Stobbe reaction succinic esters

The condensation of aldehydes and ketones with succinic esters in the presence of sodium ethoxide is known as the Stobbe condensation. The reaction with sodium ethoxide is comparatively slow and a httlo reduction of the ketonic compound to the carbinol usually occurs a shorter reaction time and a better yield is generally obtained with the more powerful condensing agent potassium ieri.-butoxide or with sodium hydride. Thus benzophenone condenses with diethyl succinate in the presence of potassium [Pg.919]

Succinic esters condense with aldehydes and ketones in the presence of bases, eg, sodium alkoxide or piperidine, to form monoesters of alkybdenesuccinic acids, eg, condensation of diethyl succinate with acetone yields ethyl 2-isopropyhdenesuccinate (eq. 3). This reaction, known as Stobbe condensation, is specific for succinic esters and substituted succinic esters (98,99). 

CH2,CH2,C02Et. From the latter the three-carbon unit of diethyl succinate may be recognised, and the Stobbe condensation is a suitable illustration of this process. Thus the reaction of aldehydes or ketones with succinic esters in the presence of potassium t-butoxide (or with sodium hydride) gives alkylidene-succinic acid esters (25). The reaction is somewhat slower in the case of the less basic sodium ethoxide. 

Instead of epoxides carbonyl compounds may be used as electrophiles to generate the y-hydroxy carboxylic acid intermediate. In the classical Stobbe reaction (equation 79) succinic esters are deprotonated and treated with aldehydes or ketones to form, via the unstable adduct (211), the paraconic ester (212). 

Stobbe reaction The addition of a 1,4-diester, i.e. a succinate derivative, under basic conditions, to a ketone, followed by an acidic work-up, resulting in an a,(3-unsaturated ester and a (3,y-unsaturated carboxylic acid functionalities. 

B.V. The Stobbe Condensation. When succinic ester derivatives (such as diethyl succinate, 215) are condensed with non-enolizable ketones or aldehydes in the presence of base, the initial condensation product is 216. The alkoxide reacts with the distal ester via acyl substitution to give a lactone intermediate (217). In the original version of this reaction, saponification of 217 gave the a-alkylidene monoester, 218. The reaction is not completely general and is limited to those a, co-diesters for which the Dieckmann condensation is not a... 

One reaction of dialkyl succinate—namely, Stobbe condensation—has played a key role in the synthesis of important pharmaceuticals. The reaction involves a base-catalyzed condensation of aldehydes or ketones with succinate esters 3 to yield itaconic acid derivatives Numerous pharmaceutical... 

Finally, the third method for synthesizing (478), developed by Johnson et al.[577,578], also starts from the Mannich base (496). Its condensation with cyanoacetic ester led to the cyanoke toes ter (493), which, by the Stobbe reaction with dimethyl succinate,formed compound (492). On hydrogenation of the double bond and angular methylation, this was converted into the cyanoester (489) which, in a similar manner to the preceding case, gave the intermediate (478) on treatment with methanolic hydrogen chloride. 

The first step of the Stobbe condensation is the deprotonation of the succinate at the a-carbon to afford an ester enolate that in situ undergoes an aldol reaction with the carbonyl compound to form a 3-alkoxy ester intermediate. The following intramolecular acyl substitution gives rise to a y-lactone intermediate which undergoes ring-opening and concomittant double bond formation upon deprotonation by the alkoxide ion. Under certain conditions the lactone intermediate can be isolated. 

The asymmetric total synthesis of (+)-codeine, the unnatural enantiomer, was accomplished by J.D. White and coworkers using an intramolecular carbenoid insertion as the key step. The first stereogenic center that directed all subsequent stereochemical events was installed by the asymmetric hydrogenation of an alkylidene succinate that was obtained using the Stobbe condensation. Dimethyl succinate and isovanillin were reacted in the presence of excess sodium methoxide at reflux and the resulting reaction mixture was acidified to obtain the monomethyl ester. 

Sommelet reaction, 33, 93 Sorbic acid, 5-hydroxy-/3-methyl, J-lactone, 32, 57 Stannic chloride, 33, 91 Stearic acid, 34, 15 Stearone, 33, 84 cis-Stilbene, 33, 88 fraws-Stilbene, 33, 89 Stirrer, for caustic fusion, 30, 104, 105 seal for, 30, 54 Stobbe condensation, 30, 18 Styrene, 33, 72 34, 85 reaction with sulfuric acid, 35, 83 Styrene dibromide, 30, 73 Styrene oxide, 31, 3 0-Styrenesulfonyl chloride, 34, 85 Succinic acid, 34, 44 Succinic acid, < -benzhydrylidene-, a-ETHYL ESTER, 30, 18 CLNNAMYL-, 31, 85 DIPHENYL ESTER, 34, 44 HEPTANOYL-, DIETHYL ESTER, 34, 51 PHENYL-, 30, 83 Succinic anhydride, 34, 40 SUCCINONITRILE, a, -DIPHENYL-, 32, 63 Sulfide, methyl 2-thienyl, 35, 85 Sulfonation of styrene, 34, 85 Sulfonyl chloride, from sodium sulfonate, 34, 85... 

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