Chemoselective esterification of α-hydroxyacids catalyzed by salicylaldehyde through induced intramolecularity

Abstract

A new, direct and chemoselective esterification of α-hydroxyacids was developed using a reversible covalent-binding strategy. By taking advantage of acetal chemistry, simple aldehydes can be used to efficiently catalyze the esterification of α-hydroxy carboxylic acids in the presence of β-hydroxyacid moieties or other carboxylic acids in amounts equal to or in excess of the alcohols. A diverse array of α-aryl, α-alkyl, α-heteroaryl, and functionalized α-hydroxyacids were smoothly esterified with 1° and 2° alcohols catalyzed by 10 mol% inexpensive and commercially available salicylaldehyde, furnishing the resultant esterification products in 83–95% yields after a simple basic aqueous workup to remove the unreacted hydroxyacids. In addition, the salicylaldehyde can be recovered through vacuum distillation or silica gel purification, thereby meeting the standards of green chemistry. A mechanistic study proved that the formation of covalent adduct III during our proposed catalytic cycle (Scheme 1A) is responsible for the real catalysis.