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

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作   者：

Hota, Pradip Kumar;  Panda, Sanjib;  Phan, Hai;  Kim, Bohee;  Siegler, Maxime A.;  Karlin, Kenneth D.; 

作者机构：

Johns Hopkins University Department of Chemistry; 

关键词：

OXYGEN-ACTIVATION;  SIDE-ON;  STRUCTURE/FUNCTION CORRELATIONS;  CRYSTAL-STRUCTURE;  SPECTROSCOPIC CHARACTERIZATION;  AEROBIC OXIDATION;  TRYPTOPHAN 2,3-DIOXYGENASE;  BOND-CLEAVAGE;  QUERCETIN 2,3-DIOXYGENASE;  ELECTRONIC-STRUCTURE; 

期刊名称：

Journal of the American Chemical Society

i s s n：

0002-7863

年卷期：

2024 年 146 卷 34 期

页   码：

23854-23871

页   码：

摘   要：

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 degrees 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 degrees C) of 73.6 x 10(2) M-1 (2-PPA) and 10.4 x 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 H-1 NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) analysis. Using O-18(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.