Aldol catalytic

Stereodivergent synthesis of 1-deoxy azasugars of the nojirimycin type by two-step enzymatic aldolization/catalytic reductive amination (a DHAP P ase H2/Pd-C). 

It turned out that the dodecylsulfate surfactants Co(DS)i Ni(DS)2, Cu(DS)2 and Zn(DS)2 containing catalytically active counterions are extremely potent catalysts for the Diels-Alder reaction between 5.1 and 5.2 (see Scheme 5.1). The physical properties of these micelles have been described in the literature and a small number of catalytic studies have been reported. The influence of Cu(DS)2 micelles on the kinetics of quenching of a photoexcited species has been investigated. Interestingly, Kobayashi recently employed surfactants in scandium triflate catalysed aldol reactions". Robinson et al. have demonshuted that the interaction between metal ions and ligand at the surface of dodecylsulfate micelles can be extremely efficient. ... 

Mercaptals, CH2CH(SR)2, are formed in a like manner by the addition of mercaptans. The formation of acetals by noncatalytic vapor-phase reactions of acetaldehyde and various alcohols at 35°C has been reported (67). Butadiene [106-99-0] can be made by the reaction of acetaldehyde and ethyl alcohol at temperatures above 300°C over a tantala—siUca catalyst (68). Aldol and crotonaldehyde are beheved to be intermediates. Butyl acetate [123-86-4] has been prepared by the catalytic reaction of acetaldehyde with 1-butanol [71-36-3] at 300°C (69). 

DIBK can be produced by the hydrogenation of phorone which, in turn, is produced by the acid-catalyzed aldol condensation of acetone. It is also a by-product in the manufacture of methyl isobutyl ketone. Diisobutyl ketone ( 1.37/kg, October 1994) is produced in the United States by Union Carbide (Institute, West Virginia) and Eastman (Kingsport, Teimessee) (47), and is mainly used as a coating solvent. Catalytic hydrogenation of diisobutyl ketone produces the alcohol 2,6-dimethyl-4-heptanol [108-82-7]. 

Induction of Asymmetry by Amino Acids. No fewer than sis types of reactions can be carried out with yields of 75—100% usiag amino acid catalysts, ie, catalytic hydrogenation, iatramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosdylation, and epoxidations (91). 

Oxadiazoles, 6, 365-391 aldol condensation, 6, 383 bond lengths, 6, 378 catalytic hydrogenation, 5, 75 chemotherapy, 6, 391 dipole moments, 6, 378 electron densities, 6, 378 electrophilic substitution, 6, 382 ethers... 

The fluoride anion has a pronounced catalytic effect on the aldol reaction between enol silyl ethers and carbonyl compounds [13] This reacbon proceeds at low temperature under the influence of catalytic amounts (5-10 mol %) of tetra-butylammonium fluoride, giving the aldol silyl ethers in high yields (equation 11). 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

Eor the application of C2-symmetric bis-oxazoline-Lewis acids in other catalytic reactions (a) Mukaiyama-aldol reactions see, e.g., D.A. Evans, M.C. Kozlowski,... 

Hie metliod involves a tegioselective, /vons-diasteteoselective, and eaantioselective tliree-component coupling, as shown in Sdieme 7.26. In tliis case, tlie zinc eaolate tesulling from tlie 1,4-addilion is trapped in a palladiuni-calalyzed allyla-tion [64] to afford /voiis-2,3-disubstituted cyclobexanone 96. Subsequent palladiuni-calalyzed Wacket oxidation [82] yields tlie metliylketone 97, wbidi in tlie presence of/-BuOK undergoes an aldol cyclization. This catalytic sequence provides tlie 5,6-i98) and 5,7- i99) annulated structures witli ees of 9696. 

For example in the so-called Mukaiyama aldol reaction of an aldehyde R -CHO and a trimethylsilyl enol ether 8, which is catalyzed by Lewis acids, the required asymmetric environment in the carbon-carbon bond forming step can be created by employing an asymmetric Lewis acid L in catalytic amounts. 

The term Knoevenagel reaction however is used also for analogous reactions of aldehydes and ketones with various types of CH-acidic methylene compounds. The reaction belongs to a class of carbonyl reactions, that are related to the aldol reaction. The mechanism is formulated by analogy to the latter. The initial step is the deprotonation of the CH-acidic methylene compound 2. Organic bases like amines can be used for this purpose a catalytic amount of amine usually suffices. A common procedure, that uses pyridine as base as well as solvent, together with a catalytic amount of piperidine, is called the Doebner modification of the Knoevenagel reaction. 

Certain starting materials may give rise to the non-selective formation of regioisomeric enolates, leading to a mixture of isomeric products. Furthermore a ,/3-unsaturated carbonyl compounds tend to polymerize. The classical Michael procedure (i.e. polar solvent, catalytic amount of base) thus has some disadvantages, some of which can be avoided by use of preformed enolates. The CH-acidic carbonyl compound is converted to the corresponding enolate by treatment with an equimolar amount of a strong base, and in a second step the a ,/3-unsaturated carbonyl compound is added—often at low temperature. A similar procedure is applied for variants of the aldol reaction. 

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

Pyrimidinopyrazines related to folic acid have been investigated in some detail for their antimeta-bolic and antineoplastic activities. A related compound, which lacks one nitrogen atom, has been described as an antiproliferative agent, indicating it too has an effect on cell replication. Aldol condensation of the benzaldehyde 99 with ethyl acetoacetate gives the cinnamate 100. This is then reduced catalytically to the acetoacetate 101. Reaction of that keto ester with 2,4,6- triami-nopyrimidine gives the product 102 which is subsequently chlorinated (103) and subjected to hydrogenolysls. There is thus formed piritrexim (104) [17]. 

On the other hand, carbonyl condensation reactions require only a catalytic amount of a relatively weak base rather than a full equivalent so that a small amount of enolate ion is generated in the presence of unreacted carbonyl compound. Once a condensation has occurred, the basic catalyst is regenerated. To carry out an aldol reaction on propanal, for instance, we might dissolve the aldehyde in methanol, add 0.05 equivalent of sodium methoxide, and then warm the mixture to give the aldol product. 

We can extend this kind of reasoning even further by imagining that subsequent transformations might be carried out on the aldol products. For example, a saturated ketone might be prepared by catalytic hydrogenation of the enone product. A good example can be found in the industrial preparation of 2-ethyl-... 

Like many other antibodies, the activity of antibody 14D9 is sufficient for preparative application, yet it remains modest when compared to that of enzymes. The protein is relatively difficult to produce, although a recombinant format as a fusion vdth the NusA protein was found to provide the antibody in soluble form with good activity [20]. It should be mentioned that aldolase catalytic antibodies operating by an enamine mechanism, obtained by the principle of reactive immunization mentioned above [15], represent another example of enantioselective antibodies, which have proven to be preparatively useful in organic synthesis [21]. One such aldolase antibody, antibody 38C2, is commercially available and provides a useful alternative to natural aldolases to prepare a variety of enantiomerically pure aldol products, which are otherwise difficult to prepare, allovdng applications in natural product synthesis [22]. 

Another SBU with open metal sites is the tri-p-oxo carboxylate cluster (see Section 4.2.2 and Figure 4.2). The tri-p-oxo Fe " clusters in MIL-100 are able to catalyze Friedel-Crafts benzylation reactions [44]. The tri-p-oxo Cr " clusters of MIL-101 are active for the cyanosilylation of benzaldehyde. This reaction is a popular test reaction in the MOF Hterature as a probe for catalytic activity an example has already been given above for [Cu3(BTC)2] [15]. In fact, the very first demonstration of the catalytic potential of MOFs had aheady been given in 1994 for a two-dimensional Cd bipyridine lattice that catalyzes the cyanosilylation of aldehydes [56]. A continuation of this work in 2004 for reactions with imines showed that the hydrophobic surroundings of the framework enhance the reaction in comparison with homogeneous Cd(pyridine) complexes [57]. The activity of MIL-lOl(Cr) is much higher than that of the Cd lattices, but in subsequent reaction rans the activity decreases [58]. A MOF with two different types of open Mn sites with pores of 7 and 10 A catalyzes the cyanosilylation of aromatic aldehydes and ketones with a remarkable reactant shape selectivity. This MOF also catalyzes the more demanding Mukaiyama-aldol reaction [59]. 

The oxime 299 is silylated in the presence of catalytic amounts of TMSOTf 20 to 300, which affords, via the Beckmann fragmentation intermediate 301 and alkylation with allyltrimethylsilane 82, 66% of the seco nitrile 302 [101, 102] (Scheme 4.39). Tris(trimethylsilyl) ketenimine 303 reacts with aldehydes such as benzaldehyde in the presence of Bp3-OEt2, via the aldol adduct 304, to give the unsaturated nitriles 305, in 99% yield, and HMDSO 7 [103]. 

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