Copper(I)-Catalyzed Asymmetric 1,4-Conjugate Hydrophosphination of α,β-Unsaturated Amides

Abstract

A catalytic asymmetric conjugate hydrophosphination of α,β-unsaturated amides is accomplished by virtue of the strong nucleophilicity of copper(I)-PPh₂ species, which provides an array of chiral phosphines bearing an amide moiety in high to excellent yields with excellent enantioselectivity. Furthermore, the dynamic kinetic resolution of unsymmetrical diarylphosphines (HPAr¹Ar²) is successfully carried out through the copper(I)-catalyzed conjugate addition to α,β-unsaturated amides, which affords P-chiral phosphines with good-to-high diastereoselectivity and high enantioselectivity. ¹H NMR studies show that the precoordination of HPPh₂ to copper(I)-bisphosphine complex is critical for the efficient deprotonation by Barton's Base. Moreover, the relative stability of the copper(I)-(R,R_P)-TANIAPHOS complex in the presence of excessive HPPh₂, confirmed by ³¹P NMR studies, is pivotal for the high asymmetric induction, as the ligand exchange between bisphosphine and HPPh₂ would significantly reduce the enantioselectivity. At last, a double catalytic asymmetric conjugate hydrophosphination furnishes the corresponding product in high yield with high diastereoselectivity and excellent enantioselectivity, which is transformed to a chiral pincer palladium complex in moderate yield. This chiral palladium complex is demonstrated as an excellent catalyst in the asymmetric conjugate hydrophosphination of chalcone.