The Tandem Chain Extension-Aldol (TCEA) Reaction of beta-keto esters with aliphatic and aromatic aldehydes yields gamma-keto-beta'-hydroxy esters with significant syn-selectivity. A control Reformatsky reaction with a methyl 2-iodo-5,5-dimethyl-4-oxo-hexanoate 53 and methyl 2-iodo-5,5-dimethylhexanoate 65 indicates that the presence of a gamma-keto-functionality in the zinc-organometallic intermediate in the TCEA reactions is key to the syn-selectivity that is observed. The gamma-keto-functionality, through complexation to zinc, may direct the bias of the reaction toward a transition state that results in the syn-product. An investigation of the zinc-organometallic intermediate with Nuclear Magnetic Resonance Spectroscopy has supported the theory that the intermediate's gamma-keto-group is coordinated to zinc-species on the reaction mixture.
Use of protected alpha-hydroxyacetaldehydes in the TCEA reaction results in an erosion in the syn-selectivity of the TCEA reaction. A study, in which the steric bulk of the hydroxyacetaldehyde's protecting group was varied, has indicated that the erosion in syn-selectivity is likely due to complexation of the aldehydes hydroxy-functionality to zinc in the transition state of the TCEA reaction.
Finally, in an attempt to develop an approach toward the synthesis of CJ-12,954 114a, the TCEA reaction has been successfully applied to the synthesis of spiroketal units, via the generation of dihydroxy-keto synthons.
","abstract_html":"<p>The Tandem Chain Extension-Aldol (TCEA) Reaction of beta-keto esters with aliphatic and aromatic aldehydes yields gamma-keto-beta'-hydroxy esters with significant syn-selectivity. A control Reformatsky reaction with a methyl 2-iodo-5,5-dimethyl-4-oxo-hexanoate 53 and methyl 2-iodo-5,5-dimethylhexanoate 65 indicates that the presence of a gamma-keto-functionality in the zinc-organometallic intermediate in the TCEA reactions is key to the syn-selectivity that is observed. The gamma-keto-functionality, through complexation to zinc, may direct the bias of the reaction toward a transition state that results in the syn-product. An investigation of the zinc-organometallic intermediate with Nuclear Magnetic Resonance Spectroscopy has supported the theory that the intermediate's gamma-keto-group is coordinated to zinc-species on the reaction mixture.</p><p>Use of protected alpha-hydroxyacetaldehydes in the TCEA reaction results in an erosion in the syn-selectivity of the TCEA reaction. A study, in which the steric bulk of the hydroxyacetaldehyde's protecting group was varied, has indicated that the erosion in syn-selectivity is likely due to complexation of the aldehydes hydroxy-functionality to zinc in the transition state of the TCEA reaction.</p><p>Finally, in an attempt to develop an approach toward the synthesis of CJ-12,954 114a, the TCEA reaction has been successfully applied to the synthesis of spiroketal units, via the generation of dihydroxy-keto synthons.</p>","abstract_has_math":false,"creators":["Aiken, Karelle S"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Charles K Zercher"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2005,"date_issued":"2005-01-01T08:00:00Z","date_published":"2005-01-01T08:00:00Z","updated_at":"2026-07-24T05:22:12Z","subjects":["Chemistry","Organic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholars.unh.edu/dissertation/297","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Charles K Zercher"]},{"key":"dc:creator","label":"Author","values":["Aiken, Karelle S"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry","Organic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholars.unh.edu/dissertation/297"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The Tandem Chain Extension-Aldol (TCEA) Reaction of beta-keto esters with aliphatic and aromatic aldehydes yields gamma-keto-beta'-hydroxy esters with significant syn-selectivity. A control Reformatsky reaction with a methyl 2-iodo-5,5-dimethyl-4-oxo-hexanoate 53 and methyl 2-iodo-5,5-dimethylhexanoate 65 indicates that the presence of a gamma-keto-functionality in the zinc-organometallic intermediate in the TCEA reactions is key to the syn-selectivity that is observed. The gamma-keto-functionality, through complexation to zinc, may direct the bias of the reaction toward a transition state that results in the syn-product. An investigation of the zinc-organometallic intermediate with Nuclear Magnetic Resonance Spectroscopy has supported the theory that the intermediate's gamma-keto-group is coordinated to zinc-species on the reaction mixture.
Use of protected alpha-hydroxyacetaldehydes in the TCEA reaction results in an erosion in the syn-selectivity of the TCEA reaction. A study, in which the steric bulk of the hydroxyacetaldehyde's protecting group was varied, has indicated that the erosion in syn-selectivity is likely due to complexation of the aldehydes hydroxy-functionality to zinc in the transition state of the TCEA reaction.
Finally, in an attempt to develop an approach toward the synthesis of CJ-12,954 114a, the TCEA reaction has been successfully applied to the synthesis of spiroketal units, via the generation of dihydroxy-keto synthons.
"]},{"key":"dc:title","label":"Title","values":["The tandem chain extension -aldol reaction of beta-keto esters"]}]}],"canonical_facts":{"dc:contributor":["Charles K Zercher"],"dc:creator":["Aiken, Karelle S"],"dc:description.abstract":["The Tandem Chain Extension-Aldol (TCEA) Reaction of beta-keto esters with aliphatic and aromatic aldehydes yields gamma-keto-beta'-hydroxy esters with significant syn-selectivity. A control Reformatsky reaction with a methyl 2-iodo-5,5-dimethyl-4-oxo-hexanoate 53 and methyl 2-iodo-5,5-dimethylhexanoate 65 indicates that the presence of a gamma-keto-functionality in the zinc-organometallic intermediate in the TCEA reactions is key to the syn-selectivity that is observed. The gamma-keto-functionality, through complexation to zinc, may direct the bias of the reaction toward a transition state that results in the syn-product. An investigation of the zinc-organometallic intermediate with Nuclear Magnetic Resonance Spectroscopy has supported the theory that the intermediate's gamma-keto-group is coordinated to zinc-species on the reaction mixture.
Use of protected alpha-hydroxyacetaldehydes in the TCEA reaction results in an erosion in the syn-selectivity of the TCEA reaction. A study, in which the steric bulk of the hydroxyacetaldehyde's protecting group was varied, has indicated that the erosion in syn-selectivity is likely due to complexation of the aldehydes hydroxy-functionality to zinc in the transition state of the TCEA reaction.
Finally, in an attempt to develop an approach toward the synthesis of CJ-12,954 114a, the TCEA reaction has been successfully applied to the synthesis of spiroketal units, via the generation of dihydroxy-keto synthons.
"],"dc:identifier":["https://scholars.unh.edu/dissertation/297"],"dc:subject":["Chemistry","Organic"],"dc:title":["The tandem chain extension -aldol reaction of beta-keto esters"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:22:12Z"}