We report the first highly diastereo- and enantioselective C–C bond-forming reaction of racemic α-branched ketones to construct tertiary alcohols with adjacent stereocenters. Accordingly, a highly stereoselective cyanosilylation of racemic ketones is developed using our bifunctional cyanating reagent, Me₂(CH₂Cl)SiCN, giving C^α-tetrasubstituted silyl cyanohydrins with two vicinal stereocenters in up to >20:1 diastereomeric ratio (dr) and 90–98% enantiomeric excess (ee) values, which can undergo various diversification reactions by manipulating the chloromethyl group. A highly selective kinetic resolution of acyclic α-branched ketones is also developed that allows facile access to acyclic α-alkyl, allyl, and propargyl ketones with good recovery and excellent ee values. The synthetic value of this protocol is further demonstrated by the formal synthesis of the anti-obesity agent, taranabant (MK-0364). The activation of Jacobsen’s privileged catalyst (salen)AlCl by a suitable phosphorane plays a crucial role in the reaction. X-ray crystallographic analysis of single crystals of phosphorane–(salen)AlCl complexes and theoretical calculations help provide a working model. The present transformation opens a new path for the catalytic stereoselective synthesis of stereochemically complex tertiary alcohols featuring two stereocenters (adjacent or not) from racemic ketones.

我们报告了外消旋α-支化酮的第一个高度非对映选择性和对映选择性C-C键形成反应，以构建具有相邻立体中心的叔醇。因此，使用我们的双功能氰化试剂 Me ₂ (CH ₂ Cl)SiCN开发了外消旋酮的高度立体选择性氰硅烷化，得到C ^α-四取代的甲硅烷基氰醇具有两个邻位立体中心，非对映体比率 (dr) 高达 >20:1，对映体过量 (ee) 值高达 90-98%，可通过操纵氯甲基进行各种多样化反应。还开发了非环状 α-支化酮的高选择性动力学拆分，可以轻松获得具有良好回收率和优异 ee 值的非环状 α-烷基、烯丙基和炔丙基酮。该协议的合成价值通过抗肥胖剂 taranabant (MK-0364) 的正式合成得到进一步证明。雅各布森的特权催化剂 (salen)AlCl 由合适的正膦活化在反应中起着至关重要的作用。正膦-(salen)AlCl 配合物单晶的 X 射线晶体学分析和理论计算有助于提供一个工作模型。