CN102321006B - Di-proline amide compound containing chiral indane framework and application thereof - Google Patents

Di-proline amide compound containing chiral indane framework and application thereof Download PDF

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CN102321006B
CN102321006B CN2011101466310A CN201110146631A CN102321006B CN 102321006 B CN102321006 B CN 102321006B CN 2011101466310 A CN2011101466310 A CN 2011101466310A CN 201110146631 A CN201110146631 A CN 201110146631A CN 102321006 B CN102321006 B CN 102321006B
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proline
amide compound
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proline amide
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赵梅欣
李升可
张志旺
施敏
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East China University of Science and Technology
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Abstract

The invention relates to a di-proline amide compound containing a chiral indane framework and application thereof. A method for preparing the di-proline amide compound comprises the following steps of: undergoing an amino protective reaction, a hydroxyl methyl sulfonylation reaction, a sodium azide substitution reaction, a reduction reaction and an amino protective group removing reaction on chiral 1-amion-2-indanol or a derivative thereof serving as a raw material in sequence to obtain a corresponding 'diamine' intermediate; and making the obtained 'diamine' intermediate react with an N-protective chiral proline amide compound and undergoing an amino protective group removing reaction in sequence to obtain the di-proline amide compound. The di-proline amide compound containing the chiral indane framework provided by the invention can be used for catalyzing an unsymmetrical synthesis reaction.

Description

Contain two proline(Pro) amidess of chirality dihydro indenes skeleton and uses thereof
Technical field
The present invention relates to a kind of two proline(Pro) amidess that contain chirality dihydro indenes skeleton and uses thereof.
Background technology
The asymmetric reaction of organic micromolecule compound catalysis obtains swift and violent development in more than ten years in the past, become the potential method of asymmetric synthesis of the 3rd class that generally acknowledged and organo-metallic catalysis, enzyme catalysis have par.Yet existing organic micromolecule compound mostly is to utilize natural product cheap and easy to get to be chiral source, and its structure type is limited.Under the prerequisite that does not change its catalyst activity, there is certain limitation again in modification and the implementation structure diversity aspect of its structure, thereby caused problems such as catalyzed reaction type universality less and catalyzed reaction is limited.
Chirality 2-amino-1-indanol and derivative thereof are a kind of very important chipal compounds, though it is to be found as the very important human immunodeficiency virus protein of a class (HIV-PR) inhibitor part at first, but it was widely used among the asymmetric reaction as the surrogate with benzene glycinol of tension force afterwards.Wherein, the dihydro indenes skeleton of rigidity is its key that obtains high enantioselectivity as prothetic group or part in asymmetric synthesis.In recent years, along with the development of organic molecule catalysis, be organic micromolecule catalyst (J.Am.Chem.Soc., 2009,131,6904 of chirality skeleton although also occurred with chirality 2-amino-1-indanol and derivative thereof; Chem.Eur.J., 2010,16,13592.).Yet, as far as we know, be that two proline(Pro) amidess of skeleton yet there are no report with chirality dihydro indenes.
Summary of the invention
One of purpose of the present invention is, a kind of two proline(Pro) amidess that contain chirality dihydro indenes skeleton are provided, and its structure is suc as formula shown in the I:
Figure BSA00000509440500011
Among the formula I, R 1, R 2And R 3Independently be selected from respectively: C 1～C 6Alkyl, the C that hexa-atomic aromatic ring yl replaces 1～C 6Alkyl, C 1～C 6Alkoxyl group, hydroxyl, a kind of in halogen (F, Cl, Br or I) or the nitro; N is 0～4 integer; M and p are 0～3 integer; C-1, C-2, C-2 ' and C-2 " the S type that is configured as or the R type in a kind of.
Two of the object of the invention is; the method of compound shown in a kind of preparation formula I is provided; its key step is: at first; be raw material with chirality 1-amino-2-indanol or derivatives thereof; successively through amido protecting reaction (as the Boc protection); the reaction of hydroxyl methylsulfonyl; the sodiumazide substitution reaction; reduction reaction (as the Pd/C catalytic reduction reaction) and remove the amido protecting group reaction reaction of Boc group (as remove) and obtain corresponding " diamines " intermediate; then, with " diamines " intermediate of gained successively through with the chiral proline reaction of N-protected (as the Boc protection) with remove amido protecting group reaction (taking off the Boc group as adopting trifluoroacetic acid) and obtain target compound (compound shown in the formula I).
Three of the object of the invention is, the purposes of compound shown in a kind of formula I is provided, namely for the preparation of the application in the catalyzer of asymmetric catalysis synthesis.
Embodiment
In optimized technical scheme of the present invention, R 1, R 2And R 3Independently be selected from respectively: C 1～C 3Alkyl, the C that phenyl replaces 1～C 3Alkyl, C 1～C 3A kind of in alkoxyl group or the hydroxyl; N is 0～4 integer; M and p are 0～3 integer; A kind of in the S type that is configured as of C-1 and C-2 or the R type;
Preferred technical scheme is: R 1, R 2And R 3Independently be selected from respectively: a kind of in methyl, ethyl, propyl group, benzyl, methoxy or the hydroxyl; N is 0～4 integer; M and p are 0～3 integer; A kind of in the S type that is configured as of C-1 and C-2 or the R type;
Best technical scheme is: n is 0, R 2And R 3Be hydroxyl, m and p are 0 or 1, and m and p are not 0 simultaneously; Or n, m and p are 0.
The method of compound shown in the preparation formula I provided by the present invention, its synthetic route is as follows:
Figure BSA00000509440500021
Specifically comprise the steps:
(1) with (Boc) 2O and raw material (compound shown in the formula II) make compound shown in the formula III in 0 ℃～30 ℃ reactions;
(2) ice bath and triethylamine is arranged and organic solvent (as methylene dichloride, methyl alcohol or acetonitrile etc.) existence condition under, in 0 ℃～50 ℃ reactions, make compound shown in the formula IV by compound shown in the formula III and p-methyl benzene sulfonic chloride;
(3) will shown in the IV compound, be dissolved in the organic solvent (as DMF etc.), add azide salt (as sodiumazide etc.) and in 30 ℃～60 ℃ reactions, make compound shown in the formula V;
(4) be catalyzer with palladium/carbon, compound shown in the formula V and organic solvent (as methyl alcohol, ethanol, ethyl acetate or DMF etc.) react under atmosphere of hydrogen in 30 ℃～50 ℃, make compound shown in the formula VI;
(5) trifluoroacetic acid is joined in the organic solution (as methylene dichloride, ethylene dichloride or chloroform etc.) that is dissolved with compound shown in the formula VI, 0 ℃～50 ℃ reactions make compound shown in the formula VII;
(6) at first, with the chiral proline of compound shown in the formula VII and N-Boc protection at alkali (as triethylamine, salt of wormwood, cesium carbonate etc.) and isobutyl chlorocarbonate exist down, reaction in organic solvent (as chloroform or methylene dichloride etc.), 30 ℃～60 ℃ reactions obtain intermediate (not marking in the synthetic route); Then, gained intermediate, trifluoroacetic acid and organic solvent (as methylene dichloride, ethylene dichloride or chloroform etc.) are obtained target compound (compound shown in the formula I) in 0 ℃～50 ℃ reactions.
The two proline derivative class organic molecule catalyzer that contain chirality indenes skeleton that the present invention is prepared can be used for the asymmetric Aldol condensation reaction of catalysis, the highest yield that obtains 60% ee value (the ee value is measured by chiral high performance liquid chromatography (HPLC)) and 89%.
The present invention is further elaborated below by embodiment, and its purpose only is better to understand content of the present invention.Therefore, the cited case does not limit protection scope of the present invention.
Except special instruction was arranged, said room temperature referred among the embodiment: 15 ℃～35 ℃; The model that thin-layer chromatography (TLC) adopts Shandong Huanghai Sea chemical reagents corporation to produce is the silica-gel plate of HSGF 254; 300～400 purpose silica gel that column chromatography adopts Shandong Huanghai Sea chemical reagents corporation to produce; Ratio described in developping agent and the eluent is volume ratio; The condition of HPLC: ChiralcelOJ-H, hexane/i-PrOH=80/20 (v/v), 1.0mL/min, 254nm.
Embodiment 1
(1) with (1R, 2S) or (1S, 2R)-1-amino-2-indanol is chiral source, through amino Boc protective reaction obtain (1R, 2S) or (1S, 2R)-1-(tert-butoxycarbonyl) amino-2-indanol.
Reaction formula is:
Figure BSA00000509440500031
Concrete steps are as follows: will (1R, 2S)-(1.5g, 10mmol) (3.1g 14mmol) is dissolved in the 40mL methyl alcohol 1-amino-2-indanol, and first reflux stirs 1h, and then stirring at room 1h with the Boc acid anhydrides.Pressure reducing and steaming solvent, thick product carry out rapid column chromatography and separate (eluent: ethyl acetate/triethylamine=100: 1), obtain product 2.5g.Faint yellow solid, productive rate are 99%.Fusing point: 67.2-67.4 ℃; [α] 25 D=-15.4 (c 1.0, CH 2Cl 2);
1H?NMR(CDCl 3，TMS，400MHz)δ7.24-7.19(m，4H)，5.31(d，J＝6.4Hz，1H)，4.98(s，1H)，4.48(d，J＝3.6Hz，1H)，3.05(dd，J＝16.4，4.8Hz，1H)，2.88-2.84(m，2H)，1.48(s，9H)；
13C?NMR(CDCl 3，TMS，100MHz)δ156.2，140.9，139.7，127.7，126.7，125.0，124.2，79.5，73.1，58.5，39.2，28.2.
(2) through methylsulfonylization and the NaN of perhydroxyl radical 3Nucleophilic substitution reaction, will (1R, 2S)-1-(tert-butoxycarbonyl) amino-2-indanol 2 be transformed into (1R, 2R)-1-1-(tert-butoxycarbonyl) amino-2-azido-indenes 4, reaction formula is:
Figure BSA00000509440500041
Concrete steps are as follows:
Ar protection down, will (1R, 2S)-1-(tert-butoxycarbonyl) amino-2-indanol 2 (1.2g, 4.8mmol) and Et 3(1.3mL 9.6mmol) is dissolved in 20mL CH to N 2Cl 2In, be cooled to 0 ℃, and the dropping methylsulfonyl chloride (0.75mL, 9.6mmol).After dropwising, continue to stir 3h down at 0 ℃.Reaction finishes the back and transfers to weakly alkaline with strong aqua, uses CH again 2Cl 2Extract three times, merge organic phase, anhydrous Na 2SO 4Dry.Filter back pressure reducing and steaming solvent, rapid column chromatography separates (eluent: petrol ether/ethyl acetate=2: 1), obtain product 3 and be white solid (1.4g), productive rate 90%; Fusing point: 154.9-155.4 ℃; [α] 25 D=+227 (c 0.1, CH 2Cl 2);
1H?NMR(CDCl 3，TMS，400MHz)δ7.28-7.26(m，4H)，5.41(s，1H)，5.35-5.32(m，1H)，5.10(d，J＝8.4Hz，1H)，3.27-3.26(m，2H)，3.01(s，3H)，1.50(s，9H)；
13C?NMR(CDCl 3，TMS，100MHz)δ155.6，139.2，138.0，128.3，127.2，124.9，123.4，83.4，79.9，57.5，37.8，37.7，28.2.
(0.68g 2.1mmol) is dissolved among the DMF (3mL), adds NaN then with compound 3 3(0.4g 6.2mmol), is heated to 60 ℃ of reaction 7h.After reaction finishes, with the reaction solution cool to room temperature, in reaction solution, strengthen water gaging then, separate out white solid, filtration drying obtain (1R, 2R)-1-1-(tert-butoxycarbonyl) amino-2-azido-indenes 4 (0.51g).Productive rate 89%; Fusing point: 137.1-137.4 ℃; [α] 25 D=-5.6 (c1.0, CH 2Cl 2);
1H?NMR(CDCl 3，TMS，400MHz)δ7.26-7.20(m，4H)，5.10(s，1H)，4.84(s，1H)，4.03(d，J＝6.4Hz，1H)，3.25(dd，J＝16.0，7.2Hz，1H)，2.85(dd，J＝16.0，7.2Hz，1H)，1.50(s，9H)；
13C?NMR(CDCl 3，TMS，100MHz)δ155.3，140.1，138.9，128.6，127.4，124.8，123.9，80.0，68.4，61.1，35.7，28.3.
(3) will (1R, 2R)-1-(tert-butoxycarbonyl) amino-2-azido-indenes 4 reduces under the Pd/C catalyzer, removes the Boc protection then under the trifluoroacetic acid effect, obtains diamine compound 6, reaction formula is:
Concrete steps are as follows:
(1.0g 3.6mmol) is dissolved in the 20mL methanol solvate, adds 10%Pd/C (0.1g) then, feeds hydrogen in reaction solution, stirs 12h under the room temperature with compound 4.Reaction finishes the back filters with sand core funnel, behind the pressure reducing and steaming solvent thick product is separated (eluent: ethyl acetate/methanol/ammoniacal liquor=100: 5: 1), obtain product 5 (0.87g) by rapid column chromatography.White solid, productive rate 96%; Fusing point: 101.1-101.3 ℃; [α] 25 D=-57.9 (c1.0, CH 2Cl 2);
1H?NMR(CDCl 3，TMS，400MHz)δ7.22-7.18(m，4H)，4.84-4.78(m，2H)，3.44(q，J＝7.2Hz，1H)，3.21(dd，J＝15.6，7.6Hz，1H)，2.67(dd，J＝15.6，8.0Hz，1H)，1.94(s，1H)，1.50(s，9H)；
13C?NMR(CDCl 3，TMS，100MHz)δ156.2，141.4，140.3，127.8，126.7，124.5，123.6，79.3，64.1，61.9，38.9，28.2.
(0.72g 2.9mmol) is dissolved in CH with compound 5 2Cl 2(4mL), add TFA (1mL) then, stir 8h under the room temperature, the carrying out of TLC monitoring reaction.Reaction finishes the back and transfers to weakly alkaline with strong aqua, uses CH again 2Cl 2Extract three times, merge organic phase, anhydrous Na 2SO 4Dry.Filter back pressure reducing and steaming solvent, rapid column chromatography separate (eluent: ethyl acetate/methanol/ammoniacal liquor=100: 10: 1), obtain product (1R, 2R)-1,2-diamino indenes 6 (0.3g), productive rate are 70%; [α] 25 D=+28 (c0.25, CH 2Cl 2);
1H?NMR(CDCl 3，TMS，400MHz)δ7.23-7.10(m，4H)，3.77(d，J＝6.8Hz，1H)，3.13-3.06(m，2H)，2.53(dd，J＝14.0，7.6Hz，1H)，2.39(s，4H)；
13C?NMR(CDCl 3，TMS，100MHz)δ144.7，139.4，127.0，126.3，124.1，122.7，64.4，63.5，38.8.
(4) with (1R; 2R)-1; the N-Boc-L-proline(Pro) reaction of 2-diamino indenes 1-amino-2-dimethylin indenes 6 and 2 times of mol ratios is contained the N-Boc-L-Prolinamide derivatives 7 of chirality dihydro indenes skeleton accordingly; and then under the trifluoroacetic acid effect, remove the proline derivative class organic molecule catalyzer 8 that the Boc protection can obtain containing chirality indenes skeleton, reaction formula is:
Concrete steps are as follows:
(0.58g 2.7mmol) is dissolved in 10mL CH with N-Boc L-proline(Pro) 7 2Cl 2In, be cooled to 0 ℃, add Et successively 3N (0.41mL, 3.0mmol) and isobutyl chlorocarbonate (0.35mL, 2.7mmol).After stirring 15min, slowly splash into (1R, 2R)-1,2-diamino indenes 6 (0.2g, CH 1.35mmol) 2Cl 2(5mL) solution.After dripping end, reaction solution is risen to room temperature gradually, continue to stir 5h.Reactant is used 1M KHSO successively 4, saturated NaCO 3The salt washing, the organic phase anhydrous Na 2SO 4Dry.Filter back pressure reducing and steaming solvent and obtain crude product 7, this compound is not purified be directly used in next step synthetic among.
Compound 7 is dissolved in CH 2Cl 2(8mL), add TFA (2mL), stir 20h under the room temperature, the carrying out of TLC monitoring reaction.Reaction finishes back pressure reducing and steaming solvent, adds water (4mL), transfers to pH=12 with 2MNaOH, and with the EtOAc extraction, organic phase is washed with salt, anhydrous Na again 2SO 4Dry.Filter, the pressure reducing and steaming solvent, thick product separates (eluent: ethyl acetate/methanol/ammoniacal liquor=100: 10: 1), obtain product 8 (0.25g), productive rate 56% with rapid column chromatography; [α] 25 D=-101.6 (c1.0, CH 2Cl 2);
1H?NMR(CDCl 3，TMS，400MHz)δ8.29(d，J＝8.0Hz，1H)，8.15(d，J＝8.0Hz，1H)，7.32-7.14(m，4H)，5.33(t，J＝8.4Hz，1H)，4.40(quint.，J＝8.8Hz，1H)，3.84(dd，J＝8.0，5.2Hz，1H)，3.76(dd，J＝8.0，5.2Hz，1H)，3.28(dd，J＝14.8，8.0Hz，1H)，3.00-2.89(m，4H)，2.73(dd，J＝14.8，10.4Hz，1H)，2.18-2.05(m，2H)，1.95-1.86(m，2H)，1.73-1.68(m，3H)，1.30-1.26(m，1H)，0.89-0.83(m，2H)；
13C?NMR(CDCl 3，TMS，100MHz)δ175.7，175.2，140.4，139.4，127.8，126.9，124.5，123.0，60.3，58.6，58.2，46.90，46.88，36.3，30.7，30.5，25.8，22.4，13.9。
Embodiment 2
Outside N-Boc-L-proline(Pro) in trans 4-hydroxy-n-Boc-L-proline(Pro) alternate embodiment 1 (4); other step is identical with embodiment 1; can make compound 9; can make compound 10 with 9 with the TERT-BUTYL DIMETHYL CHLORO SILANE reaction; compound 10 removes Boc protecting group and tertiary butyl dimethylsilyl (TBDMS of selectively removing in the presence of trifluoroacetic acid; hydroxyl protecting group), can get compound 11, reaction formula is:
Figure BSA00000509440500061
Concrete steps are as follows:
(0.39g 2.63mmol) is dissolved in 10mL CH with trans 4-hydroxy-n-Boc-L-proline(Pro) 2Cl 2In, be cooled to 0 ℃, add Et successively 3N (0.80mL, 5.8mmol) and isobutyl chlorocarbonate (0.72mL, 5.27mmol).After stirring 15min, slowly splash into (1R, 2R)-1,2-diamino indenes 6 (0.39g, CH 2.63mmol) 2Cl 2(5mL) solution.After dripping end, reaction solution is risen to room temperature gradually, continue to stir 5h.Reactant is used 1M KHSO successively 4, saturated NaCO 3The salt washing, the organic phase anhydrous Na 2SO 4Dry.Filter the thick product of back pressure reducing and steaming solvent and separate (eluent: methylene chloride /=30: 1～10: 1), obtain product 9 (1.51g), productive rate 60% with rapid column chromatography;
1H?NMR(CDCl 3，TMS，400MHz)δ7.22-7.15(m，4H)，6.80(s，br.，1H)，5.30(t，J＝8.4Hz，1H)，4.45-4.32(m，5H)，3.71-3.45(m，4H)，3.30-3.21(m，1H)，2.78-2.67(m，1H)，2.32-2.04(m，3H)，2.02-1.64(m，3H)，1.44(s，18H)，1.27-1.25(m，1H).
With compound 9 (0.574g, 1.0mmol) and TERT-BUTYL DIMETHYL CHLORO SILANE (0.36g 2.4mmol) is dissolved in CH 2Cl 2(5mL), add under the room temperature triethylamine (0.33mL, 2.4mmol) and DMAP (0.049g 0.4mmol), stirred the carrying out of TLC monitoring reaction 48 hours under the room temperature.Reaction with the reactant dilute with water, is used dichloromethane extraction after finishing, organic phase 1N salt acid elution and saturated common salt water washing, anhydrous Na 2SO 4Dry.Filter, the pressure reducing and steaming solvent, thick product separates (eluent: petrol ether/ethyl acetate /=1: 4), obtain product 10 (0.458g), productive rate 57% with rapid column chromatography;
1H?NMR(CDCl 3，TMS，400MHz)δ7.20-7.14(m，4H)，6.93-6.51(m，1H)，5.22(t，J＝8.4Hz，1H)，4.38-4.29(m，5H)，3.66-3.58(m，1H)，3.41-3.28(m，4H)，2.78-2.64(m，1H)，2.26-2.19(m，3H)，2.13-1.89(m，1H)，1.76-1.71(m，1H)，1.38(s，18H)，0.84(s，18H)，0.05(s，12H).
(0.361g 0.45mmol) is dissolved in CH with compound 11 2Cl 2(3mL), (0.45mL 6.07mmol), stirs 24h under the room temperature, the carrying out of TLC monitoring reaction to add TFA.Reaction finishes back pressure reducing and steaming solvent, adds water (4mL), transfers to pH=12 with 2M NaOH, uses CH again 2Cl 2Extraction, organic phase is washed with salt, anhydrous Na 2SO 4Dry.Filter, the pressure reducing and steaming solvent, thick product separates (eluent: methylene chloride /=30: 1～10: 1), obtain product 11 (0.114g), productive rate 52% with rapid column chromatography.
1H?NMR(CDCl 3，TMS，400MHz)δ8.38(d，J＝8.8Hz，0.5H)，8.29(d，J＝8.8Hz，0.5H)，8.24(d，J＝9.6Hz，1H)，7.24-7.10(m，4H)，5.30(td，J＝9.2，2.8Hz，1H)，4.44-4.40(m，2H)，4.38(s，1H)，4.34-3.89(m，2H)，3.26-3.19(s，2H)，3.05-2.73(m，5H)，2.27-2.09(m，2H)，1.93-1.87(m，1H)，1.82-1.74(m，1H)，1.22-1.18(m，2H)，0.83(s，9H)，0.08-0.05(m，6H).
Embodiment 3
Will by the compound of embodiment 1 preparation (compound (1R, 2R)-8) is used for the asymmetric Aldol condensation reaction of catalysis, its reaction formula and conditional filtering as follows:
Figure BSA00000509440500081
Figure BSA00000509440500082
aDetermined?by?chiral?HPLC?using?a?Chiralpak?OJ-H?column.
In reaction tubes, add m-nitrobenzaldehyde (30.2mg, 0.2mmol) and compound (1R, 2R)-8 (6.6mg, 0.02mmol), (1.1 μ L, 0.02mmol), 30 ℃ are stirred down and disappear until raw material to measure solvent (3.1mL) and acetic acid again.After reaction is finished, with saturated ammonium chloride 10mL cancellation, again with the EtOAc extraction (3 * 10mL), the organic phase anhydrous Na 2SO 4Dry.Filter back pressure reducing and steaming solvent, separate (eluent: petrol ether/ethyl acetate=4: 1) obtain product 35.9mg, productive rate: 86% through flash column chromatography; 40%ee[Chiralcel OJ-H, hexane/i-PrOH=80/20 (v/v), 1.0mL/min, 254nm, t Major=12.72min; t Minor=13.93min].
1H?NMR(CDCl 3，TMS，400MHz)δ8.24(s，1H)，8.14(dd，J＝8.0，1.2Hz，1H)，7.72(d，J＝7.6Hz，1H)，7.53(t，J＝8.0Hz，1H)，5.26(t，J＝6.0Hz，1H)，3.65(br.s，1H)，2.90-2.88(m，2H)，2.23(s，3H)。
Embodiment 4
Compound (compound (1R divided by embodiment 2 preparations, 2R)-11) (10.0mg, 0.02mmol) compound (1R in the alternate embodiment 3,2R)-8, other step is identical with embodiment 3, utilize the best solvent acetone of effect to be used for the asymmetric Aldol condensation reaction of catalysis for 30 ℃, obtain product 31.4mg, productive rate 75%; 40%ee.
Embodiment 5
Outside in-20 ℃ of alternate embodiments 4 30 ℃, other step is identical with embodiment 3, is used for the asymmetric Aldol condensation reaction of catalysis, obtains product 37.2mg, productive rate 89%; 60%ee.

Claims (6)

1. two proline(Pro) amidess that contain chirality dihydro indenes skeleton, its structure is suc as formula shown in the I:
Figure FSB00001064155200011
Among the formula I, R 1, R 2And R 3Independently be selected from respectively: C 1～C 3Alkyl, the C that phenyl replaces 1～C 3Alkyl, C 1～C 3A kind of in alkoxyl group or the hydroxyl; N is 0～4 integer; M and p are 0～3 integer; C-1, C-2, C-2 ' and C-2 " the S type that is configured as or the R type in a kind of.
2. as claimed in claim 1 pair of proline(Pro) amides is characterized in that, wherein R 1, R 2And R 3Independently be selected from respectively: a kind of in methyl, ethyl, propyl group, benzyl, methoxyl group or the hydroxyl.
3. as claimed in claim 2 pair of proline(Pro) amides is characterized in that, wherein n is 0, R 2And R 3Be hydroxyl, m and p are 0 or 1, and m and p are not 0 simultaneously.
4. as claimed in claim 3 pair of proline(Pro) amides is characterized in that, wherein n, m and p are 0, and structure is shown below:
5. two proline(Pro) amides is characterized in that wherein said pair of proline(Pro) amides is compound shown in the following formula:
Figure FSB00001064155200013
Wherein, TBDMS is tertiary butyl dimethylsilyl.
As any described compound in the claim 1～5 for the preparation of the application in the catalyzer of asymmetric catalysis synthesis; Wherein said asymmetric catalysis synthesis is asymmetric Aldol condensation reaction.
CN2011101466310A 2011-06-01 2011-06-01 Di-proline amide compound containing chiral indane framework and application thereof Expired - Fee Related CN102321006B (en)

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