Palladium-catalyzed cross-electrophilic coupling method of arylthianthaneonium salts with alkyl bromides and chlorides

Abstract

This invention provides a palladium-catalyzed method for cross-electrophilic coupling of arylthianthane onium salts with alkyl bromides and chlorides. The method involves reacting the onium salt with an alkyl bromide in the presence of a palladium catalyst, a phosphine ligand, metallic magnesium, a lithium salt, and an organic solvent to obtain alkylated aromatic hydrocarbons.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a palladium-catalyzed method for cross-electrophilic coupling of arylthianthaneon salts with alkyl bromides and chlorides. Background Technology

[0002] As an effective alternative to organohalides widely used in traditional cross-coupling reactions, the application of novel electrophilic agents has attracted widespread attention from organic chemists. Among the various electrophilic coupling agents developed to date, arylthiananthioneium salts (Ar–TT⁺ OTf⁻), as a novel, stable, and potent arylation agent, can be conveniently prepared through site-selective C–H thiathianization of aromatics with thiathracene, and has attracted considerable attention in the field of synthesis. To date, the Ritter laboratory and other research teams have fully demonstrated that arylthiananthioneium salts are highly attractive and powerful arylation agents capable of participating in various organic transformations and exhibiting significant advantages in the late-stage functionalization of complex molecules. For example, arylthiananthioneium salts can efficiently cross-couple with various organometallic reagents (such as organozinc, organoboron, and organosilicon reagents). However, the relatively unavailable, costly, and / or moisture-sensitive nature of organometallic reagents limits the widespread application of these coupling schemes in organic synthesis to some extent.

[0003] Transition metal-catalyzed reductive cross-electrophilic coupling (XEC) of two different electrophiles has proven to be a powerful platform for constructing C-C bonds. These electrophiles are widely available and relatively inexpensive compared to organometallic reagents. This method avoids the pre-synthesis and treatment of water- and / or air-sensitive organometallic reagents, thus offering procedural economy and operational convenience. In this regard, Ritter's group and our group have reported that aryl thiaanthraium salts can also efficiently cross-electrophilically couple with aryl halides and pseudohalides under palladium catalysis, achieving the construction of Csp2-Csp2 bonds. Further research by Ritter's group showed that the relatively difficult Csp2-Csp3 coupling of aryl (or vinyl) thiaanthraium salts with alkyl iodides can also be successfully achieved in the presence of a palladium catalyst and a reducing zinc medium. However, the aforementioned cross-electrophilic reactions of aryl (or vinyl) thiaanthraium salts with alkyl electrophiles are mainly applicable to the more reactive alkyl iodides. Summary of the Invention

[0004] The technical problem to be solved by this invention is to provide an efficient Csp2-Csp3 coupling method for arylthiananthium salts with alkyl bromides and chlorides. This reaction is carried out efficiently at room temperature in tetrahydrofuran via C−S bond cleavage in the presence of a palladium catalyst, phosphine ligands, magnesium, zinc chloride, and lithium chloride, yielding the corresponding alkylated aromatics in moderate to good yields. The method exhibits a broad substrate range and good functional group tolerance.

[0005] This 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 palladium catalyst, magnesium, zinc chloride, and lithium chloride to form a compound of formula III: .

[0006] Among them, R 1 Each is independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 3- to 6-membered heterocycloalkyl, -COOR 1a BnO-, PhO-, or PhS-, or adjacent R 1 Form C with adjacent atoms 3-6 Cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, or 5- or 6-heteroaryl; R 1a Selected from hydrogen or C 1-6 Alkyl; R 2 Selected from C 1-6 Alkyl, C 3-6 Cycloalkyl or 3- to 6-membered heterocycloalkyl, wherein the C 1-6 Alkyl, C 3-6 Cycloalkyl or 3- to 6-membered heterocycloalkyl groups are arbitrarily selected from one or more halogens, cyano groups, C 1-6 Alkyl, C 1-6 Alkyl, TBSO-, PhO-, Ph- or -COOR 2a ;R 2a Selected from hydrogen or C 1-6 Alkyl; X is selected from leaving groups, such as halogens; o is selected from 0, 1, 2 or 3.

[0007] In some implementation schemes, R 1 Selected from halogen, cyano, C 1-6 Alkyl groups (such as methyl or ethyl); In some implementation schemes, R 1 Selected from -COOR 1a R 1a Selected from C 1-6 Alkyl groups (such as methyl or ethyl); In some implementation schemes, R 1 Selected from 3- to 6-membered heterocyclic alkyl groups, such as 5- or 6-membered heterocyclic alkyl groups, for example, morpholinoyl. In some embodiments, R 1 Selected from BnO-, PhO-, or PhS-. In some embodiments, adjacent R 1 It can form 3 to 6-membered heterocyclic alkyl groups or 6-membered aryl groups (such as phenyl) with adjacent atoms; In some implementation schemes, R 2 Selected from C1-6 Alkyl, the C 1-6 Alkyl groups are optionally selected from one or more halogens (such as F or Br), cyano groups, C groups, etc. 1-6 Alkyl (such as methyl or ethyl), C 1-6 Alkyl groups (such as methoxy or ethoxy), TBSO-, PhO-, Ph-, or -COOR 2a ;R 2a Selected from hydrogen or C 1-6 Alkyl (such as methyl or ethyl). In some embodiments, R 2 Selected from C 3-6 Cycloalkyl, such as cyclopentyl or cyclohexyl. In some embodiments, R 2 It is selected from 3 to 6-membered heterocyclic alkyl groups, such as tetrahydrofuranyl or tetrahydropyranyl.

[0008] In some embodiments, the compound represented by Formula I is selected from: or .

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

[0010] In some embodiments, the compound represented by formula A is selected from: or .

[0011] In some embodiments, the compound represented by formula A is selected from: or

[0012] X is selected from leaving groups, such as halogens (bromine).

[0013] In some embodiments, the palladium catalyst used in the reaction is selected from Pd2(dba). 3； In some embodiments, the palladium catalyst is used in an amount of 1% to 10% of the molar amount of the compound of formula I, such as 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 10%; In some embodiments, the amount of palladium catalyst used is 2.5% of the molar amount of the compound of formula I; In some embodiments, the reaction also contains metallic magnesium, in an amount of 1 to 4 equivalents of the molar amount of the compound of formula I, for example, 3 equivalents.

[0014] In some embodiments, the reaction further contains a catalyst ligand selected from: (Ruphos).

[0015] In some embodiments, the amount of catalyst ligand used in the reaction is 1% to 10% (1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 10%) of the molar amount of the compound of formula I, for example, 5%; In some embodiments, the amount of zinc chloride used in the reaction is 1 to 4 equivalents (2 equivalents, 3 equivalents, 4 equivalents) of the molar amount of the compound of formula I, for example, 2 equivalents; In some embodiments, the amount of lithium chloride used in the reaction is 1 to 4 equivalents (2 equivalents, 3 equivalents, 4 equivalents) of the molar amount of the compound of formula I, for example, 2 equivalents; In some embodiments, the compound of Formula I reacts with the compound of Formula II in the presence of a palladium catalyst, zinc chloride, lithium chloride, Rupho, and magnesium to form the compound of Formula III.

[0016] In some embodiments, the compound represented by Formula III is selected from: and .

[0017] 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).

[0018] "Optionally" or "optionally" means that the event or environment described below may but does not have to occur, and the description includes the possibility or absence of the event or environment. For example, "optionally halogenated or cyano-substituted C1-6 alkyl" means that a halogen or cyano group may but does not have to be present, and the description includes cases where the alkyl group is substituted with a halogen or cyano group and cases where the alkyl group is not substituted with a halogen or cyano group.

[0019] "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. The alkyl group may be substituted or unsubstituted.

[0020] The term "halogenation" refers to the substitution of one or more atoms selected from fluorine, chlorine, bromine, and iodine.

[0021] "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.

[0022] 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.

[0023] 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.

[0024] The term "aryl" or "aromatic ring" refers to a 6- to 10-membered all-carbon monocyclic or fused polycyclic (i.e., a ring sharing adjacent carbon atom pairs) group with a conjugated π-electron system, such as phenyl and naphthyl. The term "heteroaryl" or "heteroary ring" refers to a heteroaryl system containing 1 to 4 heteroatoms and 5 to 10 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur, and nitrogen. The heteroaryl group is preferably 5 to 10-membered, such as 7-membered, 8-membered, or 9-membered, and more preferably 5-membered or 6-membered.

[0025] 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-substituted.

[0026] "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 groups).

[0027] 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-filtering also fall into this category.

[0028] The values ​​in this invention are instrument measurements and are subject to a certain degree of error. Generally speaking, ±20% is within the reasonable error range. Of course, the context in which the value is used needs to be considered, and it can be ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, or ±1%, preferably ±5%.

[0029] 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 deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl₃), and deuterated methanol (Methanol-d4) as solvents, and tetramethylsilane (TMS) as the internal standard. Detailed Implementation

[0030] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand and implement the present invention, but the embodiments are not intended to limit the present invention. Unless otherwise specified, all raw materials used in the examples are commercially available.

[0031] The onium salt (Formula I) used in this invention was synthesized with reference to the following literature, the relevant contents of which are incorporated herein by reference: J. Zhang, L.-C. Wang, Z.-P. Bao, X.-F. Wu, Site-Selective Carbonylation of Arenes via C(sp 2 )–H Thianthrenation: Direct Access to 1,2-Diarylethanones. Chem. Science. 2023, 14 , 7637–7641. and Org. Lett. 2023, 25, 581–586.

[0032] General preparation method:

[0033] In a 100 mL round-bottom flask equipped with a magnetic stirrer, dichloromethane (50 mL), thiathracene (5.0 g, 23 mmol, 1.0 equivalent), sodium bromide (0.10 g, 0.97 mmol, 4.2 mol%), ferric nitrate nonahydrate (9.3 g, 23 mmol, 1.0 equivalent), and acetic acid (1.0 mL, 1.1 g, 17 mmol, 0.76 equivalent) were added. The reaction mixture was stirred at 25°C for 3 hours. After the reaction was completed as monitored by TLC, water (50 mL) was added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (50 mL × 2). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The resulting solid was recrystallized from ethyl acetate. The crystallized product was collected, washed with diethyl ether (20 mL), and dried under vacuum to give thiathracene-S-oxide in 82% yield (4.38 g) as colorless needle-like crystals.

[0034] In a 100 mL round-bottom flask equipped with a magnetic stirrer, aromatic hydrocarbons (10 mmol, 1 equivalent), thiathracene-S-oxide (2.56 g, 11 mmol, 1.1 equivalent), and dichloromethane (30 mL) were added sequentially under nitrogen protection. The reaction mixture was cooled to -40°C, and trifluoromethanesulfonic anhydride (Tf₂O, 2 mL, 12 mmol, 1.2 equivalents of Example 1) was added dropwise. The reaction mixture was stirred at -40°C for 30 minutes, followed by stirring at room temperature for 12 hours. After the reaction was complete as monitored by TLC, saturated sodium bicarbonate aqueous solution (30 mL) was added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (40 mL × 2). The organic extracts were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The crude product was purified by recrystallization from a dichloromethane / diethyl ether system to obtain the corresponding arylthiathracene salt. Example 1

[0035] The process is as follows:

[0036] .

[0037] Magnesium filings (36.4 mg, 1.5 mmol, 3 equivalents) and lithium chloride (LiCl, 42.4 mg, 1 mmol, 2 equivalents) were added to a sealed test tube equipped with a magnetic stir bar. The mixture was then dried by heating with a hot air gun (320°C) under reduced pressure for 3 minutes. After cooling to room temperature, nitrogen gas was injected into the test tube three times, followed by the addition of dried THF (2 mL). Next, compound 1a (0.5 mmol, 1 equivalent), catalyst (11.4 mg, 0.0125 mmol, 2.5 mol%), and Ruphos (11.6 mg, 0.025 mmol, 5 mol%) were added to the test tube, followed by compound 2a (1.5 mmol, 3 equivalents) and zinc chloride (ZnCl2, 1 mmol, 2 equivalents, 1 M THF solution). The mixture was stirred at room temperature for 24 hours. After the reaction was complete. The yield of the target product 3aa was determined by nuclear magnetic resonance (NMR) using 1,3,5-trimethoxybenzene as an internal standard. The data are as follows:

[0038] Note: c. 5 mol% Pd catalyst used; d. 2.5 mol% Pd catalyst used; e. Separation yield; f. Room temperature conditions; g. No Mg used; h. No ZnCl2 used; i. No LiCl used.

[0039] Compound (3aa): 85% yield, 96.3 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d = 7.64 (dd, J = 8.3, 1.4 Hz, 2H), 7.60–7.56 (m, 2H), 7.48 (dd, J = 8.3, 6.9 Hz,2H), 7.40–7.35 (m, 1H), 7.32 (d, J = 8.2 Hz, 2H), 3.47 (t, J = 6.4 Hz, 2H), 3.41(s, 3H), 2.82–2.76 (m, 2H), 2.03–1.94 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d=141.04, 141.01, 138.7, 128.8, 128.7, 127.01, 126.95, 126.9, 71.8, 58.5, 31.9,31.2 ppm. IR (KBr): n = 3027, 2925, 2867, 1449, 1487, 1365, 1118, 844, 762,697 cm -1 HRMS (m / z): calcd for C 16 H 19 O + [M+H] + 227.1430, found: 227.1431. Example 2

[0040] Following the method of Example 1, ligand L1 was replaced with other ligands L2-L12, and the reaction was carried out. The yield of the target product was determined by nuclear magnetic resonance (NMR) using 1,3,5-trimethoxybenzene as an internal standard. The data are as follows: Example 3

[0041] Following the method of Example 1, the Mg metal was replaced with other metals 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 data are as follows: Example 4

[0042] Following the method of Example 1, the reaction was carried out with the other solvents replaced by tetrahydrofuran. The yield of the target product was determined by nuclear magnetic resonance (NMR) using 1,3,5-trimethoxybenzene as an internal standard. The data are as follows:

[0043] Example 5

[0044] Magnesium filings (36.4 mg, 1.5 mmol, 3 equivalents) and lithium chloride (LiCl, 42.4 mg, 1 mmol, 2 equivalents) were added to a sealed test tube equipped with a magnetic stir bar. The mixture was then dried under reduced pressure using a hot air gun (320°C). After cooling to room temperature, nitrogen gas was injected into the test tube three times, followed by the addition of dry THF (2 mL). Next, arylthiophenethiazolyl salt 1b-p (0.5 mmol, 1 equivalent), Pd2(dba)3 (11.4 mg, 0.0125 mmol, 2.5 mol%), and Ruphos (11.6 mg, 0.025 mmol, 5 mol%) were added to the test tube, followed by compound 2a (1.5 mmol, 3 equivalents) and zinc chloride (ZnCl2, 1 mmol, 2 equivalents, 1 M THF solution). The mixture was stirred at room temperature for 24 hours, then the reaction was quenched with saturated NH4Cl solution (10 mL), and extracted three times with ethyl acetate (EtOAc), 20 mL each time.

[0045] The organic layers were combined, washed with saturated brine, and dried over anhydrous Na₂SO₄. The crude product was concentrated under reduced pressure and further purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to finally obtain the product 3ba-pa.

[0046] Compound (3ba): 50% yield, 54.3 mg. Red oil. 1 H NMR (400 MHz, CDCl3): d =7.35–7.29 (m, 2H), 6.86 (d, J = 8.6 Hz, 1H), 4.11 (q, J = 7.0 Hz, 2H), 3.35 (t, J =6.3 Hz, 2H), 3.32 (s, 3H), 2.64–2.59 (m, 2H), 1.86–1.77 (m, 2H), 1.45 (t, J =7.0 Hz, 3H) ppm. 13 C NMR (100 MHz, CDCl3): d= 158.9, 134.4, 134.2, 133.2,116.7, 112.2, 101.6, 71.3, 64.6, 58.5, 31.0, 30.8, 14.5 ppm. IR (KBr): n =2983, 2931, 2869, 2831, 2226, 1503, 1476, 1365, 1290, 784, 692 cm -1 . HRMS (m / z): calcd for C 13 H 18 NO2 + [M+H] + 220.1332, found: 220.1332。

[0047] Compound (3ca): Yield 40%, 48.1 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.61 (d, J = 2.4 Hz, 1H), 7.30–7.25 (m, 1H), 6.89 (d, J = 8.5 Hz, 1H), 3.87 (s,3H), 3.86 (s, 3H), 3.35 (t, J = 6.3 Hz, 2H), 3.32 (s, 3H), 2.66–2.61 (m, 2H),1.88–1.80 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 166.8, 157.3, 133.5, 133.4,131.4, 119.6, 112.0, 71.6, 58.5, 56.0, 51.9, 31.2, 31.0 ppm. IR (KBr): n =2928, 1732, 1501, 1436, 1366, 1258, 1118, 1025, 887, 774, 699 cm -1 . HRMS (m / z): calcd for C 13 H 19 O4 + [M+H] + 239.1278, found: 239.1276。

[0048] Compound (3da): 67% yield, 66.5 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =6.94–6.89 (m, 1H), 6.88–6.84 (m, 2H), 3.86 (s, 3H), 3.36 (t, J = 6.3 Hz, 2H), 3.33 (s, 3H), 2.64–2.58 (m, 2H), 1.89–1.79 (m, 2H) ppm. 19 F NMR (376 MHz, CDCl3): d = -135.71 (s, 1F) ppm. 13 C NMR (100 MHz, CDCl3): d = 152.2 (d, J = 243.8Hz), 145.6 (d, J = 10.7 Hz), 135.0 (d, J = 5.9 Hz), 123.8 (d, J = 3.4 Hz), 116.0(d, J = 17.6 Hz), 113.3 (d, J = 1.5 Hz), 71.6, 58.5, 56.3, 31.3, 31.2 ppm. IR(KBr): n = 3025, 2834, 1599, 1480, 1294, 1031, 818, 777, 696 cm -1 HRMS (m / z):calcd for C 11 H 16 FO2 + [M+H] + 199.1129, found: 199.1124.

[0049] Compound (3ea): 47% yield, 43.1 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.25 (d, J = 2.0 Hz, 1H), 7.24 (d, J = 2.1 Hz, 1H), 7.12 (d, J= 2.0 Hz, 1H), 7.11(d, J = 2.2 Hz, 1H), 3.37 (t, J = 6.3 Hz, 2H), 3.34 (s, 3H), 2.68–2.63 (m, 2H), 1.90–1.82 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 140.4, 131.4, 129.8, 128.4, 71.6, 58.6, 31.6, 31.1 ppm. IR (KBr): n = 2832, 1948, 1493, 1365, 1324, 1120, 952, 776 cm -1 . HRMS (m / z): calcd for C 10 H 14 ClO + [M+H] + 185.0728, found: 185.0721。

[0050] Compound (3fa): Yield 57%, 42.9 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d = 7.37–7.33 (m, 2H), 7.31–7.26 (m, 2H), 7.20–7.15 (m, 1H), 3.48 (t, J = 6.1 Hz, 2H), 3.33 (s, 3H), 3.02 (t, J = 7.2 Hz, 2H), 1.94–1.88 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 136.5, 128.9, 128.8, 125.7, 70.8, 58.5, 30.1, 29.2 ppm. IR (KBr): n = 2925, 1480, 1439, 1366, 1117, 877, 739, 691 cm -1 . HRMS (m / z): calcd for C 10 H 15 O + [M+H] +151.1117, found: 151.1117.

[0051] Compound (3ga): 58% yield, 52.1 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.13 (s, 4H), 3.41 (t, J = 6.4 Hz, 2H), 3.36 (s, 3H), 2.70–2.60 (m, 4H), 1.94–1.85 (m, 2H), 1.25 (t, J = 7.6 Hz, 3H) ppm. 13 C NMR (100 MHz, CDCl3): d = 141.6,139.1, 128.4, 127.8, 72.0, 58.5, 31.9, 31.3, 28.4, 15.6 ppm. IR (KBr): n =2963, 1630, 1365, 1119, 1017, 820, 776 cm -1 HRMS (m / z): calcd for C 12 H 19 O + [M+H] + 179.1430, found: 179.1424.

[0052] Compound (3ha): 53% yield, 47.5 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.04 (d, J = 7.6 Hz, 1H), 7.00–6.93 (m, 2H), 3.42 (t, J = 6.4 Hz, 2H), 3.37 (s,3H), 2.67–2.63 (m, 2H), 2.30 (s, 3H), 2.29 (s, 3H), 1.90–1.80 (m, 2H) ppm. 13 CNMR (100 MHz, CDCl3): d= 137.0, 135.8, 135.3, 131.0, 128.8, 126.5, 72.2, 58.5,30.1 29.2, 20.9, 19.1 ppm. IR (KBr): n = 2832, 1630, 1365, 1323, 1123, 952,776 cm -1 HRMS (m / z): calcd for C 12 H 19 O + [M+H] + 179.1430, found: 179.1435.

[0053] Compound (3ia): 82% yield, 95.0 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.15 (s, 4H), 3.43 (t, J = 6.4 Hz, 2H), 3.38 (s, 3H), 2.72–2.64 (m, 2H), 2.54–2.47 (m, 1H), 1.95–1.83 (m, 6H), 1.81–1.74 (m, 1H), 1.50–1.35 (m, 4H), 1.34–1,21 (m, 1H) ppm. 13 C NMR (100 MHz, CDCl3): d = 145.5, 139.2, 128.3, 126.7,72.0, 58.5, 44.1, 34.5, 31.8, 31.2, 26.9, 26.1 ppm. IR (KBr): n = 2924, 2851,1630, 1514, 1448, 1365, 1120, 1019, 776, 545 cm -1 HRMS (m / z): calcd forC 16 H 25 O + [M+H] + 233.1900, found: 233.1900.

[0054] Compound (3ja): 63% yield, 56.5 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d = 7.15–7.08 (m, 2H), 6.86–6.81 (m, 2H), 3.79 (s, 3H), 3.38 (t, J = 6.4 Hz, 2H), 3.35 (s, 3H), 2.66–2.60 (m, 2H), 1.91–1.82 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 157.7, 134.0, 129.3, 113.7, 71.9, 58.5, 55.2, 31.5, 31.3 ppm. IR (KBr): n = 2926, 1513, 1366, 1300, 1247, 1178, 1119, 1038, 841, 776 cm -1 . HRMS (m / z): calcd for C 11 H 17 O2 + [M+H] + 181.1233, found: 181.1233。

[0055] Compound (3ka): Yield 65%, 68.8 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d = 6.78 (d, J = 8.6 Hz, 1H), 6.73–6.70 (m, 2H), 3.85 (s, 3H), 3.84 (s, 3H), 3.37 (t, J = 6.4 Hz, 2H), 3.33 (s, 3H), 2.66–2.58 (m, 2H), 1.89–1.82 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 148.6, 147.0, 134.5, 120.1, 111.6, 111.0, 71.8, 58.5, 55.8, 55.6, 31.8, 31.4 ppm. IR (KBr): n = 2926, 1513, 1450, 1366, 1300, 1178, 1119, 1038, 841, 776, 520 cm -1HRMS (m / z): calcd for C 12 H 19 O3 + [M+H] + 211.1329, found: 211.1329.

[0056] Compound (3la): 77% yield, 74.3 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =6.75–6.67 (m, 2H), 6.65–6.61 (m, 1H), 5.91 (t, J = 0.8 Hz, 2H), 3.37 (t, J = 6.4Hz, 2H), 3.34 (d, J = 0.9 Hz, 3H), 2.63–2.58 (m, 2H), 1.88–1.80 (m, 2H) ppm. 13 CNMR (100 MHz, CDCl3): d = 147.5, 145.5, 135.7, 121.1, 108.8, 108.0, 100.7,71.7, 58.5, 31.9, 31.4 ppm. IR (KBr): n = 2926, 1504, 1489, 1442, 1365, 1246,1117, 1040, 930, 809, 776 cm -1 HRMS (m / z): calcd for C 11 H 15 O3 + [M+H] + 195.1016, found: 195.1008.

[0057] Compound (3ma): 50% yield, 60.7 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.36–7.30 (m, 2H), 7.11–7.06 (m, 1H), 7.03–6.99 (m, 2H), 6.97–6.93 (m, 2H),3.41 (t, J= 6.4 Hz, 2H), 3.36 (s, 3H), 2.72–2.66 (m, 2H), 1.94–1.85 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 141.5, 136.7, 132.0, 131.9, 130.1, 129.4, 129.1, 126.6, 71.8, 58.6, 31.9, 31.1 ppm. IR (KBr): n = 2926, 1590, 1506, 1489, 1365, 1240, 1118, 871, 776, 692 cm -1 . HRMS (m / z): calcd for C 16 H 19 O2 + [M+H] + 243.1380, found: 243.1387。

[0058] Compound (3na): Yield 56%, 71.8 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.33–7.27 (m, 6H), 7.25–7.18 (m, 1H), 7.17–7.13 (m, 2H), 3.39 (t, J = 6.3 Hz, 2H), 3.35 (s, 3H), 2.71–2.65 (m, 2H), 1.92–1.84 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 141.5, 136.7, 132.0, 131.9, 130.1, 129.4, 129.1, 126.6, 71.8, 58.6, 31.9, 31.1 ppm. IR (KBr): n = 2832, 1578, 1490, 1440, 1365, 1241, 1119, 775, 741, 691 cm -1 . HRMS (m / z): calcd for C 16 H 19 OS + [M+H] +259.1151, found: 259.1154.

[0059] Compound (3oa): 57% yield, 66.6 mg. Brown oil. 1 H NMR (400 MHz, CDCl3): d =7.14–7.08 (m, 2H), 6.90–6.82 (m, 2H), 3.90–3.82 (m, 4H), 3.38 (t, J = 6.5 Hz, 2H), 3.34 (s, 3H), 3.15–3.10 (m, 4H), 2.66–2.57 (m, 2H), 1.93–1.80 (m, 2H)ppm. 13 C NMR (100 MHz, CDCl3): d = 149.4, 133.6, 129.1, 115.9, 71.9, 66.9, 58.5,49.7, 31.34, 31.29 ppm. IR (KBr): n = 3295, 2974, 2898, 1517, 1451, 1366,1302, 1231, 1050, 881, 775, 562 cm -1 HRMS (m / z): calcd for C 14 H 22 NO2 + [M+H] + 236.1645, found: 236.1641.

[0060] Compound (3pa): 52% yield, 51.8 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =8.08 (d, J = 8.1 Hz, 1H), 7.89–7.83 (m, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.55–7.45(m, 2H), 7.44–7.38 (m, 1H), 7.35 (d, J = 7.1 Hz, 1H), 3.46 (t, J= 6.2 Hz, 2H), 3.39 (s, 3H), 3.20–3.14 (m, 2H), 2.08–2.00 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d IR (KBr): n = 2925, 1510, 1460, 1365, 1118,951, 777, 690 cm -1 HRMS (m / z): calcd for C 14 H 17 O + [M+H] + 201.1274, found:201.1274.

[0061] Example 6 Following the method in Example 5, crude compound 4 was prepared and further purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to finally obtain product 4kb-ks. .

[0062] Compound (4kb): 82% yield, 101.5 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =6.80 (d, J = 7.9 Hz, 1H), 6.70 (d, J = 8.1 Hz, 2H), 3.87 (s, 3H), 3.85 (s, 3H), 2.63 (t, J = 7.6 Hz, 2H), 2.16–1.98 (m, 2H), 1.95–1.80 (m, 2H) ppm. 19 F NMR (376MHz, CDCl3): d = -66.04 (s, 3F) ppm. 13 C NMR (100 MHz, CDCl3): d= 148.8, 147.3, 133.2, 127.1 (q, J = 274.9 Hz), 120.1, 113.4, 111.1, 55.8, 55.7, 34.1, 32.9 (q, J = 28.2 Hz), 23.6 (q, J = 2.9 Hz) ppm. IR (KBr): n = 2949, 2836, 1592, 1518, 1466, 1420, 1364, 1030, 809, 764, 547 cm -1 . HRMS (m / z): calcd for C 12 H 16 F3O2 + [M+H] + 249.1097, found: 249.1093。

[0063]

[0064] Compound (4kc): Yield 50%, 55.3 mg. Yellow oil. 1 [[ID=??]]H NMR (400 MHz, CDCl3): d = 6.79 (d, J = 8.4 Hz, 1H), 6.73–6.66 (m, 2H), 3.86 (s, 3H), 3.85 (s, 3H), 2.60 (t, J = 7.3 Hz, 2H), 2.34 (t, J = 6.9 Hz, 2H), 1.79–1.71 (m, 2H), 1.70–1.64 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 148.8, 147.2, 133.8, 120.1, 119.6, 111.5, 111.1, 55.8, 55.7, 34.5, 30.3, 24.7, 17.0 ppm. IR (KBr): n = 2938, 2834, 1516, 1465, 1419, 1365, 1261, 1236, 1028, 808, 775, 547 cm -1 . HRMS (m / z): calcd for C It seems there is a tag "??" in the original text which might be an error. I've translated it as best as possible while keeping all the tags intact. If you have any further clarifications or corrections regarding the original text, please let me know.13 H 18 NO2 + [M+H] + 220.1332, found: 220.1337.

[0065]

[0066] Compound (4kD): 46% yield, 58.3 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =6.78 (d, J = 8.6 Hz, 1H), 6.72–6.68 (m, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.86 (s,3H), 3.84 (s, 3H), 2.63–2.54 (m, 2H), 2.30 (t, J = 7.5 Hz, 2H), 1.96–1.88 (m,2H), 1.24 (t, J = 7.1 Hz, 3H) ppm. 13 C NMR (100 MHz, CDCl3): d IR (KBr): n = 2938, 2834, 1732, 1517, 1465, 1261, 1238, 1156, 1029, 806,764 cm -1 HRMS (m / z): calcd for C 14 H 21 O4 + [M+H] + 253.1434, found: 253.1431.

[0067]

[0068] Compound (4ke): 70% yield, 78.7 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d = 6.79 (d, J= 8.6 Hz, 1H), 6.71 (d, J = 7.2 Hz, 2H), 4.50 (t, J = 6.1 Hz, 1H), 4.38(t, J = 6.1 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 2.61–2.54 (m, 2H), 1.79–1.59(m, 4H), 1.50–1.40 (m, 2H) ppm. 19 19F NMR (376 MHz, CDCl3): d = -217.93 (s, 1F)ppm. 13 13C NMR (100 MHz, CDCl3): d = 148.8, 147.2, 135.2, 120.2, 111.8, 111.2, 84.2(d, J = 163.3 Hz), 56.0, 55.9, 35.5, 31.4, 30.4 (d, J = 19.3 Hz), 24.9 (d, J = 5.4Hz) ppm. IR (KBr): n = 2937, 2833, 1518, 1366, 1274, 1126, 1030, 955, 775 cm -1 .HRMS (m / z): calcd for C 13 H 20 FO2 + [M+H] + 227.​​​​​​​​​​​​​= 7.2 Hz, 2H), 1.84–1.71 (m, 4H) ppm. 13 C NMR (100 MHz, CDCl3): d = 148.7, 147.1, 134.4, 120.1, 111.5, 111.1, 55.8, 55.7, 44.8, 34.6, 32.0, 28.6 ppm. IR (KBr): n = 2936, 2833, 1516, 1417, 1365, 1262, 1142, 1029, 854, 804, 775, 763 cm -1 . HRMS (m / z): calcd for C 12 H 18 ClO2 + [M+H] + 229.0990, found: 229.0984。

[0071]

[0072] Compound (4ag): Yield 78%, 82.4 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d = 7.70–7.67 (m, 2H), 7.64–7.58 (m, 2H), 7.54–7.49 (m, 2H), 7.44–7.38 (m, 1H), 7.37–7.32 (m, 2H), 2.79–2.71 (m, 2H), 1.79–1.69 (m, 2H), 1.55–1.44 (m, 2H), 1.05 (t, J = 7.3 Hz, 3H) ppm. 13 C NMR (100 MHz, CDCl3): d = 142.0, 141.2, 138.5, 128.8, 128.72, 128.67, 127.0, 126.9, 35.3, 33.6, 22.4, 14.0 ppm. IR (KBr): n = 3027, 2929, 2857, 1486, 1465, 1365, 百 1008, 836, 775, 761, 697 cm -1 . HRMS (m / z): calcd for C 16 H It should be noted that there is an incorrect character "百" in the original text in line . It should be corrected before translation. The above translation is based on the provided text with this error.19 + [M+H] + 211.1481, found: 211.1479.

[0073]

[0074] Compound (4ah): 75% yield, 94.5 mg. Colorless oil. 1 H NMR (400 MHz, CDCl3): d =7.62–7.55 (m, 2H), 7.53–7.46 (m, 2H), 7.45–7.38 (m, 2H), 7.34–7.27 (m, 1H),7.23–7.17 (m, 2H), 2.51 (d, J = 7.1 Hz, 2H), 1.77–1.47 (m, 6H), 1.29–1.09 (m, 3H), 1.03–0.89 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 141.2, 140.5, 138.5,130.0, 128.7, 127.0, 126.9, 126.8, 43.7, 39.8, 33.2, 26.5, 26.3 ppm. IR(KBr): n = 2921, 1487, 1449, 1365, 1007, 894, 832, 775, 757, 728, 692 cm -1 .HRMS (m / z): calcd for C 19 H 23 + [M+H] + 251.1794, found: 251.1792.

[0075]

[0076] Compound (4ki): 62% yield, 64.2 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =6.78 (d, J= 7.9 Hz, 1H), 6.68–6.64 (m, 2H), 3.86 (s, 3H), 3.86 (s, 3H), 2.43(s, 2H), 0.90 (s, 9H) ppm. 13 C NMR (100 MHz, CDCl3): d = 148.0, 147.1, 132.4,122.4, 113.8, 110.5, 55.78, 55.75, 49.8, 31.7, 29.4 ppm. IR (KBr): n = 2951,1517, 1464, 1364, 1276, 1259, 1239, 1157, 1032, 856, 775 cm -1 . HRMS (m / z):calcd for C 13 H 21 O2 + [M+H] + 209.1536, found: 209.1530。

[0077]

[0078] Compound (4kj): Yield 44%, 68.7 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =6.79 (d, J = 8.6 Hz, 1H), 6.74–6.70 (m, 2H), 3.87 (s, 3H), 3.85 (s, 3H), 3.63(t, J = 6.3 Hz, 2H), 2.66–2.58 (m, 2H), 1.87–1.77 (m, 2H), 0.91 (s, 9H), 0.06(s, 6H) ppm. 13 C NMR (100 MHz, CDCl3): d = 148.7, 147.0, 134.8, 120.2, 111.7,111.1, 62.3, 55.9, 55.7, 34.6, 31.6, 25.9, 18.3, -5.3 ppm. IR (KBr): n = 2931,2857, 1516, 1365, 1259, 1157, 1101, 1032, 836, 775 cm-1 HRMS (m / z): calcd forC 17 H 31 O3Si + [M+H] + 311.2037, found: 311.2032.

[0079]

[0080] Compound (4ak): 62% yield, 80.3 mg. White solid. 1 H NMR (400 MHz, CDCl3): d =7.66 (d, J = 7.5 Hz, 2H), 7.59 (d, J = 8.1 Hz, 2H), 7.50 (t, J = 7.7 Hz, 2H), 7.42–7.33 (m, 4H), 7.32–7.26 (m, 4H), 3.03 (s, 4H) ppm. 13 C NMR (100 MHz, CDCl3): d IR (KBr): n = 2919, 2853, 1485, 1365, 860, 825,774, 762, 697, 689, 509 cm -1 HRMS (m / z): calcd for C 20 H 19 + [M+H] + 259.1481, found: 259.1483.

[0081]

[0082] Compound (4 kL): 92% yield, 118.3 mg. Colorless oil. 1 H NMR (400 MHz, CDCl3): d = 7.35–7.28 (m, 2H), 7.25–7.19 (m, 3H), 6.82 (d,J = 8.1 Hz, 1H), 6.78–6.72(m, 2H), 3.89 (s, 3H), 3.88 (s, 3H), 2.71–2.60 (m, 4H), 2.03–1.94 (m, 2H)ppm. 13 C NMR (100 MHz, CDCl3): d = 148.7, 147.0, 142.2, 134.8, 128.4, 128.2,125.7, 120.1, 111.6, 111.1, 55.8, 55.7, 35.3, 34.9, 33.0 ppm. IR (KBr): n =2934, 2833, 1515, 1463, 1260, 1236, 1155, 1030, 750, 700 cm -1 . HRMS (m / z):calcd for C 17 H 21 O2 + [M+H] + 257.1536, found: 257.1531。

[0083]

[0084] Compound (4km): Yield 56%, 75.8 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.32–7.27 (m, 2H), 6.99–6.90 (m, 3H), 6.84–6.72 (m, 3H), 3.97 (t, J = 6.2 Hz,2H), 3.87 (s, 3H), 3.82 (s, 3H), 2.82–2.76 (m, 2H), 2.14–2.06 (m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 158.9, 148.7, 147.1, 134.0, 129.3, 120.5, 120.2,114.4, 111.8, 111.1, 66.5, 55.8, 55.6, 31.6, 30.9 ppm. IR (KBr): n= 2931,1515, 1498, 1466, 1245, 1172, 1156, 1140, 1030, 755 cm -1 HRMS (m / z): calcdfor C 17 H 21 O3 + [M+H] + 273.1485, found: 273.1484.

[0085]

[0086] Compound (4ko): 86% yield, 94.3 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =6.81 (d, J = 8.7 Hz, 1H), 6.77–6.74 (m, 2H), 3.88 (s, 3H), 3.86 (s, 3H), 2.53–2.37 (m, 1H), 1.91–1.80 (m, 4H), 1.77–1.73 (m, 1H), 1.43–1.32 (m, 4H), 1.31–1.19 (m, 1H) ppm. 13 C NMR (100 MHz, CDCl3): d = 148.6, 146.9, 140.9, 118.2,111.0, 110.2, 55.8, 55.7, 44.1, 34.6, 26.9, 26.1 ppm. IR (KBr): n = 2918,2847, 1519, 1264, 1242, 1157, 1143, 1022, 804 cm -1 HRMS (m / z): calcd forC 14 H 21 O2 + [M+H] + 221.1536, found: 221.1527.

[0087]

[0088] Compound (4kp): 56% yield, 62.6 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d= 6.82 (d, J = 8.1 Hz, 1H), 6.79–6.73 (m, 2H), 4.10–4.04 (m, 2H), 3.87 (s, 3H), 3.85 (s, 3H), 3.55–3.46 (m, 2H), 2.75–2.63 (m, 1H), 1.84–1.74 (m, 4H) ppm. 13 13C NMR (100 MHz, CDCl3): d = 148.8, 147.4, 139.9, 120.9, 112.1, 110.1, 68.4, 55.9, 55.8, 41.1, 34.2 ppm. IR (KBr): n = 2936, 2835, 1518, 1464, 1366, 1235, 1129, 1111, 1086, 1029, 807 cm -1 . HRMS (m / z): calcd for C 13 H 19 O3 + [M + H] + 223.1329, found: 223.1326。

[0089]

[0090] Compound (4kq): Yield 88%, 100.4 mg. Yellow oil. 1 1H NMR (400 MHz, CDCl3): d = 7.37–7.31 (m, 2H), 7.26–7.22 (m, 3H), 6.84 (d, J = 8.0 Hz, 1H), 6.80–6.75 (m, 2H), 3.98 (s, 2H), 3.89 (s, 3H), 3.87 (s, 3H). ppm. 13 13C NMR (100 MHz, CDCl3): d = 148.7, 147.2, 141.2, 133.5, 128.6, 128.3, 125.9, 120.7, 112.0, 111.0, �5.7, 55.6, 41.3 ppm. IR (KBr): n= 2954, 1606, 1472, 1206, 1183, 1034, 772, 744,620 cm -1 HRMS (m / z): calcd for C 15 H 17 O2 + [M+H] + 229.1223, found: 229.1226.

[0091]

[0092] Compound (4ar): 58% yield, 66.1 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d =7.64 (dd, J = 7.5, 2.2 Hz, 2H), 7.61–7.55 (m, 2H), 7.52–7.45 (m, 2H), 7.41–7.29(m, 3H), 3.47 (t, J = 6.3 Hz, 2H), 3.41 (s, 3H), 2.83–2.75 (m, 2H), 2.05–1.93(m, 2H) ppm. 13 C NMR (100 MHz, CDCl3): d = 141.04, 140.99, 138.7, 128.8, 128.7,127.01, 126.95, 126.9, 71.8, 58.5, 31.9, 31.2 ppm. IR (KBr): n = 3030, 2921,2869, 1444, 1483, 1362, 1120, 843, 768, 697 cm -1 HRMS (m / z): calcd for C 16 H 19 O + [M+H] + 227.1430, found: 227.1430.

[0093] Compound (4 ks): 47% yield, 52.4 mg. Yellow oil. 1 H NMR (400 MHz, CDCl3): d=6.80–6.78 (m, 1H), 6.73–6.71 (m, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 2.57–2.53(m, 2H), 1.63–1.56 (m, 2H), 1.34–1.28 (m, 6H), 0.91–0.87 (m, 3H) ppm. 13 C NMR(100 MHz, CDCl3): d = 148.7, 146.9, 135.6, 120.0, 111.7, 111.1, 55.8, 55.7,35.5, 31.7, 31.6, 28.9, 22.6, 14.0 ppm. IR (KBr): n = 2928, 2855, 1516, 1466,1365, 1262, 1236, 1156, 1141, 1031, 776 cm -1 . HRMS (m / z): calcd for C 14 H 23 O2 + [M+H] + 223.1693, found: 223.1694。

Claims

1. 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 palladium catalyst, magnesium, zinc chloride, and lithium chloride to form a compound of formula III. ， in, R 1 Each is independently selected from halogen, cyano, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-6 Cycloalkyl, 3- to 6-membered heterocycloalkyl, -COOR 1a BnO-, PhO-, or PhS-, or adjacent R 1 Form C with adjacent atoms 3-6 Cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, or 5- or 6-membered heteroaryl; R 1a Selected from hydrogen or C 1-6 alkyl; R 2 Selected from C 1-6 Alkyl, C 3-6 Cycloalkyl or 3- to 6-membered heterocycloalkyl, wherein the C 1-6 Alkyl, C 3-6 Cycloalkyl or 3- to 6-membered heterocycloalkyl groups are optionally selected from one or more halogens, cyano groups, C 1-6 Alkyl, C 1-6 Alkyl, TBSO-, PhO-, Ph- or -COOR 2a Replaced; R 2a Selected from hydrogen or C 1-6 alkyl; X is selected from leaving groups, such as halogens; o is selected from 0, 1, 2 or 3.

2. The method according to claim 1, characterized in that, The palladium catalyst is selected from Pd2(dba)3.

3. The method according to claim 1 or 2, characterized in that, The amount of palladium catalyst used is 1% to 10% of the molar amount of the compound of formula I, for example, 2.5%.

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

5. The method according to any one of claims 1-4, characterized in that, The reaction further comprises a catalyst ligand selected from Ruphos; the amount of the catalyst ligand is 1% to 10% of the molar amount of the compound of formula I, for example 5%.

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 amount of zinc chloride used is 1 to 4 equivalents of the molar amount of the compound of Formula I, for example, 2 equivalents; the amount of lithium chloride used is 1 to 4 equivalents of the molar amount of the compound of Formula I, for example, 2 equivalents.

8. The method according to any one of claims 1-7, characterized in that, The compound shown in Formula I is selected from: 。 9. The method according to any one of claims 1-8, characterized in that, The compound shown in Formula II is selected from: or X is selected from leaving groups, such as halogens (bromine).

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