CN104803829A - Method of asymmetrically compounding chirality diaryl methyl alcohol - Google Patents
Method of asymmetrically compounding chirality diaryl methyl alcohol Download PDFInfo
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- CN104803829A CN104803829A CN201510164776.1A CN201510164776A CN104803829A CN 104803829 A CN104803829 A CN 104803829A CN 201510164776 A CN201510164776 A CN 201510164776A CN 104803829 A CN104803829 A CN 104803829A
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- Prior art keywords
- chirality
- diarylcarbinols
- compounding
- methyl alcohol
- asymmetrically
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- 0 C[*+]C(c1ccccc1)=O Chemical compound C[*+]C(c1ccccc1)=O 0.000 description 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group
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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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a method of asymmetrically compounding diaryl methyl alcohol. The equation of the compounding method refers to the Specification. In the equation, R1 and R2 are groups in an aromatic ring; a catalyzer is chirality nitrogen heterocycle ferrocene carbene salt; alkali is acetate, carbonate, bicarbonate, organic amine of alkali metal and the like. The method provides a novel and efficient method high in stereoselectivity for asymmetrical compound of chirality diaryl methyl alcohol.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of method of asymmetric synthesis chirality diarylcarbinols.
Background technology
Chirality diarylcarbinols is the important intermediate of a class and molecule fragment, be present in widely and natural and non-naturally have in the molecule of physiology and pharmacologically active, also can be used for synthesis and there is bioactive compound or medicine as diuretic(s), thymoleptic, local anesthetic, the agent of resistance amine etc.; Because chirality diarylcarbinols is of many uses, therefore, the very big concern that method that highly-solid selectively prepares diarylcarbinols causes vast chemist is studied.
It is arylation reaction by aromatic aldehyde and aryl transfering reagent that the main method of common asymmetry catalysis synthesis of diaryl methyl alcohol can be summarized as two kinds: one; Two is the asymmetric reductions by asymmetric two arone; In first method, be considered to one of most effective means always and be one challenge with the method that aromatic aldehyde and aryl boric acid cheap and easy to get prepare chirality diarylcarbinols for raw material, because the aryl boric acid in this method has cheap, functional group compatibility is good, to water and air-stable, the lower grade of toxicity a little, but this method generally need be prepared arylzinc reagent and carries out nucleophilic addition(Adn) as zinc ethyl etc. carries out metal exchange original position to aromatic aldehyde with excessive (more than general 7 equivalents) metal reagent, and ee value is not high.
Bibliographical information is had no for the method for boric acid to the nucleophilic addition(Adn) synthesis of chiral diarylcarbinols of aromatic aldehyde realizing rhodium catalysis with N-heterocyclic carbine salt.
Summary of the invention
The invention provides a kind of method of asymmetric synthesis chirality diarylcarbinols, the method does not need metal exchange original position excessive greatly to prepare arylzinc reagent, only needs the chirality of the rhodium of 0.5% equivalent and 0.2 ~ 2% equivalent carbene catalyzed; The ee value of the compound obtained by the method is higher.
Technical scheme of the present invention is summarized as follows:
By aromatic aldehyde and aryl boric acid in organic solvent, under the rhodium of 0.5% equivalent and the chirality nitrogen heterocyclic ferrocene Cabbeen effect of 0.2 ~ 2%% equivalent, aromatic aldehyde and aryl boric acid effect, i.e. obtained optically pure diarylcarbinols after aftertreatment.
Synthetic route is:
In described reactant and product, R
1and R
2for hydrogen, C
1~ C
6alkyl, halogen, C
1~ C
4haloalkyl, C
1~ C
6alkoxyl group, nitro etc.
Described catalyzer is chirality nitrogen heterocyclic ferrocene Cabbeen salt, and structure is:
Wherein, R
3for hydrogen, C
1~ C
4alkyl, C
1~ C
4haloalkyl, C
1~ C
4alkoxyl group, halogen etc.; R
4for C
1~ C
4alkyl, C
1~ C
4haloalkyl, C
1~ C
4alkoxyl group, aryl etc.
This chirality nitrogen heterocyclic ferrocene carbone catalyst catalytic efficiency is high, and its consumption is only 0.2 ~ 2% of aromatic aldehyde amount of substance.
Described alkali is alkali-metal acetate, carbonate, supercarbonate, organic amine etc., and its consumption is 0.5 ~ 10% of aromatic aldehyde amount of substance.
Described solvent is the conventional organic solvents such as tetrahydrofuran (THF), toluene, benzene, methylene dichloride, ethylene dichloride, acetonitrile, organic ether.
Present method enantioselectivity is higher, and the ee value of the diarylcarbinols prepared by present method reaches more than 90%, and the synthesis for chirality diarylcarbinols provides a kind of efficient and method of asymmetric synthesis that stereoselectivity is high.
Embodiment
Below in conjunction with specific embodiment, further illustrate the present invention; Should be understood that these embodiments are only not used in for illustration of the present invention to limit the scope of the invention.
Raw material used in embodiment or reagent, except special instruction, are analytical pure.
The synthesis of embodiment 1 (S)-2-chloro-phenyl-phenylcarbinol
Reaction formula is:
Under nitrogen protection, by 5mmol phenyl aldehyde and 5.5mmol 2-chlorophenylboronic acid, 0.1mmol Cs
2cO
3, 0.05mmol chirality nitrogen heterocyclic ferrocene salt and 0.025mmol rhodium compound add in strict dry reaction flask, then the 5mL methylene dichloride of absolute injected reaction flask, sealing bottle cork, stirring reaction 6h at 50 DEG C, stop stirring, 5mL water is added, then stirring reaction 1h.Filter, separate organic layer, water layer washed with dichloromethane twice, merge organic layer, anhydrous sodium sulfate drying, pressure reducing and steaming solvent, obtains crude product, and crude product, by silicagel column separating-purifying, obtains product, yield: 90%.
By above-mentioned for trace obtained compound dissolution in isopropanol-hexane (3: 7) solvent, adopt Chiral liquid chromatography OD-H column chromatography, recording ee value is 91%;
1h NMR (400Hz, ppm): 2.32 (s, 1H, OH), 6.24 (d, J=3.5Hz, 1H, CH), 7.17-7.31 (m, 8H, ArH), 7.41-7.53 (m, 1H, ArH).
The synthesis of embodiment 2 (S)-2-bromophenyl-4-methylbenzyl alcohol
Reaction formula is:
Under nitrogen protection; 5mmol 4-tolyl aldehyde and 5.5mmol 2-bromophenylboronic acid, 0.15mmol KOAc, 0.06mmol chirality nitrogen heterocyclic ferrocene salt and 0.025mmol rhodium compound are added in strict dry reaction flask; then the 5mL toluene of absolute is injected reaction flask; sealing bottle cork; stirring reaction 7h at 45 DEG C; stop stirring, 5mL water is added, then stirring reaction 1h.Filter, separate organic layer, water layer toluene wash twice, merge organic layer, anhydrous sodium sulfate drying, pressure reducing and steaming solvent, obtains crude product, and crude product, by silicagel column separating-purifying, obtains product, yield: 87%.
By above-mentioned for trace obtained compound dissolution in isopropanol-hexane (3: 7) solvent, adopt Chiral liquid chromatography OD-H column chromatography, recording ee value is 94%;
1h NMR (400Hz, ppm): 2.33 (s, 1H, OH), 2.36 (s, 3H, CH3), 6.16 (s, 1H, CH), 7.12-7.18 (m, 3H, ArH), 7.27-7.35 (m, 3H, ArH), (7.47-7.53 m, 1H, ArH), (7.60-7.72 m, 1H, ArH).
Claims (3)
1. a method for asymmetric synthesis chirality diarylcarbinols, is characterized in that the reaction formula of this synthetic method is:
In described reaction formula, R
1and R
2for hydrogen, C
1~ C
6alkyl, halogen, C
1~ C
4haloalkyl, C
1~ C
6alkoxyl group, nitro.
2. the method for a kind of asymmetric synthesis diarylcarbinols according to claim 1, is characterized in that: described catalyzer is chirality nitrogen heterocyclic ferrocene Cabbeen salt, and its structure is:
Wherein, R
3for hydrogen, C
1~ C
4alkyl, C
1~ C
4haloalkyl, C
1~ C
4alkoxyl group, halogen; R
4for C
1~ C
4alkyl, C
1~ C
4haloalkyl, C
1~ C
4alkoxyl group, aryl; Its consumption is 0.2 ~ 2% of aromatic aldehyde amount of substance.
3. the method for a kind of asymmetric synthesis diarylcarbinols according to claim 1, is characterized in that: described alkali is alkali-metal acetate, carbonate, supercarbonate, organic amine; And its consumption is 0.5 ~ 10% of aromatic aldehyde amount of substance.
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|---|---|---|---|
| CN201510164776.1A CN104803829B (en) | 2015-03-31 | 2015-03-31 | A kind of method of asymmetric syntheses chirality diarylcarbinols |
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|---|---|---|---|
| CN201510164776.1A CN104803829B (en) | 2015-03-31 | 2015-03-31 | A kind of method of asymmetric syntheses chirality diarylcarbinols |
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| CN104803829B CN104803829B (en) | 2017-12-12 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105906649A (en) * | 2016-05-12 | 2016-08-31 | 淮海工学院 | Method for asymmetric synthesis of spiro-lactone compound containing chiral 5-hydroxy flavone unit |
| CN106831550A (en) * | 2017-01-17 | 2017-06-13 | 三峡大学 | A kind of optical activity two（It is miscellaneous）Aryl methyl alcohol and its method of asymmetric synthesis |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003048895A (en) * | 2001-08-01 | 2003-02-21 | Daiso Co Ltd | Determination method for absolute configuration of optically active substance |
| CN103102485A (en) * | 2013-01-31 | 2013-05-15 | 商丘师范学院 | Chiral ferrocene methylene aza-small cyclic amino alcohol ligand as well as synthetic method and application thereof |
-
2015
- 2015-03-31 CN CN201510164776.1A patent/CN104803829B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003048895A (en) * | 2001-08-01 | 2003-02-21 | Daiso Co Ltd | Determination method for absolute configuration of optically active substance |
| CN103102485A (en) * | 2013-01-31 | 2013-05-15 | 商丘师范学院 | Chiral ferrocene methylene aza-small cyclic amino alcohol ligand as well as synthetic method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| ALOIS FUè RSTNER等: "Practical Method for the Rhodium-Catalyzed Addition of Aryl- and Alkenylboronic Acids to Aldehydes", 《ADV. SYNTH. CATAL.》 * |
| 古丽娜等: "手性氮杂卡宾金属络合物的合成及其在不对称催化反应中的应用", 《有机化学》 * |
| 张冲等: "氮杂环卡宾铁配合物的研究", 《化学工程师》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105906649A (en) * | 2016-05-12 | 2016-08-31 | 淮海工学院 | Method for asymmetric synthesis of spiro-lactone compound containing chiral 5-hydroxy flavone unit |
| CN106831550A (en) * | 2017-01-17 | 2017-06-13 | 三峡大学 | A kind of optical activity two（It is miscellaneous）Aryl methyl alcohol and its method of asymmetric synthesis |
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| Publication number | Publication date |
|---|---|
| CN104803829B (en) | 2017-12-12 |
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