Enantioselective Route to Terminal 2,3-Epoxy Tosylates Enabled by Cooperative Organocatalytic Desymmetrization of 2-Substituted Glycerol Derivatives.

A first enantioselective synthesis of challenging 2,2-disubstituted 2,3-epoxy tosylates has been developed via an organocatalytic desymmetrization reaction of bis tosylated 2-substituted glycerols. The intramolecular nucleophilic substitution has been cooperatively catalyzed by commercially available mixtures of L-diphenyl prolinol and (R,R)-α,α,α',α'-tetraphenyl-2,2 disubstituted 1,3-dioxolane-4,5-dimethanol (TADDOL) or the enantiomeric couple, leading to (R)- and (S)-epoxides in up to 87% yield and 76% ee. Reaction monitoring highlighted the double role of leaving group and nucleophile played by the p-toluensulfonate anion, which was found to be responsible of epoxide ring-opening back to the reagent. The latter process affects the conversion to the epoxide, but marginally the enantioselectivity. These uncommon epoxides, bearing a quaternary stereocenter, demonstrated to be versatile intermediates to prepare functionalized products and remarkably, privileged eight- and four- membered N-heterocycles.