Room-Temperature Oxidative Cyclization of Carboxylic Acids Promoted by Copper(II) Trifluoromethanesulfonate and Selectfluor

Abstract

We describe a room-temperature oxidative cyclization of carboxylic acids into γ- and δ-lactone products. First, a carboxylic acid substrate is stirred with copper(II) trifluoromethanesulfonate, Selectfluor, and potassium tert-butoxide in acetonitrile. With some substrates, lactone products are formed almost exclusively, but with others, significant amounts of overoxidized ketone side products are observed. Fortunately, these ketone products can be converted into the desired lactones by adding sodium borohydride and then 1 M aqueous hydrochloric acid solution to the cyclization flask. The reaction is scalable, can be run in the presence of air and ambient moisture, and gives useful lactone products.