Cyclic Deracemization of rac‐Sulfoxides via Alternating Biocatalytic Reduction and Light‐Dependent Oxidation Employing Eosin Y as Photocatalyst

Abstract

AbstractThe synergistic combination of biocatalysis and photocatalysis is emerging as powerful tool for the development of sustainable and atom‐efficient synthetic concepts facilitating an enormous portfolio of possible reactions which even goes beyond the capabilities found in nature. Here, a cyclic deracemization process is presented tailored for the synthesis of optically pure sulfoxides which are versatile structural motifs in asymmetric synthesis as well as in bioactive compounds. Enantioselective enzyme‐catalyzed reduction of rac‐sulfoxides was combined with a stereo‐unselective photocatalytic oxidation of the corresponding sulfide intermediate. The utilization of the readily accessible and rather inexpensive photocatalyst Eosin Y increases the usability of this synthetic method. To overcome the incompatibility between the photocatalyst Eosin Y and the biocatalytic step, the cyclic deracemization process was performed in a step‐wise fashion via alternated reduction in the darkness and oxidation under illumination. This modular system allowed precise adjustments of reaction parameters yielding the desired sulfoxide targets with up to >99 % ee. Evaluation of the substrate scope including a range of structurally diverse molecules demonstrated its broad applicability.