Further Investigation of the Intermolecular Diels–Alder Cycloaddition for the Synthesis of Bicyclo[2.2.2]diazaoctane Alkaloids

The
convergent synthesis of bicyclo[2.2.2]­diazaoctane structures
using an intermolecular Diels–Alder cycloaddition between a
pyrazinone and commercially available fumarate or maleate precursors
is reported. High reactivity and stereoselection is observed with
both dienophile substrates. Structure validation was achieved by conversion
of cycloadducts into known [2.2.2]­diazabicyclic compounds or into
crystalline derivatives suitable for X-ray analysis. The cycloadduct
derived from reaction of pyrazinone and maleic anhydride underwent
selective anhydride ring opening and intersected an established precursor
in the synthesis of brevianamide B.