Chiral Phosphite Mediated Photoredox Catalyzed Aerobic Oxidative DYKAT for C−N Atropoisomers

Atroposelective compounds with axial chirality are important structural motifs in medicinal chemistry and materials science. Among these, anilides with a chiral C(=O)−N axis are intriguing structural motifs with several applications. Traditionally, the synthesis of these compounds has relied on the direct installation of the chiral C(sp²)−N(sp²) bond or enantioselective modification to the peripheral groups to increase steric around the C−N axis. However, these methods are limited in substrate scope and are constrained by the type and size of functional groups compatible with these strategies. Here, we show that phosphite-enabled loss of planarity led to a Dynamic Kinetic Asymmetric Transformation (DYKAT) for the oxidation of iminium ions to access enantioenriched isoquinolones. This method expands the substrate scope, tolerating a wide variety of positional, steric, and electronic substitution patterns that were previously challenging or inaccessible. Furthermore, the phosphite-mediated approach is versatile, facilitating the synthesis of atroposelective pyridone, lactam, and acyclic anilide. These results demonstrate a conceptually new strategy for atroposelective synthesis that complements traditional methods in terms of substrate diversity. Computational studies support the phosphite mediated change in hybridization for DYKAT prior to the oxidation step, paving the way for future studies in the synthesis of complex axially chiral molecules.