Synthetic Strategies to Control C-N Atropisomerism in Acyclic Amines and Amides

Atropisomeric molecules are a privileged class of stereo-genic material that have important applications in catalysis, materials science and medicines. To date, the majority of work has been focused upon biaryl and heterobiaryl scaffolds involving restricted rotation be-tween a pair of cyclic fragments, but C-N atropisomeric molecules based upon amines and amides, where the nitrogen atom is not part of a ring system, are rapidly emerging as an important class of stereogenic molecules. This is the focus of this Short Review, which begins by dis-cussing the factors which influence the configurational stability of such molecules and provides a historical background to their synthesis. This is followed by a detailed discussion of state-of-the-art catalytic asym-metric strategies that are now available to access C-Nacyclic atropisomers including carboxamides, sulfonamides, sulfinamides, phosphamides and diarylamines. A variety of different synthetic approaches are dis-cussed, including kinetic resolution/desymmetrization, amination, C-H functionalization, N-functionalization, and annulation.