Organocatalytic Stereoselective Cyanosilylation of Small Ketones

B. List and G.-J. Cheng report on the stereoselective cyanosilylation of small ketones catalyzed by organic acids.

The asymmetric cyanosilylation of carbonyl compounds is a highly versatile approach to build C–C bonds, enabling access to silylcyanohydrins, which are important building blocks with wide applications in the pharmaceutical and chemical industry. In past decades, the enantioselective cyanosilylation reaction has been thoroughly studied and many fascinating methodologies have been established. Nevertheless, the enantiofacial discrimination of dialkyl ketones is difficult to control with chiral catalysts and constitutes a long-standing challenge in organic synthesis. In particular, asymmetric reactions involving 2-butanone, which carries a methyl and an ethyl group on the carbonyl group, typically can only be catalyzed by enzymes following the ‘lock-and-key principle’. Recently, the research group of Professor Benjamin List at the Max-Planck-Institute für Kohlenforschung (Mülheim a.d.R., Germany) has designed and employed a sterically confined organic superacidic imidodiphosphorimidate (IDPi) catalyst to successfully accomplish the asymmetric cyanosilylation of 2-butanone with an enantiomeric ratio of 98:2. Professor Gui-Juan Cheng and co-workers at the Chinese University of Hong Kong (P. R. of China) performed DFT calculations to support the experimental observations.

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