Thiophiles

Reactions of the Disulfide Group. Besides the thiol end groups, the disulfide bonds also have a marked influence on both the chemical and physical properties of the polysulftde polymers. One of the key reactions of disulfides is nucleophilic attack on sulfur (eq. 4). The order of reactivity for various thiophiles has been reported as (C2H O) P > R, HS , C2H5 S- >C,H,S- >C,H,P,... 

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

The first compound of this class with inhibitory activity on the enzyme and on acid secretion was the 2-(pyridylmethyl)sulfinylbenzimidazole, timopra-zole, and the fust pump inhibitor used clinically was omeprazole, 2-[[3,5-dimethyl-4-methoxypyridin-2-yl] methylsulfinyl]-5-methoxy- lH-benzimidazole. Omeprazole is an acid-activated prodrug. Omeprazole and the other PPIs are accumulated in the acidic space of the parietal cell due to the pKa of the pyridine nitrogen and these are converted due to protonation of the benzimidazole nitrogen first to a thiol-reactive cationic sulfenic acid and then dehydrated to form the sulfenamide (Fig. 1). These thiophilic cations then bind to luminally... 

Owing to the reversible nature of the allylic sulfenate/allylic sulfoxide interconversion, the stereochemical outcome of both processes is treated below in an integrated manner. However, before beginning the discussion of this subject it is important to point out that although the allylic sulfoxide-sulfenate rearrangement is reversible, and although the sulfenate ester is usually in low equilibrium concentration with the isomeric sulfoxide, desulfurization of the sulfenate by thiophilic interception using various nucleophiles, such as thiophenoxide or secondary amines, removes it from equilibrium, and provides a useful route to allylic alcohols (equation 11). 

For a review of additions of organometallic compounds to C=S bonds, both to the sulfur (thiophilic addition) and to the carbon (carbophilic addition), see Warded, J.L. Paterson, E.S. in Hartley Patai The Chemistry of the Metal-Carbon Bond, vol. 2 Wiley NY, 1985, p. 219. See pp. 261-267. 

The above-mentioned method is useful but metals that form strong M-S bonds (e.g., Hg, Ag, Sn) do not dissolve in W-Melm solutions of sulfur. This problem has been solved by the addition of Mg to the reaction mixture. Metal polysulfides having a variety of metals can be synthesized by the 7 T-Melm/ M-i-Mg/Sg method (Scheme 11) [48]. For example, a mixture of Mg, Sb powder (1 eq.), Sg (15 eq. as S) and W-Melm is heated at 80 °C for 48 h to afford the orange powder of [Mg(N-MeIm)5]Sb2Sj ( x 15) in 88% yield. Rauchfuss et al. proposed the mechanism of these reactions as follows. First, the reduction of Sg with Mg occurs to give the [Mg(W-MeIm)6] salt of Sg , which is probably in equilibrium with Sg, Ss ", Ss" and other species. Independently, the sulfuration of the thiophilic metal takes place. Next, the polysulfide an-... 

Part C of the present procedure illustrates a mild method for effecting the elimination of thiophenol from thioacetals and thioketals under essentially neutral conditions. The reaction of simple thioacetals and thioketals with bis[copper(I) trifluoro-methanesulfonate] benzene complex in benzene-tetrahydrofuran at room temperature affords vinyl sulfides in high yield (Table I). The reaction presumably occurs by coordination of the thiophilic copper(I) reagent with sulfur, heterolysis to a phenylthio-stabilized... 

In these a-phosphorylated dithioesters, the electron-withdrawing effect of the phosphono group, which strongly increases the electrophilic character of the thiocarbonyl group, makes the latter more prone to the thiophilic attack of nucleophiles and stabilizes the resulting carbanion. The main reactions of 1 with nucleophiles are summarized in Scheme 2. 

Deprotonation of allylic aryl sulfoxides leads to allylic carbanions which react with aldehyde electrophiles at the carbon atom a and also y to sulfur . With benzaldehyde at — 10 °C y-alkylation predominates , whereas with aliphatic aldehydes at — 78 °C in the presence of HMPA a-alkylation predominates . When the a-alkylated products, which themselves are allylic sulfoxides, undergo 2,3-sigmatropic rearrangement, the rearranged compounds (i.e., allylic sulfenate esters) can be trapped with thiophiles to produce overall ( )-l,4-dihydroxyalkenes (equation 24). When a-substituted aldehydes are used as electrophiles, formation of syn-diols 27 occurs in 40-67% yields with diastereoselectivities ranging from 2-28 1 (equation 24) . ... 

A similar study was undertaken on the related crown ether systems 201 <2001PS29>. They all showed moderate extraction of both Ag(l) and Hg(ll) ions and so were less selective than compounds 184a and 184b from the previous study. However, the presence of the benzo-15-crown-5 substituent offered the simultaneous complexation of the hard alkali cation Na(l) as well as the thiophilic metals Ag(l) and Hg(n) by the thieno sulfur. Interestingly, this second extraction was not influenced by the presence of the other metal. 

Radical cyclization of acyclic sulfinamides 239 provides easy access to cyclic sulfinamides 241 <06AG(E)633>. Conceivably, the reaction pathway involves thiophilic attack by the aryl radical with a concomitant or successive expulsion of the p-tolyl or tert-butyl radical. 

Dioxopentane-3-thione reacts178 with allyltributylstannane, Scheme 14, to give the expected thiophilic ene adduct and a [2+2] cycloadduct. 

The presence of EWG on 2,4-dioxopentane-3-thione favours the formation of thiophilic adducts with different allyl substrates.178 In all cases the reaction affords single thiophilic ene adducts and formation of C=C occurs with high E stereoselectivity (Scheme 17). 

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