Cyclization Reaction Of Cyanoacetanilide Derivatives:Synthesis Of Quinoline-2,4-diones And Furo[2,3-b] Quinolines

Cyanoacetanilides are widely used as building blocks in organic synthesis due to their ready accessibility and versatile reactivity.The presence of multiple nucleophilic andelectrophilic centers in cyanoacetanilides allow them to undergo a variety of heterocyclization reactions under the influence of electrophilic,nucleophilic,and radical reagents,leading to different heterocyclic compounds.On the other hand,the electrophilic substitution reaction of aromatic C-H bonds with cyano-compounds,known as Houben-Hoesch reaction,is a classical synthetic approach to aryl ketones.During the course of our studies on the synthetic applications of Houben-Hoesch reaction,we achieved a facile synthesis of 4-quinolones via triflic anhydride-mediated intramolecular Houben-Hoesch reaction of ?-arylamino acrylonitriles in N,N-dimethylformamide(DMF).As a continuation of this previous work,we prepared a series of cyanoacetanilide derivatives and explored their intramolecular Houben-Hoesch reaction.The main experimental results are summarized as bellow:1.A concise access to quinolin-2,4-diones is developed based on a methyl triflate(TfOMe)-promoted intramolecular Houben-Hoesch reaction of ?,?-dialkyl substituted cyanoacetanilides.In this reaction,the treatment of ?,?-dialkyl-N-arylcyanoacetamides with TfOMe caused the successive N-methylation of the cyano group and subsequent intramolecular cyclization to generate ketimine intermediate,which was finally hydrolyzed to yield quinolin-2,4-diones.The broad substrate scope,simple operation and mild reaction conditions make this synthetic method very attractive.2.A facile and efficient approach to 4-aminofuro[2,3-b]quinolinium triflates is developed via an alkyltrifate-mediated domino reaction of 1-cyano-l-carbamoyl cyclopropanes.The reaction features a broad substrate scope,mild reaction conditions,simple operation,and chromatography-free product purification.A mechanism involving regioselective alkylation,intramolecular cyclization,and a ring-enlargement sequence is proposed for the 4-amino-2,3-dihydrofuro[2,3-b]quinolinium synthesis.