Relaying radicals for catalytic couplings: Catalysis with SmI2

Synthetic chemistry is the engine that drives the advance of science and technology as man-made molecules and materials are vital to the work of thousands of scientists around the world. Many of the most exciting recent advances in synthetic chemistry have arisen from a renaissance in the chemistry of free-radicals; radicals are highly reactive species, well suited for molecule-building - their reactions often succeeding when other chemistry fails.

Electron transfer (ET) is commonly used to generate radicals and the well-known reagent, samarium(II) diiodide (SmI2), is one of the global community's most important ET reagents, as evidenced by its commercial availability and widespread use. Crucially, SmI2 exhibits unique reactivity; it can mediate processes that no other reagent can and its use proves pivotal in numerous high-profile scientific studies around the world each year. For example, SmI2 has been used to make the famous anti-cancer drug, Taxol, and to manufacture the drug Halaven on kilogram scale in industry. It has also been used to make polymers for electronic applications and was recently used to fix nitrogen and produce ammonia under ambient conditions.

Despite 1000s of publications describing its use, a well-known disadvantage shadows SmI2; the reagent must almost always be used in excess thus raising issues of cost and waste, and the sustainability of its future use. The unique reactivity of SmI2 can be ascribed to its ability to coordinate to and activate chemical feedstocks prior to ET; an ability that is rare amongst state-of-the-art catalysts for radical chemistry. SmI2 therefore offers unique and wide-ranging opportunities for innovation in the field of catalysis. Exploiting the rich chemistry of SmI2 in catalysis remains a grand challenge and a solution is long overdue.

We will develop a toolbox of catalytic radical reactions through the innovative marriage of SmI2 and 'radical relays'; chemical reactions in which the electron donated by the catalyst is relayed back, regenerating the catalyst after the desired chemical transformation is complete. Our studies will unlock a new field of radical catalysis that goes beyond the current state-of-the-art. Furthermore, we will exploit handed, or chiral, ligands to develop rare examples of catalytic radical couplings that selectively deliver a single isomer of a chiral product - either left or right handed - and the first ever such catalytic processes using SmI2. Throughout the project, we will use our unrivalled experience in the computational modelling of SmI2 chemistry to underpin our studies and we will showcase the power of our new catalysis by preparing molecules or relevance to drug discovery.

Prior to our breakthrough publications in 2019 and 2021, catalysis, through the union of radical relays and SmI2, was unknown; this leaves us in a unique position to undertake the proposed project and provide powerful new tools for molecule-makers, thus benefiting molecule-users, and making major scientific and societal impact.