Axial chirality-arising from restricted rotation around a single bond-is a crucial stereochemical phenomenon first identified by Christie and Kenner in 1922. This motif is widespread in nature, with compounds featuring C-C, C-N, or N-N atropisomeric axes exhibiting significant biological and pharmacological activities. Moreover, axially chiral scaffolds are crucial in asymmetric synthesis, both for organometallic catalysis and organocatalysis. Recent years have seen a surge in research on atroposelective strategies, driven by the challenges of controlling axial stability and conformational dynamics. Among them, cycloaddition reactions are particularly attractive as they allow to generate one ring while setting a stereogenic axis. This review focuses on advances from 2021-2026, highlighting cycloaddition reactions that directly generate stereogenic axes (C-C, C-N, N-N, C-B, C-O). It covers diverse cycloaddition types and catalytic systems (transition metals, chiral phosphoric acids, NHCs), categorizing findings by reaction type and emphasizing their role in atroposelective synthesis.
Duong et al. (Wed,) studied this question.