Bisoxazoline complexes

In 1997 the application of two different chiral ytterbium catalysts, 55 and 56 for the 1,3-dipolar cycloaddition reaction was reported almost simultaneously by two independent research groups [82, 83], In both works it was observed that the achiral Yb(OTf)3 and Sc(OTf)3 salts catalyze the 1,3-dipolar cycloaddition between nitrones 1 and alkenoyloxazolidinones 19 with endo selectivity. In the first study 20 mol% of the Yb(OTf)2-pyridine-bisoxazoline complex 55 was applied as the catalyst for reactions of a number of derivatives of 1 and 19. The reactions led to endo-selective 1,3-dipolar cycloadditions giving products with enantioselectivities of up to 73% ee (Scheme 6.38) [82]. In the other report Kobayashi et al. described a... 

Figure 12.24. Chiral bisoxazoline complexes giving chiral 4-tBu-styrene/CO copolymers...

Chiral, Lewis acidic bisoxazoline complexes of Mg(II) have been employed as catalysts in asymmetric Michael addition of O-benzyUiydroxylamine to unsaturated amides, (115) -> (116). The enantioselectivity (67-90% ee) was rationalized by transition state (117). This approach constimtes a promising methodology for the synthesis of jS-amino acids. °... 

Enantioselectivity of copper-catalyzed aziridination is dependent on the nitrene precursor used (Scheme 6B.32) [77]. Although the precursor of choice varies with the substrates, /j-Me0C6H4S02N=lPh orp-02NC6H4S02N=IPh is superior to TsN=IPh in many cases. For example, the aziridination of styrene in the presence of copper-bisoxazoline complex 29b gives the product with 78% ee using p-Me0C6H4S02N=IPh as the nitrene precursor, whereas the enantioselectivity is 52% ee when TsN=IPh is used as the precursor. 

Catalysis with Bisoxazoline Complexes of Sn(II) and Cu(II). The bisoxazoline Cu(IT) and Sn(II) complexes 81-85 that have proven successful in the acetate additions with aldehydes 86,87, 88 also function as catalysts for the corresponding asymmetric propionate Mukaiyama aldol addition reactions (Scheme 8B2.8) [27]. It is worth noting that eithersyn or anti simple diastereoselectivity may be obtained by appropriate selection of either Sn(II) or Cu(II) complexes (Table 8B2.12). 

In a carbonyl-ene reaction of ethyl glyoxylate with a-methylstyrene catalysed by copper triflate-bisoxazoline complexes, ees of up to 100% have been achieved, but a dramatic switchover in stereochemistry is seen for an apparently minor change in bisoxazoline structure.185 A change in the metal geometry is implicated. 

Jacobsen et al. have shown that cyanoacetate derivatives undergo conjugate addition to ,/i-unsaturated imides in the presence of a chiral Al-oxo salen complex 32 to afford the corresponding product in up to 98% ee (Scheme 16) [19]. When an a-amino cyanoacetate was used, a highly functionalized lactam 33 was obtained in one step. Another example of Lewis acid-catalyzed conjugate addition of cyclic 1,3-dicarbonyl compounds to 2-oxobutenoate employed the chiral Cu-bisoxazoline complex 34 (Scheme 17) [20]. 

Vinylogous Mukaiyama-Michael additions of 2-trimethylsilyloxyfuran to 3-alkenoyl-2-oxazolidinones to provide 7-butenolides were shown to be /7-selective. The reaction could be rendered enantioselective in the presence of a (T symmetric copper-bisoxazoline complex <1997T17015, 1997SL568> or a l,T-binaphthyl-2,2 -diamine-nickel(ii) complex as catalyst, as depicted in Equation (16) <2004CC1414>. 

Enantioselective Aziridination of Alkenes. Copper complexes with neutral methylenebis(oxazoline) ligands (1) and (2) have also been employed as enantioselective catalysts for the reaction of alkenes with (Al-tosylimino)phenyliodinane, leading to A-tosylaziridines. The best results have been reported for cinna-mate esters as substrates, using 5 mol % of catalyst prepared from CuOTf and the phenyl-substituted ligand (2) (eq 6). The highest enantiomeric excesses are obtained in benzene, whereas in more polar and Lewis basic solvents, such as acetonitrile, the selectiv-ities are markedly lower. The chemical yield can be substantially improved by addition of 4X molecular sieves. Both Cu - and Cu"-bisoxazoline complexes, prepared from Cu or Cu triflate, respectively, are active catalysts, giving similar results. In contrast to the Cu-catalyzed cyclopropanation reactions discussed above, in which only Cu complexes are catalytically active, here Cu complexes are postulated as the actual catalysts. ... 

The crystal structures of some (allyl)Pd -bisoxazoline complexes have been determined by X-ray analysis. The structural data of these complexes provide some clues about how the chiral ligand controls the stereochemical course of eq 9. 

A remarkable feature of the Evans process is its ability to mediate enantio-, chemo-, and diastereo-selective additions to 1,2-diketones (Eq. (8.18)). The Cu(II) and Sn(Il) bisoxazoline complexes display superb group selectivity, differentiating between ethyl and methyl groups in the addition of thiopropionate-derived Z-silyl ketene acetal to 84. As discussed above, the Cu(II) and Sn(ll) catalysts elicit complementary simple diastereoselectivity with the Cu(II) catalyst leading to the for-... 

In addition to bis-bisoxazolinate complexes 177 and 178, chiral and nonchi-ral bis-bisoxazolinate rare-earth metal complexes were synthesized to investigate their catalytic activity for ROP of D,L-lactide and D,L-P-butyrolactone [134]. By using the same synthetic pathway as for compounds 177 and 178, bis-bisoxazolinate complexes 179-182 were obtained via the amine elimination reactions of 2 equiv of the corresponding bisoxazolines HL33-HL35 with 1 equiv of [Ln N(SiHMe2)2 3(THF)2] (Ln = Y, La) in benzene or toluene (Scheme 68). 

However, the chiral bis-bisoxazolinate complexes did not lead to stereoselective products and only atactic polymers were produced. 

Oh and Meracz were the first to report asymmetric Diels-Alder reaction in ionic liquids [43]. It has also been shown that Diels-Alder reactions in ionic liquids give unusually high stereoselectivities at room temperature as compared to those in conventional organic solvents, where a low temperature was required to achieve good stereoselectivities. For example, the Diels-Alder reaction of cyclopentadiene and dienophile 25 with Cu(ll)-bisoxazoline complex 24 as catalyst in [dbim][BF4] showed a higher endoselectivity (endo j exo = 93/7) and regioselectivity (26/27 = 96/4) than in CHjCb (endojexo = 79/21, 26/27 = 76/24) (Scheme 7.11). 

A library of chiral dihydropyrans (226) [241] was synthesized using asymmetric hetero-Diels-Alder reactions (HAD) on polymer-bound enol ethers (221) and a, 3-unsaturated oxalyl esters (222). A chiral Lewis acidic Cu -bisoxazoline complex was used because of its high efficiency, the high predictability of the reaction outcome, and its broad substrate tolerance [280]. Enol ethers were used as alkene components bearing a hydroxy function for attachment to the resin via a silyl linkage (Scheme 49). The diene components carried allyl-ester groups, which could be readily displaced by amino functions in subsequent steps of the combinatorial synthesis. 

Fig.9. Chiral bisoxazoline complexes utilized as catalysts for enantioselective additions to chelating aldehydes...

Iron complexes can also be employed for ene cyclization of triene systems (Scheme 26). Though a chiral bisoxazoline complex exhibits not only higher 1,3-stereoinduction but also diastereoselectivity, no asymmetric induction was observed by the use of chiral bisoxazoline iron complex [70]. 

The enantioselective copolymerization of styrenes and CO has also been achieved (Scheme 12). Using bidentate pyridine-imine ligands (26), Sen synthesized optically active styrene and 4-methylstyrene copolymers [80]. Based on a microstructural analysis, a 36% ee for olefin insertion was reported. Brookhart employed a C2-symmetrical bisoxazoline complex (27) to produce styrene-based... 

Figure 6.20. (a) Acryloyloxazolidinone in bidentate coordination. strain favors the s-cis conformation, (b) Cycloaddition of Ci-symmetric bisoxazoline-magnesium complex [206]. (c) Cycloaddition of C2-symmetric bisoxazoline-copper complex [205]. (d) Rationale for the different topicities of the bisoxazoline complexes, even though both ligands have the same absolute configuration. The dienophile is awn in the plane of the paper, and the favored approach is from the direction of the viewer. 

Particularly effective catalysts are the chiral copper(ll) bisoxazoline complexes 66 and 134 (3.96). Best results are obtained when the dienophile has two sites for co-ordination to the metal. For example, the catalyst chelates to the two carbonyl groups of acrylimide dienophiles (as in structure 135) and cycloaddition with a diene leads to the adduct in high yield and with high optical purity (3.97). ... 

For an earlier example ofthe use of Cu(II) bisoxazoline complexes in conjugate addition reactions see A. Bernardi, G. Colombo and C. Scolastico, Tetrahedron Lett., 1996, 37, 8921. 

Complexes 24, 25, and 26 aU possess two neutral and two anionic ligands, respectively, and they are included in this section although they do not have halide ligands. Each of C2-symmetric bisoxazoline complexes 24 and 25 has two tiifluoroacetate ligands and is a good catalyst for asymmetric Wacker-type cyclization. Complex 26, applied to the asymmetric Fujiwara-Moritani reaction, is a rare example of having anionic chelate... 

Figure 8.12 Metal-bisoxazoline complexes catalysts for Friedel-Crafts arylations.

Transition state proposed for enantioselective Diels-Alder reactions catalyzed by a copper-bisoxazoline complex. The orientation of the diene and acrylate in this transition state resembles that in the transition state for an uncatalyzed [4+2] cycloaddition. Adapted from Evans, D. A. Barnes, D. M. Johnson, J. S. Leckta, T von Matt, R Miller, S. J. Murry, J. A. Norcross, R. D. Shaughnessy, E. A. Campos, K. R. J. Am. Chem. Soc. 1999,121,7582. 

Lewis acids such as Cu(OTf)2, its chiral bisoxazoline complex Cu(oxaz)2(OTf)2, and BiCls catalyze the intramolecular Diels-Alder reaction of 1-azadienes (eq 21). The 2-cyano-l-azadienes (4), containing an electron rich enol ether dienophile component, undergo cycloaddition to give the oxazinopiperidines (5) in 59-80% yield. o... 

An interesting example of the participation of water at the reactivation step of the catalytic cycle has been discovered recently for enantioselective reductive cyclization of di-allylmalonate in the presence of chiral bisoxazoline complexes of palladium (Scheme 6). 

Complexation of copper salts with both achiral and chiral ligands offers additional potential for modulation of Lewis acidity, reactivity, and control of stereochemistry. Most notably, the application of chiral copper complexes in enantioselective transformations has steadily increased over the past 15 years. From the extensive investigations of Cu(II)-chiral bisoxazoline complexes to more recent combinations of Cu(I) and Cu(ll) salts with chiral ligands, chiral copper Lewis acids continue to attract considerable attention for several reasons, [3]. The first of which is their ready availability and/or accessibility. Second, chiral copper Lewis acids are moderately Lewis acidic, but more importantly, their Lewis acidity is easily modified by choice of oxidation state, counterion, and ligand. Finally, chiral Cu(l) and Cu(ll) complexes offer predictable and tunable coordination geometries about... 

Chiral Cu(II)/bisoxazoline complexes have proven efficient in catalyzing Friedel-Crafts reactions to a number of substrates. Cu(OTf)2/t-Bu-bisoxazoline (13) promotes addition of a variety of electron-rich aromatic compounds (11) to ethyl glyoxylate (12) (Scheme 17.2) [5]. An interesting detail in this work was the importance of triflate as the counterion. When Cu(Sbp6)2 was employed as the Lewis acid, the yield and enantioselectivity was dramatically decreased. Furthermore, the choice of solvent had a significant effect on reactivity and selectivity. CH2CI2 generally led to improved chemical yield, while THF provided optimal enantioselectivities. 

Given the utility of chiral Cu(II)/bisoxazoline complexes in enantioselective Mukaiyama aldol reactions, a number of reports detailing the development of polymer-bound or dendritic bisoxazoline copper (I I) complexes have been developed. Development of such catalyst systems provides the potential for easy recovery and reuse of the relatively expensive catalyst. To this end, Salvadori and CO workers reported Mukaiyama aldol addition of ketene thioacetal (57) to methyl pyruvate catalyzed by a Cu(OTf)2 complex of polystyrene-supported bisoxazoline (89) (Scheme 17.18) [23]. The enantioselectivity of the addition remained high over eight cycles of the catalyst, however, reactivity was gradually reduced over time. 

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