Computational study on the mechanism of uncatalyzed and selenium-based catalyzed bromolactonization

The mechanisms of the uncatalyzed and selenium-based catalyzed bromolactonization are studied using B3LYP and MP2 method. The pathways of reaction are investigated in detail. The results suggest that the uncatalyzed reaction proceeds in three major steps involving electrophilic addition, ring-closure and hydrogen transfer, while the selenium-based catalyzed process involves Cat-NBS interaction, hydrogen transfer, and ring-closure. The electrophilic addition is the rate-determining step of the uncatalyzed process, while Cat-NBS interaction is that of the catalyzed process. Selenium of Cat is the catalytic center which changes the charge density of Br on NBS, and it makes the electrophilic addition easier. Thus, the energy barrier is sharply reduced. There are four regioselective pathways for the formation of exo-five-lactone 3 and endo-six-lactone 4. The preferred pathway is confirmed relating to exo-five-lactone 3.