Non-enzymatic dynamic kinetic resolution of racemic α-arylalkanoic acids: an advanced asymmetric synthesis of chiral nonsteroidal anti-inflammatory drugs (NSAIDs)

Abstract

An efficient protocol was developed to produce chiral 2-arylalkanoic esters in high yields (up to 99%) from racemic carboxylic acids utilizing the racemization of the mixed-anhydrides generated from acid components with pivalic anhydride in the presence of an acyl-transfer catalyst. The present DKR involves the enantio-discriminating esterification of the racemic 2-arylalkanoic acids and the rapid racemization of the chiral 2-arylalkanoic acids under suitable reaction conditions using pivalic anhydride, diisopropylethylamine, and benzotetramisole (BTM) in a polar solvent, and this method was successfully applied for the preparation of pharmacodynamically active (S)-enantiomers of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen.