The Catalytic Asymmetric Strecker Reaction

Shibasaki, Masakatsu; Kanai, Motomu; Mita, Tsuyoshi


Alpha-amino acids are important building blocks for proteins, peptides, and pharmaceuticals. Among a variety of methods to synthesize optically active alpha-amino acids, the Strecker reaction is one of the simplest and most powerful. This reaction consists of three steps (1) condensation of an aldehyde or ketone with an amine to produce and imine, (2) nucleophilic attack of cyanide on the imine to produce and amino nitrile, and (3) hydrolysis of the amino nitrile to the corresponding alpha-amino acid. These steps can be conducted in one pot. Conversion of the nitrile group to amide, amine, or aldehyde functionalities is also possible. The catalytic promotion and enantiocontrol of the cyanide addition to the imines is the main focus of the Strecker reaction. Therefore, isolated and purified imines are normally used as substrates. The catalyst turnover efficiency and enantioselectivity of this step are intimately related to the electronic and steric characteristics of the substrate imines, with nitrogen substituent greatly contributing to these factors. However, since optically active alpha-amino acids are generally the synthetic target of the catalytic asymmetric Strecker reaction, the accessibility of the starting imines and ease of final deprotection of the product are also important considerations. This chapter focuses on catalytic enantioselective Strecker and Reissert reactions.