An unexpected [1,5]-H shift in the synthesis of nitroanilines

Organic Letters

Volumn 4, Issue 3, 2002, Pages 439-441

  Davies, Ian W ^a   Marcoux, Jean François ^a   Taylor, Jeremy D O ^a   Dormer, Peter G ^a   Deeth, Robert J ^a   Marcotte, Félix Antoine ^a   Hughes, David L ^a   Reider, Paul J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE;

EID: 0042867298     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol017149f     Document Type: Article

References (26)

1. Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969, 8, 781.
2. Roth, W. R.; Konig, J. Liebigs Ann. 1966, 699, 24.
3. Houk, K. N.; Li, Y.; Evanseck, J. D. Angew. Chem., Int. Ed. Engl. 1992, 31, 682.
4. Saettel, N. J.; Wiest, O. J. Org. Chem. 2000, 65, 2331.
5. Bachrach, S. J. Org. Chem. 1993, 58, 5414. Roth, W. R. Tetrahedron Lett. 1964, 1009.
6. Bachrach, S. J. Org. Chem. 1993, 58, 5414. Roth, W. R. Tetrahedron Lett. 1964, 1009.
7. Paquette, L. A.; Crouse, G. D.; Sharman, A. K. J. Am. Chem. Soc. 1980, 102, 3972.
8. Davies, I. W.; Marcoux, J.-F.; Corley, E. G.; Journet, M.; Cai, D.-W.; Palucki, M.; Wu, J.; Larsen, R. D.; Rossen, K.; Pye, P. J.; DiMichele, L.; Dormer, P.; Reider, P. J. J. Org. Chem. 2000, 65, 8415.
9. Gupton, J. T.; Krolikowski, D. A.; Yu, R. H.; Riesinger, S. W. Sikorski, J. A. J. Org. Chem. 1990, 55, 4735. Gupton, J. T.; Petrich, S. A.; Hicks, F. A.; Wilkinson, D. R.; Vargas, M.; Hosein, K. N.; Sikorski, J. A. Heterocycles 1998, 47, 689. Kase, K.; Katayama, M.; Ishirara, T.; Yamanaka, H.; Gupton, J. T. J. Fluorine Chem. 1998, 90, 29.
10. Gupton, J. T.; Krolikowski, D. A.; Yu, R. H.; Riesinger, S. W. Sikorski, J. A. J. Org. Chem. 1990, 55, 4735. Gupton, J. T.; Petrich, S. A.; Hicks, F. A.; Wilkinson, D. R.; Vargas, M.; Hosein, K. N.; Sikorski, J. A. Heterocycles 1998, 47, 689. Kase, K.; Katayama, M.; Ishirara, T.; Yamanaka, H.; Gupton, J. T. J. Fluorine Chem. 1998, 90, 29.
11. Gupton, J. T.; Krolikowski, D. A.; Yu, R. H.; Riesinger, S. W. Sikorski, J. A. J. Org. Chem. 1990, 55, 4735. Gupton, J. T.; Petrich, S. A.; Hicks, F. A.; Wilkinson, D. R.; Vargas, M.; Hosein, K. N.; Sikorski, J. A. Heterocycles 1998, 47, 689. Kase, K.; Katayama, M.; Ishirara, T.; Yamanaka, H.; Gupton, J. T. J. Fluorine Chem. 1998, 90, 29.
12. Marcoux, J.-F.; Marcotte, F.-A.; Wu, J.; Dormer, P.; Davies, I. W.; Hughes, D.; Reider, P. J. J. Org. Chem. 2001, 66, 4194.
13. + 225.0864.
14. Nair, V.; Cooper, C. S. J. Org. Chem. 1981, 46, 6, 4759.
15. For a simple model to predict the effect of substituents on the rates of thermal pericyclic reactions, see: Carpenter, B. Tetrahedron 1978, 34, 1877.
16. 3 reduction of the chlorovinamidinium salt followed by nitration, see: Davies, I. W.; Marcoux, J.-F.; Wu, J.; Corley, E. G.; Robbins, M. A.; Palucki, M.; Tsou, N.; Ball, R. G.; Dormer, P.; Larsen, R. D.; Reider, P. J. J. Org. Chem. 2000, 65, 4571. Davies, I. W.; Taylor, M.; Hughes, D.; Reider, P. J. Org. Lett. 2000, 2, 3385.
17. 3 reduction of the chlorovinamidinium salt followed by nitration, see: Davies, I. W.; Marcoux, J.-F.; Wu, J.; Corley, E. G.; Robbins, M. A.; Palucki, M.; Tsou, N.; Ball, R. G.; Dormer, P.; Larsen, R. D.; Reider, P. J. J. Org. Chem. 2000, 65, 4571. Davies, I. W.; Taylor, M.; Hughes, D.; Reider, P. J. Org. Lett. 2000, 2, 3385.
18. The products were characterized by proton and deuterium NMR spectroscopy, elemental analysis, and high-resolution mass spectrometry. The limit of detection for the proton signal is < 0.3 mol %.
19. Almy, J.; Uyeda, R. T.; Cram, D. J. J. Am. Chem. Soc. 1967, 89, 6768.
20. In these cases, deuterium was incorporated in up to 47% at the site derived from the enolizable methyl ketone without incorporation at any other site.
21. The vinamidinium salts were prepared via amine exchange, see: Davies, I. W.; Taylor, M.; Marcoux, J.-F.; Wu, J.; Dormer, P. G.; Hughes, D.; Reider, P. J. J. Org. Chem. 2001, 66, 251.
22. -1 at 25 °C and is exothermic by -39 kcal/mol.
23. The 3-nitro-4-aminobenzoate motif is a feature of combinatorial libraries directed at G protein-coupled receptors. Pan, P.-C.; Sun, C.-M. Tetrahedron Lett. 1998, 39, 9505. For intermediates in the synthesis of influenza neuraminidase inhibitors, see: Brouillette, J. W.; Atigadda, V. R.; Luo, M.; Air, G. M.; Babu, Y. S.; Bantia, S. Bioorg. Med. Chem. Lett. 1999, 9, 1901. For the use of 3-nitro-4-aminobenzoates in the solid-phase synthesis of benzopiperazinones, see: Morales, G.; Corbett, J. W.; DeGrabo, W. F. J. Org. Chem. 1998, 63, 1172.
24. The 3-nitro-4-aminobenzoate motif is a feature of combinatorial libraries directed at G protein-coupled receptors. Pan, P.-C.; Sun, C.-M. Tetrahedron Lett. 1998, 39, 9505. For intermediates in the synthesis of influenza neuraminidase inhibitors, see: Brouillette, J. W.; Atigadda, V. R.; Luo, M.; Air, G. M.; Babu, Y. S.; Bantia, S. Bioorg. Med. Chem. Lett. 1999, 9, 1901. For the use of 3-nitro-4-aminobenzoates in the solid-phase synthesis of benzopiperazinones, see: Morales, G.; Corbett, J. W.; DeGrabo, W. F. J. Org. Chem. 1998, 63, 1172.
25. The 3-nitro-4-aminobenzoate motif is a feature of combinatorial libraries directed at G protein-coupled receptors. Pan, P.-C.; Sun, C.-M. Tetrahedron Lett. 1998, 39, 9505. For intermediates in the synthesis of influenza neuraminidase inhibitors, see: Brouillette, J. W.; Atigadda, V. R.; Luo, M.; Air, G. M.; Babu, Y. S.; Bantia, S. Bioorg. Med. Chem. Lett. 1999, 9, 1901. For the use of 3-nitro-4-aminobenzoates in the solid-phase synthesis of benzopiperazinones, see: Morales, G.; Corbett, J. W.; DeGrabo, W. F. J. Org. Chem. 1998, 63, 1172.
26. Preliminary results indicate that the reaction is not limited to MAA and 2,4-pentanedione works effectively with 1a to give a 30:1 mixture of aniline and phenol in 80% yield.