SYNTHESIS OF (+ -)-TYLOPHORINE BY THE INTRAMOLECULAR CYCLOADDITION OFAN AZIDE WITH AN OMEGA-CHLOROALKENE/

Citation
Wh. Pearson et R. Walavalkar, SYNTHESIS OF (+ -)-TYLOPHORINE BY THE INTRAMOLECULAR CYCLOADDITION OFAN AZIDE WITH AN OMEGA-CHLOROALKENE/, Tetrahedron, 50(43), 1994, pp. 12293-12304
Citations number
44
Categorie Soggetti
Chemistry Inorganic & Nuclear
Journal title
ISSN journal
00404020
Volume
50
Issue
43
Year of publication
1994
Pages
12293 - 12304
Database
ISI
SICI code
0040-4020(1994)50:43<12293:SO(-BT>2.0.ZU;2-A
Abstract
Cyclization of(Z)-1-(2-chloromethyl)phenyl-5-azidopent-1-ene 10 in ben zene at 120 degrees C followed by treatment with sodium borohydride pr oduced 1,2,3,5,10, 10a-hexahydropyrrolo[1,2-b]isoquinoline 11 in 71% y ield. A similar cyclization of 9-(5-azido-1-pentenyl)-10-chloromethylp henanthrene 3 gave the phenanthroindolizidine alkaloid (+/-)tylophorin e 5 in 82% yield. These reactions proceed by intramolecular 1,3-dipola r cycloaddition of the azide onto the alkene followed by loss of nitro gen from the triazoline intermediate to give an imine The imine is N-a lkylated in situ by the pendant benzyl chloride to provide an iminium ion, which is reduced with sodium borohydride to afford the indolizidi nes. The synthesis of (+/-)-tylophorine was accomplished in 11 steps f rom homoveratric acid in 5% overall yield.