Phosphinous Acid-Assisted Hydration of Nitriles: Understanding the Controversial Reactivity of Osmium and Ruthenium Catalysts

The synthesis and catalytic behavior of the osmium(II) complexes [OsCl2(eta(6)-p-cymene)(PR2OH)] [R=Me (2 a), Ph (2 b), OMe (2 c), OPh (2 d)] in nitrile hydration reactions is presented. Among them, the best catalytic results were obtained with the phosphinous acid derivative [OsCl2(eta(6)-p-cymene)(PMe2OH)] (2a), which selectively provided the desired primary amides in excellent yields and short times at 80 degrees C, employing directly water as solvent, and without the assistance of any basic additive (TOF values up to 200h(-1)). The process was successful with aromatic, heteroaromatic, aliphatic, and ,alpha,beta-unsaturated organonitriles, and showed a high functional group tolerance. Indeed, complex 2a represents the most active and versatile osmium-based catalyst for the hydration of nitriles reported so far in the literature. In addition, it exhibits a catalytic performance similar to that of its ruthenium analogue [RuCl2(eta(6)-p-cymene)(PMe2OH)] (4). However, when compared to 4, the osmium complex 2a turned out to be faster in the hydration of less-reactive aliphatic nitriles, whereas the opposite trend was generally observed with aromatic substrates. DFT calculations suggest that these differences in reactivity are mainly related to the ring strain associated with the key intermediate in the catalytic cycle, that is, a five-membered metallacyclic species generated by intramolecular addition of the hydroxyl group of the phosphinous acid ligand to the metal-coordinated nitrile.