Base-Free Suzuki acylation reactions of sodium (aryl trihydroxyborate) salts: a novel synthesis of substituted aryl ketones.

Abstract

Asymmetric biaryl ketones are important building block in organic chemistry since they occur in large number of biological active compounds, natural product, cosmetics as well as in organic synthesis. The aim of this project was to develop a novel base-free Suzuki-Miyaura cross-coupling of biaryl ketones from sodium (aryl trihydroxyborate) salts coupled with acyl chlorides catalysed by palladium precursor and investigate the electron effect of substituents attached to acyl chloride and sodium (aryl trihydroxyborate) salts on the yields of ketones produced. A novel synthesis of biaryl ketones was successfully developed in coupling of commercially available substituted acyl chlorides with easily accessible substituted sodium (aryl trihydroxyborate) salts catalysed by Pd(PPh3)4 in aqueous toluene. A wide range of functional groups were accommodated including CF3, OMe, SMe, Br, F, NO2, OH, NH2 yielding up to 96% in 24 hours. Encouraged by successful cross-coupling reaction between sodium (aryl trihydroxyborate) salts and acyl chlorides under the Suzuki-Miyaura cross-coupling acylation reaction conditions, we thought it would be logical to extend the scope of the developed reaction condition to include carboxylic anhydrides as electrophiles. As a result, substituted benzoic anhydrides were first synthesised following previously published procedures giving the desired products in excellent yields (87-99%). The synthesised carboxylic anhydrides were subsequently cross-coupled with boronate salts under base-free and ligandless palladium catalysed cross-coupling reaction conditions to synthesise biaryl ketones in aqueous acetone. The developed method appears sensitive to electronic effects both on the electrophile and on the nucleophile and on the nucleophile furnishing the desired ketones in moderate yields. Two novel methods have been developed to synthesise ketones from stable, easy to prepare and free flowing pure sodium (aryl trihydroxyborate) salts.