Asymmetric Cross-Dehydrogenative Coupling of Glycinates via Iodine-Mediated Photoredox/Lewis Acid Synergistic Catalysis
Jiuqi Tan, Hanyu Su, Min Chen, Fengnan Xiao, Longqing Yang, Xiaoming Feng, Liang-Wen Feng, Xiaohua Liu
Abstract
The oxidative cross-dehydrogenative coupling (CDC) via α-carbonyl radicals significantly broadens the application scope of carbonyl compounds as synthons, offering a promising approach for carbon–carbon bond formation in organic synthesis. However, achieving cross-coupling and stereocontrol under mild reaction conditions has remained a significant challenge. Here, we report a synergistic catalytic platform that enables highly diastereo- and enantioselective CDC of β-keto carbonyls with glycine derivatives. The strategy introduces a photoredox catalyst and a chiral magnesium complex catalyst, leveraging the oxidations of the two coupling partners via independent pathways through the use of peroxybenzoate and a catalytic amount of NaI under visible-light irradiation. The β-carbonyl-substituted glycine derivatives can be readily obtained with exceptional stereocontrol (up to >19:1 dr, >99% ee) and yield, spanning a series of glycinates with both electron-donating and electron-withdrawing N -aryl substitutions. Mechanistic studies reveal a radical pathway rather than oxidative polar addition, showcasing a paradigm for merging photoredox-generated open-shell intermediates in C(sp 3 )–H cross-coupling.