In-line proximity effects in extended 7-azanorbornanes. 2. a major reduction of N-inversion barriers in symmetrically flanked systems

Organic Letters

Volumn 2, Issue 6, 2000, Pages 725-728

  Malpass, John R ^a   Butler, Douglas N ^b   Johnston, Martin R ^b   Hammond, Malcom L A ^b   Warrener, Ronald N ^b  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

^b CENTRAL QUEENSLAND UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000286237     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol9911019     Document Type: Article

References (29)

1. Epibatidine, a compound with potent analgesic activity, is a chloropyridyl derivative of 7-azabicyclo[2.2.1]heptane and was discovered in 1992: Spande, T. F.; Garraffo, H. M.; Edwards, M. W.; Yeh, H. J. C.; Pannell L.; Daly, J. W. J. Am. Chem. Soc. 1992, 114, 3475-3478. References to the very wide range of syntheses of epibatidine can be found in, for example, the following: Aoyogi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. J. Org. Chem. 1998, 63, 8397-8406. Palmgren, A.; Larsson, A. L. E.; Bäckvall, J.-E.; Helquist, P. J. Org. Chem. 1999, 64, 836-842.
2. Epibatidine, a compound with potent analgesic activity, is a chloropyridyl derivative of 7-azabicyclo[2.2.1]heptane and was discovered in 1992: Spande, T. F.; Garraffo, H. M.; Edwards, M. W.; Yeh, H. J. C.; Pannell L.; Daly, J. W. J. Am. Chem. Soc. 1992, 114, 3475-3478. References to the very wide range of syntheses of epibatidine can be found in, for example, the following: Aoyogi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. J. Org. Chem. 1998, 63, 8397-8406. Palmgren, A.; Larsson, A. L. E.; Bäckvall, J.-E.; Helquist, P. J. Org. Chem. 1999, 64, 836-842.
3. Epibatidine, a compound with potent analgesic activity, is a chloropyridyl derivative of 7-azabicyclo[2.2.1]heptane and was discovered in 1992: Spande, T. F.; Garraffo, H. M.; Edwards, M. W.; Yeh, H. J. C.; Pannell L.; Daly, J. W. J. Am. Chem. Soc. 1992, 114, 3475-3478. References to the very wide range of syntheses of epibatidine can be found in, for example, the following: Aoyogi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. J. Org. Chem. 1998, 63, 8397-8406. Palmgren, A.; Larsson, A. L. E.; Bäckvall, J.-E.; Helquist, P. J. Org. Chem. 1999, 64, 836-842.
4. Lehn, J. M. Fortschr. Chem. Forsch. 1970, 15, 311-377.
5. (a) For a view based largely on transition state strain, see: Bushweller, C. H.; Brown, J. H.; DiMeglio, C. M.; Gribble, G. W.; Eaton, J. T.; LeHoullier, C. S.; Olson, E. R. J. Org. Chem. 1995, 60, 268-271.
6. (b) Belostotskii, A. M.; Gottlieb, H. E.; Hassner, A. J. Am. Chem. Soc. 1996, 118, 7783-7789.
7. For consideration of contributions to the inversion process in azabicycles from torsional strain, see: (c) Forsyth, D. A.; Zhang, W.; Hanley, J. A. J. Org. Chem. 1996, 61, 1284-1289. See also references in footnote 13.
8. For example, triisopropylamine, where serious flattening of the ground state occurs as a result of interactions between three spatially demanding groups attached directly to nitrogen: (a) Bock, H.; Goebel, I.; Havlas, S. L.; Oberhammer, H. Angew. Chem., Int. Ed. Engl. 1991, 30, 187-190.
9. (b) Anderson, J. E.; Casarini, D.; Lunazzi, L. J. Org. Chem. 1996, 61, 1290-1296.
10. (c) Wong, T. C.; Collazo, L. R.; Guziec F. S., Jr. Tetrahedron 1995, 51, 649-656.
11. 13C NMR spectrum): Wiseman, J. R.; Krabbenhoft, H. O.; Lee, R. E. J. Org. Chem. 1977, 42, 629-632. No conclusions concerning N-inversion were possible in this work. See also: Nelsen, S. F. J. Org. Chem. 1984, 49, 1891-1897.
12. 13C NMR spectrum): Wiseman, J. R.; Krabbenhoft, H. O.; Lee, R. E. J. Org. Chem. 1977, 42, 629-632. No conclusions concerning N-inversion were possible in this work. See also: Nelsen, S. F. J. Org. Chem. 1984, 49, 1891-1897.
13. 3b
14. 7
15. Butler, D. N.; Hammond, M. A. L.; Johnston, M. R.; Sun, G.; Malpass, J. R.; Fawcett, J.; Warrener, R. N. Org. Lett. 2000, 2, 721-724.
16. 3b
17. 7
18. -1.
19. Deloughry, W. J.; Sutherland, I. O. Chem. Commun. 1971, 1104-1105.
20. Davies, J. W.; Durrant, M. L.; Walker, M. P.; Belkacemi, D.; Malpass, J. R. Tetrahedron 1992, 48, 861-884.
21. 2 transition state, in which the nitrogen lone pair occupies a p-orbital. If this stabilization of the ground state does indeed operate, it will counter the destabilizing effects proposed in the present work and may therefore be expected to moderate them to some extent.
22. 2 transition state, in which the nitrogen lone pair occupies a p-orbital. If this stabilization of the ground state does indeed operate, it will counter the destabilizing effects proposed in the present work and may therefore be expected to moderate them to some extent.
23. 2 transition state, in which the nitrogen lone pair occupies a p-orbital. If this stabilization of the ground state does indeed operate, it will counter the destabilizing effects proposed in the present work and may therefore be expected to moderate them to some extent.
24. (b) Belkacemi, D.; Davies, J. W.; Malpass, J. R.; Naylor, A.; Smith, C. R. Tetrahedron 1992, 48, 10161-10176.
25. -1.
26. 2 is replaced by N and O, and this effect (C > N > O) is in the same order as that observed here. Warrener, R. N.; Margetic, D.; Sun, G.; Amarasekara, A. S.; Foley, P.; Butler, D. N.; Russell, R. A. Tetrahedron Lett. 1999, 40, 4111-4114.
27. 15N NMR spectroscopy is a useful tool for probing changes of hybridization in these systems, and this work will be published separately.
28. Martin, H.-D.; Mayer, B. Angew. Chem., Int. Ed. Engl. 1983, 22, 283-313. Altenbach, H.-J.; Constant, D.; Martin, H.-D.; Muller, M.; Vogel, E. Chem. Ber. 1991, 124, 791-801 and references therein.
29. Martin, H.-D.; Mayer, B. Angew. Chem., Int. Ed. Engl. 1983, 22, 283-313. Altenbach, H.-J.; Constant, D.; Martin, H.-D.; Muller, M.; Vogel, E. Chem. Ber. 1991, 124, 791-801 and references therein.