Date of Award
Doctor of Philosophy (PhD)
Dr. Paul Harrison
Glycoluril 1 has been shown to act as a template, facilitating intramolecular Claisen-type condensations between bound acyl units. Repetitive acylations, condensations, and functional group manipulations allow the synthesis of complex structures from simple starting materials. Thus, the natural product tetradec-2-enoic acid-4,5-epoxide 2 was prepared by condensation on 1 of decanoic acid with two units of acetate. The 1-(3'-oxodecanoyl) glycoluril 3 was prepared from 1 via 4. Conversion to the dodecenoyl derivative 5 (2 steps), followed by a second cycle of acetylation, condensation, reduction and dehydration provided tetradeca-2,4-dienoyl glycoluril 6. Direct cleavage to the carboxylic acid, followed by epoxidation gave 2. Mono- (7) and di-thio (8) analogues of 1 are readily prepared using Lawesson's reagent; this novel application of Lawesson's reagent can be extend to N-acylglycolurils, leading to monacylmonothio derivatives (9) in which thionation occurs at the least hindered urea carbonyl. The thio analogues 7 and 8 are more readily acylated than 1; acylation of 7 occurs exclusively on the NH site adjacent to sulfur to give 10. All diacetylthioglycolurils underwent the Claisen-like condensation reaction to give acetoacetyl thioglycoluril derivatives; 11 undergoes selective deprotonation of the acetyl group adjacent to oxygen to give a mixture of 12 and 13 (2.2:1). Crossed-Claisen condensations of both isomers of acetyl-butanoyl monothioglycoluril (14, 15) afforded 3-ketohexanoyl and 2-ethyl-3-ketobutanoyl thioglycolurils (16 and 17, 18 and 19, respectively). Condensation of 14 led to a highly selective crossed-Claisen condensation (16:17 6:1); while condensation of 15 led to a reversal of regioselectivity (18:19 0.75:1). The x-ray crystallographic structures of key compounds in the glycoluril cycle were compared in order to improve understanding of geometrical factors involved in the condensation reaction. Additionally, several reactions in the cycle, including the first acylation, the condensation, the reduction, and the cleavage reactions were investigated to find conditions which lead to improved yields.
Cow, Christopher N., "Orchestration of Reactions of Glycoluril Templates" (1997). Open Access Dissertations and Theses. Paper 1175.