The Role of L-Proline and Co-Catalysts in the Enantioselectivity of OXA-Michael-Henry Reactions

Abstract

The use of L-proline derivatives employed in OXA-Michael-Henry tandem reactions has been an efficient method to produce enantiomerically enriched compounds. In this work it was carried out a study of the OXA-Michael-Henry reactions between salicylaldehyde and β-nitrostyrenes, catalyzed by L-proline and its derivatives. The corresponding (R)-3-nitro-2-phenyl-2H-chromenes were obtained in 55% enantiomeric excess (ee, 20 mol% L-proline) and 70% ee (stoichiometric amount) employing Ti(O i Pr) 4 as Lewis acid. Despite the ee obtained, to the best of our knowledge, this result represents the highest enantioselectivity obtained in this reaction. Therefore, this work demonstrated that it is possible to obtain considerable enantiomeric excesses in OXA-Michael-Henry reactions using L-proline, an inexpensive and accessible amino acid.