Regioselective Functionalization of 3-Hydroxy-pyridine Carboxylates by Neighboring Group Assistance

Regioselective hydrolysis, transesterification, and aminolysis of unactivated, highly substituted pyridine esters were realized under mild conditions by employing neighboring group assisted catalysis. Excellent yields were achieved without active removal of the alcohol byproduct. Regioselective aminolysis had a considerable substrate scope ([hetero]aryl, alkyl and amino acid). A mechanism involving assistance by the deprotonated phenolic OH‐group is suggested for hydrolysis and transesterification. An unexpected docking site. Free phenolic hydroxy groups in pyridine rings were found to assist the regioselective transformation of proximal ester groups. Selective hydrolysis, transesterification, and amide bond formation can such be realized at very mild pH (8.5) even in the presence of water.