Use in Synthesis of Microbial Arene Oxidation Products

Abstract

This thesis is concerned with microbially derived cis-3,5-cyclohexadiene-1,2 dihydroxy-1-carboxylic acid and its iron tricarbonyl derivatives as precursors for the efficient and practical synthesis of useful products.

The opening chapter consists of a review of the biocatalytic cis-dihydroxylation process including its mechanism and applications in synthesis.

In a Chapter 2 the utility of cyclohexadiene iron tricarbonyl complexes to date is outlined, with particular focus on their preparation and reactivity. Synthetic routes towards the synthesis of the natural products gabaculine and carbazole alkaloids are described, followed by the preparation of tamiflu and general methods of decomplexation.

Chapter 3 presents the synthesis of novel iron tricarbonyl complexes and studies on their reactivity are disclosed. (Figure A.)

Chapter 4 describes the formation of a new rearrangement product of the acetonide protected iron tricarbonyl complexes. In order to validate this process, independent studies with labelled compounds have been employed. Following Myers’ procedure for microbial oxidation of p-deutero-benzoic acid, quantities of a novel deutero-diol product were successfully prepared and used to elucidate the mechanism of the rearrangement process. (Figure B)

In Chapter 5 the formation of the η5 cyclohexadienyl complexes is discussed followed by the outcome of the nucleophilic addition products. (Figure C.)

Chapter 7 provides detailed specific and general procedures for the synthesis of the compounds described within this thesis, along with their characterisation data. The appendices provide analytical support to this thesis and list of publications.

Each chapter includes a separate discussion of the results and Chapter 6 provides an overall summary and suggestions for possible future work.

Date of Award	6 Sept 2012
Original language	English
Awarding Institution	University of Bath
Supervisor	Simon Lewis (Supervisor)