Acid catalysed methanolysis of 2,5-diazabicyclo[2.2.2]octane-3,6-diones: scope and limitations

The selective methanolysis of 2,5-diazabicyclo[2.2.2]octane-3,6-dione systems is a key step in a synthetic procedure leading to 4-amino-6-oxo-2-piperidinecarboxylate systems. This reaction seems to be primarily governed by steric hindrance caused by the substituents at the 1- and 4-bridgehead positions of the dione. In absence of bulky substituents the methanolysis is directed by the secondary or tertiary nature of the two lactam moieties.