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

• Published in: RSC advances Vol. 3; no. 6; pp. 1976 - 1986
• Main Authors: Weng, Shiue-Shien, Li, Hsin-Chun, Yang, Teng-Mao
• Format: Journal Article
• Language: English
• Published: 01.01.2013
• Subjects: Alcohols; Arrays; Carboxylic acids; Catalysis; Covalence; Esterification; Strategy
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/C2RA23068B

A new, direct and chemoselective esterification of alpha -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 alpha -hydroxy carboxylic acids in the presence of beta -hydroxyacid moieties or other carboxylic acids in amounts equal to or in excess of the alcohols. A diverse array of alpha -aryl, alpha -alkyl, alpha -heteroaryl, and functionalized alpha -hydroxyacids were smoothly esterified with 1 degree and 2 degree 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.