Illuminating Inner-Sphere Electron Transfer: Integrating Mechanistic Probes for the Design of Base-Metal-Catalyzed Radical Functionalization Reactions

• Applicant: Professor Dr. Felix Strieth-Kalthoff
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 577666408

Developing new synthetic methods expands access to valuable functional molecules for applications in medicine, agrochemistry, or materials science. Radical-based methods enable transformations that are difficult to achieve by other approaches. In this context, photocatalytic inner-sphere electron transfer (ISET) has emerged as a sustainable and chemoselective mode of radical formation. However, the design of such ISET-mediated transformations has been largely empirical, and the structural factors that govern reactivity are often poorly understood. Mechanistic studies are further complicated by the dynamic nature of substrate-catalyst binding and the large number of possible active species. This project will (1) develop data-rich workflows to probe the mechanisms of substrate binding and radical formation in ISET catalysis, and (2) use this knowledge to design new sustainable functionalization reactions. In the first stage, UV/Vis spectroscopy and electrochemistry will be combined with statistical data interpretation to extract information from complex mixtures. Integrated with automated experimentation, this approach will enable the deconvolution of multi-component systems, and allow the identity, properties, and reactivity of active species to be resolved. In parallel, computational descriptors will be developed to capture the physicochemical foundations of coordination behavior and photochemical properties. Together, these tools will provide a framework for elucidating reaction mechanisms and structure-activity relationships in ISET catalysis. In the second stage, these mechanistic insights will guide the development of new synthetic transformations. ISET catalysis will be applied to the iron-catalyzed synthesis of organic thiocyanates, isocyanates, and cyanamides from readily available inorganic salts. Strategies for hydro-functionalization and difunctionalization of alkenes, as well as arene functionalization, will be explored. The resulting products serve as versatile intermediates for introducing e.g. carbamate and urea groups relevant to medicinal and agricultural chemistry, and provide an entry point to heterocycle synthesis. Finally, the project aims to explore the ability of ISET catalysis to spatially control radical formation, enabling inner-sphere radical cascades with complementary selectivity to free-radical reactions. This will be demonstrated through the β-functionalization of aliphatic alcohols, amines, and thiols.

• DFG Programme: Emmy Noether Independent Research Groups