Intramolecular 1,6-Addition to 2-Pyridones. Mechanism and Synthetic Scope

The scope and limitations of the intramolecular 1,6-addition of an enolate to a 2-pyridone moiety, a reaction that has found application in the synthesis of the lupin alkaloids, have been probed. This nucleophilic addition process has been shown to be reversible and favored in the case of (less stabilized) amide and lactam etiolates, which readily form five- and six-membered bi-/tricyclic products. Alternative etiolates (ketone, ester, thiolactam) and a variety of different acceptors (isoquinolinone, pyrimidinone, pyrazinone, pyridopyrazinone) have been evaluated, and a range of competing side reactions have been identified and characterized using, various techniques, including in situ IR.