NHC-Catalyzed Desymmetrizative Amidation for C–O Axially Chiral Imides

Axially chiral diaryl ethers are important structural motifs, but their catalytic atroposelective construction remains challenging due to the low racemization barrier of the C-O axis. This work introduces an N-heterocyclic carbene (NHC)-catalyzed desymmetrizative amidation strategy for the direct enantioselective synthesis of C-O axially chiral benzoimides. The reaction employs readily available aryl amides and axially prochiral diaryl ether dialdehydes and proceeds under mild conditions to deliver a wide range of atropisomers in good to excellent yields (up to 96%) with high enantioselectivities (up to 97:3 er). Its synthetic utility is demonstrated by gram-scale synthesis and diverse downstream transformations of the products without any erosion of enantiopurity. Mechanistic studies suggest that the irreversible formation of the Breslow intermediate, involving C-H bond cleavage, likely serves as the rate- and enantioselectivity-determining step.