Unusual C-6 lithiation of 2-chloropyridine-mediated by BuLi-Me2N(CH2)2OLi. New access to 6-functional-2-chloropyridines and chloro-bis-heterocycles

Organic Letters

Volumn 2, Issue 6, 2000, Pages 803-805

  Choppin, Sabine ^a   Gros, Philippe ^a   Fort, Yves ^a  

^a NANCY UNIVERSITÉ   (France)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000419106     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol005538o     Document Type: Article

References (15)

1. Shepherd, R. G.; Fedrick, J. L. Adv. Heterocycl. Chem. 1965, 4, 145.
2. Trécourt, F.; Marsais, F.; Güngor, T.; Quéguiner, G. J. Chem. Soc., Perkin Trans. 1 1990, 9, 2409-2415.
3. Marsais, F.; Quéguiner, G. Tetrahedron 1983, 39, 2009-2021.
4. Gribble, G. W.; Saulnier, M. G. Tetrahedron Lett. 1980, 21, 4137-4140.
5. For reviews on directed orthometalation, see: (a) Snieckus, V. Chem. Rev. 1990, 90, 879-933.
6. (b) Marsais, F.; Quéguiner, G.; Snieckus, V.; Epsztajn, J. Adv. Heterocycl. Chem. 1991, 52, 187-303.
7. (a) Gros, Ph.; Fort, Y.; Quéguiner, G.; Caubère, P. Tetrahedron Lett. 1995, 36, 4791-4794.
8. (b) Gros, Ph.; Fort, Y.; Caubère, P. J. Chem. Soc., Perkin Trans. 1 1997, 20, 3071-3080.
9. Gros, Ph.; Fort, Y.; Caubère, P. J. Chem. Soc., Perkin Trans. 1 1997, 24, 3597-3600.
10. Gros, Ph.; Ben Younès-Millot, C.; Fort, Y. Tetrahedron Lett. 2000, 41, 303-306.
11. Compound 4 was obtained in 20% overall yield from 2-bromo-6-chloropyridine: Newkome, G. R.; Hager, D. C. J. Am. Chem. Soc. 1978, 100, 5567-5568.
12. Typical Procedure for C-6 Functionalization of 1. To a solution of 2-dimethylaminoethanol (0.72 g; 8 mmol) in hexane (5 mL) cooled at 0 °C, under a nitrogen atmosphere, was added dropwise n-BuLi (10 mL of a 1.6 M solution in hexanes; 16 mmol). After 30 min at 0°C, the reaction medium was cooled at -78°C and a solution of 2-chloropyridine (0.3 g; 2.67 mmol) in hexane (5 mL) was added dropwise. After 1 h at this temperature, the red solution was treated with a solution of the appropriate electrophile (10.67 mmol) in THF (20 mL). The reaction medium was then allowed to warm slowly to 0°C. Hydrolysis was then performed at this temperature with water. After usual aqueous workup, the products were purified by flash chromatography.
13. Gros, Ph.; Fort, Y. J. Chem. Soc., Perkin Trans. 1 1998, 10, 1685-1689.
14. For a recent review on the Stille coupling reaction, see: Farina, V.; Krishnamurthy, V.; Scott, W. J. In The Stille Reaction; John Wiley and Sons: New York, 1998.
15. Compound 5b has been prepared in 32% yield from the corresponding pyridylpyridone. Field, J. S.; Haines, R. J.; Parry, C. J.; Sookraj, S. H. S. Afr. J. Chem. 1993, 46(3/4), 70-74.