N,N,N-Tridentate ligand promoted cobalt-catalyzed direct carbonylation of chloroacetonitrile to 2-cyano substituted acetates and amides

Abstract

2-Cyano-N-acetamides and 2-cyanoacetates are of great importance in the pharmaceutical industry, fueling the search for novel synthesis approaches. Transition-metal-catalyzed carbonylation, especially with cobalt, has potential but also suffers limitations, especially in reactions involving alkyl halides. Herein, a mild cobalt-catalyzed direct aminocarbonylation and alkoxycarbonylation of chloroacetonitrile promoted by an N,N,N-tridentate ligand was established. The targeted 2-cyano substituted acetates and amides are obtained in good to excellent yields. The preparation process is scalable and the compounds can be further transformed into bioactive molecules.