Sonogashira-Hydroamination Route to 1,2,4-Trisubstituted Pyrroles

Significance

Reported is the synthesis of 1,2,4-trisubstituted pyrroles using a protocol developed and widely used for the formation of other heterocycles (e.g., T. Sakamoto et al. Heterocycles 1986, 24, 2311). The reaction proceeds by initial Sonogashira cross-coupling, followed by hydroamination to generate the observed pyrrole products. The ­Sonogashira enyne cross-coupling products could only be isolated when electron-withdrawing groups were present on the nitrogen. In this case the reaction required a stronger Lewis acid to proceed to the pyrrole products.