Enantioselective Assembly of (Hetero)aryl Alkyl Sulfilimines via Copper-Catalyzed <i>S</i>-Arylation of <i>S</i>-Alkyl Sulfenamides with (Hetero)aryl Iodides

Currently, most sulfoximine clinical candidates feature both <i>S</i>-aryl and <i>S</i>-alkyl substituents. The asymmetric synthesis of these compounds typically relies on oxidizing corresponding enantioenriched sulfilimines. Herein, we describe an effective catalytic system comprising CuI and an azabicyclo[2.2.1] carboxylic acid-derived amide ligand. This system enables the highly enantioselective coupling of <i>S</i>-alkyl sulfenamides with (hetero)aryl iodides to afford aryl alkyl sulfilimines. A wide range of functionalized (hetero)aryl iodides and <i>S</i>-alkyl sulfenamides are compatible under the reaction conditions, providing an attractive approach for assembling enantioenriched aryl alkyl sulfilimines. The utility of this method is demonstrated by the gram-scale asymmetric synthesis of clinical candidate TNG 260 and the formal asymmetric synthesis of three additional drug candidates.