Ketones, enol, reaction with

The radicals that are formed from the enolate in this process are rapidly destroyed so that only the stable semidione species remains detectable for EPR study. Semidiones can also be generated oxidatively from ketones by reaction with oxygen in the presence of base. The diketone is presumably generated oxidatively and then reduced to the semidione via reduction by the enolate derived from the original ketone. 

Enol acetates are readily prepared from saturated ketones by reaction with acetic anhydride alone or diluted, in the presence of acetyl chloride ... 

Titanium enolates can be prepared from lithium enolates by reaction withatrialkoxy-titanium(IV)chloride,suchasfra-(isopropoxy)titaniumchloride.21 Titanium enolates are usually prepared directly from ketones by reaction with TiCl4 and a tertiary amine.22 Under these conditions, the Z-enolate is formed and the aldol adducts have syn stereochemistry. The addition step proceeds through a cyclic TS assembled around titanium. 

As was pointed out in Part A, Section 7.3, under many conditions halogenation is faster than enolization. When this is true, the position of substitution in unsymmetrical ketones is governed by the relative rates of formation of the isomeric enols. In general, mixtures are formed with unsymmetrical ketones. The presence of a halogen substituent decreases the rate of acid-catalyzed enolization and therefore retards the introduction of a second halogen at the same site. Monohalogenation can therefore usually be carried out satisfactorily. A preparatively useful procedure for monohalogenation of ketones involves reaction with cupric chloride or cupric bromide.81 82 83 84 85 86... 

Cleavage of enol estersEnol esters arc converted to oximes of the corresponding ketone by reaction with excess hydroxylamine in THF or pyridine. 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

Enol acetates are readily prepared from saturated ketones by reaction with acetic anhydride alone or diluted, in the presence of acetyl chloride179 or with catalysts such as p-toluenesulfonic acid,129 perchloric acid,12 etc. Alternatively, 3-enol acetates can be prepared by acid-catalyzed exchange enol... 

Benzofuran-3(2/f)-ones (396) exist in the keto form but undergo ready enolization. Acetylation with acetic anhydride and sodium acetate affords 3-acetoxybenzo[6]furans, but reaction under acidic conditions usually supplies these products admixed with 3-acetoxy-2-acetylbenzo[6]furans. Alkylation usually furnishes a mixture of O- and C-alkylated products. 3-Acetoxy-6-methoxy-4-methylbenzo[6]furan, on Vilsmeier reaction, supplies the 3-chlorobenzo[6]furan-2-carbaldehyde, the product expected from an enolizable ketone (72AJC545). Benzofuran-3(2//)-ones react normally with carbonyl reagents. Grignard reagents react in the expected way and dehydration of the intermediate affords a 3-substituted benzo[6]furan. The methylene group is reactive so that self condensation, condensation with aldehydes and ketones and reaction with Michael acceptors all occur readily. 

Buchwald has designed a hindered dialkylphosphino-binaphthyl ligand (3) that is much more active than the original ligand for asymmetric arylation of ketone enolates. Reactions occur at room temperature using only 2 mol % catalyst with enantioselectivities up to 94% [41]. Additionally, the Buchwald group has developed an electron-rich monodentate ligand (4) capable of vinylation of ketone enolates with up to 92% ee [42]. 

Ketone dilithio a,ft-dianion species (74) have been generated by the tin-lithium exchange reaction of the lithium enolate of /3-tributyltin-substituted ketones.291 Reaction with carbon electrophiles gives substituted ketones. 

Oxalic esters (for electronic reasons) and formic esters (because of their low steric hindrance) are reactive esters that can acylate ketone enolates formed with NaOR in equilibrium reactions. Formic esters acylate ketones to provide formyl ketones (for example, see Figure 13.61). It should be noted that under the reaction conditions the conjugate base of the active-methylene formyl ketone is formed. The neutral formyl ketone is regenerated upon acidic workup. 

Enantioselective protonation. (R)- and (S)-a-Damascone (4) have been prepared by a Grignard reaction followed by enantioselective protonation with l1 and 2,3 both available from (-)- or (+ )-ephedrine. Thus protonation of the ketone enolate 3 with (+ )-l or (- )-2 furnishes (S)- or (R)-a-damascone (4), respectively. 

The dark reaction of pinacolone enolate ion and Phi in DMSO was described167. The same reaction is stimulated by light and inhibited by radical scavengers. This system was used to study the reactivity of different ketone enolate ions with Phi. In competition experiments, the following reactivity order was determined 2-acetylcyclohexanone (unreactive) < phenylacetone (0.39) < cyclohexanone (0.67) < pinacolone (1.00) < acetone (1.09) < 2-butanone (1.10) < 3-pentanone (1.40)168. 

The photostimulated reaction of ketone enolate ions with 6-iodo-9-ethylpurine (129) in liquid ammonia leads to the substitution product 130 as a mixture of the keto and enol... 

The formation of the bicyclic intermediate, VII/157, (Scheme VII/31) was achieved by nucleophilic conjugate addition of tributyltinlithium to cyclohexe-none, reaction of the intermediate ketone enolate ion with a small excess of ethyl vinyl ketone and, subsequently, with a large excess of formaldehyde. The mechanism is analogous to that presented in Scheme VII/9 of Chapter VII. 1. 

The enolate is stable to further reduction, and protonation during the work-up will give a ketone.] But reaction with an alkyl halide is more fruitful because the enolate forms only where the double] bond of the enone was, regioselective alkylation becomes possible. 

Enolates may be converted directly into a-hydroxy-ketones by reaction with the molybdenum peroxide complex MoOs,py,HMPA. The 17-ketone (188), transformed into its enolate with lithium di-isopropylamide at —70°C, gives the 16a-hydroxy-17-ketone (189) in 75% yield.172 Carbonyl transposition to the vicinal position can be effected in high yield by a new five-step process.173 A 17-oxo-steroid (188) was transformed into the 16-ketone (193) via the phenylthioketone (190) and the 16-phenylthio-16-ene (192) by the route illustrated in Scheme 5. 

An interesting synthesis of silyl enol ethers involves chain extension of an aldehyde. Aldehydes are converted to the silyl enol ether of a ketone upon reaction with lithium (trimethylsilyl)diazomethane and then a drrhodium catalyst. Initial reaction of lithium(trimethylsilyl)diazomethane [LTMSD, prepared in situ by reaction of butyllithium with (trimethylsilyl)diazomethane] to the aldehyde (e.g., 37) gave the alkoxide addition product. Protonation, and then capture by a transition-metal catalyst, and a 1,2-hydride migration gave the silyl enol ether, 38. 

Condensation with ketones. The aminals serve as synthetic equivalent of trifluoroacetaldehyde. Thus, its condensation with ketones (catalyzed by aqueous HCl) gives 2-(l-hydroxy-2,2,2-trifluoroethyl) ketones and reaction with silyl enol ethers I catalyzed by ZnCl ) delivers the trifluoroethylidene ketones. 

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