Discovery of a New Efficient Chiral Ligand for Copper-Catalyzed Enantioselective Michael Additions by High-Throughput Screening of a Parallel Library

Abstract

The optimal ligand 1 for the enantioselective copper-catalyzed 1,4-addition of Et2Zn to cyclic enones [Eq. (1)] was established by multisubstrate (high-throughput) screening of a parallel library of chiral Schiff base ligands. The screening data show how the ligand structure is finely tuned by mutual influences of stereogenic center a (which controls the absolute configuration of the reaction product), stereogenic center b, and the substitution pattern of the aromatic ring. Tf=F3CSO2.