Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides
Fang-Xu Fan, Hui Xu, Shi-Xiong Tang, Yanfeng Dang, Fei Wang
Abstract
Transition metal-catalysed asymmetric nitrene transfer provides a powerful means to access various bioactive N-containing compounds as single enantiomers. However, enantioselective NH transfer that allows concise assembly of unprotected enantioenriched amines remains an enduring challenge. We report here an iron-catalysed stereoselective NH imidation of sulfoxide, which is integrated with photocatalytic racemisation of sulfoxide, enabling a dynamic kinetic resolution (DKR) strategy for direct and asymmetric synthesis of NH-sulfoximines. This approach is distinct from the existing methods by avoiding protecting group manipulations and/or the use of chiral substrates. Computational studies on the NH imidation reaction suggest the involvement of an iron-aminyl radical intermediate, and its reaction with sulfoxide proceeds through a synchronous nucleophilic addition of sulfoxide to nitrogen center and ligand-to-metal single electron transfer process to form the N–S bond. In addition, the stereoselectivity is primarily dictated by the difference in dispersion interactions of the transition states. Enantioselective NH transfer that allows concise assembly of unprotected enantioenriched amines remains a challenge. Here, the authors report an iron-catalysed stereoselective NH imidation of sulfoxide, which is integrated with photocatalytic racemisation of sulfoxide, enabling a dynamic kinetic resolution strategy for direct and asymmetric synthesis of NH-sulfoximines.