New methods for the functionalisation of arenes involving ruthenium catalysed C-H functionalisation and the Smiles rearrangement

Abstract

Arene rings are highly important structures that are present in a multitude of pharmaceuticals, polymers and natural products. Therefore, new methods that allow for the functionalisation of arenes in unique and efficient ways are highly desirable. Herein are described various methodologies for the functionalisation of arene rings either by ruthenium catalysed meta-C-H functionalisation or by use of the Smiles rearrangement. Chapter 1 explores the use of ruthenium catalysis to enact meta-functionalisation of arenes employing pyridine, and derivatives of, as directing groups. The attempted meta-functionalisation using a dual ruthenium and photoredox catalysis system is described. In addition, the discovery, optimisation and scope exploration of a novel meta-carboxylation is presented. The reaction utilised inexpensive carbon tetrabromide, methanol and ruthenium trichloride reagents and the scope encompassed various nitrogen heterocycle directing groups and substitution on the arene ring. The carboxylate motif is a key functional group both in biologically active molecules and as a synthetic building block. Derivatisation of the product was exemplified, and mechanistic experiments are described, providing evidence for the proposed ortho-ruthenation mechanistic pathway. Chapter 2 explores the use of the Smiles rearrangement for transition metal free arylations. The amphiphilic nature of sulfonamides is exploited in two-step one-pot procedures. First, the tandem acylation-Smiles reaction allowed for the synthesis of phenethylamines. Indazole products were obtained when 2-nitrobenzenesulfonamides were employed. Second, the tandem intramolecular Michael addition-Smiles reaction allowed for the aminoarylation of alkenes to synthesise substituted quinolin-4-ones. Also presented is preliminary work in the synthesis of tetrasubstituted alkenes from sulfone and alkyne starting materials.

Date of Award	1 Aug 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	David Leigh (Supervisor) & Michael Greaney (Supervisor)