Electrochemically Driven Enzymatic Oxidative Desymmetrization for the Enantioselective Construction of Silicon Stereocenter

ABSTRACT Chiral silicon‐stereogenic organosilanes are finding increasingly widespread applications in pharmaceutical science and biomedical materials. However, the enzymatic construction of silicon chiral centers remains underdeveloped. Here, we report the integration of thiamine diphosphate (ThDP)‐dependent radical biocatalysis and mediated electrochemical oxidation to unlock non‐natural enzymatic oxidative desymmetrization, enabling the highly enantioselective synthesis of silicon stereocenters. Using symmetric silane dialdehydes as substrates, variants of benzaldehyde lyase from Pseudomonas fluorescens ( Pf BAL) together with ferrocene methanol (FcMeOH) as a redox mediator facilitate selective oxidation. This method features a broad substrate scope, producing a range of enantioenriched silicon‐containing carboxylic acids with excellent enantioselectivity (22 examples, up to >99.5% ee). Mechanistic investigations confirm substrate binding, explain the origin of enantioselectivity, and validate the mediated electron transfer pathway. This study expands the enzyme reactivity repertoire by merging electrochemical synthesis with biocatalysis, establishing an effective biocatalytic strategy for constructing silicon chirality.