Metal-Free Atom-Economical Synthesis of Tetra-Substituted Imidazoles via Flavin-Iodine Catalyzed Aerobic Cross-Dehydrogenative Coupling of Amidines and Chalcones

Abstract

Herein, we demonstrated the oxidative cross-dehydrogenative coupling between amidines and chalcones catalyzed by flavin and iodine. The riboflavin-iodine catalytic system played multiple roles in substrate- and O2-activation, enabling the facile and atom-economical synthesis of tetra-substituted imidazoles in good yields (60–87%). This metal-free reaction consumed only 1 equiv of molecular oxygen and generated 2 equiv of environmentally benign H2O as the only byproduct.

Aerobic cross-dehydrogenative coupling of toluenes and o-phenylenediamines by flavin photocatalysis for the facile synthesis of benzimidazoles

“…ments in Scheme 4Db, the flavin catalyst enhanced the dehydrogenative aromatisation of 10 to 3. 17,20 Indeed, the generation of 10aa (m/z = 303.1492) was confirmed by electrospray ionisation mass measurement of the reaction mixture (Fig. S1 †) when 9a and 2a were reacted in the absence of the flavin catalyst (Scheme 4Da).…”

“…Because 2a is unstable under light irradiation, we carried out the reaction in a sequential manner: aerobic oxidation of 1a was performed first by stirring for 5 h, followed by imidazole-ring formation by adding 2a to the reaction mixture. The aerobic CDC of 1a with 2a was successfully achieved in the presence of the neutral flavin catalysts—isoalloxazines 4 and alloxazines 5 —and the desired benzimidazole 3aa was produced with yields in the range of 43–64%; to our delight, the simple 4a , which can be readily derived by the acetylation of commercially available riboflavin (vitamin B 2 ), 17 exhibited the best result (64% yield) among the flavin catalysts tested. It is noteworthy that riboflavin is a sustainable organic compound that is industrially produced by microbial fermentation from glucose.…”

Recent Advancements in Strategies for the Synthesis of Imidazoles, Thiazoles, Oxazoles, and Benzimidazoles

“…Takeda and co‐workers [32] have reported the first organocatalyzed aerobic cross‐dehydrogenative coupling of amidines 7 and α , β ‐unsaturated ketones 8 to deliver the tetrasubstituted imidazole 9 as a product using the dual catalytic system of Flavin‐Iodine. In this method, flavin is oxidized for the conversion of in situ generated HI to I 2 and undergoes aerobic dehydrogenative aromatization for heterocycles.…”

Synthesis of a bistriazolyl-phenanthroline–Cu(ii) complex immobilized on nanomagnetic iron oxide as a novel green catalyst for synthesis of imidazoles via annulation reactions

“…30,[33][34][35][36] Highly substituted imidazoles are heterocyclic compounds that contain nitrogen atoms in their ring structures. 37,38 These molecules have diverse structures with various functional groups, making them ideal substrates for testing the catalytic performance of new catalysts. 39 The synthesis of these compounds allows researchers to evaluate the catalyst's efficiency and selectivity in different types of reactions, such as condensation, cyclization, or hydrogenation, [40][41][42] and provides a robust platform for examining the catalytic performance of new catalysts.…”