Hota Pradip Kumar, Panda Sanjib, Phan Hai, Kim Bohee, Siegler Maxime A, Karlin Kenneth D
Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States.
J Am Chem Soc. 2024 Aug 28;146(34):23854-23871. doi: 10.1021/jacs.4c06243. Epub 2024 Aug 14.
The chemistry of copper-dioxygen complexes is relevant to copper enzymes in biology as well as in (ligand)Cu-O (or Cu-O) 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 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(BPMPO)(O)] {BPMPO-H = 2,6-bis{[(bis(2-pyridylmethyl)amino]methyl}-4-methylphenol)} and [Cu(XYLO)(O)] (XYLO = a BPMPO analogue possessing bis(2-{2-pyridyl}ethyl)amine chelating arms). Their dicopper(I) precursors are catalysts. The O-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(BPMPO)(O)] species initially reacts reversibly with the aldehydes to form detectable dicopper(II) peroxyhemiacetal intermediates, for which optical titrations provide the (at -90 °C) of 73.6 × 10 M (2-PPA) and 10.4 × 10 M (CCA). In the reaction of [Cu(XYLO)(O)] with 2-PPA, product complexes characterized by single-crystal X-ray crystallography are the anticipated dicopper(I) complex, [Cu(XYLO)] plus a mixed-valent Cu(I)Cu(II)-formate species. Formate was further identified and confirmed by H NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) analysis. Using O-isotope labeling the reaction produced a high yield of 18-O incorporated acetophenone as well as formate. The overall results signify that true reactions have occurred, supported by a thorough mechanistic investigation.
铜-双氧配合物的化学性质与生物学中的铜酶以及氧化转化中使用的（配体）铜-氧（或铜-氧）物种相关。从化学合成中适用的整体能量考虑出发，具有合适的原子经济性是有益的；氧气中的两个氧原子都转移到产物中。然而，这种双加氧酶型化学的例子极其罕见或记录不充分。在此，我们报道了过氧双铜（II）物种[Cu(BPMPO)(O)] {BPMPO-H = 2,6-双{[(双(2-吡啶甲基)氨基]甲基}-4-甲基苯酚)}和[Cu(XYLO)(O)]（XYLO = 一种具有双(2-{2-吡啶基}乙基)胺螯合臂的BPMPO类似物）的亲核氧化醛脱甲酰基反应活性。它们的双铜（I）前体是催化剂。源自氧的过氧双铜（II）中间体在-90°C下于2-甲基四氢呋喃中与2-苯基丙醛（2-PPA）和环己烷甲醛（CCA）等醛迅速反应。升温至室温（RT）然后进行后处理，得到高产率的甲酸盐（HC(O)O）以及酮（苯乙酮或环己酮）。机理研究表明，[Cu(BPMPO)(O)]物种最初与醛可逆反应形成可检测的双铜（II）过氧半缩醛中间体，光学滴定给出其在-90°C下的离解常数为73.6×10⁻⁶ M⁻¹（2-PPA）和10.4×10⁻⁶ M⁻¹（CCA）。在[Cu(XYLO)(O)]与2-PPA的反应中，通过单晶X射线晶体学表征的产物配合物是预期的双铜（I）配合物[Cu(XYLO)]加上一种混合价态的Cu（I）Cu（II）-甲酸盐物种。甲酸盐通过¹H NMR光谱和电喷雾电离质谱（ESI-MS）分析进一步鉴定和确认。使用¹⁸O同位素标记，反应产生了高产率的含有¹⁸O的苯乙酮以及甲酸盐。全面的机理研究支持了整体结果表明真正的双加氧反应已经发生。
