Stereodivergent\nSynthesis of Atropisomeric Indole-Fused\nδ-Lactams Bearing All-Carbon Quaternary Stereocenters via Cu-Catalyzed\nDesymmetric Arene Amidation

Great achievements have been made\nin constructing valuable\nchiral\nlactams via noble metal-catalyzed intramolecular γ-amidations\nusing dioxazolones as nitrene precursors. However, most of them are\nlimited to synthesizing central chirality, and the preparation of\nall-carbon quaternary stereocenters and C−N axial chirality\nis extremely challenging and still under-explored. Herein, a Cu-catalyzed\ndesymmetric arene δ-lactamizations of dioxazolones is disclosed,\nleading to the diastereodivergent synthesis of chiral indole-fused\nδ-lactams bearing all-carbon quaternary stereocenters and C−N\naxial chirality in generally good yield, stereoselectivity, and regioselectivity\nwith wide substrate scope. Interestingly, all four stereoisomers of\nδ-lactams containing all-carbon quaternary stereocenters and\nC−N axial chirality can be readily achieved simply by varying\nthe configurations of the single chiral copper catalyst and base treatments.\nAdditionally, this reaction probably undergoes a Cu-catalyzed singlet\nnitrene transfer/rearrangement and remote enantiocontrol process strongly\nsupported by control experiments and theoretical calculations.