Strategic use of transition metals for selective C-H bond functionalisation

Abstract

The ability to selectively react C-H bonds in organic molecules is a field within synthetic chemistry that has grown substantively in the last few decades. The interest in this area emanates from the desire to maximise atom economy: this approach obviates the need for pre-functionalised starting materials and stoichiometric organometallic reagents. However, organic molecules typically contain many different C-H bonds with little difference in bond energy which can make selective functionalisation difficult to achieve.Herein is described how ruthenium catalysis was shown to effect meta-bromination on substituted 2-phenylpyridines. This novel procedure shows a marked contrast to other transition metal catalysed bromination procedures which are selective for the ortho-position of the phenyl ring. It was shown that this methodology was compatible with more traditional palladium catalysed chemistries (Suzuki-Miyaura and Heck reactions) in the same pot which enabled the development of procedures for one-pot meta-arylation and meta-alkenylation. Mechanistic postulation on the meta-bromination procedure led to the discovery of several interesting new meta-selective C-H functionalisation reactions with ruthenium catalysis. The early investigations, together with the challenges faced, are described. Subsequent investigations into other halogenating agents with ruthenium catalysis showed that iodine monochloride gave interesting results, with switchable chemoselectivity through variance of catalyst giving ortho-chlorinated or ortho-iodinated products.Also presented is a copper mediated coupling of electron rich arenes and toluene-like molecules to give (halo)diarylmethanes. This formal cross dehydrogenative coupling strategy tolerates a wide range of coupling partners for both the electron rich arene and the tolyl-component. Mechanistic studies suggest that the reaction proceeds via a copper mediated coupling of an in situ generated aryl bromide with a benzylic radical species.

Date of Award	1 Aug 2016
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Michael Greaney (Supervisor) & David Leigh (Supervisor)