Copper-Catalyzed Enantioselective Oxysulfenylation of Alkenols: Synthesis of Arylthiomethyl-Substituted Cyclic Ethers

Saturated heterocycles containing oxygen and sulfur are found in biologically significant molecules. The enantioselective oxysulfenylation of alkenols provides a straightforward synthesis route. To date, organocatalytic methods have dominated this approach. Herein, a complementary approach via copper catalysis is presented. This exoselective method provides enantioenriched arylthiomethyl-substituted tetrahydrofurans, phthalans, isochromans, and morpholines from acyclic alkenols. This method provides the largest scope to date for the exocyclization mode, and with generally high enantioselectivity. The enantioselectivity of this copper-catalyzed oxysulfenylation is rationalized by a proposed mechanism involving alkene oxycupration followed by C-S bond formation via radical-mediated atom transfer.