Mechanistic Studies on a Sulfoxide Transfer Reaction Mediated by Diphenyl Sulfoxide/Triflic Anhydride

Sulfoxides are frequently used in organic synthesis as chiral auxiliaries and reagents to mediate a wide variety of chemical transformations. For example, diphenyl sulfoxide and triflic anhydride can be used to activate a wide range of glycosyl donors including hemiacetals, glycals and thioglycosides. In this way, an alcohol, enol or sulfide is converted into a good leaving group for subsequent reaction with an acceptor alcohol. However, reaction of diphenyl sulfoxide and triflic anhydride with oxathiane-based thioglycosides, and other oxathianes, leads to a different process in which the thioglycoside is oxidised to a sulfoxide. This unexpected oxidation reaction is very stereoselective and proceeds under anhydrous conditions in which the diphenyl sulfoxide acts both as oxidant and as the source of the oxygen atom. Isotopic labelling experiments support a reaction mechanism that involves the formation of oxodisulfonium (S-O-S) dication intermediates. These intermediates undergo oxygen-exchange reactions with other sulfoxides and also allow interconversion of axial and equatorial sulfoxides in oxathiane rings. The reversibility of the oxygen-exchange reaction suggests that the stereochemical outcome of the oxidation reaction may be under thermodynamic control, which potentially presents a novel strategy for the stereoselective synthesis of sulfoxides.


Introduction
Chemical transformations involving sulfoxides often involve reaction with a strong electrophile such as triflic anhydride (Tf 2 O) to activate the sulfoxide for reaction with nucleophiles. [1] For example, dimethylsulfide ditriflate will react with alkenes, alkynes and arenes to provide vinyl and aryl sulfides and sulfonium ions. [2] Alternatively, the same activated sulfoxide reagent can oxidise simple alcohols to ketones. [3] Activated sulfoxides have also had a significant impact on the synthesis of oligosaccharides, [4] ever since the introduction of sulfoxide glycosyl donors by Kahne in 1989. [5] More recently, there has been a growing interest in the use of diphenyl sulfoxide and triflic anhydride as a system for activating glycosyl donors. [6] For example, glycosyl hemiacetals can be activated directly using this combination of reagents; [6,7] glycals can be oxidised to glycosyl epoxides for reaction with alcohols; [8] and this method is also often used to activate thioglycosides. [4f, 7d, 9] We sought to apply the diphenyl sulfoxide/Tf 2 O method for activating oxathiane glycosyl donors 1 and 3 (Scheme 1) Abstract: Sulfoxides are frequently used in organic synthesis as chiral auxiliaries and reagents to mediate a wide variety of chemical transformations. For example, diphenyl sulfoxide and triflic anhydride can be used to activate a wide range of glycosyl donors including hemiacetals, glycals and thioglycosides. In this way, an alcohol, enol or sulfide is converted into a good leaving group for subsequent reaction with an acceptor alcohol. However, reaction of diphenyl sulfoxide and triflic anhydride with oxathiane-based thioglycosides, and other oxathianes, leads to a different process in which the thioglycoside is oxidised to a sulfoxide. This unexpected oxidation reaction is very stereoselective and proceeds under anhydrous conditions in which the diphenyl sulfoxide acts both as oxidant and as the source of the oxygen atom. Isotopic labelling experiments support a reac-tion mechanism that involves the formation of oxodisulfonium (S-O-S) dication intermediates. These intermediates undergo oxygen-exchange reactions with other sulfoxides and also allow interconversion of axial and equatorial sulfoxides in oxathiane rings. The reversibility of the oxygenexchange reaction suggests that the stereochemical outcome of the oxidation reaction may be under thermodynamic control, which potentially presents a novel strategy for the stereoselective synthesis of sulfoxides.

Results and Discussion
Reaction of diphenyl sulfoxide with triflic anhydride: Several methods for the preparation of 18 O-enriched diphenyl sulfoxide have been reported in the literature. [16] We chose to activate the sulfoxide 5 with Tf 2 O (1 equiv), and then quench the reaction with 18 O-enriched water (97 % 18 O-A C H T U N G T R E N N U N G incorporation; Scheme 2). The diphenyl sulfoxide isolated from this reaction was found to have an 18 O/ 16 O ratio of 87:13 (see the Supporting Information). After re-subjecting this product mixture to the same reaction conditions, the 18 O incorporation increased to 92 %. The efficiency of these labelling reactions was found to be reproducible (AE 2 %).
Incomplete transfer of the 18 O-label indicated that either a portion of diphenyl sulfoxide failed to react with Tf 2 O on the timescale of the reaction, or the reaction was not completely anhydrous, or an activated sulfoxide intermediate was hydrolysed on work-up with retention of the 16 Oatom. [17] IR spectroscopy was used to monitor the progress of the reaction in situ. Analysis of the spectra by using ConcIRT (Mettler Toledo) revealed that diphenyl sulfoxide was consumed fully within a minute of adding one equiv Tf 2 O at À32 8C, and that the reaction mixture comprised at least three species at equilibrium (see the Supporting Information).
We reasoned that identification of these intermediates would be helpful if we were to understand the oxidation reaction in Scheme 1. The triflyloxy sulfonium ion 6 (Scheme 3 a), which is presumably formed first in the re-A C H T U N G T R E N N U N G action mixture, could combine with its triflate anion to give sulfurane 9, or it could react with another molecule of diphenyl sulfoxide 5 to yield dication 8, or the analogous mono-or bis-sulfurane compounds 7 and 10. Oxo-bridged disulfonium salt 8 has been proposed previously as a re-  [18] can be prepared by mixing triphenylphosphine oxide 11 and Tf 2 O in equimolar amounts. [18a] Kelly and co-workers used X-ray crystallography studies to prove that Hendricksons reagent is indeed a P-O-P dication. [18a] Scheme 2. Preparation of [ 18 O]-diphenyl sulfoxide.
www.chemeurj.org Density functional theory calculations (B3LYP/6-31G* and M06/6-31G*) [13] support the hypothesis that all of the intermediates proposed in Scheme 3 are feasible structures with the exception of bis-sulfurane 10 which exhibited no barrier to dissociation in the gas phase. Monocation 6 and dication 8 displayed very similar SÀO bond lengths and SÀOÀS bond angles which place the sulfur atoms in dication 8 only 2.94 apart ( Figure 1). Dications with the structure [R 2 S-SR 2 ] 2 + are well documented in the literature [19] (see below) and it would appear that there may be a similar bonding interaction between the two positively charged sulfur atoms in dication 8. [20] 1 H NMR spectroscopy was used to further characterise 1:1 and 2:1 mixtures of diphenyl sulfoxide 5 and freshly distilled Tf 2 O in CD 2 Cl 2 at À60 8C ( Figure 2). In each case, the 1 H NMR spectrum revealed that all of the diphenyl sulfoxide had been consumed, to produce one or more products displaying broadened NMR signals. While the 1:1 (Fig-ure 2 b) and 2:1 (Figure 2 c) mixtures were dominated by different species (presumably 6/9 and 7/8, respectively), the 1:1 mixture also displayed some minor signals (e.g., at 7.7 ppm) that could be consistent with the partial formation of oxodisulfonium ion 8. Addition of water to the NMR samples converted each mixture to a single species (Figure 2 d) that differed from the original spectrum of diphenyl sulfoxide (Figure 2 a). We attribute these signals to protonation of the sulfoxide by TfOH. [17] The reaction mixtures were also analysed by 19 F NMR spectroscopy. The 2:1 mixture showed only a single peak in Scheme 3. a) Possible intermediates arising from the reaction of diphenyl sulfoxide and triflic anhydride. b) Preparation of Hendricksons reagent. [18]   ] were recorded at À60 8C, except spectrum (d) which was acquired at À30 8C. In each case, several spectra were acquired to check that the system had come to equilibrium. The shoulder at À78 ppm in (h) is a shimming artefact. its 19 F NMR spectrum at À79.4 ppm (Figure 2 g), with a frequency typical for a triflate anion, for example, sulfonium triflate 13 (Figure 2 h). [21] In contrast, the 1:1 mixture displayed two signals at À72.0 ppm and À79.1 ppm (Figure 2 f). The signal at À72.0 ppm corresponds to unreacted Tf 2 O (Figure 2 e), and is consistent with partial formation of the dimeric sulfonium ion 8. While one might expect to see several other fluorine signals corresponding to triflyl/triflate groups in species 6-9, the sole broadened signal at À79.1 ppm would suggest that all triflyl groups are in rapidintermediate exchange on the NMR timescale. [22] In summary, the 19 F NMR spectra indicate that the triflyloxy group in 6 is in fast to intermediate exchange with the triflate counter ion, presumably through an equilibrium with sulfurane 9. However, any equilibrium between oxygen-bridged species 7/8 lies in favour of dication 8 and free triflate anions.
As the NMR spectra ( Figure 2) demonstrate that all of the diphenyl sulfoxide was consumed under the conditions of the labelling experiment (Scheme 2), the sub-optimal incorporation of the 18 ]-5 must arise from either less than perfect anhydrous conditions or partial retention of a 16 O-atom present in one of the activated intermediates (Scheme 4). In the case of dication 8, attack by [ 18 O]-water at either sulfonium centre would result in retention of a 16 O-atom, while for sulfonium ion 6, the labelled water would have to attack the S(VI) centre to avoid introducing the label into the diphenyl sulfoxide product; [ 18 O]-TfOH 14 would also be produced as a by-product of this reaction. Gin has demonstrated that glycosyl hemiA C H T U N G T R E N N U N G acetals react with sulfonium ions such as 6 at the S(IV) centre only; [7a, 23] therefore, the reaction in Scheme 4 b is unlikely to occur.
A cross-over experiment was performed to gain further evidence for the formation of oxodisulfonium ion 8. was allowed to react at À60 8C for 10 min before addition of unlabelled water and neutralisation with triethylamine (Scheme 5). In theory,

when sulfoxides A C H T U N G T R E N N U N G [ 18 O]-5, A C H T U N G T R E N N U N G [ 16 O]-15 and
Tf 2 O are mixed in a 1:1:1 ratio, there is an equal probability that the Tf 2 O will react with diphenyl sulfoxide or ditolyl sulfoxide to give intermediates 6 a. The NMR experiments in Figure   www.chemeurj.org mixture. Transfer of 18 O label between diphenylsulfoxide and ditolyl sulfoxide could still occur through exchange of labelled triflate ions. However, the label would only be retained in the sulfoxide products 5 and 15 after aqueous work-up if the triflyl groups could be removed as shown in Scheme 4 b. This process has already been discounted as unlikely to occur, [7a] however, if it did happen, the 18  Both experiments led to an even distribution of the 18 O label between diphenyl sulfoxide and ditolyl sulfoxide. Furthermore, the incorporation of 18 O label in the reaction products was found to be higher than expected (32-33 % 18 O for 1:1:1 mixture; 26-28 % for 1:1:2 mixture). In other words, cross-over of the 18 O-label occurred without any apparent scrambling of oxygen atoms that would be associated with a triflate-exchange mechanism. These results are only consistent with a reversible 18  were used to oxidise oxathiane ketal 1 as described above. The resulting axial and equatorial sulfoxides were separated by silica gel chromatography for mass spectrometric analysis. Both isomers of the oxathiane-Soxides (2-R and 2-S) were found to have 87 % 18 O-enrichment ( Figure 3). The excess diphenyl sulfoxide 5 that was recovered from the reaction mixture also had the same 18 Ocontent as the starting material.
Two things can be concluded from this experiment: 1) The oxygen atom arises solely from the diphenyl sulfoxide, and not from either the Tf 2 O or water on aqueous work-up. 2) The reaction reaches completion before aqueous work-up, that is, there can be no activated sulfoxide species remaining at the time of work-up, or the percentage of 18 Olabel incorporation would be reduced, at very least in the case of the recovered diphenyl sulfoxide.
An identical labelling experiment using oxathiane ether 3 also afforded sulfoxide product 4-S with a very high level of 18 O-incorporation (83 %). On this occasion, it was not possible to isolate the equatorial sulfoxide isomer 4-R as it was formed in very low concentration. It is not clear if the small reduction in the isotopic enrichment (87 % to 83 %) is significant in this case. Therefore, we presume that both oxidation reactions in Scheme 1 occur by the same mechanism.
Identification of the oxidizing agent: Having determined the origin of the oxygen atom in the product, the next question to address was the nature of the oxidising agent; that is, which species becomes reduced during the reaction. Mixtures of Tf 2 O and either dimethyl sulfoxide 16 or diphenyl sulfoxide 5, have been reported to oxidise alcohols (Scheme 6 a), [25] and glycals, [8c] respectively. However, precedent for oxidative transformations using Tf 2 O alone also exists; for example, oxidation of aliphatic sulfides by Tf 2 O can provide access to sulfoxides, unless an alcohol is added to the mixture, in which case aldehydes or ketones will result (Scheme 6 b). [3] In cases where Tf 2 O acts as an oxidant, one sulfonate group will become reduced to the sulfinate 20 (Scheme 6 b). On the other hand, if the role of Tf 2 O is solely to activate a sulfoxide, for example, 16 (Scheme 6 a), then the corresponding sulfide 19 should be formed as the reduction product. Although we were never able to observe or isolate diphenyl sulfide from the sulfoxidation reaction, triaryl sulfonium salt 13 was consistently observed in the mass spectra of the crude reaction mixtures (Figure 4). The quantitative formation of aryl sulfonium salt 13 was confirmed by HPLC-mass spectrometric comparison of the crude product mixture with authentic samples of sulfonium salt 13 of known concentration (see the Supporting Information).
Sulfonium salt 13 has been synthesised previously from diphenyl sulfide and diphenyl sulfoxide activated with Tf 2 O and other electrophiles. [26] Therefore, it is reasonable to conclude that an activated sulfoxide species is responsible for oxidising the oxathiane compounds, while concomitantly producing diphenyl sulfide as a by-product. Any excess activated sulfoxide is then sequestered by the diphenyl sulfide to yield sulfonium ion 13. [27] This side-reaction has two consequences: 1) The oxidation reaction is effectively quenched by diphenyl sulfide prior to aqueous work-up (in agreement with the results of 18

O-labelling experiments). 2) The oxidation reaction cannot become catalytic in Tf 2 O.
Reversibility of the oxidation reaction: We have reported previously that oxathiane-S-oxide glycosyl donors can be converted to aryl sulfonium ions (e.g., compound 23, Scheme 7) by treatment with Tf 2 O in the presence of tri-A C H T U N G T R E N N U N G methoxybenzene. [10a] However, the analogous aryl sulfonium ion 25, derived from diphenyl sulfide 24, was not observed as a by-product of the oxidation reaction. One possible explanation would be that the triflyloxy sulfonium ion 22 is not formed during the oxidation mechanism. To test this hy-pothesis, sulfoxide 2-R was treated first with Tf 2 O (1.1 equiv), and then diphenyl sulfide (2 equiv). The major product isolated from the reaction mixture was oxathiane 1 (62 %). No evidence could be found for the formation of sulfonium ion 25; however, triaryl sulfonium ion 13 was observed in the mass spectrum of the crude product mixture. This experiment demonstrated that even if triflyloxy sulfonium ion 22 is formed during the oxidation reaction, it would react preferentially with the sulfur atom of diphenyl sulfide, rather than by electrophilic aromatic substitution. Furthermore, reduction of the oxathiane-S-oxide 2-R to give oxathiane 1 suggests that the oxidation process is potentially reversible under the conditions of the reaction.
We were thus curious to know if the oxygen-transfer process could also be reversible. Therefore equatorial sulfoxide 2-R was re-exposed to the conditions of the oxidation re-  www.chemeurj.org try confirmed that the 18 [28] A very similar result was obtained for oxathiane-S-oxide 4-S (Scheme 8 b), except this time the axial sulfoxide was the dominant product. Therefore both of these examples demonstrate that oxygen transfer is a reversible process that can occur with retention of configuration.
As pre-activation of labelled diphenyl sulfoxide results in scrambling of the label with the oxathiane-S-oxide oxygen atom, the reaction was also performed by pre-activation of oxathiane-S-oxide 2-R with Tf 2 O (1.1 equiv; Scheme 8 c). Once again, NMR spectroscopy of the crude product mixture showed that the equatorial sulfoxide was the dominant product. Furthermore, by reversing the order of addition of sulfoxides 2-R and A C H T U N G T R E N N U N G [ 18 O]-5, 18 O-enrichment close to the theoretical maximum was achieved for the equatorial isomer. Incorporation of 18 O with such high efficiency can only arise through the formation of oxygen-bridged disulfonium ion 26 (Scheme 8 c) as any other mechanism (e.g., 18 O transfer via triflate exchange) would result in significant dilution of the label. [24] Retention of configuration at the sulfoxide centre during the 18 O-crossover experiment requires a mechanism that can allow inter-conversion of axial and equatorial intermediates (Scheme 9). One can imagine two possible mechanisms for such a process: an intermolecular mechanism, in which diphenyl sulfoxide 5 acts as a nucleophile to attack an activated oxodisulfonium ion 27; and an intramolecular mechanism, in which the anomeric bond is broken to generate an oxacarbenium ion intermediate 28 which would allow re-Scheme 7. Reaction of oxathiane-S-oxide 2-R with Tf 2 O and electronrich aromatic compounds. Scheme 9. a) Intermolecular and b) intramolecular mechanisms for the inter-conversion of axial and equatorial isomers of oxodisulfonium ion 27-R/S. The intermolecular mechanism is depicted as an S N 2 process for simplicity, although it is possible it could involve addition-elimination steps via a sulfurane intermediate.
A C H T U N G T R E N N U N G orientation of the substituent on the anomeric sulfur atom. While latter mechanism cannot be excluded for glycosyl sulfoxides, we sought further evidence in support of the intermolecular mechanism.
A simple racemic oxathiane compound rac-32 lacking the sugar ring was synthesised (Scheme 10). Alkylation of b-mercaptoethanol 29 with bromoacetophenone 30 gave ketone 31. Reductive cyclisation in the presence of TMSOTf and Et 3 SiH led directly to oxathaine rac-32 in good yield. Stereoselective oxidation with diphenyl sulfoxide and Tf 2 O proceeded as observed previously for glycosyl oxathiane 3 with the axial isomer rac-33 a dominating the crude reaction mixture (88:12, ax/eq). [12] Careful column chromatography allowed the pure axial isomer rac-33 a to be isolated in 64 % yield.
The sulfoxide was added to a pre-formed mixture of labelled diphenyl sulfoxide A C H T U N G T R E N N U N G [ 18 O]-5 (2.8 equiv) and Tf 2 O (1.4 equiv) at À60 8C. The cross-over experiment was quenched after 1.5 h by addition of diphenyl sulfide and NaHCO 3 . NMR spectroscopy demonstrated that the crude product mixture was an 85:15 mixture of the axial and equatorial sulfoxides, while mass spectrometry gave an overall 18 O-incorporation of 37 %. As the level of 18 O-incorporation significantly exceeds the quantity of the minor isomer, it must be possible to have oxygen exchange with retention of configuration in this non-carbohydrate system. Therefore the intermolecular mechanism for inversion of configuration is possible. Furthermore, these experiments demonstrate that the oxidation reaction is also applicable to sulfides that lack the sugar ring.
As noted above, the oxidation reaction is highly stereoselective and for each example in Scheme 1 and Scheme 10, the thermodynamically favoured isomer is the dominant product (see the Supporting Information for DFT calculations on each structure). Considering that 1) axial and equa-torial sulfoxides can be inter-converted under the conditions of the oxidation reaction, and 2) the major 18 O-labelled product of the cross-over experiments is the thermodynamically favoured isomer, it is possible that the high stereoselectivity of the oxidation process could result from the reaction occurring under thermodynamic control. Indeed, in each case, re-equilibration of the major isomer results in a product mixture that is very similar to that for the corresponding oxidation reaction. On the other hand, the oxidation reaction is effectively self-quenching; the diphenyl sulfide produced during the reaction sequesters activated sulfoxide intermediates to form sulfonium ion 13. Therefore, equilibration of sulfoxides and/or reaction intermediates, for example, oxodisulfonium ion 27, would have to compete with reaction quenching by diphenylsulfide under kinetic control.
Possible mechanistic pathways: The aforementioned experiments provide evidence for a number of steps that must occur during the oxidation reaction: the first committed step in the mechanism must be the reaction of the oxathiane sulfur atom with an activated diphenyl sulfoxide species; [29] a diphenyl sulfoxide oxygen atom must become covalently bound to the oxathiane sulfur atom; diphenyl sulfide must be produced during the reaction, and then react with some activated diphenyl sulfoxide species to produce the triaryl sulfonium salt by-product.
Several mechanistic pathways could be consistent with these observations (Scheme 11). In pathway (a) oxathiane 34 initially attacks an electrophilic oxygen atom in triflyloxy sulfonium ion 6 to produce activated oxathiane 35 and diphenyl sulfide 24. Activated oxathiane 35 would then react with the excess diphenyl sulfoxide to provide oxodisulfonium ion 27. [30] Intermediate 27 could also be formed via route (b) which similarly involves reaction at an electrophilic oxygen atom, but this time in dication 8. Although there is evidence in the literature for activated sulfoxide species reacting through electrophilic oxygen atoms, [31] we consider routes (a) and (b) to be less likely than attack at the softer electrophilic sulfur atoms in intermediates 6 and 8 (Scheme 11 c-d). [32] If oxathiane 34 were to react at the sulfonium centres of cation 6 (route c) or dication 8 (route d), a dithiadication intermediate 36 would be produced. Dithiadications have been the subject of several reviews, [19] and this type of functional group is invariably synthesised by reaction between a sulfide and an activated sulfoxide. [33] Dithiadications have also been implicated in the mechanism of "remote Pummerer reactions" and other processes involving transfer of oxygen from sulfoxides to sulfides. [14f,g,i, 34] If a dithiadication were to form during the mechanism depicted in Scheme 11, it would still be necessary to introduce the sulfoxide oxygen atom and to release diphenyl sulfide as a by-product. Both of these steps could be achieved by diphenyl sulfoxide attack at the oxathiane sulfur atom in intermediate 36 to provide oxodisulfonium ion 27. Therefore, regardless of the initial reaction step between thioglycoside 34 and the activated sulfoxide species, all four mechanistic The final step of the reaction would involve intermediate 27 reacting with diphenyl sulfide 24 to release the oxathiane-S-oxide product 37 and form the triaryl sulfonium ion 13. [35] In this regard, it is worth reiterating that at no point have we observed the formation of an aryl sulfonium salt combining diphenyl sulfide and the oxathiane (e.g., 25, Scheme 7). Therefore, if oxygen-linked dication 27 reacts directly with diphenyl sulfide, the reaction must occur very selectively at the diphenyl sulfonium centre in intermediate 27. This may well be possible as alkyl sulfonium ions are more stable than aryl sulfonium ions. [36] It is also interesting to note that dithiadications can react with electron-rich aromatic compounds to form aryl sulfonium ions. [37] It is possible that an analogous reaction could be responsible for the reduction reaction shown in Scheme 7; reaction of diphenyl sulfide with activated sulfoxide 22 could give a dithiadication which might then react with a second molecule of diphenyl sulfide to yield oxathiane 1 and sulfonium salt 13.

Conclusion
Oxodisulfonium ions have been proposed previously as reaction intermediates, [8c, 31b] but to the best of our knowledge, no experimental evidence for their existence has been re-ported. NMR spectroscopy data and 18 O-cross-over experiments support the formation of oxodisulfonium ions when sulfoxides and Tf 2 O are mixed at low temperature. Such species undergo exchange reactions with other sulfoxides, thus facilitating oxygen exchange and inter-conversion of axial and equatorial sulfoxides in oxathiane rings.
The commonly used diphenyl sulfoxide/Tf 2 O reagent is able to oxidise sulfides to sulfoxides. In this reaction diphenyl sulfoxide acts as the oxidant (following activation by Tf 2 O) and also transfers the oxygen atom to the sulfide through an oxodisulfonium ion intermediate 27 (Scheme 11). The first step of the oxidation process most probably involves reaction of the sulfide with an activated diphenyl sulfoxide species resulting in formation of a dithiadication intermediate 36. Either oxodisulfonium ion 8 or triflyloxy sulfonium ion 6 could act as the activating agent. Although oxodisulfonium ion 8 is the dominant species at equilibrium for a 2:1 mixture of diphenyl sulfoxide and Tf 2 O, triflyloxy sulfonium ion 6 is formed first and could thus react directly with the sulfide. Either way, dithiadication 36 would then react with diphenylsulfoxide to introduce the new sulfoxide oxygen atom via oxodisulfonium intermediate 27. Diphenylsulfide produced in this step as an initial by-product, goes on to sequester activated sulfoxide species, effectively quenching the reaction prior to aqueous work-up.
Sulfoxide exchange with the oxodisulfonium intermediate 27 presents an intriguing possibility that the stereochemical Scheme 11. Possible reaction pathways for the oxidation of generic oxathiane 34. Mechanisms are depicted as S N 2 processes for simplicity, although it is likely they may involve addition-elimination mechanisms via sulfurane intermediates. outcome of the oxidation process could occur under thermodynamic control. Of course, this mechanism would require rapid equilibration of the oxodisulfonium intermediates prior to deactivation by diphenylsulfoxide. Without a detailed knowledge of the kinetics of the reaction it is not possible to conclude whether or not the original oxidation re-A C H T U N G T R E N N U N G action is under kinetic or thermodynamic control. Nevertheless, it may be possible that the system could be engineered to slow or remove the diphenyl sulfide termination step, for example by using a substituted diaryl sulfoxide. If so, this oxygen-transfer reaction would present a novel strategy for the stereoselective synthesis of sulfoxides.

Experimental Section
Full experimental details and analytical data for compounds prepared and coordinates for compounds modelled using DFT calculations are included in the Supporting Information. CCDC-733122 (2-R) [10a] and CCDC-733123 (4-S) [10c] contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. General experimental methods: All solvents were dried prior to use, according to standard methods. [38] Trifluoromethanesulfonic anhydride (Tf 2 O), was freshly distilled from phosphorus pentoxide under a N 2 (g) atmosphere and all other commercially available reagents were used as received. All reactions were performed in oven dried glassware under a N 2 (g) atmosphere.