A new strategy toward indole alkaloids involving an intramolecular cycloaddition/rearrangement cascade.


Journal Article

The intramolecular Diels-Alder reaction between an amidofuran moiety tethered onto an indole component was examined as a strategy for the synthesis of Aspidosperma alkaloids. Furanyl carbamate 23 was acylated using the mixed anhydride 26 to provide amidofuran 22 in 68% yield. Further N-acylation of this indole furnished 27 in 88% yield. Cyclization precursors were prepared by removing the carbamate moiety followed by N-alkylation with the appropriate alkyl halides. Large substituent groups on the amido nitrogen atom causes the reactive s-trans conformation of the amidofuran to be more highly populated, thereby facilitating the Diels-Alder cycloaddition. The reaction requires the presence of an electron-withdrawing substituent on the indole nitrogen in order for the cycloaddition to proceed. Treatment of N-allyl-bromoenamide 48 with n-Bu(3)SnH/AIBN preferentially led to the 6-endo trig cyclization product 50, with the best yield (91%) being obtained under high dilution conditions. The initially generated cyclohexenyl radical derived from 48 produces the pentacyclic heterocycle 50 by either a direct 6-endo trig cyclization or, alternatively, by a vinyl radical rearrangement pathway.

Full Text

Duke Authors

Cited Authors

  • Padwa, A; Brodney, MA; Lynch, SM; Rashatasakhon, P; Wang, Q; Zhang, H

Published Date

  • May 2004

Published In

Volume / Issue

  • 69 / 11

Start / End Page

  • 3735 - 3745

PubMed ID

  • 15153003

Pubmed Central ID

  • 15153003

Electronic International Standard Serial Number (EISSN)

  • 1520-6904

International Standard Serial Number (ISSN)

  • 0022-3263

Digital Object Identifier (DOI)

  • 10.1021/jo049808i


  • eng