BioLindlar Catalyst: Ene‐Reductase‐Promoted Selective Bioreduction of Cyanoalkynes to Give (Z)‐Cyanoalkenes

The direct synthesis of alkenes from alkynes usually requires the use of transition‐metal catalysts. Unfortunately, efficient biocatalytic alternatives for this transformation have yet to be discovered. Herein, the selective bioreduction of electron‐deficient alkynes to alkenes catalysed by ene‐reductases (EREDs) is described. Alkynes bearing ketone, aldehyde, ester, and nitrile moieties have been effectively reduced with excellent conversions and stereoselectivities, observing clear trends for the E/Z ratios depending on the nature of the electron‐withdrawing group. In the case of cyanoalkynes, (Z)‐alkenes were obtained as the major product, and the reaction scope was expanded to a wide variety of aromatic substrates (up to >99% conversion, and Z/E stereoselectivities of up to >99/1). Other alkynes containing aldehyde, ketone, or ester functionalities also proved to be excellent substrates, and interestingly gave the corresponding (E)‐alkenes. Preparative biotransformations were performed on a 0.4 mmol scale, producing the desired (Z)‐cyanoalkenes with good to excellent isolated yields (63‐97%). This novel reactivity has been rationalised through molecular docking by predicting the binding poses of key molecules in the ERED‐pu‐0006 active site.