Intramolecular thiol esters

Bruice and Benkovic (1964) and Bruice (1970) have noted that conversion of a bimolecular reaction into an intramolecular reaction corresponds to a reduction in kinetic order. Comparison of reactions of varying kinetic order (Table 5) reveals that a change of 4-5kcalmole in TAS accompanies reduction in order by one. These reactions include 17 displacement reactions on phenyl esters and 4 on thiol esters with an average value of rAS /(kinetic order)... 

A novel route to 2,3-dihydrothiophenes involved a titanocene-promoted carbene formation and subsequenct intramolecular cyclization onto a thiol ester <99SL1029>. Treatment of thioacetal 9 with the low-valent titanium complex 10 gave 2,3-dihydrothiophene 12 by intramolecular olefination of the thiol ester of titanium-carbene intermediate 11. Another metal-mediated cyclization onto the thiophene ring system involved the palladium-catalyzed cyclization of 1,6-diynes <99T485>. For example, treatment of thioether 1,6-diyne 13 with Pdlj in the presence of CO and Oj in methanol followed by treatment with base gave 14. 

The biosynthesis of the polyketide moiety is thought to involve the condensation of coenzyme A esters of acetic acid with malonyl coenzyme A to give thiol esters of 3-keto acids. Further Claisen condensations with malonyl coenzyme A add further ketone units, leading to 3,5-diketo, 3,5,7-triketo acids and so on as their thiol esters. Intramolecular condensations subsequently afford heterocyclic or aromatic structures (Scheme 275). 

R = H or alkyl, the thiolate salts 27 are formed but no elimination takes place because of the low acidity of the hydrogen . Dialkylsulphide elimination from dialkylsulphonium methyl sulphates of -oxocarboxylic acids proceeds readily with aqueous alkali at 0 °C to furnish predominantly high yields of alkynoic esters (equation 86)" . Very recently intramolecular thiol eliminations (i.e. ring openings)... 

Treatment of thiol ester azide 212 with PPhs in anhydrous THF (under reflux) provided thiazoline 213 in good yield (Scheme 84). In situ generation of a phosphinimine by Staudinger reaction of the azide with PPh3 allowed an intramolecular aza-Wittig reaction to take place with the thioester under the neutral and anhydrous conditions <2004PNA12067>. 

Cyclization by way of the aldehyde (22, R = CHO) provides the appropriate ester of the bicyclic nucleus (23), which on deprotection gives an unstable sodium salt. Formation of the [2,3] double bond by this intramolecular Wittig procedure has been widely used for both analogue and natural product synthesis (35). Cyclization is achievable even using a thiol ester such as (24) which leads to the protected olivanic acid MM 22383 [74819-56-0] (25), C28H26N4OiiS (36). Addition of thiols to the double bond of phosphorane-derived derivatives lacking a C-2 substituent (26) has been used for the... 

Possibly, glyoxylase, which catalyses the conversion of j8-keto aldehydes to -hydroxy thiol esters, acts by an analogous sort of intramolecular hydride transfer. 

In the presence of 5-10% palladium catalyst 34,20-45% Nal, and 4-6 equiv K2CO3, various boronic acids underwent cross-coupling with thio esters 32 in dimethylacetamide at 90-95 °C for 12-24 h to give the desired ketones in moderate to high yields. Tetrahydrothiophene, detected by GC/MS, was formed by intramolecular nucleophilic attack at the terminal carbon by a sulfur atom. Interestingly, in the absence of Nal, the bromobutyl thiol ester 32a gave only a trace amount of benzophenone when treated with phenylboronic acid in the presence of 34 in DMA at 95 °C for 22 h. In the presence of Nal, the bromide atom at the terminal carbon is replaced by an iodide atom, leading to sulfonium formation via intramolecular S-alkylative activation. 

Only a trace ofp-tolyl phenyl ketone was formed when the simple thiol ester 35a was treated with phenylboronic acid in the presence of Nal under similar reaction conditions. Although less efficient than the intramolecular system, intermolecular alkylative activation was also feasible. For example, 35b was transformed into undecyl phenyl ketone (48%) when treated with PhB(OH)2 and 1,4-dibromobutane in the presence of 6 mol% of34,30% Nal, and 4.1 equiv of K2CO3 in DMF at 90 °C for 18 h. Use of 1,2-dibromoethane and 1-bromo-hexane in place of 1,4-dibromobutane did not promote this reaction. 

Generation of Acyl Radicals from Thiol Esters by Intramolecular Homolytic Substitution at Sulfur... 

High yield intramolecular acylation reactions at the 2-position of an appropriately substituted furan thiol ester has been used in natural product synthesis. Model cyclization reactions were carried out using mercury(II) trifluoroacetate <90TL1977>. However, in the step shown in Equation (7), which... 

C-Acylation of Active Methylene Compounds. Treatment of an acylimidazole, derived from a carboxylic acid and (1), with the magnesium salt of a malonic or methyhnalonic half thiol ester results in C-acylation under neutral conditions (eq 7)7 The presence of secondary hydroxyl functionality in the carboxylic acid is tolerated, but primary alcohols require protection. Magnesium salts of malonic esters may be used equally effectively. Intramolecular C-acylation of ketones has also been reported. ... 

Sulfurization of tricoordinated phosphorus compounds by treatment with 3H-1,2-benzodithiol-3-one 1,1-dioxide results from the nucleophilic attack of, for example, a phosphite triester on the electrophilic thiosulfonate function of 2 to produce the phos-phonium sulfinate intermediate 3 (eq 2). Intramolecular condensation of the sulfinate anion with the carbonyl group of the activated thiol ester function releases the phosphorothioate triester (4) with concomitant formation of 5. Because of the... 

Generation of Acyl Radicals. The generation of acyl radicals from simple thiol esters, either by photochemical methods or in conjunction with silanes and stannanes, is complicated by low quantum yields and lack of reactivity. This problem was circumvented by the inclusion of an additional propagation step, an intramolecular homolytic substitution (Sh2) of an aryl radical on the sulfur atom of a thiol ester carbonyl group (eq 2), in a radical chain sequence. 

The intramolecular Wittig cyclisation procedure has been used extensively to prepare derivatives related to the olivanic acids, particularly since it was discovered that thiol esters would participate in the ring closure reaction 108). This methodology provided the basis for the total synthesis of ( )-MM 22383 and ( )-7V-acetyldehydrothienamycin 108, 111). 

The corresponding intramolecular carbonyl olefination of thiol esters, S-[3,3-bis(phenylthio)propyl] thioalkanoates, constitutes a practical means of preparing 2,3-dihydrothiophenes (Scheme 4.47) [108]. 

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