Ethers via Catalytic Asymmetric Thiofunctionalization of Alkenyl Alcohols

Significance

Reported is the enantioselective synthesis of thiosubstituted pyrans 2 and furans 3 via a catalytic asymmetric intramolecular sulfenylation of substituted alkene alcohols 1. Optimization studies revealed the importance of Brønsted acid and Lewis base selection. High catalytic activity was demonstrated for sulfur- and selenium-derived Lewis bases. Of these systems, selenium-derived catalysts (e.g. 5) showed the highest enantioselectivities. Examination of the substrate scope revealed that trans olefins afford pyrans 2 in good yield and high enantiomeric excess. Geminal substitution of either terminus of the alkene, that is R^² ≠ H or R^³ ≠ H, led to furans 3 with reduced enantioselectivity. Intermolecular capture of the thiiranium ions generated in this process was also conducted, as were preliminary mechanistic experiments.