Disulfides with enolates

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

Cyclopropylidenetriphenylphosphorane (1) generated by treatment of cyclopropyltriphenyl-phosphonium tetrafluoroborate (4) with lithium diisopropylamide, reacts with dialkyl disulfides (diphenyl disulfide does not react) or 7V-(phenylsulfanyl)succinimide in tetrahydrofuran to afford [1 -alkylsulfanyl(cyclopropyl]triphenylphosphonium tetrafluoroborates (5). The latter are useful three-carbon synthons, suitable for pentannulation reactions, as demonstrated with enolates of 2-methoxycarbonyl-4-methylcyclohept-4-enone and -0x0 esters. ... 

The addition of a carbanion to carbon disulfide with a subsequent S-alkylation provides a route to 2-alkylthio-thiophenes. In the example below, the carbanion is the enolate of a cyclic 1,3-diketone. 

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 disulfide dimers of 2-aminothiophenols have also been used in the syntheses of benzothiazines. In this case, nitrogen acts as a nucleophile and sulfur as an electrophile. Reagents that have nucleophilic carbons adjacent to an electrophilic carbon can be reacted with these disulfides. Examples include a,(3-unsaturated esters that undergo conjugate addition followed by enolate addition to sulfur (Equation 86) <1983J(P1)567>, and 1,3-dicarbonyl compounds such as ethyl acetoacetate <2005AXEo2716> and dimethyl malonate <2006ARK(xv)68> (Scheme 63). 

The method has been extended to other polyfunctionnal systems, such as O-ethyl S-(tetrahydro-2-oxo-3-furanyl)dithiocarbonate. Treatment of y-butyrolactone with bis [methoxy(thiocarbonyl)]disulfide in the presence of 2.2 equivalents of lithium diisopropy-lamide at —78 °C in THF provides the lithium enolate which reacts with MgCla to furnish the magnesium enolate (equation 17). 

These anhydro-bases are heterocyclic equivalents of enamines and enol ethers and react readily with electrophilic reagents to give products which can often lose a proton to give a new resonance-stabilized anhydro-base. Thus, anhydro-l,2-dimethylpyridinium hydroxide (645) reacts with phenyl isocyanate to give an adduct (646) which is converted to the stabilized product (647 - 648). A similar sequence with carbon disulfide yields the dithio acid (644). 

Methanol-0-4 methyl nitrite, and dimethyl disulfide have been examined as potential chemical probes for distinguishing between alkoxides and enolates in the gas phase.171 Methanol-0-d proved to be unsuitable and methyl nitrite reacts too slowly in contrast, the reactive ambident behaviour of dimethyl disulfide results in elimination across the C—S bond on reaction with alkoxides ( hard bases ) and attack at sulfur by enolates ( soft bases ). This probe has been applied to investigation of the anionic oxy-Cope rearrangement. The dianionic oxy-Cope rearrangement is a key step in a squarate ester cascade involving stereoinduced introduction of two alkenyllithium reagents cis to each other.172... 

With dimethyl disulfide as the electrophile the cis/trans-ratio is 90 10 even in tetrahydrofuran. Competition experiments show that this reaction is much faster than the usual alkylations, which afford mainly frans-compounds68). With the sulfur electrophile a single electron transfer (SET) seems likely generating a cyclopropyl radical as a reactive species, which naturally displays a different selectivity compared to the enolate anion. 

An attempted synthesis of dithioesters 220 by stepwise treatment of enolates from cyclopropanes 97 with carbon disulfide and methyl iodide lead to an unexpected new product without a cyclopropane ring. By spectroscopic means and study of the reactions dihydrothiophene structure 222 has been established 98). 

Thermal reactions of the iodonium enolate 279 with acetonitrile and carbon disulfide in the presence of Cu(acac)2 lead to the heterobicyclic ketones 285 and 286, respectively (98TL9073), while similar treatment of the hybrid sulfonyl-carbonyl ylide 287 with CS2 or phenylacetylene affords the tricyclic sulfones 288 and 289 (97T9365). 

Recently it has been reported that a-thio derivatives of enamines and enol ethers form 5-amino- or 5-alkoxy-l,2-dithiole-3-thiones (127a, b) by reaction with carbon disulfide (80ZOR13). Spiran compounds (128) are also formed from suitable substrates. The reaction has some similarities to an enamine synthesis below <67AG(E)294). 

Elution of the silica gel column with additional hexane afforded thiophenol (5,0 g), diphenyl disulfide (0.2 g), and BHT (0.1 g, stabilizer from the THF). Continued elution with increasing amounts of ethyl acetate (hexane EtOAc from 100 to 80 20) afforded dlnonyl ketone (2.4 g. 10%), S-phenyl decanoate (0.8 g, 2%), and the enol of 2-methyl-3,5-diketotetradecane (2.4 g, 6% the amount is probably greater). 

Carbonyl transposition.1 Tetrafluoroboric acid is the most effective acid for rearrangement of a-hydroxy ketene dithioketals to a,p-unsaturated thiol esters. This rearrangement is particularly useful for rearrangement of the tertiary allylic alcohols formed by addition of organometallic reagents to a-keto ketene dithioketals, which are readily available by reaction of ketone enolates with carbon disulfide followed by alkylation with methyl iodide. 

The sulfmylation of esters, - lactones, carboxylic acids, > amides and lactams may be effected by reacticm of the corresptHiding lithium enolates in THF at -78 to 0 C with dimethyl or difdie-nyl disulfides, or, less conunmily, with methyl or fdienyl sulfmyl halides. The enolates of ketones, however, are insufficioitly nucleq diilic to react with dialkyl sulfides unless HMPA is added to the re-acticm mixture, although they do react smoothly with diaryl sulfides. This difference allows the selective sulfenylation of esters in the presence of ketones (entry 5, Table 3). ... 

The a-protons of iron acyl complexes are acidic and these can be deprotonated with Lithium diisopropylamide (LDA) or with n-butyllithimn. Thus the corresponding enolates are readily functionalized and undergo reaction with alkyl halides, aldehydes, disulfides, trimethylsilyl chloride, and epoxides to afford the corresponding a-derivatized products. " Early work on racemic complexes revealed that these transformations occur in a highly diastereoselective fashion,... 

Potassium enolates of aldehydes, Enolates of aldehydes are somewhat difficult to generate because of competing polymerization by base. They have been obtained recently in high yield by use of potassium hydride in THF at 0° and successfully alkylated, sulfenylated with diphenyl disulfide, and converted into o-iodo aldehydes by iodine. The last two reactions have not been observed previously. Sulfenylation of aldehydes has previously used indirectly generated lithium enolates and a reactive sulfenyl chloride. All three reactions are useful, however, for aldehydes with only one a-proton. Otherwise yields of monosubstituted aldehydes are low and largely by-products are obtained. 

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