CN106478719B - A kind of chiral catalyst and preparation method thereof - Google Patents
A kind of chiral catalyst and preparation method thereof Download PDFInfo
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- CN106478719B CN106478719B CN201610879705.4A CN201610879705A CN106478719B CN 106478719 B CN106478719 B CN 106478719B CN 201610879705 A CN201610879705 A CN 201610879705A CN 106478719 B CN106478719 B CN 106478719B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/189—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms containing both nitrogen and phosphorus as complexing atoms, including e.g. phosphino moieties, in one at least bidentate or bridging ligand
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2/00—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms
- C07C2/02—Preparation of hydrocarbons from hydrocarbons containing a smaller number of carbon atoms by addition between unsaturated hydrocarbons
- C07C2/50—Diels-Alder conversion
- C07C2/52—Catalytic processes
Abstract
The invention discloses a kind of chiral catalyst and preparation method thereof.The present invention is using camphoronic acid as raw material, using benzene glycinol as oxazoline precursor, through superchlorination, condensation, cyclisation, reduction, diphenyl phosphorus chloride is connect, has finally synthesized a kind of chiral catalyst, i.e. 2 ((1R, 2R, 4R) bicyclic [2.2.1] 1 heptyl of the dimethyl of 2 diphenylphosphine epoxide 7,7) 4 phenyl, 4,5 dihydro-oxazole.The characteristics of present invention is using the stable skeleton of chiral camphor and its easy derivatization; it is integrated with reference to the catalysis advantage of oxazoline and the efficient selective of phosphorus-containing ligand; the species of organic micromolecule catalyst derived from camphor and oxazoline is expanded; new environment-friendly of design synthetic route exploitation has chiral catalyst; be advantageous to environmental protection, economize on resources.
Description
Technical field
The invention belongs to technical field of organic chemistry, more particularly to a kind of chiral catalyst and preparation method thereof.
Background technology
Asymmetric syntheses be enantioselectivity prepare the effective means of optically active substance, exploitation high efficiency, high selection
The chiral catalyst of property is the key for realizing asymmetric syntheses.Ripe exploitation is mostly chiral transition metal, and
In pharmaceutical synthesis and agriculture chemistry, even if the harmful metal elements that trace in final product be present are also not allow, therefore
People have gradually directed attention to the asymmetric catalysis synthesis of metal-free chiral organic micromolecule catalysis.It is general organic small
Molecule as asymmetric reaction catalyst have high catalytic efficiency and selectivity it is good, it is applied widely, it is simple in construction, it is nontoxic honest and clean
Valency, the advantages that being easy to load and easily reclaim.
Camphor is a kind of natural products with chirality cheap and easy to get, and its own skeleton is stable, is easy to derivatization, chiral ring
Border is survivable, so as to be widely used in asymmetric syntheses.China is the big export country of artificial camphor, but camphor is first
Level product, its price are relatively low.The chiral ligand synthesized by camphor derivatives, led in organic asymmetric syntheses and organic optical materials
Domain, is just playing great effect, and market application foreground is also gradually increasing.
The key of asymmetry catalysis synthesis is how to design and synthesize the chiral catalyst of high selectivity and catalytic activity.It is many
In more chiral ligands, the heteroatomic part such as nitrogenous, oxygen, phosphorus increasingly shows its importance in some reactions.Oxazole
Quinoline is more outstanding a kind of chiral ligand, and oxazoline was once used for synthesizing various chipal compounds as substrate, and is obtained
Certain success, this causes it to be had broad prospects as part in terms of asymmetry catalysis.From the 1980s with
Come, chemists have synthesized various oxazoline parts, and these parts are applied in various asymmetric catalytic reactions.Such as：
Asymmetric allylic substitution, propylene position oxidation reaction, the cyclopropanization reaction of alkene and imines, D-A reactions, free radical add
Into reaction, imines and the nucleophilic addition of aldehyde and silicon hydrogen reduction reaction etc..
Because phosphorus atoms volume is bigger, polarizability is big, therefore alkylphosphines nucleophilicity is strong, and alkalescence is but much weaker than corresponding
Amine, be widely used in asymmetric organic reactions.
The content of the invention
For above mentioned problem of the prior art, it is an object of the invention to provide a kind of chiral catalyst and its preparation side
Method.The catalyst of the present invention enriches the species of camphor derivatives and oxazoline part, combines camphor skeleton, oxazoline ring
Advantage, while the efficient selective of phosphorus-containing ligand is make use of, good catalytic activity is shown in asymmetry catalysis.
Technical scheme is specifically described as follows.
The present invention provides a kind of chiral catalyst, its chemical name be 2- ((1R, 2R, 4R) -2- diphenylphosphines epoxide -7,
Bicyclic [the 2.2.1] -1- heptyl of 7- dimethyl) -4- phenyl -4,5- dihydro-oxazoles, structure is shown below：
For the present invention using chiral camphor as skeleton, benzene glycinol is oxazoline precursor, through superchlorination, condensation, cyclisation, reduction,
Diphenyl phosphorus chloride is connect, has finally synthesized a kind of novel chiral catalyst 2- ((1R, 2R, 4R) -2- diphenylphosphine epoxides -7,7-
Bicyclic [the 2.2.1] -1- heptyl of dimethyl) -4- phenyl -4,5- dihydro-oxazoles.Its reaction equation is as follows：
Comprise the following steps that：
(1) ketone group pinic acid and benzene glycinol are reacted to obtain (1R, 4R)-N- benzene glycinol -2- carbonyl -7,7- dimethyl pair
Ring [2.2.1] -1- heptamides；
(2) by bicyclic [the 2.2.1] -1- heptamides of (1R, 4R)-N- benzene glycinol -2- carbonyl -7,7- dimethyl and methylsulfonyl
Chlorine reacts under acid binding agent effect, and it is bicyclic to obtain (1S, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) -7,7- dimethyl
[2.2.1] -2-HEPTANONE；
(3) by (1S, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) -7,7- dimethyl bicyclic [2.2.1] -2- heptan
Ketone reduces to obtain (1R, 2R, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) -7,7- dimethyl bicyclic [2.2.1] -2- heptan
Alcohol；
(4) by (1R, 2R, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) bicyclic [the 2.2.1] -2- of -7,7- dimethyl
The reaction under alkali effect of enanthol and diphenyl phosphorus chloride obtain chiral catalyst 2- ((1R, 2R, 4R) -2- diphenylphosphines epoxide -7,
Bicyclic [the 2.2.1] -1- heptyl of 7- dimethyl) -4- phenyl -4,5- dihydro-oxazoles.
In the present invention, in step (2), acid binding agent is selected from one or both of triethylamine, diisopropyl ethylenediamine.
In the present invention, in step (3), reducing agent uses Lithium Aluminium Hydride.
In the present invention, in step (4), alkali is potassium tert-butoxide or sodium hydride.
Compared to the prior art, the beneficial effects of the present invention are：The chiral catalyst of the present invention is using ketone group pinic acid as original
Material, using its chiral environment is stable and the characteristics of easy derivatization, by the efficient choosing of the catalysis advantage of oxazoline ring and phosphorus-containing ligand
Selecting property combines, and has not only expanded the species of camphor derivatives and oxazoline part, moreover, it is in catalysis asymmetric D iels-
Alder shows good catalytic activity and efficient enantioselectivity during reacting, and has in organic catalysis field wide
Application prospect.
Embodiment
The present invention is described further with reference to concrete instance, embodiments of the invention are merely to illustrate the present invention's
Technical scheme, and the non-limiting present invention.
Embodiment 1
(1) ketone group pinic acid (1.0g, 5.5mmol) and SOCl are added in flask2(4.5mL), flow back 2h, after reaction terminates
Revolving, removes excessive SOCl2, the product after revolving is dissolved in CH2Cl2In (3.8mL), labeled as a.Add in another flask
Enter L- benzene glycinol (0.75g, 5.5mmol), Et3N (0.75mL, 5.5mmol) and CH2Cl2(3mL), it is 0 DEG C to control temperature, N2
A is added dropwise under protection dropwise, reacts 1h.By obtained mixture with EtOAc (150mL) dilute, with 2mol/L HCl (2 ×
30mL), the NaHCO of saturation3(2 × 30mL), salt solution (30mL) washing, MgSO4Dry, crude product is obtained after being concentrated under reduced pressure, thick production
Product hexane/CH2Cl2It is bicyclic to be recrystallized to give White crystalline product (1R, 4R)-N- benzene glycinol -2- carbonyl -7,7- dimethyl
[2.2.1] -1- heptamide 1.38g, yield 83.2%.1H-NMR(501MHz,CDCl3):δ 8.40 (d, J=5.8Hz, 1H),
7.34 (ddd, J=24.8,15.7,7.7Hz, 5H), 5.17 (q, J=5.8Hz, 1H), 3.90-3.88 (m, 2H), 2.62-2.51
(m, 2H), 2.18 (dtd, J=15.7,7.7,4.3Hz, 1H), 2.10 (t, J=4.3Hz, 1H), 2.02 (d, J=18.8Hz,
1H), 1.71 (ddd, J=13.9,9.3,4.8Hz, 1H), 1.47 (ddd, J=12.8,9.3,4.0Hz, 1H), 1.24 (s, 3H),
0.96(s,3H)ppm.
(2) bicyclic [the 2.2.1] -1- oenanthyl of (1R, 4R)-N- benzene glycinol -2- carbonyl -7,7- dimethyl is added in flask
Amine (1.03g, 3.4mmol), Et3N (5.8mL), diisopropylethylamine (1.2mL), CH2Cl2(17mL), it is 0 DEG C to control temperature,
N2MsCl (6.75mmol) is added dropwise under protection dropwise, reaction is stirred overnight.After reaction terminates, product is dilute with EtOAc (200mL)
Release, H2O (2 × 25mL), salt solution (25mL) washing, MgSO4Dry, carried out after being concentrated under reduced pressure with petrol ether/ethyl acetate eluent
Elution, it is bicyclic to obtain White crystalline product (1S, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) -7,7- dimethyl
[2.2.1] -2-HEPTANONE 0.78g, yield 81.5%.1H-NMR(501MHz,CDCl3):δ7.40–7.26(m,5H),5.23(t,
J=9.0Hz, 1H), 4.70-4.58 (m, 1H), 4.15 (td, J=8.2,2.9Hz, 1H), 2.66-2.56 (m, 1H), 2.55-
2.44 (m, 1H), 2.19 (t, J=4.1Hz, 1H), 2.09 (dtd, J=11.3,7.1,6.6,3.1Hz, 1H), 2.02 (d, J=
18.3Hz, 1H), 1.90 (ddd, J=14.2,9.4,4.8Hz, 1H), 1.47 (ddd, J=12.7,9.6,3.8Hz, 1H), 1.23
(s,3H),1.16(s,3H)ppm.
(3) it is bicyclic that (1S, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) -7,7- dimethyl is added in flask
[2.2.1] -2-HEPTANONE (0.47g, 1.67mmol), the THF (17mL) of water removal, it is -40 DEG C to control temperature, N2Dripped dropwise under protection
Add [LiAlH42THF] solution (1mol/L, 1.5mL, 1.5mmol), TCL is followed the trail of untill raw material has reacted.Reaction terminates
Afterwards, Na is used2SO4·10H2LiAlH is quenched in O4, after filtering, filtrate is diluted with EtOAc (150mL), salt solution (3 × 10mL) washing,
MgSO4Dry, eluted after being concentrated under reduced pressure with petrol ether/ethyl acetate eluent, obtain White crystalline product (1R, 2R,
4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) bicyclic [2.2.1] -2- enanthol 0.42g yields of -7,7- dimethyl are
89.1%.1H-NMR(501MHz,CDCl3):δ 7.48-7.18 (m, 5H), 5.89 (s, 1H), 5.24 (t, J=9.3Hz, 1H),
4.62 (t, J=9.3Hz, 1H), 4.19-3.93 (m, 2H), 2.30-2.19 (m, 1H), 2.01-1.95 (m, 1H), 1.94-1.88
(m, 1H), 1.86 (s, 1H), 1.80 (dd, J=12.7,8.0Hz, 1H), 1.33 (s, 3H), 1.29 (s, 1H), 1.23-1.16
(m,1H),1.12(s,3H)ppm.
(4)N2Under protection, by NaH (52mg, 1.30mmol, the 60wt%) suspension being stored in mineral oil first with water removal
Pentane (2 × 2ml) washes clean, then add it to (1R, 2R, 4R) -1- (the 4- benzene for the THF (8ml) for being dissolved in water removal
Base -4,5- dihydro-oxazole -2- bases) in bicyclic [the 2.2.1] -2- enanthol (0.3g, 1.0mmol) of -7,7- dimethyl, back flow reaction 2
~4h, then it is cooled at room temperature, diphenyl phosphorus chloride (290mg, 1.31mmol) is slowly added dropwise, after stirring 1h, back flow reaction
7h, after reaction completely, NaH is quenched with absolute ethyl alcohol, after filtering, filtrate product through column chromatography, obtain final product 2- ((1R,
2R, 4R) bicyclic [the 2.2.1] -1- heptyl of -2- diphenylphosphine epoxide -7,7- dimethyl) -4- phenyl -4,5- dihydro-oxazole 0.34g,
Yield is 72%.1H-NMR(501MHz,CDCl3):δ 7.81 (dd, J=12.1,7.6Hz, 4H), 7.53-7.42 (m, 6H),
7.33-7.21 (m, 5H), 5.07 (t, J=8.7Hz, 1H), 4.82 (t, J=6.6Hz, 1H), 4.19 (t, J=9.2Hz, 1H),
3.86 (t, J=7.8Hz, 1H), 2.21 (d, J=13.1Hz, 1H), 2.07 (t, J=10.6Hz, 1H), 1.83 (dd, J=
13.5,7.4Hz, 4H), 1.55 (s, 3H), 1.22 (s, 3H), 1.13 (t, J=8.6Hz, 1H) ppm.
Catalytic activity is tested
1st, using isoprene and styrene as substrate, to the catalyst synthesized by the present embodiment in catalysis asymmetric D iels-
Activity in Alder reactions is tested.
At 0 DEG C, the alkadienes of styrene and 7 times of equivalents is dissolved in organic solvent, adds Cu (OTf)2With it is made
Catalyst, after TLC tracking raw material reactions completely, obtain target product.Table 1 have rated different catalysts dosage and different solvents pair
The influence of Asymmetric Diels-Alder Reaction activity.
Table 1
2nd, using isoprene and styrene as substrate, synthesized catalyst has been investigated at different temperatures to asymmetry
The influence of Diels-Alder reactivities.
At a certain temperature, the isoprene of styrene and 7 times of equivalents is dissolved in organic solvent, adds Cu (OTf)2
With made catalyst (10mol%), after TLC tracking raw material reactions completely, product 5- methyl isophthalic acids are obtained, 2,3,6- tetrahydrochysene -1,1 ' -
Biphenyl.Table 2 have rated under different temperatures, influence of the made catalyst to Asymmetric Diels-Alder Reaction activity.
Table 2
3rd, using isoprene and styrene as substrate, synthesized catalyst is investigated by changing substrate to asymmetry
The stability of Diels-Alder reactions.
At a certain temperature, the alkadienes of styrene and 7 times of equivalents (R) is dissolved in organic solvent, adds Cu
(OTf)2With made catalyst (10mol%), after TLC tracking raw material reactions completely, target product is obtained.Table 3 have rated difference
Under substrate, stability of the made catalyst to Asymmetric Diels-Alder Reaction.
Table 3
Such scheme is only the preferred technical solution of the present invention, but protection scope of the present invention is not limited thereto, according to
The equivalents that technical scheme is done, belong to protection scope of the present invention.
Claims (5)
1. a kind of chiral catalyst, it is characterised in that its chemical name is 2- ((1R, 2R, 4R) -2- diphenylphosphine epoxides -7,7-
Bicyclic [the 2.2.1] -1- heptyl of dimethyl) -4- phenyl -4,5- dihydro-oxazoles, structure is shown below：
2. a kind of preparation method of chiral catalyst as claimed in claim 1, it is characterised in that comprise the following steps that：
(1) ketone group pinic acid and benzene glycinol are reacted to obtain (1R, 4R)-N- benzene glycinol -2- carbonyl -7,7- dimethyl bicyclic
[2.2.1] -1- heptamides；
(2) bicyclic [the 2.2.1] -1- heptamides of (1R, 4R)-N- benzene glycinol -2- carbonyl -7,7- dimethyl and mesyl chloride are existed
Acid binding agent effect is lower to react, and obtains (1S, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) -7,7- dimethyl is bicyclic
[2.2.1] -2-HEPTANONE；
(3) by (1S, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases), bicyclic [the 2.2.1] -2-HEPTANONE of -7,7- dimethyl is also
Original obtains (1R, 2R, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) bicyclic [2.2.1] -2- enanthol of -7,7- dimethyl；
(4) by (1R, 2R, 4R) -1- (4- phenyl -4,5- dihydro-oxazole -2- bases) bicyclic [the 2.2.1] -2- enanthol of -7,7- dimethyl
Reaction obtains chiral catalyst 2- ((1R, 2R, 4R) -2- diphenylphosphine epoxides -7,7- two under alkali effect with diphenyl phosphorus chloride
Methyl bicycle [2.2.1] -1- heptyl) -4- phenyl -4,5- dihydro-oxazoles.
3. preparation method as claimed in claim 2, it is characterised in that in step (2), acid binding agent is selected from triethylamine, diisopropyl
One or both of base ethylenediamine.
4. preparation method as claimed in claim 2, it is characterised in that in step (3), reducing agent uses Lithium Aluminium Hydride.
5. preparation method as claimed in claim 2, it is characterised in that in step (4), alkali is potassium tert-butoxide or sodium hydride.
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Non-Patent Citations (3)
| Title |
|---|
| "有机双功能团小分子催化剂的研究进展";潘聪等;《广州化工》;20101231;第38卷(第7期);第24-27页 * |
| "有机小分子催化剂在硝基烯类化合物与醛酮的不对称 Michael加成反应中的应用探究";田洪迎等;《辽宁化工》;20130531;第42卷(第5期);第452-455页 * |
| "樟脑衍生的噁唑啉配体的合成与表征";冯萧;《中国优秀硕士学位论文全文数据库 工程科技I辑》;20130115(第1期);第1-45页 * |
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