NHC-Catalyzed and Brønsted Acid Copromoted E → Z Isomerization Mode of Breslow Intermediates Leading to Ralfuranones.

Abstract

Different Z/E-isomers of functional molecules display distinct chemical and biological activities. The E → Z isomerization reaction is a contra-thermodynamic direction and presents a long-standing challenge in synthetic transformation. To date, organic catalysis methods for manipulating E/Z isomerization are still under development. Here we show a new N-heterocyclic carbene (NHC)-catalyzed E/Z isomerization mode. The E-isomer enedial undergoes E/Z isomerization to give a Z-isomer Breslow intermediate via NHC catalysis, and an intramolecular hydrogen bond can greatly stabilize this conformation. Subsequently, the Brønsted acid promotes the further redox-neutral reaction. The desired ralfuranone products obtained from our method can be readily transformed to various functional molecules.