Reaction Using Cyclic Amides: 2,3-Pyrrolidinediones, 2,4-Pyrrolidinediones, 4-Piperidine-3-carboxylates, and 2,4-Piperidinediones

Nitrogen heterocycles widely occur in nature and as structural subunits in many families of alkaloids, and possess wide-ranging biological and pharmaceutical activities. The 2,3-pyrrolidinediones, 2,4-pyrrolidinediones (tetramic acids), 4-piperidine-3-carboxylates, and 2,4-piperidinediones are a particularly important subgroup, and are well known for their potent antibiotic, antiviral, antifungal and cytotoxic activities [107-116]. The pyrrolidinedione derivatives were also synthesized as endothelin receptor antagonists [117, 118]. The 1,2-dioxane scaffold containing nitrogen heterocycles is particularly important in nature as a metabolite and biologically active substance [1,2,119-121]. Some plants produce 1,2-dioxane derivatives in order to protect themselves and their territory (Fig. 2) [4-11,13,18-21,122,123]. Artemisinin (quighaosu) is a unique antimalarial drug consisting of the 1,2,4-trioxane skeleton (Fig. 1) [4-16], and it was reported that the synthesized N-substituted azaartemisinins were more active than the naturally occurring artemisinin [5]. Since the 2,3-pyrrolidinediones, 2,4-pyrrolidinediones, 4-piperidine-3-carboxylates, and 2,4-piperidinediones exist as the enol form, they could be effective candidates for forming carbon radicals during the manganese(III) acetate oxidation [99,124]. Therefore, the Mn(III)-catalyzed aerobic oxidation of these heterocycles would be expected to produce aza-dioxabicyclic compounds. The synthesis of the heterocycle-fused endoperoxide framework has attracted considerable attention from the viewpoint of the development of new antibiotics, in spite of its instability.

Alkenes and 2,3-pyrrolidinediones were treated with manganese(III) acetate to give the desired 1-hydroxy-8-aza-2,3-dioxabicyclo[4.3.0]nonan-9-ones, which were obtained in good yields (Scheme 17) [125,126].

A similar reaction of various alkenes with 2,4-pyrrolidinediones was carried out in acetic acid at room temperature under a dry air stream in the presence of manganese(III) acetate to give the 1-hydroxy-8-aza-2,3-dioxabicyclo[4.3.0]nonan-7-ones in good to quantitative yields [127,

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