甲酰胺(37.4mg)，60℃反应24小时，得化合物I-31(白色固体，84％产率，91％ee)。1H NMR(400MHz,CDCl3):δ10.13(s,1H),8.44(d,J＝7.9Hz, 1H),8.35–8.30(m,2H),7.84(d,J＝8.1Hz,1H),7.76(dd,J＝8.0,1.9Hz,1H),7.74–7.64(m, 2H),7.54(t,J＝7.6Hz,1H),7.38(t,J＝7.4Hz,1H),7.21(d,J＝9.1Hz,1H),7.09(d,J＝8.0Hz, 1H),7.03–6.91(m,1H),2.97(s,3H),1.29(s,9H)；13C NMR(100MHz,CDCl3):δ191.95,164.54, 148.89,146.38,137.52,136.36,135.03,134.84,134.80,134.52,132.57,132.06,128.58,128.57, 127.77,127.07,126.91,126.24,125.61,125.44,124.81,123.31,122.69,117.52,36.95,31.52, 25.09；HRMS(ESI-TOF):calc’d forC29H26NO2[M+H+]420.1958,found 420.1947；HPLC: Daicel Chiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝20.68 min,tR(minor)＝12.22min；
-8.4(c 2.00,CHCl3).
实施例32：化合物I-32的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为2-溴-3- 甲基-N-(2-叔丁基-4-苯乙烯基苯基)苯甲酰胺(44.8mg)，70℃反应24小时，得化合物I-32 (黄色油状液体，91％产率，97％ee)。1H NMR(400MHz,CDCl3):δ8.45(dd,J＝7.9,1.4Hz, 1H),8.30(d,J＝8.9Hz,1H),7.82–7.80(m,2H),7.69–7.65(m,2H),7.60–7.55(m,2H),7.54– 7.50(m,1H),7.46(dd,J＝8.2,2.0Hz,1H),7.41–7.32(m,4H),7.31–7.26(m,1H),7.24–7.12 (m,2H),7.04–6.99(m,1H),6.91(d,J＝8.1Hz,1H),2.95(s,3H),1.23(s,9H)；13C NMR(100 MHz,CDCl3):δ164.77,147.38,139.77,137.79,137.35,137.18,135.73,134.94,134.85,134.33, 131.83,129.49,129.17,128.85,128.51,128.38,127.89,127.55,127.37,126.95,126.73,126.20, 126.12,125.46,125.19,124.70,123.76,122.32,117.25,36.58,31.63,25.08；HRMS(ESI-TOF): calc’d for C36H32NO[M+H+]494.2478,found 494.2470；HPLC:Daicel Chiralpak AD-H column, 15％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝17.89min,tR(minor)＝14.86min；
22.5(c2.00,CHCl3).
实施例33：化合物I-33的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物为2-溴-3- 甲基-N-(2-叔丁基-4-苯乙炔基苯基)苯甲酰胺(44.6mg)，60℃反应36小时，得化合物I-33 (无色油状液体，78％产率，97％ee)。1H NMR(400MHz,CDCl3):δ8.46(dd,J＝7.9,1.6Hz, 1H),8.32(d,J＝8.9Hz,1H),7.93(d,J＝1.9Hz,1H),7.84(dd,J＝8.1,1.6Hz,1H),7.71–7.68 (m,2H),7.62–7.60(m,2H),7.54(t,J＝7.6Hz,1H),7.44(dd,J＝8.1,1.9Hz,1H),7.42–7.35(m, 4H),7.32(d,J＝9.1Hz,1H),7.09–7.04(m,1H),6.93(d,J＝8.0Hz,1H),2.97(s,3H),1.24(s, 9H)；13C NMR(100MHz,CDCl3):δ164.69,147.64,140.68,137.29,135.52,134.94,134.85, 134.39,133.78,131.84,131.71,130.82,128.54,128.45,127.63,127.30,126.95,126.19,126.04, 125.45,124.82,123.94,123.62,123.26,122.44,117.34,90.05,89.48,36.66,31.57,25.08；HRMS (ESI-TOF):calc’d for C36H30NO[M+H+]492.2322,found 492.2316；HPLC:Daicel Chiralpak AD-H column,15％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝10.59min,tR(minor)＝ 12.90min；
28.6(c2.00,CHCl3).
实施例34：化合物I-34的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物如产物结构式所示(46.3mg)，得化合物I-34(无色油状液体，62％产率，92％ee)。1H NMR(400MHz,CDCl3):δ8.45(dd,J＝7.9,1.5Hz,1H),8.30(d,J＝8.9Hz,1H),8.08(dd,J＝8.2,1.6Hz,1H), 7.81(dd,J＝8.1,1.4Hz,1H),7.69(t,J＝7.9Hz,2H),7.53(td,J＝8.4,8.0,1.7Hz,2H),7.38– 7.34(m,1H),7.31–7.25(m,2H),7.00–6.95(m,1H),6.89(dd,J＝7.8,1.4Hz,1H),2.96(s,3H), 1.50(s,3H),1.29(s,3H),0.89(s,9H),0.07(s,3H),-0.03(s,3H)；13CNMR(100MHz,CDCl3):δ 164.35,147.24,138.36,137.23,135.58,134.88,134.77,134.36,130.65,130.51,128.83,128.51, 128.22,127.59,127.28,126.87,126.19,126.15,125.30,124.79,123.70,122.40,117.28,76.28, 32.26,30.22,26.07,25.10,18.39,-1.89,-1.92；HRMS(ESI-TOF):calc’d for C33H37NNaO2Si [M+Na+]530.2486,found530.2488；HPLC:Daicel Chiralpak IA column,5％iPrOH in nhexane,1 mL/min,λ＝254nm,tR(major)＝10.22min,tR(minor)＝11.91min；
45.4(c 1.00,CHCl3).
实施例35：化合物I-35的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物如产物结构式所示(47.6mg)，得化合物I-35(无色油状液体，82％产率，98％ee)。1H NMR(400MHz,CDCl3):δ8.45(dd,J＝7.9,1.5Hz,1H),8.29(d,J＝8.9Hz,1H),7.81(dd,J＝8.1,1.4Hz,1H), 7.78(dd,J＝8.2,1.5Hz,1H),7.73–7.62(m,2H),7.57–7.46(m,2H),7.38–7.34(m,1H),7.32– 7.28(m,1H),7.15(dd,J＝9.1,0.9Hz,1H),6.98–6.94(m,2H),3.59–3.48(m,2H),2.95(s,3H), 1.17(s,3H),1.15(s,3H),0.76(s,9H),-0.18(s,3H),-0.24(s,3H)；13CNMR(100MHz,CDCl3):δ 164.79,144.51,141.03,137.12,135.76,135.02,134.90,134.32,131.91,131.05,128.74,128.32, 128.02,127.54,127.44,126.87,126.36,126.06,125.45,124.63,123.73,122.31,117.18,71.45, 41.91,25.96,25.56,25.51,24.94,18.34,-5.59,-5.63；HRMS(ESI-TOF):calc’d for C34H40NO2Si [M+Na+]522.2823,found522.2814；HPLC:Daicel Chiralpak AD-H column,5％iPrOH in nhexane, 1mL/min,λ＝254nm,tR(major)＝7.00min,tR(minor)＝7.67min；
-61.5(c 2.00,CHCl3).
实施例36：化合物I-36的制备
操作步骤同实施例1，区别在于所使用的碘化物为1-碘萘(38.1mg)，溴化物如产物结构式所示(36.2mg)，得化合物I-36(无色油状液体，95％产率，97％ee)。1H NMR(400MHz,CDCl3):δ8.49(dd,J＝7.9,1.4Hz,1H),8.34(d,J＝8.9Hz,1H),7.84(dd,J＝8.1,1.5Hz,1H), 7.80(dd,J＝8.2,1.5Hz,1H),7.74–7.71(m,2H),7.58–7.53(m,2H),7.41–7.37(m,1H),7.33– 7.29(m,1H),7.22(d,J＝9.0Hz,1H),7.04–6.99(m,1H),6.85(dd,J＝7.8,1.5Hz,1H),3.62– 3.53(m,2H),2.98(s,3H),1.43(s,3H),1.10(s,3H)；13C NMR(100MHz,CDCl3):δ165.93, 143.41,142.08,137.68,135.09,135.01,134.90,134.44,131.30,131.20,129.25,128.81,128.53, 127.87,127.13,126.64,126.20,126.09,125.39,124.74,123.61,122.93,117.72,73.91,42.44, 29.15,25.07,24.54；HRMS(ESI-TOF):calc’d for C28H26NO2[M+H+]408.1958,found 408.1952； HPLC:Daicel Chiralpak AD-Hcolumn,20％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major) ＝12.65min,tR(minor)＝11.38min；
-58.6(c 2.00,CHCl3).
实施例37：化合物I-37的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-碘苯乙酸甲酯(41.4mg)，溴化物如产物结构式所示(36.2mg)，70℃反应48小时，得化合物I-37(无色油状液体，61％产率，92％ee)。1H NMR(400MHz,CDCl3):δ8.41(dd,J＝7.9,1.5Hz,1H),8.30(dd,J＝8.1,1.7Hz,1H),7.70–7.67(m,2H),7.52–7.46(m,2H),7.31–7.26(m,2H),7.20(dd,J＝7.5,1.7Hz,1H),6.97(dd,J＝7.8,1.5Hz,1H),3.54–3.43(m,5H),3.22(s,2H),2.94(s,3H),1.38(s,3H),1.07(s, 3H)；13C NMR(100MHz,CDCl3):δ171.81,165.45,143.76,140.56,137.90,135.14,134.58, 134.52,131.63,131.07,129.34,128.38,128.30,127.84,127.39,126.58,122.29,121.84,121.29, 73.84,51.86,42.30,39.74,28.68,25.68,24.61；HRMS(ESI-TOF):calc’d for C27H27NNaO4 [M+Na+]452.1832,found 452.1828；HPLC:DaicelChiralpak IG column,25％iPrOH in nhexane, 1mL/min,λ＝254nm,tR(major)＝26.06min,tR(minor)＝31.34min；
-25.8(c 1.00,CHCl3).
实施例38：化合物I-38的制备
操作步骤同实施例1，区别在于所使用的碘化物为2-碘苯丙酸甲酯(43.5mg)，溴化物如产物结构式所示(36.2mg)，70℃反应60小时，得化合物I-38(无色油状液体，52％产率，88％ee)。1H NMR(400MHz,CDCl3):δ8.43(dd,J＝7.9,1.5Hz,1H),8.25–8.21(m,1H),7.70–7.66(m,2H),7.51–7.44(m,2H),7.32(td,J＝7.5,1.5Hz,1H),7.28–7.22(m,2H),6.98(dd,J＝ 7.8,1.5Hz,1H),3.58(s,3H),3.56(s,2H),3.19(s,1H),2.93(s,3H),2.61–2.50(m,1H),2.38– 2.28(m,2H),2.27–2.15(m,1H),1.38(s,3H),1.15(s,3H)；13C NMR(100MHz,CDCl3):δ172.88,165.48,144.07,141.35,137.84,137.73,134.63,134.47,132.33,130.90,129.13,128.20, 128.00,127.77,127.43,127.22,126.62,122.28,121.96,74.41,51.62,42.45,35.63,28.84,28.58, 25.72,24.60；HRMS(ESI-TOF):calc’d for C28H30NO4[M+H+]444.2169,found 444.2156；HPLC: Daicel Chiralpak IG column,25％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝26.49min, tR(minor)＝24.50min；
-32.5(c 1.00,CHCl3).
实施例39：化合物I-39的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-甲基碘苯(32.7mg)，溴化物如产物结构式所示(34.8mg)，得化合物I-39(无色油状液体，43％产率，92％ee)。1H NMR(400MHz,CDCl3):δ8.51(dd,J＝8.1,1.6Hz,1H),8.39(d,J＝8.4Hz,1H),7.81(dd,J＝8.0,1.6Hz, 1H),7.65–7.63(m,1H),7.53(td,J＝7.7,1.6Hz,1H),7.49–7.45(m,2H),7.11–7.08(m,2H), 6.42(s,1H),2.99(s,3H),2.84(s,1H),2.29(s,3H),1.53(s,3H),1.30(s,3H)；13CNMR(100MHz, CDCl3):δ163.55,145.89,139.92,138.52,137.54,135.81,134.49,133.71,131.45,129.37,129.35, 128.69,127.72,127.15,127.10,123.28,118.63,118.08,72.65,31.81,30.94,26.33,21.66；HRMS (ESI-TOF):calc’d for C24H23NNaO2[M+Na+]380.1621,found 380.1616；HPLC:Daicel Chiralpak IA column,15％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major)＝9.21min,tR(minor)＝9.97 min；
-111.2(c 0.5,CHCl3).
实施例40：化合物I-40的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-三氟甲基碘苯(40.8mg)，溴化物如产物结构式所示(34.8mg)，75℃反应36小时，得化合物I-39(无色油状液体，43％产率，92％ee)。1H NMR(400MHz,CDCl3):δ8.61(d,J＝8.6Hz,1H),8.55(d,J＝7.7Hz,1H),7.76(dd,J＝8.0,1.6Hz,1H),7.70(d,J＝7.3Hz,1H),7.59–7.54(m,2H),7.52–7.47(m,2H),7.09(dd,J＝7.7,1.5Hz,1H),6.85(s,1H),3.02(s,3H),2.48(s,1H),1.55(s,3H),1.29(s,3H)；13C NMR(100MHz,CDCl3):δ163.25,145.92,140.12,137.92,135.34,134.87,132.47,131.24, 129.91,129.80(q,J＝32.8Hz),129.61,128.97,128.72,128.36,128.08,127.91,123.76(q,J＝ 270.8Hz),123.56,118.16(q,J＝3.7Hz),114.50(q,J＝4.4Hz),72.98,32.08,31.07,26.21；19F NMR(376MHz,CDCl3)δ-62.9；HRMS(ESI-TOF):calc’d forC24H20F3NNaO2[M+Na+] 434.1338,found 434.1327；HPLC:Daicel Chiralpak IA column,15％iPrOH in nhexane,1mL/min, λ＝230nm,tR(major)＝9.12min,tR(minor)＝10.11min；
-107.1(c 1.00,CHCl3).
实施例41：化合物I-41的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-三氟甲基碘苯(40.8mg)，溴化物如产物结构式所示(37.6mg)，70℃反应48小时，得化合物I-41(无色油状液体，73％产率，90％ee)。1H NMR(400MHz,CDCl3):δ8.59(d,J＝8.7Hz,1H),8.55(dd,J＝7.9,1.5Hz,1H),7.69(d,J＝7.1Hz,1H),7.58–7.46(m,5H),7.11(d,J＝7.6Hz,1H),6.85(s,1H),3.02(s,3H), 2.32(s,1H),1.93(dq,J＝14.7,7.4Hz,1H),1.80–1.64(m,2H),1.44(dq,J＝14.7,7.4Hz,1H), 0.84(t,J＝7.4Hz,2H),0.64(t,J＝7.4Hz,3H)；13C NMR(100MHz,CDCl3):δ163.24,143.33, 140.40,137.78,136.18,135.28,132.50,131.85,130.19,129.51(q,J＝32.8Hz),129.29,129.18, 128.62,128.25,128.18,127.86,123.79(q,J＝270.8Hz),123.43,117.95(q,J＝3.7Hz),114.52(q, J＝4.3Hz),78.58,33.68,33.48,26.24,8.39,7.79；19F NMR(376MHz,CDCl3)δ-62.9；HRMS (ESI-TOF):calc’d for C26H24F3NNaO2[M+Na+]462.1651,found 462.1649；HPLC:Daicel Chiralpak AD-H column,20％iPrOH innhexane,1mL/min,λ＝254nm,tR(major)＝11.73min,tR (minor)＝10.05min；
-76.6(c1.00,CHCl3).
实施例42：化合物I-42的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-三氟甲基碘苯(40.8mg)，溴化物为 2-溴-3-甲基-N-(2-异丙基苯基)苯甲酰胺(33.2mg)，60℃反应36小时，得化合物I-42(黄色固体，52％产率，91％ee)。1H NMR(400MHz,CDCl3):δ8.61(d,J＝8.6Hz,1H),8.57(dd,J＝7.9,1.5Hz,1H),7.72(d,J＝7.2Hz,1H),7.61–7.54(m,3H),7.50(dd,J＝8.7,1.9Hz,1H),7.45 –7.41(m,1H),7.16(dd,J＝7.8,1.3Hz,1H),6.89(s,1H),3.04(s,3H),2.58(hept,J＝7.1Hz,1H), 1.17(d,J＝6.9Hz,3H),1.04(d,J＝6.9Hz,3H)；13C NMR(100MHz,CDCl3):δ161.70,146.84, 139.67,137.77,135.33,135.12,132.47,130.12,130.03(q,J＝32.8Hz),128.85,128.68,128.38, 128.24,128.04,127.96,127.76,123.74(q,J＝270.7Hz),123.34,118.15(q,J＝3.6Hz),113.65(q, J＝4.2Hz),28.32,26.22,24.00,23.36；19F NMR(376MHz,CDCl3)δ-62.9；HRMS(ESI-TOF): calc’d for C24H20F3NNaO[M+Na+]418.1389,found 418.1385；HPLC:Daicel Chiralpak IA column,10％iPrOH in nhexane,1mL/min,λ＝230nm,tR(major)＝6.91min,tR(minor)＝8.66 min；
-13.4(c 1.00,CHCl3).
实施例43：化合物I-43的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-三氟甲基碘苯(40.8mg)，溴化物为2-溴-3-甲基-N-(2-溴-3-甲基苯基)苯甲酰胺(38.3mg)，45℃反应72小时，得化合物I-43(无色油状液体，57％产率，96％ee)。1H NMR(400MHz,CDCl3):δ8.62(d,J＝8.6Hz,1H),8.57 (dd,J＝7.9,1.6Hz,1H),7.72(dd,J＝7.5,1.5Hz,1H),7.59(t,J＝7.7Hz,1H),7.52(dd,J＝8.7, 1.9Hz,1H),7.50–7.43(m,2H),7.22(dd,J＝6.7,2.6Hz,1H),6.86(d,J＝1.9Hz,1H),3.03(s, 3H),2.56(s,3H)；13C NMR(100MHz,CDCl3):δ161.19,141.31,138.54,137.99,137.13,135.39, 132.52,131.84,130.19(q,J＝33.1Hz),128.87,128.69,128.52,128.04,127.96,127.8,125.83, 123.75(q,J＝270.8Hz),123.47,118.48(q,J＝3.6Hz),112.95(q,J＝4.2Hz),26.22,23.82；19F NMR(376MHz,CDCl3)δ-62.7；HRMS(ESI-TOF):calc’d for C22H16BrF3NO[M+H+]446.0362, found 446.0351；HPLC:Daicel Chiralpak AD-Hcolumn,15％iPrOH in nhexane,1mL/min,λ＝ 254nm,tR(major)＝11.44min,tR(minor)＝8.86min；
-84.7(c 2.00,CHCl3).
实施例44：化合物I-44的制备
操作步骤同实施例1，区别在于所使用的碘化物为3-三氟甲基碘苯(40.8mg)，溴化物为 2-溴-3-甲基-N-(2-碘-3-甲基苯基)苯甲酰胺(43mg)，50℃反应72小时，得化合物I-44(黄色固体，65％产率，98％ee)。1H NMR(400MHz,CDCl3):δ8.63(d,J＝8.6Hz,1H),8.58(dd, J＝7.9,1.4Hz,1H),7.72(dd,J＝7.7,1.5Hz,1H),7.59(t,J＝7.7Hz,1H),7.54–7.48(m,2H), 7.42(dd,J＝7.7,1.6Hz,1H),7.18(dd,J＝7.6,1.6Hz,1H),6.83(s,1H),3.04(s,3H),2.61(s,3H)；13C NMR(100MHz,CDCl3):δ161.12,145.31,140.88,138.46,138.01,135.39,132.51,130.47, 130.16(q,J＝32.8Hz),129.98,128.69,128.54,128.23,128.00,127.20,123.75(q,J＝270.8Hz), 123.54,118.48(q,J＝3.6Hz),113.13(q,J＝4.2Hz),106.16,29.40,26.26；19F NMR(376MHz, CDCl3)δ-62.7；HRMS(ESI-TOF):calc’d forC22H16F3INO[M+H+]494.0223,found 494.0213； HPLC:Daicel Chiralpak AD-H column,15％iPrOH in nhexane,1mL/min,λ＝254nm,tR(major) ＝13.45min,tR(minor)＝10.34min；
-111.4(c 2.00,CHCl3).
实施例45：化合物I-45的制备
操作步骤同实施例1，区别在于所使用的碘化物为4,4'-二碘-3,3'-二甲基-1,1'-联苯(43.4mg， 0.1mmol)，溴化物2-溴-3-甲基-N-(2-叔丁基苯基)苯甲酰胺(76.2mg，0.22mmol)，反应时间为72小时，得化合物I-45(白色固体，85％产率，>99％ee)。1H NMR(400MHz,CDCl3):δ 8.50(s,2H),8.46(d,J＝7.8Hz,2H),7.68(d,J＝7.4Hz,2H),7.63(d,J＝8.1Hz,2H),7.51(t,J＝ 7.6Hz,2H),7.48–7.38(m,4H),7.32–7.24(m,2H),7.16(d,J＝7.7Hz,2H),3.07(s,6H),1.81(s, 6H),1.24(s,18H)；13C NMR(100MHz,CDCl3):δ164.18,147.83,139.03,137.67,137.33,134.65, 134.24,132.99,132.88,129.53,128.99,127.65,127.62,127.35,126.60,126.07,125.08,122.18, 36.47,31.65,26.08,24.01；HRMS(ESI-TOF):calc’d for C50H49N2O2[M+H+]709.3789,found 709.3790；HPLC:DaicelChiralpak AD-H column,20％iPrOH in nhexane,1mL/min,λ＝254nm, tR(major)＝6.64min；
-31.4(c 2.00,CHCl3).
实施例46：化合物I-28的克级制备
在氩气保护下，向干燥并装有磁力搅拌子的50mL反应管中加入醋酸钯(33.7mg，0.15 mmol)、三(2-呋喃基)膦(76.6mg，0.33mmol)、碳酸钾(1.04g,7.5mmol)和干燥的乙腈(15mL)，然后加入(1S,4R)-2-降冰片烯-2-甲酸乙酯(125mg，0.75mmol)、1-碘萘(1.02g，4mmol)和1-溴-N-(2-叔丁基苯基)-2-萘甲酰胺(1.15g，3mmol)。所得混合物于70℃在氩气保护氛围下反应72小时。反应结束后冷却至室温，混合物用硅藻土过滤，乙酸乙酯洗涤，减压蒸馏除去溶剂，柱层析分离纯化得化合物I-28(1.1g，白色固体，84％产率，98％ee)。同时以71％的回收率回收手性降冰片烯。
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)
1.一种基于手性转移策略合成C–N轴手性菲啶酮类化合物的方法，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和芳基溴化物B为起始原料，在钯催化剂C、膦配体D、手性降冰片烯衍生物E和碱F的作用下，于有机溶剂G中搅拌反应至完全，反应结束后将反应物分离即可得到式I所示的C–N轴手性菲啶酮类化合物；
反应方程式如下：
其中，R1-R5为芳基、杂环芳基、烷基、酯基、醛基、羧基、羟基、巯基、硅基、氨基、氰基、硝基、酰胺基、磺酰基、烷氧基、烯基、炔基、卤素中的一种或几种；x表示R1的个数，0≤x≤4；y表示R4的个数，0≤y≤4；z表示R5的个数，0≤z≤3；Ar1、Ar2和Ar3为芳烃或杂环芳烃。
2.根据权利要求1所述的方法，其特征在于：所述钯催化剂C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。
3.根据权利要求1所述的方法，其特征在于：所述膦配体D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。
4.根据权利要求1所述的方法，其特征在于：所述手性降冰片烯衍生物E的结构式为：
其中：
i)R6为左边五元环上的取代基，p代表取代基个数，0≤p≤8；R7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)R6和R7取代基的种类可以相同，也可以不相同；
iii)每个R6和R7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。
5.根据权利要求1所述的方法，其特征在于：所述碱F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。
6.根据权利要求1所述的方法，其特征在于：所述溶剂G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。
7.根据权利要求1所述的方法，其特征在于：所述保护气体选自氩气或氮气。
8.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℃。
9.根据权利要求1所述的方法，其特征在于：所述反应时间为1-72h。
10.根据权利要求1所述的方法，其特征在于：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。
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| WO2023016562A1 (zh) * | 2021-08-12 | 2023-02-16 | 浙江同源康医药股份有限公司 | 多环类化合物及其用途 |
| CN117623839A (zh) * | 2023-11-28 | 2024-03-01 | 华中师范大学 | 一种联芳基轴手性吡咯化合物及其合成方法和应用 |
-
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Non-Patent Citations (2)
| Title |
|---|
| OSAMU KITAGAWA: "Chiral Pd-Catalyzed Enantioselective Syntheses of Various N−C Axially Chiral Compounds and Their Synthetic Applications", ACC. CHEM. RES. * |
| ZE-SHUI LIU: "Construction of axial chirality via palladium/chiral norbornene cooperative catalysis", NATURE CATALYSIS * |
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| CN114456022A (zh) * | 2022-02-08 | 2022-05-10 | 南京工业大学 | 氮杂环卡宾催化不饱和醛与α-芳基草酸酯反应合成轴手性化合物的制备方法 |
| CN117623839A (zh) * | 2023-11-28 | 2024-03-01 | 华中师范大学 | 一种联芳基轴手性吡咯化合物及其合成方法和应用 |
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