Atroposelective Catalysis for Pharmaceutically Relevant Chemistry

Atropisomerism has emerged as an increasingly important consideration in pharmaceutical synthesis, driving substantial interest in methods for the enantioselective synthesis of atropisomeric compounds. Here, we analyze the reported syntheses of FDA-approved drugs from 2013–2024, categorizing individual synthetic steps by reaction type and ranking these transformations according to their frequency of use. This analysis identifies several common reaction classes for which atroposelective methods have been developed, highlighting opportunities to incorporate asymmetric strategies into pharmaceutically relevant syntheses. We then review recent advances in atroposelective methods for four of the most frequently employed reaction types: heterocycle formation, nucleophilic aromatic substitution (SNAr), cross-coupling, and electrophilic aromatic substitution (SEAr). By combining a data-driven analysis of pharmaceutical synthesis with a focused survey of atroposelective methodology, this review provides a practical framework for identifying opportunities to leverage atroposelective chemistry in the synthesis of complex, pharmaceutically relevant molecules.