Questioning the Role of Solvent Coordination in Pd ⁽⁰⁾ -Mediated Selectivity Reversal: Insights from Quantum Chemical Calculations

Solvent has been shown experimentally to exert a strong influence on chemoselectivity in Pd-catalyzed cross-coupling reactions of arenes bearing competing C–Cl and C–OTf sites. In particular, polar and coordinating solvents such as DMF and MeCN reverse the expected preference for C–Cl activation observed with Pd(0)/PtBu3 in THF or toluene. This effect has been attributed to changes in the active catalytic species, with polar solvents proposed to favor either anionic palladium or solvent-coordinated palladium complexes, thereby shifting selectivity toward C–OTf. Here, we present a computational study of solvent coordination as a potential origin of the reported selectivity reversal and show that, when larger basis sets are used and basis-set superposition errors are minimized, solvent coordination is not necessarily predicted to be favored, calling into question its role as the primary mechanistic explanation.