Enol substrates

In 1989, Rebek and co-workers reported a simple system based on Kemp s triacid that served as a mimic of an enolizing enzyme [86]. This early mimic, however, had the enolizing substrate covalently attached to the triacid skeleton. In addition, the mimic did not possess any oxyanion hole functionalities. However, 2 years later the Rebek group reported a true enolizing catalyst that hosted a carboxylic acid as the oxyanion hole component (Scheme 4.8) [87]. The rate of enolization of the quinuclidone substrate was enhanced by a factor of 10 in the presence of 2.5 mM of the receptor (R = n-Pr). 

Enantiotopos discrimination, 93, 128, 142, 234, 235, 331 Ene reactions asymmetric, 223 binaphthol, 222 chiral metal complexes, 222 intramolecular, 226 methyl glyoxylate, 290 Enol silyl ether substrates, 128, 228, 230 Enol substrates, 28 Enolates ... 

O- and C-Phenylation. The reagent can be used to effect either O- or C-phenylation of enolic substrates, depending on conditions. O-Phenylation is favored under neutral conditions under strongly basic conditions, C-phenylation is favored. Addition of Cl3CCOOH significantly improves yields of phenyl ethersr1 Example ... 

The leaving group had no significative influence on the reaction time as shown in Scheme 54. In all cases, only the (Z)-vinylic tellurides 86a and 89 were obtained starting from mixtures of the enolic substrates 84, 87, 91-94 (Scheme 54).170... 

In this latter structure, roughly depicted as (154), there are two different lithium atoms as well as two different anion residues. In one of the residues a lithium is -coordinated and in the other residue the lithium is T) -coordinated. Hie possible origins of the selectivity of the alkylations of the metallated hydiazones are discussed relative to this structure. Hie lithiated hydrazone enolate (155) prepared from (S)-(-)-l-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazone of 2-acetylnaphthalene (156) yields the monomeric bis-THF-solvated species (157) as ruby red crystals. Hiis is one of the few examples of the crystallization of a resolved enolate substrate. ... 

Alkylations.1 Pentaethoxyphosphorane is a powerful ethylating agent no acidic or basic catalyst is required, and no acids or bases are generated. It converts acids quantitatively into ethyl esters phenols into ethyl phenolates enolic substrates into enol ethers. Diethyl malonate reacts slowly to give diethyl ethylmalonate in 88% yield. 

Interest centers on the extent to which the reported crystal structures of individual glycosylascs (a) arc able to identify an active-site residue which, by nature and spatial disposition, might serve to protonate a bound enolic substrate or wrong glycosyl fluoride anomer and (b) are able to identify protein structural features that, could dictate the direction of approach of acceptor cosubstratcs to the reaction center. 

Calculations for the case of fluorination suggest that the reaction of the coordinated enolate substrate involves a single electron transfer (SET) process. Given the... 

Citrate synthase catalyzes the metabolically important formation of citrate from ace-tyl-CoA and oxaloacetate [68]. Asp-375 (numbering for pig CS) has been shown to be the base for the rate-limiting deprotonation of acetyl-CoA (Fig. 5) [69]. An intennediate (which subsequently attacks the second substrate, oxaloacetate) is believed to be formed in this step the intermediate is thought to be stabilized by a hydrogen bond with His-274. It is uncertain from the experimental data whether this intermediate is the enolate or enol of acetyl-CoA related questions arise in several similar enzymatic reactions such as that catalyzed by triosephosphate isomerase. From the relative pK values of Asp-375... 

Figure 5 A suggested mechanism for the enolization of acetyl-CoA by the enzyme citrate synthase (CS). The keto, enolate, and enol forms of the substrate are shown.

Addition of hydride ion from the catalyst gives the adsorbed dianion (15). The reaction is completed and product stereochemistry determined by protonation of these species from the solution prior to or concurrent with desorption. With the heteroannular enolate, (13a), both cis and trans adsorption can occur with nearly equal facility. When an angular methyl group is present trans adsorption (14b) predominates. Protonation of the latter species from the solution gives the cis product. Since the heteroannular enolate is formed by the reaction of A" -3-keto steroids with strong base " this mechanism satisfactorily accounts for the almost exclusive formation of the isomer on hydrogenation of these steroids in basic media. The optimum concentration of hydroxide ion in this reaction is about two to three times that of the substrate. 

The use of A -enol ethers as substrates for dehydrogenation is often attractive. Aqueous acetone at room temperature gives yields ranging from 70 to 88% other systems with acid catalysis have also been used, e.g. ... 

The most satisfactory use of manganese dioxide for double bond introduction employs enol ethers as substrates ... 

The enamines, enol ethers and enol acetates of A -3-keto steroids provide important substrates for fluorination with FCIO3. Reaction of such A -enol ethers and acetates (6) with perchloryl fluoride results in 6a- and 6jff-fluoro-A -3-ketones (7) and (8), the latter representing the more abundant isomer. Tetrahydrofuran or dioxane-water mixtures appear to be particu-... 

Trimelhylsilyl enol ethers are effective substrates in fluorination with fluo-roxytrifluoromethanefor the preparation of a-fluoro esters, amides and aldehydes [J7] (equations 13-15)... 

For some condensations with silylated substrates as starting compounds, trimethylsilyl inflate can be used as a catalyst [103, 104, 105] Atypical example of such a reaction is the aldol type condensation of silyl enol ethers and acetals catalyzed by 1-5 mol% of trimethylsilyl inflate [103] (equation 53)... 

FITS reagents), has undergone considerable development recently [141,142,143, 144, 14S. These compounds, available fromperfluoroalkyhodides (equation 76), are very effective electrophilicperfluoroalkylating agents They react with carban-lons, aromatic compounds, alkenes, alkynes, silyl enol ethers, and other nucleophiles under mild conditions to introduce the perfluoroalkyl moiety mto organic substrates (equation 77) (see the section on alkylation, page 446). 

FIGURE 19.13 (a) A mechanism for the fructose-l,6-bisphosphate aldolase reaction. The Schlff base formed between the substrate carbonyl and an active-site lysine acts as an electron sink, Increasing the acidity of the /3-hydroxyl group and facilitating cleavage as shown. (B) In class II aldolases, an active-site Zn stabilizes the enolate Intermediate, leading to polarization of the substrate carbonyl group. 

In recent years, several modifications of the Darzens condensation have been reported. Similar to the aldol reaction, the majority of the work reported has been directed toward diastereo- and enantioselective processes. In fact, when the aldol reaction is highly stereoselective, or when the aldol product can be isolated, useful quantities of the required glycidic ester can be obtained. Recent reports have demonstrated that diastereomeric enolate components can provide stereoselectivity in the reaction examples include the camphor-derived substrate 26, in situ generated a-bromo-A -... 

The first asymmetric Mn(salen)-catalyzed epoxidation of silyl enol ethers was carried out by Reddy and Thornton in 1992. Results from the epoxidation of various silyl enol ethers gave the corresponding keto-alcohols in up to 62% ee Subsequently, Adam and Katsuki " independently optimized the protocol for these substrates yielding products in excellent enantioselectivity. 

Ironically, auxiliary-induced control via the alkene failed to generate synthetically useful selectivities, but direct substrate-induced control did. In particular, chiral silyl enol ethers with stereocenters in the y-position allowed the synthesis of enantiomerically... 

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