Enantioselective Synthesis of Cyclic Enol Ethers and All-Carbon Quaternary Stereogenic Centers Through Catalytic Asymmetric Ring-Closing Metathesis

The first examples of catalytic asymmetric ring-closing metathesis (ARCM) reactions of enol
ethers are reported. To identify the most effective catalysts, various chiral Mo- and Ru-based catalysts
were screened. Although chiral Ru catalysts (those that do not bear a phosphine ligand) promote ARCM
in some cases, such transformations proceed in <10% ee. In contrast, Mo-based alkylidenes give rise to
efficient ARCM and deliver the desired products in the optically enriched form. Thus, Mo-catalyzed
enantioselective transformations allow access to various five- and six-membered cyclic enol ethers in up
to 94% ee from readily available achiral starting materials. The first examples of catalytic ARCM that lead
to the formation of all-carbon quaternary stereogenic centers are also disclosed. Mechanistic models that
offer a plausible rationale for the identity of major enantiomers as well as the observed levels of
enantioselectivity are provided. Representative examples demonstrate that the enol ether moiety and the
unreacted alkene of the ARCM products can be discriminated with excellent site selectivity (>98%).