Stereoselective tetrahydrofuran synthesis

This thesis begins in Chapter One with a discussion of the role of electrophilic cyclisation in the synthesis of tetrahydrofurans. Chapter Two begins with a discussion of the synthesis of iodo-olactones, by the iodolactonisation of β-silyloxy-δ-alkenoic acids (Scheme A). It will show how the potential of this chemistry has been expanded by proving the absolute stereochemistry at the iodine centre. Chapter Two goes on to consider the stereospecific synthesis of 2,3,5-trisubstituted iodo-tetrahydrofurans by the related iodo-etherification of homoallylic alcohols (Scheme B). This is facilitated by the use of anhydrous conditions. The synthesis of 2,3,5-trisubstituted iodo-tetrahydrofuranacetic acid esters and 2,3,5-trisubstituted hydroxy-tetrahydrofuranacetic acid esters by the iodocyclisation of geometrically pure (E)- and (Z)-β-hydroxy-δ-alkenoates was then developed and the stereochemical outcome of the reactions was proven (Scheme C). Targets were chosen which illustrated the utility of the key cyclisations of β-hydroxy-δ-alkenoates. Chapter Three discusses the synthesis of muscarine 93. It was chosen to synthesise muscarine from the cyclisation of the (Z)-β-hydroxy-δ-alkenoate 146. This synthesis is particularly versatile as it not only allows the preparation of muscarine itself, but also of various potentially highly biologically active analogues 146a. The second target selected was Goniofufurone 170. Approaches to this molecule will be discussed in Chapter Four. Model work in the synthesis of goniofufurone began with the cyclisation of the (E)-β-hydroxy-δ-alkenoate 53b, which indeed, led to the facile synthesis of the iodolactone 204. However, early attempts to incorporate the natural side chain met with limited success. Chapter Five discusses an approach to the 2-oxabicyclo-2.2.11-heptane ring system, which has been synthesised by the radical cyclisation of various β,y-unsaturated tetrahydrofurans of the general form shown in Scheme D.