Bisoxazoline/copper complexes

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. 

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.

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. 

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. 

Jorgensen has recently reported similar enantioselective reactions between N-tosylimines 107 and trimethylsilyldiazomethane (TMSD) catalyzed by chiral Lewis acid complexes (Scheme 1.32) [57, 53]. The cis-aziridine could be obtained in 72% ee with use of a BINAP-copper(i) catalyst, but when a bisoxazoline-copper(i) complex was used the corresponding trans isomer was fonned in 69% ee but with very poor diastereoselectivity. 

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. 

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],... 

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

An hDA reaction between Danishefsky s diene and glyoxylate esters proceeds in the presence of bisoxazoline-lanthanide complexes with moderate levels of enantioselectivity <2000TL2203>. A similar reaction between Danishefsky s diene and a-keto esters proceeds with excellent enantioselectivity in the presence of bisoxazoline-copper <2001TL6231, 2003EJ0317, 2004TA1987> or Cr(m), Co(n and m)-salen complexes <2004TA3189>. 

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. ... 

Independently, the groups of Evans [375,376,377] and J0rgensen [378] have shown that /3,y-unsaturated a-keto esters react with ethyl vinyl ether in the presence of enantiomerically pure bisoxazoline copper(II) complexes as catalysts leading to enantiomerically enriched dihydropyrans. For instance 212 and 213 in ether at 20 °C and in the presence of complex 214 add to give the endo adduct 215 in 60% yield and with 96.5% ee. The latter is then converted into ethyl -D-ma no-p)Tanoside tetraacetate 216 (O Scheme 77) [379]. 

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. 

Analogous alkylations with unsaturated ketones can also be effected with silica-supported benzenesul-fonic acid sodium salt or, with some stereoselectivity, using a chiral imidazolidinone organo-catalyst. Optical induction can also be achieved in the addition of indole to alkyhdene malonates using bisoxazoline copper(II) complexes. ... 

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]. 

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). 

The enantioselective a-chlorination of -keto esters was achieved with up to 88% ee using NCS with a commercially available TADDOL ligand. The chiral bisoxazoline copper(II) complexes have also been reported to induce the asymmetric a-chlorination of -keto esters when reacted with NCS. The asymmetric a-chlorination of aldehydes has been achieved using NCS and (2/ ,5/ )-diphenylpyrrolidine as a chiral catalyst. For example, the enantioselective chlorination of 3-methylbutanal with NCS proceeds in 95% yield and 94% ee (eq 17). ... 

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. 

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. 

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