Developing P-Stereogenic Phosphine Ligand for Transition Metal Catalyzed Asymmetric Hydrogenation

Abstract

This dissertation focusses on the discussion of how empirical ligand design works on the development of chiral pincer ligands in the field of asymmetric hydrogenation. Although the design art of bisphosphine ligands was well-established, this empirical guide for pincer ligand design is still ambiguous. Developing a ligand design guide based on the nature of metals enables synthetic chemists to improve the catalytic performance without investing large numbers of time, develop highly efficient catalysts for industrial uses, or explore new areas and mechanistic insights. Learning from the history of chiral pincer ligand development, over 14 categories of pincer ligands were reported according to the coordinating atoms by the time that this dissertation was prepared. Firstly, the ligand design and relevant catalytic performance of different ligand categories were summarized and discussed in prevalent noble metal catalysis such as Ru(II), Ir(III). Based on the nature of Fe(II) with respect to noble metals, a novel PNP-type ligand HengPNP (L) was designed and successfully synthesized. Empirical design perspectives were discussed, and the ligand was characterized by NMR, HRMS. Its corresponding Fe(II) complex was studied by X-ray crystallographic technique. However, the Fe(II) carbonyl complex was thermodynamically unstable under decent pressure. To better understand the catalytic performance and enantioselectivity of HengPNP(L), its corresponding Ir(III) complex was employed in the asymmetric hydrogenation of various ketone substrates. A C-H bond activation Ir(III) compound was successfully isolated. The Ir(III)/HengPNP was efficient on the asymmetric hydrogenation of orthosubstituted benzophenones with excellent ee and up to 500 TON. The catalyst was superior on the hydrogenation of bis-ortho-substituted benzophenones, excellent ee was achieved over the state-of-the-art Ir/f-amphox. DFT studies was conducted to shed light on the enantio-induction model of Ir/HengPNP. A novel enantio-induction mechanism was established-the change of rotation energy of ketone substrate under the steric pressure from rigid Ir/HengPNP, was responsible for the enantioselectivity. IrH/NH bifunctional mechanism was proposed for this protocol.