Sequential coupling/desilylation-coupling/cyclization in a single pot under Pd/C-Cu catalysis: Synthesis of 2-(hetero)aryl indoles

Abstract

A new one-pot synthesis of 2-(hetero)aryl indoles via sequential C-C coupling followed by C-Si bond cleavage and a subsequent tandem C-C/C-N bond forming reaction is described. A variety of functionalized indole derivatives were prepared by conducting this four step reaction under Pd/C-Cu catalysis. The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh3 and triethylamine in MeOH, followed by treating the reaction mixture with K2CO3 in aqueous MeOH, and finally coupling with o-iodoanilides. The single crystal X-ray data of a synthesized indole derivative is presented. Application of the methodology, in vitro pharmacological properties of the synthesized compound, along with a docking study is described. © 2011 The Royal Society of Chemistry.