A Synthesis of Functionalized Dihydro-1H-pyrroles from Nef-Isocyanide Adducts and Enamines

Abstract

α-Ketoimidoyl chlorides, obtained from α-addition of acyl chlorides onto alkyl isocyanides, are treated with enamines to afford 5-(alkylimino)-4-hydroxy-4,5-dihydro-1H-pyrrole-2,3,4-tricarboxylates and 2-(alkylimino)-3-hydroxy-2,3-dihydro-1H-pyrrole-3,4-dicarboxylates in good to excellent yields.

Isocyanide-based multicomponent reactions in the synthesis of heterocycles

“…Isocyanide-based syntheses of pyrrole derivatives have been studied extensively. [138][139][140][141][142][143][144][145] Using Ag 2 CO 3 as catalyst, Lei et al developed an efficient, rapid and atom economy click-type synthetic method for preparing multisubstituted pyrroles 16. The reaction was based on co-cyclization of terminal alkynes 14 and isocyanide 15 (Scheme 4).…”

“…Given the influence of isocyanides in research front of synthesis of wide variety of heterocyclic systems, we also tried to provide more insight to isocyanide chemistry, including some reaction mechanisms and discussing their optimal reaction conditions. Isocyanide-based syntheses of pyrrole derivatives have been studied extensively [138][139][140][141][142][143][144][145] . Using Ag 2 CO 3 as catalyst, Lei et al developed an efficient, rapid and atom economy click-type synthetic method for preparing multi-substituted pyrroles 16.…”

The Nef Reaction of Isocyanides

“…Nef adducts were recently trapped by an enamine to afford dihydropyrrole derivatives such as 122 (Scheme 30). 45 The reaction was only described for carboethoxysubstituted adducts. For these, the high electrophilicity of the ketone led to a stabilization of tetrahedral intermediate 121 formed after nucleophilic addition, giving time for further cyclization onto the imidoyl chloride moiety.…”

Nef‐Isocyanide ‐Based One‐pot Two‐step Three Component Dihydrobenzo[4,5]Imidazo[2,1‐b]thiazoles Synthesis

“…The interaction of isocyanides with acyl chlorides for the preparation of active α‐keto imidoyl chloride was first reported by Nef in 1892 . Recently, Nef ‐isocyanide‐based multicomponent reaction was used for the synthesis of new biologically interesting heterocycles . In this context, benzoimidazothiazoles show interesting features, which make them attractive targets for the synthesis via Nef ‐isocyanide‐based multicomponent reaction.…”