Asymmetric (Transfer) Hydrogenation of Imines

Abstract

The chapter “Asymmetric (Transfer) Hydrogenation of Imines” summarizes the recent advances in chiral amine synthesis through asymmetric imine hydrogenation using transition metals, chiral ligands, and biocatalysts. Different strategies are considered along the chapter. The first part focuses on the catalytic hydrogenation of imines using transition metals under high pressure of molecular hydrogen. This section is classified according to metal and ligand types including not only Ir, the most studied and efficient metal for these transformations, but also Rh and Pd. In the case of Ir, the chapter describes the most successful and efficient catalytic systems using (P, P) and (P, N) ligands as well as remarkable results obtained with the more accessible monodentate P ligands. This section also covers the recent examples employing Rh and Pd as alternative metals using P and N ligands, particularly chiral diphosphines applied to a variety of substrates. The second part focuses on the asymmetric transfer hydrogenation of imines where the use of methanol as the hydrogen source provides an alternative and safe system. In this process the chapter describes extensively the use of Ru as the most efficient metal to design effective catalytic systems mainly in combination with chiral diamine ligands. Particularly interesting in this section is the description of several immobilization methods for catalyst recycling. Finally, the chapter includes novel approaches such as biocatalytic imine reduction, metal-free catalysts, and artificial metalloenzymes which behave as synthetic biocatalysts providing novel and alternative processes in asymmetric imine hydrogenation. In summary, the interest of the chapter lies in the presentation of recent advances and applications in chiral amine synthesis through a variety of catalytic processes offering different approaches in terms of efficiency and sustainability. The content of this chapter is aimed at researchers, graduate students, and synthetic chemists at all levels in both academia and industry.