Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles by a Sequential Aza-Wittig/Michael/Isomerization Reaction

Abstract

Carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aryl isocyanates, reacted with secondary amines in the presence of a catalytic amount of sodium alkoxide to give 1,2,4,5-tetrasubstituted imidazoles 7 in good yields. However, 4-acylimidazoles 11 were obtained, as phenols were used in the presence of a catalytic amount of potassium carbonate due to further air oxidation of the expected products 10.

A Facile FeCl3/I2-Catalyzed Aerobic Oxidative Coupling Reaction: Synthesis of Tetrasubstituted Imidazoles from Amidines and Chalcones

“…8 Current synthesis methods for imidazole derivatives are mainly restricted to less-substituted imidazoles, 9 while only a handful of them provided access to tetrasubstituted imidazoles. 10 Particularly during the last decades, several new methodologies have emerged, such as cross-coupling of aldimines, 11 the coupling reaction of 2-azido acrylates and nitrones, 12 Cu-catalyzed cycloaddition of amidines and nitroolefins, 13 the three-component reaction, 14 Ni-catalyzed dehydrogenation of benzylic-type imines, 15 and Zn-catalyzed cyclization of 2-(tetrazol-5-yl)-2H-azirines and imines. 16 However, most approaches encounter some drawbacks, including high catalyst loading, substrates unavailable, limited applications, long reaction time or low yields under harsh reaction conditions.…”

One‐Pot Evolution of Ageladine A through a Bio‐Inspired Cascade towards Selective Modulators of Neuronal Differentiation

“…This naturally occurring arginine modification is particularly interesting in that the reactionr egioselectively gives the N1-substituted 2-aminoimidaozle 5,b ut not the 2Nsubstituted isomer 6.I ndeed, among many methods for the formation of substituted 2-aminoimidazoles, only af ew are knownt or egioselectively provide N1-substituted 2-aminoimidazoles. [36][37][38] With the assumption that such PTM-inspired reactions could be applicable to the key aminoimidazole intermediate (see structure 11 in Figure 2b), the rapid and straightforward accesst ov arious N1-and C4-substituted natural products was designedi naone-pot and one-flask procedure. Our one-pot strategy consists of the following seven steps ( Figure 2b): 1) the guanylation of the startinga mines 7 by cyanamide, 2) an imine formation with the dialdehyde 9,3 )ani ntramolecular 1,4-addition and aromatization towards the 2-amioimidazole 11,w hich is the PTM-inspired key intermediate of the total synthesis, 4) an enamine formation (12)w ith ammonia, 5) an azatriene formation ( 14)w ith the aldehydes 13,6 )an thermala za-electrocyclic ring closure, and finally 7) the autoxidation to 3.T he last two steps (14!3)m imic the biosynthetic route of natural ageladineA.…”

Reactivities of vinyl azides and their recent applications in nitrogen heterocycle synthesis

“…This process proceeded through carbodiimide intermediates 138 , which could add various amines 139 or phenols 143 under base catalysis to give 1,2,4,5-tetrasubstituted imidazoles 142 (Scheme 24). 37 Carbodiimides 138 were derived from aza-Wittig reactions of iminophosphoranes 136 with aryl isocyanates 137 . Surprisingly, when phenols 143 were used as nucleophiles to trap the carbodiimide intermediate, 4-acylimidazoles 146 were obtained.…”