A convenient synthesis of enaminones using tandem acetonitrile condensation Grignard addition

Tetrahedron Letters

Volumn 38, Issue 24, 1997, Pages 4191-4194

  Haight, Anthony R ^a   Stuk, Timothy L ^a   Menzia, Jerome A ^a   Robbins, Timothy A ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID DERIVATIVE;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; METHODOLOGY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS;

EID: 0031006749     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00866-6     Document Type: Article

References (18)

1. Kempf, D. J.; Marsh, K. C.; Denissen, J. F.; McDonald, E.; Vasavanonda, S.; Flentge, C. A.; Green, B. E.; Fino, L.; Park, C. H.; Kong, X-P.; Wideburg, N. E.; Saldivar, A.; Ruiz, L.; Kati, W. M.; Sham, H. L.; Robins, T.; Stewart, K. D.; Hsu, A.; Plattner, J. J.; Leonard, J. M.; Norbeck, D. W., Proc. Natl. Acad. Sci. USA, 1995, 92, 2484.
2. For routes to 2 see: (a) Kempf, D. J.; Norbeck, D. W.; Codacovi, L.; Wang, X. C.; Kohlbrenner, W. F.; Wideburg, N. E.; Saldivar, A.; Craig-Kennard, A.; Vasavanonda, S.; Clement, J. J.; Erikson, J. In Recent Advances in the Chemistry of Anti-infective Agents, Cambridge Press, Cambridge, 1993, 297.
3. (b) Baker, W. R.; Pratt, J. K., Tetrahedron, 1993, 49, 8739.
4. (c) Rao, A. V. R.; Gurjar, M. K.; Pal, S.; Pariza, R. J.; Chorghade, M. S., Tetrahedron Lett, 1995, 36, 2505.
5. (d) Nishikawa, M.; Murai, Y.; Onomura, O.; Ueda, Y., Abstracts of the 15th International Congress of Heterocyclic Chemistry, Taipei, 1995, PO2-134.
6. (e) Yamasaki, T.; Kumobayashi, H.; Sayo, N.; Murayama, T.; Sano, N.; Ishizaki, T., US Patent 5,523,458, 1996.
7. (a) Stuk, T. L,.; Haight, A. R.; Scarpetti, D.; Allen, M. S.; Menzia, J. A.; Robbins, T. A.; Parekh, S. I.; Langridge, D. C.; Tien, J-H. J.; Pariza, R. J.; Kerdesky, F. A. J., J. Org. Chem., 1994, 59, 4040.
8. (b) Stuk, T. L.; Allen, M. S.; Haight, A. R.; Reno, D. S.; Sham, H. L.; Sowin, T. J., US Patent 5,508,409, 1996.
9. (c) Stuk, T. L.; .Allen, M. S.; Haight, A. R.; Lijewski, L. M.; Morton, H. E.; Reno, D. S.; Sham, H. L.; Sowin, T. J., US Patent 5,565,604, 1996.
10. The chiral purity of 3a was >99% prior to the acetonitrile condensation. Exposure of 4 to stressed reaction conditions (room temperature/24hrs) did not cause racemization.
11. Use of bases such as KOH, KOtBu, NaH, KHMDS, LiHMDS, led to incomplete reactions, slow conversions, or racemization.
12. HPLC determination of enantiomeric ratios: Diacel Chiracel OD (250mm×4.6mm) column, hexane/isopropyl alcohol, 98/2 to 85/15.
13. 13C NMR spectra.
14. D -147° (c=0.5, DMF).
15. Isolated as a 1:1 ratio of diastereomers.
16. Compare Hrubiec, R. T.; Smith, M. B., J. Org. Chem., 1984, 49, 431 to Ihara, M.; Tokunaga, Y.; Fukumoto, K., J. Org. Chem., 1990, 55, 4497
17. Compare Hrubiec, R. T.; Smith, M. B., J. Org. Chem., 1984, 49, 431 to Ihara, M.; Tokunaga, Y.; Fukumoto, K., J. Org. Chem., 1990, 55, 4497
18. Additional benzylmagnesium chloride can be added if the reaction is incomplete.