Chiral copper Schiff base

The catalytic asymmetric Henry reaction has been reviewed.42 Mild and efficient enantioselective nitroaldol reactions of nitromethane with various aldehydes have been catalysed by chiral copper Schiff-base complexes yielding the corresponding adducts with high yields and good enantiometric excess.43,44... 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

In 2000, Gennaii et al. discovered a new family of chiral Schiff-base ligands, with the general structure, Af-alkyl-p-(A -salicylideneamino)alkanesulfonamide, depicted in Scheme 2.28. These ligands were successfully implicated in the copper-catalysed conjugate addition of ZnEt2 to cyclic enones (Scheme 2.28) and, less efficiently, to acyclic enones such as benzalacetone (50% ee) or chalcone... 

In 1966, Nozaki et al. reported that the decomposition of o-diazo-esters by a copper chiral Schiff base complex in the presence of olefins gave optically active cyclopropanes (Scheme 58).220 221 Following this seminal discovery, Aratani et al. commenced an extensive study of the chiral salicylaldimine ligand and developed highly enantioselective and industrially useful cyclopropanation.222-224 Since then, various complexes have been prepared and applied to asymmetric cyclo-propanation. In this section, however, only selected examples of cyclopropanations using diazo compounds are discussed. For a more detailed discussion of asymmetric cyclopropanation and related reactions, see reviews and books.17-21,225... 

Asymmetric ring-opening of saturated epoxides by organocuprates has been studied, but only low enantioselectivities (< 15% ee) have so far been obtained [49, 50]. Muller et al., for example, have reported that the reaction between cyclohexene oxide and MeMgBr, catalyzed by 10% of a chiral Schiff base copper complex, gave trans-2-methylcyclohexanol in 50% yield and with 10% ee [50]. 

A group at the Academy of Sciences in Moscow 197) has synthesized chiral threonine. Derivatives of cyclic imino acids form copper complexes with glacine and carbonyl compounds. Hydroxyethylation with acetaldehyde and decomposition of the resulting complexes produced threonine with an optical purity of up to 97-100% and with threo/allo ratios of up to 19 1 197). The chiral reagents could be recovered and re-used without loss of stereoselectivity. The mechanism of this asymmetric synthesis of amino acids via glacine Schiff base/metal complexes was also discussed 197). 

The authors reported the chiral separation of proline and thereonine amino acid up to 20 and 6g, respectively, in a single run. Micropreparative resolution of lecucine was presented. The resolution was discussed with respect to the degree of sorbent saturation with copper(II), elution rate, eluent concentration, temperature, and column loading condition [16]. Weinstein [74] reported the micropreparative separation of alkylated amino acids on a Chiral ProCu column. In another article, a preparative chiral resolution of 3-methylene-7-benzylidene-bicyclo[3.3.1]nonane was achieved on 7.5% silver(I)-d-camphor- 10-sulfonate CSP [75]. Later, Shieh et al. [71] used L-proline-loaded silica gel for the chiral resolution of (ft,5 )-phcnylcthanolaminc as the Schiff base of 2-hydroxy-4-methoxyacetophenone. Gris et al. [76] presented the preparative separations of amino acids on Chirosolve L-proline and Chirosolve L-pipecolic acid CSPs. 

Chiral iminopyridines catalyse nitro aldol reactions with good ees in the pres- ence of copper(II) acetate, without the need for exclusion of air or moisture.143 A (g) phenylalanine-derived Schiff base - also complexed to copper(II) - is also effective, with the advantage that product configuration is easily reversed (by using the enantiomeric phenylalanine).144... 

Formyl-5-hydroxy[2.2]paracyclophane (153) was used as a chiral auxiliary in the synthesis of a-amino acids [98]. The reported enantiomeric excess was in the range of 90-98%. Racemic 153 was first prepared by Hopf and Barrett [99]. To separate the enantiomers, their Schiff bases with the dipeptide (S)valyl-(S)valine was prepared. The diastereomeric copper(II) complexes of this compound show different solubility in 2-propanol. Alternatively they can be separ-... 

Copper-Catalyzed Asymmetric Cyclopropanation with Chiral Schiff Bases... 

There are several other reports of successful application of this type of chiral Schiff base ligand in copper-catalyzed asymmetric cyclopropanation44" 51- 93-94 including intramolecular versions52. 

The copper-catalyzed cyclopropanation of alkenes with diazoalkanes is a particularly important synthetic reaction (277). The reaction of styrene and ethyl diazoacetate catalyzed by bis[/V-(7 )- or (5)-a-phenyl-ethylsalicylaldiminato]Cu(II), reported in 1966, gives the cyclopropane adducts in less than 10% ee and was the first example of transition metal-catalyzed enantioselective reaction of prochiral compounds in homogeneous phase (Scheme 90) (272). Later systematic screening of the chiral Schiff base-Cu catalysts resulted in the innovative synthesis of a series of important cyclopropane derivatives such as chrysanthemic acid, which was produced in greater than 90% ee (Scheme 90) (273). The catalyst precursor has a dimeric Cu(II) structure, but the actual catalyst is in the Cu(I) oxidation state (274). (S)-2,2-Dimethylcyclopropanecar-boxylic acid thus formed is now used for commercial synthesis of ci-lastatin, an excellent inhibitor of dehydropeptidase-I that increases the in vivo stability of the caibapenem antibiotic imipenem (Sumitomo Chemical Co. and Merck Sharp Dohme Co.). Attempted enantioselective cyclopropanation using 1,1-diphenylethylene and ethyl diazoacetate has met with limited success (211b). A related Schiff base ligand achieved the best result, 66% optical yield, in the reaction of 1,1-diphenylethylene and ethyl diazoacetate (275). 

Chiral copper (I) semicorrin complex Chiral copper(II) Schiff base complex... 

Enantioselective copper-catalyzed desymmetrization of meso cyclic allylic bisdiethyl-phosphates has alsobeen conducted with dialkylzinc reagents. Piarulli and Gennari initially showed that the copper(l) complex of a chiral Schiff base catalyzed tlie enantioselective desymmetrization of 4-cyclopentene-l,3-bis(diethylphosphate) with diethyzinc (Equation 20.75). Piarulli, Gennari, and Feringa then improved upon the enantioselectivities... 

After the introduction of chiral Schiff base and semicorrin ligands as enan-tioselective copper catalysts, the next major advance in copper systems is based on bis(oxazoline) ligand 7 (65) and 8 (66) (Scheme 11). With 7, up to 99% ee of cyclopropane was obtained for the cyclopropanation of styrene with EDA. Same enantioselections but higher diastereoselectivity (transrcis = 94 6) was obtained when 2,6-di-Zert-butyl-4-methylphenyl diazoacetate (BDA) was used instead of EDA. It was noted that the catalytic system with 7 was the only copper sys-... 

Copper complexes are also able to catal) e the insertion of a carbene into a silicon-hydrogen bond. Associated with C2-symmetric Schiff bases, CuOTf allows the formation of chiral... 

The ligand L48 belongs to the class of reduced Schiff base ligands that contains ferrocenealdehyde, instead of salicylaldehyde, and amino acid side arm. Several copper complexes of L48 are explored for their potential host-guest properties associated with the chiral cavity. 

Reactions of A-tosyliminophenyliodinanes (PhI=NTs) as nitrene source with alkenes in the presence of chiral ligands also present a valuable method to achieve asymmetric aziridination reactions. Cinnamate esters 73 yield enantiomeric aziridinate products in good selectivities on reaction with chiral bisoxazolines 23 and Al-tosyliminophenyliodinanes in the presence of copper salts (Scheme 29) [87]. Biaryl Schiff bases 74 can also be used as ligands in the enantioselective aziridination of ciimamate esters, chromenes and st5renes [88]. Chiral C2-symmetric salen-type ligands 75 were also found to be highly effective for the... 

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