Aldol condensation, aldehydes intramolecular

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]. 

Give the structure of the product denved by intramolecular aldol condensation of the keto aldehyde shown... 

Original Synthesis. The first attempted synthesis of i7-biotin in 1945 afforded racemic biotin (Fig. I). In this synthetic pathway, L-cysteine [52-90-4] (2) was converted to the methyl ester [5472-74-2] (3). An intramolecular Dieckmaim condensation, during which stereochemical integrity was lost, was followed by decarboxylation to afford the thiophanone [57752-72-4] (4). Aldol condensation of the thiophanone with the aldehyde ester [6026-86-4]... 

The reaction of hexa-2,4-diyn-l-al (64) with mercaptoacetaldehyde leads to 2-formyl-5-(prop-l-ynyl)thiophene (65). The addition direction is governed by the aldehyde group via intramolecular aldol condensation in the intermediate (77HOU947). 

The aldol reaction is a carbonyl condensation that occurs between two aldehyde or ketone molecules. Aldol reactions are reversible, leading first to a /3-hydroxy aldehyde or ketone and then to an cr,/6-unsaturated product. Mixed aldol condensations between two different aldehydes or ketones generally give a mixture of all four possible products. A mixed reaction can be successful, however, if one of the two partners is an unusually good donor (ethyl aceto-acetate, for instance) or if it can act only as an acceptor (formaldehyde and benzaldehyde, for instance). Intramolecular aldol condensations of 1,4- and 1,5-diketones are also successful and provide a good way to make five-and six-inembered rings. 

Scheme 2.10 illustrates intramolecular aldol condensations. Entries 1 and 2 are cases of formation of five-membered rings, with aldehyde groups serving as the electrophilic center. The regioselectivity in Entry 1 is due to the potential for dehydration of only one of the cyclic aldol adducts. 

Recently, Trost et al. reported the vanadium-catalyzed addition reaction of 2,3-allenols [180], Here the oxygen in 401 served as an intramolecular nucleophile to attack the center carbon atom of allene to form a vanadium enolate 402. Aldol condensation of 402 with an aldehyde afforded (2-hydroxy)alkyl vinylic ketones 403. 

The proline-mediated intramolecular aldol condensation of dialdehyde substrates was also reported by List in 2003, affording enantioselective synthesis of cyclic p-hydroxy aldehydes via a 6-e ofexo-aldolization reaction (Scheme 11.7d). 

J0rgensen has also reported a sequential Michael/Michael/aldol condensation for the three component coupling of malonitrile 111 and a,P-unsaturated aldehydes that involves two iminium ion catalysed Michael additions followed by an intramolecular aldol condensation (Scheme 43) [170]. Using diarylprolinol ether 55 (10 mol%) in a concentrated toluene solution of malonitrile 111 and 3 equivalents of a,P-unsaturated aldehyde the reaction products can be isolated in just 1 8 h (57-89% yield 97-99% ee). The atom efficiency of this three component reaction is remarkable and the ability to prepare these complex products under... 

Intramolecular methanesulfonamide anion alkylation and aldol condensation reactions have been employed for the synthesis of 2,1-benzothiazine 2,2-dioxides. For instance, Blondet and Pascal have utilized such a process for the formation of compounds 225 and 226 from ortV o-substituted aldehyde 227 and alkyl chloride 228, respectively (Scheme 30) <1994TL2911>. 

Aldehydes and ketones, obtained by Swern oxidation, may suffer in situ intramolecular aldol condensations, resulting in very elegant construction of cycles.237b... 

The catalyzed reaction of 1 with a,P-enals takes an unexpected course. The adduct with methacrolein, for example, obtained after silyl ether cleavage does not contain the expected aldehyde group, but has the bicyclic structure 5. Apparently the initial product a undergoes an intramolecular aldol condensation to give b. which undergoes silyl transfertoc, which is hydrolyzed by acid to the 7-hydroxy-bicyclo[2.2.1 Jheptanone 5. 

Cyclization of the resulting keto aldehyde is an intramolecular aldol condensation. Base is required. 

Intramolecular aldol condensations occur best when a five- or six-membered ring is formed. Carbon-carbon bond formation therefore involves the aldehyde and the methyl group attached to the ketone carbonyl. 

A broad variety of special aldehydes and ketones are easily accessible by Heck-type reactions with allylic alcohols and their homologs [3]. The potential for the synthesis of carbocydic structures is illustrated by the macrocyde 11 [4] which obviously is the product of a fourfold Heck reaction (Scheme 3). A domino process consisting of a double Heck reaction followed by an intramolecular Aldol condensation leads to the annulated ring system 15 [5]. 

Chemoselective crossed aldol condensations between two different C,H-acidic aldehydes are impossible. There is only a single exception, and that is the intramolecular aldol condensation of an unsymmetrical dialdehyde. 

B as an ester- or lactone-substituted aldehyde enolate. Such enolates undergo condensations with all kinds of aldehydes, including paraformaldehyde. An adduct E is formed initially, acy-lating itself as soon as it is heated. The reaction could proceed intramolecularly via the tetrahedral intermediate D or intermolecularly as a retro-Claisen condensation. In both cases, the result is an acyloxy-substituted ester enolate. In the example given in Figure 13.50, this is the formyloxy-substituted lactone enolate C. As in the second step of an Elcb elimination, C eliminates the sodium salt of a carboxylic acid. The a,/)-unsaturated ester (in Figure 13.50 the 0J,/3-unsaturated lactone) remains as the aldol condensation product derived from the initial ester (here, a lactone) and the added aldehyde (here, paraformaldehyde). 

Fig (8) The transformation of lactone (53) to keto ester (58) is described. The unsaturated aldehyde (59) is converted to tricyclic ketone (60) by two steps (Michael addition, and intramolecular aldol condensation). And this on subjection to aromatization and hydrogenation respectively leads the formation of (62) whose transformation to (+)0-methyl pisiferic acid (2) is accomplished by methylation and hydrolisis. 

Ketones are less reactive electrophiles than aldehydes. Therefore, the aldol condensation of ketones is not often used because the equilibrium is unfavorable. However, the intramolecular condensation of diketones is useful if the size of the resulting ring is fa-... 

Earlier syntheses of arylquinolizidine alkaloids mainly utilized the pelletierine condensation to construct the basic skeleton, 4-aryl-2-quinolizidinone (11) (Scheme 1). Two mechanistic pathways, involving (a) initial aldol condensation of pelletierine (8) with an aromatic aldehyde followed by intramolecular Michael-type addition of the resulting enone 9 (6, 7) and (b) a Mannich-type reaction through 10 (8, 9), were proposed without any experimental evidence. Preparation and cyclization studies of the intermediate 9, however, gave conclusive evidence to show that the pelletierine condensation proceeded through pathway a (10). 

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