Dynamic Kinetic Resolution Approach to C-O Axially Chiral Benzonitriles via NHC-Catalyzed Atroposelective Imine Umpolung

Despite the potential applications of axially chiral benzonitriles and dual C-O axis containing diaryl ethers, the synthesis of C-O axially chiral benzonitriles remains a significant challenge. Herein, we report a metal- and cyanide-free strategy for the first atroposelective access to C-O axially chiral benzonitriles via a desymmetrization/dynamic kinetic resolution sequence. The strategy utilized the N-heterocyclic carbene (NHC)-catalyzed polarity reversal of imines generated in situ from the symmetric isophthalaldehydes and sulfonamides to afford atropoisomeric benzonitriles proceeding via the aza-Breslow intermediates. DFT studies towards the mechanism revealed that the rate determining step involves the addition of NHC to the in situ generated imines. The racemization barrier studies reveal robust configurational stability of C-O axis allowing for diverse downstream functionalizations.