Decarboxylation aldol condensation

Scheme 3 Aldol condensation/decarboxylation of two adsorbed carboxylates...

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 method was applied to the synthesis of (-t-)-l9-nortestosterone by the following sequence of reactions. Michael addition of the bisannulation reagent 124 to the optically active keto ester 129 and decarboxylation afforded 130, and subsequent aldol condensation gave 131. Selective Pd-catalyzed oxidation of the terminal double bond afforded the diketone 132 in 78% yield. Reduction of the double bond and aldol condensation gave ( + )-19-nortestosterone (133)[114]. 

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]... 

One of the several mechanisms for decarboxylation is the reverse of the familiar carboxylation reaction of organometallic compounds or carbanions. Many of the acids RCOOH that are readily decarboxylated in basic media are compounds for which the corresponding R( ) is a comparatively stable carbanion.405 The postulated intermediate has actually been trapped or diverted in a few cases as the product of an aldol condensation.406... 

Figure 5.8 Examples of formation and cleavage of carbon-carbon bonds (a) aldol condensation, (b) Claisen ester condensation and (c) decarboxylation of a P-keto acid. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

Pyrrolo[3,4-c][l,5]-benzothiazepin-3-ones 300 are available from ketoester 299 by a three-step sequence which includes hydrolysis and decarboxylation, aldol condensation and cyclization with o-aminothiophenol (Equation (35) (1993CE773)). 

A pentopyranoside-fused butenolide is the key intermediate for the synthesis of the natural micotoxin patulin [226, 227]. Its synthesis involves Wittig olefination of a 3,4-di-O-protected arabinopyran-2-uloside, followed by protecting group removal and dehydration (Scheme 47). In other research, the glucopyranosid-2-uloside 190 was converted into the butenolide derivative 191 by aldol condensation with diethyl malonate and transesterification [228]. The latter was shown to be prone to autoxi-dation, leading to 192. Subsequent Michael addition with hydroxide ion, followed by decarboxylation, furnishes C-branched-chain sugar 193. 

The dibasic side chain at position 7 can be alternatively provided by a substituted amino alkyl pyrrolidine. Preparation of that diamine in chiral form starts with the extension of the ester function in pyrrolidone (46-1) by aldol condensation with ethyl acetate (46-2). Acid hydrolysis of the (3-ketoester leads to the free acid that then decarboxylates to form an acetyl group (46-3). The carbonyl group is next converted to an amine by sequential reaction with hydroxylamine to form the oxime, followed by catalytic hydrogenation. The desired isomer (46-4) is then separated... 

Diethyl 2-oxobutanedioate undergoes an aldol condensation with aldehydes to yield the substituted dione which after hydrolysis and decarboxylation affords the 2,6-dicarboxylic acid (Scheme 16). The cyclization of this acid provides a useful synthesis of 4//-pyran-2,6-dicarboxylic acids (74ACS(B)517). It is unfortunate that attempted decarboxylation to the simple pyran fails, resulting in extensive decomposition. An earlier report (710PP243) summarizes previous work in this area and gives preparative details for the dicarboxylic acids. 

One hydroxyl is missing, and a new hydroxyl has been incorporated adjacent to the methyl. Without any evidence for the sequence of such reactions, the structure of intermediate 2 shows the result of three aldol condensations and reduction of a carbonyl. A dehydration reaction, two oxidations, and a decarboxylation are necessary to attain the islandicin structure. In chrysophanol, aloe-emodin, and rhein, the same oxygen function is lost by reduction as in islandicin, and decarboxylation also occurs. The three compounds... 

Many compounds will undergo dimerization reactions those containing thiols (e.g., disulfide formation) olefins, alcohols, and carboxylic acids (or other carbonyl chemistry e.g., aldol condensation reactions). Indoles have been shown to dimerize under acidic conditions. The dimerization is presumed to occur as shown in Figure 120 via protonation at C3 and nucleophilic attack of a second indole on C2. Phenols have been shown to dimerize under free radical initiated oxidative conditions, usually to ortho phenols. Nalidixic acid API undergoes dimerization under thermolysis conditions to decarboxylate and produce a dimeric structure (Fig. 121) (172). 

Step 2 Dimethyl acetal hydrolysis ester hydrolysis followed by decarboxylation intramolecular acid-catalyzed aldol condensation followed by dehydration. 

Which of the following steps doesn t occur in the synthesis of isopentenyl diphosphate (a) Claisen condensation (b) oxidation (c) aldol condensation (d) decarboxylation... 

The interest in the mechanisms of SchifF base hydrolysis stems largely from the fact that the formation and decomposition of SchifF base linkages play an important role in a variety of enzymatic reactions, for example, carbonyl transfers involving pyridoxal phosphate, aldol condensations, /3-decarboxylations and transaminations. The mechanisms for the formation and hydrolysis of biologically important SchifF bases, and imine intermediates, have been discussed by Bruice and Benkovic (1966) and by Jencks (1969). As the consequence of a number of studies (Jencks, 1959 Cordes and Jencks, 1962, 1963 Reeves, 1962 Koehler et al., 1964), the mechanisms for the hydrolysis of comparatively simple SchifF bases are reasonably well understood. From the results of a comprehensive kinetic investigation, the mechanisms for the hydrolysis of m- and p-substituted benzylidine-l,l-dimethylethylamines in the entire pH range (see, for example, the open circles in Fig. 13) have been discussed in terms of equations (23-26) (Cordes and Jencks, 1963) ... 

Many arylated cyclohexanone and 1,3-cyclohexadione derivatives are synthesized through aldol condensations, in many cases in combination with Michael additions. Some examples are given below Petrows ketone98 via bromination at low temperature, hydrolysis and decarboxylation gives 3,5-diphenylphenol... 

Certain substituted cyclohexenones are made by an analogous internal aldol condensation and decarboxylation of his-estets resulting from condensation of aldehydes with acetoacetic ester. 

---