CN100537636C - Dendritic molecular chiral phosphine ligand and use thereof - Google Patents
Dendritic molecular chiral phosphine ligand and use thereof Download PDFInfo
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- CN100537636C CN100537636C CNB021243913A CN02124391A CN100537636C CN 100537636 C CN100537636 C CN 100537636C CN B021243913 A CNB021243913 A CN B021243913A CN 02124391 A CN02124391 A CN 02124391A CN 100537636 C CN100537636 C CN 100537636C
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Abstract
The present invention discloses a bendritic molecular chiral phosphine ligand, and it is characterized by that it is made up by using dendritic molecular synthom and correspondent small molecular chiral phosphine compound through condensation reaction and connection by using amido, ester group or ureido group, perfectly, by using amino group to make connection, and the terminal group of described dendritic molecular synthon is a reactable group which can be carboxyl group amino group, hydroxyl group or isocyanate group, and the described small molecular chiral phosphine compound at least has one amino group, hydroxyl group or carboxyl group. Said invention also discloses its application in asymmetric hydrogenation reaction.
Description
Technical field
The present invention relates to a kind of dendrimer chiral phosphine ligand and the application in the asymmetric catalytic hydrogenation reaction thereof.
Background technology
Chiral phosphine ligand is the important chiral ligand of a class, and the title complex that they and transition metal form is a catalysis asymmetry hydrogenation reaction, obtains the effective catalyst of chipal compounds.But, because chiral phosphine ligand and metal catalyst thereof are very expensive, and very unstable in air, easily oxidized and therefore inactivation has limited their application in industry to a certain extent.A kind of terms of settlement is that chiral phosphine ligand is loaded on organism or the inorganic matter carrier, and this catalyzer can be realized separating of catalyzer and product by the simple filtering technology after catalyzed reaction is finished, and the recovery of catalyzer and utilization again.Yet the chirality phosphine metal catalyst of this class loadization often causes activity of such catalysts and stereoselectivity to descend.The report that does not also have at present industrial application.
In recent years, with the linear macromolecule is carrier, the existing report of chiral phosphine ligand of preparation soluble high-molecular load, the chiral catalyst of this method load can carry out asymmetric catalysis under the homogeneous condition fully, therefore can reach catalytic activity and the stereoselectivity similar to homogeneous catalyst, after reaction finishes, can utilize the method realization catalyzer of solvent deposition and separating of product again, and the recovery of catalyzer and utilization again.Such as, chirality phosphine BINAP part with the load of solubility polyester has obtained stereoselectivity similar to micromolecule catalyst and the catalytic activity that is higher than micromolecule catalyst in the catalytic asymmetric hydrogenation of metal Ru, and this catalyzer can be reused (US patent 5 more than ten times at least, 990,318).
Dendrimer is a kind of in the soluble polymer, it is by branching base (as the multi-functional basic monomer) macromole with dendroid highly branched structure that obtains of multiple reaction progressively, it has very regular, exquisite structure, molecule volume, shape and functional group all can accurately be controlled, and are monodispersed, and typical molecular structure is spherical (Chen Yongming etc., " chemical journal ", 1995,10,1.).The chiral phosphine ligand that with the dendrimer is the preparing carriers load can accurately be controlled position and the number of active centre in carrier, obtains highly active macromole chiral phosphine ligand and realizes the separation and the recovery of catalyzer.For example: the paper that Fan Qinghua and co-worker deliver (Chem Commun, 2000,789), in this example report, chiral phosphine ligand BINAP is that the mode by chemical bond loads on the core of surface for the polyarylether dendrimer of phenyl group.The separation of such dendrimer chiral phosphine ligand and metal catalyst thereof need be added a large amount of alcoholic solvents and make precipitation agent, and throw out is very thin powder, generally will separate by ultra-filtration or centrifugation method, and is more many than liquid-liquid two difficulty that is separated.
Summary of the invention
The object of the present invention is to provide a kind of new dendrimer chiral phosphine ligand and the application in asymmetric hydrogenation thereof.This chiral phosphine ligand can separate and realize the recovery and reuse of catalyzer easily with reaction product in the asymmetric catalytic hydrogenation reaction.
The dendrimer chiral phosphine ligand that the present invention relates to, chirality phosphine partly are positioned at the core or the end of dendrimer carrier.
The dendrimer chiral phosphine ligand that the present invention relates to is to be connected with amide group, ester group or ureido groups through condensation reaction with corresponding small molecules chiral phosphine compound by the dendrimer synthon, preferably connects with amide group.Available general formula is expressed as follows:
Wherein, A
1Represent dendrimer, A
2Be linking group, A
3Represent chiral phosphine ligand, n 〉=1.
Specifically, the dendrimer chiral phosphine ligand that the present invention relates to, preferred dendrimer chiral phosphine ligand structural formula is as follows:
Wherein, A
1The polyarylether dendrimer substituting group (Percec, the V. that have alkyl group for the surface; Cho, W.; Ungar, G.and Yeardley, D.J.P., J.Am.Chem.Soc., 2001,123,1302.)
Described small molecules chiral phosphine compound is a bibliographical information, has the functional group that can react on the molecular skeleton of phosphine compound.Such as paper (Achiwa, K., J.Am.Chem.Soc., 1976,98,8265.Nagel, U.; Kinzel, E.; Andrade, J.and Prescher, G., Chem.Ber., 1986,119,3326.Holz, J.; Quirmbach, M.and Bomer, A., Synthesis, 1997,983) and the last chiral phosphine compound of reporting of patent (U.S.Patent 4,705,895).These chiral phosphine compounds have groups such as at least one amino, hydroxyl or carboxyl.
The dendrimer chiral phosphine ligand that the present invention relates to, the structure of preferred small molecules chiral phosphine compound is as follows:
Described dendrimer synthon is the macromolecular construction unit of synthesizing tree-like, is made up of terminal group, internal layer district and outer layer zone.The terminal group of the dendrimer synthon that the present invention relates to is the group that can react, and as carboxyl, amino, hydroxyl or isocyanate group etc., the outer layer zone surface has alkyl group, and it is 1-20 straight chain or straight chained alkyl that described alkyl preferably contains carbon number.
The dendrimer chiral phosphine ligand that the present invention relates to, preferred dendrimer synthon is that terminal group is the dendrimer of carboxyl, and the surperficial polyarylether dendrimer synthon that has alkyl group, as paper (Percec, V.; Cho, W.; Ungar, G.and Yeardley, D.J.P., J.Am.Chem.Soc., 2001,123,1302.) the polyarylether dendrimer synthon described.
The dendrimer chiral phosphine ligand that the present invention relates to preferentially is dissolved in non-polar solvent.
Dendrimer chiral phosphine ligand of the present invention can be used for asymmetric hydrogenation, and the preferred reaction substrate is prochiral α-unsaturated aromatic carboxylic acid and α-dehydration amino acid.
The reaction solvent of the asymmetric hydrogenation that the present invention relates to is the mixture of nonpolar alkane solvents and polar alcoholic solvent.In the asymmetric hydrogenation process, system is a homogeneous, after reaction finishes, make reaction system by all being phase-changed into two-phase by in system, adding a spot of water, wherein dendrimer chiral phosphine ligand (catalyzer) be dissolved in non-polar solvent mutually in, reaction product be dissolved in polar solvent mutually in, by the operation of simple liquid-liquid separation, reach dendrimer chiral phosphine ligand (catalyzer) and the isolating purpose of reaction product.
Description of drawings
Fig. 1 is embodiment 1 a small molecules chiral phosphine ligand (R)-5,5 '-NH
2The synthetic route of-BINAP
Fig. 2 is the synthetic route of embodiment 2 dendrimer synthons 2
Fig. 3 is the synthetic route of embodiment 3 dendrimer synthons 7
Fig. 4 is embodiment 4 AB
2-G
1The synthetic route of-BINAP
Fig. 5 is embodiment 5 AB
2-G
2The synthetic route of-BINAP
Fig. 6 is embodiment 6 AB
3-G
1The synthetic route of-BINAP
Fig. 7 is embodiment 7 AB
3-G
2The synthetic route of-BINAP
Fig. 8 is embodiment 8 AB
2-G
2The synthetic route of-PyrPhos
Fig. 9 is not full of carboxylic acid asymmetric catalytic hydrogenation reaction formula for embodiment 9 α-fragrance
Figure 10 is embodiment 10 dehydration amino acid asymmetric catalytic hydrogenation reaction formula
Embodiment
With embodiment the present invention is further described in detail below, these embodiment only describe method of the present invention, and scope of the present invention is not had any restriction.In following examples, " benzene " is phenyl, and " ethanol " is ethanol, and " found " is measured value, and " calcd " is calculated value, " Pyrphos " be (R, R)-3,4-two (diphenylphosphino) tetramethyleneimine.[embodiment 1] small molecules chiral phosphine ligand (R)-5,5 '-NH
2The synthetic route of-BINAP is seen Fig. 1, and is synthetic with reference to patent (U.S.Patent 4,705,895) method.
R-5,5 '-NO
2-BINAPO's is synthetic:
Add 1g (R)-BINAP in the 50ml round-bottomed flask, 10ml THF stirs and drips excessive H down
2O
2The aqueous solution, room temperature reaction spends the night, and removing desolvates obtains quantitative oxidation products (R)-BINAPO.In the 50ml round-bottomed flask, add 1g R-BINAPO (1.50mmol), 20ml diacetyl oxide, stir 10min down, add 0.4ml concentrated nitric acid, a small amount of dense H then at-10 ℃
2SO
4Mixture-5 ℃ down stir 6h after, add ice cube, neutralize with 30% NaOH solution then.Use CH
2Cl
2Extract three times, wash organic phase with water three times, use anhydrous Na
2SO
4Drying, filtration, removal of solvent under reduced pressure.Use ethyl acetate and sherwood oil crystallization at last, obtain 5,5 '-NO
2-BINAPO1.04g, productive rate 95%.
[α]
20 D＝+243.0°(c0.5，benzene)；
1H?NMR(CDCl
3)：6.83(t，J＝8.03Hz，2H)，7.06(d，J＝8.50Hz，2H)，7.27～7.45(m，16H)，7.66～7.73(m，6H)，8.09(d，J＝7.66Hz，2H)，8.64(dd，J
1＝1.73Hz，J
2＝9.13Hz，2H)；
31P?NMR(CDCl
3)：27.27。
R-5,5 '-NH
2-BINAPO's is synthetic:
In the 100ml flask, add 30ml ethanol, 2.5g SnCl
22H
2O (11mmol) and 12ml concentrated hydrochloric acid.Stir and add 1g 5,5 '-NO down in batches
2-BINAPO (1.34mmol).Mixture reacts 5h down at 50 ℃.Be cooled to room temperature, remove most of solvent, add 30% NaOH solution neutralization then.Filter out undissolved part, with EtOH and CH
2Cl
2The washing solid part.The filtrate of collecting is used CH
2Cl
2Extraction is washed three times, uses anhydrous Na
2SO
4Partial solvent is removed in drying, filtration, decompression, adds re-crystallizing in ethyl acetate, gets yellow solid 0.87g, productive rate 95%.
[α]
20 D＝+168.2°(c?0.5，ethanol)；
1H?NMR(CDCl
3)：4.05(s，4H)，6.27(d，J＝8.28Hz，2H)，6.51(d，J＝7.09Hz，2H)，6.59(t，J＝8.32Hz，2H)，7.21～7.45(m，18H)，7.66～7.76(m，6H)；
31P?NMR(CDCl
3)：28.14。
R-5,5 '-NH
2-BINAP's is synthetic:
In a 500ml two-mouth bottle, add 0.8g (1.17mmol) 5,5 '-NH
2-BINAPO, the new toluene that steams of 300ml, 1g (7.38mmol) HSiCl
3With 2ml triethylamine, N
2Protect following 100 ℃ to stir 1h, 110 ℃ are stirred 1h, begin the 40h that refluxes then.After being cooled to room temperature, slowly add 30% NaOH solution, tell organic phase, wash twice with water, use anhydrous Na then
2SO
4Most of solvent is removed in drying, filtration, decompression, uses recrystallizing methanol, gets yellow solid (R)-5,5 '-NH
2-BINAP 0.69g, productive rate are 91%.
[α]
20 D＝+218.0°(c?0.20，benzene)；
1H?NMR(CDCl
3)：4.06(s，4H)，6.30(d，J＝8.38Hz，2H)，6.59(d，J＝7.30Hz，2H)，6.70(t，J＝7.66Hz，2H)，6.99～7.13(m，20H)，7.32dd，J
1＝2.09Hz，J
2＝8.79Hz，2H)，7.79(d，J＝8.82Hz，2H)；
31P?NMR(CDCl
3)：-16.78。
The synthetic route of [embodiment 2] dendrimer synthon 2 is seen Fig. 2, reference literature (Percec, V.; Cho, W.; Ungar, G.and Yeardley, D.J.P., J.Am.Chem.Soc., 2001,123,1302) method is synthetic.
Synthesizing of compound 1:
In the 250ml flask, add K
2CO
3(6.0g, 43.0mmol), 3, (1.5g 8.9mmol), adds 60ml acetone as solvent to the 5-methyl dihydroxy benzoate.Adding 1-bromine certain herbaceous plants with big flowers alkane under stirring (5.8ml, 26.7mmol), reflux 12 hours.Remove most of solvent under the decompression behind the cool to room temperature, add the extraction of methylene dichloride and water, organic phase washes twice with water, with removing most of solvent under anhydrous magnesium sulfate drying, the decompression, uses recrystallizing methanol, gets white crystal 3.8g, productive rate 98%.
1H?NMR(CDCl
3)：δ＝7.16(d，J＝2.13，2H)，6.63(t，J＝2.12，1H)，3.97(t，J＝6.52)，3.90(s，3H)，1.81-1.75(m，4H)，1.50-1.28(m，28H)，0.91(t，6H)。
Synthesizing of compound 2:
In the 100ml flask, add 2.0g 1 (4.48mmol), 50ml tetrahydrofuran (THF), KOH (8.99mmol) O.50g, 3ml water, 2ml methyl alcohol, reflux 10 hours.Be neutralized to slightly acidic with 1N HCl after being chilled to room temperature, with dichloromethane extraction, washing, anhydrous magnesium sulfate drying, decompression revolve desolvate white solid 1.84g, 95% productive rate.
1H?NMR(CDCl
3)：δ＝7.14(d，2H，J＝2.3)，6.61(t，J＝2.2，1H)，3.90(t，4H，J＝6.2)，1.71(m，4H)，1.40-1.20(m，28H)，0.81(m，6H)。
The synthetic route of [embodiment 3] dendrimer synthon 7 is seen Fig. 3, reference literature (Percec, V.; Cho, W.; Ungar, G.and Yeardley, D.J.P., J.Am.Chem.Soc., 2001,123,1302) method is synthetic.
Synthesizing of compound 3:
In the 250ml flask, add 6.0g (43.0mmol) K
2CO
3, 1.2g (6.7mmol) 3,4,5-trihydroxybenzoic acid methyl esters adds 60ml acetone as solvent.Stir and add 5.8ml (26.7mmol) 1-bromine certain herbaceous plants with big flowers alkane, reflux 12 hours down.Spin off most of solvent under the decompression behind the cool to room temperature, add the extraction of methylene dichloride and water, wash twice with water, the organic phase anhydrous magnesium sulfate drying.Adding methyl alcohol is put into the refrigerator crystallization after spinning off most of solvent, gets white crystal 3.8g, productive rate 95%.
1H?NMR(CDCl
3)：δ＝7.27(s，2H)，4.01(t，6H，J＝6.2)，3.90(s，3H)，1.89-1.71(m，6H)，1.51-1.29(m，42H)，0.90(t，9H，J＝6.5)。
Synthesizing of compound 4:
In flask, add 2.0g (3.3mmol) 3,155mg (3.8mmol) LiAlH
4, add the new ether that steams then as solvent, reflux 4 hours.Add 2ml water carefully after being chilled to room temperature, add 30% aqueous sodium hydroxide solution 3ml again, add suitable quantity of water at last solid precipitation is got off, inclining clear liquid.Boil off solvent under the decompression and add methylene dichloride and water extraction, anhydrous magnesium sulfate drying.The pressure reducing and steaming solvent gets colourless aqueous product 1.8g, productive rate 90%.
1H?NMR(CDCl
3)：δ＝6.58(s，2H)，3.51(s，2H)，1.84-1.73(m，6H)，1.55-1.29(m，42H)，0.92-0.88(t，9H，J＝6.2)。
Synthesizing of compound 6:
In flask, add 1.9g (3.3mmol) 4, with the dissolving of 20ml methylene dichloride, the SOCl of Dropwise 5 ml (3.3mmol) then
2Solution.Pressure reducing and steaming solvent after 30 minutes adds 1.7g (12.0mmol) K after the thorough drying
2CO
3, 30ml DMF, 20ml THF, 0.17g (0.94mmol) 3,4,5-trihydroxybenzoic acid methyl esters.70 ℃ were stirred 15 hours down, added methylene dichloride/water extraction, anhydrous magnesium sulfate drying after being chilled to room temperature.Use alkaline Al
2O
3Column purification gets oily product 1.4g, productive rate 80%.
1H?NMRCDCl
3)：δ＝7.39(s，2H)，6.58(t，6H，J＝10.5)，5.01(s，6H)，4.00-3.75(m，21H)，1.89-1.66(m，18H)，1.46-1.28(m，126H)，0.97(t，27H，J＝6.0)。
Synthesizing of compound 7:
In the 100ml flask, add 1.45g (0.78mmol) 6,50ml tetrahydrofuran (THF), 0.25g (4.50mmol) KOH, 2ml water, 2ml methyl alcohol, reflux 10 hours.Adding 1N HCl is neutralized to slightly acidic after being chilled to room temperature, uses dichloromethane extraction, washing, anhydrous magnesium sulfate drying.The decompression revolve desolvate white solid 1.3g, 90% productive rate.
1H?NMR(CDCl
3)：δ＝7.46(s，2H)，6.62(d，6H，J＝12.0，)，5.06(d，6H，J＝.3.9)，3.97-3.76(m，18H)，1.79-1.69(m，18H)，1.47-1.28(m，126H，)，0.90(t，27H，J＝6.0).
[embodiment 4] AB
2-G
1The synthetic route of-BINAP is seen Fig. 4.
Under the nitrogen protection, in 25ml single port bottle, add AB
2-G
1-COOH 124mg (0.28mmol), 5,5 '-diamino-BINAP 90mg (0.14mmol), Calcium Chloride Powder Anhydrous 100mg (0.9mmol), triphenyl phosphite 0.1ml (0.38mmol), pyridine 0.1ml (1.24mmol), N-N-methyl-2-2-pyrrolidone N-1ml (10mmol), 100 ℃ were stirred 6 hours down.Behind the reactant cool to room temperature, pour in the methanol solution, precipitation after filtration, dry white solid AB
2-G
1-BINAP 172mg (productive rate 80%).
1H?NMR(CDCl
3)：δ?8.15(s，2H，)，7.99(d，2H，J＝9.0Hz)，7.9(d，2H，J＝10.0Hz)，7.50(m，2H)，7.20-6.93(m，26H)，6.70(d，2H，J＝11.5Hz)，6.64(t，2H，J＝2.0Hz)，4.01(t，8H，J＝6.5Hz)，1.83-1.78(m，8H)，1.48-1.26(m，56H)，0.90-0.87(t，12H，J＝6.5Hz)；
31P?NMR(CDCl3)：δ-14.7；
[α]
20 D＝+88.0°(c＝0.5，CH
2Cl
2)；
Ms(TOF)：C
98H
122N
2O
6P
2(calcd?1485.9)，found?1485.9。
[embodiment 5] AB
2-G
2The synthetic route of-BINAP is seen Fig. 5.
Under the nitrogen protection, in 25ml single port bottle, add AB
2-G
2-COOH269mg (0.28mmol), 5,5 '-diamino-BINAP 90mg (0.14mmol), Calcium Chloride Powder Anhydrous 100mg (0.9mmol), triphenyl phosphite 0.1ml (0.38mmol), pyridine 0.1ml (1.24mmol), N-N-methyl-2-2-pyrrolidone N-1ml (10mmol), 100 ℃ were stirred 6 hours down.Behind the reactant cool to room temperature, pour in the methanol solution, precipitation after filtration, dry white solid AB
2-G
2-BINAP 323mg (productive rate 90%).
1H?NMR(CDCl
3)：δ?8.19(s，2H)，8.00-7.93(m，4H)，7.52(d，2H，J＝9.0Hz)，7.55-6.60(m，38H)，6.44(s，4H)，5.05(s，8H)，3.96(t，16H，J＝6.5Hz)，1.83-1.74(m，16H)，1.47-1.29(m，112H)，0.9(t，24H，J＝6.6Hz)；
31P?NMR(CDCl3)：δ-14.6；
[α]
20 D＝+47.1°(c＝2.3，CH
2Cl
2).
Ms(TOF)：C
166H
226N
2O
14P
2(calcd?2533.6)，found2533.8。
[embodiment 6] AB
3-G
1The synthetic route of-BINAP is seen Fig. 6.
Under the nitrogen protection, in 25ml single port bottle, add AB
3-G
1-COOH 165mg (0.28mmol), 5,5 '-diamino-BINAP 90mg (0.14mmol), Calcium Chloride Powder Anhydrous 100mg (0.9mmol), triphenyl phosphite 0.1ml (0.38mmol), pyridine 0.1ml (1.24mmol), N-N-methyl-2-2-pyrrolidone N-1ml (10mmol), 100 ℃ were stirred 8 hours down.Behind the reactant cool to room temperature, pour in the methanol solution, precipitation after filtration, dry white solid AB
3-G
1-BINAP 217mg (productive rate 85%).
1H?NMR(CDCl
3)：δ?8.09(s，2H)，7.84(d，2H，J＝7.5Hz)，7.51(d，2H，J＝8.5Hz)，7.27-7.04(m，24H)，6.98-6.95(t，2H，J＝8.5Hz)，6.73(d，2H，J＝8.6Hz)，4.08-4.03(m，12H)，1.87-1.76(m，12H)，1.58-1.28(m，84H)，0.88(m，18H)；
31P?NMR(CDCl3)：δ-14.8；
[α]
20 D＝+74.0°(c＝0.7，CH
2Cl
2)；
Ms(TOF)：C
118H
162N
2O
8P
2(calcd?1798.5)，found?1798.4。
[embodiment 7] AB
3-G
2The synthetic route of-BINAP is seen Fig. 7.
Under the nitrogen protection, in 25ml single port bottle, add AB
3-G
2-COOH 515mg (0.28mmol), 5,5 '-2 amino-BINAP 90mg (0.14mmol), Calcium Chloride Powder Anhydrous 100mg (0.9mmol), triphenyl phosphite 0.1ml (0.38mmol), pyridine 0.1ml (1.24mmol), N-N-methyl-2-2-pyrrolidone N-1ml (10mmol), 100 ℃ were stirred 8 hours down.Behind the reactant cool to room temperature, pour in the methanol solution, precipitation after filtration, dry white solid AB
3-G
2-BINAP 556mg (productive rate 92%).
1H?NMR(CDCl
3)：δ?8.05(s，2H)，8.00(d，2H，J＝7.0Hz)，7.83(d.2H，J＝7.0Hz)，7.53(d，2H，J＝8.0Hz)，7.31-6.95(m，24H)，6.8-6.54(m，16H)，5.09-5.03(q，12H，J＝10.0Hz)，3.94-3.87(m，36H)，1.76-1.69(m，36H)，1.63-1.26(m，252H)，0.88-0.76(m，54H)；
31P?NMR(CDCl3)：δ-14.7；
[α]
20 D＝+28.0°(c＝2.9，CH
2Cl
2)；
Ms(TOF)：C
280H
438N
2O
26P
2(calcd?4310.4)，found?4310.9。
[embodiment 8] AB
2-G
2The synthetic route of-PyrPhos is seen Fig. 8.
Under the nitrogen protection, in 25ml single port bottle, add AB
2-G
2-COOH 240mg (0.25mmol), 5ml SOCl
2, add the 2h that refluxes behind several DMF, remove SOCl then
2In above-mentioned reaction flask, add 10ml CH
2Cl
2, a small amount of triethylamine, 0 ℃ of following Dropwise 5 ml (0.228mmol) (3R, 4R)-PyrPhos CH
2Cl
2Solution.Be warming up to room temperature afterreaction 2h.Decompression is down removed most of organic solvent, pour in the methanol solution, throw out after filtration, dry must white solid AB
2-G
2-PyrPhos 299mg (productive rate 95%).
1H?NMR(CDCl
3)：δ?7.5-7.1(m，22H)，6.8-6.4(m，7H)，5.1(s，4H)，4.0(t，8H，J＝6.5Hz)，4.0-3.8(m，2H)，3.3-3.1(m，2H)，2.9-2.8(m，2H)，1.83-1.74(m，8H)，1.47-1.29(m，56H)，0.9(t，12H，J＝6.6Hz)；
31P?NMR(160MHz，CDCl
3)：-12.6，-12.8。
[embodiment 9] dendrimer chiral phosphine ligand is not full of application in the carboxylic acid asymmetric catalytic hydrogenation reaction at α-fragrance, sees Fig. 9.
Under the nitrogen protection, in 25ml single port bottle, add AB successively
2-G
1-BINAP (0.0011mmol), [RuCl
2(benzene)]
2(0.0005mmol), the new N that steams, dinethylformamide 1ml heated 20 minutes down at 100 ℃.30 ℃ of following removal of solvent under reduced pressure add the 2ml normal hexane, 2ml ethanol, the reaction substrate different Ibuprofen BP/EP 20mg that dewaters, triethylamine 20ul.With the reactor of these mixtures addings 50ml, charge into the hydrogen of 80atm.Reaction bled off hydrogen after 4 hours under the room temperature, and removal of solvent under reduced pressure adds methyl alcohol and removes catalyzer, obtains the different Ibuprofen BP/EP 19mg of reduzate at last.Reduzate is through the generation methyl esters of deriving, and the ee value that obtains product with the chiral chromatographic column analysis in gas chromatograph is 91%.
Figure 10 is seen in the application of [embodiment 10] dendrimer chiral phosphine ligand in the reaction of dehydration amino acid asymmetric catalytic hydrogenation.
Under the nitrogen protection, with 3.5mg (0.0025mmol) AB
2-G
2-PyrPhos, 1.1mg[Rh (COD)
2] BF
4(0.0024mmol), 100mg dehydrobenzene L-Ala, the 2ml normal hexane, 2ml ethanol joins in the reactor of 50ml, charges into the hydrogen of 50atm.Reaction bled off hydrogen after 10 hours under the room temperature, and removal of solvent under reduced pressure adds methyl alcohol and removes catalyzer, obtains reduzate 96mg at last.Reduzate is through the generation methyl esters of deriving, and the ee value that obtains product with the chiral chromatographic column analysis in gas chromatograph is 90%.
Separation and Recovery of [embodiment 11] dendrimer chiral phosphine ligand metal catalyst and utilization again:
Under the nitrogen protection, in 25ml single port bottle, add AB
2-G
1-BINAP (0.0011mmol), [RuCl
2(benzene)]
2(0.0005mmol), the new N that steams, dinethylformamide 1ml heated 20 minutes down at 100 ℃.30 ℃ of following removal of solvent under reduced pressure add the 2ml normal hexane, 2ml ethanol, the different Ibuprofen BP/EP 20mg that dewaters, triethylamine 20ul.With the reactor of these mixtures addings 50ml, charge into the hydrogen of 80atm.Reaction bled off hydrogen after 2 hours under the room temperature, added 0.075ml water in system, made it be divided into two-phase, told upper strata hexane phase, used catalyzer with recirculation behind the anhydrous sodium sulfate drying.Add hexane to 2ml, add 2ml ethanol again, the different Ibuprofen BP/EP 20mg that dewaters, triethylamine 20ul.Reaction is after 2 hours under the room temperature, and adopting uses the same method separates and recycle catalyzer.Catalyzer recycles 4 times altogether, and the analytical results of reduzate sees Table:
| Access times | Part | E.e. be worth (%) | Transformation efficiency (%) |
| 1 | AB 2-G 1-BINAP | 90 | 94 |
| 2 | AB 2-G 1-BINAP | 90 | 93 |
| 3 | AB 2-G 1-BINAP | 89 | 93 |
| 4 | AB 2-G 1-BINAP | 89 | 91 |
Claims (6)
1. a dendrimer chiral phosphine ligand is to be connected with amide group through condensation reaction with corresponding small molecules chiral phosphine compound by the dendrimer synthon;
But described dendrimer synthon terminal group is a reactive group, and dendrimer synthon outer layer zone surface has alkyl group; But described reactive group is a carboxyl; Described small molecules chiral phosphine compound has at least one amino.
2. according to the dendrimer chiral phosphine ligand of claim 1, it is characterized in that: described dendrimer synthon has the polyarylether dendrimer synthon of alkyl group for the surface.
3. according to the dendrimer chiral phosphine ligand of claim 1, it is characterized in that: described small molecules chiral phosphine compound is the following compound of structure:
Described Ph is a phenyl.
4. according to the dendrimer chiral phosphine ligand of claim 1, it is characterized in that: described dendrimer chiral phosphine ligand structural formula is as follows:
Described Ph is a phenyl,
Wherein, A
1The polyarylether dendrimer substituting group that has alkyl group for the surface.
5. the application of dendrimer chiral phosphine ligand in asymmetric hydrogenation of claim 1.
6. according to the application of claim 5, it is characterized in that: the reaction substrate in the described asymmetric hydrogenation is prochiral α-unsaturated aromatic carboxylic acid and α-dehydration amino acid.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5567795A (en) * | 1995-08-18 | 1996-10-22 | Hoechst Celanese Corporation | Process for preparing hyperbranched polymers |
| CN1059211C (en) * | 1996-10-24 | 2000-12-06 | 中国科学院成都有机化学研究所 | Chirality epoxy phosphine ligand compound and its synthesis and application |
| EP1060226A1 (en) * | 1998-02-26 | 2000-12-20 | The Secretary Of State For Defence | Liquid crystal polymer devices and materials |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5567795A (en) * | 1995-08-18 | 1996-10-22 | Hoechst Celanese Corporation | Process for preparing hyperbranched polymers |
| CN1059211C (en) * | 1996-10-24 | 2000-12-06 | 中国科学院成都有机化学研究所 | Chirality epoxy phosphine ligand compound and its synthesis and application |
| EP1060226A1 (en) * | 1998-02-26 | 2000-12-20 | The Secretary Of State For Defence | Liquid crystal polymer devices and materials |
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