The ability of chemists to produce specific organic molecules on demand, at low cost and on scales ranging from milligrams to multi-tonnes, has been central to many of the advances on which our quality of life now relies. The UK's fine chemical industry - particularly within the pharmaceutical and agrochemical sectors - continually faces new synthetic challenges, and is under increasing pressure to reduce the environmental impact of its operations. As such, there is constant demand for new synthetic methods that either provide more efficient access to known classes of compounds, or that open up previously unexplored areas of chemical space. Aryl-sulfur motifs feature in many societally-important molecules, including the sulfa drugs, anti-infectives that paved the way towards the modern healthcare we enjoy today. Formation of the C(aryl)-S linkage is often critical to the assembly of new aryl-sulfur-containing therapies, agrochemicals and materials, but - in many cases - is challenging to achieve in a mild and convenient fashion. Our research seeks to address these challenges through development of a robust and scalable method for C-S bond formation that avoids the malodorous, toxic and air sensitive intermediates that pervade organosulfur chemistry. The initial reaction products will then be exploited as a branching point from which to access all of the most important aryl-sulfur architectures, thereby demonstrating the ability of our methodology to deliver diverse, drug- and agrochemical-like scaffolds rapidly and under mild conditions. We will support this new methodology with detailed insight into how the system operates, and which variables are most critical for its successful application. Ultimately, this project will provide new tools to aid synthetic chemists in the preparation of a more diverse range of sulfur-containing molecules, in a more efficient manner. Given the contribution of pharmaceutical and agrochemical companies to the UK economy, this increased capability will be of benefit to UK plc. In addition, this project will provide a wealth of useful information and fundamental academic understanding that could guide the future development of new synthetic methods.

Organic synthesis allows humans to develop molecules that treat disease, efficiently grow crops, power our homes with innovative fuels and lubricants, and develop materials and plastics that are essential for modern life. Redox reactions are an important class of organic transformation where electrons are added or removed from molecules to engender a chemical reaction. This reaction is typically driven by the addition of a reactive redox reagent, which creates large quantities of waste that are often toxic and expensive to dispose of. Electrochemistry is an enabling technology for organic synthesis, as it replaces these reagents by directly transferring electrons at the surface of electrodes submerged in the reaction solution. There are two main advantages to this technique. The first is that lower amounts of waste, or no waste at all, is produced and less energy is needed, providing a more efficient and environmentally sustainable way to conduct redox reactions. The second is that the applied potential, or driving force, can be readily tuned, which provides greater selectivity, new reactivity, higher functional group tolerance and less undesired side-products. While providing efficiency, selectivity and environmental benefits, there are practical challenges associated with electrochemical reactions when compared to standard synthetic organic reactions. The greatest challenge with using the technique is often associated with the set-ups, which can be complex, expensive, are not well suited for parallelisation/reaction development and often lead to poor reproducibility. Thus, there is an urgent need to tackle these problems in order to advance the field. In this project, we will develop new reactor systems to aid each stage of reaction development, namely; discovery, optimisation, dissemination and replication. We will focus on additive manufacturing (3D printing) as an inexpensive, rapid and flexible prototyping tool to generate systems that are accessible, inexpensive and, importantly, highly reproducible for organic synthesis. We will develop new materials, innovative designs, print procedures and optimisation tools for reactors, which will be used in the development of a number of synthetic transformations, for which we have preliminary data, but require new reactor-systems to advance further. We will also conduct fundamental studies to further understand the reproducibility issues that currently plague the use of electrochemistry in synthesis. Specifically, the high-level objectives are to a) invent a screening system for organic electrochemistry, b) solve the reproducibility problem, c) create Super-Cells: the next generation of reactors of organic electrochemistry. This 3D printed approach to organic electrochemistry will increase the speed and ease with which novel organic transformations are developed and reproduced, ensuring electrochemistry can deliver on its potential of highly efficient and sustainable chemical reactions. This project will facilitate wide-spread adoption of the technique in organic synthesis, and deliver fundamental understanding, environmental and economic benefits to industry, academia and society as a whole.