Achiral Trisubstituted Thioureas as Secondary Ligands to CuI Catalysts: Direct Catalytic Asymmetric Addition of α-Fluoronitriles to Imines

Thioureas have emerged as effective hydrogen-bonding catalysts over the last two decades, and they are broadly utilized in asymmetric catalysis. We report that achiral trisubstituted thioureas function as beneficial secondary ligands to Cu-I catalysts, thereby enabling highly diastereo- and enantioselective addition of alpha-fluoronitriles to imines. The structure of the thiourea significantly affects the reaction outcome, and kinetic experiments indicate that the thioureas enhance the stereocontrol by binding to the Cu-I complex. The reaction products can be readily transformed into valuable beta-amino acid derivatives bearing a fluorinated tetrasubstituted stereogenic center.