A method for trans-hydroboration of biaryl internal alkyne compounds

Abstract

The present invention provides a method for trans-hydroboration of a biaryl internal alkyne compound, comprising the following steps: in the presence of a nickel catalyst, a nitrogen ligand and a base, a biaryl internal alkyne compound represented by formula (I) is subjected to a trans-hydroboration reaction with bipyralidone diboric acid to obtain a compound represented by formula (II); the synthetic route is as follows: wherein R 1 and R 2 are independently selected from hydrogen, C 1 ‑C 6 Alkyl, methoxy, methylthio, halogen, nitro, cyano, trifluoromethyl, C 6 ‑C 14 Any of the aromatic groups. #imgabs0#

Description

Technical Field

[0001] The invention relates to the technical field of selective hydroboration of alkynes, and in particular to a trans hydroboration method of a diaryl internal alkyne compound. Background Art

[0002] The selective hydroboration of alkynes is a very important reaction and an effective method for the rapid preparation of organoboron compounds. At present, the selective hydroboration of terminal alkynes is relatively mature, while the highly stereoselective hydroboration of internal alkynes is still a difficult and hot topic in research, especially the trans hydroboration of internal alkynes. As far as we know, there are limited literatures on the trans hydroboration of internal alkynes, and there are obvious limitations, such as the use of noble metal catalysts, high cost, poor stereoselectivity, and the fact that internal alkynes are activated alkynes and are not suitable for diaryl alkynes. Therefore, it is extremely necessary to establish a cheap metal-catalyzed and highly stereoselective trans hydroboration method for diaryl internal alkynes.

[0003] In recent years, the transition metal-catalyzed selective hydroboration of alkynes has become a hot topic of research, not only because it can quickly construct organoboron compounds, but also because the generated alkenyl boron compounds are an important tool molecule for introducing other functional groups. With the deepening of research, the regioselectivity of the hydroboration of internal alkynes has been greatly improved, and trans hydroboration has also made some progress.

[0004] In 2011, Yun, J et al. (Chem. Commun. 2011, 47, 2943–2945) reported a highly regioselective and stereoselective hydroboration reaction of disubstituted internal alkynes using CuCl as a catalyst, and obtained the corresponding olefin borate compounds in high yields. However, its trans hydroboration has high requirements for substrate steric hindrance and poor substrate universality, making it unsuitable for the hydroboration of diaryl-substituted internal alkynes.

[0005] In 2013, Fürstner, A. et al. (Angew. Chem. Int. Edit. 2013, 52, 14050-14054.) used the noble metal ruthenium as a catalyst to study the trans-hydroboration reaction of internal alkynes with boranes alone, and synthesized alkenyl borate compounds with moderately high yields. However, the trans-hydroboration of dialkyl symmetrical internal alkynes was mainly discussed, while the stereoselectivity of diaryl internal alkynes and asymmetric internal alkynes was poor (E:Z=

[0006] 87:13), there are obvious limitations and high costs.

[0007] Although transition metal-catalyzed hydroboration of alkynes is a research focus and hotspot, researchers have gradually used bases or phosphine reagents (such as tri-n-butyl phosphine) to replace transition metal-catalyzed trans hydroboration of internal alkynes to reduce damage to the environment. However, they study partially activated alkynes (alkyne esters, etc.), and the trans hydroboration of diaryl internal alkynes is still a difficult point in research.

[0008] So far, there are few reports on the trans-hydroboration of internal alkynes with boron reagents, and most of the existing literature studies partially activated internal alkynes or alkyl-substituted alkynes, while the hydroboration of diaryl-substituted internal alkynes is still a difficult problem to study. At present, there are related literatures that use bases or phosphine reagents instead of transition metal catalysts. Although the impact of residual metal reagents on the environment is avoided, the requirements for substrates are relatively strict. Therefore, it is extremely necessary to develop a cheap metal-catalyzed trans-hydroboration method for diaryl-substituted internal alkynes. Summary of the invention

[0009] In order to solve the above technical problems, the present invention aims to provide a method for trans-hydroboration of biaryl internal alkyne compounds. The method uses a relatively low-cost metal nickel catalyst, and in a protective atmosphere, nitrogen ligands and directing groups (-CH 2 CN) dual regulation, the biaryl internal alkyne benzonitrile substrate and the biboric acid pinacol ester (B 2 pin 2 ) to undergo trans-hydroboration to obtain a series of diphenylethylene benzonitrile compounds with (E)-configuration. This method overcomes the defects of the prior art methods for selective hydroboration of alkynes, such as the use of noble metal catalysts, partially activated alkynes as substrates, insufficient stereoselectivity, and poor substrate universality, and provides an efficient, low-cost, and environmentally friendly method for highly stereoselective hydroboration of aromatic alkyne benzonitrile compounds. It is worth noting that in the absence of a directing group (-CH 2 CN) exists, the reaction cannot obtain the expected target product under the same conditions.

[0010] To achieve the above objectives, the technical solution of the present invention is as follows.

[0011] A method for trans-hydroboration of a biaryl internal alkyne compound comprises the following steps:

[0012] Under the action of a nickel catalyst, a nitrogen ligand and a base, a biaryl internal alkyne compound represented by formula (I) is subjected to a trans-hydroboration reaction with biboric acid pinacol ester to obtain a compound represented by formula (II);

[0013] The synthetic route is as follows:

[0014]

[0015] Among them, R1 and R 2 are independently selected from hydrogen, C 1 -C 6 Alkyl, methoxy, methylthio, halogen, nitro, cyano, trifluoromethyl, C 6 -C 14 Any one of the aromatic groups.

[0016] Furthermore, the nickel catalyst is any one of bis(triphenylphosphine)nickel dichloride, nickel acetylacetonate, nickel acetate tetrahydrate, and nickel iodide.

[0017] Furthermore, the nitrogen ligand is any one of terpyridine, 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 4,5-diazafluorene-9-one, 1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, and 2,9-dimethyl-1,10-o-phenanthroline.

[0018] Furthermore, the base is any one of potassium phosphate, potassium acetate, potassium carbonate, potassium tert-butoxide, potassium fluoride, potassium hydroxide, potassium methoxide, potassium tert-butoxide, sodium carbonate, sodium hydroxide, sodium tert-butoxide, and sodium methoxide.

[0019] Furthermore, the trans-hydroboration reaction is carried out in an organic solvent, and the organic solvent is any one of cyclohexane, toluene, ethylene glycol dimethyl ether, methyl tert-ether, and tetrahydrofuran.

[0020] Furthermore, the trans-hydroboration reaction is carried out under gas protection, and the gas is nitrogen, argon or helium.

[0021] Further, the reaction conditions of the trans-hydroboration reaction are as follows:

[0022] The reaction temperature is 90-150°C and the reaction time is 6-30 hours.

[0023] Furthermore, the compound represented by formula (II) is a (E)-configured distyrene benzonitrile compound.

[0024] Furthermore, the molar ratio of the biaryl internal alkyne compound represented by formula (I) to the biphenyl pinacol borate, the nickel catalyst, the nitrogen ligand and the base is 0.2: 0.24-0.4: 0.01-0.03: 0.01-0.04: 0.3-0.4.

[0025] Beneficial effects of the present invention:

[0026] 1. The present invention adopts a relatively low-cost metal nickel catalyst, and in an inert gas atmosphere, nitrogen ligands and directing groups (-CH 2CN) dual regulation, the biaryl internal alkyne benzonitrile substrate and the biphenyl borate pinacol ester (B 2 pin 2 ) to undergo a trans-hydroboration reaction to obtain a series of diphenylethylene benzonitrile compounds with (E)-configuration. This method overcomes the defects of the prior art regarding the selective hydroboration of alkynes, such as the use of noble metal catalysts, the use of partially activated alkynes as substrates, insufficient stereoselectivity, and poor substrate universality, and provides an efficient, low-cost, and environmentally friendly method for the highly stereoselective hydroboration of aromatic alkyne benzonitrile compounds.

[0027] 2. The method of the present invention has the advantages of low cost, simple operation, high catalytic activity, high regio- and stereo-selectivity, high yield, wide substrate applicability, easy product separation and less environmental pollution, and is not only suitable for gram-scale reactions, but also suitable for industrial-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the X-ray diffraction structure diagram of the product obtained in Example 2 of the present invention. DETAILED DESCRIPTION

[0029] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0030] Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without making any creative work shall fall within the scope of protection of the present invention.

[0031] Unless otherwise specified, the experimental methods described in the following embodiments of the present invention are all conventional methods; the reagents and materials described are all commercially available unless otherwise specified.

[0032] In the following embodiments of the present invention, a method for trans-hydroboration of a biaryl internal alkyne compound is provided, and the synthetic route is as follows:

[0033]

[0034] The specific preparation method is as follows: the aromatic alkyne benzonitrile compound represented by formula (I), bipyrine, nickel catalyst, nitrogen ligand, base and organic solvent are added into a 25 mL Shrek tube respectively, and the mixture is placed at 90-150° C. for sufficient reaction for 6-30 hours under nitrogen protection. After the reaction is completed, the reaction is quenched with a saturated ammonium chloride solution, extracted with ethyl acetate, and the ethyl acetate layer is washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated in vacuo. Then, the mixture is separated by purification methods such as silica gel column chromatography or high-efficiency silica gel plate to prepare the corresponding diphenylethylene benzonitrile compound having (E)-configuration (compound represented by formula (II)).

[0035] Wherein, the biaryl internal alkyne compound represented by formula (I) is selected from one of the following compounds:

[0036]

[0037]

[0038] Next, we will specifically describe the trans-hydroboration method of the biaryl internal alkyne compound represented by formula (I).

[0039] Example 1

[0040] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method includes the following steps:

[0041] Add [2-(phenylethynyl)phenyl]acetonitrile (Ⅰ-1) into a 25 mL Shrek tube

[0042] (0.2mmol), pinacol borate (1.5eq, 0.3mmol), bis(triphenylphosphine)nickel dichloride (0.05eq, 0.01mmol), terpyridine (0.10eq, 0.02mmol), potassium phosphate (1.5eq, 0.3mmol), cyclohexane (2.0mL), filled with nitrogen, placed in a 130°C oil bath for full reaction for 24 hours. After the reaction, saturated ammonium chloride solution was used to quench the reaction, and ethyl acetate (15mL×3) was used for extraction. The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. It was separated by silica gel column chromatography (petroleum ether / ethyl acetate=12 / 1-10 / 1) to obtain a white solid with a yield of 85%.

[0043] The structural characterization data of the product obtained in Example 1 are as follows:

[0044] 1H NMR (400MHz, Chloroform-d) δ7.51–7.43(m,3H),7.42–7.26(m,7H),3.80(s,2H),1.14(s,12H).

[0045] 13 C NMR(101MHz,Chloroform-d)δ141.18,138.28,136.72,129.44,128.64,128.55,128.34,128.01,127.82,127.51,126.89,117.89,84.06,24.63,22.03. 11 B NMR(128MHz,Chloroform-d)δ30.51.HRMS-ESI(m / z):calcd for C 22 H 24 BNO 2 ,[M+H] + :346.1978,found,346.1963.

[0046] According to the above data, the structure of the obtained product is inferred to be:

[0047] Example 2

[0048] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method includes the following steps:

[0049] Into a 25 mL Shrek tube, {2-[(4-methylphenyl)ethynyl]phenyl}acetonitrile (I-2) (0.2 mmol), biboric acid pinacol ester (1.5 eq, 0.3 mmol), bis(triphenylphosphine)nickel dichloride (0.05 eq, 0.01 mmol), terpyridine (0.10 eq, 0.02 mmol), potassium phosphate (1.5 eq, 0.3 mmol), cyclohexane (2.0 mL) were added respectively, nitrogen was filled, and the mixture was placed in an oil bath at 130° C. for sufficient reaction for 24 hours. After the reaction was completed, a saturated ammonium chloride solution was used to quench the reaction, and ethyl acetate (15 mL×3) was used for extraction. The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. The mixture was separated by silica gel column chromatography (petroleum ether / ethyl acetate=10 / 1-8 / 1) to obtain a white solid with a yield of 87%.

[0050] The structural characterization data of the product obtained in Example 2 are as follows:

[0051] 1H NMR(400MHz,Chloroform-d)δ7.41(d,J=7.0Hz,1H),7.37–7.34(m,1H),7.32(d,J=8.1Hz,2H), 7.29–7.24(m,2H),7.21(s,1H),7.14(d,J=8.0Hz,2H),3.75(s,2H),2.32(s,3H),1.10(s,12H).

[0052] 13 C NMR(101MHz,Chloroform-d)δ138.41,138.37,137.31,135.82,129.46,129.35 ,128.58,128.23,127.97,127.79,126.78,117.92,84.01,24.65,22.00,21.20. 11 BNMR(128MHz,Chloroform-d)δ30.30.HRMS-ESI(m / z):calcd for C 23 H 26 BNO 2 ,[M+H] + :360.2135,found,360.2140.

[0053] According to the above data, the structure of the obtained product is inferred to be: Its X-ray diffraction structure is shown in Figure 1 .

[0054] Example 3

[0055] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0056] Example 4

[0057] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0058] Example 5

[0059] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0060] Example 6

[0061] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0062] Example 7

[0063] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0064] Example 8

[0065] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0066] Example 9

[0067] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0068] Example 10

[0069] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0070] Embodiment 11

[0071] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0072] Example 12

[0073] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0074] Embodiment 13

[0075] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0076] Embodiment 14

[0077] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0078] Embodiment 15

[0079] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0080] Example 16

[0081] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0082] Embodiment 17

[0083] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0084] Embodiment 18

[0085] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0086] Embodiment 19

[0087] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0088] Embodiment 20

[0089] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nickel catalyst is nickel acetylacetonate.

[0090] Embodiment 21

[0091] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nickel catalyst is nickel acetate tetrahydrate.

[0092] Embodiment 22

[0093] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nickel catalyst is nickel iodide.

[0094] Embodiment 23

[0095] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that 4,4′,4″-tri-tert-butyl-2,2′:6′,2″-terpyridine is used.

[0096] Embodiment 24

[0097] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nitrogen ligand is 4,4'-di-tert-butyl-2,2'-bipyridine.

[0098] Embodiment 25

[0099] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nitrogen ligand is 4,5-diazafluorene-9-one.

[0100] Embodiment 26

[0101] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nitrogen ligand is 1,10-phenanthroline.

[0102] Embodiment 27

[0103] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nitrogen ligand is 4,7-dimethyl-1,10-phenanthroline.

[0104] Embodiment 28

[0105] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that the nitrogen ligand is 2,9-dimethyl-1,10-phenanthroline.

[0106] Embodiment 29

[0107] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1, except that [2-(phenylethynyl)phenyl]acetonitrile (I-1) (0.2mmol), pinacol borate (0.24mmol), bis(triphenylphosphine)nickel dichloride (0.02mmol), terpyridine (0.01mmol), and potassium phosphate (0.35mmol).

[0108] Embodiment 30

[0109] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1, except that [2-(phenylethynyl)phenyl]acetonitrile (I-1) (0.2mmol), pinacol borate (0.40mmol), bis(triphenylphosphine)nickel dichloride (0.03mmol), terpyridine (0.04mmol), and potassium phosphate (0.4mmol).

[0110] Comparative Example 1

[0111] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0112] Comparative Example 2

[0113] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0114] Comparative Example 3

[0115] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0116] Comparative Example 4

[0117] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0118] Comparative Example 5

[0119] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0120] Comparative Example 6

[0121] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0122] Comparative Example 7

[0123] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0124] Comparative Example 8

[0125] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is basically the same as that of Example 1.

[0126] Comparative Example 9

[0127] A method for trans-hydroboration of a biaryl internal alkyne compound, wherein the biaryl internal alkyne compound has a structure of: The specific method is substantially the same as that of Example 1, except that no nitrogen ligand is added.

[0128] The above embodiments of the present invention mainly use biaryl internal alkyne compounds (1a) to (1s) as substrates, and react with nitrogen ligands and directing groups (-CH 2 CN) under dual regulation, and with pinacol borate (B 2 pin 2 ) to optimize the conditions for the trans-hydroboration reaction. The above reaction conditions are shown in Table 1-3.

[0129] Table 1 Nickel catalyst optimization

[0130]

[0131]

[0132] As can be seen from the results in Table 1, through the screening of nickel catalysts including bis(triphenylphosphine)nickel dichloride, nickel acetylacetonate, nickel acetate tetrahydrate, and 1,2-bis(diphenylphosphine)ethane nickel chloride, we found that the reaction yield was the best (yield 85%) when bis(triphenylphosphine)nickel dichloride was used as the nickel catalyst.

[0133] Table 2 Nitrogen ligand optimization

[0134]

[0135]

[0136] As can be seen from the results in Table 2, by screening nitrogen ligands including terpyridine, 4,4',4"-tri-tert-butyl-2,2':6',2"-terpyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, 4,5-diazafluorene-9-one, 1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 2,9-dimethyl-1,10-o-phenanthroline, we found that terpyridine had the best reaction yield (yield 85%) when used as a nitrogen ligand. Comparing Example 1 with Comparative Example 11, it was found that it was difficult to obtain (E)-configured diphenylethylene benzonitrile compounds without adding nitrogen ligands.

[0137] Table 3 Screening of directing groups

[0138]

[0139]

[0140] From the results in Table 1, it can be seen that by screening the directing groups including -CH 2 CN、-OCH 3 、-CN、-COCH 3 , -H, We found that -CH 2 The reaction yield was the best when CN was used as the directing group (yield 85%).

[0141] The following is an exploration of the applicability of the substrates for the trans-hydroboration of different bisaryl internal alkyne compounds, and a validation exploration of the above-mentioned optimized conditions. See Table 4 for details.

[0142] Table 4 Investigation of the suitability of reaction substrates

[0143]

[0144]

[0145]

[0146]

[0147] It can be seen from the results in Table 4 that, compared with Comparative Examples 1 to 4, Examples 1 to 19 of the present invention use biaryl internal alkyne compounds (1a) to (1s) as substrates, and react with nitrogen ligands and directing groups (-CH 2 CN) under dual regulation, and with pinacol borate (B 2 pin 2 ) can be subjected to trans-hydroboration reaction to generate (E)-configured diphenylethylene benzonitrile compounds in high yield (yield 71-91%).

[0148] The above results show that the method of the embodiment of the present invention has the advantages of low cost, simple operation, high catalytic activity, high regio- and stereo-selectivity, high yield, wide substrate applicability, easy product separation and less environmental pollution, and is not only suitable for gram-scale reactions, but also suitable for industrial-scale production.

[0149] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for trans-hydroboration of a biaryl internal alkyne compound, characterized in that: The following steps are involved: Under the action of a nickel catalyst, a nitrogen ligand and a base, a biaryl internal alkyne compound represented by formula (I) is subjected to a trans-hydroboration reaction with biboric acid pinacol ester to obtain a compound represented by formula (II); The synthetic route is as follows: ； Among them, R 1 and R 2 are independently selected from hydrogen, C1-C6 alkyl, methoxy, methylmercapto, halogen, nitro, cyano, trifluoromethyl, C6-C 14 Any one of the aromatic groups; The trans-hydroboration reaction is carried out in an organic solvent, and the organic solvent is cyclohexane; The nickel catalyst is bis(triphenylphosphine)nickel dichloride; The nitrogen ligand is terpyridine; The base is potassium phosphate; The trans-hydroboration reaction is carried out under gas protection, and the gas is nitrogen, argon or helium; The reaction conditions of the trans-hydroboration reaction are as follows: The reaction temperature is 90-150°C and the reaction time is 6-30 hours; The compound represented by the formula (II) is a (E)-configured distyrene benzonitrile compound.

2. The method for trans-hydroboration of bisaryl internal alkyne compounds according to claim 1, characterized in that: The molar ratio of the biaryl internal alkyne compound shown in formula (I) to the biphenyl pinacol borate, the nickel catalyst, the nitrogen ligand and the base is 0.2: 0.24-0.4: 0.01-0.03: 0.01-0.04: 0.3-0.4.

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