Divergent Synthesis of Atropisomeric Diarylamines Enabled by Bromine-Masked Indolines

Abstract

Herein, we report the use of a bromine atom as a masking group for the synthesis atropisomeric diarylamines via organocatalytic N-arylation of 7-bromoindolines. The bromine atom acts as a bulky group to temporarily stabilize the configuration by steric hindrance. Upon unmasking, less sterically hindered diarylamines are obtained, with configurational stability potentially maintained through intramolecular hydrogen bonding. Moreover, the gram-scale reaction and post-modifications of the axially chiral diarylamines demonstrated the utility of this protocol. Thermal racemization experiments combined with X-ray crystallography revealed the respective contributions of steric repulsion and intramolecular hydrogen bonding in stabilizing the configurations. This approach not only provides a useful method for the atroposelective construction of conical diarylamines, but also paves the way for a better understanding of stable axial chirality and its role in shaping chemical reactivity and biological activity.