LITHIATION OF METHOXYPYRIDINES DIRECTED BY ALPHA-AMINO ALKOXIDES

The addition of methoxypyridinecarboxaldehydes to certain lithium dialkylamides gave a-amino alkoxides in situ that were ring-lithiated with alkyllithium bases. Alkylation and hydrolysis on workup provided ring-substituted methoxypyridinecarboxaldehydes via a one-pot reaction. The one-pot methylation of isomeric methoxypyridinecarboxaldehydes was examined. The regioselectivity of the lithiation-methylation was dependent on the aldehyde, the amine component of the a-amino alkoxide, and the metalation conditions. When lithiated N,N,N’-trimethylethylenediamine was used as the amine component of the a-amino alkoxide, methylation generally occurred ortho to the aldehyde function. The analogous reactions using lithium N-methylpiperazide as the amine component gave substitution next to the methoxy group. Several new methylated methoxypyridinecarboxaldehydes were prepared in a regioselective manner by using this one-pot procedure. © 1990, American Chemical Society. All rights reserved.