Kinetic Resolution of Acylsilane Cyanohydrins via Organocatalytic Cycloetherification

An asymmetric cyanation of acylsilanes involving the in‐situ formation of chiral acylsilane cyanohydrins followed by their kinetic resolution via organocatalytic cycloetherification is described. The highly enantio‐ and diastereoselective cycloetherification was crucial for achieving a high efficiency in the kinetic resolution. Consequently, acylsilane cyanohydrins containing a tetrasubstituted chiral carbon atom bearing silyl, cyano, and hydroxy groups were obtained in an enantioenriched form. This protocol therefore offers an efficient catalytic approach to optically active acylsilane cyanohydrins, which exhibit potential as chiral building blocks for the synthesis of pharmaceutically relevant chiral organosilanes.     

Cover Picture: From Three- to Six-Membered Heterocycles Bearing a Quaternary Stereocenter: an Asymmetric Organocatalytic Approach (Chem. Rec. 5/2023)

The development of procedures useful to form quaternary stereocenters stands out as a highly challenging task in asymmetric synthesis. With the arrival of organocatalysis, different activation strategies became available to pursue this intriguing target, thus leading to notable advancements of the area. In this account, our achievements, spanning over a decade, on asymmetric methodologies to access novel three-, five-, six-membered heterocycles, including spiro compounds bearing quaternary stereocenters, will be highlighted. The Michael addition reaction has been often exploited to trigger cascade reactions, using organocatalysts mostly derived from Cinchona alkaloids, and operating under non-covalent activation of the reagents. Further manipulations of the enantioenriched heterocycles, attested them as useful compounds to prepare functionalized building blocks.