Dihydropyridine-based multicomponent reactions. Efficient entry into new tetrahydroquinoline systems through Lewis acid-catalyzed formal [4 + 2] cycloadditions

Organic Letters

Volumn 5, Issue 5, 2003, Pages 717-720

  Lavilla, Rodolfo ^a   Bernabeu, M Carmen ^a   Carranco, Inés ^a   Díaz, José Luis ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIHYDROPYRIDINE; 4 METHYLANILINE; ALDEHYDE; DIHYDROPYRIDINE DERIVATIVE; PYRIDINIUM DERIVATIVE; QUINOLINE DERIVATIVE; ANILINE DERIVATIVE; METHYLANILINE;

ADDITION REACTION; ARTICLE; BIOTRANSFORMATION; CATALYSIS; CATALYST; COMBINATORIAL CHEMISTRY; CYCLOADDITION; ENANTIOSELECTIVITY; QUANTUM YIELD; STEREOCHEMISTRY; SUBSTITUTION REACTION; CHEMISTRY; CYCLIZATION; STEREOISOMERISM; SYNTHESIS;

ALDEHYDES; ANILINE COMPOUNDS; CYCLIZATION; DIHYDROPYRIDINES; QUINOLINES; STEREOISOMERISM;

EID: 0037529208     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol027545d     Document Type: Article

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18. For some relevant examples of this process, also called the Poparov reaction, see: (a) Grieco, P. Bahsas, A. Tetrahedron Lett. 1988, 29, 5855. (b) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995, 1195. (c) Kiselyov, A. S.; Smith, L., II; Armstrong, R. W. Tetrahedron 1998, 54, 5089. (d) Ma, Y.; Qian, C.; Xie, M.; Sun, J. J. Org. Chem. 1999, 64, 6462. (e) Stevenson, P. J.; Nieuwenhuyzen, M.; Osborne, D. Chem. Commun. 2002, 444. (f) Powell, D. A.; Batey, R. A. Org. Lett. 2002, 4, 2913.
19. For some relevant examples of this process, also called the Poparov reaction, see: (a) Grieco, P. Bahsas, A. Tetrahedron Lett. 1988, 29, 5855. (b) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995, 1195. (c) Kiselyov, A. S.; Smith, L., II; Armstrong, R. W. Tetrahedron 1998, 54, 5089. (d) Ma, Y.; Qian, C.; Xie, M.; Sun, J. J. Org. Chem. 1999, 64, 6462. (e) Stevenson, P. J.; Nieuwenhuyzen, M.; Osborne, D. Chem. Commun. 2002, 444. (f) Powell, D. A.; Batey, R. A. Org. Lett. 2002, 4, 2913.
20. For some relevant examples of this process, also called the Poparov reaction, see: (a) Grieco, P. Bahsas, A. Tetrahedron Lett. 1988, 29, 5855. (b) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995, 1195. (c) Kiselyov, A. S.; Smith, L., II; Armstrong, R. W. Tetrahedron 1998, 54, 5089. (d) Ma, Y.; Qian, C.; Xie, M.; Sun, J. J. Org. Chem. 1999, 64, 6462. (e) Stevenson, P. J.; Nieuwenhuyzen, M.; Osborne, D. Chem. Commun. 2002, 444. (f) Powell, D. A.; Batey, R. A. Org. Lett. 2002, 4, 2913.
21. For some relevant examples of this process, also called the Poparov reaction, see: (a) Grieco, P. Bahsas, A. Tetrahedron Lett. 1988, 29, 5855. (b) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995, 1195. (c) Kiselyov, A. S.; Smith, L., II; Armstrong, R. W. Tetrahedron 1998, 54, 5089. (d) Ma, Y.; Qian, C.; Xie, M.; Sun, J. J. Org. Chem. 1999, 64, 6462. (e) Stevenson, P. J.; Nieuwenhuyzen, M.; Osborne, D. Chem. Commun. 2002, 444. (f) Powell, D. A.; Batey, R. A. Org. Lett. 2002, 4, 2913.
22. 3 seems to promote also the reductive pathway: Itoh, T.; Nagata, K.; Kurihara, A.; Miyazaki, M.; Ohsawa, O. Tetrahedron Lett. 2002, 43, 3105. For a general overview, see ref 4.
23. (a) Babu, G.; Perumal, P. T. Aldrichimica Acta 2000, 33, 16.
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25. Other lanthanide Lewis acids were preliminarily tested (cerium, ytterbium, and lanthanum triflates) and also showed good reactivity profiles. Interestingly, the stereoselectivity of the process is affected by the nature of the catalyst. Details on these reactions will be reported in due curse.
26. 4 reduction of the corresponding N-alkylpyridinium salts.
27. 2 were ineffective, no cycloadducts being detected in these experiments.
28. Products are racemic mixtures. Only one enantiomer is depicted. The stereochemical assignment was performed on purified compounds (column chromatography) through NOE experiments, molecular modelling and coupling constant analysis.
29. To speed up the processes, the reactions involving the more labile DHPs 1 were conducted at 60°C. The isolated yields were somewhat lower, probably due to partial decomposition of the starting DHPs. Other activation techniques (for instance, high pressure, microwave irradiation) are under study and may result in faster reactions. On the other hand, the use of ionic liquids (Yadav, J. S.; Reddy, B. V. S.; Uma Gayathri, K.; Prasad, A. R. Synthesis 2002, 2537) or microencapsulated scandium triflate (Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1998, 120, 2985) can also be considered for catalyst immobilization.
30. To speed up the processes, the reactions involving the more labile DHPs 1 were conducted at 60°C. The isolated yields were somewhat lower, probably due to partial decomposition of the starting DHPs. Other activation techniques (for instance, high pressure, microwave irradiation) are under study and may result in faster reactions. On the other hand, the use of ionic liquids (Yadav, J. S.; Reddy, B. V. S.; Uma Gayathri, K.; Prasad, A. R. Synthesis 2002, 2537) or microencapsulated scandium triflate (Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1998, 120, 2985) can also be considered for catalyst immobilization.
31. Interaction of aromatic aldehydes with N-alkylDHPs (1) under the same conditions affords the expected addition compounds. The influence of the substituents in the aromatic ring on the reactivity and the stereo-selectivity is under study.
32. Huang, T.; Li, C.-J. Tetrahedron Lett. 2000, 41, 6715.
33. For the related interaction of a dihydropyridine with the Eschenmoser's salt, see: Bennasar, M.-L.; Vidal, B.; Bosch, J. J. Org. Chem. 1997, 62, 3597.
34. Direct 4CR would probably result in the interception of the imine by the nucleophile in a Strecker-type reaction.
35. 4 reduction of pyridinium salts and subsequent reaction with ethyl glyoxalate and p-methylaniline resulted in failure, and no adducts (4-4′) were detected.