The application of mechanochemical techniques towards organic synthesis and catalysis

This thesis describes a series of studies of organic synthesis and catalysis under mechanochemical conditions. Initial investigations outline the development of the first known C-S coupling under mechanochemical conditions, which builds upon previous work in the group describing a mechanochemical C-N coupling. In this study, oxidation of thiols to disulfides proved a detrimental side reaction, which was overcome with the use of a reductant and subsequent studies revealed a possibility for careful control of this interconversion which led to a 2-step, 1-pot coupling of disulfides. Also discussed in this study is the concept of phase transition induced reactivity, which was demonstrated by alteration of the reactor design to promote a melt-phase phenomenon that enabled reactivity in some cases. Transition metal catalysed cross-electrophile coupling has recently emerged as a powerful strategy for the construction of C-C bonds. Firstly, a mechanochemical cross-electrophile coupling reaction of aryl halides and alkyl halides was developed, demonstrating the excellent capability of ball-milling for the activation of zero-valent metals. A broad scope was shown, including tolerance to a range of metal forms. Further work in this area led to the development of a reductive coupling reaction of twisted amides with alkyl halides for the construction of a range of ketone products. The degree of bond angle distortion for the amide component was examined for its effect in the reaction. Finally, the reactivity of a fluoroiodane reagent was investigated for use under mechanochemical conditions. Initial work showed excellent reactivity for a known fluorocyclisation of unsaturated carboxylic acids to give fluorinated lactones. These promising results then led to development of mechanochemical protocols for the fluorocyclisation of unsaturated hydrazones and oximes to access novel fluorinated tetrahydropyridazines and dihydrooxazines respectively