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 enolates, which readily form five- and six-membered bi-/tricyclic products. Alternative enolates (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.
Gallagher
Timothy
T
School of Chemistry, University of Bristol, Bristol, BS8 1TS, United Kingdom. t.gallagher@bristol.ac.uk
Derrick
Ian
I
Durkin
Patrick M
PM
Haseler
Claire A
CA
Hirschhäuser
Christoph
C
Magrone
Pietro
P
D000470:Alkaloids / Q000138:chemical synthesis; D004952:Esters / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry*
D000470:Alkaloids; D004952:Esters; D011728:Pyridones; C017679:2-hydroxypyridine