Harnessing the Potential of Alkoxy Radicals

这一提议将建立电化学作为最先进的方法来访问和利用特权烷氧基自由基中间体。这将通过引入第一种广泛适用的方法来实现，该方法用于从未保护的醇电化学产生烷氧基，并将其应用于开发各种各样的新型电合成转化，获得有价值的产品，同时解决该领域的一个重要的现有缺陷。该提案中概述的研究将在几个领域显着推进有机电合成和自由基化学领域方法，包括：一。第一个广泛适用的电化学产生和利用的烷氧基自由基的方法将被介绍。这一领域是显着欠发达，并仍然在很大程度上限于在高电位下从甲醇阳极生成甲氧基自由基，这排除了在合成中的一般使用。电化学驱动的分子间PCET过程将用于访问烷氧基自由基的第一次。将采用各种不同的策略用于C-中心自由基中间体的不同官能化，包括用SOMO亲体捕获，通过会聚成对电化学的Ni催化的C-C交叉偶联，以及通过自由基极性交叉用亲核试剂捕获。我们的新的电合成方法的应用到后期功能化的天然产物和药物，木质素解聚，商品化学品的直接功能化，和形成苯甲醚生物电子等排体（双环[1.1.1]戊基醚）。一个全面的培训计划已经建成，除了机制，以促进主机和研究员之间的双向知识转移。拟议的主办组织和主要主管分别是巴斯大学和路易斯莫里尔博士，因为他们在这一领域的专业知识。

This proposal will establish electrochemistry as the state-of-the-art method to access and utilize privileged alkoxy radical intermediates. This will be achieved by introducing the first broadly applicable approach for the electrochemical generation of alkoxy radicals from unprotected alcohols and applying this to the development of a diverse range of novel electrosynthetic transformations, accessing valuable products whilst addressing an important existing deficiency in the area.The research outlined in this proposal will significantly advance the fields of organic electrosynthesis and radical chemistry in several ways, including:i. The first broadly applicable approach for the electrochemical generation and utilization of alkoxy radicals will be introduced. This area is significantly underdeveloped and remains largely limited to the anodic generation of methoxy radicals from methoxide at high potentials, which precludes general use in synthesis.ii. Electrochemically driven intermolecular PCET processes will be used to access alkoxy radicals for the first time.iii. The utilization of various distinct strategies for the diverse functionalization of C-centered radical intermediates will be employed, including trapping with SOMOphiles, Ni-catalyzed C-C cross-coupling via convergent paired electrochemistry, and trapping with nucleophiles via radical-polar crossover.iv. The application of our new electrosynthetic methods to the late-stage functionalization of (derivatives of) natural products and pharmaceuticals, lignin depolymerization, the direct functionalization of commodity chemicals, and the formation of anisole bioisosteres (bicyclo[1.1.1]pentyl ethers).A comprehensive training programme has been constructed in addition to mechanisms to facilitate a two-way knowledge transfer between host and fellow. The proposed host organisation and primary supervisor are the University of Bath and Dr Louis Morrill, respectively, due to their expertise in this area.