A Novel Catalyst System for the Efficient Syntheses of Chiral Alcohols

OVERVIEW

Georgetown University is seeking a partner to commercialize a novel ligand catalyst system. Chiral alcohols represent a fundamental component of many active pharmaceuticals and intermediates. The chiral bisoxazolidine ligand developed at Georgetown is very effective in mediating the syntheses of a variety of chiral alcohols from aldehydes. Reactions performed with this system employ low-cost alkyl zincs, making this catalyst an economical and cost-effective tool for synthesizing chiral alcohol products and intermediates. The successful use of the chiral catalysts in asymmetric bond-forming reactions has been demonstrated.

BACKGROUND

The demand for pure chiral compounds has surged, especially in the pharmaceutical industry, where enantiomerically pure drugs offer fewer side effects and increased potency compared to racemic mixtures. Traditional methods were optimized for racemic materials, relying on limited natural sources or time-consuming racemate resolution. To meet the growing need, efficient chiral catalysts emerged, such as those derived from C2-symmetric ligands like BINOL, BOX, salen, DIOP, DUPHOS, and TADDOL. Notably, cost-effective chiral catalysts from accessible chiral bisoxazolidines derived from amino alcohols and diketones have been developed and successfully applied in asymmetric bond-forming reactions.

Benefit

• The chiral ligand may be recycled.
• Provides high yields (>87%) and enantioselectivities (>90%) for a wide range of substrates in various reactions
• The catalyst system uses inexpensive alkyl-zinc reagents

Market Application

• Versatile Application: Enables synthesis of chiral alcohols from non-chiral aldehydes, with broad potential in pharmaceuticals and intermediates.
• Diverse Reaction Scope: Successfully applied in aldehyde alkylation, alkynylation, and nitroaldol (Henry) reactions

Publications

• US patent No. 7,763,734
• Bisoxazolidine-Catalyzed Enantioselective Alkynylation of Aldehydes. J. Am. Chem. Soc., 2006, 128 (34), 10996-10997Chiral Amplification based on enantioselective dual-phase distribution of a scalemic bisoxazolidine catalyst. Org. Lett., 2007, 9(16), 2965-8.Bisoxazolidine-catalyzed enantioselective alkynylation of aldehydes.”J. Am. Chem. Soc., 2006, 128(34), 10996-7.