Hydration of Cyanohydrins by Highly Active Cationic Pt Catalysts: Mechanism and Scope

Cyanohydrins
(α-hydroxy nitriles) are a special type of nitriles
that readily decompose into hydrogen cyanide (HCN) and the corresponding
carbonyl compounds. Hydration of cyanohydrins that are readily available
through cyanation of aldehydes and ketones provides the most straightforward
route to valuable α-hydroxyamides. However, due to low stability
of cyanohydrins and deactivation of the catalysts by the released
HCN, catalytic direct hydration of cyanohydrins still remains largely
unsolved. As a general trend, cyanohydrins containing bulkier substituents,
such as α,α-diaryl cyanohydrins, degrade more quickly
and thus are more difficult to be hydrated. Here, we report development
of cationic platinum catalysts that exhibit high reactivity for hydration
of various cyanohydrins. Detailed mechanistic investigations for hydration
of nitriles by (P∼P)­Pt­(PR2OH)­X­(OTf) reveal a catalytic
cycle involving the formation of a five-membered metallacyclic intermediate
and subsequent hydrolysis via attacking on the phosphorus of the secondary
phosphine oxide (PR2OH) ligand by H2O. We discovered
that Pt catalyst A bearing the electron-rich, appropriately
small-bite-angle bisphosphine ligand provides super reactivity for
hydration of cyanohydrins. The hydration reactions catalyzed by A proceed at ambient temperatures and occur with a wide variety
of cyanohydrins, including the most difficult α,α-diaryl
cyanohydrins, with good turnover numbers.