Elimination from aldol product

These investigations revealed that 2-alkyl substituents are eliminated from 47 during oxidation under standard conditions (5% aqueous alkali) as their corresponding carboxylic acids to form 48 (Scheme 10). Compounds such as 46 readily decompose when exposed to alkaline solution to give 47 (R = H) via retro aldol reaction and the final oxidation product is therefore also 48. 

Another common trapping method is an intramolecular aldol reaction of the initially formed anion, as shown in equation (91) and Schemes 53 and 54.% In the first case, an aldol-like trapping of the iminium salt produced (411 equation 91 ).96b The initial heteronucleophile in the other two cases is ultimately lost from the product by oxidation and elimination, so that the overall process is C—C bond formation at the a-center of an enone. Thus, treatment of the formyl enone (412 Scheme 53) with an aluminum thiolate afforded in 60% yield the trapped product (413) which could be oxidized and eliminated to give (414).96c Addition of the corresponding aluminate species to the ketoacrylate (415 Scheme 54) produced only one diastereomer of the aldol product (416) which was converted into the alkene (417) in excellent yield.96 1... 

Two extreme pathways may be envisaged for this transformation. One involves a pericyclic reaction followed by desilylation and elimination of methoxide from the product silyl enol ether. The alternative proceeds via a Lewis acid promoted aldol reaction to give an intermediate which cyclizes to the product dihydropyrone (Figure Si3.6). The actual pathway in an individual case is affected to a considerable degree by the nature of the Lewis acid used and lies somewhere between these two extremes. 

We haven t yet considered In detail the geometry of the double bonds arising from aldol condensations. Those that are El or ElcB eliminations give mainly the more stable E-alkene products for the reasons described in Chapter 19. These Wittig variants are usually highly 8-selective we shall consider why in Chapter 31. where we deal with the question of howto control double bond geometry. 

The use of a relatively soluble base such as CS2CO3 allows good product yield. No products are formed via carbopalladation. Therefore the reaction is considered to occur on a dienolate anion generated from the enal to give an aryl(7r-allyl)palladium intermediate. The regioselectivity seems to be determined in the reductive elimination of the product. Treatment of aliphatic aldehydes with aryl bromides brings about aldol condensation followed by y-aryla-tion to afford 2 1 coupling products (Eq. 27). Note that y-arylation products are also produced in the arylation of a tin-masked dienolate [65,66]. 

The resulting cyclic products 335 and 337 are usually unsalurated ketones, except in the case that the hydroxy group arising from aldol condensation is not eliminated... 

Anions formed from group 6 and manganese Fischer carbene complexes undergo aldol condensations with aldehydes and ketones. Allylic carbenes exclusively react in the y position with aldehydes affording dienyl-substituted carbenes. For alkoxy-substituted carbenes, the presence of an excess Lewis acid see Lewis Acids Bases), such as boron trifluoride etherate, titanium tetrachloride, or tin tetrachloride is required for the reaction to proceed in reasonable yield. The initial aldol product can be isolated without elimination (Scheme 12). ... 

As we know, an alkene in which the carbon-carbon double bond is conjugated with an aromatic ring is particularly stable (Sec. 12.17) in those cases where elimination of water from the aldol product can form such a conjugated alkene, the unsaturated aldehyde or ketone is the product actually isolated from the reaction. For example ... 

Dehydration of the aldol products of a Refoimatsky reaction does not normally occur under the usual reaction conditions but is often accomplished in a separate step to prepare unsaturated esters. Acid-promoted dehydration of -hydroxy esters can give significant amounts of nonconjugated unsaturated esters by either kinetic or thermodynamic control. Mirrington and cowoikers found that acetates can be prepared directly from Refoimatsky reaction mixtures by addition of acetyl chloride. Base-promoted elimination of the acetates produced conjugated esters in high yield. For the reaction shown in Scheme 14, the thermodynamic ratio of products (32) (33) is 40 60 and four different acid-promoted dehydration procedures gave at best a 68 32 ratio of products. ... 

The reactant ratio had a considerable effect on the product distribution a higher formaldehyde-to-butyraldehyde ratio increased the selectivity towards aldol. This observation is not surprising from a kinetic viewpoint, as water elimination from a-hydroxymethyl-substituted aldehyde (aldol 1) leading to the corresponding unsaturated aldehyde (ethylacrolein) is in competition with the... 

Confirmation of the molecular structure of the enzyme-inactivator adduct has been obtained for few modified PLP-dependent enzymes. In the case of the reaction of aspartate transaminase (aspartate aminotransferase) with L-serine 0-sulfate, the surprising result thus obtained by Metzler and co-workers has forced reevaluation of the mechanism of similar inactivators (Ueno et al., 1982). Conventional wisdom argued that the reaction should involve elimination of sulfate from the inactivator followed by addition of an enzyme nucleophile to the resulting double bond (Fig. 8). When subjected to high pH, however, the inactivated enzyme releases a yellow PLP adduct which has been identified as the aldol product of the cofactor and C-3 of pyruvate (9, Fig. 9) as previously prepared by... 

A common method for forming alkenes by -elimination involves the dehydration of an aldol product (see Section 1.1.3). Under appropriate conditions or with suitable substituents, both the aldol reaction and the dehydration steps can be carried out in the same pot. For example, elimination occurs in situ to give the conjugated alkene chalcone, on aldol condensation between acetophenone and benzaldehyde (2.11). This reaction works well, as only one component (acetophenone) is enoUz-able and as benzaldehyde is more electrophilic. Mixtures of products result from... 

With the ketone, there is a question of regioselectivity in enolate formation, but the aldol product can lose water only if the enolate from the methyl group is the nucleophile. If we draw both enolates and combine them with the ketone in an aldol reaction, it is clear that one can dehydrate as it has two enolizable H atoms but the other cannot dehydrate as it has no H atoms on the vital carbon atom (in grey). The mechanism is the same as the one with the aldehyde and the elimination in both cases is by the ElcB mechanism. 

The resonant anion can act as a typical carbanion and add to C=0 or C=N bonds, just as a Gtignard reagent does. In a true aldol condensation, the anion after formation proceeds to interact with another molecule of the starting aldehyde or ketone, giving a product that is a beta-hydroxy aldehyde or ketone known as an aldol (Scheme 4.29). Frequently, water is eliminated from this compound to produce an a, P-unsaturated carbonyl compound this process is made easy by the resonance stabilization of such conjugated systems. 

P-hydride elimination to produce Morita-Baylis-Hilman type products [74]. In addition, Ru - H species also were found to work as the same catalyst [75]. For example, the coupling of vinyl methyl ketone and propanal (200 mol %) was catalyzed with RhH(PPh3)4 (lmol%) and RuH2(PPh3)4 (lmol%) at 40 °C for 40 h without solvent to form the unsaturated ketone 169 in good yields, 78% and 82%, respectively (Scheme 43). It was proposed that P-hydride elimination from metal-aldolates could release the a, -imsaturated P -hydroxy ketones, which were Morita-Baylis-Hilman type products. 

The use of silyl enol ethers can be illustrated in a synthesis of manicone, a conjugated enone that ants use to leave a trail to a food source. It can be made by an aldol reaction between pentan-3-one (as the enol component) and 2-methylbutanal (as the electrophile). Both partners are enolizable so we shall need to form a specific enol equivalent from the ketone. The silyl enol ether works well. The aldol product will be a mixture of diastereoisomers but it eliminates to give a single compound. 

Subsequent elimination of water from the aldol product leads to a,6-unsaturated carbonyl compounds, for example, in the Claisen-Schmidt reaction (reference 142). 

What does all of this mean The reaction of 2-pentanone with LDA in THF at -78°C constitutes typical kinetic control conditions. Therefore, formation of the kinetic enolate and subsequent reaction with benzaldehyde to give 34 is predictable based on the kinetic versus thermodynamic control arguments. In various experiments, the reaction with an unsymmetrical ketone under what are termed thermodynamic conditions leads to products derived from the more substituted (thermodynamic) enolate anion. Thermodynamic control conditions typically use a base such as sodium methoxide or sodium amide in an alcohol solvent at reflux. The yields of this reaction are not always good, as when 2-butanone (37) reacts with NaOEt in ethanol for 1 day. Self-condensation at the more substituted carbon occurs to give the dehydrated aldol product 38 in 14% yield. Note that the second step uses aqueous acid and, under these conditions, elimination of water occurs. 

FIGURE 19.70 The base-catalyzed elimination of water from aldol. The reaction mechanism is ElcB. If no a hydrogen is available for eUmination, then the initial aldol product can he isolated as shown in... 

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