Bis-oxazoline copper complex

Fig. 19 Model for surface effects in laponite-supported bis(oxazoline)-copper complexes...

In the case of the Diels-Alder reaction [68] (Scheme 12), several soUds (AlSBA-15, MCM-41, MSU-2 and zeolite HY) were tested as supports for the bis(oxazoline)-copper complexes. The best enantioselectivity results were obtained with the zeolite HY, although the yield was the poorest (16% yield, 41% ee). As happened with the aziridination reaction, the enantioselectivity changed with time. Short reaction times led to the same major enantiomer as observed in homogeneous reactions. However, at higher conversions, i.e., longer reaction times, the opposite major enantiomer was obtained. 

Table 12 Results of reactions of ethyl glyoxylate with different alkenes, catalyzed by several bis(oxazoline)-copper complexes immobilized on Y zeolite...

Bis(oxazoline)-copper complexes 158 have been used by Evans group as chiral catalysts for the enantioselective aziridination of olefins.116 Aryl-substituted olefins have been found to be particularly suitable substrates, which can be efficiently converted to A-tosylaziridines with ee of up to 97% (R = Ph... 

Bis(oxazoline)-copper complexes supported on clays were investigated as heterogeneous catalysts in the cyclopropanation reaction (37, 38). Optimal results were obtained from chloride-derived complexes in nitroethane as reaction medium. Laponite clay was found to provide higher selectivities than montmorillonite or bentonite. In every case, the heterogeneous reaction afforded increased amounts of the cis cyclopropane relative to the homogeneous reaction. 

In an approach to planar chiral ferrocenes, Siegel and Schmalz (85) report that bis(oxazoline)-copper complexes induce efficient aromatic C-H insertion from a... 

K. A. Woerpel, Ph.D. Thesis, Bis(oxazoline)-Copper Complexes as Catalysts for Enantioselective Cyclopropanation of Olefins, Harvard University, Cambridge, MA, 1992. 

More recently, Pfaltz has reported high enantioselectivities for the cyclopropanation of monosubstituted alkenes and dienes with diazo carbonyl compounds using chiral (semicorrinato)copper complexes (P-Cu) (23-25), and Evans, Masamune, and Pfaltz subsequently discovered exceptional enantioselectivities in intermolecular cyclopropanation reactions with the analogous bis-oxazoline copper complexes (26-28). With the exception of the chiral (camphorquinone dioximato)cobalt(II) catalysts (N-Co) reported by Nakamura and coworkers (29,30), whose reactivities and selectivities differ considerably from copper catalysts, chiral complexes of metals other than copper have not exhibited similar promise for high optical yields in cyclopropanation reactions (37). 

A stereoselective insertion of phenyldiazoacetate-derived carbene into the a-C-H bond of tetrahydrofuran, catalyzed by a laponite clay-immobilized chiral bis(oxazoline) copper complex, depicted below, was also described <07OL731>. 

Semicorrinato)copper catalysts have also been used for intramolecular cyclopropanation reactions of alkenyl diazo ketones (eq 9 and eq 10). In this case the (semicorrinato)copper catalyst derived from complex (5) proved to be superior to related methylene-bis(oxazoline)copper complexes. Interestingly, analogous allyl diazoacetates react with markedly lower enantioselectivity under these conditions, in contrast to the results obtained with chiral Rh complexes which are excellent catalysts for intramolecular cyclopropanations of allyl diazoacetates but give poor enantioselectivities with alkenyl diazo ketones (see Dirhodium(II) Tetrakis(methyl 2-pyrrolidone-5(S -carboxylate ) Moderate enantioselectivities in the reactions... 

Cycloaddition Reactions. Bis(oxazoline) copper complexes such as 2 (and its hydrated congener) facilitate the [2 + 2] cycloaddition between silylketenes and glyoxylate/pyruvate esters (eq 18). The reaction is tolerant to various silyl substituents and structural variation on the dicarbonyl reactant. 

Cycloaddition Reactions. Bis(oxazoline) copper complex 2 catalyzes the dipolar cycloaddition reaction between electron deficient nitrones and electron rich alkenes. While exo.endo selectivities are marginal, products can be obtained in as high as 94% enantiomeric excess (eq 19). Based on the stereochemical outcome of the reaction, a five-coordinate intermediate has been postulated in which both the nitrone (as a bidentate ligand) andl alkene are coordinated to the Cu center. 

Convergent dendrimers, with their versatile three-dimensional scaffold, may be tailored to mimic, perhaps crudely, some elements of enzymatic structures. Numerous catalytic moieties, including manganese porphyrins,253,254 bis(oxazoline) copper complexes,304 305 tertiary amines,306 binaphthol titanium complexes,285 307 titanium taddolates,292,308 thiazolio-cyclophanes,309 and fullerene-bound bisoxazoline copper complexes,310 have been incorporated at the core of dendritic molecules to determine the effect of dendritic encapsulation on their catalytic activity. 

In 2006, Zhou s group reported a copper-catalyzed asymmetric synthesis (it was described in the paper as Friedel-Crafts-type reaction) using Al-sulfonyl aldimines with indoles to provide a simple approach to optically active 3-indolylmethanamine derivatives with high enantioselectivity. A bis-oxazoline-copper complex was used (Scheme 6.37) [50]. 

A glyoxylate-ene reaction has been catalysed by a chiral bis(oxazoline)-copper complex with 94% ee in an ionic liquid." ° ... 

Johnson J. S., Evans D. A. Chiral Bis(Oxazoline) Copper(II) Complexes Versatile Catalysts for Enantioselective Cycloaddition, Aldol, Michael, and Carbonyl Ene Reactions Acc. Chem. Res. 2000 33 325-335... 

Keywords hefero-Diels-Alder reaction, chiral bis(oxazoline) copper(ll) complexes... 

Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

The first examples of cationic exchange of bis(oxazoline)-metal complexes used clays as supports [49,50]. Cu(II) complexes of ligands ent-6a, 6b, and 6c (Fig. 15) were supported on three different clays laponite (a synthetic clay), bentonite, and montmorillonite KIO. The influence of the copper salt from which the initial complexes were prepared, as well as that of the solvent used in the cationic exchange, was analyzed. 

A highly enantioselective dihydropyran synthesis results from the use of bis(oxazoline) copper(II) complexes as catalysts <00JA1635 00JA7936> and the value of this approach to carbohydrate synthesis has been noted . 

The analogous cationic pyridylbis(oxazoline)-copper complexes exhibit square pyramidal geometries in the solid state. As in the bis(oxazoline) series, the triflate is closer to the metal than the SbF6 counterion (2.36 and 2.49 A vs 2.90 A). A single molecule of water is bound to the copper center in the triflate complex 267b, whereas the SbF6 complex 268b accommodates two water molecules in the coordination sphere, Fig. 24 (197). 

Given the prevalence of bis(oxazoline)-copper catalysts as chiral Lewis acids, it seems appropriate to comment briefly on catalyst preparations, since differences arise in the nature of the catalyst complex. Triflate-derived catalysts are formed simply by combining the ligand and Cu(OTf)2 in a given solvent and stirring for an appropriate length of time (typically >2 h) to achieve complete dissolution and complexation, Scheme 14. The hydrated version is formed by addition of 2 equiv of water to this catalyst solution, followed by removal of solvent after 15 min of stirring. The hydrated triflate catalyst is bench stable for months. 

The considerable Lewis acidity of bis(oxazoline)-copper(II) complexes held promise for catalyzing the ene reaction, a process that usually requires strong Lewis acids. Indeed, these catalysts effect a highly selective ene reaction between a variety of alkene partners and glyoxylate esters to produce a-hydroxy esters in good yield, Eq. 210 (245). The ene reaction between cyclohexene and ethyl glyoxylate proceeds in excellent diastereoselectivity and enantioselectivity, Eq. 211. As a testament to the Lewis acidity of these complexes, it is noteworthy that... 

Jprgensen and co-workers (247) investigated the asymmetric 1,3-dipolar cycloaddition reaction catalyzed by bis(oxazoline)-copper(II) complexes. In the presence of 25 mol% 269c, nitrone (401) reacts with ethyl vinyl ether and methoxypropene to afford the [3 + 2] adducts in modest diastereoselectivity and high enantioselectivity, Eq. 217. Ethyl vinyl ether preferentially forms the exo adduct while methoxypropene prefers the endo mode for reasons that are unclear. 

Bis(oxazoline)copper(II) complexes elaborated with polyether dendrons (e.g.,... 

Mukiayama aldol reactions between silyl enol ethers and various carbonyl containing compounds is yet another reaction whose stereochemical outcome can be influenced by the presence of bis(oxazoline)-metal complexes. Evans has carried out a great deal of the work in this area. In 1996, Evans and coworkers reported the copper(II)- and zinc(II)-py-box (la-c) catalyzed aldol condensation between benzyloxyacetaldehyde 146 and the trimethylsilyl enol ether [(l-ferf-butylthio)vinyl]oxy trimethylsilane I47. b82,85 Complete conversion to aldol adduct 148 was achieved with enantiomeric excesses up to 96% [using copper(II) triflate]. The use of zinc as the coordination metal led to consistently lower selectivities and longer reaction times, as shown in Table 9.25 (Eig. 9.46). 

Chiral bis(oxazoline)/Copper(II) complexes are evaluated for asymmetric Diels-Alder reaction of naphthoquinone derivatives, and moderate levels of enantiomeric excess are observed in certain cases [56] (Eq. 8A.33). 

Jorgensen et al. reported that C2-symmetric bis(oxazoline)-copper(II) complex 25 also acts as chiral Lewis acid catalyst for a reaction of allylic stannane with ethyl glyoxylate [37]. Meanwhile, p-Tol-BINAP-CuCl complex 26 was shown to be a promising chiral catalyst for a catalytic enantioselective allylation of ketones with allyltrimethoxysilane under the influence of the TBAT catalyst [38]. Evans and coworkers have developed (S,S)-Ph-pybox-Sc(OTf)3 complex 27 as a new chiral Lewis acid catalyst and shown that this scandium catalyst promotes enantioselective addition reactions of allenyltrimethylsilanes to ethyl glyoxylate [39]. But, when the silicon substituents become bulkier, nonracemic dihydrofurans are predominantly obtained as products of [3+2] cycloaddition. 

The Mukaiyama aldol reaction could be catalyzed by chiral bis(oxazoline) copper(II) complexes resulting in excellent enantioselectivities (Fig. 7) [23]. A wide range of silylketene acetals 46 and 49 were added to (benzyloxy[acetaldehyde 45 and pyruvate ester 48 in a highly stereoselective manner. The authors were also able to propose a model to predict the stereochemical outcome of these reactions. 

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