A high-yielding preparation of β-ketonitriles

Organic Letters

Volumn 8, Issue 6, 2006, Pages 1161-1163

  Ji, Yaohui ^a   Trenkle, William C ^a   Vowles, James V ^a  

^a BROWN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33646442757     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol053164z     Document Type: Article

References (15)

1. Elnagdi, M. H.; Elgemeie, G. E. H. Synthesis 1984, 1-26.
2. Ranatunge, R. R.; Garvey, D. S.; Janero, D. R.; Letts, L. G.; Martino, A. M.; Murty, M. G.; Richardson, S. K.; Young, D. V.; AZemetseva, I. S. Bioorg. Med. Chem. 2004, 12, 1357-1366.
3. Eddington, N. D.; Cox, D. S.; Roberts, R. R.; Butcher, R. J.; Edafiogho, I. O.; Stables, J. P.; Cooke, N.; Goodwin, A. M.; Smith, C. A.; Scott, K. R. Eur. J. Med. Chem. 2002, 37, 635-648.
4. Hauser, C. R.; Eby, C. J. J. Am. Chem. Soc. 1957, 79, 728-731.
5. Laufer, S. A.; Zimmermann, W.; Ruff, K. J. J. Med. Chem. 2004, 47, 6311-6325.
6. Barkin, J. L.; Faust, M. D.; Trenkle, W. C. Org. Lett. 2003, 5, 3333-3335.
7. For a review of nitrile-stabilized carbanion reactivity, see: Arseniyadis, S.; Kyler, K. S.; Watt, D. S. Org. React. (N.Y.) 1984, 31, 1-364.
8. For a review of the chemistry of cyclic nitriles, see: Fleming, F. F.; Zhang, Z. Y. Tetrahedron 2005, 61, 747-789.
9. For an early example of intramolecular nitrile anion acylation using an alkoxide base, see: Blake, J.; Wilson, C. D.; Rapoport, H. J. Am. Chem. Soc. 1964, 86, 5293-5299.
10. For a recent example of nitrile carbanion acylation with an activated benztriazole ester, see: Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2003, 68, 4932-4934.
11. Eby, C. J.; Hauser, C. R. J. Am. Chem. Soc. 1957, 79, 723-725.
12. 13C NMR spectra.
13. Addition of the base to a mixture of the nitrile and ester gave identical yields in the cases examined.
14. 4), concentrated, and chromatographed (silica gel, EtOAc/Hex) to provide 149.5 mg (99%) of 6bw as a colorless oil.
15. β-Ketonitrile 6ay is exceptionally volatile, which made isolation difficult.