Aldol Condensation and Michael Addition

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 Pd enolates also undergo intramolecular Michael addition when an enone of suitable size is present in the allyl d-keto ester 744[465]. The main product is the saturated ketone 745, hut the unsaturated ketone 746 and ally-lated product 747 are also obtained as byproducts. The Pd-catalyzed Michael 

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Several examples exist of the application of chiral natural N-compounds in base-catalyzed reactions. Thus, L-proline and cinchona alkaloids have been applied [35] in enantioselective aldol condensations and Michael addition. Techniques are available to heterogenize natural N-bases, such as ephedrine, by covalent binding to mesoporous ordered silica materials [36]. 

Surfaces with basic sites form enolates from both the aldehydes and ketones, leading to multiple aldol condensations and Michael additions. " Candidate molecules must be enolizable, i.e., contain an a-hydrogen atom. Aldol condensation / Michael addition products cover the range from a,p-unsaturated aldehydes, saturated aldehydes, hydrogenated products (alcohols), and the heavier aromatics resulting from multiple condensations. The presence of coordina-... 

The same research group accomplished a benign synthesis of Krohnke pyridines via sequential solventless aldol condensation and Michael addition (Scheme 2.2-3) [21b] these are prominent building blocks in supramolecular chemistry characterized by their jt-stacldng ability, H-bonding, and coordination. The reaction has been... 

Typical reactions of metal enolates are aldol condensation and Michael addition. As expected, Pd enolates undergo these two reactions. So far intramolecular reactions proceed efficiently. Intermolecular reactions are competitive with other reactions. Aldol condensation of the keto aldehyde 601 at room temperature provided the aldol product 602 in 82% yield [215]... 

Nitrile reacts with an aldehyde or an electron-withdrawing olefin, an aldol condensation or a Michael addition proceeds under neutral reaction conditions and a carbon-carbon bond forms selectively at the a-position of nitrile [66a,93]. For example, the aldol condensation and Michael addition are shown in eqs. (16.40) and (16.41). 

In principle, the synthesis of a consonant molecule or a bifunctional relationship within a more complex polyfunctional molecule, does not offer too many difficulties. In fact, all the classical synthetic methods of carbon-carbon bond formation that utilise reactions which are essentially reversible, lead to consonant relationships. For instance, the book by H.O. House "Modem Synthetic Reactions" [22], after dealing, for almost 500 pages, with functional group manipulations, devotes the last 350 pages to carbon-carbon bond formation, all of which lead to consonant relationships. These methods can, actually, be reduced to the following four classical condensations (and their variants) Claisen condensation, aldol condensation, Mannich condensation and Michael addition (Table 2.5). 

Shimizu. S. Shirakawa. S. Suzuki, T. Sasaki, Y. Water-soluble calixarenes as new inverse phase-transfer catalysts. Their application to aldol-type condensation and Michael addition reaction in water. Tetrahedron 2001. 57, 6169-6173. 

This chapter introduced the use of enolates and/or enamines as nucleophiles in several reactions, including aldol reactions, Claisen condensations and Michael additions, alkylations, and acylations. We can also use LDA to generate the enolate anions and perform the same reactions, as shown here for cyclohexanone and a few specific electrophiles. Similar reactions are possible for aldehydes and esters with a-hydrogens. The synthetic versatility of this approach has made LDA a very popular and important reagent in modem synthetic organic chemistry. 

This chapt er covered many C—C bond-forming reactions, including aldol reactions, Claisen condensations, and Michael addition reactions. Two or more of these reactions are often performed sequentially, providing a great deal of versatility and complexity in the type of stmctures that can be prepared. Propose a plausible mechanism for each of the following transformations. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Whilst simple alkylations of enolates and Michael additions have been successfully catalyzed by phase-transfer catalysts, aldol-type processes have proved more problematic. This difficulty is due largely o the reversible nature of the aldol reaction, resulting in the formation of a thermodynamically more stable aldol product rather than the kinetically favored product. However, by trapping the initial aldol product as soon as it is formed, asymmetric aldol-type reactions can be carried out under phase-transfer catalysis. This is the basis of the Darzens condensation (Scheme 8.2), in which the phase-transfer catalyst first induces the deprotonation of an a-halo... 

The intramolecular nucleophilic addition of the formyl group to the electron deficient alkene unit in the propenoate (10) affords a benzofuranone when catalysed by a thiazolium salt. However, when NaCN is used as the catalyst, an initial Michael addition to the acrylate function is followed by an intramolecular aldol condensation and the chroman (11) is formed. The corresponding butanoates afford chroman-4-ones under the influence of thiazolium cations, but give benzoxepins in the presence of a basic catalyst (95S1311). 

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. 

This is one of the more complicated-looking syntheses that we have seen. First, analyze the product for the two Michael components. The carbon-carbon double bond arises from dehydration of the aldol addition product, and is located where one of the two C=0 groups of the original diketone used to be. The Michael addition takes place at the carbon between these ketone groups. The Michael acceptor is an enone that can also enter into the aldol condensation and furnishes the methyl group attached to the double bond. 

Corma et al. have also tested MCM-410H in the aldol condensation between benzaldehyde and 2 -hydroxyacetophenone. They showed that this material catalyzed successive aldol condensation and intramolecular Michael reaction addition to give flavone with good selectivity. Chromenes can be also produced by condensation of salicylaldehyde derivatives and diethylglucotaconate under mild conditions (Figure 9). 

In this article, we describe the first total syntheses of oscillatoxin D and 30-methyloscillatoxin D. The construction of the spiroether moiety has been achieved by biomimetic intramolecular aldol condensation and intramolecular Michael-type addition as key steps. Furthermore, some analogues of oscillatoxin D, which play an important role on the structure-activity relationship, can be prepared by our synthetic route. 

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