中心金属或配体刚性调控的α-酮酸酯对硝基烯的不对称共轭加成

通过手性二胺配体与Cu或Ni络合合成了手性金属催化剂,并将其应用于α-酮酸酯对硝基烯的不对称共轭加成反应中,发展了通过改变中心金属或调节配体刚性实现反应对映选择性反转的策略.使用同一手性二胺配体(1S,1'S)-1,1'-联异吲哚啉,与不同的金属前体(Cu(OAc)2·H2O与Ni(OAc)2·4H2O)络合,可以高选择性地得到绝对构型相反的共轭加成产物(ee值高达94%与93%).同样,使用同一金属前体Cu(OAc)2·H2O,与同一手性源出发合成的两种刚性不同的二胺配体络合,也可以在这个反应中实现产物绝对构型的反转(ee值高达94%与94%).     

Carboranylphosphites—new effective ligands for rhodium-catalyzed asymmetric hydrogenation of dimethyl itaconate

Novel monodentate phosphites containing ortho- and meta-closo-dodecarboranyl groups have been synthesized and applied in the asymmetric Rh-catalyzed hydrogenation of dimethyl itaconate, providing excellent enantioselectivities (up to 99.8% ee in CH₂Cl₂ and up to 93% ee in supercritical CO₂).     

Enantioselective copper-catalyzed cyclopropanation of styrene by means of chiral bispidine ligands

Enantiopure C₁- and C₂-symmetric bispidine ligands have been synthesized and screened in the asymmetric copper-catalyzed cyclopropanation of styrene. In order to improve the enantiomeric excesses (ee) of the cyclopropane derivatives, the best performing C₁-symmetric diamine ligand was selected for studies on the reaction conditions. The optimized procedure allowed us to obtain up to 91% ee for the cis-cyclopropane derivative and up to 79% ee for the trans one.     

Convenient preparation of optically active cibenzoline and analogues from 3,3-diaryl-2-propen-1-ols

(R)-(+)-Cibenzoline (95% ee) was synthesized in two steps from (+)-2,2-diphenylcyclopropylmethanol 3a (98% ee), which was oxidized with IBX in DMSO, followed by treatment with ethylenediamine in the presence of I₂ and K₂CO₃ in tBuOH. Compound (R)-(+)-3a (98% ee) was prepared by cyclopropanation of 3,3-diphenyl-2-propen-1-ol 1 with Et₂Zn and CH₂I₂ in the presence of a catalytic amount of (S)-2-(methanesulfonyl)amino-1-(p-toluenesulfonyl)amino-3-phenylpropane 2, followed by esterification with 3,5-dinitorobenzoyl chloride, recrystallization, and hydrolysis.     

A chiral bidentate phosphoramidite (Me-BIPAM) for Rh-catalyzed asymmetric hydrogenation of α-dehydroamino esters, enamides, and dimethyl itaconate

High performance of Me-BIPAM for enantioselective hydrogenation of α-dehydroamino esters, enamides, and dimethyl itaconate was demonstrated. [Rh(Me-BIPAM)(diene)]X (diene = cod, nbd; X = BF₄, PF₆, SbF₆) gave optically active β-aryl α-amino esters up to 99% ee, 1-arylethylamines up to 97% ee, methyl 2-acetylaminobutanoate with 90% ee, and dimethyl 2-methylsuccinate with 97% ee under 0.3−0.8 MPa dihydrogen with 0.1−1 mol % catalyst loading.     

Synthesis of novel chiral Schiff-base ligands and their application in asymmetric nitro aldol (Henry) reaction

Chiral Schiff-bases prepared from chiral amino alcohols catalyze the enantioselective Henry (nitro aldol) reaction between nitromethane and p-nitrobenzaldehyde in the presence of Cu(OTf)₂ and Zn(OTf)₂. Zn(OTf)₂ promoted the reaction yield, while Cu(OTf)₂ promoted the enantiomeric excess. The highest enantioselectivities were observed with ligand 3 (44% ee) and ligand 5 (47% ee).     

Inverse electron demand asymmetric cycloadditions of cyclic carbonyl ylides catalyzed by chiral Lewis acids—Scope and limitations of diazo and olefinic substrates

High enantioselectivities (94-96% ee) were obtained for the inverse electron-demand 1,3-dipolar cycloadditions between cyclohexyl vinyl ether and 2-benzopyrylium-4-olate generated via Rh₂(OAc)₄-catalyzed decomposition of o-methoxycarbonyl-α-diazoacetophenone. The reactions were effectively catalyzed by Eu(OTf)₃, Ho(OTf)₃, or Gd(OTf)₃ complexes (10 mol %) of chiral 2,6-bis[(4S,5S)-4,5-diphenyl-2-oxazolinyl]pyridine. The reactions with the other electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, and butyl-tert-butyldimethylsilylketene acetal showed moderate enanantioselectivities (60-73% ee). Good to high enantioselectivities (73-97% ee) were also obtained for the cycloadditions between 3-acyl-2-benzopyrylium-4-olates, generated from methyl 2-(2-diazo-1,3-dioxoalkyl)benzoates and butyl or cyclohexyl vinyl ethers, in the presence of binaphthyldiimine (BINIM)-Ni(II) complexes (10 mol %). Under similar conditions, the reaction between methyl 2-(2-diazo-1,3-dioxohexyl)benzoate and 2,3-dihydrofuran was highly endo-selective, and moderately enantioselective (70% ee). For the BINIM-Ni(II)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction. The scope of the cyclic carbonyl ylides was extended to those generated from 1-diazo-2,5-pentanedione derivatives, which were reacted with butyl or TBS vinyl ether and catalyzed using the (4S,5S)-Pybox-4,5-Ph₂-Lu(OTf)₃ complex to give good levels of asymmetric inductions (75-84% ee).     

Enantioselective intramolecular amidation of sulfamate esters catalyzed by chiral manganese(III) Schiff-base complexes

Enantioselective intramolecular amidation of sulfamate esters catalyzed by chiral manganese(III) Schiff-base complexes under mild conditions (PhI(OAc)₂, Al₂O₃, C₆H₆, 5 °C) was achieved in moderate to good yields (up to 92%), substrate conversions (up to 99%), with virtually complete cis-selectivity and with ee values up to 79% ee.     

Copper-catalyzed enantioselective 1,4-conjugate addition of dialkylzinc reagents to α,β- and α,β,γ,δ-unsaturated ketones

An enantioselective Cu(II)-catalyzed conjugate addition of dialkylzinc reagents to α,β- or α,β,γ,δ-unsaturated ketones with chiral cyclohexane-based amidophosphine ligands was developed. With 2 mol% of Cu(OAc)₂·H₂O/L5, the conjugate addition of diethylzinc to α,β-unsaturated ketones was achieved in good-to-excellent yields (up to 98%) and high enantioselectivities (up to 92% ee). This catalytic system was shown to be efficient for the 1,4-conjugate addition of Et₂Zn to (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one with 85% yield and 90% ee. Moreover, with 1 mol% of Cu(OTf)₂/L11, the conjugate addition of α,β,γ,δ-unsaturated ketones was accomplished with 1,4-regioselectivity, good yields (79–86%) and excellent enantioselectivities (up to 97% ee).     

Stereoselective reductions with macrocyclic NADH models

Macrocyclic NADH models with two (C₂ symmetry) or four (D₂ symmetry) nicotinamide units comprised in a ring have been prepared and found to reduce activated carbonyl compounds in good yields and high enantiomeric excess. The roles of magnesium ions as a cocatalyst and the temperature have also been investigated. The smaller, C₂-symmetric macrocycle gave 96% ee upon reduction of ethyl benzoylformate whereas the best result with the larger D₂-symmetric model was 81% ee for the reduction of methyl benzoylformate.     

Enantioselective water-soluble iron–porphyrin-catalyzed epoxidation with aqueous hydrogen peroxide and hydroxylation with iodobenzene diacetate

The asymmetric epoxidation of styrene derivatives by H₂O₂ (or UHP) to give optically active epoxides (ee up to 81%) and hydroxylation of alkanes to give optically active secondary alcohols (ee up to 78%) were carried out in methanol and water using chiral water-soluble iron porphyrins as catalysts.     

Determination of enantiomeric excess for organic primary amine compounds by chiral recognition fast-atom bombardment mass spectrometry

Enantiomeric excess (ee) of organic primary amine compounds such as phenylglycine methyl ester hydrochloride (2) has been determined by fast-atom bombardment (FAB) mass spectrometry (NBA matrix). Chiral recognition in host–guest complexation systems between crown ethers [H] and amino acid ester ammonium ions [G] has been extended to the ee determination. The method characteristically uses a 1/1 mixture of a pair of enantiomeric hosts whose enantiomer is isotopically labeled [(RRRR)-1 and (SSSS)-1-d₆]. Chiral recognition of a given guest is simply measured with the given host–pair reagent from the relative peak intensities of the two corresponding diastereomeric host–guest complex ions in I[(H_RRRR · G)⁺]/I[(H_SSSS-d6 · G)⁺ = I_R/I_S-d6, so called IRIS value. The IRIS value varies in a linear fashion with the ee quantitiy of 2 and produces a symmetric linear V-shaped plot, indicating that in the case of a primary amine guest (such as 2) with unknown ee, one can determine the ee by this type of chiral recognition FAB mass spectometry. Further, based on the observed concentration effects on the IRIS values, it is suggested that the present IRIS value reflects the concentration ratio of the diastereomeric complex ions formed in the matrix.     

介孔载体负载Pt催化剂上α-酮酸酯的不对称氢化

以介孔材料SBA-15、经或未经Al2O3修饰的具有三维立方孔道结构的SiO2为载体,制备了负载型Pt催化剂,并用于催化α-酮酸酯底物2-氧代-4-苯基-丁酸乙酯(EOPB)和丙酮酸乙酯(Etpy)的不对称氢化反应中.结果表明,当SBA-15孔径由6.2,7.6和9.2nm依次增加时,EOPB不对称氢化的活性和手性选择...     

BINAM-prolinamides as recoverable catalysts in the direct aldol condensation

New BINAM-prolinamides were developed and tested as organocatalysts in the direct aldol condensation between aldehydes and several aliphatic ketones. C₂-symmetrical (Sa)-BINAM-l-prolinamide gives the best enantioselectivities for this transformation, being recovered and reused after the reaction by simple extractive techniques. The reaction was performed in DMF/H₂O at 0 °C to give the aldol products in up to 95% ee for acetone. For 2-butanone, the corresponding iso-regioisomers were regioselectively obtained in up to 96% ee working in DMF at rt. In the case of cyclohexanone, dr up to 10:1 in favour of the anti products, which were obtained in 90–93% ee, was achieved.     

Heterogeneous asymmetric reactions, 14. Epicinchona alkaloids in the enantioselective hydrogenation of ethyl pyruvate over Pt/alumina. What determines the sense of enantioselection?

The enantioselective hydrogenation of ethyl pyruvate to (R)-and (S)-ethyl lactate over Pt/Al₂O₃ catalyst was investigated using epiquinine (42% ee) and epiquinidine (22% ee) as modifiers and the results were compared with those found for quinine (85% ee) and quinidine (81% ee). The experimental results show that the sense of enantioselection is determined by the conformation of the entire alkaloid, and the structure of the intermediate is a 1∶1 complex of the pyruvate and the ‘anti open’ conformer of the cinchona alkaloid.     

Nitration of Halterman porphyrin: a new route for fine tuning chiral iron and manganese porphyrins with application in epoxidation and hydroxylation reactions using hydrogen peroxide as oxidant

A methodology is reported for the regioselective nitration of the phenyl groups of Halterman porphyrin, using NaNO₂. These nitro-porphyrins can be reduced to aminoporphyrins and then N-dimethylated to give new optically active porphyrins. Applications to the asymmetric epoxidation of styrene derivatives by H₂O₂ to give optically active epoxides (ee up to 60%) and hydroxylation of alkanes to give optically active secondary alcohols (ee up to 69%) were carried out in organic solvents (dichloromethane/methanol) using chiral iron and manganese porphyrins as catalysts.     

Metal/linked-BINOL complexes: Applications in direct catalytic asymmetric Mannich-type reactions

Development of metal/linked-BINOL complexes and their applications in direct catalytic asymmetric Mannich-type reactions of hydroxyketones are reviewed. A Et₂Zn/linked-BINOL complex was effective for diastereo- and enantioselective synthesis of β-amino alcohols. By choosing the proper protective groups on the imine nitrogen, either anti- or syn-β-amino alcohol was obtained in excellent enantioselectivity (up to >99.5% ee) using the same zinc catalysis. Y{N(SiMe₃)₂}₃/linked-BINOL complex was effective for various hydroxyketones, affording syn-β-amino alcohols with high enantioselectivity (up to 98% ee). To broaden the nucleophile scope to carboxylic acid derivatives, N-acylpyrrole was utilized as an ester equivalent donor. In(O-iPr)₃/linked-BINOL complex was effective for generating an In-enolate from N-acylpyrrole in situ, giving Mannich adducts with high enantioselectivity (up to 98% ee).     

Palladium-catalyzed asymmetric allylic nucleophilic substitution reactions using chiral tert-butanesulfinylphosphine ligands

The asymmetric allylic alkylation of racemic 1,3-diphenyl-2-propenyl acetate 3 with dimethyl malonate proceeded smoothly in the presence of lithium acetate, BSA (N,O-bis(trimethylsilyl)acetamide), [Pd(η³-C₃H₅)Cl]₂, and chiral tert-butanesulfinylphosphine ligand 2c to give the allylic alkylation product in good yield and high enantiomeric excess (up to 93% ee), while the enantioselectivities of allylic amination of 3 with various amines were moderate (up to 76% ee).     

Catalytic asymmetric hydrogenation of indoles using a rhodium complex with a chiral bisphosphine ligand PhTRAP

Highly enantioselective hydrogenation of N-protected indoles was successfully developed by use of the rhodium catalyst generated in situ from [Rh(nbd)₂]SbF₆ and the chiral bisphosphine PhTRAP, which can form a trans-chelate complex with a transition metal atom. The PhTRAP–rhodium catalyst required a base (e.g., Cs₂CO₃) for the achievement of high enantioselectivity. Various 2-substituted N-acetylindoles were converted into the corresponding chiral indolines with up to 95% ee. The hydrogenations of 3-substituted N-tosylindoles yielded indolines possessing a stereogenic center at the 3-position with high enantiomeric excesses (up to 98% ee).     

A P-chiral bisdiamidophosphite ligand with a 1,4:3,6-dianhydro-d-mannite backbone and its application in asymmetric catalysis

A novel readily available P,P-bidentate diamidophosphite ligand with P^∗-stereocentres is prepared from an inexpensive C₂-symmetric 1,4:3,6-dianhydro-d-mannite. By using this efficient ligand, up to 98% ee is achieved in Pd-catalysed asymmetric allylic alkylation, up to 92% ee in Pd-catalysed asymmetric allylic amination and up to 87% ee in Rh-catalysed asymmetric hydrogenation. The influence of the precatalyst, substrate and solvent on the enantioselectivity is discussed.