Sulfenate ester cleavage

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. 

In some of the more complex molecules, there are instances in which the low energy chromophore is probably not localized on the sulfoxide, yet the sulfinyl (SO) group is involved in the observed transformations. Some attempt will be made to differentiate photochemical reactions of molecules that merely happen to contain a sulfinyl group and those for which the sulfoxide is the critical functional group and/or chromophore. Section IX is reserved for the chemistry of ketosulfoxides in which the chemistry is clearly carbonyl but the reaction involves of sulfinyl site. The photochemistry of sulfenic esters (R-S-0-R ) appears throughout the text, particularly in Section III—the discussion of sulfoxide a-cleavage reactions. A short additional section on these sulfoxide isomers is also included at the end. 

The photochemistry of dibenzyl sulfoxide 10 was briefly reported in the mid 1960s [21,22]. It was said to decompose mainly to benzyl mercaptan (isolated as the disulfide 17) and benzaidehyde 16. Though no mechanism was suggested at the time, it is now clear that these products arise from a standard a-cleavage mechanism, followed by secondary photolysis of the sulfenic ester 13. The careful reader will note that the yield of bibenzyl (19) is very low in comparison to photolysis of dibenzyl ketone. Sulfinyl radicals rarely lose SO, though some net extrusions are discussed later. 

Evidence for such an additional mechanism also comes from the work of Guo, in the form of the quantum yields for loss of optical activity and for loss of starting material for compounds 157, 158, and 3-CH3 [61]. It is unlikely that the quantum yield for cleavage by methyl p-tolyl sulfoxide is higher than that for the benzyl compound, and that the sulfinyl methyl pair would be so overwhelmingly returned to the sulfoxide, as compared to escape products or sulfenic ester formation. Current evidence does not exist to establish the actual mechanism(s) firmly. 

In spite of the CIDNP polarization pattern, we believe the sulfinyl mechanism can be dismissed. First, the SO bond in a sulfinyl radical is very strong. Using Benson s estimate for the heat of formation of the phenylsulfinyl radical (13 kcal/mol) [63] and standard values for the other relevant compounds [98], the S-0 bond energy is ca. 102 kcal/mol, whereas the C-S bond is some 35 kcal/mol weaker. Transfer of an O atom from phenylsulfinyl to a methyl radical is endothermic by 11 kcal/mol, and to epoxidize ethylene endothermic by 40 kcal/mol. (The relevance of the latter example will become clear below.) Furthermore, from the a-cleavage work discussed previously, it is clear that the expected product from reaction to an arylsulfmyl radical and a carbon radical is a sulfenic ester or disproportionation product. 

A singlet a-cleavage mechanism (d> = 0.14, independent of solvent) is presented to account for most of the products, but there are quirks that do not appear in other sulfoxides. First, no sulfenic ester is observed, although it is likely that the GC analysis used would not have detected it. Generally, only trace ethane was observed. Furthemore, photolysis of DMSO-dg in non-deuterated solvents (water, benzene, acetonitrile) results nearly exclusively in CHDj, which eliminates the usual disproportionation reaction ... 

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. 

The photochemistry of sulfenic esters has come up repeatedly in this review as a result of their formation from sulfoxide a-cleavage. With the exception of 50, the result is S-0 homolysis, just as one would expect intuitively. Indeed, photolysis of both simple and more complex sulfenic esters that will be discussed in this section appear to proceed along this pathway. 

Similarly, sulfenimino-P-lactam 205 [107] reacted with diazomethane to give y-lactam 206 by methylene insertion into the C-6/C-7 azetidinone bond (Scheme 58). A spiro-aziridine intermediate was probably formed [106]. Sulfen-amide cleavage initiated by triphenylphosphine followed by acylation and ester deprotection led to the acid 207 which does not have any significant antimicrobial or p-lactamase inhibitory activity [106]. 

The cleavage of allylic sulfenate esters by phosphites (80) may actually involve attack at sulfur, even though the products indicate otherwise. 

If the condensation is effected with magnesium methoxide in methanol, y-hydroxy-a,/f-unsaturated esters (3) are obtained directly via isomerization of the double bond, u [2,3] sigmatropic rearrangementof the sulfoxide group, and cleavage of the sulfenate. The same transformation of 1 to 3 can be conducted in two steps, as formulated in cq uation (I). The overall yield is about the same as in the direct method. 

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

As depicted in Scheme 26, a closely related route to the alkoxyl radical entailed the preparation of sulfenate 30. Upon photoactivation with a radical initiator such as (Bu3Sn)2, the heterolytic cleavage of the O-S bond could have enabled the transfer of the phenylsulfanyl group to C9a, leading to 31. This methodology was reported by Cekovic for the 1,5-functionalization of the phenylsulfenate ester of heptan-2-ol. Applied to phenylsulfenate 30, this process induced only the isomerization of olefins. 

An alternate method of preparing the azetidinone sulfenic acid was developed by initially trapping the sulfenic acid as its trimethylsilyl ester (32) (Chou et al., 1976). Careful cleavage of the trimethylsilyl protecting group with methanol afforded the sulfenic acid (31) (Chou et al., 1974). 

In a weakly alkaline solution, isothiocyanate reacts with the a-amino group of cysteine (Figure 2.64). The reaction of isothiocyanates with cystine leads to the cleavage of disulfide bond (-S-S-) with the formation of cysteine sulfenic acid and a dithiocarbamic acid ester. Dehydration of this ester yields 5-amino-l,3-thiazine-4-one-3-thione derivative and elimination of hydrogen sulfide produces a cyclic 2-thiazoline-4-carboxylic acid derivative (Figure 2.65). Reaction of cystine with thiocyanates (R-S-C=N), formed by spontaneous isomerisation of isothiocyanates, produces disulfide Cys-S-S-R and -thiocyanoalanine, which cyclises to 2-thiazoline derivative (Figure 2.66). 

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