Ni(II) bis(oxazoline)-catalyzed enantioselective syn aldol reactions of N-propionylthiazolidinethiones in the presence of silyl triflates

An enantioselective aldol reaction of N-propionylthiazolidinethione and representative aldehydes is disclosed. The reaction is catalyzed by [Ni(S,S)-t-BuBox](Otf)2. Enolization is effected by 2,6-lutidine, and TMSOTf facilitates catalyst turnover. Syn diastereoselectivities range from 88:12 to 97:3, and enantioselectivities are 90% or greater. Both aromatic and enolizable aliphatic aldehydes are included within the scope of this aldol addition process.     

Surface-enhanced stereoselectivity in Mukaiyama aldol reactions catalyzed by clay-supported bis(oxazoline)-copper complexes

Surface effects on a laponite-exchanged bis(oxazoline)-copper complex modify the stereochemical course of the Mukaiyama aldol reaction between 2-(trimethylsilyloxy)furan and alpha-ketoesters, leading up to 90% ee (dr 86 : 14) becoming the best overall result obtained for this reaction and significantly improving the homogeneous process.     

Amino acid recognition of pyridine bis(oxazoline)-copper(II) complex in aqueous solvent

Enantioselective recognition of amino acids has been studied with C₂-symmetric chiral pyridine bis(oxazoline)-copper(II) complexes at physiological pH condition. UV-visible titration revealed strong binding of submillimolar dissociation constant between pyridine bis(oxazoline)-copper(II) complex and amino acids in aqueous solution. Moderate selectivity of up to 2:1 between d- and l-amino acids was achieved. The enantiomers were baseline resolved by capillary electrophoresis, using the bis(l-lysine)-copper(II) complex as a chiral selector.     

Heterogeneous asymmetric Henry reaction using a chiral bis(oxazoline)-copper complex immobilized on magnetically separable mesocellular mesoporous silica support

A chiral bis(oxazoline) ligand was immobilized onto a magnetically separable hierarchically-ordered mesocellular mesoporous silica (M-HMMS) and this new catalytic system was examined in the asymmetric Henry reaction between various aldehydes and nitromethane at ambient temperature. Good enantioselectivity (upto 86.0% ee) was observed when the free silanol groups of the mesoporous silica were capped by trimethylsilyl group. This catalyst was separated magnetically and reused several times without significant loss of reactivity or enantioselectivity. This magnetic separation of catalysts could lead to further development toward practical industrial scale application due to simplicity without cumbersome filtration.     

Catalytic and highly enantioselective reactions of alpha-sulfonyl carbanions with chiral bis(oxazoline)s

The enantioselective reactions of lithiated benzyl trifluoromethyl sulfones with a substoichiometric amount of a bis(oxazoline) and various aldehydes is disclosed. The products were formed with excellent diastereo- and enantioselectivities. Fluorination of the sulfone with N-fluorobenzenesulfonimide and a stoichiometric amount of a bis(oxazoline) gave products with extremely high enantioselectivities (up to 99% ee; ee=enantiomeric excess). The enantioselective reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway.     

Polymer-bound bis(oxazoline) as a chiral catalyst

A chiral bis(oxazoline) was grafted on ArgoGel and used in the palladium-catalysed substitution of (±)-1,3-diphenyl-2-propenyl acetate with dimethyl malonate. The enantioselectivity was the same as that observed when the analogous monomeric catalyst was used (94–95% e.e.), despite the fact that the C₂ symmetry of the ligand was affected when coupled to the polymer. The polymer-supported catalyst could be recycled several times after removal of precipitated Pd(0). The polymer-bound bis(oxazoline) was also applied in a zinc-catalysed Diels–Alder reaction but lower selectivity and reactivity than the monomer was observed.     

Polymer-supported Bis(oxazoline)-copper complexes as catalysts in cyclopropanation reactions

Bis(oxazolines) are easily immobilized by functionalization of the central methylene bridge with polymerizable groups and subsequent polymerization. Polymers are transformed into copper catalysts active in the cyclopropanation of styrene with ethyl diazoacetate. The results are similar or even better than those obtained with the similar homogeneous systems, and the catalysts can be easily recovered and reused. The substitution in the methylene bridge leads to a slight reduction in the enantioselectivity and an unexpected cis-preference.     

Modular synthesis of chiral pentadentate bis(oxazoline) ligands

Highly modular N,Y,Z,Y,N-ligands (Y=N, O, S; Z=N, NO, OH, OMe) have been prepared using bis(oxazoline) building blocks either as nucleophiles or as electrophiles in coupling reactions with central aromatic units. This way, a great variety of pentadentate bis(oxazoline) ligands in diastereo- and enantiomerically pure form become readily available, which are useful for the construction of helical metal complexes with predetermined chirality.     

Enantioselective and diastereoselective Mukaiyama-Michael reactions catalyzed by bis(oxazoline) copper(II) complexes.

The scope of highly enantioselective and diastereoselective Michael additions of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these additions are useful synthons that contain termini capable of differentiation under mild conditions. Michael acceptor pi-facial selectivity is consistent with two-point binding of the imide substrate and can be viewed as an extension of substrate enantioselection in the corresponding Diels-Alder reactions. A model analogous to the one employed to describe the hetero Diels-Alder reaction is proposed to account for the observed relation between enolsilane geometry and product absolute diastereocontrol. Insights into modes of catalyst inactivation are given, including spectroscopic evidence for inhibition of the catalyst by a dihydropyran intermediate that evolves during the course of the reaction. A procedure is disclosed in which an alcohol additive is used to hydrolyze the inhibiting dihydropyran and afford the desilylated Michael adduct in significantly shortened reaction time.     

Enhanced reactivity and enantioselectivity in catalytic glyoxylate-ene reactions using chiral bis(oxazoline)–copper complex in an ionic liquid

An optimal hydrophobic ionic liquid was discovered as a solvent for highly enantioselective glyoxylate-ene reactions catalyzed by a chiral bis(oxazoline)–copper complex. The reactivity and stereoselectivity were highly dependent upon the property of the ionic liquids; reactions between olefins and ethyl glyoxylate in [Bmim]SbF₆ at ambient temperature provided remarkably enhanced reactivity and stereoselectivity, which greatly exceed those of the corresponding reactions in dichloromethane. Furthermore, the metal–ligand complex was readily recycled up to eight times while exhibiting no significant decrease in reaction efficiency.     

Enantioselective reaction of alpha-lithiated dithioacetals using chiral bis(oxazoline)s: new chiral formyl anion equivalents

The enantioselective reaction of various alpha-lithiated dithioacetals with aldehydes or a ketone in the presence of bis(oxazoline)s was examined. Among them, unsymmetrical dithioacetals were found to be the best choice for attaining high enantioselectivity. The reaction of lithiated tert-butylthio(2-pyridylthio)methane with aldehydes proceeded with good diastereoselectivity as well as with good enantioselectivity. The enantioselective reaction was shown to proceed through dynamic thermodynamic resolution. Mercury(II) chloride effected hydrolysis of the dithioacetal moiety of the products to 2-hydroxyaldehydes, which were directly reduced to give the optically active 1,2-diols.     

On the intermediates in chiral bis(oxazoline)copper(II)-catalyzed enantioselective reactions--experimental and theoretical investigations

The intermediates in the chiral bis(oxazoline)copper(II)-catalyzed reactions have been investigated by means of experimental and theoretical investigations. It is shown that the absolute configuration of the hetero-Diels-Alder adduct obtained from the reaction of ethyl glyoxylate with 1,3-cyclohexadiene in the presence of the chiral bis(phenyloxazoline)copper(II) is dependent on the solvent. In this case, a linear relationship between the enantiomeric excess (ee) and the dielectric constant of the solvent was observed. However, the enantiomeric excess for the adduct obtained with the chiral bis(tert-butyloxazoline)copper(II) complex is independent of the solvent. The addition of different coordinating solvents to the chiral catalysts was investigated and no effect on the enantioselectivity of the reaction was observed. A series of chiral bis(tert-butyloxazoline)-, bis(phenyloxazoline)-, and bis(indaneoxazoline)copper(II) complexes has been prepared and characterized by X-ray analysis, and the similarity between the structures is discussed. For comparison, two related chiral bis(tert-butyloxazoline)- and bis(phenyloxazoline)zinc(II) complexes were also prepared and characterized. A series of chiral bis(oxazoline)copper(II)-substrate (the substrate being glyoxal or methyl glyoxylate) complexes was investigated by means of ab initio calculations. Calculation of the total energy of the optimized structure of 17-, 19-, and 21-electron bis(oxazoline)copper(II)-substrate complexes give the 17-electron complex as the most stable and the most reactive complex, while the 21-electron complex is less stable and also much less reactive. The optimized structures of both the 17-electron bis(tert-butyloxazoline)- and bis(phenyloxazoline)copper(II)-substrate complexes show that the plane of the substrate molecule is twisted by approximately 40-45 degrees out of the bis(oxazoline)copper(II) plane, in agreement with the X-ray structures. On the basis of the experimental results, X-ray structures, and ab initio calculations, the structure of the intermediate(s) and reactivity of the chiral bis(oxazoline)copper(II)-substrate complexes are discussed.     

Synthetic, spectral and solution studies on imidazolate-bridged copper(II)-copper(II) and copper(II)-zinc(II) complexes

Synthesis, spectral and solution studies on 2-ethyl imidazolate-bridged (2-EtIm) homo-binuclear copper(II)-copper(II) and hetero-binuclear copper(II)-zinc(II) homologue are described. Magnetic moment values of homo-binuclear complexes indicate that the imidazolate group can mediate antiferromagnetic interactions. Optical spectra of hetero-binuclear complex at varying pH values suggest that the imidazolate-bridged complex is stable over the pH-range 7.15–10.0.     

Asymmetric Henry reactions catalyzed by metal complexes of chiral oxazoline based ligands

Chiral oxazolines have been synthesized from norephedrine and pyrrole nitrile or benzoyl chloride and applied to the catalytic asymmetric Henry reactions of p-nitro aldehydes with nitromethane to provide β-hydroxy nitroalkanols in high conversion (up to 92%). The reaction was then optimized in terms of the metal, solvent, temperature, and amount of chiral ligand. The corresponding catalyst with Cu(OTf)₂ and isopropanol as the solvent gave the best enantioselectivities (up to 84% ee) of the corresponding β-nitroalkanol for p-nitrobenzaldehyde.     

Asymmetric Friedel-Crafts alkylation of methoxyfuran with nitroalkenes catalyzed by diphenylamine-tethered bis(oxazoline)-Zn(II) complexes

The first catalytic asymmetric Friedel-Crafts reaction of 2-methoxyfuran with nitroalkenes was developed under the catalysis of diphenylamine-tethered bis(oxazoline)-Zn(OTf)2 complexes. The reaction conditions and ligands were optimized, and the scope of the reaction was tested by varying the nitroalkenes. For most of aromatic and heteroaromatic nitroalkenes, good yields and high enantioselectivities (86-96% ee) were obtained. The methoxyfuran group in the product can be transformed to carboxylic acid via oxidative fragmentation with full retention of the configuration.     

新型C2对称的手性双(亚)唑啉化合物的合成

手性双噁唑啉化合物因其在不对称合成领域的广泛应用,而成为有机合成的一个研究热点。具有C2对称的手性双噁唑啉化合物因其在不对称合成反应中表现出较好的对映选择活性而倍受关注,其合成方法有由羧基转化为噁唑啉基;     

DFT study of bis(picolinato-N,O)-copper(II) complex

The geometry of bis(pyridine-2-carboxylato-N,O)-copper(II) complex is optimized at B3LYP/6-311G^∗ level of theory and compared with experimental data. Comparing the electronic structure of this complex with that of its anionic ligand does not indicate any mechanical strain in the five-membered Cu–O–C–C–N metallocycle. The copper d-electron population of 9.2 corresponds to Cu(II) oxidation state. Using 6-31G^∗ basis sets produces an incorrect non-planar structure of the complex.     

Asymmetric Friedel-Crafts alkylation of indoles with 3-nitro-2H-chromenes catalyzed by diphenylamine-linked bis(oxazoline) and bis(thiazoline) Zn(II) complexes

An efficient diastereo- and enantioselective Friedel-Crafts alkylation of indoles with 3-nitro-2H-chromenes catalyzed by diphenylamine-linked bis(oxazoline) and bis(thiazoline) Zn(II) complexes has been developed. This asymmetric Friedel-Crafts alkylation led to medicinally privileged indolyl(nitro)chromans in good yields with high enantioselectivities (up to 95% ee) and diastereoselectivities under mild reaction conditions.     

The zero-field splitting tensors of dimeric bis(dialkyldithiocarbamato)-copper(II) and -silver(II)

The zero-field splitting tensor of dimeric bis(dialkyldithiocarbamato)-copper(II) is separated into a dipolar and a spin—orbit part, which both have been calculated using the results of an extended Hückel molecular orbital calculation. It has been established that the zero-field splitting tensor of the corresponding Ag dimer is determined by spin—orbit interactions.