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. Sending out an SOS: The diphenyl sulfoxide/triflic anhydride combination is widely used as an activating agent for glycosylation reactions. However, oxathiane glycosyl donors are instead oxidised to sulfoxides in a stereoselective and reversible reaction. NMR spectroscopy and isotopic labelling experiments reveal the presence of oxodisulfonium (S‐O‐S) dication intermediates that can undergo oxygen exchange with other sulfoxides (see scheme).