Fused triazoles via tandem reactions of activated Cinchona alkaloids with azide ion. Second Cinchona rearrangement exemplified

Organic Letters

Volumn 5, Issue 16, 2003, Pages 2773-2776

  Roper S ^a   Franz, M H ^a   Wartchow, R ^a   Hoffmann, H M R ^a  

^a LEIBNIZ UNIVERSITY HANNOVER   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AZIDE; CINCHONA ALKALOID; O MESYLCINCHONIDINE; TRIAZOLE DERIVATIVE; TRIAZOLINE DERIVATIVE; TRIFLUOROETHANOL; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CINCHONA; CYCLOADDITION; MOLECULAR INTERACTION; REACTION ANALYSIS; X RAY DIFFRACTION;

EID: 0141631798     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol034719y     Document Type: Article

References (23)

1. Goldhill, J. Pharma Report Alert: New Targets and Drug Discovery Platforms in Antifungal R&D, Nov. 25, 2002. This report can be obtained by sending an e-mail request to the following address: leaddisc@leaddiscovery.co.uk.
2. Huisgen, R. Angew. Chem. 1963, 75, 604-637; 742-754. Katritzky, A. R., Rees, C. W., Eds. Comprehensive Heterocyclic Chemistry; Pergamon Press: Oxford, 1984. Applications: Wolf, M. E., Ed. In Burger's Medical Chemistry and Drug Discovery; Wiley: New York, 1997.
3. Huisgen, R. Angew. Chem. 1963, 75, 604-637; 742-754. Katritzky, A. R., Rees, C. W., Eds. Comprehensive Heterocyclic Chemistry; Pergamon Press: Oxford, 1984. Applications: Wolf, M. E., Ed. In Burger's Medical Chemistry and Drug Discovery; Wiley: New York, 1997.
4. Huisgen, R. Angew. Chem. 1963, 75, 604-637; 742-754. Katritzky, A. R., Rees, C. W., Eds. Comprehensive Heterocyclic Chemistry; Pergamon Press: Oxford, 1984. Applications: Wolf, M. E., Ed. In Burger's Medical Chemistry and Drug Discovery; Wiley: New York, 1997.
5. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596.
6. Review: Padwa, A. Angew. Chem., Int. Ed. Engl. 1976, 15, 123.
7. Braje, W. M.; Frackenpohl, J.; Schrake, O.; Wartchow, R.; Beil, W.; Hoffmann, H. M. R. Helv. Chim. Acta 2000, 83, 777. Frackenpohl, J.; Braje, W.; Hoffmann, H. M. R. J. Chem. Soc., Perkin Trans. 1 2001, 47.
8. Braje, W. M.; Frackenpohl, J.; Schrake, O.; Wartchow, R.; Beil, W.; Hoffmann, H. M. R. Helv. Chim. Acta 2000, 83, 777. Frackenpohl, J.; Braje, W.; Hoffmann, H. M. R. J. Chem. Soc., Perkin Trans. 1 2001, 47.
9. See Braje, W.; Holzgrefe, J.; Wartchow, R.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. 2000, 39, 2085.
10. Cycloadducts 3 and 5 have a bis-azahomotwistane skeleton. For oxazahomotwistane analogues, see: von Riesen, C.; Hoffmann, H. M. R. Chem. Eur. J. 1996, 2, 680. Braje, W.; Frackenpohl, J.; Langer, P.; Hoffmann, H. M. R. Tetrahedron 1998, 54, 3495.
11. Cycloadducts 3 and 5 have a bis-azahomotwistane skeleton. For oxazahomotwistane analogues, see: von Riesen, C.; Hoffmann, H. M. R. Chem. Eur. J. 1996, 2, 680. Braje, W.; Frackenpohl, J.; Langer, P.; Hoffmann, H. M. R. Tetrahedron 1998, 54, 3495.
12. 3) are prone to enamine formation. Proton H8 is antiperiplanar to the C9 leaving group and more exposed to base in the epi series but more screened by the quinolyl group in the 9-nat series. For the possibility of Winstein-Parker E2C reactions, see: Beltrame, P.; Biale, G.; Lloyd, D. J.; Parker, A. J.; Ruane, M.; Winstein, S. J. Am. Chem. Soc. 1972, 94, 2240. See also Scheme 4. In the case at hand, azide ion might attack H8 as a base and C9 as a nucleophile within a cyclic six-membered transition state.
13. Röper, S.; Franz, M. H.; Wartchow, R.; Hoffmann, H. M. R. J. Org. Chem. 2003, 68, 4944.
14. Generation of closed σ-bridged ion i is considered to be favored for cinch bases with a C9 leaving group. An open classical C9 cation is more favorable in quinine and quinidine due to oxonium resonance via a 6′-OMe donor. See ref 9. The four nearest neighbors of the bridging nitrogen in cation i are not bonded in classical tetrahedral fashion. Instead, these four coordinating atoms are constrained in one hemisphere; the nitrogen lone pair is in the other hemisphere.
15. McClelland, R. A. Tetrahedron 1996, 52, 6823. Mayr, H.; Minegishi, S. Angew. Chem., Int. Ed. 2002, 41, 4493 and references therein.
16. McClelland, R. A. Tetrahedron 1996, 52, 6823. Mayr, H.; Minegishi, S. Angew. Chem., Int. Ed. 2002, 41, 4493 and references therein.
17. Preparation of 8 from 9-nat-configured 7-OMs requires two steps fewer than preparation from an epi-configured substrate (cf. Scheme 1).
18. Triazolines 12 and 14 are single isomers, suggesting that the fused five-membered heterocycles arise in a concerted cycloaddition.
19. Braje, W.; Holzgrefe, J.; Wartchow, R.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. 2000, 39, 2085. Röper, S.; Frackenpohl, J.; Schrake, O.; Wartchow, R.; Hoffmann, H. M. R. Org. Lett. 2000, 2, 1661. Röper, S.; Wartchow, R.; Hoffmann, H. M. R. Org. Lett. 2002, 4, 3179.
20. Braje, W.; Holzgrefe, J.; Wartchow, R.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. 2000, 39, 2085. Röper, S.; Frackenpohl, J.; Schrake, O.; Wartchow, R.; Hoffmann, H. M. R. Org. Lett. 2000, 2, 1661. Röper, S.; Wartchow, R.; Hoffmann, H. M. R. Org. Lett. 2002, 4, 3179.
21. Braje, W.; Holzgrefe, J.; Wartchow, R.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. 2000, 39, 2085. Röper, S.; Frackenpohl, J.; Schrake, O.; Wartchow, R.; Hoffmann, H. M. R. Org. Lett. 2000, 2, 1661. Röper, S.; Wartchow, R.; Hoffmann, H. M. R. Org. Lett. 2002, 4, 3179.
22. For applications as tranquilizers, see: Ullmann's Encyclopedia of Industrial Chemistry; 6th Completely Revised Edition; Wiley-VCH: Weinheim, Germany, 2003.
23. Supplementary publications nos. CCDC-208992 (3) and CCDC-208993 (10). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: (+44) 1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).