Iridium Artificial Metalloenzymes Enabled Photo‐Enzymatic Radical Indolone Synthesis
Nandita Ahalyan, Hirak Jyoti Deka, Subal Mondal, Argha Saha, Jhilik Mondal, Nikhil Ranjan Panigrahi, Abhishek Dubey, Ekta Pandey, Kaushal S., Debabrata MaitiABSTRACT
Biotin–streptavidin artificial metalloenzymes (ArMs) provide a platform to integrate transition‐metal catalysis within a protein‐defined microenvironment. Traditional indolone syntheses often rely on transition metal catalysts, high temperatures, and strong oxidants, limiting functional‐group tolerance, and sustainability. In this study, we report a visible‐light‐driven radical cyclization of acrylamides and diazo‐esters to indolones mediated by a biotinylated iridium‐photocatalyst. Incorporation into engineered streptavidin generates highly active photo‐ArMs, enabling reactions under mild aqueous conditions at 0.01 mol% Ir loading, broad substrate scope, and TONs up to 6300. Confinement of the iridium center within the protein binding pocket enhances turnover efficiency, establishing indolone formation as a new transformation accessible via biotin–streptavidin ArMs and highlighting their potential as sustainable platforms for bioactive motif synthesis.