Investigation into the reactivity of pentafluorophenyl vinylsulfonate in the formation of functionalized sulfonamides of biological importance
Sulfonamides constitute a vital and diverse class of therapeutic agents hence the development of convenient and straightforward synthetic routes to such species is a valuable endeavour. This thesis describes an exploration into the reactivity of the novel bifunctional acceptor pentafluorophenyl vinylsulfonate in the formation of biologically interesting sulfonamide species. A variety of transformations were carried out effectively at the electron-deficient olefinic portion of pentafluorophenyl vinylsulfonate to provide functionalized pentafluorophenyl esters. Subsequent displacement of the pentafluorophenyl moiety via an established aminolysis procedure then delivered the corresponding sulfonamide products. During the course of this investigation, it was established that both radical and cycloaddition routes were successful in furnishing desirable compounds. It was found that intermolecular radical addition of alkyl halides occurred readily and permitted the formation of a number of sulfonamide addition products. In addition, Diels-Alder cycloaddition with carbocyclic dienes and furan formed stable exo-bicyclic sulfonamides. Notably, 1,3-dipolar cycloaddition with a diverse library of A/-methyl-nitrones gave the corresponding isoxazolidine species with unprecedented regio- and stereoselectivity. Subsequent aminolysis delivered functionalized heterocyclic sulfonamides with potential biological importance.