Evans copper complex

Since Evans s initial report, several chiral Lewis acids with copper as the central metal have been reported. Davies et al. and Ghosh et al. independently developed a bis(oxazoline) ligand prepared from aminoindanol, and applied the copper complex of this ligand to the asymmetric Diels-Alder reaction. Davies varied the link between the two oxazolines and found that cyclopropyl is the best connector (see catalyst 26), giving the cycloadduct of acryloyloxazolidinone and cyclopentadiene in high optical purity (98.4% ee) [35] (Scheme 1.45). Ghosh et al., on the other hand, obtained the same cycloadduct in 99% ee by the use of unsubstituted ligand (see catalyst 27) [36] (Scheme 1.46, Table 1.19). 

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... 

Evans et al.43 and Thorhauge et al.44 report that hetero Diels-Alder reactions in the presence of 81 or 83 coordinated copper complex proceed smoothly, resulting in excellent yields and enantiomeric excess. 

Evans suggests that the catalyst resting state in this reaction is a 55c Cu alkene complex 58, Scheme 4 (35). Variable temperature NMR studies indicate that the catalyst complexes one equivalent of styrene which, in the presence of excess alkene, undergoes ready alkene exchange at ambient temperature but forms only a mono alkene-copper complex at -53°C. Addition of diazoester fails to provide an observable complex. These workers invoke the metallacyclobutane intermediate 60 via a formal [2 + 2] cycloaddition from copper carbenoid alkene complex 59. Formation of 60 is the stereochemistry-determining event in this reaction. The square-planar S Cu(III) intermediate 60 then undergoes a reductive elimination forming the cyclopropane product and Complex 55c-Cu, which binds another alkene molecule. 

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. 

Palmer, F. B., Butler, C. A., Timperley, M. H. and Evans, C. W. (1998). Toxicity to embryo and adult zebrafish of copper complexes with two malonic acids as models for dissolved organic matter, Environ. Toxicol. Chem., 17, 1538-1545. 

For intermolecular cyclopropanations with unsubstituted diazoacetates the highest asymmetric inductions can be achieved with the copper(I) complexes of C2-symmetric, bidentate ligands developed by Pfaltz (e.g. 1) and Evans (2). The chiral rhodium(II) complexes known today do not generally lead to such high enantiomeric excesses as copper complexes in intermolecular cyclopropanations. For intramolecular cyclopropanations, however, chiral rhodium(II) complexes are usually superior to enantiomerically pure copper complexes [1374]. 

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],... 

Attempts to aziridinate alkenes with iron catalysts in an asymmetric manner have met with only limited success to date [101], In an early report on the use of various chiral metal salen complexes, it was found that only the Mn complex catalyzed the reaction whereas all other metals investigated (Cr, Fe, Co, Ni etc.) gave only unwanted hydrolysis of the iminoiodinane to the corresponding sulfonamide and iodoben-zene [102], Later, Jacobsen and coworkers and Evans et al. achieved good results with chiral copper complexes [103]. 

Wood, A.M., Evans, D.W. and Alberts, 3.3., 1983. Use of an ion exchange technique to measure copper complexation capacity on the continental shelf of the southeastern United States and in the Sargasso Sea. Mar. Chem., 13 305-326. 

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). 

Evans DA, Barnes DM, Johnson JS, Lectka T, von Matt P, Miller SJ, Murry JA, Norcross RD, Shaughnessy EA, Campos KR (1999) Bis(oxazoline) and bis(oxazolinyl)pyridine copper complexes as enantioselective Diels-Alder catalysts reaction scope and synthetic applications. J Am Chem Soc 121 7582-7594... 

Evans and coworkers [852] recommended copper complexes generated from Cu(OTf)2 and bisimines 3.29 derived from (IR, 2R)-cyclohexanediamine for similar purposes. The highest enantioselectivities are observed when R = 2.6-C12C6H3, but the endo/exo selectivity depends on the structure of the acyclic dienophile. 

Scheme 5.69 Stereodivergent Evans aldol addition mediated by copper complex 216a and tin complex 218. Model 233 for rationalizing the topicity in the copper-BOX-catalyzed aldol...

Evans et al. reported that the his(oxazolinyl)pyridine (pybox) complex of copper(II) 17 is a selective catalyst of Diels-Alder reactions between a-bromoacrolein or methacrolein and cydopentadiene affording the adducts in high enantioselectivity [23] (Scheme 1.30). Selection of the counter-ion is important to achieve a satisfactory reaction rate and enantioselectivity, and [Cu(pyhox)](ShFg)2 gave the best result. This catalyst is also effective for the Diels-Alder reaction of acrylate dieno-philes (vide infra). 

Evans et al. reported that the bis(imine)-copper (II) complex 25, prepared from chiral bis(imine) ligand and Cu(OTf)2, is also an effective chiral Lewis acid catalyst [34] (Scheme 1.44, Table 1.18). By tuning the aryl imine moiety, the bis(2,6-dichlor-ophenylimine) derivative was found to be suitable. Although the endojexo selectivity for 3-alkenoyloxazolidinones is low, significant improvement is achieved with the thiazolidine-2-thione analogs, for which both dienophile reactivity and endojexo selectivity are enhanced. 

The chiral BOX-copper(ll) complexes, (S)-21a and (l )-21b (X=OTf, SbFg), were found by Evans et al. to catalyze the enantioselective cycloaddition reactions of the a,/ -unsaturated acyl phosphonates 49 with ethyl vinyl ether 46a and the cyclic enol ethers 50 giving the cycloaddition products 51 and 52, respectively, in very high yields and ee as outlined in Scheme 4.33 [38b]. It is notable that the acyclic and cyclic enol ethers react highly stereoselectively and that the same enantiomer is formed using (S)-21a and (J )-21b as the catalyst. It is, furthermore, of practical importance that the cycloaddition reaction can proceed in the presence of only 0.2 mol% (J )-21a (X=SbF6) with minimal reduction in the yield of the cycloaddition product and no loss of enantioselectivity (93% ee). 

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... 

Evans D. A., Rovis T., Johnson J. S. Chiral Copper(II) Complexes As Lewis Acids for Catalyzed Cycloaddition, Carbonyl Addition, and Conjngate Addition Reactions. Pure Appl. Chem 1999 71 1407-1415... 

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]. 

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%. 

In a study published concurrently with the Evans bis(oxazoline) results, Jacobsen and co-workers (82) demonstrated that diimine complexes of Cu(I) are effective catalysts for the asymmetric aziridination of cis alkenes, Eq. 66. These authors found that salen-Cu [salen = bis(salicylidene)ethylenediamine] complexes such as 88b Cu are ineffective in the aziridination reaction, in spite of the success of these ligands in oxo-transfer reactions. Alkylation of the aryloxides provided catalysts that exhibit good selectivities but no turnover. The optimal catalyst was found to involve ligands that were capable only of bidentate coordination to copper. 

Helmchen and co-worker investigated the use of phosphinooxazolines as ligands for copper(II) catalyzed Diels-Alder reactions (Scheme 19) (214). Optimal selectivities are found for a-naphthyl-substituted phosphinooxazoline (299). These catalysts require 2.5 h to induce complete conversion to cycloadduct, compared to 18 h using the triflate complex 269c under identical conditions. Helmchen invokes a square-planar metal geometry to explain the stereochemistry of the adducts, similar to the model proposed by Evans. He suggests that the bulky phosphine substituents are required to orient binding of the dienophile in such a way as to place the olefin directly below the terf-butyl substituent on the oxazoline. 

Evans and coworkers262 demonstrated the utility of bis(oxazolidine)copper(II) complexes 425 as Lewis acid catalysts in Diels-Alder reactions of iV-enoyl-l,3-oxazolidin-2-ones 423 with cyclopentadiene, which gave adducts 424 (equation 128, Table 25). Their best results were obtained using catalyst 425c. Surprisingly, only 30% ee was obtained in the reaction between cyclopentadiene and 17a when catalyzed by 425a. Similar results were obtained for the thiazolidine-2-thione analogs of the iV-enoyl-l,3-oxazolidin-2-ones. 

Direct, controlled preparation of copper(I) complexes was achieved by Evans [7] from bisoxazolines and copper(I)triflate, which avoids the use of other methods for reduction or accidental reduction by the substrate, which may not always be efficient. When isobutene is the substrate one obtains only two enantiomers and no other products for styrene we obtain a cis and a trans product each occurring as a pair of enantiomers. We will illustrate this with styrene and the results of Pfaltz s semicorrin-copper. 

Evans and coworkers developed C2-symmetrical copper(II) complexes as chiral Lewis acids that rely on two-dentate substrates for their catalysis. Consequently,... 

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