Synthesis of 1,2-dihydropyridines using vinyloxiranes as masked dienolates in imino-aldol reactions

Organic Letters

Volumn 8, Issue 16, 2006, Pages 3473-3476

  Brunner, Bernhard ^a   Stogaitis, Nicole ^a   Lautens, Mark ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33747285252     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol061086p     Document Type: Article

References (31)

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3. (b) Restorp, P.; Somafai, P. Chem. Commun. 2004, 2086-2087,
4. (c) Pineschi, M.; Bertolini, F.; Haak, R. M.; Crotti, P.; Macchia, F. Chem. Commun. 2005, 1426-1428.
5. For recent examples with transition metals, see: (a) Marion, F.; Calvet, S.; Marie, J.-C.; Courillon, C.; Malacria, M. Eur. J. Org. Chem. 2006, 453-462.
6. (b) Courillon, C.; Fol, R. F.; Vandendris, E.; Malacria, M. Tetrahedron Lett. 1997, 38, 5493-5496
7. For recent examples with Lewis acids, see: (a) Deng, X.-M.; Sun, X.-L.; Tang, Y. J. Org. Chem. 2005, 70, 6537-6540.
8. (b) Jung, M. E.; Anderson, K. L. Tetrahedron Lett. 1997, 38, 2605-2608.
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13. For a review of vinylogous aldol reactions, see: (a) Denmark, S. E.; Heemstra, J. R., Jr.; Beutner, G. L. Angew. Chem., Int. Ed. 2005, 44, 4682-4698.
14. For a review on vinylogous Mannich reactions, see: (b) Bur, S. K.; Martin, S. F. Tetrahedron 2001, 57, 3221-3242.
15. For reviews of dihydropyridines, see: (a). Lavilla, R. J. Chem. Soc., Perkin Trans. 1 2002, 1141-1156.
16. (b) Stout, D. M.; Meyers, A. I. Chem. Rev. 1982, 82, 223-243.
17. For representative procedures for the preparation of 1,2- dihydropyridines, see: (c) Charette, A. B.; Grenon, M.; Lemire, A.; Pourashraf, M.; Martel, J. J. Am. Chem. Soc. 2001, 123, 11829-11830.
18. (d) Comins, D. L.; Hong, H.; Salvador, J. M. J. Org. Chem. 1991, 56, 7197-7199.
19. Bennasar, M. L.; Roca, R.; Monerris, M.; Juan, C.; Bosch, J. Tetrahedron 2002, 58, 8099-8106.
20. For the preperation of the vinyloxiranes 1a and 1b, see Supporting Information.
21. Other N-alkyl aldimines (e.g., N-phenyl, N-allyl) showed no or poor reactivity, and no or just minor product formation was observed.
22. For a solvent screening, see Supporting Information.
23. It is highly recommended to perform the reactions at a scale of at least 0.5 mmol; otherwise reduced yields are obtained as a result of decomposition of the product on silica gel.
24. Product 4f gave also crystals suitable for X-ray analysis. See Supporting Information.
25. For a previously reported crystal structure, see: Krow, G. R.; Raghavachari, R. J. Org. Chem. 1986, 51, 1916-1918.
26. 3, 18% isolated yield of 4a.
27. 3, which results in an inhibition of the catalytic cycle and therefore product inhibition.
28. The E-configuration of the double bond was confirmed by ROESY NMR spectroscopy.
29. The diastereomeric ratios of the products are 1.3:1 for 3n and 1.9:1 for 3i.
30. (a) This is not just an effect of the lower concentration of the reaction mixture (0.25 M). When the reaction was performed solely in THF (0.25 M) or toluene (0.25 M), messy reactions were observed in both cases.
31. (b) Application of this solvent system for the synthesis of the 1,2-dihydropyridines in Tables 1 and 2 gave no improvement in the yields.