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

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.