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.