Active Pharmaceutical Ingredients by Photochemical Deracemization: Chromanes as a Test Case

Chromanes are frequently encountered as chiral structure elements in active pharmaceutical ingredients (APIs). We have now discovered an access to enantiopure chromanes, which employs a 1:1 mixture of their enantiomers (racemate) in a photochemical deracemization reaction. A chiral photocatalyst acts by selective hydrogen abstraction at one chromane enantiomer and establishes a photostationary state in which the other enantiomer prevails. A thiol additive secures the stability of the photocatalyst and guarantees a high number of turnovers. The method was applied to the concise preparation of five chromane-containing drugs (Doxazosin, Fidarestat, Nebivolol, Repinotan, Sarizotan) as single enantiomers. Given the increasing need for enantiomerically pure compounds in medicinal chemistry, we anticipate that this study will have a broad impact in the field of enantioselective API synthesis.