title: Regioselective, unconventional Pictet-Spengler cyclization strategy toward the synthesis of benzimidazole-linked imidazoquinoxalines on a soluble polymer support.
abstract: A novel strategy for an unconventional Pictet-Spengler reaction has been developed for the regioselective cyclization of the imidazole ring system at the C2 position. The developed strategy was utilized to develop a diversity-oriented parallel synthesis for bis(heterocyclic) skeletal novel analogs of benzimidazole-linked imidazoquinoxalines on a soluble polymer support under microwave conditions. Condensation of polymer-immobilized o-phenylenediamines with 4-fluoro-3-nitrobenzoic acid followed by nucleophilic aromatic substitution with an imidazole motif affords bis(heterocyclic) skeletal precursors for the Pictet-Spengler reaction. The unconventional Pictet-Spengler cyclization with various aldehydes was achieved regioselectively at the C2 position of the imidazole ring to furnish rare imidazole-fused quinoxaline skeletons. During the Pictet-Spengler cyclization, aldehydes bearing electron-donating groups afford 4,5-dihydro-imidazoquinoxalines, which then auto-aromatize into benzimidazole-linked imidazo[1,2-a]quinoxalines. However, interestingly, aldehydes bearing electron-withdrawing groups directly provide aromatized imidazo[1,2-a]quinoxalines, which unexpectedly afford novel benzimidazole-linked 4-methoxy-4,5-dihydro-imidazo[1,2-a]quinoxalines after polymer cleavage.
authors.affiliation: Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300-10, Taiwan.
authors.forename: Chih-Hau
authors.initials: CH
authors.lastname: Chen
authors.forename: Jaren
authors.initials: J
authors.lastname: Kuo
authors.forename: Gorakh S
authors.initials: GS
authors.lastname: Yellol
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Sun
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D003500:Cyclization; D007093:Imidazoles / Q000737:chemistry*; D008872:Microwaves; D011108:Polymers / Q000737:chemistry*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001562:Benzimidazoles; D007093:Imidazoles; D011108:Polymers; D011810:Quinoxalines; C029899:imidazole; C031000:benzimidazole