Dioxygenase Chemistry in Nucleophilic Aldehyde Deformylations Utilizing Dicopper O 2 -Derived Peroxide Complexes.

The chemistry of copper-dioxygen complexes is relevant to copper enzymes in biology as well as in (ligand)Cu-O 2 (or Cu 2 -O 2 ) 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 [Cu 2 II (BPMPO - )(O 2 2- )] 1+ {BPMPO-H = 2,6-bis{[(bis(2-pyridylmethyl)amino]methyl}-4-methylphenol)} and [Cu 2 II (XYLO - )(O 2 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 [Cu 2 II (BPMPO - )(O 2 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 × 10 2 M -1 (2-PPA) and 10.4 × 10 2 M -1 (CCA). In the reaction of [Cu 2 II (XYLO - )(O 2 2- )] 1+ with 2-PPA, product complexes characterized by single-crystal X-ray crystallography are the anticipated dicopper(I) complex, [Cu 2 I (XYLO - )] 1+ plus a mixed-valent Cu(I)Cu(II)-formate species. Formate was further identified and confirmed by 1 H NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) analysis. Using 18 O 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.