Harnessing the Potential of Alkoxy Radicals

该提案将建立电化学作为最先进的方法来获取和利用特权烷氧基中间体。这将通过引入第一种广泛适用的方法，从无保护的醇中电化学生成烷氧基自由基，并将其应用于各种新型电合成转化的开发，获得有价值的产品，同时解决该领域现有的一个重要缺陷来实现。本提案中概述的研究将在几个方面显著推进有机电合成和自由基化学领域，包括：1。介绍了第一种广泛适用的电化学生成和利用烷氧基自由基的方法。这一领域明显不发达，并且仍然主要局限于甲氧基在高电位下的阳极生成，这妨碍了在合成中的普遍应用。电化学驱动的分子间PCET工艺将首次用于获取烷氧基。将采用各种不同的策略来实现c中心自由基中间体的不同功能化，包括与亲som试剂捕获，通过聚合配对电化学镍催化的C-C交叉偶联，以及通过自由基-极性交叉与亲核试剂捕获。我们的新电合成方法应用于天然产物和药物（衍生物）的后期功能化，木质素解聚，商品化学品的直接功能化，以及苯乙烯类生物异构体（双环[1.1.1]戊醚）的形成。除了促进东道国和研究员之间双向知识转移的机制外，还制订了一项全面的培训方案。提议的主办机构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.