A Novel Tandem Sequence to Pyrrole Syntheses by 5-endo-dig Cyclization of 1,3-Enynes with Amines

Abstract

The synthesis of pentasubstituted pyrroles has been described using molecular iodine from 1,3-enynes and amines via a sequential tandem aza-Michael addition, iodocyclization, and oxidative aromatization. The protocol is simple and efficient to afford the target products at ambient conditions.

Recent advances in the synthesis of pyrroles by multicomponent reactions

“…This reaction is presumed to start by an aza-Michael reaction of the amine to the electron-deficient 1,3-enyne system, followed by activation of the triple bond by its reaction with iodine, cyclization of the resulting iodonium species and a final iodine-mediated dehydrogenative aromatization step (Scheme 73). 97 Duche ˆne and Parrain have investigated the synthesis of pyrroles from 3,4-diiodo-2-alkenoic acids, primary amines and terminal alkynes in the presence of a palladium catalyst. The reaction was proposed to start by an initial amine allylation via nucleophilic displacement of iodide, followed by a Sonogashira cross-coupling reaction and a 5-endo-dig cyclization by Pd-catalyzed intramolecular hydroamination that gives an exocyclic double bond that finally rearranges to afford aromatic pyrroles (Scheme 74).…”

Iodine-mediated synthesis of heterocycles via electrophilic cyclization of alkynes

“…42 The mechanism for the reaction goes via intermolecular aza-Michael addition of the amine with the electrondeficient conjugated 1,3-enyne in the presence of iodine followed by intramolecular cyclization to give the dihydropyrrole derivative 42 The mechanism for the reaction goes via intermolecular aza-Michael addition of the amine with the electrondeficient conjugated 1,3-enyne in the presence of iodine followed by intramolecular cyclization to give the dihydropyrrole derivative …”

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

“…Based on the previous studies on heterocycle synthesis, Punniyamurthy and co-workers designed the electrophilic iodocyclization of 2-nitro-1,3-enynes 34 for the synthesis of pyrrole derivatives. In 2013, they reported an efficient route to pentasubstituted pyrroles from 2-nitro-1,3-enynes 34 , amines, and iodine under mild conditions ( Scheme 12 ) [ 55 ]. The reaction was performed in CH 2 Cl 2 at ambient conditions in the presence of 2.0 equiv of K 2 CO 3 .…”