Thiosulfinates

The esters of thiosulfinic acid R -SO,-S-R are used as fungicides and antibacterial prepai ations. These compounds have similar stiaicture fragments to allicin - natural insecticide from garlic with following structure (CH =CH-CH ),[SO-S] (http //www.ALLICIN.com). For deter-mination of ethyl S-ester of 4-aminobenzenthiosulfinic acid (esulan) in the ointment RP-HPLC was proposed [1] with acetonitrile water=30 70 as eluent. For seai ching bioactive compounds the synthesis of new esters of thiosulfinic acid is perspective that was confirmed by results of recent studies as instance [2]. Therefore requirements ai e existed for investigation HPLC sepai ations of these substances. 

Under the reaction conditions the initially formed thiosulfinate (143) is quantitatively transformed into the disulfide 144 by a Pummerer-type rearrangement125. 

Within the biooxidation of disulfides, chiral thiosulfinates become available. Tert-Butyl tert-butanethiosulfinate represents a particularly valuable chiral auxiliary for the preparation of several chiral sulfoxides and sulfinimines, which can be subsequently transformed into branched amine compounds, P-aminoacids, and chiral aziridines. This product is accessible readily by mediated biooxidation of tert-butyl... 

The thermolysis of acyclic- and/or six- and larger ring sulfoxides to yield olefins and sulfenic acids is well documented . The formation of allylic sulfenic acids and thiosulfinates in the thermolysis of thiirane oxides containing hydrogen on the a-carbon of the ring substituent (which is syn to the S—O bond) has been discussed previously in terms of /i-elimination of hydrogen, which is facilitated by relief of strain in the three-membered ring (Section llI.C.l). 

Aliphatic unstable thioketones can be generated by thermolysis of their thiosulfinates in toluene.91... 

Thiaziridines,145 thiiranes,167 and elemental sulfur168 (in the presence of Ph3P) can react with a thioketone to give thiosulfines then trapped as 1,2,4-trithiolane. 

In the case of 1,2,4-trithiolanes, both els and trans isomers are obtained with a different reaction mechanism involving a molecule of thioketone and a molecule of thiosulfine.50... 

The oxidation of sulfides is a complex process involving a number of conversions [32,46], Disulfides are oxidized by hydroperoxide via the intermediate thiosulfinate RSSOR, which is very reactive to ROOH [32,52-54], The interaction of ROOH with phenolsulfoxides also gives rise to intermediate catalytic compounds, as a result of which the reaction proceeds as an autocatalytic process [46,55], The rate of the catalytic decomposition of R OOH is described by one of the following equations ... 

Thermolysis of alkyl thiosulfinates in the presence of added alkynes or... 

We noted earlier that the sulfinyl group of a thiolsulfinate is believed to have a basicity somewhat less than that of a sulfoxide but somewhat greater than that of a sulfinate ester (Engberts and Zuidema, 1970).+Thus, in an acid solution a thiosulfinate will be protonated to some extent to RS(OH)SR. A whole series of reactions is known that are initiated by attack of a nucleophile on the dico-ordinate sulfur of RS(OH)SR with cleavage of the S—S bond and displacement of RSOH. 

Let us return now to a brief further consideration of the acid- and nucleophile-catalyzed reactions of thiosulfinates. We have seen that in the various acid- and nucleophile-catalyzed reactions of PhS(0)SPh the attack of... 

So far all of the mechanistic studies discussed have involved the use of thiosulfinates lacking hydrogens on both the carbon a to the sulfenyl sulfur and the carbon(s) / to the sulfinyl sulfur. There has been a good reason for this. When hydrogen atoms are present in such locations cycloelimination reactions can take place quite readily and a whole new dimension of complexity is added to the chemistry of thiolsulfinates. The details of these cycloelimination reactions and the chemistry that follows them have been brilliantly worked out in detail by Block and his co-workers (Block and O Connor, 1974a, 1973 Block and Weidman, 1973 Block, 1972a,b). We will now outline their findings. 

The separation of the diastereomeric cystine-5-monoxides 69 by Savige et al. (Ill) in 1964 demonstrated that the chiral, pyramidal configuration at the sulfinyl sulfur in thiosulfinates can be maintained. 

However, the synthetic approaches to simple chiral thiosulfinates with sulfur as a sole center of chirality are relatively few in number, and for the most part their applicability is limited. 

Optically active aromatic thiosulfinates were first prepared by asymmetric oxidation of diaryl disulfides with (+)-percamphoric acid (105,112). Apart from the fact that the optical purity of diaryl... 

The polarimetric method, in combination with the results of chemical correlation, made it possible to determine the optical purity of a range of chiral sulftnates (105-107), thiosulfinates (35,105), and sulfinamides (83) with the sulfur atom as a sole center of chirality. These compounds were converted by means of Grignard or alkyl-lithium reagents into sulfoxides of known specific rotations. This approach to the determination of optical purity of chiral sulfinyl compounds has at least two limitations. The first is that it cannot be applied to sterically hindered compounds [e.g., t-butyl /-butanethio-sulfinate 72 does not react with Grignard reagents]. Second, this... 

NMR spectral differentiation of enantiomers as solutes in chiral solvents has been achieved with sulfoxides, sulfinates, thiosulfinates, sulfinamides, and sulfites (86,108,242). The usefulness and high sensitivity of this method is confirmed by its successful application... 

Much attention has been devoted to the acid- and nucleophile-catalyzed racemization of thiosulfinates. As a result of the extensive studies by Kice and his co-workers (112) and by Fava (281), it is clear now that the easy racemization of thiosulfinates caused by acids and bases (e.g., pyridine) is related to the scission of the sulfur-sulfur bond and the formation of sulfenic acid or its anion as an achiral intermediate. As expected, introduction of steric hindrance... 

With regard to nucleophilic substitution at sulfur in thiosulfinates, it is interesting to note that methanolysis of (-)-(iS)-r-butyl p-toluene-thiosulfinate 70 in the presence of A -bromosuccinimide (NBS) proceeds with predominant inversion at the sulfinyl center. Most... 

---