Straightforward α‐Amino Nitrile Synthesis Through Mo(CO)6‐Catalyzed Reductive Functionalization of Carboxamides

The selective reduction of amides into an intermediate hemiaminal catalyzed by Mo(CO)₆ together with the inexpensive and easy to handle TMDS (1,1,3,3‐tetramethyldisiloxane) as reducing agent, followed by subsequent trapping of the hemiaminal with a cyanide source, allows for the straightforward synthesis of α‐amino nitriles. The methodology presented here, displays high levels of chemoselectivity allowing for the reduction of amides in the presence of functional groups such as ketones, imines, aldehydes, and acids, which affords a simple route for the synthesis of α‐amino nitriles with a broad scope of functionalities in high yields. Furthermore, the applicability of this methodology is demonstrated by scale up experiments and by derivatization of the target compounds into synthetically interesting products. The selective cyanation is successfully applied in late stage functionalizations of amide containing drugs and prolinol derivatives.