Exploration and development of benzimidazole-based phosphine ligands towards suzuki-miyaura cross-coupling

Abstract

The research study is focused on the development of easily accessible heterocyclic phosphine ligands. The first part of the investigation is the attempted study of electronic effects towards the reactivity of indolyl phosphine ligands while the second part is the design and synthesis of newly developed benzimidazole-based phosphine ligands and their applications on Suzuki-Miyaura Coupling. In the study of indolyl phosphine ligand, we tried to examine the electronic effect by the incorporation of different substituted groups on the 5-position of the indole ring on the ligand template. We aim to study the importance of the electronic density on the phosphorus atom over the reactivity of the ligands. We propose that the reactivity of the ligands should be directly proportional to the electron density of P donor atom of ligands. A family of 5-substituted indolyl phosphine ligands were successfully prepared and their reactivity was compared by the same Suzuki coupling reaction under mild reaction conditions in order to demonstrate their reactivity differences. We believe this research findings will contribute to the future development of related ligands. In my second project, a new scaffold, benzimidazole, was used for the ligand design. Benzimidazole is attractive as it is commercially available with a reasonable price. In addition, the synthesis of benzimidazole-based phosphine ligand is atom economic that less side products are formed. However, using ligands with benzimidazole scaffold is not electron-rich enough for Suzuki coupling. Based on the research concept of my first project, we modified the ligand design by adding two methyl groups on the benzimidazole scaffold. The new dimethyl benzimidazole-based phosphine ligand is highly effective for Suzuki coupling of both activated and deactivated aryl chlorides with moderate catalytst loading.