A new approach to indolo[2,3-a]quinolizidines through radical cyclization of 2-acyl-1-phenylthiotetrahydro-β-carbolines bearing pendent α,β-unsaturated esters

Myles W. Smith, Roger Hunter, Devendren J. Patten, Wolfgang Hinz

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

A new method is reported for the preparation of indolo[2,3-a]quinolizidines based on radical cyclization of a 2-acyl-1-phenylthiotetrahydro-β-carboline bearing a pendent α,β-unsaturated ester. The required radical cyclization precursor is efficiently assembled from E-5-ethoxycarbonyl-4-pentenoic acid and 3,4-dihydro-β-carboline through a DCC/HOBt-activation/N-acylation and BF3·Et2O/PhSH iminium-ion trapping sequence. Tin-mediated radical cyclization of the radical cyclization precursor affords stereoselectively a cis-lactam (dr = 7:1) in good yield (81%), bearing the correct D/E ring fusion stereochemistry for the Tacaman alkaloids. The methodology has been applied to formal syntheses of the indoloquinolizidine alkaloids, (±)-eburnaminol and (±)-larutensine.

Original languageEnglish (US)
Pages (from-to)6342-6346
Number of pages5
JournalTetrahedron Letters
Volume50
Issue number46
DOIs
StatePublished - Nov 18 2009
Externally publishedYes

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Bearings (structural)
Quinolizidines
Carbolines
Cyclization
Esters
Alkaloids
Lactams
Acylation
Stereochemistry
Tin
Fusion reactions
Chemical activation
Ions

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

A new approach to indolo[2,3-a]quinolizidines through radical cyclization of 2-acyl-1-phenylthiotetrahydro-β-carbolines bearing pendent α,β-unsaturated esters. / Smith, Myles W.; Hunter, Roger; Patten, Devendren J.; Hinz, Wolfgang.

In: Tetrahedron Letters, Vol. 50, No. 46, 18.11.2009, p. 6342-6346.

Research output: Contribution to journalArticle

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