Ruthenium Catalysed C-H Functionalisation of Heteroaromatics

  • Po Man Liu

Student thesis: Doctoral ThesisPhD

Abstract

Two methods of C-H functionalisation of sp2 C-H bonds via ruthenium catalysis have been developed in this thesis. The first methodology is the preparation of meta-sulfonated heteroaromatics. Individual substrate optimisations were performed on various nitrogen containing heteroaromatics such as 2-phenylpyridine, 1-phenylpyrazole and benzo[h]quinoline. It was discovered that 2-phenylpyridine was the best substrate for C-H sulfonation with aryl sulfonyl chlorides and gave yields of 4 – 63% and provided functional handles allowing for further synthetic manipulations. The second methodology developed is a ruthenium(II) catalysed ortho-C-H acylation of heteroaromatics. Initial optimisation was performed on 2-phenylpyridine with ortho-toluoyl chloride for C-H acylation and it was found tricyclohexylphosphine was the best ligand for this reaction. Unfortunately, the scope of this reaction is limited, as only a couple of aryl acid chlorides were compatible for the acylation of 2-phenylpyridine. This methodology was then applied to 1-phenylpyrazole and demonstrated the first example of C-H acylation of 1-phenylpyrazole with acid chloride as the coupling partner. C-H acylation of 1-phenylpyrazole is more versatile than 2-phenylpyridine, as the reaction scope is much broader. Various aryl and alkyl acid chlorides were compatible for the acylation of 1-phenylpyrazole derivatives and gave yields of 4 – 91%. Sterically hindered acid chlorides provided the higher yields, which is indicative of a steric acceleration during the reductive elimination step.Ruthenium-substrate complexes were synthesised and employed in stoichiometric experiments under the meta-sulfonation and ortho-acylation conditions independently, to attempt to elucidate the mechanistic pathways of these two reactions. 1H NMR spectroscopy on the meta-sulfonations of 1-phenylpyrazole and benzo[h]quinoline complexes indicated the formation of sulfonated ruthenium-substrate complexes, where the sulfone is substituted para to the ruthenium-carbon bond. C-H activation of 1-phenylpyrazole with a ruthenium-phosphine complex was attempted, and found it was difficult to synthesise the C-H activated substrate-ruthenium complex in the presence of phosphine ligands.
Date of Award13 Jan 2015
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorChristopher Frost (Supervisor)

Keywords

  • organic chemistry
  • C-H functionalisation
  • catalysis

Cite this

Ruthenium Catalysed C-H Functionalisation of Heteroaromatics
Liu, P. M. (Author). 13 Jan 2015

Student thesis: Doctoral ThesisPhD