Modelling of Mono and Bimetallic Amides for C-H Metalation

Abstract

Understanding the origins of reactivity and selectivity in metal amide-mediated C�H metalation remains a central challenge in organometallic chemistry. This thesis investigates the fundamental factors controlling selective C�H activation through computational mechanistic study of alkali metal and transition metal amide complexes. Focusing on both bimetallic systems (NaCo and KCo) and monometallic Fe and Co complexes supported by sterically rigid TMP ligands, this thesis applies DFT, energy decomposition analysis, non-covalent interaction and independent gradient model analyses, as well as microkinetic model to understand divergent reactivity profiles. For the reactivity with the NaCo system, a �seesaw effect� was uncovered, whereby the strength of Na�X interactions (X = F, Cl, Br, H) tunes the balance between mono-aryl and tetra-aryl Co(II) square planar complex formation pathways. It rationalises the experimentally observed selectivity trends and provides design rules for modulating reactivity. For the KCo system we reveal a striking sequence-dependent reactivity, whereby the stepwise addition of K(HMDS) and Co(HMDS)2 enables formation of reactive potassium amide dimers that undergo SN2-type methyl C�H activation of toluene. In contrast, simultaneous reagent mixing yields a thermodynamically stable but catalytically inert KCo(HMDS)3 cobaltate, precluding further activation. Monometallic studies contrast the behaviour of Fe(TMP)2 and Co(TMP)2 in the metalation of pentafluoroarene; while both exhibit low-coordinate geometries, only Fe(TMP)2 shows polybasicity, effecting polybasic behaviour. Co(TMP)2 performs a single activation before stabilising as a dimeric complex. This divergence is traced to stronger Fe�N bonding and favourable THF exchange equilibria, as shown by the activation strain, natural bond orbital and independent gradient model analyses. Hybrid solvation models are employed to accurately reproduce solvent effects and microkinetic simulations validated against experimental rates, which capture the interplay of reaction barriers and product speciation. Together, these studies illuminate how subtle variations in the choice of metal, ligand, and solvent govern the energy landscape of C�H metalation and product formation. The results lay the groundwork for predictive design of cooperative, earth-abundant metal-based C�H activation systems.