Bifunctional Chiral Agent Enables One‐pot Spontaneous Deracemization of Racemic Compounds

Abstract A novel one‐pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α‐diphenyl‐2‐pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2 R ,3 R )‐enantiomer and (2 S ,3 S )‐enantiomer in solution, achieving a one‐pot spontaneous deracemization. This strategy was also successfully extended to the deracemization of three other racemic compound drugs: ( R,S )‐carprofen, ( R,S )‐indoprofen, and ( R,S )‐indobufen. The one‐pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization‐induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy.