Studies Towards the Total Synthesis of Grandilodine C and New Methods For Reversible Formation of Nitroxyl Radicals

Abstract

This thesis contains two separate research projects within the broad topic of synthetic organic chemistry. The preparation of intermediates that could be used in total synthesis of a complex natural product and an experimental verification of a computational study are reported. The first part of this thesis deals with the synthesis of organostannane carbamate reagents and their Stille cross coupling reactions with a triflate, which delivers an advanced precursor to a biologically active natural product indole alkaloid, grandilodine C. Intramolecular conjugate addition between an α,β-unsaturated methyl ester and carbamate is studied and alternative approaches towards the target compound, such as iodolactonization and oxymercuration are investigated. The second part of this thesis describes the synthesis of nitroxides and alkoxyamines containing carboxylic acid functional groups and the concept of pH switchable nitroxide mediated polymerization is explored. Several synthetic and analytical experiments are designed in an effort to verify the computational studies of stabilizing interactions in radical anions. Investigations into a hydrogen atom transfer reaction between profluorescent nitroxide and 4-carboxy TEMPO hydroxylamine reveal significant rate acceleration in low polarity solvent, which is in good agreement with computational predictions. More generally, these findings provide the first experimental proof of the theoretical concept that electrostatic stabilization of delocalized radicals remains particularly significant in low polarity environments. Show more