Synergistic gold-palladium catalytic processes have been intensively sought during the past decade, because the combination of the carbophilic Lewis acidity of Au with the redox properties of Pd within a catalytic cycle is particularly appealing for the synthesis of novel functionalized compounds. We demonstrate here the feasibility of a Au-Pd bimetallic catalytic system based on the generation of competent Au and Pd species by anionic ligand exchange. This strategy enabled the preparation of a variety of substituted butenolides in a simple and efficient way.

CO2 at atmospheric pressure is used in two Pd-catalyzed multicomponent reactions to produce functionalized 5-methylene-1,3-oxazolidin-2-ones from propargylamines and aryl halides.

The total synthesis of the suggested structure of (−)-novofumigatamide, a natural product containing a C3-reverse prenylated N -acetyl- exo -hexahydropyrrolo[2,3- b ]indole motif fused to a 10-membered ring lactam, was achieved using the macrolactam formation in advance of a diastereoselective bromocyclization and reverse prenylation steps. Since the NMR data of the synthetic sample did not match those of the natural product, the endo -bromo precursor of a N -Boc analogue and additional diastereomers derived from l -Trp were also synthesized. Five alternative synthetic routes, which differed in the order of final key steps used for the construction of the 10-membered ring lactam and the hexahydropyrrolo[2,3- b ]indole framework within the polycyclic skeleton and also in the amide bond selected for the ring-closing of the macrolactam, were thoroughly explored. Much to our dismay, the lack of spectroscopic correlations between the proposed structure of natural (−)-novofumigatamide and the synthetic products suggested a different connectivity between the atoms. Additional synthetic efforts to assemble alternative structures of the natural product and isomers thereof (see accompanying paper; DOI: ) further highlighted the frustrating endeavors toward the identification of a natural product.

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Natural products chemists addressing global genome mining and heterologous expression, purification and structural determination, and the synthetic campaigns conspire to generate dimeric tryptophan-derived dioxopiperazines.