Dispersion Makes the Difference: Bisligated Transition States Found for the Oxidative Addition of Pd(PtBu3)2 to Ar-OSO2R and Dispersion-Controlled Chemoselectivity in Reactions with Pd[P(iPr)(tBu2)]2

The manipulation of the steric nature of ligands is a key design principle in organometallic reactivity. While general intuition assumes steric effects to be repulsive, recent reports counterintuitively suggested that highly crowded hydrocarbon molecules may be stabilized more strongly than their less bulky analogues as a consequence of dispersion interactions. With the objective of investigating the significance of such attractive intramolecular dispersion forces in organometallic catalysis, we herein studied the effect of dispersion on the accessible geometries and reactivities for two trialkylphosphine ligands of different sizes in Pd-catalyzed cross-coupling reactions: i.e., L = PtBu3 and its smaller analogue L = P(iPr)(tBu(2)). Those methods that account well for dispersion (e.g., omega B97XD, B3LYP-D3) allowed the first location of bisphosphine-ligated transition states for the oxidative addition of (PdL2)-L-0 to aromatic C-O bonds, involving the bulky and widely employed ligand L = PtBu3. DFT methods without dispersion gave rise to dissociation of one phosphine ligand in all cases examined. To probe whether dispersion may even be a reactivity-controlling factor, we also examined the favored site selectivity of the reaction of (PdL2)-L-0 with 4-chlorophenyl triflate, for which the selectivity has previously been shown to be dependent on the ligation state of the reactive palladium species. Various DFT methods (PBE, B3LYP, M06L) and basis sets and different solvent models (COSMO-RS, CPCM) were assessed. While for Pd(PtBu3)(2) dispersion-free and dispersion-containing methods predicted the monophosphine pathway via PdL and reaction at C-Cl to be favored, striking differences were observed for Pd[P(Pr-i)(tBu(2))](2). Dispersion-free DFT predicted C-OTf addition by Pd[P(iPr)(tBu2)]2 to be disfavored by Delta Delta G double dagger approximate to 20 kcal/mol, despite being experimentally accessible. In stark contrast, the involvement of dispersion adequately described the selectivity. The attractive dispersion forces of the crowded trialkyl substituents are therefore a key controlling factor in the competition between mono- and bisligated pathways.