Trimethylsilyl-directed 1,3-dipolar cycloaddition reactions in the solid-phase synthesis of 1,2,3-triazoles

Organic Letters

Volumn 7, Issue 8, 2005, Pages 1469-1472

  Coats, Steven J ^a   Link, Jeffrey S ^a   Gauthier, Diane ^a   Hlasta, Dennis J ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3 TRIAZOLE DERIVATIVE; ACETYLENE DERIVATIVE; AZIDE; RESIN; TRIAZOLE DERIVATIVE; TRIMETHYLSILYL DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; CYCLOADDITION; REACTION ANALYSIS; SOLID; STRUCTURE ANALYSIS; SUBSTITUTION REACTION;

EID: 17844397956     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol047637y     Document Type: Article

References (20)

1. Gilchrist, T. L.; Gymer, G. E. Adv. Heterocycl. Chem. 1974, 16, 33-85 and references therein.
2. Blass, E.; Coburn, K. R.; Faulkner, A. L.; Hunn, C. L.; Natchus, M. G.; Parker, M. S.; Portlock, D. E.; Tullis, J. S.; Wood, R. Tetrahedron Lett. 2002, 43, 4059-4061.
3. Birkhofer, L.; Franz, M. Chem. Ber. 1972, 105, 1759-1767.
4. Guillerm, G.; L'Honore, A.; Veniard, L.; Pourcelot, G.; Benaim, J. Bull. Soc. Chim. Fr. 1973, 105, 2739-2746.
5. Padwa, A.; Wannamaker, M. W. Tetrahedron 1990, 46, 1145-1162.
6. Hlasta, D. J.; Ackerman, J. H. J. Org. Chem. 1994, 59, 6184-6189.
7. This work was presented in a preliminary form: Link, J. S.; Coats, S. J.; Hlasta, D. J. Metal Directed 1,3-Dipolar Cycloadditions in Solution and Solid-Phase Synthesis; Abstract at the 223rd National Meeting of the American Chemical Society, Orlando, FL, April 7-11, 2002; ORGN 228.
8. Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057-3064.
9. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596-2599. Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6, 3897-3899. Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003, 8, 1128-1137 and references therein.
10. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596-2599. Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6, 3897-3899. Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003, 8, 1128-1137 and references therein.
11. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596-2599. Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6, 3897-3899. Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003, 8, 1128-1137 and references therein.
12. Krasinski, A.; Fokin, V. V.; Sharpless, K. B. Org. Lett. 2004, 6, 1237-1240.
13. 13C, and two-dimensional NMR studies. For example, triazole 8 in an HMBC experiment shows a three-bond proton-carbon correlation between the benzylic protons and the carbon of the triazole ring with the carbonyl attached, whereas no correlation is seen to the carbon with the trimethylsilyl group attached.
14. 8 for 24 h. Because we used 5 equiv of the 1-trimethylsilylacetylene in the cycloaddition reaction and the fact that ethyl propynoate undergoes a more rapid cycloaddition with 14, a small impurity of desilylated acetylene would have explained our leakage of regioselectivity.
15. In a solution-phase reaction designed to mimic the Wang resin linker, a benzyl azide 20 on reaction with trimethylsilyl-propynoic acid gave two desilylated triazoles 21 and 22, analogous to 17 and 18 (see Supporting Information).
16. Brown, A. R.; Rees, D. C.; Rankovic, Z.; Morphy, J. R. J. Am. Chem. Soc. 1997, 119, 3288-3295. Cameron, K. S.; Morphy, J. R.; Rankovic, Z.; York, M. J. Comb. Chem. 2002, 4, 199-203.
17. Brown, A. R.; Rees, D. C.; Rankovic, Z.; Morphy, J. R. J. Am. Chem. Soc. 1997, 119, 3288-3295. Cameron, K. S.; Morphy, J. R.; Rankovic, Z.; York, M. J. Comb. Chem. 2002, 4, 199-203.
18. Barn, D.; Caulfield, W.; Cowley, P.; Dickins, R.; Bakker, W. I.; McGuire, R.; Morphy, J. R.; Rankovic, Z.; Thorn, M. J. Comb. Chem. 2001, 3, 534-541.
19. A series of coupling agents were evaluated for their ability to form this sterically hindered amide bond. The following coupling agents are listed in order of increasing coupling efficiency for the reaction of 23 with 5 equiv of benzylamine: EEDQ < 1,3-dimethyl-2-fluoropyridinium toluene-4-sulfonate < MSNT < 2-chloro-1,3-dimethylimidazolinium chloride < DIC/HOBT < PyBrop < PyBop.
20. Recently, we have found that precleavage desilylation can be accomplished by exposure of the REM trimethylsilyl triazole 23 to KF/aq HCl in THF (see Supporting Information).