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.