Mechanistic investigations of metal-catalyzed (poly)esterification reactions

The ester bond is an important structural motif in organic molecules, that among others find application as pharmaceuticals, fragrances or coatings. Although the direct coupling of carboxylic acids and alcohols is known for more than a century, it is still the most prominent route to synthesize the ester moiety. This chemical transformation affords the desired ester bond and water as the only by-product, but high reaction temperatures are required. Therefore, the use of a catalyst that can lower the reaction temperature and enable mild reaction conditions is highly desirable. Lewis acidic metals exclusively catalyze the desired esterification reaction and are therefore intensively explored as catalysts. Although a wide variety of different metal salts were found to be effective catalysts, understanding the origin of their catalytic activity is still limited. Mechanistic studies are severely complicated due to in situ transformation of the catalyst, since all reaction components (carboxylic acid, alcohol, ester and water) have the ability to coordinate to the Lewis acidic metal center. In this thesis, we have shed light on the structure of various in situ formed Lewis acidic metal catalysts, potential intermediates and have provided deeper mechanistic understanding of the catalytic cycle. Besides the direct (poly)esterification reaction also the nickel-catalyzed carbon-oxygen bond forming reaction between an organic halide and a carboxylic acid is investigated. Also here, mechanistic understanding of the catalytic cycle is hindered by many side reactions, either by reaction with one of the reaction components, or by other (deactivation) reactions.