Thioesters from esters

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... 

The thioester hypothesis can be summed up as follows the formation of thiols was possible, for example, in volcanic environments (either above ground or submarine). Carboxylic acids and their derivatives were either formed in abiotic syntheses or arrived on Earth from outer space. The carboxylic acids reacted under favourable conditions with thiols (i.e., Fe redox processes due to the sun s influence, at optimal temperatures and pH values) to give energy-rich thioesters, from which polymers were formed these in turn (in part) formed membranes. Some of the thioesters then reacted with inorganic phosphate (Pi) to give diphosphate (PPi). Transphosphorylations led to various phosphate esters. AMP and other nucleoside monophosphates reacted with diphosphate to give the nucleoside triphosphates, and thus the RNA world (de Duve, 1998). In contrast to Gilbert s RNA world, the de Duve model represents an RNA world which was either supported by the thioester world, or even only made possible by it. 

Silicon enolates derived from ketones, thioesters, and esters reacted smoothly with different types of aldehyde in the presence of 5mol.% Sc(OTf)3 to afford the aldol adducts in high yields. 

Further investigation with various silyl ketene acetals is summarized in Table 6. Silyl ketene acetals derived from various esters were reacted with /V-benzyloxy-carbonylamino sulfones 1 in the presence of 0.5-1 mol% Bi(0Tf)3-4H20. The corresponding (3-amino esters 24 were obtained in moderate to good yields (Table 6). Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. The /V - be n z v I o x v c ar bo n v I a m i n o sulfone derived from n-butvraldehyde lp led to moderate yields of (3-amino esters when reacted with (thio)acetate-derived silyl ketene acetals (Table 6, entries 1 and 2). A very good yield was obtained when the same sulfone was subjected to a tetrasubstituted silyl ketene acetal (Table 6, entry 3). The latter afforded moderate to good yields of (3-amino esters 24 with phenylacetaldehyde, / -tolu aldehyde, and o-tolualdehyde-derived sulfones (Table 6, entries 4-6). 

Table 13 Mannich-type reaction with silyl ketene acetals derived from esters or thioesters...

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

In Yb(OTf)3-catalyzed Mannich-type reaction of the imine with silicon enolate conducted in SCCO2, the desired product is obtained in only 10 % yield after 3 h due to the low solubility of reactants in scC02 (Scheme 3.11, R1, R2, R3, R4, Rs=Ph, Bn, Me, Me, OMe) [57]. Addition of PEG is found to improve the yield to 72 %. The formation of emulsions can be observed in the presence of PEG. The highest yield (72 %) can be reached at 15 MPa CO2 pressure using PEG400 (MW = 400). This system has been applicable to various substrates including imines derived from aromatic and heterocyclic as well as aliphatic aldehydes and silicon enolates derived from esters, thioesters, and a ketone as depicted in Scheme 3.11. 

Various substrates have been successfully used in the present LASC-catalysed aldol reaction. Aromatic as well as aliphatic, a, 3-unsaturated and heterocyclic aldehydes worked well. As for silicon enolates, silyl enol ethers derived from ketones as well as ketene silyl acetals derived from thioesters and esters reacted well to give the corresponding adducts in high yields. It is noted that highly water-sensitive ketene silyl acetals reacted smoothly in water under these conditions. 

Several examples of Sc(OTf)3-catalyzed aldol reactions of silyl enolates with aldehydes were been examined. Silyl enolates derived from ketones, thioesters, and esters reacted smoothly with different types of aldehyde in the presence of 5 mol % Sc(OTf)3 to afford the aldol adducts in high yields. Sc(OTf)3 was also found to be an effective catalyst in aldol-type reactions of silyl enolates with acetals. The reactions proceeded smoothly at -78 °C or room temperature to give the corresponding aldol-typc adducts in high )delds without side-reaction products. It should be noted that aldehydes were more reactive than acetals. For example, while 3-phenylpropionalde-hyde reacted with the ketene silyl acetal of methyl isobutyrate at -78 °C to give the aldol adduct in 80 % yield, no aldol-type adduct was obtained at -78 °C in the reaction of the same ketene silyl acetal with 3-phenylpropionaldehyde dimethyl acetal. The acetal reacted with the ketene silyl acetal at 0 °C to room temperature to give the... 

Michael reactions of silyl enolates or ketene silyl acetals with a, -unsaturated carbonyl compounds are among the most important carbon-carbon bond-forming processes in organic synthesis. Sc(OTf)3 was found to be effective [4], and the reactions proceeded smoothly in the presence of a catalytic amount of Sc(OTf)3, under extremely mild conditions, to give the corresponding 1,5-dicarbonyl compounds in high yields after acid work-up (Eq. 2). Silyl enolates derived from ketones, thioesters, and esters were applicable, and no 1,2-addition products were obtained. The products could, furthermore, be isolated as synthetically valuable silyl enol ethers (I) when acid-free work-up was performed. The catalyst could be recovered almost quantitatively and could be re-used. 

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. 

Various types of silyl nucleophiles derived from esters, thioesters, and ketones were employed. In a few cases, moderate stereoselectivity was observed. 

A small number of hemiterpenes are used in perfumery, the most important of which are prenyl acetate and benzoate. Thioesters, such as those shown in Scheme 4.11, have extremely intense green odours reminiscent of galbanum, in which they occur naturally. The esters are usually prepared from prenyl chloride and the thioesters from the corresponding thiol and acid chloride. 

With esters there is yet another variable that may be used - the nature of the esterifying alcohol. In fact, we saw the enolates resulting from esters 61 and 64 earlier in the chapter when we were discussing the transition states. The ester may have a hindered aromatic component16 61 or be a thioester 64 instead of an ester. 

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%). 

The discovery of the Lewis acid-mediated addition of enol silanes to aldehydes and acetals by Mukaiyama and coworkers pioneered a novel approach to the construction of molecules via the crossed aldol reaction (Eq. 1) [6a6bj. Importantly, this development proved to be a key lead for the subsequent evolution of this C-C bond forming reaction into a catalytic Si atom-transfer process. Typical enol silanes derived from esters, thioesters, and ketones are unreactive towards aldehydes at ambient temperatures. However, stoichiometric quantities of Lewis acids such as TiCl4, SnCl4, AlClj, BClj, BF3-OEt2, and ZnCl2 were found to pro-... 

In every case, b-amino esters were obtained in high yields. Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. 

For the preparation of amides, peptides, thioesters and esters in either aqueous or anhydrous solutions in about 2 hours. The following scheme, p. 169, from Lowe and Dean, Affinity Chromatography, J. Wiley Sons, 1974, illustrates the reaction sequence for carbodiimides in general. 

The enolates of other carbonyl compounds can be used in mixed aldol condensations. Extensive use has been made of the enolates of esters, thioesters, and amides. Of particular importance are several modified amides, such as those derived from oxazolidinones, that can be used as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, tin, and titanium derivatives have all been used. Because of their usefulness in aldol additions and other synthetic methods (see especially Section 6.4.2.3, Part B), there has been a good deal of interest in the factors that control the stereoselectivity of enolate formation from esters. For simple esters such as ethyl propanoate, the E-enolate is preferred under kinetic conditions using a strong base such as EDA in THE solution. Inclusion of a... 

Figure 737 Erythromycin C-labehng pattern from the incorporation of [ 1 - CJpropionate, [2- C] propionate, [3- C] propionate, and C- and H-labeling patterns by incorporation of the At-acetylcysteamine thioesters (SNAC esters) 142 and 143.

Substitution on nitrogen of cyclopropyl alkylamines and cyclobutylamines takes an unexceptional course, as does the formation of esters and thioesters from... 

In addition, reductive elimination of palladium and nickel complexes to form esters (Equations 8.67 and 8.68), amides, and tiiioesters has been reported. -" The reductive eliminations of esters and amides were observed during mechanistic studies on the palladium-catalyzed formation of esters and amides from aryl halides, carbon monoxide, and alcohols or amines. This catalytic process is presented in Qiapter 17 (carbonylation processes). The reductive elimination of thioesters from nickel complexes were studied, in part, to understand the C-S bond-forming process of acetyl coenzyme A synthase. Prior to this work, an iron-mediated synthesis of p-lactams had been reported that appears to occur by reductive elimination to form the amide C-N bond of the lactam. ... 

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