Aldol reactions General considerations

Allyltributyltin, 10 Boron trifluoride etherate, 43 Di-jjL-carbonylhexacarbonyldicobalt, 99 Grignard reagents, 138 Ketenylidenetriphenvlphosphorane, 154 Methoxyamine, 177 Reformatsky reagent, 346 Tin(IV) chloride, 300 Tributylcrotyltin, 10 Aldol reactions General considerations, 202 Directed aldols using imines Norephedrine, 200... 

Aldoses generally undergo benzilic acid-type rearrangements to produce saccharinic acids, as well as reverse aldol (retro-aldol) reactions with j3-elimination, to afford a-dicarbonyl compounds. The products of these reactions are in considerable evidence at elevated temperatures. The conversions of ketoses and alduronic acids, however, are also of definite interest and will be emphasized as well. Furthermore, aldoses undergo anomerization and aldose-ketose isomerization (the Lobry de Bruyn-Alberda van Ekenstein transformation ) in aqueous base. However, both of these isomerizations are more appropriately studied at room temperature, and will be considered only in the context of other mechanisms. 

III. Aldol Additions and Other C-C Bond-forming Reactions 1. General Considerations... 

In particular, we have described selected examples of the application of monofunctional supported catalysts in reactions of considerable synthetic interest such as aldol, Michael and Knoevenagel condensations. In general. 

The rate of the reaction changes depending upon the partial pressure of CO it reaches a maximum at ca 3 MPa. The yield of the reaction decreases as the temperature increases. At low temperatures the rate of the hydroformylation is small and therefore higher temperatures are applied. Hydroformylation allows the preparation of various valuable products because the oxo synthesis may utilize different compounds containing a carbon-carbon double bond, for example, dienes, polyenes, and unsaturated aldehydes, ketones, nitriles, alcohols, esters, etc. For example, dienes may afford dialdehydes. A substantial amount of aldehydes is converted to alcohols which find considerable application in the preparation of detergents, plasticizers, and lubricants. The aldol condensation generally is not desired in hydroformylation processes. Nevertheless, via aldol condensation followed by hydrogenation, 2-ethylhexanol is obtained from n-butyraldehyde see equation (13.117). 

Furthermore, at pH 9 the equihbrium between P-pyranone and cyclopentenone is significantly shifted in fiivor to the latter. This ct can be explained, because the isomerization proceeds via an intramolecular aldol reaction ch is generally favored at higher pH values (Figure 10). Moreover fiiranoneamine (8), a condensation product of amine and glucosyl isomaltol, can be detected in considerable amounts under these conditions. 

The reaction starts by a proton transfer from the reaction molecule (aldehyde) to the catalyst base B forming an intermediate which can further react in the second step with another molecule of aldehyde, giving the second intermediate X2. This second step is usually considered in the hterature as irreversible, while the last step (abstraction of proton from a conjugate acid leading to aldol) is assumed to be fast thus, the rate of this step does not appear in the rate equation. Following the general considerations discussed in Chapter 4, we can directly write the expression for the reaction rate, if the second step is irreversible ... 

The careful mechanistic studies that have been documented by Evans are a highly attractive aspect associated with these catalyst systems, and the work is well worth consulting for the practical and mechanistic insight it provides [152, 154, 155]. The investigations have permitted an understanding of the structural and coordination chemistry of the metal complexes, which is sure to have a positive impact on the evolution of enantioselective catalysts. For example, Evans has noted that the general addition of TMSOTf can lead to considerable acceleration in the aldol reaction. Thus, the addition reaction of pyruvate and trimethylsilyl tert-butyl thioketene acetal mediated by 2 mol % of copper(bisoxazoline) affords product in 97 % ee over the course of 14 hours when the same reaction is conducted with one equivalent of TMSOTf and Cu catalyst under otherwise identical conditions, reaction is observed to reach completion in 35 minutes, with no deterioration in enan-... 

With these two relationships, if reliable values of and Wp can be determined and G established for a reaction series, the activation barriers can be calculated from the thermodynamic data that provide AG°. Relationships of this kind have been shown to occur in many different organic reactions, so the principles appear to have considerable generality. For example, Guthrie investigated both the addition (Step 2) and elimination (Step 4) parts of the aldol condensation reaction (see p. 283-285). Steps (1) and (3) are proton transfers that are fast under the reaction conditions. 

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