Ruthenium Complex-Catalyzed Tandem Reactions of Alcohols with Acetonitriles for Synthesis of α-Substituted Amides

A ruthenium complex-catalyzed tandem reaction of alcohols with nitriles in one pot has been developed, providing a green and atom-economic synthetic method of alpha-substituted amide. This method features high reactivity, high selectivity and good substrate compatibility. Good to high yields are obtained for most substrates and the highest yield is 96%. Mechanistic studies reveal that the alcohol first undergoes an acceptorless dehydrogenation into aldehyde. the resulting aldehyde occurs a nucleophilic addition with the alpha-position carbon of phenylacetonitrile to form alpha,ss-unsaturated nitrile and water. Subsequently, the unsaturated nitrile is hydrogenated with ruthenium-hydride species formed by the dehydrogenation of alcohol to give saturated nitrile, and then the water, generated by the nucleophilic addition, causes the catalytic hydrolysis of cyano group to finally generate alpha-arylamide.