The synthesis of novel C2-symmetric P,N-chelation ruthenocene ligands and their application in palladium-catalyzed asymmetric allylic substitution

Novel air-stable C₂-symmetric tetrasubstituted ruthenocene-based ligands were readily synthesized and used for palladium-catalyzed asymmetric allylic substitution showing excellent enantioselectivity and high catalytic activity.     

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).     

Asymmetric addition of phenylacetylene to aldehydes catalyzed by soluble optically active polybinaphthols ligand

A chiral polymer ligand was synthesized by the polymerization of (S)-5,5′-dibromo-6,6′-dibutyl-2,2′-binaphthol (S-M-1) with (S)-2,2′-bishexyloxy-1,1′-binaphthyl-6,6′-boronic acid (S-M-2) via Pd-catalyzed Suzuki reaction. The application of the chiral polymer ligand to the asymmetric addition of phenylethynyl zinc to various aldehydes has been studied. The results show that the soluble chiral polybinaphthols ligand in combination with Et₂Zn and Ti(OⁱPr)₄ can exhibit excellent enantioselectivity for phenylacetylene addition to both aromatic and aliphatic aldehydes. The catalytically active center of the repeating unit S-1 used as a catalyst produced the opposite configuration of the propargylic alcohols to that of S-1, on the contrary, the chiral polymer gave the same configuration as the optically active binaphthol moiety of the polybinaphthols ligand. Moreover, the chiral polymer ligand can be easily recovered and reused without loss of catalytic activity as well as enantioselectivity.     

Catalytic asymmetric brominative dearomatization reaction of benzofurans

A catalytic asymmetric brominative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4-phthalazinediyl diether [(DHQ)₂PHAL] as the catalyst and N-bromoacetamide (NBAc) as the brominating reagent. A series of brominated spiro[benzofuran-2,5'-oxazoles] bearing two contiguous stereogenic centers were obtained in high yields (up to 99%) with excellent enantioselectivity (up to 97% ee).     

General and practical catalytic enantioselective Strecker reaction of ketoimines: significant improvement through catalyst tuning by protic additives

Significant improvement in enantioselectivity and catalyst activity was achieved for the catalytic enantioselective Strecker reaction. Using a catalyst (1-2.5 mol %) prepared from Gd(OⁱPr)₃ and d-glucose derived ligand 1, and in the presence of 2,6-dimethylphenol as an additive, high enantioselectivity was obtained from a wide range of ketoimines, including heteroaromatic and cyclic ketoimines. The new method was applied to an efficient catalytic asymmetric synthesis of sorbinil, a therapeutic agent for diabetic complications.     

Highly efficient and solvent-free direct aldol reaction catalyzed by glucosamine-derived prolinamide

The catalytic activity of novel sugar-based prolinamides in the aldol reaction between ketones and aryl aldehydes has been examined. The prolinamide 1c was found to be an efficient organocatalyst for the asymmetric aldol reaction under solvent-free conditions. A variety of ketones and aldehydes were used as substrates and the corresponding aldol products were obtained in excellent chemical yields with high levels of anti diastereoselectivity (up to 99:1) and enantioselectivity (up to >99%).     

Enantioselective hydrogenation of functionalized olefins catalyzed by Rh-chiral bidentatephosphite complexes

A novel catalytic system for the hydrogenation of dimethyl itaconate has been developed by using rhodium–diphosphite complexes. These chiral diphosphite ligands were derived from glucopyranoside, d-mannitol derivatives, and binaphthyl or H₈-binaphthyl phosphochloridites. The ligands based on the methyl 3,6-anhydro-α-d-glucopyranoside backbone and (R)- and (S)-binaphthol and/or (R)- and (S)-2,2′-dihydroxy-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthol gave almost complete conversion of the dimethyl itaconate and both enantiomers of dimethyl 2-methylsuccinate with excellent enantioselectivities. The stereochemically matched combination of methyl 3,6-anhydro-α-d-glucopyranoside and H₈-(S)-binaphthyl in ligand 2,4-bis{[(S)-1,1′-H₈-binaphthyl-2,2′-diyl]-phosphite} methyl 3,6-anhydro-α-d-glucopyranoside was essential to afford dimethyl 2-methylsuccinate with up to 98% ee. The sense of the enantioselectivity of products was predominantly determined by the configuration of the biaryl moieties of the ligands. An initial screening of [Rh(cod)₂]BF₄ with these ligands in the hydrogenation of (E)-2-(3-butoxy-4-methoxybenzylidene)-3-methylbutanoic acid was carried out. Good enantioselectivity (75% ee) and low yield for (R)-2-(3-butoxy-4-methoxybenzyl)-3-methylbutanoic acid were obtained.     

Efficient novel 1,2-diphosphite ligands derived from d-mannitol in the Pd-catalyzed asymmetric allylic alkylation

A novel Pd/1,2-diphosphite catalyzed asymmetric allylic alkylation of 1,3-diarylpropenyl acetate with malonates was developed. Catalyst optimization via a variation in the protecting groups at the 1,2- and/or 5,6-positions of d-mannitol skeleton and in biaryl moieties of the ligands led to a ‘lead’ catalyst, which efficiently mediated the allylic alkylations. The activities and enantioselectivities of the reaction clearly showed that the stereogenic centers of the skeleton and the axially chiral diaryl moieties of the ligands had a synergic effect. The ligand 1,2:5,6-di-O-isopropylidene-3,4-bis[(S)-1,1′-binaphthyl-2,2′-diyl]phosphite-d-mannitol afforded excellent yields (up to 99%) and high levels of enantioselectivies (ee up to 98%) in 1,4-dioxane/CH₂Cl₂ mixture (v/v, 1:1) using [Pd(π-allyl)Cl]₂ as catalytic precursor and LiOAc as base. Dramatic changes in the sense and in the degree of the enantioselectivity depending on the configuration of the diaryl moieties of the ligands and reaction conditions were observed.     

Chiral sulfur-containing ligands for iridium(I)-catalyzed asymmetric transfer hydrogenation of aromatic ketones

New efficient catalyst systems, coupled with IrCl(COD)PPh₃ and chiral [SNNS]-type ligands, were employed in the asymmetric transfer hydrogenation of aromatic ketones under mild reaction conditions. The corresponding optically active alcohols were obtained in high yield and good to excellent enantioselectivities (up to 96% ee). The chiral Ir(I) complexes with the ligands of [SNNS]-type were also prepared and characterized, which showed good enantioselectivity and high activity. The reactions can be performed in air and the catalytic experiments are greatly simplified.     

Efficient bimetallic titanium catalyst for carbonyl-ene reaction

A new family of achiral 3,3′,5,5′-tetrasubstituted-2,2′,6,6′-tetrahydroxy biphenyl ligand 4 was developed. The axial chirality of the ligand could be induced by the chelation of 2,2′,6,6′-tetrahydroxy groups with (R)-BINOL-Ti(OⁱPr)₂ to form an axially chiral bimetallic titanium catalyst 9. Compared with (R)-BINOL-Ti(OⁱPr)₂ catalyst, this novel catalyst 9 exhibited excellent activity and enantioselectivity for the carbonyl-ene reaction of methylstyrene and ethyl glyoxylate. 3,3′,5,5′-Tetrasubstituted groups showed a remarkable effect on both enantioselectivity and yield. With 9d prepared from 3,3′,5,5′-tetramethyl-2,2′,6,6′-tetrahydroxy biphenyl 4d as the catalyst, the best result, up to 97.6% ee and 99% yield, was obtained. Additionally, the bimetallic catalyst 9 also showed better catalytic capability than the corresponding monometallic catalyst.     

Rigid backbone 1,8-anthracene-linked bis-oxazolines (AnBOXes): design,synthesis, application and characteristics in catalytic asymmetric aziridination

A series of rigid backbone 1,8-anthracene-linked bis-oxazolines (AnBOXes) have been designed, synthesized, and evaluated in the catalytic asymmetric aziridination with [N-(p-toluenesulfonyl)imino]phenyliodinane (PhINTs) as a nitrene source. The results indicate that highly enantioselective aziridination of chalcones catalyzed by an AnBOX and CuOTf complex with up to >99% ee and the opposite enantioselectivity, compared with the ligands of Evans et al., can be achieved. The enantioselectivity is substituent dependent with respect to chalcones. Chalcones with electron-donating substituents show higher enantioselectivities due to the stronger Lewis basicity of the oxygen of their carbonyl groups than those with electron-withdrawing substituents. The results also indicate that the coordination between the oxygen of the carbonyl group in chalcones and the ether group in alkenes with the copper in the catalyst is essential for high enantioselectivity, while the π–π stacking interaction between two reactants plays an importantly additional role for high enantioselectivity in asymmetric aziridination. An excellent backbone-controlled stereoselectivity was observed for the AnBOX ligands in asymmetric aziridination, as this will provide very important information for designing novel ligands.     

Chemoselective and enantioselective transfer hydrogenation of β,β-disubstituted nitroalkenes catalyzed by a water-insoluble chiral diamine–rhodium complex in water

Asymmetric transfer hydrogenation of β,β-disubstituted nitroalkenes catalyzed by a chiral diamine–rhodium complex in combination with HCO₂Na–HCO₂H as a hydrogen source in water was successfully realized with high reactivity, excellent chemoselectivity and good enantioselectivity. The metal precursor and pH value of the aqueous solution have a large influence on the reactivity and chemoselectivity. The substituents on the benzene rings and the sulfonyl groups of TsDPEN have significant effects on the enantioselectivity. This catalytic asymmetric transformation is one of the most practical pathways to obtain optically active nitroalkanes.     

Asymmetric synthesis of cyclopropyl phosphonates using chiral terpenyl sulfonium and selenonium ylides

The asymmetric cyclopropanation of a vinylphosphonate using optically active sulfonium and selenonium ylides derived from (−)-menthol and (+)-limonene was developed. The ylides were generated in situ by the reaction of the corresponding sulfonium or selenonium salt in the presence of potassium carbonate or DBU as a base. The transfer of the CHPh and CHCO₂Et groups into the cyclopropane ring showed moderate diastereoselectivity and excellent enantioselectivity (up to 99:1) for the trans- and cis-products. The absolute configuration of phenyl cyclopropyl was assigned based on comparison to their tolyl analogues.     

Synthesis of (Z)-organylthioenynes using KF/Al2O3/solvent as recyclable system

PEG-400 and glycerol were successfully used as recyclable solvents for the synthesis of several organylthioenynes in good to excellent yields and high selectivity using solid supported catalyst (KF/Al₂O₃). This easy, general and improved method furnishes the corresponding alkenyl sulfides preferentially with Z configuration. The catalytic system and the glycerol or PEG-400 can be reused up to three times without previous treatment with comparable activity.     

The synthesis of dendritic BINOL ligands and their applications in the enantioselective Lewis acid catalyzed addition of diethylzinc to aldehydes

Novel dendritic chiral BINOL ligands have been synthesized through coupling of MOM-protected 3,3′-dihydroxymethyl-binaphthol with Fréchet-type polyether benzyl bromide dendrons followed by deprotection of the MOM groups using TsOH. These dendritic chiral BINOL ligands were found to be effective in the enantioselective addition of diethylzinc to benzaldehyde both in the presence and absence of Ti(O-iso-Pr)₄. The enantioselectivity decreased with increasing generation in both cases. In the latter case, the dendritic chiral BINOL ligands showed much higher catalytic activity and enantioselectivity than BINOL.     

Synthesis of cinchonidinium salts containing sulfonamide functionalities and their catalytic activity in asymmetric alkylation reactions

Various kinds of 4-(bromomethyl)benzenesulfonamides were prepared as quaternization reagent of cinchonidine. Cinchonidinium salts obtained from the quaternization of cinchonidine with 4-(bromomethyl)benzenesulfonamide showed highly enantioselective catalytic activity in the asymmetric benzylation of N-(diphenylmethylene)glycine tert-butyl ester. The corresponding phenylalanine derivative was obtained in high yield with a high level of enantioselectivity, up to 98% ee.     

PEG-400-H2O as a green and recyclable medium for asymmetric hydrogenations of aromatic ketones catalyzed by RuCl2(TPPTS)2-(S,S)-DPENDS

PEG-400-H₂O was found to be a green and recyclable reaction medium for asymmetric hydrogenations of aromatic ketones catalyzed by a ruthenium achiral monophosphine complex RuCl₂(TPPTS)₂ [TPPTS: P(m-C₆H₄SO₃Na)₃] modified by (S,S)-DPENDS [disodium salt of sulfonated (S,S)-1,2-diphenyl-1,2-ethylene-diamine]. The acetophenone product was obtained with 86.3% ee under the optimized conditions. The resulting products can be easily separated from the catalyst by extraction with n-hexane. The catalyst immobilized in PEG-400-H₂O not only exhibits excellent activity and enantioselectivity, but also can be recycled and reused several times without a loss of activity or enantioselectivity.     

Direct catalytic asymmetric Mannich-type reactions of isomerizable aliphatic imines: chemoselective enolate formation from a hydroxyketone by a Zn-catalyst

A direct catalytic asymmetric Mannich-type reaction of isomerizable aliphatic imines is described. A Et₂Zn/(S,S)-linked-BINOL complex was suitable for chemoselective enolate formation from a hydroxyketone in the presence of isomerizable aliphatic N-diphenylphosphinoyl imines. The reaction proceeds smoothly and β-alkyl-β-amino-α-hydroxyketones were obtained in good yield and high enantioselectivity (up to 99% ee), albeit in modest to low diastereoselectivity.     

Highly active and enantioselective copper-catalyzed conjugate addition of diethylzinc to cyclohexenone using sugar derivative diphosphites

High enantioselectivity combined with unprecedented high catalytic activity (81% ee and TOF≈1200 h⁻¹) are achieved in the copper-catalyzed 1,4-addition of diethylzinc to 2-cyclohexenone with new C₁-chiral diphosphites derived from the readily available d-(+)-xylose.     

Enantioselective Palladium(II)‐Catalyzed Intramolecular Aminoarylation of Alkenes by Dual N−H and Aryl C−H Bond Cleavage

An asymmetric palladium‐catalyzed intramolecular oxidative aminoarylation of alkenes has been developed with quinoline–oxazoline chiral ligands and Ag₂CO₃ as the oxidant. Various indolines containing a quaternary stereogenic center were synthesized in high yield with excellent enantioselectivity. Preliminary mechanistic studies suggest that the addition of a catalytic amount of phenylglyoxylic acid significantly accelerates the reaction and slightly enhances the enantioselectivity.