Synthesis of Axially Chiral QUINAP Derivatives by Ketone-Catalyzed Enantioselective Oxidation.

Abstract

QUINAPs have emerged as a pivotal class of axially chiral compounds with remarkable features in the stereoinduction of diverse enantioselective transformations. Despite their significant achievements, the confined substrate range and extravagant price still pose challenges, limiting their broader utilization. Herein, we have achieved the first atroposelective oxidation of N-atom using a chiral ketone catalyst. This innovative approach allows the kinetic resolution of QUINAPOs, resulting in both the unreacted substrates and their corresponding N-oxides with excellent enantiocontrol. Importantly, the enantioenriched products can be easily converted to the QUINAP targets without any loss of stereochemical integrity. Mechanistic investigations indicate that dioxirane, generated through the oxidation of ketone with oxone, acts as the active catalytic species. Furthermore, we have successfully extended this catalytic system to the kinetic resolution of QUINOLs and the dynamic kinetic transformation of pyridine analogs of QUINAPO possessing a labile stereogenic axis. The practicality of the developed protocol is further demonstrated by the successful application of QUINAPO N-oxide as a Lewis base catalyst in a series of enantioselective transformations.