Lewis acids chiral acid-ligand system

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]. 

The ferrocene moiety is not just an innocent steric element to create a three-dimensional chiral catalyst environment. Instead, the Fe center can influence a catalytic asymmetric process by electronic interaction with the catalytic site, if the latter is directly coimected to the sandwich core. This interaction is often comparable to the stabilization of a-ferrocenylcarbocations 3 (see Sect. 1) making use of the electron-donating character of the Cp2Fe moiety, but can also be reversed by the formation of feirocenium systems thereby increasing the acidity of a directly attached Lewis acid. Alternative applications in asymmetric catalysis, for which the interaction of the Fe center and the catalytic center is less distinct, have recently been summarized in excellent extensive reviews and are outside the scope of this chapter [48, 49], Moreover, related complexes in which one Cp ring has been replaced with an ri -arene ligand, and which have, for example, been utilized as catalysts for nitrate or nitrite reduction in water [50], are not covered in this chapter. 

A combination of the Lewis acid zinc triflate and the bases NEt, or pyridine acted as an achiral catalyst for this reaction. Instead, using a chiral base which incorporates a bipy ligand to bind zinc gave 26% ee of the product (Scheme 5-42a). Alternatively, diethylzinc was an active precatalyst, but attempts to use chiral amino alcohols as ligands in this system gave low ees (Scheme 5-42b) [31]. 

Asymmetric reactions using chiral copper Lewis acids are also performed in aqueous media. It has been reported that an asymmetric Diels-Alder reaction proceeds smoothly in water using Cu(OTf)2 and abrine as a chiral ligand (Scheme 49).214 The Cu -bis(oxazoline) system is effective in asymmetric aldol reactions in an aqueous solvent such as water/ethanol and even in pure water.215... 

Friestad and co-workers recently demonstrated that N-acyl hydrazones were excellent radical acceptors in the presence of a chiral Lewis acid [84], Valerolactam-derived hydrazone 117 proved to be the optimal substrate for enantioselective radical additions. Upon further optimization it was found that Cu(OTf )i and f-bulyl bisoxazoline ligand 96 gave the best yields and ee s (Scheme 31). Interestingly, a mixed solvent system (benzene dichloromethane in a 2 1 ratio, respectively) in the presence of molecular sieves (4 A) were necessary to achieve high yields and selectivities. 

Due to increasing demands for optically active compounds, many catalytic asymmetric reactions have been investigated in this decade. However, asymmetric catalysis in water or water/organic solvent systems is difficult because many chiral catalysts are not stable in the presence of water [19]. In particular, chiral Lewis acid catalysis in aqueous media is extremely difficult because most chiral Lewis acids decompose rapidly in the presence of water [20, 21]. To address this issue, catalytic asymmetric reactions using water-compatible Lewis acids with chiral ligands have been developed [22-29]. 

In 2000, a catalytic enantioselective addition was reported using a chiral Lewis acid-ligand system. Tomioka and coworkers reported the enantioselective addition of... 

With Chiral Bis(oxazoline)/metal Complexes Several research groups have developed chiral Lewis acids by using chiral 1,3-bis(oxazoline) ligands for asymmetric Diels-AIder reactions. Evans designed C2-symmetric bis(oxazoline)/Cu(II) complexes derived from chiral bis(oxa-zoline)and Cu(OTf)2, and applied them to asymmetric cycloadditions of acryloyl oxazolidinones and thiazolidine-2-thione analogues. Attractive features of this catalyst system include a clearly interpretable geometry for the catalyst-dienophile complex, which rationalizes the sense of asymmetric induction for the cycloaddition process [26] (Eq. 8A.14). 

An enantioselective reaction also occurs in a system in which the alkene itself does not contain any chiral auxiliary, but a chiral ligand is used in combination with a Lewis acid. In the following example, a chiral bisoxazoline (BOX) ligand is successfully employed together with zinc triflate as a Lewis acid to achieve an enantiomeric excess as high as 90% (Scheme 6.21) [37]. 

It should be noted that not only the Lewis base but also typical Lewis acid roles can be emulated by organocatalytic systems. The proton is arguably the most common Lewis acid found in Nature, and these exist in two forms classified by the nature of the hydrogen bond polar covalent (RX-H) and polar ionic (RX+H-Y ). In the former case, in asymmetric transformations the chiral information is dictated by the chiral anion, whilst in the latter case the anion is non-chiral and the enantioselectivity is introduced by a chiral ligand (usually an amine base), which complexates the proton. This activation is discussed more extensively in Chapter 7. 

The allylation reactions of carbonyl compounds catalyzed by chiral Lewis acids represent a powerful new direction in allylmetal chemistry. Yamamoto and coworkers reported the first example of the catalytic enantioselective allylation reaction in 1991, using the chiral (acyloxy)borane (CAB) catalyst system (see below) [288]. Since then, several additional reports of the catalytic allylation reaction have appeared. To date, the most effective catalyst systems reported for the enantioselective reaction of aldehydes and Type II allyl- and crotylstannane and silane reagents include the Yamamoto CAB catalyst and catalysts complexes composed of various Lewis acidic metals and either the BINOL or BINAP chiral ligands [289-293]. Marshall and Cozzi have recently reviewed progress in the enantioselective catalytic allylation reaction [294, 295]. 

Like BINOL, salicylaldehyde imines have become very important in asymmetric catalysis and a variety of polydentate ligands prepared from chiral monoamines and diamines are employed in oxidation reactions, carbenoid reactions and Lewis acid catalyzed reactions. As in the previous section, this section emphasizes the effect of the phenol moiety on the asymmetric catalysis. An imine derived from a chiral 1-phenethylamine and salicylaldehyde was employed in the copper catalyzed asymmetric cyclopropanation by Nozaki, Noyori and coworkers in 1966, which is the first example of the asymmetric catalysis in a homogeneous system . Salicylaldehyde imines with ethylenediamine (salen) have been studied extensively by Jacobsen and Katsuki and their coworkers since 1990 in asymmetric catalysis. Jacobsen and coworkers employed the ligands prepared from chiral 1,2-diamines and Katsuki and coworkers sophisticated ligands possess chirality not only at the diamine moiety but also at the 3,3 -positions. 

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