Ketone into an enolate

A mixture of an acid anhydride and a ketone is saturated with boron trifluoride this is followed by treatment with aqueous sodium acetate. The quantity of boron trifluoride absorbed usually amounts to 100 mol per cent, (based on total mola of ketone and anhydride). Catalytic amounts of the reagent do not give satisfactory results. This is in line with the observation that the p diketone is produced in the reaction mixture as the boron difluoride complex, some of which have been isolated. A reasonable mechanism of the reaction postulates the conversion of the anhydride into a carbonium ion, such as (I) the ketone into an enol type of complex, such as (II) followed by condensation of (I) and (II) to yield the boron difluoride complex of the p diketone (III) ... 

An activating group could be put at the nucleophilic site (27) but that leaves no proton, so the double bond must be moved (28). The anion (28) is starting to look like a Birch reduction product (Chapter 36) and the conversion of the ketone into an enol ether (29) completes the design. Reagent (29) would be derived from a salicylate (30) and the regiochemistry of the reduction is correct (Chapter 36). 

In the dehydration the ketone is first converted into an enol by protonation and deprotonation. Protonation of the alcohol O is then followed by an El elimination reaction (loss of H2O and then loss of H+) to give the product. It s not absolutely necessary to convert the ketone into an enol before executing El elimination, but the intermediate carbocation is much lower in energy when the ketone is in the enol form. 

Sodium hydride or LDA will irreversibly and completely convert an aldehyde or ketone into an enolate. 

We saw that, by definition, tautomers wiU differ in the position of one proton. So, the conversion of a ketone into an enol requires two steps 1) introduce a proton, and 2) remove a proton ... 

Now let s think about what kind of base we would need to make an enolate. If we use bases such as HO" or RO" (bases with a negative charge on oxygen), we find that these bases are not strong enough to completely convert the ketone into an enolate. Rather, an equilibrium is established between the ketone, the enolate, and the enol. This equilibrium only produces very small amounts of the enolate, but that doesn t matter. Once an enolate reacts with an electrophile, the equilibrium produces more enolate to replenish the supply. Over time, all of the ketone can convert into the enolate and then react with some electrophile. This is very similar to the situation we saw with enols. Once again, we are relying on the equilibrium to continuously produce more of the enolate. The major difference here is that enolates are so much more reactive than enols. Therefore, the chemistry of enolates is more robust than the chemistry of enols. 

The Simmons-Smith cyclopropanation method has also found application for the a-methylation of ketones via an intermediate cyclopropane. The starting ketone—e.g. cyclohexanone 9—is first converted into an enol ether 10. Cyclopropanation of 10 leads to an alkoxynorcarane 11, which on regioselective hydrolytic cleavage of the three-membered ring leads to the semiketal 12 as intermediate, and finally yields the a-methylated ketone 13 ... 

Unless a proton donor is added, the lithium-ammonia reduction of an cnone leads to the lithium enolate and lithium amide. The latter is a sufficiently strong base to rapidly convert the mono-alkylated ketone into its enolate, which can be further alkylated. The function of the... 

The conversion of an a, -unsaturated aldehyde or ketone into an allylic acetal or ketal, followed by SN2 -type attack of a nucleophile, leads, after hydrolysis of an initially formed enol ether, to a fi-sub-stituted carbonyl compound. The overall sequence (Scheme 23) is equivalent to a direct conjugate addition, but has the advantage that it allows the temporary introduction of a chiral auxiliary group if a chiral (C2-symmetric) diol is used in the acetalization step, die subsequent nucleophilic addition leads to a mix-... 

The Robinson annulation consists of a Michael addition, an aldol reaction, and a dehydration. In the Michael addition the nucleophilic ketone is converted into an enol by protonation and deprotonation. The enol then adds to the protonated Michael acceptor. Deprotonation of the positively charged O, protonation of C of the enol, and deprotonation of O then give the overall Michael addition product. 

Gent-dichlorides can be obtained from ketones that are not capable of conversion into an enol form by using phosgene in the presence of an organic phosphorus compound [316], For example, PhjC=0 was converted into PhjCClj in the presence of one of a wide variety of phosphine or phosphine oxide catalysts between 100 and 190 C. Further, PhC(0)C(0)Ph, when treated with COClj in the presence of PPhjO at 130-140 C, resulted in the conversion of one of the CO groups into a CClj moiety. PhC(0)-4-C 4C(0)Ph reacted in the... 

Opening to the -rr-allyl complex 9.214, which was reduced by hydride transfer from formate. Unlike most other nucleophiles (see Schemes 9.32 and 9.34), formate transfers hydrogen with retention, giving the required stereochemistry for the natural product. Completion of the synthesis included a nickel-catalysed Kumada coupling to convert the ketone, via an enol phosphate 9.216, into a methyl group and a McMurry reaction to close the seven-membered ring. 

The mechanism for conversion of a ketone into an enamine was discussed in Section 20.6. To see the similarity between an enolate and an enamine, compare the resonance structures of an enolate with the resonance structures of an enamine. 

Instead of using an enolate as the nucleophile, suppose we convert the ketone into an enamine ... 

If we carefully inspect the solution to the previous problem, we find that the final step of the mechanism is deprotonation of the a position, thereby converting the resonance-stabihzed cationic intermediate into an enol. Therefore, the reverse of this process must begin with protonation of the a position, thereby converting the enol into a resonance-stabilized cationic intermediate. Subsequent deprotonation of this intermediate gives the ketone. Notice that the acid for the protonation step is a hydronium ion, and the base for the deprotonation step is water, consistent with acidic conditions. 

The 4-kcto group in the alkyne 262 as an enol form adds to the triple bond to give the furan 263[133], Even the conjugated keto alkyne 264 was converted into the furan 266 via isomerization to the allenyl ketone 265[134],... 

The crude ketal from the Birch reduction is dissolved in a mixture of 700 ml ethyl acetate, 1260 ml absolute ethanol and 31.5 ml water. To this solution is added 198 ml of 0.01 Mp-toluenesulfonic acid in absolute ethanol. (Methanol cannot be substituted for the ethanol nor can denatured ethanol containing methanol be used. In the presence of methanol, the diethyl ketal forms the mixed methyl ethyl ketal at C-17 and this mixed ketal hydrolyzes at a much slower rate than does the diethyl ketal.) The mixture is stirred at room temperature under nitrogen for 10 min and 56 ml of 10% potassium bicarbonate solution is added to neutralize the toluenesulfonic acid. The organic solvents are removed in a rotary vacuum evaporator and water is added as the organic solvents distill. When all of the organic solvents have been distilled, the granular precipitate of 1,4-dihydroestrone 3- methyl ether is collected on a filter and washed well with cold water. The solid is sucked dry and is dissolved in 800 ml of methyl ethyl ketone. To this solution is added 1600 ml of 1 1 methanol-water mixture and the resulting mixture is cooled in an ice bath for 1 hr. The solid is collected, rinsed with cold methanol-water (1 1), air-dried, and finally dried in a vacuum oven at 60° yield, 71.5 g (81 % based on estrone methyl ether actually carried into the Birch reduction as the ketal) mp 139-141°, reported mp 141-141.5°. The material has an enol ether assay of 99%, a residual aromatics content of 0.6% and a 19-norandrost-5(10)-ene-3,17-dione content of 0.5% (from hydrolysis of the 3-enol ether). It contains less than 0.1 % of 17-ol and only a trace of ketal formed by addition of ethanol to the 3-enol ether. 

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