Aldol metal salts effect

HjOiTHF = 1 9, rt, 12 h Table 14-3. Effect of metal salts in the aldol reaction ). 

Mukaiyama aldol reactions using a catalytic amount of a Lewis acidic metal salt afford silylated aldols (silyl ethers) as major products, but not free aldols (alcohols). Three mechanistic pathways which account for the formation of the silylated aldols are illustrated in Scheme 10.14. In a metal-catalyzed process the Lewis acidic metal catalyst is regenerated on silylation of the metal aldolate by intramolecular or intermolecular silicon transfer (paths a and b, respectively). If aldolate silylation is slow, a silicon-catalyzed process (path c) might effectively compete with the metal-catalyzed process. Carreira and Bosnich have concluded that some metal triflates serve as precursors of silyl triflates, which promote the aldol reaction as the actual catalysts, as shown in path c [46, 47]. Three similar pathways are possible in the triarylcarbenium ion-catalyzed reaction. According to Denmark et al. triarylcarbenium ions are the actual catalysts (path b) [48], whereas Bosnich has insisted that hydrolysis of the salts by a trace amount of water generates the silicon-based Lewis acids working as the actual catalysts (path c) [47]. Otera et al. have reported that 10-methylacridinium perchlorate is an efficient catalyst of the aldol reaction of ketene triethylsilyl acetals [49]. In this reaction, the perchlorate reacts smoothly with the acetals to produce the actual catalyst, triethylsilyl perchlorate. 

We recently disclosed that salts of alkali and alkaline earth metals effectively promote fhe aldol reaction of DMS enolates (Scheme 10.34) [101]. For example, fhe CaCl2-catalyzed reaction of propiophenone DMS enolate with aldehydes proceeds smoothly in DMF at 30 °C with high reaction efficiency. In the metal salt-catalyzed aldol reaction fhe counter anion of fhe metal salt plays a crucial role in rate acceleration. The activity of metal salt increases with increasing intrinsic nucleophilicity of fhe counter anion TfO metal salts work as Lewis bases to activate DMS enolates. To our surprise, the... 

For example, an effective procedure for the synthesis of LLB (where LL = lanthanum and lithium) is treatment of LaCls 7H2O with 2.7 mol equiv. BINOL dilithium salt, and NaO-t-Bu (0.3 mol equiv.) in THF at 50 °C for 50 h. Another efficient procedure for the preparation of LLB starts from La(0-/-Pr)3 [54], the exposure of which to 3 mol equiv. BINOL in THF is followed by addition of butyllithium (3 mol equiv.) at 0 C. It is worthy of note that heterobimetallic asymmetric complexes which include LLB are stable in organic solvents such as THF, CH2CI2 and toluene which contain small amounts of water, and are also insensitive to oxygen. These heterobimetallic complexes can, by choice of suitable rare earth and alkali metals, be used to promote a variety of efficient asymmetric reactions, for example nitroaldol, aldol, Michael, nitro-Mannich-type, hydrophosphonylation, hydrophosphination, protonation and Diels-Alder reactions. A catalytic asymmetric nitroaldol reaction, a direct catalytic asymmetric aldol reaction, and a catalytic asymmetric nitro-Mannich-type reaction are discussed in detail below. 

Alkaline Earth Metals. In the early literature, similar to alkali earth metals, alkaline earth metals were usually used to form the enolates, especially magnesium enolates, in the aldol reaction (128,129). Inspired by heterogeneous MgO solid base catalysis (130), alkaline earth metals have been applied successfully as homogeneous catalysts in the aldol reaction (Scheme 23). In 1998, Corey and co-workers described a new magnesium-catalyzed diastereoselective anti-aldol reaction as a key step for the total synthesis of lactacystin (131). The metal requirement is strict, since several salts were tested, for example, TiCl4, SnCL, ZnCl2, and Cu(OTf)2, only Mgl2 functioned as an effective catalyst (Scheme 24). 

A substantial enhancement of the condensation rate of these substances is observed by using hydrotropes such as sodium butylmonoglycosulfate (NaBMGS) and the sodium salts of aromatic sulfonic acids in alkaline media [8]. In the absence of NaOH, the reaction does not proceed, which indicates that the hydrotropes do not catalyze the reaction and that the effect is simply that of the solubilization of the reactants at higher concentrations. The selectivity of the reaction of p-nitrobenzaldehyde with acetone can be controlled in aqueous media by working in the presence of zinc nitrate hexahydrate and A,A-dimethylaminoethanol [9]. The amino alcohol-zinc combination favors aldol addition at pH 9.1-9.5 and aldol condensation at pH 11.4. The same reaction catalyzed by metal complexes bearing ligands of the a-amino acids... 

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