Asymmetric Strecker Reactions: An Update

The Strecker reaction enables the straightforward, one-step synthesis of α-amino nitriles, which serve as valuable building blocks for a wide range of important products, including α-amino acids and their derivatives. α-Amino acids play a fundamental role in biological systems, and both natural and synthetic α-amino acids are extensively employed in medicinal chemistry. Among the available strategies, the asymmetric Strecker reaction remains the most widely used approach for synthesizing α-amino acids. Over the past few decades, asymmetric versions of this reaction have been intensively explored, encompassing diastereoselective reactions-particularly in the total synthesis of natural and bioactive compounds-as well as enantioselective metal- and organocatalyzed cyanations of imines. The diversity of catalysts employed in these enantioselective transformations highlights the considerable potential for further developments in the near future. In addition to the traditionally used, but highly toxic, HCN and TMSCN, greener and more cost-effective cyanide sources such as KCN, NaCN, acetone cyanohydrin, and ethyl cyanoformate are gaining attention for industrial applications. While metal-promoted enantioselective cyanations of imines are well-established, the more economical and environmentally friendly organocatalytic approaches are expected to be increasingly preferred, in line with the principles of green chemistry. Today, the asymmetric Strecker reaction continues to represent the simplest and most efficient methodology for synthesizing chiral α-amino acids and their derivatives. This review provides an update on the field of asymmetric Strecker reactions since 2014. It is organized into four sections, covering diastereoselective Strecker reactions, organocatalyzed enantioselective Strecker reactions, metal/boron-catalyzed enantioselective Strecker reactions, and asymmetric Strecker reactions facilitated by crystallization processes.