Diastereo- and Enantioselective Pd-Catalyzed C-P Coupling for Axially and P-Chiral Phosphine Oxides via Simultaneous Dynamic Kinetic Asymmetric Transformation and Kinetic Resolution.

Abstract

The catalytic asymmetric synthesis of atropisomers bearing axial and P-chirality is highly appealing yet remains a significant synthetic challenge. Herein, we report a Pd-catalyzed diastereo- and enantioselective C-P coupling reaction that enables the atroposelective construction of P-stereogenic heterobiaryls via the combination of dynamic kinetic asymmetric transformation of heterobiaryls and kinetic resolution of nonsymmetric secondary phosphine oxides. This protocol exhibits a broad substrate scope with excellent functional group tolerance, delivering a diverse array of axial and P-chiral phosphine oxides in high yields and excellent diastereoselectivities with near-perfect enantioselectivities. The synthetic utility of this method is further demonstrated by the facile preparation of multichiral Lewis base catalysts and the asymmetric synthesis of chiral P,N-ligands such as QUINAP.