Episulfonium ion intermediates

Toremifene also undergoes oxidative metabolism to form a QM.59 The 4-hydro-xytoremifene QM has a half-life of lh at physiological pH and temperature (Table 10.2), while its half-life in the presence of GSH is approximately 6 min.59 The 4-hydroxytoremifene QM reacts with two molecules of GSH and loses chlorine to yield the corresponding di-GSH conjugate (Scheme 10.9). This reaction mechanism likely involves an electrophilic episulfonium ion intermediate, which could contribute to the potential cytotoxicity of toremifene. 

An intramolecular regioselective sulfenocyclization of unsaturated ureas 447 resulted in formation of 5,6-dihydro-4//-l,3-oxazine derivatives 449 (Scheme 86). The procedure employed phenylsulfenyl chloride and ethyldiisopro-pylamine to generate an episulfonium ion intermediate 448, from which the cyclic products 449 were formed by internal nucleophilic displacement <1995M609>. 

Pearson, PG, Soderlund, E.J., Dybing, E. Nelson, S.D. (1990b) Metabolic activation of 1,2-dibromo-3-chloropropane evidence for the formation of reactive episulfonium ion intermediates. Biochemistry, 29, 4971-4981... 

The acid-catalysed rearrangement of 2,4,5-triols leads to the thermodynamic product, a tetrahydrofuran. However, cyclisation using trimethyl orthoacetate and pyridinium toluene-p-sulfonate gives a mixture of the THF and a tetrahydropyran, in which the former predominates, by attack of the primary hydroxy group at different ends of the episulfonium ion intermediate. This route nevertheless provides a useful route to THPs through equilibration of this reaction mixture <02JCS(P1)2646,02JCS(P1)2652>. 

Molecules with more extensive separation between sulfur and leaving groups, such as chlorine (e.g., C1(CH2)6S(CH2)6C1), behave like simple aliphatic halides (or sulfides) since three-membered ring (episulfonium ion) formation is no longer possible. One convenient method for verifying the formation of an episulfonium ion intermediate involves isotopic carbon labeling. Since this ion is symmetric, it would ultimately lead to a nearly 1 1 distribution of an appropriately placed label, something not observed in a direct displacement. 

The deoxynucleoside problem was approached from another sequence, in which 3,5-di-O-benzoyl-D-arabinofuranosyl chloride was prepared, and then treated with sodium ethanethioxide to give, in a stereoselective reaction, ethyl 3,5-di-O-benzoyl-l-thio-a-D-arabinofuranoside, a thiogly-coside having the proper structure for neighboring-group transfer of the ethylthio group to C-2 by way of an episulfonium ion intermediate. This approach was later expanded in a successful synthesis of 2 -S-methyl-2 -thioadenosine and other derivatives of 2 -thioadenosine, all of which were potential precursors to 2 -deoxyadenosine. 

Johnston BD, Pinto BM (2000) Synthesis of thio-linked disaccharides by 1 — 2 intramolecular thioglycosyl migration oxocarbenium versus episulfonium ion intermediates. J Org Chem 65 4607 17... 

We have previously reported on the excellent properties of the mustard-type sulfur compound 12 (Fig. 11.3) as a scaffold for the synthesis of functional molecules. The nucleophilic displacement of the chlorides in 12 occurs in high efficiency with a variety of nucleophiles using on water conditions. These reactions occur via episulfonium ion intermediates, and are therefore uniquely assisted by the aqueous medium. ... 

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