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Catalytic Enantioselective Addition of Prochiral Radicals to Vinylpyridines

Cao, Kangning, Tan, Siu Min, Lee, Richmond, Yang, Songwei, Jia, Hongshao, Zhao, Xiaowei, Qiao, Baokun, Jiang, Zhiyong
Journal of the American Chemical Society 2019 v.141 no.13 pp. 5437-5443
Bronsted acids, aldehydes, catalytic activity, enantioselectivity, free radicals, hydrogen bonding, imines, ketones, light, pyridines, redox reactions
Pyridine, one of the most important azaarenes, is ubiquitous in functional molecules. The electronic properties of pyridine have been exploited to trigger asymmetric transformations of prochiral species as a direct approach for accessing chiral pyridine derivatives. However, the full potential of this synthetic strategy for the construction of enantioenriched γ-functionalized pyridines remains untapped. Here, we describe the first enantioselective addition of prochiral radicals to vinylpyridines under cooperative photoredox and asymmetric catalysis mediated by visible light. The enantioselective reductive couplings of vinylpyridines with aldehydes, ketones, and imines were achieved by employing a chiral Brønsted acid to activate the reaction partners and provide stereocontrol via H-bonding interactions. Valuable chiral γ-secondary/tertiary hydroxyl- and amino-substituted pyridines were obtained in high yields with good to excellent enantioselectivities.