Nucleophilic Addition to Azoalkenes; Diastereoselective Synthesis of β-Hydroxy Ketones and β,γ-Fused γ-Lactams

The α-alkylation of ketones and their derivatives by the addition of their corresponding enolates to alkyl halides is a fundamental synthetic transformation, but its utility is limited because the key bond-forming step proceeds in a bimolecular nucleophilic substitution fashion. Here in the first part of the dissertation, we describe how an umpolung strategy that involves the addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones–directed by the alkoxide of 1-azo-3-alkoxy propenes formed in situ via base-induced ring opening of the epoxide–leads to the syn-selective production of α-alkyl-β-hydroxy N-sulfonyl hydrazones with α-quaternary centers. This transformation is remarkable in its ability to incorporate an unprecedented range of carbon-based substituents, which include primary, secondary, and tertiary alkyl, as well as alkenyl, aryl, allenyl, and alkynyl groups. Subsequent hydrolysis of the β-hydroxy N-sulfonyl hydrazone products produces the corresponding β-hydroxy ketones. In addition to hydrolysis, the hydrazone products are poised to undergo different known synthetic transformations via well-established chemistry, which would provide access to a wide array of useful structures. The second part of this dissertation describes the development of a new functional group, namely the 3-amino-1-azopropene, and its use in the novel annulation strategies leading to nitrogen heterocycles, which are important structures found in drugs and biologically active natural products. The 3-amino-1-azopropene functional group possesses multiple nucleophilic and electrophilic sites and, as such, is expected to inspire the development of a wide range of new synthetic methods and/or find applications in the development of new drugs, and materials.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Houston

Year dc:date.issued

2017

Author dc:creator

• Uteuliyev, Maulen M. 1985-

Advisor dc:contributor.advisor

• Coltart, Don M.

Committee members dc:contributor.committeemember

• Daugulis, Olafs
• May, Jeremy A.
• Xu, Shoujun
• Cuny, Gregory D.

• Azoalkene
• Ketone alpha alkylation
• 3-amino-1-azopropene

Statement dc:rights

• The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10657/2904

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/2904