Tandem radical reactions involving cyclisations onto nitriles
Chapter 1 is the introduction to the thesis. The general principles of radical cyclisation reactions are highlighted with a focus upon the reactivity of iminyl radicals. A more detailed discussion follows on radical cyclisations onto nitriles including examples of tandem cyclisations. The final section is concerned with cyano migration reactions, and provides evidence for the reversibility of these translocations. The investigation into tandem radical cyclisations of nitriles is discussed in Chapter 2. The aim of the project was to form bicyclic nitrogen heterocycles from acyclic precursors by utilising the nitrile function as a radical acceptor which could then undergo further cyclisation onto a suitably placed alkene. We found a surprising chemoselectivity for 1,5-exo-cyclisation of alkyl, aryl and vinyl radicals onto the cyano group over 1,6-exo-cyclisation onto suitably placed alkenes. The presence of an electron-withdrawing group on the carbon a- to the nitrile group resulted in an overall 1,4-cyano migration reaction. The intermediate cyclic iminyl radical does not undergo further cyclisation, nor does it abstract hydrogen from tributyltin hydride. Instead, fragmentation by β-scission yields a stabilised radical, e.g. by an ester or nitrile group. In order to investigate the effect of substituents on the cyclisation of aryl radicals onto nitriles, and the β-scission reactions of the iminyl radical intermediates, a series of aryl radical precursors were prepared. a-Nitrile, amide, sulfone and phenyl groups favoured β-scission and a-alkyl groups favoured cyclisation or reduction of the aryl radicals. The study indicated the existence of a Thorpe-Ingold effect on the cyclisation of aryl radicals onto nitriles. In Chapter 3 the largely unsuccessful studies of the reversibility of radical cyclisations onto nitriles is reported. Finally, in Chapter 4, the results obtained from our research into vinyl radicals as precursors for tandem radical cyclisations of nitriles are presented. A vinyl iodide underwent complete conversion when standard radical cyclisation conditions were applied; the cyclic ketone resulting from a single 5-exo cyclisation was isolated in the absence of any other products. The experimental relevant to the discussion is detailed in Chapter 5.