Alkyl Radical-Free Cu(I) Photocatalytic Cross-Coupling: A Theoretical Study of Anomerically Specific Photocatalyzed Glycosylation of Pyranosyl Bromide.

Previously, we reported a visible light-activated Cu(I) photocatalyst capable of facilitating C-O bond formation of glycosyl bromides and aliphatic alcohols with a high degree of diastereoselectivity. This catalyst functions equally well in the presence of radical traps, suggesting an entirely inner sphere mechanism atypical for heteroleptic Cu photocatalysis. Further, experimental estimates put the chromophore reducing power at -1.30 V vs Ag/AgCl. This is much more positive than the ∼-2.0 V vs Ag/AgCl onset observed for irreversible reduction of glycosyl bromides in our experiments. Theoretical investigations were undertaken to explain the function of the catalyst. Outer sphere electron transfer from a chromophore to substrate was discounted based on thermodynamics and electron transfer barriers determined by Marcus theory and non-equilibrium solvation calculations. Unactivated and activated chromophores were found to disproportionate to Cu(0) and Cu(II) species. The resulting Cu(0) species undergoes oxidative addition with a glycosyl bromide generating a Cu(II) species. Addition of a nucleophilic alcohol and oxidation of the Cu(II) species to Cu(III) result in rapid reductive elimination forming products and resetting the catalytic cycle.