Intramolecular anodic olefin coupling reactions: Probing the effect of the radical cation polarization on carbon-carbon bond formation. An approach to the total synthesis of ineleganolide

Anodic cyclization reactions are proved to be a powerful tool for generating reactive radical cation intermediates and initiating umpolungs. In these reactions, one nucleophilic functional group is oxidized at anode to form an electrophilic radical cation intermediate, which is allowed to be trapped by another nucleophilic functional group. In this way, the reactions generate new bonds and ring skeletons without giving up the functionality used to initiate the reactions. Furthermore, by taking advantage of the opportunity that anodic oxidation offers for carrying out oxidations under same conditions, radical cation intermediates from a wide variety of groups can be studied systematically, which is a benefit from the ability of anodic cyclization to carry out oxidations under the same conditions.;In this thesis, an anodic cyclization reaction initiated by ene-diol ether derived radical cation intermediate was utilized toward the total synthesis of Ineleganolide. A bicyclic model substrate was designed and synthesized, a substrate with all the functional groups for the electrolysis and imposed structural constraints. This electrolysis reaction, which lead to no carbon-carbon bond formation though, stimulated efforts to investigate the reactivity of new radical cation intermediates toward carbon-carbon bond formation. A series of anodic coupling reactions were studied in order to probe the effect of polarization on carbon-carbon bond formation. The result is that oxidation of the more polar double bonds led to carbon-carbon bond formation regardless of their electron richness. The preparative experiments were supported by both NMR and cyclic voltammetry data. The work suggested that for ene-diol ether type substrates, the reactions were only successful when the second oxygen substituent on the initiating olefin either increased or maintained the polarization of the radical cations.;With this information in hand, an ene-diol ether functional group was implanted into a bicyclic ring structure, a structure needed in the total synthesis of Ineleganolide. However, in this case, anodic cyclization is challenged by the approach of the side-chain to form the seven-membered ring on the concave face of a bicyclic system.;Meanwhile, a strategy for generating highly functionalized bicyclic molecules containing four contiguous stereogenic atoms, one of which was quaternary was discovered. Both six-membered ring and five-membered ring were constructed successfully, which indicate a possible general methodology for construction of quanternary carbons. The scope and limitation of this approach are currently under investigation.