Copper (I) mediated radical cyclisation novel approaches to nitrogen heterocycles

• Main Author: Geden, Joanna V.
• Published: University of Warwick 2005
• Subjects: 547.2; QD Chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422122

This thesis describes novel catalysts and methods for the synthesis of nitrogen heterocycles using copper (I) mediated atom transfer radical cyclisation (A TRC). It is divided into six chapters. The first chapter provides a short review on the use of copper (I) salts In radical cyclisation chemistry. The second chapter describes the synthesis and copper (I) mediated A TRC of novel a-halo dienamides derived from a,B-unsaturated ketones. A range of multifunctional heterocyclic building blocks were prepared including pyrrolidinones, tetrahydroisoquinolinones and p-Iactams by 5-exo, 6-endo and 4-exo cyclisation. The third chapter extends the methodology discussed in chapter two to the synthesis and cyclisation of further a-halo dienamides derived from a,B-unsaturated aldehydes. This class of radical precursor was found to cyclise exclusively in the 4-exo mode to give B-lactam products. The fourth chapter looks at the copper (I) mediated 5-endo cyclisation of a-halo keto enamides as a potential route to the synthesis of the heterocyclic ring fragment of natural product ZG-1494a. The fifth chapter describes the synthesis of novel solid supported copper (I) catalysts and their application to the atom transfer radical cyclisation of a-halo amides. A comparison of the activity of these catalysts to solution ligand/copper (I) halide mixtures is made. The reusability of polystyrene supported catalysts in the cyclisation of one radical precursor is discussed. The sixth chapter gives the detailed preparative methods and analytical data for the compounds described in chapters two, three, four and five.