Transition Metal-Free Decarboxylative Halogenation: New Routes for Decarboxylative Cross-Coupling

Abstract

In the ten years since Gooßen and co-workers published their first report on decarboxylative cross-coupling, the field of decarboxylative activation has grown tremendously. Benzoic acids are now recognised as atom-economic alternatives to traditional cross-coupling partners and they also benefit from being cheap, readily-available and shelf-stable reagents. This thesis describes the development of a decarboxylative halogenation procedure and its application in cross-coupling reactions for biaryl synthesis (Scheme 1).We first detail the development of a transition-metal free decarboxylative iodination and its application to a variety of electron-rich benzoic acids (Chapter 2). Preliminary mechanistic studies also shed some light on the nature of the decarboxylation. Analogously, the procedure can be applied to decarboxylative brominations by simply switching iodine with tetrabutylammonium tribromide, nBu4NBr3. The advantages and disadvantages of these decarboxylative halogenations over previous procedures, in particular the classical aromatic Hunsdiecker reaction, will be discussed during this chapter.We then look to achieve our ultimate goal of biaryl synthesis by exploiting this decarboxylative halogenation method in cross-couplings with a simple arene or a second benzoic acid (Chapter 3). This decarboxylative arylation occurs in one-pot and has potential as a more economical and general route to biaryls in comparison to current decarboxylative procedures.Before revealing our experimental results, we shall discuss recent developments in decarboxylative couplings and their benefits over traditional cross-coupling methods (Chapter 1). A thorough analysis of this topic will cover reactivity trends in transition metal catalysed decarboxylations and the current state of decarboxylative cross-couplings for biaryl synthesis.

Date of Award	31 Dec 2016
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Igor Larrosa (Supervisor) & Michael Greaney (Supervisor)