Abstract
Atropisomeric molecules are a privileged class of stereogenic 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 between 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 discussing 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 asymmetric
strategies that are now available to access C–Nacyclic atropisomers including carboxamides, sulfonamides, sulfinamides, phosphamides and
diarylamines. A variety of different synthetic approaches are discussed, including
kinetic resolution/desymmetrization, amination, C–H functionalization, N-functionalization,
and annulation.
1 Introduction
2 Atropisomerism in Acyclic Amines and Amides
3 Synthesis Directed by a Chiral Auxiliary
4 Atropselective Synthesis
4.1 Kinetic Resolution and Desymmetrization
4.2 Electrophilic Amination
4.3 C–H Functionalization
4.4 N-Functionalization
4.5 Annulation
5 Conclusions and Outlook
Key words
atropisomerism - axial chirality - amide - amine - asymmetric catalysis - anilide
- stereoselectivity
