Silver‐Catalyzed [3+1+1] Annulation of Nitrones with Isocyanoacetates as an Approach to 1,4,5‐Trisubstituted Imidazoles

Abstract

A silver‐catalyzed protocol for [3+1+1] annulation of nitrones and isocyanoacetates is reported. The reaction is proposed to proceed through sequential [3+2] cycloaddition, ring‐opening, cyclization‐oxidation, and dealkylation, allowing access to a broad scope of valuable polysubstituted imidazoles in high yields.

Copper-assisted Wittig-type olefination of aldehydes with p-toluenesulfonylmethyl isocyanide

“…Recently, we disclosed copper- and silver-catalyzed heteroaromatization protocols proceeding through condensation between propargylic alcohols and TosMIC, thus revealing a conceptually novel reactivity profile of the latter. 9 Based on these findings and our continued efforts in copper- and silver-catalyzed reactions involving isocyanides, 9,10 we herein report the first example of copper-assisted Wittig-type olefination reaction of aldehydes with TosMIC via sequential (3 + 2) cycloaddition—retro-(3 + 2) cycloaddition (Fig. 1).…”

Studies towards the Design and Synthesis of Novel 1,5-Diaryl-1H-imidazole-4-carboxylic Acids and 1,5-Diaryl-1H-imidazole-4-carbohydrazides as Host LEDGF/p75 and HIV-1 Integrase Interaction Inhibitors

“…These α-isocyanoacetates are useful multipurpose reagents for the construction of various nitrogen-containing heterocycles [34,35]. Different five-membered nitrogen-containing heterocycles like thiazole [36,37], imidazole [31][32][33][38][39][40][41][42][43], indole [44][45][46], oxazole [47], pyrrole [48,49], and triazole [50,51] have been built using these synthons. Isocyanoacetate building blocks have attracted the interest of researchers owing to their structural characteristics, reactivity, and reliability.…”

“…However, only two examples were reported utilizing ester isocyanoacetate synthons in this approach. More recently, Lv and co-workers [43] in 2021 described the construction of these compounds in good yields by reacting α-isocyanoacetates with nitrones catalyzed by silver trifluoromethanesulfonate (AgOTf) in the presence of potassium trifluo-romethanesulfonate (KOTf) in toluene (PhMe) as a solvent under a nitrogen atmosphere (Scheme 1g). Scheme 1.…”

“…Herein we describe a novel and efficient approach for the synthesis of diaryl-imidazole-4-carboxylate esters via cycloaddition of an α-isocyanoacetate with stable N-aryl-benzimidoyl chloride in-termediates (Scheme 1h). None of the previously reported synthetic methods to these compounds [33,[40][41][42][43]] make use of diarylimidoyl chlorides and isocyanoacetate esters. The carboxylate esters prepared using this new methodology were subsequently converted into the corresponding 1,5-diaryl-1H-imidazole-4-carboxylic acids and 1,5-diaryl-1H-imidazole-4-carbohydrazides, which were then evaluated for their ability to bind to the novel HIV-1 IN dimer interface pocket.…”

Silver-Promoted (4 + 1) Annulation of Isocyanoacetates with Alkylpyridinium Salts: Divergent Regioselective Synthesis of 1,2-Disubstituted Indolizines

“…To date, the only example of such reactivity was disclosed by Bi and co-workers in a pioneering work on silver-catalyzed chemoselective annulation of isocyanides with 2-pyridylpropargyl alcohols to provide 1,3-disubstituted indolizines (Figure , route D) . We recently described a series of related reaction manifolds, including silver- and copper-catalyzed regioselective (3 + 2) cycloadditions of nitrones, acyl chlorides, and aryl diazonium salts with isocyanoacetates, divergently furnishing a variety of nitrogen-containing heterocyclic compounds . As part of our interest in developing novel copper- and silver-catalyzed reactions involving isocyanides, , we herein report the first regioselective (4 + 1) annulation of isocyanoacetates with alkylpyridinium salts (Figure ), which provides two types of 1,2-disubstituted indolizines in good to excellent yields for a variety of substrates.…”