| dc.description.abstract | Novel Intramolecular Nucleophilic Addition Reactions: Formation of unusual N-O-Heterocyclic Enones Adwait R. Ranade, B. Tech. The University of Kansas, 2008 Cyclic enaminones, which possess vinylogous amide functionality in a closed ring structure, have been extensively studied and their versatility continues to spark interest in newer and more efficient methods for their enantiospecific synthesis and chemical modification. Due to their unique structural and chemical properties, enaminones are of interest in natural product and diversity-oriented synthesis (DOS). Many biologically active natural products and alkaloids belong to the indolizidine, pyrrolizidine, and quinolizidine classes of molecules. They can be synthesized via enaminones as intermediates. Therefore, the goal of this project was to develop a general methodology for the facile and enantiospecific synthesis of the enaminone scaffolds and then generate a library using this method. It was hypothesized that one-pot Boc deprotection/cyclization of β-hydroxylaminoynones would render N-oxy enaminones, which can be easily converted to enaminones by reductive cleavage of the N-O bond. Due to complications observed with such type of chemistry, the route was modified and a one-pot TBS deprotection/cyclization of β-hydroxylaminoynones was carried out. This approach yielded novel seven-membered N-O heterocyclic compounds. The mechanism is thought to be a 7-endo-dig cyclization to yield seven-membered 3,4-dihydro-1,2-oxazepin-5(2H)-ones. Reductive cleavage of the N-O bond in 3,4-dihydro-1,2-oxazepin-5(2H)-ones rendered 2,3-dihydropyridin-4-(1H)-ones (enaminones). Thus, the 7-membered novel oxazepinone scaffold and the known enaminone scaffold can be used for constructing diverse compound libraries. Additional chemical transformations can also be carried out on these scaffolds to obtain additional diverse chemotypes. | |
