A Direct Cycloaminative Approach to Imidazole Derivatives via Dual C–H Functionalization

Abstract

Organoiodine(III)-promoted C(sp)-H azidation was a key step for the cycloaminative process. An unprecedented method for metal-free dehydrogenative N-incorporation into C(sp)-H and C(sp)-H bonds for the synthesis of diverse imidazoles has been disclosed. The overall transformation involves the construction of four C-N bonds through hydroamination-azidation-cyclization sequence. The reaction can be easily handled and proceeds under mild conditions. Further, the potential of the present strategy is revealed by the practical synthesis of N-heterocyclic carbene (NHC) precursors.

Studies via X-ray analysis on intermolecular interactions and energy frameworks based on the effects of substituents of three 4-aryl-2-methyl-1H-imidazoles of different electronic nature and their in vitro antifungal evaluation

“…Imidazoles are an important class of very stable aromatic N-heterocycles frequently found in natural products, metalloenzymes, pharmaceuticals and other functional synthetics (Fox, 1943;Sezen & Sames, 2003;Ritterskamp et al, 2017;Vargas-Oviedo et al, 2017). Today, the wide variety of studies on imidazole synthesis have become a 'master key' of research due to the wide range of applications of imidazole derivatives in diverse biological and industrial processes (Vichier-Guerre et al, 2016;Arepally et al, 2017;Rajendiran et al, 2018). Recently, we reported the synthesis and in vitro antifungal evaluation of novel N-fenacyl-2-methylimidazoles, (4a)-(4d), by a pseudo-tricomponent reaction between acetamidine hydrochloride, (2), and -bromoketones (1a)-(1d) (Elejalde et al, 2018) (see Scheme 1).…”

C1‐Functionalization of 1,2,3,4‐Tetrahydroisoquinolines (THIQs)

“…synthesized derivatives of imidazole 107 using catalytic system PIFA phenyliodine‐bis(trifluoroacetate)/TMSN 3 31 in dichloroethane at −5 °C (Scheme 21). [38] Among the synthesized fused imidazoles 107 , four derivatives were obtained in good yields (71–75%) from the reaction of THIQs 20 with electron deficient alkynes 103 . Based on the proposed mechanism, first, hydroamination of alkynes 103 by THIQs 20 gives intermediates 104 that undergo PIFA/TMSN 3 31 to produce intermediates 105 .…”

Stereoselective Aminoiodination of Activated Alkynes with Organoiodine(III) Reagents and Amines via Multiple‐Site Functionalization: Access to Iodinated Enamines and N‐Aryl Indoles

“…[13b] Despite this progress, developing the multiple‐site functionalization of C‐C multiple bonds with reagents as both halogen source as well as promoter in a stereoselective manner remains an intriguing challenge. As part of our ongoing study on multiple functionalization reactions of alkynes and amines using azides as nitrogen source and organoiodine compounds as promoter, we fancied to synthesize iodinated enamines directly from alkynes and amines by using organoiodine reagents as both iodine and aryl group source.…”