gem-Dihalocyclopropanes as precursors to alkaloidal ring systems
Date
2010
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Lehmann, Anna Louise
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Abstract
gem-Dihalocyclopropanes (1) are an important class of compound that play significant roles in contemporary organic synthesis. This is largely due to their ease of preparation, (which is normally accomplished via addition of the relevant dihalocarbene to an alkene), and the wide range of reactions they can undergo. These reactions can be divided into two broad subgroups, those that proceed with retention of the three membered ring, and those where one of the C-C bonds is broken, thus leading to ring cleavage. The vast majority of gem-dihalocyclopropanes described in the literature are the dibromo- or dichloro- systems, as these are the most synthetically accessible (1, where X = Br or Cl). Chapter One of this thesis provides an introduction to the preparation and synthetic utility of gem-dihalocyclopropanes, while the work described in the remainder of this thesis utilises such systems in work directed toward the synthesis of a number of alkaloidal ring-systems. Chapter Two of this thesis outlines work undertaken in the pursuit of a synthesis of pcrhydrohistrionicotoxin (50), a derivative of the alkaloid histrionicotoxin. A silver(l)-promoted cyclopropane ring-opening/spirocyclisation reaction was to be used as the key step in this work. Thus, starting from cyclopentanone, a pair of diastereoisomeric substrates, 124 and 125, has been prepared that contain all the functionality thought necessary for generating a substrate capable of engaging in the key reaction. Chapter Three outlines work undertaken in the pursuit of a synthesis of the core cis-3a-arylhydroindole structure of a number of Amaryllidaceae alkaloids. Starting with gem-dibromoeyclopropane 146, iodide 163 was prepared over' 7 steps, and upon subjection of the latter compound to reductive radical cyclisation conditions resulted in the production of the cis-3a-arylhydroindole 164. Chapter Four outlines the preparation of a senes of N-protected and propargylated l-amino-2-aryl-2-cyclohexenes (213), from gem-dibromocyclopropanes such as 212. Several of these have been showu to undergo an intramolecular Alder-ene (IMAE) reaction in the presence of palladium acetate and the ligand BBEDA to afford C3aarylhexahydroindoles of the general form 214. Certain of these products may serve as precursors to the alkaloid tazettine (133). Chapter Five contains the experimental procedures and data to support all work outlined in this thesis.
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