Four-Component Synthesis of β-Enaminone and Pyrazole through Phosphine-Free Palladium-Catalyzed Cascade Carbonylation

• Published in: ChemCatChem 2014-09, Vol.6 (9), p.2560-2566
• Main Authors: Shi, Lijun, Xue, Liqin, Lang, Rui, Xia, Chungu, Li, Fuwei
• Format: Article
• Language: English
• Subjects: carbonylation; domino reactions; heterocycles; homogeneous catalysis; palladium
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.201402277

The carbonylative domino synthesis of enaminones and pyrazoles has been performed with the NN bidentate palladium catalyst to achieve excellent selectivity. These results have confirmed that the carbonylative Sonogashira coupling of iodobenzenes with terminal alkynes is accompanied by the Michael addition of amines or phenylhydrazine in a one‐pot method, which generates the desired products. This protocol demonstrates wide substrate tolerance, including hitherto unused aromatic amines, to yield the corresponding pure aromatic β‐enaminones, which are subsequently converted into the 3‐acylindole derivatives under mild conditions. One thing leads to another: A carbonylative domino reaction with a hemilabile palladium complex as a catalyst is used to synthesize β‐enaminones and pyrazoles. This method demonstrates good functional group tolerance, with even scarcely used aromatic amines and phenylhydrazine as substrates. The pure aromatic enaminones are readily converted to indole‐3‐ketones, which are key structural units in many biologically active compounds. This transformation confirms the versatile use of such a carbonylative domino reaction.