Nitrilation of carboxylic acids by P^III/P^V-catalysis

A mild and catalytic method for the direct conversion of carboxylic acids into their corresponding nitriles is reported. In contrast to common nitrile preparations that rely on hazardous cyanide and cyanogen precursors, the present protocol employs a P^III/P^V-catalyzed 'oxidation-reduction condensation' approach to effect iterative amidation/retro-Ritter reaction of carboxylic acids with 1-phenethylamine. Primary, secondary, tertiary, and aromatic carboxylic acids all undergo nitrilation in synthetically viable yields, including several pharmaceuticals and natural products. Using homochiral 1-phenethylamine, both resolution and nitrilation of racemic carboxylic acids can be achieved, allowing synthetic access to chiral nitriles.