Ligand Substitution, Catalyst Activation, and Oxidative Addition Studies of a Stable Dialkyl Palladium Precatalyst

Palladium-catalyzed cross-coupling reactions are indispensable in chemical synthesis, but efficient in situ catalyst activation remains a persistent challenge. Current Pd(II) precatalysts often lead to inefficient catalyst activation, necessitating higher catalyst loadings and limiting selectivity. We investigated the ligand substitution and activation mechanism of the stable Pd(II) dialkyl complex (^DMPDAB)Pd(CH₂SiMe₃)₂ in real-time using mass spectrometric monitoring. The introduction of charge-tagged phosphine ligands enabled the detection of key catalytic intermediates and identification of off-cycle species. Our findings demonstrate a low activation energy for the ligand dissociation of the ^DMPDAB ligand and the reductive elimination of (Me₃SiCH₂)₂ resulting in rapid formation of monoligated LPd(0) species, the active catalytic species for oxidative addition. These mechanistic insights offer a path toward developing more efficient and selective Pd-catalyzed processes, offering valuable guidance for the future design of precatalysts with improved performance.