Copper-mediated C3-cyanation of indoles by the combination of amine and ammonium

Abstract

A copper-promoted C3-cyanation of both the free N–H and N-protected indoles by N,N,N′,N′-tetramethyl-ethane-1,2-diamine (TMEDA) and ammonium is achieved. The iminium ion acts as the intermediate in this transformation, which is sequentially electrophilically attacked by indole and H₂O followed by hydrolyzation to form the aldehyde. Then the reaction between the aldehyde and ammonium afforded nitriles. The reaction employs O₂ as a clean oxidant with good efficiency and functional group tolerance. Thus, it represents a facile and safe procedure leading to 3-cyano indoles.