Schiff bases, chiral metal complexes

The first chiral transition-metal catalyst designed for an enantioselective transformation was applied to the reaction between a diazo ester and an alkene to form cyclopropanes [1]. In that application Nozaki and coworkers used a Schiff base-Cu(II) complex (1), whose chiral ligand was derived from oc-phenethylamine, to catalyze the cyclopropanation of styrene with ethyl diazoacetate (Eq. 5.1) [2],... 

A tridentate Schiff base Cr(III) complex derived from l-amino-2-indanol catalyzes the enantioselective ring opening of meso A-2,4-dinitrobenzyl aziridines with TMSN3 (Sch. 18) [96]. The chiral (salen)metal complexes, used in the enantioselective ring opening of epoxides, were found to be much less effective (for Cr) or inactive (for Co). 

The selective S3mthesis of tri- and dichlorotitanium complexes 140-142 bearing chiral tridentate Schiff base ligands derived from (lf ,25)-( )-l-aminoindanol (Fig. 20) has been recently reported. X-ray structural studies of these complexes revealed a mononuclear feature with an octahedral coordination sphere at the metal center, and a meridional occupation of the Schiff base. Surprisingly, though these complexes lack the typical ROP-initiating units such as aUcoxides or amides, they are effective catalysts for the controlled ROP of L-lactide, as evidenced by the linearity of the molecular weight versus [l-LA] [Ti] ratio as well as the narrow PDIs (1.17-1.33) [127]. 

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). 

Rh(II) carboxylates, especially Rh2(OAc)4> have emerged as the most generally effective catalysts for metal carbene transformations [7-10] and thus interest continues in the design and development of dirhodium(II) complexes that possess chiral51igands. They are structurally well-defined, with D2h symmetry [51] and axial coordination sites at which carbene formation occurs in reactions with diazo compounds. With chiral dirhodium(II) carboxylates the asymmetric center is located relatively far from the carbene center in the metal carbene intermediate. The first of these to be reported with applications to cyclopropanation reactions was developed by Brunner [52], who prepared 13 chiral dirhodium(II) tetrakis(car-boxylate) derivatives (16) from enantiomerically pure carboxylic acids RlR2R3CC OOH with substituents that were varied from H, Me, and Ph to OH, NHAc, and CF3. However, reactions performed between ethyl diazoacetate and styrene yielded cyclopropane products whose enantiopurities were less than 12% ee, a situation analogous to that encountered by Nozaki [2] in the first applications of chiral Schiff base-Cu(II) catalysts. 

Sigman and Jacobsen reported the first example of a metal-catalyzed enantioselective Strecker-type reaction using a chiral Alnl-salen complex (salen = N,N -bis(salicyhdene)-ethylenediamine dianion) [4]. A variety of N-allylimines 4 were evaluated in the reaction catalyzed by complex 5 to give products 6, which were isolated as trifluoroacetamides in good yields and moderate-to-excellent enantioselectivities (Scheme 3). Substituted arylimines 4 were the best substrates, while alkyl-substituted imines afforded products with considerably lower ee values. Jacobsen and co-workers also reported that non-metal Schiff base catalysts 8 and 9 proved to be effective in the Strecker reaction of imines 7 with hydrogen cyanide to afford trifluoroacetamides 10 after reaction with trifluoroacetic anhydride, since the free amines were not stable to chromatography (Scheme 4) [5]. 

The assymetric Strecker reaction of diverse imines, including aldimines as well as ketoimines, with HCN or TMSCN provides a direct access to various unnatural and natural amino acids in high enantiomeric excesses, using soluble or resin-linked non-metal Schiff bases the corresponding chiral catalysts are obtained and optimized by parallel combinatorial library synthesis [93]. A rather general asymmetric Strecker-type synthesis of various imines and a, 9-unsaturated derivatives is catalyzed by chiral bifunctional Lewis acid-Lewis base aluminum-containing complexes [94]. When chiral (salen)Al(III) complexes are employed for the hydrocyanation of aromatic substituted imines, excellent yields and enatio-selectivities are obtained [94]. 

A tripod-type Schiff-base ligand, (127), was prepared by a 3 1 condensation reaction of 2-phenyl-4-formylimidazole in methanol.204 In two nickel(II) complexes, the screw coordination arrangement of the tripod ligand (127) around the metal ion induces chirality, resulting in a A (clockwise) or a A (anticlockwise) enantiomer.204 A multifunctional tripodal ligand possessing two different functionalities, such as pyridine and cyano moieties, (128), has been prepared by the reaction of 2-aminomethylpyridine, excess acrylonitrile, and glacial acetic acid. 

Stereoselective epoxidation of alkenes, desymmetrization of maso-TV-sulfonylaziri-dines, Baeyer-Villiger oxidation of cyclobutanones, Diels-Alder reactions of 1,2-dihydropyridines, and polymerization of lactides using metal complexes of chiral binaphthyl Schiff-base ligands 03CCR(242)97. 

The addition of diethylzinc to aldehydes produces secondary alcohols. This process can be stereoselectively catalyzed by chiral amino alcohols that form Schiff-base zinc complexes with the aldehyde and the metal. With the aim of simplifying the work-up of these reactions and to use continuous-flow processes, the polymer-supported amino alcohols 115 and 116 were synthesized (Scheme 21) [91]. The polymers were obtained by co-polymerization of the chiral monomer 117 and styrene 58 in the presence of divinylbenzene (118) or cross-tinldng agent 119 containing a flexible oxyethylene chain. The latter was used to ensure sufficient flexibility within the cross-linked network of the polymer and to further activate the nucleophile by coordination of the oxyethylene chain to the metal. 

Several metallic species other than titanium have been reported. Kobayashi showed that the tin(II) complex (16, Fig. 4) modified by cinchonine, a natural alkaloid, catalyzed the reaction to give the chiral cyanohydrin of cyclohexanecar-baldehyde in 90% ee [54]. Corey applied a magnesium complex of chiral bisox-azoline (17, Fig. 4) to the asymmetric silylcyanation. High selectivity of up to 95% ee was observed in the reactions of aliphatic aldehydes compared with benzaldehyde (52% ee) [55]. An aluminum complex of a peptide containing the phenolic Schiff base (7) was shown by Mori and Inoue to be an efficient catalyst for the addition of TMSCN to aldehydes [56,57]. 

A difficult challenge in developing ARO reactions with carbon nucleophiles is identifying a reagent that is sufficiently reactive to open epoxides but at the same time innocuous to chiral metal catalysts. A recent contribution by Crotti clearly illustrates this dehcate reactivity balance. The lithium enolate of acetophenone added in the presence of 20 mol % of the chiral Cr(salen) complex 1 to cyclohexene oxide in very low yield but in 84% ee (Scheme 10) [23]. That less than one turnover of the catalyst was observed strongly suggests that the lithium enolate and the Schiff base catalyst are not compatible under the reaction conditions. 

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