Biphasic electroenzymatic catalysis-enabled chiral alkyl aldehydes synthesis from allylic alcohols

Here, we present an efficient electroenzymatic strategy for transforming allyl alcohols into chiral alkyl aldehydes with excellent enantioselectivity. Adverse interactions between the two are effectively prevented by employing a biphasic system to physically separate the anode from the enzymes. Furthermore, using the redox mediator 2,2,6,6-tetramethyl-1-piperinedinyloxy (TEMPO) significantly lowers the overpotential and enhances the efficiency of the allyl alcohol electrooxidation step. The ene-reductase OYE1 is employed to catalyze the reduction of the resulting E-alkenes, typically yielding chiral alkyl aldehyde. Additionally, the ene-reductase GluER-T36A is capable of reducing both E- and Z-alkenes, yielding chiral alkyl aldehyde with the same configuration. This electroenzymatic system is characterized by outstanding yields (up to 93%) and excellent stereoselectivity (>99% enantiomeric excess, ee). Molecular docking provides a detailed understanding of the internal mechanism of GluER-T36A. This study introduces a complementary approach to traditional transition-metal-catalyzed methods, where the transformation of E- and Z-allylic alcohols typically results in products with opposite stereochemical configurations.