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

在可持续发展将成为关键驱动力的未来，我们必须以一种权宜的方式从简单的原料合成高价值分子。所谓的“C-H活化”将是未来合成的关键策略，因为它允许几乎所有原料化学品中存在的C-H键转化为例如更有价值的C-C键。不幸的是，目前大多数C-H活化方法都涉及昂贵/有毒的金属催化剂，并且在存在许多C-H键的原料中控制特定C-H键的选择性仍然是一个巨大的挑战。在这个项目中，我们提出可见光催化和生物催化的结合将允许以牺牲芳香族原料中的C-H键为代价选择性地形成重要的C-C键，从而促进具有工业相关性的高价值产品的可持续综合。我们的方法将使用酶来控制C-H官能化的选择性，使用有机光催化剂来产生自由基，并使用生物启发的锍盐作为自由基前体。一系列的锍盐将通过化学或生物催化作用来获得，并将允许使用所提出的光酶方法来制备各种高价值的产品。两个在各自领域的领导者将首次联手，并在监督该项目时汇集他们互补的专业知识。Procter集团在锍盐1和自由基2的化学方面处于世界领先地位，并且最近报道了使用锍盐对芳族底物进行无金属光催化C-H官能化。3 Micklefield集团在使用S-腺苷甲硫氨酸（SAM）类似物方面处于世界领先地位-自然使用的锍盐-最近报道了SAM类似物在生物学中的几种应用。4该项目非常适合对生物催化感兴趣的合成化学家。由国际领先科学家组成的多学科监督团队将提供独特的培训计划。

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.