Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Main Authors: Biljana M. Šmit, Radoslav Z. Pavlović, Dejan A. Milenković, Zoran S. Marković
• Format: Article
• Language: English
• Published: Beilstein-Institut 2015-10-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: density functional theory; fused bicyclic hydantoins; intermediate; reaction mechanism; regioselectivity; selenocyclization
• Online Access: https://doi.org/10.3762/bjoc.11.200

The mechanism and selectivity of a bicyclic hydantoin formation by selenium-induced cyclization are investigated. The proposed mechanism involves the intermediates formed by an electrophilic addition of the selenium reagent on a double bond of the starting 5-alkenylhydantoin prior the cyclization. These intermediates are readily converted into the more stable cyclic seleniranium cations. A key step of the mechanism is an intramolecular cyclization which is realized through an anti-attack of the internal nucleophile, the amidic nitrogen, to the seleniranium cation yielding the intermediate imidazolinium cations. Their deprotonation is followed by the formation of the fused bicyclic reaction products. Important intermediates and key transition states are studied by using density functional theory (DFT) methods. The pathways of the reaction are investigated in detail. There are two regioselective pathways related to 5-exo and 6-endo products. Theoretical calculations and the monitoring of the cyclization reaction using 1H NMR spectroscopy are in a good agreement with the proposed mechanism and are consistent with our experimental results. The preferred pathway for formation of 5-exo products is confirmed.