Nickel-catalyzed cross electrophilic coupling of tetraarylphosphonium salts with aryl bromides

Abstract

The present application provides a method for nickel-catalyzed cross electrophilic coupling of tetraaryl phosphonium salt and aryl bromide, which comprises reacting tetraaryl phosphonium salt with bromide in the presence of nickel catalyst and lithium chloride to obtain a coupling compound.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a nickel-catalyzed method for cross-electrophilic coupling of tetraarylphosphonium salts and aryl bromides. Background Technology

[0002] Transition metal-catalyzed cross-coupling reactions of organohalides with various organometallic compounds have revolutionized modern organic synthesis. Besides the widespread use of organohalides and pseudohalides in classic cross-coupling schemes, the search for novel coupling electrophiles as alternatives to organohalides and pseudohalides has also attracted considerable attention in the synthetic community. Among the various alternative coupling partners reported to date, organophosphonium salts have also attracted the interest of synthetic chemists and have proven to be highly efficient coupling electrophiles for a variety of organic reactions. Of particular note is the fact that tetraarylphosphonium salts can be conveniently prepared from triarylphosphine and other phosphorus sources and can also participate in certain organic transformations as effective arylating agents, such as the Heck reaction, Suzuki reaction, Sonogashira reaction, Stille reaction, and carbonylation reactions. However, compared to pyridyltriphenylphosphonium salts and alkyl (aryl)phosphonium salts, which are widely used in various organic reactions, the application of tetraarylphosphonium salts as effective arylating electrophiles in coupling reactions has not been extensively studied and remains to be further explored.

[0003] In recent decades, cross-electrophilic coupling between two readily available electrophilic reagents has developed into a powerful platform for the rapid construction of C-C bonds, avoiding the pre-synthesis and treatment of sensitive organometallic reagents. Against this backdrop, although cross-coupling of tetraphenylphosphonium salts with arylboronic acids and aryltinanes has been reported, the corresponding cross-electrophilic coupling reactions of tetraarylphosphonium salts still require further investigation.

[0004] Cross-electrophilic coupling with aryl halides (which is more step-economical, cost-effective, and simple to operate) has not yet been developed. The only relevant work is the cross-electrophilic coupling of tetraphenylphosphonium salts with allyl alcohols, which is carried out in the presence of nickel catalyst, bpy ligand, manganese, ZrCl4, and LaCl3. In addition, although cross-electrophilic coupling of pyridyl (or thiazolyl) triphenylphosphonium salts, alkyl (triaryl) phosphonium salts, and even triarylphosphine with aryl halides has been reported, most of the reported methods use relatively reactive organophosphonium salts and aryl iodides (or benzyl bromides) as substrates, and / or use more expensive palladium salts as catalysts. Summary of the Invention

[0005] This invention reports a nickel-catalyzed cross-electrophilic coupling method for tetraarylphosphonium salts and aryl bromides: in the presence of a nickel catalyst and lithium chloride, tetraarylphosphonium and bromides are reacted to yield the corresponding biaryl compounds in good yields, which have a broad substrate range and good functional group tolerance.

[0006] Specifically, the present invention provides a method for preparing a compound of formula III or a salt thereof, the method comprising the step of reacting a compound of formula I with a compound of formula II in the presence of a nickel catalyst and lithium chloride to form a compound of formula III: The process is as follows: ; Among them, R 1 Selected from phenyl, wherein the phenyl group is optionally selected from one or more halogens, cyano groups, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkyloxy and benzyloxy; R 2 The group is selected from phenyl, naphthyl, oxofluorenyl, and carbazole, wherein the phenyl, naphthyl, oxofluorenyl, and carbazole are optionally selected from one or more halogens, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 The substituents are alkoxy, phenyl, and tert-butyldimethylsiloxy; or, two adjacent substituents form a 3- to 6-membered heterocyclic alkyl group with an adjacent atom; X is selected from halogens, such as bromine.

[0007] In some implementation schemes, R 1 Selected from phenyl. In some embodiments, R 1 Selected from phenyl, wherein the phenyl is selected from one or more halogens, C 1-6 Alkyl groups (such as methyl, ethyl, and tert-butyl), C 1-6 Alkoxy groups (such as methoxy or ethoxy groups), halogenated C 1-6 Alkyl groups (such as trifluoromethyl), halogenated C 1-6 Alkyl and phenyl substituents are used. In some embodiments, R 1 The phenyl group is selected from phenyl, wherein the phenyl group is selected from one or more benzyloxy groups.

[0008] In some implementation schemes, R 1 Selected from: , , , , , , , , , , , and .

[0009] In some embodiments, the compound represented by Formula I is selected from... , , , , , , , , , , , and .

[0010] In some implementation schemes, R 2 Selected from phenyl, wherein the phenyl group is optionally selected from one or more halogens, cyano groups, amino groups, C6 groups, etc. 1-6 Alkyl, Halogenated C 1-6 Alkyl and C 1-6 Substituted by alkoxy groups.

[0011] In some implementation schemes, R 2 Selected from naphthyl groups. In some embodiments, R 2 The group is selected from naphthyl groups, which may optionally be substituted with one or more methoxy substituents. In some embodiments, R... 2 Selected from oxofluorene groups. In some embodiments, R 2 The group is selected from carbazolyl, wherein the carbazolyl group is optionally substituted with one or more phenyl substituents.

[0012] In some embodiments, the compound represented by Formula II is selected from... , , , , , , , , , , , , , , , , and , where X is selected from halogens, such as bromine.

[0013] In some embodiments, the compound represented by Formula II is selected from... , , , , , , , , , , , , , , , and .

[0014] In some embodiments, the nickel catalyst used in the reaction is selected from NiCl2 and Ni(PPh3)2Cl2.

[0015] In some embodiments, the amount of nickel catalyst used is 5% to 20% of the molar amount of the compound of Formula I, such as 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 10%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, 15%, 16%, 17%, 18%, 19%, and 20%. In some embodiments, the amount of nickel catalyst used is 10% of the molar amount of the compound of Formula I.

[0016] In some embodiments, the amount of lithium chloride used is 1 to 3 equivalents of the molar amount of the compound of Formula I, including but not limited to 1 equivalent, 1.5 equivalent, 2 equivalent, 2.5 equivalent, and 3 equivalent. In some embodiments, the amount of lithium chloride used is 2 equivalents of the molar amount of the compound of Formula I.

[0017] On the other hand, the reaction also contains metallic magnesium. In some embodiments, the amount of metallic magnesium is 2 to 5 equivalents of the molar amount of the compound of formula I, including but not limited to 2 equivalents, 2.5 equivalents, 3 equivalents, 3.5 equivalents, 4 equivalents, 4.5 equivalents, and 5 equivalents.

[0018] In some embodiments, the amount of metallic magnesium used is 4 equivalents of the molar amount of the compound of formula I.

[0019] In some embodiments, the molar ratio of the compound of Formula I to the compound of Formula II in the reaction is 1:1 to 1:5. In some embodiments, the molar ratio of the compound of Formula I to the compound of Formula II in the reaction is 1:4.

[0020] In some embodiments, the solvent used in the reaction is selected from tetrahydrofuran. In some embodiments, the reaction conditions are NiCl2, lithium chloride, and metallic magnesium.

[0021] In some embodiments, the compound represented by Formula III is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0022] The preparation method of the present invention also includes one or more steps such as filtration, extraction, drying, concentration or purification (e.g., column chromatography).

[0023] "Optionally" means that the event or situation subsequently described may, but does not have to, occur; the description includes the possibility or possibility that the event or situation may or may not occur. For example, "optionally halogenated or cyano-substituted C..." 1-6 "Alkyl" means that halogens or cyano groups may or may not be present. This description includes cases where alkyl groups are substituted by halogens or cyano groups and cases where alkyl groups are not substituted by halogens or cyano groups.

[0024] "alkyl" refers to a saturated aliphatic hydrocarbon group, including straight-chain and branched groups with 1 to 8 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, and their various branched isomers. Alkyl groups can be substituted or unsubstituted; the term "halogenated" refers to substitution by one or more atoms selected from fluorine, chlorine, bromine, and iodine.

[0025] "Substituted" refers to one or more hydrogen atoms in a group, preferably up to five, more preferably one to three hydrogen atoms, which are independently substituted by the corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without much effort.

[0026] The term "alkoxy" refers to -O-(alkyl), where alkyl is defined as described above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentoxy, and cyclohexyloxy. Alkoxy groups can be substituted or unsubstituted. When substituted, the substituent can be replaced at any usable connection point, preferably one or more of the following groups, including but not limited to halogens.

[0027] The term "heterocycloalkyl" or "alicyclic heterocycle" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing 3 to 14 ring atoms, such as 4 or 5 ring atoms, wherein one or more ring atoms are selected from nitrogen, oxygen, or S(O). m Heteroatoms (where m is an integer from 0 to 2), excluding the ring moiety of -OO-, -OS-, or -SS-, with the remaining ring atoms being carbon. Non-limiting examples of "heterocyclic alkyl" include: , or And so on. Heterocyclic alkyl groups can be optionally substituted or unsubstituted.

[0028] The term "aryl" or "aromatic ring" refers to a 6- to 10-membered all-carbon monocyclic or fused polycyclic (i.e., rings sharing adjacent carbon atom pairs) group having a conjugated π-electron system, such as phenyl and naphthyl; the term "heteroaryl" or "heteroaromatic ring" refers to a heteroaromatic system containing 1 to 4 heteroatoms and 5 to 10 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. Heteroaryl groups are preferably 5 to 10-membered, such as 7-, 8-, or 9-membered, and more preferably 5- or 6-membered.

[0029] The "substituents" of this invention include, but are not limited to, halogens (such as chlorine and fluorine), cyano, nitro, amino, and C. 1-6 Alkyl, C 1-6 Alkoxy, the C 1-6 Alkyl, C 1-6 The alkoxy group may be optionally replaced by one or more halogens, hydroxyl groups, cyano groups, nitro groups, amino groups, or C groups. 1-6 Alkyl or C 1-6 Alkyl substitution. "Hydroxy" refers to the -OH group. "Cyano" refers to the -CN group. "Halogen" refers to fluorine, chlorine, bromine, or iodine. "Amino" refers to -NR. a 2, R a Each independently selects hydrogen and C 1-6 Alkyl groups (such as methyl) and phenyl groups. The term "filtration" in this invention is merely a description of one method of separating solids and liquids, and does not refer to only one specific operation. In actual production, methods such as centrifugation or spin-drying also fall into this category.

[0030] The numerical values ​​in this invention are instrument measurements and are subject to a certain degree of error. Generally, ±20% is within a reasonable error range. Of course, the context in which these values ​​are used must be considered; they can be ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, or ±1%, preferably ±5%. The structure of the compounds was determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shifts (δ) are given in units of 10⁻⁶ (ppm). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer, with the solvents being deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl₃), and deuterated methanol (Methanol-d4), and the internal standard being tetramethylsilane (TMS). Detailed Implementation

[0031] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments are not intended to limit the present invention. Unless otherwise specified, the raw materials used in the embodiments are all commercially available.

[0032] The tetraarylphosphonium salts in this invention were synthesized with reference to the following literature, and the relevant content is incorporated herein by reference for illustration: D. Marcoux, AB Charette, Palladium-Aatalyzed Synthesis of Functionalized Tetraarylphosphonium Salts. J. Org. Chem. 2008, 73, 590–593; D. Han, A. Wen, Z. Tian, ​​X. Zhan, C. Hu, Z. Luo, P. Liu, B. Liu, Copper-Mediated Phosphoniumation of Aryl / Vinyl Boronic Acids. Org. Lett. 2025, 27, 2480–2484; N.-N. Ma, J.-A. Ren, X. Liu, X.-Q. Chu, W. Rao, Z.-L. Shen, Nickel-Catalyzed Direct Cross-Coupling of Aryl Sulfonium Salt with Aryl Bromide. Org. Lett. 2022, 24, 1953–1957.

[0033] The general preparation process in this case is as follows: Butyllithium (12 mL, 30 mmol, 1.0 equivalent, 2.5 M hexane solution) was added dropwise at -78 °C to a stirred solution of aryl bromide (30 mmol, 1.0 equivalent) in anhydrous tetrahydrofuran (60 mL). After stirring at -78 °C for 1 hour, phosphorus trichloride (0.78 mL, 9 mmol, 0.3 equivalent) was added dropwise, forming a yellow suspension. The mixture was then stirred at room temperature for another 30 minutes. The reaction was quenched with brine and extracted with ethyl acetate (50 mL × 3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid chromatography to give triarylphosphine.

[0034] In a 10 mL round-bottom flask equipped with a magnetic stirrer, triarylphosphine (5 mmol, 1.0 equivalent), arylbromine (5 mmol, 1.0 equivalent), and Pd₂(dba)₃ (46 mg, 0.05 mmol, 1 mol%) were added under nitrogen protection, with anhydrous o-xylene (3 mL) as the solvent, and the mixture was reacted at 140°C for 6 hours. The mixture was then cooled to room temperature. After filtration, the resulting solid was washed with diethyl ether (20 mL × 3) and then dried under reduced pressure to obtain the pure product.

[0035] Example 1 .

[0036] Magnesium filings (48.2 mg, 2.0 mmol, 4 equivalents) and lithium chloride (43.3 mg, 1.0 mmol, 2 equivalents) were added to a dry, sealed tube equipped with a magnetic stirrer. The tube was purged three times with nitrogen, followed by the addition of anhydrous tetrahydrofuran (2 mL), then tetraarylphosphonium salt 1 (0.5 mmol, 1 equivalent), the catalyst, and aryl bromide 2 (2.0 mmol, 4 equivalents). The reaction mixture was stirred at 60 °C for 12 hours. After the reaction was complete, the yield of target product 3a was determined by nuclear magnetic resonance (NMR) using 1,3,5-trimethoxybenzene as an internal standard. The data are as follows: .

[0037] Note: c. Separation yield; d. Using 3 equivalents of 2a and magnesium; e. Reaction at room temperature; f. No metallic magnesium was used; g. No LiCl was used.

[0038] Compound (3a): White solid. 1H NMR (400 MHz, CDCl3): δ = 7.59-7.52 (m, 4H), 7.44-7.41 (m, 2H), 7.34-7.29 (m, 1H), 7.01-6.97 (m, 2H), 3.86 (s, 3H) ppm. 13 CNMR (100 MHz, CDCl3): δ = 159.1, 140.8, 133.8, 128.7, 128.1, 126.7, 126.6,114.2, 55.3 ppm. IR (KBr): 2988, 2901, 1604, 1394, 1012, 834, 760, 556, 498cm -1 HRMS (m / z): calcd for C 13 H 13 O [M+H] + 185.0961, found: 185.0960.

[0039] Example 2 Refer to the method in Example 1;

[0040] The relevant data is as follows: ; Note: c represents the separation yield.

[0041] Example 3 Following the method of Example 1, tetrahydrofuran was replaced with other solvents for the reaction. The yield of the target product was determined by nuclear magnetic resonance (NMR) using 1,3,5-trimethoxybenzene as an internal standard. The process formula is as follows: ; The relevant data is as follows: ; Note: c represents the separation yield.

[0042] Example 4 The process is as follows: ; Magnesium shavings (48.2 mg, 2.0 mmol, 4 equivalents) and lithium chloride (43.3 mg, 1.0 mmol, 2 equivalents) were added to a dry, sealed tube. The mixture was then dried under reduced pressure using a hot air gun (320 °C) for 3 minutes. After cooling to room temperature, the sealed tube was purged three times with nitrogen, followed by the addition of anhydrous tetrahydrofuran (2 mL). Then, 1a (0.5 mmol, 1 equivalent), nickel chloride (6.5 mg, 0.05 mmol, 10 mol%), and 2b (2.0 mmol, 4 equivalents) were added sequentially. The reaction mixture was stirred at 60 °C for 12 hours, quenched with saturated ammonium chloride solution (2 mL) and water (20 mL), and extracted with ethyl acetate (20 mL × 3). The combined organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. The extract was concentrated under reduced pressure to give a crude product, which was further purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to give product 3b, 49%, 61.8 mg.

[0043] 1 H NMR (400 MHz, CDCl3): δ = 7.83-7.80 (m, 1H), 7.74-7.71 (m, 1H), 7.57-7.54 (m, 2H), 7.48-7.44 (m, 2H), 7.39-7.34 (m, 1H), 7.09 (d, J = 8.6 Hz, 1H), 3.96 (s, 3H) ppm.

[0044] 19 F NMR (376 MHz, CDCl3): δ = -62.20 (s, 3F) ppm.

[0045] 13 C NMR (100 MHz, CDCl3): δ = 156.8, 139.6, 133.3, 131.6, 128.9,127.3, 126.7, 125.8 (q, J = 5.4 Hz), 123.7 (q, J = 271.3 Hz), 119.0 (q, J =30.9 Hz), 112.4, 56.0 ppm.

[0046] IR (KBr): 3415, 2988, 2901, 1605, 1394, 1012, 665, 556, 464 cm -1 .

[0047] HRMS (m / z): calcd for C 14 H12 F3O [M+H] + 253.0835, found: 253.0828.

[0048] Example 5 Referring to the method in Example 4, compound 1a or 1j was reacted with 2c-2r to generate crude compound 3c-3r, which was then further purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to finally obtain product 3c-3r as follows: .

[0049] The molecular formula is: (2c) (2d) (2e) (2f) (2g) (2h) (2i) (2j) (2k) (2l) (2m) (2n) (2o) (2p) (2q) and (2r) .

[0050] Compound (3c): Yield = 58%, 58.6 mg. White solid.

[0051] 1 H NMR (400 MHz, CDCl3): δ = 7.55-7.52 (m, 2H), 7.45-7.41 (m, 2H), 7.36-7.30 (m, 3H), 7.05-7.01 (m, 1H), 3.94 (s, 3H) ppm.

[0052] 19 F NMR (376 MHz, CDCl3): δ = -135.03 - -135.09 (m, 1F) ppm.

[0053] 13C NMR (100 MHz, CDCl3): δ = 152.5 (d, J = 244.1 Hz), 147.0 (d, J =10.7 Hz), 139.7 (d, J = 1.3 Hz), 134.4 (d, J = 6.2 Hz), 128.8, 127.2, 127.6, 122.6 (d, J = 3.4 Hz), 114.8 (d, J = 19.0 Hz), 113.6 (d, J = 2.4 Hz), 56.3ppm.

[0054] IR (KBr): 3659, 2988, 2900, 1601, 1394, 1008, 665, 556, 467 cm -1 .

[0055] HRMS (m / z): calcd for C 13 H 12 FO [M+H] + 203.0867, found: 203.0866.

[0056] The structural formula is: .

[0057] Compound (3d): Yield = 53%, 56.5 mg. White solid.

[0058] 1 H NMR (400 MHz, CDCl3): δ = 7.56-7.48 (m, 4H), 7.29-7.26 (m, 2H), 7.01-6.97 (m, 2H), 3.86 (s, 3H), 2.71 (q, J = 7.6 Hz, 2H), 1.30 (t, J = 7.6Hz, 3H) ppm.

[0059] 13 C NMR (100 MHz, CDCl3): δ = 156.7, 142.1, 138.2, 133.8, 128.2, 128.0, 126.6, 114.1, 55.3, 28.5, 15.6 ppm.

[0060] IR (KBr): 2964, 1607, 1498, 1394, 1251, 1000, 823, 665, 556 cm -1 .

[0061] HRMS (m / z): calcd for C 15 H 17 O [M+H] + 213.1274, found: 213.1277.

[0062] The structural formula is: .

[0063] Compound (3e): Yield = 49%, 58.8 mg. White solid.

[0064] 1 H NMR (400 MHz, CDCl3): δ = 7.59 -7.52 (m, 4H), 7.48 (d, J = 8.5 Hz,2H), 7.03-6.98 (m, 2H), 3.87 (s, 3H), 1.40 (s, 9H) ppm.

[0065] 13 C NMR (100 MHz, CDCl3): δ = 158.9, 149.6, 137.9, 133.6, 128.0, 126.3, 125.6, 114.1, 55.3, 34.4, 31.4 ppm.

[0066] IR (KBr): 3555, 2972, 2901, 1604, 1393, 1004, 823, 664, 556 cm -1 .

[0067] HRMS (m / z): calcd for C 17 H 21 O [M+H] + 241.1587, found: 241.1584.

[0068] The structural formula is: .

[0069] Compound (3f): Yield = 60%, 55.2 mg.

[0070] 1 H NMR (400 MHz, CDCl3): δ = 7.61-7.58 (m, 2H), 7.49-7.44 (m, 2H), 7.41-7.35 (m, 3H), 7.12-7.02 (m, 2H), 3.86 (s, 3H) ppm.

[0071] 13 C NMR (100 MHz, CDCl3): δ = 156.4, 138.5, 130.8, 130.6, 129.5, 128.6, 127.9, 126.9, 120.8, 111.1, 55.5 ppm.

[0072] IR (KBr): 3556, 2988, 2901, 1601, 1483, 1394, 754, 698, 556, 467 cm -1 .

[0073] HRMS (m / z): calcd for C 13 H 13 O [M+H] + 185.0961, found: 185.0963.

[0074] The structural formula is: .

[0075] Compound (3g): Yield = 75%, 69.0 mg. White solid.

[0076] 1 H NMR (400 MHz, CDCl3): δ = 7.62-7.59 (m, 2H), 7.48-7.43 (m, 2H), 7.40-7.34 (m, 2H), 7.22-7.18 (m, 1H), 7.16-7.14 (m, 1H), 6.93-6.90 (m, 1H),3.88 (s, 3H) ppm.

[0077] 13 C NMR (100 MHz, CDCl3): δ = 159.9, 142.7, 141.1, 129.7, 128.7, 127.4, 127.2, 119.7, 112.9, 112.6, 55.3 ppm.

[0078] IR (KBr): 3555, 3413, 1616, 1358, 1004, 805, 758, 556, 466 cm -1 .

[0079] HRMS (m / z): calcd for C 13 H 13O [M+H] + 185.0961, found: 185.0960.

[0080] The structural formula is: .

[0081] Compound (3h): Yield = 70%, 91.0 mg. White solid.

[0082] 1 H NMR (400 MHz, CDCl3): δ = 7.59-7.53 (m, 4H), 7.50-7.40 (m, 6H), 7.38-7.30 (m, 2H), 7.09-7.05 (m, 2H), 5.13 (s, 2H) ppm.

[0083] 13 C NMR (100 MHz, CDCl3): δ = 158.3, 140.7, 136.9, 134.0, 128.7, 128.6, 128.2, 128.0, 127.5, 126.7, 126.7, 115.1, 70.0 ppm.

[0084] IR (KBr): 3556, 2834, 1605, 1522, 1358, 973, 826, 760, 556 cm -1 .

[0085] HRMS (m / z): calcd for C 19 H 17 O [M+H] + 261.1274, found: 261.1272.

[0086] The structural formula is: .

[0087] Compound (3i): Yield = 63%, 89.5 mg.

[0088] 1 H NMR (400 MHz, CDCl3): δ = 7.59-7.56 (m, 2H), 7.52-7.47 (m, 2H), 7.46-7.41 (m, 2H), 7.35-7.29 (m, 1H), 6.96-6.91 (m, 2H), 1.03 (s, 9H), 0.27(s, 6H) ppm.

[0089] 13 C NMR (100 MHz, CDCl3): δ = 155.3, 140.9, 134.3, 128.7, 128.1, 126.7, 126.6, 120.3, 25.7, 18.2, -4.4 ppm.

[0090] IR (KBr): 3409, 2975, 1614, 1520, 1393, 1306, 880, 556, 446 cm -1 .

[0091] IR (KBr): 3409, 2975, 1614, 1520, 1393, 1306, 880, 556, 446 cm -1 .

[0092] HRMS (m / z): calcd for C 18 H 25 OSi [M+H] + 285.1669, found: 285.1670.

[0093] The structural formula is: .

[0094] Compound (3j): Yield = 68%, 72.8 mg. White solid.

[0095] 1 H NMR (400 MHz, CDCl3): δ = 7.59-7.56 (m, 2H), 7.46-7.41 (m, 2H), 7.35-7.30 (m, 1H), 7.18-7.12 (m, 2H), 6.97-6.95 (m, 1H), 3.96 (s, 3H), 3.93(s, 3H) ppm.

[0096] IR (KBr): 3234, 2961, 2835, 1688, 1520, 1358, 1004, 760, 556, 466 cm -1 .

[0097] HRMS (m / z): calcd for C 14 H 15 O2 [M+H] + 215.1067, found: 215.1070.

[0098] The structural formula is: .

[0099] Compound (3k): Yield = 62%, 65.7 mg. White solid.

[0100] 1 H NMR (400 MHz, CDCl3): δ = 7.58-7.54 (m, 2H), 7.45-7.41 (m, 2H), 7.35-7.30 (m, 1H), 7.16 -7.09 (m, 2H), 6.97-6.95 (m, 1H), 4.31 (s, 4H) ppm.

[0101] 13 C NMR (100 MHz, CDCl3): δ = 143.6, 143.1, 140.5, 134.8, 128.7, 126.8, 126.7, 120.1, 117.5, 115.8, 64.4 ppm.

[0102] IR (KBr): 3236, 1638, 1517, 1309, 1226, 1003, 874, 763, 556 cm -1 .

[0103] HRMS (m / z): calcd for C 14 H 13 O2 [M+H] + 213.0910, found: 213.0916.

[0104] The structural formula is: .

[0105] Compound (3l): Yield = 56%, 55.5 mg.

[0106] 1 H NMR (400 MHz, CDCl3): δ = 7.55-7.51 (m, 2H), 7.45-7.40 (m, 2H), 7.35-7.30 (m, 1H), 7.10-7.06 (m, 2H), 6.91-6.89 (m, 1H), 6.01 (s, 2H)ppm.

[0107] 13C NMR (100 MHz, CDCl3): δ = 148.1, 147.0, 140.9, 136.5, 128.7, 126.90, 126.86, 119.3, 108.5, 106.1, 101.1 ppm.

[0108] IR (KBr): 3413, 2976, 1608, 1394, 1050, 880, 825, 556, 464 cm -1 .

[0109] HRMS (m / z): calcd for C 13 H 11 O2 [M+H] + 199.0754, found: 199.0755.

[0110] The structural formula is: .

[0111] Compound (3m): Yield = 54%, 53.2 mg.

[0112] 1 H NMR (400 MHz, CDCl3): δ = 7.60-7.56 (m, 2H), 7.55-7.51 (m, 2H), 7.44-7.39 (m, 2H), 7.30-7.27 (m, 1H), 6.85-6.82 (m, 2H), 3.01 (s, 6H)ppm.

[0113] 13 C NMR (100 MHz, CDCl3): δ = 150.0, 141.3, 129.4, 128.8, 127.8, 126.4, 126.1, 112.9, 40.7 ppm.

[0114] IR (KBr): 3661, 2988, 2900, 1601, 1394, 1004, 775, 556, 466 cm -1 .

[0115] HRMS (m / z): calcd for C 14 H 16 N [M+H] + 198.1277, found: 198.1275.

[0116] The structural formula is: .

[0117] Compound (3n): Yield = 57%, 91.5 mg. White solid.

[0118] 1 H NMR (400 MHz, CDCl3): δ = 7.58-7.55 (m, 2H), 7.48-7.45 (m, 2H), 7.43-7.39 (m, 2H), 7.33-7.23 (m, 5H), 7.14-7.12 (m, 6H), 7.05-7.00 (m, 2H) ppm.

[0119] 13 C NMR (100 MHz, CDCl3): δ = 147.7, 147.2, 140.6, 135.1, 129.3, 128.7, 127.7, 126.8, 126.6, 124.4, 123.9, 122.9 ppm.

[0120] IR (KBr): 3482, 3413, 2988, 1593, 1485, 1004, 762, 453 cm -1 .

[0121] HRMS (m / z): calcd for C 24 H 20 N [M+H] + 322.1590, found: 322.1594.

[0122] The structural formula is: .

[0123] Compound (3o): Yield = 69%, 82.8 mg.

[0124] 1 H NMR (400 MHz, CDCl3): δ = 7.63-7.55 (m, 6H), 7.47-7.41 (m, 2H), 7.38-7.33 (m, 1H), 5.57 (s, 1H), 4.33-4.27 (m, 2H), 4.06-3.99 (m, 2H), 2.32-2.20 (m, 1H), 1.51-1.43 (m, 1H) ppm.

[0125] 13C NMR (100 MHz, CDCl3): δ = 141.7, 140.9, 137.7, 128.7, 127.3, 127.2, 127.1, 126.4, 101.4, 67.4, 25.7 ppm.

[0126] IR (KBr): 3556, 3412, 2970, 2870, 1698, 1430, 1280, 824, 765, 556 cm -1 .

[0127] HRMS (m / z): calcd for C 16 H 17 O2 [M+H] + 241.1223, found: 241.1229.

[0128] The structural formula is: .

[0129] Compound (3p): Yield = 72%, 84.3 mg. White solid.

[0130] 1 H NMR (400 MHz, CDCl3): δ = 7.98 (s, 1H), 7.83-7.79 (m, 2H), 7.74-7.69 (m, 3H), 7.50-7.45 (m, 2H), 7.39-7.34 (m, 1H), 7.20-7.16 (m, 2H), 3.95(s, 3H) ppm.

[0131] 13 C NMR (100 MHz, CDCl3): δ = 157.7, 141.2, 136.4, 133.7, 129.7,129.1, 128.8, 127.23, 127.21, 127.1, 126.0, 125.6, 119.1, 105.5, 55.3ppm.

[0132] IR (KBr): 3660, 3233, 2988, 1601, 1358, 1003, 855, 738, 665, 556 cm -1 .

[0133] HRMS (m / z): calcd for C 17 H 15 O [M+H]+ 235.1117, found: 235.1120.

[0134] The structural formula is: .

[0135] Compound (3q): Yield = 51%, 62.2 mg.

[0136] 1 H NMR (400 MHz, CDCl3): δ = 8.16 (d, J = 2.6 Hz, 1H), 8.02-8.00 (m,1H), 7.71-7.68 (m, 3H), 7.66-7.58 (m, 2H), 7.52-7.47 (m, 3H), 7.41-7.36 (m,2H) ppm.

[0137] 13 C NMR (100 MHz, CDCl3): δ = 156.6, 155.7, 141.3, 136.4, 128.8,128.3, 127.4, 127.3, 127.0, 126.6, 124.7, 124.2, 122.8, 120.7, 119.2, 111.8ppm.

[0138] IR (KBr): 3566, 2988, 2900, 1601, 1393, 1358, 1001, 664, 556 cm -1 .

[0139] HRMS (m / z): calcd for C 18 H 13 O [M+H] + 245.0961, found: 245.0962.

[0140] The structural formula is: .

[0141] Compound (3r): yield = 53%, 84.6 mg.

[0142] 1H NMR (400 MHz, CDCl3): δ = 8.27-8.22 (m, 2H), 7.73-7.71 (m, 2H), 7.69-7.64 (m, 5H), 7.63-7.60 (m, 1H), 7.55-7.48 (m, 5H), 7.42-7.36 (m, 2H) ppm.

[0143] 13 C NMR (100 MHz, CDCl3): δ = 141.9, 141.41, 141.38, 139.4, 137.6,129.9, 128.7, 127.5, 127.2, 127.0, 125.9, 123.1, 122.5, 120.5, 120.3, 120.0,119.6, 109.7, 108.2 ppm.

[0144] IR (KBr): 3474, 2972, 2900, 1601, 1393, 1001, 665, 556, 467 cm -1 .

[0145] HRMS (m / z): calcd for C 24 H 18 N [M+H] + 320.1434, found: 320.1429.

[0146] Example 6 Following the method in Example 4, compound 1b-1m was reacted with 2a or 2s to generate crude compound 4b-4m, which was then further purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent). The final product 4b-4m data are as follows: ; The structural formulas are as follows: (1b) (1c) (1d) (1e) (1f) (1g) (1h) (1i) (1j) (1k) (1l) and (1m) .

[0147] Compound (4b): Yield = 56%, 70.6 mg. White solid.

[0148] 1 H NMR (400 MHz, CDCl3): δ = 7.68-7.64 (m, 4H), 7.57-7.53 (m, 2H), 7.03-6.99 (m, 2H), 3.87 (s, 3H) ppm.

[0149] 19 F NMR (376 MHz, CDCl3): δ = -62.20 (s, 3F) ppm.

[0150] 13 C NMR (100 MHz, CDCl3): δ = 159.8, 144.3, 132.2, 128.8, 128.5 (q, J= 46.8), 126.9, 125.6 (q, J = 3.8 Hz), 123.9 (q, J = 273.9 Hz), 114.4, 55.4ppm.

[0151] IR (KBr): 3674, 3233, 2988, 1601, 1394, 1004, 813, 659, 556 cm -1 .

[0152] HRMS (m / z): calcd for C 14 H 12 F3O [M+H] + 253.0835, found: 253.0829.

[0153] The structural formula is: .

[0154] Compound (4c): Yield = 45%, 60.3 mg. White solid.

[0155] 1 H NMR (400 MHz, CDCl3): δ = 7.57-7.53 (m, 2H), 7.52-7.47 (m, 2H), 7.27-7.25 (m, 2H), 7.01-6.97 (m, 2H), 3.86 (s, 3H) ppm.

[0156] 19F NMR (376 MHz, CDCl3): δ = -57.73 (s, 3F) ppm.

[0157] 13 C NMR (100 MHz, CDCl3): δ = 159.4, 148.2, 139.6, 132.4, 128.1, 128.0, 121.2, 120.5 (q, J = 254.5), 114.3, 55.3 ppm.

[0158] IR (KBr): 3558, 3413, 3235, 1615, 1497, 1254, 1001, 828, 556 cm -1 .

[0159] HRMS (m / z): calcd for C 14 H 12 F3O [M+H] + 269.0784, found: 269.0784.

[0160] The structural formula is: .

[0161] Compound (4d): Yield = 67%, 67.7 mg. White solid.

[0162] 1 H NMR (400 MHz, CDCl3): δ = 7.52-7.46 (m, 4H), 7.14-7.07 (m, 2H), 7.00-6.96 (m, 2H), 3.85 (s, 3H) ppm.

[0163] 19 F NMR (376 MHz, CDCl3): δ = -116.61 (s, 1F) ppm.

[0164] 13 C NMR (100 MHz, CDCl3): δ = 162.1 (d, J = 304.2 Hz), 159.1, 136.9 (d, J = 304.2 Hz), 132.8, 128.2 (d, J = 8.0 Hz), 128.0, 115.5 (d, J = 21.3Hz), 114.2, 55.3 ppm.

[0165] IR (KBr): 3554, 3413, 2975, 2900, 1616, 1394, 880, 556, 467 cm -1 .

[0166] HRMS (m / z): calcd for C 13 H 12 FO [M+H] + 203.0867, found: 203.0857.

[0167] The structural formula is: .

[0168] Compound (4e): Yield = 42%, 45.8 mg. White solid.

[0169] 1 H NMR (400 MHz, CDCl3): δ = 7.52-7.45 (m, 4H), 7.40-7.36 (m, 2H), 7.00-6.96 (m, 2H), 3.86 (s, 3H) ppm.

[0170] 13 C NMR (100 MHz, CDCl3): δ = 159.3, 139.2, 132.6, 132.5, 128.8, 128.0, 127.9, 114.3, 55.3 ppm.

[0171] IR (KBr): 3558, 3413, 2996, 1637, 1522, 1289, 1011, 812, 556 cm -1 .

[0172] HRMS (m / z): calcd for C 13 H 12 ClO [M+H] + 219.0571, found: 219.0571.

[0173] The structural formula is: .

[0174] Compound (4f): Yield = 74%, 73.3 mg. White solid.

[0175] 1H NMR (400 MHz, CDCl3): δ = 7.55-7.50 (m, 2H), 7.49-7.44 (m, 2H), 7.25-7.23 (m, 2H), 7.00-6.96 (m, 2H), 3.86 (s, 3H), 2.40 (s, 3H) ppm.

[0176] 13 C NMR (100 MHz, CDCl3): δ = 158.9, 137.9, 136.3, 133.7, 129.4, 127.9, 126.6, 114.1, 55.3, 21.0 ppm.

[0177] IR (KBr): 3675, 3233, 2988, 2901, 1601, 1394, 1004, 813, 556 cm -1 .

[0178] HRMS (m / z): calcd for C 14 H 15 O [M+H] + 199.1117, found: 199.1115.

[0179] The structural formula is: .

[0180] Compound (4g): yield = 62%, 65.8 mg. White solid.

[0181] 1 H NMR (400 MHz, CDCl3): δ = 7.54-7.45 (m, 4H), 7.27-7.24 (m, 2H), 6.99-6.94 (m, 2H), 3.84 (s, 3H), 2.68 (q, J = 7.6 Hz, 2H), 1.27 (t, J = 7.6Hz, 3H) ppm.

[0182] 13 C NMR (100 MHz, CDCl3): δ = 158.9, 142.7, 138.2, 133.7, 128.2, 128.0, 126.6, 114.1, 55.3, 28.5, 15.6 ppm.

[0183] IR (KBr): 2964, 1607, 1498, 1394, 1251, 1000, 823, 665, 556 cm -1 .

[0184] HRMS (m / z): calcd for C 15 H 17 O [M+H] + 213.1274, found: 213.1272.

[0185] The structural formula is: .

[0186] Compound (4h): Yield = 52%, 62.4 mg. White solid.

[0187] 1 H NMR (400 MHz, CDCl3): δ = 7.59-7.52 (m, 4H), 7.50-7.47 (m, 2H), 7.03-6.98 (m, 2H), 3.87 (s, 3H), 1.40 (s, 9H) ppm.

[0188] 13 C NMR (100 MHz, CDCl3): δ = 158.9, 149.6, 137.9, 133.6, 128.0, 126.3, 125.6, 114.1, 55.3, 34.4, 31.4 ppm.

[0189] IR (KBr): 3555, 2972, 2901, 1604, 1393, 1004, 823, 664, 556 cm -1 .

[0190] HRMS (m / z): calcd for C 17 H 21 O [M+H] + 241.1587, found: 241.1590.

[0191] The structural formula is: .

[0192] Compound (4i): Yield = 66%, 65.4 mg. White solid.

[0193] 1H NMR (400 MHz, CDCl3): δ = 7.57-7.52 (m, 2H), 7.41-7.30 (m, 3H), 7.16-7.14 (m, 1H), 7.02-6.97 (m, 2H), 3.87 (s, 3H), 2.44 (s, 3H) ppm.

[0194] 13 C NMR (100 MHz, CDCl3): δ = 159.0, 140.8, 138.3, 133.9, 128.6, 128.1, 127.5, 127.4, 123.8, 114.1, 55.3, 21.5 ppm.

[0195] IR (KBr): 3675, 3231, 2987, 2901, 1602, 1394, 822, 556, 446 cm -1 .

[0196] HRMS (m / z): calcd for C 14 H 15 O [M+H] + 199.1117, found: 199.1110.

[0197] The structural formula is: .

[0198] Compound (4j): Yield = 57%, 52.5 mg. White solid.

[0199] 1 H NMR (400 MHz, CDCl3): δ = 7.61-7.53 (m, 4H), 7.47-7.42 (m, 2H), 7.36-7.30 (m, 1H), 7.04-6.98 (m, 2H), 3.87 (s, 3H) ppm.

[0200] 13 C NMR (100 MHz, CDCl3): δ = 159.1, 140.8, 133.7, 128.7, 128.1, 126.7, 126.6, 114.2, 55.3 ppm.

[0201] IR (KBr): 2988, 2901, 1604, 1394, 1012, 834, 760, 556, 498 cm -1 .

[0202] HRMS (m / z): calcd for C 13 H 13 O [M+H] + 185.0961, found: 185.0960.

[0203] The structural formula is: .

[0204] Compound (4k): Yield = 59%, 76.7 mg. White solid.

[0205] 1 H NMR (400 MHz, CDCl3): δ = 7.60-7.52 (m, 4H), 7.50-7.39 (m, 6H), 7.38-7.30 (m, 2H), 7.10-7.05 (m, 2H), 5.13 (s, 2H) ppm.

[0206] 13 C NMR (100 MHz, CDCl3): δ = 158.3, 140.7, 136.9, 134.0, 128.7, 128.6, 128.2, 128.0, 127.5, 126.72, 126.67, 115.1, 70.0 ppm.

[0207] IR (KBr): 3556, 2834, 1605, 1522, 1358, 973, 826, 760, 556 cm -1 .

[0208] HRMS (m / z): calcd for C 19 H 17 O [M+H] + 261.1274, found: 261.1273.

[0209] The structural formula is: .

[0210] Compound (4l): Yield = 50%, 57.0 mg. White solid.

[0211] 1 H NMR (400 MHz, CDCl3): δ = 7.53-7.47 (m, 2H), 7.37-7.34 (m, 2H), 7.00-6.94 (m, 2H), 6.91-6.87 (m, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 2.30 (s,3H) ppm.

[0212] 13 C NMR (100 MHz, CDCl3): δ = 158.6, 156.9, 133.7, 133.0, 129.1, 127.7, 126.8, 124.9, 114.1, 110.2, 55.4, 55.3, 16.4 ppm.

[0213] IR (KBr): 3578, 2700, 1605, 1393, 1358, 1004, 665, 556, 465 cm -1 .

[0214] HRMS (m / z): calcd for C 15 H 17 O2 [M+H] + 229.1223, found: 229.1222.

[0215] The structural formula is: .

[0216] Compound (4m): Yield = 43%, 55.9 mg. White solid.

[0217] 1 H NMR (400 MHz, CDCl3): δ = 7.79-7.61 (m, 6H), 7.60-7.57 (m, 2H), 7.50-7.44 (m, 2H), 7.39-7.34 (m, 1H), 7.04-6.99 (m, 2H), 3.87 (s, 3H)ppm.

[0218] 13 C NMR (100 MHz, CDCl3): δ = 159.2, 140.8, 139.7, 139.5, 133.2, 128.8, 128.0, 127.5, 127.2, 127.03, 126.98, 114.3, 55.3 ppm.

[0219] IR (KBr): 3624, 3235, 1601, 1358, 1037, 1004, 665, 556, 464 cm -1 .

[0220] HRMS (m / z): calcd for C 19 H 17 O [M+H] + 261.1274, found: 261.1273. This solution can be achieved through the above embodiments.

Claims

1. A method for the cross-electrophilic coupling of a nickel-catalyzed tetraarylphosphonium salt and an aryl bromide, i.e., a method for preparing the compound of formula III or a salt thereof, the method comprising the step of reacting the compound of formula I with the compound of formula II in the presence of a nickel catalyst and lithium chloride to form the compound of formula III: ； in, R 1 Selected from phenyl, wherein the phenyl group is optionally selected from one or more halogens, cyano groups, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 Alkyloxy and benzyloxy; R 2 The group is selected from phenyl, naphthyl, oxofluorenyl, and carbazole, wherein the phenyl, naphthyl, oxofluorenyl, and carbazole are optionally selected from one or more halogens, cyano, amino, C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyl, Halogenated C 1-6 The substituents are alkoxy, phenyl, and tert-butyldimethylsiloxy; or, two adjacent substituents form a 3- to 6-membered heterocyclic alkyl group with an adjacent atom; X is selected from halogens, such as bromine.

2. The method according to claim 1, characterized in that, The nickel catalyst is selected from NiCl2 and Ni(PPh3)2Cl2, with NiCl2 being preferred.

3. The method according to claim 1 or 2, characterized in that, The amount of the nickel catalyst used is 5% to 20% of the molar amount of the compound of Formula I, for example, 10%.

4. The method according to any one of claims 1-3, characterized in that, The amount of lithium chloride used is 1 to 3 equivalents of the molar amount of the compound of Formula I, for example, 2 equivalents.

5. The method according to any one of claims 1-4, characterized in that, The reaction also contains metallic magnesium, in an amount of 2 to 5 equivalents of the molar amount of the compound of Formula I, for example, 4 equivalents.

6. The method according to any one of claims 1-5, characterized in that, The solvent used in the reaction was selected from tetrahydrofuran.

7. The method according to any one of claims 1-6, characterized in that, The reaction conditions are NiCl2, lithium chloride, and magnesium metal.

8. The method according to any one of claims 1-7, characterized in that, The compound shown in Formula I is selected from: , , , , , , , , , , , and .

9. The method according to any one of claims 1-8, characterized in that, The compound shown in Formula II is selected from: , , , , , , , , , , , , , , , , and , where X is selected from halogens, such as bromine.

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