Electro‐Biocatalytic Dearomative Oxidation–Asymmetric Aldol Cascade Enables Direct Synthesis of Chiral 3‐Hydroxyindolin‐2‐Ones From Indoles

We present a sustainable electro‐biocatalytic cascade for the highly diastereo‐ and enantioselective synthesis of pharmaceutically relevant 3‐hydroxyindolin‐2‐ones by combining electrochemical dearomative oxidation of indole followed by an abiotic CALB‐catalyzed asymmetric aldol reaction in the same reaction vessel. The versatility of the electro‐biocatalytic cascade was well explored with a wide range of substrates, including indole‐bearing electron‐donating, ‐withdrawing, and halide substituents, along with two representative cyclic ketones, which were successfully transformed into the desired products in moderate to excellent yields (up to 91%) with outstanding stereocontrol, providing up to 99% ee and 99% de . Furthermore, mechanistic investigations, including control experiments and cyclic voltammetry studies, revealed distinct roles for electricity and enzyme catalysis and provided evidence for the involvement of iodinated intermediates in dearomative electrochemical oxidation of indole. The synthetic utility of the cascade protocol was further demonstrated through gram‐scale synthesis. This work establishes a versatile electro‐biocatalytic cascade platform that integrates the sustainability of electrosynthesis with the exceptional selectivity of enzyme catalysis, providing a sustainable and efficient process for the stereoselective synthesis of chiral 3‐hydroxyindoline‐2‐ones.