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DOI: 10.1055/s-0030-1258787
Highly Efficient Kinetic Resolution of Racemic Carboxylic Acids
Contributor(s):Benjamin List, Ji-Woong LeeTokyo University of Science and Sumitomo Chemical Co., Osaka, Japan
Kinetic Resolution of Racemic α-Arylalkanoic Acids with Achiral Alcohols via the Asymmetric Esterification Using Carboxylic Anhydrides and Acyl Transfer Catalysts
J. Am. Chem. Soc. 2010, 132: 11629-11641
Publication History
Publication Date:
21 October 2010 (online)
Key words
kinetic resolution - acyl transfer catalysis - α-arylalkanoic acids - anti-inflammatory drugs
Significance
Shiina and co-workers report a highy efficient kinetic resolution of racemic α-aryl-alkanoic acids using acyl transfer Birman catalyst 1 (V. B. Birman, X. Li Org. Lett. 2006, 8, 1351) to afford optically enriched esters utilizing achiral alcohols (s-factor: up to 484). The obtained bis-(α-naphthyl)-methyl esters could be easily transformed into the corresponding chiral acids, such as ibuprofen and naproxen, without loss of optical purity.
Comment
Herein, the authors demonstrate a new protocol to produce optically enriched 2-arylalkanoic acids and their esters under mild conditions. Detailed mechanistic investigations revealed mixed anhydrides generated from the first intermediate. The second intermediate, which is a mixture of diastereomers, can be selectively attacked by the achiral alcohol to achieve high enantioselectivity.