Enolization of carbonyl compounds

Ketones with a hydrogen atoms undergo substitution by halogen as shown in equation 7.62. 

Lapworth found that the substitution reaction is catalyzed by both acids and bases. Since the HX produced as a by-product of the reaction can serve as a catalyst, the acid-catalyzed reaction is said to be autocatalytic because the rate of the reaction increases with time. The rate law for the reaction was found to be first order in ketone but zero order in halogen, meaning that halogen is not 

Lapworth mechanism for acid-catalyzed a-halogenation of a ketone. 

Obviously, the rate of the reaction is not totally independent of halogen concentration, because no reaction can occur in the total absence of halogen. Dependence on [XJ has been observed at low halogen concentration. At [X2] greater than 10 to 10 M , however, flie reaction is apparently zeroth order in halogen. Dubois, J.-E. El-Alaoui, M. Toullec, J. /. Am. Chem. Soc. 1981,103,5393. 

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In Methods 3a to 3d. enolization of carbonyl compound and reduction of RMgX are side reactions that become important for hindered ketones and bulky Grignard reagents (Section 14-12A). Ammonium chloride is used to hydrolyze the reaction mixtures in preparation of tertiary alcohols to avoid dehydration. Organolithium compounds are superior to RMgX for preparation of bulky tertiary alcohols. 

We have seen that LDA forms enolates of carbonyl compounds, carboxylic esters, and carboxylic amides via cychc and six-membered transition states with the chair conformation. This geometry of the transition state for enoiate formation has consequences if a stereogenic C=C double bond is generated. 

These are the first reagents known to effect enantioselective fluorination of enolates of carbonyl compounds. The highest enantioselectivity is observed in the reaction of (-)-l with a p-keto ester (equation I). 

We introduced the chemistry of malonate esters in Chapters 21 and 26 as a useful way of controlling the enolization of carbonyl compounds. Alkylation followed by decarboxylation means that we can treat acetoacetate and malonate esters as equivalent for these synthons. 

A greater degree of regiocontrol over the above methods can be achieved by quenching the enolate of carbonyl compounds with either brominei or iodine.Thus, in the case of unsymmetrical ketones (Scheme 3), low temperature formation of the enolate allows exclusive bromination of the kinetic enolate to afford foe haloketone (1), which on elimination gives foe enone (2). A similar procedure allows... 

Abstraction of acidic protons a to a carbonyl or nitrile function can occur in competition with desired Grignard addition reactions (see Section 5.6). In HMPA, this is the major reaction, and is useful for preparing magnesium enolates of carbonyl compounds, sulfones, and so on. 

Metal enolates of carbonyl compounds are important nucleophiles in C—C bondforming reactions for the synthesis of nonfluorinated compounds. However, the metal enolates of fluorinated carbonyl compounds have been severely limited to a-F metal enolates, which can be stabilized by chelate structures containing the M—F moiety. In sharp... 

In a series of papers on the total syntheses of alkaloids, Baran and coworkers have recently reported that enolates of carbonyl compounds undergo oxidative coupling with indoles and pyrroles in the presence of oxidants such as copper(II) and iron(III) salts . A detailed study of the oxidative cyclization reported in equation 15 has shown that 26 is converted into 27 with the highest yields when Fe(acac)3 is the oxidant, presumably due to its high redox potential (+1.1 V vs. the ferrocenium/ferrocene couple in THF solution ), which is the most positive among all the oxidizing agents tested for the transformation. 

Condensation with enolates of carbonyl compounds (cf. Trichloroethylene, 9,479-480). The reagent can react in two ways with carbonyl enolates. The first one evidently is a direct addition-elimination (equation 1) the second one is considered to involve perchlorobutenyne (a) as an intermediate (equation II).1... 

In general, the experimental procedures for nucleophilic addition of organolithiums to aldehydes or ketones are straightforward [20]. Reduction via (3-hydride transfer and via ketyl formation is usually less troublesome in the case of organolithiums. On the other hand, a-deprotonation i.e., enolization of carbonyl compounds resulting from the high basicity of many organolithium compounds can be a real problem. 

This reaction resembles the reaction of ketones with nitriles in the presence of acyl cations (equation 64) since acetylenes are the dehydration products of the enols of carbonyl compounds (Sections I and IV). 

Direct enolization of carbonyl compounds using dialkylboryl trifluoromethanesulfonate (dialkylboryl triflate R2BOTf) in the presence of a tertiary amine base is versatile and advantageous in many ways compared with the foregoing indirect methods (see Sections 1.7.2.3 and 1.7.2.4).2° The resulting boryl enolates, e.g. (10), react cleanly with various aldehydes to provide high yields of crossed aldol products (Scheme 7). 

Dithians. - 1,3-Dithienium fluoroborate (258) effects regiospecific alkylation of 0-silylated enolates of carbonyl compounds to produce 1,3-dicarbonyl derivatives, e.g. (259). A wider variety of substituents in 1,3-dithians is obtainable by allowing aromatic aldehydes to react with the sul-phone (260). ... 

Neutral enols can be preformed by photochemical enolization of carbonyl compounds. The enols in the presence of oxygen are then rapidly converted into hydroperoxides under thermal conditions (Scheme 10) [24, 27]. 

Cyclohexadienes. The reagent reacts with enolates of carbonyl compounds in THF (25°, 6-18 hr.) to form 1,3-cyclohexadienes in moderate yields (35-60%). It may react in the i-c -form to give a cw-allyl ylide, which... 

The reagent has been used for the enolization of carbonyl compounds in a number of syntheses. For ketones and aldehydes which do not have enolizable protons, NaHMDS may be used to prepare the corresponding TMS-imine. ... 

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