An Enantioselective Iodolactonization/Cross-Coupling Protocol for the Synthesis of Highly Substituted Enol Lactones

Abstract

γ-Alkynoic acids readily undergo iodolactonization to give iodoenol lactones. Using commercially available (DHQD)2PHAL this transformation can be rendered asymmetric. In desymmetrization reactions of dialkynoic acids, good to very good enantioselectivities can be observed. Alternatively, kinetic resolution of already chiral, racemic γ-alkynoic acids can be carried out. The products of these iodolactonizations, iodoenol lactones, are suitable substrates for Palladium catalyzed cross-couplings. Negishi- as well as Sonogashira couplings can be carried out and allow the efficient synthesis of highly substituted enol lactones.