CN115073399B - Cinchona alkaloid catalyst and method for preparing chiral beta-butyrolactone compound from cinchona alkaloid catalyst - Google Patents

Cinchona alkaloid catalyst and method for preparing chiral beta-butyrolactone compound from cinchona alkaloid catalyst Download PDF

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CN115073399B
CN115073399B CN202210733914.3A CN202210733914A CN115073399B CN 115073399 B CN115073399 B CN 115073399B CN 202210733914 A CN202210733914 A CN 202210733914A CN 115073399 B CN115073399 B CN 115073399B
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catalyst
ketene
reaction
borane
aldehyde
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CN115073399A (en
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黄文学
张明
赵付龙
杨树武
张永振
黎源
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Wanhua Chemical Group Co Ltd
Wanhua Chemical Sichuan Co Ltd
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Wanhua Chemical Sichuan Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
    • C07D305/02—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D305/10—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having one or more double bonds between ring members or between ring members and non-ring members
    • C07D305/12—Beta-lactones
    • 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
    • B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
    • B01J31/14—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides of aluminium or boron
    • B01J31/146—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides of aluminium or boron of boron
    • 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
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/027—Organoboranes and organoborohydrides
    • 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
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N

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Abstract

The invention provides a cinchona alkaloid catalyst and a method for preparing chiral beta-butyrolactone compounds from the cinchona alkaloid catalyst. The method comprises the following steps: carrying out hydroboration reaction on cinchona alkaloid and borane to prepare a cinchona alkaloid derived difunctional catalyst; the catalyst catalyzes aldehyde and ketene compound to generate [2+2] addition reaction to obtain chiral beta-butyrolactone compound. The catalyst is a novel difunctional catalyst containing Lewis base (N) active center and Lewis acid (B) active center, and can be applied to catalyzing an aldehyde and ketene [2+2] addition reaction to obtain chiral beta-butyrolactone derivatives. The catalyst has the advantages of short preparation process, convenient operation and low cost; the catalyst improves the activity and yield of the addition reaction of aldehyde and ketene [2+2], and the product has excellent chiral control.

Description

Cinchona alkaloid catalyst and method for preparing chiral beta-butyrolactone compound from cinchona alkaloid catalyst
Technical Field
The invention belongs to the field of fine chemical engineering, and in particular relates to a cinchona alkaloid catalyst and a method for preparing chiral beta-butyrolactone compounds from the cinchona alkaloid catalyst.
Background
Cinchona alkaloid, also called cinchona frost, cinchona alkaloid and the like, is a natural alkaloid and mainly derived from bark of cinchona trees and plants of the same genus. Cinchona alkaloid is generally white particles or microcrystalline powder and has breeze property; no smell, bitter taste. Is easily dissolved in organic solvents such as ethanol, chloroform, dichloromethane, etc., and can form salts with a plurality of acids. According to analysis and detection, the cinchona alkaloid bark contains more than 30 kinds of active alkaloids, the largest content of which is quinine, and the second is quinidine, cinchonidine, cinchonine and the like. As early as 19 th century, cinchona alkaloid has been found to have good antimalarial efficacy, and later researches have found that quinine is the main active ingredient, and the preparation can eliminate the propagation of various malaria parasites and stop malaria attacks. Since the 21 st century, organic micromolecule catalysis has emerged, and cinchona alkaloid can be used as an organic micromolecule catalyst due to the unique chiral structure and low cost source.
Chiral beta-butyrolactone structures are widely existing in many natural products, and are also very important synthetic intermediates due to the fact that quaternary ring structures have large ring tension and active chemical properties. The [2+2] cycloaddition of ketene to carbonyl compounds (aldehydes, ketones, etc.) is one of the simplest and efficient ways to synthesize β -butyrolactone, which has been discovered for a long time, but chiral [2+2] cycloaddition of ketene to carbonyl compounds has not been reported until recently. In 1982, wynberg and Staring et al used quinidine as a catalyst to achieve asymmetric [2+2] cycloaddition of ketene and chloral, and the ee value of the product was as high as 93%; unfortunately, this catalytic system is only effective for activated aldehydes, ketones, i.e. the alpha position of the carbonyl group is substituted with at least two or more chlorine atoms, and the substrate application range is limited (H.Wynberg, E.G.J.Staring, J.Am.Chem.Soc.1982,104,166).
In 2004, nelson et al developed and improved the Wynberg method by using trimethylsilyl protected quinine (10 mol%) and lithium perchlorate (15-300 mol%) as a catalyst to efficiently achieve a series of [2+2] asymmetric cycloaddition reactions of ketene substrates and simple aldehydes, greatly expanding the substrate use range of the reaction (C.Zhu, X.Shen, S.G.Nelson, J.Am.Chem.Soc.2004,126,5352.). The catalyst system requires a large amount of expensive lithium perchlorate, and the catalyst cost is high. Fu et al reported in 2004 a chiral DMAP-type catalyst and applied it in the [2+2] cycloaddition of disubstituted ketene and aldehyde to give highly stereoselective α -disubstituted β -butyrolactone; the solvent tetrahydrofuran and extremely low reaction temperature (-78 ℃) are necessary conditions for achieving high selectivity (J.E.Wilson, G.C.Fu, angew.Chem.Int.Ed.2004,43,6358;Angew.Chem.2004,116,6518.). In 2010, kerrigan et al used chiral phosphine ligands for catalyzing [2+2] cycloaddition of disubstituted ketene and aromatic aldehyde, the R-BinaPhane catalyst was most effective, and the reaction was carried out at-78 ℃ to obtain α -disubstituted β -butyrolactone in moderate yields (M.Mondal, A.A.Ibrahim, K.A.Wheeler, N.J.Kerrigan, org.Lett.2010,12,1664.).
In conclusion, the [2+2] cycloaddition reaction of ketene and aldehyde stereoselectivity is the simplest and efficient synthesis method for synthesizing chiral beta-butyrolactone, and researchers at home and abroad also conduct a great deal of research on the reaction, but the reaction has the defects of large catalyst consumption, harsh reaction conditions and the like at present. Chiral beta-butyrolactone is an important synthetic intermediate, and in order to obtain the intermediate more cheaply, a novel catalyst and a novel catalytic system need to be developed, so that the beta-butyrolactone can be prepared under mild conditions and at low cost.
Disclosure of Invention
The invention aims to provide a cinchona alkaloid catalyst and a method for preparing chiral beta-butyrolactone compounds from the cinchona alkaloid catalyst. The catalyst has novel structure, mild preparation condition and simple operation, and can efficiently catalyze the [2+2] cycloaddition reaction of a series of ketene and aldehyde derivatives, thereby obtaining chiral beta-butyrolactone derivatives with high yield and high selectivity.
In order to achieve the above purposes and achieve the above technical effects, the present invention adopts the following technical scheme:
a process for preparing chiral β -butyrolactone compounds by an addition reaction, the process comprising the steps of:
s1: carrying out hydroboration reaction on cinchona alkaloid and borane to prepare a cinchona alkaloid derived difunctional catalyst;
s2: the catalyst of S1 catalyzes aldehyde and ketene compound to generate [2+2] addition reaction to obtain chiral beta-butyrolactone compound.
Wherein the cinchona alkaloid derived difunctional catalyst is prepared from cinchona alkaloid serving as a raw material. The novel bifunctional catalyst containing Lewis base (N) active center and Lewis acid (B) active center is obtained by carrying out in-situ borohydride reaction on cinchona base and borane serving as raw materials, and further chiral beta-butyrolactone compound can be prepared by catalytic addition reaction. The boron atom in the catalyst activates aldehyde carbonyl and tertiary amine activates ketene, and the two are in synergistic catalysis, so that the activity and the yield of the addition reaction of ketene and aldehyde [2+2] are greatly improved, the yield of the product beta-butyrolactone is high, and the chiral control is good.
The reaction for preparing the S1 catalyst is schematically shown as follows:
the route of the S2 reaction is schematically as follows:
in the invention, the cinchona alkaloid S1 is one or more of quinine, quinidine, cinchonine and cinchonine.
In the invention, the borane in S1 is one or more of disubstituted boranes, preferably bis (pentafluorophenyl) borane and/or diphenyl borane; preferably, the molar ratio of cinchona alkaloid to borane is 1:1.0-1.5.
In the present invention, the hydroboration reaction of S1 is carried out in the presence of a solvent, preferably one or more of toluene, xylene, methyl tertiary butyl ether, ethyl acetate, methylene chloride, chloroform, dichloroethane, ethyl acetate, butyl acetate, acetone, butanone, methyl tertiary butyl ketone.
In the invention, the reaction temperature of the S1 is room temperature, and the reaction time is 5-20 min.
In the invention, the catalyst dosage in the addition reaction of S2 is 0.1-1.0% of the molar quantity of aldehyde substrate.
In the invention, the aldehyde in S2 is fatty aldehyde and/or aromatic aldehyde, preferably one or more of benzaldehyde, 2-methylbenzaldehyde, 2-chlorobenzaldehyde, n-butyraldehyde, acetaldehyde and propionaldehyde.
In the invention, the ketene compound in S2 is a compound containing a vinyl ketone structure, preferably one or more of ketene, methyl ketene, trimethylsilyl ketene, dimethyl ketene, diphenyl ketene and methyl phenyl ketene; preferably, the molar ratio of aldehyde to ketene compound is from 1:1.0 to 1.2, preferably a slight excess of ketene substrate, for example, may preferably be from 1:1.01 to 1.10.
In the present invention, the reaction of S2 is performed in the presence of a solvent, preferably an aprotic solvent, more preferably one or more solvents selected from toluene, xylene, methyl tertiary butyl ether, ethyl acetate, methylene chloride, chloroform, dichloroethane, ethyl acetate, butyl acetate, acetone, butanone, and methyl tertiary butyl ketone.
In the invention, the temperature of the addition reaction of S2 is 0-50 ℃; the reaction pressure is normal pressure; the reaction time is 1-6 h.
Another object of the present invention is to provide a cinchona-derived bifunctional catalyst.
The cinchona alkaloid derived difunctional catalyst is prepared by the method, and the catalyst is a product of a boration reaction between cinchona alkaloid and borane.
In the invention, the catalyst raw material cinchona alkaloid is one or more of quinine, quinidine, cinchonine and cinchonine.
In the invention, the catalyst raw material borane is one or more of disubstituted boranes, preferably di (pentafluorophenyl) borane and/or diphenyl borane.
It is a further object of the present invention to provide the use of a cinchona-derived bifunctional catalyst.
The use of a cinchona alkaloid derived difunctional catalyst, wherein the catalyst is prepared by the method or is used for catalyzing an aldehyde and ketene compound to generate [2+2] addition reaction to prepare a chiral beta-butyrolactone compound.
It is still another object of the present invention to provide a chiral β -butyrolactone compound.
A chiral β -butyrolactone compound prepared by the method described above, or obtained by catalytic reaction using the catalyst described above, wherein the aldehyde is one or more of aliphatic aldehyde and/or aromatic aldehyde, preferably benzaldehyde, 2-methylbenzaldehyde, 2-chlorobenzaldehyde, n-butyraldehyde, acetaldehyde and propionaldehyde, and the ketene compound is one or more of ketene, preferably ketene, methyl ketene, trimethylsilyl ketene, dimethyl ketene, diphenyl ketene and methyl phenyl ketene.
In the present invention, the pressures are gauge pressures unless otherwise indicated.
Compared with the prior art, the invention has the following positive effects:
1. the method takes natural cinchona alkaloid as a raw material, the catalyst is prepared in situ and is used for catalytic reaction, the yield can reach 99%, the ee value of the product beta-butyrolactone can reach 97%, the operation is convenient, and the cost is low.
2. The boron atom in the catalyst activates aldehyde carbonyl and tertiary amine activates ketene, and the two are in synergistic catalysis, so that the activity and the yield of the addition reaction of ketene and aldehyde [2+2] are greatly improved, the yield of the product beta-butyrolactone is high, and the chiral control is good.
3. The reaction conditions are mild, the reaction temperature is even as high as 0 ℃ or normal temperature, which is superior to most of the existing literature reports, and the method is convenient to operate and easy to amplify.
Detailed Description
The present invention will be described in detail with reference to examples, but the present invention is not limited to the examples.
The main raw material information is as follows:
benzaldehyde, 2-methylbenzaldehyde, 2-chlorobenzaldehyde, n-butyraldehyde, carbofuran, 99%; acetaldehyde, propionaldehyde, AR, national drugs; dichloromethane, toluene, dichloroethane, AR, alaa Ding Shiji; quinine, quinidine, cinchonine, and carbofuran reagent, purity 98-99%; bis (pentafluorophenyl) borane, milin, 98%. Ketene, dimethylketene, 98%, wanhua chemistry (acetic anhydride and isobutyric anhydride cleavage products, respectively).
3,3' -bis (triphenylsilyl) -binaphthol, 98%, carbofuran; trimethylaluminum, 98%, enokak.
Mass spectrometry instrument information: applied Biosystems Mariner System 5303HRMS.
The gas chromatography test conditions of the present invention are as follows:
instrument model: agilent 7890B; chromatographic column: capillary column DB-3 (40 m 0.30mm 0.25 μm); the initial temperature is 50 ℃, and the temperature is increased to 110 ℃ at the speed of 10 ℃/min; then the temperature is raised to 180 ℃ at the speed of 5 ℃/min and kept for 9min. The carrier gas is high-purity nitrogen, the split ratio is 40:1, and the split flow is 45mL/min. Carrier gas saving: 20mL/min, and a wait time of 2min was started. The sample injection temperature is 280 ℃, the detector is FID, the detector temperature is 280 ℃, the air flow rate is 350mL/min, the hydrogen flow rate is 35mL/min, the tail blowing flow rate is 30mL/min, and the sample injection amount is 0.2 mu L.
Example 1
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of benzaldehyde and ketene.
At room temperature, adding a magnetic rotor into a 500mL three-mouth bottle after drying, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.24 g,0.8 mmol) was weighed into a chiral box and placed in a single-mouth bottle, anhydrous dichloromethane (20 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.42 g,1.2 mmol) was slowly added, after stirring for 20 minutes, the single-mouth bottle was sealed, the glove box was taken out, and nitrogen sphere was protected. The resulting catalyst solution was added by syringe to a 500mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (80 mL) and reaction raw material benzaldehyde (31.8 g,0.3 mol) were sequentially added, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.2mol/h for a total of 0.33mol with nitrogen. The vinyl ketone is stopped from being introduced, the reaction is continued for 1h at the temperature of 0 ℃, the GC sampling detection is carried out, the raw material benzaldehyde is basically reacted completely, and the yield of the product 4-phenylpropiolactone is 94%, and the ee value is 80%. High resolution mass spectrum HRMS-EI M of catalyst prepared from quinine and bis (pentafluorophenyl) borane in situ + calcd C32H25BF10N2O2:670.1849,found 670.1851。
Example 2
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of benzaldehyde and ketene.
At room temperature, adding a magnetic rotor into a 100mL three-mouth bottle after drying, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.32 g,1.0 mmol) was weighed into a chiral box and placed into a single-mouth bottle, anhydrous dichloromethane (10 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.42 g,1.2 mmol) was slowly added, stirring was performed for 20 minutes, and after stirring, the single-mouth bottle was sealed, the glove box was taken out and protected with nitrogen balls. The resulting catalyst solution was added by syringe to a 100mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (20 mL) and reaction raw material benzaldehyde (10.6 g,0.1 mol) were sequentially added, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.12mol with nitrogen. Stopping the introduction of ketene, continuing the reaction for 1h at 0 ℃, sampling and detecting by GC, wherein the raw material benzaldehyde is basically reacted completely, and the yield of the product 4-phenylpropiolactone is 99%, and the ee value is 82%.
Example 3
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of benzaldehyde and ketene.
At room temperature, adding a magnetic rotor into a 500mL three-mouth bottle after drying, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.19 g,0.6 mmol) was weighed into a chiral box and placed into a single-mouth bottle, anhydrous dichloroethane (10 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.25 g,0.7 mmol) was slowly added, after stirring for 20 minutes, the single-mouth bottle was sealed, the glove box was taken out, and nitrogen sphere was used for protection. The resulting catalyst solution was added by syringe to a 500mL three-necked flask which had been replaced with nitrogen gas in advance, followed by sequential addition of solvent dichloroethane (180 mL) and reaction raw material benzaldehyde (63.7 g,0.6 mol), stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.3mol/h for a total of 0.66mol with nitrogen. The vinyl ketone is stopped from being introduced, the reaction is continued for 1h at 50 ℃, the GC sampling detection is carried out, the raw material benzaldehyde is basically reacted completely, and the yield of the product 4-phenylpropiolactone is 87%, and the ee value is 76%.
Example 4
Quinidine and-bis (pentafluorophenyl) borane catalyze the reaction of benzaldehyde and ketene.
At room temperature, adding a magnetic rotor into 200mL of dried three-mouth bottle, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths at two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbling device for preventing reverse suction, and placing anhydrous acetic acid in the bubbling device. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinidine (0.24 g,0.8 mmol) was weighed into a chiral box and placed in a single-necked flask, anhydrous dichloromethane (20 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.31 g,0.9 mmol) was slowly added, after stirring for 20 minutes, the single-necked flask was sealed, the glove box was taken out, and nitrogen sphere was used for protection. The resulting catalyst solution was added by syringe to a 200mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (80 mL) and reaction raw material benzaldehyde (31.8 g,0.3 mol) were sequentially added, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.33mol with nitrogen. Stopping the introduction of ketene, continuing the reaction for 1h at 0 ℃, sampling and detecting by GC, wherein the raw material benzaldehyde is basically reacted completely, and the yield of the product 4-phenylpropiolactone is 93%, and the ee value is-80%.
Example 5
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of 2-methylbenzaldehyde with ketene.
At room temperature, adding a magnetic rotor into 200mL of dried three-mouth bottle, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths at two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbling device for preventing reverse suction, and placing anhydrous acetic acid in the bubbling device. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.24 g,0.8 mmol) was weighed into a chiral box and placed in a single-mouth bottle, anhydrous dichloromethane (20 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.31 g,0.9 mmol) was slowly added, after stirring for 20 minutes, the single-mouth bottle was sealed, the glove box was taken out, and nitrogen sphere was protected. The resulting catalyst solution was added by syringe to a 200mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (80 mL) and the reaction raw material 2-methylbenzaldehyde (36.0 g,0.3 mol) were sequentially added, stirring was turned on, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.33mol with nitrogen. Stopping vinyl ketone to be introduced, continuing to react for 1h at 0 ℃, sampling and detecting by GC, wherein the raw material 2-methylbenzaldehyde is basically reacted completely, and the yield of the product 4- (2-methylphenyl) propiolactone is 96%, and the ee value is 95%.
Example 6
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of 2-chlorobenzaldehyde and ketene.
At room temperature, adding a magnetic rotor into 200mL of dried three-mouth bottle, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths at two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbling device for preventing reverse suction, and placing anhydrous acetic acid in the bubbling device. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinidine (0.24 g,0.8 mmol) was weighed into a chiral box and placed in a single-necked flask, anhydrous dichloromethane (20 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.31 g,0.9 mmol) was slowly added, after stirring for 20 minutes, the single-necked flask was sealed, the glove box was taken out, and nitrogen sphere was used for protection. The resulting catalyst solution was added by syringe to a 200mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (80 mL) and 2-chlorobenzaldehyde (42.2 g,0.3 mol) as reaction materials were sequentially added, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.33mol with nitrogen. The vinyl ketone is stopped from being introduced, the reaction is continued for 1h at 5 ℃, the GC sampling detection is carried out, the raw material 2-chlorobenzaldehyde is basically reacted completely, the yield of the product 4- (2-chlorophenyl) propiolactone is 95%, and the ee value is 96%.
Example 7
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of acetaldehyde and ketene.
At room temperature, adding a magnetic rotor into 250mL of dried three-mouth bottle, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.24 g,0.8 mmol) was weighed into a chiral box and placed in a single-necked flask, anhydrous dichloromethane (20 mL) was added, stirring was turned on to dissolve quinine, then bis (pentafluorophenyl) borane (0.35 g,1.0 mmol) was slowly added, stirring was performed for 20 minutes, the single-necked flask was sealed, the glove box was removed, and nitrogen sphere was used for protection. The resulting catalyst solution was added by syringe to a 250mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (60 mL) and acetaldehyde (11.0 g,0.25 mol) as reaction raw materials were sequentially added, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.29mol with nitrogen. Stopping ketene feeding, continuing reacting for 1h at 0 ℃, sampling and detecting by GC, wherein the raw material acetaldehyde basically reacts completely, and the yield of the product beta-butyrolactone is 95%, and the ee value is 71%.
Example 8
Cinchonine and bis (pentafluorophenyl) borane catalyze the reaction of acetaldehyde and ketene.
At room temperature, adding a magnetic rotor into a 500mL three-mouth bottle after drying, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Cinchonine (0.39 g,1.2 mmol) was weighed into a chiral box and placed in a single-necked flask, anhydrous dichloromethane (20 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.55 g,1.6 mmol) was slowly added, after stirring for 20 minutes, the single-necked flask was sealed, the glove box was taken out, and nitrogen sphere was used for protection. The resulting catalyst solution was added by syringe to a 500mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (120 mL) and reaction raw material acetaldehyde (17.6 g,0.4 mol) were sequentially added, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.46mol with nitrogen. Stopping ketene feeding, continuing reacting for 1h at 0 ℃, sampling and detecting by GC, wherein the raw material acetaldehyde basically reacts completely, and the yield of the product beta-butyrolactone is 93%, and the ee value is 67%.
Example 9
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of propionaldehyde and ketene.
At room temperature, adding a magnetic rotor into 250mL of dried three-mouth bottle, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.24 g,0.8 mmol) was weighed into a chiral box and placed into a single-mouth bottle, anhydrous toluene (30 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.31 g,1.2 mmol) was slowly added, after stirring for 20 minutes, the single-mouth bottle was sealed, the glove box was taken out, and nitrogen sphere was used for protection. The resulting catalyst solution was added by syringe to a 250mL three-necked flask, which had been replaced with nitrogen gas in advance, followed by sequential addition of toluene (30 mL) as a solvent and propionaldehyde (8.7 g,0.15 mol) as a reaction raw material, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.18mol with nitrogen. The vinyl ketone is stopped from being introduced, the reaction is continued for 1h at the temperature of 0 ℃, the GC sampling detection is carried out, the raw material propionaldehyde is basically reacted completely, the yield of the product 4-ethyl propiolactone is 95%, and the ee value is 71%.
Example 10
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of butyraldehyde and ketene.
At room temperature, adding a magnetic rotor into 250mL of dried three-mouth bottle, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.24 g,0.8 mmol) was weighed into a chiral box and placed in a single-mouth bottle, anhydrous dichloromethane (20 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.31 g,1.2 mmol) was slowly added, after stirring for 20 minutes, the single-mouth bottle was sealed, the glove box was taken out, and nitrogen sphere was protected. The resulting catalyst solution was added by syringe to a 250mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (40 mL) and butyraldehyde (10.8 g,0.15 mol) as reaction materials were added in this order, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and the reactor was slowly purged with ketene gas at a feed rate of 0.1mol/h for a total of 0.18mol with nitrogen. The vinyl ketone is stopped from being introduced, the reaction is continued for 1h at the temperature of 0 ℃, the raw material butyraldehyde is subjected to GC sampling detection, the basic reaction is complete, and the yield of the product 4-propyl propiolactone is 95%, and the ee value is 74%.
Example 11
Quinine and-bis (pentafluorophenyl) borane catalyze the reaction of butyraldehyde and dimethylketene.
At room temperature, adding a magnetic rotor into 250mL of dried three-mouth bottle, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. Quinine (0.23 g,0.7 mmol) was weighed into a chiral box and placed in a single-mouth bottle, anhydrous dichloromethane (20 mL) was added, stirring was started to dissolve quinine, then bis (pentafluorophenyl) borane (0.29 g,0.8 mmol) was slowly added, after stirring for 6 minutes, the single-mouth bottle was sealed, the glove box was taken out, and nitrogen sphere was protected. The resulting catalyst solution was added by syringe to a 250mL three-necked flask which had been replaced with nitrogen gas in advance, then solvent methylene chloride (40 mL) and butyraldehyde (10.1 g,0.14 mol) as reaction materials were added in this order, stirring was started, and the three-necked flask was placed in an ice-water bath so that the temperature in the flask was maintained at 0 ℃. A nitrogen inlet was connected to the ketene generator, and a dimethylketene gas was slowly introduced into the reaction flask, with a nitrogen drive, at a dimethylketene feed rate of 0.1mol/h, and a total of 0.18mol. Stopping the dimethyl ketene from being introduced, continuing to react for 5 hours at the temperature of 0 ℃, sampling and detecting by GC, wherein the butyraldehyde as a raw material is basically reacted completely, and the yield of the 3, 3-dimethyl 4-propyl propiolactone is 82%, and the ee value is 86%.
Comparative example 1
3,3'-bis (triphenylsilyl) -binaphthol (3, 3' -bis (triphenylsilyl) - [1,1 '-binaphthene ] -2,2' -diol) and trimethylaluminum catalyze the reaction of benzaldehyde and ketene (ref. J. Chem. Soc., perkin trans.1,1994, 1549-1550.).
At room temperature, adding a magnetic rotor into a 500mL three-mouth bottle after drying, sealing a middle bottle mouth by using a rubber plug, facilitating feeding, respectively connecting an air inlet conduit and an air outlet conduit with the bottle mouths on two sides, connecting nitrogen with the air inlet conduit, connecting an air outlet conduit with a bubbler for preventing reverse suction, and placing anhydrous acetic acid in the bubbler. After readiness, the entire system was purged with nitrogen for 20 minutes to displace the air in the bottle thoroughly. 3,3' -bis (triphenylsilyl) -binaphthol (2.81 g,3.5 mmol) was weighed into a chiral box and placed in a 250mL single-necked flask, anhydrous toluene (100 mL) was added, stirring was started to dissolve the binaphthol, then trimethylaluminum n-hexane solution (1.75 mL,3.5mmol,2.0 mol/L) was slowly added, and after stirring and reaction for 1 hour, the single-necked flask was sealed, taken out of the glove box and protected by nitrogen balls. The resulting catalyst solution was added with a syringe to a 500mL three-necked flask which had been replaced with nitrogen gas in advance, stirring was started, and the three-necked flask was placed in a dry ice-acetone bath so that the temperature in the three-necked flask was maintained at-78 ℃. Then, benzaldehyde (0.425 g,4.0 mmol) as a reaction raw material was added, a nitrogen inlet was connected to a ketene generator, and a ketene gas was slowly introduced into the reaction flask at a feeding rate of 0.1mol/h under nitrogen driving, and 0.45mol was introduced in total. The ketene is stopped from being introduced into the reaction kettle for continuous reaction for 1h at the temperature of minus 78 ℃, a small amount of benzaldehyde is remained by GC sampling detection, the reaction conversion rate is 87%, the selectivity of 4-phenylpropionic lactone is 90%, and the ee value is 21%.

Claims (14)

1. A process for preparing chiral β -butyrolactone compounds by addition reaction, said process comprising the steps of:
s1: carrying out hydroboration reaction on cinchona alkaloid and borane to prepare a cinchona alkaloid derived difunctional catalyst;
s2: the catalyst of S1 catalyzes aldehyde and ketene compound to generate [2+2] addition reaction to obtain chiral beta-butyrolactone compound.
2. The method of claim 1, wherein S1 the cinchona alkaloid is one or more of quinine, quinidine, cinchonine, cinchonidine;
and/or the borane in the S1 is one or more of disubstituted boranes.
3. The method according to claim 2, wherein S1 said borane is bis (pentafluorophenyl) borane and/or diphenylborane;
the molar ratio of cinchona alkaloid to borane is 1:1.0-1.5.
4. The process according to claim 1 or 2, characterized in that the borohydride reaction of S1 is carried out in the presence of a solvent;
and/or the temperature of the reaction in the step S1 is room temperature, and the reaction time is 5-20 min.
5. The method of claim 4, wherein the solvent of S1 is one or more of toluene, xylene, methyl tertiary butyl ether, ethyl acetate, methylene chloride, chloroform, dichloroethane, ethyl acetate, butyl acetate, acetone, butanone, methyl tertiary butyl ketone.
6. The method according to claim 1, wherein the catalyst is used in the addition reaction in an amount of 0.1 to 1.0% based on the molar amount of aldehyde substrate;
and/or, the aldehyde in S2 is aliphatic aldehyde and/or aromatic aldehyde;
and/or, the vinyl ketone compound in S2 is a compound containing a vinyl ketone structure.
7. The method according to claim 6, wherein the aldehyde S2 is one or more of benzaldehyde, 2-methylbenzaldehyde, 2-chlorobenzaldehyde, n-butyraldehyde, acetaldehyde, propionaldehyde;
and/or, the ketene compound in S2 is one or more of ketene, methyl ketene, trimethylsilyl ketene, dimethyl ketene, diphenyl ketene and methyl phenyl ketene;
the molar ratio of the aldehyde to the ketene compound is 1:1.0-1.2.
8. The process of claim 1, wherein the reaction of S2 is carried out in the presence of a solvent;
and/or the temperature of the addition reaction of S2 is 0-50 ℃; the reaction pressure is normal pressure; the reaction time is 1-6 h.
9. The method of claim 8, wherein the solvent of S2 is an aprotic solvent.
10. The method of claim 9, wherein the solvent of S2 is one or more of toluene, xylene, methyl tertiary butyl ether, ethyl acetate, methylene chloride, chloroform, dichloroethane, ethyl acetate, butyl acetate, acetone, butanone, methyl tertiary butyl ketone.
11. A cinchona-derived bifunctional catalyst prepared by the method of any one of claims 1-10, wherein the catalyst is a product of a hydroboration reaction of cinchona-derived borane.
12. The catalyst according to claim 11, wherein the catalyst raw material cinchona alkaloid is one or more of quinine, quinidine, cinchonine and cinchonidine;
and/or the catalyst raw material borane is one or more of disubstituted boranes.
13. The catalyst according to claim 12, wherein the catalyst starting material borane is di (pentafluorophenyl) borane and/or diphenylborane.
14. Use of a cinchona-derived bifunctional catalyst obtainable by a process according to any one of claims 1 to 10 or as claimed in any one of claims 11 to 13 for the preparation of chiral β -butyrolactone compounds by catalytic [2+2] addition of aldehyde and ketene compounds.
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102971285A (en) * 2010-07-21 2013-03-13 隆萨有限公司 A process for the production of carnitine

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CN102971285A (en) * 2010-07-21 2013-03-13 隆萨有限公司 A process for the production of carnitine

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Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination;Lokasz Górecki et al;Beilstein Journal of Organic Chemistry;第10卷;883-889 *
Asymmetric [2 + 2] cycloaddition of ketene with aldehydes catalyzed by chiral bissulfonamide-trialkylaluminium complexes;Yasufumi Tamai et al;Journal of the Chemical Society, Chemical Communications;第19卷;2281-2282 *
ASYMMETRIC SYNTHESIS OF (S)-METHYL-3-HYDROXYALKANOATES FROM KETENE AND 2,2-DICHLOROALDEHYDES VIA 4-(1,1-DICHLOROALKYL)-2-OXETANONES;Peter E.F. Ketelaar et al;Tetrahedron Letters;第26卷(第38期);4665-4668 *
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Sridhar Chidara et al.Reaction Rate Acceleration Enabled by Tethered Lewis Acid–Lewis Base Bifunctional Catalysis: A Catalytic, Enantioselective [2+2] Ketene Aldehyde Cycloaddition Reaction.SYNLETT.2009,(第10期),1675-1679. *
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