Rhodium(I) Carbene-Promoted Enantioselective C−H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights

Wang，Tian Yi1,2; Chen，Xiao Xuan2; Zhu，Dong Xing1; Chung，Lung Wa2; Xu，Ming Hua1,2,3

2022

10.1002/anie.202207008

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   Impact Factor & Quartile

1433-7851

1521-3773

A rhodium(I)-diene catalyzed highly enantioselective C(sp)−H functionalization of simple unprotected indoles, pyrroles, and their common analogues such as furans, thiophenes, and benzofurans with arylvinyldiazoesters has been developed for the first time. This transformation features unusual site-selectivity exclusively at the vinyl terminus of arylvinylcarbene and enables a reliable and rapid synthetic protocol to access a distinctive class of diarylmethine-bearing α,β-unsaturated esters containing a one or two heteroarene-attached tertiary carbon stereocenter in high yields and excellent enantioselectivities under mild reaction conditions. Mechanistic studies and DFT calculations suggest that, compared to the aniline substrate, the more electron-rich indole substrate lowers the C−C addition barrier and alters the rate-determining step to the reductive elimination, leading to different isotope effect.

Asymmetric Catalysis Carbene Insertion Chiral Diene C−H Functionalization Unprotected Indoles

SCI ; EI

English

NI Journal Papers

Others

WOS:000821522700001

20222812336264

Aniline ; Enantioselectivity ; Olefins ; Rhodium compounds

Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Organic Compounds:804.1

CHEMISTRY

2-s2.0-85133617053

Scopus

1.State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,and School of Pharmacy,University of Chinese Academy of Sciences,Shanghai,201203,China
2.Shenzhen Grubbs Institute and Department of Chemistry,Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,518055,China
3.School of Chemistry and Chemical Engineering,Henan Normal University,Xinxiang,Henan 453007,China

Wang，Tian Yi,Chen，Xiao Xuan,Zhu，Dong Xing,et al. Rhodium(I) Carbene-Promoted Enantioselective C−H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2022.

Wang，Tian Yi,Chen，Xiao Xuan,Zhu，Dong Xing,Chung，Lung Wa,&Xu，Ming Hua.(2022).Rhodium(I) Carbene-Promoted Enantioselective C−H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION.

Wang，Tian Yi,et al."Rhodium(I) Carbene-Promoted Enantioselective C−H Functionalization of Simple Unprotected Indoles, Pyrroles and Heteroanalogues: New Mechanistic Insights".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2022).