NSF-DFG Echem: Hydrofunctionalization by Non-redox Paired Electroatalysis

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This collaborative proposal focuses on establishing a new strategy based on paired electrolysis for the hydrofunctionalization of alkenes. Hydrochlorination, hydrofluorination, and hydrocyanation reactions are classic synthetic transformations with broad applications in organic synthesis and medicinal chemistry. The traditional methods for such reactions use abundant inorganic acids (HX; X = F, Cl, Br, CN, etc.) but are often carried out under harsh conditions and exhibit limited chemoselectivity. Recently, metal-hydride-mediated hydrogen atom transfer has been creatively employed to achieve the radical hydrofunctionalization of alkenes under mild conditions. These systems, however, feature the addition of a pair of [H–] and [X+] equivalents to the substrate and thus remain reliant on stoichiometric radical precursors such as hydrosilanes and electrophilic (pseudo)halogen sources. In this proposal, we aim to advance a new catalytic strategy, namely non-redox paired electrocatalysis, to establish efficient, selective, and sustainable hydrofunctionalization reactions using readily available mineral acids (HX). Specifically, two catalytic cycles will operate in parallel on the cathode and anode, each generating a metal-bound radical precursor (M1–H and M2–X) prior to reaction with an alkene. The overall objectives include: 1. Establishing non-redox paired electrocatalysis in the context of hydrochlorination. We aim to achieve alkene hydrochlorination using a pair of Co (cathode, + H+) and Mn (anode, + Cl–) complexes as the H-atom transfer and Cl-atom transfer catalysts, respectively. 2. Mechanistic investigation of non-redox paired electrocatalysis. We will study in detail the mechanism of electrochemical catalyst activation and radical addition processes. The mechanistic information will be used to guide reaction optimization and strategy expansion. 3. Strategy expansion to other electrochemical hydrofunctionalization reactions. We will expand the same catalytic strategy towards other reactions such as hydrofluorination, hydrocyanation, and hydrothiocyanation. We will also develop enantioselective variants of these reactions. 4. Developing educational opportunities for student participants and the broader community. Intellectual Merit The past several years have seen a renewal of research interest in electrochemistry from the organic chemistry community. Despite significant advancements in the field of electrosynthesis, the potential of electrochemistry for synthetic innovation has yet to be fully explored. This proposal will advance a new catalytic strategy that elaborates on canonical paired electrolysis. This strategy, which we name non-redox paired electrocatalysis, will combine a pair of cathodic and anodic catalytic cycles in a convergent manner to provide new solutions to challenging redox-neutral transformations. The mechanistic understanding of synergistic electrocatalysis will also advance fundamental knowledge of redox reactions and meta