Against the Odds: Regioselective Hydroaddition via Single-Electron Catalysis with Noble Metals

A fundamentally novel, bioinspired concept exploiting ligand-based redox-activity in combination with late transition (noble) metals is envisioned to address synthetic (in)organic challenges. These relate to odd-electron hydrocarbon and small molecule functionalization for regioselective anti-Markovnikov hydroaddition to C=C bonds. Our recently established proof-of-principle ligand-to-substrate single electron transfer (LtS SET) serves as inspiration for the reverse process, i.e. substrate-to-ligand single electron transfer (StL SET). This innovative concept gives access to ligand-induced and metal-mediated pathways for the generation of oxidized substrate species in the coordination sphere of closed-shell Group 8-11 metal ions. This strategy combines well-defined metal-based substrate coordination with ligand-induced chemical reactivity. In this proposal, the addition of N-H bonds across non-activated C=C bonds (hydroamination) will be explored. StL SET is envisioned to generate aminium species that enable anti-Markovnikov addition to afford highly valuable amines in an atom-efficient and regioselective manner. Substrate-to-ligand SET will be investigated using a combination of spectroscopic and analytical techniques on both stoichiometric reactions and catalytic versions thereof. Both intramolecular (cycloaddition of e.g. aminoalkenes) and challenging intermolecular versions of this C-N bond forming reaction will be probed. Furthermore, the team will study the StL SET of metal-amide species to generate metal-bound aminyl derivatives that may show fascinating complementary reactivity toward hydrocarbon π-systems. This ligand-based methodology offers opportunities to go beyond the well-known organometallic chemistry of “redox-inert” metals and current-day strategies to generate amines. We foresee that these principles are interesting for a range synthetic applications, also outside of the immediate scope of hydroaddition reactions.