Efficient Synthesis of Amine Compounds by Catalytic Reductive Amination

Amine compounds are widely used in various fields and many synthetic methods have been developed. Reductive amination is an excellent one-step reaction to synthesize the corresponding amine compound from a carbonyl compound, but there are some problems such as the use of toxic and stoichiometric reductant or low catalytic activity. We challenged to develop new catalysts to solve these problems of reductive amination reactions. We examined various ligands and developed an Ir-PA complex having a picolinamidato ligand and an Ir-QN complex having a quinolinolato ligand. These catalysts exhibit high catalytic activity and functional group tolerance under mild transfer hydrogenation conditions using formic acid or formate as a hydrogen source and do not require a high-pressure vessel. We have also developed an asymmetric catalyst based on the knowledge of reductive amination catalysts. As a result of various tuning of the ligand structure, an iridium complex with a N-(2-picolyl)sulfonamidato ligand (Ir-PSA) was developed for the efficient synthesis of optically active amines from ketones by using an inexpensive amino alcohol as an auxiliary chiral group and nitrogen source. The asymmetric auxiliary groups used can be removed under mild oxidative conditions, and the catalytic reaction and deprotection can be performed in a one-pot process. Furthermore, this reaction can be adapted to α-keto carboxylic acids, enabling the synthesis of α-amino acids, including various unnatural α-amino acids. This article describes the properties of the developed catalysts and their reaction applications.