Strategies for chiral separation: from racemate to enantiomer

Abstract

Chiral separation has become a crucial topic for effectively utilizing superfluous racemates synthesized by chemical means and satisfying the growing requirements for producing enantiopure chiral compounds. However, the remarkably close physical and chemical properties of enantiomers present significant obstacles, making it necessary to develop novel enantioseparation methods. This review comprehensively summaries the latest developments in the main enantioseparation methods, including preparative-scale chromatography, enantioselective liquid-liquid extraction, crystallization-based methods for chiral separation, deracemization process coupling racemization and crystallization, porous material method and membrane resolution method, focusing on significant cases involving crystallization, deracemization and membranes. Notably, potential trends and future directions are suggested based on the state-of-art “coupling” strategy, which may greatly reinvigorate the existing individual methods and facilitate the emergence of cross-cutting ideas among researchers from different enantioseparation domains.