Construction of Tetrasubstituted α‐Amino‐ and α‐Alkoxy Phosphine Oxides via Pd‐Catalyzed Regio‐ and Enantioselective Hydrophosphinylation of Dienes

Abstract Significant progress has been made in the asymmetric hydrofunctionalization of dienes to construct vinylic stereogenic carbon centers. However, achieving enantioselective hydrofunctionalization of substituted dienes with heteroatom nucleophiles to form vinylic tetrasubstituted carbon centers remains a formidable challenge. This difficulty arises primarily from issues of regio‐control, steric hindrance, and stereo‐discrimination. In this study, we present a palladium‐catalyzed regio‐ and enantioselective hydrophosphinylation of 2‐amido and 2‐alkoxyl dienes using phosphine oxides. This approach successfully constructs chiral allylic α‐aminophosphine oxides and α‐alkoxyphosphine oxides with tetrasubstituted carbon centers. Our method demonstrates a broad substrate scope with excellent enantioselectivity (up to > 99% ee) and high yields (up to 99%), achieving exclusive regio‐control under mild conditions. Additionally, the versatile post‐functionalization of the allyl group facilitates the synthesis of a wide variety of tetrasubstituted carbon centers featuring distinct heteroatom.