Oxidation of Thiols with IBX or DMP: One-pot Access to Thiosulfonates or 2-Iodobenzoates and Applications in Functional Group Transformations

Abstract

Thiosulfonates are accessed by oxidation of feed-stock thiols using either DMP in DCM or IBX in MeCN at rt (~30 degree C). The protocol gives access to a variety of thiosulfonates in good to excellent yields from both aromatic and aliphatic thiols. The reaction with DMP is found to be better than IBX in terms of reaction rate and conversion, whereas the oxidation with DMP requires lower equivalent than IBX. Benzyl thiols are however found to follow a different reaction pathway when treated with DMP; O-benzyl esters of o-iodobenzoates were isolated. The 1H NMR spectroscopic monitoring studies for the IBX-mediated oxidation of thiol found disulfide as an initial intermediate, which is proposed to undergoes a cascade of oxidations to produce thiosulfonate

Oxidation of Thiols with IBX or DMP: One-Pot Access to Thiosulfonates or 2-Iodobenzoates and Applications in Functional Group Transformations

“…When the reaction of a thiol with IBX (1.0 equiv) in MeCN was conducted at rt, after 24 h, both disulfide 3d and thiosulfonate 2d were isolated in 18 and 75% yields, respectively (SI, entry 4, Table S2). Hence, with a longer reaction time of 24 h than the previously reported of 2 h, the in situ generated disulfides could be further oxidized to thiosulfonates (entries 8 vs 4). Therefore, IBX was employed in an excess amount to further facilitate oxidation and reduce the reaction time.…”

“…For instance, the reaction with 1.0 equiv of IBX producing thiosulfonate in 75% and disulfide in 18% indicated that IBA is participating in the oxidation (SI, Table S2, entry 4). In fact, the oxidation with PIFA also suggested that the disulfides can be obtained from thiols . Consolidating the above observations, a plausible reaction mechanism for the conversion of thiols to thiosulfonates with IBX through the intermediary disulfides is shown.…”

“…It is worth mentioning that a similar nucleophilic attack with disubstituted sulfides/disulfide is proposed to be energetically unfavorable due to steric encumbrances around the sulfur atom . Thus, the reaction of disulfide with IBX to generate the thiosulfonate through the thiosulfinate should be following an electron/oxygen transfer process, SI, Scheme S2b. , It is worth mentioning that, unlike IBX (λ 5 -iodane), the T-shaped and planar IBA (λ 3 -iodane) can offer disulfide addition to the iodine center …”

“…It can be assumed that the acetate ligands in DMP can facilitate the ligand exchange process, which can offer thiol addition to the electrophilic hypervalent iodine center of DMP to produce TAP DMP , Scheme and SI, Scheme S7 . The formation of the purported periodinane adduct TAP DMP can also be possible through a SET process . We proposed that TAP DMP undergoes a cascade of intramolecular [1,2]-OAc shifts (i.e., through sulfanes 9a and 9b ) to produce sulfoxide species 9c .…”

“…Consolidating the above observations, a plausible reaction mechanism for the conversion of thiols to thiosulfonates with IBX through the intermediary disulfides is shown. The single electron transfer (SET) from electron-rich thiols to I­(V) species should lead to the thiyl radicals that dimerizes to the disulfide, where IBX is subsequently reduced to IBA, cf. SI, Scheme S2a.…”