Three-Component Synthesis of Substituted N-Boc-4-iodopyrroles

Significance

Reported is a one-pot three-component synthesis of 2-substituted N-Boc-4-iodo­pyrroles by reaction of a propargyl amide 2 with acid chlorides 1 involving a Pd-catalyzed coupling-addition-cyclocondensation process. Based on previous results (T. J. J. Müller and co-workers Chem. Commun. 2005, 2581 and 2006, 4817), alkynone 3, obtained through an acylative Sonogashira reaction, is converted into 4-iodo-pyrroles 4 under Brønsted acid conditions induced by PTSA˙H₂O. Aromatic substituted (electroneutral, EWG, EDG), heteroaryl, alkenyl, cyclopropyl and sterically demanding adamantyl substituents are effectively carried through the sequence. However, for nonaromatic acid chlorides, slow reactivity was observed. As suggested by the formation of 4, further addition of an alkyne results in the formation of 4-alkynyl-N-Boc-pyrrole 6 in a one-pot procedure.