- Regioselective α-Lithiation of Unsymmetrical 1-(tert-Butoxycarbonyl)-1,4-dihydropyridines
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The α-lithiation-methylation of unsymmetrical C-3-substituted 1-(tert-butoxycarbonyl)-1,4-dihydropyridines was studies.The yield and regioselectivity, C-2 vs C-6, of the metalation was dependent upon the C-3 substituent, the metalation base, and the reaction conditions.When the C-3 substituent was a methyl or methoxy group, and mesityllithium was the base, C-6 lithiation-methylation occurred predominately.With a strongly ortho-directing C-3 substituent , i.e., Cl, Br, OCONEt2, metalation with phenyllithium occurred mainly at C-2.An α-amino alkoxide function at C-3 acted only as a blocking group, forcing lithiation to occur mainly at C-6.Two new trisubstituted pyridines, 3--2,4-dimethylpyridine and 2,4-dimethyl-3-pyridinecarboxaldehyde, were prepared by aromatization of regioselectively alkylated 1,4-dihydropyridine intermadiates with o-chloranil or sulfur in refluxing decalin, demonstrating a new approach to pyridine substitution.
- Comins, Daniel L.,Weglarz, Michael A.
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- SYNTHESIS OF 3-HALO- AND 3-FORMYL-4-ALKYLPYRIDINES
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In the presence of a catalytic amount of cuprous iodide, the addition of Grignard reagents to the 1-phenoxycarbonyl salts of 3-halopyridines gives 4-alkyl-3-halo-1-phenoxycarbonyl-1,4-dihydropyridines.The crude dihydropyridines were aromatized with o-chloroanil to give 4-alkyl-3-halopyridines.Several 4-alkylnicotinaldehydes were synthesized in a similar manner from the cyclic acetal (1,3-dioxolane) of 3-pyridinecarboxaldehyde.After aromatization with sulfur, the crude acetals were hydrolyzed with oxalic acid to give the desired pyridinecarboxaldehydes.
- Comins, Daniel L.,Smith, Roy K.,Stroud, Eric D.
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p. 339 - 344
(2007/10/02)
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