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

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.