Enolate anions carbonyl compounds

Enolates of carbonyl compounds are ambident anions. Although the negative charge resides predominantly at the oxygen, reactions of enolates with electrophiles can take place at the carbon terminus. C-Monoalkylation of enolates is usually accompanied by di- and polyalkylation owing to a rapid... 

The anion B is just the enolate anion of a carbonyl compound, actually the same as A. So there is no need to use a Grignard reagent or any other synthetic equivalent in this reaction anion B itself can be the intermediate and we simply treat the aldehyde with mild base ... 

So far in this section we have combined enolate anions with other carbonyl compounds by direct attack at the carbonyl group. We can expand the scope of this reaction by using a,p-unsaturated carbonyl compounds as the electrophiles. This is the Michael reaction. Remind yourself of tliis by writing out the mechanism of a Michael reaction such as ... 

If boranes (K. Utimoto, 1973 H.C. Brown, 1975, 1980 A. Pelter, 1979) are used as donor synthons for the alkylation of a, -unsatarated carbonyl compounds, no enolate anion is formed, and the, 8-position of the C=C bond is the only reaction site. 

A classical reaction leading to 1,4-difunctional compounds is the nucleophilic substitution of the bromine of cf-bromo carbonyl compounds (a -synthons) with enolate type anions (d -synthons). Regio- and stereoselectivities, which can be achieved by an appropiate choice of the enol component, are similar to those described in the previous section. Just one example of a highly functionalized product (W.L. Meyer, 1963) is given. 

The ff-oxidation of carbonyl compounds may be performed by addition of molecular oxygen to enolate anions and subsequent reduction of the hydroperoxy group, e.g. with triethyl phosphite (E.J. Bailey, 1962 J.N. Gardner, 1968 A,B). If the initially formed a-hydroperoxide possesses another enolizable a-proton, dehydration to the 1,2-dione occurs spontaneously, and further oxidation to complex product mitctures is usually observed. 

The proton transfer equilibrium that interconverts a carbonyl compound and its enol can be catalyzed by bases as well as by acids Figure 18 3 illustrates the roles of hydroxide ion and water m a base catalyzed enolization As m acid catalyzed enolization protons are transferred sequentially rather than m a single step First (step 1) the base abstracts a proton from the a carbon atom to yield an anion This anion is a resonance stabilized species Its negative charge is shared by the a carbon atom and the carbonyl oxygen... 

Ordinarily nucleophilic addition to the carbon-carbon double bond of an alkene is very rare It occurs with a p unsaturated carbonyl compounds because the carbanion that results IS an enolate which is more stable than a simple alkyl anion... 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

Carbanions derived from carbonyl compoimds are often referred to as etiolates. This name is derived from the enol tautomer of carbonyl compounds. The resonance-stabilized enolate anion is the conjugate base of both the keto and enol forms of carbonyl... 

The fluoride anion has a pronounced catalytic effect on the aldol reaction between enol silyl ethers and carbonyl compounds [13] This reacbon proceeds at low temperature under the influence of catalytic amounts (5-10 mol %) of tetra-butylammonium fluoride, giving the aldol silyl ethers in high yields (equation 11). 

The reaction can be performed with base catalysis as well as acid catalysis. The former is more common here the enolizable carbonyl compound 1 is depro-tonated at the a-carbon by base (e.g. alkali hydroxide) to give the enolate anion 5, which is stabilized by resonance ... 

The 1,4-addition of an enolate anion 1 to an o ,/3-unsaturated carbonyl compound 2, to yield a 1,5-dicarbonyl compound 3, is a powerful method for the formation of carbon-carbon bonds, and is called the Michael reaction or Michael addition The 1,4-addition to an o ,/3-unsaturated carbonyl substrate is also called a conjugate addition. Various other 1,4-additions are known, and sometimes referred to as Michael-like additions. 

The enolate anion 1 may in principle be generated from any enolizable carbonyl compound 4 by treatment with base the reaction works especially well with /3-dicarbonyl compounds. The enolate 1 adds to the a ,/3-unsaturated compound 2 to give an intermediate new enolate 5, which yields the 1,5-dicarbonyl compound 3 upon hydrolytic workup ... 

Q Base removes an acidic hydrogen from the a position of the carbonyl compound, yielding an enolate anion that has two resonance structures. 

Carbonyl compounds are more acidic than alkanes for the same reason that carboxylic acids are more acidic than alcohols (Section 20.2). In both cases, the anions are stabilized by resonance. Enolate ions differ from carboxylate ions, however, in that their two resonance forms are not equivalent—the form with the negative charge on oxygen is lower in energy than the form with the charge on carbon. Nevertheless, the principle behind resonance stabilization is the same in both cases. 

Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, acids, and amides, can be converted into enolate ions by reaction with LDA. Table 22.1 lists the approximate pKa values of different types of carbonyl compounds and shows how these values compare to other acidic substances we ve seen. Note that nitriles, too, are acidic and can be converted into enolate-like anions. 

Alkylation (Sections 8.8, 16.3, 18.2. 22.7) Introduction of an alkyl group onto a molecule. For example, aromatic rings can be alkylated to yield arenes, and enolate anions can be alkylated to yield a-substituted carbonyl compounds. 

Allyl anion synthons A and C, bearing one or two electronegative hetero-substituents in the y-position are widely used for the combination of the homoenolate (or / -enolate) moiety B or D with carbonyl compounds by means of allylmetal reagents 1 or 4, since hydrolysis of the addition products 2 or 5 leads to 4-hydroxy-substituted aldehydes or ketones 3, or carboxylic acids, respectively. At present, 1-hetero-substituted allylmetal reagents of type 1, rather than 4, offer the widest opportunity for the variation of the substitution pattern and for the control of the different levels of stereoselectivity. The resulting aldehydes of type 3 (R1 = H) are easily oxidized to form carboxylic acids 6 (or their derivatives). 

Few a-ketosulphoxides 123 were prepared by trapping the enolate anions 124, which are generated by the Michael addition of Grignard reagents to easily available a, jS-unsaturated carbonyl compounds 125, with methanesulphinyl chloride174 (equation 65). 

The decarboxylation reaction usually proceeds from the dissociated form of a carboxyl group. As a result, the primary reaction intermediate is more or less a carbanion-like species. In one case, the carbanion is stabilized by the adjacent carbonyl group to form an enolate intermediate as seen in the case of decarboxylation of malonic acid and tropic acid derivatives. In the other case, the anion is stabilized by the aid of the thiazolium ring of TPP. This is the case of transketolases. The formation of carbanion equivalents is essentially important in the synthetic chemistry no matter what methods one takes, i.e., enzymatic or ordinary chemical. They undergo C—C bond-forming reactions with carbonyl compounds as well as a number of reactions with electrophiles, such as protonation, Michael-type addition, substitution with pyrophosphate and halides and so on. In this context,... 

Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions is initiated by a Michael addition [1]. Due to the attack of a nucleophile at the 4-position of usually an enone, a reactive enolate is formed which can easily be trapped in a second anionic reaction by, for example, another n,(5-urisalurated carbonyl compound, an aldehyde, a ketone, an inline, an ester, or an alkyl halide (Scheme 2.1). Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN-type sequences have been found in the literature. These reactions can be considered as very reliable domino processes, and are undoubtedly of great value to today s synthetic chemist... 

Deprotection of 2,2-disubstituted-l,3-dithiolanes to give carbonyl compounds can be achieved using Oxone with KBr in aq. MeCN <06TL8559> and a review of silylated heterocycles as formyl anion equivalents includes reference to 64 <06CC4881>. A method for transformation of propargylic dithiolanes 43 into tetrasubstituted furans has been reported <06SL1209> and Michael addition of enolates to the chiral dithiolane dioxide 65 takes place... 

In 1,3-dicarbonyI compounds such as acetylace-tone, the protons between the two carbonyls will be even more acidic (p Ta 9), since there are now two carbonyl groups exerting their combined influence. It can also be seen that resonance in the enolate anion is even more favourable with two carbonyl... 

Now for some interesting features of the reaction, though they become fairly obvious with a little thought. First, the central methylene contains the more acidic protons (pATa 9) since it is flanked by two carbonyls, so the enolate anion formed involves this carbon (see Section 4.3.5). In other words, alkylation occurs on the central carbon of acetylacetone, not on the terminal carbons. Second, it is possible to use carbonyl compounds such as acetone as a solvent without these reacting under the reaction conditions. Acetone will have similar acidity (pATa 19) to the acetyl groups of acetylacetone, so likewise will not... 

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