Novel Electrochemical syntheses of important heterocyclic scaffolds

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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.