Cu(OAc)₂-Triggered Cascade Reaction of Malonate-Tethered Acyl Oximes with Indoles, Indole-2-alcohols, and Indole-2-carboxamides

Abstract

A Cu­(OAc)2-promoted cascade reaction of malonate-tetherd acyl oximes with indoles, indole-2-alcohols, or indole-2-carboxmides provides facile access to polysubstituted 3-pyrrolin-2-ones. The reaction features the generation of two adjacent electrophilic centers at the same time as cyclization to lactam. The subsequent double addition with nucleophiles followed by oxidation realizes the difunctionalization of the imine sp2-carbon and the adjacent α-sp3-carbon.

Copper-Catalyzed Cascade Annulation of Malonate-Tethered O-Acyl Oximes with Cyclic 1,3-Dicarbonyl Compounds for the Synthesis of Spiro-Pentacyclic Derivatives

“…On the basis of our previous investigation of the reaction of malonate-tethered O -acetyl oximes with indole derivatives, 3-ethoxycarbonyl-5-substituted-2 H -pyrrol-2-one ( IM ) was deemed as the key intermediate (Scheme ). We envisaged its reaction with different 1,3/1,4-dinucleophiles would lead to structurally diverse bicyclic compounds.…”

“…Starting materials 1a–c , 1e–g , and 1o were known products, which has been reported in our previous work . Compound 2c was prepared according to the reported procedure …”

“…The construction of tricyclic skeletons from O -acyl oximes is still a blank so far. Recently, we have developed a novel reaction mode of O -acyl oximes based on the key cyclic intermediate bearing two vicinal electrophilic centers, which undergoes double addition with indole derivatives followed by oxidation to generate polysubstituted 3-pyrrolin-2-ones . As a continuation of our interest in the construction of new heterocyclic frameworks from O -acyl oximes, , herein, we reported the cascade annulation of malonate-tethered O -acetyl oximes with 2 equiv of cyclic 1,3-dicarbonyl compounds for the preparation of spiro-pentacyclic derivatives, in which a fused triheterocyclic core was constructed in a one-step reaction (Scheme ).…”

“…On the basis of our previously reported reaction of malonate-tetherd O -acyl oximes with indole derivatives, a plausible mechanism is described in Scheme . The in situ -generated Cu­(I), which can be formed in situ via reduction or disproportionation of Cu­(OAc) 2 , would initiate the reaction to generate the key intermediate 3-ethoxylcarbonyl-5-substituted-2 H -pyrrol-2-one 9 .…”

Copper-Catalyzed Annulation of Oxime Acetates with α-Amino Acid Ester Derivatives: Synthesis of 3-Sulfonamido/Imino 4-Pyrrolin-2-ones

“…Exploring their application in the synthesis of new heterocyclic scaffolds is challenging and interesting. Most recently, we developed a Cu­(OAc) 2 -promoted reaction of malonate-tethered oxime ester with indole derivatives for the synthesis of polysubstituted 3-pyrrolin-2-ones . In continuing our efforts aimed at extending the application of oxime esters for constructing new nitrogen-containing frameworks, herein, we reported a redox strategy to synthesize 4-pyrrolin-2-ones from oxime esters and α-amino acid ester derivatives.…”