Asymmetric N‐Alkylation of 1H‐Indoles via Carbene Insertion Reaction

Author:

Peng Quanxin1,Huang Meirong2,Xu Guangyang1,Zhu Yan1,Shao Ying1,Tang Shengbiao1,Zhang Xinhao2,Sun Jiangtao1ORCID

Affiliation:

1. Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology School of Petrochemical Engineering Changzhou University 1 Gehu Road 213164 Changzhou China

2. Shenzhen Bay Laboratory Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School 518055 Shenzhen China

Abstract

AbstractAn intermolecular enantioselective N‐alkylation reaction of 1H‐indoles has been developed by cooperative rhodium and chiral phosphoric acid catalyzed N−H bond insertion reaction. N‐Alkyl indoles with newly formed stereocenter adjacent to the indole nitrogen atom are produced in good yields (up to 95 %) with excellent enantioselectivities (up to >99 % ee). Importantly, both α‐aryl and α‐alkyl diazoacetates are tolerated, which is extremely rare in asymmetric X−H (X=N, O, S et al.) and C−H insertion reactions. With this method, only 0.1 mol % of rhodium catalyst and 2.5 mol % of chiral phosphoric acid are required to complete the conversion as well as achieve the high enantioselectivity. Computational studies reveal the cooperative relay of rhodium and chiral phosphoric acid, and the origin of the chemo and stereoselectivity.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

General Medicine

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