CN109265319B - Preparation method of di (hetero) arylcarbinol compound - Google Patents

Preparation method of di (hetero) arylcarbinol compound Download PDF

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CN109265319B
CN109265319B CN201710582989.5A CN201710582989A CN109265319B CN 109265319 B CN109265319 B CN 109265319B CN 201710582989 A CN201710582989 A CN 201710582989A CN 109265319 B CN109265319 B CN 109265319B
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CN109265319A (en
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樊新衡
陈强
杨联明
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    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/18Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
    • C07C33/24Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part polycyclic without condensed ring systems
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    • C07C213/00Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/06Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
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    • C07C215/68Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
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    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C29/36Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
    • C07C29/38Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
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    • C07C67/00Preparation of carboxylic acid esters
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Abstract

The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a di (hetero) aryl methanol compound. The method of the invention prepares the di (hetero) aryl methanol compound with high yield by using (hetero) aryl aldehyde and (hetero) aryl boric acid which are available in the market as raw materials and using a cheap and stable divalent nickel source as a catalyst. The method of the invention overcomes the defects of harsh reaction conditions, more side reactions, difficult post-treatment and the like of the commonly used metal reagent, and also avoids the defects of high cost and difficult large-scale preparation of catalytic reactions of noble metal palladium and the like. The method has the characteristics of mild conditions, convenient operation, low cost, high efficiency and environmental friendliness, and is convenient to popularize into practical scale-modulus preparation.

Description

Preparation method of di (hetero) arylcarbinol compound
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a di (hetero) aryl methanol compound.
Background
Di (hetero) arylcarbinols are important organic synthesis intermediates, and the most common synthesis method is to prepare the di (hetero) arylcarbinols by reduction of (hetero) aryl ketones or addition of metal reagents such as (hetero) aryl Grignard reagents, (hetero) aryl lithium reagents, organic tin and the like and (hetero) aryl aldehydes. However, the reduction reaction conditions for preparing the bis (hetero) aryl carbinol compound by using the bis (hetero) aryl ketone as a reaction substrate are harsh, and the reduction reaction needs to be carried out under anhydrous conditions, which is not beneficial to large-area popularization. On the other hand, the compatibility of the reaction is not high due to the high activity of the Grignard reagent and the lithium reagent, so that the preparation of complex organic molecules is greatly limited; meanwhile, the application range of the reaction is greatly limited due to the high toxicity of reagents such as organic tin and the like.
The arylboron reagent has the characteristics of good functional group compatibility, stability to water and air, low toxicity and the like, and is widely applied to organic reactions. From 1998 Miyaura et al [ m.sakai, m.ueda, n.miyaura, angelw.chem., int.ed.1998,37,3279.]The transition metal catalyzed addition of arylboronic acids to arylformaldehydes has made a major advance since the rhodium catalyzed addition of arylboronic acids to arylformaldehydes was first reported. However, these efforts have been mainly focused on noble metals such as Pd and Rh, and on Ni (cod) which is highly toxic and dangerous2、Ni(ClO4)2Obtained as a catalyst. Because the price of palladium and rhodium is high, the ligand required by catalytic reaction is special; in addition, the toxicity of zero-valent nickel and the instability of nickel perchlorate limit that the methods can only be applied to laboratory small-scale preparation, are difficult to meet the requirements of scale-scale or productive preparation, and cannot become practical preparation methods of bis (hetero) arylcarbinol compounds.
In summary, the bis (hetero) arylcarbinol compounds have important and wide applicability, and some of the existing synthetic methods have harsh synthetic conditions and low yield, and some of the existing synthetic methods have mild conditions and high efficiency but are expensive. Therefore, the development of a preparation method of the compound, which has simple reaction conditions, high efficiency and is convenient for scale-up, is needed.
Disclosure of Invention
In order to improve the above problems, the present invention provides a method for preparing a compound of the following formula 3, comprising:
reacting a compound of formula 1 and a compound of formula 2 in the presence of a catalyst, a carbene ligand and a base to obtain a compound of formula 3:
Figure BDA0001352771010000021
wherein A is1、A2Identical or different, independently of one another, from unsubstituted or substituted aryl or heteroaryl;
the substituted aryl or heteroaryl group can include substituted aryl or substituted heteroaryl groups, which can be aryl or heteroaryl groups optionally substituted with one or more R;
each R may be independently selected from the group-CHO, -B (OH)2Or a group inert to the above reaction, and may be selected from F, Cl, Br, I, OH, NH, for example2SH, CN, unsubstituted or optionally substituted by one or more RaSubstituted of the following groups: alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkyloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, heterocyclyloxy, aryloxy, heteroaryloxy, NRbRc
Ra、Rb、RcMay independently have the meaning indicated for the radicals R; as an example, RaCan be selected from F, Cl, Br, I, OH, NH2、SH、CN、-OC(O)CH3
As an example, Rb、RcIdentical or different, independently of one another, from the group consisting of unsubstituted or optionally substituted by one or more RaSubstituted C1-40An alkyl group;
the base can be organic base or inorganic base, and can be one or more of sodium carbonate, potassium carbonate, sodium acetate, potassium phosphate and the like, and potassium phosphate is preferred;
the catalyst may be a nickel catalyst, for example a divalent nickel containing compound or complex thereof, for example NiCl2·6H2O、Ni(acac)2、NiCl2(PPh3)2、Ni(PPh3)2(1-naphthyl) Cl and the like, preferably NiCl2(PPh3)2
The carbene ligand is preferably an azacyclic carbene, and is one or more selected from 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride (IPr · HCl), 1, 3-di-tert-butylimidazolium chloride (ItBu · HCl), 1, 3-dicyclohexylimidazolium chloride (ICy · HCl), 1, 3-bis (2, 6-dimethylphenyl) imidazolium chloride (IXy · HCl), 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride (IMes · HCl), etc., preferably 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride (IPr · HCl).
According to the preparation method, the molar ratio of the catalyst to the compound of the formula 1 is (0.001-0.1): 1.
The molar ratio of the compound of formula 1 to the compound of formula 2 is 1 (1-4), for example 1:1.5 or 1: 3.
The molar ratio of the base to the compound of formula 1 may be (0.5-5):1, preferably (2-4):1, for example 2.5: 1.
According to the production method of the present invention, the reaction may be carried out in an organic solvent, for example, toluene, xylene or the like, preferably toluene.
According to the preparation method of the present invention, the temperature of the reaction may be 80 to 130 ℃.
According to the preparation method of the present invention, the reaction time may be 5 to 15 hours.
According to the preparation process of the present invention, the reaction is preferably carried out in an inert gas atmosphere, for example under nitrogen protection.
As an embodiment, the preparation method of the present invention may employ the following steps:
sequentially adding a compound of a formula 1, a compound of a formula 2, a catalyst, a carbene ligand and alkali into a reaction tube;
vacuumizing the reaction tube, introducing nitrogen, repeating the operation for three times, adding an organic solvent into the reaction tube, and reacting at 80-130 ℃ for 5-15 hours;
and after the reaction is finished, evaporating the organic solvent under reduced pressure, and separating and purifying the mixture in the reaction solution by utilizing column chromatography to obtain the compound shown in the formula 3.
The invention also provides a catalyst composition, which comprises a catalyst, a carbene ligand and a base;
the base can be organic base or inorganic base, and can be one or more of sodium carbonate, potassium carbonate, sodium acetate, potassium phosphate and the like, and potassium phosphate is preferred;
the catalyst may be a nickel catalyst, for example it may be a divalent nickel containing compound or complex thereof, for example NiCl2·6H2O、Ni(acac)2、NiCl2(PPh3)2、Ni(PPh3)2(1-naphthyl) Cl and the like, preferably NiCl2(PPh3)2
The carbene ligand is preferably an azacyclic carbene, and may be one or more of 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride (IPr · HCl), 1, 3-di-tert-butylimidazolium chloride (ItBu · HCl), 1, 3-dicyclohexylimidazolium chloride (ICy · HCl), 1, 3-bis (2, 6-dimethylphenyl) imidazolium chloride (IXy · HCl), 1, 3-bis (2,4, 6-trimethylphenyl) imidazolium chloride (IMes · HCl), and the like, for example, 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride (IPr · HCl);
the molar ratio of the catalyst, the carbene ligand, the base and the reaction substrate in the catalyst composition can be (0.001-0.1): (0.5-5): 1.
Use of a catalyst composition as described above as a catalyst for the reaction of a compound of formula 1 as described above with a compound of formula 2 to prepare a compound of formula 3.
Terms and definitions
"alkyl" used herein alone or as suffix or prefix, is intended to include both branched and straight chain saturated aliphatic hydrocarbon groups having from 1 to 40 carbon atoms. For example, "C1-6Alkyl "denotes straight-chain and branched alkyl groups having 1,2, 3,4,5 or 6 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, and hexyl.
"alkenyl" as used herein alone or as suffix or prefix, is intended to include both branched and straight chain aliphatic hydrocarbon groups containing alkenyl or alkene groups having 2 to 40 carbon atoms. For example, "C2-6Alkenyl "denotes alkenyl having 2,3, 4,5 or 6 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methylbut-2-enyl, 3-methylbut-1-enyl, 1-pentenyl, 3-pentenyl, and 4-hexenyl.
"alkynyl" used herein alone or as a suffix or prefix is intended to include both branched and straight chain aliphatic hydrocarbon groups containing alkynyl or alkyne groups having 2 to 40 carbon atoms. For example ethynyl, propynyl (e.g., l-propynyl, 2-propynyl), 3-butynyl, pentynyl, hexynyl and 1-methylpent-2-ynyl.
The term "aryl" as used herein is intended to include aromatic ring structures consisting of 5 to 20 carbon atoms. For example: the aromatic ring structure containing 5, 6, 7 and 8 carbon atoms may be a monocyclic aromatic group such as phenyl; the ring structure containing 8, 9, 10, 11, 12, 13 or 14 carbon atoms may be polycyclic, for example naphthyl. The aromatic ring may be substituted at one or more ring positions with those substituents described above. The term "aryl" also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings (the rings are "fused rings"), wherein at least one of the rings is aromatic and the other cyclic rings can be, for example, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, and/or heterocyclyl. Examples of polycyclic rings include, but are not limited to, 2, 3-dihydro-1, 4-benzodioxine and 2, 3-dihydro-1-benzofuran.
The term "cycloalkyl" as used herein is intended to include saturated cyclic hydrocarbon groups having from 3 to 40 carbon atoms. These terms may include fused or bridged polycyclic ring systems. For example, cycloalkyl groups have 3 to 20 carbon atoms in their ring structure. In one embodiment, the cycloalkyl group has 3,4,5, or 6 carbon atoms in its ring structure. For example, "C3-6Cycloalkyl "denotes a group such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
As used herein, "heteroaryl" refers to a heteroaromatic heterocycle having at least one ring heteroatom (e.g., sulfur, oxygen, or nitrogen). Heteroaryl groups include monocyclic ring systems and polycyclic ring systems (e.g., having 2,3, or 4 fused rings). Examples of heteroaryl groups include, but are not limited to, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, furyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuryl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2, 4-thiadiazolyl, isothiazolyl, benzothienyl, purinyl, carbazolyl, benzimidazolyl, benzoxazolyl, azabenzoxazolyl, imidazothiazolyl, benzo [1,4] dioxanyl, benzo [1,3] dioxolyl, and the like. In some embodiments, heteroaryl groups have from 3 to 40 carbon atoms and in other embodiments from 3 to 20 carbon atoms. In some embodiments, heteroaryl groups contain 3 to 14, 4 to 14, 3 to 7, or 5 to 6 ring-forming atoms. In some embodiments, heteroaryl has 1 to 4, 1 to 3, or 1 to 2 heteroatoms. In some embodiments, the heteroaryl group has 1 heteroatom.
The term "heterocyclyl", as used herein, unless otherwise specified, refers to a saturated, unsaturated or partially saturated monocyclic, bicyclic or tricyclic ring containing 3 to 40 atoms, wherein 1,2, 3,4 or 5 ring atoms are selected from nitrogen, sulfur or oxygen, which may be attached through carbon or nitrogen, unless otherwise specified, wherein-CH is2-the group is optionally replaced by-c (o) -; and wherein unless otherwise stated to the contrary, the ring nitrogen atom or the ring sulfur atom is optionally oxidized to form an N-oxide or S-oxide or the ring nitrogen atom is optionally quaternized; wherein-NH in the ring is optionally substituted with acetyl, formyl, methyl or methanesulfonyl; and the ring is optionally substituted with one or more halogens. It is understood that when the total number of S and O atoms in the heterocyclic group exceeds 1, these heteroatoms are not adjacent to each other. If the heterocyclyl is bicyclic or tricyclic, at least one ring may optionally be a heteroaromatic ring or an aromatic ring, provided that at least one ring is non-heteroaromatic. If the heterocyclic group is monocyclic, it is not necessarily aromatic. Examples of heterocyclyl groups include, but are not limited to, piperidinyl, N-acetylpiperidinyl, N-methylpiperidinyl, N-formylpiperazinyl, N-methylsulfonylpiperazinyl, homopiperazinyl, piperazinyl, azetidinyl, oxetanyl, morpholinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, indolinyl, tetrahydropyranyl, dihydro-2H-pyranyl, tetrahydrofuranyl, tetrahydrothiopyranyl, tetrahydrothiopyran-1-oxide, tetrahydrothiopyran-1, 1-dioxide, 1H-pyridin-2-one, and 2, 5-dioxoimidazolidinyl.
The above definitions of terms apply equally to other terms that contain the term, e.g., the term "alkyl" also applies to "alkoxy" and the like.
The invention has the beneficial effects that:
the preparation method has the characteristics of simplicity, convenience, high efficiency and the like. The preparation of the di (hetero) arylcarbinol with the specific modulus is easy to realize. The method of the invention prepares the di (hetero) aryl methanol compound with high yield by using (hetero) aryl aldehyde and (hetero) aryl boric acid which are available in the market as raw materials and using a cheap and stable divalent nickel source as a catalyst. The method of the invention overcomes the defects of harsh conditions, more side reactions, difficult post-treatment and the like of using metal reagents in the process of preparing the bis (hetero) aryl methanol in the prior art, and also avoids the defects of high cost and difficult large-scale preparation of noble metal palladium catalytic reaction.
The preparation method has the advantages of mild reaction conditions, high product yield and low cost of the used catalyst, and is suitable for industrial production of the bis (hetero) aryl methanol.
Detailed Description
The preparation method of the present invention will be described in further detail with reference to specific examples. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
Example 1: preparation of benzhydrol
Figure BDA0001352771010000071
A25 mL reaction tube was charged with 0.106 g (1.0mmol) of benzaldehyde, 0.183 g (1.5mmol) of phenylboronic acid, and 0.0327 g (0.05mmol) of NiCl in that order2(PPh3)20.0424 g (0.1mmol) IPr HCl, 0.53 g (2.5mmol) K3PO4(ii) a Vacuumizing the reaction tube, introducing nitrogen, repeating the operation for three times, and adding 5mL of toluene into the reaction tube; the reaction is carried out for 5 to 15 hours at 110 ℃, after the reaction is finished, the organic solvent is removed by reduced pressure distillation, and column chromatography is used for concentratingThe condensed reaction solution was separated and purified to obtain 0.149 g of benzhydrol (81% yield).
Example 2: preparation of phenyl-3, 4, 5-trimethoxyphenyl-methanol
Figure BDA0001352771010000072
The procedure and procedure as described in example 1 were followed, except that benzaldehyde was changed to 3,4, 5-trimethoxybenzaldehyde, as in example 1. The final product was 0.238 g (87% yield).
Example 3: preparation of phenyl-4-hydroxymethylphenyl-methanol
Figure BDA0001352771010000081
The procedure and procedure as described in example 1 were followed, except that benzaldehyde was changed to 4-hydroxymethylbenzaldehyde, in contrast to example 1. Finally, 0.150 g of the target product is obtained (yield 70%).
Example 4: preparation of phenyl-4-acetoxymethylphenyl-methanol
Figure BDA0001352771010000082
The procedure and procedure as described in example 1 were followed, except that benzaldehyde was changed to benzyl 4-formylacetate as in example 1. Finally, 0.197 g of the target product is obtained (77% yield).
Example 5: preparation of phenyl-6-methoxy-2-naphthyl-methanol
Figure BDA0001352771010000083
The procedure and procedure as described in example 1 were followed, except that benzaldehyde was changed to 6-methoxy-2-naphthaldehyde, which was used in example 1. Finally, 0.235 g of the target product is obtained (89% yield).
Example 6: preparation of 3,4, 5-trimethoxyphenyl-naphthyl-methanol
Figure BDA0001352771010000091
The procedure and procedures as described in example 1 were followed except that in example 1, benzaldehyde was changed to 3,4, 5-trimethoxybenzaldehyde and phenylboronic acid was changed to 1-naphthylboronic acid. Finally, 0.269 g of the expected product is obtained (yield 83%).
Example 7: preparation of phenyl-4-dimethylaminophenyl-methanol
Figure BDA0001352771010000092
The procedure is as described in example 1, except that in example 1 the benzaldehyde is replaced by p-dimethylaminobenzaldehyde, 3 times the amount of phenylboronic acid and 0.0392 g (0.06mmol) of NiCl are used2(PPh3)2Finally, 0.184 g of the target product is obtained (yield 81%).
Example 8: preparation of 4-trifluoromethylphenyl-6-methoxy-2-naphthyl-methanol
Figure BDA0001352771010000093
The procedure and procedure as described in example 1 were followed, except that benzaldehyde was changed to 6-methoxy-2-naphthaldehyde and phenylboronic acid was changed to 3-fold equivalent of p-trifluoromethylphenylboronic acid, unlike example 1. Finally, 0.309 g of the target product is obtained (yield 93%).
Example 9: preparation of 4-fluorophenyl-6-methoxy-2-naphthyl-methanol
Figure BDA0001352771010000101
The procedure and procedures as described in example 1 were followed, except that benzaldehyde was changed to 6-methoxy-2-naphthaldehyde and phenylboronic acid was changed to 3-fold equivalent of p-fluorophenyl boronic acid, unlike example 1. Finally, 0.243 g of the target product is obtained (yield 86%).
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (9)

1. A preparation method of a compound of formula 3 comprises the following steps of reacting a compound of formula 1 and a compound of formula 2 in the presence of a catalyst, a carbene ligand and a base to prepare the compound of formula 3,
Figure FDA0002695515750000011
wherein A is1、A2Identical or different, independently of one another, from the following groups, unsubstituted or substituted by one or more R: c6-20Aryl, heteroaryl of 3 to 14 ring-forming atoms with 1 to 4 heteroatoms;
each R is independently selected from: F. cl, Br, I, OH, NH2SH, CN, unsubstituted or optionally substituted by one or more RaSubstituted of the following groups: alkyl, NRbRc
RaSelected from F, Cl, Br, I, OH, NH2、SH、CN、-OC(O)CH3
Rb、RcIdentical or different, independently of one another, from C1-6An alkyl group;
the catalyst is selected from NiCl2(PPh3)2The carbene ligand is selected from 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride IPr & HCl.
2. The method of claim 1, wherein the base is selected from one or more of sodium carbonate, potassium carbonate, sodium acetate, potassium phosphate.
3. The process of claim 2 wherein the molar ratio of catalyst to compound of formula 1 is (0.001-0.1): 1;
the molar ratio of the compound shown in the formula 1 to the compound shown in the formula 2 is 1 (1-4);
the molar ratio of the base to the compound of formula 1 is (0.5-5): 1.
4. The preparation process according to claim 3, wherein the molar ratio of the compound of formula 1 to the compound of formula 2 is 1 (1-3);
the molar ratio of the base to the compound of formula 1 is (2-4): 1.
5. The production process according to claim 4, wherein the reaction is carried out in an organic solvent selected from the group consisting of toluene, xylene;
the reaction temperature is 80-130 ℃;
the reaction is carried out in an inert gas.
6. The method of claim 5, wherein the reaction is carried out under nitrogen.
7. The production method according to any one of claims 1 to 6, comprising the steps of:
sequentially adding a compound of a formula 1, a compound of a formula 2, a catalyst, a carbene ligand and alkali into a reaction tube;
vacuumizing the reaction tube, introducing nitrogen, repeating the operation for three times, adding an organic solvent into the reaction tube, and reacting at 80-130 ℃ for 5-15 hours;
and after the reaction is finished, evaporating the organic solvent under reduced pressure, and separating and purifying the mixture in the reaction solution by utilizing column chromatography to obtain the compound shown in the formula 3.
8. A catalyst composition comprising a catalyst, a carbene ligand and a base, wherein:
the alkali is selected from one or more of sodium carbonate, potassium carbonate, sodium acetate and potassium phosphate;
the catalyst is selected from NiCl2(PPh3)2
The carbene ligand is selected from 1, 3-bis (2, 6-diisopropylphenyl) imidazolium chloride;
the molar ratio of the catalyst, the carbene ligand and the alkali to the reaction substrate in the catalyst composition is (0.001-0.1): (0.5-5): 1.
9. Use of the catalyst composition of claim 8 as a catalyst for the reaction of a compound of formula 1 with a compound of formula 2 to produce a compound of formula 3,
Figure FDA0002695515750000031
wherein A is1And A2Having the definition set forth in claim 1.
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