Title of article :
Ortho-selectivity in the nucleophilic aromatic substitution (SNAr) reactions of 3-substituted, 2,6-dichloropyridines with alkali metal alkoxides
Author/Authors :
Yap، نويسنده , , Jeremy L. and Hom، نويسنده , , Kellie and Fletcher، نويسنده , , Steven، نويسنده ,
Issue Information :
هفته نامه با شماره پیاپی سال 2011
Pages :
5
From page :
4172
To page :
4176
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.
Keywords :
ortho , regioselective , 2 , coordination , 6-Dichloro-3-nitropyridine , Nucleophilic aromatic substitution (SNAr)
Journal title :
Tetrahedron Letters
Serial Year :
2011
Journal title :
Tetrahedron Letters
Record number :
1878961
Link To Document :
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