Cascade Annulation and Ring-Opening Reactions of Castagnoli-Cushman-Derived Allylic and Benzylic Thiomorpholinonates
Date of Degree Completion
Master of Science (MS)
Timothy K. Beng
Second Committee Member
Third Committee Member
Fourth Committee Member
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 in-situ 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.
Farah, Abdikani Omar, "Cascade Annulation and Ring-Opening Reactions of Castagnoli-Cushman-Derived Allylic and Benzylic Thiomorpholinonates" (2018). All Master's Theses. 937.