Acid, Metal and Peroxide-Free Synthesis of 2,4,5-Trisubstituted Imidazoles Commencing from Internal Alkenes Using an Iodine/DMSO System

Abstract

An efficient acid, metal and peroxide-free synthesis of 2,4,5trisubstituted imidazoles commencing from internal alkenes and aldehydes using an inexpensive and eco-friendly iodine/DMSO system has been reported. This simple methodology affords a plethora of 2,4,5-trisubstituted imidazoles in moderate to good yields under mild reaction conditions. Based on preliminary control studies, a reasonable mechanism to the target imidazole is proposed.Oxidations play a vital role in academia and industry as it assists in the creation of new, complex molecules or the modification of existing ones. 1 Given the importance of this transformation, the demand for novel, environmentally benign, and cost-effective oxidation methods have steadily increased. 2 Within this context, the oxidation of alkenes, in particular, continues to be of importance as it is used to prepare epoxides, 3 carbonyls, 4 and 1,2-diols. 5 Additionally, the conversion of internal alkenes to α-diketones is of interest to organic chemists as it allows for the generation of synthetically useful compounds such as quinoxalines and spirocycles. 6 Hence, a multitude of synthetic routes have been devised for the conversion of internal alkenes to α-diketones and selected examples include the use of potassium permanganate in acetic anhydride 7 and ruthenium-catalyzed hydrogen abstraction. 8 2,4,5-Trisubstituted imidazoles are important heterocyclic compounds as they display interesting biological 9,10 and synthetic applications. 11 The traditional route towards these fascinating molecules involves the multicomponent reaction of a α-diketone, aldehyde and ammonium acetate in the presence of a metal or acid catalyst (Scheme 1a) such as acetic acid, 12 ytterbium triflate, 13 and (NH4)6Mo7O24•4H2O, 14 to name but a few. Surprisingly, there are limited synthetic routes towards 2,4,5-trisubstituted imidazoles commencing from alkenes and one of the earliest reports involves the use of a rhodium oxide catalyst and ammonia in a methanol-water mixture in the presence of carbon monoxide (Scheme 1b). 15 The challenges associated with this approach include the use of an expensive rhodium catalyst, employment of toxic carbon 186