{"id":{"repo_id":"wvu","oai_identifier":"oai:researchrepository.wvu.edu:etd-2151"},"canonical_url":"https://search.dev.ndltd.org/etd/wvu/oai:researchrepository.wvu.edu:etd-2151","repository":{"repo_id":"wvu","name":"West Virginia University","base_url":"https://researchrepository.wvu.edu/do/oai/"},"display":{"title":"Novel palladium-catalyzed synthesis of 3-substituted indoles and its application toward the total synthesis of indolactam V","abstract":"A novel synthesis of indoles having electron withdrawing substituents in the 3-position has been developed. Various 2-nitrostyrenes were prepared via Stille coupling of 2-tributyl stannyl-2-propenoic acid ethyl ester with substituted 2-bromo-l-nitrobenzenes. Alternatively, sequential vicarious nucleophilic substitution of substituted nitrobenzenes and Knoevenagel condensation with formaldehyde was used to prepare 2-nitrostyrenes. Palladium catalyzed N-heteroannulation of 2-nitrostyrenes yielded indoles in 61--99%. For example, reaction of a 0.5 M solution of 1,1-dimethylethyl 2-(1-nitro-2-napthyl)propenoate (65) in N,N-dimethylformamide with carbon monoxide (4 atm), in the presence of a catalytic amount of bis(dibenzylideneacetone)palladium(0) (6 mol %), 1,3-bis(diphenylphosphino)propane (6 mol %), and 1,10-phenanthroline monohydrate (12 mol %), gave 1H-benzo[g]indole-3-carboxylic acid tert-butyl ester (83) in 99% isolated yield. Substituents on the benzene ring such as methoxy, ester, and halide groups were compatible with the reaction conditions all giving indoles. Additionally, a substituent in the 2-position of the indole can be introduced using aldehydes other than formaldehyde in the condensation step.;This methodology for the preparation of 3-substituted indoles is a key step in a proposed total synthesis of indolactam V. A retrosynthetic analysis of indolactam V affords 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene, allyl glycine, and L-valine as the starting materials. Coupling of L-valine with 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene in the presence of a palladium catalyst unexpectantly gave amination between the nitro and the triflate functionalty. This led to a study of the amination of various bromo-triflate and bromo-nitro-triflate substituted benzenes using cesium carbonate, palladium acetate, 2,2'bis(diphenylphosphino)-1,1 '-binapthyl, and morpholine. The purpose of this was to evaluate the site of amination, that is, bromo vs triflate, and examine if conditions can be developed to selectively substitute one.","abstract_html":"A novel synthesis of indoles having electron withdrawing substituents in the 3-position has been developed. Various 2-nitrostyrenes were prepared via Stille coupling of 2-tributyl stannyl-2-propenoic acid ethyl ester with substituted 2-bromo-l-nitrobenzenes. Alternatively, sequential vicarious nucleophilic substitution of substituted nitrobenzenes and Knoevenagel condensation with formaldehyde was used to prepare 2-nitrostyrenes. Palladium catalyzed N-heteroannulation of 2-nitrostyrenes yielded indoles in 61--99%. For example, reaction of a 0.5 M solution of 1,1-dimethylethyl 2-(1-nitro-2-napthyl)propenoate (65) in N,N-dimethylformamide with carbon monoxide (4 atm), in the presence of a catalytic amount of bis(dibenzylideneacetone)palladium(0) (6 mol %), 1,3-bis(diphenylphosphino)propane (6 mol %), and 1,10-phenanthroline monohydrate (12 mol %), gave 1H-benzo[g]indole-3-carboxylic acid tert-butyl ester (83) in 99% isolated yield. Substituents on the benzene ring such as methoxy, ester, and halide groups were compatible with the reaction conditions all giving indoles. Additionally, a substituent in the 2-position of the indole can be introduced using aldehydes other than formaldehyde in the condensation step.;This methodology for the preparation of 3-substituted indoles is a key step in a proposed total synthesis of indolactam V. A retrosynthetic analysis of indolactam V affords 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene, allyl glycine, and L-valine as the starting materials. Coupling of L-valine with 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene in the presence of a palladium catalyst unexpectantly gave amination between the nitro and the triflate functionalty. This led to a study of the amination of various bromo-triflate and bromo-nitro-triflate substituted benzenes using cesium carbonate, palladium acetate, 2,2'bis(diphenylphosphino)-1,1 '-binapthyl, and morpholine. The purpose of this was to evaluate the site of amination, that is, bromo vs triflate, and examine if conditions can be developed to selectively substitute one.","abstract_has_math":false,"creators":["Turner, Michael Robert"],"institution":null,"degree_name":"MS","degree_level":"Thesis","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Bjorn C. Soderberg."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2000,"date_issued":"2000-08-01T07:00:00Z","date_published":"2000-08-01T07:00:00Z","updated_at":"2026-07-24T06:15:23Z","subjects":["Organic chemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://researchrepository.wvu.edu/etd/1148"],"render_values":[{"text":"https://researchrepository.wvu.edu/etd/1148","href":"https://researchrepository.wvu.edu/etd/1148","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.33915/etd.1148","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bjorn C. 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Various 2-nitrostyrenes were prepared via Stille coupling of 2-tributyl stannyl-2-propenoic acid ethyl ester with substituted 2-bromo-l-nitrobenzenes. Alternatively, sequential vicarious nucleophilic substitution of substituted nitrobenzenes and Knoevenagel condensation with formaldehyde was used to prepare 2-nitrostyrenes. Palladium catalyzed N-heteroannulation of 2-nitrostyrenes yielded indoles in 61--99%. For example, reaction of a 0.5 M solution of 1,1-dimethylethyl 2-(1-nitro-2-napthyl)propenoate (65) in N,N-dimethylformamide with carbon monoxide (4 atm), in the presence of a catalytic amount of bis(dibenzylideneacetone)palladium(0) (6 mol %), 1,3-bis(diphenylphosphino)propane (6 mol %), and 1,10-phenanthroline monohydrate (12 mol %), gave 1H-benzo[g]indole-3-carboxylic acid tert-butyl ester (83) in 99% isolated yield. Substituents on the benzene ring such as methoxy, ester, and halide groups were compatible with the reaction conditions all giving indoles. Additionally, a substituent in the 2-position of the indole can be introduced using aldehydes other than formaldehyde in the condensation step.;This methodology for the preparation of 3-substituted indoles is a key step in a proposed total synthesis of indolactam V. A retrosynthetic analysis of indolactam V affords 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene, allyl glycine, and L-valine as the starting materials. Coupling of L-valine with 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene in the presence of a palladium catalyst unexpectantly gave amination between the nitro and the triflate functionalty. This led to a study of the amination of various bromo-triflate and bromo-nitro-triflate substituted benzenes using cesium carbonate, palladium acetate, 2,2'bis(diphenylphosphino)-1,1 '-binapthyl, and morpholine. The purpose of this was to evaluate the site of amination, that is, bromo vs triflate, and examine if conditions can be developed to selectively substitute one."]},{"key":"dc:title","label":"Title","values":["Novel palladium-catalyzed synthesis of 3-substituted indoles and its application toward the total synthesis of indolactam V"]}]}],"canonical_facts":{"dc:contributor":["Bjorn C. Soderberg."],"dc:creator":["Turner, Michael Robert"],"dc:date.available":["2019-01-17T08:00:00Z"],"dc:description.abstract":["A novel synthesis of indoles having electron withdrawing substituents in the 3-position has been developed. Various 2-nitrostyrenes were prepared via Stille coupling of 2-tributyl stannyl-2-propenoic acid ethyl ester with substituted 2-bromo-l-nitrobenzenes. Alternatively, sequential vicarious nucleophilic substitution of substituted nitrobenzenes and Knoevenagel condensation with formaldehyde was used to prepare 2-nitrostyrenes. Palladium catalyzed N-heteroannulation of 2-nitrostyrenes yielded indoles in 61--99%. For example, reaction of a 0.5 M solution of 1,1-dimethylethyl 2-(1-nitro-2-napthyl)propenoate (65) in N,N-dimethylformamide with carbon monoxide (4 atm), in the presence of a catalytic amount of bis(dibenzylideneacetone)palladium(0) (6 mol %), 1,3-bis(diphenylphosphino)propane (6 mol %), and 1,10-phenanthroline monohydrate (12 mol %), gave 1H-benzo[g]indole-3-carboxylic acid tert-butyl ester (83) in 99% isolated yield. Substituents on the benzene ring such as methoxy, ester, and halide groups were compatible with the reaction conditions all giving indoles. Additionally, a substituent in the 2-position of the indole can be introduced using aldehydes other than formaldehyde in the condensation step.;This methodology for the preparation of 3-substituted indoles is a key step in a proposed total synthesis of indolactam V. A retrosynthetic analysis of indolactam V affords 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene, allyl glycine, and L-valine as the starting materials. Coupling of L-valine with 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene in the presence of a palladium catalyst unexpectantly gave amination between the nitro and the triflate functionalty. This led to a study of the amination of various bromo-triflate and bromo-nitro-triflate substituted benzenes using cesium carbonate, palladium acetate, 2,2'bis(diphenylphosphino)-1,1 '-binapthyl, and morpholine. The purpose of this was to evaluate the site of amination, that is, bromo vs triflate, and examine if conditions can be developed to selectively substitute one."],"dc:identifier":["https://doi.org/10.33915/etd.1148","https://researchrepository.wvu.edu/etd/1148"],"dc:subject":["Organic chemistry"],"dc:title":["Novel palladium-catalyzed synthesis of 3-substituted indoles and its application toward the total synthesis of indolactam V"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["MS"]},"updated_at":"2026-07-24T06:15:23Z"}