Stereospecific Negishi and Suzuki-Miyaura Csp3-Csp2 Cross-Coupling Reactions
There is growing interest in the pharmaceutical industry in 3-D drug compounds but their synthesis often remains challenging. Indeed, the pharmaceutical industry has recently highlighted the need for the development of new methods for the synthesis of such 3-D drug motifs: “With the success of the Suzuki-Miyaura coupling reaction in generating biaryl motifs, a variant allowing routine sp3–sp2 and sp3–sp3 couplings – ideally in an enantioselective manner – is both highly desirable and could fundamentally change the motifs being generated.” In collaboration with the Fairlamb group and a range if pharmaceutical partners, we are currently exploring new Negishi and Suzuki-Miyaura cross-coupling variants which aim to provide a modular, programmable method for stitching together medicinal chemistry motifs. This wide-ranging project makes use of high-throughput screening on a ChemSpeed robotic platform together with associated rich data analysis. Furthermore, in-depth mechanistic studies will be deployed to tackle these challenging cross-coupling reactions. This project is being carried out in collaboration with AstraZeneca and GlaxoSmithKline, together with EPSRC funding.