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

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.