Enol ether reaction

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. 

Enol ether Reaction conditions Product % yield... 

Methyl enol ethers. Reaction of ISi(CH3)3 and HN[Si(CH3)3]2 with dimethyl acetals or kctals in CH2C12 or CHC13 results in methyl enol ethers.6 Cyclopropylcar-biny 1 methyl kelals under these conditions undergo ring opening to give iodo methyl enol ethers. 

By way of Mannich reaction (step 1) and /1-elimination (step 2), the transformations shown in Figures 12.14 and 12.15 demonstrate how an aldol condensation (for the term see Section 13.4.1) can be conducted under acidic conditions as well. Both the enamine reaction in Figure 12.18 and the enol ether reaction in Figure 12.23 illustrate the same thing differently. Many aldol condensations, however, start from carbonyl compounds only and proceed under basic conditions. They follow a totally different mechanism (Section 13.4.1). 

Silyl enol ethers, Reaction of carbonyl compounds with in situ generated BrSi(CH3)3 and triethylamine results mainly in the thermodynamic silyl ether, usually the (Z)-isomer. 

Lewis acid catalysis (T iCIJ is normally required for silyl enol ether reactions... 

Enol ethers. Reaction of ketones, even highly hindered ones, with this reagent and triethylamine provide TBDMS enol ethers in 90-100% yield. The method is not useful for selective formation of the kinetic isonu rs. 

Lithium enolates of carboxylic acids Enamines and silyl enol ethers Reactions with Other Electrophiles... 

The catalyzed reaction of enol ethers with carbonyl compounds (Scheme 1) has become an important reaction in synthesis. Compared to the metal enolate reactions (Part 1, Volume 2), the catalyz enol ether reactions offer the following distinct differences. Enol ethers are often isolable, stable covalent compounds, whereas the metal enolates are usually generated and used in situ. Under Lewis acid catalyzed conditions, a number of functional equivalents such as acetals, orthoesters, thioacetals, a-halo ethers and sulfides can participate as the electrophilic components, whereas many of them are normally unreactive towards metal enolates. In synthesis, enol ether reactions now rival and complement the enolate reactions in usefulness. Enol silyl ethers are particularly useful because of their ease of preparation, their reasonable reactivity and the mildness of the desilylation process. 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

Bis(trimethylsiloxy)cyclohexadienes. LDA and related lithium dialkyl-amides appear to be specific for generation of the anion of keto trimethylsilyl enol ethers reaction of these anions with (CHajaSiCI gives the disiloxycyclohexa-dienes 1 and 2, which cannot be prepared directly from the 1,2- and 1,3-dike-... 

Since research on the total synthesis of carotenoids began, the enol ether and the aldol condensations have been frequently used for the formation of carbon-carbon double bonds. In general, the enol ether reaction has been employed successfully for the condensation of a wide range of acetals and sometimes of ketals with enol ethers and dienol ethers. 

We were able to envision a reasonable catalytic cycle for the use of silyl enol ethers in the asymmetric alkylation reaction, but there were several complications that could potentially lead to lower enantioinduction in the silyl enol ether reactions (Scheme 6). The generation of the enolate independent of the palladium(II) 7t-allyl complex and the presence of a tetrabutylammonium counter ion could shift the mechanism of the reaction. We had very httle proof at the time, but our working hypothesis was that the C-C bond-forming step occurred in the inner sphere of the palladium atom. We considered the possibihty that the conditions used in the silyl enol ether reactions might facilitate an outer sphere pathway resulting in lower ee products. In the event, we found that the ketone products generated from silyl enol ethers did not significantly differ in ee from the equivalent products of allyl enol carbonate reactions (e.g., Table 8 vs. Table 2). 

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