Catalysts,chiral

Asymmetric induction in the intermolecular Diels-Alder cycloaddition reactions can be achieved with chirally modified dienes and dienophiles as well as with chiral Lewis-acid catalysts [54-56]. 

Aluminum-based catalyst (S,S)-diazaaluminolidine 54 promoted the cycloaddition [57] between 5-(benzyloxymethyl)-l,3-cyclopentadiene and 3-acryloyl-l, 3-oxazolidin-2-one, leading to the cycloadduct in high yield and high enantiomeric excess (94%) (Equation 3.14). 

In contrast, modest enantioselection has been observed in the asymmetric Diels-Alder reaction between cyclopentadiene (18) with methylacrylate and methylpropiolate catalyzed by chiral organoaluminum reagents 58 [59] (Equation 3.15) prepared from trimethylaluminum and (R)-(+)-3,3 -bis(triphenylsi-lyl)-l,l -bi-2-naphthol [60]. The reaction was highly cnJo-diastereoselective. 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200 

Matsumoto and coworkers have introduced a new strategy for asymmetric induction under high pressure. The Michael addition of nitromethane to chalcone is performed at 10 kbar in the presence of a catalytic amount of chiral alkaloids. The extent of asymmetric induction reaches up to 50% ee with quinidine in toluene.201 

Chiral monoaza-crown ethers containing glucose units have been applied as phase-transfer catalysts in the Michael addition of 2-nitropropane to a chalcone to give the corresponding adduct in up to 90% ee. (Eq. 4.138).202 

Yamaguchi and coworkers have found that proline rubidium salts catalyze the asymmetric Michael addition of nitroalkanes to prochiral acceptors. When (25)-L-prolines are used, acyclic ( )-enones give (S)-adducts. Cyclic (Z)-enones give (R)-adducts predominantly (Eq. 4.139).203 Recently, Hanessianhas reported that L-proline (3 7% mol equiv) and 2,5-dimethylpiperazine are more effective to induce catalytic asymmetric conjugate addition of nitroalkanes to cycloal-kanones.204 

Heterobimetallic asymmetric complexes contain both Bronsted basic and Lewis acidic functionalities. These complexes have been developed by Shibasaki and coworkers and have proved to be highly efficient catalysts for many types of asymmetric reactions, including catalytic asymmetric nitro-aldol reaction (see Section 3.3) and Michael reaction. They have reported that the multifunctional catalyst (f )-LPB [LaK3tris(f )-binaphthoxide] controls the Michael addition of nitromethane to chalcones with 95% ee (Eq. 4.140).205 

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Most importantly, enantioselectivity benefits considerably from the use of water. This effect could be a result of water exerting a favourable influence on the cisoid - transoid equilibrium. Unfortunately, little is known of the factors that affect this equilibrium. Alternatively, and more likely, water enhances the efficiency of the arene - arene interactions. There is support for this observation"" . Since arene-arene interactions are held responsible for the enantioselectivify in many reactions involving chiral catalysts, we suggest that the enhancement of enantioselectivity by water might well be a general phenomenon. 

Another type of synthetic polymer-based chiral stationary phase is formed when chiral catalyst are used to initiate the polymerisation. In the case of poly(methyl methacrylate) polymers, introduced by Okamoto, the chiraUty of the polymer arises from the heUcity of the polymer and not from any inherent chirahty of the individual monomeric subunits (109). Columns of this type (eg, Chiralpak OT) are available from Chiral Technologies, Inc., or J. T. Baker Inc. 

This chemical bond between the metal and the hydroxyl group of ahyl alcohol has an important effect on stereoselectivity. Asymmetric epoxidation is weU-known. The most stereoselective catalyst is Ti(OR) which is one of the early transition metal compounds and has no 0x0 group (28). Epoxidation of isopropylvinylcarbinol [4798-45-2] (1-isopropylaHyl alcohol) using a combined chiral catalyst of Ti(OR)4 and L-(+)-diethyl tartrate and (CH2)3COOH as the oxidant, stops at 50% conversion, and the erythro threo ratio of the product is 97 3. The reason for the reaction stopping at 50% conversion is that only one enantiomer can react and the unreacted enantiomer is recovered in optically pure form (28). 

The synthesis of optically active epoxy-1,4-naphthoquinones (69) using ben2ylquininium chloride as the chiral catalyst under phase-transfer conditions has been reported (67). 2-Meth5l-l,4-naphthoquinone (R = CH ) (31) yields 70% of levorotatory (37). 2-Cyclohexyl-l,4-naphthoquinone... 

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

Another important example of an enantioselective reaction mediated by a chiral catalyst is the hydrogenation of 3-substituted 2-acetamidoacrylic acid derivatives. 

Depending on the stereoselectivity of the reaction, either the or the 5 configuration can generated at C-2 in the product. This corresponds to enantioselective synthesis of the d md L enantiomers of a-amino acids. Hydrogenation using chiral catalysts has been carefully investigated. The most effective catalysts for the reaction are ihodiiun... 

Enantioselective processes involving chiral catalysts or reagents can provide sufficient spatial bias and transition state organization to obviate the need for control by substrate stereochemistry. Since such reactions do not require substrate spatial control, the corresponding transforms are easier to apply antithetically. The stereochemical information in the retron is used to determine which of the enantiomeric catalysts or reagents are appropriate and the transform is finally evaluated for chemical feasibility. Of course, such transforms are powerful because of their predictability and effectiveness in removing stereocenters from a target. 

The necessity for producing large amounts of synthetic prostaglandins and analogs provided the impetus for a number of improvements in the bicyclo[2.2.1]heptene approach. Especially important was the development of an enantioselective modification for the synthesis of chiral prostanoids without resolution (1975) and the invention of a chiral catalyst for the stereocontrolled conversion of 15-keto prostanoids to either 15(5)- or 15(7 )- alcohols. 

The rhodium-catalyzed isomerization can also be carried out with the chiral catalyst, Ru2Cl4(diop)3 (H2, 20-80°, 1-6 h, 47-90% yield). In this case, optically enriched enol ethers are obtained. ... 

In 1990, Jacobsen and subsequently Katsuki independently communicated that chiral Mn(III)salen complexes are effective catalysts for the enantioselective epoxidation of unfunctionalized olefins. For the first time, high enantioselectivities were attainable for the epoxidation of unfunctionalized olefins using a readily available and inexpensive chiral catalyst. In addition, the reaction was one of the first transition metal-catalyzed... 

Dirhodium tetra(A-arylsulfonylprolinates) as chiral catalysts for asymmetric transformations of vinyl and aryldiazoacetates 99EJ02459. 

Addition of p-tert-butylthiophenol 178 to the racemic furanone 168 in dry toluene, and in the presence of quinidine as a chiral catalyst, provided (/ )-168 together with the Michael adduct 179. The enantiomeric excess of the recovered furanone (R)-168 was determined via the addition of (/)-Q -methylbenzylamine This amine addition showed complete diastereofacial control to give the adduct 180 in quantitative yield (Scheme 50) (94T4775). 

Kobayashi et al. have reported the use of a chiral lanthanide(III) catalyst for the Diels-Alder reaction [51] (Scheme 1.63, Table 1.26). Catalyst 33 was prepared from bi-naphthol, lanthanide triflate, and ds-l,2,6-trimethylpiperidine (Scheme 1.62). When the chiral catalyst prepared from ytterbium triflate (Yb(OTf)3) and the lithium or sodium salt of binaphthol was used, less than 10% ee was obtained, so the amine exerts a great effect on the enantioselectivity. After extensive screening of amines, ds-1,2,6-... 

I would like to thank Professors E. J. Corey and K. Narasaka for giving me a chance to work with super-reactive chiral catalyst 9 and TADDOL-based chiral titanium catalyst 31, respectively. 

Some of the developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds have origin in Diels-Alder chemistry, where many of the catalysts have been applied. This is valid for catalysts which enable monodentate coordination of the carbonyl functionality, such as the chiral aluminum and boron complexes. New chiral catalysts for cycloaddition reactions of carbonyl compounds have, however, also been developed. 

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)... 

Other substrates were tested the results are summarized in Table 5.2. Vinyl ethers (2b-2d) also worked well to afford the corresponding tetrahydroquinoline derivatives (3a-3e) in good to high yields with good to excellent diastereo- and en-antioselectivity (entries 1-10). Use of 10 mol% of the chiral catalyst also gave the adducts in high yields and selectivity (entries 2 and 6). As for additives, 2,6-di-t-bu-... 

Chiral Catalyst Optimization 201 Tab. 5.8 Catalyst optimization using 20 in the reaction of Id with 7a... 

Thus, a novel chiral zirconium complex for asymmetric aza Diels-Alder reactions has been developed by efficient catalyst optimization using both solid-phase and liquid-phase approaches. High yields, high selectivity, and low loading of the catalyst have been achieved, and the effectiveness of chiral catalyst optimization using a combination of solid-phase and liquid-phase methods has been demonstrated. 

Although the first metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction involved azomethine ylides, there has not been any significant activity in this area since then. The reactions that were described implied one of more equivalents of the chiral catalyst, and further development into a catalytic version has not been reported. 

The rhodium-catalyzed tandem carbonyl ylide formation/l,3-dipolar cycloaddition is an exciting new area that has evolved during the past 3 years and high se-lectivities of >90% ee was obtained for both intra- and intermolecular reactions with low loadings of the chiral catalyst. 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

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