CN100467479C - Phosphine-phosphoramidite ligand, its preparation method and uses - Google Patents
Phosphine-phosphoramidite ligand, its preparation method and uses Download PDFInfo
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- CN100467479C CN100467479C CNB2005100866503A CN200510086650A CN100467479C CN 100467479 C CN100467479 C CN 100467479C CN B2005100866503 A CNB2005100866503 A CN B2005100866503A CN 200510086650 A CN200510086650 A CN 200510086650A CN 100467479 C CN100467479 C CN 100467479C
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Abstract
The invention discloses a chiral phosphor-phosphorous amide ester ligand and preparing method, which is characterized by the following: dissolving phosphorochloridous acid ester in the toluene; setting the molar rate of chiral phosphor-amino, phosphorochloridous acid ester and trimethylamine at 1:1-2:3-5; adding chiral phosphor-amino and trimethylamine in the toluene to form solution; heating the solution to 18-25 deg.c; stirring for 10-30h; filtering; removing solvent to obtain the product. The invention improves catalyzing activity, which makes TON at 10000.
Description
Technical field
The present invention relates to a kind of phosphine-phosphoramidite ligand based on chirality phenylethylamine skeleton.
The invention still further relates to the preparation method of above-mentioned part.
The invention still further relates to the application of above-mentioned part in two key asymmetric hydrogenations such as C=C, C=O, C=N.
Background technology
The catalysis asymmetric hydrogenation is the core technology in the asymmetric synthesis, is one of most effectual way of synthesizing optical homochiral medicine, agricultural chemicals, foodstuff additive and spices, and the design of chiral ligand synthetic be the key factor that realizes this core technology.In ligand design, most important principle is a design symmetry, and most chirality bidentate phosphine ligands of exploitation all has C at present
2-symmetrical structure or two phosphorus ligating atoms that are close to equivalence.This symmetric existence can farthest reduce the quantity of reaction transition state, thereby guarantees that the high mapping selection of catalyzer is active.But recent studies show that, in fact the phosphorus ligating atom of two equivalences is in a kind of non-equivalent state in the active transition attitude that part-central metal-substrate forms, the formation of this asymmetry structure is to guarantee that symmetric bitooth ligand obtains the root of high enantioselectivity.Based on a kind of like this reaction pattern, some asymmetrical bitooth ligands are synthesized and obtain high enantioselectivity in asymmetric catalysis, and Josiphos type ferrocene bidentate phosphine ligands is exactly a wherein most typical example.The reason that this class part obtains high reactivity and high enantioselectivity is that its asymmetry structure makes the active transition attitude of part-central metal-substrate formation further go symmetry, thereby makes it be in a kind of optimized state.Asymmetry has become a new cardinal principle in the ligand design.Has strong asymmetry and make up the chirality bitooth ligand that forms by phosphine coordinating group and phosphoramidite coordinating group, therefore according to the reaction pattern of asymmetric active intermediate, phosphine-phosphoramidite ligand should have good mapping and select active in the asymmetric catalytic hydrogenation reaction.But up to the present, except the DICPPhos of report, have only QUNIPHOS in the asymmetric catalysis of catalysis alpha-acetamido-methyl acrylate and furoate clothing dimethyl ester, to obtain enantioselectivity preferably.Therefore developing new phosphine-phosphoramidite ligand has important theory and realistic meaning.
Summary of the invention
The object of the present invention is to provide a kind of phosphine-phosphoramidite ligand based on chirality phenylethylamine skeleton.
Another purpose of the present invention is to provide the preparation method of above-mentioned part.
For achieving the above object, chirality phosphine-phosphoramidite ligand provided by the invention, structure as shown in the formula:
In the formula:
R
1, R
2For: hydrogen; C
2～C
40Fat group; Contain one or more N, S, the heteroatomic fat group of O, P; C
7-C
60Aromatic group and the combination group of fatty group; Contain one or more N, S, the heteroatomic C of O, P
3-C
60The combination group of aromatic group and fatty group; C
6-C
60Aromatic group; Contain one or more N, S, the heteroatomic heteroaromatic group of O, P;
Ar is: C
6-C
60Aromatic group; Contain one or more N, S, the heteroatomic C of O, P
6-C
60The heteroaromatic group;
X is: chirality or achirally do not contain or contain one or more N, S, the heteroatomic fat group of O, P; Contain one or more or do not contain N, S, the heteroatomic aromatic group of O, P; Chirality or achirally do not contain or contain one or more N, S, the heteroatomic biphenyl of O, P or dinaphthalene class aromatic group; Chirality or achiral volution group.
Described chirality phosphine-phosphoramidite ligand, wherein C
2～C
40Fat group be alkyl or cycloalkyl.
Described chirality phosphine-phosphoramidite ligand, wherein C
7-C
60Aromatic group and the combination group of fatty group be benzyl.
Described chirality phosphine-phosphoramidite ligand, wherein C
6-C
60Aromatic group be aryl.
The method for preparing the chirality phosphine-phosphoramidite ligand provided by the invention, step is:
The chloro phosphorous acid ester is dissolved in the toluene, chirality phosphine-amine compound in molar ratio: chloro phosphorous acid ester: triethylamine=1:1-2:3-5, be dissolved in the solution that toluene forms in 0-5 ℃ of adding chirality phosphine-amine compound and triethylamine, reaction solution is risen to 18-25 ℃ of stirring reaction 10-30 hour, filter, slough solvent and obtain required phosphine-phosphoramidite ligand;
Described chirality phosphine-amine compound structure as shown in the formula:
Or
In the formula:
R
1, R
2For: hydrogen; C
2～C
40Fat group; Contain one or more N, S, the heteroatomic fat group of O, P; C
7-C
60Aromatic group and the combination group of fatty group; Contain one or more N, S, the heteroatomic C of O, P
3-C
60The combination group of aromatic group and fatty group; C
6-C
60Aromatic group; Contain one or more N, S, the heteroatomic heteroaromatic group of O, P;
Ar is: C
6-C
60Aromatic group; Contain one or more N, S, the heteroatomic C of O, P
6-C
60The heteroaromatic group.
Described chirality phosphine-amine compound is synthetic by following route:
Chirality phenylethylamine in molar ratio: n-Butyl Lithium: trimethylchlorosilane: n-Butyl Lithium: diphenyl phosphine chloride=1:1-2:1-2:3-5:1-2, the chirality phenylethylamine is dissolved in the ether, add n-Butyl Lithium and trimethylchlorosilane continuously in 0-5 ℃, react after 0.5-2 hour, add n-Butyl Lithium again, continue reaction 4-7 hour; Be cooled to room temperature, add the diethyl ether solution of diphenyl phosphine chloride, room temperature reaction 8-16 hour, the hydrochloric acid termination reaction of adding 2M, column chromatography obtains required phosphine-amine compound.
Chirality phosphine-phosphoramidite ligand provided by the invention can be used in C=C, C=O, the C=N key in the asymmetric hydrogenation, with chirality phosphine-phosphoramidite ligand and Rh, Ru, Ir, Pt or Pd in molar ratio 1.1:1-2.2:1 form catalyzer, the ratio of reaction substrate and catalyzer is 100-10,000, reaction times 0.1-24 hour.
Described asymmetric hydrogenation is the catalysis asymmetry hydrogenation reaction of following a few class substrates:
(1) catalysis asymmetry hydrogenation reaction of α-dehydroamino acid;
(2) catalysis asymmetry hydrogenation reaction of β-dehydroamino acid;
(3) catalysis asymmetry hydrogenation reaction of the itaconic ester compounds of itaconic ester and beta substitution thereof;
(4) catalysis asymmetry hydrogenation reaction of α-non-annularity and ring-type alkene acid amides;
(5) catalysis asymmetry hydrogenation reaction of α-non-annularity and ring-type enol ester;
(6) catalysis asymmetry hydrogenation reaction of α-acetoxyl group-beta substitution acrylate;
(7) catalysis asymmetry hydrogenation reaction of benzene or substituted benzoyl acetate esters;
(8) catalysis asymmetry hydrogenation reaction of benzene or substituted benzoyl formate ester;
(9) catalysis asymmetry hydrogenation reaction of replacement or non-substituted aroma ketone compounds;
(10) catalysis asymmetry hydrogenation reaction of N-alkyl and N-aryl imine;
(11) catalysis asymmetry hydrogenation reaction of N-acyl group hydrazone, sulfimide and phosphono imines;
(12) the catalysis asymmetric hydrogenation of fragrance and non-fragrant nitrogen heterocyclic.
The catalyst property that metal precursors such as chirality phosphine-phosphoramidite ligand of the present invention and Rh, Ru, Ir, Pd, Pt form is stable, and air and humidity are had good endurance, and the asymmetric hydrogenation mild condition of its participation can at room temperature be reacted; The pressure of hydrogen is applied widely, does not all influence activity of such catalysts and stereoselectivity from the normal pressure to the high pressure.
Embodiment
One, chirality phosphine-phosphoramidite ligand of the present invention has following structure:
Wherein: R
1, R
2Group is: hydrogen, C such as alkyl and cycloalkyl
2～C
40Fat group, contain the C of functional groups such as one or more N, S, O, P
2～C
40Fat group, C such as benzyl
7-C
60At the combination group of interior aromatic group and fatty group, contain the C of functional groups such as one or more N, S, O, P
3-C
60The combination group of aromatic group and fatty group, C such as aryl
6-C
60Interior aromatic group contains heteroatomic heteroaromatic groups such as one or more N, S, O, P.
Ar is C
6-C
60Interior aromatic group; Contain heteroatomic C such as one or more N, S, O, P
6-C
60The heteroaromatic group.
The X group is: chirality or achiral fat group that does not contain or contain functional groups such as one or more N, S, O, P, contain one or more or do not contain the aromatic group of functional groups such as N, S, O, P, chirality or achiral biphenyl and dinaphthalene class aromatic group, chirality or achiral volution group that does not contain or contain functional groups such as one or more N, S, O, P.Mainly comprise:
Wherein: R
1Be not H;
R=H, Me, Ph R
1, R
2Be H, alkyl, alkoxyl group
R
1, R
2Be H, alkyl, alkoxyl group, Ar are aryl A
1, A
2, A
3, A
4Be hydrogen, alkyl, aryl;
Y such as trialkyl silyl are alkyl and the ring that contains or do not contain functional group
Alkyl
Two, chiral ligand is synthetic
The chiral ligand of the present invention's design is from commercial chirality phenylethylamine (III), through the polystep reaction synthetic.Wherein committed step is that the direct lithiumation in ortho position and the phosphono of primary amine is combined to 1-(2-diphenylphosphine) phenylethylamine (IV).1-(2-diphenylphosphine) phenylethylamine (IV) respectively with phosphorous acid ester muriate (V) condensation, obtain having the phosphine-phosphoramide ester ligand i and the II of different chiral centres.Its concrete synthesis step is as follows:
A. chirality (S)-phenylethylamine (III): n-BuLi (n-Butyl Lithium): ClSiMe in molar ratio
3(trimethylchlorosilane): n-BuLi:ClPPh
2(diphenyl phosphine chloride)=1:1-2:1-2:3-5:1-2 is dissolved in the chirality phenylethylamine in the ether, adds n-BuLi and ClSiMe down continuously in 0 ℃
3After 1 hour, in reaction solution, add n-BuLi, continue reaction 7 hours.Under cooling conditions, add ClPPh
2Diethyl ether solution, the reaction solution room temperature reaction spends the night, and adds HCl (hydrochloric acid) termination reaction of 2M, column chromatography obtains required phosphine-amine compound (S)-IV.Use the same method and set out, can synthesize phosphine-amine compound (R)-IV by (R)-phenylethylamine.
B. chiral diol (V): PCl in molar ratio
3(phosphorus trichloride): NMP (2-methyl-2-pyrrolidone)=1:5-10:0.001-0.01 places a reaction flask with chiral diol and phosphorus trichloride, adds the 2-methyl-2-pyrrolidone of catalytic amount, and heating reflux reaction to chiral diol dissolves fully.Solvent is sloughed in decompression, and residue normal hexane recrystallization obtains required chloro phosphorous acid ester (VI).
C. chirality phosphine-amine compound (IV) in molar ratio: chloro phosphorous acid ester (VI): Et
3N (triethylamine)=1:1-2:3-5 is dissolved in the chloro phosphorous acid ester in the toluene, adds chirality phosphine-amine compound (IV) and NEt in 0-5 ℃
3Be dissolved in the solution that toluene forms, reaction solution is risen to 18-25 ℃ of stirring reaction 10-30 hour, filter, slough solvent and obtain required phosphine-phosphoramidite ligand I or II.
Three, asyininetric hydrogenation
The metal complexes that metal precursor original positions such as chirality phosphine-phosphoramidite ligand of the present invention and Rh, Ru, Ir, Pd and Pt form has very high catalytic activity and optical selective to the hydrogenation of two keys such as C=C, C=N, C=O.Be reflected at 1-100atm ,-20～200 ℃ temperature is carried out, and solvent can also can be used CH with the alcoholic solvent of protic
2Cl
2, CH
2ClCH
2Cl, CH
3Cl, CCl
4, non-protonic solvent such as tetrahydrofuran (THF), benzene, toluene and ethyl acetate.
The catalyzer that metal precursors such as chiral ligand of the present invention and Rh, Ru, Ir, Pd, Pt form is applied widely, can be applied to the asymmetric hydrogenation of two keys such as multiclass C=C, C=N, C=O.Wherein part and [Rh (COD)
2] BF
4, [Ir (COD) Cl]
2The catalyzer that forms under the condition in position with the Ru metal precursor is mainly used in following a few class substrate catalysis asymmetry hydrogenation reaction:
(1) catalysis asymmetry hydrogenation reaction of α-dehydroamino acid;
(2) catalysis asymmetry hydrogenation reaction of β-dehydroamino acid;
(3) catalysis asymmetry hydrogenation reaction of the itaconic ester compounds of itaconic ester and beta substitution thereof;
(4) catalysis asymmetry hydrogenation reaction of α-non-annularity and ring-type alkene acid amides;
(5) catalysis asymmetry hydrogenation reaction of α-non-annularity and ring-type enol ester;
(6) catalysis asymmetry hydrogenation reaction of α-acetoxyl group-beta substitution acrylate;
(7) the catalysis asymmetric hydrogenation of benzene or substituted benzoyl acetate esters;
(8) the catalysis asymmetric hydrogenation of benzene or substituted benzoyl formate ester;
(9) the catalysis asymmetric hydrogenation of replacement or non-substituted aroma ketone compounds;
(10) the catalysis asymmetric hydrogenation of N-alkyl and N-aryl imine;
(11) the catalysis asymmetric hydrogenation of N-acyl group hydrazone, sulfimide and phosphono imines;
(12) the catalysis asymmetric hydrogenation of fragrance and non-fragrant nitrogen heterocyclic.
Chiral ligand of the present invention is to air and moisture stable, easy handling and preservation; The part synthesis route is simple, need not high temperature in the building-up process, violent operational condition such as high pressure; The chiral source of synthetic usefulness can be made a big purchase in large quantities and obtain.
The catalyzer that metal precursors such as part and Rh, Ru, Ir form all can obtain enantioselectivity up to 99% to the asymmetric hydrogenation of two keys such as C=C, C=N, C=O; The catalyst activity height, TON can be up to 10000.
The catalyst property that metal precursors such as chiral ligand of the present invention and Rh, Ru, Ir, Pd, Pt form is stable, and air and humidity are had good endurance, and the asymmetric hydrogenation mild condition of its participation can at room temperature be reacted; The pressure of hydrogen is applied widely, all do not influence activity of such catalysts and stereoselectivity from the normal pressure to the high pressure, the reaction times is 0.1-24 hour, and the mol ratio of part and metal rhodium compound is 1.1:1-2.2:1, reaction substrate is 100-10 with the ratio of catalyzer, 000.
Embodiment 1
1) part is synthetic
Add 1.16 gram (S)-1-phenylethylamine and 10ml ether in the 100ml there-necked flask, slowly adding 5.98ml concentration under room temperature is the n-BuLi hexane solution of 1.6mol/l.Finish, 0 ℃ was continued stirring reaction 15 minutes, and added the 1.33ml trimethylchlorosilane then.React after 1 hour, slowly adding 17.9ml concentration is the n-BuLi hexane solution of 1.6mol/l, in 5 hours, the reaction mixture room temperature is slowly risen to room temperature.React after 1 hour, will react and be cooled to-20 ℃ night, slowly add the solution that 1.72ml diphenyl phosphine chloride and 10ml ether form.Rising to the stirring at room reaction spends the night.Add the saturated NaHCO of 40ml
3The aqueous solution finishes, and continues stirring reaction 10 minutes.The 50ml ether extracting twice of separatory, water layer, combined ether layer, 50ml washing, anhydrous Na
2SO
4Dry.Filter, removal of solvent under reduced pressure, the residue column chromatography gets viscous liquid, and the normal hexane recrystallization gets white crystal 2.22 gram phosphine-amine compound IV, yield 68%.
In the there-necked flask of 100ml, add 10 gram (R)-BINOL and 75 gram PCl
3And catalytic amount 2-methyl-2-pyrrolidone, reaction is back to solids disappeared (about 10 minutes).Most of PCl is sloughed in decompression
3, residual a small amount of PCl
3Remove with the methylbenzene azeotropic decompression.After sloughing toluene, residue gets white chloro phosphorous acid ester 11.9 grams with the normal hexane recrystallization.
In a 100ml there-necked flask, add 3.51 gram chloro phosphorous acid ester and 30ml dry toluenes, under 0 ℃, slowly drip 3.05 gram chirality phosphine-amine compound IV and 3.03 gram triethylamines and be dissolved in the solution that 20ml toluene forms.Finish, reaction solution is risen to room temperature continuation stirring reaction spend the night.Filter, toluene is washed.Residue is dissolved in CH
2Cl
2In, washing, anhydrous Na
2SO
4Dry.Slough solvent, get the phosphine-phosphoramidite ligand I4.73 gram of white powder.
2) catalysis asymmetry hydrogenation reaction
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.011mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate 2-acetamidoacrylic acid methyl esters (0.5mmol) and 1.5mlCH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get S-kharophen methyl propionate yield 100% (in 2-acetamidoacrylic acid methyl esters), enantiomeric excess is more than the 90%ee.
Embodiment 2
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.011mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate 2-kharophen methyl cinnamate (0.5mmol) and 1.5ml CH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get S-kharophen methyl phenylpropionate yield 100% (in 2-kharophen methyl cinnamate), enantiomeric excess is more than the 90%ee.
Embodiment 3
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.011mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 100ml, react after 30 minutes, add substrate 2-kharophen methyl cinnamate (50mmol) and 25mlCH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get S-kharophen methyl phenylpropionate yield 100% (in 2-kharophen methyl cinnamate), enantiomeric excess is more than the 90%ee.
Embodiment 4
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4The chirality phosphine-phosphoramidite ligand (0.011mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add the precursor (0.5mmol) of substrate DOPA, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, will filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get L-DOPA yield 100% (in the precursor of DOPA), enantiomeric excess is 90%ee.
Embodiment 5
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate dimethyl itaconate (0.5mmol) and 1.5ml CH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (R)-2-pyrovinic acid dimethyl ester 100% (in dimethyl itaconate), enantiomeric excess is more than the 99%ee.
Embodiment 6
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 100ml, react after 30 minutes, add substrate dimethyl itaconate (50mmol) and 25ml CH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (R)-2-pyrovinic acid dimethyl ester 100% (in dimethyl itaconate), enantiomeric excess is more than the 99%ee.
Embodiment 7
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate beta-phenyl dimethyl itaconate (0.5mmol) and 1.5ml CH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (R)-2-phenmethyl dimethyl succinate 100% (in the phenyl dimethyl itaconate), enantiomeric excess is more than the 99%ee.
Embodiment 8
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate 3-acetylaminohydroxyphenylarsonic acid 2-butylene acid methyl esters (0.5mmol) and 1.5ml CH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (S)-3-acetylaminohydroxyphenylarsonic acid 2-methyl-butyrate 100% (in 3-acetylaminohydroxyphenylarsonic acid 2-butylene acid methyl esters), enantiomeric excess is more than the 98%ee.
Embodiment 9
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate 3-acetylaminohydroxyphenylarsonic acid 3-cinnamylic acid methyl esters (0.5mmol) and 1.5ml CH
2Cl
2Behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (S)-3-acetylaminohydroxyphenylarsonic acid 3-phenyl-2-methyl propionate 100% (in 3-acetylaminohydroxyphenylarsonic acid 3-cinnamylic acid methyl esters), enantiomeric excess is more than the 99%ee.
Embodiment 10
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate alpha-acetamido-vinylbenzene (0.5mmol) and 1.5mlCH
2Cl
2The solution that forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (S)-1-kharophen phenylethane 100% (in alpha-acetamido-vinylbenzene), enantiomeric excess is more than the 99%ee.
Embodiment 11
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4The chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add the solution that substrate alpha-acetamido-vinylbenzene (25mmol) and 10ml solvent form, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (S)-1-kharophen phenylethane 100% (in alpha-acetamido-vinylbenzene), enantiomeric excess is more than the 99%ee.
Embodiment 12
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate 2-acetoxyl group-2-methyl acrylate (0.5mmol) and 1.5ml CH
2The solution that Cl forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (S)-2-acetoxyl group-2-methyl propionate 100% (in 2-acetoxyl group-2-methyl acrylate), enantiomeric excess is more than the 96%ee.
Embodiment 13
Under the nitrogen protection, with 2.0mg (0.005mmol) [Rh (COD)
2] BF
4, the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml, react after 30 minutes, add substrate α-acetoxy-styrene (0.5mmol) and 1.5mlCH
2The solution that Cl forms, behind the hydrogen exchange 3 times, after the hydrogen pressure of 10atm reacts 12 hours down, filter with short silicagel column, to filter after gained filtrate concentrates, carry out content and optical purity mensuration with GC, get (S)-α-acetoxyl group phenylethane 100% (in α-acetoxy-styrene), enantiomeric excess is more than the 90%ee.
Embodiment 14
Under the nitrogen protection; 0.005mmol[Ir (COD) 2] BF4; the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and methylene chloride (1.5ml) place the reactor of a 10ml; react after 30 minutes; add the solution that substrate phenylpropyl alcohol azomethine (0.5mmol) and 2ml methylene dichloride form; behind the hydrogen exchange 3 times, after the hydrogen pressure of 60atm reacts 24 hours down.Filter with short silicagel column, will filter after gained filtrate concentrates, carry out content and optical purity is measured with GC, get Vonedrine yield 100% (in the phenylpropyl alcohol azomethine), enantiomeric excess is more than the 90%ee.
Embodiment 15
Under the nitrogen protection; 0.005mmol phellandrene ruthenium chloride; the chirality phosphine-phosphoramidite ligand (0.0055mmol) of above-mentioned preparation and solvent methanol (1.5ml) place the reactor of a 10ml; react after 30 minutes; add the solution that substrate ethyl benzoylacetate (0.5mmol) and 2ml methyl alcohol form; behind the hydrogen exchange 3 times, keep 60 kilograms of stress reactions termination reaction after 6 hours.Filter with short silicagel column, will filter after gained filtrate concentrates, carry out content and optical purity is measured with GC, get S-3-hydroxyl-3-phenyl-ethyl propionate yield 100% (in ethyl benzoylacetate), enantiomeric excess is more than the 90%ee.
Claims (5)
1. chirality phosphine-phosphoramidite ligand, structure as shown in the formula:
In the formula:
R
1, R
2For: hydrogen or C
2～C
40Alkyl;
Ar is ph;
X is:
Wherein:
R=H, Me or ph.
2. the preparation method of the described chirality phosphine-phosphoramidite ligand of claim 1, step is:
The chloro phosphorous acid ester is dissolved in the toluene, chirality phosphine-amine compound in molar ratio: chloro phosphorous acid ester: triethylamine=1:1-2:3-5, add chirality phosphine-amine compound in 0-5 ℃, and the toluene solution of triethylamine, reaction solution is risen to 18-25 ℃ of stirring reaction 10-30 hour, filter, slough solvent and obtain required phosphine-phosphoramidite ligand;
Described chirality phosphine-amine compound structure as shown in the formula:
In the formula:
R
1, R
2Be hydrogen or C
2～C
40Alkyl;
Ar is ph.
3. the method for claim 2 is characterized in that, described chirality phosphine-amine compound is synthetic by following route:
Chirality phenylethylamine in molar ratio: n-Butyl Lithium: trimethylchlorosilane: n-Butyl Lithium: diphenyl phosphine chloride=1:1-2:1-2:3-5:1-2, the chirality phenylethylamine is dissolved in the ether, add n-Butyl Lithium and trimethylchlorosilane continuously in 0-5 ℃, react after 0.5-2 hour, add n-Butyl Lithium again, continue reaction 4-7 hour; Be cooled to room temperature, add the diethyl ether solution of diphenyl phosphine chloride, room temperature reaction 8-16 hour, the hydrochloric acid termination reaction of adding 2M, column chromatography obtains required phosphine-amine compound.
4. the chirality phosphine-phosphoramidite ligand of claim 1 application in the asymmetric hydrogenation in C=C, C=O, C=N key.
5. the application of claim 4 is characterized in that, described asymmetric hydrogenation is the catalysis asymmetry hydrogenation reaction of following a few class substrates:
(1) catalysis asymmetry hydrogenation reaction of α-dehydroamino acid;
(2) catalysis asymmetry hydrogenation reaction of β-dehydroamino acid;
(3) catalysis asymmetry hydrogenation reaction of the itaconic ester compounds of itaconic ester and beta substitution thereof;
(4) catalysis asymmetry hydrogenation reaction of α-non-annularity and ring-type alkene acid amides;
(5) catalysis asymmetry hydrogenation reaction of α-non-annularity and ring-type enol ester;
(6) catalysis asymmetry hydrogenation reaction of α-acetoxyl group-beta substitution acrylate;
(7) the catalysis asymmetric hydrogenation of benzene or substituted benzoyl acetate esters;
(8) the catalysis asymmetric hydrogenation of benzene or substituted benzoyl formate ester;
(9) the catalysis asymmetric hydrogenation of replacement or non-substituted aroma ketone compounds;
(10) the catalysis asymmetric hydrogenation of N-alkyl and N-aryl imine;
(11) the catalysis asymmetric hydrogenation of N-acyl group hydrazone, sulfimide and phosphono imines;
(12) the catalysis asymmetric hydrogenation of fragrance and non-fragrant nitrogen heterocyclic.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6906212B1 (en) * | 2004-06-25 | 2005-06-14 | Eastman Chemical Company | Phosphine-phosphoramidite compounds |
-
2005
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| Publication number | Priority date | Publication date | Assignee | Title |
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Non-Patent Citations (2)
| Title |
|---|
| 不对称合成中手性磷配体催化剂的研究进展(I). 李康应等.化学研究，第13卷第1期. 2002 * |
| 不对称合成中手性磷配体催化剂的研究进展(II). 李康应等.化学研究，第13卷第2期. 2002 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102153589A (en) * | 2011-02-28 | 2011-08-17 | 大连多相触媒有限公司 | Asymmetric hydrogenation catalyst for imine as well as synthesis method and application thereof |
| WO2012116493A1 (en) * | 2011-02-28 | 2012-09-07 | 大连多相触媒有限公司 | Catalyst for asymmetric hydrogenation of imine, synthesis method and application thereof |
| CN102153589B (en) * | 2011-02-28 | 2013-01-02 | 大连多相触媒有限公司 | Asymmetric hydrogenation catalyst for imine as well as synthesis method and application thereof |
| AU2011360843B2 (en) * | 2011-02-28 | 2016-05-12 | Dalian Heterogeneous Catalyst Co., Ltd. | Catalyst for asymmetric hydrogenation of imine, synthesis method and application thereof |
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