Computational Study of Intramolecular Coordination Enhanced Oxidative Addition to form PdIV-Pincer Complexes, and Selectivity in Aryloxide Attack at PdIVCH2CRR′ Motifs in Palladium-Mediated Organic Synthesis

Computational studies support the key role of intramolecular coordination by a carboxylate group in the facile oxidative addition of the iodoarene 2,6-(HO2C)2C6H3I to a PdII center to form the pincer-PdIV motif Pd­{2,6­(O2C)­C6H3-O,C,O}, Pd­(OCO). Mechanisms of attack by an aryloxide nucleophile at the methylene group in a palladacycle PdIV(OCO)­(CH2CRR′–E) to form ArOCH2CMe2–E (E = oxime) are examined; for RR′ = HEt and E = amine, it is mainly the formation of analogous ArOCH2CHEt–E together with CH2CEt–E arising from β-hydrogen elimination. Computational results are in agreement with recent experimental results by Whitehurst, Gaunt. [J. Am. Chem. Soc. 2020, 142, 14169]. For β-hydrogen elimination, computation demonstrates that the conformational flexibility in the chelate ring is required to allow the hydrogen atom to be in an axial orientation relative to Pd–C, thus maximizing the dihedral angle Pd···C–C···H in the transition-state fragment Pd···CH2C­(R)···H···OAr. Bulky substituents R′ at the β-position, CHR′, favor nucleophilic attack at the methylene carbon.

计算研究证实，羧酸根基团的分子内配位在碘代芳烃2,6-二羟基羰基碘苯（2,6-(HO₂C)₂C₆H₃I）与二价钯（Pd(II)）中心发生的易进行氧化加成反应中起到关键作用，该反应生成钳形四价钯（Pd(IV)）结构Pd{2,6-(O₂C)₂C₆H₃-O,C,O}与Pd(OCO)。本研究考察了芳氧基亲核试剂对钯杂环Pd(IV)(OCO)(CH₂CRR'-E)中亚甲基的进攻机理，该反应生成ArOCH₂CMe₂-E（E为肟基）。当RR'为HEt且E为氨基时，主要生成类似物ArOCH₂CHEt-E，同时伴随由β-氢消除反应产生的CH₂=CEt-E。计算结果与怀特赫斯特（Whitehurst）、冈特（Gaunt）近期发表于《美国化学会志》的实验研究结果相符（J. Am. Chem. Soc. 2020, 142, 14169）。针对β-氢消除反应，计算结果表明，螯合环需具备构象灵活性，才能使氢原子处于与Pd-C键相对的轴向取向，从而最大化过渡态片段Pd···CH₂C(R)···H···OAr中的二面角Pd···C-C···H。β位CHR'上的大位阻取代基R'有利于亚甲基碳发生亲核进攻。