Aldol-dehydration, double

The final two stages are very straightforward. Oxidative scission of the C3-C5 double bond in 6 with ozone provides triketone 5 which, without purification, is subjected to a base-induced intramolecular aldol/dehydration reaction. The crystalline product obtained from this two-step sequence (45 % overall yield) was actually an 85 15 mixture of ( )-progesterone and a diastereomeric substance, epimeric at C-17. Two recrystallizations afforded racemic progesterone [( )-(1)] in diastereomerically pure form. 

Conjugation of the newly formed double bond with the carbonyl group stabilizes the a p unsaturated aldehyde provides the driving force for the dehydration and controls Its regioselectivity Dehydration can be effected by heating the aldol with acid or base Normally if the a p unsaturated aldehyde is the desired product all that is done is to carry out the base catalyzed aldol addition reaction at elevated temperature Under these conditions once the aldol addition product is formed it rapidly loses water to form the a p unsaturated aldehyde... 

The product is a P-hydroxy aldehyde (called an aldol) or ketone, which in some cases is dehydrated during the course of the reaction. Even if the dehydration is not spontaneous, it can usually be done easily, since the new double bond is in conjugation with the C=0 bond so that this is a method of preparing a,P-unsaturated aldehydes and ketones as well as P-hydroxy aldehydes and ketones. The entire reaction is an equilibrium (including the dehydration step), and a,P-unsaturated and P-hydroxy aldehydes and ketones can be cleaved by treatment with OH (the retrograde aldol reaction). There is evidence that an SET mechanism can intervene when the substrate is an aromatic ketone. ... 

Example Ester (59) was needed for a photochemical synthesis of chrysanthemate ester (60), a component of the pyrethrin insecticides. The a,B disconnection (59a) gives synthon (61) and aldehyde (62). This 8,y-unsaturated compound could be made by dehydration of (63) as the double bond can appear in only the required position. On page T 149 we discussed the synthesis of (62) by the aldol dimerisation of (64), An alternative strategy is to work at the ester oxidation level (65) which means synthon (66) is needed to combine with (64). 

Aldol reaction of the aldehyde with itself In some instances, dehydration of the aldol and subsequent hydrogenation of the double bond was also observed, as was reductive alkylation of the monoalkylglucamine by aldol-derived aldehydes. 

SAMPLE SOLUTION (a) Dehydration of the product of aldol addition of pen-tanal introduces the double bond between C-2 and C-3 to give an a,p-unsaturated aldehyde. 

Cyclic products can be formed by aldol additions provided the donor carbanion and acceptor carbonyl are part of the same molecule. For example, consider how the synthesis of 3-methyl-2-cyclohexenone could be achieved from acyclic substances. The carbon-carbon bond formed in this process of aldol addition closes the ring and ultimately becomes the double bond in the conjugated system when the aldol product undergoes dehydration. Working backwards, we have the sequence... 

The most generally useful preparation of a,/3-unsaturated carbonyl compounds is by dehydration of aldol addition products, as described in Section 17-3D. Conjugation of the carbonyl group and double bond has a marked influence on spectroscopic properties, particularly on ultraviolet spectra, as the result of... 

Trifluoracetic acid-promoted cyclization/dehydration is used to construct a dihydropyran-4-one ring during the total synthesis of (—)-maurenone, establishing the relative stereochemistry of the natural product <2006JOC117>. A double aldol reaction forms two dihydropyran-4-one rings during the total syntheses of (—)- and (+)-membrenone C <20030L1729>. 

Mixed aldol condensations can be employed if one of the aldehydes has no hydrogens on the a-carbon, so it cannot form an enolate ion and can only act as the electrophilic partner in the reaction. Aromatic aldehydes are especially useful in this role because the dehydration product has additional stabilization from the conjugation of the newly formed CC double bond with the aromatic ring. This stabilization makes the equilibrium for the formation of this product more favorable. 

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