Computer-aided mechanism elucidation of acetylene hydrocarboxylation to acrylic acid based on a novel union of empirical and formal methods

In the elucidation of complex multistep reactions, it is easy to overlook significant mechanistic hypotheses. Hence, the use of computer programs to search for mechanisms is attractive, but these programs must respect the prior knowledge held by the investigator. Virtually all knowledge-based programs accommodate prior knowledge of either what can or what cannot happen, but there are advantages in exploiting both types of knowledge simultaneously. We report a novel alliance of two programs that enables these advantages and which represents an advance in the capabilities of computational chemistry, as illustrated here on the complex synthesis of acrylic acid from acetylene, CO, and water catalyzed by palladium complexes. The pathways reported by the programs were categorized as hydride, hydroxycarbonyl (alcoholate-like), and metallocyclic, the mechanistic types that are known from publications on hydrocarboxylation and hydrocarbalkoxylation of unsaturated molecules in solutions of transition metal complexes. Many specific pathways were not considered before in the absence of comprehensive computerized searches.