Study of heteroaromatic enediyne and substituted benzothiophene synthesis with relative reactivity of substituted aryl iodides in the Sonogashira reaction

Abstract

Enediyne compounds have captured the imagination of chemists since their discovery as a class of natural products. Because of their cytotoxicity, these compounds are not suitable for use in cancer treatment. As a result, chemists have aimed to reduce their toxicity, improve stability and elucidate the mechanism of their cyclization reaction. The Sonogashira coupling reaction is used to synthesize a number of heteroaromatic enediynes and has been examined. By coupling a number of alkynes with 2,3- dibromothiphene a number of corresponding disubstituted enediynes were produced. In order to get fused bicyclic heteroaromatic products both thermal and photochemical Bergman cyclizations have been performed with these enediynes. To date, the attempted cyclizations have not been successful. Beside this, a series of competitive reactions was carried out to determine the relative reactivity of substituted aryl iodides in the Sonogashira reactions. These reactions were carried out in co-catalyst system composed of Pd/Cul. The competitive reactions between iodobenzene and a number of 3- and 4-substituted iodobenzenes provided relative rates which were compared to the theoretical electron densities of the iodidebearing carbon. Generally, electron withdrawing substituents in the para- and metapositions increased the reactivity, while donating substituents decreased the rate of reaction. It was found that resonance effects have a greater effect on reactivity than inductive effects.