Aldol reactions driving force

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 investigation of the driving forces and robnstness of proline-catalyzed aldol reaction is performed by ntilizing the methodology of reaction progress kinetic analysis. 

The general mechanistic features of the aldol addition and condensation reactions of aldehydes and ketones were discussed in Section 7.7 of Part A, where these general mechanisms can be reviewed. That mechanistic discussion pertains to reactions occurring in hydroxylic solvents and under thermodynamic control. These conditions are useful for the preparation of aldehyde dimers (aldols) and certain a,(3-unsaturated aldehydes and ketones. For example, the mixed condensation of aromatic aldehydes with aliphatic aldehydes and ketones is often done under these conditions. The conjugation in the (3-aryl enones provides a driving force for the elimination step. 

Second step. The elements of CH4O3 are eliminated. The most likely by-products are H20 and HCOOH. Make None. Break C4-C5, C6-O8, 010-011. The base can deprotonate the OH on C5, and the lone pair on O can then push down to form a n bond with C5, causing the C4-C5 bond to break. The electrons keep getting pushed around until they end up on O again and the 0-0 bond is broken, providing the driving force for the step. A keto-aldehyde and formate anion are obtained. Now C7 (deprotonated) is nucleophilic and C6 is electrophilic, so an aldol reaction followed by dehydration gives the observed product. 

Driving Force of Aldol Additions and Survey of Reaction Products... 

Remember what we discussed in the context of Figure 13.44 ketones usually do not undergo aldol additions if they are deprotonated to only a small extent by an alkaline earth metal alkox-ide or hydroxide. The driving force behind that reaction simply is too weak. In fact, only a very few ketones can react with themselves in the presence of alkaline earth metal alkoxides or alkaline earth metal hydroxides. And if they do, they engage in an aldol condensation. Cyclopentanone and acetophenone, for example, show this reactivity. 

Remember what we discussed in the context of Figure 10.39 ketones usually do not undergo aldol additions if they are deprotonated to only a small extent by an alkaline earth metal alkoxide or hydroxide. The driving force behind that reaction simply is... 

The Michael-aldol process with methacrylates described in Section II.B can be also applied to the synthesis of substituted tetrahydrofurans, 245. If the reaction is carried out in THF, the yield and selectivity of the sequence decrease. It was proposed that the lithium coordination with THF molecules hinders the formation of the product 245. The authors concluded that the Lewis acidity of naked lithium cation is the key driving force for the reaction to proceed successfully. The tandem reaction with lithium thiophenolate, fumarate ester and benzaldehyde constitutes an useful methodology for the preparation of y-butyrolactone (Scheme 75)89,90. 

Aldol reactions are reversible, and you need to be able to recognize the reverse reaction, the retro-aldol reaction. Because a C—C cr bond is broken in the retro-aldol reaction, some driving force (e.g., relief of strain) is usually required for it to proceed to completion. 

Of course, under many conditions, the preformed enolate aldol reaction appears to be significantly exothermic. The additional driving force is presumably provided by the enthalpy of coordination of the ambident aldolate ion with a cation. The importance of cation solvation in providing a driving force for the aldol reaction has been elegantly demonstrated by Noyori and coworkers.In this important experiment, the tris(dimethylamino)sulfonium (TAS" ) enolate of l-phenyl-2-propanone was prepared as shown in equation (6). The naked enolate was obtained as a yellow crystalline material, free of trimethylsilyl fluoride, by concentration of the THF solution. 

For aldol reactions carried out under catalytic conditions, dehydration of the initial aldol may provide an additional driving force, due to formation of water (with two strong O—H bonds) and the enone system. Such reactions are almost always thermodynamically favorable. 

A model for the porphyrin metalation indicates its driving force empty space for the metal ion is provided in the protein-porphyrin complex. Antibody 38C2 efficiently catalyzes a wide variety of ketone-ketone, ketone-aldehyde, aldehyde-ketone, and aldehyde-aldehyde intermolecular cross-aldol reactions. 

The driving force for an aldol condensation is formation of a conjugated system. The reaction conditions required for an aldol condensation are only sfighdy more vigorous than the conditions required for an aldol addition reaction. Usually, an aldol condensation can be achieved by simply performing the reaction at an elevated temperature. In fact, in some cases, it is not even possible to isolate the p-hydroxyketone. As an example, consider the following case ... 

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