Aldol reactions catalysis

Asymmetric Phase Transfer Catalysis Aldol Reactions... 

The use of indium in acpieous solution has been reported by Li and co-workers as a new tool in org nometallic chemistry. Recently Loh reported catalysis of the Mukaiyama-aldol reaction by indium trichloride in aqueous solution". Fie attributed the beneficial effect of water to a eg tion phenomena in connection with the high internal pressure of this solvenf This woric has been severely criticised by... 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

Cationic bis(oxazoline) and pyridil-bis(oxazoline) Cu(ll) and Zn(ll) Lewis-acid catalysts. A comparative study in catalysis of Diels-Alder and aldol reactions [101]... 

Togni A., Pastor S. D. Cooperativity of Chirality in Homogeneous Catalysis The Gold(I)-Catalyzed Aldol Reaction and the Vanadium(IV)-Catalyzed Hetero-Diels-Alder Cycloaddition Chirality 1991 3 331-340... 

Figure 10.41 Natural aldol reaction catalyzed by RibA, acceptance of nonnatural aldol donors, and azasugar precursors prepared by stereoselective RibA catalysis.

Gruttadauria, M., Riela, S., Lo Meo, P., D Anna, F., Noto, R. (2004) Supported Ionic Liquid Asymmetric Catalysis A New Method for Chiral Catalysts Recycling, the Case of ProUne-Catalysed Aldol Reaction. Tetrahedon Letters, 45(32), 6113-6116. 

Asymmetric Lewis-Acid Catalyzed. Another important advance in aqueous Mukaiyama aldol reaction is the recent success of asymmetric catalysis.283 In aqueous ethanol, Kobayashi and co-workers achieved asymmetric inductions by using Cu(OTf)2/chiral >A(oxazoline) ligand,284 Pb(OTf)2/chiral crown ether,285 and Ln(OTf)3/chiral Mv-pyridino-18-crown-6 (Eq. 8.105).286... 

Exactly the same distinction can be made over catalysis by bases as was made above for acids. Thus in specific base catalysis the reaction rate is again found to be oc pH, this time rising as the pH rises, i.e. is oc [eOH]. Thus in the reversal of an aldol condensation (cf. p. 224) it is found that,... 

The reaction can, however, be made preparative for (91) by a continuous distillation/siphoning process in a Soxhlet apparatus equilibrium is effected in hot propanone over solid Ba(OH)2 (as base catalyst), the equilibrium mixture [containing 2% (91)] is then siphoned off. This mixture is then distilled back on to the Ba(OH)2, but only propanone (b.p. 56°) will distil out, the 2% of 2-methyl-2-hydroxypentan-4-one ( diacetone alcohol , 91, b.p. 164°) being left behind. A second siphoning will add a further 2% equilibrium s worth of (91) to the first 2%, and more or less total conversion of (90) — (91) can thus ultimately be effected. These poor aldol reactions can, however, be accomplished very much more readily under acid catalysis. The acid promotes the formation of an ambient concentration of the enol form (93) of, for example, propanone (90), and this undergoes attack by the protonated form of a second molecule of carbonyl compound, a carbocation (94) ... 

Over the last few years several examples have been reported in the field of asymmetric catalysis that are based on the interaction of two centers.6,119 Recently, Shibasaki and coworkers have developed an asymmetric two-center catalyst. Scheme 3.14 shows preparation of optically active La binaphthol (BINOL). This catalyst is effective in inducing the asymmetric nitro-aldol reaction, as shown in Scheme 3.15. 

The isomerization of an O-silyl ketene acetal to a C-silyl ester is catalyzed by a cationic zirconocene—alkoxide complex [92], This catalysis was observed as a side reaction in the zirconocene-catalyzed Mukaiyama aldol reactions and has not yet found synthetic use. The solvent-free bis(triflate) [Cp2Zr(OTf)2] also catalyzes the reaction in nitromethane (no reaction in dichloromethane), but in this case there may be competitive catalysis by TMSOTf (cf. the above discussion of the catalysis of the Mukaiyama aldol reaction) [91] (Scheme 8.51). 

Lewis acids as water-stable catalysts have been developed. Metal salts, such as rare earth metal triflates, can be used in aldol reactions of aldehydes with silyl enolates in aqueous media. These salts can be recovered after the reactions and reused. Furthermore, surfactant-aided Lewis acid catalysis, which can be used for aldol reactions in water without using any organic solvents, has been also developed. These reaction systems have been applied successfully to catalytic asymmetric aldol reactions in aqueous media. In addition, the surfactant-aided Lewis acid catalysis for Mannich-type reactions in water has been disclosed. These investigations are expected to contribute to the decrease of the use of harmful organic solvents in chemical processes, leading to environmentally friendly green chemistry. 

Judging from these findings, the mechanism of Lewis acid catalysis in water (for example, aldol reactions of aldehydes with silyl enol ethers) can be assumed to be as follows. When metal compounds are added to water, the metals dissodate and hydration occurs immediatdy. At this stage, the intramolecular and intermolecular exchange reactions of water molecules frequently occur. If an aldehyde exists in the system, there is a chance that it will coordinate to the metal cations instead of the water molecules and the aldehyde is then activated. A silyl enol ether attacks this adivated aldehyde to produce the aldol adduct. According to this mechanism, it is expected that many Lewis acid-catalyzed reactions should be successful in aqueous solutions. Although the precise activity as Lewis acids in aqueous media cannot be predicted quantitatively... 

The surfactant-aided Lewis acid catalysis was first noted1151 in the model reaction shown in Table 2. While the reaction proceeded sluggishly in the presence of 20 mol% Yb(OTf)3 in water, remarkable enhancement of the reactivity was observed when the reaction was carried out in the presence of 20 mol% Yb(OTf)3 in an aqueous solution of SDS (20 mol%, 35 mM). The corresponding aldol adduct was obtained in 50% yield. The yield was improved when Sc(OTf)3 was used as the Lewis acid catalyst. It was found that different kinds of surfactants influenced the product yield, and that TritonX-100, a neutral surfactant, was effective in the aldol reaction (but required long reaction time), while only a... 

S. Kobayashi, T. Wakabayashi, S. Nagayama, H. Oya-mada, Lewis Add Catalysis in MiceUar Systems. Sc(OTf)3-Catalyzed Aqueous Aldol Reactions of Silyl Enol Ethers with Aldehydes in the Presence of a Surfactant Tetrahedron Lett. 1997,38, 4559-4562... 

The most interesting developments involve catalysis of simple aldol reactions. The key to reactive immunisation is the use of a hapten that is chemically reactive, rather than a passive template. This means that (i) relevant chemistry is going on during the course of antibody induction, which thus happens in the presence of intermediates involved in the reaction, and so may be modified to favor the formation of antibodies which bind these intermediates (and perhaps transition states leading to them). Furthermore (ii) it becomes possible to select for antibodies that react with, rather than just bind, to the hapten. The system used for the development of aldolase antibodies is outlined in Scheme 2... 

The addition of an enolsilane to an aldehyde, commonly referred to as the Mukaiyama aldol reaction, is readily promoted by Lewis acids and has been the subject of intense interest in the field of chiral Lewis acid catalysis. Copper-based Lewis acids have been applied to this process in an attempt to generate polyacetate and polypropionate synthons for natural product synthesis. Although the considerable Lewis acidity of many of these complexes is more than sufficient to activate a broad range of aldehydes, high selectivities have been observed predominantly with substrates capable of two-point coordination to the metal. Of these, benzy-loxyacetaldehyde and pyruvate esters have been most successful. 

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