Enols reaction at oxygen

Enol and enolate reactions at oxygen preparation of enol ethers... 

ENOL AND ENOLATE REACTIONS AT OXYGEN PREPARATION OF ENOL ETHERS... 

You have seen reaction at oxygen before, Enolates react on oxygen with silicon electrophiles and we found the products, silyl enol ethers, useful in further reactions. Enol esters also have their uses—as precursors of lithium enolates, for example. You saw one being used like this on p. 683,... 

In Chapter 27, we mentioned no trouble with reaction at oxygen in the aldol reaction. This may now seem surprising, in view of what we have said about esters, as the electrophiles were aldehydes and ketones—not so very different from esters. We can resolve this by looking at what would happen if an aldehyde did attack an enolate on the oxygen atom. 

The extended enolate problem1 is easily stated but not so easily solved. If an unsaturated ester 1 is treated with base, a conjugated enolate 2 is formed. The conjugated ester 3 can form the same enolate 2 by loss of one of the marked protons. This intermediate 2 is an extended enolate, extended by conjugation into a double bond and interesting because a new dimension of versatility is added to its reactions. Enolates normally have to choose between reaction at oxygen or carbon, but the extended enolate may also choose at which carbon to react. This chapter is about the reasons for that choice. 

The enolate attacks the oxygen atom of 273 in an unusual SN2 reaction at oxygen 276. The leaving group is the sulfonamide anion, which is why a sulfonamide is necessary. The anion returns 277 to form the original imine 272 and ejects the anion 278 of the a-hydroxy-carbonyl compound 275. 

Two competing intramolecular cyclizations (see the aldol condensation-sec. 9.4.A.ii) are illustrated for triketone 205.jn this case, only the favored 6-enolendo-exo-trig product (206) was obtained and not the disfavored 5-enol-endo-exo-trig products (207 and 208). Enolates generally tend to undergo 5-exo-tet reactions at oxygen, whereas 6-enolendo-exo-tet reactions prefer carbon. In order to form a five-membered... 

The enolate of methyl 4,6-0-benzylidene-3-deoxy-3-C-methyl-a-D-arabino-hexopyranosid-2-ulose (1) has been trapped by reaction at oxygen to give (2) and at carbon to give (3) and submitted to Robinson annulation to give (4) (Scheme 1)... 

An enolate is a nucleophile that can displace a leaving group from a primary alkyl halide by an Sj j2 mechanism. Although the enolate has two sites of reactivity, we have already seen that reaction of an electrophile with an enolate. The reaction usually occurs at the a-carbon atom to give a substimted keto product called the C-alkylated product. The reaction at oxygen to give an O-alkylated product is much less common. 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both very stable enolates, such as those derived from (i-ketoesters, / -diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships between reactivity, stereochemistry, and mechanism have been clarified. A starting point for the discussion of these reactions is the structure of the enolates. Because of the delocalized nature of enolates, an electrophile can attack either at oxygen or at carbon. 

The acylation of enamino ketones can take place on oxygen or on carbon. While reaction at nitrogen is a possibility, the N-acylated products are themselves acylating agents, and further reaction normally takes place. The first reported acylation of enamino ketones (72) was that of 129, prepared by acylation of the enamine (113), which was shown to have undergone O acylation because on mild hydrolysis the enol ester (130) could be isolated. A similar reaction took place with other aliphatic acid chlorides (80) and with dibasic acid chlorides [e.g., with succinyl chloride to give 118 above]. 

Still another possibility in the base-catalyzed reactions of carbonyl compounds is alkylation or similar reaction at the oxygen atom. This is the predominant reaction of phenoxide ion, of course, but for enolates with less resonance stabilization it is exceptional and requires special conditions. Even phenolates react at carbon when the reagent is carbon dioxide, but this may be due merely to the instability of the alternative carbonic half ester. The association of enolate ions with a proton is evidently not very different from the association with metallic cations. Although the equilibrium mixture is about 92 % ketone, the sodium derivative of acetoacetic ester reacts with acetic acid in cold petroleum ether to give the enol. The Perkin ring closure reaction, which depends on C-alkylation, gives the alternative O-alkylation only when it is applied to the synthesis of a four membered ring ... 

The second main aspect of reactions of carbonyl compounds is one we have already touched upon in Chapter 3. The carbonyl group increases the acidity of C—H bonds on a carbon directly attached to it by many powers of ten over an unactivated carbon-hydrogen bond. Removal of such a proton leaves the conjugated ambident enolate ion (29), which can be reprotonated either at the carbon, to give back the original keto tautomer, or at oxygen to give the enol (Equation 8.61).135 Acid also promotes interconversion between enol and keto... 

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