Aldol reactions products

Other multifunctional hydroxycarboxylic acids are mevalonic and aldonic acids which can be prepared for specialized uses as aldol reaction products (mevalonic acid [150-97-0] (13)) and mild oxidation of aldoses (aldonic acids). 

Neopentyl glycol (2,2-dimethyl-1-propanol [126-30-7]) another important iadustrial derivative of isobutyraldehyde, is obtained from the aldol reaction product of isobutyraldehyde with formaldehyde followed by hydrogenation. 

Problem 23.1 Predict the aldol reaction product of the following compounds ... 

The reaction of an a-halo carbonyl compound with zinc, tin, or indium together with an aldehyde in water gave a direct cross-aldol reaction product (Eq. 8.90).226,227 A direct Reformatsky-type reaction occurred when an aromatic aldehyde reacted with an a-bromo ester in water mediated by zinc in low yields. Recently, it was found that such a reaction mediated by indium was successful and was promoted by son-ication (Eq. 8.91).228 The combination of BiCl3-Al,229 CdCl2-Sm,230 and Zn-Et3B-Eb0231 is also an effective mediator. Bismuth metal, upon activation by zinc fluoride, effected the crossed aldol reaction between a-bromo carbonyl compounds and aldehydes in aqueous media. The reaction was found to be regiospecific and syn-diastereoselective (Eq. 8.92).232... 

Selective retro-aldol has also been reported by using aqueous HC1 in THF.243 Recently, catalytic aldol reactions in aqueous media have generated great interest due to the atom-economy related to the reaction. Reaction of 2-alkyl-1,3-diketones with the aqueous formaldehyde using aqueous 6-10 M potassium carbonate as base afforded aldol reaction products, which are cleaved by the base to give vinyl ketones (Eq. 8.96).244... 

Table 3-3). Although the initial step is an a-acylation reaction, the final resultant compound can still be considered an aldol reaction product.

Entries 1 and 2 in Scheme 2.1 illustrate the preparation of aldol reaction products by the base-catalyzed mechanism. In entry 1, the product is a /< -hydroxya I dehyde, whereas in entry 2 dehydration has occurred and the product is an a,/f-unsaturated aldehyde. 

The quite complicated configurational assignments of the aldol reaction products from... 

If the above reaction is carried out with heating, then a different product is obtained (Fig.K). This arises from elimination of a molecule of water from the Aldol reaction product. The two reasons for occurrence of this reaction are First, the product still has an... 

The mechanism of dehydration is shown below (Fig.L). First of all, the acidic proton is removed and a new enolate ion is formed. The electrons in the enolate ion can then move in such a fashion that the hydroxyl group is expelled to give the final product, i.e. an a, p-unsaturated aldehyde. In this example, it is possible to change the conditions such that one gets the Aldol reaction product or the a, P-unsaturated aldehyde, but in some cases only the a, p-unsaturated carbonyl product is obtained, particularly when extended conjugation is possible. 

Benzoyl-4,6-dihydrothieno[3,4-c]furan-5,5-dioxide (206) has been prepared from compound (200) via the stannane (204) and benzoyl chloride in the presence of Pd(PPh3)4 as a catalyst. The aldol reaction product (205) is oxidized to the same product (206) (Scheme 13) <92CC870>. 

Aromatic ketones bearing a-hydrogens give aldol reaction products readily, but in this case the aldol product spontaneously loses water to form the unsaturated ketone. When benzaldehyde is used in the crossed-aldol condensation the final product is the unsaturated aldehyde or ketone. Conjugation of the double bond with the aromatic ring is the reason for the spontaneous dehydration (Scheme 3.13). 

Let s now consider the stoichiometry of the added base needed when performing an enolate reaction. In an aldol reaction carried out with an aldehyde and hydroxide, the amount of hydroxide has a minimal effect on yield. The hydroxide catalyst produces very little enolate in the equilibrium established for the first deprotonation step (about one part in a thousand). The addition of more hydroxide leads to slightly more enolate intermediate (up to a few parts per thousand), speeding up the overall aldol reaction but not changing the outcome. The key is that even with an excess of hydroxide, unreacted aldehyde persists. Therefore, using more than an equivalent of hydroxide would not substantially change aldol reaction product yields. 

Several methods have been developed for the preparation of a,3-unsaturated iron acyl complexes, a class of complex which is synthetically valuable because its members may be stereoselectively elaborated at two positions. Methylation of the hydroxy group of an aldol reaction product to give 16 followed by sodium hydride-promoted elimination generates the ( )-unsatu-rated iron acyl complex 17, in many cases exclusively (Scheme 4.9) Since this selectivity is irrespective of the hydroxy group configuration, it is not... 

The antibodies also catalyzed retro-aldol reactions of secondary [9, 11, 16] and tertiary aldols [10]. In these retro-aldol reactions antibodies 38C2 and 33F12 processed hydroxyketones whose stereochemistry was the same as that of the aldol reaction product. Kinetic resolution by the retro-aldol reaction therefore provided the opposite enantiomer from the forward aldol reaction (Scheme 6.5 and Table 6.2). For example, (K)-14 (> 99% ee) was obtained by the 38C2-catalyzed kinetic resolution of ( )-14 (Table 6.2) whereas... 

The key to a successful two-step aldol strategy is that the first aldol reaction product must not form a stable cyclic hemiacetal (Table 10.19) [167,168]. The starting aldehyde acceptor must therefore be carefully selected or strategically protected to prevent the reaction stopping after the first addition step. Higher order sequences are usually impossible after two successive additions due to... 

Chocolate represents a highly complex flavor system for which no single character impact has been identified. Vanillin and Furaneol contribute to the sweet, caramel background character of milk chocolate (57). 5-Methyl-2-phenyl-2-hexenal provides a deep bitter, cocoa note, and is the aldol reaction product from phenylacetaldehyde and 3-methylbutanal, two Strecker aldehydes formed in chocolate (58). 2-Methoxy-5-methylpyrazine and isoamyl phenylacetate have chocolate, cocoa, nutty and cocoa-like notes, respectively, and both are used in synthetic chocolate flavors (59). Systematic studies of key odorants in milk chocolate were performed using aroma extract dilution analysis however, character impact compounds unique to chocolate flavor were not reported (57,60). 

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