Aryl radical triggered hydrogen atom abstraction in synthesis

The role of radicals in organic synthesis is discussed with particular emphasis on carbon-centred radicals. The chemistry of the 5-hexenyl radical cyclisation is described and the regio- and stereochemical outcomes of the reactions are discussed. The concept of 'remote-functionalisation' termed 'radical translocation' is introduced where a carbon radical is generated at a favourable site and then 'translocated' to a new site by intramolecular 1,5-hydrogen atom transfer at an unfunctionalised carbon. This concept is outlined with examples from the literature. This thesis describes a systematic study of the radical translocation (1,5-hydrogen transfer) reactions of N,N-disubstituted o-bromobenzamines. The initial radical is generated on a modified N-protecting group and then translocated followed by 5-exo cyclisation. The course of these reactions is followed by using tri-n-butyltin deuteride and deuterium nmr studies. The synthesis of a range of substituted radical precursors is presented. The substituents are chosen to enhance the rate of cyclisation reactions. The radical chemistry of these substrates are explored. Further investigations are presented in which the group carrying the initial radical contains a stereogenic centre. This not only provides the radical trigger but may act as a chiral auxiliary. Finally, the synthetic utility of this radical translocation/cyclisation sequence is demonstrated by the short synthesis of a bicyclic lactam. (author)