Unveiling an Alternative Mechanism for Lewis Basic Selenium as a C─H Hydrogen Bond Catalyst and Its Application in the Halogenation of Arenes

Electrophilic halogenation is a fundamentally useful transformation, and Lewis basic selenium catalysts together with N-haloimides are known to promote the reaction under mild conditions. Selenourea is a frequently used platform for the Lewis base catalyst design. In literature, it is generally believed that the Lewis basic selenium can form a Lewis adduct with the halogen as the active halogenating species. Herein, we report our recent finding that unveils an alternative mechanism of this type of reaction. It was found that the Lewis basic selenourea is first oxidized by the halogen source to give a benchtop stable and non-hygroscopic imidazolium hypervalent selenium dibromide compound that acts as the actual catalyst. The negative charge in the hypervalent selenium compound is stabilized by the electronegative bromide, leading to the site-isolated and unoccupied imidazolium cationic moiety. Mechanistic studies suggest that the electropositive C-Hs of the imidazolium cation can act as a strong hydrogen bond donor to activate the N-haloimide reagent for efficient halogenation reaction, including late-stage halogenation of drug molecules, with low catalyst loading. Further study revealed that hypervalent imidazolium selenium dibromide can generally be applied to other mechanistically unrelated hydrogen bond-catalyzed reactions.