Cu /bisoxazoline complexes

Scheme 8C.9. Ene vr. hetero Diels-Alder reaction catalyzed by BINOL-A1 or bisoxazoline-Cu complex.

Solvent effects on the reaction of ethyl glyoxylate and 2,3-dimethyl-1,3-butadiene catalyzed by the cationic bisoxazoline-Cu complex have also been reported (Scheme 8C.9) [26]. In a less polar solvent, CH2C12, the ene product is obtained predominantly, whereas the reaction in a more polar solvent, CH3N02, leads to the preferential formation of the HDA product. 

For the cyclopropanation of terminal mono- and disubstituted alkenes, the cationic Cu complex derived from ligand (1) is clearly the most efficient catalyst available today, giving consistently higher enantiomeric excesses than related neutral semicorrin or bisoxazoline Cu complexes of type (3), - which can induce enantiomeric excesses of up to 92% ee in the cyclopropanation of styrene with ethyl diazoacetate. High enantioselectivities, ranging between the selectivities of the Evans catalyst (eq 3) and complex (3) (M = Cu, R = t-Bu), have also been observed with cationic Cu complexes of azasemicorrins. ... 

Scbcme 9C.9. Ene vs. hetero Diels-AUer reaction catalyzed by BIN[Pg.548]

Arylation of activated double bonds with diazonium salts in the presence of copper catalysts is known as the Meerwin reaction. The reaction is postulated to either proceed through an organocopper intermediate or through a chlorine atom transfer from chiral CuCl complex to the a-acyl radical intermediate. Brunner and Doyle carried out the addition of mesityldiazonium tetrafluoroborate with methyl acrylate using catalytic amounts of a Cu(I)-bisoxazoline ligand complex and were able to obtain 19.5% ee for the product (data not shown) [79]. Since the mechanism of the Meerwin reaction is unclear, it is difficult to rationalize the low ee s obtained and to plan for further modifications. 

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). 

The enantioselective alkylation of indoles catalyzed by C2-symmetric chiral bisoxazoline-metal complexes 90 encouraged many groups to develop superior asymmetric catalysts which are cheap, accessible, air-stable and water-tolerant. Other analogs of the bisoxazoline-metal complex 90 as chiral catalysts and new Michael acceptors have also been studied. The enantioselective alkylations of indole derivatives with of-hydroxy enones using Cu(II)-bis(oxazoline) catalysts 93 and 94 provided the adducts in good yields... 

The additions of indoles to ethenetricarboxylates as Michael acceptors in the presence of copper(II) complexes (10%) of chiral bisoxazolines (97-100) under mild conditions gave the alkylated products in high yield and up to 96% ee [101]. The observed enantioselectivity could be explained by secondary orbital interaction on approach of indole to the less hindered side of the 102-Cu(II)-ligand complex. The chiral ligands 97-99 of the catalyst gave similar ee%. The phenyl derivative 100 produced inferior results compared to 97-99, while (S,S)-2,6-bis(4-isopropyl-2-oxazoline-2-yl)pyridine (101) gave no reaction (Scheme 29) [56]. The enantioselective alkylation of indoles with arylidene malonates catalyzed by z-Pr-bisoxazoline-Cu(OTf)2 was also reported [102],... 

The oxo-HDA reaction of 2-carbonyl derivatives of pyridine 1-oxide with electron-rich dienes catalysed by bisoxazoline Cu(II) complexes proceeds by a Mukaiyama-aldol route and affords dihydropyran-4-ones 33 in good yield and excellent enantioselectivity <07JOC240>. 

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 stereochemical course of these reactions has been rationalized assuming a chelate complex between the (bisoxazoline)Cu catalyst and the dienophile as the reactive intermediate, with square planar coordination geometry of the Cu ion. ... 

Evans has studied the asymmetric catalysis of carbon-carbon bond forming reactions with C2 symmetric bisoxazoline-Cu(II) complexes [18, 19J. The (+)-NLE observed in asymmetric aldol reactions catalyzed by the bis(oxazolinyl)pyridine... 

The same bisoxazoline Cu(II) and Sn(II) complexes have been utilized successfully in the corresponding propionate aldol addition reactions (Scheme 8-7). A remarkable feature of these catalytic processes is that either syn or anti simple dia-stereoselectivity may be accessed by appropriate selection of either Sn(II) or Cu(II) complexes. The addition of either - or Z-thiopropionate-derived silyl ke-tene acetals catalyzed by the Cu(II) complexes afford adducts 78, 80, and 82 displaying 86 14-97 3 syn anti) simple diastereoselectivity. The optical purity of the major syn diastereomer isolated from the additions of both Z- and i -enol silanes were excellent (85-99% ee). The stereochemical outcome of the aldol addition reactions mediated by Sn(Il) are complementary to the Cu(U)-catalyzed process and furnish the corresponding anp -stereoisomers 79, 81, and 83 as mixtures of 10 90-1 99 syn/anti diastereomers in 92-99% ee. 

The high rigidity is the key feature of the chiral spirobiindane ligands, which exhibited special advantages in many asymmetric reactions. One example is the Cu complex of chiral spiro bisoxazoline ligand (S, S,S)-23a (R=Ph). Zhu et al. [33] analyzed the X-ray structures of Cu(I)-(5, 5,5)-23a with various anions (PF, C10 , and BArp). All the complexes have an unexpected binuclear Cu structure, as shown... 

Reaction A in Fig. 8 describes the Mukaiyama-type aldol condensation between (,S)-ben-zyloxypropanal and a silyl ketenethioacetal catalyzed by a (iS,.S )-bisoxazoline/Cu(II) complex. A 98.5 1.5 ratio of the (3S) (3R) aldols was obtained from this matching combination, while the reaction carried out on the (R)-aldehyde was stereorandom [41]. 

Hetero Diels-Alder cycloaddition of a,p-unsaturated carbonyl compounds and dioxygenated alkenes in the presence of a chiral bisoxazoline-Cu(OTf)2 complex as Lewis add catalyst furnished hexopyranose precursors in good yields and high enantomeric excess. In the synthesis of the precursor 6 of ethyl tetra-0-acetyl-P-D-mannopyranose outlined in Scheme 1, for example, a 69% overall yield and 99% ee were achieved. A new route to hex-2-uloses involving boron-or, preferably, lithium-enolates is exemplified in Scheme 2. Only 3,4-trans-... 

Starting from an optically active dimer, tetramer, or octamer of 2,3-dihy-droxynaphthalene derivatives, Tsubaki and co-workers realized the synthesis of numerous optically active oligonaphthalene products by second-order asymmetric transformation under amine-copper conditions (Scheme 3.17). On the other hand, Okamoto and co-workers achieved asymmetric oxidative coupling polymerization (AOCP) reactions to synthesize poly(2,3-dihy-droxy-l,4-naphthylene) derivatives (Scheme 3.18). The starting materials of AOCP reactions can be either partially protected tetrahydroxybinaphthale-nes or 2,3-dihydroxynaphthalene. The chiral Cu complexes ligated by (-)-sparteine or bisoxazolines were identified as suitable catalysts for these reactions. However, the enantioselectivity attained in these AOCP reactions was estimated to be low. 

The Pfaltz group developed a chiral boron-bridged bisoxazoline ligand (5,5)-L36 and tested its Cu complex in the Kharasch-Sosnovsky reaction of cyclic olefins. The enantioselectivity of the reaction (79% ee) was comparable with the previously reported best ones obtained using the BOX ligands. ... 

Recently, Hiersemann reported the first catalytic enantioselective Claisen rearrangement (Scheme 2.4) [11]. The 2-alkoxycarbonyl-substituted allyl vinyl ethers 11 are reactive under the Lewis acid catalysis. Therefore, the Claisen rearrangements proceed catalytically [12]. Usually the Lewis-acid-catalyzed Claisen rearrangement does not proceed catalytically because of a higher affinity of the carbonyl product for the Lewis acids than the ether substrate. But this 2-alkoxycarbo-nyl-substituted substrate 11 can coordinate to metals in a bidentate fashion. This 2-alkoxycarbonyl substrate has higher affinity for Lewis acidic Cu complexes than the simple ether substrate. In this system, chiral copper (II) bisoxazoline Cu (box) complex 13 is effective for the enantioselective Claisen rearrangement. 

Another potential advantage to polymer-bound or dendritic bisoxazoline Cu(II) complexes lies in the ability to enhance selectivity in aldol reactions conducted in aqueous media. Benaglia and coworkers studied Cu(II) complexes of poly(ethylene glycol)-supported bisoxazolines as catalysts for enantioselective aldol reactions in... 

Scheme 2.38 Cu(II)/bisoxazoline 25 complex-catalyzed asymmetric 1,3-DC of 3-oxo-pyrazolidin-1 -ium-2-ide derivatives.

In contrast to tran -selectivity (cndo-selectivity) of the Ni (n)-catalyzed reactions, Sibi et al. reported ciiy-selective (exo-selective) and highly enantioselective cycloadditions between -cyclic azomethine imines and 2-acryloyl-l-benzyl-5,5-dimethyl-3-pyrazohdinone catalyzed by the bisoxazoline-Cu(II) complex (10mol%) consisting of Cu (OTf>2 and (15,2I )-l-amino-2-indanol-deiived bisoxazoline (INDABOX) (Table 7.2) [12]. Interestingly, the use of additional chiral Lewis acid complexes prepared from INDABOX and Mg(II), Zn(II), or Ni(II) salts led to tmns-selective (emio-selective) cycloadditions of azomethine imine. The INDABOX-Mg(OTf)2- and INDABOX-Zn... 

Cu(II) and Sn(II) Bisoxazolinc Complexes. Evans has prepared and studied a family of Cu(II) complexes prepared from bisoxazoline ligands [8]. Utilizing these complexes a number of different addition reactions can be successfully conducted on pyruvate, benzyloxyacetalde-hyde, and glyoxylates. Whereas the focus of the work in the context of aldol addition reactions has been on the use of silyl ketene acetals (vide infra), the addition of ketone-derived enoxy silanes 8a-b with methyl pyruvate has been examined (Eq. 8B2.1). The additions of 8a-b proceed in the presence of 10 mol % Cu(II) catalyst at -78°C in CH2Cl2, affording adducts of acetophenone 9a and acetone 9b with 99% and 93% ee, respectively. 

Impressive advances in catalytic, enantioselective propionate aldol addition reactions have also been documented since 1992. Mikami has described a Ti(lV) catalyst readily prepared from BINOL and TiC O Pr. A propionate aldol addition process by Evans utilizes complexes prepared with bisoxazoline ligands and Sn(II) and Cu(II). In analogy to the acetate aldol... 

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]. 

Mattay et al. employed asymmetric copper(I)-catalyzed intramolecular [2 + 2]-photocycloaddition reactions in a synthetic approach to (+)- and (— )-grandisol [56]. Racemic dienol 33 was irradiated in the presence of CuOTf and a chiral ligand to yield mainly cyclobutanes 34 and ent-34 as a mixture of enantiomers. Other 1,6-dienes were also employed. A number of chiral nitrogen-containing bidentate ligands were tested, the most effective of which, (4S,4 S)-4,4 -diisopropyl-2,2 -bisoxazoline (35) and (4R,47 )-4,4 -diethyl-2,2 -bisoxazoline (36), ensured a minor enantiomeric excess of <5% ee (Scheme 12). The coordination of the diene to the chiral Cu(I) complex under formation of a complex of type 37 was proved by CD analysis. The authors suggest a lower reactivity of the chiral complex compared to the copper ion coordinated to solvent molecules as the reason for the low enantioselectivities observed. 

Intramolecular reactions using (5,5)-/-Bu-box and [Cu(MeCN)4]PFe complexes as catalysts have emerged as remarkably effective for the synthesis of macrocycles from membered ring lactones can be obtained in high enantiomeric purity with high efficiency. If two double bonds are present in the molecule, the unique preference of copper-bisoxazoline catalysts to promote the formation of the larger ring is demonstrated (eq 4). ... 

The use of catalyst 187 or 188 (see Sch. 43) in cycloadditions requires anhydrous conditions. Recently, several practical alternatives for this requirement have been reported. Evans has shown that the easily manipulated aquo complex prepared from 187 and water can be dehydrated to the active catalyst in the reaction vessel by addition of molecular sieves, without any loss of reactivity or selectivity [87]. Copper(II) perchlorate is available commercially as a hexahydrate. Ghosh and co-workers have reported that a complex 207 prepared from an aminoindanol-derived bisoxazoline and Cu(C104)2 6H2O is an excellent Lewis acid in Diels-Alder reactions (Sch. 46). It is interesting to note that the generally sluggish reactions with oxazolidinone croto-nates proceed with very high selectivity at room temperature [88]. 

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-... 

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