Mechanistic Basis for Efficient, Site-Selective, Aerobic Catalytic Turnover in Pd-Catalyzed C–H Imidoylation of Heterocycle-Containing Molecules

A recently reported Pd-catalyzed method for oxidative imidoylation of C–H bonds exhibits unique features that have important implications for Pd-catalyzed aerobic oxidation catalysis: (1) The reaction tolerates heterocycles that commonly poison Pd catalysts. (2) The site selectivity of C–H activation is controlled by an N-methoxyamide group rather than a suitably positioned heterocycle. (3) A Pd0 source, Pd2(dba)3 (dba = dibenzylideneacetone), is superior to Pd­(OAc)2 as a precatalyst, and other PdII sources are ineffective. (4) The reaction performs better with air, rather than pure O2. The present study elucidates the origin of these features. Kinetic, mechanistic, and in situ spectroscopic studies establish that PdII-mediated C–H activation is the turnover-limiting step. The tBuNC substrate is shown to coordinate more strongly to PdII than pyridine, thereby contributing to the lack of heterocycle catalyst poisoning. A well-defined PdII–peroxo complex is a competent intermediate that promotes substrate coordination via proton-coupled ligand exchange. The effectiveness of this substrate coordination step correlates with the basicity of the anionic ligands coordinated to PdII, and Pd0 catalyst precursors are most effective because they selectively afford the PdII–peroxo in situ. Finally, elevated O2 pressures are shown to contribute to background oxidation of the isonitrile, thereby explaining the improved performance of reactions conducted with air rather than 1 atm O2. These collective results explain the unique features of the aerobic C–H imidoylation of N-methoxybenzamides and have important implications for other Pd-catalyzed aerobic C–H oxidation reactions.近日报道的一种钯（Pd）催化的C-H键氧化亚胺酰基化反应，展现出独特的反应特性，其对钯催化需氧氧化催化领域具有重要的参考价值：(1) 该反应可耐受通常会使钯催化剂中毒的杂环化合物；(2) C-H活化的位点选择性由N-甲氧基酰胺基团调控，而非依赖于位置适宜的杂环；(3) 零价钯（Pd⁰）前驱体三(二亚苄基丙酮)二钯[Pd₂(dba)₃，其中dba为二亚苄基丙酮]作为预催化剂时，其催化性能优于乙酸钯(II)[Pd(OAc)₂]，其余二价钯（Pd²⁺）前驱体均无催化活性；(4) 该反应在空气氛围下的催化效果优于纯氧气氛围。本研究阐明了上述特性的根源。通过动力学、机理及原位光谱学研究，证实二价钯（Pd²⁺）介导的C-H活化是该反应的决速步骤。研究发现，叔丁基异腈（tBuNC）底物与二价钯的配位能力强于吡啶，这正是该反应不会因杂环导致催化剂中毒的原因之一。结构明确的二价钯过氧络合物是该反应的活性中间体，其可通过质子耦合配体交换机制促进底物配位。该底物配位步骤的催化效率与配位在二价钯上的阴离子配体的碱性呈正相关；而零价钯前驱体的催化效果最优，因其可选择性地原位生成二价钯过氧络合物。最后，研究证实升高的氧气压力会引发异腈的本底氧化反应，这也解释了为何该反应在空气氛围下比在1标准大气压纯氧氛围下表现更优。上述综合研究结果阐明了N-甲氧基苯甲酰胺的需氧C-H键亚胺酰基化反应的独特特性根源，并对其他钯催化的需氧C-H氧化反应具有重要的启示意义。