Elucidating the Mechanism of Tetrahydrofuran-Diol Formation through Os(VI)-Catalyzed Oxidative Cyclization of 5,6-Dihydroxyalkenes Ligated by Citric Acid

A computational study is reported here on the mechanism of tetrahydrofuran (THF)-diol formation from the Os­(VI)-catalyzed oxidative cyclization of 5,6-dihydroxyalkene ligated with citric acid and in the presence of Bro̷nsted acid. Initiated by Os­(VI) dioxo citrate formation, coordination of co-oxidant pyridine-N-oxide (PNO) and protonation of its oxo group generate the active catalyst. The catalytic cycle commences through successive steps, including dihydroxyalkene addition to the active catalyst in a concerted mechanism to form hexacoordinated alkoxy-protonated PNO-complexed Os­(VI) bisglycolate as a turnover-limiting step (TLS), cyclization to Os­(IV) THF-diolate, reoxidation to Os­(VI) THF-diolate, and hydrolysis via a dissociative mechanism to furnish the THF-diol and regenerate the active species, sustaining the catalytic cycle through an Os­(VI)/Os­(IV) cycle. Despite the overall exergonic nature of catalytic cycle (ΔG r cycle = −45.0 kcal/mol), the TLS is accelerated by the formation of an open-valence 16-electron Os­(VI) intermediate but decelerated by the undesired formation of a saturated/hexacoordinate 18-electron Os­(VI) intermediate. Bro̷nsted acid plays crucial roles in the formation of Os­(VI) citrate and the active catalyst, impediment of the second cycle, and the cyclization step. Additionally, besides its role as a co-oxidant, and in the presence of acid, PNO is found to assist the insertion of dihydroxyalkene and, importantly, in releasing the THF-diol to regenerate the active intermediate.