The oxidative cyclization of 1,5-dienes by metal-oxo species is a powerful method for stereocontrolled synthesis of tetrahydrofuran diols (THF-diols), structural motifs present in many bioactive natural products. Oxidative cyclization of (2E,6E)-octa-2,6-diene catalyzed by OsO4/NMO has been studied using density functional theory (DFT) calculations (M06-2X/aug-cc-pVDZ/Hay-Wadt VDZ (n+1) ECP), highlighting the remarkable effect of acid on the fate of the first intermediate, an Os(VI) dioxoglycolate. A strong acid promotes cyclization of the Os(VI) dioxoglycolate, or its NMO complex, through protonation of an oxo ligand to give more electrophilic species. By contrast, in the absence of acid, reoxidation may occur to afford the Os(VIII) trioxoglycolate, which is shown to favor conventional "second cycle" dihydroxylation reactivity rather than cyclization. The results of the calculations are consistent with experimental results for reactions of OsO4/NMO with 1,5-dienes with acid (oxidative cyclization) and without acid (second cycle osmylation/dihydroxylation). Detailed evaluation of potential catalytic cycles supports oxidation of the cyclized Os(IV) THF-diolate intermediate to the corresponding Os(VI) species followed by slow hydrolysis and, finally, regeneration of OsO4.