Dioxygenase Chemistry in Nucleophilic Aldehyde Deformylations Utilizing Dicopper O₂-Derived Peroxide Complexes

The chemistry of copper-dioxygen complexes is relevant to copper enzymes in biology as well as in (ligand)Cu–O2 (or Cu2–O2) species utilized in oxidative transformations. For overall energy considerations, as applicable in chemical synthesis, it is beneficial to have an appropriate atom economy; both O-atoms of O2(g) are transferred to the product(s). However, examples of such dioxygenase-type chemistry are extremely rare or not well documented. Herein, we report on nucleophilic oxidative aldehyde deformylation reactivity by the peroxo-dicopper(II) species [Cu2II(BPMPO–)(O22–)]1+ {BPMPO-H = 2,6-bis{[(bis(2-pyridylmethyl)amino]methyl}-4-methylphenol)} and [Cu2II(XYLO–)(O22–)]1+ (XYLO– = a BPMPO– analogue possessing bis(2-{2-pyridyl}ethyl)amine chelating arms). Their dicopper(I) precursors are dioxygenase catalysts. The O2(g)-derived peroxo-dicopper(II) intermediates react rapidly with aldehydes like 2-phenylpropionaldehyde (2-PPA) and cyclohexanecarboxaldehyde (CCA) in 2-methyltetrahydrofuran at −90 °C. Warming to room temperature (RT) followed by workup results in good yields of formate (HC(O)O–) along with ketones (acetophenone or cyclohexanone). Mechanistic investigation shows that [Cu2II(BPMPO–)(O22–)]1+ species initially reacts reversibly with the aldehydes to form detectable dicopper(II) peroxyhemiacetal intermediates, for which optical titrations provide the Keq (at −90 °C) of 73.6 × 102 M–1 (2-PPA) and 10.4 × 102 M–1 (CCA). In the reaction of [Cu2II(XYLO–)(O22–)]1+ with 2-PPA, product complexes characterized by single-crystal X-ray crystallography are the anticipated dicopper(I) complex, [Cu2I(XYLO–)]1+ plus a mixed-valent Cu(I)Cu(II)-formate species. Formate was further identified and confirmed by 1H NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) analysis. Using 18O2(g)-isotope labeling the reaction produced a high yield of 18-O incorporated acetophenone as well as formate. The overall results signify that true dioxygenase reactions have occurred, supported by a thorough mechanistic investigation.