Asymmetric Iodolactonization Utilizing Chiral Squaramides

Asymmetric iodolactonization of γ- and δ-unsaturated carboxylic acids has been explored in the presence of six different chiral organocatalysts 5–8. The catalyst 6b was found to facilitate the cyclization of 5-arylhex-5-enoic acids 1 to the corresponding iodolactones 2 with up to 96% ee. By this protocol, unsaturated carboxylic acids are converted enantioselectively to synthetically useful δ-lactones in high yields using commercially available NIS. Apparently, both hydrogen bonding and aryl/aryl interactions are important for efficient stereodifferentiation.