Tandem one-pot construction of indoles via palladium and copper-catalyzed coupling reactions of the blaise reaction intermediate

Abstract

The palladium-catalyzed intramolecular N-arylation of the Blaise reaction intermediate, formed by reaction of nitriles with an in situ generated Reformatsky reagent from ethyl -bromo - (2-bromophenyl)acetate and zinc, afforded indoles in good yields. Extension of this approach to the chemoselective intramolecular N-alkylation/palladium-catalyzed N-arylation of the Blaise reaction intermediate, having -chloroalkyl appendages, provided a novel route for the tandem one-pot synthesis of N-fused indole derivatives. In contrast, the intermolecular coupling reaction of the Blaise reaction intermediates with 1,2-dihalobenzene did not proceed in the presence of a palladium catalyst, but proceeded in the presence of copper(I) iodide as the catalyst and resulted in indoles. 1 Introduction 2 Results and Discussion 2.1 Palladium-Catalyzed Intramolecular C-N Coupling Reaction of the Blaise Reaction Intermediate 2.2 Chemoselective Intramolecular N-Alkylation/Palladium-Catalyzed C-N Coupling Reaction of the Blaise Reaction Intermediate 2.3 Copper-Catalyzed Intermolecular N-C/C-C Coupling Reaction of the Blaise Reaction Intermediate with 1,2-Dihaloarenes 3 Conclusion. © 2012 Georg Thieme Verlag Stuttgart • New York.