Anions enolate

2 They Formed What Is the Aldol Reaction 15.3 Used in a Ciaisen Condensation How to Determine the Starting Compounds 

3 What Are the Claisen and Dieckmann Used in a Michael Reaction 

4 How Are Aldol Reactions and Claisen Condensation, and Michael Reactions 

5 Condensations Invoived in Biological Processes What Is the Michael Reaction CHEMICAL CONNECTIONS  

1 How to Determine the Starting Compounds 15B Antitumor Compounds The Michael 

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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 ... 

The obvious diseonnection on a 1,4-dicarbonyl compoimd gives us a logieal nucleophilie synthon (an enolate anion) A but an illogieal electrophilic synthon B ... 

The obvious disconnection gives an epoxide and an enolate anion ... 

Only isomer A will be formed as the alternative cannot give a stable enolate anion (see frame 101). This is nearly the synthesis used by Raphael (Tetrahedron. 1962, 55 Proc. 

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. 

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. 

A number of novel reactions involving the a carbon atom of aldehydes and ketones involve enol and enolate anion intermediates... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

As noted earlier an aldehyde possessing at least one a hydrogen is partially converted to Its enolate anion by bases such as hydroxide ion and alkoxide 10ns... 

An a hydrogen of an aide hyde or a ketone is more acidic than most other protons bound to carbon Aldehydes and ketones are weak acids with pK s in the 16 to 20 range Their enhanced acidity IS due to the electron withdrawing effect of the carbon yl group and the resonance stabi lization of the enolate anion... 

A combination of conju gate addition of an enolate anion to an a p unsaturated ketone with subsequent intramolecular aldol condensation... 

Alkyl halides by reaction with the enolate anion derived from diethyl acetamidomalonate... 

Enmatin B [917-13-5] Enmatin C [19893-23-3] Enociamna Enol Enolase Enolate anions Enolboration Enol esters... 

Enolate Initiators. In principle, ester enolate anions should represent the ideal initiators for anionic polymeri2ation of alkyl methacrylates. Although general procedures have been developed for the preparation of a variety of alkaU metal enolate salts, many of these compounds are unstable except at low temperatures (67,102,103). Usehil initiating systems for acrylate polymeri2ation have been prepared from complexes of ester enolates with alkak metal alkoxides (104,105). 

Reaction of Enolate Anions. In the presence of certain bases, eg, sodium alkoxide, an ester having a hydrogen on the a-carbon atom undergoes a wide variety of characteristic enolate reactions. Mechanistically, the base removes a proton from the a-carbon, giving an enolate that then can react with an electrophile. Depending on the final product, the base may be consumed stoichiometricaHy or may function as a catalyst. Eor example, the sodium alkoxide used in the Claisen condensation is a catalyst ... 

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

Enamines and enolate anions react with benzofuroxan to give quinoxaline di-A -oxides (Scheme 38) (69AHC(10)1). Sydnones (274) with phenyl isocyanate give 1,2,4-triazoles (275) (76AHC(19)l), and from (276) the intermediate adduct (277) can be isolated (73JA8452). This is one of the few instances in which such primary cycloadducts have been isolated in the oxazole series of mesoionic compounds. 

Azirines react with enolate anions. Initial nucleophilic attack on phenyl 1-azirine by the enolate anion derived from acetophenone gives intermediate (223) which undergoes 1,2-bond cleavage, cyclization and hydroxyl group elimination to give pyrrole (226). 

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

The idea of kinetic versus thermodynamic control can be illustrated by discussing briefly the case of formation of enolate anions from unsymmetrical ketones. This is a very important matter for synthesis and will be discussed more fully in Chapter 1 of Part B. Most ketones, highly symmetric ones being the exception, can give rise to more than one enolate. Many studies have shown tiiat the ratio among the possible enolates that are formed depends on the reaction conditions. This can be illustrated for the case of 3-methyl-2-butanone. If the base chosen is a strong, sterically hindered one and the solvent is aptotic, the major enolate formed is 3. If a protic solvent is used or if a weaker base (one comparable in basicity to the ketone enolate) is used, the dominant enolate is 2. Enolate 3 is the kinetic enolate whereas 2 is the thermodynamically favored enolate. 

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... 

Enols are not as reactive as enolate anions, however. This lower reactivity simply reflects the presence of the additional proton in the enol, which decreases the electron density of the enol relative to the enolate. In MO terminology, the —OH and —0 donor substituents raise the energy of the tt-HOMO. 

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. 

One of the general features of the reactivity of enolate anions is the sensitivity of both the reaction rate and the ratio of C- versus O-alkylation to the degree of aggregation of the enolate. For example, addition of HMPA fiequently increases the rate of enolate alkylation... 

Prior to the work of House, most chemists seem to have regarded the radical anion (51) and the enolate anion (50) primarily as carbon bases. 

It has been suggested that in basic mixtures the reaction occurs by hydrogenation of the initially formed enolate anion, e.g. (13) which is irreversibly adsorbed on the catalyst surface (14). 

These mechanistic interpretations can also be applied to the hydrogenation of cyclohexanones. In acid, the carbonium ion (19) is formed and adsorbed on the catalyst from the least hindered side. Hydride ion transfer from the catalyst gives the axial alcohol (20). " In base, the enolate anion (21) is also adsorbed from the least hindered side. Hydride ion transfer from the catalyst followed by protonation from the solution gives the equatorial alcohol (22). 

Eliminations of this type occur very easily under both acidic and basic conditions because of the activation possible through the enol or enolate anion. 

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