Silver-Catalyzed Enantioselective Aldol Reaction of Isocyanoacetic Acid Derivatives with Prolinol-Phosphine- sec -Amine Chiral Ligand

A highly diastereo- and enantioselective silver-catalyzed aldol reaction of isocyanoacetic acid derivatives with aldehydes has been demonstrated using a prolinol–phosphine-sec-amine chiral ligand (L2). The Ag–L2 catalytic system promotes the reaction efficiently, affording the corresponding aldol products in high yields with excellent stereoselectivities (up to trans/cis >99:1 and 98% ee). Evaluation of various prolinol-phosphine chiral ligands suggests that cooperative N–H···O and sp2-C–H···O hydrogen-bonding interactions play a key role in organizing the enolate and controlling stereoselectivity.