Quaternary Ammonium (Hypo)iodite Catalysis for Enantioselective Oxidative Cycloetherification

Eye for an I Oxidative catalysis is largely the domain of transition metals, whether iron in an enzyme, or rarer palladium in a synthetic system. These metals can efficiently shuttle between oxidation states, easing the transfer of hydrogen and oxygen atoms between hydrocarbons and oxidants. Uyanik et al. (p. 1376; see the Perspective by French) now show that iodine can take the place of the metal to catalytically activate peroxide during the formation of benzofuran derivatives. Pairing iodide anions with chiral ammonium cations allowed the generation of stereoselectivity at levels similar to those seen with metal complexes bearing chiral ligands. Iodine can effectively replace a transition metal as an electron-transfer catalyst for an organic reaction. It is desirable to minimize the use of rare or toxic metals for oxidative reactions in the synthesis of pharmaceutical products. Hypervalent iodine compounds are environmentally benign alternatives, but their catalytic use, particularly for asymmetric transformations, has been quite limited. We report here an enantioselective oxidative cycloetherification of ketophenols to 2-acyl-2,3-dihydrobenzofuran derivatives, catalyzed by in situ–generated chiral quaternary ammonium (hypo)iodite salts, with hydrogen peroxide as an environmentally benign oxidant. The optically active 2-acyl 2,3-dihydrobenzofuran skeleton is a key structure in several biologically active compounds.