Computational study on the mechanism of non-catalyzed and catalyzed bromolactonization

- Uncover the mechanism for bromolactonization without and with catalyst respectively.
- Find the catalytic center, and explain the role it plays in the reaction.
- Regioselectivity is attributed to different forming ways of exo-five-lactone and endo-six-lactone.

Important intermediates and key transition states of catalyzed bromolactonization are researched by using density functional theory (DFT). The non-catalyzed process is also investigated to make a comparison with the catalyzed one. The pathways of reaction are investigated in detail. The results suggest that the non-catalyzed reaction proceeds in three major steps involving electrophilic addition, ring-closure and H transference, while the catalyzed process involves Cat-NBS interaction, H transference, and ring-closure. Electrophilic addition is the rate-determining step in the non-catalyzed process. The small discrepancy of charge density may account for the difficulty of electrophilic addition. Sulfur of Cat is the catalytic center which changes the charge density of Br on NBS to reduce the energy barrier sharply. There are four regioselective pathways related to exo-five-lactone and endo-six-lactone. The preferred pathway for exo-five-lactone is confirmed. It is the first time to uncover the catalytic mechanism by calculation method.

The mechanism for bromolactonization without and with catalyst was investigated.