High-speed couplings and cleavages in microwave-heated, solid-phase reactions at high temperatures

European Journal of Organic Chemistry

Volumn , Issue 5, 2001, Pages 919-925

  Stadler, Alexander ^a   Kappe, C Oliver ^a  

^a UNIVERSITY OF GRAZ   (Austria)

Author keywords

Combinatorial chemistry; Microwave enhanced chemistry; Solid phase synthesis

Indexed keywords

CESIUM; POLYSTYRENE; TRIFLUOROACETIC ACID;

ARTICLE; CHEMICAL REACTION; COUPLING FACTOR; IRRADIATION; METHYLATION; MICROWAVE RADIATION; REACTION TIME; SOLID PHASE EXTRACTION; SYNTHESIS;

EID: 0035118462     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/1099-0690(200103)2001:5<919::AID-EJOC919>3.0.CO;2-V     Document Type: Article

References (50)

1. For excellent overviews of solid-phase organic synthesis, see: [1a] F. Zaragoza Dörwald, Organic Synthesis on Solid Phase, Wiley-VCH, Weinheim, 2000.
2. [1b] Solid-Phase Organic Synthesis (Ed.: K. Burgess), Wiley-Interscience, New York, 2000.
3. [1c] D. Obrecht, J. M. Villalgordo, Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound-Libraries, Pergamon Press, Oxford, 1998.
4. [1d] B. A. Bunin, The Combinatorial Index, Academic Press, San Diego, 1998.
5. [2a] B. Yan, Acc. Chem. Res. 1998, 31, 621-630.
6. [2b] I. Sucholeiki, Molecular Diversity 1999, 4, 25-30.
7. [2c] W. B. Li, X. Y. Xiao, A. W. Czarnik, J. Comb. Chem. 1999, 1, 127-129.
8. [2d] W. Li, B. Yan, J. Org. Chem. 1998, 63, 4092-4097.
9. For some recent reviews, see: [3a] S. Caddick, Tetrahedron 1995, 51, 10403-10432.
10. [3b] C. R. Strauss, R. W. Trainor, Aust. J. Chem. 1995, 48, 1665-1692.
11. [3c] F. Langa, P. de la Cruz, A. de la Hoz, A. Díaz-Ortiz, E. Díez-Barra, Contemp. Org. Synth. 1997, 4, 373-386.
12. [3d] A. K. Bose, B. K. Banik, N. Lavlinskaia, M. Jayaraman, M. S. Manhas, Chemtech 1997, 27, 18-24.
13. [3e] C. Gabriel, S. Gabriel, E. H., Grant, B. S. Halstead, D. M. P. Mingos, Chem. Soc. Rev. 1998, 27, 213-223.
14. [3f] A. Loupy, A. Petit, J. Hamelin, F. Texier-Boullet, P. Jacquault, D. Mathé, Synthesis 1998, 1213-1234.
15. [3g] S. Deshayes, M. Liagre, A. Loupy, J.-L. Luche, A. Petit, Tetrahedron 1999, 55, 10851-10870.
16. [3h] C. R. Strauss, Aust. J. Chem. 1999, 52, 83-96.
17. [3i] R. S. Varma, Green Chem. 1999, 43-55.
18. For some recent applications related to combinatorial chemistry, see: [4a] M. Larhed, M. Hoshino, S. Hadida, D. P. Curran, A. Hallberg, J. Org. Chem. 1997, 62, 5583-5587.
19. [4b] K. Olofsson, S.-Y. Kim, M. Larhed, D. P. Curran, A. Hallberg, J. Org. Chem. 1999, 64, 4539-4541.
20. [4c] J. J. Vanden Eynde, D. Rutot, Tetrahedron 1999, 55, 2687-2694.
21. [4d] C. Blettner, W. A. König, W. Stenzel, T. Schotten, J. Org. Chem. 1999, 64, 3885-3890.
22. [4c] C. T. Brain, J. M. Paul, Y. Loong, P. J. Oakley, Tetrahedron Lett. 1999, 40, 3275-3278.
23. [4f] I. C. Cotterill, A. Y. Usyatinsky, J. M. Arnold, D. S. Clark, J. S. Dordick, P. C. Michels, Y. L. Khmelnitsky, Tetrahedron Lett. 1998, 39, 1117-1120.
24. [4g] C. O. Kappe, D. Kumar, R. S. Varma, Synthesis 1999, 1799-1803.
25. [5a] H.-M. Yu, S.-T. Chen, K.-T. Wang, J. Org. Chem. 1992, 57, 4781-4784.
26. [5b] M. Larhed, G. Lindeberg, A. Hallberg, Tetrahedron Lett. 1996, 37, 8219-8222.
27. [5c] G. Kuster, H. W. Scheeren, Tetrahedron Lett. 2000, 41, 515-519.
28. [5d] A. M. L. Hoel, J. Nielsen, Tetrahedron Lett. 1999, 40, 3941-3944.
29. For the description of an early prototype of this reactor, see: [6a] K. D. Raner, C. R. Strauss, R. W. Trainor, J. S. Thorn, J. Org. Chem. 1995, 60, 2456-2461.
30. [6b] A. Schmaling, M. Metzger, M. Loechner, American Laboratory, July 1998, 37-40.
31. M. Mergler, R. Nyfeler, J. Gosteli, R. Tanner, Tetrahedron Lett. 1989, 30, 6745-6748.
32. [8a] R. Frenette, R. W. Friesen, Tetrahedron Lett. 1994, 35, 9177-9180.
33. [8b] D. R. Tortolani, S. A. Biller, Tetrahedron Lett. 1996, 37, 5687-5690.
34. [8c] M. D. Collini, J. W. Ellingboe, Tetrahedron Lett. 1997, 38, 7963-7966.
35. [8d] S. Chamoin, S. Houldsworth, V. Snieckus, Tetrahedron Lett. 1998, 39, 4175-4178.
36. S. Hanessian, R.-Y. Yang, Tetrahedron Lett. 1996, 37, 5835-5838.
37. P. Trapencieris, in Encyclopedia of Reagents for Organic Synthesis (Ed.: L. A. Paquette), Wiley, Chicester, 1995, vol. 5, p. 3580-3581.
38. R. Santini, M. C. Griffith, M. Qi, Tetrahedron Lett. 1998, 39, 8951-8954.
39. Microwave-Enhanced Chemistry (Eds.: H. M. Kingston, S. J. Haswell), American Chemical Society, Washington, 1997.
40. K. S. Vallin, M. Larhed, K. Johansson, A. Hallberg, J. Org. Chem. 2000, 65, 4537-4542.
41. Temperatures above the normal boiling point are frequently observed with microwave dielectric heating owing to superheating of solvents under atmospheric pressure. For leading references, see: [14a] D. R. Baghurst, D. M. P. Mingos, J. Chem. Soc., Chem. Commun. 1992, 674-677.
42. [14b] R. Saillard, M. Poux, J. Berlan, M. Audhuy-Peaudecerf, Tetrahedron 1995, 51, 4033-4042.
43. In all experiments the loading was determined by recovery of acid after cleavage of 5 with 50% TFA (see Exp. Sect. for details).
44. In a similar experiment we have exposed a sample of resin 1 to NMP at 700 W/200 °C for 20 min. Investigation of the beads under a microscope revealed no change in physical appearance or swelling behavior (NMP), and no weight loss could be determined. Furthermore, this pretreated resin could still be quantitatively loaded with e.g. benzoic acid.
45. [3c] For some recent references on this issue, see: [17a] R. N. Gedye, J. B. Wei, Can. J. Chem. 1998, 76, 525-532.
46. [17b] P. Goncalo, C. Roussel, J. M. Milot, J. Vébrel, J. Chem. Soc., Perkin Trans. 2 1999, 2111-2115.
47. [17c] A. Stadler, C. O. Kappe, J. Chem. Soc., Perkin Trans. 2 2000, 1363-1368.
48. Whatever the reason for these apparent differences, rate enhancements in microwave irradiation experiments should only be attributed to nonthermal effects if they are substantial (100 times or more), see: D. M. P. Mingos, Res. Chem. Intermed. 1994, 20, 85-91.
49. [3e,12]
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