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 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.