新型手性环状胺膦配体的设计合成及在酮的不对称还原中的应用

新型手性配体的设计合成是不对称催化研究的重要内容,其中手性胺膦配体因同时含有"软"的磷原子和"硬"的氮原子而具有丰富的配位化学性能和优秀的不对称诱导能力.本文总结了本研究组最近设计合成的手性环状胺膦配体的制备、表征及其在铁催化酮的不对称还原中的应用.手性1,2-环己二胺与双(2-甲酰基苯基)苯基膦通过[2+2]环缩合反应能够顺利获得手性22元环的亚胺膦配体21,该配体经Na BH4还原后生成大环胺膦配体22.利用手性大环胺膦配体22与Fe3(CO)12原位生成的催化体系,能够高活性、高对映选择性地实现包括杂环芳香酮在内50多种酮的不对称转移氢化和不对称氢化反应,其S/C(底物与催化剂的摩尔比)最高可达5000:1,产物手性芳香醇的光学纯度高达99%ee.     

Novel phosphine-phosphite and phosphine-phosphinite ligands for highly enantioselective asymmetric hydrogenation

Two novel phosphine-phosphite (S,R)-o-BINAPHOS and phosphine-phosphinite (S)-o-BIPNITE ligands based on ortho phenyl substituted (S)-BINOL have been synthesized. Extremely high enantioselectivity (over 99% ee in most cases) has been achieved for the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives.     

Novel and efficient chiral sulfideoxathiane ligands for palladium-catalyzed asymmetric allylic alkylation

Easily prepared, chiral sulfideoxathiane ligands are described which give excellent enantioselectivity (up to 99% ee) in the Pd-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a range of alkyl malonate nucleophiles.     

A modular design of ruthenium catalysts with diamine and BINOL-derived phosphinite ligands that are enantiomerically-matched for the effective asymmetric transfer hydrogenation of simple ketones

A method is reported for making a potentially very wide series of ruthenium hydrido chloro complexes with diamine and readily-prepared diphosphinite ligand modules as precatalysts for the asymmetric transfer hydrogenation of simple ketones to give chiral alcohols in good yield and enantioselectivity.     

N-Benzyl-norephedrine derivatives as new,efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones

Significant catalytic activities (up to 600 h⁻¹ at 20°C) and enantiomeric excesses ranging from 56 to 89% for the asymmetric transfer hydrogenation of β-ketoesters, methoxyacetone and 2-acetylpyridine to the corresponding alcohols are achieved in the presence of catalytic combinations of [RuCl₂(η⁶-arene)]₂ and N-substituted derivatives of (1S,2R)-norephedrine such as N-benzyl-norephedrine and N-(4-biphenyl)methyl-norephedrine.     

2-Azanorbornyl alcohols: very efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic ketones

2-Azanorbornyl-derived amino alcohols were prepared and evaluated as ligands in the Ru(II)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. To improve selectivity and rate, the structure of the ligand was optimized. Acetophenone was reduced using 0.5 mol % catalyst in 40 min in 94% ee. This system was also able to reduce a wide range of aromatic ketones to the corresponding alcohols, while maintaining high enantioselectivities and yields. The effects of catalyst loading and the presence of cosolvents in the reaction vessel were examined, and a linearity study was also done.     

Chiral phosphine-phosphoramidite ligands for highly efficient Ir-catalyzed asymmetric hydrogenation of sterically hindered N-arylimines

A mild and general iridium-catalyzed, highly enantioselective hydrogenation of sterically hindered N-arylimines with a new H(8)-BINOL-derived phosphine-phosphoramidite ligand has been developed. The present catalytic system features high turnover numbers (up to 100000) and good to perfect enantioselectivities (up to 99% ee) for the hydrogenation of a variety of sterically hindered N-arylimines.     

New modular P-chiral ligands for Rh-catalyzed asymmetric hydrogenation

New modular P-chiral ligands have been prepared from commercially available (S)-α,α-diphenylprolinol. With these new types of ligands, up to 95% ee was achieved in the Rh-catalyzed asymmetric hydrogenation of functionalized olefins.     

Aziridine ring-containing chiral ligands as highly efficient catalysts in asymmetric synthesis

Enantiomerically pure bidentate heteroorganic ligands built on an achiral skeleton containing hydroxyl and aziridine moieties as nucleophilic centers, capable of binding various organometallic reagents, have proven to be highly efficient catalysts in the enantioselective addition of diethylzinc and phenylethynylzinc to aryl and alkyl aldehydes to give the desired chiral products in high chemical yields (up to 90%) and with ees of up to 95%. The influence of the stereogenic center located in the carbon atom in the aziridine moiety on the stereochemical course of the reaction is reported.     

Chiral diphosphites derived from D-glucose: new highly modular ligands for the asymmetric catalytic hydrogenation

A series of novel diphosphite ligands derived from readily available D-(+)-glucose have been synthesized. These ligands were screened in the Rh-catalyzed hydrogenation of a series of alpha,beta-unsaturated carboxylic acid derivatives. Both excellent enantioselectivities (ee up to >99%) and activities were achieved. The advantage of these ligands is that their modular nature allows an easy systematic variation in the configuration of the stereocenters (C-3, C-5) at the ligand backbone and in the biaryl substituents, so the optimum configuration for maximum enantioselectivity in asymmetric hydrogenation can be determined. Results show that enantiomeric excesses depend strongly on the absolute configuration of C-3 and slightly on the stereocenter carbon C-5, while the sense of the enantiodiscrimination is predominantly controlled by the configuration of the biaryls at the phosphite moieties. Moreover, the presence of bulky substituents at the ortho-positions of the biaryl diphosphite moieties has a positive effect on enantioselectivity.     

Novel chiral tetraaza ligands: synthesis and application in asymmetric transfer hydrogenation of ketones

Novel chiral tetraaza ligands, N¹,N²-bis(2-(piperidin-1-yl)benzylidene)cyclohexane-1,2-diamine 1 and N¹,N²-bis(2-(piperidin-1-yl)benzyl)cyclohexane-1,2-diamine 2, have been synthesized and fully characterized by analytical and spectroscopic methods. The structure of (R,R)-1 has been established by X-ray crystallography. Asymmetric transfer hydrogenation of aromatic ketones with the catalysts prepared in situ from [IrHCl₂(COD)]₂ and the chiral tetraaza ligands in 2-propanol gave the corresponding optically active secondary alcohols in high conversions and good ees (up to 91%) under mild reaction conditions.     

A very simple, highly stereoselective and modular synthesis of ferrocene-based P-chiral phosphine ligands

A very simple, highly stereoselective and modular synthesis of ferrocene-based P-chiral phosphine ligands has been developed. On the basis of this new methodology, several new families of ferrocene-based phosphine ligands have been prepared coupling chirality at phosphorus with other, more standard stereogenic features. The introduction of P-chirality into ferrocene-based phosphine ligands enhances the enantioselective discrimination produced by the corresponding Rh catalyst when a matching among the planar chirality, carbon chirality, and the chirality of phosphorus is achieved.     

Biaryl phosphite-oxazolines from hydroxyl aminoacid derivatives: highly efficient modular ligands for Ir-catalyzed hydrogenation of alkenes

High enantioselectivities and activities are achieved in the Ir-catalyzed hydrogenation of several unfunctionalized olefins using modular biaryl phosphite-oxazoline ligands from hydroxyl aminoacid derivatives; the presence of a biaryl phosphite group is crucial to this success.     

Cobalt(II)-catalyzed asymmetric hydrosilylation of simple ketones using dipyridylphosphine ligands in air

In the presence of PhSiH(3) as the hydride donor, catalytic amounts of non-racemic dipyridylphosphine and an easy-to-handle cobalt salt Co(OAc)(2)·4H(2)O formed in situ an effective catalyst system for the asymmetric reduction of a diverse range of aryl alkyl ketones with moderate-to-excellent enantioselectivities (up to 96% ee). This approach tolerated the handling of both catalyst and reactants under air without special precautions.     

2-(aminomethyl)-oxazolines: highly modular scaffolds for the preparation of novel asymmetric ligands

Highly modular chiral 2-(aminoalkyl)oxazolines have been prepared from alpha-amino acids and 1,2-amino alcohols. The amine-functionalized oxazolines were employed as scaffolds in the preparation of a number of different ligands with potential denticities varying from 2 to 5. The obtained ligands were employed and evaluated in the ruthenium-catalyzed asymmetric transfer-hydrogenation of acetophenone and in the titanium-catalyzed addition of diethylzinc to aldehydes. In the latter process, enantioselectivity up to 97% was obtained.     

Rhodium-catalysed asymmetric hydrosilylation of ketones using HETPHOX ligands

The HETPHOX ligand class was applied to the rhodium-catalysed asymmetric hydrosilylation of a range of substituted acetophenones. Enantioselective hydrosilylation of acetophenone with the tert-butyl substituted HETPHOX ligand gave (R)-phenylethanol in excellent enantioselectivity (84% ee) and in good conversion (80%). When applied to the hydrosilylation of other ketones conversions up to 93% and enantioselectivities up to 88% were observed.     

Novel sulfinyl imine ligands for asymmetric catalysis

[structure: see text] A novel class of P,N-sulfinyl imine ligands has been prepared that incorporates chirality solely at sulfur. The Pd complex of ligand 14 catalyzes the allylic alkylation reaction with high enantioselectivity (94%), and the first crystal structure of a Pd-bound sulfinyl imine provides insight into binding mode and origins of stereoselectivity.     

Furanoside thioether–phosphinite ligands for Rh-catalyzed asymmetric hydrosilylation of ketones

A series of thioether–phosphinite ligands, easily prepared in a few steps from inexpensive d-(+)-xylose, were tested in the Rh-catalyzed hydrosilylation of ketones. Systematic variation of the electronic and steric properties of the thioether moiety provided useful information about the ligand parameters which control enantiodiscrimination. The results show that the enantiomeric excesses are strongly dependent on the steric properties of the substituent on the thioether moiety and on the steric properties of the substrate. High activities and good enantiomeric excesses (up to 90%) were obtained in the hydrosilylation of several aryl ketones.     

Highly modular P-OP ligands in asymmetric allylic substitution

A library of highly modular P-OP ligands have been evaluated in Pd-catalysed allylic substitutions with C- and N-nucleophiles. Catalyst optimisation via a variation of the phosphino and phosphite substituents led to a ‘lead’ catalyst, which efficiently mediated the allylic substitutions when various combinations of substrates and nucleophiles were tested. Ground-state calculations were carried out and these allowed a clearer understanding of the stereochemical outcome of the reaction.