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.     

Synthesis of chiral cyclic β-amino ketones by Ru-catalyzed asymmetric hydrogenation

Synthesis of chiral cyclic β-amino ketones has been first reported via Ru-catalyzed asymmetric hydrogenation. High enantioselectivities were achieved by using (S)-C₃-TunePhos chiral ligand (up to 94% ee).     

Synthesis of electron-deficient (Sa,R,R)-(CF3)2-C3-TunePhos and its applications in asymmetric hydrogenation of α-iminophosphonates

A novel electron-deficient chiral diphosphine ligand bearing trifluoromethyl groups at the 6- and 6′-positions of the biphenyl backbone, (S_a,R,R)-(CF₃)₂-C₃-TunePhos, has been synthesized from the commercially available chiral 2,4-pentanediol. The above ligand was successfully applied to palladium-catalyzed asymmetric hydrogenation of linear and cyclic α-iminophosphonates with up to 99%?ee.     

BINOL-derived diphosphoramidites bearing unsymmetrical 1,2-diamine link and their application in asymmetric catalysis

New P,P-bidentate diastereomeric diphosphoramidite chiral ligands with mixed stereogenic elements and a C₁ backbone symmetry have been prepared from (S_a)- and (R_a)-1,1′-binaphthyl-2,2′-diol (BINOL) and (S)-N-benzyl-1-(pyrrolidin-2-yl)methanamine and are fully characterized. The use of these ligands provides up to 84% ee in the Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate and up to 95% ee in the Rh-catalyzed asymmetric hydrogenation of α-dehydrocarboxylic acid esters. The results indicate that the catalytic performance is highly affected by the axial chirality of the binaphthyl moieties of the ligand and the nature of the solvent.     

Iridium-catalyzed asymmetric hydrogenation of pyridine derivatives, 7,8-dihydro-quinolin-5(6H)-ones

[Ir(COD)Cl]₂/MeO-Biphep/I₂ catalyst system is highly effective for asymmetric hydrogenation of pyridine derivatives 7,8-dihydro-quinolin-5(6H)-ones with high enantioselectivities (up to 97% ee).     

Highly efficient chiral PNNP ligand for asymmetric transfer hydrogenation of aromatic ketones in water

Chiral PNNP ligand II and [IrHCl₂(COD)]₂ were applied for the first time in the asymmetric transfer hydrogenation of aromatic ketones with HCOONa in water, giving the corresponding optical alcohols in high yield and excellent enantioselectivity (up to 99% ee). Particularly, the reduction of propiophenone proceeded smoothly at a substrate to catalyst molar ratio of 8000, without compromising the ee values obtained.     

Ir(III) complexes of diamine ligands for asymmetric ketone hydrogenation

The use of a combination of IrCl₃ with a series of ligands derived from the C2-symmetric diamine diphenylethanediamine (DPEN) forms a catalyst capable of the asymmetric hydrogenation of ketones in up to 85% ee.     

Synthesis of a water-soluble cationic chiral diamine ligand bearing a diguanidinium and application in asymmetric transfer hydrogenation

A novel water-soluble cationic N-monosulfonated chiral diamine ligand diguanidinium 1c was easily prepared from (R,R)-DPEN and its rhodium complex and was successfully applied in the asymmetric transfer hydrogenation of prochiral ketones and imines in water by using sodium formate and formic acid as co-hydrogen donors. Various substrates were reduced with high yields and good to excellent enantioselectivities (up to >99% ee).     

Rh(I)/DpenPhos catalyzed asymmetric hydrogenation of enol esters and potassium (E)-3-cyano-5-methylhex-3-enoate

Rh(I) complexes of a class of modular chiral monodentate phosphoramidites were highly efficient for the asymmetric hydrogenation of enol esters bearing α-aryl or α-alkyl groups, to afford the corresponding hydrogenation products in high enantioselectivities (87–95% ee) and reactivities (turnover number up to 10,000). These ligands were also shown to be effective in Rh(I)-catalyzed asymmetric hydrogenation of the potassium salt of (E)-3-cyano-5-methylhex-3-enoate, to give the corresponding product (a precursor to CI-1008) with up to 95% ee and complete conversion of substrate.     

Asymmetric transfer hydrogenation of aromatic ketones by Rh(I)/bimorpholine complexes

The asymmetric hydride transfer reduction of aromatic ketones, using a [Rh(cod)Cl]₂ complex as a catalyst and (3S,3′S)-bimorpholine as a chiral ligand, was studied. By varying the amount of ligand, basic co-catalyst and temperature, high yields (>90%) and good enantiomeric excesses of the alcohols (ee up to 83%) were achieved.     

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).     

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).     

Palladium-catalyzed asymmetric hydrogenation of simple ketones activated by Brønsted acids

Homogeneous Pd(OCOCF₃)₂/(R)-C₄-TunePhos has been successfully applied in the asymmetric hydrogenation of simple ketones activated by catalytic amount of Brønsted acid with up to 88% ee.     

Ru-catalyzed enantioselective preparation of methyl (R)-o-chloromandelate and its application in the synthesis of (S)-Clopidogrel

The preparation of methyl (R)-o-chloromandelate via Ru-catalyzed asymmetric hydrogenation and transfer hydrogenation was investigated. With Ru-(R,R)-2,4,6-triisopropyl C₆H₂SO₂-DPEN as the catalyst and HCOOH-Et₃N azeotrope as the hydrogen donor, up to 92% ee was obtained in an optional condition. The synthesis of (S)-Clopidogrel was also studied.     

A novel and efficient total synthesis of shikonin

A novel and efficient synthesis of shikonin was accomplished with excellent enantiomeric excess (99.3% ee) and high overall yield (47%) in only six steps. The synthetic strategy involved an efficient Ru(II)-catalyzed asymmetric hydrogenation employing C₂-symmetric planar chiral ruthenocene phosphinooxazoline ligand (L-3), followed by the subsequent removal of the methyl protecting groups. Meanwhile, it could be preliminarily confirmed that the chiral side chain of shikonin was difficult to be constructed in one step with both stereoselectivity and α-regioselectivity.     

Preparation of pyrrolidine-oxazoline containing ligands and their application in asymmetric transfer hydrogenation

Nine members of a new ligand class incorporating both an oxazoline ring and a pyrrolidine unit were prepared in an efficient four-step synthesis starting from readily available chiral amino alcohols and proline. A study of these ligands in the asymmetric transfer hydrogenation of acetophenone showed that the catalysts formed from [Ir(cod)Cl]₂ were the most active while those derived from [Ru(p-cymene)Cl₂]₂ gave the highest enantioselectivities (up to 61% ee).     

A novel C2-symmetric bisphosphane ligand with a chiral cyclopropane backbone: synthesis and application in the Rh(I)-catalyzed asymmetric 1,4-addition of arylboronic acids

The synthesis of a novel C₂-symmetric bisphosphane ligand was accomplished starting from trans-(2R,3R)-bis(3′,5′-diphenylphenyl)cyclopropane-1,1-dimethanol as a key intermediate. This ligand was tested in the asymmetric rhodium(I)-catalyzed 1,4-addition to cyclic enones. We also compared the new ligand with a similar phosphane ligand with a less bulky cyclopropane backbone. Good yields (up to 99%) and enantioselectivities (up to 89% ee) were observed. We demonstrated that the presence of a more bulky cyclopropane backbone resulted in a less effective ligand.     

Development of a new class of C1-symmetric bisphosphine ligands for rhodium-catalyzed asymmetric hydrogenation

A new class of C₁-symmetric bisphosphine ligands with three hindered quadrants have been obtained through facile synthesis from chiral BINOL derivatives. Their rhodium complexes have exhibited high enantioselectivities (up to 98% ee) in the asymmetric hydrogenation of various unsaturated prochiral olefins, providing an efficient catalytic system for the enantioselective synthesis of chiral amino acids and amines.     

Highly enantioselective Ir-catalyzed hydrogenation of exocyclic enamines

[Ir(COD)Cl]₂/MeO-BiPhep/I₂ catalyst system is highly effective for the asymmetric hydrogenation of exocyclic enamines with high enantioselectivities (up to 96% ee).     

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.