Delineating the role of oxidants in Pd-catalysed C-H activation reactions

Abstract

Catalytic C-H activation reactions are valuable synthetic tools that can provide efficient routes to important molecular motifs. These reactions are often touted as being more atom economic than other catalytic reactions, this is particularly true of oxidative catalytic C H activation. However, oxidative catalytic C H activation reactions require an oxidant, and if the oxidant used generates high molecular mass and/or toxic by-products, the atom economic / environmental benefits of these reactions is questionable. According, the aims of this thesis are to investigate catalytic C-H activation reactions that proceed via an oxidative mechanism, and to implement the use of greener oxidants (e.g. O¬2). The first chapter covers the relevant literature regarding C H activation strategies and C H cleavage mechanisms. Chapter two, focus on the Fujiwara-Moritani reaction (a.k.a. oxidative Heck) between acetanilide and butyl acrylate. Initially, the use of air as a highly convenient oxidant was investigated however, this reaction was found to produce a variable result, the cause of this was investigated but not definitively determined. Following this, a mechanistic study was conduct using benzoquinone (BQ) as a stoichiometric oxidant. This study was primary comprised of kinetic experiments, but also incorporated the use of other mechanistic techniques (Job and Hammett plots). The results presented in this chapter support the involvement of a mixed acetate / tosylate active catalyst in the rate determining step, which is thought to be C H cleavage. In addition to this, a series of same excess experiments revealed that no catalyst degradation occurs throughout the reaction, with the major deactivation process being hydroquinone inhibition. In Chapter three, the steady-state rate equation is derived and kinetic modelling is used to rationalise the mechanism proposed in the previous chapter. Chapter four investigates C O bond forming oxidative catalytic C-H activation. This work initially focused on developing conditions for the acyloxylation reaction between acetanilide and benzoic acid. Reaction conditions were developed that provided a modest yield, although they were synthetically impractical. Following this, alternative oxidants were investigated for the acetoxylation reaction of acetanilide. Catalytic conditions using peracetic acid were developed and the substrate scope was investigated. The final chapter provides experimental details and characterisation data.