Highly diastereoselective esterification of ketenes generated in situ from acyl chlorides with (R)-pantolactone derivatives

Abstract

Our mechanistic investigations have revealed that Et3N is a key requirement for the highly diastereoselective formation of esters from the corresponding acyl chlorides with (R)-pantolactone via ketene-derived complexes. Furthermore, we have discovered that (R)-N-benzyl-pantolactam is a more effective chiral alcohol than (R)-pantolactone for the esterification of in situ generated ketenes. Ketene esterification with (R)-pantolactone derivatives is a powerful synthetic method for the synthesis of chiral α-arylpropionic acids. Our mechanistic investigations have revealed that Et3N is a key requirement for the predominant formation of ketenes from acyl chlorides, and (R)-N-benzylpantolactam was a much more effective chiral auxiliary. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.