Platinum-Catalyzed Selective Hydration of Hindered Nitriles and Nitriles with Acid- or Base-Sensitive Groups

Hindered tertiary nitriles can be hydrolyzed under neutral and mild conditions to the corresponding
amides using platinum(II) catalysts with dimethylphosphine oxide or other secondary phosphine
oxides (SPOs, phosphinous acids) as ligands. We have found that this procedure also works well
for nitriles with acid- or base-sensitive groups, which is unprecedented in terms of yield and
selectivity. The catalyst loading can be as low as 0.5 mol %. Amides are isolated as the only product
in high yield, and no further hydrolysis to the corresponding acids takes place. Reactions are carried
out at 80 °C but take place even at room temperature. When enantiopure secondary phosphine
oxide ligands are used in the hydrolysis of racemic nitriles, no kinetic resolution is observed,
presumably due to racemization of the ligand during the reaction.