Spectroscopic Evidence for a Cobalt-Bound Peroxyhemiacetal Intermediate

Aldehyde deformylation reactions by metal dioxygen adducts have been proposed to involve peroxyhemiacetal species as key intermediates. However, direct evidence of such intermediates has not been obtained to date. We report the spectroscopic characterization of a mononuclear cobalt­(III)-peroxyhemiacetal complex, [Co­(Me3-TPADP)­(O2CH­(O)­CH­(CH3)­C6H5)]+ (2), in the reaction of a cobalt­(III)-peroxo complex (1) with 2-phenylpropionaldehyde (2-PPA). The formation of 2 is also investigated by isotope labeling experiments and kinetic studies. The conclusion that the peroxyhemiacetalcobalt­(III) intermediate is responsible for the aldehyde deformylation is supported by the product analyses. Furthermore, isotopic labeling suggests that the reactivity of the cobalt­(III)-peroxo complex depends on the second reactant. The aldehyde inserts between the oxygen atoms of 1, whereas the reaction with acyl chlorides proceeds by a nucleophilic attack. The observation of the peroxyhemiacetal intermediate provides significant insight into the initial step of aldehyde deformylation by metalloenzymes.醛脱甲酰基化反应（aldehyde deformylation reactions）由金属双氧加合物（metal dioxygen adducts）介导，此前被提出该类反应以过氧半缩醛（peroxyhemiacetal）物种作为关键中间体。然而截至目前，此类中间体的直接实验证据仍未被获取。本工作报道了单核钴(III)-过氧半缩醛配合物（mononuclear cobalt(III)-peroxyhemiacetal complex）[Co(Me3-TPADP)(O2CH(O)CH(CH3)C6H5)]+（2）的光谱表征结果，该配合物由钴(III)-过氧配合物（cobalt(III)-peroxo complex，1）与2-苯基丙醛（2-phenylpropionaldehyde，简称2-PPA）反应生成。我们还通过同位素标记实验（isotope labeling experiments）与动力学研究（kinetic studies），对配合物2的形成过程进行了系统探究。产物分析（product analyses）结果证实，过氧半缩醛合钴(III)中间体是介导醛脱甲酰基化反应的关键物种。此外，同位素标记实验表明，钴(III)-过氧配合物的反应活性取决于第二反应物的种类：醛类底物会插入至配合物1的两个氧原子之间，而其与酰氯（acyl chlorides）的反应则通过亲核进攻（nucleophilic attack）路径进行。本次对过氧半缩醛中间体的观测，为理解金属酶（metalloenzymes）介导的醛脱甲酰基化反应的初始步骤提供了重要的机制视角。