{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/70197"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/70197","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Beta'-Lithiation of Alpha, Beta-Unsaturated Amides","abstract":"The novel (beta)'-lithiation of (alpha)-alkyl-(alpha),(beta)-unsaturated secondary and tertiary amides is reported. N-Methyl-1-cyclohexenecarboxamide and N-methyl-1-cyclopentenecarboxamide are metalated at nitrogen and at the (beta)'-carbon with either sec-butyllithium/TMEDA at -78(DEGREES)C or n-butyllithium at 0(DEGREES)C. Further reaction with a variety of electrophiles leads in good yield to the (beta)'-substituted products. Similarly, lithiation of N,N-diisopropyl-1-cyclohexenecarboxamide by sec-butyllithium/TMEDA at -78(DEGREES)C followed by treatment with electrophiles affords the (beta)'-substituted tertiary amides. N-Methyl-3-ethyl-2-methyl-2-pentenamide and (E)-N-methyl-2-methyl-2-butenamide also undergo exclusive (beta)'-metalation. However, deprotonation occurs at the (gamma)-position in N-methyl-2-ethyl-3-methyl-2-butenamide, in which the cis-(gamma)-carbon is less highly substituted than the (beta)'-carbon. The acyclic amides afford unsymmetrical allylic anions, which react with electrophiles to give mixtures of isomeric products. The dianion from N-methyl-4-t-butyl-1-cyclohexenecarboxamide is deuterated non-selectively but reacts with benzophenone to give only the diastereomer which results from addition cis to the t-butyl group. The reactions of the lithiated amides with aldehydes show only a slight erythro selectivity.","abstract_html":"The novel (beta)'-lithiation of (alpha)-alkyl-(alpha),(beta)-unsaturated secondary and tertiary amides is reported. N-Methyl-1-cyclohexenecarboxamide and N-methyl-1-cyclopentenecarboxamide are metalated at nitrogen and at the (beta)'-carbon with either sec-butyllithium/TMEDA at -78(DEGREES)C or n-butyllithium at 0(DEGREES)C. Further reaction with a variety of electrophiles leads in good yield to the (beta)'-substituted products. Similarly, lithiation of N,N-diisopropyl-1-cyclohexenecarboxamide by sec-butyllithium/TMEDA at -78(DEGREES)C followed by treatment with electrophiles affords the (beta)'-substituted tertiary amides. N-Methyl-3-ethyl-2-methyl-2-pentenamide and (E)-N-methyl-2-methyl-2-butenamide also undergo exclusive (beta)'-metalation. However, deprotonation occurs at the (gamma)-position in N-methyl-2-ethyl-3-methyl-2-butenamide, in which the cis-(gamma)-carbon is less highly substituted than the (beta)'-carbon. The acyclic amides afford unsymmetrical allylic anions, which react with electrophiles to give mixtures of isomeric products. The dianion from N-methyl-4-t-butyl-1-cyclohexenecarboxamide is deuterated non-selectively but reacts with benzophenone to give only the diastereomer which results from addition cis to the t-butyl group. The reactions of the lithiated amides with aldehydes show only a slight erythro selectivity.","abstract_has_math":false,"creators":["Kempf, Dale John"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-15T23:17:44Z","date_published":"2014-12-15T23:17:44Z","updated_at":"2026-07-22T22:26:02Z","subjects":["Chemistry, Organic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI8302907"],"render_values":[{"text":"(UMI)AAI8302907","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/70197","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Kempf, Dale John"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-15T23:17:44Z","10000-01-01","1982"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"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":["http://hdl.handle.net/2142/70197","(UMI)AAI8302907"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The novel (beta)'-lithiation of (alpha)-alkyl-(alpha),(beta)-unsaturated secondary and tertiary amides is reported. N-Methyl-1-cyclohexenecarboxamide and N-methyl-1-cyclopentenecarboxamide are metalated at nitrogen and at the (beta)'-carbon with either sec-butyllithium/TMEDA at -78(DEGREES)C or n-butyllithium at 0(DEGREES)C. Further reaction with a variety of electrophiles leads in good yield to the (beta)'-substituted products. Similarly, lithiation of N,N-diisopropyl-1-cyclohexenecarboxamide by sec-butyllithium/TMEDA at -78(DEGREES)C followed by treatment with electrophiles affords the (beta)'-substituted tertiary amides. N-Methyl-3-ethyl-2-methyl-2-pentenamide and (E)-N-methyl-2-methyl-2-butenamide also undergo exclusive (beta)'-metalation. However, deprotonation occurs at the (gamma)-position in N-methyl-2-ethyl-3-methyl-2-butenamide, in which the cis-(gamma)-carbon is less highly substituted than the (beta)'-carbon. The acyclic amides afford unsymmetrical allylic anions, which react with electrophiles to give mixtures of isomeric products. The dianion from N-methyl-4-t-butyl-1-cyclohexenecarboxamide is deuterated non-selectively but reacts with benzophenone to give only the diastereomer which results from addition cis to the t-butyl group. The reactions of the lithiated amides with aldehydes show only a slight erythro selectivity.","Elaborations of the products from the (beta)'-lithiated amides are described. The hydroxyamides prepared from secondary amides and ketones or aldehydes can be thermally cyclized to (alpha)-alkylidene-(gamma)-butyrolactones, including the naturally occurring bicyclic lactone neocnidilide. Metalation and intramolecular cyclization to a spiro system is demonstrated with N,N-diisopropyl-6-(4-chlorobutyl)-1-cyclohexenecarboxamide. The anions from N,N-diisopropyl-6-trimethylsilyl-1-cyclohexenecarboxamide and N,N-diisopropyl-6-phenylthio-1-cyclohexenecarboxamide undergo regioselective reaction with most electrophiles to give the vinyl silanes and sulfides. Treatment of N,N-diisopropyl-6-bromo-1-cyclohexenecarboxamide with silver tetrafluoroborate allows the substitution of several nucleophiles at the (beta)'-position.","Synthetically, this novel lithiation allows facile functionalization of a previously unavailable site in (alpha),(beta)-unsaturated acid derivatives. Mechanistically, the kinetically controlled metalation at the (beta)'-position is interpreted in terms of a mechanism involving initial complexation of the amide to the alkyllithium base.","Made available in DSpace on 2014-12-15T23:17:44Z (GMT). No. of bitstreams: 1 8302907.pdf: 6473258 bytes, checksum: 98b23654245835bfbe7702e2b89886b3 (MD5) Previous issue date: 1982","Embargo set by: Seth Robbins for item 70363 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","174 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1982."]},{"key":"dc:title","label":"Title","values":["Beta'-Lithiation of Alpha, Beta-Unsaturated Amides"]}]}],"canonical_facts":{"dc:creator":["Kempf, Dale John"],"dc:date":["2014-12-15T23:17:44Z","10000-01-01","1982"],"dc:description":["The novel (beta)'-lithiation of (alpha)-alkyl-(alpha),(beta)-unsaturated secondary and tertiary amides is reported. N-Methyl-1-cyclohexenecarboxamide and N-methyl-1-cyclopentenecarboxamide are metalated at nitrogen and at the (beta)'-carbon with either sec-butyllithium/TMEDA at -78(DEGREES)C or n-butyllithium at 0(DEGREES)C. Further reaction with a variety of electrophiles leads in good yield to the (beta)'-substituted products. Similarly, lithiation of N,N-diisopropyl-1-cyclohexenecarboxamide by sec-butyllithium/TMEDA at -78(DEGREES)C followed by treatment with electrophiles affords the (beta)'-substituted tertiary amides. N-Methyl-3-ethyl-2-methyl-2-pentenamide and (E)-N-methyl-2-methyl-2-butenamide also undergo exclusive (beta)'-metalation. However, deprotonation occurs at the (gamma)-position in N-methyl-2-ethyl-3-methyl-2-butenamide, in which the cis-(gamma)-carbon is less highly substituted than the (beta)'-carbon. The acyclic amides afford unsymmetrical allylic anions, which react with electrophiles to give mixtures of isomeric products. The dianion from N-methyl-4-t-butyl-1-cyclohexenecarboxamide is deuterated non-selectively but reacts with benzophenone to give only the diastereomer which results from addition cis to the t-butyl group. The reactions of the lithiated amides with aldehydes show only a slight erythro selectivity.","Elaborations of the products from the (beta)'-lithiated amides are described. The hydroxyamides prepared from secondary amides and ketones or aldehydes can be thermally cyclized to (alpha)-alkylidene-(gamma)-butyrolactones, including the naturally occurring bicyclic lactone neocnidilide. Metalation and intramolecular cyclization to a spiro system is demonstrated with N,N-diisopropyl-6-(4-chlorobutyl)-1-cyclohexenecarboxamide. The anions from N,N-diisopropyl-6-trimethylsilyl-1-cyclohexenecarboxamide and N,N-diisopropyl-6-phenylthio-1-cyclohexenecarboxamide undergo regioselective reaction with most electrophiles to give the vinyl silanes and sulfides. Treatment of N,N-diisopropyl-6-bromo-1-cyclohexenecarboxamide with silver tetrafluoroborate allows the substitution of several nucleophiles at the (beta)'-position.","Synthetically, this novel lithiation allows facile functionalization of a previously unavailable site in (alpha),(beta)-unsaturated acid derivatives. Mechanistically, the kinetically controlled metalation at the (beta)'-position is interpreted in terms of a mechanism involving initial complexation of the amide to the alkyllithium base.","Made available in DSpace on 2014-12-15T23:17:44Z (GMT). No. of bitstreams: 1 8302907.pdf: 6473258 bytes, checksum: 98b23654245835bfbe7702e2b89886b3 (MD5) Previous issue date: 1982","Embargo set by: Seth Robbins for item 70363 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","174 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1982."],"dc:identifier":["http://hdl.handle.net/2142/70197","(UMI)AAI8302907"],"dc:subject":["Chemistry, Organic"],"dc:title":["Beta'-Lithiation of Alpha, Beta-Unsaturated Amides"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:02Z"}