Abstract

Thermochemical, Photochemical and Electrochemical Synthesis Under Flow

David Harrowven, Professor, University of Southampton

Flow chemistry offers the potential to daisy-chain sequences of reactions in a fully automated manner. However, for this to become a normal expectation in chemical synthesis we need to have a series of robust and well-understood transformations available in our arsenal of chemical reactions, each capable of delivering product with little or no associated waste stream. High-yielding catalytic and ‘reagentless’ transformations that proceed with 100% atom efficiency will doubtless play a critical role if that long-term vision for synthesis is to be realised. To that end, the Southampton Flow Chemistry Team has focused its efforts on the development and study of reactions triggered by heat, light and electricity. Key to much of our success has been the use of traditional physical chemical techniques in combination with high-level computational studies. This has allowed us to gain an intimate understanding of some multi-step thermal and photochemical rearrangements, leading to their realization in close to 100% yield. Moreover, the computational models we have developed can now be applied to related but as yet untested substrates providing, with a high degree of accuracy, predictions as to the regiochemical course of such rearrangements and the optimal reaction conditions needed to achieve them in high yield. In parallel, we have developed a single channel microfluidic electrolysis cell for use in various transformations. These include a high-yielding, single pass methoxylation of N-formylpyrrolidine and a general procedure for the TEMPO mediated electrocatalytic oxidation of primary and secondary alcohols at ambient temperature.