Copper-Catalyzed Enantioselective Three-Component Carboamidation of Styrenes with Alkanes and Amides

Efficient assembly of valuable chiral molecules from readily available and low-cost chemical feedstocks remains one of the most challenging tasks in synthetic chemistry today. Radical-mediated three-component carboamination of alkenes offers an attractive strategy for addressing this challenge. However, most existing reports focus on racemic examples and are largely limited to activated alkenes, preactivated alkylation reagents, or sufficiently active nucleophiles. Herein, we report a highly enantioselective three-component carboamidation of styrenes with unactivated alkanes and weakly nucleophilic amides. Enantioselective control is achieved by using chiral cationic copper catalysts. This method enables the synthesis of a variety of optically active amides with excellent enantioselectivity. Mechanistic studies reveal that the reaction proceeds via hydrogen atom transfer from the alkane followed by radical addition to the olefin.