Asymmetric Synthesis of Axially Chiral, Unsymmetrical Diphenic Acids via Intramolecular Ullmann Coupling Reaction

A practical route to unsymmetrical diphenic acids is described. Successive esterification of ethylene glycol with two different 2-halobenzoyl chlorides gave the corresponding mixed diester, which was treated with copper powder in boiling DMF under dilution conditions. Silica-gel column chromatography allowed ready separation of the intramolecularly coupled cyclic diester (30–60% yield) from other by-products accompanying the Ullmann reaction, and alkaline hydrolysis gave unsymmetrical diphenic acid. Axially chiral, unsymmetrical diphenic acids of more than 99% enantiomeric excess were obtained from the reaction of mixed diesters prepared from (R)-1,1′-bi-2-naphthol.