Hemilability-Driven Water Activation: A NiII Catalyst for Base-Free Hydration of Nitriles to Amides

5 years ago

Hemilability-Driven Water Activation: A NiII Catalyst for Base-Free Hydration of Nitriles to Amides

Abir Sarbajna, Jitendra K. Bera, Kuldeep Singh, Pragati Pandey, Indranil Dutta

The NiII complex 1 containing pyridyl- and hydroxy-functionalized N-heterocyclic carbenes (NHCs) is synthesized and its catalytic utility for the selective nitrile hydration to the corresponding amide under base-free conditions is evaluated. The title compound exploits a hemilabile pyridyl unit to interact with a catalytically relevant water molecule through hydrogen-bonding and promotes a nucleophilic water attack to the nitrile. A wide variety of nitriles is hydrated to the corresponding amides including the pharmaceutical drugs rufinamide, Rifater, and piracetam. Synthetically challenging α-hydroxyamides are accessed from cyanohydrins under neutral conditions. Related catalysts that lack the pyridyl unit (i.e., compounds 2 and 4) are not active whereas those containing both the pyridyl and the hydroxy or only the pyridyl pendant (i.e., compounds 1 and 3) show substantial activity. The linkage isomer 1′ where the hydroxy group is bound to the metal instead of the pyridyl group was isolated under different crystallization conditions insinuating a ligand hemilabile behavior. Additional pKa measurements reveal an accessible pyridyl unit under the catalytic conditions. Kinetic studies support a ligand-promoted nucleophilic water addition to a metal-bound nitrile group. This work reports a Ni-based catalyst that exhibits functional hemilability for hydration chemistry. Water bearer: A hemilabile pyridyl unit on a Ni catalyst bearing functionalized N-heterocyclic carbene (NHC) ligands, guides a water molecule to the metal, polarizes it through hydrogen-bonding interactions, and promotes nucleophilic attack to the nitrile carbon atom for nitrile hydration to the corresponding amide under base-free condition (see scheme).

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201700816