A Diastereoselective, Nucleophile-Promoted Aldol-Lactonization of Ketoacids Leading to Bicyclic-β-Lactones

Abstract

An improved, tandem acid activation/aldol-lactonization process is described. This more practical protocol shortens reaction times for the construction of bicyclic β-lactones from ketoacids and implements the use of commercially available reagents <i>p</i>-toluenesulfonyl chloride (<i>p</i>-TsCl) as activator and 4-dimethylaminopyridine (4-DMAP) as nucleophilic promoter (Lewis base). Substrates with β-substituents, with respect to the carboxylic acid, consistently showed excellent levels of diastereoselectivity during the bis-cyclization event