Catalytic Enantioselective Cyanation: Recent Advances and Perspectives

alpha-Chiral nitrites are prevalent structural motifs in natural products, drugs, and pharmaceutically active compounds. In addition, because the cyano group can undergo various diversifying reactions, they are very versatile chiral building blocks for the synthesis of optically active aldehydes, ketones, carboxylic acids, carboxamides, amines, and N-heterocycles such as tetrazolium. Accordingly, the catalytic enantioselective cyanation reaction, as one of the most important C-C bond forming reactions, has been intensely studied in the past three decades. While traditional efforts mainly focus on the addition of the cyanide to highly polarized electrophiles as well as alkene hydrocyanation, intriguing directions in enantioselective cyanations have been opened, including the development of enantioselective alkene cyanofunctionalization, cyanation via C-H bond functionalization, and C-C bond cleavage, as well as the invention of bifunctional cyanating agents to design asymmetric tandem synthesis and to exploit enantioselective cyanide-free cyanation reactions. Additionally, significant advances have also been made in developing unprecedented chiral catalysts to address a long-term challenge, the catalytic enantioselective synthesis of structurally diverse C-alpha-tetrasubstituted or quaternary alpha-chiral nitrites. This perspective aims to highlight these impressive advances, illustrates their key advantages and future applications, and provides some inspiration for related research.