Optically active a-amino acids are vital to life as building blocks of peptides, proteins, and many other natural products. Amino acids are also applied extensively as food additives, pharmaceuticals, and agrochemicals. Furthermore, amino acids are widely used in organic synthesis as targets, and as constituents for reagents and/or catalysts in asymmetric synthesis.
The synthesis of optically active nonproteinogenic a-amino acids is an interesting and important research field which has received much attention and the application of asymmetric catalysis towards formation of these compounds from simple starting materials is a fundamental challenge.
Recently, catalysts have been developed for enantioselective addition reactions to imines, including processes such as the ene [2] , Mannich-type, allylation, [4] and aza-Diels ± Alder reactions. [5] Reports on the catalytic enantioselective addition of imines to aromatics are very few, and, according to our knowledge, only one example of the addition of an imine to indole and pyrrole systems has been reported. Recently, several catalytic asymmetric Strecker reactions have emerged for the synthesis of optically active, natural, as well as unnatural, aromatic and aliphatic a-amino acids. In this paper we present the development of a catalytic enantioselective addition reaction of imines 1 to electron-rich aromatic compounds 2 leading to protected optically active aromatic a-amino acids 3 (Scheme 1). An advantage of this reaction is that 1 is prepared by an aza-Wittig reaction and used directly without further purification (Scheme 1).
Scheme 1. Top: Addition of imines 1 to electron-rich aromatic compounds 2 to form protected aromatic a-amino acids 3. Bottom: Synthesis of the protected imine starting materials 1. Pg protecting group.