Abstract:The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials revealed that polystyrene gave better results than silica in terms of stereoselectivity. The applicability of the solid-supported catalyst of choice to the reduction of different imines was also demonstrated. Additionally, for the first time, a catalytic reactor containing a polymer-immobilized chiral picolinamide has been employed for the stereoselective reduction of imines with trichlorosilane under continuous flow conditions.
The convenient, metal‐free reduction of imines that contain an inexpensive and removable chiral auxiliary allowed for the synthesis of the immediate precursors of chiral active pharmaceutical ingredients (APIs). This protocol was carried out under batch and flow conditions to give the correspoding products in high yields with almost complete stereocontrol. In the presence of trichlorosilane, an inexpensive and nontoxic reducing agent, and an achiral Lewis base such as N,N‐dimethylformamide, the formal syntheses of Rivastgmine, calcimimetic NPS R‐568, and a Rho kinases inhibitor were successfully accomplished. For the first time, both the diastereoselective imine reduction and the auxiliary removal were efficiently performed in a micro‐ or mesoreactor under continuous‐flow conditions, which paved the way towards the development of a practical process for the syntheses of industrially relevant, biologically active, enantiopure N‐alkylamines.
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