Enantioselective Nickel-Catalyzed Cross-Dehydrogenative Coupling of Aldehydes and Alkenes toward Skipped Enones

Enantioenriched skipped enones bearing α-stereogenic centers are prevalent in natural products and bioactive molecules, yet their synthesis typically relies on prefunctionalized substrates or specially designed scaffolds. Herein, we report the first nickel-catalyzed enantioselective cross-dehydrogenative coupling of alkenes with aldehydes, furnishing skipped enones directly from two C-H feedstocks. Aryl radical serves as intermolecular hydrogen atom transfer agent for activation of allylic and aldehydic C-H bonds, enabling selective radical heterocoupling via nickel catalysis. Enantiocontrol is achieved by employment of chiral pyridine imidazoline ligand. Undesired side reactions, such as radical homocoupling, background noncatalyzed radical recombination, and β-hydride elimination, are all suppressed under the developed reaction conditions. The reaction proceeds under mild conditions with broad substrate scope, high functional-group tolerance, and good site-selectivity and enantioselectivity.