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

Cyanohydrins (alpha-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 alpha-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 alpha,alpha-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 similar to 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 alpha,alpha-diaryl cyanohydrins, with good turnover numbers.