Assembly of (hetero)aryl sulfilimines via copper-catalyzed enantioselective S-arylation of sulfenamides with (hetero)aryl Iodides

Abstract

The (hetero)aryl sulfoximines are important structures for developing bioactive molecules, whose synthesis relies on oxidation of (hetero)aryl sulfilimines. However, asymmetric approaches for assembling (hetero)aryl sulfilimines are still rare. Here we show that combination of CuI and NOBIN-derived amide ligands offers an effective catalytic system for enantioselective coupling of (hetero)aryl iodides with sulfenamides. A large number of functional groups and heterocycles are tolerated under the coupling conditions, providing a powerful approach for diverse synthesis of enantioenriched (hetero)aryl sulfilimines. The efficiency of the coupling reaction is highly dependent on the electronic nature of (hetero)aryl iodides and sulfenamides. Both (hetero)aryl- and some bulky alkyl-substituted sulfenamides give excellent enantioselectivities, while sulfenamides with smaller alkyl substituents lead to the formation of the (hetero)aryl sulfilimines with moderate enantioselectivities. Density functional theory (DFT) calculations reveal that proper steric repulsions in the transition states of the intramolecular S_NAr reaction are crucial for achieving desirable enantioselectivity.