Acyclic stereocontrol in the Claisen rearrangement

Abstract

This thesis examines the issues of acyclic stereocontrol in the Claisen rearrangement, with particular emphasis on the effects of exopericyclic stereocentres – i.e. those adjacent to the array of atoms directly involved in the sigmatropic process. It is divided into three main parts: The first section provides a review of the field of acyclic stereocontrol. The models used to explain the development of relationships between stereocenters in systems lacking well-defined conformational constraints are discussed. This is an established field and particular emphasis is given to recent developments in the modelling of such systems. The second section discusses the results of our studies. Previous examples of exopericyclic stereocontrol in sigmatropic rearrangements are shown. Studies are presented that explore the importance of heteroatom-bearing stereocenters and effects of olefin substitution pattern on the manner and extent of stereoselectivity. Our efforts to exploit these stereochemical effects in the synthesis of small molecules are then presented. A novel reaction sequence is presented in which equilibrating mixtures of allylic azides undergo stereoselective Claisen rearrangements and further chemistry of the products of this transformation is then explored. These studies, and attempts to deploy them in synthesis allow us to draw conclusions on the nature of acyclic stereocontrol in the Claisen rearrangement. The third section contains experimental procedures and characterisation data for all compounds prepared.