Benzylic thiols

A problem associated with the use of abrasive metal poHshes is that the fresh metal, which has been exposed by the cleaning, rapidly oxidizes or tarnishes. Thus, many modem poHshes contain inhibitors. Sulfur compounds, eg, alkyl benzyl thiols, commonly are used, as are mercapto esters such as lauryl thioglycolate [3746-39-2] and dialkyldisulfides (52—54). 

In the presence of sulfide or sulfhydryl anions, the quinonemethide is attacked and a benzyl thiol formed. The P-aryl ether linkage to the next phenylpropane unit is broken down as a result of neighboring-group attack by the sulfur, eliminating the aryloxy group which becomes reactive phenolate ion (eq. 2). If sulfide is not present, a principal reaction is the formation of the stable aryl enol ether, ArCH=CHOAr. A smaller amount of this product also forms in the presence of sulfhydryl anion. 

The hydrothiolation of electron-deficient alkenes [X = CN, C(=0)(0Me)] and p-nitro-styrene was catalysed by the Cu complexes 98 and 99. The reactions with phenyl- or benzyl-thiol proceed with high conversions (>90%, rt, 5 mol%). 

The reaction of diethylamine or alcohol with 2,3-allenamide 551 affords /3-diethyl-amino-a,/3-unsaturated enamide 555, indicating the migration of the C=C bond under basic conditions. The corresponding reaction of 551 with benzyl thiol proceeded to afford /j-thiobenzy 1-/1,y-unsatu rated enamide 556 the /i,y-C=C bond can migrate to the a,/3-position on the treatment with DBU in THF to afford 557 [257]. In reactions of 4,4-dichloro-2,3-butenamide 558 with amines, thiolates and alcohols, ce,/j-unsaturated enamides 560-564 are always formed on treatment with a base [258, 259]. 

Benzyl thiol 70 was deprotonated using w-butyllithium in THF at room temperature, lithiated with DTBB (5%) at 0°C to give the benzyllithium 71 and then treated with electrophiles at temperatures ranging between —30 and 0°C. Final hydrolysis afforded the expected products 72 (Scheme 29 f. The reaction applied to allyl mercaptan failed, giving an intractable mixture of products. 

The optical purity of a- and /J-thiol carboxylic esters, a-thiolamides, secondary benzylic thiols and aliphatic thiols can be measured by l3PNMR using a nonchiral divalent phosphorus... 

The pyridazine dioxide derivative (108) was made by intramolecular nitroso compound dimerization as shown (Scheme 23). 1,2-Oxathiin 2,2-dioxides are obtained by the addition of sulfuric acid to a,(3-unsaturated ketones, e.g. (109) — (110) (66HC(21-2)774). 1,2-Dithiins are synthesized from conjugated diynes using benzyl thiol reductive debenzylation of intermediate (111) by sodium in liquid ammonia at - 70°C gives, after aerial oxidation, the 1,2-dithiin (112) (67AG(E)698). 

Pracejus and co-workers also described an alternative method for preparing suitable enolates in situ, Michael addition of a thiol to an acrylate [8]. A selected example of this reaction, for which enantioselectivity is in the range 20-54% ee, is shown in Scheme 9.3, Eq. (a). Use of a catalytic amount (5 mol%) of quinidine, 7, gave the (R)-cysteine derivative 6 with 54% ee. Benzyl thiol, benzhydryl thiol, or triphenylmethyl thiol were used as the thiol component. In addition to acrylates, nitroalkenes were used as a starting material. 

Stratmann, O. Kaiser, B. Frohlich, R. Meyer, O. Hoppe, D. The configurational stability of an enantioenriched a-thiobenzyllithium derivative and the stereochemical course of its electrophilic substitution reactions synthesis of enantiomerically pure, tertiary benzylic thiols. Chem. Eur. J. 2001, 7, 423 35. 

In an earlier example of the resin-capture-release methodology trifluoracetylation of amines was achieved using polymer-bound benzyl thiol 8. Trifluoroacetic anhydride was employed in the capturing process while addition of amines to the intermediate polymer-bound thiolester released the desired trifluoroacetamide from the resin [21]. 

Aromatic nucleophilic substitution of a benzyl thiol to an aromatic ketone, nitrile or aldehyde followed by addition/elimination results in solely the formation of 2-arylbenzo[6]thiophenes 6 <03TL6665>. 

Plourde [17] has described the radical addition of alkyl, substituted alkyl and benzyl thiols to polymer-supported cychtol allyl ethers. Treatment of immobilized allyl ether 117 with benzyl thiol in the presence of AIBN provided, after base-induced cleavage from the support and purification, sulfide 119 in high yield and purity (Scheme 25). Similar reactions with hydroxyl- and carboxyl-substituted alkyl thiols also resulted in good yields of products as single regioisomers [17]. 

To further investigate the scope and utility of the reaction, Plourde [17] carried out thiol addition to supported aminocychtol 122, formed by reaction of aminocychtol 121 with Wang resin carbonate 120 (Scheme 26). Treatment of 122 with benzyl thiol and AIBN followed by cleavage from support gave the product sulfide 123 in good yield and purity. 

Reactions with Nucleophiles. The epoxide is, by far, the more reactive site and a wide variety of nucleophiles have been used (eq 2) to open the ring at C-3 such as HCl (96%), HOAc (>50%), H2S (65% as cyclized product 3-thietanol), HCN (66%), ethanol (90%), t-butanol (86%), phenyl or benzyl thiol (99% or 93%, respectively), and phenyl selenide (generated in situ from the diselenide and sodium hydroxymethyl sulfite) (>55%). If desired, the epoxide is easily formed from the chlorohydrin by treatment with excess KOH or Et3N. 

Deacetalization, the reverse of acetalization, was similarly promoted by TiCU. The example shown in Eq. (245) [561] illustrates the compatibility of functional groups. Neither demethylation of anisole nor elimination of the benzylic thiol group occurred. Equation (246) shows the regeneration of the diol moiety from an acetal [562]. 

Photochemically aided hydrogenolysis of allylic C-heteioatom bonds has anracted little interest. A few methods for debenzylation of ethers, amines and thiols, catalyzed by irradiation, have been utilized (see previous section also). An unusual desulfurization of benzyl thiol with triethyl phosphite (equation 94) in high yield, catalyzed by UV irradiation, is a useful alternative to other methods described in other parts of this chapter. 

Reacting the cyclic seleninate ester 15 with an excess (three fold) of pentanethiol gave the selenenyl sulfide 104 (Equation 18) <2005JOC9237>. Treating 105 with benzyl thiol provided the selenenyl sulfide 106 via the intermediates depicted in Scheme 5 <2002JA12104>. 

The cyclic seleninate ester 105 exhibited remarkable glutathione peroxidase-like catalytic activity in a model system where fer7-butyl hydroperoxide was reduced with benzyl thiol to afford dibenzyl disulfide and tert-h xf alcohol <2003JA13455>. 

The synthesis of unsymmetrical trisulfides is more difficult than that of the symmetrical analogues owing to their facile disproportionation they are of more interest because of their occurrence in nature and their biological activity, e.g. the natural product (74). One route to this compound is by condensation of benzyl thiol (77) with sulfur dichloride and 2-mercaptoethanol (78) (Scheme 50). 

Another route involves condensation of phthalimide (79) with sulfur monochloride to give N,N -thiobis(phthalimide) (80) which is reacted with benzyl thiol... 

Pracejus and coworkers reported the first Michael addition/enantioselective protonation mediated by cinchona alkaloids [15]. The authors put a special emphasis on the requirement of using chiral P-N,N-dialkylamino alcohol to achieve significant inductions. The addition of benzyl thiol 16 on 2-phthalimidoacrylate 17 catalyzed by 5 mol% of quinidine 3 gave the best selectivity (Scheme 7.10). 

Scheme 7.10 Pracejus s benzyl thiol addition on a-substituted Michael acceptor [15].

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