CN101954296B - Chiral catalyst for asymmetric Michael addition reaction and preparation method thereof - Google Patents

Chiral catalyst for asymmetric Michael addition reaction and preparation method thereof Download PDF

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CN101954296B
CN101954296B CN2010102958500A CN201010295850A CN101954296B CN 101954296 B CN101954296 B CN 101954296B CN 2010102958500 A CN2010102958500 A CN 2010102958500A CN 201010295850 A CN201010295850 A CN 201010295850A CN 101954296 B CN101954296 B CN 101954296B
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CN101954296A (en
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胡锋
滕明瑜
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SHANGHAI YINGJUN CHEMICAL TECHNOLOGY Co Ltd
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Abstract

The invention relates to the field of asymmetric Michael addition reaction, in particular to a chiral catalyst for asymmetric Michael addition reaction and a preparation method thereof. The catalyst is derived from the natural (L)-Proline, and is used for catalyzing the asymmetric Michael addition reaction. In the preparation of the catalyst according to the technical scheme of the invention, natural and cheap amino acid and cheaper acylthiourea are used, and the catalyst can catalyze the asymmetric Michael addition reaction of the nitroolefin and the ketone with high catalytic efficiency and good enantioselectivity.

Description

Chiral catalyst of a kind of asymmetric Michael addition reaction and preparation method thereof
Technical field
The present invention relates to asymmetric Michael addition reaction field, be specially chiral catalyst of a kind of asymmetric Michael addition reaction and preparation method thereof.
Background technology
The Michael addition reaction is that strong formation of very important carbon-to-carbon reacts, and especially the addition compound product of the addition of nitroolefin and aldehyde ketone is βThe precursor of important compound such as-amino acid.The catalytic mechanism of its secondary amine is that secondary amine and aldehydes or ketones form active very high imines, thereby the activation aldehyde ketone reaches the effect of catalysis nitroolefin and aldehyde ketone reaction.The Michael addition reaction is one type of organic reaction of great use, and asymmetric Michael addition reaction becomes the research focus now especially.In the prior art the asymmetric Michael addition reaction catalyst catalytic reaction time long, or be that the more expensive industry that is unfavorable for catalyst of synthesis material is promoted.
Summary of the invention
The objective of the invention is for a kind of chiral catalyst of asymmetric Michael addition reaction is provided, long to solve the prior art catalysis time, the problem that synthesis material is expensive.
Another object of the present invention is for preparation method's method of this chiral catalyst is provided.
The object of the invention can be realized through following technical scheme.
The chiral catalyst of asymmetric Michael addition reaction of the present invention, expression formula is:
Figure DEST_PATH_IMAGE001
。
The preparation method of the chiral catalyst of this asymmetric Michael addition reaction, concrete steps are following:
1) nitrogen protection is following incites somebody to action ( S(8.79-9.8g), the mixed solution stirring at room of the carrene of the 100-140 mL of oxalyl chloride (14-20 mL) and pyridine (0.5-0.6 mL) 4 hours refluxes and spends the night)-dinaphthol diacid then; Cooling back evaporate to dryness with the n-hexane washing, filters, and the solid that the filtrating evaporate to dryness obtains slowly splashes into solid in the acetone (10-15 mL) of KSCN (potassium rhodanate) (0.533-1.0 g) immediately, and stirring at room 2 hours is filtered, and directly is used for next step; This step synthesis type is:
；
2) with L-proline (L-proline) (8.5-13.5g), CH 2Cl 2The mixture vigorous stirring of (20-40 mL) and 1M NaOH solution (10-20mL) is then with (Boc) 2O (15.8-25.1g) is dissolved in CH 2Cl 2Splash into slowly in (10-30 mL); Vigorous stirring is spent the night, and using 1 M HCl solution adjust pH is 3 ~ 5, separatory, and water layer is used CH 2Cl 2Extraction merges organic layer, drying, and evaporate to dryness is crossed post and is obtained white solid.This step synthesis type is:
；
3) BOC-L-Proline (BOC-L-proline) (15-21.5 g) is dissolved in 20-40mL CH 2Cl 2In, add K 2CO 3(32-42 g) and 20 mL DMF (dimethyl formamide) add MeI (17-21 g) stirred overnight at room temperature then at stirring at room half an hour, washing, and drying, the quick post of crossing gets product; This step synthesis type is:
Figure 253616DEST_PATH_IMAGE004
；
4) BOC- L-proline methyl ester (17-23 g) is dissolved in 20-40 mL ethanol, adds NaBH 4(7.3-11.4 g) and LiCl (8-12.3 g), stirring at room 4 hours, washing, drying, the quick post of crossing gets product; This step synthesis type is:
Figure DEST_PATH_IMAGE005
；
5) BOC- L-dried meat ammonia alcohol (15-20.2 g) is dissolved in the middle of the pyridine of 40-60 mL, and 0 ℃ adds TsCl (18-28.5 g), stirs 3 hours, and dilute acid wash is used diluted alkaline and saturated common salt water washing then, and drying is filtered, and directly is used for next step reaction;
Figure 321058DEST_PATH_IMAGE006
；
6) BOC- L(3.56-6g) are dissolved in the middle of the DMF of 20-40mL-dried meat ammonia alcohol, add NaN to methanesulfonate ester 3(1.95-3.3g), heat up 65 ℃ and stirred 3 hours, cooling, extracted with diethyl ether is used in the cancellation of careful adding frozen water under cryosel is bathed, drying, evaporate to dryness directly is used for next step; This step synthesis type is:
Figure DEST_PATH_IMAGE007
；
7) BOC- L-dried meat ammonia nitrine (3.56-5 g) is dissolved in the middle of the THF of 20-30 mL, adds PPh 3(1.95 –, 2.5 g), temperature rising reflux 3 hours, the watery hydrochloric acid salify is used in cooling, and diluted alkaline desalts the reuse extracted with diethyl ether, merges organic facies, drying, evaporate to dryness directly is used for next step; This step synthesis type is:
Figure 670000DEST_PATH_IMAGE008
；
8) with compound 1(1 eq.) and 2(2 eq.) is dissolved in the CH of 30-50mL under nitrogen atmosphere 2Cl 2In, stirring at room is after 2 hours, revolves driedly, directly crosses post; Yellow solid, stirred 2 hours in the trifluoroacetic acid that adds 15mL then and the carrene (v:v=2:1), reaction finishes, the water of adding 50mL; With ether washing three times, the aqueous solution is separated out the pale red solid with saturated sodium bicarbonate aqueous solution furnishing alkalescence then; Filter, with water washing for several times, drying is chiral catalyst 3, this step synthesis type is:
Figure DEST_PATH_IMAGE009
；
1H?NMR(300?MHz,?CDCl 3)?δ?(ppm):?11.05?(s,?2H),?8.83?(s,?2H),?8.58-8.45?(m,?4H),?8.10-7.91?(m,?4H),?7.59-7.55?(m,?4H),?3.55-3.25?(m,?4H),?3.15?(s,?2H)?2.25-2.08?(m,?2H),?2.08-1.90（m,?8H）,?1.90-1.70?(m,?4H).
13C?NMR?(75?MHz,CDCl 3)?δ?(ppm):?187.4,?187.3,?169.3,?169.2,?140.8,?133.1,133.0,?128.7,128.6,?127.7,127.3,?127.0,?124.0,?56.0,?48.8,?47.5,?28.6,?23.1.
MS?(ESI,?positive)? m/z:?647.5?(M+Na).?。
Through the catalyst that technical scheme of the present invention prepares, used natural cheap amino acid and more cheap acylthioureas, can the catalysis nitroolefin and ketone carry out asymmetric Micheal addition reaction, and catalytic efficiency is high, corresponding selection property is good.
The specific embodiment
Below in conjunction with embodiment the present invention is described further.
Embodiment 1:
1) nitrogen protection is following incites somebody to action ( S)-dinaphthol diacid (8.79 g), the mixed solution stirring at room of the carrene of 100 mL of oxalyl chloride (14 mL) and pyridine (0.5 mL) 4 hours refluxes then and spends the night.Cooling back evaporate to dryness with the n-hexane washing, filters, and the solid that the filtrating evaporate to dryness obtains slowly splashes into solid in the acetone (10mL) of KSCN (potassium rhodanate) (0.53 g) immediately, and stirring at room 2 hours is filtered, and directly is used for next step.This step synthesis type is:
Figure 918448DEST_PATH_IMAGE002
；
2) will L-proline (8.5g), CH 2Cl 2The mixture vigorous stirring of (20 mL) and 1 MNaOH solution (10mL) is then with (Boc) 2O (15.8 g) is dissolved in CH 2Cl 2Splash into slowly in (10 mL).Vigorous stirring is spent the night, and using 1 M HCl solution to transfer pH value is 3 ~ 5, separatory, and water layer is used CH 2Cl 2Extraction merges organic layer, drying, and evaporate to dryness is crossed post and is obtained white solid.This step synthesis type is:
Figure 265115DEST_PATH_IMAGE003
；
3) BOC- L-Proline (15 g) is dissolved in 20mL CH 2Cl 2In, add K 2CO 3(32 g) and 20 mL DMF, add MeI (17 g) stirred overnight at room temperature then at stirring at room half an hour.Washing, drying, the quick post of crossing gets product.This step synthesis type is:
Figure 739959DEST_PATH_IMAGE004
；
4) BOC- L-proline methyl ester (17 g) is dissolved in the 20 mL ethanol, adds NaBH 4(7.3 g) and LiCl (8 g), stirring at room 4 hours, washing, drying, the quick post of crossing gets product.This step synthesis type is:
Figure 830275DEST_PATH_IMAGE005
；
5) BOC- L-dried meat ammonia alcohol (15 g) is dissolved in the middle of the pyridine of 40 mL, and 0 ℃ adds TsCl (18 g), stirs 3 hours, and dilute acid wash is used diluted alkaline and saturated common salt water washing then.Drying is filtered, and directly is used for next step reaction;
Figure 136491DEST_PATH_IMAGE006
；
6) BOC- L-dried meat ammonia alcohol is dissolved in methanesulfonate ester (3.56g) in the middle of the DMF of 20-40mL, adds NaN 3(1.95g), heat up 65 ℃ and stirred 3 hours, cooling, extracted with diethyl ether is used in the cancellation of careful adding frozen water under cryosel is bathed, drying, evaporate to dryness directly is used for next step.This step synthesis type is:
Figure 326164DEST_PATH_IMAGE007
；
7) BOC- L-dried meat ammonia nitrine (3.56 g) is dissolved in the middle of the THF of 20-30 mL, adds PPh 3(1.95g), temperature rising reflux 3 hours, the watery hydrochloric acid salify is used in cooling, and diluted alkaline desalts the reuse extracted with diethyl ether, merges organic facies, drying, evaporate to dryness directly is used for next step.This step synthesis type is:
Figure 288304DEST_PATH_IMAGE008
；
8) with compound 1(1 eq.) and 2(2 eq.) is dissolved in the CH of 30mL under nitrogen atmosphere 2Cl 2In, stirring at room is after 2 hours, revolves driedly, directly crosses post; Yellow solid, stirred 2 hours in the trifluoroacetic acid that adds 15mL then and the carrene (v:v=2:1), reaction finishes, the water of adding 50mL; With ether washing three times, the aqueous solution is separated out the pale red solid with saturated sodium bicarbonate aqueous solution furnishing alkalescence then; Filter, with water washing for several times, drying is chiral catalyst 3, this step synthesis type is:
；
1H?NMR(300?MHz,?CDCl 3)?δ?(ppm):?11.05?(s,?2H),?8.83?(s,?2H),?8.58-8.45?(m,?4H),?8.10-7.91?(m,?4H),?7.59-7.55?(m,?4H),?3.55-3.25?(m,?4H),?3.15?(s,?2H)?2.25-2.08?(m,?2H),?2.08-1.90（m,?8H）,?1.90-1.70?(m,?4H).
13C?NMR?(75?MHz,CDCl 3)?δ?(ppm):?187.4,?187.3,?169.3,?169.2,?140.8,?133.1,133.0,?128.7,128.6,?127.7,127.3,?127.0,?124.0,?56.0,?48.8,?47.5,?28.6,?23.1.
MS?(ESI,?positive)? m/z:?647.5?(M+Na).?。
Embodiment 2
1) nitrogen protection is following incites somebody to action ( S)-dinaphthol diacid (9.3g), the mixed solution stirring at room of the carrene of 120 mL of oxalyl chloride (17 mL) and pyridine (0.55 mL) 4 hours refluxes then and spends the night.Cooling back evaporate to dryness with the n-hexane washing, filters, and the solid that the filtrating evaporate to dryness obtains slowly splashes into solid in the acetone (12 mL) of KSCN (0.84 g) immediately, and stirring at room 2 hours is filtered, and directly is used for next step.This step synthesis type is:
Figure 218400DEST_PATH_IMAGE002
；
2) will L-proline (11.2g), CH 2Cl 2The mixture vigorous stirring of (30 mL) and 1 M NaOH solution (15mL) is then with (Boc) 2O (22.2g) is dissolved in CH 2Cl 2Splash into slowly in (22 mL).Vigorous stirring is spent the night, and using 1 M HCl solution to transfer pH value is 3 ~ 5, separatory, and water layer is used CH 2Cl 2Extraction merges organic layer, drying, and evaporate to dryness is crossed post and is obtained white solid.This step synthesis type is:
Figure 641291DEST_PATH_IMAGE003
；
3) BOC- L-Proline (18.8 g) is dissolved in 30mL CH 2Cl 2In, add K 2CO 3(39 g) and 20 mL DMF, add MeI (19.5 g) stirred overnight at room temperature then at stirring at room half an hour.Washing, drying, the quick post of crossing gets product.This step synthesis type is:
Figure 90727DEST_PATH_IMAGE004
；
4) BOC- L-proline methyl ester (20.9 g) is dissolved in the 32 mL ethanol, adds NaBH 4(9.8 g) and LiCl (10.9 g), stirring at room 4 hours, washing, drying, the quick post of crossing gets product.This step synthesis type is:
Figure 460528DEST_PATH_IMAGE005
；
5) BOC- L-dried meat ammonia alcohol (18.1 g) is dissolved in the middle of the pyridine of 50 mL, and 0 ℃ adds TsCl (24.5 g), stirs 3 hours, and dilute acid wash is used diluted alkaline and saturated common salt water washing then.Drying is filtered, and directly is used for next step reaction;
；
6) BOC- L-dried meat ammonia alcohol is dissolved in methanesulfonate ester (4.92g) in the middle of the DMF of 30mL, adds NaN 3(2.9g), heat up 65 ℃ and stirred 3 hours, cooling, extracted with diethyl ether is used in the cancellation of careful adding frozen water under cryosel is bathed, drying, evaporate to dryness directly is used for next step.This step synthesis type is:
；
7) BOC- L-dried meat ammonia nitrine (4.5 g) is dissolved in the middle of the THF of 26 mL, adds PPh 3(2.2 g), temperature rising reflux 3 hours, the watery hydrochloric acid salify is used in cooling, and diluted alkaline desalts the reuse extracted with diethyl ether, merges organic facies, drying, evaporate to dryness directly is used for next step.This step synthesis type is:
Figure 949824DEST_PATH_IMAGE008
；
8) with compound 1(1 eq.) and 2(2 eq.) is dissolved in the CH of 40mL under nitrogen atmosphere 2Cl 2In, stirring at room is after 2 hours, revolves driedly, directly crosses post; Yellow solid, stirred 2 hours in the trifluoroacetic acid that adds 15mL then and the carrene (v:v=2:1), reaction finishes, the water of adding 50mL; With ether washing three times, the aqueous solution is separated out the pale red solid with saturated sodium bicarbonate aqueous solution furnishing alkalescence then; Filter, with water washing for several times, drying is chiral catalyst 3, this step synthesis type is:
；
1H?NMR(300?MHz,?CDCl 3)?δ?(ppm):?11.05?(s,?2H),?8.83?(s,?2H),?8.58-8.45?(m,?4H),?8.10-7.91?(m,?4H),?7.59-7.55?(m,?4H),?3.55-3.25?(m,?4H),?3.15?(s,?2H)?2.25-2.08?(m,?2H),?2.08-1.90（m,?8H）,?1.90-1.70?(m,?4H).
13C?NMR?(75?MHz,CDCl 3)?δ?(ppm):?187.4,?187.3,?169.3,?169.2,?140.8,?133.1,133.0,?128.7,128.6,?127.7,127.3,?127.0,?124.0,?56.0,?48.8,?47.5,?28.6,?23.1.
MS?(ESI,?positive)? m/z:?647.5?(M+Na).?。
Embodiment 3
1) nitrogen protection is following incites somebody to action ( S)-dinaphthol diacid (9.8g), the mixed solution stirring at room of the carrene of 140 mL of oxalyl chloride (19 mL) and pyridine (0.6 mL) 4 hours refluxes then and spends the night.Cooling back evaporate to dryness with the n-hexane washing, filters, and the solid that the filtrating evaporate to dryness obtains slowly splashes into solid in the acetone (15 mL) of KSCN (1.0 g) immediately, and stirring at room 2 hours is filtered, and directly is used for next step.This step synthesis type is:
Figure 196315DEST_PATH_IMAGE002
；
2) will L-proline (13.5g), CH 2Cl 2The mixture vigorous stirring of (40 mL) and 1 M NaOH solution (20mL) is then with (Boc) 2O (25.1g) is dissolved in CH 2Cl 2Splash into slowly in (30 mL).Vigorous stirring is spent the night, and using 1 M HCl solution to transfer pH value is 3 ~ 5, separatory, and water layer is used CH 2Cl 2Extraction merges organic layer, drying, and evaporate to dryness is crossed post and is obtained white solid.This step synthesis type is:
；
3) BOC- L-Proline (21.5 g) is dissolved in 40mL CH 2Cl 2In, add K 2CO 3(42 g) and 20 mL DMF, add MeI (21 g) stirred overnight at room temperature then at stirring at room half an hour.Washing, drying, the quick post of crossing gets product.This step synthesis type is:
Figure 322720DEST_PATH_IMAGE004
；
4) BOC- L-proline methyl ester (23 g) is dissolved in 20-40 mL ethanol, adds NaBH 4(11.4 g) and LiCl (12.3 g), stirring at room 4 hours, washing, drying, the quick post of crossing gets product.This step synthesis type is:
；
5) BOC- L-dried meat ammonia alcohol (20.2 g) is dissolved in the middle of the pyridine of 60 mL, and 0 ℃ adds TsCl (28.5 g), stirs 3 hours, and dilute acid wash is used diluted alkaline and saturated common salt water washing then.Drying is filtered, and directly is used for next step reaction;
Figure 961829DEST_PATH_IMAGE006
；
6) BOC- L-dried meat ammonia alcohol is dissolved in methanesulfonate ester (6g) in the middle of the DMF of 40mL, adds NaN 3(3.3g), heat up 65 ℃ and stirred 3 hours, cooling, extracted with diethyl ether is used in the cancellation of careful adding frozen water under cryosel is bathed, drying, evaporate to dryness directly is used for next step.This step synthesis type is:
；
7) BOC- L-dried meat ammonia nitrine (5 g) is dissolved in the middle of the THF of 30 mL, adds PPh 3(2.5 g), temperature rising reflux 3 hours, the watery hydrochloric acid salify is used in cooling, and diluted alkaline desalts the reuse extracted with diethyl ether, merges organic facies, drying, evaporate to dryness directly is used for next step.This step synthesis type is:
Figure 808748DEST_PATH_IMAGE008
；
8) with compound 1(1 eq.) and 2(2 eq.) is dissolved in the CH of 50mL under nitrogen atmosphere 2Cl 2In, stirring at room is after 2 hours, revolves driedly, directly crosses post; Yellow solid, stirred 2 hours in the trifluoroacetic acid that adds 15mL then and the carrene (v:v=2:1), reaction finishes, the water of adding 50mL; With ether washing three times, the aqueous solution is separated out the pale red solid with saturated sodium bicarbonate aqueous solution furnishing alkalescence then; Filter, with water washing for several times, drying is chiral catalyst 3, this step synthesis type is:
Figure 58464DEST_PATH_IMAGE009
；
1H?NMR(300?MHz,?CDCl 3)?δ?(ppm):?11.05?(s,?2H),?8.83?(s,?2H),?8.58-8.45?(m,?4H),?8.10-7.91?(m,?4H),?7.59-7.55?(m,?4H),?3.55-3.25?(m,?4H),?3.15?(s,?2H)?2.25-2.08?(m,?2H),?2.08-1.90（m,?8H）,?1.90-1.70?(m,?4H).
13C?NMR?(75?MHz,CDCl 3)?δ?(ppm):?187.4,?187.3,?169.3,?169.2,?140.8,?133.1,133.0,?128.7,128.6,?127.7,127.3,?127.0,?124.0,?56.0,?48.8,?47.5,?28.6,?23.1.
MS?(ESI,?positive)? m/z:?647.5?(M+Na).?。
The catalytic reaction instance
With catalyst 3(0.01mmol) and ketone (50 μ L) at room temperature stirred 5 minutes, then nitroolefin (0.5mmol) is joined in the mixture, TLC monitors and reacts completely, and adds ethyl acetate extraction, organic layer is dry, solvent evaporated, the direct post of crossing obtains product.
Figure 106054DEST_PATH_IMAGE010
Figure DEST_PATH_IMAGE011

Claims (3)

1. asymmetric Michael addition reaction catalyst, it is characterized in that: its expression formula is:
Figure FDA0000120532430000011
2. method for preparing the said catalyst of claim 1 is characterized in that: may further comprise the steps:
1) under the nitrogen protection with 8.79-9.8g (S)-dinaphthol diacid, the mixed solution stirring at room of the carrene of the 100-140mL of 14-20mL oxalyl chloride and 0.5-0.6mL pyridine 4 hours refluxes then and spends the night; Cooling back evaporate to dryness with the n-hexane washing, filters, and the solid that the filtrating evaporate to dryness obtains slowly splashes into 10-15mL with solid immediately and contains in the acetone of 0.533-1.0g potassium rhodanate, and stirring at room 2 hours is filtered, and directly is used for next step, and this step synthesis type is:
Figure FDA0000120532430000012
2) with 8.5-13.5g L-proline, the CH of 20-40mL 2Cl 2With the mixture vigorous stirring of the NaOH solution of 10-20mL 1M, then with (Boc) of 15.8-25.1g 2O is dissolved in the CH of 10-30mL 2Cl 2In, slowly splash into; Vigorous stirring is spent the night, and using 1M HCl solution adjust pH is 3～5, separatory, and water layer is used CH 2Cl 2Extraction merges organic layer, drying, and evaporate to dryness is crossed post and is obtained white solid, and this step synthesis type is:
Figure FDA0000120532430000013
3) BOC-L-Proline of 15-21.5g is dissolved in 20-40mL CH 2Cl 2In, the K of adding 32-42g 2CO 3And 20mLDMF, stirring at room half an hour, add the MeI stirred overnight at room temperature of 17-21g then; Washing, drying, the quick post of crossing gets product, and this step synthesis type is:
Figure FDA0000120532430000021
4) the BOC-L-proline methyl ester of 17-23g is dissolved in the 20-40mL ethanol, adds the NaBH of 7.3-11.4g 4With the LiCl of 8-12.3g, stirring at room 4 hours, washing, drying, the quick post of crossing gets product, and this step synthesis type is:
5) the BOC-L-dried meat ammonia alcohol of 15-20.2g is dissolved in the middle of the pyridine of 40-60mL, and 0 ℃ adds 18-28.5g TsCl, stirred 3 hours; Dilute acid wash is used diluted alkaline and saturated common salt water washing, drying then; Filter, directly be used for next step reaction, this step synthesis type is:
Figure FDA0000120532430000023
6) the BOC-L-dried meat ammonia alcohol of 3.56-6g is dissolved in methanesulfonate ester in the middle of the DMF of 20-40mL, adds the NaN of 1.95-3.3g 3, be warming up to 65 ℃ and stirred 3 hours, cooling, extracted with diethyl ether is used in the cancellation of careful adding frozen water under cryosel is bathed, drying, evaporate to dryness directly is used for next step, and this step synthesis type is:
Figure FDA0000120532430000024
7) the BOC-L-dried meat ammonia nitrine of 3.56-5g is dissolved in the middle of the THF of 20-30mL, adds the PPh of 1.95-2.5g 3, temperature rising reflux 3 hours, the watery hydrochloric acid salify is used in cooling, and diluted alkaline desalts the reuse extracted with diethyl ether, merges organic facies, drying, evaporate to dryness directly is used for next step, and this step synthesis type is:
Figure FDA0000120532430000031
8) with compound 1 and compound 2 under nitrogen atmosphere, be dissolved in the CH of 30-50mL 2Cl 2In, stirring at room is after 2 hours, revolves driedly, directly crosses post; Yellow solid, stirred 2 hours in the trifluoroacetic acid that adds 15mL then and the carrene, reaction finishes, the water of adding 50mL; With ether washing three times, the aqueous solution is separated out the pale red solid with saturated sodium bicarbonate aqueous solution furnishing alkalescence, filters then; With water washing for several times, drying is chiral catalyst 3, and this step synthesis type is:
Figure FDA0000120532430000032
3. the method for catalyst according to claim 2, it is characterized in that: in the step 8), the volume ratio of trifluoroacetic acid and carrene is: V: V=2: 1.
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