Enantioselective direct aldol reactions catalyzed by proline-derived dipeptides: Catalyst, solvent, additive, and temperature effects

ORGN 706

Yi-Hui Chen, l3895103@mail.ncku.edu.tw and Kuangsen Sung, kssung@mail.ncku.edu.tw. Department of Chemistry, National Cheng Kung university, Tainan, Taiwan
A series of dipeptides, including L-Pro-Gly, L-Pro-D-Val, L-Pro-L-Val, L-Pro-D-Phe, L-Pro-L-Phe, were synthesized to evaluate the catalytic effect for asymmetric direct aldol reactions. In the direct aldol reaction, a catalyst of L-proline-L-amino acid achieves better enantioselectivity than the corresponding L-proline-D-amino acid catalyst. Solubility of the dipeptide catalysts in the solvents is a key point for achieving a better yield of the direct aldol reaction, while hydrogen-bonding of solvent does not play an important role in attaining better enantioselectivity and yield. NMM and SDS additives improved yield and enantioselectivity of the direct aldol reaction in water. DMSO is the best of protic and aprotic dipolar solvents for the catalytic asymmetric synthesis; the highest enantiomer excess and yield could be up to 82% ee and 98%, respectively.