Novel Electrochemical syntheses of important heterocyclic scaffolds

近年来，化学活化的新方法如有机催化、光氧化还原催化、C-C键偶联和各种键插入反应(如C-H活化)应运而生。这些相对较少的“催化活化概念”导致了许多强有力的反应。然而，仍然有相当大的需要新的小分子激活模式，特别是不对称版本。这个项目建议通过研究一种新的键活化方法来解决这个问题，即电化学C-H活化。电化学经常被视为一门不合时宜的“黑色艺术”，这种观点完全忽视了它在工业上的巨大重要性。根据《电化学百科全书》，目前有31个大规模的工业有机过程在关键步骤中涉及到电化学。此外，电化学一直是实验室合成化学家的重要工具，但可能是隐藏的工具，合成有机电化学已经迅速从英国化学界消失。该项目的总体目标是在我们结合电化学、自由基化学和流动化学的初步结果的基础上，将这些技术应用于各种新型杂环支架的绿色和可持续合成。特别是，我们将利用我们的羧酸或半草酸盐化学获得的初步结果来开发Prins和aza-Prins循环的电化学版本，电化学方法生成自由基，然后电化学氧化形成氧离子，生成四氢吡喃、四氢呋喃、四氢吡啶和哌啶。我们将通过在起始原料中司法引入取代基，以及通过在反应结束时可能捕获的各种亲核试剂(包括卤化物、叠氮化物、氧和氮亲核试剂、里特反应或弗里德尔-克雷夫茨反应)来调查将多样性纳入产品中。最后，这些产品将进一步用于开发电化学螺环化反应以生成螺螺酮。

Recent years have seen a burgeoning in novel methods for chemical activation, including organocatalysis, photoredox catalysis, methods for C-C bond coupling and various -bond insertion reactions, such as C-H activation. These relatively few 'catalysis activation concepts' have resulted in many powerful reactions. However, there is still considerable need for new modes of small molecule activation, and particularly asymmetric versions. This project proposes to address this issue by examining a novel method of -bond activation, namely electrochemical C-H activation. Electrochemistry is often seen as being an unfashionable 'black art', a view which completely disregards its huge industrial importance. According to the Electrochemical Encyclopaedia, there are currently 31 large scale industrial organic processes which involve electrochemistry in the key step. Further, electrochemistry has always been a significant but perhaps hidden tool for the lab synthetic chemist and synthetic organic electrochemistry has been rapidly disappearing from the UK chemistry community.The overall aim of the project is to build on our preliminary results combining electrochemistry, radical chemistry and flow chemistry and apply these techniques to the green and sustainable synthesis of a variety of novel heterocycle scaffolds. In particular, we shall look to develop electrochemical versions of the Prins and aza-Prins cyclisations using preliminary results obtained using our carboxylic acid or hemioxalate chemistry electrochemical route to radical generation, followed by electrochemical oxidation to form an oxonium ion to generate tetrahydropyrans, tetrahydrofurans, tetrahydropyridines and piperidines. We will investigate incorporating diversity into the products through the judicial introduction of substitutents in the starting materials and also via the variety of nucleophiles that may be trapped at the termination of the reaction (including halides, azide, oxygen and nitrogen nucleophiles, a Ritter reaction or a Friedel-Crafts reaction). Finally the products will be further utilised in developing electrochemical spirocyclisations to generate spiroketals.