Chiral C2-symmetric 2,5-disubstituted pyrrolidine derivatives as catalytic chiral ligands in the reactions of diethylzinc with aryl aldehydes

Abstract

Two kinds of chiral C₂-symmetric 2,5-disubstituted pyrrolidine derivatives having a β-aminoalcohol moiety have been successfully synthesized and their catalytic abilities of chiral induction have been examined in the reactions of diethylzinc with aryl aldehydes. The production of sec-alcohols having R-absolute configuration could be achieved in very high chemical yield (85–95%) and very high enantiomeric excess (ee) (70–96%) when N-(2′,2′-diphenyl-2′-hydroxyethyl)-(2R,5R)-bis(methoxymethyl)pyrrolidine is used as a chiral ligand. On the other hand, when an N-methyl-(2R,5R)-bis(diarylhydroxymethyl)pyrrolidine is used as a catalyst ligand, the ee of the corresponding sec-alcohols decreases to 20–45% and an interesting inversion of the enantioselectivity is observed in the addition reaction of m-chloro-, p-chloro- and m-fluoro-benzaldehyde with diethylzinc under the same reaction conditions. In the meantime, we have also synthesized some chiral C₂-symmetric N-(β-hydroxyethyl)pyrrolidine derivatives which have differently steric sized bulky substituents on the 2,5-position of the pyrrolidine ring and their chiral induction abilities have also been examined under the same reaction conditions. Furthermore, we have prepared a simple chiral C₂-symmetric β-aminothiol pyrrolidine derivative. It has also been employed as a chiral ligand for the same addition reaction.