Multicomponent Synthesis of Imidazo[1,2-a]pyridines: Aerobic Oxidative Formation of C–N and C–S Bonds by Flavin–Iodine-Coupled Organocatalysis

Abstract

Herein, we report an aerobic oxidative C−N bond-forming process that enables the facile synthesis of imidazo[1,2a]pyridines and takes advantage of a coupled organocatalytic system that uses flavin and iodine. Furthermore, the dual catalytic system can be applied to the one-pot, three-step synthesis of 3-thioimidazo[1,2-a]pyridines from aminopyridines, ketones, and thiols.

Aerobic Oxidative C–H Azolation of Indoles and One-Pot Synthesis of Azolyl Thioindoles by Flavin–Iodine-Coupled Organocatalysis

“…15,16 Inspired by the aerobic system of the flavoenzymes, we recently developed a novel strategy for green, oxidative transformations by combining the flavin catalyst and iodine catalyst. 17,18 The flavin−iodine-coupled organocatalytic system successfully promoted the aerobic oxidative sulfenylation of indole analogues 19 and imidazo[1,2-a]pyridine ring formation 20 under metal-free conditions. In these reactions, the flavin catalyst activated O 2 through electron transfer from the coupled iodine catalyst, thereby allowing a green oxidative coupling reaction with O 2 (1 atm or air).…”

“…Green aerobic systems have drawn considerable attention because molecular oxygen (O 2 ) utilized in these systems is an ideal oxidant with many advantages such as sustainable abundance, safety, cost-effectiveness, atom-economy, and minimal pollution. , Flavin catalysts, which are prepared by mimicking the function of flavin-dependent monooxygenase, have attracted significant interest because of their biomimetic organocatalytic ability to activate O 2 . , Inspired by the aerobic system of the flavoenzymes, we recently developed a novel strategy for green, oxidative transformations by combining the flavin catalyst and iodine catalyst. , The flavin–iodine-coupled organocatalytic system successfully promoted the aerobic oxidative sulfenylation of indole analogues and imidazo­[1,2- a ]­pyridine ring formation under metal-free conditions. In these reactions, the flavin catalyst activated O 2 through electron transfer from the coupled iodine catalyst, thereby allowing a green oxidative coupling reaction with O 2 (1 atm or air).…”

Iodine-Catalyzed Multicomponent Synthesis of Highly Fluorescent Pyrimidine-Linked Imidazopyridines

“… 15 Zeng et al demonstrated the synthesis of chloroimidazo[1,2- a ]pyridines from the reactions of aryl methyl ketones, 2-aminopyridine, and SOCl 2 in the presence of H 2 SO 4 in CHCl 3 medium ( Scheme 1 , eq b). 16 Iida et al developed a three-component reaction for the synthesis of thioether-linked imidazopyridines using the dual catalysis of flavin and iodine as shown in Scheme 1 , eq c. 17 Very recently, Ma et al have reported a one-pot three-component reaction for the synthesis of 3-arylimidazopyridines employing iodine catalysis and DMSO as the one-carbon source ( Scheme 1 , eq d). 18 In this paper, we report an iodine-catalyzed three-component reaction in DMSO medium for the synthesis of pyrimidine-linked imidazopyridine hybrids and study their photophysical properties ( Scheme 1 , eq e).…”

Green Aerobic Oxidation of Thiols to Disulfides by Flavin–Iodine Coupled Organocatalysis

“…6 This metal-free dual-catalytic system was successfully applied to oxidative formation of C-S or C-N bonds, such as those observed during the sulfenylation 7 or azolation of indole analogues, 8 as well as oxidative formation of heteroaromatic rings through dual or multistep aerobic oxidations. 9 In this flavin-iodine coupled system, thiols are converted into disulfides; however, the disulfide intermediates generated in situ are immediately consumed by successive transformations. 7a Consequently, a flavin-iodine catalysis system has never been applied to a practical synthesis of disulfides, although the dual catalytic system would be expected to permit green and efficient aerobic oxidation of thiols under metal-free mild conditions.…”