Acyl radical cascade reactions : the synthesis of azasteroids
Our work has been concerned with the synthesis of azasteroid ring systems, utilising acyl radical cascade reactions. Chapter 1 comprises an overview of published work relevant to our studies: an analysis of steroid biosynthesis and synthesis; a review of the use of azasteroids, their biological activity and current synthetic techniques in azasteroid formation. This initial chapter also includes an introduction to published work in the area of nitrogen heterocycle synthesis using radical reactions and finally the use of acyl radicals in synthesis, particularly cascade reactions. Chapter 2 starts by describing the requirements of a reaction system for use in acyl radical cascades and then discusses the relevance of this to the synthesis of ring junction azasteroids. Our attempts to synthesise ring junction azasteroids and the problems that we encountered are then discussed. Subsequent sections describe the disconnection of azasteroids where nitrogen is part of the body of the ring and the synthetic work that we performed in this area. Using cyclohexenyl enamides as the terminal electrophore in cascade reactions we were able to synthesise a 12-aza-D-homosteroid in nine steps. The final step was a cascade reaction involving three consecutive 6-endo-trig cyclisations starting from an acyl radical and terminating on an cyclohexenyl enamide electrophore. An extensive, though unsuccessful, study attempting to use linear enamides in cascade reactions is described showing routes towards the synthesis of steroid models. Finally we reveal the work that was performed in the use of highly stabilised enamides as radical acceptors. This work resulted in the formation of a bicyclo[8.3.0]tridecene after a 10-endo-trig, 5-exo-trig cascade from a linear precursor designed to form a 7-azaandrostane skeleton.