Palladium-Catalyzed Three-Component Synthesis of Pyrroles

Significance

The palladium-catalyzed synthesis of pyrrole acetic acid derivatives 4 via the three-component coupling of diiodide 1, amines 2, and acetylenes 3 is reported. A wide range of functional groups on the acetylene are tolerated, although the yields are only moderate due to competing formation of lactone by-products arising from ­intramolecular cyclization of the iodo acid 1. The silyl and germyl alkynes were found to be good ­substitutes for acetylene, giving the disubstituted pyrroles after protonolysis of the carbon-metal bond on acidic work-up. The scope with respect to the amine component was found to be narrower. Although simple alkyl and aryl amines are tolerated, α-substituted alkyl amines and electron-poor amines are not competent in the reaction. The acid in 1 may also be replaced by an ester as demonstrated in the synthesis of retinoid 5.