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

利用双铜O(2)衍生的过氧化物络合物进行亲核醛脱甲酰化反应中的双加氧酶化学

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Abstract

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.

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