Carbohydrate-Based Chiral Ligands for the Enantioselective Addition of Diethylzinc to Aldehydes

Abstract

Background: Carbohydrate-derived chiral ligands are promising tools in asymmetric catalysis due to their structural diversity, chirality, and availability. However, ligands based on galactose or sorbose have been scarcely explored in the enantioselective addition of dialkylzinc reagents to aldehydes. Methods: A series of chiral diols and β-amino alcohols was synthesized from methyl D-glucopyranoside, methyl D-galactopyranoside, and D-fructose. These ligands were tested in the titanium tetraisopropoxide-promoted enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes. Results: Several ligands, particularly those with a D-fructopyranose backbone, exhibited excellent catalytic activity, with conversion rates up to 100% and enantioselectivities up to 96% ee. Notably, this study reports for the first time the use of β-amino alcohols derived from fructose and sorbose in this transformation. Conclusions: Carbohydrate-based ligands represent effective, inexpensive, and structurally versatile scaffolds for developing highly enantioselective catalysts, expanding the utility of sugars in asymmetric organometallic reactions.