A method for the synthesis of seven-membered phosphine oxide compounds by nickel-aluminium catalysis

Abstract

The application provides a simple and efficient synthesis method, and realizes the method for generating a seven-membered phosphine oxide compound by C-P bond activation insertion of an alkyne of a five-membered phosphine oxide compound through a phosphine oxygen ligand connected nickel-aluminum bimetallic catalyst, and belongs to the technical field of method development. The key to solving the problem of the application lies in that: 1. A five-membered phosphine oxide compound which is efficient and specific in reaction activity and site selectivity is found, and a method for realizing C-P bond activation by means of a tension ring is found; 2. A bimetallic catalytic system is designed by using the characteristics of the phosphine oxygen ligand, so that the reaction activity is greatly improved, and therefore the preparation is more efficient.

Description

TECHNICAL FIELD

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

[0002] Starting from inexpensive and readily available starting materials, realizing intermolecular carbon functionalization of conjugated systems by a two-electron or single-electron pathway is a better way to realize molecular complexity. A classical method is to use functionalization reagents to carbon functionalize alkynes or alkenes, which needs to sacrifice stoichiometric molecular fragments even with stoichiometric oxidants or reductants (see Figure One , Path i). Another more attractive alternative is to directly insert alkynes or alkenes into a chemical bond (see Figure One , Path ii), which can solve the problem of great loss of molecular fragments and other stoichiometric reagents, and provide higher atom and step economy.

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

[0004] On the contrary, directly inserting into relatively inert chemical bonds (such as C-C, C-N or C-P 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 polar chemical bonds, alkynes or alkenes have also successfully inserted C-C and C-N bonds, providing a large number of intermolecular two-carbon functionalization or carbon amination reactions (Scheme 1b, right). However, compared with these progresses, the development of intermolecular carbon phosphidation reactions by directly inserting alkynes or alkenes into C-P bonds is very lagging, which may be attributed to the following difficulties: unreacted C-P chain, highly strained P-containing small rings that are not easy to obtain, strong coordination of P atom with metal catalyst, and difficulty in forming C-P bond.

[0005] In summary, although a number of cross-coupling reactions using P-containing substrates as aryl or alkyl coupling reagents have been reported, intermolecular carbon phosphidation reactions of alkynes or alkenes with C-P bonds remain a elusive challenge. SUMMARY

[0006] The application aims to provide a simple and practical method, which uses Ni-Al bimetallic catalysis to realize intermolecular carbon-phosphorization reaction of alkyne and easily obtained five-membered phosphorus oxide, a series of seven-membered phosphines are provided, which are promising candidates for optoelectronic applications, and the yield is up to 94%.

[0007]

[0008] 1. In a nitrogen atmosphere, a reaction bottle is sequentially added with a ligand, a metal catalyst, a raw material and a solvent, and then a Lewis acid is added, and stirred for 12 hours at a specified temperature, 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 is dried with anhydrous sodium sulfate, and column chromatography is used to separate the target product 3, and the single crystal structure of the compound is shown in Figure Three );

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

[0010] 3. The ligand involved in the application is chiral triphenylphosphine, and the amount is generally 10 mol%.

[0011] 4. The AlMe2Cl involved in the application is a 1 mol / L n-hexane solution, and the amount is generally 40 mol%.

[0012] 5. The solvent used in the application is toluene solution, and the amount is 5 mL per millimole of raw material.

[0013] 6. In the raw material 1 used in the application, R is a phenyl, cyclohexyl, cyclopropane, tert-butyl, isopropyl and the like, but is not limited to these groups; R' is a phenyl, butyl, pentyl, hexyl, but is not limited to these groups.

[0014] The application has the following advantages:

[0015] 1. Most of the reagents used in the application are commercially available, the chiral ligand raw material needs to be synthesized, the source is wide, the price is low, and it can exist stably at normal temperature and pressure, the operation is convenient, and no special treatment is needed.

[0016] 2. The ligand structure involved in the application is simple and easy to operate, which avoids the defect that the synthesis steps of the ligand used in the previous method are long, and the equipment requirement is simple. The production cost of synthesizing the compound is greatly reduced.

[0017] 3. The seven-membered ring phosphine oxide compound can be obtained in one step, and the post-treatment is simple and convenient, which avoids the method that the phosphine oxide product can be obtained by relay reaction, and the product reaction cost is greatly reduced.

[0018] 4. The catalyst used in the present application is inexpensive, and the amount of metal, ligand, etc. is low, thus maintaining good catalytic effect, reducing cost, facilitating post-treatment process, and reducing environmental pollution.

[0019] 5. The reaction of the present application is completely atom-economic, meets the requirements of green chemistry, and has no other by-products in mass production, thus achieving the requirements of simplifying process, reducing cost, and reducing environmental pollution. Specific implementation method

[0020] The activation reaction of the five-membered phosphine oxide compound C-P bond will be better illustrated by the following examples, but it should be emphasized that the present application is by no means limited to the content represented by these examples. The following examples show different aspects of the present application. The data given include specific operations and reaction conditions and products. The product purity is identified by nuclear magnetic resonance.

[0021] Example 1: Synthesis of 5-Phenyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0022]

[0023] In a nitrogen atmosphere, the ligand PPh3(5.2 mg, 10 mol%) was added to the reaction bottle, followed by Ni(cod)2(5.5 mg, 10 mol%), 1a(55.3 mg, 0.2 mmol), toluene(1.0 mL), and then 2a(44.1 mg, 0.4 mmol), dimethyl aluminum chloride(1M, 80 μL, 40 mol%), 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, the organic phase was dried with anhydrous sodium sulfate, concentrated and separated by column chromatography to obtain the target product 3a, white solid, yield 95%, melting point 147-149°C. 1 H NMR (400 MHz, CDC13) 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 C NMR (100 MHz, CDC13) 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 = 8.3 Hz), 24.2, 21.6 (d, J = 1.6 Hz), 14.3, 13.5. 31 P NMR (162 MHz, CDC13) δ 22.4. HRMS (ESI) m / z: [M+H] + Calcd. for C 26 H 28 OP 387.1872; Found 387.1869.

[0024] Example 2: Synthesis of 6,7-Diethyl-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0025]

[0026] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2b(32.8 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3b as white solid in 90% yield, m.p. 78-80 °C. 1H NMR (400 MHz, CDC13) δ 8.35-8.24 (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, CDC13) 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 (162 MHz, CDC13) δ 22.3. HRMS (ESI) m / z: [M + H] + Calcd. for C 24 H 24 OP 359.1559; Found 359.1556.

[0027] Example 3: Synthesis of 6,7-Dibutyl-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0028]

[0029] To a reaction flask was added 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), followed by 2c (55.3 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the target product 3c as a white solid in 94% yield, m.p. 164-166 °C. 1 H NMR (400 MHz, CDC13) 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). 13 C NMR (100 MHz, CDC13) 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, CDC13) δ 22.3. HRMS (ESI) m / z: [M+H] + Calcd. for C 28 H 32OP 415.2185; Found 415.2188.

[0030] Example 4: Synthesis of (R,E)-5-(((tert-Butyldimethylsilyl)oxy)methyl)-2-(4- phenylbut-3-en-2-yl)pyridine

[0031]

[0032] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la (55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2d (77.7 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3d as a white solid in 90% yield, m.p. 86-88 °C. 1 H NMR (400 MHz, CDC13) 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). 13C NMR (100 MHz, CDC13) δ 145.0 (d, J = 9.1 Hz), 141.2 (d, J = 10.3 Hz), 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 P NMR (162 MHz, CDC13) δ 22.1. HRMS (ESI) m / z: [M + H] + Calcd. for C 30 H 36 OP443.2498; Found 443.2495.

[0033] Example 5: Synthesis of 6,7-Dihexyl-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0034]

[0035] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2e(77.7 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3e as a white solid in 90% yield, m.p. 63-65 °C. 1H NMR (400 MHz, CDC13) δ 8.33-8.23 (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), 2.54-2.42 (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, CDC13) 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, CDC13) δ 22.2. HRMS (ESI) m / z: [M + H] + Calcd. for C 32 H 40 OP 471.2811; Found 471.2808.

[0036] Example 6: Synthesis of 6,7-Bis(3-((tert-butyldimethylsilyl)oxy)propyl)-5- phenyldibenzo[b,d]phosphepine 5-oxide

[0037]

[0038] To a reaction flask was added 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), followed by 2f (148.1 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the target product 3f, yellow liquid, yield 70%. 1 H NMR (400 MHz, CDC13) δ 8.26-8.15 (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, 2H), 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). 13 C NMR (100 MHz, CDC13) 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. 31P NMR (162 MHz, CDC13) δ 22.1. HRMS (ESI) m / z: [M+H] + Calcd. for C 38 H 56 O3PSi 2647.3500; Found 647.3497.

[0039] Example 7: Synthesis of 5,6,7-Triphenyldibenzo[b,d]phosphepine 5-oxide

[0040]

[0041] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2g (71.2 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3g as a yellow liquid in 90% yield, m.p. 120-122 °C. 1 H NMR (400 MHz, CDC13) 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). 13CNMR (100 MHz, CDC13) 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 P NMR (162 MHz, CDC13) δ 19.7. HRMS (ESI) m / z: [M + H] + Calcd. for C 32 H 24 OP 455.1559; Found 455.1556.

[0042] Example 8: Synthesis of 5-Phenyl-6,7-di-p-tolyldibenzo[b,d]phosphepine 5-oxide

[0043]

[0044] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2h(82.4 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase with anhydrous sodium sulfate, concentrated and separated by column chromatography to give the target product 3i as white solid in 93% yield, m.p. 171-173 °C. 1H NMR (400 MHz, CDC13) δ 8.34-8.18 (m, IH), 7.80-7.68 (m, 2H), 7.67-7.55 (m, IH), 7.47-7.34 (m, 2H), 7.29-7.24 (m, IH), 7.21-7.13 (m, 5H), 7.12-6.95 (m, 7H), 6.92-6.78 (m, 3H), 6.78-6.65 (m, IH). 13 CNMR (100 MHz, CDC13) 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 P NMR (162 MHz, CDC13) δ 19.7. HRMS (ESI) m / z: [M + H] + Calcd. for C 32 H 24 OP 455.1559; Found 455.1556.

[0045] Example 9: Synthesis of (R)-l-Isopropyl-6-methyl-3,4-di-o-tolyl-5,6- dihydropyridin-2(lH)-one

[0046]

[0047] To a reaction flask was added 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), followed by 2i(116.1 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), 120 °C, stirring for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, partitioned, dried the organic phase over anhydrous sodium sulfate, concentrated and column chromatography to isolate the target product 3i, white solid, yield 84%, m.p. 192-194 °C. 1 H NMR (400 MHz, CDC13) δ 8.31-8.21 (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). 13 C NMR (100 MHz, CDC13) δ 150.3, 149.8, 149.5 (d, J = 11.0 Hz), 141.1 (d, J = 10.5 Hz), 140.4 (d, J = 1.7 Hz), 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 = 4.1 Hz), 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, CDC13) δ 19.8. HRMS (ESI) m / z: [M+H] + Calcd. for C 40 H 40OP567.2811; Found 567.2814.

[0048] Example 10: Synthesis of 6,7-Bis(4-methoxyphenyl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0049]

[0050] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL) under nitrogen atmosphere, followed by 2j (116.1 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3j as a white solid in 84% yield, m.p. 192-194 °C. 1 H NMR (400 MHz, CDC13) 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). 13CNMR (100 MHz, CDC13) 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, 113.1 1, 55.2, 55.2. 31 P NMR (162 MHz, CDC13) δ 20.0. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 28 O3P 515.1771; Found 515.1771.

[0051] Example 11: Synthesis of 5-Phenyl-6,7-bis(4-(trifluoromethoxy)phenyl)dibenzo[b,d]phosphepine 5-oxide

[0052]

[0053] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2k (346.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 hours, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase with anhydrous sodium sulfate, concentrated and separated by column chromatography to give the target product 3k as white solid in 55% yield, melting point 257-259 °C. 1H NMR (400 MHz, CDC13) δ 8.29 - 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, CDC13) 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, CDC13) δ -57.8, -58.0. 31 P NMR (162 MHz, CDC13) δ 19.5. HRMS (ESI) m / z: [M+H] + Calcd. for C 34 H 22 F6O3P 623.1205; Found 623.1203.

[0054] Example 12: Synthesis of (R)-1-Isopropyl-6-methyl-3,4-bis(4- (trifluoromethoxy)phenyl)-5,6-dihydropyridin-2(lH)-one

[0055]

[0056] To a reaction flask was added 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), followed by 21(128.9 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3l as a white solid in 69% yield, m.p. 301-303 °C. 1 H NMR (400 MHz, CDC13) δ 8.21-8.08 (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). 13 C NMR (100 MHz, CDC13) 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 = 2.4 Hz), 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, CDC13) δ 19.7. HRMS (ESI) m / z: [M+H] + Calcd. for C 38 H 40 OPSi2599.2350; Found 599.2345.

[0057] Example 13: Synthesis of 6,7-Bis(4-fluorophenyl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0058]

[0059] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2m (85.6 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3m as a white solid in 87% yield, m.p. 250-252 °C. 1 H NMR (400 MHz, CDC13) 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). 13C NMR (100 MHz, CDC13) 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 F NMR (376 MHz, CDC13) δ -113.4, -114.4. 31 P NMR (162 MHz, CDC13) δ 19.7. HRMS (ESI) m / z: [M + H] + Calcd. for C 32 H 22 F2OP 491.1371; Found 491.1366.

[0060] Example 14: Synthesis of (R)-3,4-Bis(3-Fluorophenyl)-l-isopropyl-6-methyl-5,6- dihydropyridin-2(lH)-one

[0061]

[0062] To a reaction flask was added 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), followed by 2n (125.6 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the target product 3n as a white solid in 36% yield, m.p. 290-292 °C. 1 H NMR (400 MHz, CDC13) δ 8.26-8.12 (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, CDC13) 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). 19 F NMR (376 MHz, CDC13) δ -62.6, -62.7.31 P NMR (162 MHz, CDC13) δ 19.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 22 F6 OP 591.1307; Found 591.1302.

[0063] Example 15: Synthesis of 5-Phenyl-6,7-di-m-tolyldibenzo[b,d]phosphepine 5-oxide

[0064]

[0065] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2o(82.4 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3o as a white solid in 77% yield, m.p. 187-189 °C. 1 H NMR (400 MHz, CDC13) δ 8.42-8.24 (m, 1H), 7.87-7.76 (m, 2H), 7.73-7.66 (m, 1H), 7.55-7.45 (m, 2H), 7.33 (d, J = 7.3 Hz, 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, CDC13) 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, CDC13) δ 19.9. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 28 OP 483.1872; Found 483.1870.

[0066] Example 16: Synthesis of 5-Phenyl-6,7-bis(3-(trifluoromethoxy)phenyl)dibenzo[b,d]phosphepine 5-oxide

[0067]

[0068] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2p(138.4 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3p as a white solid in 47% yield, m.p. 154-156 °C. 1H NMR (400 MHz, CDC13) 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 C NMR (100 MHz, CDC13) 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 F NMR (376 MHz, CDC13) δ -58.2. 31 P NMR (162 MHz, CDC13) δ 19.3. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 22 F6O3P 623.1205; Found 623.1202.

[0069] Example 17: Synthesis of (R)-1-Isopropyl-6-methyl-3,4-di(thiophen-3-yl)-5,6- dihydropyridin-2(lH)-one

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

[0071] To a reaction flask was added 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) sequentially under nitrogen atmosphere, followed by 2q (85.6 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3q as a white solid in 67% yield, m.p. 214-216 °C. 1 H NMR (400 MHz, CDC13) δ 8.32 - 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), 7.23 - 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). 13C NMR (100 MHz, CDC13) 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 P NMR (162 MHz, CDC13) δ 19.5. HRMS (ESI) m / z: [M + H] + Calcd. for C 32 H 22 F2OP491.1371; Found 491.1367.

[0072] Example 18: Synthesis of Dimethyl 3,3'-(5-oxido-5-phenyldibenzo[b,d]phosphepine-6,7-diyl)dibenzoate

[0073]

[0074] To a reaction flask was added 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), followed by 2r(117.6 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3r as a white solid in 57% yield, m.p. 214-216 °C. 1 H NMR (400 MHz, CDC13) δ 8.28 - 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, CDC13) δ 166.8, 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, CDC13) δ 19.6. HRMS (ESI) m / z: [M + H] + Calcd. for C36 H 28 O5P 571.1669; Found 571.1667.

[0075] Example 19: Synthesis of 6,7-Bis(2-fluorophenyl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0076]

[0077] To a reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2s (85.6 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3s as a white solid in 86% yield, m.p. 193-195 °C. 1 H NMR (400 MHz, CDC13) δ 8.38-8.17 (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, CDC13) 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, CDC13) δ 19.4, 18.2. HRMS (ESI) m / z: [M + H] + Calcd. for C 32 H 22 F2OP 491.1371; Found 491.1368.

[0078] Example 20: Synthesis of 6,7-Bis(l-methyl-lH-indol-6-yl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0079]

[0080] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2t(113.7 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3t as a white solid in 41% yield, m.p. 202-204 °C.1 H NMR (400 MHz, CDC13) 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 CNMR (100 MHz, CDC13) 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 P NMR (162 MHz, CDC13) δ 20.5. HRMS (ESI) m / z: [M+H] + Calcd. for C 38 H 30 N2OP 561.2090; Found 561.2087.

[0081] Example 21: Synthesis of 6,7-Bis(3,4-dimethylphenyl)-5-phenyldibenzo[b,d]phosphepine 5-oxide

[0082]

[0083] To a reaction flask was added 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), followed by 2u (93.7 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3u as a white solid in 82% yield, m.p. 139-141 °C. 1 H NMR (400 MHz, CDC13) δ 8.29-8.19 (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 = 7.3 Hz, 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, CDC13) 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 = 10.4 Hz), 128.83 (d, J = 78, 9 Hz), 128.77, 128.7, 127.8, 127.7, 127.5, 127.4, 126.8, 19.8, 19.7, 19.6, 19.6. 31P NMR (162 MHz, CDC13) δ 20.1. HRMS (ESI) m / z: [M+H] + Calcd. for C 36 H 32 OP 511.2185; Found 511.2185.

[0084] Example 22: Synthesis of 5,7-Diphenyl-6-(trimethylsilyl)dibenzo[b,d]phosphepine 5-oxide

[0085]

[0086] To a reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2v(69.6 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3v, 3v', white solid, yield 38% (3.8:1), melting point 183-185 °C. 1 H NMR (400 MHz, CDC13) δ 8.40-8.30 (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, CDC13) δ 161.7, 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 = 10.5 Hz), 128.1 (d, J = 19.3 Hz), 127.7 (d, J = 27.9 Hz), 127.7, 127.64, 127.55, 126.4, 1.9. 31 PNMR (162 MHz, CDC13) δ 23.8. HRMS (ESI) m / z: [M + H] + Calcd. for C 29 H 28 OPSi 451.1642.; Found 451.1636. 1 H NMR (400 MHz, CDC13) δ 1 H NMR (400 MHz, CDC13) δ 8.51 - 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, CDC13) δ 154.5, 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, CDC13) δ 18.7.

[0087] Example 23: Synthesis of 6-(tert-Butyl)-5,7-diphenyldibenzo[b,d]phosphepine 5-oxide

[0088]

[0089] To a reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2w(63.2 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3w, 3w', white solid, yield 50% (3.6:1), m.p. 183-185 °C. 1H NMR (400 MHz, CDC13) δ 8.41-8.30 (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, CDC13) δ 157.3 (d, J = 7.6 Hz), 142.7 (d, J = 91.9 Hz), 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 = 2.8 Hz), 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 = 12.0 Hz), 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, CDC13) δ 21.0. HRMS (ESI) m / z: [M+H] + Calcd. for C 30 H 28 OP 435.1872; Found 435.1867. 1 H NMR (400 MHz, CDC13) δ 8.49-8.33 (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, CDC13) 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, CDC13) δ 26.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 30 H 28 OP 435.1872; Found 435.1867.

[0090] Example 24: Synthesis of 6-Methyl-5-phenyl-7-(trimethylsilyl)dibenzo[b,d]phosphepine 5-oxide

[0091]

[0092] To a reaction vial was added sequentially ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la(55.3 mg, 0.2 mmol), toluene (1.0 mL), followed by 2x (44.8 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, partitioned, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 3x, 3x', colorless liquid, 30% yield (3.1:1). 1H NMR (400 MHz, CDC13) δ 8.36 - 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, CDC13) δ 152.2, 147.7 (d, J = 82.8 Hz), 141.8 (d, J = 9.6 Hz), 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 = 10.2 Hz), 128.8 (d, J = 2.2 Hz), 128.6 (d, J = 12.3 Hz), 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 = 11.1 Hz), 0.9. 31 P NMR (162 MHz, CDC13) δ 21.7. HRMS (ESI) m / z: [M+H] + Calcd. for C 24 H 26 OPSi 389.1485; Found 389.1482. 1 H NMR (400 MHz, CDC13) δ 8.38 - 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, CDC13) δ 158.8, 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 = 100.7 Hz), 131.7 (d, J = 2.5 Hz), 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, CDC13) δ 24.1.

[0093] Example 25: Synthesis of 6,7-Dipropyl-5-(p-tolyl)dibenzo[b,d]phosphepine 5-oxide

[0094]

[0095] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), la'(58.0 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4a as a colorless liquid in 82% yield. 1H NMR (400 MHz, CDC13) δ 8.33-8.21 (m, IH), 7.62-7.51 (m, 2H), 7.50-7.41 (m, IH), 7.09-7.04 (m, 2H), 7.01-6.89 (m, 4H), 6.79-6.67 (m, 2H), 2.88-2.77 (m, IH), 2.76-2.67 (m, IH), 2.67-2.54 (m, IH), 2.53-2.42 (m, IH), 2.10 (s, 3H), 1.81-1.55 (m, 2H), 1.17-1.07 (m, IH), 1.03 (t, J = 7.3 Hz, 3H), 0.96-0.83 (m, IH), 0.52 (t, J = 7.6 Hz, 3H). 13 C NMR (100 MHz, CDC13) δ 147.8 (d, J = 8.9 Hz), 141.2 (d, J = 10.3 Hz), 140.8 (d, J = 2.8 Hz), 139.4, 139.3, 137.2 (d, J = 98.4 Hz), 137.1 (d, J = 93.2 Hz), 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 = 8.3 Hz), 24.2, 21.4 (d, J = 14.6 Hz), 14.3, 13.5. 31 P NMR (162 MHz, CDC13) δ 22.0. HRMS (ESI) m / z: [M + H] + Calcd. for C 27 H 30 OP 401.2029; Found 401.2031.

[0096] Example 26: Synthesis of 5-(4-Methoxyphenyl)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0097]

[0098] To a reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1b (61.2 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the target product 4b as a colorless liquid in 78% yield. 1 H NMR (400 MHz, CDC13) δ 8.34 - 8.20 (m, 1H), 7.71 - 7.62 (m, 1H), 7.62 - 7.53 (m, 2H), 7.52 - 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, 1H), 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, CDC13) 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, CDC13) δ 29.2, 21.3. HRMS (ESI) m / z: [M+H]+ Calcd. for C 27 H 30 O2P417.1978; Found 417.1974.

[0099] Example 27: Synthesis of 5-(4-Fluorophenyl)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0100]

[0101] To the reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1c(58.8 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a(44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4c as a colorless liquid in 83% yield. 1 H NMR (400 MHz, CDC13) δ 8.35 - 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 - 6.55 (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, CDC13) 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 = 10.1 Hz), 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, CDC13) δ 21.3. 19 F NMR (376 MHz, CDC13) δ -108.3. HRMS (ESI) m / z: [M + H] + Calcd. for C 26 H 27 OP 405.1778; Found 405.1776.

[0102] Example 28: Synthesis of 5-Isopropyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0103]

[0104] To the reaction flask was added ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1d (48.1 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4d as colorless liquid in 62% yield. 1H NMR (400 MHz, CDC13) 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 C NMR (100 MHz, CDC13) 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 P NMR (162 MHz, CDC13) δ 33.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 23 H 30 OP 353.2029; Found 353.2024.

[0105] Example 29: Synthesis of 5-(tert-Butyl)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0106]

[0107] To the reaction flask was added ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1e (51.2 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4e as a colorless liquid in 90% yield. 1 H NMR (400 MHz, CDC13) δ 8.24-8.12 (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, CDC13) 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, CDC13) δ 38.6. HRMS (ESI) m / z: [M+H] + Calcd. for C 24 H 32 OP 367.2185; Found 367.2181.

[0108] Example 30: Synthesis of 5-(Dimethylamino)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0109]

[0110] To the reaction flask was added ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1f (48.6 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4f as a yellow liquid in 82% yield. 1 H NMR (400 MHz, CDC13) 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, CDC13) 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, CDC13) δ 22.1. HRMS (ESI) m / z: [M + H] + Calcd. for C 22 H 29 NOP 354.1981; Found 354.1982.

[0111] Example 31: Synthesis of 5-(Diethylamino)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0112]

[0113] To the reaction flask was added ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1g (54.2 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%) under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4g as a yellow liquid in 81% yield. 1 H NMR (400 MHz, CDC13) δ 8.21-8.07 (m, 1H), 7.59-7.50 (m, 2H), 7.50-7.45 (m, OH), 7.43-7.37 (m, 2H), 7.35-7.27 (m, 2H), 2.75-2.62 (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, CDC13) 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 (162 MHz, CDC13) δ 22.0. HRMS (ESI) m / z: [M + H] + Calcd. for C 24 H 33 NOP 382.2294. ; Found 382.2290.

[0114] Example 32: Synthesis of 5-(Diisopropylamino)-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0115]

[0116] To the reaction flask was added ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1h (59.8 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4h as yellow liquid in 81% yield. 1H NMR (400 MHz, CDC13) δ 8.25-8.12 (m, 1H), 7.56-7.44 (m, 3H), 7.43-7.38 (m, 2H), 7.36-7.28 (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 (100 MHz, CDC13) δ 147.4 (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, CDC13) δ 19.3. HRMS (ESI) m / z: [M + H] + Calcd. for C 26 H 37 NOP 410.2607; Found 410.2602.

[0117] Example 33: Synthesis of 5-Methoxy-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0118]

[0119] To a reaction flask under nitrogen atmosphere was added sequentially ligand 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 (1 M, 80 μL, 40 mol%), 120 °C, stirring for 12 h, cooling to room temperature, dilution with ethyl acetate, washing with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separation of the layers, drying of the organic phase over anhydrous sodium sulfate, concentration and column chromatography to give the target product 4i as a colorless liquid in 54% yield. 1 H NMR (400 MHz, CDC13) δ 8.06 (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 = 7.2 Hz, 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, CDC13) 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 = 6.8 Hz), 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, CDC13) δ 28.7. HRMS (ESI) m / z: [M + H] + Calcd. for C 21 H 26 O2P 341.1665; Found 341.1663.

[0120] Example 34: Synthesis of 5-Ethoxy-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0121]

[0122] Into a reaction flask was added sequentially ligand 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), followed by 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and separated by column chromatography to give the target product 4j as a colorless liquid in 65% yield. 1 H NMR (400 MHz, CDC13) δ 8.03-7.94 (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 (100 MHz, CDC13) 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, CDC13) δ 26.3. HRMS (ESI) m / z: [M + H] + Calcd. for C 22 H 28 O2P 355.1821; Found 355.1820.

[0123] Example 35: Synthesis of 2,3,9,10-Tetramethyl-5-phenyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0124]

[0125] Into a reaction flask was added sequentially ligand 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), followed by 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4k as a white solid in 81% yield, m.p. 72-74 °C. 1 H NMR (400 MHz, CDC13) δ 7.96 (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 = 7.4 Hz, 3H). 13C NMR (100 MHz, CDC13) 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, CDC13) δ 23.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 30 H 36 OP 443.2498; Found 443.2494.

[0126] Example 36: Synthesis of 2,3,9,10-Tetramethoxy-5-phenyl-6,7-dipropyldibenzo[b,d]phosphepine 5-oxide

[0127]

[0128] To the reaction flask was added sequentially ligand 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), followed by 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4l as a white solid in 82% yield, m.p. 107-109 °C. 1H NMR (400 MHz, CDC13) 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 C NMR (100 MHz, CDC13) δ 151.6 (d, J = 2.1 Hz), 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 = 95.6 Hz), 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 P NMR (162 MHz, CDC13) δ 23.4. HRMS (ESI) m / z: [M + H] + Calcd. for C 30 H 36 O5P 507.2295; Found 507.2293.

[0129] 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

[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] To a reaction flask was added sequentially ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1m (78.4 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL 5% aqueous ethylenediaminetetraacetic acid disodium salt, partitioned, dried the organic phase over anhydrous sodium sulfate, concentrated and column chromatography to isolate the target product 4m as a white solid in 68% yield, m.p. 249-251 °C. 1 H NMR (400 MHz, CDC13) δ 7.68 (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, CDC13) 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, CDC13) δ 22.6. HRMS (ESI) m / z: [M + H] + Calcd. for C 30 H 32 O5P 503.1982; Found 503.1980.

[0132] 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

[0133]

[0134] To the reaction flask was added ligand Ph2P(O)H (4.0 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), In(n) (72.8 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), dimethylaluminum chloride (1 M, 80 μί, 40 mol%), and stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4n as a yellow solid in 62% yield, m.p. 171-173 °C. 1 H NMR (400 MHz, CDC13) δ 7.70 (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, CDC13) δ 150.7, 147.41 (d, J = 23.9 Hz), 147.38, 146.2 (d, J = 17.6 Hz), 136.7 (d, J = 83.7 Hz), 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, CDC13) δ 23.1. HRMS (ESI) m / z: [M + H] + Calcd. for C 28 H 28 O5P 475.1669; Found 475.1664.

[0135] Example 39: Synthesis of 3-Phenyl-4,5-dipropyldinaphtho[2, l-b: l',2'-d]phosphepine 3-oxide

[0136]

[0137] To a reaction flask was added sequentially under nitrogen atmosphere ligand 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), followed by 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1 M, 80 μL, 40 mol%), stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4o as a yellow solid in 71% yield, m.p. 118-120 °C. 1H NMR (400 MHz, CDC13) δ 8.47-8.35 (m, IH), 8.13 (d, J = 8.4 Hz, IH), 7.97 (d, J = 8.9 Hz, IH), 7.74-7.62 (m, IH), 7.54-7.46 (m, 2H), 7.43 (d, J = 8.9 Hz, IH), 7.26-7.16 (m, 3H), 7.12-7.04 (m, IH), 7.03-6.93 (m, 2H), 6.85 (d, J = 8.6 Hz, IH), 6.81-6.72 (m, IH), 6.65-6.51 (m, 2H), 2.91-2.66 (m, 3H), 2.64-2.50 (m, IH), 1.85-1.54 (m, 2H), 1.21-1.09 (m, IH), 1.02 (t, J = 6.5 Hz, 3H), 0.96-0.81 (m, IH), 0.40 (t, J = 6.6 Hz, 3H). 13 C NMR (100 MHz, CDC13) 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 P NMR (162 MHz, CDC13) δ 24.2. HRMS (ESI) m / z: [M + H] + Calcd. for C 34 H 32 OP487.2185; Found 487.2182.

[0138] Example 40: Synthesis of 3-Phenyl-4,5-dipropyldinaphtho[2,l-b: 1',2'-d]phosphepine 3-oxide

[0139]

[0140] To a reaction flask was added ligand PPh3(5.2 mg, 10 mol%), Ni(cod)2(5.5 mg, 10 mol%), 1p (75.2 mg, 0.2 mmol), toluene (1.0 mL), followed by 2a (44.0 mg, 0.4 mmol), trimethylaluminum (1 M, 80 μL, 40 mol%), under nitrogen atmosphere, stirred at 120 °C for 12 h, cooled to room temperature, diluted with ethyl acetate, washed with 2 mL of 5% aqueous ethylenediaminetetraacetic acid disodium salt solution, separated, dried the organic phase over anhydrous sodium sulfate, concentrated and purified by column chromatography to give the target product 4p as a yellow solid in 72% yield, m.p. 118-120 °C. 1 H NMR (400 MHz, CDC13) δ 8.83 (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, CDC13) 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, CDC13) δ 22.7. HRMS (ESI) m / z: [M+H] + Calcd. for C 34 H 32 OP 487.2185; Found 487.2185. BRIEF DESCRIPTION OF DRAWINGS

[0141] 1: Figure 1 Two general strategies for alkyne / alkene carbon functionalization

[0142] 2: Figure 2 Alkyne / alkene carbon functionalization via single bond insertion

[0143] 3: Figure 3 Schematic representation of the single crystal structure of compound 3.

Claims

1. A method for synthesizing a seven-membered phosphine oxide, characterized in that... The synthetic route and specific steps of this method are as follows: Under a nitrogen atmosphere, the ligand, metal catalyst, raw material 1, and solvent were added sequentially to the reaction flask, followed by raw material 2 and Lewis acid solution. 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. Column chromatography was then used to separate the target product 3, in which: The metal catalyst is Ni(cod)2; The raw material 1 is a five-membered phosphine oxide compound with the following structural formula: ； The structural formula of the raw material 2 is: ; in: R is phenyl, cyclohexyl, cyclopropane, tert-butyl, or isopropyl; R ’ It is phenyl, butyl, pentyl, or hexyl; The Lewis acid solution is an AlMe2Cl n-hexane solution; The structural formula of the target product 3 is: 。 2. The synthesis method according to claim 1, characterized in that: The amount of the metal catalyst used is 10 mol of the five-membered phosphine oxide.

3. The synthesis method according to claim 1, characterized in that: The ligand is a chiral triphenylphosphine, and its amount is 10 mol of the five-membered phosphine oxide.

4. The synthesis method according to claim 1, characterized in that: The concentration of the Lewis acid solution is 1 mol / L, and the amount used is 40 mol of the five-membered phosphine oxide compound.

5. The synthesis method according to claim 1, characterized in that: The solvent is toluene, and the amount used is 5 mL per millimole of the five-membered phosphine oxide compound.

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