Total synthesis of (±)-cis-trikentrin B, (±)-herbindole A and (±)-herbindole B. investigation into the regioselectivity of 6,7-Indole aryne cycloadditions

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry (UMKC)

Grantor

University of Missouri--Kansas City

Year dc:date.issued

2013

Author dc:creator

• Chandrasoma, Deekirikewage Nalin Laksiri

Advisor dc:contributor.advisor

• Buszek, Keith R.

Handle dc:identifier.uri

http://hdl.handle.net/10355/39546

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/39546