Chemistry of Cyanide Adducts of Aldimines

Strecker products, generated by the addition of HCN to imines derived from carbonyls and amines, have been widely utilized as versatile intermediates in various synthetic transformations.However, since cyanide adducts of aldimines have been known to readily undergo an elimination reaction (retro-Strecker reaction), the cyanide adducts have been far less utilized as synthetic intermediates and few synthetic protocols have been developed based on these intermediates (Figure 1).

To address this issue, our group initiated a program to develop novel synthetic protocols utilizing cyanide adducts of aldimines as synthetic intermediates. For example, we developed a protocol for the synthesis of benzoxazoles from aldimines obtained from o-aminophenol and aldehydes via metal-free aerobic oxidative cyclization using cyanide as the nucleophilic catalyst. Furthermore, a new protocol for the synthesis of 2-aminoquinoxalines was developed from cyanide adducts of imines derived from o-phenylenediamine via 6-exo-tet cyclization. In addition, a novel method to generate umpolung of aldimines was developed from cyanide adducts via intramolecular proton transfer. Based on this umpolung of aldimines with cyanide, the metal-free aerobic oxidation of aldimines was developed, affording the corresponding amides. Furthermore, a highly efficient protocol for the synthesis of 2-substituted indole-3-acetic acid derivatives from 2-aminocinnamic acid derivatives and aldehydes has been developed through the imino-Stetter reaction.