Intermediates sulfenes

The intermediate sulfenic acid derived from a penicillin sulfoxide has been trapped by a large assortment of reagents and, in one case, the sulfenic acid itself has been isolated (74JA1609). Only some of these products will be discussed here, and the reader is referred to the cited reviews (especially B-80MI51102) for additional examples. 

Various other reagents have been used to trap the intermediate sulfenic acid, and Scheme 14 shows some of these (74JCS(P1)1459, 74TL725, 74JCS(P1)1456, 77JCS(P1)1477, 70TL4897, 78TL4167). 

However, alcohol-free solutions of diazomethane146 must be used to avoid destruction of the intermediate sulfene and a stronger base such as 1,5-diazabicyclo [4.3.0] non-5-ene is required for the final dehydrohalogenation step to obtain sulfones 19a,d. 

The attack by the thiolate anion on the N-oxide oxygen of 62 produces the intermediate sulfenic acid derivative 65, which, in the presence of thiols, further reacts with the thiolate anion, to give the oxime 66, which has been isolated among the reaction products. By contrast, spontaneous loss of the halide anion from 65 affords the ni-troso intermediate 67 that, by losing NO and the thiyl radical directly, or through 68, produces the a-nitrosoolefm 69. By a Michael type reaction with water this last product immediately yields the final oxime 70, which has been isolated among the reaction products. 

Hydrolysis of 2,2,2-trifluoroethanesulfonyl chloride has been found to proceed via intermediate sulfene (CF3CH=S02) formed by iilcB reaction. At pH 1.8-5.0 the (ElcB) mechanism applies, whereby water and hydroxide ion act, respectively, as the carbanion-forming base at low and high pH extremes. The ( lcB)rev reaction applies in dilute acid and is accompanied by the expected H-D exchange of substrate protons when D2O is used as solvent. 

Mislow s [2,3]-sigmatropic rearrangement of sulfoxides is more than a mechanistic curiosity, because the intermediate sulfenate 5.83 can be intercepted by a suitably thiophilic reagent, converting an enantiomerically enriched sulfoxide 5.82 into a comparably enriched rearranged allyl alcohol 5.84, with suprafacial shift 5.85 of the functionality. 

It has been reported that treatment of methyl 1-methylsulfanylvinyl sulfoxides with sodium thiophenolate in methanol affords l-methylsulfanylalk-l-en-3-ols. A sequence has been proposed218 (see Scheme 45) in which the thiophilic base first causes an in situ isomerization of the vinyl sulfoxide moiety into an allylic sulfoxide which then undergoes a [2,3]-sigmatropic rearrangement and subsequent thiophilic cleavage of the intermediate sulfenic ester. 

The initial adduct 9 undergoes a series of sigmatropic rearrangements under the reaction conditions to give tetra- and dihydrothiophene 1-oxides 11 and 1289. The cis relationship between the sulfinyl oxygen and the adjacent methyl group in 11 and 12 is a consequence of the stereoelectron-ic requirements of the addition of the intermediate sulfenic acid 10 to the C-C double bond. 

Sultones undergo photolytic ring cleavage and the intermediate sulfenes are trapped by methanol to form esters , viz. 

Sulfenic acids also react with alkynes, and (r-butylsulfinyl)alkynes (85) eliminate 2-methylpropene on thermolysis to give the ( )-alkenyl sulfoxides (87) stereoselectively via cyclization of the intermediate sulfenic acids (86 Scheme 20)7 The stereochemistry of the adduct (87) is established by the mechanism of sulfenic acid addition. For the intermolecular trapping of sulfenic acids by alkynes, generation of the sulfenic acids by thermolysis of the corresponding 3-sulfinylpropionitrile (88 equation 35) is the preferred route. Sterically hindered sulfenic acids have also been generated by flash vacuum pyrolysis of sulfoxides and trapped intermolecularly by alkynes. ... 

Some sulfenic acids have been generated by flash vacuum pyrolysis of alkyl sulfoxides thus, t-butanesulfenic acid (54) was detected as an intermediate in the thermolysis of the t-butyl sulfoxide (55) in various solvents (Scheme 31). Sulfenic acids (45) may also be obtained by thermolysis of thiol sulfinates (56) (Scheme 31). The intermediate sulfenic acids formed in these reactions can be characterised by IR and NMR spectroscopy and may be trapped by addition to ethyl acrylate (57) (Scheme 32). 

The most important application of sulfoxide thermolysis is probably in the field of p-lactam antibiotics.6 Penicillin sulfoxide (34) by heating is converted into the more stable isomer (35). The reaction occurs via the intermediate sulfenic acid (36). This sulfenic acid, by treatment with trimethyl phosphite in glacial acetic acid, can be reduced to the thiol acetate (37), which can be isolated (Scheme 20). 

Sulfenes when generated in the presence of tricarbonyl partners give rise to 1,3,4-dioxathiane S,S-dioxides <82AP(315)57>. Typically, the treatment of propane-2-sulfonyl chloride (305) with tri-ethylamine in the presence of 1,2,3-indanetrione (307) gives initially the )S-sultone (308) that arises by cycloaddition of the intermediate sulfene (306). Thereafter, attack by chloride ion on (308) furnishes the jS-chlorosulfonate (309). At the same time, further cycloaddition occurs with excess of (307) to generate the doubly spirocyclic 1,3,4-dioxathiane dioxide (310) (Scheme 46). 

Sulfur Nucleophiles. Thiolsulfinates are known to readily disproportionate with the generation of intermediate sulfenic and sulfinic acids as in reactions 3, 4, and 5 (4). 

Also reported in the early 1970s was the photochemistry of some alkyl a-substituted p-ketosulfoxides 290 [148]. Stereomutation at suliiir was observed in all cases where it could be detected due to diastereomeric interconversions. In addition to the products that are parallel to the previous example, ketone 293 and thioester 294 were observed. A mechanism in which Type I cleavage competed with p-cleavage was proposed. It included a cyclic sulfuranyl radical 297 in order to accomplish the oxygen migration. An alternative h3rpothesis has formation of a sulfenic ester 301, secondary photolysis, and typical chemistry of alkoxy radicals to get to the same intermediates. Sulfenic esters were not detected, but analysis was by GC or after column chromatography, neither of which would have been survived by such compounds. 

---