Reversal of enantioselectivity by mixing two chiral ligands in asymmetric addition of dialkylzinc in conjunction with asymmetric autocatalysis

ORGN 750

Tsuneomi Kawasaki, Yuki Wakushima, Mai Asahina, Tomoyuki Kinoshita, Francois Lutz, and Kenso Soai. Department of Applied Chemistry, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan
N,N-Dialkylnorephedrines can act as highly efficient chiral ligand in the enantioselective addition reaction of dialkylzincs to aldehydes to afford chiral secondary alcohols with high enantiomeric excess (ee). When diisopropylzinc addition to pyrimidine-5-carbaldehyde is performed in the presence of (1R,2S)-N,N-dimethylnorephedrine (DMNE) as chiral catalyst, (R)-pyrimidyl alkanol is formed in high ee and yield. When the reaction is performed in the presence of (R)-(+)-2-(phenethylamino)ethanol (PEAE) instead of DMNE, (R)-pyrimidyl alkanolis formed. However, we observed the reversal of the enantioselectivity by mixing these two chiral catalysts, i.e., (S)-pyrimidyl alkanol was synthesized in high ee by using (1R,2S)-DMNE and (R)-PEAE as the mixed catalyst in diisopropylzinc addition in conjunction wth asymmetric autocatalysis with amplification of ee. This reversal of enantioselectivity may be caused by the interactions between the two chiral catalysts, which form catalytically active aggregate possessing the opposite face-selectivity.