α‐Amino Acids and α,β‐Dipeptides Intercalated into Hydrotalcite: Efficient Catalysts in the Asymmetric Michael Addition Reaction of Aldehydes to N‐Substituted Maleimides

Abstract

AbstractIn this work, a series of α‐amino acids (L‐Phe, D‐Phe, L‐Trp) and several α,β‐dipeptides (H2N‐L‐Val‐N‐Bn‐β‐Ala‐COOH and H2N‐L‐Leu‐N‐Bn‐β‐Ala‐COOH) intercalated into hydrotalcite (Mg/Al, x=0.333) were prepared by high speed ball milling (HSBM) assisted rehydration/reconstruction methods, followed by sonication and mechanical stirring. All organic‐inorganic hybrid samples were characterized by powder X‐ray diffraction (XRD) and FTIR‐ATR spectroscopy. The catalytic activity of the resulting hydrotalcite‐supported materials (natural and hybrid) was evaluated in the asymmetric Michael addition reaction of α,α‐disubstituted‐aldehydes to N‐substituted‐maleimides. Pristine (HTS), calcined (HTC) and water‐reconstructed (HTR‐l) hydrotalcite‐derived materials exhibited very low catalytic activities, affording racemic mixtures of the anticipated Michael adduct. By contrast, hybrid materials showed better activities, especially HTR‐α‐amino acid catalysts afforded Michael products in up to 94 % yield and with rather high enantioselectivity (enantiomeric ratio (e.r.) up to 99 : 1) at room temperature under neat reaction conditions. The effect of solvents and Brønsted basic or acidic additives was evaluated using the best hybrid catalyst, HTR‐L‐Phe. In addition, recycling and reuse of the catalyst (up to 4 cycles) and large‐scale experiments was successfully carried out.