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Hemilability‐Driven Water Activation: A Ni II Catalyst for Base‐Free Hydration of Nitriles to Amides
Author(s) -
Singh Kuldeep,
Sarbajna Abir,
Dutta Indranil,
Pandey Pragati,
Bera Jitendra K.
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700816
Subject(s) - nitrile , chemistry , nucleophile , catalysis , amide , ligand (biochemistry) , nitrile hydratase , combinatorial chemistry , polymer chemistry , base (topology) , medicinal chemistry , organic chemistry , mathematical analysis , biochemistry , receptor , mathematics
The Ni II 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 p K a 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.