Asymmetric Cyclopropanation of Primary N-Vinylamides via Carbene Transfer Catalyzed by Cationic Rh(I)/Diene Complexes: An Unexpected Outer-Sphere Mechanism

Zhang, Junyou1,2,3; Ma, Zhifeng1,2,4; Xu, Weici1,2; Wang, Zengwei1,2; Chung, Lung Wa1,2; Xu, Ming-Hua1,2,5

2024-06-06

10.1021/acscatal.4c02340

ACS CATALYSIS   影响因子和分区

2155-5435

A highly enantioselective intermolecular [2 + 1] cycloaddition of primary N-vinylamides with carbene intermediates was developed by taking advantage of cationic rhodium(I)/diene catalysis under mild conditions at room temperature. This cyclopropanation method facilitates rapid access to enantioenriched cyclopropylamides, an important motif in drug discovery, in generally good yields and high stereoselectivities (>20:1 dr, up to 99% ee). This approach employs a cationic rhodium(I) catalyst to form a pre-equilibrium complex with an enamide substrate. Kinetic experiments and comprehensive density functional theory (DFT) calculations were performed to elucidate the reaction mechanism. The kinetic data and DFT results support the existence of a resting-state complex between the rhodium(I)/diene catalyst and two enamide substrates. The computational studies show that the reaction involves an interesting, unexpected outer-sphere mechanistic pathway involving a sole Rh(I) catalytic cycle to form the major product and reveal that the diazo decomposition step is the rate-determining step.

asymmetric cyclopropanation metal-carbenetransfer rhodium(I) catalysis chiral diene N-vinylamide

SCI ; EI

英语

第一 ; 通讯

National Natural Science Foundation of China["21971103","21672229","21933003","22193020","22193023"] ; National Natural Science Foundation of China[2019CX01Y251] ; Guangdong Science and Technology Department[2020B121201002] ; Guangdong Provincial Key Laboratory of Catalysis["JCYJ20200109141408054","JCYJ20220530115408019","(1R,4R)-5"]

Chemistry

Chemistry, Physical

WOS:001245597800001

AMER CHEMICAL SOC

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Guangdong Prov Key Lab Catalysis, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Dept Chem, Guangdong Prov Key Lab Catalysis, Shenzhen 518055, Peoples R China
3.Harbin Inst Technol, Sch Chem & Chem Engn, Harbin 150001, Peoples R China
4.Yunnan Minzu Univ, Sch Chem & Environm, Yunnan Key Lab Chiral Funct Subst Res & Applicat, 2929 Yuehua Rd, Kunming 650504, Peoples R China
5.Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Henan, Peoples R China

Zhang, Junyou,Ma, Zhifeng,Xu, Weici,et al. Asymmetric Cyclopropanation of Primary N-Vinylamides via Carbene Transfer Catalyzed by Cationic Rh(I)/Diene Complexes: An Unexpected Outer-Sphere Mechanism[J]. ACS CATALYSIS,2024,14(12).

Zhang, Junyou,Ma, Zhifeng,Xu, Weici,Wang, Zengwei,Chung, Lung Wa,&Xu, Ming-Hua.(2024).Asymmetric Cyclopropanation of Primary N-Vinylamides via Carbene Transfer Catalyzed by Cationic Rh(I)/Diene Complexes: An Unexpected Outer-Sphere Mechanism.ACS CATALYSIS,14(12).

Zhang, Junyou,et al."Asymmetric Cyclopropanation of Primary N-Vinylamides via Carbene Transfer Catalyzed by Cationic Rh(I)/Diene Complexes: An Unexpected Outer-Sphere Mechanism".ACS CATALYSIS 14.12(2024).