Self-Assembled Supramolecular Gels for Catalyzing Asymmetric Aldol and Mannich Reactions in Aqueous Media

Abstract

Supramolecular hydrogels have broad application prospects in asymmetric catalysis due to their unique properties, and the water environment inside the hydrogels plays an important role in green catalysis. This paper reports a novel C2-symmetric proline derivative gelator (p-L-Phe-Pro-COOH) with a hydrophobic benzene ring in the center and hydrophilic groups on both sides. The C2-symmetric structure can provide the gelator with more catalytically active sites. p-L-Phe-Pro-COOH can self-assemble in H₂O or H₂O/dimethyl sulfoxide (DMSO) mixed solvents to form gels with a three-dimensional network of left-handed intertwined helical nanofibers, namely, L-Hyd and L-Hyd-DMSO. The L-Hyd and L-Hyd-DMSO gels are used as catalysts for the aldol and Mannich reactions, achieving high yields (>90%), diastereoselectivity (dr >90/10 (anti/syn)), and enantioselectivity (ee value of 99%) of the products without requiring additional additives. Results indicated that the L-Hyd and L-Hyd-DMSO gels exhibited higher catalytic activity compared to that of the gelator. Further, the Mannich reaction catalyzed by L-Hyd-DMSO revealed that introducing DMSO considerably enhanced the reaction yield while maintaining a high enantioselectivity. The L-Hyd-DMSO effectively addresses the issue of low yield in Mannich reactions conducted in aqueous systems. In addition, the L-Hyd and L-Hyd-DMSO gels acting as catalysts can be recovered by simple extraction and maintain good reactivity after five cycles. The findings of this study indicate that supramolecular hydrogels show potential in asymmetric catalytic reactions, which closely align with the principles of green chemistry.