title: Towards the isolation of α-\(N\)-metallated free \(N\)-heterocyclic carbenes
Creators: name: Leow, MY
Publisher: name: University of Tasmania
Year: 2019

description: Great strides have been made in the synthesis and understanding of \(N\)-heterocyclic carbenes (NHCs). This has led to tremendous success in their use in catalytic transformations, either directly or as ligands for transition metals. Although NHCs spanning a vast range of \(N\)-heterocycle classes are known, those derived from imidazolium and benzimidazolium frameworks are especially popular for their steric and electronic tunability. The two \(N\)-substituents constitute major sites for structural modification, and currently, NR,NR (R = alkyl, aryl), NR,NH, NH,NH and naked N,NR substitution patterns are known. This work attempts to expand the scope of free benzimidazolium-derived NHCs to include NM,NR (M = metal) types. These free NM,NR NHCs may possess capabilities for dual catalysis as a result of the proximal Lewis acidic metal centre and Lewis basic free carbene. A modular \(N,N’,N’’,N’’’\)-tetradentate bis(benzimidazolyl) ligand framework “MeRLH\(_2\)” (R = bridging group) designed specifically for the demonstration of proof-of-concept would coordinatively saturate the metal centre, preventing its migration to the adjacent carbene site and thus preserving the α-\(N\)-metallated free NHC motif. The figure below illustrates the proposed formation of the target NHC from a precursor MeRLH\(_2\) complex, with the desired free NM,NR NHC motif highlighted in blue. (Figure not included but can be viewed in the thesis PDF). Synthetic pathways towards a C\(_2\)-symmetric ethylene-bridged bis(benzimidazolyl) ligand Me(en)LH\(_2\) from three different precursors, namely 2-amino-3-nitrophenol, 2-amino-3-nitrotoluene and methyl 2-amino-3-nitrobenzoate, are described. An efficient protocol for the multigram-scale synthesis of Me(en)LH\(_2\) was successfully established. The preparation of its respective cyclohexyl- and phenylene-bridged analogues, MeCyLH\(_2\) and MePhLH\(_2\) are also discussed. The challenges encountered during attempts to prepare them as free ligands are circumvented using metal-templated condensation of the cyclic diamines and key precursor aldehyde. A series of nickel(II), copper(II), cobalt(II), silver(I), zinc(II) and palladium(II) complexes of these novel \(N,N’,N’’,N’’’\)-tetradentate bis(benzimidazolyl) ligands was synthesised. Their suitability as precursors to the free NM,NR NHC was assessed based on their stability, solubility, geometric and spectroscopic properties. In accordance with initial predictions, the palladium(II) complexes were shown to be the prime candidate for further studies, as they consistently exhibited square planar coordination geometries, diamagnetic behaviour, and in some cases, greater stability compared to their nickel(II), copper(II), cobalt(II) or silver(I) counterparts. Counterion effects in the nickel(II), copper(II) and cobalt(II) complexes and the structural impacts of bridging group variations in the nickel(II) and palladium(II) complexes of MeRLH\(_2\) are also discussed. NMR-scale deprotonation trials using a range of inorganic and organic bases were conducted on the palladium(II) suite of complexes [PdMeRLH\(_2\)](OTf)\(_2\) (R = en, Cy, Ph). The results suggest that the NM,NR NHC decomposes too rapidly to be observed or isolated. Increasing the rigidity of the bridging group between the imine donor atoms failed to prevent decomposition. However, base-assisted deuterium exchange experiments with [PdMe(en)LH\(_2\)](OTf)\(_2\) support the transient existence of the NM,NR NHC. It is suspected that competitive deprotonation at the aldimines and the limited solubility of these complexes in inert solvents both contributed to the formation of complex product mixtures. Alternative approaches to the NM,NR NHC such as simultaneous complexation/deprotonation with alkylmetal reagents or stepwise deprotonation-then-complexation were found to be unsuccessful. These findings suggest that future endeavours to isolate a free NM,NR NHC may benefit from replacing the benzimidazolyl core structure with imidazolyls, which have more acidic C2 protons; increasing steric bulk around the ligand for improved solubility, and eliminating other potential deprotonation sites on the ligand.