Electrophiles with disulfides

Another example for gem-functionalization is demonstrated in the reaction with disulfides. The tandem sulfenylation and carbonylation to 1-alkylthiocy-clopropanecarbothioates 168 are realized, indicating that disulfides can serve both as nucleophiles and electrophiles [81], (Scheme 63)... 

The direct electrosynthesis of S—N bonds from disulfides and amines has been shown to occur through a reaction of the amine with the oxidized disulfide being a strong electrophile. In contrast to the results, the cross-coupling of phthahmide (16) with disulfide does not proceed in a direct electrolysis. However, the electrosynthesis of sulfenimides (17) can be achieved by a [Br]" "-mediated cross-coupling reaction of imides with disulfides (Scheme 7). The electrolysis of a mixture of (16) and dicyclohexyl disulfide in an MeCN-NaBr-(Pt) system affords... 

The metalation chemistry of the imidazoline system has received attention only recently, with the lithiation of l-benzyl-2-imidazoline being found to occur at the 2-position (90TL1767). Although the reactivity of the lithi-ated species with alkyl halides was poor, better results were achieved with disulfide and carbonyl electrophiles (90TL1767,90TL1771). The products formed by reaction with ketones were found to be unstable with respect to fragmentation, and this result was utilized to provide a new route for the synthesis of unsymmetric ketones (Scheme 138). 

The disulfide sulfur of 263 acts as an electrophile with the enolate anion resulting in ring closure (Equation 54) <1980LA1917>. DMSO oxidizes the sulfur of 264 which then reacts with the enamine double bond (Equation 55) <2001JFC(108)51>. 

The same alkyl thiocarbamates 95 can be prepared in 35-72% yield by reaction with disulfides and with carbon disulfide followed by alkylation with alkyl halides100. When carbonyl sulfide was used as electrophile, lithium /V,/V-dialkyldioxamates were formed, which after reaction with benzyl bromide gave thiooxamates 96 in 37-56% yield100. 

The superficially similar carbene 4.116, another carbene stable enough to be isolated, has the best of all worlds. With six electrons for the n system coming from the double bond and the two nitrogen lone pairs, it has an aromatic sextet without having to fill the pz orbital. The pz orbital is empty and the px orbital is filled, making this a nucleophilic carbene, which reacts with the electrophile carbon disulfide to give the zwitterion 4.117. 

Carbon disulfide reacts as an electrophile with amines in the presence of sodium hydroxide to give dithiocarbamates (15) the reaction involves nucleophilic addition of the amine to the electrophilic thiocarbonyl bond (Scheme 13). The reaction is industrially important for the manufacture of some widely used agricultural fungicides (see chapter 9, p. 148). Carbon disulfide undergoes a similar type of reaction with alcohols to give xanthates (16) (Scheme 14). 

The electrophilic nature of thiyl radicals expresses itself also in a pronounced tendency to couple the unpaired electron at sulfur with free electron pairs of another heteroatom. The most prominent example is the reaction of thiyl with thiolate and the establishment of an equilibrium with disulfide radical anions, formulated in eq. 26. 

The similar alkoxide- or hydroxide-induced trifluoromethylation was also found to work with other electrophiles. Diphenyl disulfide can be trifluoromethylated to give trifluoromethyl phenyl sulfide in 87% yield (eq 4). Methyl benzoate can be trifluoromethylated to generate 2,2,2-trifluoroacetophenone in 30% yield at temperatures between —50°C and —20°C. Trifluo-romethylcopper (CF3CU) can be generated in situ with trifluoromethyl sulfone, f-BuOK, and copper iodide (Cul), and it then further reacts with iodobenzene at 80 °C for 20 h to give a,a,a-trifluorotoluene in 26% 3neld. ... 

The KF-S reaction presumably involves attack of a fluonnated caibanion on sulfur, whereas the S-Sbp5 reaction may involve electrophilic attack by a cationic sulfur species on the olefin under the strong Lewis acid conditions Electrophilic attack on a fluonnated olefin may also account for formation of a perfluorinated sulfide from reaction of bis(pentafluorophenyl)disulfide with hexafluoropropylene under superacid conditions [IS5] (equation 28)... 

Carbon disulfide can act as an electrophilic agent with enamines at room temperature. Therefore, treatment of an enamine with both elemental sulfur and carbon disulfide in a polar solvent can result in the formation of a 3H-l,2-dithiole-3-thione (such as 108) and/or a 2H-l,3-dithiole-2-thione (such as 109) (135,139,140). These products are the result of competing... 

In an attempt to protect thiophenols during electrophilic substitution reactions on the aromatic ring, the three substituted thioethers were prepared. After acetylation of the aromatic ring (with moderate yields), the protective group was converted to the disulfide in moderate yields, 50-60%, by oxidation with hydrogen peroxide/boiling mineral acid, nitric acid, or acidic potassium permanganate. ... 

As well as for metalated epoxides, the trifluoromethyl moiety also proved an effective organyl-stabilizing group for metalated aziridines. Lithiated aziridine 241 reacted stereoselectively with carbonyl-containing electrophiles, and phenyl disulfide and chlorotrimethylsilane were also trapped in good yield (Scheme 5.60) [70b, 85],... 

Zhu, Z., Petering, D.H. and Shaw, C.F. Ill (1995) Electrostatic Influences on the Kinetics of the Reactions of Lobster Metallothioneins with the Electrophilic Disulfides 2,2 -Difhiodipyridine (PySSPy) and 5,5 -Dithiobis(2-nitrobenzoic acid) (ESSE). Inorganic Chemistry, 34, 4477-4483. 

Various new phosphonium salts were prepared in a one-pot reaction of carbon disulfide, phosphines, and 1 followed by an exchange reaction of the zirconated metal fragment with 2 equiv. of electrophiles (Scheme 8-23) [206],... 

The interaction of carbon disulfide as a substrate in carbonic anhydrase model systems has been studied using density functional theory methods. A higher activation energy of CS2 compared to C02 in the reaction with [L3ZnOH]+ was due to the reduced electrophilicity of CS2. The reversibility of the reaction on the basis of these calculations is questionable with [L3ZnSC(0)SH]+ as intermediate.572... 

Alternatively, l,3-dithiol-2-ones have been obtained by reacting di-isopropylxanthogen disulfide with unsaturated substrates, such as disubstituted alkynes R2C2, in the presence of AIBN (azoisobutyrylnitrile), a radical initiator.78 Finally, vinylene dithiocarbonates can be obtained by reacting mer-cury(II) acetate with the corresponding trithiocarbonates, generated by reaction of electrophilic alkynes with ethylene trithiocarbonate.79 Analogously,... 

As with other haloaromatic systems, Barbier reactions are also suitable for heterocyclic systems. For example, the lithio derivatives formed in situ from iodide 187 upon sonication reacted immediately with electrophiles such as benzaldehyde, hexanal and diphenyl disulfide, to give good yields of 188 <00T3709>. Similar chemistry was also successful with pyrazines, pyrimidines, and pyridazines. 

Similar to 67, the oxanickelacycle 69 prepared from 3-hexyne, Ni(cod)2/bipy, and C02 also acted as a nucleophilic reagent. The reaction of 69 with p-tolyl disulfide took place at the Ni-C bond to give vinyl sulfide 70 in 53% yield after esterification (Scheme 23).37 In the case of 2-bromopropiophenone as an electrophile, the cycloadduct 71 was obtained in 47% yield after acidic workup. 

Addition of diphenyl disulfide (PhS)2 to terminal alkynes is catalyzed by palladium complexes to give l,2-bis(phe-nylthio)alkenes (Table 3)168-172 The reaction is stereoselective, affording the (Z)-adducts as the major isomer. A rhodium(i) catalyst system works well for less reactive aliphatic disulfides.173 Bis(triisopropylsilyl) disulfide adds to alkynes to give (Z)-l,2-bis(silylsulfanyl)alkenes, which allows further transformations of the silyl group to occur with various electrophiles.174,175 Diphenyl diselenide also undergoes the 1,2-addition to terminal alkynes in the presence of palladium catalysts.176... 

Scheme 8.13 and Eqs. 8.6-8.10 reveal that lithiated methoxyallene 42 is sufficiently reactive towards a variety of electrophiles such as alkyl halides [44, 45], ethylene oxide [12c], tosylated aziridine 45 [46], dimethyl disulfide [12b], trialkylstannyl and trialkylsilyl chlorides [47, 48] and iodine [49]. These substitution reactions proceed with excellent regioselectivity and the corresponding a-functionalized products are obtained in good to high yields. An exceptional case was found by treatment of 42 with a guanidinium salt, which led to a 60 40 mixture of a- and y-adducts 50 and 51 (Eq. 8.11) [50],... 

While the vast majority of the chemistry of thiolsulfonates involves reactions in which the sulfenyl sulfur acts as an electrophilic center and is attacked by nucleophiles, one example has been reported (Douglass, 1959) in which this same sulfur acts as a nucleophile. Methyl methanethiolsulfonate undergoes a very slow reaction with methanesulfenyl chloride that leads to the formation of methanesulfonyl chloride and dimethyl disulfide. The mechanism is believed... 

A cyclohexadienyl Lewis adduct or salt formed by the reaction of a Lewis base with an aromatic compound. Such an adduct is apparently formed from the reaction of OH with 4-(A/-2-aminoethyl-2 -pyridyl disulfide)- -nitrobenzo-2-oxa-l,3-diazole (2PROD). 2PROD is a two-protonic-state electrophile used as a probe for enzyme active site nucleophiles and as a fluorescent re-... 

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