Aldol reactions general features

Note that harsher conditions may lead to further changes, e.g. epimerization at C-3 in fmctose, plus isomerization, or even reverse aldol reactions (see Section 10.3). In general, basic conditions must be employed with care if isomerizations are to be avoided. To preserve stereochemistry, it is usual to ensure that free carbonyl groups are converted to acetals or ketals (glycosides, see Section 12.4) before basic reagents are used. Isomerization of sugars via enediol intermediates features prominently in the glycolytic pathway of intermediary metabolism (see Box 10.1). 

In addition to broad-scope substrate specificity, 38C2 exhibits high enantioselectivity for the aldol reaction. Although this high degree of enantioselectivity has been observed for antibody-catalyzed ester hydrolysis reactions, it is certainly not a feature common to all such catalysts (Janda et al., 1989 Lo et al., 1997 Pollack et al., 1989 Tanaka et al., 1996 Wade and Scanlan, 1996). Furthermore, the rules for the enantioselectivity for 38C2-catalyzed aldol reactions are both simple and general (Hoffmann et al., 1998). For most ketone donors, attack occurs on the si side of the acceptor. However, when a ketone with an a-hydroxy substituent (such as hydroxyacetone) acts as donor, attack occurs on the reside (Scheme 5). 

These two examples illustrate the general features of the aldol reaction. The a carbon of one carbonyl component becomes bonded to the carbonyl carbon of the other component. 

The use of Ln(OTf)3 in the activation of aldehydes other than formaldehyde was also investigated [18], Several examples of the present aldol reaction of silyl enol ethers with aldehydes are listed in Table 14-1. In every case, the aldol adducts were obtained in high yields in the presence of a catalytic amount of Yb(OTf)3, Gd(OTf)3, or Lu(OTf)3 in aqueous media. Diastereoselectivities were generally good to moderate. One feature in the present reaction is that water-soluble aldehydes, for instance, acetaldehyde, acrolein, and chloroacetaldehyde, can be reacted with silyl enol ethers to afford the corresponding cross aldol adducts in high yields (entries 5-7). Some of these aldehydes are commercially supplied as water solutions and are appropriate for direct use. Phenylglyoxal monohydrate also worked well (entry 8). It is known that water often interferes with the aldol reactions of aldehydes with metal enolates and that, in the cases where such water... 

Unlike the parent ene reaction, where both the ene and eneophile are alkenes, in this modification the reacting partners are clearly differentiated. Furthermore, the carbonyl group is activated as an eneophile in the presence of Lewis acids and virtually all useful examples of both relative and absolute stereochemical control are effected in this fashion. Nonetheless, the intermolecular variant is generally only practical when the carbonyl group has special features that both enhance its reactivity, typically by introducing a functionality that destabilizes the partial positive charge on the carbonyl carbon, and limit or prevent alternative processes such as aldol reactions. 

An interesting feature of the Crimmins thiazoldinethione is that either the Evans syn or non-Evans syn adducts can be prepared through a variation in the amount of (-)-sparteine (or other diamine bases, such as DIEA and TMEDA) utilized. The yields, diastereoselectivities and enantioselectivities of the reaction are generally high and can be used in the acetate aldol reaction. ... 

The traditional aldol reaction has been the subject of several revie vs, among vhich the summary by Nielsen and Houlihan in Organic Reactions in 1968 is a classical contribution and a very valuable survey [1]. The subject has also been treated in House s monograph [2] and, more recently, by Heathcock [3]. Thus, only general features and few representative examples of traditional aldol addition vill be given here the reader is referred to the above-mentioned surveys for more details. 

An aldol reaction of preformed enolates requires three individual steps the irreversible generation of the metal enolate 143 (mostly by deprotonation but also by alternative methods outlined in Chapter 2), the addition of the aldehyde that leads to a metal aldolate 144, and, finally, the hydrolysis that yields the fi-hydroxy carbonyl compound (Scheme 4.28). Usually, the first two steps are performed in a one-pot reaction and the third one in the course of a quenching operation at the beginning of the work-up procedure. In the aldolate 144, the metal is generally chelated, a feature that contributes to its thermodynamic stability and... 

The Henry reaction is a base-catalyzed C-C bond-forming reaction between nitroalkanes and aldehydes or ketones. It is similar to the aldol addition, and is also referred to as the nitroaldol reaction. Since its discovery in 1895 [1] the Henry reaction has become one of the most useful reactions for the formation of C-C bonds, and most particularly for the synthesis of P-nitroalcohol derivatives [2]. The general features of this reaction are (i) the potential offered by the nitro and hydroxyl groups on the products for transformation into other compound families such as P-amino alcohols, P-amino acids, or nitroalkenes (ii) only a catalytic amount of base is required (iii) up to two contiguous stereogenic centers may be created in a single step concomitantly to the C-C bond formation. Several recent reviews with a focus on the asymmetric Henry reaction and its applications have appeared [3j. 

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. 

---