Enantioselective Synthesis of Tetrahydrofuran Derivatives by Sequential Henry Reaction and Iodocyclization of γ,δ-Unsaturated Alcohols

A sequential one-pot Cu-catalyzed asymmetric Henry reaction and iodocyclization is disclosed. The transformation provides efficient access to biologically and synthetically useful 2,2,5-trisubstituted tetrahydrofuran derivatives. The combination of Cu(OAc)(2)center dot H2O with a novel chiral sulfoxide-Schiff base hybrid ligand under mild reaction conditions tolerates a wide range of 4-substituted gamma,delta-unsaturated aldehydes, and the subsequent iodocyclization furnishes the corresponding products in generally high yields with excellent enantio-selectivities. The products can be easily converted into amines with excellent diastereo- and enantioselectivities.