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Ortho-selectivity in the nucleophilic aromatic substitution (SNAr) reactions of 3-substituted, 2,6-dichloropyridines with alkali metal alkoxides
- Source :
-
Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry . Aug2011, Vol. 52 Issue 32, p4172-4176. 5p. - Publication Year :
- 2011
-
Abstract
- Abstract: 3-Substituted, 2,6-dichloropyridines have featured in the syntheses of small molecule inhibitors of a wide variety of biological targets. Hence, the regioselective displacement of the chlorines is of significant interest. Through conducting an extensive solvent study, we have found that non-polar, aprotic solvents of low hydrogen bond basicities favour substitution of the chlorine ortho to the 3-substituent by alkali metal alkoxides. We present convincing evidence that coordination of the alkali metal counter-ion to the 3-substituent (nitro, ester, amide) is the origin of the ortho-selectivity to give a cyclic, six-membered transition state. Excellent ortho-selectivities (⩾98:2) for secondary and tertiary alkoxides were realized with the sodium counter-ion, whereas the more reactive primary alkoxides required the harder, more Lewis acidic lithium counter-ion. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00404039
- Volume :
- 52
- Issue :
- 32
- Database :
- Academic Search Index
- Journal :
- Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 62554837
- Full Text :
- https://doi.org/10.1016/j.tetlet.2011.06.007