Design and Synthesis of Lactose‐Derived Ligands and Their Application in Asymmetric Friedel–Crafts Alkylation
Year: 2026
Type: article
Abstract: D‐Lactose is a multi‐tonne waste product from the dairy industry, it is enantiopure and therefore of interest for potential use as a key component in chiral ligands for asymmetric catalysis. Owing to the development of successful carbohydrate‐containing ligands in the past, we now report the development of a series of bi‐ and tridentate lactose‐derived ligands with a variety of protecting groups, all of which are accessible in 3–5 synthetic steps. This is a novel application of lactose, as most carbohydrate ligands applied in metal‐catalysed asymmetric transformations are monosaccharides and none contain a lactose moiety. The lactose‐derived ligands prepared were applied in the asymmetric Friedel–Crafts alkylation of indole with various trans ‐β‐nitrostyrenes affording ee s up to 93% and yields up to 93%. Additionally, a γ,β‐unsaturated‐α‐ketoester was employed in the Friedel–Crafts alkylation with indole, resulting in a 95% ee and 100% conversion. To probe the functionality of the galactose unit of the lactose ligand, we applied an analogous glucose ligand in the same transformation furnishing inferior results of up to 82% ee and up to 66% yield. This demonstrates the advantage of using a disaccharide ligand.
Institution: University College Dublin
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,330
Funder: Science Foundation Ireland
OpenAlex ID: W7154698829