Thiophenols addition

Table 11.2 Selectivity of product formation and relative rate constants for thiophenol addition to 1-substituted allenes Id and lg-i [44],...

The 1,4-addition of selenophenols to cycloalkenones proceeds smoothly under the same conditions used in the thiophenol addition (see Section V) (eq. [18]). Although the e.e. of the products is 40 to 65%, compared with the 60 to 80% achieved in the thiol addition reaction, the solid adducts are readily purified to enantiomeric purity by crystallization (63). 

Although the mechanism of this reaction has not been studied as thoroughly as that of the thiol addition reaction, there appears to be considerable similarity in the main features of the reaction. Thus, although the transition state may well differ in a number of details, the transition state shown earlier (Figure 10) appears to predict the correct configuration for the products of the selenophenol addition as well as of the thiophenol addition to cyclohexenones. 

Extensive kinetic studies of addition of thiophenols to an A -acridinyl quinonediimide (19) are interpreted in terms of (i) acridine nitrogen protonation followed by thiophenol addition at low pH and (ii) thiophenolate addition to neutral (19) at moderate to high pH.37 For hydrolysis, a similar mechanistic competition was observed,38 i.e. (i) water attack on acridmium substrate at low pH and (ii) hydroxide attack on (19) at higher pH. 

Scheme 7.11 Tandem thiophenol addition/enantioselective protonation on a-phenylacrylates [16].

The action of sulfur nucleophiles like sodium bisulfite and thiophenols causes even pteridines that are unreactive towards water or alcohols to undergo covalent addition reactions. Thus, pteridin-7-one smoothly adds the named S-nucleophiles in a 1 1 ratio to C-6 (65JCS6930). Similarly, pteridin-4-one (73) yields adducts (74) in a 2 1 ratio at C-6 and C-7 exclusively (equation 14), as do 4-aminopteridine and lumazine with sodium bisulfite. Xanthopterin forms a 7,8-adduct and 7,8-dihydropterin can easily be converted to sodium 5,6,7,8-tetrahydropterin-6-sulfonate (66JCS(C)285), which leads to pterin-6-sulfonic acid on oxidation (59HCA1854). 

Diphenyl sulfide can best be prepared by treating benzene and aluminum chloride with sulfur chloride, sulfur dichloride, or sulfur. In addition to diphenyl sulfide there are found traces of thiophenol and varying amounts of thianthrene. 

Copper (I) thiophenolate [1192-40-1] M 172.7, m ca 280°, pKj 6.62 (for PhS ). The Cu salt can be extracted from a thimble (Soxhlet) with boiling MeOH. It is a green-brown powder which gives a yellow-green soln in pyridine. Wash with EtOH and dry in a vacuum. It can be ppted from a pyridine soln by addition of H2O, collect ppte, wash with EtOH and dry in a vacuum. [Synthesis 662 1974, J Am Chem Soc 79 170 1957-, Chem Ber 90 425 1957.]... 

At room temperature, base-catalyzed addition of thiophenol to phenyl trifluo-romethyl acetylene gives exclusively (Z)-3-phenyl-3-phenylthio-l,1,1-tnfluoro-propene. At 150 °C, the predominant isomer is the E isomer (64%), with 23% of the Z isomer and 13% of the other two regioisomers [4] (equation 5). 

While carboxylate anions do not add to the imonium function of ketone derived enamines, such as morpholinocyclohexene, when these are combined with carboxylic acids (38), the addition of thiophenol or benzyl mercaptan leads to a-aminothioethers (509,510). 

Although a sulfhydryl group generally is not converted to an 5-phenyl thioether, the conversion can be accomplished through the use of a Pd-catalyzed arylation with an aryl iodide. Thiophenol can be used to introduce sulfur into molecules by simple displacement or by Michael additions, and thus, the phenyl group serves as a suitable protective group that can be removed by electrolysis (—2.7 V, DMF, R N X-). ... 

When having an Q ,/3-unsaturated carbonyl moiety, 2(5/7)-furanones are capable of undergoing 1,4-Michael-type additions. It was found that 1,4-addition reactions of thiophenols to the furanones 168,170, and 172 take place at room temperature in the presence of triethylamine to give a quantitative yield of the adducts 169, 171, and 173. Complete diastereoselective Michael-type addition occurred in all cases (Scheme 48) (88T7213). 

Enantioselectivities were found to change sharply depending upon the reaction conditions including catalyst structure, reaction temperature, solvent, and additives. Some representative examples of such selectivity dependence are listed in Scheme 7.42. The thiol adduct was formed with 79% ee (81% yield) when the reaction was catalyzed by the J ,J -DBFOX/Ph aqua nickel(II) complex at room temperature in dichloromethane. Reactions using either the anhydrous complex or the aqua complex with MS 4 A gave a racemic adduct, however, indicating that the aqua complex should be more favored than the anhydrous complex in thiol conjugate additions. Slow addition of thiophenol to the dichloromethane solution of 3-crotonoyl-2-oxazolidinone was ineffective for enantioselectivity. Enantioselectivity was dramatically lowered and reversed to -17% ee in the reaction at -78 °C. A similar tendency was observed in the reactions in diethyl ether and THF. For example, a satisfactory enantioselectivity (80% ee) was observed in the reaction in THF at room temperature, while the selectivity almost disappeared (7% ee) at 0°C. 

No addition products with S-nucleophiles have yet been reported except for the reaction of 2-methylthio-4,6-diphenylthiopyrylium iodide with sodium thiophenolate involving a 2//-thiopyran intermediate (86S916). 

As expected, the addition of arenediazonium ions to thiophenols does not involve the thiophenol molecule, but rather the thiophenoxide ion (Price and Tsunawaki, 1963). Dediazoniation with the formation of a diarylsulfide (6.16) is competitive with the formation of the diazo thioether 6.15 (Scheme 6-9 van Zwet et al., 1970). Whereas the early investigators detected only one isomer, (Z)- and (ii)-forms were... 

Shono et al. (1979) describe a method for hydro-de-diazoniations which is simple, gives excellent yields, and is claimed to show no unfavorable substituent effects (14 examples). It consists of the addition of thiophenol (7 equiv.) to a suspension of an arenediazonium tetrafluoroborate in a mixture of water and pentane (10 1) at room temperature. After the completion of N2 evolution, excess thiophenol is removed by addition of Na2C03. The usual work-up gave the corresponding hydrocarbon in 84-100% yield and diphenylsulfide. The deuterated compounds are obtained if one uses C6H5SD and D20. 

Konig et al. have achieved thioether functionalization of T8[CH = CH2]8 via the radical addition of thiols such as thiophenol, cyclohexylthiol, and 2-mercaptopyridine in the presence of azobisisobutyronitrile (AIBN) as a radical initiator (Table 13), while Gao et al. have also used this method to prepare very highly functionalized POSS by reacting T8[CH = CH2]8 with thiol-terminated glycosides giving glycoclusters in 70% yield (Figure 22). 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

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