Thiol esters conversion

Scheme 68 shows the conversion of the phenoxymethylpenicillin-derived disulfide (see Scheme 10) to penem derivative (91) (78JA8214). Of particular interest in this sequence is the reductive acylation step to afford (89) and the Wittig ring closure to give (90). The rate of the latter reaction was found to be greatly infiuenced by the steric and electronic character of both the thiol ester and the carboxyl blocking group. 

Barrett and coworkers have explored hetero-substituted nitroalkenes in organic synthesis. The Michael addition of nucleophiles to 1-alkoxynitroalkenes or 1-phenylthionitroalkenes followed by oxidative Nef reaction (Section 6.1) using ozone gives a-substituted esters or thiol esters, respectively.41 As an alternative to nucleophilic addition to l-(phenylthio)-nitroalkenes, Jackson and coworkers have used the reaction of nucleophiles with the corresponding epoxides (Scheme 4.4).42 Because the requisite nitroalkenes are readily prepared by the Henry reaction (Chapter 3) of aldehydes with phenylthionitromethane, this process provides a convenient tool for the conversion of aldehydes into ot-substituted esters or 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)... 

R S(Q)CH, R2 — R AC(0)R2The conversion of sulfoxides (2) into thiol esters (5) is possible via the sulfoxide phosphines (3), which rearrange slowly at 0-20° or, more efficiently, in the presence of iodine, to phosphine oxides 4. These can be oxygenated via the a-lithio derivative to thiol esters 5. 

The double bond is saturated. The result of steps 1—4 is the conversion of two acetate groups to a four-carbon acid group in the form of its thiol ester. 

Thiol esters have recently found broad applications in organic synthesis. Two methods for their preparation from acid chlorides and acids are described in the preparation of 2-METHYLPROPANE-2-THIOL ESTERS OF CYCLOHEXANECARBOXYLIC ACID AND CHOLIC ACID. Conversion of the former thiol ester to the corresponding O-t-butyl ester illustrates a general method for the preparation of O-ESTERS FROM THE CORRESPONDING THIOL ESTERS. 

Other methods that can be used to prepare thiol esters from carboxylic acids include the use of aryl thiocyanates,12 thiopyridyl chloroformate,13 2-fIuoro- V-methylpyridinium tosylate,14 1-hydroxybenzotriazole, 5 and boron thiolate.16 Direct conversion of 0-esters to 5-esters can also be effected via aluminum and boron reagents.17 However, the applicability of these 1217 and other more recent methods18 to the selective thiol ester formation discussed above has not been clearly defined. 

Thiol esters have recently been utilized, with and without activation, for the preparation of 0-esters for lactones, in particular, in macrolide syntheses. The accompanying procedure illustrates this conversion.19... 

The azolides are able to participate in a wide variety of nucleophilic olysis reactions which form aldehydes, ketones, carboxylic acids, esters, amides, thiol esters, hydrazides and anhydrides (Scheme 143). In addition, 1-trifluoroacetylimidazole (252) is a convenient reagent for the conversion of aldoximes into nitriles (Scheme 144) (81601579). 

The products of the isoleucine catabolic pathway are propionyl-CoA and ace-tyl-CoA valine catabolism produces one molecule of propionyl-CoA and two molecules of carbon dioxide. Propionyl-CoA is further cataboli25ed to succinyl-CoA, an intermediate of the Krebs cycle (Figure 8.7). This pathway is also used for catabolism of the short-chain fatty acid propionic acid, after its conversion to the thiol ester form by thiokinase. The first step in propionyl-CoA breakdown is catalyzed by propionyl-CoA carboxylase, a biotin-requiring enzyme. The second step is catalyzed by methylmalonyl-CoA mutase, a vitamin Bi2-requiring enzyme. 

The first two stages of catabolism result in the conversion of fats and carbohydrates into acetyl groups that are bonded throi h a thiol ester link to coenzyme A. These acetyl groups now enter the third stage of catabolism— the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs. cycle. The steps of the citric acid cycle are given in Figure 29.6. ... 

Selenol esters are expected to be a more reactive species than the corresponding thiol esters or 0x0 esters due to the comparatively weak bonding between carbon and selenium. The ability of the selenol esters to serve as active acyl transfer agents has been readily demonstrated by the easy conversion of the selenol ester (34 equation 15) to its corresponding acid (35), ester (36) or amide (37). This acyl-selenium bond cleavage has also been promoted by Cu and Cu" salts. - The isopropylidene derivative (38 equation 16) of ribofuranosylacetate has been converted to a lactone (40) in good yield via the selenol ester (39). 

Other phosphorus compounds, e.g. PBrs, mixtures of PBrs and Br or PCI3/CI2 and phenyltetra-chlorophosphorane (PhPCU) have been used to convert amides to imidoyl halides. The formation of imidoyl halides proceeds under mild conditions by action of triphenylphosphine/CCU or triphenylphos-phine dihalides on secondary amides or ketoximes. The work-up procedure can be facilitated by use of polymer-supported triphenylphosphine/CCU. By the action of POCI3, phenyl- or methyl-phos-phonic acid dichloride on aminocarboxylic acid thiol esters in the presence of triethylamine the imidoyl chlorides (205 equation 114) are formed in moderate to good yields. The mechanism of this reaction has not been established. The methylene dialkylchlorophosphorane (206 equation 115) allows the conversion of secondary aromatic amides to imidoyl chlorides under very mild conditions. ... 

Scheme 28, by application of the known thiol ester-thiopyrone phototransformation to selenium-containing systems. 5/f-[l]Benzoselenino[2,3-6]-pyridine, 4.ff-selenolo[2,3-6][l]benzoselenine, and 9/f-seleno[3,2-6][l]benzo-selenine have similarly been obtained by the corresponding selenol ester-seleninone conversion. Phenyl areneselenosulphonates undergo facile photo-induced homolysis of the selenium-sulphur bond in the presence of alkenes, a free-radical chain reaction leads to the formation of -phenylselenosulphones. ... 

In all the acetyl coenzyme-A-utilising enzymes which catalyse Claisen-type condensations the reaction involves the conversion of the acetyl methyl into a methylene group. A simple example illustrates the use of thiol esters both as carbanion-stabilis-ing systems and as readily hydrolysable esters. The conversion of glyoxalate to malate uses acetyl coenzyme. A probable mechanism is outlined below ... 

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

In 1960, it was reported that reacting thiols, disulfides, and sulfides with carbon monoxide gave thiol esters in the presence of Co2(CO)8 or metal oxide catalysts at 250-300 °C and under 100-1000 atm, as shown in Eqs. 1 to 3 [2]. Both aliphatic and aromatic thiols undergo carbonylation to give thiol esters in yields up to 46% with conversions up to 73%. No reaction took place between carbon monoxide and benzenethiol at 70 °C in the presence of Co2(CO)8, nor at 275 °C without the catalyst. Reaction conditions for carbonylation of disulfides and sulfides were similar to those used for thiols, but yields were low (up to 30%). 

Selenol esters are more reactive than thiol esters and are useful as acyl-transfer reagents as shown by the conversion of 2 into an acid, an ester, and an amide. 

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