Characterization of essential ligand properties in palladium catalyzed cross coupling of alkyls using density functional theory

Palladium catalyzed cross coupling reactions are one of the most utilized synthetic method(s) in carbon-carbon bond formation. But this synthetic method is problematic for alkyl reactants, due in part to undesirable beta-hydride elimination side reaction. This work aims at understanding the mechanistic aspects of alkyl cross coupling and the role of ligand in suppressing this undesired side reaction. Density Functional Theory (DFT) calculations suggest that the rate of beta-hydride elimination depends on relative stabilities of agostic stereo-isomers. The stability of agostic Pd complexes are dictated by the mutual electronic trans influences of ligands and their steric properties. Both sigma and pi effects contribute to the ligand's trans influencing ability. Steric effects modulate the extent of trans influence(s) and preferentially stabilize cis isomer(s). This interplay of trans influence and steric effect gives some proposed "design rules" on ligand choices in alkyl couplings. Selectivity is also increased when ligands/reactants have hemilabile properties. These results motivate rational design of improved alkyl cross coupling catalysts.