Computational study of intramolecular coordination enhanced oxidative addition to form Pd^IV-pincer complexes, and selectivity in aryloxide attack at Pd^IVCH₂CRR′ 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 Pd^II center to form the pincer-Pd^IV 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 Pd^IV(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.