Copper-Catalyzed Asymmetric Radical 1,2-Carboalkynylation of Alkenes with Alkyl Halides and Terminal Alkynes

• Published in: Journal of the American Chemical Society 2020-05, Vol.142 (20), p.9501-9509
• Main Authors: Dong, Xiao-Yang, Cheng, Jiang-Tao, Zhang, Yu-Feng, Li, Zhong-Liang, Zhan, Tian-Ya, Chen, Ji-Jun, Wang, Fu-Li, Yang, Ning-Yuan, Ye, Liu, Gu, Qiang-Shuai, Liu, Xin-Yuan
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c03130

A copper-catalyzed intermolecular three-component asymmetric radical 1,2-carboalkynylation of alkenes has been developed, providing straightforward access to diverse chiral alkynes from readily available alkyl halides and terminal alkynes. The utilization of a cinchona alkaloid-derived multidentate N,N,P-ligand is crucial for the efficient radical generation from mildly oxidative precursors by copper and the effective inhibition of the undesired Glaser coupling side reaction. The substrate scope is broad, covering (hetero)­aryl-, alkynyl-, and aminocarbonyl-substituted alkenes, (hetero)­aryl and alkyl as well as silyl alkynes, and tertiary to primary alkyl radical precursors with excellent functional group compatibility. Facile transformations of the obtained chiral alkynes have also been demonstrated, highlighting the excellent complementarity of this protocol to direct 1,2-dicarbofunctionalization reactions with C­(sp 2/sp 3)-based reagents.