The asymmetric synthesis and reactions of α-functionalised organometallic reagents

This thesis describes the development of new methods for the asymmetric synthesis of α-alkoxy and α-amino organometallic reagents. Two approaches were taken: (i)
sulfoxide → magnesium exchange; (ii) asymmetric lithiation-trapping using chiral bases. A review of this area is provided in Chapter One.

Chapter Two details the synthesis of α-alkoxy sulfoxides A in 99:1 er by asymmetric lithiation using s-BuLi and chiral diamines and trapping with Andersen’s sulfinate. In
addition, an investigation into the lack of stereospecificity at sulfur during the trapping
process is presented. Finally, a sulfoxide → magnesium exchange was used to convert the α-alkoxy sulfoxides into α-alkoxy Grignard reagents B and subsequent trapping
allows access to a range of products as single enantiomers. The remarkable configurational stability of α-alkoxy Grignard reagents when compared to their organolithium counterparts is of particular note.

Attempts to use a similar method to synthesise α-amino sulfoxides in 99:1 er is described in Chapter Three. Furthermore, insights are given into the surprising
instability of unsubstituted α-amino sulfoxides. Novel α-amino sulfoxides C were designed to prohibit sulfoxide elimination. From the isolatable α-amino sulfoxides, the
synthesis and reactions of α-amino Grignard reagents D in 99:1 er via sulfoxide → magnesium exchange is reported.

In Chapter Four, an investigation into the mechanism of the asymmetric lithiation trapping of N-thiopivaloyl azetidine E using s-BuLi and chiral diamines is presented. The configurational stability of the organolithium intermediate F was determined at −78°C and the scope of electrophilic trapping was investigated.