Chiral ligands Lewis acid catalysts

Lewis-acid catalysis of Diels-Alder reactions involving bidentate dienophiles in water is possible also if the beneficial effect of water on the catalyzed reaction is reduced relative to pure water. There are no additional effects on endo-exo selectivity. As expected, catalysis by Cu ions is much more efficient than specific-acid catalysis.Using a-amino acids as chiral ligands, Lewis-acid enan-tioselectivity is enhanced in water compared to organic solvents. Micelles, in the absence of Lewis acids, are poor catalysts, but combining Lewis-acid catalysis and micellar catalysis leads to a rate accelaration that is enzyme-like. 

Li, H. J., Tian, H. Y., Chen, Y. J., Wmg, D. and Li, C. J., Novel chiral galhum Lewis acid catalysts with semi-crown ligands for aqueous asymmetric Mukayama aldol reactions, Chem. Commurt, 2002, 2994 2995. 

In 2005, Trost et al. developed enantioselective addition of TMSCN to aldehydes using chiral aluminum Lewis acid catalyst based on their inventive chiral ligand 58 (Scheme 41) [74]. 

Chiral aluminum catalyst 2, prepared from Et2AlCl and a Vaulted biaryl ligand, is reported to be an effective Lewis acid catalyst of the Diels-AIder reaction between methacrolein and cyclopentadiene, affording the adduct in 97.7% ee [4] (Scheme 1.2). Although the Diels-AIder reaction with other a,/ -unsaturated aldehydes has not been described, that only 0.5 mol% loading is sufficient to promote the reaction is a great advantage of this catalyst. 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

Several titanium(IV) complexes are efficient and reliable Lewis acid catalysts and they have been applied to numerous reactions, especially in combination with the so-called TADDOL (a, a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) (22) ligands [53-55]. In the first study on normal electron-demand 1,3-dipolar cycloaddition reactions between nitrones and alkenes, which appeared in 1994, the catalytic reaction of a series of chiral TiCl2-TADDOLates on the reaction of nitrones 1 with al-kenoyloxazolidinones 19 was developed (Scheme 6.18) [56]. These substrates have turned out be the model system of choice for most studies on metal-catalyzed normal electron-demand 1,3-dipolar cycloaddition reactions of nitrones as it will appear from this chapter. When 10 mol% of the catalyst 23a was applied in the reaction depicted in Scheme 6.18 the reaction proceeded to give a yield of up to 94% ee after 20 h. The reaction led primarily to exo-21 and in the best case an endo/ exo ratio of 10 90 was obtained. The chiral information of the catalyst was transferred with a fair efficiency to the substrates as up to 60% ee of one of the isomers of exo3 was obtained [56]. 

Scheme 6.7 shows some other examples of enantioselective catalysts. Entry 1 illustrates the use of a Co(III) complex, with the chirality derived from the diamine ligand. Entry 2 is a silver-catalyzed cycloaddition involving generation of an azome-thine ylide. The ferrocenylphosphine groups provide a chiral environment by coordination of the catalytic Ag+ ion. Entries 3 and 4 show typical Lewis acid catalysts in reactions in which nitrones are the electrophilic component. 

The Lewis acid catalyst 53 is now referred to as the Narasaka catalyst. This catalyst can be generated in situ from the reaction of dichlorodiisopropoxy-titanium and a diol chiral ligand derived from tartaric acid. This compound can also catalyze [2+2] cycloaddition reactions with high enantioselectivity. For example, as depicted in Scheme 5-20, in the reaction of alkenes bearing al-kylthio groups (ketene dithioacetals, alkenyl sulfides, and alkynyl sulfides) with electron-deficient olefins, the corresponding cyclobutane or methylenecyclobu-tene derivatives can be obtained in high enantiomeric excess.18... 

A chiral dinuclear Ti(IV) Lewis acid catalyst 18 can be prepared in situ from a 1 2 molar mixture of (7 )-3,3 -di(2-mesitylethynyl)binaphthol and Ti(Oi-Pr)4 at ambient temperature. The 3- and 3 -substituents on the chiral ligand are effective for preventing undesired aggregation between Ti(IV) complexes and increasing the enantioselectivity (up to 82% ee) in the Diels-Alder reaction of methacrolein with cyclopentadiene (Scheme 12.16). ... 

Chiral tetranuclear Ti(IV) cluster 19, a cubic structure that consists of four Ti atoms and OHs, and six (7 )-BINOL ligands bridging two Ti atoms as ligands, has been shown to be a novel chiral Lewis acid catalyst for the [2 + 3] cycloaddition reaction with nitrones. Chiral Ti(IV) clusters with 7,7 -substituted (7 )-BINOL ligands have been synthesized to give enhanced enantiomeric excesses up to 78% ee (Scheme 12.17). ... 

Chiral Lewis acid catalysts are powerful tools for asymmetric synthesis, combining a metal or metaloid central atom with a chiral ligand [1, 2], Such chiral Lewis acids activate electrophiles 1 for a nucleophilic attack. Various metals can be used as the center element (Scheme 1). 

Domling et al. [21] identified the first enantioselective Passerini MCR using a Lewis acid catalyst Ti(i-OPr)4 in combination with (4S,5S)-4,5-bis(diphenylhydrox-ymethyl)-2,2-dimethyldioxolane as a chiral ligand by a massive parallel catalyst screening (Scheme 9.13). 

Sibi and Chen [42] reported a related tandem intermolecular nucleophilic free-radical addition-trapping reaction of enoate 168 establishing chirality at both a and /(-centers with control over both absolute and relative stereochemistry (Scheme 9.30) using a Lewis acid catalyst and the bisoxazoline ligand 169. They observed... 

Organogallium reagents, RsGa, have been added enantioselectively to aldehydes, using TiCl4 as a Lewis acid catalyst, with a chiral salan ligand.258... 

The effectiveness of various substituted BINOL ligands 12-16 in the Zr(IV)-or Ti(IV)-catalyzed enantioselective addition of allyltributyltin to aldehydes was also investigated by Spada and Umani-Ronchi [21], The number of noteworthy examples of asymmetric allylation of carbonyl compounds utilizing optically active catalysts of late transition metal complexes has increased since 1999. Chiral bis(oxazolinyl)phenyl rhodium(III) complex 17, developed by Mo-toyama and Nishiyama, is an air-stable and water-tolerant asymmetric Lewis acid catalyst [23,24]. Condensation of allylic stannanes with aldehydes under the influence of this catalyst results in formation of nonracemic allylated adducts with up to 80% ee (Scheme 3). In the case of the 2-butenyl addition reac-... 

The remarkable affinity of the silver ion for hahdes can be conveniently applied to accelerate the chiral palladium-catalyzed Heck reaction and other reactions. Enantioselectivity of these reactions is generally increased by addition of silver salts, and hence silver(I) compounds in combination with chiral ligands hold much promise as chiral Lewis acid catalysts for asymmetric synthesis. Employing the BINAP-silver(I) complex (8) as a chiral catalyst, the enantioselective aldol addition of tributyltin enolates (9) to aldehydes (10) has been developed." This catalyst is also effective in the promotion of enantioselective allylation, Mannich, ene, and hetero Diels-Alder reactions. 

Chiral Lewis Acid. These chiral titanium reagents are widely used as chiral Lewis acid catalysts. The Diels-Alder reaction of methyl acrylate and cyclopentadiene affords the endo adduct in moderate enantioselectivity when a stoichiometric amount of the chiral titanium reagent (5) is employed (eq 6). Use of 3-(2-alkenoyl)-l,3-oxazolidin-2-ones as dienophiles greatly improves the optical purity of the cycloadduct when the 2-phenyl-2-methyl-1,3-dioxolane derivative (6) is used as a chiral ligand. Most importantly, the reaction proceeds with the same high enantioselectivity for the combination of various dienophiles and dienes even when 5-10 mol % of the chiral titanium reagent is employed in the presence of molecular sieves 4A (eqs 7 and 8). ... 

Attempts were then made to perform asymmetric catalytic reactions using chiral Lewis acid catalysts [59]. Reaction of the nitrone 73 and the oxazolidinone 76 with 10 mol % of the bis(oxazoline) 12-Mg(II) catalyst, prepared by Corey s method [13], in the presence of 4-A molecular sieves afforded the cycloadduct 77 in high yield (>95 %) and high (> 95 %) endo selectivity and 82 % ee (Sch. 33). The presence of activated powdered 4-A molecular sieves was essential to the endo and enantioselec-tivity of the reaction in their absence they were 65 % and < 2 %, respectively. The reaction proceeded via an intermediate XXIX, proposed by Corey [13], in which the bis(oxazoline) ligand 12 and the oxazolidinone 76 are both bidentately coordinated to the magnesium and addition to the re face is favored because the si face of the bound oxazolidinone is masked by one of the phenyl substituents on the oxazoline rings. 

Along with the development of chiral Lewis acid catalysts, a chiral trialkanolamine (42) has been used to prepare the catalyst (43) (Eq. 19). By use of this zirconium complex as a catalyst, enantioselective addition of the azide to meso epoxides was achieved [20a]. Thus, the oxirane ring was opened by /-PrMe2SiN3 to give the adduct (44) with high enantioselectivity (Eq. 20). In another example, a diamide ligand (45), which behaves as a tetradentate ligand, was used to achieve a similar reaction (Eqs 21 and 22) [20b]. 

Optically active l,l -binaphthols are among the most important chiral ligands of a variety of metal species. Binaphthol-aluminum complexes have been used as chiral Lewis acid catalysts. The l,T-binaphthyl-based chiral ligands owe their success in a variety of asymmetric reactions to the chiral cavity they create around the metal center [107,108]. In contrast with the wide use of these binaphthyls, the polymer-supported variety has been less popular. The optically active and sterically regular poly(l,l -bi-naphthyls) 96 have been prepared by nickel-catalyzed dehalogenating polycondensation of dibromide monomer 95 (Sch. 7) [109] and used to prepare the polybinaphthyl aluminum(III) catalyst 97 this had much greater catalytic activity than the corresponding monomeric catalyst when used in the Mukaiyama aldol reaction (Eq. 29). Unfortunately no enantioselectivity was observed in the aldol reaction. 

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