Enolates aldol condensation reactions

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

The best method to achieve a high regioselectivity is the use of preformed enolates. A double annulation reaction is possible if, for example, a diketone such as 11 is used as starting material. The product of the Michael addition 12 can undergo two subsequent aldol condensation reactions to yield the tricyclic dienone 13 ... 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

Crossed aldol condensation reactions may present a problem because multiple products can be formed. For example, a mixture of carbonyl A and carbonyl B can give two different enolates, each of which can then attack either an A or a B molecule. Therefore, four products are possible (Ag, A + B, B + A, and B2). 

The carbon alpha to the carbonyl of aldehydes and ketones can act as a nucleophile in reactions with other electrophilic compounds or intermolecu-larly with itself. The nucleophilic character is imparted via the keto-enol tau-tomerism. A classic example of this reactivity is seen in the aldol condensation (41), as shown in Figure 23. Note that the aldol condensation is potentially reversible (retro-aldol), and compounds containing a carbonyl with a hydroxyl at the (3-position will often undergo the retro-aldol reaction. The aldol condensation reaction is catalyzed by both acids and bases. Aldol products undergo a reversible dehydration reaction (Fig. 23) that is acid or base catalyzed. The dehydration proceeds through an enol intermediate to form the a,(3-unsaturated carbonyl containing compound. 

Asymmetric. syn-aldol condensation reactions employing chiral auxiliaries were reported in 1981 by both Masamune et al.2 and Evans et al.3 Masamune et al. introduced boron enolates obtained from (.S )-mandclic acid, which underwent... 

Aldol condensation reaction (Section 23.1) the nucleophilic addition of an enol or enolate ion to a ketone or aldehyde, yielding a p-hydroxy ketone. 

Stereoselective aldol condensations. Reaction of these substrates (1) with LDA results in decomposition, but the tin(II) enolates can be obtained by use of tin(II) triflate (11, 525) in the presence of N-ethylpiperidine. Addition of aldehydes to the enolates results in formation of p-hydroxy ketones (2) with high iyn-selectivity. 

The tin(IV) enolate can be quenched with a variety of electrophiles to form new carbon-carbon bonds, including carbonyl addition (aldol-type) reactions, alkylations and conjugate additions of tin(IV) enolates. Tin(IV) enolates react readily with aldehydes in both intra- and intermolecular aldol-type reactions [5J]. The best conditions for the intermolecular aldol condensation reaction were to initially generate the tin enolate by reacting the desired enone with tributyltin hydride and then... 

It is also possible to induce aldol condensation reactions under acidic conditions. When 137 was treated with tosic acid in hot benzene (40-50°C), the normal keto-enol tautomerism equilibrium was shifted to favor enol 138. The enol attacked the carbonyl on the pyridone in an intramolecular aldol cyclization, producing aldol 139. Elimination of water under the reaction conditions gave an 84% yield of 140 in Comins synthesis... 

A similar model has been applied to aldol condensation reactions of boron enolates. O The reaction of E) enolate 369, for example, can lead to either transition state 371 or 372. Transition state 371 generates the... 

Condensation Reactions. Traditionally, intermolecular aldol condensation reactions have been performed under equilibrating conditions using weaker bases than r-BuOK in protic solvents. Since the mid-1970s, new methodology has focused on directed aldol condensations which involve the use of preformed Lithium and (jroup 2 enolates, (Troup 13 enolates, and transition metal enolates. Although examples of the use of f-BuOK in intramolecular aldol condensations are limited, complex diketones... 

Kim, H. Y, Li, J-Y, Oh, K. (2013). A Soft Vinyl Enolization Approach to a-Acylvinyl Anions Direct Aldol/Aldol Condensation Reactions of (E)-P-Chlorovinyl Ketones. Angewandte Chemie International Edition, 52, 3736-3740. 

This simple example illustrates that mixed aldol condensation reactions may be problematic. If the enolate anion is formed in the presence of an aldehyde or ketone with no a-hydrogens, there is a short list of possible partners. This situation constituted the state of the art for nearly a century, until chemists eventually found experimental conditions that permit a mixed aldol to proceed under conditions that allow one to predict one product as the msgor product. 

When acetone reacts with NaOEt in ethanol to form enolate anion 27, it is a reversible acid-base reaction. Therefore, unreacted ketone or aldehyde always remains in the reaction, and this fact allows self-condensation to occur. Is it possible to choose a base that will generate the enolate anion, but the equilibrium is pushed far to the right (toward the enolate anion product) If such a base is available, self-condensation is much less of a problem, which is particularly important for mixed aldol condensation reactions. As chemists experimented to find such a base, it was discovered that amide bases (RaNr), derived from secondary amines (R2NH) accomplished this goal. 

You attempt a mixed aldol condensation reaction with pentanal as the enolate anion precursor and hexanal as the carbonyl reactant in the following way. You add pentanol to ethanol, add NaOEt, and bring the reaction to reflux. After 1 hour, you add hexanal and then reflux for an hour before cooling... 

Scheme 9.48. The use of a (Z)-silyl enol ether derivative of ethyl phenyl ketone in the aldol condensation reaction with ethanal (acetaldehyde, CH3CHO) in the presence of a Lewis acid (MXn). The Miikaiyama aldol reaction.

A remote alkoxy group on optically active o ,jS-epoxyaldehydes has been found not to influence noticeably the diastereoselectivity of their aldol condensation reactions with ester enolate. ... 

Although aminocatalysis of the aldol reaction via enamine intermediates is an important enzymatic strategy and several bioorganic studies of the subject have appeared, applications in preparative organic synthesis, particularly in intermolecular aldol addition reactions, have been published only sporadically. Despite the often-used Mukaiyama-aldol reaction of enol ethers and Stork s vell-developed enamine chemistry [37, 38], aldolizations of preformed enamines are rare. One report describes Le vis acid-catalyzed aldolizations of preformed enamines vith aldehydes that furnish aldol addition products [39]. Aldol condensation reactions of preformed enamines vith aldehydes have also been described [40]. Only enamine-catalytic aldolizations, vhich are primary and secondary amine-catalyzed aldol reactions, vill be discussed in this chapter, ho vever. 

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