Application of copper-based complex Cu (dppf) (BH4) in nucleophilic addition reaction of arylboronic acid

Abstract

The invention discloses an application of a copper-based complex Cu (dppf) (BH4) in a nucleophilic addition reaction of arylboronic acid. According to the method, the optimal reaction yield is obtained by adjusting parameters such as reaction temperature, solvent types, reaction additives and the like. In addition, a plurality of groups of control experiments are carried out to verify the synergistic effect of Cu (dppf) (BH4) in catalyzing the addition reaction of arylboronic acid and aromatic aldehyde. The final experiment shows that the assembly of Cu (dppf) (BH4) can effectively catalyze the addition reaction of arylboronic acid and aromatic aldehyde, which brings another possibility for the application of Cu (dppf) (BH4) in organic reaction, and also expands the copper-based reaction system of non-noble metal for the nucleophilic addition reaction of arylboronic acid.

Description

Technical Field

[0001] The present invention relates to the application of a copper-based complex Cu(dppf)(BH4) in the nucleophilic addition reaction of arylboronic acid. Background Art

[0002] Diarylcarbinol is a key structural unit for constructing numerous natural products and bioactive compounds and has extensive applications in the fields of pharmacy and materials science (Angewandte Chemie, 2021, 133: 6375-6379). Currently, the methods for synthesizing diarylcarbinol are mainly divided into two categories. The first method is to reduce diaryl ketone to generate diarylcarbinol. The key to this method lies in the need to select appropriate reaction conditions and reducing agents, and the reducing agent is placed in a specific solvent system to reduce diaryl ketone to generate diarylcarbinol. However, it has been found that some by-products often occur during the reduction of diaryl ketone, which will reduce the purity and yield of the target product. The second method is to use some organometallic reagents for nucleophilic addition to aldehydes to react to generate diarylcarbinol. This method has relatively mild reaction conditions compared with the first method and is more operable in both laboratory and industrial production (Chemical reviews, 1999, 99: 991-1046). However, the organometallic reagents (organolithium, organomagnesium, organotin, organozinc, etc.) used in this method, on the one hand, pose challenges to experimental operations due to their high toxicity; on the other hand, the compatibility of these reagents with specific functional groups is poor, and side reactions are likely to occur when reacting with substrates with sensitive functional groups, and these organometallic reagents are sensitive to air and water, which also increases the reaction cost of the experiment to some extent. The application of organoboron reagents in the nucleophilic addition reaction with aldehydes has gradually become an emerging method for synthesizing diarylcarbinol. Organoboron reagents have excellent stability in air and are insensitive to moisture. Therefore, during storage and experimental operations, there is no need to spend a lot of time and cost on maintenance like traditional organometallic reagents, which greatly reduces the difficulty and risk of experimental operations. In addition, organoboron reagents also have good functional group tolerance, so when they react with substrates containing multiple functional groups, side reactions can be effectively avoided, showing high catalytic selectivity.

[0003] At present, a series of progress has been made in the application of organoboron reagents in the synthesis of diarylmethanol. As shown in Table 1, the table details the effects of different catalytic systems on the catalytic performance of organoboron reagent addition reactions from multiple perspectives such as the loading of the metal, the type of solvent, the reaction temperature, and the scope of substrates applicable. From this, we can conclude that most of the catalytic systems currently applied to the nucleophilic addition reaction of arylboronic acid and aryl aldehyde to form diarylmethanol are noble metal catalysts containing phosphine ligands. Chemists improve the yield and expand the scope of application by changing the solvent, reaction temperature, and ligand. Non-noble metals have also been found to have catalytic activity, such as nickel, cobalt, and zinc. However, the scope of application and yield of non-noble metal systems are still limited, and the catalyst dosage is relatively large. Compared with nickel and cobalt, copper is the cheapest metal. Among them, the reported copper catalytic systems mainly use copper acetate with alkali metals and phosphine ligands, and this system has been proven to have high catalytic efficiency in the addition reaction of organoboron reagents (Organic Chemistry, 2009, 74: 943-945). However, the experimental operation of this catalytic system is relatively complex, requiring the use of multiple substances for the reaction, and its applicability to some substrates containing both carbonyl and methoxy groups is relatively low. Based on this research, we wondered whether a single copper-based complex could be applied to such reactions.

[0004] Summary of the Invention

[0005] The present invention addresses the problems existing in the above-mentioned prior art and provides an application of a copper-based complex Cu(dppf)(BH4) in the nucleophilic addition reaction of arylboronic acid. We synthesized the copper-based complex Cu(dppf)(BH4) and applied it to the nucleophilic addition reaction of arylboronic acid. This experiment is mainly divided into two parts, a control experiment and a substrate expansion experiment. The control experiment proves that the copper-based complex Cu(dppf)(BH4) has a certain synergistic effect in the catalytic addition reaction of arylboronic acid and aromatic aldehyde; the substrate expansion experiment proves that the copper-based complex Cu(dppf)(BH4) can effectively catalyze the nucleophilic addition reaction of arylboronic acid under the reaction conditions (110 °C, atmospheric pressure), achieving good yields, with a low catalyst dosage and being applicable to a variety of substrates. Based on this, the present invention successfully realizes a method for effectively synthesizing diarylmethanol using a copper-based complex and verifies the synergistic effect of Cu(dppf)(BH4) in the catalytic addition reaction of arylboronic acid and aromatic aldehyde through a control experiment. This not only expands the direction for the application of Cu(dppf)(BH4) in organic catalysis but also lays a rich foundation for the exploration of catalysts for arylboronic acid coupling reactions.

[0006] Application of copper-based complex Cu(dppf)(BH4) in nucleophilic addition reaction of arylboronic acid, which is to catalyze the addition reaction of arylboronic acid and aromatic aldehyde with the copper-based complex.

[0007] The copper-based complex Cu(dppf)(BH4) has a structure composed of one Cu atom, one bis(diphenylphosphino)ferrocene ligand and one BH4 - ion. The copper-based complex Cu(dppf)(BH4) is synthesized by a one-pot method under the reduction of NaBH4 from the complex formed by copper acetylacetonate (Cu(acac)2) and 1,1'-bis(diphenylphosphino)ferrocene (dppf).

[0008] The reaction process is as follows:

[0009] Using aromatic aldehyde and arylboronic acid as raw materials, adding the catalyst copper-based complex and NaOAc, and heating and reacting in a solvent system and air atmosphere to obtain the target product.

[0010] The aromatic aldehyde is selected from one of p-nitrobenzaldehyde, m-nitrobenzaldehyde, o-nitrobenzaldehyde, p-cyanobenzaldehyde, methyl p-formylbenzoate, etc.

[0011] The arylboronic acid is selected from one of benzeneboronic acid, m-methoxybenzeneboronic acid, p-methylbenzeneboronic acid, o-methylbenzeneboronic acid, p-bromobenzeneboronic acid, p-fluorobenzeneboronic acid, p-chlorobenzeneboronic acid, etc.

[0012] The molar ratio of the aromatic aldehyde to the arylboronic acid in the feed is 1:2; the addition amount of the copper-based complex is 0.3 equivalent, and the addition amount of NaOAc is 3 equivalents, based on the aromatic aldehyde.

[0013] The feeding temperature is controlled at room temperature to -20°C, preferably -20°C.

[0014] The solvent is toluene.

[0015] The specific steps include:

[0016] Adding aromatic aldehyde (0.2 mmol), arylboronic acid (0.4 mmol), catalyst copper-based complex (0.3 equivalent) and NaOAc (3 equivalents) to the reaction system, in an air atmosphere, refluxing and reacting in 3 mL of solvent at 110°C for 24 hours. The yield is the isolated yield.

[0017] The present invention has the following advantages compared with the prior art:

[0018] 1. The application research of the copper-based complex Cu(dppf)(BH4) in the nucleophilic addition reaction of arylboronic acid of the present invention uses a non-noble metal copper-based complex, which can be used as an economical alternative to precious metal catalysts.

[0019] 2. The copper-based complex Cu(dppf)(BH4) of the present invention can synthesize diarylmethanol under relatively mild conditions (110 °C, atmospheric pressure) with good yields.

[0020] 3. The application research of the copper-based complex Cu(dppf)(BH4) of the present invention in the nucleophilic addition reaction of arylboronic acid has a wide range of substrate expansion.

[0021] 4. The application research of the copper-based complex Cu(dppf)(BH4) of the present invention in the nucleophilic addition reaction of arylboronic acid emphasizes the importance of the synergistic effect of the binuclear Cu-Fe complex in homogeneous organic reactions. This not only opens up a new direction for the wide application of Cu(dppf)(BH4) in the field of organic catalysis, but also provides a solid foundation and rich data support for the research of catalysts for arylboronic acid addition reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a reaction route diagram.

[0023] Figure 2 It is the 1H NMR characterization diagram of the product obtained in Example 5.

[0024] Figure 3 It is the 13C NMR characterization diagram of the product obtained in Example 5.

[0025] Figure 4 It is the 1H NMR characterization diagram of the product obtained in Example 6.

[0026] Figure 5 It is the 13C NMR characterization diagram of the product obtained in Example 6.

[0027] Figure 6 It is the 1H NMR characterization diagram of the product obtained in Example 7.

[0028] Figure 7 It is the 13C NMR characterization diagram of the product obtained in Example 7.

[0029] Figure 8 It is the 1H NMR characterization diagram of the product obtained in Example 8.

[0030] Figure 9 It is the 13C NMR characterization diagram of the product obtained in Example 8.

[0031] Figure 10 It is the 1H NMR characterization diagram of the product obtained in Example 9.

[0032] Figure 11 It is the 13C NMR characterization diagram of the product obtained in Example 9.

[0033] Figure 12It is the 1H NMR characterization diagram of the product obtained in Example 10.

[0034] Figure 13 It is the 13C NMR characterization diagram of the product obtained in Example 10.

[0035] Figure 14 It is the 1H NMR characterization diagram of the product obtained in Example 11.

[0036] Figure 15 It is the 13C NMR characterization diagram of the product obtained in Example 11.

[0037] Figure 16 It is the 1H NMR characterization diagram of the product obtained in Example 12.

[0038] Figure 17 It is the 13C NMR characterization diagram of the product obtained in Example 12.

[0039] Figure 18 It is the 1H NMR characterization diagram of the product obtained in Example 13.

[0040] Figure 19 It is the 13C NMR characterization diagram of the product obtained in Example 13.

[0041] Figure 20 It is the 1H NMR characterization diagram of the product obtained in Example 14.

[0042] Figure 21 It is the 13C NMR characterization diagram of the product obtained in Example 14.

[0043] Figure 22 It is the 1H NMR characterization diagram of the product obtained in Example 15.

[0044] Figure 23 It is the 13C NMR characterization diagram of the product obtained in Example 15. Detailed implementation manners

[0045] The technical solutions of the present invention will be further elaborated below in conjunction with specific examples.

[0046] The synthesis and characterization of the copper-based complex Cu(dppf)(BH4) can be referred to CN119331033A.

[0047] Under the reaction conditions of stirring in a 36 °C oil bath, copper acetylacetonate (180 mg, 0.69 mmol, 1.0 equivalent) was added to a flask containing methanol (12.5 ml, 0.309 mmol, 0.45 equivalent) and dichloromethane (37.5 ml, 0.585 mmol, 0.85 equivalent) to obtain a dark blue solution. After 10 min, dppf (762 mg, 1.375 mmol, 2 equivalents) was added under stirring conditions to obtain a yellowish-brown Cu-dppf complex solution. After reacting for 20 min, NaBH4 / H2O (150 mg / 3 mL) was added, and the solution turned orange-yellow, and stirring was continued for 8 h. Then the solution was filtered and retained, and the crude product obtained by rotary evaporation was washed 3 times with n-hexane to obtain a yellow precipitate. Finally, it was crystallized with ethanol and n-hexane to obtain crystals.

[0048] Condition optimization experiment:

[0049] Charged at -20 °C, p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (x equivalents) and NaOAc (y equivalents) were added, and refluxed in 3 ml of solvent in air for 24 hours to obtain the product 4-nitro diarylmethanol, and the yields and details are shown in Table 2.

[0050] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.46 - 7.29 (m, 5H), 5.93 (s, 1H), 2.37 (s, 1H). 13 C NMR (101MHz, Chloroform-d) δ 150.71, 142.68, 128.91, 128.37, 127.03, 127.03, 126.67, 123.64, 75.49.

[0051]

[0052] Control experiment:

[0053] Example 1:

[0054] Charge the materials at -20 °C, then add p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equivalent) and NaOAc (3 equivalents), reflux in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product 4-nitro diarylmethanol with a yield of 62%.

[0055] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.4 Hz, 2H), 7.58 (d, J= 8.4 Hz, 2H), 7.46 -7.29 (m, 5H), 5.93 (s, 1H), 2.37 (s, 1H). 13 C NMR (101MHz, Chloroform-d) δ 150.71, 142.68, 128.91, 128.37, 127.03, 127.03, 126.67,123.64, 75.49.

[0056] Example 2:

[0057] Charge the materials at room temperature, then add p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equivalent) and NaOAc (3 equivalents), reflux in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product 4-nitro diarylmethanol with a yield of 54.8%.

[0058] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.4 Hz, 2H), 7.58 (d, J= 8.4 Hz, 2H), 7.46 -7.29 (m, 5H), 5.93 (s, 1H), 2.37 (s, 1H). 13 C NMR (101MHz, Chloroform-d) δ 150.71, 142.68, 128.91, 128.37, 127.03, 127.03, 126.67,123.64, 75.49.

[0059] Example 3:

[0060] The reaction was carried out by charging at -20 °C, then adding p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), CuCl (0.3 equiv), dppf (0.3 equiv) and NaOAc (3 equiv), and refluxing in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product 4-nitro diarylmethanol with a yield of 48.9%.

[0061] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.4 Hz, 2H), 7.58 (d, J= 8.4 Hz, 2H), 7.46 -7.29 (m, 5H), 5.93 (s, 1H), 2.37 (s, 1H). 13 C NMR (101MHz, Chloroform-d) δ 150.71, 142.68, 128.91, 128.37, 127.03, 127.03, 126.67,123.64, 75.49.

[0062] Example 4:

[0063] The reaction was carried out by charging at room temperature, then adding p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), CuCl (0.3 equiv), dppf (0.3 equiv) and NaOAc (3 equiv), and refluxing in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product 4-nitro diarylmethanol with a yield of 24%.

[0064] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.4 Hz, 2H), 7.58 (d, J= 8.4 Hz, 2H), 7.46 -7.29 (m, 5H), 5.93 (s, 1H), 2.37 (s, 1H). 13 C NMR (101MHz, Chloroform-d) δ 150.71, 142.68, 128.91, 128.37, 127.03, 127.03, 126.67,123.64, 75.49.

[0065] Substrate expansion experiment:

[0066] Example 5:

[0067] The feedstock was charged at -20 °C, and then p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equiv.) and NaOAc (3 equiv.) were added. It was refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product 4-nitrodiarylmethanol with a yield of 62%.

[0068] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.4 Hz, 2H), 7.58 (d, J= 8.4 Hz, 2H), 7.46 -7.29 (m, 5H), 5.93 (s, 1H), 2.37 (s, 1H). 13 C NMR (101MHz, Chloroform-d) δ 150.71, 142.68, 128.91, 128.37, 127.03, 127.03, 126.67,123.64, 75.49.

[0069] Example 6:

[0070] The feedstock was charged at -20 °C, and then p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), m-methoxyphenylboronic acid (60.8 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equiv.) and NaOAc (3 equiv.) were added. It was refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (3-methoxyphenyl)(4-nitrophenyl)methanol with a yield of 95.4%.

[0071] 1 H NMR (400 MHz, Chloroform-d) δ 8.15 (d, J = 8.7 Hz, 2H), 7.55 (d, J= 8.7 Hz, 2H), 7.26 (t, J = 7.9 Hz, 1H), 6.97-6.75 (m, 3H), 5.85(s, 1H), 3.77(s, 3H), 2.68(s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 159.92, 150.60,147.11, 144.25, 129.85, 126.91, 123.68, 118.81, 113.43, 112.43, 75.29, 55.13.

[0072] Example 7:

[0073] Charged at -20 °C, then p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), p-tolylboronic acid (54.4 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 eq.) and NaOAc (3 eq.) were added, and refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (4-nitrophenyl)(p-tolyl)methanol with a yield of 93.8%.

[0074] 1 H NMR (400 MHz, Chloroform-d) δ 8.20 (d, J = 8.6 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.37 - 7.12 (m, 4H), 5.90 (s, 1H), 2.79 (s, 1H), 2.38 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 151.01, 146.97, 139.8, 138.14, 129.5, 126.91, 126.61, 123.52, 75.22, 21.04.

[0075] Example 8:

[0076] Charged at -20 °C, then p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), 2-methylphenylboronic acid (54.4 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 eq.) and NaOAc (3 eq.) were added, and refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (4-nitrophenyl)(o-tolyl)methanol with a yield of 45.8%.

[0077] 1 H NMR (400 MHz, Chloroform-d) δ 8.19 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 8.6 Hz, 2H), 7.39 - 7.29 (m, 1H), 7.26 - 7.16 (m, 3H), 6.11 (s, 1H), 2.32 (s, 3H), 2.28 (s, 1H). 1313C NMR (101 MHz, Chloroform-d) δ 150.21, 147.08, 140.39, 135.59, 131.02, 128.34, 127.50, 126.97, 126.5, 123.56, 72.66, 19.36.

[0078] Example 9:

[0079] Charged at -20 °C, then p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), p-bromophenylboronic acid (80.3 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equiv.) and NaOAc (3 equiv.) were added, and refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (4-bromophenyl)(4-nitrophenyl)methanol with a yield of 34.5%.

[0080] 1 1H NMR (400 MHz, Chloroform-d) δ 8.21 - 8.17 (m, 2H), 7.51 (dd, J = 24.4, 7.7 Hz, 4H), 7.23 (d, J = 7.5 Hz, 2H), 5.89 (s, 1H), 2.54 (s, 1H). 13 13C NMR (101 MHz, Chloroform-d) δ 150.18, 147.30, 141.61, 132.00, 128.31, 127.05, 123.78, 122.31, 74.81.

[0081] Example 10:

[0082] Charged at -20 °C, then p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), p-fluorophenylboronic acid (55.9 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equiv.) and NaOAc (3 equiv.) were added, and refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (4-fluorophenyl)(4-nitrophenyl)methanol with a yield of 48.7%.

[0083] 11H NMR (400 MHz, Chloroform-d) δ 8.11 (d, J = 8.3 Hz, 2H), 7.48 (d, J= 8.5 Hz, 2H), 7.30 -7.17 (m, 2H), 6.97 (t, J = 8.4 Hz, 2H), 5.84 (s, 1H),2.47 (s, 1H). 13 13C NMR (101 MHz, Chloroform-d) δ 163.73, 150.51, 147.21,138.49, 128.49, 126.99, 123.73, 115.70, 74.77.

[0084] Example 11:

[0085] Charged at -20 °C, then p-nitrobenzaldehyde (30.2 mg, 0.2 mmol), p-chlorophenylboronic acid (62.5 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equiv.) and NaOAc (3 equiv.) were added, and refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (4-chlorophenyl)(4-nitrophenyl)methanol in a yield of 42.6%.

[0086] 1 1H NMR (400 MHz, Chloroform-d) δ 8.18 (d, J = 8.5 Hz, 2H), 7.54 (d, J= 8.4 Hz, 2H), 7.30 (q, J = 8.4 Hz, 4H), 5.89 (s, 1H), 2.61 (s, 1H). 13 13C NMR(101 MHz, Chloroform-d) δ 150.27, 147.26, 141.09, 134.16, 129.04, 127.99,127.03, 123.76, 74.75.

[0087] Example 12:

[0088] Charged at -20 °C, then m-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equiv.) and NaOAc (3 equiv.) were added, and refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (3-nitrophenyl)(phenyl)methanol in a yield of 63.9%.

[0089] 1 1H NMR (600 MHz, Chloroform-d) δ 8.31 (s, 1H), 8.17 - 8.05 (m, 1H), 7.72 (d, J = 7.7 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.39 - 7.28 (m, 5H), 5.94 (s, 1H), 2.38 (s, 1H). 13 13C NMR (101 MHz, Chloroform-d) δ 148.31, 145.74, 142.75, 132.43, 129.34, 128.93, 128.36, 126.62, 122.41, 121.28, 75.36.

[0090] Example 13:

[0091] Charged at -20 °C, then 2-nitrobenzaldehyde (30.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 equiv.) and NaOAc (3 equiv.) were added, and refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product (2-nitrophenyl)(phenyl)methanol with a yield of 97.6%.

[0092] 1 1H NMR (400 MHz, Chloroform-d) δ 7.92 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.7 Hz, 1H), 7.35 - 7.27 (m, 5H), 6.42 (s, 1H), 2.99 (s, 1H). 13 13C NMR (101 MHz, Chloroform-d) δ 148.3, 141.49, 138.43, 133.37, 129.35, 128.52, 128.43, 127.97, 126.89, 124.65, 71.41.

[0093] Example 14:

[0094] The materials were fed at -20 °C, then p-cyanobenzaldehyde (26.2 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 eq.) and NaOAc (3 eq.) were added, and the mixture was refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product 4-(hydroxyphenyl)methylbenzonitrile with a yield of 62.7%.

[0095] 1 H NMR (400 MHz, Chloroform-d) δ 7.63 (d, J = 8.0 Hz, 2H), 7.54 (d, J= 7.8 Hz, 2H), 7.37 (q, J = 7.2, 6.7 Hz, 5H), 5.88 (d, J = 2.2 Hz, 1H), 2.78(s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 148.85, 142.75, 132.18, 128.78,128.18, 126.93, 126.61, 118.77, 110.94, 75.49.

[0096] Example 15:

[0097] The materials were fed at -20 °C, then methyl formylformate (32.8 mg, 0.2 mmol), phenylboronic acid (48.7 mg, 0.4 mmol), Cu(dppf)(BH4) (0.3 eq.) and NaOAc (3 eq.) were added, and the mixture was refluxed in 3 ml of toluene in air for 24 hours at a reaction temperature of 110 °C to obtain the product methyl 4-(hydroxyphenyl)methylbenzoate with a yield of 91.7%.

[0098] 1 H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 8.3 Hz, 2H), 7.44 (d, J= 8.2 Hz, 2H), 7.31 (dd, J = 17.8, 3.9 Hz, 5H), 5.82(s, 1H), 3.87(s, 3H),2.92(s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 166.94, 148.77, 143.22, 129.68,129.03, 128.57, 127.80, 126.58, 126.26, 75.74, 52.02。

Claims

1. Application of copper-based complex Cu(dppf)(BH4) in nucleophilic addition reaction of aromatic boronic acid, characterized in that: The copper-based complex Cu(dppf)(BH4) is used to catalyze the addition reaction of arylboronic acid and aromatic aldehyde; The copper-based complex Cu(dppf)(BH4) is composed of a Cu atom, a bis(diphenylphosphinoferrocene) ligand and a BH4 - Ion composition.

2. The use according to claim 1, characterized in that: Aromatic aldehyde and aromatic boronic acid are used as raw materials, a catalyst copper-based complex Cu(dppf)(BH4) and NaOAc are added, and the mixture is heated in a solvent system and air atmosphere to obtain the target product. The aromatic aldehyde is selected from one of p-nitrobenzaldehyde, m-nitrobenzaldehyde, o-nitrobenzaldehyde, p-cyanobenzaldehyde and methyl p-formylbenzoate; The aryl boronic acid is selected from one of phenylboronic acid, m-methoxyphenylboronic acid, p-methylphenylboronic acid, o-methylphenylboronic acid, p-bromophenylboronic acid, p-fluorophenylboronic acid and p-chlorophenylboronic acid.

3. The use according to claim 2, characterized in that: The molar ratio of the aromatic aldehyde to the aromatic boronic acid is 1:

2.

4. The use according to claim 2, characterized in that: The amount of the copper-based complex Cu(dppf)(BH4) added is 0.3 equivalents, calculated based on the aromatic aldehyde.

5. The use according to claim 2, characterized in that: The amount of NaOAc added was 3 equivalents based on the aromatic aldehyde.

6. The use according to claim 2, characterized in that: The feeding temperature is controlled between room temperature and -20°C.

7. The use according to claim 6, characterized in that: The feeding temperature is -20℃.

8. The use according to claim 2, characterized in that: The solvent is toluene.

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