Biomimetic Catalytic Atroposelective Ring-Opening Aminolysis of N-Sulfonylated Biaryl Lactams

Amide functional groups are common structural motifs found in many pharmaceuticals and natural compounds. Because of the resonance stability of the amide bond, catalytic enantioselective cleavage of amide C-N bonds still presents stubborn challenges and remains largely unexplored. In nature, metallo-β-lactamases (mβls) cause bacterial resistance toward β-lactam antibiotics via bizinc-catalyzed hydrolytic ring opening of the four-membered β-lactam ring. Inspired by the structures and functions of bizinc mβls, we present here a biomimetic atroposelective ring-opening aminolysis of biaryl lactams via enantioselective cleavage of amide C-N bonds with functional mimics of bizinc mβls, affording two structurally diverse sets of axially chiral biaryl amino amides in high yield with excellent enantioselectivity.