Chiral Cobalt Complexes Research Articles

不斉触媒および反応場の設計に基づく高エナンチオ選択的不斉合成反応の研究

Highly enantioselective asymmetric syntheses, i.e., enantioselective addition of alkylmetal reagents to aldehydes and imines, enantioselective conjugate addition of dialkylzincs to enones, and asymmetric autocatalysis have been developed by designing asymmetric catalysts (or chiral ligands) and chiral environment of the reactions. Automultiplication of chiral compounds by asymmetric autocatalysis was discovered where a chiral product acts as a chiral catalyst for its own production. Asymmetric autocatalysis with>99.5% ee in a yield of > 99% was attained using pyrimidyl alkanol as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. The asymmetric autocatalysis exhibits significant positive non-linear effect on ee. Asymmetric autocatalyst with very low (ca. 0.00005%) ee enhances its ee significantly up to > 99.5% ee during the consecutive asymmetric autocatalysis without the assistance of any other chiral auxiliary. Moreover, amino acids and [6] helicene with very low ee which are produced by asymmetric photolysis and photosynthesis using circularly polarized light serve as chiral initiators of asymmetric autocatalysis, and pyrimidyl alkanol with high ee is obtained. Inorganic chiral crystals such as quartz and sodium chlorate, [2.2] paracyclophanes, allenes, chiral cobalt complexes due to the topology of coordination, chiral primary alcohols due to the deuterium substitution also work as chiral initiators. Asymmetric autocatalysis is capable to discriminate efficiently the chirality of various chiral compounds. Moreover, the reactions of pyrimidinecarbaldehyde with diisopropylzinc without adding chiral substance exhibit the formation of enantioenriched S or R pyrimidyl alkanols with approximate stochastic distribution, which indicates the reaction is a spontaneous absolute asymmetric synthesis. These results correlate for the first time the proposed origins of chirality of organic compounds with the chirality of organic compounds with very high ee.

Fluorous biphasic hydrolytic kinetic resolution of terminal epoxides

Although application of light-fluorous techniques facilitates the isolation of reaction products from the hydrolytic kinetic resolution (HKR) of terminal epoxides catalysed by cobalt complexes of salen ligands, the extension of the original fluorous biphasic approach to this reaction is far from being a trivial exercise. The nature of the counter anion has a dramatic effect on the catalytic activity of heavily fluorinated chiral (salen) cobalt(III) complexes. Excellent enantioselectivities are obtained in the fluorous biphasic HKR of 1,2-hexene oxide when fluorinated anions are introduced (e.e.s up to 99% both for the diol and the epoxide), with C 8F 17COO – affording reaction rates even higher than those observed with non-fluorous systems.

Kinetic resolution of rac-phenylalanine by stereoselective complexation to a chiral cobalt complex through pi-pi stacking interaction.

A cobalt(III) complex with chiral ligand, H2cpel (N-carboxymethyl-N-pyridylethyl-l-leucine), was prepared for chiral recognition of amino acids. Through the competitive coordination of racemic phenylalanine to the chiral cobalt complex, [Co(cpel)(CO(3))](-) (1), enantioselective recognition was achieved on the ternary complex, which was determined on the basis of HPLC analysis with a chiral column. The formation rate for the [Co(cpel)(l-phe)] complex (2) was 6-times superior to that of [Co(cpel)(d-phe)] (3). The preferential formation of 2 might be illustrated by the interligand pi-pi stacking interaction. Crystal structural analysis for 2 and 3 revealed that aromatic rings, pyridine ring of CPEL and phenylalanine sidechain, in 2 were very close each other but those in 3 were far apart. Such interligand aromatic interaction in 2 was also examined by the use of (1)H NMR spectra.

New Asymmetric Catalysis by (Salen)cobalt(III) Complexes (Salen=[Bis(salicylidene)ethylenediaminato]={{2,2′-[ethane-1,2-diyl]bis[(nitrilo-N)methylidyne]bis[phenolato-O]}(2−)}) of cis--Structure: Enantioselective Baeyer-Villiger Oxidation of Prochiral Cyclobutanones

A series of chiral (salen)cobalt(III) complexes (salen=[bis(salicylidene)ethylenediaminato]={{2,2′-[(ethane-1,2-diyl)bis[(nitrilo-κN)methylidyne]bis[phenolato-κO]}(2−)}) of cis-β structure were prepared and used for the enantioselective Baeyer-Villiger oxidation of prochiral cyclobutanones with hydrogen peroxide as terminal oxidant. Both cationic (salen)cobalt(III) and neutral iodo(salen)cobalt(III) complexes 3–5 and 7–12, respectively, all having a chiral binaphthalenediamine unit, were found to be effective catalysts for the enantioselective Baeyer-Villiger oxidation (Tables 1, 3, and 4). In particular, complex 8 bearing electron-withdrawing F-atoms showed a good level of enantioselectivity (75–79% ee) in the reactions of 3-arylcyclobutanones (Scheme 4). On the other hand, complex 12 bearing tBu groups at C(3) and C(3′) and electron-withdrawing NO2 groups at C(5) and C(5′) (trivial numbering) exhibited a high enantioselectivity of 98% ee in the reaction of a tricyclic cyclobutanone (Table 4).

Spontaneous resolution of chiral cobalt(III) complexes

Two novel methods for inducing partial spontaneous resolution of conglomerates by crystallisation were proposed. The first one, termed ‘internal entrainment’, involves using a single crystal as the seed from a primary racemic mixture in its resolution by entrainment. The second method involves crystallisation under deficiency of a conglomerator, which causes homochiral packing of the crystals. Both methods were applied to Co(III) complexes with the effect of resolution up to 83% e.e.

Conditions for chiral asymmetry generation in the preparation of the chiral octahedral cobalt complex.

We have reported that the random chiral asymmetry generation, which is a spontaneous preferential generation of one enantiomer, was observed in the synthesis of a chiral octahedral cobalt complex, cis-[CoBr(NH(3))(en)(2)]Br(2). In this article, we review our studies to explain in this system the autocatalytic growth of small enantiomeric excess that arises due to statistical fluctuations. One important experimental finding was that the rate of chiral autocatalysis increased with increasing the degree of supersaturation. Furthermore, our numerical simulation indicates that even small inhomogeneities in the reaction system may play a significant role because their effect is amplified by the autocatalytic reaction under appropriate conditions. In a small volume, fluctuations in concentration can grow if the autocatalytic growth overcomes the diffusional loss of the excess concentration from this volume. This may makes the enantiomeric excess of the chiral complex randomly fluctuate from run to run.

Highly enantioselective asymmetric autocatalysis induced by chiral cobalt complexes due to the topology of the coordination of achiral ligands

Chiral octahedral cobalt complexes, K[Co(edta)]·2H2O and K[Co(trdta)]·2H2O, induce enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde, affording the pyrimidyl alkanol with high (85–94%) enantiomeric excesses.

Cocrystallization of chiral cobalt complexes via formation of quasiracemates

Starting from the enantiomerically pure or racemic nucleophile 1-phenylethylamine (L) chiral cobalt complexes with the general formula [Co(Hdmg)2XL] (Hdmg = dimethylglyoximate, X = CN, NO2) were obtained as homochiral or heterochiral crystalline solids, respectively. The crystal structures of the resulting cyano and nitro complexes were determined by single crystal X-ray diffraction. The homochiral solids crystallize in space group P21 with two molecules per asymmetric unit, the racemates in P21/c with only one independent molecule. From a solution containing equimolar amounts of enantiomerically pure S-L cyano and R-L nitro complexes a stable and well-ordered binary solid could be crystallized and structurally characterized. The molecular constituents of opposite chirality are arranged in pairs in the vicinity of pseudo inversion centers forming a quasi-racemate in space group P21. The driving force for the formation of this cocrystal is discussed in terms of intermolecular geometry and energy: The crystal structures of all five complexes are similar with respect to lattice parameters and intermolecular arrangement, but comparisons based on space filling and lattice energy confirm higher packing efficiency for the racemates and the quasi-racemate than for the enantiopure compounds.

Asymmetric Radical Polymerization of Maleimides Using a Chiral Cobalt(II) Complex

Asymmetric Radical Polymerization of Maleimides Using a Chiral Cobalt(II) Complex

Asymmetric hetero-Diels–Alder reaction of 1-alkyl-3-silyloxy-1,3-dienes with ethyl glyoxylate catalyzed by a chiral (salen)cobalt(II) complex

The hetero-Diels–Alder reactions of 1-alkyl-3-( tert-butyldimethylsilyl)oxy-1,3-butadienes with ethyl glyoxylate catalyzed by chiral salen–metal complexes have been studied. With a cobalt(II) complex as the catalyst, the reaction of 1-(2-benzyloxyethyl)-3-( tert-butyldimethylsilyl)oxy-1,3-butadiene with ethyl glyoxylate gave the Diels–Alder product in 75% isolated yield with the endo: exo ratio >99:1 and the enantiomeric excess ≥52%. The effects of temperature, catalyst and solvent are also discussed.

ChemInform Abstract: Asymmetric Cyclopropanation Catalyzed by Chiral Cobalt(II) Complexes from (1R)‐3‐Hydroxymethylenebornane‐2‐thione.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Stereoselective isomerization of chiral cobalt(III) complexes

The isomerization reactions among the geometrical isomers of chiral complexes, [Co(edma) 2] +, [Co(ida)(edma)], and [Co(mida)(edma)], have been studied in a weakly basic aqueous solution. Some of the optical active isomers exhibited stereoselective isomerization without the loss of optical activity. It was suggested that the isomerization of the isomer with facially or meridionally chelated-ligands proceeded through the deprotonated five-coordinated intermediate formed by CoO bond-rupture in the conjugate-base form.

ChemInform Abstract: Stereoselectivity in Reactions of Metal Complexes. Part 15. Structure and Stability of Chiral Cobalt(III) Complexes with Pentadentate Ligands.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthese chiraler Kobalt‐Komplexe mit planoid‐tetradentatem Ligand‐System

Synthesis of Chiral Cobalt Complexes with Planoid‐Tetradentate Ligand SystemThe synthesis of a series of Cbl‐related, achiral CoIII complexes 9a–c as well as enantiomerically pure, C2‐symmetric CoIII complexes 15 and 18, is reported (Schemes 3, 5, and 7). The crystal structures of 9c and 15 were determined. Complex 18 acts as an enantioselective catalyst in the isomerization of 1,4‐epiperoxides to hydroxycycloalkenones.

Asymmetric Cyclopropanation Catalyzed by Chiral Cobalt(II) Complexes from (1R)-3-Hydroxymethylene-Bornane-2-Thione.

Asymmetric Cyclopropanation Catalyzed by Chiral Cobalt(II) Complexes from (1R)-3-Hydroxymethylene-Bornane-2-Thione.

Stereoselectivity in Reactions of Metal Complexes. Part XV. Structure and stability of chiral cobalt(III) complexes with pentadentate ligands

AbstractThe syntheses and characterization of four new linear pentadentate ligands and their CoIII complexes are described: N,N′‐[(pyridine‐2,6‐diy)bis(methylene)]bis[sarcosine] (sarmp), N,N′‐[(pyridine‐2,6‐diyl)bis(methylene)]bis[(R)‐ or (S)‐proline] ((R,R)‐ or (S,S)‐promp), N,N′‐[(pyridine‐2,6‐diyl)bis(methylene)]bis[N‐(methyl)‐(R)‐ or (S)‐alanine] ((R,R)‐ or (S,S)‐malmp); 2,2′‐[pyridine‐2,6‐diyl]bis[(S)‐ or rac‐N‐(acetic acid)pyrrolidine] ((S,S)‐ or rac‐bapap). The complexes were characterized and, with but one exception, complex formation is stereospecific: Δ‐exo‐(R,R) (or Λ‐exo‐(S,S)) for promp and Λ‐(R,R) (or Δ‐(S,S)) for bapap. The exception is [Co((R,R)‐ or (S,S)‐malmp)H2O]ClO4 for which two forms are obtained, to which Λ‐endo‐(R,R) (or Δ‐endo‐(S,S)) and, tentatively, Δ‐unsymmetric‐(R,R)‐ (or Λ‐unsymmetric‐(S,S)‐) configurations are assigned. X‐Ray crystal structures are presented for the complexes [Co(sarmp)H2O]ClO4, [Co((S,S)‐promp)H2O]ClO4, [Co(rac‐bapap)H2O]ClO4 and endo‐[Co(rac‐malmp)H2O]ClO4. Ligand acid dissociation and CoII and FeII complex‐formation constants are reported.

Metal Ion Cages: Capping Reactions With Bifunctional Methylene Compounds and Formaldehyde

[(1,1,1-Tris(4-amino-2-azabutyl)ethane)cobalt(III)](3+) ([co(sen)]3+) and [(tris(4-amino-2- azabutyl)amine)cobalt(III)](3+) ([Co(azasen)]3+) react with formaldehyde and diethyl malonate or cyanoacetic acid ethyl ester in the presence of base to form macrobicyclic cages [ox- osarcophagine (oxosar) and oxoazasarcophagine (azaoxosar)] about the metal ion. The cage structure of the complexes has been established by an X-ray crystallographic analysis of [(1-carboxy-8-methyl-2-oxo-3,6,10,13, 16,19-hexaazabicyclo[6.6.6]icosanato)cobalt(III)] diperchlorate [Co(Me,CO2H-oxosar- H)]2+ which crystallizes in the orthorhombic space group Pbcn, with cell parameters a 33.61, b 10.42, c 13.743 � , and V 4813 � 3 , and Z 8. The chiral cobalt(III) complex is characteristically inert to substitution and racemization, but the cobalt(II) complex, obtained by reduction of the appropriate cobalt(III) compound, is surprisingly stable both to loss of Co2+ ion and to racemization at 25°C (pH 7.1, t½4.5 days). The syntheses, spectroscopic and chemical properties are reported. The kinetics of the electron self exchange for the cage system [Co(Me,CO2Et-oxosar-H)]+/2+, and of H2O2 formation from [coII(Me,co2Et-oxosar - H)]+ and O2 are reported. Similar syntheses have been carried out to half-cap the [co(en)3]3+ ion (en = ethane-1,2-diamine). These and related reactions have allowed substituents such as COOR, COOH, CN, COCl, CONR2, NH2 and NO2 to be placed on the bridgehead carbon atoms, and have altered the redox potentials of the systems by at least 0.3 V. The oxosar COII ions are useful as powerful reducing agents [from c. -0.3 to -0.6 V (v. n.h.e.)], and the cages are capable of further derivatization to build larger macromolecules.

Effects of Six-Membered Chelate Rings in the Oxidant Cobalt(III) Complexes on the Stereoselective Oxidation of [Co(en)3]2+

Abstract The stereoselectivities in the oxidation of [Co(en)3]2+ by chiral cobalt(III) complexes containing six-membered chelate ligands, such as malonate, β-alaninate, and acetylacetonate ions, were examined. All of the oxidant complexes with the Δ-configuration studied here, like the corresponding oxalato and glycinato complexes containing five-membered chelate rings, led to an excess of Λ-[Co(en)3]3+, with the exception of Δ-[Co(ox)(acac)2]−.

Synthesis of chiral square planar cobalt(III) complexes and catalytic asymmetric epoxidations with these complexes

The chiral square planar cobalt(III) complexes, Na[Co(η4-(R)-HMBA-DMP)](2), {H4(R)-HMBA-DMP =(–)2,4-bis[(R)-2-hydroxy-2-methylbutyramido]-2,4-dimethylpentan-3-one} and complexes with two or four chiral centres, Co{[OC(R)R′C(O)N]2L}[(3; R = Et, R′= Ph, L = CMe2COCMe2); (4; R = Et, R′= Me, L =o-phenylene); (5; R = Et, R′= Me, L = CH(Me)CH2CHMe); (6; R = Et, R′= Ph, L = CH(Me)CH2CHMe)] have been prepared and characterized by 1H NMR spectroscopy, solution magnetic properties, and X-ray crystallography. Asymmetric epoxidations of styrenes with these chiral cobalt(III) complexes and iodosylbenzene have been investigated. Various substituted styrenes were epoxidized with chemical yields of (25–86%) and enantiomeric excesses between 0 and 17%.

In vivo photoreaction of a chiral cobalt complex: DNA cleavage by Co(DIP) 33+ in mammalian cells

The chiral complex tris (diphenylphenanthroline) cobalt (III) (Co(DIP) 3 3+ provides a photoreactive probe for chromatin structure in mammalian cells. The complex, which upon photoactivation cleaves DNA in a conformation-specific fashion in vitro, is shown also to cleave DNA in vivo upon irradiation with ultraviolet light (>300 nm). Δ- and Λ-Co (DIP) 3 3+ isomers are taken up efficiently into cultured Chinese hamster ovary cells and concentrate within cell nuclei. In the absence of light the complexes are toxic to the cells (10% survival at ∼ 300 nM), but after ultraviolet irradiation, the toxicity is markedly (>10-fold) increased. The synergism between irradiation and Co(DIP) 3 3+ administration may lie in photoreactions with DNA elicited by the cobalt complex. Alkaline sucrose gradient of DNA from cells exposed to Λ-Co(DIP) 3 3+ and irradiation show single-stranded DNA fragmentation under conditions where little cleavage is seen in cells either incubated with Λ-Co(DIP) 3 3+ or irradiated with > 300 nm A ultraviolet light. Cellular DNA is cleaved with lower efficiency than naked DNA, likely due to decreased accessibility of sites in vivo. Hybridization of fragments obtained from the alkaline sucrose gradients to a probe specific for the amplified dihydrofolate reductase gene reveals a similar distribution of dhfr sequences and total DNA, indicating that the family of conformations recognized by Λ-Co(DIP) 3 3+ are dispersed throughout the genome.