Organocatalytic C3-Selective Friedel-Crafts Alkylations Of Indoles With A,β-Unsaturated Ketones

The Friedel-Crafts alkylation reaction is one of the most important C-C bond forming reactions in organic chemistry. Regioselective Friedel-Crafts alkylation at the 3-position of indoles represents one of the most straightforward methods for the synthesis of many naturally occurring alkaloids. 3-Substituted indoles are important building blocks for the synthesis of biologically active compounds and natural products. Recently , the synthesis of B-indolylketones has received much attention due to their important biological activities and key role as versatile building bocks in the synthesis of natural products. Therefore, a variety of methods have been reported for the preparation of this class of compounds. The development of new, more efficient, more selective synthetic methods of B-indolylketones continues to receive considerable attention for organic chemists. In this context, we document the organocatalytic C3-selective Friedel-Crafts alkylations of indoles with a,β-unsaturated ketones. An attempts to carry out the organocatalytic asymmetric version of this reaction has been also examined. The main results are summarized as follows:1.We studied the organocatalytic C3-selective Friedel-Crafts alkylations of indoles with a,β-unsaturated ketones, which resulted in β-indolylketones in high yields. The effects of co-catalyst and solvent on the reactions have been examined. A series of β-indolyketones were synthesized with the use of pyrroline-HClO₄ as the catalyst and dichloromethane as the solvent. All target compounds were characterized by ¹HNMR, ¹³CNMR, MS and element analysis.2.The organocatalytic asymmetric reaction of indoles with a,β-unsaturated ketones has been examined. Catalysts, co-catalyst, solvents and substrates were investigated in details. Using the MacMillan second generation organocatalyst and HOAc as the catalytic system,the reaction gave promising results in dichloromethane. The enantiomer excess of the product was up to 28%.