Enolates haloform reactions

Acylation of enol ethers. Reaction of 1 with ethyl vinyl ether in ether provides an intermediate that undergoes dehydrochlorination when heated to provide the trichloromethyl ketone 2, which is converted by base (haloform reaction) to the ester 3 in high yield. 

The methyl ketone shown in the example can enolize in only one direction and typifies the kind of reactant that can be converted to a carboxylic acid in synthetically acceptable yield by the haloform reaction. When C-3 of a methyl ketone bears enolizable hydro-O... 

The synthesis of ethyl 3,3-diethoxypropanoate, 5, described here implies acylation of an enol ether followed by a haloform reaction. The procedure is superior to other methods, which afford mixtures of acetals and acrylates,4 give only moderate yields,5 6 7 require the troublesome use of ketene8 or expensive ethyl propiolate,9 10 11 need palladium(ll) catalysis,12 or equipment for electrochemical reactions.13... 

Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Substitution of an Enolate on an Ester (a Condensation) 1046 Base-Catalyzed Keto-EnolTautomerism 1047 Acid-Catalyzed Keto-EnolTautomerism 1047 Base-Promoted Halogenation 1054 Final Steps of the Haloform Reaction 1056 Acid-Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

Oxidation of ketones requires breaking of carbon-carbon bonds, and (except for the haloform reaction) takes place only under vigorous conditions. Cleavage involves the double bond of the enol form (Sec. 8.13) and, where the structure... 

Halogenation of Enolate Ions The Haloform Reaction Alkylation of Enolate Ions 917... 

The biomimetic total synthesis of (+)-20-epiervatamine was accomplished by J. Bosch et al. The authors used the addition of 2-acetylindole enolate to a 3-acylpyridinium salt as akey step to connect the two main fragments. The in situ formed 1,4-dihydropyridine was trapped with trichloroacetic anhydride to afford the corresponding trichloroacetyl-substituted 1,4-dihydropyridine derivative. The conversion of the trichloroacetyl group to a methyl ester was achieved by treatment with sodium methoxide. This transformation can be regarded as the second step of the haloform reaction. 

Bartlett, P. D. Enolization as directed by acid and basic catalysts. II. Enolic mechanism of the haloform reaction. J. Am. Chem. Soc. 1934,... 

Many reactions of ketones and aldehydes as for instance the aldol condensation or the haloform reaction 55 are initiated by enolate anions. In these cases, a proton linked to the a carbon is removed, producing an enolate that reacts with electrophiles 1A. It has been found that in gas phase, the oxygen is the most reactive site, whereas the a carbon is mostly attacked in condensed phase. 

Same measures of stereocontrol had previously been observed in approaches to pyrethroid acids involving intramolecular enolate alkylation. As outlined in Figure 3, workers at Sumitomo have investigated the cyclization of a methyl ketone enolate (5). They obtained a 9 1 ratio of cis trans products upon ring closure initiated by sodium hydroxide. The methyl ketone was subsequently converted to the corresponding carboxylic acid via the haloform reaction. 

The mechanism of the haloform reaction begins with a halogenation via the enolate. The electron-attracting effect of an a halogen increases the acidity of the protons on the carbon to which it is bonded, making each subsequent halogenation at that carbon faster than the preceding one. 

The mechanism of the Haloform reaction involves base-catalyzed generation of an enolate 6 followed by in situ halogenation to afford an a-haloketone 7. Two subsequent repetitions afford trihaloketone 8, which then is susceptible to cleavage by alkali to furnish carboxylic acid 5 and haloform 4, after acidification. 

Several reported kinetic studies shed light on the various steps in the Haloform reaction. Bartlett showed in 1934 that the reaction of acetone with strong alkaline solutions of hypobromite and hypoiodite involves enolization of acetone as the ratedetermining step, but the rate of the same reaction with alkaline hypochlorite involves as the slow step reaction of acetone enol with hypochlorite.15 Likewise, the mechanism of the iodoform reaction and its optimization for quantitative analysis have received much scrutiny16 including studies of acetone-1-C-l4 7 and deuterated acetone18 for isotope... 

The classical organic reaction for the synthesis of THMs, the so-called haloform reaction, is actually a series of reactions of enolizable compounds whose rate is usually determined by the rate of enolization of a precursor molecule. It is outlined in Figure 5.5. 

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