Novel multicomponent reaction for the combinatorial synthesis of 2-imidazolines

Organic Letters

Volumn 5, Issue 20, 2003, Pages 3759-3762

  Bon, Robin S ^a   Hong, Chongen ^a   Bouma, Marinus J ^a   Schmitz, Rob F ^a   De Kanter, Frans J J ^a   Lutz, Martin ^a,b   Spek, Anthony L ^a   Orru, Romano V A ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

^b UTRECHT UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

IMIDAZOLINE DERIVATIVE;

ARTICLE; POLYMERIZATION; REACTION ANALYSIS; SUBSTITUTION REACTION; SYNTHESIS;

EID: 0142042901     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol035521g     Document Type: Article

References (41)

1. Newton, R. sp2 2002, November, 16-18 (see: http://www.sp2.uk.com).
2. (b) Teague, S. J.; Davis, A. M.; Leeson, P. D.; Oprea, T. Angew. Chem., Int. Ed. 1999, 38, 3743-3748.
3. (c) Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123-131.
4. (d) Schreiber, S. L. Science 2000, 287, 1964-1969.
5. (a) Orru, R. V. A.; de Greef, M. Synthesis 2003, 1471-1499.
6. (b) Dömling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168-3210.
7. (c) Bienaymé, H.; Hulme, C.; Oddon, G.; Schmitt, P. Chem. Eur. J. 2000, 6, 3321-3329.
8. For example, see: Hassner, A.; Fischer, B. Heterocycles 1993, 35, 1441-1465.
9. (a) Betschart, C.; Hegedus, L. S. J. Am. Chem. Soc. 1992, 114, 5010-5017.
10. (b) Hsiao, Y.; Hegedus, L. S. J. Org. Chem. 1997, 62, 3586-3591.
11. (a) Schäfer, U.; Burgdorf, C.; Engelhardt, A.; Kurz, T.; Richardt, G. J. Pharmacol. Exp. Ther. 2002, 303, 1163-1170.
12. (b) Rondu, F.; le Bihan, G.; Wang, X.; Lamouri, A.; Touboul, E.; Dive, G.; Bellahsene, T.; Pfeiffer, B.; Renard, P.; Guardiola-Lemaitre, B.; Manechez, D.; Penicaud, L.; Ktorza, A.; Godfroid, J.-J. J. Med. Chem. 1997, 40, 3793-3803.
13. (c) Gust, R.; Keilitz, R.; Schmidt, K. J. Med. Chem. 2001, 44, 1963-1970.
14. (d) Gust, R.; Keilitz, R.; Schmidt, K.; Von Rauch, M. J. Med Chem. 2002, 45, 3356-3365.
15. Gentili, F.; Bousquet, P.; Brasili, L.; Dontenwill, M.; Feldman, J.; Ghelfi, F.; Gianella, M.; Piergentili, A.; Quaglia, W.; Pigini, M. J. Med. Chem. 2003, 46, 2169-2176.
16. (a) Dunn, P. J.; Haner, R.; Rapoport, H. J. Org. Chem. 1990, 55, 5017-5025 and references therein.
17. (b) Han, H.; Yoon, J.; Janda, K. D. J. Org. Chem. 1998, 63, 2045-2048.
18. (a) Jones, R. C. F.; Howard, K. J.; Snaith, J. S. Tetrahedron Lett. 1996, 37, 1707-1710.
19. (b) Jones, R. C. F.; Howard, K. J.; Snaith, J. S. Tetrahedron Lett. 1996, 37, 1711-1714.
20. (c) Dalko, P. I.; Langlois, Y. Chem. Commun. 1998, 331-332.
21. Menges, F.; Neuburger, M.; Pfaltz, A. Org. Lett. 2002, 4, 4713-4716.
22. Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290-1309 and references therein.
23. (a) Riebsomer, J. L. J. Am. Chem. Soc. 1948, 70, 1629-1631.
24. (b) Jones, R. C. F.; Howard, K. J.; Snaith, J. S. Tetrahedron Lett. 1996, 37, 1707-1710.
25. (a) Meyer, R.; Schöllkopf, U.; Böhme, P. Liebigs Ann. Chem. 1977, 1183-1193.
26. (b) van Leusen, A. M.; Wildeman, J.; Oldenziel, O. H. J. Org. Chem. 1977, 42, 1153-1159.
27. Recently, a multicomponent synthesis of imidazoles using van Leusen's TosMIC chemistry was published: Sisko, J.; Kassick, A. J.; Mellinger, M.; Filan, J. J.; Allen, A.; Olsen, M. A. J. Org. Chem. 2000, 65, 1516-1524.
28. (a) Hayashi, T.; Kishi, E.; Soloshonok, V. A.; Uozumi, Y. Tetrahedron Lett. 1996, 37, 4969-4972.
29. (b) Lin, Y.-R.; Zhou, X.-T.; Dai, L.-X.; Sun, J. J. Org. Chem. 1997, 62, 1799-1803.
30. (c) Zhou, X.-T.; Lin, Y.-R.; Dai, L.-X.; Sun, J.; Xia, L.-J.; Tang, M.-H. J. Org. Chem. 1999, 64, 1331-1334.
31. Notable exception is the highly diastereoselective multicomponent synthesis of imidazolines employing oxazolones in 1,3-dipolar cycloaddition reactions reported by: Peddibhotla, S.; Jayakumar, S.; Tepe, J. J. Org. Lett. 2002, 4, 3533-3535.
32. Schöllkopf reported that reactions between the isocyanoacetate 6 and imines at 10 mmol scale in methanol were usually complete after 3 h. See also ref 12a.
33. (a) Lehnhoff, S.; Goebel, M.; Karl, R. M.; Klösel, R.; Ugi, I. Angew. Chem. 1995, 107, 1208-1211.
34. (b) Cheng, J.-F.; Chen, M.; Arrhenius, T.; Nadzan, A. Tetrahedron Lett. 2002, 43, 6293-6296.
35. (c) Bradley, H.; Fitzpatrick, G.; Glass, W. K.; Kunz, H.; Murphy, P. V. Org. Lett. 2001, 3, 2629-2632.
36. (a) Cristau, P.; Vors, J.-P.; Zhu, J. Org. Lett. 2001, 3, 4079-4082.
37. (b) Isocyanoacetate 16 turned out to be somewhat unstable toward silica column chromatography and possesses an unpleasant odor. Other reagents for the dehydration of N-formamide 15 were tested, like Burgess' reagent, TsCl/pyridine, and triphosgene/NMM. Unfortunately, no optically active isocyanide could be obtained.
38. 1H NMR spectra revealed for H(5) a characteristic Aδ(anti-syn) = 0.6 ± 0.05. The upfield shift of H(5) in the spectra of the syn diastereomers can be explained by a shielding effect of the Ph-group at C(4). This is confirmed by NOE measurements.
39. Considerable amounts of imine are isolated in this case, and 16 presumably decomposes before the reaction is complete. That 2-imidazoline formation with sterically demanding amines proceeds relatively slow is supported by the observation that combination of benzhydrylamine, 11, 12, and 16 only gave (within 18 h) the corresponding Ugi-4CC product in 60% yield.
40. 4 to remove water, which is formed during initial imine formation. See Supporting Information for details.
41. When 29 is combined with 10, 11, and propionic acid 12, the same trend as for 16 can be recognized. Formation of 2-imidazoline 31 was exclusive (70%) and no Ugi-4CC product was observed. However, a similar reaction, but now with benzhydrylamine instead of isopropylamine (10) as amine input, gave no 2-imidazoline. The bisamide, resulting from an Ugi-4CC, was isolated as the only reaction product in 67%.