Stable enols

Thermodynamic Enolate- Reversible deprotonation to give the most stable enolate more highly substituted C=C of the enol form... 

Only the more stable enolate (101 A) is formed and this reacts well with allyl bromide. This activating group (CHO) can be removed by basecatalysed hydrolysis. Mechanism ... 

The condensation conditions must be as mild as possible, because we want to get only the most stable of the three possible enols (from the aldehyde). Though you could not haye predicted the exact conditions either for the double bond. cleayage or for the condensation, you should haye seen that control was possible as in each case the two functional groups are different enough. ( J. Amer. Chem. Soc.. 1960, 636 J. Org. Chem.. 1964, 29, 3740 ... 

The altematiye condensation to giye A does not happen because A cannot form a stable enolate ion, whereas TM 219 can. Zhur. Obshchei Khim., 1957, 27, 742 Chem. Abs.. 1957. 51, 16313. 

The trick is to make the enol - the stable enol of the p-keto ester ... 

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. 

The ketone is added to a large excess of a strong base at low temperature, usually LDA in THF at -78 °C. The more acidic and less sterically hindered proton is removed in a kineti-cally controlled reaction. The equilibrium with a thermodynamically more stable enolate (generally the one which is more stabilized by substituents) is only reached very slowly (H.O. House, 1977), and the kinetic enolates may be trapped and isolated as silyl enol ethers (J.K. Rasmussen, 1977 H.O. House, 1969). If, on the other hand, a weak acid is added to the solution, e.g. an excess of the non-ionized ketone or a non-nucleophilic alcohol such as cert-butanol, then the tautomeric enolate is preferentially formed (stabilized mostly by hyperconjugation effects). The rate of approach to equilibrium is particularly slow with lithium as the counterion and much faster with potassium or sodium. 

The addition of large enolate synthons to cyclohexenone derivatives via Michael addition leads to equatorial substitution. If the cyclohexenone conformation is fixed, e.g. as in decalones or steroids, the addition is highly stereoselective. This is also the case with the S-addition to conjugated dienones (Y. Abe, 1956). Large substituents at C-4 of cyclic a -synthons direct incoming carbanions to the /rans-position at C-3 (A.R. Battersby, 1960). The thermodynamically most stable products are formed in these cases, because the addition of 1,3-dioxo compounds to activated double bonds is essentially reversible. 

Only relatively few examples of interesting target molecules containing rings are known. These include caryophyllene (E.J. Corey, 1963 A, 1964) and cubane (J.C. Barborak, 1966). The photochemical [2 + 2]-cycloaddition applied by Corey yielded mainly the /ranr-fused isomer, but isomerization with base leads via enolate to formation of the more stable civ-fused ring system. 

E. Vedejs (1978) developed a general method for the sterically controlled electrophilic or-hydroxylation of enolates. This uses a bulky molybdenum(VI) peroxide complex, MoO(02)2(HMPTA)(Py), which is rather stable and can be stored below 0 °C. If this peroxide is added to the enolate in THF solution (base e.g. LDA) at low temperatures, oneO—O bond is broken, and a molybdyl ester is formed. Excess peroxide is quenched with sodium sulfite after the reaction has occurred, and the molybdyl ester is cleaved to give the a-hydroxy car-... 

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

Owing to the instability of a-halogenoaldehydes it is occasionally preferable to use more stable derivatives, such as enol acetate prepared according to Bedoukian s method (204) and a-bromoacetals (4, 8, 10, 16, 22, 67, 101, 426). An advantage is said to be in the yield however, this appears to be slight. The derivatives react in the same sense as the aldehydes themselves, that is, the acetal group as the more polarized reacts first and enters the C-4 position. It is likely that the condensation and cyclization occur by direct displacement of alkoxide ions. Ethyl-a,/3-dihalogeno ethers (159, 164, 177, 248) have also been used in place of the free aldehydes in condensation with thioamides. 

In general ketones are more stable than their enol precursors and are the products actually isolated when alkynes undergo acid catalyzed hydration The standard method for alkyne hydration employs aqueous sulfuric acid as the reaction medium and mer cury(II) sulfate or mercury(II) oxide as a catalyst... 

In these and numerous other simple cases the keto form is more stable than the enol by some 45-60 kJ/mol (11-14 kcal/mol) The chief reason for this difference is that a carbon-oxygen double bond is stronger than a carbon-carbon double bond... 

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... 

Terreic acid is a naturally occumng antibiotic substance Its actual structure is an enol iso mer of the structure shown Wnte the two most stable enol forms of terreic acid and choose which of those two IS more stable... 

Enols are in equilibrium with an isomeric aldehyde or ke tone but are normally much less stable than aldehydes and ketones... 

In equation 7, ttimer radical (4) is produced when (3) dissociates. Whenever (4) couples with the other product of equation 7, ie, the 2,6-dimethylphenoxy radical, the tetramer is produced as described. These redistribution reactions of oligomers that proceed by ketal formation and subsequent dissociation ultimately generate terminal quinol ethers which enolize to the more stable terminal phenol (eq. 8). 

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

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