Regioselective Synthesis of Pyrroles from Alkyne-Isocyanide Click Reactions: An Angle Strain-Induced Bond Migration Approach

The direct regioselective synthesis of highly functionalized pyrroles with two different electron-withdrawing groups has been developed using an angle strain-induced 1,2-shift of an electron-withdrawing group in 2H-pyrroles. The preferential migration aptitude of an electron-withdrawing group over alkyl and aryl groups is believed to be the result of the orbital overlap between the internal alkene and the electron-withdrawing group. The newly developed regioselective synthesis of pyrroles features a wide substrate scope, simple reaction set-up, and high yields (60–82%), capturing the essence of alkyne-isocyanide “click” reactions.