Thiophenol elimination

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... 

The temperature at which elimination of thiophenol occurs depends on the substituents on the sulfur-bearing carbon. Thioke-tals react rapidly at 25°. In some cases the elimination of thiophenol from the less reactive thioacetals may also be performed at 25°. However, in the present case the combined inductive effects of the vinyl and methoxy groups evidently destabilize the incipient car-bonium ion and necessitate a higher temperature for the reaction. 

This explanation is in accordance with the reaction of a ring size isomer of 2-365 containing a cyclopentene instead of a cyclohexene moiety as ring C. With catalytic amounts of thiophenolate and thiophenol, little reaction was observed nevertheless, with stoichiometric amounts of thiophenol a tetraquinane, still containing the SPh-group, was obtained in 76% yield. Inspection of a molecular model revealed that the corresponding enolate is not proximately disposed to facilitate the E2 elimination step. 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Recently Ikegami used the thiol addition reaction in the preparation of optically pure 4-phenylthioazetidin-2-one, the starting material for an elegant ( + )-thienamycin synthesis (58). When 4-phenylsulfonylazetidin-2-one was treated with cinchonidine and thiophenol, the intermediate azetinone underwent a thiol addition reaction and the 4-phenylthioazetidin-2-one was obtained in 54% optical and 96% chemical yield (eq. [13]). Recrystallization of the optically active aze-tidinone allows isolation of the pure enantiomer from the mother liquor. The phenylthio group is eliminated later in the synthesis of thienamycin. 

Phenylthioacetylene has been prepared by elimination of thiophenol and dehydrobromination of cis-1,2-bis(phenylthio)ethylene5 and cis-1-bromo-2-phenylthioethylene,2 7 respectively. The latter was obtained by addition of thiophenol to propiolic acid in ethanol and subsequent one-pot bromine addition, decarboxylative dehalogenation, and careful distillation to remove the trans isomer.2.7 on the other hand, cis-1,2-bis(phenylthio)ethylene was prepared by double addition of thiophenol to cis-1,2-dichloroethylene.5a d Although these procedures can provide useful amounts of phenylthioacetylene, they were found to be somewhat less satisfactory in our hands as far as operation and/or overall yields are concerned. Furthermore, we have encountered problems with regard to the reproducibility of one-pot dehydrobrominations of phenylthio-1,2-dibromoethane.6 However, the stepwise execution of the double dehydrobromination, as described in the modified procedure reported here, provides preparatively useful quantities of phenylthioacetylene in a practical manner. 

Swartz and Stenzel (1984) proposed an approach to widen the applicability of the cathode initiation of the nucleophilic substitution, by using a catalyst to facilitate one-electron transfer. Thus, in the presence of PhCN, the cathode-initiated reaction between PhBr and Bu4NSPh leads to diphe-nydisulfide in such a manner that the yield increases from 10 to 70%. Benzonitrile captures an electron and diffuses into the pool where it meets bromobenzene. The latter is converted into the anion-radical. The next reaction consists of the generation of the phenyl radical, with the elimination of the bromide ion. Since generation of the phenyl radical takes place far from the electrode, this radical is attacked with the anion of thiophenol faster than it is reduced to the phenyl anion. As a result, instead of debromination, substitution develops in its chain variant. In other words, the problem is to choose a catalyst such that it would be reduced more easily than a substrate. Of course, the catalyst anion-radical should not decay spontaneously in a solution. 

The chemical entrainment method was used by Ono et al. (1979) to eliminate the nitro group in nitroalkene derivatives. On simple mixing with thiophenol and sodium sulfide in DMF, nitro aryl olefins substitute hydrogen for the nitro group (Scheme 5.9). 

Reduction of dibenzothiophene with sodium in liquid ammonia has been shown to be sensitive to the experimental methods employed however, the major product is usually 1,4-dihydrodibenzothiophene. 27 -28i The electrochemical reduction of dibenzothiophene in ethylene-diamine-lithium chloride solution has been shown to proceed via stepwise reduction of the aromatic nucleus followed by sulfur elimination. In contrast to the reduction of dibenzothiophene with sodium in liquid ammonia, lithium in ethylenediamine, or calcium hexamine in ether, electrolytic reduction produced no detectable thiophenol intermediates. Reduction of dibenzothiophene with calcium hexamine furnished o-cyclohexylthiophenol as the major product (77%). Polaro-graphic reduction of dibenzothiophene 5,5-dioxide has shown a four-electron transfer to occur corresponding to reduction of the sulfone group and a further site. ... 

Kita has introduced a novel one-pot preparation of 5-methoxylated indoline 55 and indole 56 derivatives by intermolecular addition followed by cyclization between A-tosylaniline derivatives 53 and activated olefins 54 using phenyliodine(III) bis(trifluoroacetate) (FIFA) <99H511785>. In the reaction of 53 with phenyl vinyl sulfides, indoles were produced directly by the spontaneous elimination of thiophenol. 

Thiophenol as the nucleophile eliminates the 1.1-substituents to form 2.4.6-triphenyl-X -phosphorin22. A similar elimination takes place if 1,1-di-alkyl-thio-X -phosphorins 169 are heated in toluene. This method is thus an excellent way to remove the dialkylamino groups which had been introduced before as protecting groups ... 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Formation of cinnamoyl esters of thiophenols is readily accomplished. These esters cyclize, with elimination of benzene, by the action of aluminum chloride (Scheme 3). An alternative approach, exemplified in Scheme 4, utilizes the ready thermal isomerization of thiochromones to thiocoumarins (see p. 121), the former being derived from phenylthioacrylic esters. ... 

The three-component reaction of bis(phenylthio)-(trimethylsilyl)methyl lithium (243), phenyloxirane and a terminal alkene yields cyclopropanes 245142 (equation 82). It is assumed that a-elimination of LiSPh from the carbenoid-like species 243 generates phenylthio(trimethylsilyl)carbene (244) which is in equilibrium with 243 although this equilibrium is probably far on the side of the latter, trapping of the thiophenolate ion by the... 

Interestingly, cyclopropane 245 (R = SPh) is also formed when 243 is combined with (trimethylsilyl)oxirane. In this case, the necessary alkene (phenylthioethylene) is provided by silanolate elimination from the alkoxide arising from regiospecific ring-opening of the oxirane by thiophenolate (equation 82)142. 

Data assembled by Parker (201 demonstrate these effects for bimolecular reactions involving sulfur nucleophiles and haloaliphatic substrates. As an illustration for the case of Reactions 4, the S 2 displacement of iodide from CH3I by SCN at 25°C is accelerated relative to its rate in water tty 0.2 log units in methanol, by 1.1 log units in 10% aqueous dimethyl sulfoxide (v/v), and tty approximately 2.4 log units in dimethyl formamide (DMF). Furthermore, the rates of bimolecular elimination and substitution of cyclohexyl bromide in the presence of thiophenolate at 25°C both increase by 2.7 log units when the solvent is changed from ethanol to dimethylfonnamide (20). 

Gramme is a common precursor for indol-3-ylmethylation of enolates and other nucleophiles. Such reactions normally occur by an elimination-addition mechanism. Following development of procedures for 4-substitution via directed lithiation with l-(tri-/w-propylsilyl)-gramine, Iwao and Motoi have developed conditions for tandem nucleophilic substitution of the dimethylamino group. Quatemization followed by reaction with a nucleophile in the presence of TBAF leads to alkylation. <95TL5929> The carbon nucleophiles which were successfully used include nitromethane, methyl acetoacetate, diethyl malonate and diethyl 2-(acetamido)malonate. Phthalimide, thiophenol, TMS-CN and TMS-Nj were also used as sources of nucleophiles. 

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