Fundamental Palladium Catalyzed Oxidative Addition Reactions
Authors:   , Moloto Bryan Phuti 
Published: September 2023

This thesis focuses on investigating fundamental oxidative addition (OA) reactions catalysed by palladium. OA, being the first and rate determining step in cross-coupling reactions, is a reaction of vital importance in synthetic chemistry. The findings in this thesis were successfully obtained using the Activation Strain Model of chemical reactivity in combination with computations based on Density Functional Theory (DFT) as implemented in the ADF program. The ASM model is a fragment-based approach that characterizes reactions in terms of the rigidity and the bonding capabilities of the original reactants, and the extent to which the reactants must deform along the reaction pathway of a particular reaction mechanism. Thus, the total energy profile of a particular chemical reaction can be decomposed into contributions from the deformation of the reactants (the strain energy) and their mutual interaction (the interaction energy). The interaction energy can then be further decomposed using the canonical energy decomposition analysis of ADF into electrostatic interactions, destabilizing Pauli repulsion, and stabilizing orbital interactions. In Chapter 3, with the aim of understanding the underlying mechanism and trends found by the OA, we detailed our quantum chemical exploration of the palladium-mediated activation of C(spn)–X bonds (n = 1–3; X = F, Cl, Br, I) in the archetypal model substrates H3C–CH2–X, H2C=CH–X, and HC≡C–X by a model bare palladium catalyst. First and foremost, we investigated the bond dissociation enthalpies (BDEs) of the bonds to be activated. So, we started from the C(sp3)–X moving to C(sp2)–X and then to C(sp)–X bonds for each of the selected set of X atoms above. We found that as we move down group 17, the C(spn)–X bond becomes weaker and as such easier to break. Based on our state-of-the-art analyses, we discovered that as we vary the substituent X, going down Group 17 from X = F to Cl to Br to I on the C(spn)–X substrate, the oxidative addition barriers drastically decrease. This favorable activation barrier stabilization originates from two factors: (i) a less destabilizing activation strain; and remarkably (ii) a more favorable electrostatic attraction between the catalyst and the substrate. When changing the substrate from C(spn)–F to C(spn)–I, consequently, the electrostatic interaction between the catalyst and substrate also becomes more favorable. Iodine, being the largest halogen of the selected substituents, has a more diffuse and electron-rich density and a higher nuclear charge that in turn engage in favorable electrostatic attractions with the palladium nucleus and electron density, respectively. This effect makes the OA reaction involving the C(spn)–X bond with a larger halogen atom correspond to a more stabilizing interaction and hence lower reaction barrier. Next, in Chapter 4 we have quantum chemically investigated the palladium-mediated activation of HnA–AHn bonds (AHn = CH3, NH2, OH, F) by catalysts PdLn with Ln = no ligand, PH3, (PH3)2. Herein, we found that as we move from C to F along the period, i.e., from H3C–CH3 to H2N–NH2 to HO–OH to F–F, the activation barriers decrease and more interestingly the activation of the F–F bond is even barrierless. As we move from C to F on the selected substrates, the number of the substituents around the A–A bond become less and as such enabling the catalyst to approach the substrate with ease, thereby resulting in a decreasing activation barriers. The causal effects of this barrier stabilizations stem from: (i) a reduced activation strain due to a weaker HnA–AHn bond; (ii) a decreased Pauli repulsion as a result of a difference in steric shielding of the HnA–AHn bond; and (iii) an enhanced backbonding interaction between the occupied 4d atomic orbitals of the palladium catalyst and * acceptor orbital of the substrate.