A cross-coupling approach for sulfoximine synthesis: new reagents for medicinal chemistry

To access new areas of biologically relevant chemical space, the incorporation of "unusual" functional groups becomes essential, particularly groups that can offer improved physicochemical properties, or provide novel bioisosteres. Sulfoximines present an important opportunity in this context and are becoming increasingly validated in drug candidates, most notable in oncology. Currently there are no modular methods for the construction of sulfoximines, nor for the late stage introduction of the intact functional group.
This project will develop reagents for the direct introduction of the sulfoximine group through cross-coupling methods i.e. a sulfoximine 'building block' for the formation of the sulfoximine C-S bond. Suitable designed reagents, nucleophilic at sulfur, will be prepared relying on our recently developed N-transfer methods (eg Angew. Chem. Int. Ed. 2016, 55, 7203; Chem. Commun. 2017, 53, 348). Subsequently cross-coupling reactions with various electrophiles will be developed, including transition metal catalysed couplings with aryl halides. Reagents will be fine-tuned through variation of N-functionality and metal anion to ensure desired reactivity. This work presents a novel approach to the synthesis of sulfoximines.