Atroposelective Bromination for the Synthesis of Chiral Biaryl Phosphines via Cross-Assembled Catalysis with Chiral Phosphoric Acid and Achiral Phenol.

Enantioselective electrophilic halogenation using organocatalysts has emerged as a powerful tool in asymmetric synthesis, yet its application has been largely concentrated on substrates bearing hydrogen bond donors. This prerequisite aligns with the design of conventional bifunctional catalysts, which operate through complementary hydrogen bond interactions with both the substrate and N-haloamide reagents. Chiral Buchwald-type ligands are useful monophosphine ligands, but their preparation mainly relies on kinetic resolution. Catalytic atroposelective halogenation of achiral Buchwald-type ligands would be an efficient strategy to prepare valuable C1-symmetric axially chiral biaryl monophosphine ligands. However, Buchwald-type ligands lack hydrogen bond donors, making them incompatible with typical asymmetric halogenation systems. We hypothesized that an achiral halophenol additive could cross-assemble with a chiral phosphoric acid catalyst in situ, reconfiguring the active site from a electron donor/acceptor to an acceptor/acceptor bifunctional system. This strategy bridges the functional group mismatch between the catalyst and substrate. Herein, we report a catalytic desymmetrization of achiral Buchwald-type ligand derivatives via this cross-assembled catalysis. The resulting axially chiral halogenated ligands are amenable to late-stage diversification, providing facile access to a diverse array of chiral monodentate phosphine ligands for asymmetric catalysis.