Esters cleavage with thiols

See Wallace, O.B. Springer, D.M. Tetrahedron Lett., 1998, 39, 2693 for cleavage of thiol esters to thiols with NaSMe in methanol and Choi, J. Yoon, N.M. Synth. Commun., 1995, 25, 2655 for borohydride exchange resin-Pd(OAc)2 reductive cleavage of thiol esters to thiols. 

Carboxylic acids can also be attached to solid supports as amides, imides, and thiol esters. Illustrative examples of the saponification of such linkers are listed in Table 3.5. Thiol esters are more sensitive towards nucleophilic attack than the corresponding esters, and can be readily saponified. Resin-bound thiol esters have, however, mainly been used for the preparation of amides by nucleophilic cleavage with amines (see Section 3.3.3). 

Hydroxamic acids and hydrazides can also be prepared by nucleophilic cleavage of resin-bound esters, activated amides, or thiol esters [359] with hydroxylamine and... 

Ester cleavage processes have been most frequently investigated in enzyme model studies. Macrocyclic polyethers fitted with side chains bearing thiol groups... 

Reaction of CBT with thiol esters results in their cleavage and the formation of /V-acetylbenzotriazole 132 (77CL1095). Sulfinamides 133 react with CBT in the presence of sodium benzoate to give benzotriazolylsulfin-imides 134 [72JCS(CC)151] (Scheme 128). 

Hydration in the presence of mercury(II) sulphate yields an (oxoalkyl) compound (equation The treatment of the phosphonic ester 364 (R = Et, Z= P03Et2) with a thiolate leads, via diethyl ethynylphosphonate, to the ethenylphosphonic diester 365 with the concomitant formation of thiophosphate ester in this particular case, the product 365 as initially formed, is of Z geometry, but isomerizes when distilled . In other cases of the reactions with thiols, for instance with 364 (R = Et, Z = Cl), the direct replacement of Z is accompanied by overall displacement plus addition at each carbon to give products of types 366 (as a mixture of E and Z stereoisomers) and 367. The same substrate 364 (R = Et, Z = Cl) with the monosodium salt of ethane-1,2-diol represents an alternative route (substitution followed by addition) to 361, but with more basic nucleophiles such as Bu O, and even MeO , cleavage of the phosphorus-carbon bond occurs, although the extent of this decreases, and the extent of addition (with EtO and PhO ) increases, when R = Me is replaced by R = Et. The additions of arylsulphenyl chlorides to 364 (R = Et, Z = Me) occur stereoselectively to give only the E products . 

Succinyl-CoA is a high-energy thiol ester compound with a AG for hydrolysis of about -33-5 kJ (-8 kcal) mol", i.e. of the same order as that required for the synthesis of ATP from ADP. In the course of the cycle, cleavage of the thioester bond is coupled with the phosphorylation of guanosine diphosphate (GDP) and the AG of the overall reaction, which is reversible and is catalysed by succinyl-CoA synthase, is close to zero. 

Sealants obtained by curing polysulfide liquid polymers with aryl bis(nitrile oxides) possess stmctural feature of thiohydroximic acid ester. These materials exhibit poor thermal stability when heated at 60°C they soften within days and liquefy in 3 weeks. Products obtained with excess nitrile oxide degrade faster than those produced with equimolar amounts of reagents. Spectroscopic studies demonstrate that, after an initial rapid addition between nitrile oxide and thiol, a second slower reaction occurs which consumes additional nitrile oxide. Thiohydroximic acid derivatives have been shown to react with nitrile oxides at ambient temperature to form 1,2,4-oxadiazole 4-oxides and alkyl thiol. In the case of a polysulfide sealant, the rupture of a C-S bond to form the thiol involves cleavage of the polymer backbone. Continuation of the process leads to degradation of the sealant. These observations have been supported by thermal analysis studies on the poly sulfide sealants and model polymers (511). 

In the case of La3 + - and Zn2+-catalyzed methanolysis of the phosphorothioate esters the observed / ig values of —0.87 and —0.74 also signify an associative mechanism with some departure of the leaving group, but it is difficult to assign the extent of the bond cleavage since the /ieq value is not known for the phosphoryl transfer between thiol and oxygen nucleophiles. 

Thiol esters RC(0)SR have been prepared by nucleophilic cleavage of polystyrene-bound /V-acylsulfonamides with mixtures of a thiol and sodium thiophenolate [377] or LiBr [378], or by treatment of Wang or PAM resin bound carboxylic esters with ethanethiol in the presence of a Lewis acid (AlMe2Cl or AlMe3, DCM, 20 °C, 3 h [379,380]). The latter method can also give rise to the formation of orthoesters RC(SEt)3 and ketene thioacetals, which can, however, be hydrolyzed to the desired thiol esters by treatment with TFA [379]. 

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