C−X Bond Activation by Palladium: Steric Shielding versus Steric Attraction

The C−X bond activation (X = H, C) of a series of substituted C(n°)−H and C(n°)−C(m°) bonds with C(n°) and C(m°) = H3C− (methyl, 0°), CH3H2C− (primary, 1°), (CH3)2HC− (secondary, 2°), (CH3)3C− (tertiary, 3°) by palladium were investigated using relativistic dispersion‐corrected density functional theory at ZORA‐BLYP‐D3(BJ)/TZ2P. The effect of the stepwise introduction of substituents was pinpointed at the C−X bond on the bond activation process. The C(n°)−X bonds become substantially weaker going from C(0°)−X, to C(1°)−X, to C(2°)−X, to C(3°)−X because of the increasing steric repulsion between the C(n°)‐ and X‐group. Interestingly, this often does not lead to a lower barrier for the C(n°)−X bond activation. The C−H activation barrier, for example, decreases from C(0°)−X, to C(1°)−X, to C(2°)−X and then increases again for the very crowded C(3°)−X bond. For the more congested C−C bond, in contrast, the activation barrier always increases as the degree of substitution is increased. Our activation strain and matching energy decomposition analyses reveal that these differences in C−H and C−C bond activation can be traced back to the opposing interplay between steric repulsion across the C−X bond versus that between the catalyst and substrate. Bulk up! Our computational study shows how increasing steric bulk at the C−X bond systematically decreases the bond strength along the series C(0°)−X to C(1°)−X to C(2°)−X to C(3°)−X. These weaker C−H and C−C bonds are not always more reactive in oxidative addition reactions with palladium catalysts. Instead, we illustrate the interplay between steric repulsion across the C−X bond versus that of the catalyst and substrate.