Stereoselective catalytic synthetic strategies for active pharmaceutical ingredients (API) precursors

In the field of APIs (Active Pharmaceutical Ingredients), the industry is gradually progressing towards enantiopure formulations. In this context, chiral amines are unanimously considered a class of paramount importance, due to their widespread diffusion in a plethora of compounds. In the present study it is reported a catalytic, metal-free approach to the synthesis of chiral amines, direct precursors of two important APIs: Letermovir (a), a drug that shows great promise for the next-generation treatment of HCMV (human Cytomegalovirus) infection; fluorinated Retro-thiorphan peptide mimetic (b), a potent and selective inhibitor of the metalloproteinase NEP (neutral endopeptidase). The key step in both synthesis is the stereoselective catalytic reduction of an enamine moiety; we decided to perform this transformation using a metal-free reducing agent, trichlorosilane (HSiCl3), in combination with a catalytic amount of a chiral Lewis base (LB) as organocatalyst.