Dynamic Kinetic Resolution Approach to C–O Axially Chiral Benzonitriles via N-Heterocyclic Carbene-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 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 aza-Breslow intermediates. Density functional theory studies toward 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 the C–O axis allowing for diverse downstream functionalizations.