Synthesis of dihydropyridines and pyridines from imines and alkynes via C-H activation

Journal of the American Chemical Society

Volumn 130, Issue 11, 2008, Pages 3645-3651

  Colby, Denise A ^a   Bergman, Robert G ^a   Ellman, Jonathan A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKENYLATION; COPASI SOFTWARE; DIHYDROPYRIDINES; ELECTROCYCLIZATION;

ACTIVATION ENERGY; AROMATIZATION; HYDROCARBONS; LIGANDS; SYNTHESIS (CHEMICAL); X RAY ANALYSIS;

AMINES;

ALKYNE; DIHYDROPYRIDINE; IMINE; KETIMINE; N BENZYLALDIMINE; PYRIDINE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; COMPUTER PROGRAM; DRUG DETERMINATION; DRUG STRUCTURE; KINETICS; ONE POT SYNTHESIS; SIMULATION; X RAY ANALYSIS;

ALKYNES; CRYSTALLOGRAPHY, X-RAY; DIHYDROPYRIDINES; IMINES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRIDINES; STEREOISOMERISM; TIME FACTORS;

EID: 41449111035     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja7104784     Document Type: Article

References (47)

1. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 4th ed.; Blackwell: Oxford, UK, 2000.
2. Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2006, 4, 2337-2347.
3. For recent reviews on pyridine syntheses, see the following and references therein: (a) Varela, J.; Saa, C. Chem. Rev. 2003, 103, 3787-3801.
4. (b) Zeni, G.; Larock, R. L. Chem. Rev. 2006, 106, 4644-4680.
5. For recent examples of transition-metal facilitated pyridine syntheses, see: (c) Trost, B. M.; Gutierrez, A. C. Org. Lett. 2007, 9, 1473-1476.
6. (d) Movassaghi, M.; Hill, M. D. J. Am. Chem. Soc. 2006, 128, 4592-4593.
7. (e) McCormick, M. M.; Duong, H. A.; Zuo, G.; Louie, J. J. Am. Chem. Soc. 2005, 127, 5030-5031.
8. (f) Yamamoto, Y.; Kinpara, K.; Ogawa, R.; Nishiyama, H.; Itoh, K. Chem. Eur. J. 2006, 12, 5618-5631.
9. (g) Tanaka, R.; Yuza, A.; Watai, Y.; Suzuki, D.; Takayama, Y.; Sato, F.; Urabe, H. J. Am. Chem. Soc. 2005, 127, 7774-7780.
10. (h) Takahashi, T.; Tsai, F.-Y.; Li, Y.; Wang, H.; Kondo, Y.; Yamanaka, M.; Nakajima, K.; Kotora M. J. Am. Chem. Soc. 2002, 124, 5059-5067.
11. For pyridine syntheses from Diels Alder inputs, see: (i) Boger, D. L. Chem. Rev. 1986, 86, 781-793.
12. (j) Fletchter, M. D.; Hurst, T. E.; Miles, T. J.; Moody, C. J. Tetrahedron 2006, 62, 5454-5463.
13. (k) Saito, A.; Hironaga, M.; Oda, S.; Harzawa, Y. Tetrahedron Lett. 2007, 48, 6852-6855.
14. Movassaghi, M.; Hill, M. D.; Ahmad, O. K. J. Am. Chem. Soc. 2007, 129, 10096-10097.
15. For an example of pyridine synthesis from oxime and alkyne inputs via C-H activation, see: Parthasarathy, K.; Jeganmohan, M.; Cheng, C.-H. Org. Lett. 2008, 10, 325-328.
16. For previous studies on chelation-assisted alkenylation proceeding via C-H activation, see the following: (a) Lim, S.-G.; Lee, J. H.; Moon, C. W.; Hong, J.-B.; Jun, C.-H. Org. Lett. 2003, 5, 2759-2761.
17. (b) Lim, Y.-G.; Lee, K.-H.; Koo, B. T.; Kang, J.-B. Tetrahedron Lett. 2001, 42, 7609-7612.
18. (c) Kakiuchi, F.; Uetsuhara, T.; Tanaka, Y.; Chatani, N.; Murai, S. J. Mol. Cat. A 2002, 183-183, 511-514.
19. Colby, D. A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2006, 128, 5604-5605.
20. Similar reactivity was reported by Odom in the β-alkylation of the N-phenyl imine of 1-acetylcyclohexene, which was prepared in situ by Ti - mediated hydroamination of cyclohexenylacetylene. See: Cao, C.; Li, Y.; Shi, Y.; Odom, A. L. Chem. Commun. 2004, 2002-2003.
21. (a) Thalji, R. L.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J. A. J. Org. Chem. 2005, 70, 6775-6781.
22. (b) O'Malley, S. J.; Tan, K. L.; Watzke, A.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 13496-13497.
23. Guram, A. S.; King, A. O.; Allen, J. G.; Wang, X.; Schenkel, L. B.; Chan, J.; Bunel, E. E.; Faul, M. M.; Larsen, R. D.; Martinelli, M. J.; Reider, P. J. Org. Lett. 2006, 8, 1787-1789.
24. Many of the DHP products are not stable to chromatographic purification, and therefore only NMR yields are reported.
25. The Diels-Alder reaction of aza-dienes with activated alkynes provides 1,4-DHP products, which can be converted to the corresponding pyridines. However, the scope of this transformation is limited to highly activated alkynes. (See refs 3i,j.)
26. Wallace, D. J.; Gibb, A. D.; Cottrell, I. F.; Kennedy, D. J.; Brands, K. M. J.; Dolling, U. H. Synthesis 2001, 12, 1784-1789.
27. Eynde, J. J. V.; Delfosse, F.; Mayence, A.; van Haverbeke, Y. Tetrahedron 1995, 23, 6511-6516.
28. Lemire, A.; Grenon, M.; Pourashraf, M.; Charette, A. B. Org. Lett. 2004, 6, 3517-3520.
29. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Org. Lett. 2002, 4, 3955-3957.
30. Bennasar, M.-L.; Zulaica, E.; Roca, T.; Alonso, Y.; Monerris, M. Tetrahedron Lett. 2003, 44, 4711-4714.
31. (a) Zhu, X.-Q.; Zhao, B.-J.; Cheng, J.-P. J. Org. Chem. 2000, 65, 8158-8163.
32. (b) For a review on the chemistry of dihydropyridines see: Lavilla, R. J. Chem. Soc., Perkin Trans. 1 2002, 1141-1156.
33. (a) Albinati, A.; Arz, C.; Pregosin, P. S. J. Organomet. Chem. 1987, 335, 379-394.
34. (b) Hara, T.; Yamagata, T.; Mashima, K.; Kataoka, Y. Organometallics 2007, 26, 110-118.
35. See supporting information for further spectroscopic discussion and evidence for the identity and purity of isolated 17.
36. For mechanistic studies on other chelation-assisted C-H alkylations, see: (a) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem. Eur. J. 2002, 8, 2423-2328.
37. (b) Kakiuchi, F.; Ohtaki, H.; Sonoda, M.; Chatani, N.; Murai, S. Chem. Lett. 2001, 918-919.
38. (c) Lenges, C. P.; Brookhart, M. J. Am. Chem. Soc. 1999, 121, 6616-6623.
39. Alternatively, carbometalation of the alkyne could occur generating a seven-membered aza-metallacycle. In addition to the instability of the seven-membered intermediate, carbometalation should place the more sterically hindered substituent distal to the nitrogen, which is opposite to the regioselectivity observed in our case (Table 2 entries 2-4, 8, 10-12).
40. Copasi, version 4.2 was employed for these simulations. See Hoops, S.; Sahle, S.; Gauges, R.; Lee, C.; Pahle, J.; Simus, N.; Singhal, M.; Xu, L.; Mendes, P.; Kummer, U. Bioinformatics 2006, 22, 3067-3074. For further information or to download Copasi, see http://www.copasi.org/tiki- index.php.
41. For recent examples of transition-metal mediated systems modeled using an early version of the Copasi software Gepasi, see: (a) Watson, M. P.; Overman, L. E.; Bergman, R. G. J. Am. Chem. Soc. 2007, 129, 5031-5044.
42. (b) Ghosh, R.; Zhang, X.; Achord, P.; Emge, T. J.; Krogh-Jespersen, K.; Goldman, A. S. J. Am. Chem. Soc. 2007, 129, 853-866.
43. (c) Wiedemann, S. H.; Lewis, J. C.; Ellman, J. A.; Bergman, R. G. J. Am. Chem. Soc. 2006, 128, 2452-2462.
44. 2, and 5 equiv of alkyne were used.
45. For another example where rate constants were determined for 6π electrocyclizations of azatrienes, see: Maynard, D. F.; Okamura, W. H. J. Org. Chem. 1995, 60, 1763-1771.
46. For examples of DHP formation via azatriene intermediates see the following and references therein: (a) Sydorenko, N.; Hsung, R. P.; Vera, E. L. Org. Lett. 2006, 8, 2611-2614.
47. (b) Tanaka, K.; Mori, H.; Yamamoto, M.; Katsumura, S. J. Org. Chem. 2001, 66, 3099-3110.