Synthesis method of seven-element phosphine oxide through nickel-aluminum catalysis

Abstract

The invention provides a simple and efficient synthesis method, in particular to a method for realizing activation and insertion of alkyne into a C-P bond of a pentabasic phosphine oxide to generate a heptabasic phosphine oxide by connecting a phosphorus-oxygen ligand with a nickel-aluminum bimetallic catalyst, and belongs to the technical field of methodology development. The key points of the invention to solve the problems are as follows: 1, a method for realizing C-P bond activation by virtue of a tension ring of a five-membered phosphorus oxide compound which is efficient and specific in reaction activity and site selectivity is found; and 2, a bimetallic catalytic system is designed by utilizing the characteristics of phosphine oxide ligands, so that the reaction activity is greatly improved, and efficient preparation is easier.

Description

Technical Field

[0001] The invention relates to a method for realizing CP bond activation by using a nickel-aluminum bimetallic catalyst, provides a synthesis method of a series of seven-membered ring phosphine oxide compounds, and belongs to the technical field of methodology research and application. Background Art

[0002] Starting from inexpensive and readily available starting materials, two-electron or one-electron approaches are good ways to achieve molecular complexity in the intermolecular carbon functionalization of conjugated systems. A classic approach is to carbon-functionalize alkynes or alkenes with functionalizing agents, which, even with stoichiometric amounts of oxidants or reductants, require sacrificial amounts of molecular fragments (see Figure 1 , Path i). Another more attractive alternative is to insert the alkyne or alkene directly into a chemical bond (see Figure 1 , Path ii), which can solve the problem of significant loss of molecular fragments and other stoichiometric reagents and provide higher atom and step economy.

[0003] Due to this advantage, a wide range of intermolecular carbon functionalization reactions have been established over the past few decades by directly inserting alkynes and alkenes into relatively reactive chemical bonds such as C-Cl (Br, I), CO (S, Se), C-Al, and others (see Figure 2 ,Left).

[0004] In contrast, direct insertion into relatively inert chemical bonds such as CC, CN, or CP bonds faces greater challenges because these bonds are more difficult to activate. By introducing various substrate activation strategies, such as highly strained small rings, directing groups, or polarized chemical bonds, alkynes or alkenes have also been successfully inserted into CC and CN bonds, providing a large number of intermolecular dicarbon functionalization or carboamination reactions (Scheme 1b, right). However, compared with these advances, the development of intermolecular carbophosphide reactions via direct insertion of alkynes or alkenes into CP bonds has lagged far behind, which may be attributed to the following difficulties: unreacted CP chains, highly strained P-containing small rings that are not easily accessible, strong coordination of the P atom to metal catalysts, and difficulty in forming CP bonds.

[0005] In summary, although many cross-coupling reactions using P-containing substrates as aryl or alkyl coupling reagents have been reported, the intermolecular carbophosphination of alkynes or alkenes with CP bonds remains an elusive challenge. Summary of the invention:

[0006] The present invention aims to provide a simple and practical method for the first time to realize the intermolecular carbophosphination reaction of alkynes with readily available five-membered phosphorus oxides using Ni-Al bimetallic catalysis. A wide range of alkynes and phosphorus oxides are well compatible with the reaction, providing a series of seven-membered phosphines, which are promising candidates for optoelectronic applications with yields as high as 94%.

[0007]

[0008] 1. In a nitrogen atmosphere, add the ligand, metal catalyst, raw material and solvent to the reaction bottle in sequence, then add Lewis acid, stir at the specified temperature for 12 hours, cool to room temperature, add ethyl acetate to dilute, add 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution to wash, separate the liquids, dry the organic phase with anhydrous sodium sulfate, and separate by column chromatography to obtain the target product 3. The single crystal structure of the compound is shown in ( Figure 3 );

[0009] 2. The metal catalyst involved in the present invention is Ni(cod)2, and the amount of the catalyst used is generally 10 mol%.

[0010] 3. The ligand involved in the present invention is chiral triphenylphosphine, and its usage is generally 10 mol%.

[0011] 4. The AlMe2Cl involved in the present invention has a concentration of 1 mol / L n-hexane solution, and its usage is generally 40 mol%.

[0012] 5. The solvent used in the present invention is toluene solution, and the amount used is 5 mL per mmol of raw material 1.

[0013] 6. In the raw material 1 used in the present invention, R is a substituted group such as phenyl, cyclohexyl, cyclopropane, tert-butyl, isopropyl, etc., but is not limited to these groups; R' is phenyl, butyl, pentyl, hexyl, but is not limited to these groups.

[0014] The advantages of the present invention are:

[0015] 1. Most of the reagents used in the present invention are commercially available. The chiral ligand raw materials to be synthesized are widely available and inexpensive. They can exist stably at room temperature and pressure, are easy to operate and handle, and do not require special treatment.

[0016] 2. The ligand involved in the present invention has a simple structure and is easy to operate, avoiding the defect of long ligand synthesis steps used in the previous method, and has simple equipment requirements, which greatly reduces the production cost of synthesizing such compounds.

[0017] 3. The present invention can obtain a seven-membered ring phosphine oxide compound in one step, and the post-treatment is simple and convenient, avoiding the previous method of obtaining a phosphine oxide product by a relay reaction, and greatly reducing the product reaction cost.

[0018] 4. The catalyst used in the present invention is cheap, and the amount of metal, ligand, etc. used is relatively low. While maintaining a good catalytic effect and reducing costs, it is convenient for post-processing procedures and reduces environmental pollution.

[0019] 5. The reaction of the present invention is completely atom-economical, meets the requirements of green chemistry, and will not produce other by-products in large-scale production, thereby achieving the requirements of simplifying the process, reducing costs, and reducing environmental pollution.

[0020] Specific implementation methods

[0021] The examples of the CP bond activation reaction of the pentaphosphine oxide compound will better illustrate the present invention, but it should be emphasized that the present invention is by no means limited to the contents represented by these examples. The following examples show different aspects of the present invention. The data given include specific operation and reaction conditions and products. The purity of the product is identified by nuclear magnetic resonance.

[0022] Example 1: Synthesis of 5-Phenyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0023]

[0024] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.1 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 3a by column chromatography as a white solid with a yield of 95% and a melting point of 147-149°C. 11H NMR (400 MHz, CDCl3) δ 8.35 - 8.20 (m, 1H), 7.67 - 7.53 (m, 2H), 7.52 - 7.43 (m, 1H), 7.14 - 7.03 (m, 5H), 7.00 - 6.90 (m, 4H), 2.88 - 2.69 (m, 2H), 2.69 - 2.55 (m, 1H), 2.53 - 2.40 (m, 1H), 1.84 - 1.72 (m, 1H), 1.70 - 1.59 (m, 1H), 1.16 - 1.07 (m, 1H), 1.05 (t, J = 7.3 Hz, 3H), 0.99 - 0.84 (m, 1H), 0.54 (t, J = 7.4 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 148.1 (d, J = 9.1 Hz), 141.2 (d, J = 10.2 Hz), 139.42, 139.36 (d, J = 7.4 Hz), 137.02 (d, J = 98.4 Hz), 136.95 (d, J = 93.1 Hz), 132.5 (d, J = 104.3 Hz), 131.7 (d, J = 2.4 Hz), 130.7 (d, J = 2.7 Hz), 130.5, 130.3 (d, J = 6.3 Hz), 130.0 (d, J = 11.3 Hz), 129.4 (d, J = 10.1 Hz), 127.7, 127.5 (d, J = 12.7 Hz), 127.2, 127.1, 126.9, 37.1 (d, J = 13.0 Hz), 31.2 (d, J = 8.3Hz), 24.2, 21.6 (d, J = 1.6 Hz), 14.3, 13.5. 31 31P NMR (162 MHz, CDCl3) δ 22.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 26 H 28 OP 387.1872; Found 387.1869.

[0025] Example 2: Synthesis of 6,7 - Diethyl - 5 - phenyldibenzo[b,d]phosphepine 5 - oxide

[0026]

[0027] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2b (32.8 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3b was separated by column chromatography as a white solid with a yield of 90% and a melting point of 78-80°C. 1 H NMR(400 MHz, CDCl3) δ8.35-8.24(m, 1H), 7.67-7.54(m, 2H), 7.53-7.48(m, 1H), 7.16-7.04(m, 5H), 7.00-6.88(m, 4H), 2.93-2.75(m, 2H), 2.75-2.65(m, 1H), 2.56-2.39(m, 1H), 1.26(t, J=7.5 Hz, 3H), 0.65 (t, J=7.5 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 148.8 (d, J = 9.1 Hz), 141.2 (d, J = 10.2 Hz), 139.7, 139.1 (d, J = 6.6 Hz), 137.6 (d, J = 93.5 Hz), 137.0 (d, J = 98.2 Hz), 132.5 (d, J = 104.5 Hz), 131.7 (d, J = 2.4 Hz), 130.7 (d, J = 2.7 Hz), 130.5, 130.3 (d, J = 6.2 Hz), 130.0 (d, J = 11.3 Hz), 130.0 (d, J = 10.1 Hz), 127.6 (d, J=2.1 Hz), 127.5, 127.2, 127.1, 126.9, 28.4 (d, J=13.2 Hz), 22.4 (d, J=8.5 Hz), 15.6, 13.0 (d, J=1.9 Hz). 31 P NMR (162MHz, CDCl3) δ22.3.HRMS (ESI) m / z: [M+H] + Calcd.for C 24 H 24 OP 359.1559; Found 359.1556.

[0028] Example 3: Synthesis of 6,7-Dibutyl-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0029]

[0030] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2c (55.3 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3c was separated by column chromatography as a white solid with a yield of 94% and a melting point of 164-166°C. 1 H NMR(400 MHz, CDCl3) δ 8.35-8.21 (m, 1H), 7.69-7.54 (m, 2H), 7.52-7.46 (m, 1H), 7.19-7.04 (m, 5H), 7.01-6.91 (m, 4H), 2.91-2.71 (m, 2H), 2.71-2.56 (m, 1H), 2.54-2.41 (m, 1H), 1.83-1.69 (m, 1H), 1.67-1.55 (m, 1H), 1.54-1.40 (m, 2H), 1.15-1.00 (m, 2H), 0.98 (t, J=7.3 Hz, 3H), 0.94-0.80 (m, 2H), 0.65 (t, J=6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 148.0 (d, J = 8.9 Hz), 141.3 (d, J = 10.2 Hz), 139.6, 139.48, 137.1 (d, J = 98.3 Hz), 136.9 (d, J = 93.2 Hz), 132.6 (d, J = 104.1 Hz), 131.7 (d, J = 2.3 Hz), 130.7 (d, J = 2.7 Hz), 130.6, 130.4 (d, J = 6.3 Hz), 130.0 (d, J = 11.4 Hz), 129.4 (d, J = 10.0 Hz), 127.7, 127.6 (d, J=12.5 Hz), 127.2, 127.1 (d, J = 2.2 Hz), 126.9, 35.0 (d, J = 12.9 Hz), 33.2, 30.4, 29.0 (d, J = 8.4 Hz), 23.1, 22.3, 14.1, 13.8. 31 P NMR (162 MHz, CDCl3) δ22.3.HRMS (ESI) m / z: [M+H] + Calcd.for C 28 H 32 OP 415.2185; Found 415.2188.

[0031] Example 4: Synthesis of (R, E)-5-(((tert-Butyldimethylsilyl)oxy)methyl)-2-(4-phenylbut-3-en-2-yl)pyridine

[0032]

[0033] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2d (77.7 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3d was separated by column chromatography as a white solid with a yield of 90% and a melting point of 86-88°C. 11H NMR (400 MHz, CDCl3) δ 8.38 - 8.23 (m, 1H), 7.64 - 7.53 (m, 2H), 7.51 - 7.45 (m, 1H), 7.13 - 7.01 (m, 5H), 6.99 - 6.87 (m, 4H), 2.91 - 2.70 (m, 2H), 2.68 - 2.53 (m, 1H), 2.51 - 2.38 (m, 1H), 1.80 - 1.59 (m, 2H), 1.55 - 1.43 (m, 1H), 1.31 - 1.18 (m, 1H), 0.98 (d, J = 6.4 Hz, 6H), 0.94 - 0.86 (m, 1H), 0.85 - 0.76 (m, 1H), 0.68 (t, J = 6.4 Hz, 6H). 13 13C NMR (100 MHz, CDCl3) δ 145.0 (d, J = 9.1 Hz), 141.2 (d, J = 10.3Hz), 139.5 (d, J = 6.6 Hz), 139.4, 137.0 (d, J = 98.3 Hz), 136.7 (d, J = 93.3 Hz), 132.5 (d, J = 104.2 Hz), 131.6 (d, J = 2.2 Hz), 130.6 (d, J = 2.6 Hz), 130.5, 130.3 (d, J = 6.3 Hz), 130.0 (d, J = 11.4 Hz), 129.4 (d, J = 10.2 Hz), 127.6, 127.4, 127.04 (d, J = 10.6 Hz), 127.03, 126.8, 39.9, 37.2, 33.3 (d, J = 13.0 Hz), 28.5, 27.9, 27.1 (d, J = 8.3 Hz), 22.7, 22.5, 22.3. 31 31P NMR (162 MHz, CDCl3) δ 22.1. HRMS (ESI) m / z: [M + H] + Calcd. for C 30 H 36 OP 443.2498; Found 443.2495.

[0034] Example 5: Synthesis of 6,7 - Dihexyl - 5 - phenyldibenzo[b,d]phosphepine 5 - oxide

[0035]

[0036] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2e (77.7 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 3e by column chromatography as a white solid with a yield of 90% and a melting point of 63-65°C. 1 H NMR(400 MHz, CDCl3) δ8.33-8.23 (m, 1H), 7.65-7.53 (m, 1H), 7.51-7.45 (m, 1H), 7.16-7 .03(m, 5H), 6.99-6.89(m, 4H), 2.92-2.71(m, 2H), 2.70-2.56(m, 1H), 2.54-2.4 2(m, 1H), 1.81-1.68(m, 1H), 1.66-1.55(m, 1H), 1.52-1.40(m, 2H), 1.38-1.28( m, 4H), 1.12-0.99 (m, 4H), 0.99-0.94 (m, 2H), 0.92-0.81 (m, 5H), 0.70 (t, J=6.9 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 148.0 (d, J = 9.1 Hz), 141.3 (d, J = 10.1 Hz), 139.50, 139.46, 137.1 (d, J = 98.2 Hz), 137.0 (d, J = 93.2 Hz), 132.7 (d, J = 104.3 Hz), 131.6 (d, J = 2.1 Hz), 130.6 (d, J = 2.5 Hz), 130.5, 130.4 (d, J = 6.3 Hz), 130.0 (d, J = 11.3 Hz), 129.4 (d, J = 10.2 Hz), 127.7, 127.5 (d, J = 12.6 Hz), 127.1, 127.0, 126.8, 35.1 (d, J=13.0 Hz), 31.8, 31.5, 30.9, 29.6, 29.2 (d, J=8.4 Hz), 28.7, 28.2, 22.8, 22.5, 14.2, 14.0. 31 P NMR (162 MHz, CDCl3) δ22.2.HRMS (ESI) m / z: [M+H] + Calcd.for C32 H 40 OP 471.2811; Found 471.2808.

[0037] Example 6: Synthesis of 6,7-Bis(3-((tert-butyldimethylsilyl)oxy)propyl)-5-phenyldibenzo[b,d]phosphepine5-oxide

[0038]

[0039] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2f (148.1 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 3f by column chromatography as a yellow liquid with a yield of 70%. 1 H NMR(400 MHz, CDCl3) δ8.26-8.15 (m, 1H), 7.59-7.48 (m, 2H), 7.44-7.40 (m, 1H), 7.06-6.96 (m, 5H), 6 .95-6.82(m, 4H), 3.80-3.60(m, 2H), 3.21-3.04(m, 2H), 2.92-2.81(m, 1H), 2.80-2.67(m, 2 H), 2.56-2.44(m, 1H), 1.98-1.87(m, 1H), 1.85-1.75(m, 1H), 1.28-1.16(m, 1H), 1.13-1.03 (m, 1H), 0.84 (s, 9H), 0.70 (s, 9H), 0.00 (s, 3H), -0.01 (s, 2H), -0.22 (s, 3H), -0.23 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.8 (d, J = 9.2 Hz), 141.2 (d, J = 10.2 Hz), 139.5, 139.2 (d, J = 6.5 Hz), 137.0 (d, J = 98.3 Hz), 136.9 (d, J = 93.3 Hz), 132.5 (d, J = 104.3 Hz), 131.8 (d, J = 2.0 Hz), 130.7 (d, J = 2.6 Hz), 130.6, 130.4 (d, J = 6.4 Hz), 130.0 (d, J = 11.3 Hz), 129.5 (d, J = 10.1 Hz), 127.8, 127.6 (d, J=12.6 Hz), 127.3, 127.2, 127.0, 62.9, 62.0, 34.0, 31.4, 31.3, 31.3, 26.1 (d, J=13.8 Hz), 25.6 (d, J=8.3 Hz), 18.4 (d, J=14.4 Hz), -5.1, -5.2, -5.4. 31 P NMR (162 MHz, CDCl3) δ22.1.HRMS (ESI) m / z: [M+H] + Calcd.forC 38 H 56 O3PSi2647.3500; Found 647.3497.

[0040] Example 7: Synthesis of 5,6,7-Triphenyldibenzo[b,d]phosphepine 5-oxide

[0041]

[0042] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2 g (71.2 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, 3 g of the target product was separated by column chromatography as a yellow liquid with a yield of 90% and a melting point of 120-122°C. 11H NMR (400 MHz, CDCl3) δ 8.34 - 8.18 (m, 1H), 7.80 - 7.68 (m, 2H), 7.67 - 7.55 (m, 1H), 7.47 - 7.34 (m, 2H), 7.29 - 7.24 (m, 1H), 7.21 - 7.13 (m, 5H), 7.12 - 6.95 (m, 7H), 6.92 - 6.78 (m, 3H), 6.78 - 6.65 (m, 1H). 13 13C NMR (100 MHz, CDCl3) δ 149.5 (d, J = 10.6 Hz), 142.6 (d, J = 14.8 Hz), 141.0 (d, J = 10.6 Hz), 140.4 (d, J = 1.7 Hz), 139.5 (d, J = 5.0 Hz), 138.8 (d, J = 90.8 Hz), 136.2 (d, J = 100.0 Hz), 136.1 (d, J = 5.6 Hz), 132.3 (d, J = 106.1 Hz), 132.1 (d, J = 2.5 Hz), 131.5 (d, J = 3.4 Hz), 131.5, 131.14, 131.09 (d, J = 2.9 Hz), 130.9, 130.5, 130.3, 130.2, 130.1, 127.9, 127.8 (d, J = 4.0 Hz), 127.7, 127.6, 127.4, 127.3, 126.9. 31 31P NMR (162 MHz, CDCl3) δ 19.7. HRMS (ESI) m / z: [M + H] + Calcd. for C 32 H 24 OP 455.1559; Found 455.1556.

[0043] Example 8: Synthesis of 5 - Phenyl - 6,7 - di - p - tolyldibenzo[b,d]phosphepine 5 - oxide

[0044]

[0045] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2h (82.4 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3i was separated by column chromatography as a white solid with a yield of 93% and a melting point of 171-173°C. 1 H NMR(400 MHz, CDCl3) δ 8.34-8.18 (m, 1H), 7.80-7.68 (m, 2H), 7.67-7.55 (m, 1H), 7.47-7.34 (m, 2H), 7. 29-7.24(m, 1H), 7.21-7.13(m, 5H), 7.12-6.95(m, 7H), 6.92-6.78(m, 3H), 6.78-6.65(m, 1H). 13 CNMR (100MHz, CDCl3) δ149.5 (d, J=10.6 Hz), 142.6 (d, J=14.8 Hz), 141.0 (d, J=10.6 Hz), 140.4 (d, J=1.7 Hz), 139.5 (d, J=5.0 Hz), 138.8 (d, J=90.8 Hz), 136.2 (d, J = 100.0 Hz), 136.1 (d, J = 5.6 Hz), 132.3 (d, J = 106.1 Hz), 132.1 (d, J = 2.5 Hz), 131.5 (d, J=3.4Hz), 131.5, 131.14, 131.09 (d, J=2.9 Hz), 130.9, 130.5, 130.3, 130.2, 130.1, 127.9, 127.8 (d, J=4.0 Hz), 127.7, 127.6, 127.4, 127.3, 126.9. 31 P NMR (162 MHz, CDCl3) δ19.7.HRMS (ESI) m / z: [M+H] + Calcd.for C 32 H 24 OP 455.1559; Found 455.1556.

[0046] Example 9: Synthesis of (R)-1-Isopropyl-6-methyl-3,4-di-o-tolyl-5,6-dihydropyridin-2(1H)-one

[0047]

[0048] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2i (116.1 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3i was separated by column chromatography as a white solid with a yield of 84% and a melting point of 192-194°C. 1 H NMR (400MHz, CDCl3) δ8.31-8.21(m, 1H), 7.76-7.66(m, 2H), 7.65-7.56(m, 1H), 7.45-7.33(m, 2H), 7.31-7.21(m, 2H), 7.17-7.10( m, 3H), 7.09-7.04 (m, 2H), 7.02-6.93 (m, 4H), 6.90-6.82 (m, 1H), 6.79-6.74 (m, 1H), 6.73-6.68 (m, 2H), 1.23 (s, 9H), 1.19 (s, 9H). 13C NMR (100 MHz, CDCl3) δ150.3, 149.8, 149.5 (d, J=11.0 Hz), 141.1 (d, J=10.5 Hz), 140.4 (d, J=1.7Hz), 139.82 (d, J=20.2 Hz), 139.78, 138.3 (d, J = 91.5 Hz), 136.5 (d, J = 99.5 Hz), 133.5 (d, J = 5.8 Hz), 132.6 (d, J = 105.8 Hz), 131.9 (d, J = 2.5 Hz), 131.7, 131.2 (d, J=4.1Hz), 131.03 (d, J=9.4 Hz), 131.01, 130.6, 130.5, 130.2 (d, J = 11.4 Hz), 130.1 (d, J = 10.3 Hz), 127.8 (d, J = 12.8 Hz), 127.6, 127.5 (d, J = 10.6 Hz), 126.8, 124.6, 124.3, 34.5, 31.4. 31 P NMR (162 MHz, CDCl3) δ19.8.HRMS (ESI) m / z: [M+H] + Calcd.for C 40 H 40 OP567.2811; Found 567.2814.

[0049] Example 10: Synthesis of 6,7-Bis(4-methoxyphenyl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0050]

[0051] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2j (116.1 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3j was separated by column chromatography as a white solid with a yield of 84% and a melting point of 192-194°C. 11H NMR (400 MHz, CDCl3) δ 8.31 - 8.19 (m, 1H), 7.79 - 7.69 (m, 2H), 7.67 - 7.56 (m, 1H), 7.46 - 7.35 (m, 2H), 7.30 - 7.27 (m, 1H), 7.21 - 7.15 (m, 1H), 7.13 - 7.06 (m, 3H), 7.06 - 7.00 (m, 1H), 6.92 - 6.84 (m, 1H), 6.83 - 6.78 (m, 2H), 6.78 - 6.70 (m, 2H), 6.69 - 6.57 (m, 2H), 3.78 (s, 3H), 3.73 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 158.7, 148.6 (d, J = 11.4 Hz), 141.0 (d, J = 10.7 Hz), 140.4, 140.0 (d, J = 5.0 Hz), 137.2 (d, J = 92.1 Hz), 136.3 (d, J = 99.5 Hz), 135.2 (d, J = 15.0 Hz), 132.9 (d, J = 2.2 Hz), 132.8 (d, J = 4.1 Hz), 132.4, 131.9, 131.0 (d, J = 123.2 Hz), 131.0 (d, J = 2.6 Hz), 130.2, 130.1, 130.0, 129.9, 128.7 (d, J = 5.7 Hz), 127.8, 127.7, 127.6, 127.5 (d, J = 10.7 Hz), 126.8, 113.6, 113.11, 55.2, 55.2. 31 31P NMR (162 MHz, CDCl3) δ 20.0. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 28 O3P 515.1771; Found 515.1771.

[0052] Example 11: Synthesis of 5 - Phenyl - 6,7 - bis(4 - (trifluoromethoxy)phenyl)dibenzo[b,d]phosphepine 5 - oxide

[0053]

[0054] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2k (346.0 mg, 0.4 mmol) and dimethylaluminum chloride (1 M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3k was separated by column chromatography as a white solid with a yield of 55% and a melting point of 257-259°C. 1 H NMR (400MHz, CDCl3) δ8.29-8.18(m, 1H), 7.82-7.69(m, 2H), 7.68-7.62(m, 1H), 7.42-7.33(m, 2H), 7.32-7.25(m, 1H) , 7.24-7.17(m, 2H), 7.14-7.06(m, 4H), 7.06-7.00(m, 2H), 6.97-6.89(m, 3H), 6.88-6.82(m, 2H), 6.72-6.64(m, 1H). 13 C NMR (100 MHz, CDCl3) δ 148.8 (d, J = 10.8 Hz), 148.6 (d, J = 13.2 Hz), 140.5, 138.7 (d, J = 4.9 Hz), 137.8, 135.7 (d, J = 99.8 Hz), 134.5 (d, J = 5.9 Hz), 133.0 (d, J = 3.8 Hz), 135.7 (d, J = 58.0 Hz), 132.4, 131.4, 131.31 (d, J = 27.9 Hz), 131.29 (d, J = 36.4 Hz), 130.8, 130.4, 130.3, 130.1 (d, J=11.3 Hz), 128.4, 128.1, 128.0, 127.9 (d, J=10.7 Hz), 127.2, 127.5 (q, J=256.0 Hz), 127.4 (q, J=256.0 Hz), 120.4, 120.2. 19 F NMR (376 MHz, CDCl3) δ-57.8, -58.0. 31 P NMR (162 MHz, CDCl3) δ19.5.HRMS (ESI) m / z: [M+H] + Calcd.for C 34 H 22 F6O3P 623.1205; Found 623.1203.

[0055] Example 12: Synthesis of (R)-1-Isopropyl-6-methyl-3,4-bis(4-(trifluoromethoxy)phenyl)-5,6-dihydropyridin-2(1H)-one

[0056]

[0057] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2l (128.9 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3l was separated by column chromatography as a white solid with a yield of 69% and a melting point of 301-303°C. 1 H NMR (400MHz, CDCl3) δ8.21-8.08(m, 1H), 7.62-7.56(m, 2H), 7.52-7.45(m, 1H), 7.34-7.27(m, 2H), 7.23-7.09(m, 3H), 7.06-7.01( m, 3H), 7.00-6.92 (m, 4H), 6.92-6.85 (m, 1H), 6.77-6.70 (m, 1H), 6.70-6.64 (m, 2H), 6.64-6.58 (m, 1H), 0.08 (s, 9H), 0.04 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 149.6 (d, J = 10.5 Hz), 142.9 (d, J = 14.6 Hz), 141.1 (d, J = 10.7 Hz), 140.4 (d, J = 2.1 Hz), 139.6, 139.5 (d, J = 5.0 Hz), 138.8 (d, J = 90.9 Hz), 138.9, 136.6 (d, J = 5.5 Hz), 136.2 (d, J = 99.9 Hz), 132.7, 132.41, 132.41 (d, J = 106.1 Hz), 132.0 (d, J=2.4Hz), 131.6, 131.1 (d, J=2.1 Hz), 131.0, 130.6 (d, J=4.1 Hz), 130.4 (d, J=24.3 Hz), 130.14, 130.11, 130.0, 127.9, 127.8, 127.6 (d, J=10.8 Hz), 126.9, -1.1, -1.2. 31 P NMR (162 MHz, CDCl3) δ19.7.HRMS (ESI) m / z: [M+H] + Calcd.for C 38 H 40 OPSi2599.2350; Found599.2345.

[0058] Example 13: Synthesis of 6,7-Bis(4-fluorophenyl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0059]

[0060] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2m (85.6 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3m was separated by column chromatography as a white solid with a yield of 87% and a melting point of 250-252°C. 11H NMR (400 MHz, CDCl3) δ 8.33 - 8.20 (m, 1H), 7.79 - 7.67 (m, 2H), 7.67 - 7.58 (m, 1H), 7.45 - 7.30 (m, 2H), 7.29 - 7.24 (m, 1H), 7.20 - 7.14 (m, 1H), 7.14 - 6.99 (m, 5H), 6.94 - 6.85 (m, 3H), 6.85 - 6.73 (m, 3H), 6.72 - 6.64 (m, 1H). 13 13C NMR (100 MHz, CDCl3) δ 162.21 (d, J = 248.6 Hz), 161.97 (d, J = 248.6 Hz), 148.8 (d, J = 11.0 Hz), 140.71 (d, J = 54.2 Hz), 140.67 (d, J = 41.1 Hz), 139.2 (d, J = 4.6 Hz), 138.5, 138.3 (d, J = 3.6 Hz), 138.0 (d, J = 95.6 Hz), 136.0 (d, J = 100.2 Hz), 133.3 (d, J = 4.4 Hz), 133.2 (d, J = 4.3 Hz), 132.7 (d, J = 8.1 Hz), 132.5, 132.3 (d, J = 2.5 Hz), 132.11 (d, J = 3.5 Hz), 132.05 (d, J = 3.5 Hz), 131.4 (d, J = 2.8 Hz), 131.1 (d, J = 6.3 Hz), 131.1 (d, J = 70.2 Hz), 130.3, 130.2, 130.1, 128.1 (d, J = 10.9 Hz), 127.9, 127.8 (d, J = 10.9 Hz), 127.1, 115.3, 115.1, 114.9. 19 19F NMR (376 MHz, CDCl3) δ -113.4, -114.4. 31 31P NMR (162 MHz, CDCl3) δ 19.7. HRMS (ESI) m / z.: [M + H] + Calcd. for C 32 H 22 F2OP 491.1371; Found 491.1366.

[0061] Example 14: Synthesis of (R)-3,4-Bis(3-Fluorophenyl)-1-isopropyl-6-methyl-5,6-dihydropyridin-2(1H)-one

[0062]

[0063] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2n (125.6 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3n was separated by column chromatography as a white solid with a yield of 36% and a melting point of 290-292°C. 1 H NMR (400MHz, CDCl3) δ8.26-8.12(m, 1H), 7.80-7.67(m, 2H), 7.66-7.56(m, 1H), 7.47-7.39(m, 2H), 7.39-7.34(m, 2H), 7.33-7. 29(m, 3H), 7.29-7.25(m, 1H), 7.21-7.15(m, 2H), 7.12-7.00(m, 3H), 6.98-6.92(m, 2H), 6.89-6.82(m, 1H), 6.63-6.55(m, 1H). 13 C NMR (100 MHz, CDCl3) δ 149.0 (d, J = 10.2 Hz), 145.5 (d, J = 14.0 Hz), 140.8 (d, J = 10.8 Hz), 140.5 (d, J = 2.3 Hz), 139.4 (d, J = 5.6 Hz), 139.2 (d, J = 89.5 Hz), 138.4 (d, J = 4.7 Hz), 135.5 (d, J = 100.9 Hz), 132.5 (d, J = 2.6 Hz), 131.7 (d, J = 4.1 Hz), 131.6 (d, J = 2.8 Hz), 131.5 (d, J = 107.5 Hz), 131.29, 131.25, 131.18, 131.15, 130.9, 130.4 (d, J=10.6 Hz), 130.1 (d, J=11.4 Hz), 129.9 (q, J=32.0 Hz), 129.6 (q, J=23.0 Hz), 128.6, 128.2, 128.1, 127.9, 127.3, 125.1 (q, J=4.0 Hz), 124.9 (q, J=4.0 Hz), 124.2 (q, J=271.1 Hz), 123.9 (q, J=270.9 Hz). 19F NMR (376 MHz, CDCl3) delta -62.6, -62.7. 31 P NMR (162 MHz, CDCl3) δ19.4.HRMS (ESI) m / z: [M+H] + Calcd.for C 34 H 22 F6OP 591.1307; Found 591.1302.

[0064] Example 15: Synthesis of 5-Phenyl-6,7-di-m-tolyldibenzo[b,d]phosphepine 5-oxide

[0065]

[0066] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2o (82.4 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3o was separated by column chromatography as a white solid with a yield of 77% and a melting point of 187-189°C. 1 H NMR (400 MHz, CDCl3) δ8.42-8.24 (m, 1H), 7.87-7.76 (m, 2H), 7.73-7.66 (m, 1H), 7.55-7.45 (m, 2H), 7.33 (d, J=7.3Hz, 1H), 7.23 (d, J=7.4 Hz, 1H), 7.21-7.12 (m, 2H), 7.12-7.06 (m, 2H), 7.06-6.98 (m, 2H), 6.97-6. 90(m, 3H), 6.86-6.81(m, 1H), 6.78-6.68(m, 2H), 2.29(s, 3H), 2.18(s, 3H). 13C NMR (100 MHz, CDCl3) δ 149.5 (d, J = 10.6 Hz), 142.5 (d, J = 14.6 Hz), 141.0 (d, J = 10.6 Hz), 140.2 (d, J = 2.1 Hz), 139.6 (d, J = 5.0 Hz), 138.7 (d, J = 91.1 Hz), 137.08, 137.06, 136.8, 136.3 (d, J = 99.8 Hz), 136.0 (d, J = 5.6 Hz), 132.4 (d, J = 105.7 Hz), 132.0 (d, J = 2.1 Hz), 131.5, 131.4, 131.1, 131.0 (d, J=2.6 Hz), 130.4, 130.2 (d, J = 11.6 Hz), 130.1, 130.0, 128.5 (d, J = 4.2 Hz), 128.1 (d, J = 1.8 Hz), 128.0, 127.9 (d, J = 8.3 Hz), 127.7 (d, J = 9.1 Hz), 127.6, 127.5 (d, J=10.9 Hz), 127.4, 126.8, 21.4, 21.2. 31 p NMR (162 MHz, CDCl3) δ19.9.HRMS (ESI) m / z: [M+H] + Calcd.for C 34 H 28 OP 483.1872; Found 483.1870.

[0067] Example 16: Synthesis of 5-Phenyl-6,7-bis(3-(trifluoromethoxy)phenyl)dibenzo[b,d]phosphepine 5-oxide

[0068]

[0069] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2p (138.4 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3p was separated by column chromatography as a white solid with a yield of 47% and a melting point of 154-156°C. 11H NMR (400 MHz, CDCl3) δ 8.30 - 8.18 (m, 1H), 7.81 - 7.70 (m, 2H), 7.68 - 7.62 (m, 1H), 7.38 (dd, J = 13.4, 7.6 Hz, 3H), 7.30 (d, J = 7.9 Hz, 2H), 7.24 - 7.17 (m, 1H), 7.15 - 7.07 (m, 4H), 7.07 - 7.02 (m, 1H), 6.94 - 6.87 (m, 1H), 6.78 - 6.72 (m, 2H), 6.74 (d, J = 5.8 Hz, 3H), 6.69 (d, J = 8.0 Hz, 1H). 13 13C NMR (100 MHz, CDCl3) δ 149.0 (d, J = 5.0 Hz), 148.9 (d, J = 8.2 Hz), 143.8 (d, J = 14.3 Hz), 140.7 (d, J = 30.6 Hz), 140.6 (d, J = 21.8 Hz), 138.6 (d, J = 90.1 Hz), 138.3 (d, J = 4.9 Hz), 137.6 (d, J = 5.7 Hz), 135.6 (d, J = 100.7 Hz), 132.5 (d, J = 2.5 Hz), 131.6 (d, J = 107.4 Hz), 131.5 (d, J = 2.8 Hz), 131.3, 131.2 (d, J = 6.5 Hz), 131.0, 130.9, 130.4 (d, J = 10.5 Hz), 130.2, 130.1, 129.42, 129.38, 129.2, 128.5, 128.2, 128.0, 127.9, 127.2, 124.1 (q, J = 4.0 Hz), 123.4, 120.4, 120.32 (q, J = 256.0 Hz), 120.29 (q, J = 257.0 Hz). 19 19F NMR (376 MHz, CDCl3) δ -58.2. 31 31P NMR (162 MHz, CDCl3) δ 19.3. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 22 F6O3P 623.1205; Found 623.1202.

[0070] Example 17: Synthesis of (R)-1-Isopropyl-6-methyl-3,4-di(thiophen-3-yl)-5,6-dihydropyridin-2(1H)-one

[0071]

[0072] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2q (85.6 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3q was separated by column chromatography as a white solid with a yield of 67% and a melting point of 214-216°C. 1 H NMR(400 MHz, CDCl3) δ8.32-8.20 (m, 1H), 7.82-7.69 (m, 2H), 7.68-7.60 (m, 1H), 7.45-7.33 (m, 2H), 7.29 (s, 1H), 7.2 3-7.15 (m, 2H), 7.13-7.01 (m, 4H), 6.96-6.86 (m, 2H), 6.86-6.77 (m, 1H), 6.75-6.64 (m, 2H), 6.55 (d, J=9.7 Hz, 1H). 1313C NMR (100 MHz, CDCl3) δ 162.4 (d, J = 244.0 Hz), 162.3 (d, J = 246.0 Hz), 148.8 (d, J = 11.0 Hz), 144.2 (d, J = 7.3 Hz), 144.1 (d, J = 7.4 Hz), 140.8 (d, J = 10.7 Hz), 140.4, 138.6 (d, J = 90.2 Hz), 138.5 (d, J = 4.6 Hz), 137.93 (d, J = 6.2 Hz), 137.86 (d, J = 5.8 Hz), 135.7 (d, J = 100.8 Hz), 132.4 (d, J = 2.5 Hz), 131.8 (d, J = 91.0 Hz), 131.4 (d, J = 2.8 Hz), 131.3, 131.1 (d, J = 6.6 Hz), 130.7, 130.3 (d, J = 10.7 Hz), 130.1 (d, J = 11.4 Hz), 129.43 (d, J = 16.7 Hz), 129.43, 128.3, 128.0 (d, J = 13.1 Hz), 127.9 (d, J = 12.4 Hz), 127.2, 127.1, 126.5 (d, J = 3.1 Hz), 118.2 (d, J = 22.6 Hz), 117.7 (d, J = 22.2 Hz), 114.8 (d, J = 21.1 Hz), 114.7 (d, J = 20.9 Hz). 31 31P NMR (162 MHz, CDCl3) δ 19.5. HRMS (ESI) m / z: [M+H] + Calcd. for C 32 H 22 F2OP491.1371; Found 491.1367.

[0073] Example 18: Synthesis of Dimethyl 3,3′-(5-oxido-5-phenyldibenzo[b,d]phosphepine-6,7-diyl)dibenzoate

[0074]

[0075] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2r (117.6 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 3r by column chromatography as a white solid with a yield of 57% and a melting point of 214-216°C. 1 H NMR (400MHz, CDCl3) δ8.28-8.15 (m, 1H), 7.84 (d, J=7.7 Hz, 1H), 7.81-7.71 (m, 3H), 7.68-7.59 (m, 1H), 7.51 (s, 1H), 7.41 (dd, J=13.3, 7.5 Hz, 3H), 7.47-7.38 (m, 2H), 7.32-7.24 (m, 2H), 7.24-7.17 (m, 1H), 7.15-7.01 (m, 5H), 6.92-6.82 (m, 1H), 6.67 (d, J=7.9 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ166.8, 166.6, 149.3 (d, J = 10.7 Hz), 142.4 (d, J = 14.4 Hz), 140.8 (d, J = 10.7 Hz), 140.5, 138.9 (d, J = 90.4 Hz), 138.6 (d, J=4.8 Hz), 136.3, 136.2, 136.0, 135.3, 132.5, 132.4 (d, J=2.3 Hz), 131.7 (d, J=107.2 Hz), 131.4 (d, J=87.6 Hz), 131.4 (d, J=2.7 Hz), 131.3, 131.1 (d, J=6.4 Hz), 130.9, 130.5 (d, J = 10.6 Hz), 130.2 (d, J = 11.4 Hz), 130.0, 128.78, 128.77, 128.3, 128.12, 128.08, 128.0 (d, J = 5.9 Hz), 127.9, 127.8, 127.1, 52.2, 52.1. 31 P NMR (162 MHz, CDCl3) δ19.6.HRMS (ESI) m / z: [M+H] + Calcd.for C36 H 28 O5P 571.1669; Found 571.1667.

[0076] Example 19: Synthesis of 6,7-Bis(2-fluorophenyl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0077]

[0078] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2s (85.6 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3s was separated by column chromatography as a white solid with a yield of 86% and a melting point of 193-195°C. 1 H NMR(400 MHz, CDCl3) δ8.38-8.17(m, 1H), 7.77-7.72(m, 1H), 7.70-7.62(m, 2H), 7.59-7.50(m, 1H), 7.48-7.39(m, 1H), 7.31-7.27( m, 1H), 7.23-7.14 (m, 3H), 7.14-6.99 (m, 5H), 6.97-6.87 (m, 2H), 6.87-6.77 (m, 2H), 6.75-6.60 (m, 1H), 6.56-6.40 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 161.5 (d, J = 246.0 Hz), 161.5 (d, J = 245.4 Hz), 140.5 (d, J = 69.6 Hz), 140.0, 136.1 (d, J = 100.8 Hz), 132.5 (d, J = 118.3 Hz), 132.1 (d, J = 3.1 Hz), 131.3 (d, J = 2.9 Hz), 131.1 (d, J = 6.2 Hz), 130.9, 130.8, 130.7, 130.6 (d, J = 2.8 Hz), 130.5, 130.4, 130.2, 130.0 (d, J=8.5 Hz), 129.8, 129.7 (d, J = 9.4 Hz), 128.0, 128.0, 127.8 (d, J = 13.5 Hz), 127.59, 127.59 (d, J = 10.8 Hz), 127.1, 124.9 (d, J = 16.4 Hz), 123.7 (d, J = 3.6 Hz), 123.4 (d, J = 3.6 Hz), 115.5 (d, J = 21.9 Hz), 115.3 (d, J = 23.9 Hz). 31 P NMR (162 MHz, CDCl3) δ19.4, 18.2.HRMS (ESI) m / z: [M+H] + Calcd.for C 32 H 22 F2OP 491.1371; Found 491.1368.

[0079] Example 20: Synthesis of 6,7-Bis(1-methyl-1H-indol-6-yl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0080]

[0081] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2t (113.7 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3t was separated by column chromatography as a white solid with a yield of 41% and a melting point of 202-204°C.1 1H NMR (400 MHz, CDCl3) δ 8.30 - 8.13 (m, 1H), 7.81 - 7.70 (m, 2H), 7.65 - 7.55 (m, 1H), 7.54 - 7.43 (m, 1H), 7.20 - 7.13 (m, 1H), 7.12 - 7.04 (m, 4H), 7.02 - 6.95 (m, 2H), 6.93 - 6.87 (m, 3H), 6.86 - 6.83 (m, 1H), 6.81 - 6.70 (m, 2H), 6.31 (s, 1H), 6.22 (d, J = 3.1 Hz, 1H), 3.65 (s, 3H), 3.62 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 149.84, 149.7, 141.2 (d, J = 10.8 Hz), 141.0 (d, J = 3.1 Hz), 135.9, 135.6, 134.7, 134.6, 132.0, 131.7, 131.0 (d, J = 3.0 Hz), 130.8, 130.3, 130.2, 130.1, 129.8 (d, J = 10.1 Hz), 129.0, 128.5, 127.74 (d, J = 105.0 Hz), 127.74, 127.6, 127.4, 127.3, 126.9 (d, J = 68.1 Hz), 125.50, 125.47, 125.1, 124.6 (d, J = 111.8 Hz), 124.33, 124.30, 108.6, 108.2, 101.6, 101.3, 32.7. 31 31P NMR (162 MHz, CDCl3) δ 20.5. HRMS (ESI) m / z: [M + H] + Calcd. for C 38 H 30 N2OP 561.2090; Found 561.2087.

[0082] Example 21: Synthesis of 6,7 - Bis(3,4 - dimethylphenyl)-5 - phenyldibenzo[b,d]phosphepine 5 - oxide

[0083]

[0084] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2u (93.7 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 3u was separated by column chromatography as a white solid with a yield of 82% and a melting point of 139-141°C. 1 H NMR (400 MHz, CDCl3) δ8.29-8.19 (m, 1H), 7.76-7.67 (m, 2H), 7.65-7.56 (m, 1H), 7.45-7.35 (m, 2H), 7.23 (dd, J=8.0, 1.4 Hz, 1H), 7.20-7.13(m, 1H), 7.10-7.04(m, 2H), 7.02-6.96(m, 1H), 6.89(d , J=7.3Hz, 1H), 6.87-6.81 (m, 1H), 6.81-6.72 (m, 2H), 6.62 (dd, J=7.8, 1.9 Hz, 1H), 6.56 (s, 1H), 2.16 (s, 3H), 2.13 (s, 3H), 2.12 (s, 3H), 2.00 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 149.1 (d, J = 11.0 Hz), 141.1 (d, J = 10.7 Hz), 140.2 (d, J = 14.9 Hz), 140.2 (d, J = 2.3 Hz), 140.0 (d, J = 5.2 Hz), 138.0 (d, J = 91.6 Hz), 136.4 (d, J = 99.8 Hz), 135.7, 135.7, 135.5 (d, J = 1.8 Hz), 133.6 (d, J = 5.4 Hz), 133.0, 132.5 (d, J = 3.9 Hz), 132.1, 131.9 (d, J = 2.1 Hz), 131.6, 131.1 (d, J=6.7 Hz), 131.0 (d, J=2.8 Hz), 130.4, 130.3, 130.2, 130.0 (d, J=10.4Hz), 128.83 (d, J=78, 9Hz), 12 8.77, 128.7, 127.8, 127.7, 127.5, 127.4, 126.8, 19.8, 19.7, 19.6, 19.6. 31P NMR (162 MHz, CDCl3) δ20.1.HRMS (ESI) m / z: [M+H] + Calcd.for C 36 H 32 OP511.2185; Found 511.2185.

[0085] Example 22: Synthesis of 5,7-Diphenyl-6-(trimethylsilyl)dibenzo[b,d]phosphepine 5-oxide

[0086]

[0087] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2v (69.6 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target products 3v, 3v' were separated by column chromatography as white solids with a yield of 38% (3.8:1) and a melting point of 183-185°C. 1 H NMR (400MHz, CDCl3) δ8.40-8.30 (m, 1H), 7.75-7.60 (m, 3H), 7.34-7.27 (m, 3H), 7.24 (dd, J=7.8, 1.4 Hz, 1H), 7.21-7.13 (m, 3H), 7.12-7.04 (m, 2H), 7.01-6.94 (m, 4H), 6.79-6.68 (m, 1H), 6.53 (d, J=8.0 Hz, 1H), 0.05 (s, 9H). 13C NMR(100 MHz,CDCl3)δ161.7,145.3(d,J=20.9 Hz),142.6(d,J=59.3 Hz),141.3(d,J=9.7 Hz),140.7(d,J=10.3 Hz),140.4(d,J=1.8 Hz),137.4(d,J=93.6 Hz),133.9(d,J=103.2 Hz),131.7(d,J=1.8 Hz),130.9,130.8(d,J=6.1 Hz),130.4(d,J=2.8 Hz),129.94,129.86,129.8,129.5(d,J=10.5Hz),128.1(d,J=19.3 Hz),127.7(d,J=27.9Hz),127.7,127.64,127.55,126.4,1.9. 31 PNMR(162 MHz,CDCl3)δ23.8.HRMS(ESI)m / z:[M+H] + Calcd.for C 29 H 28 OPSi 451.1642.;Found451.1636. 1 H NMR(400 MHz,CDCl3)δ 1 H NMR(400 MHz,CDCl3)δ8.51-8.43(m,1H),7.78-7.68(m,2H),7.68-7.61(m,2H),7.42-7.35(m,5H),7.23-7.18(m,2H),7.17-7.10(m,2H),7.05-6.97(m,3H),6.96-6.90(m,2H),-0.34(s,9H). 13C NMR (100 MHz, CDCl3) δ154.5, 153.2 (d, J = 80.9 Hz), 140.8 (d, J = 9.6 Hz), 139.8 (d, J = 10.3 Hz), 138.0 (d, J = 8.4 Hz), 136.9, 135.9 (d, J = 96.9 Hz), 131.5 (d, J = 103.6 Hz), 131.3 (d, J = 2.5 Hz), 130.2 (d, J = 6.6 Hz), 130.0 (d, J = 3.0 Hz), 129.9, 129.0 (d, J = 11.4 Hz), 128.4 (d, J = 10.2 Hz), 127.9 (d, J=12.5 Hz), 127.6 (d, J = 14.2 Hz), 127.4 (d, J = 1.9 Hz), 127.2, 127.1 (d, J = 1.9 Hz), 126.7 (d, J = 12.8 Hz), 126.5 (d, J = 10.8 Hz), 125.6 (d, J = 9.4 Hz), 0.0. 31 P NMR (162 MHz, CDCl3) δ 18.7.

[0088] Example 23: Synthesis of 6-(tert-Butyl)-5,7-diphenyldibenzo[b,d]phosphepine 5-oxide

[0089]

[0090] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2w (63.2 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target products 3w, 3w' were separated by column chromatography as white solids with a yield of 50% (3.6:1) and a melting point of 183-185°C. 1H NMR(400MHz,CDCl3)δ8.41-8.30(m,1H),7.75-7.70(m,1H),7.69-7.59(m,3H),7.57-7.47(m,2H),7.47-7.39(m,2H),7.38-7.28(m,3H),7.19-7.08(m,5H),7.04-6.95(m,4H),6.86-6.76(m,1H),0.80(s,9H). 13 C NMR(100 MHz,CDCl3)δ157.3(d,J=7.6 Hz),142.7(d,J=91.9Hz),142.0(d,J=9.2 Hz),139.0(d,J=8.0 Hz),138.2,138.1,137.2(d,J=100.3 Hz),133.4(d,J=105.1 Hz),132.3(d,J=2.5 Hz),132.2(d,J=9.8 Hz),132.1(d,J=2.8Hz),131.5(d,J=6.5 Hz),130.5(d,J=2.9 Hz),130.1,130.0(d,J=5.1 Hz),129.4(d,J=11.2 Hz),128.7,128.6(d,J=12.0Hz),128.1(d,J=9.6 Hz),127.8(d,J=11.8 Hz),127.6(d,J=13.2 Hz),127.3(d,J=11.1 Hz),127.2,126.0,39.9(d,J=12.9 Hz),32.3. 31 P NMR(162 MHz,CDCl3)δ21.0.HRMS(ESI)m / z:[M+H] + Calcd.for C 30 H 28 OP 435.1872;Found 435.1867. 1 H NMR(400 MHz,CDCl3)δ8.49-8.33(m,1H),7.79-7.62(m,3H),7.52-7.43(m,1H),7.37-7.28(m,1H),7.23-7.15(m,4H),7.14-7.06(m,2H),7.04-6.95(m,2H),6.93-6.84(m,1H),6.68-6.58(m,1H),6.51(dd,J=8.2,1.3 Hz,1H),6.49-6.43(m,1H),1.30(s,9H). 13C NMR (100 MHz, CDCl3) δ 146.8 (d, J = 82.5 Hz), 145.2 (d, J = 11.9 Hz), 144.9 (d, J = 17.3 Hz), 141.2, 141.2 (d, J = 18.6 Hz), 138.9 (d, J = 1.8 Hz), 137.1 (d, J = 95.5 Hz), 134.6 (d, J = 107.8 Hz), 132.2, 131.9 (d, J = 2.5 Hz), 131.4 (d, J = 6.8 Hz), 130.3, 130.2 (d, J = 2.8 Hz), 129.8, 129.5, 128.9 (d, J=10.8 Hz), 128.7 (d, J = 9.8 Hz), 128.2, 127.8 (d, J = 12.8 Hz), 127.5 (d, J = 10.7 Hz), 127.2, 126.8 (d, J = 10.5 Hz), 41.21 (d, J = 8.2 Hz), 32.57 (d, J = 4.4 Hz). 31 P NMR (162 MHz, CDCl3) δ26.4.HRMS (ESI) m / z: [M+H] + Calcd.for C 30 H 28 OP 435.1872; Found 435.1867.

[0091] Example 24: Synthesis of 6-Methyl-5-phenyl-7-(trimethylsilyl)dibenzo[b,d]phosphepine5-oxide

[0092]

[0093] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a (55.3 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2x (44.8 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target products 3x, 3x' were separated by column chromatography as colorless liquids with a yield of 30% (3.1:1). 1H NMR(400 MHz,CDCl3)δ8.36-8.25(m,1H),7.72-7.62(m,2H),7.61-7.51(m,2H),7.49-7.42(m,1H),7.14-7.02(m,4H),7.00-6.93(m,2H),6.90-6.82(m,2H),6.80-6.72(m,1H),2.49(d,J=12.1 Hz,3H),0.08(s,9H). 13 C NMR(100 MHz,CDCl3)δ152.2,147.7(d,J=82.8 Hz),141.8(d,J=9.6Hz),140.6(d,J=11.1 Hz),137.8,135.8(d,J=97.0 Hz),132.2(d,J=9.8 Hz),132.02(d,J=2.2 Hz),131.99(d,J=102.5 Hz),130.9(d,J=4.1 Hz),130.8(d,J=11.7 Hz),129.8(d,J=11.4 Hz),129.2(d,J=10.2Hz),128.8(d,J=2.2 Hz),128.6(d,J=12.3Hz),127.6(d,J=12.6 Hz),127.0(d,J=10.7 Hz),126.1(d,J=6.4 Hz),19.5(d,J=11.1Hz),0.9. 31 P NMR(162 MHz,CDCl3)δ21.7.HRMS(ESI)m / z:[M+H] + Calcd.for C 24 H 26 OPSi389.1485;Found 389.1482. 1 H NMR(400 MHz,CDCl3)δ8.38-8.27(m,1H),7.69-7.56(m,2H),7.55-7.49(m,1H),7.13-7.03(m,5H),7.01-6.91(m,4H),2.32(d,J=1.5 Hz,3H),0.49(s,9H). 13C NMR (100 MHz, CDCl3) δ158.8, 143.7 (d, J = 11.0 Hz), 140.8 (d, J = 9.9 Hz), 140.3 (d, J = 62.8 Hz), 138.1, 137.4 (d, J = 53.9 Hz), 134.0 (d, J=100.7Hz), 131.7 (d, J=2.5Hz), 130.9 (d, J=6.4 Hz), 130.4 (d, J=2.8 Hz), 130.3, 129.7 (d, J=11.0 Hz), 129.2 (d, J=9.8 Hz), 127.6 (d, J=12.4 Hz), 127.4, 127.4, 127.3, 127.1, 28.2 (d, J=20.1 Hz), 3.2. 31 P NMR (162 MHz, CDCl3) δ 24.1.

[0094] Example 25: Synthesis of 6,7-Dipropyl-5-(p-tolyl)dibenzo[b,d]phosphepine 5-oxide

[0095]

[0096] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1a' (58.0 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction flask in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1 M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 4a by column chromatography as a colorless liquid with a yield of 82%. 11H NMR (400 MHz, CDCl3) δ 8.33 - 8.21 (m, 1H), 7.62 - 7.51 (m, 2H), 7.50 - 7.41 (m, 1H), 7.09 - 7.04 (m, 2H), 7.01 - 6.89 (m, 4H), 6.79 - 6.67 (m, 2H), 2.88 - 2.77 (m, 1H), 2.76 - 2.67 (m, 1H), 2.67 - 2.54 (m, 1H), 2.53 - 2.42 (m, 1H), 2.10 (s, 3H), 1.81 - 1.55 (m, 2H), 1.17 - 1.07 (m, 1H), 1.03 (t, J = 7.3 Hz, 3H), 0.96 - 0.83 (m, 1H), 0.52 (t, J = 7.6 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 147.8 (d, J = 8.9 Hz), 141.2 (d, J = 10.3Hz), 140.8 (d, J = 2.8 Hz), 139.4, 139.3, 137.2 (d, J = 98.4 Hz), 137.1 (d, J = 93.2Hz), 131.5 (d, J = 2.4 Hz), 130.4, 130.3 (d, J = 6.3 Hz), 130.0 (d, J = 11.7 Hz), 129.4 (d, J = 10.1 Hz), 129.2 (d, J = 106.7 Hz), 128.2 (d, J = 13.1 Hz), 127.6, 127.1, 126.9, 126.7, 37.0 (d, J = 13.0 Hz), 31.2 (d, J = 8.3Hz), 24.2, 21.4 (d, J = 14.6 Hz), 14.3, 13.5. 31 31P NMR (162 MHz, CDCl3) δ 22.0. HRMS (ESI) m / z: [M+H] + Calcd. for C 27 H 30 OP 401.2029; Found 401.2031.

[0097] Example 26: Synthesis of 5-(4-Methoxyphenyl)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0098]

[0099] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1b (61.2 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1 M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 4b by column chromatography as a colorless liquid in a yield of 78%. 1 H NMR(400 MHz, CDCl3) δ8.34-8.20 (m, 1H), 7.71-7.62 (m, 1H), 7.62-7.53 (m, 2H), 7.5 2-7.42 (m, 2H), 7.15-7.08 (m, 1H), 7.07-6.92 (m, 3H), 6.47 (dd, J=8.7, 2.2 Hz, 2H), 3.64 (s, 3H), 2.87-2.68 (m, 2H), 2.67-2.57 (m, 1 H), 2.54-2.44 (m, 1H), 1.80-1.58 (m, 2H), 1.20-1.08 (m, 1H), 1.04 (t, J=7.3 Hz, 3H), 0.99-0.82 (m, 1H), 0.54 (t, J=7.3 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 161.8 (d, J = 2.6 Hz), 148.4 (d, J = 9.0 Hz), 141.7 (d, J = 10.0 Hz), 139.9, 137.7 (d, J = 98.8 Hz), 137.6 (d, J = 93.6 Hz), 132.6 (d, J = 9.9 Hz), 132.5 (d, J = 2.8 Hz), 132.4 (d, J = 12.8 Hz), 132.0 (d, J = 2.4 Hz), 130.9, 130.8 (d, J = 6.3 Hz), 129.9 (d, J = 10.1 Hz), 129.1 (d, J = 12.1 Hz), 128.1, 127.6, 127.5, 127.3, 124.5 (d, J = 110.2 Hz), 113.6 (d, J = 13.7 Hz), 55.7, 37.6 (d, J = 13.0 Hz), 31.7 (d, J = 8.4 Hz), 24.7, 22.1, 14.8, 14.0. 31 P NMR (162 MHz, CDCl3) δ29.2, 21.3.HRMS (ESI) m / z: [M+H]+ Calcd.for C 27 H 30 O2P417.1978; Found 417.1974.

[0100] Example 27: Synthesis of 5-(4-Fluorophenyl)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0101]

[0102] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1c (58.8 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 4c by column chromatography as a colorless liquid with a yield of 83%. 1 H NMR(400 MHz, CDCl3) δ8.35-8.21 (m, 1H), 7.67-7.54 (m, 2H), 7.52-7.46 (m, 1H), 7.17-7.04 (m, 4H), 7.03-6.91 (m, 2H), 6.71-6.5 5(m, 2H), 2.90-2.68(m, 2H), 2.68-2.53(m, 1H), 2.53-2.44(m, 1H), 1.81-1.51(m, 2H), 1.16-1.07(m, 1H), 1.04(t, J=7.3 Hz, 3H), 0.98-0.86 (m, 1H), 0.53 (t, J=7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 164.0 (d, J = 248.3 Hz), 148.4 (d, J = 9.1 Hz), 141.2 (d, J = 10.3 Hz), 139.4, 139.3 (d, J = 6.8 Hz), 136.9 (d, J = 94.0 Hz), 136.8 (d, J = 99.3 Hz), 132.5 (d, J = 21.7 Hz), 132.5 (d, J = 4.2 Hz), 131.9 (d, J = 2.7 Hz), 130.5, 130.3 (d, J = 6.4 Hz), 129.5 (d, J=10.1Hz), 128.7 (d, J=103.0 Hz), 127.6, 127.2 (d, J = 10.8 Hz), 127.2 (d, J = 17.3 Hz), 114.8 (d, J = 7.6 Hz), 114.8 (d, J = 35.3 Hz), 37.1 (d, J = 13.1 Hz), 31.2 (d, J = 8.5 Hz), 24.2, 21.6 (d, J=1.7 Hz), 14.3, 13.5. 31 P NMR (162 MHz, CDCl3) δ 21.3. 19 F NMR (376 MHz, CDCl3) δ-108.3.HRMS (ESI) m / z: [M+H] + Calcd.for C 26 H 27 OP 405.1778; Found 405.1776.

[0103] Example 28: Synthesis of 5-Isopropyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0104]

[0105] In a nitrogen atmosphere, ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1d (48.1 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 4d by column chromatography as a colorless liquid in a yield of 62%. 11H NMR (400 MHz, CDCl3) δ 8.12 - 8.01 (m, 1H), 7.74 - 7.63 (m, 1H), 7.59 - 7.48 (m, 2H), 7.47 - 7.39 (m, 2H), 7.39 - 7.33 (m, 2H), 2.75 - 2.57 (m, 2H), 2.56 - 2.47 (m, 1H), 2.46 - 2.34 (m, 1H), 1.65 - 1.51 (m, 1H), 1.51 - 1.36 (m, 1H), 1.17 - 1.05 (m, 2H), 1.00 - 0.88 (m, 6H), 0.87 - 0.80 (m, 1H), 0.70 (dd, J = 16.6, 6.4 Hz, 3H), 0.57 - 0.50 (m, 3H). 13 13C NMR (100 MHz, CDCl3) δ 145.9 (d, J = 9.6 Hz), 140.2 (d, J = 10.5 Hz), 139.4, 138.5 (d, J = 66.8 Hz), 138.0 (d, J = 70.5 Hz), 132.1 (d, J = 9.6 Hz), 131.3 (d, J = 2.5 Hz), 130.9, 130.1 (d, J = 5.3 Hz), 129.2 (d, J = 10.1 Hz), 128.5 (d, J = 11.8 Hz), 127.9, 127.6 (d, J = 29.4 Hz), 127.2 (d, J = 9.8 Hz), 37.0 (d, J = 12.8 Hz), 31.3 (d, J = 7.1 Hz), 24.0, 23.5 (d, J = 70.2 Hz), 21.4, 15.2 (d, J = 2.3 Hz), 15.1 (d, J = 3.1 Hz), 14.3, 13.6. 31 31P NMR (162 MHz, CDCl3) δ 33.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 23 H 30 OP 353.2029; Found 353.2024.

[0106] Example 29: Synthesis of 5-(tert-Butyl)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0107]

[0108] In a nitrogen atmosphere, ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1e (51.2 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 4e by column chromatography as a colorless liquid with a yield of 90%. 1 H NMR(400 MHz, CDCl3) δ8.24-8.12 (m, 1H), 7.60-7.51 (m, 2H), 7.50-7.45 (m, 2H), 7.43-7.40 (m, 1H), 7.38-7.28 (m, 2H), 2.85-2.68(m, 2H), 2.66-2.56(m, 1H), 2.55-2.38(m, 1H), 1.58-1.44(m, 3H), 1.22-1.11(m, 1H), 0.98(t, J=7.3 Hz, 3H), 0.68 (d, J=15.5 Hz, 9H), 0.57 (t, J=7.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 148.2 (d, J = 8.2 Hz), 141.1 (d, J = 9.8 Hz), 140.1, 139.9 (d, J = 4.9 Hz), 138.4 (d, J = 61.0 Hz), 137.6 (d, J = 64.4 Hz), 132.2, 131.9, 131.8, 130.1, 129.3 (d, J=9.6 Hz), 129.1, 127.4 (d, J=4.5 Hz), 126.9 (d, J=9.6 Hz), 37.4 (d, J=12.9 Hz), 35.8 (d, J=67.2 Hz), 32.4 (d, J=6.8 Hz), 25.3, 24.0, 21.3, 14.3, 13.4. 31 P NMR (162 MHz, CDCl3) δ38.6.HRMS (ESI) m / z: [M+H] + Calcd.for C 24 H 32 OP 367.2185; Found 367.2181.

[0109] Example 30: Synthesis of 5-(Dimethylamino)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0110]

[0111] In a nitrogen atmosphere, ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1f (48.6 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 4f by column chromatography as a yellow liquid with a yield of 82%. 1 H NMR(400 MHz, CDCl3) δ 8.13-7.99 (m, 1H), 7.54-7.45 (m, 2H), 7.44-7.35 (m, 2H), 7.25-7.17 (m, 2H), 2.68-2.51 (m, 2H), 2.49-2.31 (m, 1H), 1.91 (d, J=10.0 Hz, 6H), 1.63-1.52 (m, 1H), 1.52-1.40 (m, 1H), 1.09-0.97 (m, 1H), 0.92 (t, J=7.3 Hz, 3H), 0.88-0.77 (m, 1H), 0.46 (t, J=7.3 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 148.1 (d, J = 7.2 Hz), 141.2 (d, J = 8.2 Hz), 140.0 (d, J = 5.6 Hz), 139.5, 136.4 (d, J = 58.5 Hz), 136.2 (d, J = 62.0 Hz), 131.7 (d, J = 8.0 Hz), 131.4 (d, J = 2.5 Hz), 129.8, 129.6 (d, J = 10.7 Hz), 127.2 (d, J = 11.9 Hz), 127.0, 126.6, 126.6, 126.5, 37.3 (d, J = 13.7 Hz), 35.4 (d, J = 5.2 Hz), 32.2 (d, J = 10.0 Hz), 24.1, 21.6 (d, J = 1.8 Hz), 14.4, 13.6. 31P NMR (162 MHz, CDCl3) δ22.1.HRMS (ESI) m / z: [M+H] + Calcd.forC 22 H 29 NOP 354.1981; Found 354.1982.

[0112] Example 31: Synthesis of 5-(Diethylamino)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0113]

[0114] In a nitrogen atmosphere, ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1g (54.2 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain 4 g of the target product by column chromatography as a yellow liquid with a yield of 81%. 1 H NMR(400 MHz, CDCl3) δ8.21-8.07 (m, 1H), 7.59-7.50 (m, 2H), 7.50-7.45 (m, 0H), 7.43-7.37 (m, 2H), 7.35-7.27 (m, 2H), 2.75-2.6 2(m, 2H), 2.60-2.49(m, 3H), 2.49-2.37(m, 2H), 1.69-1.55(m, 1H), 1.57-1.45(m, 1H), 1.16-1.03(m, 1H), 0.98(t, J=7.3 Hz, 3H), 0.94-0.81 (m, 2H), 0.63 (t, J=7.1 Hz, 6H), 0.52 (t, J=7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 147.9 (d, J = 7.4 Hz), 141.2 (d, J = 8.2 Hz), 140.0, 139.7, 136.6 (d, J = 119.4 Hz), 132.1 (d, J = 9.4 Hz), 131.9 (d, J = 7.9 Hz), 131.7 (d, J = 2.9 Hz), 130.6 (d, J = 113.2 Hz), 129.6 (d, J = 10.9 Hz), 128.4 (d, J = 11.6 Hz), 127.1 (d, J = 11.9 Hz), 126.9, 126.6 (d, J=22.6 Hz), 38.2 (d, J=4.2 Hz), 37.3 (d, J = 13.6 Hz), 32.3 (d, J = 9.9 Hz), 24.0, 21.5, 14.3, 13.6, 13.6, 13.5. 31 P NMR (162MHz, CDCl3) δ22.0.HRMS (ESI) m / z: [M+H] + Calcd.for C 24 H 33 NOP 382.2294.;Found382.2290.

[0115] Example 32: Synthesis of 5-(Diisopropylamino)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0116]

[0117] In a nitrogen atmosphere, ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1h (59.8 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction flask in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate and concentrated to obtain the target product 4h by column chromatography as a yellow liquid with a yield of 81%. 1H NMR(400 MHz, CDCl3) δ8.25-8.12 (m, 1H), 7.56-7.44 (m, 3H), 7.43-7.38 (m, 2H), 7.36-7.2 8(m, 2H), 3.28-3.12(m, 2H), 2.73-2.59(m, 2H), 2.58-2.42(m, 2H), 1.51(p, J=7.5 Hz, 2H), 1.15-1.03 (m, 1H), 0.99 (d, J=7.0 Hz, 6H), 0.95 (t, J=7.4 Hz, 3H), 0.55 (d, J=6.9 Hz, 6H), 0.51 (t, J=7.3 Hz, 3H). 13 C NMR (100MHz, CDCl3) δ147.4 (d, J=6.9 Hz), 141.4 (d, J=8.6 Hz), 140.1, 140.0, 139.2 (d, J=36.2 Hz), 138.0 (d, J=30.5 Hz), 131.9 (d, J=7.6 Hz), 131.2, 130.92, 130.90, 129.9 (d, J=10.7 Hz), 127.8, 127.2 (d, J=11.6 Hz), 126.7 (d, J=21.9 Hz), 47.6 (d, J=3.8 Hz), 37.5 (d, J=13.6 Hz), 32.8 (d, J=10.0 Hz), 24.0, 23.8 (d, J=3.4 Hz), 23.2 (d, J=4.5 Hz), 21.6, 14.6, 13.6. 31 P NMR (162 MHz, CDCl3) δ19.3.HRMS (ESI) m / z: [M+H] + Calcd.for C 26 H 37 NOP 410.2607; Found 410.2602.

[0118] Example 33: Synthesis of 5-Methoxy-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0119]

[0120] In a nitrogen atmosphere, add the ligands tBu-DAPO (4.4 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1i (46.0 mg, 0.2 mmol), toluene (1.0 mL), then 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1M, 80 μL, 40 mol%) were added, stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, the organic phase was dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the target product 4i as a colorless liquid with a yield of 54%. 1 H NMR (400 MHz, CDCl3) δ8.06 (dd, J=12.7, 7.5 Hz, 1H), 7.58 (q, J=6.2, 4.7 Hz, 2H), 7.47 (t, J=7.8 Hz, 3H), 7.35 (p, J=7.2Hz, 2H), 3.07 (d, J=11.9 Hz, 3H), 2.75-2.62 (m, 1H), 2.62-2.40 (m, 3H), 1.66-1.44 (m, 2H), 1.19-1.03 (m, 1H), 0.96 (t, J=7.3 Hz, 3H), 0.53 (t, J=7.3 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 150.0 (d, J = 7.9 Hz), 141.6 (d, J = 9.4 Hz), 140.0 (d, J = 5.3 Hz), 139.4, 136.0 (d, J = 122.6 Hz), 135.3 (d, J = 128.9 Hz), 132.0 (d, J = 2.5 Hz), 131.0 (d, J = 8.5 Hz), 130.5, 129.6 (d, J = 11.4 Hz), 127.4, 127.2, 127.1 (d, J = 12.3 Hz), 127.0, 51.1 (d, J=6.8Hz), 36.9 (d, J=14.9 Hz), 31.9 (d, J=10.3 Hz), 21.4 (d, J=1.9 Hz), 14.2, 13.6. 31 P NMR (162 MHz, CDCl3) δ28.7.HRMS (ESI) m / z: [M+H] + Calcd.for C 21 H 26 O2P 341.1665; Found 341.1663.

[0121] Example 34: Synthesis of 5-Ethoxy-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0122]

[0123] In a nitrogen atmosphere, add the ligands t Bu-DAPO (4.4 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1j (48.8 mg, 0.2 mmol), toluene (1.0 mL), then 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1M, 80 μL, 40 mol%) were added, stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, the organic phase was dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the target product 4j as a colorless liquid with a yield of 65%. 1 H NMR(400 MHz, CDCl3) δ8.03-7.94 (m, 1H), 7.51-7.45 (m, 2H), 7.43-7.33 (m, 3H), 7.32-7.19 (m, 2H), 3.50-3.39 (m, 1H), 3.39-3.29 (m, 1H), 2.70-2.54 (m, 1H), 2.54-2.32 (m, 3H), 1.60-1.33 (m, 2H), 1.11-0.98 (m, 1H), 0.88 (t, J=7.3 Hz, 3H), 0.85-0.76 (m, 1H), 0.53 (t, J=7.0 Hz, 3H), 0.44 (t, J=7.4 Hz, 3H). 13 C NMR (100MHz, CDCl3) δ 149.5 (d, J = 8.0 Hz), 141.4 (d, J = 9.2 Hz), 139.7 (d, J = 5.2 Hz), 139.4, 136.1 (d, J = 122.2 Hz), 135.5 (d, J = 128.4 Hz), 131.7 (d, J = 2.5 Hz), 130.4, 130.2, 129.4 (d, J = 11.5 Hz), 127.2, 127.0, 126.9 (d, J = 12.6 Hz), 126.7, 60.4 (d, J = 6.3 Hz), 36.7 (d, J = 14.7 Hz), 31.7 (d, J=10.3 Hz), 23.8, 21.2 (d, J=2.0 Hz), 15.4 (d, J=8.3 Hz), 14.1, 13.4. 31P NMR (162 MHz, CDCl3) δ26.3.HRMS (ESI) m / z: [M+H] + Calcd.forC 22 H 28 O2P 355.1821; Found 355.1820.

[0124] Example 35: Synthesis of 2,3,9,10-Tetramethyl-5-phenyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0125]

[0126] In a nitrogen atmosphere, add the ligands t Bu-DAPO (4.4 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1k (66.4 mg, 0.2 mmol), toluene (1.0 mL), then 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1M, 80 μL, 40 mol%) were added, stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, the organic phase was dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the target product 4k as a white solid with a yield of 81% and a melting point of 72-74°C. 1 H NMR (400 MHz, CDCl3) δ7.96 (d, J=12.0 Hz, 1H), 7.23 (d, J=4.9 Hz, 1H), 7.11-6.99 (m, 3H), 6.92-6.83 (m, 2H), 6.77 (s, 1H), 6.73 (s, 1H), 2.83-2.73 (m, 1H), 2.73-2.63 (m, 1H), 2.62-2.49 (m, 1H), 2.48- 2.39 (m, 1H), 2.36 (s, 3H), 2.33 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H), 1.86-1.70 (m, 1H), 1.70-1.59 (m, 1H), 1.16-1.07 (m, 1H), 1.04 (t, J=7.2 Hz, 3H), 0.99-0.86 (m, 1H), 0.55 (t, J=7.4Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 148.1 (d, J = 9.3 Hz), 140.4 (d, J = 2.6 Hz), 138.9 (d, J = 10.3 Hz), 137.1, 136.9, 136.7 (d, J = 56.6 Hz), 135.5 (d, J = 4.5 Hz), 135.3, 135.0 (d, J = 19.3 Hz), 133.9 (d, J = 78.1 Hz), 132.9 (d, J = 81.4 Hz), 131.3, 131.1 (d, J = 6.8 Hz), 130.3 (d, J = 10.9 Hz), 130.0, 129.9, 128.4, 127.0 (d, J=12.6 Hz), 36.9 (d, J=13.2 Hz), 31.0 (d, J=8.6 Hz), 24.2, 21.6, 20.0, 19.2, 19.1, 19.1, 14.3, 13.6. 31 P NMR (162 MHz, CDCl3) δ23.4.HRMS (ESI) m / z: [M+H] + Calcd.for C 30 H 36 OP 443.2498; Found 443.2494.

[0127] Example 36: Synthesis of 2,3,9,10-Tetramethoxy-5-phenyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0128]

[0129] In a nitrogen atmosphere, add the ligands t Bu-DAPO (4.4 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1l (79.2 mg, 0.2 mmol), toluene (1.0 mL), then 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1M, 80 μL, 40 mol%) were added, stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, the organic phase was dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the target product 4l as a white solid with a yield of 82% and a melting point of 107-109°C. 11H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 12.0 Hz, 1H), 7.16 - 7.03 (m, 3H), 6.99 - 6.89 (m, 3H), 6.49 (s, 1H), 6.45 (s, 1H), 4.01 (s, 3H), 3.93 (s, 3H), 3.71 (s, 3H), 3.68 (s, 3H), 2.84 - 2.62 (m, 2H), 2.61 - 2.49 (m, 1H), 2.47 - 2.33 (m, 1H), 1.83 - 1.70 (m, 1H), 1.72 - 1.58 (m, 1H), 1.17 - 1.08 (m, 1H), 1.03 (t, J = 7.1 Hz, 3H), 0.99 - 0.88 (m, 1H), 0.56 (t, J = 7.3 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 151.6 (d, J = 2.1Hz), 148.6 (d, J = 13.4 Hz), 147.6, 147.3 (d, J = 9.2 Hz), 136.6 (d, J = 67.9 Hz), 136.5 (d, J = 95.6Hz), 134.5 (d, J = 9.6 Hz), 133.0, 132.8 (d, J = 7.3 Hz), 132.6, 130.8, 129.8 (d, J = 11.3 Hz), 128.5 (d, J = 103.1 Hz), 127.4 (d, J = 12.6 Hz), 112.9, 112.5 (d, J = 8.3 Hz), 112.2 (d, J = 12.3 Hz), 110.6, 56.5, 56.3, 56.2, 56.1, 36.9 (d, J = 12.6 Hz), 31.1 (d, J = 8.0 Hz), 24.3, 21.8, 14.4, 13.7. 31 31P NMR (162 MHz, CDCl3) δ 23.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 30 H 36 O5P 507.2295; Found 507.2293.

[0130] Example 37: Synthesis of 1,4,10,13 - Tetrahydro - 6 - phenyl - 7,8 - dipropyl - 1,2,3,4,10,11,12,13 - octahydrodinaphtho[2,3 - b:2′,3′ - d]phosphepine 6 - oxide

[0131]

[0132] In a nitrogen atmosphere, ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1m (78.4 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 4m was separated by column chromatography as a white solid with a yield of 68% and a melting point of 249-251°C. 1 H NMR (400MHz, CDCl3) δ7.68 (d, J=12.5 Hz, 1H), 7.12-7.04 (m, 3H), 7.03-6.94 (m, 2H), 6.88 (d, J=4.9 Hz, 1H), 6.46 (s, 1H), 6.44 (s, 1H), 4.34-4.20 (m, 4H), 4.14-4.02 (m, 2H), 3.99-3.87 (m, 2H), 2.79-2.68 (m, 1H), 2.67-2. 59 (m, 1H), 2.57-2.45 (m, 1H), 2.39-2.25 (m, 1H), 1.74-1.65 (m, 1H), 1.64-1.53 ​​(m, 0H), 1.14-1.04 (m, 1H), 1.00 (t, J=7.3 Hz, 3H), 0.96-0.85 (m, 1H), 0.55 (t, J=7.4 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 147.4 (d, J = 9.1 Hz), 146.3 (d, J = 2.8 Hz), 143.1 (d, J = 14.4 Hz), 141.9 (d, J = 13.6 Hz), 136.2, 135.9 (d, J = 67.0 Hz), 134.0 (d, J = 91.6 Hz), 133.17, 133.15, 132.8 (d, J = 58.1 Hz), 130.3 (d, J = 2.7 Hz), 129.9 (d, J = 11.4 Hz), 129.3 (d, J = 103.1 Hz), 127.3 (d, J = 12.8 Hz), 119.4 (d, J = 7.8 Hz), 118.3, 118.0 (d, J = 11.8 Hz), 115.9, 64.6, 64.3, 64.3, 36.9 (d, J = 12.8 Hz), 30.9 (d, J = 8.5 Hz), 24.1, 21.6, 14.3, 13.6. 31P NMR (162 MHz, CDCl3) δ22.6.HRMS (ESI) m / z: [M+H] + Calcd.for C 30 H 32 O5P 503.1982; Found 503.1980.

[0133] Example 38: Synthesis of 1,3,9,11-Tetrahydro-5-phenyl-6,7-dipropyl-1,2,3,9,10,11-hexahydrodiindeno-[5,6-b:5′,6′-d]phosphepine 5-oxide

[0134]

[0135] In a nitrogen atmosphere, ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1n (72.8 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and dimethylaluminum chloride (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous solution of disodium ethylenediaminetetraacetic acid, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 4n was separated by column chromatography as a yellow solid with a yield of 62% and a melting point of 171-173°C. 1 H NMR (400MHz, CDCl3) δ7.70 (d, J=11.5 Hz, 1H), 7.21-7.08 (m, 3H), 7.08-6.99 (m, 2H), 6.88 (d, J=4.1 Hz, 1H), 6.47 (d, J=2.0 Hz, 2H), 6.11-6.06 (m, 2H), 5.84 (s, 1H), 5.69 (s, 1H), 3.18-3.01 (m, 1H), 2.82-2.63 (m, 2H) , 2.62-2.51(m, 1H), 2.41-2.25(m, 1H), 1.79-1.56(m, 2H), 1.17-1.09(m, 2H), 1.05(t, J=7.3 Hz, 3H), 0.59 (t, J=7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ150.7, 147.41 (d, J=23.9Hz), 147.38, 146.2 (d, J=17.6 Hz), 136.7 (d, J=83.7Hz), 136.1, 133.9, 133.8 (d, J=9.3 Hz), 132.8 (d, J = 105.7 Hz), 132.1, 132.0, 130.7 (d, J = 2.6 Hz), 129.8 (d, J = 11.6 Hz), 129.0 (d, J = 130.5 Hz), 128.5 (d, J = 11.6 Hz), 127.5 (d, J=12.7 Hz), 110.0 (d, J=8.2 Hz), 109.8 (d, J = 12.2 Hz), 109.6, 106.9, 101.8, 101.2, 36.8 (d, J = 12.6 Hz), 31.0 (d, J = 8.7 Hz), 24.2, 21.5, 14.3, 13.6. 31 P NMR (162 MHz, CDCl3) δ23.1.HRMS (ESI) m / z: [M+H] + Calcd.for C 28 H 28 O5P 475.1669; Found 475.1664.

[0136] Example 39: Synthesis of 3-Phenyl-4,5-dipropyldinaphtho[2,1-b:1′,2′-d]phosphepine 3-oxide

[0137]

[0138] In a nitrogen atmosphere, add the ligands t Bu-DAPO (4.4 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1o (75.2 mg, 0.2 mmol), toluene (1.0 mL), then 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1M, 80 μL, 40 mol%) were added, stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, the organic phase was dried over anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the target product 4o as a yellow solid with a yield of 71% and a melting point of 118-120°C. 11H NMR (400 MHz, CDCl3) δ 8.47 - 8.35 (m, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 8.9 Hz, 1H), 7.74 - 7.62 (m, 1H), 7.54 - 7.46 (m, 2H), 7.43 (d, J = 8.9 Hz, 1H), 7.26 - 7.16 (m, 3H), 7.12 - 7.04 (m, 1H), 7.03 - 6.93 (m, 2H), 6.85 (d, J = 8.6 Hz, 1H), 6.81 - 6.72 (m, 1H), 6.65 - 6.51 (m, 2H), 2.91 - 2.66 (m, 3H), 2.64 - 2.50 (m, 1H), 1.85 - 1.54 (m, 2H), 1.21 - 1.09 (m, 1H), 1.02 (t, J = 6.5 Hz, 3H), 0.96 - 0.81 (m, 1H), 0.40 (t, J = 6.6 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 148.6, 140.1 (d, J = 94.7 Hz), 138.3 (d, J = 6.2 Hz), 138.1 (d, J = 101.5 Hz), 135.8 (d, J = 9.4 Hz), 134.6, 133.9, 132.9 (d, J = 11.4 Hz), 131.8 (d, J = 105.8 Hz), 131.6 (d, J = 14.7 Hz), 129.9, 128.7, 128.6, 128.4, 128.3, 128.1, 127.8, 127.6, 127.1, 126.9, 126.8, 126.5, 126.3, 126.0 (d, J = 7.1 Hz), 125.8, 123.9, 35.6 (d, J = 12.1 Hz), 31.1 (d, J = 8.6 Hz), 24.1, 21.6, 14.3, 13.4. 31 31P NMR (162 MHz, CDCl3) δ 24.2. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 32 OP 487.2185; Found 487.2182.

[0139] Example 40: Synthesis of 3 - Phenyl - 4,5 - dipropyldinaphtho[2,1 - b:1′,2′ - d]phosphepine 3 - oxide

[0140]

[0141] In a nitrogen atmosphere, ligand PPh3 (5.2 mg, 10 mol%), Ni(cod)2 (5.5 mg, 10 mol%), 1p (75.2 mg, 0.2 mmol), and toluene (1.0 mL) were added to the reaction bottle in sequence, followed by 2a (44.0 mg, 0.4 mmol) and trimethylaluminum (1M, 80 μL, 40 mol%). The mixture was stirred at 120°C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, and the organic phase was dried over anhydrous sodium sulfate. After concentration, the target product 4p was separated by column chromatography as a yellow solid with a yield of 72% and a melting point of 118-120°C. 1 H NMR (400 MHz, CDCl3) δ8.83 (d, J=13.6 Hz, 1H), 8.17-7.91 (m, 3H), 7.68-7.56 (m, 4H), 7.54-7.49 (m, 1H), 7.44-7.35 (m, 2H), 7.16 (ddd, J=13.0, 7.4, 1.9 Hz, 2H), 6.78 (dt, J=7.8, 4.0 Hz, 3H), 2.97-2.80 (m, 2H), 2.74-2.53 (m, 2H), 1.87-1.63 (m, 1H), 1.10 (t, J=7.3 Hz, 3H), 1.05-0.92 (m, 1H), 0.57 (t, J=7.3 Hz, 3H). 13 C NMR (100 MHz, CDCl3) δ 149.0 (d, J = 8.9 Hz), 138.2 (d, J = 10.6 Hz), 137.73, 137.70, 137.7 (d, J = 123.9 Hz), 135.5 (d, J = 97.7 Hz), 135.5, 134.5 (d, J = 1.7 Hz), 132.3 (d, J = 104.4 Hz), 131.8, 131.7, 131.61, 131.58, 131.6, 131.4 (d, J = 11.6 Hz), 130.3 (d, J = 2.6 Hz), 130.2, 130.09, 129.98, 128.7 (d, J=9.9 Hz), 128.5, 127.9 (d, J = 13.1 Hz), 127.2 (d, J = 7.6 Hz), 127.0 (d, J = 12.7 Hz), 126.9 (d, J = 16.0 Hz), 126.4 (d, J = 11.7 Hz), 38.0 (d, J = 13.0 Hz), 31.1 (d, J=8.3 Hz), 24.1, 21.5, 14.3, 13.5. 31P NMR (162 MHz, CDCl3) δ22.7.HRMS (ESI) m / z: [M+H] + Calcd.for C 34 H 32 OP 487.2185; Found 487.2185. BRIEF DESCRIPTION OF THE DRAWINGS

[0142] 1: Figure 1 Two general strategies for carbon functionalization of alkynes / alkenes

[0143] 2: Figure 2 Carbon functionalization of alkynes / alkenes via single bond insertion

[0144] 3: Figure 3 Schematic diagram of the single crystal structure of compound 3.

Claims

1. The present invention provides a method for synthesizing a seven-membered phosphine oxide compound, and realizes a method for activating the CP bond of a five-membered phosphine oxide compound by nickel-aluminum catalysis, characterized in that The specific steps of this method are: In a nitrogen atmosphere, the ligand, metal catalyst, raw material and solvent were added to the reaction bottle in sequence, and then Lewis acid was added. The mixture was stirred at a specified temperature for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% ethylenediaminetetraacetic acid disodium salt aqueous solution, separated, and the organic phase was dried over anhydrous sodium sulfate. The target product 3 was separated by column chromatography. The single crystal structure of the compound is shown in (Figure 3).

2. The metal catalyst involved in the present invention is Ni(cod)2, and the amount of the catalyst used is generally 10 mol%.

3. The ligand involved in the present invention is chiral triphenylphosphine, and its usage is generally 10 mol%.

4. The AlMe2Cl involved in the present invention has a concentration of 1 mol / L n-hexane solution, and its usage is generally 40 mol%.

5. The solvent used in the present invention is a toluene solution, and its usage is 5 mL per mmol of the raw material 1.

6. In the raw material 1 used in the present invention, R is a substituted group such as phenyl, cyclohexyl, cyclopropane, tert-butyl, isopropyl, etc., but is not limited to these groups; R' is phenyl, butyl, pentyl, hexyl, but is not limited to these groups.

Images