Stereoselective Alkene Dicarbo-Functionalization via Synergistic Electro-Catalysis

The development of innovative and sustainable solutions for the manufacturing of fine chemicals from raw materials and chemical waste is a topical societal challenge. Within this context, alkenes are predominant carbon feedstocks, industrial by-products and biogenic compounds, thus there is an ever-growing demand for efficient, selective and green synthetic methods for their manipulation. State-of-the-art strategies for alkene functionalization often rely on the use of transition metal catalysts, in order to secure high levels of selectivity and efficiency. This, in turn, raises concerns over the cost, safety, and environmental impact of these processes. To meet this challenge, this proposal introduces a brand-new strategy for the metal-free, regio- and stereo-selective functionalization of unsaturated C–C bonds within alkenes, named Sew&Cut (S&C). This approach combines the selectivity and versatility of 1,3-dipolar cycloadditions (1,3-DCs) – a fundamental transformation in organic chemistry, where 1,3-dipoles engage alkenes to form heterocycles – with the complexity-generating ability of radical reactivity. Specifically, by designing novel reagents containing both a 1,3-dipole precursor and a redox-active moiety (which generates radical species upon single electron transfer activation), we will click “raw atoms” across C–C double bonds, and shape them into synthetically useful functionalities by means of radical fragmentation reactions, triggered by electrochemical methods. This approach converts – in a single operation – “flat” ubiquitous feedstock into stereodefined three-dimensional fine chemicals, using electricity as the main source of energy. Furthermore, our strategy elevates a fundamental process in polar chemistry (1,3-DC) into a powerful synthetic tool for radical reactivity. Preliminary work in our group has demonstrated the successful implementation of the S&C strategy. Capitalizing on these studies, this project aims to expand the potential of our electrosynthetic approach, by implementing the following objectives: i) the development of new reagents enabling the programmable and selective syn-dicarbo-functionalization of alkenes, under electrochemical conditions; ii) the exploitation of these reagents to implement multicomponent reactions, leveraging on both the radical and polar reactivity of the intermediates formed during the electrochemical S&C process; and iii) the application of these radical multicomponent protocols to the development of asymmetric synergistic dual catalytic cascades, combining electrochemistry with both enantioselective organo- and Lewis-acid catalysis. This programme provides fresh opportunities for the design and development of a whole new class of reagents and reactions. These will be exploited to develop highly valuable multicomponent reactions, enabling the rapid and modular assembly of complex 3D-molecules, from simple and readily-available materials. Our research will enrich academic science with a new way for synthetic chemists to conceive and devise the functionalization of unsaturated C–C bonds. Meanwhile, it will impact UK industry and society by delivering sustainable synthetic procedures that take advantage of a renewable energy source (i.e. electricity) to convert noxious/redundant carbon feedstock into functional fine chemicals, new molecules, and building blocks for the manufacturing of medicines, materials and agrochemicals.