Synthesis of 5-Iodopyrrolo[1,2-a]quinolines and Indolo[1,2-a]quinolines via Iodine-Mediated Electrophilic and Regioselective 6-endo-dig Ring Closure

Abstract

The endo-cyclic ring closure of 1-(2-(substituted ethynyl)phenyl)-1H-pyrroles 3a-t and 1-(2-(substituted ethynyl)phenyl)-H-indole 4a-o mediated by Lewis acid (I(2)) under mild conditions afforded substituted 5-iodopyrrolo[1,2-a]quinolines 5a-t and 5-iodoindolo[1,2-a]quinolines 6a-o in good to excellent yields. The reaction shows selective C-C bond formation on the more electrophilic alkynyl carbon, resulting in the regioselective 6-endo-dig-cyclized product. Iodo derivatives of pyrrolo- and indoloquinolines allow functional group diversification on the quinoline nucleus, which proves to be highly advantageous for structural and biological activity assessments.

Iodine-mediated synthesis of heterocycles via electrophilic cyclization of alkynes

“…53 The reaction progressed by the coordination of I 2 with an acetylene bond of substrate 112 to form an iodonium complex, 113 which undergoes intramolecular nucleophilic attack by the C-2 of pyrrole and indole on the activated triple bond to form iodo-substituted quinoline 114 (Scheme 38). 53 The reaction progressed by the coordination of I 2 with an acetylene bond of substrate 112 to form an iodonium complex, 113 which undergoes intramolecular nucleophilic attack by the C-2 of pyrrole and indole on the activated triple bond to form iodo-substituted quinoline 114 (Scheme 38).…”

Iodine Mediated Base‐Controlled Regio‐Selective Annulation of 2‐(Pyridin‐2‐yl)acetate Derivatives with Acrylic Esters for the Synthesis of Indolizines

“…[9] Considering the wide range of biological activities, developing efficient synthetic methods of indolizines has attracted wide attention in the fields of organic chemistry and chemical biology. [10] The majority for the preparations of indolizines include Tschitschibabin reaction, [11] 1,3-dipolar cycloaddition, [12] 1,5-dipolar cycloaddition, [13] I 2 -mediated oxidative cyclization, [14] transition-metal-catalyzed intramolecular cyclization [15] and intermolecular cyclization. [16] To the best of our knowledge, oxidant and solvent were proven to switch the regio-selectivity for the annulation reaction of 2alkyl pyridines with cinnamic acids by copper catalysis.…”

Primary Ammonium Monocarboxylate Synthon in Designing Supramolecular Gels: A New Series of Chiral Low‐Molecular‐Weight Gelators Derived from Simple Organic Salts that are Capable of Generating and Stabilizing Gold Nanoparticles

“…In this context, we found that the reaction of aldehyde with various indoles in the presence a catalytic amount of iodine produced the corresponding bisindole in high yields. On the other hand, recently, Verma and his co‐workers have reported the synthesis of indolo[1,2‐ a ]quinolines via (6‐ endo‐dig ) iodocyclization using molecular iodine 7d. Moreover, recently, Enders and co‐workers observed the formation of seven‐membered (7‐ endo‐dig ) fused tetracyclic azulene derivatives using a gold catalyst 4c.…”