A chemoenzymatic strategy has been developed for the deracemization of secondary alcohols. The approach combines a non-selective oxidation step using an iron-based deep eutectic solvent (in conjunction with TEMPO) with a subsequent stereoselective reduction of the corresponding ketone intermediates catalyzed by highly selective and stereocomplementary alcohol dehydrogenases.

Abstract

The use of deep eutectic solvents (DESs) has gained increasing attention over the past two decades as green (co)solvents for performing organic reactions and biotransformations under mild conditions. In this study, we report a deracemization strategy that highlights the potential of FeCl₃·6H₂O/urea (2:1 mol/mol) as a task-specific DES. This neoteric solvent not only enhances substrate solubility but also plays a crucial role in the oxidation step of various racemic alcohols. The chemoenzymatic process consists of two consecutive sequential redox steps, starting with an initial non-selective oxidation of the hydroxyl group using TEMPO in the FeCl₃·6H₂O/urea medium, followed by a stereoselective bioreduction of the resulting carbonyl intermediate. Notably, the use of stereocomplementary alcohol dehydrogenases (ADHs)—namely ADH-A (Prelog selectivity), LbADH, and evo 1.1.200 (anti-Prelog selectivity)—is shown to be compatible with the DES system, enabling the efficient conversion of racemic alcohols into enantiomerically enriched products. Enantiomeric excesses of up to >99% were achieved, demonstrating the effectiveness of this DES-based chemoenzymatic platform in producing optically active alcohols from racemic mixtures.