Synthesis 2012(10): 1464-1476  
DOI: 10.1055/s-0031-1289753
FEATUREARTICLE
© Georg Thieme Verlag Stuttgart ˙ New York

Tandem One-Pot Construction of Indoles via Palladium and Copper-Catalyzed Coupling Reactions of the Blaise Reaction Intermediate

Ju Hyun Kim, Sang-gi Lee*
Department of Chemistry and Nano Science (BK21), Ewha Womans University, 120-750 Seoul, Korea
Fax: +82(2)32774505; e-Mail: sanggi@ewha.ac.kr;
Further Information

Publication History

Received 3 January 2012
Publication Date:
29 March 2012 (online)

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 α-bromo-α-(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 ω-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