Palladium-catalyzed C-3 Benzylation of Indoles with Benzyltributylammonium Chloride

Abstract

The indole scaffold probably represents one of the most important structural subunits for the discovery of new drug candidates. In recent years the transition metal induced-synthesis of indole compounds has gained increased popularity. However, simple alkylation of indole suffers problems such as regioselectivity at C-3, C-2, and N-1 positions.1 The purpose of this study is to study the benzylation of indole, specifically at the C-3 position, with benzyltributylammonium chloride (Fig. 1) using palladium catalysts. Using Pd(OAc)2 (II), a 40% conversion from indole to 3-benzylindole was achieved. The product was determined via GC-MS and H1-NMR. Optimization of reaction conditions followed by using various Pd catalysts with different oxidation states which found ammonium hexachloropalladate (IV) to obtain the highest conversion of 82%. Substituted indoles were then reacted to determine C-3 regioselectivity. Percent conversion varied between substituted indoles.