Quaternization at the picolinic carbon. Application to the synthesis of pyridylalkanecarboxylic acids

Abstract

The paper describes two different methodologies for the construction of a quaternary center at the picolinic site, and their application to the synthesis of pyridylalkanecarboxylic acids. The first one involves a one-pot acetylation–Michael addition procedure followed by an alkylative quaternization of the picolinic carbon. The second one is based on the deprotonation at the picolinic carbon of 2-(α,α-dialkyl)pyridines using the superbasic mixture BuLi–diisopropylamine–Bu^tOK (“KDA”). Both routes give very good yields.