| Autor: |
Padwa A; Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA., Beall LS, Heidelbaugh TM, Liu B, Sheehan SM |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of organic chemistry [J Org Chem] 2000 May 05; Vol. 65 (9), pp. 2684-95. |
| DOI: |
10.1021/jo991742h |
| Abstrakt: |
A highly effective method for the synthesis of the core indolo[2,3-alpha]quinolizidine skeleton found in yohimbine is described. The reaction of N-monosubstituted thioamides with bromoalkenoyl chlorides furnishes thioisomünchnones as transient 1,3-dipoles that undergo ready intramolecular cycloaddition across the tethered pi-bond to give thio-bicycloannulated products in a one-pot operation. The stereochemical outcome of the intramolecular reaction is the consequence of an endo cycloaddition of the neighboring pi-bond across the transient thioisomünchnone dipole. A major limitation of the method is that when a hydrogen is present in the alpha-position of the thioamide the initially formed thio-N-acyliminium ion undergoes proton loss to produce a S,N-ketene acetal at a faster rate than dipole formation. Treatment of tetrahydro-beta-carboline-1-thione with 2-bromooct-7-enoyl chloride followed by reductive removal of sulfur from the cycloadduct resulted in the formation of (+/-)-alloyohimbanone. Attempts to cycloadd the thioisomünchnone dipole across several nucleophilic pi-bonds failed, and instead, products derived from cyclization of the pi-bond onto the initially formed thio-N-acyliminium ion were formed. The resulting N,S-ketals were further converted into several tetrahydroisoquinoline alkaloids in good yield. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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