CN1626524A - Dual functions ligand compound of chirality dioxazoline, preparation and application - Google Patents

Dual functions ligand compound of chirality dioxazoline, preparation and application Download PDF

Info

Publication number
CN1626524A
CN1626524A CN 200310117218 CN200310117218A CN1626524A CN 1626524 A CN1626524 A CN 1626524A CN 200310117218 CN200310117218 CN 200310117218 CN 200310117218 A CN200310117218 A CN 200310117218A CN 1626524 A CN1626524 A CN 1626524A
Authority
CN
China
Prior art keywords
chirality
bisoxazoline
cycloalkyl
aryl
alkyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN 200310117218
Other languages
Chinese (zh)
Inventor
杜大明
罗梅
吕少峰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Peking University
Original Assignee
Peking University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Peking University filed Critical Peking University
Priority to CN 200310117218 priority Critical patent/CN1626524A/en
Publication of CN1626524A publication Critical patent/CN1626524A/en
Pending legal-status Critical Current

Links

Landscapes

  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

A bifunctional chiral bioxazoline ligand used as the catalyst for asymmetrical reactions, such as cyanosiliconizing reaction, is prepared from propylbinitrile or its derivative through substitution reaction and cyclizing reaction on chiral aminoalcohol, or from the bioxazoline methane through substitution reaction.

Description

A kind of bifunctional chiral bisoxazoline ligand compound and preparation thereof and application
Technical field:
The invention belongs to organic compound and asymmetric synthesis technical field, be specifically related to a kind of bifunctional chiral bisoxazoline ligand compound and preparation and application with good catalytic.
Background technology:
Oxazoline and derivative thereof are the very important organic synthesis intermediates of a class, have widely in fields such as medicine, agricultural chemicals and Materials science and use.In recent years, the chirality bisoxazoline part of different types of structure continues to bring out, and the good catalytic effect that chirality bisoxazoline metal complexes is shown in various asymmetric reactions owing to them has been subjected to paying close attention to widely (Ghosh, A.K.; Mathivanan, P.; Cappiello, J.Tetrahedron:Asymmetry 1998,9,1.; Johnson, J.S.; Evas, D.A.Acc.Chem.Res.2000,33,325.).Chirality in the chirality bisoxazoline part derives from various natural and non-natural optically active amino acids or chiral amino alcohol that is very easy to obtain, and can obtain the chirality bisoxazoline part of two configurations at an easy rate.
Along with the development of medicine industry, a kind of preparation that both had been easy to is sought in the rise of chiral technology, has the chiral ligand compound of good catalytic to have crucial meaning for asymmetric synthesis research and industrial application again.The design of new chirality bisoxazoline part is synthetic to cause a lot of scientists' very big interest with asymmetry catalysis research, though these parts are all obtained asymmetry catalysis effect preferably in reactions such as asymmetric cyclopropanization reaction, Diels-Alder reaction, allyl group alkylated reaction, hydrosilylation reaction, aldol reaction, Ene reaction and Henry reaction, yet the application in the cyanogen silicification reaction is seldom reported.The research of difunctional metal catalyst is field, a forward position, and it is fewer that relevant bifunctional chiral bisoxazoline part is reported.Existing Lewis acid position in the complex structure that bifunctional chiral bisoxazoline ligand compound and metal form, Lewis alkali position is arranged again, thereby both can play synergy priming reaction substrate simultaneously and reagent can be induced various organic reactions highly-solid selectively.Therefore bifunctional chiral bisoxazoline ligand compound will have important significance for theories and wide application prospect in asymmetric catalysis research.
Summary of the invention:
The purpose of this invention is to provide a kind of novel bifunctional chiral bisoxazoline ligand compound.
Another purpose of the present invention provides the preparation method of described bifunctional chiral bisoxazoline ligand compound.A kind of method is that propane dinitrile and derivative are introduced in the cyclic tertiary amine unit, obtains the bisoxazoline part with the chiral amino alcohol reaction then; Another kind method is that the cyclic tertiary amine unit is introduced in the substitution reaction of chirality bisoxazoline.
Another purpose of the present invention provides the purposes of described chiral ligand compound.
Technical scheme of the present invention is as follows:
A kind of bifunctional chiral bisoxazoline ligand compound is characterized in that this compound is the chirality bisoxazoline that is replaced by cyclic tertiary amine, has following general structure:
In the formula:
X represents-(CH 2) m-(m=0,1,2,3 ...) ,-(CH 2CH 2OCH 2CH 2) m-(m=1,2,3,4 or 5) ,-(CH 2CH 2NCH 2CH 2) m-(m=1,2,3,4 or 5) ,-CH 2C 6H 4CH 2-,-CH 2C 6H 4-C 6H 4CH 2-etc.;
Y represents CH 2, O, S, NH, NR (R=alkyl, aryl, alkoxyl group, cycloalkyl) etc.;
N represents 0,1,2,3,4,5 or 6;
R 1Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, alkynyl,
Deng, wherein cycloalkyl and aryl can be fused rings;
R 2Expression hydrogen, alkyl, alkoxyl group, aryl, cycloalkyl, nitro or halogen etc.;
R 3Expression alkyl, alkoxyl group, aryl, cycloalkyl, CO 2R 4Or (R 5) 2COR 6, R wherein 4Expression alkyl, aryl or cycloalkyl, R 5Expression hydrogen, alkyl, aryl or cycloalkyl, R 6Expression hydrogen, alkyl, trimethyl silicon based or tertiary butyl dimethyl is silica-based; R 2And R 3Can connect into ring or become a pair of horses going side by side connection ring.
4 of oxazolines or/and 5 be chiral carbon atom, can have (R) or (S) configuration, also can be racemic modification.Racemic modification can split into a pair of enantiomorph.
Described bifunctional chiral bisoxazoline ligand compound is a kind of among ten kinds of the following 1a to 1f:
1a:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=Ph, chirality: (S, S);
1b:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=CH 2CH (CH 3) 2, chirality: (S, S);
1c:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=CH 2Ph, chirality: (S, S);
1d:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=CH (CH 3) 2, chirality: (S, S);
1e:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=C (CH 3) 3, chirality: (S, S);
1f:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=Ph, chirality: (S, S);
1g:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=CH 2CH (CH 3) 2, chirality: (S, S);
1h:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=CH 2Ph, chirality: (S, S);
1i:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=CH (CH 3) 2, chirality: (S, S);
1j:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=C (CH 3) 3, chirality: (S, S).
Bifunctional chiral bisoxazoline ligand compound, its preparation method comprise following two kinds of routes:
The step of route A can be as follows:
(1) replaces: under the effect of alkali, react 0.5-24h with propane dinitrile or derivatives thereof (2), then with corresponding alkylating reagent generation substitution reaction, at 50-200 ℃ of reacting by heating 1-36h.After organic solvent extraction concentrates, separate and replaced dintrile intermediate (3) accordingly;
(2) cyclisation: replace dintrile intermediate (3) and amino alcohol under Lewis acid (5%-20%mol/mol (3)) catalysis, in inert organic solvents, stirring reaction 1～36h carries out cyclisation under 50 ℃-200 ℃ temperature, water and organic solvent are handled, and separate to obtain corresponding bifunctional chiral bisoxazoline (1).
The substitution reaction of route B Shi bisoxazoline.Step can be reacted 0.5-24h by following: Yong bisoxazoline (4) under the effect of alkali, react with corresponding alkylating reagent then, and at 50-200 ℃ of reacting by heating 1-36h, water and organic solvent are handled, and separates obtaining corresponding bisoxazoline (1).
Among the above-mentioned preparation route A, the cyano group substituting group in the described raw material propane dinitrile or derivatives thereof (2) can substitute for ester group.
Among above-mentioned the preparation route A or B, the alkaline reagents in the described substitution reaction is selected from RONa, ROK, NaH, KH, NaNH 2, RLi, LDA or LiHMDS.Reaction solvent is selected from DMSO, THF, DMF, MeOH or EtOH.
Among the above-mentioned preparation route A, the chiral amino alcohol in the described cyclization has (+) and (-) two kinds of different optical activity, and Lewis acid used in this step cyclization is selected from BF 3-etherate, SnCl 4, ZnCl 2, solvent can be pyridine, chlorobenzene, dimethylbenzene isopolarity or non-polar organic solvent.
Among above-mentioned the preparation route A or B, described product can separate with silica gel column chromatography method or crystalline method, and described separation is selected from methylene dichloride, trichloromethane, ethylene dichloride, tetrahydrofuran (THF), benzene, ethyl acetate, sherwood oil, hexanaphthene, ether or toluene with organic solvent.
New compound 1 of the present invention can be used as the bifunctional chiral part, forms complex compound with metal ions such as copper, zinc, nickel, titanium, transition metal and lanthanide series metals.The chirality of synthetic new compound 1 of the present invention derives from chiral amino alcohol, and it can be obtained by natural or alpha-non-natural amino acid reduction, and major part is commercialization all, therefore is easy to obtain.
Bifunctional chiral bisoxazoline ligand compound of the present invention, one of its purposes are that this compound is made metal complex catalysts such as dysprosium, lanthanum, copper, zinc, nickel, are used for the following asymmetric cyanogen silicification reaction of catalysis:
R 1And R 2Expression hydrogen, alkyl, cycloalkyl, aryl
The cyanogen silicification reaction of 1 pair of aromatic ketone of chiral ligand has stereoselectivity preferably, and the ee value can reach more than 98%.
Advantage of the present invention and positively effect: bifunctional chiral bisoxazoline ligand compound of the present invention is easy to preparation, has good catalytic performance, can form the complex compound chiral catalyst with transition metal, study the catalytic activity of these new chiral catalysts, can develop the asymmetry catalysis synthetic method efficient, that selectivity is good.Preparation method of the present invention is a chiral source with the chiral amino alcohol, in the cyclic tertiary amine unit Yin Ru oxazoline ligand structure, and synthetic a series of novel bifunctional chiral bisoxazoline ligand compounds.Existing Lewis acid position has Lewis alkali position again in the complex structure that bifunctional chiral bisoxazoline ligand compound and metal form, both can play synergy simultaneously and highly-solid selectively induce asymmetric reaction.
Embodiment:
The invention is not restricted to following embodiment.
Embodiment one:
Synthesizing of N-(3,3-dicyano propyl group) hexahydropyridine:
(1.0g 43.5mmol), stirs 1h to add dehydrated alcohol (30mL) and sodium in the 100mL round-bottomed flask.Add then propane dinitrile (2.75mL, 43.3mmol) and potassiumiodide (0.6g 3.6mmol), continue to stir 0.5h.Add subsequently N-chloroethyl hexahydropyridine hydrochloride (8.43g, 45.8mmol), reaction mixture refluxed 24h.In reactant, add entry (10mL), with chloroform extraction (20ml * 2).Merge organic layer, use anhydrous Na 2SO 4Drying obtains thick product after concentrating, and silica gel column chromatography (sherwood oil/chloroform 1: 4) obtains N-(3,3-dicyano propyl group) hexahydropyridine 3.82g, productive rate 50%.IR：2938，2854，2806，2256，1470，1455，1444，1379，1353，1156，1126，1039cm -1； 1H?NMR(300MHz，CDCl 3)：δ4.18(t，J＝7.3Hz，1H)，2.53(t，J＝7.1Hz，2H)，2.39(s，4H)，2.13-2.18(m，4H)，1.54-1.59(m，4H)，1.42-1.46(m，2H). 13CNMR(50MHz，CDCl 3)：19.73，24.12，25.81，28.62，53.76，54.35，113.08.MS(EI)：m/z(％)177(M +，8)，112(5)，98(100).HRMS(EI)calcd?for?C 10H 15N 3：177.1266.Found：177.1262.
Embodiment two:
1,1-two [(4S)-4-phenyl-1,3-oxazoline-2-yl]-3-(piperidino) propane (1a) synthetic:
(50mg, 0.37mmol), heating and melting cools off the system room temperature under the nitrogen protection to add Zinc Chloride Anhydrous in two mouthfuls of flasks of 100mL.Add then chlorobenzene (20ml) and N-(3,3-dicyano propyl group) piperidines (0.55g, 3.1mmol) and L-benzene glycinol (0.93g, 6.82mmol), mixture backflow 24h.Steaming under reduced pressure desolventizes and obtains oily matter, and methylene dichloride (20mL) is added wherein.Solution with water extraction (20mL * 3), water extracts with methylene dichloride (20ml).Merge organic phase, use anhydrous sodium sulfate drying.Decompression is steamed down and is desolventized, and the oily resistates obtains 1 with silica gel chromatography (eluent sherwood oil/chloroform 4: 1), 1-pair [(4S)-and 4-phenyl-1,3-oxazoline-2-yl]-3-(piperidino) propane 0.59g (46%).[α] D 20＝-16.5°(c0.2，CH 3OH).IR：3062，3030，2936，2855，2811，2188，1656，1578，1510，1494，1454，1354，1271，1239，1119，1070，1030，985，926，759，701cm -1. 1H?NMR(CDCl 3)：δ7.25-7.34(m，10H)，5.18-5.29(m，2H)，4.64-4.70(m，2H)，4.13-4.20(m，1H)，3.76-3.91(m，1H)，2.46-2.48(m，2H)，2.35-2.42(m，4H)，2.22-2.34(m，2H)，1.54-1.60(m，3H)，1.42-1.51(m，3H). 13C?NMR(50MHz，CDCl 3)：24.33，25.86，27.09，37.72，54.46，54.71，56.50，69.47，69.51，75.13，75.16，126.61，126.77，127.53，128.65，142.16，166.80.MS(EI)：417(M +，0.63)，306(16)，297(5)，251(10)，229(5)，111(35)，98(100).
Embodiment three:
1,1-two [(4S)-4-isobutyl--1,3-oxazoline-2-yl]-3-(piperidino) propane (1a) synthetic:
With the L-benzene glycinol among the L-leucinol replacement embodiment two, all the other obtain 1 with embodiment two, 1-pair [(4S)-and 4-isobutyl--1,3-oxazoline-2-yl]-3-(piperidino) propane, productive rate 48%.[α] D 20=-30.3 ° of (c0.7, CH 3OH)
IR：2956，2870，1749，1656，1542，1468，1367，1256，1067cm -1. 1H?NMR(CDCl 3)：δ4.21-4.27(m，2H)，4.02-4.07(m，2H)，3.72-3.78(m，2H)，3.36-3.40(t，J＝7.1Hz，1H)，2.20-2.29(m，4H)，1.98-2.03(m，2H)，1.61-1.65(m，2H)，1.47-1.52(m，6H)，1.32(m，2H)，1.15-1.22(m，2H)，0.81-0.85(m，12H). 13C?NMR(50MHz，CDCl 3)：22.53，22.59，22.78，22.83，24.34，25.24，25.88，26.91，37.69，45.30，45.39，54.41，56.50，64.43，64.47，73.15，73.25，164.37，164.42.MS(EI)：377(M +，2)，279(35)，249(12)，209(20)，168(18)，98(100).
Embodiment four:
1,1-two [(4S)-4-hydrocinnamyl-1,3-oxazoline-2-yl]-3-(piperidino) propane (1c) synthetic:
With the L-benzene glycinol among the L-phenylalaninol replacement embodiment two, all the other obtain 1 with embodiment two, 1-pair [(4S)-and 4-hydrocinnamyl-1,3-oxazoline-2-yl]-3-(piperidino) propane, productive rate 78%.[α] D 20=-75.4 ° of (c1.1, CH 3OH).
IR：2924，2359，1661，1532，1449，1264，1069，803，742，700?cm -1. 1H?NMR(CDCl 3)：δ6.99-7.22(m，10H)，4.34-4.37(m，1H)，4.16-4.22(m，1H)，3.96-4.02(m，1H)，3.63-3.74(m，2H)，2.97-3.04(m，1H)，2.54-2.67(m，1H)，2.29-2.43(m，5H)，1.87-2.05(m，2H)，1.19-1.47(m，8H)，0.78-0.90(m，3H). 13C?NMR(50MHz，CDCl 3)：24.26，25.89，29.08，41.01，54.40，55.06，67.19，72.59，126.41，126.78，128.65，128.94，129.25，161.84.MS(EI)：445(M +，1)，347(16)，252(8)，243(60)，111(30)，98(100).
Embodiment five:
1,1-two [(4S)-4-sec.-propyl-1,3-oxazoline-2-yl]-3-(piperidino) propane (1d) synthetic:
With the L-benzene glycinol among the L-valerian ammonia alcohol replacement embodiment two, all the other obtain 1 with embodiment two, 1-pair [(4S)-and 4-sec.-propyl-1,3-oxazoline-2-yl]-3-(piperidino) propane, productive rate 43%.[α] D 20=-40.0 ° of (c0.1, CH 3OH).
IR：2961，2360，1746，1652，1462，1262，1061，802，675cm -1. 1H?NMR(CDCl 3)：δ4.23-4.37(m，1H)，3.98-4.05(m，1H)，3.89-3.93(m，1H)，3.76-3.78(m，1H)，3.55-3.65(m，3H)，2.60-2.65(m，1H)，2.26-2.39(m，4H)，1.85-2.10(m，2H)，1.66-1.70(m，4H)，1.47-1.50(m，2H)，1.33-1.35(m，1H)，1.24-1.26(m，1H)，1.15-1.23(m，1H)，0.78-0.98(m，12H). 13C?NMR(50MHz，CDCl 3)：24.28，27.21，29.09，31.85，46.75，54.44，56.59，60.77，61.95，68.39，70.98，161.07.MS(EI)：347(M +，4)，331(20)，243(10)，162(12)，111(38)，98(100).
Embodiment six:
1,1-two [(4S)-4-hydrocinnamyl-1,3-oxazoline-2-yl]-3-(1-morpholinyl) propane (1f) synthetic:
(115mg 0.375mmol) and THF (5mL), is cooled to solution-10 ℃ to add two [(4S)-4-hydrocinnamyl-1,3-oxazoline-2-yl] methane in the 50mL round-bottomed flask.(0.24mL 1.6M 0.38mmol) dropwise adds in the above-mentioned solution with the diethyl ether solution of MeLi under nitrogen protection.Behind-10 ℃ of stirring 1h, (reaction mixture is at stirring at room 5h for 57mg, THF solution (3mL) 0.38mmol) dropwise to add N-chloroethyl morpholine.The saturated NH of reaction 4Cl solution (10mL) cancellation, gained mixture CH 2Cl 2(3 * 10mL).Merge organic layer, use anhydrous Na 2SO 4Drying obtains thick product after concentrating.Obtain oily product 1f 102mg, productive rate 65% with silica gel column chromatography (petrol ether/ethyl acetate 9: 1).IR：3061，3025，2935，2850，2810，1655，1580，1510，1495，1450，983，925，760cm -1. 1H?NMR(CDCl 3)：δ7.25-7.34(m，10H)，5.18-5.29(m，2H)，4.64-4.70(m，2H)，4.13-4.20(m，2H)，3.76-3.91(m，2H)，2.46-2.48(m，2H)，2.35-2.42(m，4H)，2.22-2.34(m，2H)，1.54-1.60(m，3H).MS(EI)：419(M +).
Embodiment seven:
The asymmetric cyanogen silicification reaction of methyl phenyl ketone:
Part 2 (20mg, 0.053mmol) and DyCl 3(14mg 0.052mmol) adds in the toluene (1mL), and mixture stirs 1h at 70 ℃.Then 0 ℃ add TMSCN (20 μ l, 0.148mmol).Behind stirring at room 1h, under reduced pressure steam and remove toluene.Resistates continues dry 1h under the vacuum.The resistates that obtains is dissolved in methylene dichloride (1mL).-20 ℃ in above-mentioned solution, add methyl phenyl ketone (434 μ l, 3.72mmol) and TMSCN (740 μ l, 5.58mmol).Stopped reaction after 88 hours.Solvent remove the back with silica gel column chromatography separate (petroleum ether/ethyl ether 4: 1) purifying obtain product (816mg, productive rate 100%, 97.5%ee). product is configured as (S). 1HNMR (CDCl 3): δ 7.45-7.47 (m, 2H, ArH), 7.25-7.32 (m, 3H, ArH), 1.76 (s, 3H, CH 3), 0.087 (s, 9H, (CH 3) 3Si).

Claims (10)

1. bifunctional chiral bisoxazoline ligand compound is characterized in that this compound is the chirality bisoxazoline that is replaced by cyclic tertiary amine, has following general structure:
Figure A2003101172180002C1
In the formula:
X represents-(CH 2) m-(m=0,1,2,3 ...) ,-(CH 2CH 2OCH 2CH 2) m-(m=1,2,3,4 or 5) ,-(CH 2CH 2NCH 2CH 2) m-(m=1,2,3,4 or 5) ,-CH 2C 6H 4CH 2-or-CH 2C 6H 4-C 6H 4CH 2-;
Y represents CH 2, O, S, NH or NR (R=alkyl, aryl, alkoxyl group or cycloalkyl);
N represents 0,1,2,3,4,5 or 6;
R 1Expression hydrogen, alkyl, cycloalkyl, aryl, thiazolinyl, alkynyl or
Figure A2003101172180002C2
Wherein cycloalkyl and aryl can be fused rings;
R 2Expression hydrogen, alkyl, alkoxyl group, aryl, cycloalkyl, nitro or halogen;
R 3Expression alkyl, alkoxyl group, aryl, cycloalkyl, CO 2R 4Or (R 5) 2COR 6, R wherein 4Expression alkyl, aryl or cycloalkyl, R 5Expression hydrogen, alkyl, aryl or cycloalkyl, R 6Expression hydrogen, alkyl, trimethyl silicon based or tertiary butyl dimethyl is silica-based, R 2And R 3Can connect into ring or become a pair of horses going side by side connection ring;
4 of oxazolines or/and 5 be chiral carbon atom, can have (R) or (S) configuration, also can be racemic modification, racemic modification can split into a pair of enantiomorph.
2. bifunctional chiral bisoxazoline ligand compound according to claim 1 is characterized in that this compound is a kind of among the following 1a to 1i:
1a:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=Ph, chirality: (S, S);
1b:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=CH 2CH (CH 3) 2, chirality: (S, S);
1c:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=CH 2Ph, chirality: (S, S);
1d:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=CH (CH 3) 2, chirality: (S, S);
1e:X=-CH 2CH 2-, Y=CH 2, n=2, R 1=R 2=H, R 3=C (CH 3) 3, chirality: (S, S);
1f:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=Ph, chirality: (S, S);
1g:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=CH 2CH (CH 3) 2, chirality: (S, S);
1h:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=CH 2Ph, chirality: (S, S);
1i:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=CH (CH 3) 2, chirality: (S, S);
1j:X=-CH 2CH 2-, Y=O, n=2, R 1=R 2=H, R 3=C (CH 3) 3, chirality: (S, S).
3. prepare the method for the described bifunctional chiral bisoxazoline of claim 1 ligand compound, may further comprise the steps successively:
(1) replace: react 0.5-24 hour under the effect of alkali with propane dinitrile or derivatives thereof (2), then with corresponding alkylating reagent at 50-200 ℃ of reacting by heating 1-36 hour, separation is replaced dintrile intermediate (3) accordingly;
(2) cyclisation: replace dintrile intermediate (3) and amino alcohol under Lewis acid (5%-20%mol/mol (3)) catalysis, in inert organic solvents, stirring reaction carried out cyclisation in 1～36 hour under 50 ℃-200 ℃ temperature, separated to obtain corresponding bisoxazoline (1).
4. preparing the method for the described bifunctional chiral bisoxazoline of claim 1 ligand compound, is the substitution reaction of Cai Yong oxazoline, may further comprise the steps successively:
Yong oxazoline (4) reacted 0.5-24 hour under the effect of alkali, then with corresponding alkylating reagent at 50-200 ℃ of reacting by heating 1-36 hour, separate to obtain corresponding bisoxazoline (1).
5. preparation method according to claim 3 is characterized in that the cyano group substituting group can substitute for ester group in the described raw material propane dinitrile or derivatives thereof (2).
6. according to claim 3 or 4 described preparation methods, it is characterized in that the alkali in the described substitution reaction is selected from RONa, ROK, NaH, KH, NaNH 2, RLi, LDA or LiHMDS, reaction solvent is selected from DMSO, THF, DMF, MeOH or EtOH.
7. preparation method according to claim 3 is characterized in that the chiral amino alcohol in the described cyclization has (+) and (-) two kinds of different optical activity, and Lewis acid used in the cyclization is selected from BF 3-etherate, SnCl 4, ZnCl 2, reaction solvent is selected from pyridine, chlorobenzene, dimethylbenzene.
8. preparation method according to claim 3, the method that it is characterized in that the separation employing of described replacement dintrile intermediate (3) or described product bisoxazoline (1) is silica gel column chromatography method or crystalline method, separates used organic solvent and is selected from methylene dichloride, trichloromethane, ether, hexanaphthene, ethylene dichloride, tetrahydrofuran (THF), benzene, ethyl acetate, sherwood oil or toluene.
9. preparation method according to claim 4, the method that it is characterized in that the separation employing of described product bisoxazoline (1) is silica gel column chromatography method or crystalline method, separates used organic solvent and is selected from methylene dichloride, trichloromethane, ether, hexanaphthene, ethylene dichloride, tetrahydrofuran (THF), benzene, ethyl acetate, sherwood oil or toluene.
10. the described bifunctional chiral bisoxazoline of claim 1 ligand compound, its purposes are that this compound makes dysprosium, lanthanum, copper, zinc, nickel metal complex catalyst, are used for the following asymmetric cyanogen silicification reaction of catalysis:
Figure A2003101172180004C1
R 1And R 2Expression hydrogen, alkyl, cycloalkyl, aryl.
CN 200310117218 2003-12-08 2003-12-08 Dual functions ligand compound of chirality dioxazoline, preparation and application Pending CN1626524A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 200310117218 CN1626524A (en) 2003-12-08 2003-12-08 Dual functions ligand compound of chirality dioxazoline, preparation and application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN 200310117218 CN1626524A (en) 2003-12-08 2003-12-08 Dual functions ligand compound of chirality dioxazoline, preparation and application

Publications (1)

Publication Number Publication Date
CN1626524A true CN1626524A (en) 2005-06-15

Family

ID=34760938

Family Applications (1)

Application Number Title Priority Date Filing Date
CN 200310117218 Pending CN1626524A (en) 2003-12-08 2003-12-08 Dual functions ligand compound of chirality dioxazoline, preparation and application

Country Status (1)

Country Link
CN (1) CN1626524A (en)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100425598C (en) * 2006-09-09 2008-10-15 合肥工业大学 Chiral oxazoline and its production
CN101684105A (en) * 2008-09-23 2010-03-31 赢创德固赛有限责任公司 Process for preparing heterocycles
CN102040594A (en) * 2010-05-26 2011-05-04 北京理工大学 C2 axisymmetric chiral bisoxazoline ligand compound containing imidazole salt ion pair group, and preparation and application thereof
CN102199130A (en) * 2011-03-22 2011-09-28 罗梅 Preparation and synthesis method for chiral oxazoline
CN102617499A (en) * 2012-03-09 2012-08-01 罗梅 Chiral zinc complex
CN102627616A (en) * 2012-03-21 2012-08-08 罗梅 Chiral zinc complex
CN102850383A (en) * 2012-04-05 2013-01-02 罗梅 Chiral zinc complex
CN103319474A (en) * 2013-06-17 2013-09-25 福建省北理展华医药技术研发有限公司 Ion group modified 4,4'-bit chiral oxazoline ligand and synthesis method thereof
CN104926747A (en) * 2015-06-01 2015-09-23 中国科学院上海有机化学研究所 Synthetic method and application of cyclohexyl oxazoline ligand with optical activity
CN106045985A (en) * 2016-06-14 2016-10-26 华中师范大学 Bisoxazoline compound and preparation method and application thereof
CN106362725A (en) * 2016-08-26 2017-02-01 安徽金邦医药化工有限公司 Solid catalyst and application thereof to preparing methyl formate isothiocyanate through catalysis
CN111992254A (en) * 2020-08-19 2020-11-27 苏州大学 Application of deprotonated phenyl bridged beta-ketimine lithium complex in cyanide silicification reaction
CN114369248A (en) * 2020-10-15 2022-04-19 中国科学院大连化学物理研究所 Chiral silicon-containing polyester and synthesis method thereof

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100425598C (en) * 2006-09-09 2008-10-15 合肥工业大学 Chiral oxazoline and its production
CN101684105B (en) * 2008-09-23 2014-09-10 赢创德固赛有限责任公司 Process for preparing heterocycles
CN101684105A (en) * 2008-09-23 2010-03-31 赢创德固赛有限责任公司 Process for preparing heterocycles
CN102040594A (en) * 2010-05-26 2011-05-04 北京理工大学 C2 axisymmetric chiral bisoxazoline ligand compound containing imidazole salt ion pair group, and preparation and application thereof
CN102040594B (en) * 2010-05-26 2012-11-07 北京理工大学 C2 axisymmetric chiral bisoxazoline ligand compound containing imidazole salt ion pair group, and preparation and application thereof
CN102199130A (en) * 2011-03-22 2011-09-28 罗梅 Preparation and synthesis method for chiral oxazoline
CN102617499A (en) * 2012-03-09 2012-08-01 罗梅 Chiral zinc complex
CN102627616A (en) * 2012-03-21 2012-08-08 罗梅 Chiral zinc complex
CN102627616B (en) * 2012-03-21 2013-12-25 罗梅 Chiral zinc complex
CN102850383A (en) * 2012-04-05 2013-01-02 罗梅 Chiral zinc complex
CN102850383B (en) * 2012-04-05 2015-11-25 罗梅 A kind of chiral zinc nitrogen complexes
CN103319474A (en) * 2013-06-17 2013-09-25 福建省北理展华医药技术研发有限公司 Ion group modified 4,4'-bit chiral oxazoline ligand and synthesis method thereof
CN103319474B (en) * 2013-06-17 2015-09-02 福建省北理展华医药技术研发有限公司 Ionic group modifies 4,4 ' position Shou bisoxazoline part and synthetic method thereof
CN104926747A (en) * 2015-06-01 2015-09-23 中国科学院上海有机化学研究所 Synthetic method and application of cyclohexyl oxazoline ligand with optical activity
CN106045985A (en) * 2016-06-14 2016-10-26 华中师范大学 Bisoxazoline compound and preparation method and application thereof
CN106045985B (en) * 2016-06-14 2018-11-09 华中师范大学 A kind of bisoxazoline class compound and preparation method and purposes
CN106362725A (en) * 2016-08-26 2017-02-01 安徽金邦医药化工有限公司 Solid catalyst and application thereof to preparing methyl formate isothiocyanate through catalysis
CN111992254A (en) * 2020-08-19 2020-11-27 苏州大学 Application of deprotonated phenyl bridged beta-ketimine lithium complex in cyanide silicification reaction
CN114369248A (en) * 2020-10-15 2022-04-19 中国科学院大连化学物理研究所 Chiral silicon-containing polyester and synthesis method thereof
CN114369248B (en) * 2020-10-15 2022-09-02 中国科学院大连化学物理研究所 Chiral silicon-containing polyester and synthesis method thereof

Similar Documents

Publication Publication Date Title
JP3497165B2 (en) Chiral catalyst, catalytic oxidation and disproportionation reaction, and method for producing epoxy chroman and taxol
CN1626524A (en) Dual functions ligand compound of chirality dioxazoline, preparation and application
KR100870227B1 (en) Alanine racemase chiral binaphthol analogue with powerful hydrogen bonding donor, and the methods for optical resolution and optical transformation
CN1238361C (en) Spiro-diphosphine ligand
Reddy et al. Di-n-butyl ammonium chlorosulfonate ionic liquids as an efficient and recyclable catalyst for the synthesis of 1, 4-dihydrobenzo [4, 5] imidazo [1, 2-a] pyrimidine-3-carboxylates under solvent-free ultrasound irradiation
JP5968537B2 (en) Method for synthesizing ezetimibe and intermediates used in the method
SAFAEI et al. Nano silica supported ferric chloride as a green and efficient catalyst for one pot synthesis of 1, 2-dihydro-1-arylnaphtho [1, 2-e][1, 3] oxazine-3-ones
CN110357801A (en) A kind of method that three component reaction of catalysis of iodine synthesizes nitrogenous five member ring heterocyclic compound
Muench et al. A Mannich-cyclization approach for the asymmetric synthesis of saturated N-heterocycles
EP0925279A1 (en) Catalytic selective sulfonylation process
CN102718768A (en) Chiral five-membered bicyclic guanidine compound, preparation method and application thereof
Hashimoto et al. Design of an axially chiral dicarboxylic acid and its application in syntheses of optically active β-amino acids and β-amino phosphonic acid derivatives
CN117303993A (en) Nickel-catalyzed olefin asymmetric hydroarylation method and application
CN104130204A (en) Method for preparing N-sulfonyl-1,4-oxazine derivative
CN112694430B (en) Preparation method of 1, 5-dihydro-2H-pyrrole-2-ketone compound
CN112209850B (en) Method for preparing (S) -3-amino-2-benzyl methyl propionate
CN102260224B (en) Method for synthesizing 2-morpholone derivatives
EP1935896A1 (en) Novel optically active biaryl phosphorus compound and production process thereof
CN109020860A (en) A kind of 2- aryl -3- ester group polysubstituted pyrrole class compound and its method for synthesizing and refining
Cheng et al. Synthesis of novel C3 symmetric tris (thiazoline) ligands and their application in the allylic oxidation reaction
JP2003221395A (en) Method for totally synthesizing ecteinascidin, intermediate used for the total synthesis and having structure analogous to the ecteinascidin, and method for synthesizing the intermediate
Zhao et al. Asymmetric Synthesis of Novel Axially Chiral 2, 2′‐Bipyridine N, N′‐Dioxides Bearing α‐Amino Acid Residues and Their Applications in Enantioselective Allylation of Aromatic Aldehydes with Allyltrichlorosilane
Zhou et al. A series of new C2‐symmetric amino alcohols with multicoordination groups: Promising catalysts for synthesis of both enantiomers in the borane‐mediated reduction of prochiral ketones
CN114160206B (en) Catalyst for catalytic synthesis of optically active indole compound, application and synthesis method thereof, and optically active indole compound
Haukaas et al. De Novo Asymmetric Approaches to 2-Amino-N (benzyloxycarbonyl)-1-(2'-furyl)-ethanol and 2-Amino-N-(tert-butoxycarbonyl)-1-(2'-furyl)-ethanol

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C12 Rejection of a patent application after its publication
RJ01 Rejection of invention patent application after publication