Chiral Cu

Chiral Cu(II)-complexes as catalysts in hetero-Diels-Alder reaction 99PAC1407. 

Chiral Cu(ll)-complexes ofbis-oxazolines as Lewis acids for catalyzed cycloaddition, carbonyl addition, and conjugate addition reactions 99PAC1407. 

In the presence of 10 mol% chiral Cu(II) catalyst 25, 2-azadienes 26 reacted with dienophiles 27 to afford the corresponding piperidone derivatives in high yields... 

Inverse electron-demand Diels-Alder reaction of (E)-2-oxo-l-phenylsulfo-nyl-3-alkenes 81 with enolethers, catalyzed by a chiral titanium-based catalyst, afforded substituted dihydro pyranes (Equation 3.27) in excellent yields and with moderate to high levels of enantioselection [81]. The enantioselectivity is dependent on the bulkiness of the Ri group of the dienophile, and the best result was obtained when Ri was an isopropyl group. Better reaction yields and enantioselectivity [82, 83] were attained in the synthesis of substituted chiral pyranes by cycloaddition of heterodienes 82 with cyclic and acyclic enolethers, catalyzed by C2-symmetric chiral Cu(II) complexes 83 (Scheme 3.16). 

Corey et al. [19] simultaneously reported similar studies using a2,2 -bis(oxazolyl)-6,6 -dimethyl-l,l -biphenyl as copper(I)triflate chelate. This hgand afforded a stable monomeric chiral Cu(I) complex providing a highly... 

Corma et al. [55] have prepared chiral Cu(I) complexes with substituted pyrrolidine ligands bearing a triethoxysilyl group (Scheme 24). 

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]. 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

The Lewis acidic properties of chiral Cu(I) complexes have recently been exploited to augment the chemistry of the more developed Cu(II) Lewis acids. As a corollary, much less is known about the chemistry of Cu(I) Lewis acids. They have traditionally been categorized as soft Lewis acids, compared to the borderline-hard Cu(II) Lewis acids (1). 

AUcyl transfer from the magnesium hahde to the chiral Cu complexes generates the Cu complex A, as deduced from NMR experiments. Very likely, this complex functions in a similar manner as previously postulated for organocuprate additions . 

Mukund Sibi of North Dakota State University has developed (J. Am. Chem. Soc. 2004,126,718) a powerful three-component coupling, combining an a,(5-unsaturated amide 9, a hydroxylamine 10, and an aldehyde 11. The hydroxylamine condenses with the aldehyde to give the nitrone, which then adds in a dipolar sense to the unsaturated ester. The reaction proceeds with high diastereocontrol, and the absolute configuration is set by the chiral Cu catalyst. As the amide 9 can be prepared by condensation of a phosphonacetate with another aldehyde, the product 12 can be seen as the product of a four-component coupling, chirally-controlled aldol addition and Mannich condensation on a starting acetamide. 

Cul, methyllithium, and a camphor-derived /3-amino alcohol (239). Reaction of methylmagnesium iodide and benzylideneacetone in the presence of a small amount of a chiral Cu(I) thiolate complex gives the conjugate addition product in 57% ee (240). 

Cu catalysts for metal carbene transformations are active as Cu(I) complexes and not as Cu(II). Although in the distant past there was some disagreement with this proposition, bis-oxazoline, semicorrin, and even the Aratani catalysts are active only when Cu is in its +1 oxidation state [6,34,39,40], The chiral Cu(I) catalysts have been produced from the correspond-... 

Once again, cis-disubstituted olefins lead to higher enantioselectivities than do trans-disubstituted olefins, but here the differences are not as great as they were with allyl diazoacetates. Both allylic and homoallylic diazoacetamides also undergo highly enantioselective intramolecular cyclopropanation (40-43) [93,94], However, with allylic a-diazopropionates enantiocontrol i s lower by 10-30% ee [95], The composite data suggest that chi ral dirhodium(II) carboxamide catalysts are superior to chiral Cu or Ru catalysts for intramolecular cyclopropanation reactions of allylic and homoallylic diazoacetates. 

A catalytic asymmetric amination of enecarbamates has been attained using a chiral Cu(II) complex of diamine (210) as catalyst. Thus, azodicarboxylates have been shown to react with various enecarbamates (208) derived from aromatic and aliphatic ketones and aldehydes to provide acylimines (209) in good yields with high enantioselectivity (<99% ee). The catalyst loading required for high enantioselectivity was generally low (0.2 mol% in some cases).259... 

In another study Feringa et al. [20] reported a catalytic enantioselective three-component tandem conjugate addition-aldol reaction of dialkyl zincs. Here, zinc enolates were generated in situ via catalytic enantioselective Michael addition of dialkylzinc compounds to cydohexenone in the presence of a chiral Cu catalyst. Their diastereoselective reaction with an aldehyde then gave trans-2,3-disubstituted cyclohexanones in up to 92% yields and up to >99% ees (Scheme 9.11). 

Jacobsen et al. have shown that cyanoacetate derivatives undergo conjugate addition to ,/i-unsaturated imides in the presence of a chiral Al-oxo salen complex 32 to afford the corresponding product in up to 98% ee (Scheme 16) [19]. When an a-amino cyanoacetate was used, a highly functionalized lactam 33 was obtained in one step. Another example of Lewis acid-catalyzed conjugate addition of cyclic 1,3-dicarbonyl compounds to 2-oxobutenoate employed the chiral Cu-bisoxazoline complex 34 (Scheme 17) [20]. 

The chiral Cu(OTf)2/BOX complexes 8 and 9 are also catalysts of asymmetric Mannich-type additions of unmodified malonates and /3-ketoesters to activated N-tosyl-a-imino esters [22]. 

Chiral Cu Schiff bases were entrapped in zeolites and used as catalysts for sulfoxidation with H2C>2 or t-BuOOH, but no useful EE was observed... 

Other terminal olefins were transformed to the corresponding cyclopropane esters with Z-menthyl and d-menthyl diazoacetates with high stereoselectivity up to 98% ee (Scheme 3). Intramolecular reaction of the phenyl-allyl ester 9 was carried out to give the bicyclic compound 10 with 86% ee and 93% yield. The enantioselectivity for intramolecular cyclopropanation of the 3-methylbutenyl ester 11 was compared with chiral Cu(I), Rh(II), and Ru Pybox catalysts Rh>Ru>Cu [26]. 

Tran -fused pyranopyrans are formed in good yield and with high ee when butenoate esters react with pent-4-en-l-ols in the presence of chiral Cu oxazoline complexes. An initial transesterification is followed by an intramolecular hDA <02TL9397>. 

To our knowledge, topologically chiral molecules have not yet been resolved into enantiomers. However, we may anticipate that their energy barrier to racemization will be extremely high, compared to Euclidean chiral molecules. Therefore they are expected to be useful in enantioselective interactions or reactions. For example, it has been shown that tetrahedral copper(I) bis-2,9-diphenyl-l,10-phenanthroline complexes (which form the catenate subunits) are good reductants in the excited state [97] therefore the chiral Cu(I) catenates could be used for enantioselective electron-transfer reactions. Alternatively, the resolution of topologically chiral molecules would allow to answer fundamental questions, such as what are the chiroptical properties of molecular trefoil knots ... 

On account of their very important biological activity, /9-lactams are important synthetic targets [4-9]. Fused polycyclic -lactam subunits appear in many natural products such as penicillins [4-6] and trinems/tribac-tams [10-13]. Fu et al. reported that such frameworks can be prepared with high levels of enantioselectivity via the intramolecular Kinugasa reaction [ 14, 15] of alkyne-nitrone in the presence of a planar chiral Cu/phosphaferrocene-oxazoline catalyst [16]. For instance, compound 1 was transformed into tricyclic /9-lactam 3 in good stereoselectivity and yielded (88% ee and 74% yield) using 5 mol % of CuBr and 5.5 mol % of complex 2 (Scheme 1). 

Mattay et al. employed asymmetric copper(I)-catalyzed intramolecular [2 + 2]-photocycloaddition reactions in a synthetic approach to (+)- and (— )-grandisol [56]. Racemic dienol 33 was irradiated in the presence of CuOTf and a chiral ligand to yield mainly cyclobutanes 34 and ent-34 as a mixture of enantiomers. Other 1,6-dienes were also employed. A number of chiral nitrogen-containing bidentate ligands were tested, the most effective of which, (4S,4 S)-4,4 -diisopropyl-2,2 -bisoxazoline (35) and (4R,47 )-4,4 -diethyl-2,2 -bisoxazoline (36), ensured a minor enantiomeric excess of <5% ee (Scheme 12). The coordination of the diene to the chiral Cu(I) complex under formation of a complex of type 37 was proved by CD analysis. The authors suggest a lower reactivity of the chiral complex compared to the copper ion coordinated to solvent molecules as the reason for the low enantioselectivities observed. 

Asymmetric Baeyer-Villiger oxidation reaction In 1994, Bolm et al used chiral Cu and Ni complexes (7.23) in catalytic amount with different oxidation systems. 

Fig. 8 CD spectra for (a) the chiral Cu(ll)-L-tartrate metal complex and for mixed complexes of this host with equimolar amounts of (b) kanamycin, (c) amikacin, (d) gentamycin, and (e) streptomycin.

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