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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Farah, Abdikani Omar"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":null,"degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Timothy K. Beng","Levente Fabry-Asztalos","Gil Belofsky"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-01-01T08:00:00Z","date_published":"2018-01-01T08:00:00Z","updated_at":"2026-07-24T01:37:23Z","subjects":["Cascade annulation","ring-opening reactions","Castagnoli-Cushman","Thiomorpholinonates","Materials Chemistry","Organic Chemistry"],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.cwu.edu/etd/937","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Timothy K. Beng","Levente Fabry-Asztalos","Gil Belofsky"]},{"key":"dc:creator","label":"Author","values":["Farah, Abdikani Omar"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2020-06-28T07:00:00Z"]},{"key":"dc:type","label":"Dc Type","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cascade annulation","ring-opening reactions","Castagnoli-Cushman","Thiomorpholinonates","Materials Chemistry","Organic Chemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.cwu.edu/etd/937"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Cascade Annulation and Ring-Opening Reactions of Castagnoli-Cushman-Derived Allylic and Benzylic Thiomorpholinonates"]}]}],"canonical_facts":{"dc:contributor":["Timothy K. Beng","Levente Fabry-Asztalos","Gil Belofsky"],"dc:creator":["Farah, Abdikani Omar"],"dc:date.available":["2020-06-28T07:00:00Z"],"dc:description.abstract":["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.
"],"dc:identifier":["https://digitalcommons.cwu.edu/etd/937"],"dc:language":["English"],"dc:subject":["Cascade annulation","ring-opening reactions","Castagnoli-Cushman","Thiomorpholinonates","Materials Chemistry","Organic Chemistry"],"dc:title":["Cascade Annulation and Ring-Opening Reactions of Castagnoli-Cushman-Derived Allylic and Benzylic Thiomorpholinonates"],"dc:type":["Text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T01:37:23Z"}