Four-component synthesis of fully substituted 1,2,4-triazoles

Angewandte Chemie - International Edition

Volumn 49, Issue 2, 2010, Pages 325-328

  Staben, Steven T ^a   Blaquiere, Nicole ^a  

^a GENENTECH INC   (United States)

Author keywords

C C coupling; Carbonylation; Homogeneous catalysis; Multicomponent reactions; Nitrogen heterocycles

Indexed keywords

ARYL HALIDES; C-C COUPLING; CHEMICAL EQUATIONS; COMPONENT SYNTHESIS; HOMOGENEOUS CATALYSIS; MULTI-COMPONENT REACTIONS; NITROGEN HETEROCYCLES; REGIO-SELECTIVE;

CARBONYLATION; CATALYSIS; PALLADIUM; REACTION KINETICS;

SYNTHESIS (CHEMICAL);

ACETAMIDINE; AMIDINE; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; HETEROCYCLIC COMPOUND; TRIAZOLE DERIVATIVE;

ARTICLE; CATALYSIS; CHEMISTRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; ISOLATION AND PURIFICATION; STEREOISOMERISM; SYNTHESIS;

AMIDINES; CATALYSIS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; HETEROCYCLIC COMPOUNDS; INDICATORS AND REAGENTS; STEREOISOMERISM; TRIAZOLES;

EID: 73349112251     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200905897     Document Type: Article

References (54)

1. For example, mild zincation of several heterocycles: a) S. H. Wunderlich, M. Kienle, P. Knochel, Angew. Chem. 2009, 121, 7392;
2. Angew. Chem. Int. Ed. 2009, 48, 7256;
3. b) C. J. Rohbogner, S. H. Wunderlich, G. C. Clososki, P. Knochel, Eur. J. Org. Chem. 2009, 1781.
4. Trifluoroborate salts: a) G. A. Molander, N. Ellis, Acc. Chem. Res. 2007, 40, 275;
5. b) G. A. Molander, B. Canturk, L. E. Kennedy, J. Org. Chem. 2009, 74, 913; Silanoates:
6. c) S. E. Denmark, J. D. Baird, Org. Lett. 2006, 8, 793;
7. d) S. E. Denmark, C. S. Regens, Acc. Chem. Res. 2008, 41, 1486.
8. MIDA boronates: D. M. Knapp, E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2009, 131, 6961.
9. For recent examples see: a) N. Kudo, M. Perseghini, G. C. Fu, Angew. Chem. 2006, 118, 1304;
10. Angew. Chem. Int. Ed. 2006, 45, 1282;
11. b) D. X. Yang, S. L. Colletti, K. Wu, M. Song, G. Y. Li, H. C. Shen, Org. Lett. 2009, 11, 381;
12. c) K. L. Billingsley, S. L. Buchwald, Angew. Chem. 2008, 120, 4773;
13. Angew. Chem. Int. Ed. 2008, 47, 4695.
14. For recent summary articles see: a) D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174;
15. b) B. Liégault, D. Lapointe, L. Caron, A. Vlassova, K. Fagnou, J. Org. Chem. 2009, 74, 1826;
16. c) L.-C. Campeau, D. R. Stuart, J.-P. Leclerc, M. Bertrand-Laperle, E. Villemure, H.-Y. Sun, S. Lasserre, N. Guimond, M. Lecavallier, K. Fagnou, J. Am. Chem. Soc. 2009, 131, 3291;
17. d) O. Daugulis, H.-Q. Do, D. Shabashov, Acc. Chem. Res. 2009, 42, 1074. The authors note that the generality of reaction conditions remains a prominent issue;
18. e) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2009, DOI: 10.1021/cr900005n.
19. For a review on the transition-metal-catalyzed multicomponent synthesis of heterocycles see: a) D. M. D'Souza, T. J. J. Müller, Chem. Soc. Rev. 2007, 36, 1095;
20. See also b) A. S. Karpov, E. Merkul, F. Rominger, T. J. J. Müller, Angew. Chem. 2005, 117, 7112;
21. Angew. Chem. Int. Ed. 2005, 44, 6951;
22. c) J. R. Young, R. J. DeVita, Tetrahedron Lett. 1998, 39, 3931;
23. H.-C. Ryu, Y.-T. Hong, S.-K. Kang, Heterocycles 2000, 54, 985.
24. For metal-assisted carbon monoxide mediated heterocycle ring formation see: d) M. D. Mihovilovic, P. Stanetty, Angew. Chem. 2007, 119, 3684;
25. Angew. Chem. Int. Ed. 2007, 46, 3612;
26. e) R. D. Dghaym, R. Dhawan, B. A. Arndtsen, Angew. Chem. 2001, 113, 3328;
27. Angew. Chem. Int. Ed. 2001, 40, 3228;
28. f) R. Dhawan, B. A. Arndtsen, J. Am. Chem. Soc. 2004, 126, 468;
29. g) B. A. Arndtsen, Chem. Eur. J. 2009, 15, 302.
30. For a review on the cross-coupling of azoles see: a) M. Schnürch, R. Flasik, A. F. Khan, M. Spina, M. D. Mihovilovic, P. Stanetty, Eur. J. Org. Chem. 2006, 3283-3307.
31. Stille coupling of 1-methyl-5-(tributylstannyl)-1H-1,2,4-triazole: b) K. C. Nicolaou, B. A. Pratt, S. Arseniyadis, M. Wartmann, A. O'Brate, P. Giannakakou, ChemMedChem 2006, 1, 41;
32. c) P. Jones, M. Chambers, Tetrahedron 2002, 55, 9973.
33. Negishi coupling of (1-methyl-1H-1,2,4-triazol-5-yl)zinc(II) chloride: d) H. J. Barbosa, et al., WO 102194, 2006;
34. e) D. S. Middleton, et al., WO 51972, 2000.
35. For notes on the instability of metalated azoles with two or more nitrogen atoms see: M. R. Grimmett, B. Iddon, Heterocycles 1995, 41, 1525.
36. a) H.-Q. Do, O. Daugulis, J. Am. Chem. Soc. 2007, 129, 12404;
37. b) H.-Q. Do, R. M. K. Khan, O. Daugulis, J. Am. Chem. Soc. 2008, 130, 15185;
38. For examples of an intramolecular cyclization see c) B. Laleu, M. Lautens, J. Org. Chem. 2008, 73, 9164.
39. An intermediate in the Einhorn-Brunner synthesis of triazoles from imides: a) K. Brunner, Ber. Dtsch. Chem. Ges. 1914, 47, 2671;
40. b) A. Einhorn, E. Bischkopff, B. Szelinski, G. Schupp, E. Spröngerts, C. Ladisch, T. Mauermayer, Justus Liebigs Ann. Chem. 1905, 343, 207.
41. a) J. R. Martinelli, D. A. Watson, D. M. M. Freckmann, T. E. Barder, S. L. Buchwald, J. Org. Chem. 2008, 73, 7102.
42. For an excellent review of recent advances in the carbonylation of aryl halides see: b) A. Brennführer, H. Neumann, M. Beller, Angew. Chem. 2009, 121, 4176;
43. Angew. Chem. Int. Ed. 2009, 48, 4114.
44. 13CNMR, and HRMS data.
45. A typical synthesis of a 5-aryl-1,2,4-triazole from an aryl halide involves conversion of the aryl halide to a primary benzamide followed by formation of an acylamidine by heating with a dimethylamide dialkyl acetal (i.e. dimethylacetamide dimethyl acetal) and addition/cyclization of a monosubstituted hydrazine.
46. To the best of our knowledge, this is the first report of a carbonylative coupling of an amidine to an aryl halide.
47. 3. Compound 3 was also synthesized in a stepwise fashion. The acylamidine intermediate shown was isolated in 66% yield by reverse-phase HPLC to support its intermediacy in the triazole synthesis (see the Supporting Information for details). chemical equation presented
48. No regioisomers were observed by LCMS analysis of the crude reaction mixtures. Regiochemistry was determined by 2D NOESY for compounds 4, 10, 11, and 13 as well as by HMBC correlation for 10 and 13. The remaining compounds were assigned by analogy.
49. The cyclization stage is typically run at ≈80°C to ensure complete conversion of the acylamidine intermediate, although the reaction is often complete at room temperature.
50. http://www.exjade.com/index.jsp (aka ICL670);
51. a) H. Nick, P. Acklin, R. Lattmann, P. Buehlmayer, S. Hauffe, J. Schupp, D. Alberti, Curr. Med. Chem. 2003, 10, 1065;
52. b) U. Heinz, K. Hegetschweiler, P. Acklin, B. Faller, R. Lattmann, H. P. Schnebli, Angew. Chem. 1999, 111, 2733;
53. Angew. Chem. Int. Ed. 1999, 35, 2568.
54. Notably, all aryl halides, amidines, and hydrazines used are commercially available.