A versatile cascade of intramolecular Vilsmeier-Haack and azomethine ylide 1,3-dipolar cycloaddition toward tricyclic cores of alkaloids

Organic Letters

Volumn 10, Issue 21, 2008, Pages 4939-4942

  Lévesque, François ^a   Bélanger, Guillaume ^a  

^a UNIVERSITÉ DE SHERBROOKE   (Canada)

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EID: 60949085268     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol802010n     Document Type: Article

References (22)

1. (a) Tietze, L. F.; Brasche, G.; Gericke, K. M. Domino Reactions in Organic Chemistry; WILEY-VCH: Weinheim, 2006; p 672.
2. (b) Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int. Ed. 2006, 45, 7134.
3. (a) Bélanger, G.; Larouehe-GautMer, R.; Ménard, F.; Nantel, M.; Barabé, F. Org. Lett. 2005, 7, 4431.
4. (b) Bélanger, Q.; Larouche-Gauthier, R.; Ménard, F.; Nantel, M.; Barabé, F. J. Org. Chem. 2006, 71, 704.
5. For reviews on azomethine ylides, see: (a) Coldham, I. ; Hufton, R. Chem. Rev. 2005, 105, 2765.
6. (b) Tsuge, O.; Kanemasa, S. Adv. Heterocycl. Chem. 1989, 45, 231.
7. Coelho. R. M.; De Souza, M. C.; Sarragiotto, M. H. Phytochemistry 1998, 49, 893.
8. Methyl enol ether 5 is obtained from a Wittig olefination of y-butyrolactol. See: Wasserman, H. H.; Cook, J. D.; Vu, C. B. J. Org. Chem. 1990, 55, 1701.
9. Jones, R. C. F.; Howard. K. J.; Nichols, J. R.; Snaith, J. S. J. Chem. Soc., Perkin Trans, 1 1998, 13, 2061.
10. dipolarophile interaction in such 1,3-dipolar cycloadditions. See: Houk, K. N.; Sims, J.; Watts, C, R.; Luskus, L. J. J. Am. Chetn. Soc. 1968, 90, 543.
11. The increased thermal stability of methyl enol ether over silyl enol ether was dramatic: for substrate 9, when the methyl group is substituted for a TBDMS, only 29% overall yield of tricyclic adduct was obtained.
12. Preparation of models 14a and 14e is described in Supporting Information.
13. 3.
14. (b) KHMDS, LTMP, and NaH.
15. (c) Nucleophilie bases (such as DBU) initiated undesired anionic polymerization of N-phenylmaleimide presumably via Michael addition of the base onto N-phenylmaleimide.
16. Any attempts to form the azomethine ylide prior to the addition of the dipolarophile led to low yield of cycloadduct.
17. Compounds 15a/16a decomposed slowly upon purification on silica gel.
18. For another example of chemoselective amide activation in the presence of a ketone, see: Barbe, G.; Charette, A. B. J. Am. Chem. Soc. 2008, 130, 18.
19. 1H NMR spectroscopy (see Supporting Information).
20. Even though the resulting enamine was not observed, its formation has been proven in several occasions. For example, see: Smith, R.; Livinghouse, T. Tetrahedron 1985, 41, 3559.
21. Tsuge, O.; Kanemasa, S.; Takenaka, S. Chem. Lett. 1985, 355.
22. Tom, G.; Frank, J.; Bende, Z.; Weber, L.; Simon, K. J. Chem. Soc., Perkin Trans, 1 1985, 1961.