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 O_2(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 [Cu₂^II(BPMPO^-)(O₂^2-)]¹⁺ {BPMPO-H = 2,6-bis{[(bis(2-pyridylmethyl)amino]methyl}-4-methylphenol)} and [Cu₂^II(XYLO^-)(O₂^2-)]¹⁺ (XYLO^- = a BPMPO^- analogue possessing bis(2-{2-pyridyl}ethyl)amine chelating arms). Their dicopper(I) precursors are dioxygenase catalysts. The O_2(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 [Cu₂^II(BPMPO^-)(O₂^2-)]¹⁺ species initially reacts reversibly with the aldehydes to form detectable dicopper(II) peroxyhemiacetal intermediates, for which optical titrations provide the K_eq (at -90 °C) of 73.6 × 10² M^-1 (2-PPA) and 10.4 × 10² M^-1 (CCA). In the reaction of [Cu₂^II(XYLO^-)(O₂^2-)]¹⁺ with 2-PPA, product complexes characterized by single-crystal X-ray crystallography are the anticipated dicopper(I) complex, [Cu₂^I(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 ¹⁸O_2(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.