Microwave-assisted solid-phase Ugi four-component condensations

Tetrahedron Letters

Volumn 40, Issue 20, 1999, Pages 3941-3944

  Hoel, Andreas M L ^a,b   Nielsen, John ^a  

^a TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

^b Labwell AB ^*  (Sweden)

Author keywords

Combinatorial chemistry; Microwave heating; Solid Phase synthesis; Ugi Passerini reactions

Indexed keywords

ALDEHYDE; CARBOXYLIC ACID; CYANIDE;

ARTICLE; CHEMICAL STRUCTURE; MICROWAVE RADIATION; POLYMERIZATION; REACTION ANALYSIS; REACTION TIME; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 0033553530     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)00616-4     Document Type: Article

References (34)

1. 2. Ugi, I.; J. Prakt. Chem. 339 (6), 499-516, 1997 and references cited therein.
2. 3. For review, see a) Gokel, G., Lüdke, G., Ugi, I. in Isonitrile Chemistry; Ugi, I., Ed. Academic Press, New York, 1971, pp. 145-195;
3. b) Ugi, I., Lohberger, S., Karl, R.,: The Passerini and Ugi Reactions. In Comprehensive Organic Synthesis: Selectivity, Strategy & Efficiency in Modern Organic Chemistry, Trost, B. M. and Heathcock, C. H., Ed., Pergamon, Oxford, 1991.
4. 4. Short, K. M., Ching, B. W., Mjalli, A. M. M., Tetrahedron 53 (19), 6653-6679, 1997 and references cited therein.
5. 5. a) Keating, T. A., and Armstrong, R. W., J. Org. Chem. 61, 8935-8939, 1996;
6. b) Hulme, C., Peng, J., Tang, S-Y., Burns, C. J., Morize, I., Labaudiniere, R., J. Org. Chem. 63, 8021-8023, 1998.
7. 6. Hulme, C., Morrissette, M. M., Volz, F. A., Burns, C. J., Tetrahedron Lett. 39, 1113-1116, 1998.
8. 7. Harriman, G. C. B., Tetrahedron Lett. 38, 5591-5594, 1997.
9. 8. a) Ugi, I., Dömling, A., Hörl, W., Endeavour 18, 115-123, 1994;
10. b) Cotterill, I. C., Usyatinsky, A. Y., Arnold, J. M., Clark, D. S., Dordick, J. S., Michels, P. C., Khmelnitsky, Y. L., Tetrahedron Lett. 39, 1117-1120, 1998.
11. 9. The term "collections of compounds" refers to what now is called a combinatorial library; see a) Ugi, I. and Steinbrückner, C., Chem. Ber. 94, 734-742, 1961;
12. b) Dömling, A., Comb. Chem. & High Troughp. Screen. 1, 1-22, 1998.
13. 10. a) Szardenings, A. K., Burkoth, T. S., Lu, H. H., Tien, D. W., Campell, D. A, Tetrahedron 53 (19), 6573-6593, 1997;
14. b) Kim, S. W., Bauer, S. M., Armstrong, R. W., Tetrahedron Lett. 39, 7031-7034, 1998 and references herein;
15. c) Ugi, I., Angew. Chem. Int. Ed. Engt. 21, 810-819, 1982.
16. 11. a) Tempest, P. A., Brown, S. D., Armstrong, R. W., Angew. Chem. Int. Ed. Engl. 35 (6), 640-642, 1996;
17. b) Armstrong, R. W., Combs, A. P., Tempest, P. A., Brown, S. D., Keating, T. A., Acc. Chem. Res. 29, 123-131, 1996;
18. c). Kim, S. W., Bauer, S. M., Armstrong, R. W., Tetrahedron Lett. 39, 6993-6996, 1998.
19. 12. Majetich, G. and Hicks, R., Res. Chem. Intermed. 20 (1), 61-77, 1994.
20. 13. Loupy, A., Petit, A., Hamelin, J., Texier-Boullet, F., Jacquault, P., Mathé, D., Synthesis 1213-1234, Sept. 1998.
21. 14. Yu, H-M., Chen, S-T., Wang, K-T., J. Org. Chem. 57 (18), 4781-4784, 1992.
22. 15. Larhed, M., Lindeberg, G., Hallberg, A., Tetrahedron Lett. 37 (45), 8219-8222, 1996.
23. 16. a) Strocker, A. M., Keating, T. A., Tempest, P. A., Armstrong, R. W., Tetrahedron Lett. 37 (8), 1149-1152, 1996;
24. b) Zhang, C., Moran, E. J., Woiwode, T. F., Short, K. M., Mjalli, A. M. M., Tetrahedron Lett. 37 (6), 751-754, 1996.
25. 17. Gabriel, C., Gabriel, S., Grant, E. H., Halstead, B. S. J., Mingos, D. M. P., Chem. Soc. Rev. 27, 213-223, 1998.
26. 18. Santini, R., Griffith, M. C., Qi, M., Tetrahedron Lett. 39, 8951-8954, 1998.
27. 19. The model experiments were all carried out with 1Bc. The oven used in these experiments was a Microwell 10 from Labwell AB. The oven is monomodal and can be adjusted with 1 W intervals between 1 and 500 W. Warning! Suitable precautions must always be taken to avoid explosions due to pressure build-up. In particular, use of silicon septa as pressure relief devices is advised.
28. 20. All reactions with 1 were irradiated for 5 min. except 1Aa and 1Ab which were irradiated for 4 min 45 s. 2Aa, 2Ab and 2Ac were irradiated for 4 min 45 s. 2Ba, 2Bb and 2Bc were irradiated for 5 min. 2Ca, 2Cb and 2Cc were irradiated for 3 min 45 s.
29. 21. HPLC (LC-MS) were recorded on Micromass LC-Platform using Quatropole Analyzer, APcI probe (atmospheric pressure chemical ionization) and Masslynx software v.2.3 with YMC reverse-phase C-18 column 50 x 4.6 I.D., S-3 μm 120 A. Data: 1Aa: retention time (r.t.) 8.1 min, m/z: 348; 2Aa: r.t. 5.9 min, m/z: 379; 1Ab. r.t. 6.7 min, m/z: 294; 2Ab: r.t. 4.5 min, m/z: 325; 1Ac: r.t. 6.7 min, m/z: 342; 2Ac: r.t. 5.4 min, m/z: 373; 1Ba: r.t. 6.3 min, m/z: 308; 2Ba: r.t. 5.0 min, m/z: 339; 1Bb: r.t. 5.0 min, m/z: 254; 2Bb: r.t. 3.6 min, m/z: 385; 1Bc: r.t. 6.0 min, m/z: 302; 2Bc: r.t. 4.6 min, m/z: 333; 1Ca: r.t. 6.4 min, m/z: 342; 2Ca: r.t. 5.6 min, m/z: 373; 1Cb: r.t. 5.5 min, m/z: 288; 2Cb: r.t. 4.0 min, m/z: 319; 1Cc: r.t. 6.4 min, m/z: 336; 2Cc: r.t. 5.0 min, m/z: 367.
30. 22. According to integrated areas recorded at λ = 254 nm. Generally α-acylamino amides with 1 as the isocyanide component were quite insoluble, whereas products obtained from 2 were more soluble. The chromatograms showed very little or no products from side reactions. In some cases small amounts of unreacted starting material were not removed completely from the resin in the washing procedure.
31. 23. TentaGel S RAM-resin (S30 023, 0.24 mmole/g capacity) purchased from Rapp Polymere.
32. 24. The reactions were carried out in custom made vials with a total volume of 10 ml, fitted with screw caps and 1/8 * 1/2 inch teflon coated silicon septa. The total volume of resin and liquid was approximately 1.5 ml, thereby allowing headspace for pressure build-up during the microwave treatment.
33. 25. Note that most isocyanides have a very obnoxious smell! All operations should therefore be performed in fume hood!
34. 26. When the products were cleaved off the TentaGel small amounts of PEG leaked from the resin. This has as a standard procedure been subtracted from the yield.