Highly Enantioselective Iodolactonization

Significance

A highly enantioselective iodolactonization of hexenoic acids 1 and pentenoic acid derivatives mediated by a bifunctional tertiary ­aminourea catalyst is reported. Using N-iodo-4-fluorophthalimide as the I⁺ source and 15 mol% of catalyst together with a catalytic amount of ­iodine at -80 ˚C, various five- and six-membered iodo­lactones 2 can be obtained with high levels of enan­tioselectivity. For the iodolactonization of 4-phenylpent-4-enoic acid, decreasing the iodine loading from 15 to 0.1 mol% can dramatically ­improve the enantiomeric ratio from 65.5:34.5 to 95:5. The use of catalytic iodine in the reaction is critical to enhancing both the reactivity and enantioselectivity of the stoichiometric I⁺ source.