Lanthanide metal enolates aldol reaction

The use of lanthanide metal enolates in the aldol reaction has, to date, only been developed to a synthetically useful level in the case of cerium (Scheme S and Table 7). Stereoselectivities are no better than those of lithium enolates, but the cerium enolates of ketones woik well in crossed aldol additions to ketones (Table 7, entries 1-7) and sterically hindered aldehydes (Table 7, entries 9 and 10). Such crossed aldol reactions do not often work well with lithium enolates as enolate equilibration, retroaldolization and steric retardation of addition occur. Imamoto et al. have shown that cerium enolates (44), formed from anhydrous CeCb (1.2 equiv.) and the preformed lithium enolates of ketones in THF at -78 C, undergo such aldol reactions to give the corresponding p-hydroxy ketones (46), usually in high yield. The cerium suppresses the retroaldol reaction by efficient chelation of the aldolate (45). A similar effect is known for zinc halide mediated aldol reactions (Volume 2, (Chapter 1.8). The stereoselectivity of the... 

To facilitate an analysis of enolate reactivity and as an aid to the rationalization of the stereochemical outcome of the aldol reaction, a consideration of the enolate structure is necessary.1 For convenience, the following classification of transition metal and lanthanide metal enolates will be used here T)1-0-bound metal enolates (1) of carbonyl compounds V-C-bound metal enolates (2) and T)3-metal enolates (3) of... 

A recent notable finding in this field is Mukaiyama aldol reactions in aqueous medium (THF H20 = 9 1) catalyzed by metal salts. Lewis acids based on Fe(II), Cu(II), and Zn(II), and those of some main group metals and lanthanides are stable in water. Remarkably, the aldol reaction shown in Sch. 29 occurs more rapidly than the hydrolysis of the silyl enol ether [137]. In the presence of surfactants (dodecyl sulfates or dodecane sulfonate salts), reactions of thioketene silyl acetals with benzaldehyde can be performed in water [138]. 

Although lanthanide triflates are the first metal salts which were foimd to catalyze aldol reactions of aldehydes with silyl enol ethers efficiently in aqueous media, it has been difficult to realize asymmetric versions of lanthanide triflate-catalyzed reactions in such media. Recently, the first example of this type of reaction using chiral bis-pyridino-18-crown-6 (1) has been developed [38]. In the reaction of benzaldehyde with silyl enol ethers in water-ethanol (1 9), the cation size of lanthanide triflates strongly affected the diastereo- and enantioselectivities of the aldol adduct. For the larger cations such as La, Ce, Pr, and Nd, both diastereo- and enantioselectivities were high, while the smaller cations such as Sc and Yb showed no enantioselection. 

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