Catalytic Transfer Hydration of Cyanohydrins to α-Hydroxyamides

Papers published
Tomoya Kanda, Asuka Naraoka, and Hiroshi Naka, J. Am. Chem. Soc. ASAP, (2019). DOI: 10.1021/jacs.8b12877
  • Hydration of cyanohydrins (1) to α-hydroxycarboxamides (2) is one of the most important reactions in both laboratory and industrial synthetic chemistry. However, hydration of cyanohydrins is not always straightforward because cyanohydrins often decompose into carbonyl compounds and hydrogen cyanide (HCN) and because HCN often deactivates catalysts. 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.

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