A study of vinyl radical cyclization using N-alkenyl-7-bromo-substituted hexahydroindolinones

Albert Padwa*, Paitoon Rashatasakhon, Ayse Daut Ozdemir, Jerremey Willis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

(Chemical Equation Presented) A new method for the synthesis of the octahydropyrrolo[3,2,1-ij]quinoline ring system that possesses the characteristic skeleton of the aspidosperma family of alkaloids has been developed. The method utilizes an intramolecular Diels-Alder reaction of an amido-substituted furan across a tethered indole π-bond. To apply this strategy to the synthesis of the indole alkaloid spegazzinidine, it was necessary to address the problem of assembling the final D-ring of the pentacyclic skeleton. Radical cyclization of a model N-allyl-7-bromo-3a- methylhexahydroindolinone system was found to preferentially lead to the 6-endo-trig cyclization product, with the best yield being obtained under high dilution conditions. The six-membered cyclized product is generated through two reaction pathways: (a) 6-endo-trig ring closure and (b) rearrangement of an intermediate methylene-cyclopentyl radical obtained by 5-exo-trig cyclization. A number of related 7-bromo-substituted hexahydroindolinones containing tethered olefinic groups were prepared and found to undergo efficient cyclization under both radical and palladium-mediated reaction conditions. Vinyl radical cyclization with several N-butenyl-substituted systems afforded a mixture of 6-exo and 7-endo cyclization products. A protocol to introduce an ethyl substituent into the C20-position of the aspidospermidine skeleton was also developed.

Original languageEnglish
Pages (from-to)519-528
Number of pages10
JournalJournal of Organic Chemistry
Volume70
Issue number2
DOIs
Publication statusPublished - 21 Jan 2005
Externally publishedYes

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