Next Article in Journal
Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription
Next Article in Special Issue
Enantioselective Michael Addition of 3-Aryl-Substituted Oxindoles to Methyl Vinyl Ketone Catalyzed by a Binaphthyl-Modified Bifunctional Organocatalyst
Previous Article in Journal
Ring-Expansion Reaction of Oximes with Aluminum Reductants
Previous Article in Special Issue
Cooperative Al(Salen)-Pyridinium Catalysts for the Asymmetric Synthesis of trans-Configured β-Lactones by [2+2]-Cyclocondensation of Acylbromides and Aldehydes: Investigation of Pyridinium Substituent Effects
Molecules 2012, 17(6), 7356-7378; doi:10.3390/molecules17067356
Article

A New Method for Production of Chiral 2-Aryl-2-fluoropropanoic Acids Using an Effective Kinetic Resolution of Racemic 2-Aryl-2-fluoropropanoic Acids

 and *
Received: 2 May 2012 / Revised: 4 June 2012 / Accepted: 8 June 2012 / Published: 14 June 2012
(This article belongs to the Special Issue Asymmetric Catalysis)
Download PDF [606 KB, uploaded 18 June 2014]

Abstract

We report a new method for the preparation of chiral 2-aryl-2-fluoropropanoic acids, including 2-fluoroibuprofen, a fluorinated analogue of non-steroidal anti-inflammatory drugs (NSAIDs), by the kinetic resolution of racemic 2-aryl-2-fluoropropanoic acids using enantioselective esterification. By applying pivalic anhydride (Piv2O) as a coupling agent, bis(α-naphthyl)methanol [(α-Np)2CHOH] as an achiral alcohol, and (+)-benzotetramisole (BTM) as a chiral acyl-transfer catalyst, a series of racemic 2-aryl-2-fluoropropanoic acids were kinetically separated to afford the optically active carboxylic acids and the corresponding esters with good to high enantiomeric excesses. This technology can provide a convenient approach to furnish the chiral α-fluorinated drugs containing quaternary carbons at the α-positions in the 2-aryl-2-fluoropropanoic acid structure.
Keywords: kinetic resolution; asymmetric esterification; 2-aryl-2-fluoropropanoic acids; fluorinated drugs; 2-fluoroibuprofen; ibuprofen kinetic resolution; asymmetric esterification; 2-aryl-2-fluoropropanoic acids; fluorinated drugs; 2-fluoroibuprofen; ibuprofen
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplement

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote
MDPI and ACS Style

Tengeiji, A.; Shiina, I. A New Method for Production of Chiral 2-Aryl-2-fluoropropanoic Acids Using an Effective Kinetic Resolution of Racemic 2-Aryl-2-fluoropropanoic Acids. Molecules 2012, 17, 7356-7378.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

Cited By

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert