Metal enantio-selectivity

For the reactions of other 1,3-dipoles, the catalyst-induced control of the enantio-selectivity is achieved by other principles. Both for the metal-catalyzed reactions of azomethine ylides, carbonyl ylides and nitrile oxides the catalyst is crucial for the in situ formation of the 1,3-dipole from a precursor. After formation the 1,3-di-pole is coordinated to the catalyst because of a favored chelation and/or stabiliza-... 

The cationic aqua complexes prepared from traws-chelating tridentate ligand, R,R-DBFOX/Ph, and various transition metal(II) perchlorates induce absolute enantio-selectivity in the Diels-Alder reactions of cyclopentadiene with 3-alkenoyl-2-oxazoli-dinone dienophiles. Unlike other bisoxazoline type complex catalysts [38, 43-54], the J ,J -DBFOX/Ph complex of Ni(C104)2-6H20, which has an octahedral structure with three aqua ligands, is isolable and can be stored in air for months without loss of catalytic activity. Iron(II), cobalt(II), copper(II), and zinc(II) complexes are similarly active. 

The complexation procedure included addition of an equimolar amount of R,R-DBFOX/Ph to a suspension of a metal salt in dichloromethane. A clear solution resulted after stirring for a few hours at room temperature, indicating that formation of the complex was complete. The resulting solution containing the catalyst complex was used to promote asymmetric Diels-Alder reactions between cyclopen-tadiene and 3-acryloyl-2-oxazolidinone. Both the catalytic activity of the catalysts and levels of chirality induction were evaluated on the basis of the enantio-selectivities observed for the endo cycloadduct. 

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

Enantioselective allylations of a-nitro ketones and a-nitro esters with allyl acetates are carried out in the presence of 2 equiv of alkali metal fluorides (KF, RbF, CsF) and 1 mol% palladium catalysts prepared in situ from Pd2(dba)3-CHC13 and chiral phosphine ligands. Moderate enantio-selectivity (ca 50% ee) is reported for allylation of cx-nitroketones (Eq. 5.60). The highest selectivity (80% ee) is observed for allylation of the reaction of tert-butyl ester (Eq. 5.61).93... 

In the very recent past, metal complex catalysis has been used with advantage for the stereo- and enantio selective syntheses based on the Henry and Michael reactions with SENAs (454-458). The characteristic features of these transformations can be exemplified by catalysis of the reactions of SENAs (327) with functionalized imides (328) by ligated trivalent scandium complexes or mono-and divalent copper complexes (454) (Scheme 3.192). Apparently, the catalyst initially forms a complex with imide (328), which reacts with nitronate (327) to give the key intermediate A. Evidently, diastereo- and enantioselectivity of the process are associated with preferable transformations of this intermediate. 

For an excellent review covering enantio-selective metal-catalyzed cycloisomerization of 1,6- and 1,7-enynes, see I.J.S. Fairlamb, Angew. Chem. Int. Ed. 2004,... 

Metal alkyl peroxides can be used for the epoxidation of electron-deficient alkenes such as enones. The use of a combination of diethylzinc, oxygen, and A-methylephedrine gave epoxides in very high yield and generally high enantio-selectivity (Figure 11.8). " ... 

SEGPHOS [271, 272]. Using this complex as a precatalyst, transfer hydrogenation of 1,1-dimethylallene in the presence of diverse aldehydes mediated by isopropanol delivers products of ferf-prenylation in good to excellent yield and with excellent levels of enantioselectivity. In the absence of isopropanol, enantio-selective carbonyl reverse prenylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts. Notably, enantioselective ferf-prenylation is achieved under mild conditions (30-50°C) in the absence of stoichiometric metallic reagents. Indeed, for reactions conducted from the alcohol oxidation level, stoichiometric byproducts are completely absent (Scheme 13). 

Optically active epoxides are important building blocks in asymmetric synthesis of natural products and biologically active compounds. Therefore, enantio-selective epoxidation of olefins has been a subject of intensive research in the last years. The Sharpless [56] and Jacobsen [129] epoxidations are, to date, the most efficient metal-catalyzed asymmetric oxidation of olefins with broad synthetic scope. Oxidative enzymes have also been successfully utilized for the synthesis of optically active epoxides. Among the peroxidases, only CPO accepts a broad spectrum of olefinic substrates for enantioselective epoxidation (Eq. 6), as shown in Table 8. 

Ruthenium complexes containing this phosphine ligand are able to reduce a variety of double bonds with enantiomeric excesses above 95%. In order to achieve high enantio-selectivity, the compound to be reduced must show a strong preference for a specific orientation when complexed with the catalyst. This ordinarily requires the presence of a fimctional group that can coordinate with the metal. The ruthenium binaphthyldiphosphine catalyst has been used successfully with unsaturated amides,11 allylic and homoallylic alcohols,12 and unsaturated carboxylic acids.13... 

The above azomethine ylide cycloadditions have been extended to an enantio-selective version involving amino alcohols both as chiral ligands and amine bases. Thus, reactions of the N-metalated azomethine ylides derived from achiral methyl 2-(arylmethyleneamino)acetates, cobalt(II) chloride [or manganese(II) bromide], and chiral amino alcohols, 1 and 2 equiv each, with methyl acrylate as solvent have been performed to provide the enantiomer-enriched pyrrolidine-2,4-dicarboxylates with the enantioselectivities of up to 96% enantiomeric excess (ee) (128,129). However, a large excess of the metal ions and the chiral source (ligand and base) have to be employed. 

The symmetry of the ligand can influence the product stereoselectivity and enantio-selectivity. Enantiomerically pure chemicals are extremely important for the agrochemical, pharmaceutical, and food industries. Many of the bidentate ligands used in these processes feature C2-type symmetry, dividing the space around the metal center into two empty quadrants and two full quadrants (see Section 3.1.3 on asymmetric homogeneous catalysis) [61,62], Ligand symmetry is also important in polymerization catalysis [63], where it can influence the polymer s tacticity (Figure 3.22). 

The first catalytic asymmetric allylation of imines has been reported using allyltri- -butyltin in the presence of a chiral 7r-allylpalladium complex.179 Zirconium is also demonstrated as a metal center for the design of chiral Lewis acid catalysts that are suitable for the activation of bidentate imino compounds.180 Jprgensen reports high enantio-selective allylation of ct-imino esters (Equation (52)).181... 

Metal-bis(oxazoline) complexes were widely used as effective catalysts for enantioselective Diels-Alder reactions. Two research groups could achieve excellent diastereo- and enantio-selectivity for the reaction of cyclopentadiene (54) and the acrylamide 55 (Fig. 9) [27]. Yet the decisive feature is only recognizable when both studies are analyzed together. In both cases the endo products are obtained in high selectiv-ities using either the magnesium- or the copper-containing catalyst. However, despite the same... 

A major limitation to the Sharpless-Katsuki epoxidation is that its utility is largely confined to oxidation of allylic alcohols. Homoallylic alcohols are oxidized less cleanly and the oxidation of simple olefins shows little enantio-selectivity. This is presumably because the stereochemical control depends on anchoring the substrate to a particular site on the metal by means of an auxiliary coordinating function. 

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