Nonsilyl Bicyclic Secondary Amine Catalysts for the Asymmetric Transfer Hydrogenation of α,β-Unsaturated Aldehydes

The first chiral synthesis of nonsilyl bicyclic secondary amine organocatalysts and their application to the asymmetric transfer hydrogenation of alpha,beta-unsaturated aldehydes are disclosed. A lower catalytic loading (5 mol %) is demonstrated for the reduction of a wide range of alpha,beta-unsaturated aldehydes (up to 97% yield and up to 99% ee). The application of this scalable methodology is showcased for the asymmetric synthesis of bioactive molecules such as phenoxanol, citronellol, ramelteon, and terikalant.