Stereodivergent Synthesis of Atropisomeric Indole-Fused δ-Lactams Bearing All-Carbon Quaternary Stereocenters via Cu-Catalyzed Desymmetric Arene Amidation

Abstract

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