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.