Dioxygenase Chemistry\nin Nucleophilic Aldehyde Deformylations\nUtilizing Dicopper O<sub>2</sub>‑Derived Peroxide Complexes

The chemistry of copper-dioxygen complexes is relevant\nto copper\nenzymes in biology as well as in (ligand)Cu–O<sub>2</sub> (or\nCu<sub>2</sub>–O<sub>2</sub>) species utilized in oxidative\ntransformations. For overall energy considerations, as applicable\nin chemical synthesis, it is beneficial to have an appropriate atom\neconomy; both O-atoms of O<sub>2(g)</sub> are transferred to the product(s).\nHowever, examples of such dioxygenase-type chemistry are extremely\nrare or not well documented. Herein, we report on nucleophilic oxidative\naldehyde deformylation reactivity by the peroxo-dicopper(II) species\n[Cu<sub>2</sub><sup>II</sup>(BPMPO<sup>–</sup>)(O<sub>2</sub><sup>2–</sup>)]<sup>1+</sup> {BPMPO-H = 2,6-bis{[(bis(2-pyridylmethyl)amino]methyl}-4-methylphenol)}\nand [Cu<sub>2</sub><sup>II</sup>(XYLO<sup>–</sup>)(O<sub>2</sub><sup>2–</sup>)]<sup>1+</sup> (XYLO<sup>–</sup> = a\nBPMPO<sup>–</sup> analogue possessing bis(2-{2-pyridyl}ethyl)amine\nchelating arms). Their dicopper(I) precursors are <i>dioxygenase</i> catalysts. The O<sub>2(g)</sub>-derived peroxo-dicopper(II) intermediates\nreact rapidly with aldehydes like 2-phenylpropionaldehyde (2-PPA)\nand cyclohexanecarboxaldehyde (CCA) in 2-methyltetrahydrofuran at\n−90 °C. Warming to room temperature (RT) followed by workup\nresults in good yields of formate (HC(O)O<sup>–</sup>) along\nwith ketones (acetophenone or cyclohexanone). Mechanistic investigation\nshows that [Cu<sub>2</sub><sup>II</sup>(BPMPO<sup>–</sup>)(O<sub>2</sub><sup>2–</sup>)]<sup>1+</sup> species initially reacts\nreversibly with the aldehydes to form detectable dicopper(II) peroxyhemiacetal\nintermediates, for which optical titrations provide the <i>K</i><sub>eq</sub> (at −90 °C) of 73.6 × 10<sup>2</sup> M<sup>–1</sup> (2-PPA) and 10.4 × 10<sup>2</sup> M<sup>–1</sup> (CCA). In the reaction of [Cu<sub>2</sub><sup>II</sup>(XYLO<sup>–</sup>)(O<sub>2</sub><sup>2–</sup>)]<sup>1+</sup> with 2-PPA, product complexes characterized by single-crystal\nX-ray crystallography are the anticipated dicopper(I) complex, [Cu<sub>2</sub><sup>I</sup>(XYLO<sup>–</sup>)]<sup>1+</sup> plus a\nmixed-valent Cu(I)Cu(II)-formate species. Formate was further identified\nand confirmed by <sup>1</sup>H NMR spectroscopy and electrospray ionization\nmass spectrometry (ESI-MS) analysis. Using <sup>18</sup>O<sub>2(g)</sub>-isotope labeling the reaction produced a high yield of 18-O incorporated\nacetophenone as well as formate. The overall results signify that\ntrue <i>dioxygenase</i> reactions have occurred, supported\nby a thorough mechanistic investigation.