Esters and Thioesters

In the formate esters, the free energy difference decreases from esters to thioesters and amides for the methyl and tert-butyl groups, and E-methyl formate is only observed in very small amounts ( 0.3%) at low temperature (190 K), as shown by 13C NMR spectroscopy [3], The energy is significantly lower for the bulky tert-butyl moiety relative to the methyl group and this seems to be a function of steric hindrance since ethyl formate and iso-propyl formate have intermediary values [4,5]. In the tert-butyl formate, a strong electronic repulsion accounts for the relatively high proportion of E isomer (10%). 

E and Z isomers of esters can display significantly different properties such as acidity, as observed in the case of methyl acetate the E isomer has been calculated to be more acidic than the Z form [6], and this theoretical result has been related to the unusually low pKa of Meldrum s acid (pKa = 7.3 to be compared to dimethyl malonate pKa = 15.9) [7,8], In contrast, the Z E ratio of methyl thio-noformate (HCOSMe) is 97 3 in acetone (AG° = 1.29 kcal mol-1) in the 177-192 K range, whereas the ratio is 77 29 for cyclopropyl thionoformate in the same conditions (AG° = 0.31 kcal mol-1). The energy difference is even dose to zero (AG° = 0.13 kcal mol-1) in the particular case of phenyl thioformate [9]. 

Steric interactions dramatically increase the free energy difference for acetates and thioacetates. For example, AG° is respectively 9.3 and 4.9 kcal mol-1 for methyl acetate and methyl thioacetate, compared to AG° = 2.1 and 1.3 kcal moT1 for methyl formate and methyl thioformate respectively. In turn, the barrier to rotation remains the same order of magnitude with AGtE z = 12.4 (methyl acetate) and 10.1 kcal mol-1 (methyl thioacetate). 

the Cys988-Gln991 Z-thioester linkage may react with nucleophilic groups (mainly OH and to a lesser extent NH) at cell surfaces and proteins in order to increase internalization [12]. Thioesters also reversibly connect cysteine residues to palmitate [13] and other fatty acids [14] in order to facilitate protein-membrane interactions and protein trafficking. 

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The predominant formation of ann -carboxylic esters and thioesters results when the additives 13 or 14 are used to mediate aldol additions of silylketene acetals derived from propionates and propanethioates37. The enantioselective addition of a-unsubstituted esters or thioesters is also feasible with the borane 1437. 

Hydrazides (RCONHNH2) are highly useful starting materials and intermediates in the synthesis of heterocyclic molecules.2 They can be synthesized by hydrazinolysis of amides, esters and thioesters.3 The reaction of hydrazine with acyl chlorides or anhydrides is also well known,4 but it is complicated by the formation of 1,2-diacylhydrazines, and often requires the use of anhydrous hydrazine which presents a high thermal hazard. Diacylation products predominate when hydrazine reacts with low molecular weight aliphatic acyl chlorides, which makes the reaction impractical for preparatory purposes.5... 

In a comparison of fluorescence spectra between the ester and thioester derivative crystals of PDA, the ester crystal shows a strong emission whereas the thioester crystal fluoresces much more weakly. For example, the intensity of a PDA methyl thioester crystal is about one-thousandth of that of a PDA methyl ester crystal. Furthermore, the fluorescence lifetime of mixed crystals which consist of a large amount of PDA methyl ester and a small amount of the corresponding thioester moiety is much shortened, compared to the lifetime of pure PDA methyl ester crystals. In quenching experiments in solutions of PDA ester, the fluorescence of the PDA ester is dramatically quenched by thioacetate. Similar behaviour has been obtained with several types of diolefin derivatives having a thioester moiety, where crystal structures are isomorphous with the corresponding ester derivatives. 

Derivatives with various substituted sulfonamides have been developed and used to form enolates from esters and thioesters.137 An additional feature of this chiral auxiliary is the ability to select for syn or anti products, depending upon choice of reagents and reaction conditions. The reactions proceed through an acyclic TS, and diastereoselectivity is determined by whether the E- or Z-enolate is formed.138 /-Butyl esters give A-enolates and anti adducts, whereas phenylthiol esters give syn adducts.136... 

Despite the many simple methods for preparation of carboxylic esters and thioesters, in some instances, use of 1-acylbenzotriazoles 915 as O and S acylating agents may be advantageous. For example, easy to prepare salicylic acid derivative 941 reacts with cyclopentanol under microwave irradiation to give 92% yield of cyclopentyl salicylate in 10 min <2006JOC3364>. In another example, L-phenylalanine derivative 942 reacts with benzyl mercaptan... 

Dominant Ri R2 steric control elements are predicted to disfavor transition state T and promote enolization to give the (Z)-geometry, whereas dominant R2 L nonbonded interactions should disfavor transition state C and promote enolization to afford the ( )-enolate geometry. As summarized below in Table 10, under conditions of apparent kinetic control, esters and thioesters afford largely ( > enolates (transition state T ), and the dialkylamides exhibit predominant to exclusive (Z)-enolization (transition state C ). 

A similar aldol reaction is encountered in the Krebs cycle in the reaction of acetyl-CoA and oxaloacetic acid (see Section 15.3). This yields citric acid, and is catalysed by the enzyme citrate synthase. This intermediate provides the alternative terminology for the Krebs cycle, namely the citric acid cycle. The aldol reaction is easily rationalized, with acetyl-CoA providing an enolate anion nucleophile that adds to the carbonyl of oxaloacetic acid. We shall see later that esters and thioesters can also be converted into enolate anions (see Section 10.7). 

Bode and co-workers further extended redox esterification to include carbon-carbon bond breaking of formyl-cyclopropanes [113]. Both esters and thioesters are formed in high yield and good enantioselectivities (Scheme 31). The M-mesityl substituted triazolium salt 191 proved to be the most efficient pre-catalyst providing complete suppression of the benzoin reaction. Electron-deficient substituents, such as phenyl ketone, readily provide ester formation. 

After the first report this isocyanide was not followed up until the studies of Armstrong and co-workers, which signaled the renaissance of 1-cyclohexen-l-yl isocyanide for synthetic purposes. Effectively, the Ugi-4CR adducts 5 obtained from 1 can be cleaved into the corresponding acids, esters, and thioesters 6 upon treatment with acids, alcoholic HC1, and thiols, respectively (Scheme 2.2) [6]. 

Iwata, C. Watanabe, M. Okamoto, S. Fuji-moto, M. Sakae, M. Katsurada, M. Imanishi, T. 3-Acyl-2-(N-cyanoimino)thiazolidines as an acylating agent. Preparation of amides, esters, and thioesters. Heterocydes 1988, 27, 323—326. 

The Preparation of Phosphorus Esters and Thioesters from White Phosphorus... 

CO2-PEG system is also effective for the scandium-catalyzed aldol reactions, and poly(ethylene glycol) dimethyl ether (PEG(OMe)2, MW = 500) is more effective than PEG (Scheme 3.12) [57]. Emulsions in C02-PEG(0Me)2 medium are observed when the concentration of the additive is 1 g/L. Not only benzal-dehyde but also substituted aromatics, aliphatic, and a, /]-unsaturated aldehydes react smoothly, and various silicon enolates derived from a ketones, esters, and thioesters also react well to afford the corresponding aldol adducts in high yields. 

In addition to their direct role in cheese flavor, FFAs also act as precursors for a range of other volatile flavor compounds such as K-methyl ketones (alkan-2-ones), secondary alcohols, hydroxyacids, lactones, esters, and thioesters (Collins et al., 2003a, 2004 McSweeney, 2004). General pathways though which FFAs are catabolised are shown in Figure 8. 

The synthetic utility of azolides is exemplified by many examples of their use in the synthesis of carboxylic acids, esters, and thioesters, amides and thioamides, aldehydes and ketones, and phosphorylated imidazoles and benzimidazoles. 

Esters and thioesters of alcohols require higher temperatures for elimination (Schemes 4.15 and 4.16). This is expected because of the stronger C-0 bond and the lower polarity of C=Z bond. 

Hydroxyls have often been observed to participate in intramolecular cyclization reactions to form lactones from carboxylic acids, esters, and thioesters, especially if lactone is a five- or six-membered ring [21]. 

It was first observed that reactions of imines with ketene silyl acetals proceeded smoothly in the presence of 5 mol % Yb(OTf)3 (a representative lanthanide triflate) to afford the corresponding /3-amino ester derivative in a moderate yield. The yield was improved when Sc(OTf)3, rather than Yb(OTf)3, was used as catalyst (Eq. 3) [10]. Not only silyl enolates derived from esters, but also one derived from a thioester worked well to give the desired /3-amino esters and thioester in high yield. In the reactions of the silyl enolate derived from benzyl propionate, anti adducts were obtained with good selectivity. In addition, the catalyst could be recovered when the reaction was complete, and could be re-used. 

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