(3S,4S)‐N‐substituted‐3,4‐dihydroxypyrrolidines as ligands for the enantioselective Henry reaction

Abstract

The enantioselective Henry reaction is a very important and useful carbon–carbon bond forming reaction. The execution of this reaction requires the use of efficient chiral catalysts. In this work, in situ formed complexes of N‐substituted dihydroxypyrrolidines, chiral ligands derived from L‐tartaric acid and amines, were evaluated as catalysts in the enantioselective Henry reaction. The results showed that the nature of the N‐substituent on the ligand significantly influences the outcome of the reaction. Best results were obtained using a Cu (II) complex of (3S,4S)‐N‐benzyl‐3,4‐dihydroxypyrrolidine, in the presence of DIPEA, for the reaction of aromatic aldehydes with nitromethane, at room temperature, originating products with er up to 92:8 (R:S) and conversions up to 96%. The interaction between the pyrrolidine ligand and the copper ion, in isopropanol, was followed by UV‐vis spectrophotometry, showing a 1:1 stoichiometry and a binding constant of 4.4. The results obtained will contribute to the design and development of more efficient chiral catalysts for this type of reaction.