CuOTf complexes cyclopropanation

Tanner et al. (58) investigated the use of chelating diaziridines (85) as ligands for transition metals. The cyclopropanation of styrene using CuOTf complexes of phenyl-substituted aziridine (85a) proceeds in modest enantioselectivity and dias-tereoselectivity, but improved enantioselectivity is observed with complexes derived from benzyl-substituted bis(aziridine) (85b), Eq. 42 (59). Complexes derived... 

Chiral bis(oxazoline)-CuOTf complexes also have been found to catalyze enantioselective cyclopropanation with diazomethane (eq 76) and (trimethylsilyl)diazomethane, the latter giving rise to higher diastereoselectivities particularly in the case of CuPFe. Copper catalysts are, however, of no help with donor-acceptor diazo reagents such as aryl- and vinyldiazoesters, which are preferentially transferred with very good selectivities in the presence of Rh2(DOSP)4. ... 

A complex of a chiral, nonracemic bis(oxazoline) with CuOTf is a highly effective catalyst for asymmetric cyclopropanation of alkenes. Copper(ll) triflate complexes do not catalyze the reaction unless they are first converted to Cu by reduction with a diazo compound or with phenylhydrazine. CuOTf complexes are uniquely effective. Thus the observed enantioselectivity and catalytic activity, if any, are much lower with other Cu or Cu" salts including halide, cyanide, acetate, and even perchlorate. Both enantiomers of the bis(oxazoline) ligand are readily available. Spectacularly high levels of asymmetric induction are achieved with both mono- (eq 8) and 1,1-disubstituted alkenes (eq 9). 

The same difference in regioselectivity holds for cyclopropanation with ethyl diazoacetate 25 K It is assumed that Cu(OTf)2 or Cu(BF4)2 are reduced to the Cu(I) salts by the diazo compound the ability of CuOTf to form stable complexes with olefins may then explain why, with these catalysts, cyclopropanation is governed by the steric environment around a double bond rather than by its electron-richness. 

Evans et al. (34) reported preliminary results showing that 55c CuOTf is moderately selective in mediating the aziridination of styrene, producing the heterocycle in 61% ee. Lowenthal and Masamune (44) mention in a footnote to their cyclopropanation paper that the copper complex of camphor-derived bis(oxa-zoline) (103) provides the aziridine of styrene in 91% yield and 88% ee. However, this reaction has been found to be irreproducible (76,77) and further reports of aziridination from the Masamune laboratories have not appeared. 

More recently, Burgess et al. (34) used the same approach in the synthesis of a constrained phenylalanine derivative, 3-phenyl-2,3-methanophenylalanine (123). Libraries of metal complexes were screened to determine the best combination for the asymmetric cyclopropanation reaction (35). The ligands shown below were combined with AgSbFg, (CuOTf)2 PhH, RuC12(C10H14)]2, Sc(OTf)3, where tri-... 

In 1991, Evans and co-workers employed CuOTf-derived complexes of bis-(oxazoline) ligands 2, 3, 7b, 38, and 45 in the same cyclopropanation reaction of... 

Cyclopropanation. The cationic Cu(I) complex, which is readily prepared from (5, 5)-r-Bu-box and CuOTf, is the most efficient catalyst available today for the cyclopropanation of mono-and 1,1-disubstituted olefins with diazoacetates. For example, in the reaction of ethyl diazoacetate with 2-methylpropene, >99% ee and high yields can be obtained with this catalyst using substrate to catalyst ratios as high as 1000 1. 

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. ... 

Copper and rhodium complexes catalyze the reaction of alkenes with diazoacetate to give alkyl cyclopropanecarboxylates [13]. In the presence of Cu(acac)2, the reaction of carbohydrate enol ether 20 with methyl diazoacetate afforded a 1 4 mixture of cis- and frani-cyclopropanes 21 and 22 (c -product 21 was obtained with 95% de). When the reaction was catalyzed by CuOTf in the presence of hgand 23, the tranj -product 22 was obtained with 60% de (Scheme 10.4). The absolute configuration of the major diastereomer was not given [19]. 

Enantioselective cyclopropanation (16, 38-39). The bis(oxazoline) I, prepared from t-leucinol and 2,2-dimethylpropanc-l,3-dioy chloride), forms a white, crystalline complex (2) with CuOTf which is an effective catalyst for asymmetric cyclopropanation with ethyl diazoacetate. 

The use of metal complexes in cyclopropanation reactions allows the formation of metal carbenes or carbenoids, which are endowed with increasing stability, in comparison to free carbene. Although most of these metal carbenes and carbenoids are highly electrophilic, their reactivity profile is dependent on the metal [68]. Thus, for the cyclopropanation of methyl 1//-indole-1-carboxylate with EDA (Table 4.2), the best yield was observed using 5 mol % of [Cu(hacac)2] (hfa-cac = hexafluoroacetylacetonato) [110] as catalyst in CH2CI2 at room temperature, affording the desired cyclopropanated product III-39 in 72 % yield (Table 4.2, entry 1). The reaction was less eflftcient with [Rh2(OAc)4], Cu(OTf)2 and CuOTf (Table 4.2, entries 2-4). 

The conditions reported by the Qin group for the intermolecular cyclopropanation of 3-substituted hexahydropyrroloindole provided unsuccessful results (Table 4.3, entry 3) [65, 69]. Furthermore, no conversion was observed using Cu(OTf)2, CuOTf, IMF copper(l) 27 or IMes gold(I) 15 complexes as catalysts (Table 4.3, entries 3-7) [116, 117]. Only starting material was recovered under the optimized conditions. This is probably due to the higher steric hindrance of the indole III-35, in comparison with methyl l//-indole-l-carboxylate, preventing the nucleophilic attack of the enamine moiety. 

Polyfluorinated BOX ligand 228 provides a useful copper complex catalyst, which can be recovered easily from the reaction mixture by a fluorous solvent system [159]. Benaglia and coworkers reported that an F-BOX ligand with CuOTf catalyzed the asymmetric cyclopropanation of diazoacetate in a CgFig/CHaCN biphasic mixture the F-BOX ligand was readily separated from products by phase separation and recovered from the reaction mixture (Scheme 1.105). 

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