Radical Cross Coupling and Enantioselective Protonation through Asymmetric Photoredox Catalysis

An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine-derived chromophore (DPZ) as a photosensitizer and a chiral phosphoric acid catalyst, and Hantzsch ester as a sacrificial reductant, the transformations between alpha-substituted enones and cyanoazaarenes or 2-(chloromethyl)azaaren-1-iums can proceed a tandem reduction, radical coupling, and enantioselective protonation process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain a synthetically versatile ketone-substituted tertiary carbon stereocenter at the beta- or gamma-position of the azaarenes, are synthesized with high yields and ees. The first radical coupling and enantioselective protonation is developed. Under cooperative photoredox and chiral hydrogen-bonding catalysis, the transformations of alpha-substituted enones with cyanoazaarenes or 2-(chloromethyl)azaaren-1-iums could render two classes of valuable azaarene variants with high yields and ees, which contain a synthetically useful ketone-substituted tertiary carbon stereocenter at the beta- or gamma-position of the azaarenes.image