Enolate compounds reactions

Bravo et al. studied the reaction of various ylides with monooximes of biacetyl and benzil. Dimethylsulfonium methylide and triphenylarsonium methylide gave 2-isoxazolin-5-ol and isoxazoles, with the former being the major product. Triphenylphosphonium methylide and dimethyloxosulfonium methylide gave open-chain products (Scheme 135) (70TL3223, 72G395). The cycloaddition of benzonitrile oxide to enolic compounds produced 5-ethers which could be cleaved or dehydrated (Scheme 136) (70CJC467, 72NKK1452). 

In general bromination of 20-ketones is directed to the introduction of functionality at C-21. However, on occasion 17-bromo compounds are required for dehydrobromination to A -20-ketones, although these are generally obtained in other ways. Kinetic enolization of a 20-ketone gives the A °-enol, whereas the thermodynamic product is the A kjsomer. An interesting enolate trapping reaction has been used recently to prepare 16-methyl-A -20-ketones ... 

Suggestions as to the methods for identifying the above classes of compounds will be found under Class Reactions in Section XI,7. Some further remarks upon enolic compounds (see Table IV,114A) may be made here. Enols may be divided into (o) p-keto esters and (6) 1 3-diketones. With 5 per cent, sodium hydroxide solution, a p-keto ester yields the salt of the corresponding acid, which when heated with dilute hydrochloric acid is decarboxylated to a ketone ... 

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

There are also reactions in which electrophilic radicals react with relatively nucleophilic alkenes. These reactions are represented by a group of procedures in which a radical intermediate is formed by oxidation of the enol of a readily enolized compound. This reaction was initially developed for /i-kctoacids.227 The method has been extended to /1-diketones, malonic acids, and cyanoacetic acid.228... 

The acyclic, enolic compounds 7 and 9 may exist in either cis or trans forms. Methyl ethers of 7 have been isolated in the cis form,8 but it is not known whether the trans forms, which must be acyclic, exist. The relative proportion of isomers is controlled by the geometry of the parent sugar enediol. Although the acyclic forms are readily interconvertible tautomers, it appears that, in acidic medium, further reaction occurs much more rapidly than any equilibrating reactions. Compound 7 undergoes rapid elimination of a second hydroxyl group to give 11. This acyclic product, also, may exist as either a cis or a trans isomer, both forms of which have been isolated.8 The loss of a third molecule of water per molecule occurs after, or simultaneously with, the cyclization of 11 (see Section II, 3 p. 171), and results in formation of 5-(hydroxymethyl)-2-furaldehyde (5). 

Several reactions of carbonyl compounds that have one or more a hydrogens proceed through the enol form. Reaction of ketones with chlorine, bromine, and iodine result in substitution of halogen for a hydrogen rates are typically first-order in ketone and independent of halogen concentration and even of which halogen is used. Racemization of ketones with asymmetric centers adjacent to the... 

By way of Mannich reaction (step 1) and /1-elimination (step 2), the transformations shown in Figures 12.14 and 12.15 demonstrate how an aldol condensation (for the term see Section 13.4.1) can be conducted under acidic conditions as well. Both the enamine reaction in Figure 12.18 and the enol ether reaction in Figure 12.23 illustrate the same thing differently. Many aldol condensations, however, start from carbonyl compounds only and proceed under basic conditions. They follow a totally different mechanism (Section 13.4.1). 

Aldehydes, ketones, carboxylic esters, carboxylic amides, imines and N,A-disubstiluted hydrazones react as electrophiles at their s/ 2-hybridized carbon atoms. These compounds also become nucleophiles, if they contain an H atom in the a-position relative to their C=0 or C=N bonds. This is because they can undergo tautomerization to the corresponding enol as seen in Chapter 12. They are also C,H-acidic at this position, i.e., the H atom in the a-position can be removed with a base (Figure 13.1). The deprotonation forms the conjugate bases of these substrates, which are called enolates. The conjugate bases of imines and hydrazones are called aza enolates. The reactions discussed in this chapter all proceed via enolates. 

Silyl enol ethers, Reaction of carbonyl compounds with in situ generated BrSi(CH3)3 and triethylamine results mainly in the thermodynamic silyl ether, usually the (Z)-isomer. 

Treatment of silyl enolates with methyllithium followed by an addition of gallium trichloride affords the corresponding gallium enolates. The reaction of the resulting gallium enolates with a-halo carbonyl compounds in the presence of triethylborane provides 1,4-dicarbonyl compounds in good yields (Scheme 142).433... 

The substrate arachidonic aeid, whieh often leads to formation of inflammatory prostaglandins, is stored in tissues as one of a number of phospholipids these compounds, as the name indicates, comprise complex phosphate-containing esters. The antiinflammatory corticosteroids inhibit the action of the enzyme, phospholipase A2, that frees arachidonic acid. The many undesired effects of those steroids has led to the search for non-steroidal inhibitors of that enzyme. A highly substituted indole derivative has shown good activity as a phospholipase A2 inhibitor. Alkylation of the anion from treatment of indole (32) with benzyl chloride affords the corresponding A-benzylated derivative (33). The methyl ether at the 4 position is then cleaved by means of boron tribromide to yield 34. Alkylation of the enolate from reaction of the phenol with sodium hydride with tert-butylbromoacetate affords the corresponding... 

Henderson and coworkers studied the reaction of MesAl with a series of aromatic ketones (25, 27, 29) to yield the precipitation of either dimethylaluminum enolates or alkoxides (see equations 9-11). In situ H NMR spectroscopic studies of the reaction between MesAl and acetophenone (29) revealed a complex mixture of products, whereas under the same conditions 2,4,6-trimethylacetophenone (25) reacts cleanly to give the corresponding enolate. The enolate compounds 26 and 28 were isolated and 26 as well as the representative alkoxide 30 were characterized by X-ray crystallography. Both 26 and 30 form dimers with a central AI2O2 core. Ab initio calculations at the HF/6-31G level indicated that both 26 and 30 are the thermodynamic products of the reactions. Equation 12 shows the alkylation and enolization reactions for the ketones 25 and 29 and... 

In modern organic chemistry, silyl enol ethers, as well as the corresponding titanium, tin, boron, or zirconium derivatives, are widely employed as nucleophilic components in enolate alkylation reactions. Their usefulness prompted the elaboration of numerous methods for the selective production of isomeri-cally pure enol ethers from almost any type of carbonyl compounds. 

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