A one-pot access to 6-substituted phenanthridines from fluoroarenes and nitriles via 1,2-arynes

Organic Letters

Volumn 4, Issue 16, 2002, Pages 2687-2690

  Pawlas, Jan ^a   Begtrup, Mikael ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE;

EID: 0042691466     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol026197c     Document Type: Article

References (47)

1. For reviews, see: (a) Hoffmann, R. W. Dehydrobenzene and Cycloalkynes; Academic Press: New York, 1967.
2. (b) Reinecke, M. G. Tetrahedron 1982, 38, 427-498.
3. Biehl, E. R.; Khanapure, S. P. Acc. Chem. Res. 1989, 22, 275-281.
4. Kessar, S. V. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, Chapter 2.3.
5. Kitamura, T.; Yamane, M.; Inoue, K.; Todaka, M.; Fukatsu, N.; Meng, Z.; Fujiwara, Y. J. Am. Chem. Soc. 1999, 121, 11674-11679.
6. (a) Clark, A. E.; Davidson, E. R. J. Am. Chem. Soc. 2001, 123, 10691-10698.
7. (b) Liu, H.-C.; Wang, C-S.; Guo, W.; Wu, Y.-D.; Yang, S. J. Am. Chem. Soc. 2002, 124, 3794-3798.
8. (a) Escudero, S.; Pérez, D.; Guitian, E.; Castedo, L. Tetrahedron Lett. 1997, 38, 5375-5378.
9. (b) Cobas, A.; Guitian, E.; Castedo, L. J. Org. Chem. 1997, 62, 4896-4897.
10. Rigby, J. H.; Laurent, S. J. Org. Chem. 1998, 63, 6742-6744.
11. Bailey, W. F.; Longstaff, S. C. J. Org. Chem. 1998, 63, 432-433.
12. (e) Frid, M.; Pérez, D.; Peat, A. J.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 9469-9470.
13. (f) Tripathy, S.; LeBlanc, R.; Durst, T. Org. Lett. 1999, 1, 1973-1975.
14. (h) Tomori, H.; Fox, J. M.; Buchwald, S. L. J. Org. Chem. 2000, 65, 5334-5341.
15. Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 7280-7286.
16. (j) Beller, M.; Breindl, C.; Riermeier, T. H.; Tillack, A. J. Org. Chem. 2001, 66, 1403-1412.
17. (k) Chatani, N.; Kamitani, A.; Oshita, M.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc. 2001, 123, 12686-12687.
18. Rayabarapu, D. K.; Majumdar K. K.; Sambaiah, T.; Cheng, C.-H. J. Org. Chem. 2001, 66, 3646-3649.
19. Rao, U. N.; Biehl, E. J. Org. Chem. 2002, 67, 3409-3411.
20. (n) Barluenga, J.; Fañanás, F. J.; Sanz, R.; Fernández, Y. Chem. Eur. J. 2002, 8, 2034-2045.
21. Biehl, E. R. In Advances in Nitrogen Heterocycles; Moody, C. J., Ed.; JAI Press Inc: New York, 2000; Vol. 4, pp 251-293 and references therein.
22. (a) For a leading reference on metal-catalyzed pyridine formation from two alkynes and a nitrile, see: Takahashi, T.; Tsai, F.-Y.; Li, Z.; Wang, H.; Kondo, Y.; Yamanaka, M.; Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 2002, 124, 5059-5067.
23. (b) For a novel method to construct pyridines from lithiobutadienes and nitriles, see: (1) Cheng, J.; Song, Q.; Wang, C.-S.; Xi, Z. J. Am. Chem. Soc. 2002, 124, 6238-6239.
24. For a benzyne-mediated pyridine formation in benzo[c]phenanthridines, see: Kessar, S. V.; Gupta, Y. P.; Balakrishnan, P.; Sawal, K. K.; Mohammad, T.; Dutt, M. J. Org. Chem. 1988, 53, 1708-1713.
25. 3 receptor ligands: Cappelli, A.; Anzini, M.; Vomero, S.; Mennuni, L.; Makovec, F.; Doucet, E.; Hamon, M.; Bruni, G.; Romeo, M. R.; Menziani, M. C.; De Benedetti, P. G.; Langer, T. J. Med. Chem. 1998, 41, 728-741.
26. (b) As topoisomerase inhibitors: Lynch, M. A.; Duval, O.; Sukhanova, A.; Devy, J.; MacKey, S. P.; Waigh, R. D.; Nabiev, I. Bioorg. Med. Chem. 2001, 11, 2643-2646.
27. As a tether in enzyme-controlled cycloaddition: Lewis, W. G.; Green, L. G.; Grynszpan, F.; Radic, Z.; Carlier, P. R.; Taylor, P.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 1053-1056.
28. (a) For a recent three-step protocol, see: Lysén, M.; Kristensen, J. L.; Vedsø P.; Begtrup, M. Org. Lett. 2002, 4. 257-259.
29. (b) Katritzky, A. R.; Yang, B.; Dalal, N. S. J. Org. Chem. 1998, 63, 1467-1472.
30. Patra, P. K.; Suresh, J. R.; H., I.; Junjappa, H. Tetrahedron 1998, 54, 10167-10178; see also references therein for listing of earlier methods.
31. For a route to pyrazoloquinolines by adding nitriles to a 2-fluorophenylpyrazolyllithium, see: Pawlas, J.; Vedsø, P.; Jakobsen, P.; Huusfeldt, P. O.; Begtrup, M. J. Org. Chem. 2001, 66, 4214-4219.
32. Gilman, H.; Gorsich, R. D. J. Am. Chem. Soc. 1955, 77, 3919-3920.
33. Snieckus, V. Chem. Rev. 1990, 90, 879-933.
34. Gilman, H.; Gorsich, R. D. J. Am. Chem. Soc. 1956, 78, 2217-2122.
35. PhLi can be formed from an alkylithium and benzyne: Franzen, V.; Joschek, H.-I. Angew. Chem. 1960, 72, 564.
36. 4), ca. 50 mL EtOAc was added, and filtration through a pad of silica gel (ca. 4 g) followed by evaporation afforded 257 mg (63%) of the title compound as yellow crystals, mp 100-101°C (EtOAc/heptane).
37. According to GC-MS, n-BuLi, MeLi, PhLi, and LDA gave only traces of 5.
38. 2O, or THF/dioxane as solvent gave <20% of 5, while the reactions performed at concentrations higher than those given in Table 1 provided 6 as the main product. Phenanthridine 5 was not obtained when PhCl was used instead of PhF.
39. Large amounts of 2-fluorobiphenyl were detected in the crude reaction mixture by GC-MS.
40. Free amino, nitro, and ester groups are not compatible witn this chemistry.
41. 3CN did not give 6-methylphenanthridine. An α-proton was abstracted by 2 instead to give 2-fluorobiphenyl as the major product. See ref 9a for a method enabling introduction of α-hydrogen-containing alkyl groups.
42. Bisphenanthridines of type 10 are unknown, and the potential uses of such systems are thus unexplored. On the other hand, the related terpyridines are well-known and have been used, e.g., in Ru-based cyclometalated complexes. See for example: (a) Beley, M.; Collin, J.-P.; Louis, R.; Metz, B.; Sauvage, J.-P. J. Am. Chem. Soc. 1991, 113, 8521-8522.
43. (b) Beley, M.; Chodorowski, S.; Collin, J.-P.; Sauvage, J.-P. Tetrahedron Lett. 1993, 2933-2936.
44. Chavarot, M.; Pikramenou, Z. Tetrahedron Lett. 1999, 6865-6868.
45. For a general discussion on addition of nucleophiles to unsymmetrically substituted arynes, see ref 1a, pp 134-150.
46. Both 3-and 2-fluorotoluenes also provided ca. 1:1 mixtures of regioisomers, but in much lower yields than 4-fluorotoluene.
47. 22