Tropylium-Catalyzed Domino Reactions for the Thioetherification of Levoglucosenone

Approaches to substitute the chiral platform chemicals levoglucosenone and Cyrene with aryl and alkylthiols have been developed via the α-haloketones. Substitution of the 3-chloroalkene was catalyzed by Lewis acids, with the tropylium cation showing excellent activity and yield. When thiolate was replaced with methoxide, an alkoxyoxirane could be isolated, suggesting an analogous mechanism for the thiol substitution reaction. Substitution of the 3-bromo derivative of Cyrene with thiolate nucleophiles proceeded with retention of configuration in high yield, with an intermediate oxirane also demonstrated when using methoxide. Computed LUMO energies for the α-haloketones support pathways dependent on the type of halogen, with large contributions at the carbonyl, and a sterically inaccessible σ* orbital due to the bicyclic ring system.