Catalytic Transfer Hydration of Cyanohydrins to α-Hydroxyamides.

We report the palladium(II)-catalyzed transfer hydration of cyanohydrins to α -hydroxyamides by using carboxamides as water donors. This method enables selective hydration of various aldehyde- and ketone-derived cyanohydrins to afford α-mono- and α,α-disubstituted-α -hydroxyamides, respectively, under mild conditions (50 °C, 10 min). The direct conversion of fenofibrate, a drug bearing a benzophenone moiety, into a functionalized α,α-diaryl-α -hydroxyamide was achieved by means of a hydrocyanation-transfer hydration sequence. Preliminary kinetic studies and the synthesis of a site-specifically 18O-labeled α -hydroxyamide demonstrated the carbonyl oxygen transfer from the carboxamide reagent into the α -hydroxyamide product.