Novel free radical protocols for the synthesis of heterocycles

The tributyltin hydride/AIBN combination used to mediate radical cyclisations has become a common protocol in organic chemistry. This system which allows good substrate flexibility is a useful complement to ionic annulation reactions. However, the tin residues are highly toxic and difficult to separate from reaction mixtures. In this project, alternatives to tin have been used with varying success and a SPOS approach was adopted to minimise the problems associated with tin. Acyl radical addition to 2- and 3-substituted electron deficient pyrroles was used to construct a variety of interesting bicyclic compounds including pyrrolizine alkaloids nordanaidone and hydroxydanaidol. Acyl radical reduction was retarded by slow syringe-pump addition of tributyltin hydride in cyclohexane to the acyl selenide and AIBN in acetonitrile as a two-phase solvent system. Carbon monoxide saturation of the reaction vessel and solution was also necessary to inhibit decarbonylation in slow cyclisations. [Continues.]