Abstract
Palladium-catalysed cross-coupling reactions have been used extensively in academia and various industries around the globe. The choice of ligand plays an important role in Pd-catalysed cross-coupling reactions mainly influencing the oxidative addition as well as the reductive elimination step in the catalytic cycle. The bulky, electron-deficient secondary phosphine 1, 3, 5, 7-tetramethyl-2, 4, 8-trioxa-6- phospha adamantane (PA-H) and tertiary phosphine 1, 3, 5, 7-tetramethyl-6- tetradecyl-2, 4, 8-trioxa-6-phospha adamantane (PA-C14) ligands (received as a gift from Sasol Pty (Ltd) R & D laboratories) were investigated for catalytic efficiency in Heck cross-coupling reactions. The starting point involved an extensive study to investigate various reaction parameters in order to gain better understanding of the reaction conditions influencing the outcome of the PA / Pd catalyst systems. Following the discovery of optimal reaction conditions, a diverse range of aryl halides (iodide, bromide, chloride) with varying electronic and steric properties were evaluated using the PA / Pd catalyst systems. Although n-butyl acrylate was extensively used as the olefin in this study, the Heck reactions using these ligands were also demonstrated using other structurally diverse olefins. The outcome of this study was that PA / Pd ligand catalysts were efficient in Heck reactions furnishing high yields when applied to coupling reactions of aryl iodides and bromides with different coupling or substitution patterns. This new protocol using PA / Pd was also found to be efficient in coupling reactions of some challenging aryl chlorides with olefins. It was however observed that aryl halides with ortho-substituents furnished low to moderate yields due to steric hindrance imposed on the Pd metal. In short, this study has demonstrated the first successful use of sterically encumbered PA ligands as efficient supporting ligands for the Pd-catalysed Heck cross-coupling reactions. Importantly, active Pd catalysts for Heck reactions could be developed using both secondary and tertiary phosphine ligands of the same family. To exemplify the effectiveness of the new PA / Pd catalyst system, the method was applied in the synthesis of industrial important products shown below. The products were synthesised and isolated in good yields.
M.Sc. (Chemistry)