Enantioselective chemoenzymatic synthesis of 3-hydroxytetrahydrofurans

The research described in this thesis is concerned with the synthesis and stereoselective transformations of 4,5-dihydro-3(2H)-furanones and their 3-hydroxy derivatives. In Chapter 1, a review of synthetic routes to 3-hydroxytetrahydrofurans is presented. This incorporates the wide range of applications for these types of compounds. Preparative routes to and stereoselective transformations of the furanones investigated in this study are discussed in Chapter 2. The bulk of the work centers on stereoselective carbonyl group reductions to generate the 3-hydroxytetrahydrofuran derivatives in racemic form followed by kinetic resolution via lipase mediated esterification, resulting in enantioenriched 3-acetoxy and 3-hydroxytetrahydrofuran derivatives. In many cases, these processes proceed in a highly enantioselective manner. The influence of the lipase species and concentration of enzyme employed on the yield and stereochemical outcome of the reactions is examined in detail. Access to the complementary series of furanone and hydroxytetrahydrofuran derivatives by oxidation or reduction of the enantioenriched compounds was achieved through conventional synthetic methods. Chapter 2 also contains details of a novel synthetic route to a range of 2,3,5-trisubstituted furans from α-hydroxyenones and 4,5-dihydro-3(2H)-furanones. The mechanistic rationale for these transformations and the migratory aptitude of alkyl groups towards the formation of these furans is discussed in detail. Finally, Chapter 2 outlines the synthesis of a series of diarylcyclopentenones that were synthesised as part of our investigations. Chapter 3 contains a description of the synthetic procedures and biotransformations carried out together with key analytical and spectroscopic properties of the compounds studied and where appropriate, their analysis using chiral HPLC analysis.

Synthesis of 4-substituted-3(2H)-furanones with novel luminescence properties

The objective of this project was to prepare a range of 4-substituted 3-(2H)-furanones, and to investigate the relationship between their molecular structures and photoluminescence properties. The effects of substituents and conjugated linker unit were also investigated. After generation of the key 3(2H)-furanone heterocycle, extension of the conjugated framework at the C-4 position was achieved through Pd(0)-catalysed coupling reactions. Chapter one of the thesis comprises a review of the relavent literature and is split into three sections. These include information about the prevalence of 3-(2H)-furanones as natural products and synthetic routes to 3-(2H)-furanones in general. The synthetic routes are divided according to the synthetic precursor employed. The final section of chapter one outlines the fundamental principles and application of photoluminescence to organic compounds in general. Chapter two contains the results of the research achieved in the course of this work and a discussion of the findings. Two routes were successfully employed to generate 4-unsubstituted 3-(2H)-furanone moieties: (i) base induced cyclisation of hydroxyenones and (ii) isoxazole chemistry. A number of methods which proved ineffective in the production of furanones with the desired substitution pattern are also detailed. The majority of this study was focused on the introduction of substituents at the C-4 position of the 3-(2H)-furanone ring. This was achieved through the use of Sonogashira and Suzuki cross coupling protocols for Pd(0) catalysed C-C bond formation. The further functionalisation of some compounds was performed using transfer hydrogenation and “click chemistry” methodologies. Finally, the photophysical properties of 3-(2H)-furanones prepared in this project are discussed and the effect of substitution patterns in a complementary “push push” and “push pull” manner have also been investigated. All the experimental data and details of the synthetic methods employed, for the compounds prepared during the course of this research is contained in chapter three together with the spectroscopic and analytical properties of the compounds prepared.