Copper complexes, bisoxazolines

Jorgensen et al. [84] studied how solvent effects could influence the course of Diels-Alder reactions catalyzed by copper(II)-bisoxazoline. They assumed that the use of polar solvents (generally nitroalkanes) improved the activity and selectivity of the cationic copper-Lewis acid used in the hetero Diels-Alder reaction of alkylglyoxylates with dienes (Scheme 31, reaction 1). The explanation, close to that given by Evans regarding the crucial role of the counterion, is a stabilization of the dissociated ion, leading to a more defined complex conformation. They also used this reaction for the synthesis of a precursor for highly valuable sesquiterpene lactones with an enantiomeric excess superior to 99%. 

Chiral dirhodium(II) carboxamidates are preferred for intramolecular cyclopropanation of allylic and homoallylic diazoacetates (Eq. 2). The catalyst of choice is Rh2(MEPY)4 when R " and R are H, but Rh2(MPPIM)4 gives the highest selectivities when these substituents are alkyl or aryl. Representative examples of the applications of these catalysts are listed in Scheme 15.1 according to the cyclopropane synthesized. Use of the catalyst with mirror image chirality produces the enantiomeric cyclopropane with the same enantiomeric excess [33]. Enantioselectivities fall off to a level of 40-70% ee when n is increased beyond 2 and up to 8 (Eq. 2) [32], and in these cases the use of the chiral bisoxazoline-copper complexes is advantageous. 

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

Lowenthal and Masamune also reported that the copper complex bearing a bisoxazoline ligand 30 was an effective catalyst for aziridination of styrene (88% ee) (Scheme 6B.31) [76], However, Evans et al. later claimed that this result was not reproducible [75],... 

Another bisoxazoline ligand 31 was prepared from tartrate and applied to asymmetric aziridination. However, enantioselectivity observed was modest (Scheme 6B.33) [78], Bisaz-iridine ligand 32 was prepared, but its copper complex showed only modest enantioselectivity in the aziridination of styrene (Scheme 6B.34) [79],... 

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. 

Jorgensen and coworkers have developed direct asymmetric reactions catalyzed by chiral copper(II)bisoxazoline (BOX) complexes [19]. On the basis of this... 

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. ... 

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. 

Table 7.11 Asymmetric cyclopropanation of styrene with ethyl diazoacetate catalyzed by bisoxazoline-copper complexes in an ionic liquid.

Corey et al. [42] have developed an interesting new bisoxazoline ligand with a biphenyl backbone [71] which was successfully applied in the key-step of the synthesis of the chemotactic factor sirenin (Scheme 14). The crystalline copper complex 21 emerged as the most effective catalyst for this reaction after extensive screening of a series of chiral Cu and Rh complexes. Other reactions with catalyst 21 have not been reported. 

Bisoxazoline copper complexes have also been used as chiral Lewis acids that give high yields and enantioselec-tivities (10.55).124... 

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. 

Although less commonly investigated, several catalytic, enantioselective aziridination reactions have also been developed. As an example, copper complexed to a chiral bisoxazoline ligand such as shown in Scheme 8.12a has been shown to catalyze the addition of A-(p-toluenesulfonylimino)phenyliodinane across a double bond [58]. Some promising results have been obtained (Scheme 8.12b), but work to fully define and optimize the range of olefins susceptible to this process is still ongoing. 

Copper complexes bearing bisoxazolines were described by Cahard [44]. Ligand 7 induces moderate to good enantiomeric excesses in the fluorination of 3-keto esters. Bolm described the application of chiral sulfoximine 8 as ligand for copper triflate and subsequent application of this catalyst in all three halogenation reactions of chlorination, bromination and fluorination employing various 3-keto esters [45]. 

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). ... 

Copper complexes of the bisoxazoline ligands have been shown to be excellent asymmetric catalysts not only for the formation of carbocyclic systems, but also for the hetero-Diels-Alder reaction. Chelation of the two carbonyl groups of a 1,2-dicarbonyl compound to the metal atom of the catalyst sets up the substrate for cycloaddition with a diene. Thus, the activated diene 20 reacts with methyl pyruvate in the presence of only 0.05 mol% of the catalyst 66 to give the adduct 138 with very high enantiomeric excess (3.99). 

This stabilization of a transition state related to tihe uncatalyzed process can also occur in reactions catalyzed by transition metal complexes, such as those catalyzed by Lewis acids. For example, Diels-Alder reactions catalyzed by transition metal complexes sometimes ocau" by mechanisms related to the concerted [4+2] mechanism of tiie imcatalyzed process. In tiiis case, the catalyst changes the electronic properties of the substrate bound to the Lewis add in a fashion that reduces the barrier for tihe [4+2] cycloaddition. Figure 14.3 shows the transition state proposed for enantioselective Etiels-Alder reactions catalyzed by copper complexes. The transition state structure is proposed on tiie basis of the calculated structure of the Lewis add complex formed between tiie copper-bisoxazoline fragment and the acrylate. 

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. 

Copper complexes of bisoxazoline ligands [90] such as 76 with a more rigid structure and other optimized bisoxazoline ligands [91] can asymmetrically aziridinate chalcone substrates with high enantioselectivities. 

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... 

Very recently a number of additional copper complexes with chirality derived from sources other than bisoxazoline ligands have been reported for application in enantioselective nitroaldol reactions [46]. Of particular interest was an application of iminopyridine ligand (161) in a Cu(II)-catalyzed nitroaldol reaction, Pedro and CO workers reported efficient addition of (154) to o-anisaldehyde (160) with good enantioselectivity (Scheme 17.33) [47]. 

Benaglia, M., Cinquini, M., Cozzi, F. and Celentano, G., Enantioselective catalysis in water Mukaiyama aldol condensation promoted by copper complexes of bisoxazolines supported on poly(ethylene glycol), Org. Biomol. Chem., 2004,2, 3401-3407. 

The first Lewis acid-catalyzed exo and enantioselective cycloaddition of azome-thine imines with pyrazolidinone acrylates 147 was developed by Sibi in 2008 [54]. By using in situ formed copper(II)/bisoxazoline 25 complex as the catalyst, cycloadducts 149 derived from a variety of azomethine imines 148 were prepared in good to high yields with moderate to good exo selectivity and high enantioselectivity (Scheme 2.38). 

For the highly enantioselective rearrangement of ester-substituted allyl vinyl ethers catalyzed by copper(ll) bisoxazoline complexes, see ... 

Chiral C2-symmetric bisoxazoline-copper(II) complexes [30, 31] were introduced as catalysts for cycloaddition and ene reactions of glyoxylates with dienes [9] leading to intense activity in the use of these catalyst for different cycloaddition reactions. 

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. 

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