Enantioselective Synthesis of N–N Amide–Pyrrole Atropisomers via Paal–Knorr Reaction

The catalytic asymmetric construction of monoheteroaryl N–N axially chiral compounds and chiral five-membered aryl-based scaffolds remains challenging. Herein, we present a highly efficient enantioselective synthesis of monoheteroaryl N–N atropisomers via an asymmetric Paal–Knorr reaction, affording a diverse array of N–N amide–pyrrole atropisomers with excellent enantioselectivities. Gram-scale synthesis and post-transformations of the product demonstrated the synthesis utility of this method. Racemization experiments confirmed the configurational stability of these N–N axially chiral products. This study not only provides the first de novo cyclization example for accessing an asymmetric monoheteroaryl N–N scaffold but also offers a new member of the N–N atropisomer family with potential synthetic and medicinal applications.