1.2- Dithioles intermediates

In the 1970s, Kishi published a series of landmark papers [36] describing the total syntheses of ( )-dehydrogliotoxin (1973) [36b], ( )-sporidesmin A (1973) [36c], ( )-gliotoxin (1976) [36d], and ( )-hyalodendrin (1976) [36e] in which he employed a new method for epidithiodiketopiperazine synthesis (Scheme 9.4). Cognizant of the harsh conditions required in all of the sulfur incorporation methods developed at the time, it was determined that thiolation would be performed in the early stages of the syntheses. A dithiol intermediate obtained in a similar fashion to Trown s epidithiodiketopiperazine was protected as a dithioacetal, and after elaboration of this core diketopiperazine structure, the dithioacetal was unraveled under mild conditions in the final steps to afford the target epidisulfides. 

Scheme 9.10 Schmidt s structural elucidation of a dithiol intermediate...

Aryl-4,6-bis(alkylthio)-l,3,5-oxa(thia)diazenium salts (231) are converted to 1,2,4-dithiazolines (233) by H2S presumably through ring opening under nucleophilic attack of H2S on C-2 and oxidation of the dithiol intermediate (232) by atmospheric oxygen (Scheme 48) <85LA1874,88LA729). 

We have suggested a mechanism of formation of these compounds that involves a dithiol intermediate which interacts with ammonia giving the corresponding amino derivative, followed by a nucleophilic attack of the amino group upon another molecule of an aldehyde, the formation of a precursor intermediate, and heterocyclization with an elimination of a molecule of water. 

Finally, the reaction of 374 with cyclic unsaturated substrates such as 1,3-cyclohexadiene, 1,4-dihydronaphthalene 1,4-dioxide, or acenaphthalene resulted in formation of cycloadducts 405, 407, and 409, respectively. These compounds could be subsequently aromatized by the use of DDQ in the case of 405 and 409 or polyphosphoric acid (PPA) in the case of 407 to generate l,3-dithiole-2-thiones 406, 408, and 410 (Scheme 55) <1996TL8085, 1999TL801>. The compound 410 was further treated with potassium /< r7-butoxide to give the dithiolate intermediate 411, which underwent dialkylation leading to 412 (Scheme 56) <1999J(P2)755, 1999TL801>. 

Condensation of the iV-acetates 342 with CS2 (LHMDS) afforded the lithium dithiolate intermediates 349. Quenching with bromoacetone, or phos-... 

Two efficient syntheses of strained cyclophanes indicate the synthetic potential of allyl or benzyl sulfide intermediates, in which the combined nucleophilicity and redox activity of the sulfur atom can be used. The dibenzylic sulfides from xylylene dihalides and -dithiols can be methylated with dimethoxycarbenium tetrafiuoroborate (H. Meerwein, 1960 R.F. Borch, 1968, 1969 from trimethyl orthoformate and BFj, 3 4). The sulfonium salts are deprotonated and rearrange to methyl sulfides (Stevens rearrangement). Repeated methylation and Hofmann elimination yields double bonds (R.H. Mitchell, 1974). 

Thioketals are readily formed by acid-catalyzed reaction with ethane-dithiol. Selective thioketal formation is achieved at C-3 in the presence of a 6-ketone by carrying out the boron trifluoride catalyzed reaction in diluted medium. Selective protection of the 3-carbonyl group as a thioketal has been effected in high yield with A" -3,17-diketones, A" -3,20-diketones and A" -3,l 1,17-triones in acetic acid at room temperature in the presence of p-toluenesulfonic acid. In the case of thioketals the double bond remains in the 4,5-position. This result is attributed to the greater nucleophilicity of sulfur as compared to oxygen, which promotes closure of intermediate (66) to the protonated cyclic mercaptal (67) rather than elimination to the 3,5-diene [cf. ketal (70) via intermediates (68) and (69)]." " ... 

In the synthesis of l,3-dithiolan-2-ones from spirocyclic intermediates, via episulfides, substituted tetrathiacyclododecane and the related pentathiacyclopentadecane were isolated in good yields <96JCS(P1)289>. Preparation and molecular dynamics studies of 2,5,8,17,20,23-hexathia[9.9]-p-cyclophane have been reported <96P4203>. The syntheses and properties of thiocrowned l,3-dithiole-2-thiones and their conversion to tetrathiafiilvenes via treatment with triethylphosphine have been described <96LA551>. 

Four-coordinate, planar iron(II)-dithiolate complexes also exhibit intermediate spin. The first example described was the tetraphenylarsonium salt of the square-planar bis(benzene-l,2-dithiolate)iron(II) dianion, (AsPh4)2[Fe(II)bdt2], which showed 5 = 0.44 mm s and AEq = 1.16 mm s at 4.2 K [157]. The electronic structure of a different salt was explored in depth by DFT calculations, magnetic susceptibility, MCD measurements, far-infra red spectroscopy and applied-field Mossbauer spectroscopy [158]. 

In the synthesis of l,3-dithiole-2-thione derivatives as intermediates for electropolymerization precursors, the bicyclic 462 was found to be inert to normal cyclization conditions <1999JOC6418>. This is believed to be due to steric hindrance, from the boat conformation of the dithiin ring. Cyclization was achieved, albeit in only moderate yields, by heating with P2S3 to give the thiophene 463a or HBr/AcOH for the furan 463b (Equation 125). 

A novel synthesis of alkylsulfanylisothiazoles 230 starts with sodium a-cyanoketene dithiolates 227, obtained by the reaction of cyanoacetamides 226 with carbon disulfide in the presence of sodium ethoxide <06SC825>. Treatment of 227 with sulphur and piperidine acetate generates sodium isothiazole-3,5-dithiolates 229. The formation of 229 is assumed to arise from the addition of anionic sulphur to the nitrile group in 227 to give the intermediate 228, which cyclizes upon elimination of anionic sulphur to yield 229. Salts 229 are readily alkylated to furnish 3,5-bis(alkylthio)isothiazole derivatives 230. 

In structural terms, djenkolic has two units of L-cysteine joined through a CH2 group linked to sulfur atoms. It has also been found in seeds of Albizzia lophanta and Parkia speciosa32 and, as noted earlier, is the source of CS2 in Mimosa pudica (Section 11.1.2.2.2). An enzyme in A. lophanta seeds converted djenkolic acid to an unstable material with a leek-like odor, methylene dithiol 39.92 This was presumably an elimination of aminoacrylic acid 28 via intermediates 37 and 38 (Scheme 13). The methylene dithiol decomposed to H2S and possibly, thioformaldehyde, CH2S the latter might be a source for polysulfides. 

The argument against Scheme 1 is a negative one. Its basis derives from extensive studies carried out on the ligand replacement reactions of oxorhenium complexes of the family MeReO(dithiolate)L (20,34-37). Those studies (Sections V.B and V.C) show that all such processes studied to date proceed by direct displacement reactions without a recognizable intermediate from unassisted Re-L dissociation. (Indeed, in an early work, a dissociative step was written, but that formulation has since been revised see Section V.D.)... 

Another example of a polymer formation is the oxidation of l,3,4-thiadiazole-2,5-dithiol [27] including the formation of an intermediate disulfide (5). As the latter is... 

Thus, the thiol sulfur may act as either a leaving group in car-tap or as an electrophile in bensultap on route to the formation of nereistoxin. Therefore, the number of nereistoxin analogs which may be prepared for insecticidal evaluation is very large. This includes the possibility of derivatives formed from the reaction between 2-dimethylamino-propane-l,3-dithiol and the chlorosulfenyl and chlorosulfinyl intermediates described in Figure 2. 

Benzotrithiole 2-oxide (41) was obtained in 76% yield from the reaction of benzene-1,2-dithiol with thionyl chloride <93TL673>. Similarly, 1,3,2-benzodioxathiole 2-oxide was prepared from 1,2-dihydroxybenzene and thionyl chloride <66HC(2i-i)i>, and 1,2,3-benzoxadithiole 2-oxide was obtained from 2-mercaptophenol and thionyl chloride <81AG(E)570>. Reaction of the monosodium salt of 1,2-dihydroxybenzene with sulfuryl chloride afforded an intermediate chlorosulfate ester, which was dehydrochlorinated to 1,3,2-benzodioxathiole 2,2-dioxide by the action of pyridine <66HC(21-l)l>. The substituted 1,3,2-benzodioxathiole 2,2-dioxide (121) was isolated from the photolysis of pyrenedione in the presence of sulfur dioxide <87TL2057>. 

The meso-ionic l,3-dithiol-4-ones (134) participate - in 1,3-dipolar cycloaddition reactions giving adducts of the general type 136. They show a remarkable degree of reactivity toward simple alkenes including tetramethylethylene, cyclopentene, norbomene, and norbor-nadiene as well as toward the more reactive 1,3-dipolarophilic olefins dimethyl maleate, dimethyl fumarate, methyl cinnamate, diben-zoylethylene, A -phenylmaleimide, and acenaphthylene. Alkynes such as dimethyl acetylenedicarboxylate also add to meso-ionic 1,3-dithiol-4-ones (134), but the intermediate cycloadducts are not isolable they eliminate carbonyl sulfide and yield thiophenes (137) directly. - ... 

Irradiation of a benzene solution of anhydro-4-benzoylamino-2-phenyl-l,3-dithiolium hydroxide (141, R = Ph, R = H, R = COPh) yields the 1,2-dithiole (145, 80%). This photoisomerization has been interpreted as involving the bicyclic intermediate 144. ... 

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