Organocatalytic Dynamic Kinetic Resolution for the Stereoconvergent Synthesis of N-N Axially Chiral Compounds.

Abstract

Dynamic kinetic resolution (DKR) serves as a fundamental approach in asymmetric synthesis which enables the efficient conversion of racemic starting materials into a single stereoisomer, yet its extension to racemic diastereomers remains a formidable challenge, and reported DKR processes have largely been restricted to substrates bearing a single stereogenic element. Herein, we report an organocatalytic DKR with catalyst-accelerated racemization and epimerization for the asymmetric construction of significant N-N axially chiral compounds through the merger of a reversible Pudovik addition with an irreversible, stereoselective phospha-Brook rearrangement. Under bioinspired peptide-phosphonium salt catalysis, a wide range of N-N axially chiral products were obtained in good yields and high enantioselectivities. Scale-up synthesis and product derivatization further underscore the synthetic utility of this protocol. Mechanistic studies support a DKR process involving reversible racemization and epimerization through prochiral intermediates, identify the phospha-Brook rearrangement as the stereodetermining step, and reveal key roles of hydrogen-bonding and ion-pairing interactions in catalyst-controlled stereochemical induction. This work establishes a new paradigm for the catalytic asymmetric synthesis of axially chiral molecules.