Enantioselective Synthesis of Quaternary Stereocenter Aldehydes by Palladium-Catalyzed Intermolecular Propargylation Reaction

A highly efficient palladium-catalyzed enantioselective α-propargylation of α-alkyl-α-aryl disubstituted aldehydes with propargylic acetates has been developed using BINOL-derived chiral phosphoramidite ligands. This protocol affords a series of enantioenriched aldehydes bearing all-carbon quaternary stereocenters in moderate to good yields with high enantioselectivities. The reaction features a broad substrate scope, mild reaction conditions, facile scalability, and versatile downstream transformations. Density functional theory (DFT) calculations were conducted to elucidate the reaction mechanism and the origin of the enantioselectivity.