Synthesis of Sulfoximines by C-S bond Formation

Sulfoximines present an important opportunity for broader exploration of chemical space for drug discovery. The sulfoximine motif is becoming increasingly validated in drug candidates most notably in oncology, where Bayer's BAY1000394 and BAY1143572, as well as AstraZeneca's ATR inhibitor AZD6738 have entered clinical trials. The sulfoximine group provides a polar, solubilising motif that offers H-bond donor and acceptor properties and chirality at sulfur, providing increased complexity. As such these present interesting replacements for sulfones and sulfonamides. However, methods for their synthesis remain limited to preformation of the C-S skeleton and then oxidation chemistry to install the N/O functionality.
This project will develop reagents for the direct introduction of the sulfoximine group i.e. a sulfoximine 'building block' for the formation of the sulfoximine C-S bond. A variety of new building blocks will be examined in new reactions for sulfoximine synthesis.