{"id":{"repo_id":"umkc","oai_identifier":"oai:mospace.umsystem.edu:10355/39546"},"canonical_url":"https://search.dev.ndltd.org/etd/umkc/oai:mospace.umsystem.edu:10355/39546","repository":{"repo_id":"umkc","name":"University of Missouri - Kansas City","base_url":"https://mospace.umsystem.edu/oai/request"},"display":{"title":"Total synthesis of (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B. investigation into the regioselectivity of 6,7-Indole aryne cycloadditions","abstract":"Total synthesis of benzannulated indole alkaloid natural products (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B via intermolecular indole aryne cycloaddition are described. The 5,6,7-tribromoindole was synthesized via Leimgruber-Batcho indole synthesis protocols. The main question would be whether the key intermediate 5,6,7-tribromo-N-TBSindole would undergo selective metal-halogen exchange at C-7. The success of this novel step is the cornerstone of this synthesis. Gratifyingly the indole underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. To complete the synthesis of (±)-cis-trikentrin B, Stille cross-coupling with trans-butenyl tin reagent was employed. The 4,6,7-tribromo-5-methylindole was synthesized via Bartoli indole synthesis. The advantage of using the Bartoli indole synthesis is that it affords the desired indole in only a few steps. The 4,6,7-tribromo-5-methyl-N-TBS-indole also underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. The single common intermediate was obtained via the Fujimoto protocol and subjected to Negishi cross-coupling with dimethyl zinc and diethyl zinc to complete the synthesis of (±)-herbindole A and (±)- herbindole B respectively. Our group has previously shown that 3-phenyl-6,7-indole aryne undergoes regioselective cycloaddition with 2-tert-butylfuran giving the contrasteric isomer as the major product. A series of 6,7-dibromoindoles were synthesized to investigate the effect of 3- and 4-substitution on the regioselectivity of 6,7-indole aryne cycloadditions with 2-tertbutylfuran. The results of this investigation disclose that substitution at the 3-position on the indole ring in particular results in remarkable regiocontrol that favored the contrasteric products. Aromatic conjugation at this site significantly enhanced this effect. However, the presence of most 4- or 5-substituents generally resulted in markedly reduced selectivity.","abstract_html":"Total synthesis of benzannulated indole alkaloid natural products (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B via intermolecular indole aryne cycloaddition are described. The 5,6,7-tribromoindole was synthesized via Leimgruber-Batcho indole synthesis protocols. The main question would be whether the key intermediate 5,6,7-tribromo-N-TBSindole would undergo selective metal-halogen exchange at C-7. The success of this novel step is the cornerstone of this synthesis. Gratifyingly the indole underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. To complete the synthesis of (±)-cis-trikentrin B, Stille cross-coupling with trans-butenyl tin reagent was employed. The 4,6,7-tribromo-5-methylindole was synthesized via Bartoli indole synthesis. The advantage of using the Bartoli indole synthesis is that it affords the desired indole in only a few steps. The 4,6,7-tribromo-5-methyl-N-TBS-indole also underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. The single common intermediate was obtained via the Fujimoto protocol and subjected to Negishi cross-coupling with dimethyl zinc and diethyl zinc to complete the synthesis of (±)-herbindole A and (±)- herbindole B respectively. Our group has previously shown that 3-phenyl-6,7-indole aryne undergoes regioselective cycloaddition with 2-tert-butylfuran giving the contrasteric isomer as the major product. A series of 6,7-dibromoindoles were synthesized to investigate the effect of 3- and 4-substitution on the regioselectivity of 6,7-indole aryne cycloadditions with 2-tertbutylfuran. The results of this investigation disclose that substitution at the 3-position on the indole ring in particular results in remarkable regiocontrol that favored the contrasteric products. Aromatic conjugation at this site significantly enhanced this effect. However, the presence of most 4- or 5-substituents generally resulted in markedly reduced selectivity.","abstract_has_math":false,"creators":["Chandrasoma, Deekirikewage Nalin Laksiri"],"institution":"University of Missouri--Kansas City","degree_name":"Ph.D.","degree_level":"Doctoral","degree_discipline":"Chemistry (UMKC)","degree_department":null,"school":null,"contributors":[],"advisors":["Buszek, Keith R."],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013","date_published":"2013","updated_at":"2026-07-24T05:16:57Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10355/39546","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Buszek, Keith R."]},{"key":"dc:creator","label":"Author","values":["Chandrasoma, Deekirikewage Nalin Laksiri"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2013-11-07T16:40:55Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2013-11-07T16:40:55Z"]},{"key":"dc:date.issued","label":"Date","values":["2013"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry (UMKC)","Pharmaceutical Sciences (UMKC)"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Missouri--Kansas City"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10355/39546"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Title from PDF of title page, viewed on November 7, 2013","Dissertation advisor: Keith R. Buszek","Vita","Includes bibliographic references (pages 213-230)","Thesis (Ph.D.)--Dept. of Chemistry and School of Pharmacy. University of Missouri--Kansas City, 2013"]},{"key":"dc:description.abstract","label":"Abstract","values":["Total synthesis of benzannulated indole alkaloid natural products (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B via intermolecular indole aryne cycloaddition are described. The 5,6,7-tribromoindole was synthesized via Leimgruber-Batcho indole synthesis protocols. The main question would be whether the key intermediate 5,6,7-tribromo-N-TBSindole would undergo selective metal-halogen exchange at C-7. The success of this novel step is the cornerstone of this synthesis. Gratifyingly the indole underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. To complete the synthesis of (±)-cis-trikentrin B, Stille cross-coupling with trans-butenyl tin reagent was employed. The 4,6,7-tribromo-5-methylindole was synthesized via Bartoli indole synthesis. The advantage of using the Bartoli indole synthesis is that it affords the desired indole in only a few steps. The 4,6,7-tribromo-5-methyl-N-TBS-indole also underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. The single common intermediate was obtained via the Fujimoto protocol and subjected to Negishi cross-coupling with dimethyl zinc and diethyl zinc to complete the synthesis of (±)-herbindole A and (±)- herbindole B respectively. Our group has previously shown that 3-phenyl-6,7-indole aryne undergoes regioselective cycloaddition with 2-tert-butylfuran giving the contrasteric isomer as the major product. A series of 6,7-dibromoindoles were synthesized to investigate the effect of 3- and 4-substitution on the regioselectivity of 6,7-indole aryne cycloadditions with 2-tertbutylfuran. The results of this investigation disclose that substitution at the 3-position on the indole ring in particular results in remarkable regiocontrol that favored the contrasteric products. Aromatic conjugation at this site significantly enhanced this effect. However, the presence of most 4- or 5-substituents generally resulted in markedly reduced selectivity."]},{"key":"dc:title","label":"Title","values":["Total synthesis of (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B. investigation into the regioselectivity of 6,7-Indole aryne cycloadditions"]}]}],"canonical_facts":{"dc:contributor.advisor":["Buszek, Keith R."],"dc:creator":["Chandrasoma, Deekirikewage Nalin Laksiri"],"dc:date.accessioned":["2013-11-07T16:40:55Z"],"dc:date.available":["2013-11-07T16:40:55Z"],"dc:date.issued":["2013"],"dc:description":["Title from PDF of title page, viewed on November 7, 2013","Dissertation advisor: Keith R. Buszek","Vita","Includes bibliographic references (pages 213-230)","Thesis (Ph.D.)--Dept. of Chemistry and School of Pharmacy. University of Missouri--Kansas City, 2013"],"dc:description.abstract":["Total synthesis of benzannulated indole alkaloid natural products (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B via intermolecular indole aryne cycloaddition are described. The 5,6,7-tribromoindole was synthesized via Leimgruber-Batcho indole synthesis protocols. The main question would be whether the key intermediate 5,6,7-tribromo-N-TBSindole would undergo selective metal-halogen exchange at C-7. The success of this novel step is the cornerstone of this synthesis. Gratifyingly the indole underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. To complete the synthesis of (±)-cis-trikentrin B, Stille cross-coupling with trans-butenyl tin reagent was employed. The 4,6,7-tribromo-5-methylindole was synthesized via Bartoli indole synthesis. The advantage of using the Bartoli indole synthesis is that it affords the desired indole in only a few steps. The 4,6,7-tribromo-5-methyl-N-TBS-indole also underwent selective metalhalogen exchange at C-7 and subsequent elimination to give exclusively the 6,7-indole aryne which underwent Diels-Alder cycloaddition with cyclopentadiene. The single common intermediate was obtained via the Fujimoto protocol and subjected to Negishi cross-coupling with dimethyl zinc and diethyl zinc to complete the synthesis of (±)-herbindole A and (±)- herbindole B respectively. Our group has previously shown that 3-phenyl-6,7-indole aryne undergoes regioselective cycloaddition with 2-tert-butylfuran giving the contrasteric isomer as the major product. A series of 6,7-dibromoindoles were synthesized to investigate the effect of 3- and 4-substitution on the regioselectivity of 6,7-indole aryne cycloadditions with 2-tertbutylfuran. The results of this investigation disclose that substitution at the 3-position on the indole ring in particular results in remarkable regiocontrol that favored the contrasteric products. Aromatic conjugation at this site significantly enhanced this effect. However, the presence of most 4- or 5-substituents generally resulted in markedly reduced selectivity."],"dc:identifier.uri":["http://hdl.handle.net/10355/39546"],"dc:title":["Total synthesis of (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B. investigation into the regioselectivity of 6,7-Indole aryne cycloadditions"],"dc:type":["Thesis"],"thesis:degree_discipline":["Chemistry (UMKC)","Pharmaceutical Sciences (UMKC)"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Missouri--Kansas City"]},"updated_at":"2026-07-24T05:16:57Z"}