Desymmetric Cyanosilylation of Acyclic 1,3‐Diketones

Diastereo‐ and enantioselective construction of vicinal stereocenters from easily available starting materials is a challenging task. Here, we report that a bifunctional catalyst prepared from dibutylmagnesium and a pipecolinol‐derived tetradentate ligand can enable an asymmetric cyanosilylation of 1,3‐diketones to forge a pair of neighboring and acyclic tetrasubstituted carbons. The high stereoselectivity results from the rigid conformation of the diketone in the catalyst pocket, where the Lewis acidic magnesium center, together with the free hydroxyl group as a putative hydrogen bond donor, bind with both carbonyls. Consequently, stereochemically well‐defined cyanohydrin silyl ethers with a diverse collection of substituents were prepared. Their rapid derivatization to molecules of higher complexity, such as heterocycles, triols, and fused rings, were also demonstrated. A new bifunctional complex containing both a hydrogen bond donor and a Lewis acidic magnesium center was discovered to be a stereoselective cyanosilylation catalyst for structurally flexible acyclic 1,3‐diketones. Stereochemically defined vicinal tertiary and quaternary stereocenters can be obtained and further derived to polyfunctionalized molecules.