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
✍ Scribed by Myles W. Smith; Roger Hunter; Devendren J. Patten; Wolfgang Hinz
- Publisher
- Elsevier Science
- Year
- 2009
- Tongue
- French
- Weight
- 515 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
A new method is reported for the preparation of indolo [2,3-a]quinolizidines based on radical cyclization of a 2-acyl-1-phenylthiotetrahydro-b-carboline bearing a pendent a,b-unsaturated ester. The required radical cyclization precursor is efficiently assembled from E-5-ethoxycarbonyl-4-pentenoic acid and 3,4-dihydro-b-carboline through a DCC/HOBt-activation/N-acylation and BF 3 ÁEt 2 O/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.