Rhodium carbenoid route to oxazoles
thesisposted on 2018-05-22, 09:13 authored by Kevin J. Doyle
This thesis describes investigations by the author into the preparation of the oxazole heterocyclic system, by the use of rhodium carbenoid methodology. Chapter 1 is a review of the literature on the formation of oxazoles, by the reaction between diazocarbonyl compounds and nitrites. The various conditions that have been employed in the reaction are detailed, as well as developments into the understanding of its mechanism. Chapter 2 reports the study into the preparation of 4-functionalised oxazoles. A series of 4- benzenesulfonyloxazoles, oxazole-4-phosphates and oxazole-4-carbonitriles were prepared by a rhodium(II)-catalysed reaction. The effect of varying the rhodium(II) catalyst on oxazole formation is detailed. The oxazole-4-carbonitrile methodology was extended to form bis-oxazoles. Attempts to extend this chemisiry towards tris-oxazoles is discussed. Chapter 3 describes the synthesis of the oxazolylindole alkaloids pimprinine, pimprinethine and WS-30581A. This was achieved by the reaction of tert-butyl 3-diazoacetylindole-1- carboxylate with the appropriate nitrile, under rhodium(II) catalysis, followed by deprotection. Studies into varying the substituents at the 2- and 4-positions of the oxazole ring is described. Chapter 4 relates investigations into the synthesis of the cytotoxic cyclic peptides, diazonamide A and B, isolated from the ascidian, Diazona chinensis. These investigations were centred on key skeletal features: an oxazolylindole moiety, an oxazole based around (S)-valine and a functionalised benzofuranol. Model studies towards the oxazolylindole and the valine oxazole sections were undertaken, utilising rhodium carbenoid methodology to prepare the azote heterocycle. Formation of the benzofuranol model involved a one step deprotection and cyclisation, the precursor being prepared via a Claisen rearrangement and an ozonolysis. Chapter 5 contains the experimental data, whilst Chapter 6 contains the references.