Stabilised 2,3-pyridyne reactive intermediates of exceptional dienophilicity

European Journal of Organic Chemistry

Volumn , Issue 16, 2004, Pages 3477-3483

  Connon, Stephen J ^a   Hegarty, Anthony F ^b  

^a TRINITY COLLEGE DUBLIN   (Ireland)

^b UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

Lithium; Metalation; Nitrogen heterocycles; Substituent effects

Indexed keywords

CARBON; HYDROGEN; LITHIUM CHLORIDE; METHYL GROUP; PYRIDINE;

ARTICLE; CYCLOADDITION; DIELS ALDER REACTION; LITHIATION; REACTION ANALYSIS; TEMPERATURE;

EID: 4544232728     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/ejoc.200400232     Document Type: Article

References (34)

1. For reviews see: [1a] H. Hart, The Chemistry of Triple Bonded Functional Groups, Wiley, Chichester, 1994, supplement C2, p. 1113.
2. [1b] M. G. Reinecke, Tetrahedron 1982, 38, 427.
3. [1c] H. C. Van der Plas, F. Roeterdink, The Chemistry of Functional Groups, Wiley, Chichester, 1983, supplement C, p. 421.
4. [2a] T. Kauffmann, F. P. Boettcher, Chem. Ber. 1962, 95, 949.
5. [2b] G. W. Fleet, I. Fleming, J. Chem. Soc. C 1969, 1758.
6. [2c] W J. Van Zoest, H. J. Den Hertog, Recl. Trav. Chim. Pays-Bas 1974, 93, 166.
7. [2d] C. May, C. J. Moody, J. Chem. Soc., Perkin Trans. 1 1988, 247.
8. [2e] M. Tsukazaki, V. Snieckus, Heterocycles 1992, 33, 533.
9. [2f] G. W. Gribble, M. G. Saulnier, Heterocycles 1993, 35, 151.
10. [2g] N. Mariet, M. Ibrahim-Ouali, M. Santelli, Tetrahedron Lett. 2002, 43, 5789.
11. [3a] G. W. Gribble, M. G. Saulnier, M. P. Sibi, J. A. Obaza-Nutaitis, J. Org. Chem. 1984, 49, 4518.
12. [3b] M. Diaz, A. Cobas, E. Guitian, L. Castedo, Eur. J. Org Chem. 2001, 4543.
13. J. D. Cook, B. J. Wakefield, J. Chem. Soc. C 1969, 1973.
14. J. J. Shay, M. A. Walters, Synth. Commun. 1997, 27, 3573.
15. For an isolated example of 2,3-pyridyne in synthesis see: J. Kurita, N. Kakusawa, S. Yasuike, T. Tsuchiya, Heterocycles 1990, 31, 1937.
16. S. J. Connon, A. F. Hegarty, J. Chem. Soc., Perkin Trans. 1 2000, 1245.
17. Recent computational studies have also suggested that 2,3-pyridyne is considerably less stable than the 3,4-isomer. These studies have also indicated that zwitterionic resonance forms make a greater contribution to the overall structure of pyridyne isomers which possess at least one dehydro centre adjacent on the ring nitrogen atom relative to either other isomeric pyridynes or benzyne: [8a] C. J. Cramer, S. Debbert, Chem. Phys. Lett. 1998, 287, 320.
18. [8b] S. L. Debbert, C. J. Cramer, Int. J. Mass. Spectrom. 2000, 201, 1.
19. S. Banerjee, P. H. Carter, M. A. Walters, Synth. Commun. 1992, 22, 2829.
20. J. Shay, M. A. Walters, Tetrahedron Lett. 1995, 36, 7575.
21. H. C. Van der Lans, H. J. Den Hertog, Recl. Trav. Chim. Pays-Bas 1968, 87, 549.
22. S. J. Connon, A. F. Hegarty, Tetrahedron Lett. 2001, 42, 735.
23. L. Lai, P. Lin, J. Wang, J. Hwu, M. Shiao, S. Tsay, J. Chem. Res. (S) 1996, 4, 194.
24. T. R. Kasturi, H. Jois, L. Matthew, Synthesis 1984, 9, 743.
25. G. Finger, L. Starr, J. Am. Chem. Soc. 1959, 81, 2674.
26. a = 26): G. Seconi, C. Eaborn, A. Fischer, J. Organomet. Chem. 1979, 177, 129.
27. Comins et al. have found that 39 can be selectively lithiated at C-3, demonstrating the superiority of the 2-methoxy moiety over the 6-halogeno in terms of ortho-directing ability in these reactions. This would indicate that 41b, which is also stabilised by the inductive withdrawing ability of the 4-bromo atom is the most likely intermediate, although the formation of 41a,c,d in situ cannot be fully discounted: D. Comins, M. Baevsky, H. Hong, J. Am. Chem. Soc. 1992, 114, 10971.
28. It is acknowledged that the success of the 4-alkoxypyridyne in the Diels-Alder reaction may also be in part related to kinetic factors such as hetaryne-furan LUMO-HOMO interactions.
29. For review, see: H. Hauptmann, W. Walter, Chem. Rev. 1962, 12, 347.
30. BCHD rearrangements are known in similar systems and are a ubiquitous problem associated with hetaryne formation by bromine/metal exchange reactions; for examples, see ref.[1c] and: [20a] M. Mallet, F. Marsais, G. Queguiner, P. Pastour, C. R. Acad. Sci. Ser. C 1972, 275, 1439.
31. [20b] M. J. Pieterse, H. J. den Hertog, Recl. Trav. Chim. Pays-Bas 1961, 80, 1376.
32. The product ratio 17/18 was found to be independent of the order of addition of tBuLi and 16.
33. M. Adger, P. Ayrey, R. Bannister, M. A. Forth, Y. Hajikarumian, N. Lewis, C. O'Farrell, N. Owens, A. Shamji, J Chem. Soc., Perkin Trans. 1 1988, 2791.
34. H. Schoelkopf, I. Hoppe, Justus Liebigs Ann. Chem. 1972, 765, 153.