Catalytic enantioselective desymmetrization of phosphorus (v) centers
Compounds containing one or more phosphorous atoms in the P(V) oxidation state are important to chemistry, biology and medicine. These include marketed antiviral drugs such as Remdesivir, and Sofosbuvir; the former garnering interest as a potential treatment for COVID-19, and the latter being on the WHO list of essential medicines for the treatment of Hepatitis C. Accordingly, new and improved methods for the efficient synthesis of P(V) containing compounds, especially in an enantioselective fashion are essential. Although promising protocols are beginning to arise for the synthesis of racemic P(V) compounds, new strategic approaches for the stereoselective synthesis of P-stereogenic centres are limited and catalytic enantioselective approaches remain unknown. Herein we propose to exploit our modular and tunable superbase catalyst platform, to design, discover and develop new iminophosphorane catalyst systems that will allow the direct and enantioselective synthesis of chiral phosphates, phosphonates and their analogues, in a single enantioselective step. We wish to capitalise on the abundance of commercial phosphorous (V) starting materials to allow the ready and scalable preparation of suitable symmetric prochiral precursors and through a suitable catalyst-enabled desymmetrization generate, in high enantiomeric excess, synthetically relevant chiral phosphorous intermediates. The fellow has already acquired a notable, high-level skill set and has demonstrated his excellence throughout his career, however this challenging project will extend his capabilities and improve his skill base and further enhance his scientific potential. DESYPHOR will therefore bring vital new knowledge to the field of catalytic enantioselective desymmetrization, deliver important methodological tools to researchers across the globe and accordingly will advance the excellent standing of the candidate, the host laboratory in Oxford, and of European science in general.