Non-oxidative preparation, detection and application in synthesis of alkene radical cations

Extensive research aimed at generating radical cations under non-oxidative reaction conditions and better understanding the complicated mechanism of the beta-(phosphatoxy)alkyl radical chemistry is described in this thesis. Solvent caged radical cations were obtained from beta-(phosphatoxy)alkyl radicals generated from PTOC Barton esters under photolytic conditions. In the presence of alcoholic nucleophiles, a novel radical nucleophilic substitution reaction was discovered which resulted in the formation of a new C-O bond. Kinetic results were obtained for a series of beta-(phosphatoxy)alkyl radicals under LFP reaction conditions. The mechanism of beta-(phosphatoxy)alkyl radical reactions was elucidated based on this kinetic data. It is concluded that all beta-aryl-beta-ester radical reactions likely have a mechanism with a common intermediate. These radicals initially undergo heterolytic fragmentation to give a tightly caged radical cation, followed by trapping of the radical cation to give products or proceeding to solvent separated ion pairs and further to diffusion-controlled ion pairs. Simple analogs of the C4' -DNA radical were synthesized and their radical reactions were carried out under LFP reaction conditions. From the kinetic results of these reactions, it is concluded that the same mechanism as for the beta-aryl-beta-ester radical reactions is applicable to alpha-alkoxy-beta-ester radical reactions. These results put the formation of C3',4' radical cations in the fragmentation of DNA C4' radicals beyond reasonable doubt.;With the enhanced understanding of the reaction mechanism of the beta-(phosphatoxy)alkyl radicals and the discovery of the novel radical nucleophilic substitution reaction, the synthetic applications of this radical cation chemistry were explored. It has been demonstrated that beta-(phosphatoxy)alkyl radicals may be displaced in an inter- or intramolecular hydroxy fashion. A series of tetrahydrofuran derivatives was obtained this way with high regioselectivety and excellent yield. Trisubstituted pyrrolizidines were synthesized efficiently using tandem intramolecular 1,2-radical nucleophilic substitution/5- exo-trig radical cyclization reactions. These reactions afford an efficient way to introduce a carbon substituent at the bridgehead position of the pyrrolizidine compound, which is a difficult problem in synthetic chemistry. Nucleophiles like carboxylic acids and amides were also employed in the radical nucleophilic substitution process, resulting in the formation of gamma-lactones.;Finally, numerous problems in the synthesis of an intramolecular stereochemical probe for the reaction of beta-(phosphatoxy)alkyl radicals were surmounted. This probe will ultimately help to elucidate the stereochemistry of the radical nucleophilic substitution reactions and to examine the properties of the caged radical cation generated from beta-(phosphatoxy)alkyl radicals.;Overall, it is concluded that beta-(phosphatoxy)alkyl radicals are useful sources of alkene radical cations under non-oxidative conditions.