Visible Light Induced Cu-Catalyzed Asymmetric C(sp3)–H Alkylation

• Published in: Journal of the American Chemical Society Vol. 143; no. 32; pp. 12777 - 12783
• Main Authors: Qi, Rupeng, Wang, Chao, Huo, Yumei, Chai, Hongli, Wang, Hongying, Ma, Zijian, Liu, Liangyu, Wang, Rui, Xu, Zhaoqing
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18-08-2021
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.1c05890

The asymmetric functionalization of C–H is one of the most attractive strategies in asymmetric synthesis. In the past decades, catalytic enantioselective C­(sp3)–H functionalization has been intensively studied and successfully applied in various asymmetric bond formations, whereas asymmetric C­(sp3)–H alkylation was not well developed. Photoredox catalysis has recently emerged as an efficient way to synthesize organic compounds under mild conditions. Despite many photoinduced stereoselective reactions that have been achieved, the related enantioselective C­(sp3)–C­(sp3) coupling is challenging, especially of the photocatalytic asymmetric C­(sp3)–H radical alkylation. Here, we report a visible light induced Cu catalyzed asymmetric sp 3 C–H alkylation, which is effective for coupling with unbiased primary, secondary, and tertiary alkyl fragments in high enantioselectivities. This reaction would provide a new approach for the synthesis of important molecules such as unnatural α-amino acids and late-stage functionalization of bioactive compounds, and will be useful for modern peptide synthesis and drug discovery.