Photoenzymatic C-H radical alkylation of arenes using S-adenosyl methionine analogues

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In a future where sustainability will be a key driver, we must synthesise high value molecules from simple feedstocks in an expedient fashion. So called 'C-H activation' will be a key strategy in future synthesis as it allows C-H bonds present in almost every feedstock chemical to be converted to, for example, more valuable C-C bonds. Unfortunately, most methods for C-H activation currently involve expensive/toxic metal catalysts and controlling the selectivity for a particular C-H bond, in feedstocks where there are many, remains a grand challenge.In this project, we propose that the marriage of visible light photocatalysis and biocatalysis will allow the selective formation of important C-C bonds at the expense of C-H bonds in aromatic feedstocks, thus facilitating the sustainable synthesis of high-value products of industrial relevance. Our approach will use enzymes to control the selectivity of C-H functionalization, organic photocatalysts to generate radicals, and bioinspired sulfonium salts as radical precursors. A suite of sulfonium salts will be accessed using either chemo- or bio-catalysis and will allow a wide range of high value products to be prepared using the proposed photoenzymatic approach.Two leaders in their respective fields will join forces for the first time and pool their complementary expertise in supervising the project. The Procter group is world-leading in the chemistry of sulfonium salts1 and radicals2 and has recently reported a metal-free photocatalyzed C-H functionalized of aromatic substrates using sulfonium salts.3 The Micklefield group is world-leading in the use of S-adenosylmethionine (SAM) analogues - sulfonium salts used by Nature - in biocatalysis and has recently reported several applications of SAM analogues in biology.4The project is ideally suited to a synthetic chemist with an interest in biocatalysis. A multidisciplinary supervisory team of internationally-leading scientists will deliver a unique training programme.