Degree Name

Doctor of Philosophy


Department of Chemistry


This thesis describes new approaches to the asymmetric synthesis of cyclic non-proteinogenic α-amino acids (NPAAs) and amino acid derivatives from (2R)-3-benzoyl-4-methylene-2-phenyloxazolidin-5-one. In the first Chapter, an overview of the strategies used for the synthesis of these compounds and also their biological activities was provided. It was found that for the preparation of cyclic α-amino acids in high enantiomeric purity, starting materials with a chiral auxiliary have generally been employed.

In Chapter Two, the synthesis of cyclic NPAAs, through the thermally induced Diels-Alder reactions of (2R )-3-benzoyl-4-methylene-2- phenyloxazolidin-5-one (8) and substituted 1,3-butadienes and substituted 1,3-cyclohexadienes was explored. In general, the reactions were found to be highly regioselective and exo-diastereoselective. The exo selectivity of these reactions was explained by a secondary orbital interaction between the N-donor group of the oxazolidinone ring of (8) (a captodative alkene) and the diene. The NPAA, (2S,4S)-2-aminobicyclo[2.2.2]octane-2- carboxylic acid, was prepared in optically active form starting with (8) and cyclohexadiene.

In Chapter Three, the 1,3-dipolar cycloaddition reactions of (2R)-3- benzoyl-4-methylene-2-phenyloxazolidin-5-one (14) with nitrones and nitrile oxides are reported. In general the nitrone reactions occur under equilibrating conditions to give the more stable adducts that result from addition to the exo -cyclic methylene of (14) from the sterically more hindered π-face. The major adducts from the reaction of (14) and nitrile oxides (2) and (37) had the expected stereochemistry, addition of the 1,3- dipole occurred from the least hindered π-face of the exo-cyclic methylene of (14). Hydrogenation / hydrolysis of the cycloadduct of (14) and C,Ndiphenylnitrone gave the novel compound, cw-(2/?,45)-l,4-diphenyl-2- benzoylazethane (58).

In Chapter Four, a new method for the synthesis of polyfunctional prolines was established through exo-diastereoselective 1,3-dipolar cycloaddition reaction of (2/?)-3-benzoyl-4-methylene-2-phenyloxazolidin-5-one (22) and N-benzylidene α-amino acid eaters. The proline derivatives (49) and (50) were synthesised in high enantiomeric purity (92% e.e.) by methanolysis of the oxazolidinone moiety of their respective cycloadducts. In the case of ethyl N-benzylidene glycinate, a Michael addition product (35) and two novel tricyclic compounds (30a) and (30b) were also isolated and characterized.

In each Chapter, the stereochemistry of the products was determined by a combination of single crystal X-ray structural analysis, ID and 2D NMR spectroscopy and molecular modelling.



Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.