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

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 over-oxidized 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.