Atroposelective catalysis

Atropisomeric compounds—stereoisomers that arise from the restricted rotation about a single bond—have attracted widespread attention in recent years due to their immense potential for applications in a variety of fields, including medicinal chemistry, catalysis and molecular nanoscience. This increased interest led to the invention of new molecular motors, the incorporation of atropisomers into drug discovery programmes and a wide range of novel atroposelective reactions, including those that simultaneously control multiple stereogenic axes. A diverse set of synthetic methodologies, which can be grouped into desymmetrizations, (dynamic) kinetic resolutions, cross-coupling reactions and de novo ring formations, is available for the catalyst-controlled stereoselective synthesis of various atropisomer classes. In this Review, we generalize the concepts for the catalyst-controlled stereoselective synthesis of atropisomers within these categories with an emphasis on recent advancements and underdeveloped atropisomeric scaffolds beyond stereogenic C(sp2)–C(sp2) axes. We also discuss more complex systems with multiple stereogenic axes or higher-order stereogenicity. The catalyst-controlled stereoselective synthesis of atropisomers is feasible by four main concepts: desymmetrization, (dynamic) kinetic resolution, direct formation of the stereogenic axis and de novo ring construction. In this Review, pioneering work in atroposelective catalysis is discussed alongside recent advances.