Three-Stage Conversion of Chemically Inert n-Heptane to α-Hydrazino Aldehyde Based on Bioelectrocatalytic C–H Bond Oxyfunctionalization

[Image: see text] Simple petrochemical feedstocks are often the starting material for the synthesis of complex commodity and fine and specialty chemicals. Designing synthetic pathways for these complex and specific molecular structures with sufficient chemo-, regio-, enantio-, and diastereo-selectivity can expand the existing petrochemicals landscape. The two overarching challenges in designing such pathways are selective activation of chemically inert C–H bonds in hydrocarbons and systematic functionalization to synthesize complex structures. Multienzyme cascades are becoming a growing means of overcoming the first challenge. However, extending multienzyme cascade designs is restricted by the arsenal of enzymes currently at our disposal and the compatibility between specific enzymes. Here, we couple a bioelectrocatalytic multienzyme cascade to organocatalysis, which are two distinctly different classes of catalysis, in a single system to address both challenges. Based on the development and utilization of an anthraquinone (AQ)-based redox polymer, the bioelectrocatalytic step achieves regioselective terminal C–H bond oxyfunctionalization of chemically inert n-heptane. A second biocatalytic step selectively oxidizes the resulting 1-heptanol to heptanal. The succeeding inherently simple and durable l-proline-based organocatalysis step is a complementary partner to the multienzyme steps to further functionalize heptanal to the corresponding α-hydrazino aldehyde. The “three-stage” streamlined design exerts much control over the chemical conversion, which renders the collective system a versatile and adaptable model for a broader substrate scope and more complex C–H functionalization.