Phosphorus(III)-Compatible Asymmetric Suzuki–Miyaura Cross-Coupling (P-ASMC) Reaction

The Suzuki-Miyaura cross-coupling (SMC) is a cornerstone method in the synthesis of biaryls. The enantioselective variant of this reaction typically involves an exogenous chiral ligand to induce enantioselectivity. Nonetheless, the application of coupling partners adorned with phosphorus(III) functionalities has been hindered by their strong coordination with transition metals and the challenges in identifying compatible chiral ligands. Here, we report the development of a P(III)-compatible asymmetric Suzuki-Miyaura cross-coupling (P-ASMC) reaction that enables the one-step assembly of axially chiral biaryl monophosphines. Employing a palladium catalyst, an achiral phosphine, and a chiral phosphine ligand, <i>ortho</i>-bromo-substituted arylphosphines undergo coupling with aryl boronate esters, demonstrating high reactivity and enantioselectivity. The resultant atropisomers exhibit exceptional efficacy as ligands in enantioselective palladium, rhodium, and gold catalysis, highlighting the practical promise of the P-ASMC reaction. Comprehensive experimental and computational studies have elucidated the reaction pathway and identified key factors contributing to cluster inhibition and enantioinduction.