Intramolecular attack on coordinated nitriles: metallacycle intermediates in catalytic hydration and beyond

Hydration of nitriles is catalyzed by the enzyme nitrile hydratase, with iron or cobalt active sites, and by a variety of synthetic metal complexes. This Perspective focuses on parallels between the reaction mechanism of the enzyme and a class of particularly active catalysts bearing secondary phosphine oxide (SPO) ligands. In both cases, the key catalytic step was proposed to be intramolecular attack on a coordinated nitrile, with either an S-OH or S-O^- (enzyme) or a P-OH (synthetic) nucleophile. Attack of water on the heteroatom (S or P) in the resulting metallacycle and proton transfer yields the amide and regenerates the catalyst. Evidence for this mechanism, its relevance to the formation of related metallacycles, and its potential for design of more active catalysts for nitrile hydration is summarized.