Enols highly stabilized

The intermediate N-acylpyridinium salt is highly stabilized by the electron donating ability of the dimethylamino group. The increased stability of the N-acylpyridinium ion has been postulated to lead to increased separation of the ion pair resulting in an easier attack by the nucleophile with general base catalysis provided by the loosely bound carboxylate anion. Dialkylamino-pyridines have been shown to be excellent catalysts for acylation (of amines, alcohols, phenols, enolates), tritylation, silylation, lactonization, phosphonylation, and carbomylation and as transfer agents of cyano, arylsulfonyl, and arylsulfinyl groups (lj-3 ). 

This suggestion is supported by the high stability of the ester bond in the easily obtained acetates 70 (R2 = Me), under conditions of both acidic and basic hydrolysis. Also, an jpso-substitution of the bromine atom in the acetate 70 (R1 = R2 = Me, R3 = Br) takes place in PPA, resulting in 5-oxoniachrysene67(R = R2 = Me). This behavior is contrary to that of the enol acetate 71, which does not form any 2-benzopyrylium salt in PPA, but breaks down to deoxybenzoin 72 (77ZOR631 79TH1). 

The oxidative insertion of zinc into a-halo carbonyl compounds and the subsequent reaction of the zinc enolates formed with various electrophiles can either be carried out in a one-pot Barbier-type fashion or in two consecutive steps.1-3 Zinc enolates exhibit a reasonably high stability over a wide temperature range (from -78°C to above 80°C for short periods of time) compared to other metal enolates. Although it has been reported that solutions of BrZnCH2COOtBu can be stored for several days without loss in activity,5 it is generally advisable to use freshly prepared reagents in order to avoid... 

The first step is conjugate addition of the highly stabilized anion. The intermediate enolate then closes the three-membered ring by favourable nucleophilic attack on the allylic carbon. The leaving group is the sulfinate anion and the stereochemistry comes from the most favourable arrangement in the transition state for this ring closure. The product is the methyl ester of the important chrysan-themic acid found in the natural pyrethrum insecticides. 

The high stability of isolated 2 was confirmed by collisional activation (+NCR+) that caused only minor dissociation by elimination of water forming furan. The latter reaction is calculated to be the lowest-energy unimolecular dissociation of 2 that is 4 kj mol-1 exothermic, but is kinetically hampered by an energy barrier to intramolecular hydrogen transfer [69]. The kinetic stability of isolated 2 in the gas phase contrasts its properties in aqueous solution, where the enol is predicted to react rapidly with H30+ or OH- and isomerizes to the more stable lactone 3. The equilibrium constant for the isomerization 3 2 is calculated to be extremely small in water, Keq=5.7xlO 20, so enol 2 would be very difficult to generate and study in solution. 

Most barbiturates are made from diethyl malonate. The methylene protons between the two carbonyl groups are acidic and will give a highly stabilized enolate anion. 

P,P-Disubstituted alkylidene derivatives of oxindole, azlactone, and y-butyrolactone are used as precursors of vinylogous enolates, which are highly stabilized owing to the heteroaromatic nature of the enolate components. Although these a,p-unsaturated carbonyl systems can act as electrophilic Michael acceptors, the presence of two p-substituents seems to suppress nucleophilic attack on the P-carbon. 

The reactions discussed in section 4.1 obviously describe enolate anion reactions. The reactions in this section involve malonate derivatives that react with bases such as sodium hydride or lithium dialkylamides to generate the malonate anion, a highly stabilized enolate. This section also includes reactions of enolate anions derived from mono-esters and other acid derivatives. 

The aluminium enolates generated after ECA do not react directly with electrophiles, probably due to their high stability. However, they can be trapped in situ by silylation, carbonation and 0-acylation in good yields (Scheme 6). These intermediates 7-9 can eventually be used in Tsuji reactions or ozonolysis, for example, to generate more elaborated adducts [36]. 

A fairly consistent relationship is found in these and related data. Conditions of kinetic control usually favor the less-substituted enolate. The principal reason for this result is that removal of the less hindered hydrogen is more rapid, for steric reasons, than removal of more hindered protons, and this more rapid reaction leads to the less substituted enolate. Similar results are obtained using either lithium diisopropylamide or triphenylmethyllithium. On the other hand, at equilibrium it is the more substituted enolate that is usually the dominant species. The stability of carbon-carbon double bonds increases with increasing substitution, and it is this substituent effect that leads to the greater stability of the more substituted enolate. Highly substituted enolates, especially if the substituents are bulky, are not solvated effectively, however, and may be present in only minor amounts at equilibrium. 

When the ketone has two nonequivalent a-carbon atoms, the acid-catalyzed reaction yields the a-haloketone with the halogen on the more substituted atom. We can explain this observation by considering the two possible enol intermediates. The more highly substituted site gives the more highly substituted double bond of the enol. Because halogenation under acidic conditions requires the formation of an enol, the stability of the enol controls the formation of the halogen product. 

To overcome the limitation of the high stability of the aluminum enolates, the oxygen atom has been transformed to silyl enol ethers, enol acetates, and allyl enol carbonates. Silyl enol ethers and enol acetates are precursors to lithium enolates. Enol acetates and allyl enol carbonates are precursors of cx-allylated adducts via the Tsuji-Trost rearrangement [75-77]. The silylation of aluminum enolates using TMSOTf is well established [78], although in some cases the isolation is difficult [33]. Silyl enol ethers allow further modification to be performed as they behave as lithium enolates (Scheme 15). A recent application can be found in the silylation of the conjugate addition adduct (/ )-((3-(but-3-en-l-yl)-3-methylcyclopent-l-en-l-yl)oxy)triethylsilane which allows aldol condensation to form an intermediate in the synthesis of Clavirolide C [79], a diterpene with a trans-bicyclo[9.3.0] tetradecane structure (Scheme 16) [80]. 

Schmittel et ah investigated highly stabilized silyl enol ethers such as 13 by cyclic voltammetry (CV). They found irreversible first oxidation potentials for their substances at low scan rates, which is consistent with findings for other silyl enol ethers and consistent with a mechanism including a fast follow-up... 

Under acid-catalyzed conditions, the starting material is first protonated (much the way an enol is protonated) to generate a resonance-stabilized cation. This step requires two curved arrows. Notice that the k bond is protonated (rather than protonating the nitrogen atoms), because protonation of the k bond results in a cation that is highly stabilized by resonance (notice that there are three resonance structures). This resonance-stabilized cation is then deprotonated by water, which also requires two curved arrows, as shown ... 

When the aldol reaction is carried Wt under thermodynamic conditions, the product selectivity is often not as high as under kinetic conditions. All the regioisomeric and stereoisomeric enolates may participate as nucleophiles. The adducts can return to reactants, and so the difference in stability of the stereoisomeric anti and syn products will determine the product composition. 

The high enantioselectivity observed was interpreted in terms of the face selectivity of the (Z)-enolate 59 (Scheme 1.20). The phenyl moiety is thought to stabilize the enolate through a n-n interaction and effectively shield its Re face such that the incoming ketone approaches preferentially from the Si face. 

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