Intermolecular and intramolecular Diels-Alder cycloadditions of 3-ylidenepiperazine-2,5-diones and 5-acyloxy-2(1H)-pyrazinones

The 3-ylidenepiperazine-2,5-diones 16 and 39 and 5-acyloxy-2(1H)-pyrazinone s 17 can serve as starting materials for the Diels-Alder reactions of alken es and alkynes to the piperazine ring, under acidic conditions or in the pr esence of acetyl chloride, to afford tricyclic piperazine-2,5-diones 19, 20 , 23-25, 27, 44, and 45. Intramolecular cycloadditions occur if 3-ylidenepi perazine-2,5-diones 30 and 32 are used as the starting materials. This proc edure is a convenient path to bridged bicyclo[2.2.2]diazaoctane ring system s such as 31 and 33, the former being found in biologically active secondar y mold metabolites, such as VM55599 (I) or brevianamide A (5), which have b een isolated from various fungi. The synthesis of the indole compound 31 pr ovided evidence for the proposed biochemical pathway with a Diels-Alder rea ction as key step. Quantum chemical calculations have revealed that piperaz inones with a cationic azadiene moiety are the most reactive species in Die ls-Alder cycloadditions.