Cascade Annulation and Ring-Opening Reactions of Castagnoli-Cushman-Derived Allylic and Benzylic Thiomorpholinonates

<p>Sulfur-containing compounds are prevalent in antibiotics, essential amino acids, bacterial RNA, food flavors, and enzymes. The divalent sulfur atom introduces a metabolic liability from a drug discovery standpoint. Indeed, it is quite telling that all the top ten best-selling drugs in 2012 contained sulfur. In this context, there is a growing need for the synthesis of sulfur-containing compounds in ways that are practical and cost-effective. One approach taken to achieve this goal is to employ diversity-oriented synthesis (DOS), which produces diverse complex molecules with similar core structures from a common precursor. When a DOS features a cascade or domino reaction in the key steps, the process becomes even more cost- and time-efficient. In this embodiment, a transition metal-free, base-mediated cascade reaction featuring methylesterification of allylic thiomorpholinonyl acids and concomitant regioselective intramolecular hydroalkylation is described. The method hinges on the <em>in-situ</em> generation of a transient [4.1.0] bicycle, which undergoes selective C˗C bond cleavage to afford sulfur-bearing cross-conjugated dienes. Post-diversification of this versatile intermediate to other pharmaceutically pertinent motifs such as β-enaminoates, 1,1-enediamines, and enethiols is investigated.</p>

Name thesis:degree_name

Master of Science (MS)

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2018

Author dc:creator

• Farah, Abdikani Omar

Contributors dc:contributor

• Timothy K. Beng
• Levente Fabry-Asztalos
• Gil Belofsky

• Cascade annulation
• ring-opening reactions
• Castagnoli-Cushman
• Thiomorpholinonates
• Materials Chemistry
• Organic Chemistry

Language dc:language

English

Repository record dc:identifier

https://digitalcommons.cwu.edu/etd/937

OAI identifier oai:identifier

oai:digitalcommons.cwu.edu:etd-1955