Method for synthesizing compound with rotation-resistant 1, 3-diene structure through catalytic reduction coupling reaction of transition metal

Abstract

The invention relates to a method for synthesizing a compound with a rotation-resistant 1, 3-diene structure through a transition metal catalytic reduction coupling reaction, and discloses a method for synthesizing a compound with a rotation-resistant 1, 3-diene structure by taking 1-bromo-3, 4-dihydronaphthalene-2-formic acid phenyl ester and a derivative thereof as a substrate, ethylene glycol dimethyl ether nickel bromide (II) as a catalyst, activated zinc powder as a reducing agent, cobalt phthalocyanine (II) as a single electron transfer agent, (3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS, 3aS According to the method, 2, 2 '-[(phenyloxy) carbonyl]-1-(3, 4-dihydro)-dinaphthalene with a non-planar 1, 3-diene structure and enantioselectivity and the derivative thereof are obtained through reaction at the temperature of 30 DEG C by taking 2, 2'-[(phenyloxy) carbonyl]-1-(3, 4-dihydro)-dinaphthalene as a raw material, taking (3aR, 8aR)-2-(6-benzhydrylpyridine-2-yl)-8, 8a-dihydrotetrahydro-3aH-indeno [1, 2-d] oxazole as a chiral ligand, taking tetraethylammonium iodide as an additive and taking anhydrous toluene as a solvent. The method has the advantages of high efficiency, simplicity, wide substrate application range, convenience in operation and the like, and an efficient and novel preparation method is provided for the rotation-resistant 1, 3-diene compound.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing a compound with a hindered 1,3-diene structure through a transition metal catalyzed reductive coupling reaction. BACKGROUND

[0002] Axially chiral compounds are widely present in natural products, such as vancomycin (anti-colon cancer activity), Diazonamide A, (-)-gossypol (insecticide, male contraceptive) and Dioncophylline C (anti-malaria), etc. In addition, such compounds are also often used as chiral catalysts in asymmetric synthesis, and representative examples include BINAP, BINOL, MOP and chiral phosphoric acid, etc. In asymmetric organic synthesis and industrial catalytic processes, axially chiral skeleton ligands exhibit excellent stereochemical control ability, and can obtain enantioselective single target product with high yield, thereby significantly improving reaction efficiency and meeting the principle of "atom economy" advocated by green chemistry.

[0003] With the increasing in-depth study of axially chiral compounds, the synthesis methodology thereof is also continuously expanding. So far, various axially chiral skeleton structures have been developed, including biaryl type, aryl amide type, aryl amine type, styrene type, and 1,3-diene type which has attracted much attention in recent years. Among them, the 1,3-diene type axially chiral skeleton has higher conformational flexibility than other types, and exhibits good application potential in certain specific catalytic asymmetric reactions, and has broad research prospects. However, due to the low rotation energy barrier of such structure, the synthesis difficulty is significantly increased, and important breakthroughs in related research have not been made until 2024, and currently, there are still problems such as complex substrate structure and many reaction condition limitations. Therefore, if the 1,3-diene type axially chiral skeleton can be efficiently constructed from simple structure substrates by means of mature coupling reaction strategy, it will have important promoting significance for the synthesis research and subsequent application of such compounds. SUMMARY

[0004] The purpose of the present application is to improve the deficiencies of the existing preparation synthesis method, and provide a method for synthesizing a compound with a hindered 1,3-diene structure through a transition metal catalyzed reductive coupling reaction, which has efficient and simple reaction conditions, wide substrate applicability and convenient operation.

[0005] The technical scheme of the present application is that the substrate, reducing agent, catalyst, single electron transfer agent, ligand are put into a sealed tube under an argon environment, a solvent is added, and the coupling product is obtained under stirring at 30 DEG C under sealed conditions, and the reaction formula is as follows:

[0006]

[0007] (1) R 1 is selected from R 1selected from the group consisting of phenyl, 4-methylphenyl, methyl, cyclopropyl, sec-butyl, methoxy, fluoro, chloro;

[0008] (2) R is selected from the group consisting of phenyl, 3,4-dimethylphenyl, 3,4-dichlorophenyl, 2-naphthyl, cyclohexyl; 2 selected from the group consisting of phenyl, 3,4-dimethylphenyl, 3,4-dichlorophenyl, 2-naphthyl, cyclohexyl;

[0009] (3) X is selected from the group consisting of -CH2-, -O-, -NTs-;

[0010] (4) the organic solvent used is selected from the group consisting of anhydrous 1,2-dichloroethane, dichloromethane, N,N-dimethylformamide, toluene, N,N-dimethylacetamide, 1,4-dioxane, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, anisole, xylenes, preferably anhydrous toluene;

[0011] (5) the reducing agent used is selected from the group consisting of activated zinc dust, manganese powder, preferably activated zinc dust;

[0012] (4) the metal catalyst (cat. 1) used is selected from the group consisting of ethylene glycol dimethyl ether nickel (II) bromide, ethylene glycol dimethyl ether nickel (II) chloride, bis(triphenylphosphine) nickel (II) chloride, bis(1,5-cyclooctadiene) nickel (0), bis(tricyclohexylphosphine) nickel (II) chloride, ethylene glycol dimethyl ether cobalt (II) bromide, preferably ethylene glycol dimethyl ether nickel (II) bromide;

[0013] (5) the heating temperature used is selected from the range of 25 to 50 °C, preferably 30 °C;

[0014] (6) the single electron transfer catalyst (cat. 2) used is preferably cobalt (II) phthalocyanine;

[0015] (7) the additive used is selected from the group consisting of tetrabutylammonium iodide, tetrabutylammonium bromide, tetraethylammonium iodide, preferably tetraethylammonium iodide;

[0016] (8) the ligand used is preferably (3aS,8aR)-2-(6-diphenylmethyIpyridin-2-yl)-8,8a- dihydro-3aH-indeno[l,2-d]oxazole;

[0017] (9) the optimal ratio of substrate / cat. 1 / cat. 2 / ligand / reductant / additive used in the reaction is 1 / 0.08 / 0.10 / 0.12 / 1 / 2, the amount of solvent used is preferably 0.8 mL per 0.1 mmol of substrate. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 shows the synthesis conditions for the coupling reaction;

[0019] Figure 2 shows the preparation reaction scheme for compound 2a;

[0020] Figure 3 is a reaction scheme for the preparation of compound 2b;

[0021] Figure 4 is a reaction scheme for the preparation of compound 2c;

[0022] Figure 5 is a reaction scheme for the preparation of compound 2d;

[0023] Figure 6 is a reaction scheme for the preparation of compound 2e;

[0024] Figure 7 is a reaction scheme for the preparation of compound 2f;

[0025] Figure 8 is a reaction scheme for the preparation of compound 2g;

[0026] Figure 9 is a reaction scheme for the preparation of compound 2h;

[0027] Figure 10 is a reaction scheme for the preparation of compound 2i;

[0028] Figure 11 is a reaction scheme for the preparation of compound 2j;

[0029] Figure 12 is a reaction scheme for the preparation of compound 2k;

[0030] Figure 13 is a reaction scheme for the preparation of compound 2l;

[0031] Figure 14 is a reaction scheme for the preparation of compound 2m;

[0032] Figure 15 is a reaction scheme for the preparation of compound 2n;

[0033] Figure 16 is a reaction scheme for the preparation of compound 2o;

[0034] Figure 17 is a reaction scheme for the preparation of compound 2p;

[0035] Figure 18 is a reaction scheme for the preparation of compound 2q;

[0036] Figure 19 is a reaction scheme for the preparation of compound 2r;

[0037] Figure 20 is a reaction scheme for the preparation of compound 2s;

[0038] Figure 21 is a reaction scheme for the preparation of compound 2t;

[0039] Figure 22 is a reaction scheme for the preparation of compound 2u;

[0040] Figure 23 is a reaction scheme for the preparation of compound 2v;

[0041] Figure 24 is a reaction scheme for the preparation of compound 2w;

[0042] Figure 25 is a reaction scheme for the preparation of compound 2x. DETAILED DESCRIPTION

[0043] The application will be further described by the following examples, but it should not be understood that the scope of the above-mentioned subject matter of the application is limited to the following examples. Any technology realized based on the above-mentioned content of the application falls within the scope of the application.

[0044] Example 1

[0045] Using substrate (1a) as raw material (reaction scheme 1)

[0046]

[0047] Reaction scheme 1

[0048] In an argon-filled glove box, a reaction tube (the reaction tube was previously baked in an oven for 1 h) was added with substrate 1a (1.0 equiv., 35.9 mg), ethylene glycol dimethyl ether nickel (II) bromide (0.08 equiv., 2.5 mg), cobalt (II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand (3aS, 8aR)-2-(6-benzhydrylpyridin-2-yl)-8,8a-dihydro-3aH-indeno[1,2-d]oxazole (hereinafter referred to as L in subsequent steps, 0.12 equiv., 4.8 mg), followed by 0.8 mL of anhydrous toluene solvent, and the reaction was placed in 30 °C for 24 h. After the reaction was detected to be completed by TLC (petroleum ether / acetone = 4:1), ethyl acetate was directly added for dilution and insoluble impurities were filtered, and the filtrate was distilled under reduced pressure, and the residue was purified by silica gel column chromatography, to finally obtain product 2a (92% yield, 92% ee).

[0049] The product detection data are as follows:

[0050] 1 H NMR (400 MHz, CDCl3) δ 7.22-7.26 (m, 4H), 7.09-7.13 (m, 4H), 6.76-6.79 (m, 2H), 6.71-6.74 (m, 6H), 3.66 (s, 6H), 2.73-2.85 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 166.13, 158.40, 150.61, 146.18, 135.33, 129.82, 129.32, 128.27, 126.32, 125.56, 121.45, 113.75, 113.25, 55.28, 26.96, 25.11; HPLC analysis: The ee was determined tobe 92% on a CHIRALCEL IA-3 column (5% iPrOH in n-hexane, flow rate = 1.0 mL / min, λ = 210 nm, 30 o C): 14.208 min (major), 13.115 min (minor).

[0051] Implementation Case 2

[0052] Using substrate (1b) as a raw material (reaction formula 2)

[0053]

[0054] Reaction 2

[0055] In an argon-filled glove box, substrate 1b (1.0 equiv., 32.9 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2b (94% yield, 92% ee) was obtained.

[0056] The product test data are as follows:

[0057] 1 H NMR (400 MHz, CDCl3) δ 7.23-7.28 (m, 6H), 7.17-7.22 (m, 4H), 7.11-7.16 (m, 4H), 6.68-6.71 (m, 4H), 2.77-2.93 (m, 8H);13 C NMR (100 MHz, CDCl3) δ 166.22, 150.61, 146.54, 137.70, 134.62, 129.46, 129.34, 127.69, 127.01, 126.74, 125.70, 125.60, 121.44, 27.83, 24.74; HPLC analysis: The ee was determined to be 92% on aCHIRALCEL IA-3 column (5% iPrOH in n-hexane, flow rate = 1.0 mL / min, λ = 254nm, 30 o C): 9.641 min (major), 8.687 min (minor).

[0058] Implementation Case 3

[0059] Using substrate (1c) as raw material (reaction formula 3)

[0060]

[0061] Reaction 3

[0062] In an argon-filled glove box, substrate 1c (1.0 equiv., 35.9 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2c (85% yield, 92% ee) was obtained.

[0063] The product test data are as follows:

[0064] 1H NMR (400 MHz, CDCl3) δ 7.24-7.28 (m, 4H), 7.07-7.16 (m, 4H), 6.83-6.88 (m, 4H), 6.73-6.76 (m, 4H), 3.84 (s, 6H), 2.92-3.02 (m, 2H), 2.74-2.87 (m, 6H); 13 C NMR (100 MHz, CDCl3) δ 166.31, 155.97, 150.65, 146.43, 135.47, 129.28, 126.98, 125.92, 125.81, 125.52, 121.45, 119.47, 111.82, 55.71, 24.19, 19.84; HPLC analysis: The ee was determined to be 92% on a CHIRALCEL AD-H column (5% iPrOH in n-hexane, flowrate = 1.0 mL / min, λ = 254 nm, 30 o C): 12.664 min (major), 16.374 min (minor).

[0065] Implementation Case 4

[0066] Using substrate (1d) as raw material (reaction formula 4)

[0067]

[0068] Reaction 4

[0069] In an argon-filled glove box, substrate 1d (1.0 equiv., 36.4 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and silica gel column chromatography to obtain product 2d (70% yield, 90% ee).

[0070] The product test data are as follows:

[0071] 1 H NMR (400 MHz, CDCl3) δ 7.23-7.31 (m, 6H), 7.15-7.19 (m, 4H), 7.08 (d, J =2.0 Hz, 2H), 6.79-6.82 (m, 4H), 2.81-2.95 (m, 8H); 13 C NMR (100 MHz, CDCl3) δ 165.58, 150.43, 144.54, 135.91, 135.59, 132.59, 129.45, 129.38, 129.07, 127.44, 126.13, 125.81, 121.35, 27.16, 24.56; HPLC analysis: The ee was determined to be 90% on aCHIRALCEL IA-3 column (5% iPrOH in n-hexane, flow rate = 1.0 mL / min, λ = 254nm, 30 o C): 8.945 min (major), 9.533 min (minor).

[0072] Implementation Case 5

[0073] Using substrate (1e) as raw material (reaction formula 5)

[0074]

[0075] Reaction 5

[0076] In an argon-filled glove box, substrate 1e (1.0 equiv., 35.9 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and the residue was purified by silica gel column chromatography to finally obtain product 2e (90% yield, 91% ee).

[0077] The product test data are as follows:

[0078] 1 H NMR (400 MHz, CDCl3) δ 7.24-7.29 (m, 4H), 7.10-7.16 (m, 4H), 6.75-6.77 (m, 6H), 6.65-6.68 (m, 2H), 3.80 (m, 6H), 2.78-2.89 (m, 8H); 13 C NMR (100 MHz, CDCl3) δ166.26, 160.46, 150.76, 146.96, 139.83, 129.29, 128.51, 127.58, 125.44, 122.76, 121.50, 113.50, 111.86, 55.34, 28.37, 24.56; HPLC analysis: The ee was determined to be 91% on a CHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 230nm, 30 o C): 21.420 min (major), 14.139 min (minor).

[0079] Implementation Case Six

[0080] Using substrate (1f) as raw material (reaction formula 6)

[0081]

[0082] Reaction 6

[0083] In an argon-filled glove box, substrate 1f (1.0 equiv., 34.3 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and the residue was purified by silica gel column chromatography to finally obtain product 2f (80% yield, 88% ee).

[0084] The product test data are as follows:

[0085] 1 H NMR (400 MHz, CDCl3) δ 7.22-7.27 (m, 4H), 7.08-7.16 (m, 6H), 6.97 (s, 2H), 6.64-6.68 (m, 4H), 2.76-2.88 (m, 8H), 2.24 (s, 6H); 13 C NMR (100 MHz, CDCl3) δ166.30, 150.60, 146.75, 136.37, 134.84, 134.78, 130.12, 129.27, 127.47, 127.24, 125.51, 121.43, 27.46, 24.90, 21.40; HPLC analysis: The ee was determined to be 88% on aCHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 8.285 min (minor), 7.534 min (major).

[0086] Implementation Case Seven

[0087] Using substrate (1g) as raw material (reaction formula 7)

[0088]

[0089] Reaction 7

[0090] In an argon-filled glove box, 1 g of substrate (1.0 equiv., 34.7 mg), nickel(II) ethylene glycol dimethyl ether bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and the residue was purified by silica gel column chromatography to finally obtain 2 g of product (87% yield, 92% ee).

[0091] The product test data are as follows:

[0092] 1 H NMR (400 MHz, CDCl3) δ 7.29-7.33 (m, 4H), 7.16-7.21 (m, 4H), 6.96-7.00 (m, 2H), 6.81-6.87 (m, 6H), 2.84-2.95 (m, 8H); 13 C NMR (100 MHz, CDCl3) δ 165.7, 161.8 (d, J = 243.4 Hz)., 150.5, 144.8 (d, J = 2.6 Hz), 135.6 (d, J = 7.4 Hz), 133.1 (d, J = 3.1 Hz), 129.4, 129.0 (d, J = 7.9 Hz), 127.4, 125.8, 121.4, 116.1 (d, J = 21.5 Hz), 113.3 (d, J = 23.2 Hz), 27.0, 24.8; 19 F NMR (377 MHz, CDCl3) δ -115.45; HPLC analysis: The ee was determined to be 92% on a CHIRALCEL IA-3 column (5% iPrOHin n-hexane, flow rate = 1.0 mL / min, λ = 254 nm, 30 oC): 9.120 min (major), 9.711 min (minor).

[0093] Implementation Case 8

[0094] Using substrate (1h) as raw material (reaction formula 8)

[0095]

[0096] Reaction 8

[0097] In an argon-filled glove box, substrate 1h (1.0 equiv., 36.4 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The residue of the filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2h (78% yield, 91% ee) was obtained.

[0098] The product test data are as follows:

[0099] 1 H NMR (400 MHz, CDCl3) δ 7.28-7.32 (m, 4H), 7.22-7.23 (br, 2H), 7.11-7.20 (m, 4H), 7.06 (d, J = 8.3 Hz, 2H), 6.78-6.82 (m, 4H), 2.79-2.93 (m,8H); 13C NMR (100MHz, CDCl3) δ 165.69, 150.47, 145.06, 139.38, 135.20, 132.59, 129.45, 127.90, 127.77, 127.09, 126.19, 125.77, 121.32, 27.62, 24.42; HPLC analysis: The ee was determined to be 91% on a CHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 10.484 min (major), 9.480 min (minor).

[0100] Implementation Case Nine

[0101] Using substrate (1i) as a starting material (reaction formula 9)

[0102]

[0103] Reaction 9

[0104] In an argon-filled glove box, substrate 1i (1.0 equiv., 34.7 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2i (90% yield, 92% ee) was obtained.

[0105] The product test data are as follows:

[0106] 1H NMR (400 MHz, CDCl3) δ 7.27-7.32 (m, 4H), 7.12-7.19 (m, 4H), 6.93-6.96 (dd, J = 2.5 Hz, 8.9 Hz, 2H), 6.82-6.87 (m, 2H), 6.78-6.81 (m, 4H), 2.79-2.94 (m, 8H); 13 C NMR (100 MHz, CDCl3) δ 165.84, 163.12 (d, J = 251.0 Hz), 150.55, 145.44, 140.49 (d, J = 8.2 Hz), 130.42 (d, J = 3.1 Hz), 129.41, 128.55 (d, J = 8.7 Hz), 125.69, 125.12 (d, J = 2.3 Hz), 121.33, 114.93 (d, J = 21.9 Hz), 113.72 (d, J = 21.6 Hz), 27.95 (d, J = 1.2 Hz), 24.34.; 19 F NMR (377 MHz, CDCl3) δ -110.83; HPLC analysis: The ee was determined to be 92% on a CHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 12.224 min (major), 10.354 min (minor).

[0107] Implementation Case 10

[0108] Using substrate (1j) as raw material (reaction formula 10)

[0109]

[0110] Reaction 10

[0111] In an argon-filled glove box, substrate 1j (1.0 equiv., 36.4 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and silica gel column chromatography to obtain product 2j (81% yield, 91% ee).

[0112] The product test data are as follows:

[0113] 1 H NMR (400 MHz, CDCl3) δ 7.28-7.36 (m, 6H), 7.16-7.20 (m, 2H), 7.06-7.12 (m, 4H), 6.77-6.80 (m, 4H), 2.80-3.15 (m, 8H); 13 C NMR (100 MHz, CDCl3) δ 165.67, 150.41, 145.12, 136.00, 135.19, 133.33, 130.39, 129.45, 127.55, 126.94, 125.82, 125.20, 121.28, 24.19, 24.05; HPLC analysis: The ee was determined to be 91% on aCHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 8.592 min (minor), 9.972 min (major).

[0114] Implementation Case Eleven

[0115] Using substrate (1k) as raw material (reaction 11)

[0116]

[0117] Reaction 11

[0118] In an argon-filled glove box, substrate 1k (1.0 equiv., 40.5 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The residue of the filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2k (87% yield, 90% ee) was obtained.

[0119] The product test data are as follows:

[0120] 1 H NMR (400 MHz, CDCl3) δ 7.43-7.46 (m, 2H), 7.36-7.40 (m, 6H), 7.30-7.34 (m, 4H), 7.19-7.24 (m, 8H), 7.01-7.11 (m, 2H), 6.66-6.69 (m, 4H), 2.82-2.91 (m, 8H); 13 CNMR (100 MHz, CDCl3) δ 166.20, 150.57, 146.10, 140.88, 140.03, 136.75, 134.91, 129.34, 128.82, 128. 24, 128.14, 127.25, 127.03, 126.36, 125.59, 125.24, 121.39, 27.56, 24.88; HPLC analysis: The ee was determined to be 90% on a CHIRALCEL AD-Hcolumn (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 19.160min (major), 13.981min (minor).

[0121] Implementation Case Twelve

[0122] Using substrate (1l) as raw material (reaction formula 12)

[0123]

[0124] Reaction 12

[0125] In an argon-filled glove box, substrate 1L (1.0 equiv., 40.5 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and the residue was purified by silica gel column chromatography to finally obtain product 2L (86% yield, 92% ee).

[0126] The product test data are as follows:

[0127] 1 H NMR (400 MHz, CDCl3) δ 7.36-7.42 (m, 6H), 7.28-7.33 (m, 6H), 7.24-7.27 (m, 4H), 7.15-7.19 (m, 6H), 6.59-6.63 (m, 4H), 2.75-2.86 (m, 4H), 2.54-2.69 (m, 4H); 13 CNMR (100 MHz, CDCl3) δ 166.28, 150.49, 147.26, 140.79, 140.73, 136.03, 135.40, 131.24, 129.35, 129. 28, 128.17, 127.16, 126.56, 126.05, 125.84, 125.64, 121.40, 25.18, 24.75; HPLC analysis: The ee was determined to be 92% on a CHIRALCEL AD-Hcolumn (15% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 10.038min (major), 12.286min (minor).

[0128] Implementation Case Thirteen

[0129] Using substrate (1m) as raw material (reaction formula 13)

[0130]

[0131] Reaction 13

[0132] In an argon-filled glove box, substrate 1m (1.0 equiv., 40.5 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The residue of the filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2m (89% yield, 99% ee) was obtained.

[0133] The product test data are as follows:

[0134] 1 H NMR (400 MHz, CDCl3) δ 7.59-7.61 (m, 4H), 7.33-7.47 (m, 10H), 7.23-7.30 (m, 6H), 7.12-7.17 (m, 2H), 6.74-6.77 (m, 4H), 2.85-3.03 (m,8H); 13 C NMR (100 MHz, CDCl3) δ 166.14, 150.64, 146.35, 142.16, 140.44, 138.19, 133.66, 129.35, 128.88, 127.70, 127 .22, 127.06, 126.45, 125.66, 125.59, 125.57, 121.45, 28.06, 24.79; HPLC analysis: The ee was determined to be 99% on a CHIRALCEL AD-H column (5% iPrOHin n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 oC): 13.535 min (minor), 19.948 min (major).

[0135] Implementation Case Fourteen

[0136] Using substrate (1n) as raw material (reaction formula 14)

[0137]

[0138] Reaction 14

[0139] In an argon-filled glove box, substrate 1n (1.0 equiv., 36.9 mg), nickel(II) ethylene glycol dimethyl ether bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The residue of the filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2n (76% yield, 85% ee) was obtained.

[0140] The product test data are as follows:

[0141] 1 H NMR (400 MHz, CDCl3) δ 7.22-7.27 (m, 4H), 7.09-7.14 (m, 4H), 6.90-6.93 (m, 4H), 6.64-6.68 (m, 4H), 2.75-2.84 (m, 8H), 1.73-7.80 (m, 2H), 0.83-0.88 (m, 4H), 0.51-0.55 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 166.27, 150.61, 146.56, 142.52, 134.83, 134.52, 129.27, 127.51, 125.9 8, 125.67, 125.50, 124.56, 121.44, 27.47, 24.90, 15.24, 9.30, 9.19; HPLC analysis: The ee was determined to be 85% on a CHIRALCEL Amy-Dcolumn (8% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 9.255 min (major), 11.578 min (minor).

[0142] Implementation Case 15

[0143] Using substrate (1o) as raw material (reaction formula 15)

[0144]

[0145] Reaction 15

[0146] In an argon-filled glove box, substrate 1o (1.0 equiv., 38.5 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and the residue was purified by silica gel column chromatography to finally obtain product 2o (67% yield, 86% ee).

[0147] The product test data are as follows:

[0148] 1H NMR (400 MHz, CDCl3) δ 7.22-7.27 (m, 4H), 7.11-7.15 (m, 4H), 7.03-7.06 (m, 2H), 6.92 (br, 2H), 6.64-6.67 (m, 4H), 2.73-2.88 (m, 8H), 2.30-2.39 (m, 4H), 1.63-1.72 (m, 2H), 0.75-0.79 (m, 12H); 13 C NMR (100 MHz, CDCl3) δ 166.24, 150.63, 147.07, 140.07, 135.15, 134.64, 130.13, 129.24, 127.53, 12 7.24, 125.46, 125.21, 121.44, 45.00, 30.16, 27.50, 24.86, 22.18, 22.06; HPLC analysis: The ee was determined to be 86% on a CHIRALCEL Amy-D column (3% iPrOH in n-hexane, flow rate = 1 mL / min, λ =254 nm, 30 o C): 10.443 min (minor), 7.027 min (major).

[0149] Implementation Case Sixteen

[0150] Using substrate (1p) as raw material (reaction formula 16)

[0151]

[0152] Reaction 16

[0153] In an argon-filled glove box, substrate 1p (1.0 equiv., 41.9 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and silica gel column chromatography to obtain product 2p (80% yield, 88% ee).

[0154] The product test data are as follows:

[0155] 1 H NMR (400 MHz, CDCl3) δ 7.43-7.46 (m, 2H), 7.40 (br, 2H), 7.28-7.30 (br, 4H), 7.21-7.25 (m, 6H), 7.10-7.16 (m, 6H), 6.69-6.71 (m, 4H), 2.83-2.93 (m, 8H), 2.32 (s, 6H); 13 C NMR (100 MHz, CDCl3) δ 166.20, 150.59, 146.26, 139.95, 138.05, 137.06, 136.44, 134.86, 129.51, 129.47, 129.32, 128.05, 126.88, 126.20, 125.55, 125.13, 121.41, 27.55, 24.89, 21.07; HPLC analysis: The ee was determined to be 88% on aCHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 14.476 min (minor), 10.546 min (major).

[0156] Implementation Case Seventeen

[0157] Using substrate (1q) as raw material (reaction formula 17)

[0158]

[0159] Reaction 17

[0160] In an argon-filled glove box, substrate 1q (1.0 equiv., 35.7 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The residue of the filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2q (65% yield, 92% ee) was obtained.

[0161] The product test data are as follows:

[0162] 1 H NMR (400 MHz, CDCl3) δ 7.23-7.27 (m, 2H), 7.17-7.21 (m, 4H), 7.11-7.15 (m, 2H), 6.93 (br, 2H), 6.86-6.88 (m, 2H), 6.42-6.44 (d, J = 8.1 Hz, 2H), 2.77-2.95 (m, 8H), 2.25 (s, 6H), 1.84 (s, 6H); 13 C NMR (100 MHz, CDCl3) δ 165.71, 147.01, 146.99, 137.79, 135.25, 134.87, 131.58, 129.75, 129.31, 127 .54, 127.36, 126.84, 126.78, 125.12, 121.19, 27.84, 24.47, 20.80, 15.90; HPLC analysis: The ee was determined to be 92% on a CHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1.0 mL / min, λ =254 nm, 30 oC): 21.698 min (minor), 14.692 min (major).

[0163] Implementation Case 18

[0164] Using substrate (1r) as raw material (reaction formula 18)

[0165]

[0166] Reaction 18

[0167] In an argon-filled glove box, substrate 1r (1.0 equiv., 37.9 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2r (70% yield, 93% ee) was obtained.

[0168] The product test data are as follows:

[0169] 1 H NMR (400 MHz, CDCl3) δ 7.70-7.72 (m, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.59-7.61 (m, 2H), 7.36-7.43 (m, 4H), 7.27-7.31 (m, 2H), 7.16-7.24 (m, 6H), 7.08 (d, J = 2.1 Hz, 2H), 6.78 (dd, J = 2.2 Hz, 8.8 Hz, 1H), 2.76-2.91 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 166.46, 148.24, 146.74, 137.86, 134.92, 133.74, 131.37, 129.50, 129.25, 127.75, 127. 72, 127.62, 127.11, 126.77, 126.40, 125.72, 125.56, 121.04, 118.35, 27.83, 24.76; HPLC analysis: The ee was determined to be 93% on a CHIRALCEL AD-Hcolumn (5% iPrOH in n-hexane, flow rate = 1.0 mL / min, λ = 254 nm, 30 o C): 31.473min (minor), 19.261min (major).

[0170] Implementation Case 19

[0171] Using substrate (1s) as raw material (reaction formula 19)

[0172]

[0173] Reaction 19

[0174] In an argon-filled glove box, substrate 1S (1.0 equiv., 39.8 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2S (63% yield, 91% ee) was obtained.

[0175] The product test data are as follows:

[0176] 1H NMR (400 MHz, CDCl3) δ 7.32-7.36 (m, 4H), 7.28 (br, 2H), 7.15-7.23 (m, 4H), 6.72 (d, J = 2.6 Hz, 2H), 6.53 (dd, J = 2.6 Hz, 8.7 Hz, 2H), 2.76-2.95 (m, 8H); 13 CNMR (100 MHz, CDCl3) δ 165.46, 149.09, 147.35, 137.72, 134.52, 132.83, 130.61, 129.93, 129.58, 127 .87, 127.21, 126.59, 124.97, 123.70, 121.09, 27.68, 24.61; HPLC analysis: The ee was determined to be 91% on a CHIRALCEL AD-H column (20%iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 6.871 min (major), 15.536 min (minor).

[0177] Implementation Case 20

[0178] Using substrate (1t) as raw material (reaction formula 20)

[0179]

[0180] Reaction 20

[0181] In an argon-filled glove box, substrate 1t (1.0 equiv., 33.5 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The residue of the filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2t (82% yield, 75% ee) was obtained.

[0182] The product test data are as follows:

[0183] 1 H NMR (400 MHz, CDCl3) δ 7.14-7.21 (m, 4H), 7.09-7.11 (m, 2H), 7.01-7.05 (m, 2H), 4.62-4.69 (m, 2H), 2.93-3.01 (m, 4H), 2.66-2.85 (m, 4H), 1.70-1.75 (m, 2H), 1.50-1.60 (m, 6H), 1.41-1.48 (m, 2H), 1.17-1.26 (m, 6H), 0.98-1.15 (m, 4H); 13 C NMR (100 MHz, CDCl3) δ HPLC analysis: The eewas determined to be 75% on a CHIRALCEL IC-3 column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 6.614 min (minor), 7.228 min (major).

[0184] Implementation Case 21

[0185] Using substrate (1u) as raw material (reaction formula 21)

[0186]

[0187] Reaction 21

[0188] In an argon-filled glove box, substrate 1u (1.0 equiv., 41.9 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and the residue was purified by silica gel column chromatography to finally obtain product 2u (57% yield, 90% ee).

[0189] The product test data are as follows:

[0190] 1 H NMR (400 MHz, CDCl3) δ 7.30-7.32 (m, 2H), 7.27-7.29 (m, 4H), 7.21-7.25 (m, 8H), 7.14-7.18 (m, 2H), 7.06 (d, J = 7.6 Hz, 4H), 2.74-2.87 (m, 4H), 2.53-2.68 (m, 4H), 2.41 (s, 6H); 13 C NMR (100 MHz, CDCl3) δ 166.32, 150.49, 147.35, 140.66, 137.84, 136.88, 136.04, 135.43, 131.27, 129.33, 129.17, 128.86, 126.52, 125.91, 125.75, 125.61, 121.40, 25.21, 24.76, 21.21; HPLC analysis: The ee was determined to be 90% on aCHIRALCEL AD-H column (2% iPrOH in n-hexane, flow rate = 1 mL / min, λ = 254 nm, 30 o C): 12.938 min (major), 15.192 min (minor).

[0191] Implementation Case 22

[0192] Using substrate (1v) as raw material (reaction formula 22)

[0193]

[0194] Reaction 22

[0195] In an argon-filled glove box, substrate 1v (1.0 equiv., 33.1 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was completed by TLC (petroleum ether / acetone = 4:1). Ethyl acetate was added directly to dilute the product, and insoluble impurities were filtered out. The residue of the filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2v (70% yield, 94% ee) was obtained.

[0196] The product test data are as follows:

[0197] 1 H NMR (400 MHz, CDCl3) δ 7.25-7.33 (m, 6H), 7.13-7.20 (m, 4H), 6.95-6.97 (m, 2H), 6.87-6.91 (m, 6H), 5.28 (dd, J = 13.9 Hz, 59.0 Hz, 4H); 13 C NMR (100 MHz, CDCl3) δ 162.47, 155.56, 150.23, 143.46, 132.40, 129.47, 126.97, 125.95, 122.25, 121.89, 121.30, 118.59, 116.76, 64.87; HPLC analysis: The ee was determined to be 94% on a CHIRALCEL AD-H column (5% iPrOH in n-hexane, flow rate = 1 mL / min, λ =254 nm, 30 o C): 18.702 min (major), 17.137 min (minor).

[0198] Implementation Case 23

[0199] Using the substrate (1w) as a raw material (reaction formula 23)

[0200]

[0201] Reaction 23

[0202] In an argon-filled glove box, substrate 1w (1.0 equiv., 36.6 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by silica gel column chromatography after vacuum distillation, and the final product 2w (72% yield, 88% ee) was obtained.

[0203] The product test data are as follows:

[0204] 1 H NMR (400 MHz, CDCl3) δ 7.37-7.41 (m, 4H), 7.24-7.30 (m, 4H), 7.07 (d, J = 2.4 Hz, 2H), 6.95-7.01 (m, 6H), 5.33 (d, J = 14.2 Hz, 2H), 5.17 (d, J = 14.2 Hz, 2H); 13 C NMR (100 MHz, CDCl3) δ 161.99, 154.07, 150.00, 141.86, 132.33, 129.61, 127.25, 126.22, 125.94, 122.76, 121.26, 119.97, 118.39, 64.98; HPLC analysis: The ee was determined to be 88% on a CHIRALCEL AD-H column (5% iPrOH in n-hexane, flowrate = 1 mL / min, λ = 254 nm, 30 o C): 9.925 min (major), 14.539 min (minor).

[0205] Implementation Case 24

[0206] Using substrate (1x) as raw material (reaction formula 24)

[0207]

[0208] Reaction 24

[0209] In an argon-filled glove box, substrate 1x (1.0 equiv., 48.4 mg), ethylene glycol dimethyl ether nickel(II) bromide (0.08 equiv., 2.5 mg), cobalt(II) phthalocyanine (0.1 equiv., 5.7 mg), tetraethylammonium iodide (2.0 equiv., 51.4 mg), activated zinc powder (1.0 equiv., 6.5 mg), and ligand L (0.12 equiv., 4.8 mg) were added to a reaction tube (pre-dried in an oven for 1 h). Then, 0.8 mL of anhydrous toluene solvent was added, and the reaction was carried out at 30 °C for 24 h. The reaction was detected by TLC (petroleum ether / acetone = 4:1) after which ethyl acetate was added to dilute the product and the insoluble impurities were filtered out. The filtrate was purified by vacuum distillation and the residue was purified by silica gel column chromatography to finally obtain product 2x (68% yield, 76% ee).

[0210] The product test data are as follows:

[0211] 1 H NMR (400 MHz, CDCl3) δ 7.37-7.41 (m, 4H), 7.24-7.30 (m, 4H), 7.07 (d, J = 2.4 Hz, 2H), 6.95-7.01 (m, 6H), 5.33 (d, J = 14.2 Hz, 2H), 5.17 (d, J = 14.2 Hz, 2H); 13 C NMR (100 MHz, CDCl3) δ 161.99, 154.07, 150.00, 141.86, 132.33, 129.61, 127.25, 126.22, 125.94, 122.76, 121.26, 119.97, 118.39, 64.98; HPLC analysis: The ee was determined to be 76% on a CHIRALCEL AD-H column (30% iPrOH in n-hexane, flowrate = 1 mL / min, λ = 254 nm, 30 oC): 33.909 min (major), 10.234 min (minor).

Claims

1. A method for synthesizing compounds with an enantiomeric 1,3-diene structure via a transition metal-catalyzed reductive coupling reaction, characterized by using phenyl 1-bromo-3,4-dihydronaphthyl-2-carboxylic acid ester and its derivatives as substrates, nickel(II) bromide in ethylene glycol dimethyl ether as catalyst, activated zinc powder as reducing agent, cobalt(II) phthalocyanine as single electron transfer agent, (3aS,8aR)-2-(6-diphenylmethylpyridin-2-yl)-8,8a-dihydrotetrahydro-3aH-indeno[1,2-d]oxazole as chiral ligand, tetraethylammonium iodide as additive, and anhydrous toluene as solvent. The reaction is carried out at 30°C to obtain 2,2'-[(phenyloxy)carbonyl]-1-(3,4-dihydro)-binaphthyl and its derivatives with an enantioselective nonplanar 1,3-diene structure, as shown in the following reaction formula: Equation (1) in: R 1 Selected from phenyl, 4-methylphenyl, methyl, cyclopropyl, sec-butyl, methoxy, fluorine, and chlorine; R 2 Selected from phenyl, 3,4-dimethylphenyl, 3,4-dichlorophenyl, 2-naphthyl, cyclohexyl; X is selected from -CH2-, -O-, -NTs-.

2. The method for synthesizing compounds with a blocked 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The organic solvent used is selected from anhydrous 1,2-dichloroethane, dichloromethane, N,N-dimethylformamide, toluene, N,N-dimethylacetamide, 1,4-dioxane, ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether, anisole, and xylene compounds, preferably anhydrous toluene.

3. The method for synthesizing compounds with a hindered 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The reducing agent used is selected from activated zinc powder and manganese powder, with activated zinc powder being preferred.

4. The method for synthesizing compounds with a blocked 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The heating temperature used is selected from 25-50℃, preferably 30℃.

5. The method for synthesizing compounds with a blocked 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The metal catalyst used (cat. 1) is selected from nickel(II) bromide of ethylene glycol dimethyl ether, nickel(II) chloride of ethylene glycol dimethyl ether, nickel(II) chloride of bis(triphenylphosphine) chloride, nickel(II) of bis(1,5-cyclooctadiene) chloride, nickel(II) chloride of bis(tricyclohexylphosphine) chloride, and cobalt(II) bromide of ethylene glycol dimethyl ether, preferably nickel(II) bromide of ethylene glycol dimethyl ether.

6. The method for synthesizing compounds with a blocked 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The preferred single-electron transfer catalyst used (cat.2) is cobalt(II) phthalocyanine.

7. The method for synthesizing compounds with a blocked 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The additives used are selected from tetrabutylammonium iodide, tetrabutylammonium bromide, and tetraethylammonium iodide, with tetraethylammonium iodide being preferred.

8. The method for synthesizing compounds with a blocked 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The preferred ligand used is (3aS,8aR)-2-(6-diphenylmethylpyridin-2-yl)-8,8a-dihydrotetrahydro-3aH-indeno[1,2-d]oxazole.

9. The method for synthesizing compounds with a blocked 1,3-diene structure via a transition metal-catalyzed reduction coupling reaction according to claim 1, characterized in that: The optimal ratio of substrate / cat.1 / cat.2 / L / reductant / additive is 1 / 0.08 / 0.10 / 0.12 / 1 / 2, and the preferred amount of solvent is 0.8 mL / 0.1 mmol substrate.

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