CN103951686A - Chiral bridged aryloxyalkyloxy scandium chloride, and preparation method and application thereof - Google Patents
Chiral bridged aryloxyalkyloxy scandium chloride, and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a chiral bridged aryloxyalkyloxy scandium chloride. The chiral bridged aryloxyalkyloxy scandium chloride is characterized in that the chiral bridged aryloxyalkyloxy scandium chloride has a general formula of LScCl(THF), and has a chemical structural formula shown in the specification, and L is (S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)-phenolate. The above compound has the advantages of simple synthesis, clear structure and high yield. The invention also provides a preparation method of the compound, and an application method of the compound in the catalysis of the asymmetric hydrogen phosphorization reaction of alpha, beta-unsaturated ketone as a catalyst. The application method has the advantages of mild conditions, high selectivity, good antipodal selectivity and wide substrate adaptation range.
Description
Technical field
The present invention relates to asymmetric catalysis field, be specifically related to a kind of chirality bridging aryloxy alcoxyl base scandium muriate and preparation method thereof and the application in asymmetric hydrogen phosphineization reaction.
Background technology
Optically pure phosphine compound tool has been widely used, and the effective ways of the pure phosphine compound of development synthesizing optical have great importance.Form chirality P-C key the most directly, the most effectively, the method for tool Atom economy is exactly the asymmetric reduction reaction with C=C pair of keys by P-H key.At present, to this type of reaction, there is the catalyzer of catalytic effect to have a variety of, mainly include two kinds of machine small molecules catalyst system and metal complexes catalyst system.
Report about organic molecule system:
(1) 2007 year, the people such as Terada utilize 1 of the derivative a kind of axle chirality guanidine compound catalysis diphenyl phosphite of dinaphthol and nitro alkene first, 4-addition, under the consumption of 1mol% catalyzer, take t-butyl methyl ether as solvent,-40 ℃ of reaction 0.5-6h, have successfully realized the asymmetric hydrogen phosphine addition reaction of aliphatics and aromatic nitro alkene.(referring to: Terada, M.; Ikehara, T.; Ube, H.J.Am.Chem.Soc.2007,129,14112.).
(2) 2007 years, the people such as Melchiorre designed and have synthesized a kind of chirality quaternary ammonium compound, found that they can be used as catalyst secondary phosphine and react with the asymmetric hydrogen phosphine of nitroolefin.(referring to: Bartoli, G.; Bosco, M.; Carlone, A.; Locatelli, M.; Mazzanti, A.; Sambriand, L.; Melchiorre, P.Chem.Commun., 2007,722.).
(3) 2007 years, Tan seminar has reported that chirality bicyclic guanidine derivatives can catalysis diaryl phosphine oxide and the asymmetric phospha-Michael addition of nitro alkene, the method of a kind of direct synthesizing chiral beta-amino phosphine oxide and beta-amino phosphine is provided, the highest yield reaches 99%, and e.e. value is the highest by 96%.(referring to: Fu, X.; Jiang, Z.Y.; Tan, C.H.Chem.Commun.2007,5058.).
(4) 2007 years, Wang seminar found that quinine is the effective catalyst of the asymmetric hydrogen phosphine addition reaction of catalysis diphenyl phosphite and nitroolefin, with yield and the 45-88%e.e. value of 60-85%, obtained corresponding product.This reaction conditions is harsher, long reaction time.(referring to: Wang, J.; Heikkinen, L.D.; Li, H.; Zu, L.; Jiang, W.; Xie, H.X.; Wang, W.Adv.Synth.Catal.2007,349,1052.).
(5) 2011 years, the people such as Herrer find chirality organic bases-thiocarbamide as catalyzer preferably catalysis diphenyl phosphite react with the hydrogen phosphine of nitro alkene, in dichloromethane solution ,-10 ℃ reaction 3 days with high yield, medium e.e. value obtains product.(referring to: Alcaine, A.; Marqu ' es-L ' opez, E.; Merino, P.; Tejeroa, T.; Herrer, R.P.Org.Biomol.Chem., 2011,9,2777.).
(6) people such as Melchiorre finds that diaryl dried meat ammonia alcohol can react with the asymmetric hydrogen phosphine of phenylacrolein and derivative thereof by catalysis diaryl phosphine, and original position is reduced to phosphine-borane-ol compound by product, and productive rate is 60-90%, and e.e. value is 74-94%.(referring to: Carlone, A.; Bartoli, M.; Bosco, L.; Sambri; Melchiorre, P.Angew.Chem., Int.Ed., 2007,46,4504.).
(7) people such as Cordova finds to take that L-PROLINE and derivative thereof can catalysis unsaturated aldehydes and the asymmetric hydrogen phosphineization reaction of phosphine as catalyzer, and product is reduced to γ-hydroxyl phosphine to original position or in-situ oxidation is β-formyl radical phosphine oxide.The corresponding e.e. value of product of in-situ method reduction is 90-99%.(referring to: Ibrahem, I.; Rios, R.; Vesely, J.; Hammar, P.; Eriksson, L.; Himo, F.; Co ' rdova, A.Angew.Chem., Int.Ed., 2007,46,4507.).
(8) people such as Lattanzi finds that 2-hydroxyl quinine can the hydrogen phosphine addition reaction of catalysis diphenyl phosphine oxide to trans cinnamophenone, and-22 ℃ of reactions 75-160 hour obtain the hydrogen phosphine product of various chalcone derivatives, and e.e. value is up to 89%.(referring to: Russo, A.; Lattanzi, A.Eur.J.Org.Chem.2010,6736.).
Report about metal complexes catalyst system:
(1) 2004 year, the people such as Togni found that a kind of dication type title complex of Chiral Nickel can catalysis di-t-butyl phosphine and the asymmetric addition of isopropene cyanide, and successful separation obtains intermediate.(referring to: Sadow, A.D.; Haller, I.; Fadini, L.; Togni, A.J.Am.Chem.Soc.2004,126,14704.).
(2) 2009 years, the Wang Rui of Lanzhou University etc. found with 40mol%Et
2zn and 20mol%Trost part are catalyst system, can realize the asymmetric 1.4-addition reaction of diethyl phosphite and alpha, beta-unsaturated ketone, and the yield with 99% and 99% e.e. value obtain corresponding γ-oxo phosphoric acid ester.(referring to: Zhao, D.; Yuan, Y.; Chan, Albert, S.C.; Wang, R.Chem.Eur.J.2009,15,2738.);
(3) Wang Rui of Lanzhou University etc. also finds with 40mol%Et
2the catalyst system that Zn and 20mol%Trost part form can catalysis diethyl phosphite and α, and the asymmetric 1.4-addition reaction of β-unsaturated pyrrolidone and imines, obtains final product with the yield of 91-99% and the e.e value of 98-99%.(referring to: Zhao, D.; Wang, Y.; Mao, L.J.; Wang, R.Chem.Eur.J.2009,15,10983.).
(4) 2010 years, Wang Rui etc. were with derivative Trost part and the Et of two thiophene dried meat ammonia alcohol
2zn is catalyst system, has realized diphenyl phosphine oxide and has reacted with the imines hydrogen phosphine of alpha, beta-unsaturated ketone and N-sulfinyl.(referring to: Zhao, D.P.; Mao, L.J; Yang, D.X.; Wang, R.J.Org.Chem.2010,75,6756.).
(5) 2013 years, Ishihara
[45]seminar has reported dinaphthol: di-t-butyl magnesium: water=3:2:2 situ catalytic diaryl phosphine oxide and α, Isosorbide-5-Nitrae-the addition reaction of beta-unsaturated esters, in tetrahydrofuran solvent,-40 ℃ of reactions, obtain corresponding hydrogen phosphine product with medium above yield and higher e.e. value.(referring to: Hatano, M.; Horibe, T.; Ishihara, K.Angew.Chem.Int.Ed.2013,52,4549.).
Up to the present, there is not yet and take the asymmetric hydrogen phosphineization reaction that chirality bridging aryloxy alcoxyl base rare earth compound is catalyst alpha, beta-unsaturated ketone, prepare the report of chiral alpha-hydroxyphosphonate.
Summary of the invention
The present invention seeks to: a kind of chirality bridging aryloxy alcoxyl base scandium muriate is provided, this chirality bridging aryloxy alcoxyl base scandium muriate can be used as catalyst α, alpha, beta-unsaturated ketone reacts with the asymmetric hydrogen phosphine of phosphinate, prepare chiral alpha-hydroxyphosphonate, its catalytic activity is high, enantioselectivity is good, and substrate wide accommodation can overcome the deficiency of indented material well.
The present invention in order to realize the technical scheme of above-mentioned technical purpose is:
A chirality bridging aryloxy alcoxyl base scandium muriate, is characterized in that: general formula is: LScCl (THF), and its chemical structural formula is as follows:
Wherein: L=(S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl) pyrrolidin-1-yl) methyl)-phenolate.
The present invention provides a kind of described chirality bridging aryloxy alcoxyl base scandium muriatic preparation method simultaneously, and it is simple to operate, separating-purifying is convenient, raw materials cost is low, reaction conditions is gentle, compound structure is clear and definite.
The chiral hydroxyl group phenol precursor LH relating in the present invention
2for prior art, its preparation method can reference " synthetic, the sign of bridging virtue oxygen (alcoxyl) base rare earth compounding and catalytic performance thereof "-Feng Tao, University Of Suzhou's master thesis, 2011.
The described muriatic preparation method of chirality bridging aryloxy alcoxyl base scandium specifically comprises the following steps:
Step 1) synthesis of chiral ligand precursor LH
2, described LH
2=(S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl) pyrrolidin-1-yl) methyl)-phenol:
By (S)-α, α-diphenylprolinol and formaldehyde solution are pressed mol ratio condensation in methyl alcohol of 1:1.5, and after completion of the reaction, original position adds 2,4-DI-tert-butylphenol compounds, in methyl alcohol, reflux is 24 hours, has a large amount of white solids to separate out, suction filtration, cold methanol wash for filter cake, drain, obtain white solid and be product, its reaction equation is as follows:
Step 2) synthesis of chiral bridging aryloxy alcoxyl base scandium muriate:
One, dewater in the reaction flask of deoxygenation argon shield and add ligand precursor LH
2, with ether solvent, dissolving, the cryosel that is placed in-10～-15 ℃ is bathed, and after 8～15min, with syringe, slowly drips the n-Butyl Lithium of two equivalents; After dripping, rise to room temperature reaction half an hour, by reaction solution according to LH
2: ScCl
3the mol ratio of=1:0.95～1.05 joins ScCl
3ethers suspension liquid in, solution becomes clarification gradually, finally obtains faint yellow clear liquor; Except desolventizing, add varsol extraction, heating, the centrifugal LiCl that removes, gets upper strata glassy yellow clear liquid, concentrated, and room temperature is standing until separate out clear crystal, is chirality bridging aryloxy alcoxyl base scandium muriate LScCl (THF); The reaction equation of above-mentioned steps is as follows:
Further, ether solvent above-mentioned steps 2 of the present invention) is a kind of in tetrahydrofuran (THF), ether and glycol dimethyl ether.
Further, varsol above-mentioned steps 2 of the present invention) is a kind of in toluene, benzene and hexane.
The present invention also provides the application of the asymmetric hydrogen phosphineization reaction using the above-mentioned chirality bridging aryloxy alcoxyl base scandium muriate making as catalyst alpha, beta-unsaturated ketone.
Further, above-mentioned application method comprises the following steps:
(1) under anhydrous and oxygen-free, protection of inert gas, by α, alpha, beta-unsaturated ketone adds in reaction flask, add solvent and as the chirality bridging aryloxy alcoxyl base scandium muriate of catalyzer, being placed in and setting temperature of reaction is that the thermostatic bath of 20～-60 ℃ stirs, finally add the phosphorous acid ester of 1～1.5 times of amount of alpha, beta-unsaturated ketone molar weight to react, react 4～72 hours; Described solvent is alkane solvents, ether solvent or amine solvent, and the mol ratio of alpha, beta-unsaturated ketone and catalyzer is 5～20:1;
The actual reaction times is relevant with the mol ratio of temperature of reaction and alpha, beta-unsaturated ketone and catalyzer, and along with the wherein molar ratio rising of temperature of reaction rising and alpha, beta-unsaturated ketone and catalyzer, the reaction times shortens.
(2), after the reaction in step (1) finishes, water cancellation reaction, is then extracted with ethyl acetate, then through column chromatography for separation, finally uses the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains chiral product.
The reaction equation of step (1) and (2) synthesis technique is as follows:
Further, in the step of above-mentioned application method (1), more preferred temperature of reaction is 0～-40 ℃.
Further, in the step of above-mentioned application method (1), described alkane solvents is selected from one of hexane, toluene, benzene, dimethylbenzene, methylene dichloride and ethylene dichloride; Ether solvent is selected from one of tetrahydrofuran (THF), ether, glycol dimethyl ether and dioxane; Amine solvent is selected from triethylamine, Tetramethyl Ethylene Diamine, Isosorbide-5-Nitrae-lupetazin, N, N, N', N'', one of N''-PMDETA and 1,8-diazabicylo, 11 carbon-7-alkene.
The step of above-mentioned application method of the present invention (1) is when actually operating, and catalyzer can first add in reaction vessel by solid form, then adds organic solvent, can certainly in advance catalyzer and organic solvent be mixed with to solution, then add in reaction vessel.And be not restricted for the concentration of catalyst solution, only need guarantee that the volume of catalyst solution is no more than the cumulative volume of end reaction system, with handled easily.
Advantage of the present invention is:
The invention provides a kind of chirality bridging aryloxy alcoxyl base scandium muriate and preparation method thereof and react with the asymmetric hydrogen phosphine of phosphinate it as catalyst alpha, beta-unsaturated ketone, to obtain the application of chiral alpha-hydroxyphosphonate.The preparation method of the chirality bridging aryloxy alcoxyl base scadium compound providing is simple to operate, separating-purifying convenient, raw materials cost is low, reaction conditions is gentle, compound structure is clear and definite; And high with the catalytic activity that the asymmetric hydrogen phosphine of phosphinate reacts as catalyst alpha, beta-unsaturated ketone by this compound, enantioselectivity is good, substrate wide accommodation, can overcome the deficiency of indented material well.
Embodiment
Below in conjunction with embodiment, describe the present invention in detail.
Core of the present invention is that chirality bridging aryloxy alcoxyl base is prepared to chirality bridging aryloxy alcoxyl base scandium muriate as part, and the general formula of this compound is: LScCl (THF).
Embodiment mono-: preparation LScCl (THF)
1) before carrying out the preparation of chirality bridging aryloxy alcoxyl base scadium compound, first to prepare LH
2, its preparation method is as follows:
3 milliliters of formaldehyde solutions (30 mmole) are added in the two neck bottles with stirrer, add dissolve with methanol, then add (S)-α, 5.07 grams of α-diphenylprolinol (20 mmole), stirring reaction half an hour, then add 4.12 grams of 2,4-DTBPs (20 mmole).At 60 ℃, react 24 hours, have a large amount of white solids to separate out.Suction filtration, uses methanol wash filter cake, drains, and obtains compound L H
2, productive rate 80%.Nuclear magnetic data:
1h NMR (400MHz, CDCl
3): 7.60 (dd, 4H), 7.32 (m, 4H), 7.21 (t, 1H), 7.18-7.08 (m, 2H), 6.70 (s, 1H), 3.99 (m, 1H), 3.41 (dd, 2H), 2.90 (s, 1H), 2.43 (m, 1H), 2.15-2.01 (m, 1H), 1.96-1.83 (m, 1H), 1.70 (m, 2H), 1.39 (s, 9H), 1.24 (s, 9H).
2) prepare LScCl (THF)
One, strictly dewater in the reaction flask of deoxygenation and add LH
2the tetrahydrofuran solution of (0.47 gram, 1.00 mmoles), is positioned over during the cryosel of-10～-15 ℃ bathes, and after 10min, with syringe, slowly drips the n-Butyl Lithium (2.00 mmole) of 2 equivalents.Dropwise, recover room temperature reaction half an hour, reaction solution is joined to ScCl
3in the tetrahydrofuran (THF) suspension of (0.15 gram, 1.00 mmoles).React 24 hours, obtain the solution that achromaticity and clarification is transparent.Except desolventizing, add 20 milliliters of toluene extractions.The centrifugal LiCl precipitation of removing, gets upper strata glassy yellow clear liquid.Again, except desolventizing, add 10 milliliters of normal hexanes, envelope bottle is separated out 0.53 gram of clear crystal after a couple of days, is chirality bridging aryloxy alcoxyl base scandium muriate LScCl (THF), productive rate 85%.Ultimate analysis: C, 69.82; H, 7.25; N, 2.47; Sc, 7.01; C
36h
47clNO
3sc theoretical value: C, 69.45; H, 7.61; N, 2.25; Sc, 7.23.
1h NMR (400MHz, C
6d
6, 25 ℃): δ 8.20 (d, J=8.0MHz, 1H, Ph), 8.07 (d, J=8.0MHz, 1H, Ph), 8.02 (d, J=8.0MHz, 2H, Ph), 7.68 (s, 1H, Ph), 7.64 (t, J=8.0MHz, 1H, Ph), 7.46 (t, J=8.0MHz, 1H, Ph), 7.38 (m, 1H, Ph), 7.20 (m, 4H, Ph), 3.76 (m, 1H, NCH
2(Ar)), 3.67 (t, J=12.0MHz, 1H, NCH
2(Ar)), 3.57 (t, J=12.0MHz, 1H, CH), 3.04 (d, J=12.0MHz, 1H, CH
2), 2.64 (m, 3H, CH
2), 1.61 (s, 9H, C (CH
3)
3), 1.48 (m, 2H, CH
2), 1.23 (s, 9H, C (CH
3)
3).
13c NMR (400MHz, C
6d
6, 25 ℃): δ 157.9 (Ph), 149.7 (Ph), 143.5 (Ph), 142.9 (Ph), 139.9 (Ph), 136.22 (Ph), 125.2 (Ph), 123.7 (Ph), 122.6 (Ph), 89.3 (N (CH
2) (Ar)), 77.9 (CH
2), 68.9 (CH
2), 62.6 (CH
2), 55.7 (CH
2), 33.9 (CH
3), 31.9 (CH
3), 31.7 (CH
3), 30.9 (CH
3), 30.0 (CH
3), 29.5 (CH
3), 25.5 (CH
3), 19.1 (CH
3).Infrared absorption spectrum data: 3421s, 3128w, 3069m, 2830s, 2688w, 2583w, 2210w, 1984m, 1805w, 1771m, 1605s, 1488s, 1342m, 1315m, 1230m, 1284w, 1165w, 1123m, 1040m, 910s, 837m, 742s, 706m.
Embodiment bis-: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0625 gram of cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of tetrahydrofuran (THF)s, add 0.058 milliliter of phosphonous acid diethyl ester stir 5 minutes in design temperature is the thermostatic bath of 10 ℃ after.At 10 ℃, continue, after reaction 4h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 45.72 milligrams of alpha-hydroxyphosphonates, productive rate 44%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 37%.
Embodiment tri-: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0625 gram of cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of toluene, add 0.058 milliliter of phosphonous acid diethyl ester stir 5 minutes in design temperature is the thermostatic bath of 10 ℃ after.At 10 ℃, continue, after reaction 4h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 56.11 milligrams of alpha-hydroxyphosphonates, productive rate 54%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 42%.
Embodiment tetra-: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0625 gram of cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of dioxane, add 0.058 milliliter of phosphonous acid diethyl ester stir 5 minutes in design temperature is the thermostatic bath of 10 ℃ after.At 10 ℃, continue, after reaction 4h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 7.27 milligrams of alpha-hydroxyphosphonates, productive rate 7%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 50%.
Embodiment five: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0625 gram of cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.038 gram of muriate of scandium (0.06 mmole); add 2.0 milliliters of toluene, add 0.058 milliliter of phosphonous acid diphenyl ester stir 5 minutes in design temperature is the thermostatic bath of 10 ℃ after.At 10 ℃, continue, after reaction 4h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 98.65 milligrams of alpha-hydroxyphosphonates, productive rate 81%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 39%.
Embodiment six: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0625 gram of cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.009 gram of muriate of scandium (0.015 mmole); add 2.0 milliliters of Tetramethyl Ethylene Diamines, at design temperature, after stirring 5 minutes in the thermostatic bath of-20 ℃, add 0.058 milliliter of phosphonous acid diethyl ester.At 0 ℃, continue, after reaction 20h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 35.33 milligrams of alpha-hydroxyphosphonates, productive rate 34%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 89%.
Embodiment seven: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0625 gram of cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of Tetramethyl Ethylene Diamines, at design temperature, after stirring 5 minutes in the thermostatic bath of-30 ℃, add 0.058 milliliter of phosphonous acid diphenyl ester.At-30 ℃, continue, after reaction 25h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 49.75 milligrams of alpha-hydroxyphosphonates, productive rate 41%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 98%.
Embodiment eight: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0625 gram of cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of Tetramethyl Ethylene Diamines, at design temperature, after stirring 5 minutes in the thermostatic bath of-30 ℃, add 0.058 milliliter of phosphonous acid diethyl ester.At-30 ℃, continue, after reaction 50h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 66.50 milligrams of alpha-hydroxyphosphonates, productive rate 64%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 99%.
Embodiment nine: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0667 gram of cinnamophenone of 1-phenyl-3-(4-aminomethyl phenyl) (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of Tetramethyl Ethylene Diamines, at design temperature, after stirring 5 minutes in the thermostatic bath of-30 ℃, add 0.058 milliliter of phosphonous acid diethyl ester.At-30 ℃, continue, after reaction 72h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 96.76 milligrams of alpha-hydroxyphosphonates, productive rate 90%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 98%.
Embodiment ten: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0714 gram of cinnamophenone of 1-phenyl-3-(4-p-methoxy-phenyl) (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of Tetramethyl Ethylene Diamines, at design temperature, after stirring 5 minutes in the thermostatic bath of-30 ℃, add 0.058 milliliter of phosphonous acid diethyl ester.At-30 ℃, continue, after reaction 72h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 103.32 milligrams of alpha-hydroxyphosphonates, productive rate 92%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 97%.
Embodiment 11: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 1-(4-p-methoxy-phenyl)-0.0714 gram of 3-phenyl cinnamophenone (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of Tetramethyl Ethylene Diamines, at design temperature, after stirring 5 minutes in the thermostatic bath of-30 ℃, add 0.058 milliliter of phosphonous acid diethyl ester.At-30 ℃, continue, after reaction 72h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 99.95 milligrams of alpha-hydroxyphosphonates, productive rate 89%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 99%.
Embodiment 12: adopt the asymmetric hydrogen phosphineization reaction of the above-mentioned LScCl making (THF) catalysis alpha, beta-unsaturated ketone:
In the reaction flask of processing through dehydration and deoxidation; under argon shield, add 0.0594 gram of cinnamophenone of 1-furyl-3-phenyl (0.3 mmole); chirality bridging aryloxy alcoxyl base 0.019 gram of muriate of scandium (0.03 mmole); add 2.0 milliliters of Tetramethyl Ethylene Diamines, at design temperature, after stirring 5 minutes in the thermostatic bath of-30 ℃, add 0.058 milliliter of phosphonous acid diethyl ester.At-30 ℃, continue, after reaction 72h, to use deionized water termination reaction.
Product is separated through silicagel column, finally adopts the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains 90.82 milligrams of alpha-hydroxyphosphonates, productive rate 90%.Enantio-selectivity is measured with chirality HPLC, Daicel Chiralpak AS-H post, leacheate i-PrOH/hexane (10/90), flow velocity 1.0mL/min, ee value 98%.
Certainly above-described embodiment is just non exhaustive for exemplifying of illustrating that technical conceive of the present invention and feature do, and its object is to allow person skilled in the art can understand content of the present invention and implement according to this, can not limit the scope of the invention with this.All modifications that the spirit of main technical schemes is done according to the present invention, within all should being encompassed in protection scope of the present invention.
Claims (8)
1. a chirality bridging aryloxy alcoxyl base scandium muriate, is characterized in that: general formula is: LScCl (THF), and its chemical structural formula is as follows:
Wherein: L=(S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl) pyrrolidin-1-yl) methyl)-phenolate.
2. the muriatic preparation method of chirality bridging aryloxy alcoxyl base scandium described in claim 1, is characterized in that, comprises the following steps:
(1) synthesis of chiral ligand precursor LH
2, described LH
2=(S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl) pyrrolidin-1-yl) methyl)-phenol;
(2) synthesis of chiral bridging aryloxy alcoxyl base scandium muriate
One, dewater in the reaction flask of deoxygenation, argon shield and add ligand precursor LH
2, with ether solvent, dissolving, the cryosel that is placed in-10～-15 ℃ is bathed, and after 8～15min, with syringe, slowly drips the n-Butyl Lithium of two equivalents; After dripping, rise to room temperature reaction half an hour, by reaction solution according to LH
2: ScCl
3the mol ratio of=1:0.95～1.05 joins ScCl
3ethers suspension liquid in, solution becomes clarification gradually, finally obtains faint yellow clear liquor; Except desolventizing, add varsol extraction, heating, the centrifugal LiCl that removes, gets upper strata glassy yellow clear liquid, concentrated, and room temperature is standing until separate out clear crystal, is chirality bridging aryloxy alcoxyl base scandium muriate LScCl (THF); Its reaction equation is as follows:
3. the muriatic preparation method of chirality bridging aryloxy alcoxyl base scandium according to claim 2, is characterized in that: the ether solvent in described step (2) is a kind of in tetrahydrofuran (THF), ether and glycol dimethyl ether.
4. the muriatic preparation method of chirality bridging aryloxy alcoxyl base scandium according to claim 2, is characterized in that: the varsol in described step (2) is a kind of in toluene, benzene and hexane.
5. chirality bridging aryloxy alcoxyl base scandium muriate as claimed in claim 1 is as the application of the asymmetric hydrogen phosphineization reaction of catalyst alpha, beta-unsaturated ketone.
6. chirality bridging aryloxy alcoxyl base scandium muriate as claimed in claim 5, as the application of the asymmetric hydrogen phosphineization reaction of catalyst alpha, beta-unsaturated ketone, is characterized in that, the method for this application comprises the following steps:
(1) under anhydrous and oxygen-free, protection of inert gas, by α, alpha, beta-unsaturated ketone adds in reaction flask, add solvent and as the chirality bridging aryloxy alcoxyl base scandium muriate of catalyzer, being placed in and setting temperature of reaction is that the thermostatic bath of 20～-60 ℃ stirs, finally add the phosphorous acid ester of 1～1.5 times of amount of alpha, beta-unsaturated ketone molar weight to react, react 4～72 hours; Described solvent is alkane solvents, ether solvent or amine solvent, and the mol ratio of alpha, beta-unsaturated ketone and catalyzer is 5～20:1;
(2), after the reaction in step (1) finishes, water cancellation reaction, is then extracted with ethyl acetate, then through column chromatography for separation, finally uses the eluent drip washing of ethyl acetate: sherwood oil=1:1, obtains chiral product.
7. chirality bridging aryloxy alcoxyl base scandium muriate according to claim 6, as the application of the asymmetric hydrogen phosphineization reaction of catalyst alpha, beta-unsaturated ketone, is characterized in that, in step (1), temperature of reaction is 0～-40 ℃.
8. chirality bridging aryloxy alcoxyl base scandium muriate according to claim 6 is as catalyst α, the application of the asymmetric hydrogen phosphineization reaction of alpha, beta-unsaturated ketone, it is characterized in that, in step (1), alkane solvents is selected from one of hexane, toluene, benzene, dimethylbenzene, methylene dichloride and ethylene dichloride; Ether solvent is selected from one of tetrahydrofuran (THF), ether, glycol dimethyl ether and dioxane; Amine solvent is selected from triethylamine, Tetramethyl Ethylene Diamine, Isosorbide-5-Nitrae-lupetazin, N, N, N', N'', one of N''-PMDETA and 1,8-diazabicylo, 11 carbon-7-alkene.
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| CN111423351B (en) * | 2019-01-09 | 2024-03-29 | 中国科学技术大学 | Chiral copper compound and preparation method and application thereof |
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