Mild Metal-Free Hydrosilylation of Secondary Amides to Amines

The combination of amide activation by Tf2O with B(C6F5)(3)-catalyzed hydrosilylation with TMDS constitutes a method for the one-pot reduction of secondary amides to amines under mild conditions. The method displays a broad applicability for the reduction of many types of substrates, and shows good compatibility and excellent chemoselectivity for many sensitive functional groups. Reductions of a multifunctionalized alpha,beta-unsaturated amide obtained from another synthetic methodology, and a C-H functionalization product produced the corresponding amines in good to excellent yield. Chemoselective reduction of enantiomeric pure (ee >99%) tetrahydro-5-oxo-2-furaneamides yielded 5-(aminomethyl)dihydrofuran-2(3H)-ones in a racemization-free manner. The latter were converted in one pot to N-protected 5-hydroxypiperidin-2-ones, which are building blocks for the synthesis of many natural products. Further elaboration of an intermediate led to a concise four step synthesis of (-)-epi-pseudoconhydrine.