Highly Diastereoselective Multicomponent Synthesis of Unsymmetrical Imidazolines

Abstract

We report here a highly diastereoselective multicomponent synthesis of imidazolines. These low molecular weight scaffolds contain a four-point diversity applicable to alkyl, aryl, acyl, and hetereocyclic substitutions. [structure: see text]

Chemistry of α-Oxoesters: A Powerful Tool for the Synthesis of Heterocycles

“…In the proposed reaction mechanism, 1,3-dipolar component 222, generated by N-silylation followed by deprotonation of oxazoline, underwent 1,3-dipolar cycloaddition with glyoxalate imine to give 223, which afforded the imidazole 225 by rearrangement to 224 and desilylation (Scheme 61). 121 Recently, Medda et al 122 reported the construction of hydantoin and thiohydantoin scaffolds 227 via a TMSN 3 −Ugi/ RNCX cyclization reactions sequence. Ethyl 2-(tetrazol-5-yl)-2-(alkylamino)acetates 226, obtained by TMSN 3 −Ugi reaction between glyoxalate imines, in situ generated from ethyl glyoxalate and amines, TMSN 3 , and isocyanides in CF 3 CH 2 OH at room temperature, were transformed into the corresponding hydantoins or thiohydantoins 227 when treated with isocyanate or isothiocyanate in dry EtOH under a N 2 atmosphere at room temperature for 2−36 h or under MW irradiation for 1.5−2 h. TMSN 3 −Ugi products 226 and hydantoins or thiohydantoins 227 were obtained in 21−60% and 25−99% yields, respectively (Scheme 62).…”

Five‐Membered Heterocycles: 1,3‐Azoles

“…The proposed mechanism proceeds through a 1,3-dipolar cycloaddition reaction of the mesoionic intermediate 233 (Scheme 10.129) [365]. Another multicomponent reaction (MCR) has been developed using aldehydes, primary amines and isonitriles with AgOAc as catalyst.…”

Structural–activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production

“…[47][48][49][50] Cyclodehydration of N-benzoyl protected amino acid derivatives with TFAA provided azlactones without the need for further purification. The azlactones were subsequently treated with the desired imine in the presence of TMSCl to provide the imidazoline carboxylate, which was isolated by filtration.…”

“…Next, we examined the variability that could be tolerated at the R 2 position by synthesizing esters 6-8 via the acid chloride (Table 2). Imidazolines 9 and 10 were synthesized by treating dl-(4R,5R)-1-benzyl-4,5-dihydro-2,4,5-triphenyl-1H-imidazole-4-carboxylic acid 48 with EDCI and DMAP in the presence of benzyl alcohol and (NH 4 ) 2 CO 3 , respectively. To study the effect of the R 3 and R 4 domains, a number of imines (prepared from their corresponding aldehydes and amines) underwent the 1,3-dipolar cycloaddition to afford imidazolines 11-25 (Tables 3 and 4).…”