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

Abstract

An unprecedented silver-promoted regioselective (4 + 1) annulation of isocyanoacetates with pyridinium salts is reported. The established protocol provides controlled, facile, and modular access to a range of synthetically useful N-fused heterocyclic scaffolds containing indolizines, pyrrolo[1,2-a]quinolines, pyrrolo[2,1-a]isoquinolines, and 1H-imidazo[4,5-a]indolizin-2(3H)-ones. A mechanistic pathway involving nucleophilic addition/protonation/elimination/cycloisomerization is proposed.

Construction of Phenanthridinone Skeletons through Palladium-Catalyzed Annulation

“…In this context, we recently reported that 2-(2-bromophenyl)-1Hbenzo [d]-imidazole derivatives can be harnessed as an effective coupling partner in combination with 2-bromobenzoic acids to give the corresponding N-fused (benzo)imidazophenanthridine scaffolds in high yields. 16 In continuation of our previous studies directed to transition-metal-assisted synthesis of heterocycles, 17 we envisaged that phenanthridin-6(5H)-one derivatives could be directly assembled from N-substituted 2bromobenzamides 1 and 2-bromobenzoic acids 2 in the presence of a metal catalyst (Figure 1, bottom).…”

Silver‐Catalyzed and Silver‐Promoted Reactions of Isocyanides

“…Later, Liu, Kärkäs and Wang's group reported a silver‐promoted regioselective [4+1] annulation of pyridinium salts 201 with isocyanoacetates 202 , which provided controlled and modular access to two types of 1,2‐disubstituted indolizinesindolizines 203 and 204 in good to excellent yields (Scheme 25a) [37] . In this reaction, the generation of final products depended on the amount of the silver salt, the solvent, and the temperature.…”

Recent Applications of Quinolinium Salts in the Synthesis of Annulated Heterocycles

“…During their synthetic programme, Kärkäs, Wang and co-workers developed an unprecedented [4+1] annulation of alkylpyridinium/quinolium salts with isocyanoacetates which provided two kinds of 1,2-disubstituted indolizines in good to excellent yields. 58…”

“…During their synthetic programme, Kärkäs, Wang and co-workers developed an unprecedented [4+1] annulation of alkylpyridinium/quinolium salts with isocyanoacetates that provided two kinds of 1,2-disubstituted indolizines in good to excellent yields. 58 They observed that the reaction of 1-(2-oxo-2-arylethyl)pyridinium bromides 80 with isocyanoacetate 81 in the presence of Ag 2 CO 3 in DMF afforded isocyano substituted indolizine 82 (Scheme 21). The use of the corresponding quinoline salts resulted indolizine carboxylate derivative 83.…”