Amidation of Aldehydes and Alcohols through α-Iminonitriles and a Sequential Oxidative Three-Component Strecker Reaction/Thio-Michael Addition/Alumina-Promoted Hydrolysis Process to Access β-Mercaptoamides from Aldehydes, Amines, and Thiols

Mild and general alumina-promoted hydrolysis conditions for converting alpha-iminonitriles into carboxamides have been developed. In combination with the oxidative three-component Strecker reaction, the one-pot direct amidation of aldehydes and alcohols is reported. Subsequently, an Yb(OTf)(3)-catalyzed Michael addition of thiols to alpha,beta-unsaturated a-iminonitriles is reported for the synthesis of beta-mercapto-alpha-iminonitriles. The successful integration of an oxidative Strecker reaction, thio-Michael addition, and neutral-alumina-promoted hydrolysis of beta-mercapto-alpha-iminonitriles into a three-component one-pot process allowed us to develop the direct conversion of amines, aldehydes, and thiols into beta-mercaptoamides. All of these procedures were applicable to aromatic and aliphatic amines and aldehydes.