A method for preparing a biaryl compound

Abstract

The application provides a preparation method of a biaryl compound, and particularly relates to a preparation method of a compound shown in formula III.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, and specifically relates to a method for preparing biaryl compounds. Background Technology

[0002] In organic synthesis and pharmaceutical chemistry, transition metal-catalyzed cross-coupling reactions are one of the most important strategies for constructing carbon-carbon single bonds, especially biaryl skeletons. Traditional cross-coupling reactions typically rely on the coupling between organometallic compounds (such as organozinc, organoboron, or organosilicon reagents) and electrophilic reagents. However, these organometallic reagents have significant limitations in practical applications: on the one hand, they are difficult and expensive to obtain commercially; on the other hand, most of these reagents are highly sensitive to air and moisture, and their pre-synthesis, storage, and reaction operations all require strict anhydrous and oxygen-free conditions, making the process cumbersome and greatly limiting their widespread application in modern organic synthesis and industrial production.

[0003] To address the aforementioned limitations, cross-electrophilic coupling reactions involving two different electrophiles under reducing conditions have emerged. This strategy eliminates the need for pre-preparation or the use of nucleophilic organometallic species, offering not only greater procedural economy, cost-effectiveness, and ease of operation, but also superior functional group compatibility. Furthermore, electrophiles (such as organohalides and pseudohalides) are abundant, inexpensive, and readily commercially available, providing an ideal raw material basis for the construction of novel cross-coupling systems.

[0004] Against this backdrop, arylthianthaneonium salts have attracted considerable attention as a novel class of aryl electrophilic reagents. They can be conveniently prepared via regioselective C–H bond thianization of aromatics with thianthracene, and exhibit stable properties at room temperature and pressure, making them particularly suitable for the late-stage functionalization modification of complex molecules. Existing research indicates that arylthianthaneonium salts can undergo cross-electrophilic coupling with aryl halides or trifluoromethanesulfonates under the catalysis of reducing metal mediators (such as Zn and Mg) and palladium; however, the range of alternative electrophilic coupling reagents still needs further expansion.

[0005] On the other hand, aryl nonafluorobutyrate sulfonates can be easily prepared by reacting inexpensive nonafluorobutyryl fluoride with widely available phenolic compounds under weakly alkaline conditions. Compared with commonly used aryl trifluoromethanesulfonates, aryl nonafluorobutyrate sulfonates have significant advantages in benchtop storage stability and cross-coupling reactivity, and have been successfully applied in various organic transformations such as Heck, Negishi, and Suzuki.

[0006] Given the good availability, stability, and reactivity of both arylthiananthraium salts and aryl nonafluorobutyrate sulfonates, the development of direct cross-electrophilic coupling reactions between them is highly anticipated. Therefore, developing a novel, efficient, mild, and widely applicable method for the cross-electrophilic coupling of arylthiananthraium salts and aryl nonafluorobutyrate sulfonates has significant scientific and practical value. Summary of the Invention

[0007] This invention discloses 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 catalyst, a ligand, a reducing agent, and a basic reagent to form a compound of formula III.

[0008] ,

[0009] Among them, R1 and R2 are each independently selected from C. 1-6 Alkyl, halogen, -CN, -NO2, -OR4, -COOR4, -SR4, -NR5R6, 6- to 10-membered aryl, 5- to 10-membered heterocyclic, C2-C6 alkenyl, or two adjacent R1 or two adjacent R2 together with the attached carbon atom to form a 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 cycloalkyl, 5- to 10-membered heterocyclic groups, wherein the C 1-6 Alkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 The cycloalkyl group, the 5- to 10-membered heterocyclic group, and the C2-C6 alkenyl group are each optionally surrounded by one or more groups selected from oxo, halogen, cyano, amino, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Substituted by alkoxy groups or R7 substituents;

[0010] R3 is selected from halogenated C 1-6 alkyl;

[0011] R4 is selected from H and C. 1-6 Alkyl, 6- to 8-membered aryl, 5- to 8-membered heteroaryl, C 3-8 cycloalkyl, 5- to 8-membered heterocyclic groups, wherein the C 1-6 Alkyl, 6- to 8-membered aryl, 5- to 8-membered heteroaryl, C 3-8 The cycloalkyl group and the 5- to 8-membered heterocyclic group are each optionally surrounded by one or more groups selected from halogen, cyano, amino, C 1-6 Alkyl, Halogenated C 1-6 Alkyl groups and R8 substituents are used to replace them;

[0012] R5 and R6 are each independently selected from H and C. 1-6 Alkyl, 6 to 10 aryl;

[0013] R7 is selected from 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 Cycloalkyl, 5- to 10-membered heterocyclic groups, said 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 Cycloalkyl groups, 5 to 10-membered heterocyclic groups optionally surrounded by one or more groups selected from oxo, halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Substituted with alkoxy or 6- to 8-membered aryl groups;

[0014] R8 is selected from C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, the C 1-6 Alkoxy, halogenated C 1-6 Alkyl groups are optionally surrounded by one or more C16 groups. 1-6 Alkyl, Halogenated C 1-6 Alkyl groups and -OR7 substituents are used;

[0015] n and m are each independently selected from 0, 1, 2, 3, 4, and 5.

[0016] In some embodiments, the catalyst is selected from Pd(OAc)2, Pd(PPh3)4, Pd2(dba3), Pd(P t Bu3)2, Pd(CH3CN)2Cl2, Pd(PPh3)2Cl2.

[0017] In some embodiments, the catalyst is selected from Pd(PPh3)2Cl2.

[0018] In some embodiments, the amount of catalyst used is 1% to 15% of the molar amount of the compound of formula I.

[0019] In some embodiments, the amount of catalyst used is 3%, 5%, 8%, 10%, 12%, or 15% of the molar amount of the compound of formula I.

[0020] In some embodiments, the amount of catalyst used is 5% or 10% of the molar amount of the compound of formula I.

[0021] In some implementations, the ligand is selected from... , , , , , , , , , .

[0022] In some implementations, the ligand is selected from... (SPhos).

[0023] In some embodiments, the amount of the ligand used is 1% to 15% of the molar amount of the compound of formula I.

[0024] In some embodiments, the amount of the ligand is 3%, 5%, 8%, 10%, 12%, or 15% of the molar amount of the compound of formula I.

[0025] In some embodiments, the amount of the ligand is 10% of the molar amount of the compound of formula I.

[0026] In some embodiments, the reducing agent is selected from B2Pin2 (pinacol diboronate) and B2(OH)4.

[0027] In some embodiments, the reducing agent is selected from B2(OH)4.

[0028] In some embodiments, the amount of the reducing agent is 1-5 equivalents of the molar amount of the compound of formula I.

[0029] In some embodiments, the amount of the reducing agent is 1, 1.5, 2.0, 2.5, 3.0, or 3.5 equivalents of the molar amount of the compound of Formula I.

[0030] In some embodiments, the amount of the reducing agent is 1.5 equivalents of the molar amount of the compound of formula I.

[0031] In some embodiments, the alkaline reagent is selected from K3PO4, K2CO3, KOH, Cs2CO3, Na2CO3, t BuOK, CsF, Et3N.

[0032] In some embodiments, the alkaline reagent is selected from Na2CO3, K3PO4, and K2CO3.

[0033] In some embodiments, the basic reagent is used in amounts of 1-5 molar equivalents of the compound of formula I.

[0034] In some embodiments, the basic reagent is used in amounts of 1.0, 2.0, or 3.0 equivalents of the molar amount of compound I.

[0035] In some embodiments, the basic reagent is used in an amount of 3.0 equivalents of the molar amount of compound I.

[0036] In some embodiments, the method further comprises a solvent selected from MeOH, DMF, DMA, DMSO, NMP, THF, 1,4-dioxane, etc. tBuOMe, MeCN, EtOH.

[0037] In some embodiments, the solvent is selected from MeOH.

[0038] In some implementations, the method is carried out at 0-80°C.

[0039] In some implementations, the method is carried out at 0°C, 10°C, 20°C, 25°C, 30°C, and 60°C.

[0040] In some embodiments, the method is carried out under a nitrogen atmosphere.

[0041] In some embodiments, the amount of compound II is 1-5 equivalents of the molar amount of compound I.

[0042] In some embodiments, the amount of compound II is 1.5, 2.0, or 3.0 equivalents of the molar amount of compound I.

[0043] In some embodiments, the amount of compound II is 1.5 molar equivalents of compound I.

[0044] In some embodiments, the amount of compound II is 3.0 molar equivalents of compound I.

[0045] In some embodiments, the method further contains a free radical scavenger or 1,1-stilbene.

[0046] In some embodiments, the method further comprises a free radical scavenger selected from 2,6-di-tert-butyl-4-methylphenol (BHT).

[0047] In some embodiments, the method further contains 1,1-stilbene.

[0048] In some embodiments, the method further includes a step of converting formula I' into formula I.

[0049] , where R1 and n are as defined above.

[0050] In some embodiments, the method further includes the step of converting formula II' into formula II.

[0051] , where R2 and m are as defined above.

[0052] In some embodiments, the method includes a step of converting Formula I' to Formula I in the presence of a catalyst, ligand, reducing agent, and basic reagent, and a step of reacting with Formula II to convert to Formula III.

[0053] R1, R2, R3, n, m, catalyst, ligand, reducing agent, and basic reagent are as defined above.

[0054] In some embodiments, the method includes a step of converting Formula II' to Formula II in the presence of a catalyst, a ligand, a reducing agent, and a basic reagent, and a step of reacting with Formula I to convert to Formula III.

[0055] R1, R2, R3, n, m, catalyst, ligand, reducing agent, and basic reagent are as defined above.

[0056] In some embodiments, this disclosure also 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-1 with a compound of formula II in the presence of a catalyst, a ligand, and a basic reagent to form a compound of formula III.

[0057] R1, R2, R3, n, m, catalyst, ligand and basic reagent are as defined above.

[0058] In some embodiments, this disclosure also 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-1 in the presence of a catalyst, a ligand, and a basic reagent to form a compound of formula III.

[0059] R1, R2, R3, n, m, catalyst, ligand and basic reagent are as defined above.

[0060] In some implementations, R1 is selected from C 1-6 Alkyl, halogen, -CN, -NO2, -OR4, -COOR4, -NR5R6, 5- to 10-membered heterocyclic groups, or two adjacent R1 groups forming 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 cycloalkyl, 5- to 10-membered heterocyclic groups, wherein the C 1-6 Alkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 The cycloalkyl group and the 5- to 10-membered heterocyclic group are each optionally surrounded by one or more groups selected from oxo, halogen, cyano, amino, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 The substituents are alkoxy groups and R7, and R4, R5, R6, and R7 are as defined above.

[0061] In some implementations, R1 is selected from C1-6 Alkyl, halogen, -CN, -NO2, -OR4, -COOR4, 5- to 10-membered heterocyclic groups, or two adjacent R1 groups forming a 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 5- to 10-membered heterocyclic group together with the attached carbon atom, wherein the 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 1-6 The alkyl group is optionally substituted by one or more substituents selected from oxo, halogen, cyano, amino, and R7, where R4 and R7 are as defined above.

[0062] In some implementations, R4 is selected from H and C. 1-6 Alkyl, 6- to 8-membered aryl, 5- to 8-membered heterocyclic, wherein the C 1-6 Alkyl, 6- to 8-membered aryl, and 5- to 8-membered heterocyclic groups are each optionally surrounded by one or more groups selected from halogen, cyano, amino, C 1-6 Alkyl, Halogenated C 1-6 Alkyl groups are substituted, and R8 is substituted as defined above.

[0063] R5 and R6 are each independently selected from H and C. 1-6 alkyl.

[0064] In some embodiments, R7 is selected from 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 Cycloalkyl, 5- to 10-membered heterocyclic groups, said 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 Cycloalkyl groups, 5 to 10-membered heterocyclic groups optionally surrounded by one or more groups selected from oxo, halogen, C 1-6 Alkyl, C 1-6 It is substituted by alkoxy groups and 6 to 8 aryl groups.

[0065] In some implementations, R8 is selected from C 1-6 Alkoxy, the C 1-6 Alkyl groups are optionally surrounded by one or more C16 groups. 1-6 Alkyl groups are substituted with -OR7 substituents, where R7 is as defined above.

[0066] In some embodiments, R1 is selected from -OMe, -OEt, -COOMe, -COOEt, halogen, -CN, methyl, ethyl, -OPh, , , .

[0067] In some embodiments, two adjacent R1 atoms together with the attached carbon atom form a 6- to 10-membered aryl group, a 5- to 10-membered heteroaryl group, or a C-membered aryl group. 3-10 Cycloalkyl, 5- to 10-membered heterocyclic groups, said 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10The cycloalkyl group and the 5- to 10-membered heterocyclic group are each optionally replaced by one or more substituents selected from oxo and halogen groups, R4, R5, R6, and R7 as defined above.

[0068] In some implementations, R2 is selected from C 1-6 Alkyl, halogen, -CN, -NO2, -OR4, -COOR4, -NR5R6, C2-C6 alkenyl, or two adjacent R2 atoms together with the attached carbon atom to form a 6- to 10-membered aryl, 5- to 10-membered heteroaryl, or 5- to 10-membered heterocyclic group, wherein the C 1-6 Alkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 The cycloalkyl group, the 5- to 10-membered heterocyclic group, and the C2-C6 alkenyl group are each optionally surrounded by one or more groups selected from oxo, halogen, cyano, amino, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 The substituents are alkoxy groups and R7, and R4, R5, R6, and R7 are as defined above.

[0069] In some embodiments, R2 is selected from methyl, ethyl, tert-butyl, halogen, -CN, -NO2-, OMe, -OEt, -COOMe, -COOEt, -OCF3, -CF3, -N(CH3)2.

[0070] In some embodiments, R2 is selected from C2-C6 alkenyl groups, which are optionally substituted with one or more R7 groups, wherein R7 is optionally substituted with one or more C2-C6 alkenyl groups. 1-6 Alkoxy-substituted 6 to 10 aryl groups.

[0071] In some implementations, two adjacent R2 atoms together with the attached carbon atom form a 6- to 10-membered aryl, a 5- to 10-membered heteroaryl, or a 5- to 10-membered heterocyclic group.

[0072] In some embodiments, R3 is selected from halogenated C 1-6 alkyl.

[0073] In some implementations, R3 is selected from -C4F9 and -CF3.

[0074] In some implementations, n and m are each independently selected from 1, 2, and 3.

[0075] In some embodiments, the compound represented by Formula I is selected from: , , , , , , , , , , , , , ,in OTf represents trifluoromethanesulfonate.

[0076] In some embodiments, the compound represented by Formula II is selected from: , , , , , , , , , , , , , , , , ,in .

[0077] In some embodiments, the compound represented by Formula III is selected from: , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

[0078] In some embodiments, the compound represented by formula I' is selected from: , , , .

[0079] In some embodiments, the compound represented by formula II' is selected from: , , .

[0080] In some embodiments, the compound represented by Formula I-1 is selected from: .

[0081] In some embodiments, the compound represented by Formula II-1 is selected from: .

[0082] 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).

[0083] The method disclosed in this invention is highly efficient by promoting the breaking of CS and CO bonds, enabling the convenient synthesis of various biaryl compounds in moderate to good yields. This reaction exhibits a wide substrate applicability, broad functional group compatibility, and potential for scale-up synthesis. It is also suitable for the late-stage functionalization modification of complex bioactive molecules. Notably, this method can also be implemented via a one-pot, two-step approach: first, aryl thiaanthracite salts and aryl nonafluorobutane sulfonates are prepared from abundant and simple aromatic and phenolic raw materials under different conditions; then, they are directly cross-coupled with their respective coupling pairs under palladium catalysis, further demonstrating the synthetic practicality of this coupling scheme.

[0084] In this invention, "to form" and "to transform" do not specifically refer to a single-step transformation reaction between two substrates; they can be single-step or multi-step reactions between two substrates. For example, if the intermediate contains an amino protecting group, the intermediate undergoes a deamination step with a protecting agent before reacting with the corresponding substrate to obtain the target product.

[0085] "Optional" or "optional" 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.

[0086] "alkyl" refers to a saturated aliphatic hydrocarbon group, including straight-chain and branched groups with 1 to 10 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.

[0087] The term "halogenation" refers to the substitution of one or more atoms selected from fluorine, chlorine, bromine, and iodine.

[0088] "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.

[0089] 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.

[0090] The term "heterocyclic alkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic 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 -OO-, -OS-, or -SS- ring moieties, 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.

[0091] The term "heteroaryl" refers to a heteroaryl system comprising 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-, 8-, or 9-membered, and more preferably 5- or 6-membered. Heteroaryl groups include monocyclic and fused polycyclic groups, and can be optionally substituted or unsubstituted.

[0092] 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.

[0093] The term "alkenyl" refers to a branched, unbranched, or cyclic carbon chain containing one or more double bonds, including but not limited to vinyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, etc. Alkenyl groups can be optionally substituted or unsubstituted.

[0094] The term "heterocyclic group" refers to a non-aromatic heterocyclic group (which contains one or more heteroatoms selected from nitrogen, oxygen, or optionally oxidized sulfur as ring members, wherein the remaining ring members are carbon), including monocyclic, fused, bridged, and spirocyclic groups, i.e., containing monocyclic, bridged, spirocyclic, and fused heterocyclic groups. Heterocyclic groups can be optionally substituted or unsubstituted.

[0095] 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.

[0096] "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).

[0097] 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.

[0098] 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%.

[0099] 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

[0100] The present invention will be further described in conjunction with specific embodiments to enable those skilled in the art to better understand and implement the present invention, but the embodiments are not intended to limit the present invention.

[0101] Unless otherwise stated, all reagents (purity ≥98%) were purchased from commercial suppliers and used directly without further purification.

[0102] Analytical thin-layer chromatography (TLC) was performed using a silica gel plate (0.2 mm thick); after development, it was visualized using ultraviolet light (254 nm).

[0103] Rapid column chromatography was performed using Merck silica gel (200–300 mesh) and freshly evaporated solvent.

[0104] Infrared (IR) spectra were measured using an FT-IR spectrophotometer equipped with KBr optics.

[0105] ¹H, ¹³C, and ¹F NMR spectra were determined using CDCl3 as solvent on a Bruker Avance or Jeol 400 MHz spectrometer; tetramethylsilane (TMS) was used as an internal standard for ¹H, ¹³C, and ¹F NMR analysis.

[0106] High-resolution mass spectrometry (HRMS) was performed on a Waters Q-TOF Premier mass spectrometer (ESI source).

[0107] General preparation method 1:

[0108]

[0109] Under nitrogen protection, 10 mmol (1 equivalent), thiamethoxam-S-oxide (2.56 g, 11 mmol, 1.1 equivalent), and dichloromethane (DCM, 30 mL) were added to a 100 mL round-bottom flask equipped with a magnetic stirrer. The reaction mixture was cooled to -40 °C, and trifluoromethanesulfonic anhydride (Tf₂O, 2 mL, 12 mmol, 1.2 equivalent) was added dropwise. The reaction mixture was stirred at -40 °C for 30 minutes, followed by stirring at room temperature for 12 hours. After TLC analysis confirmed the completion of the reaction, 30 mL of saturated sodium bicarbonate aqueous solution was added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (40 mL × 3). The organic extracts were combined, washed successively 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 give compound I. R₁ and n are as defined above.

[0110] General preparation method 2:

[0111]

[0112] Under a nitrogen atmosphere, 10 mmol (1.0 equivalent), thiamethoxam-S-oxide (TTSO, 2.32 g, 10 mmol, 1 equivalent), and dichloromethane (DCM, 30 mL) were added to a 100 mL round-bottom flask equipped with a magnetic stirrer. The reaction mixture was cooled to -40 °C, and then trifluoroacetic anhydride (TFAA, 4.17 mL, 30 mmol, 3 equivalent) and trifluoromethanesulfonic acid (TfOH, 1.3 mL, 15 mmol, 1.5 equivalent) were added dropwise. The reaction mixture was stirred at -40 °C for 30 min, followed by stirring at room temperature for 12 h. After the reaction was confirmed to be complete by TLC analysis, 30 mL of saturated NaHCO3 aqueous solution was added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with dichloromethane (40 mL × 3). The combined organic extracts were washed sequentially with NaOTf aqueous solution (20 mL × 3; 5% w / w), dried over anhydrous Na2SO4, and concentrated to dryness under reduced pressure. The crude product was purified by recrystallization from a dichloromethane / diethyl ether system to give compound I. R1 and n are as defined above.

[0113] General preparation method 3:

[0114]

[0115] In a 100 mL single-necked round-bottom flask, dissolve formula II' (10 mmol) in anhydrous dichloromethane (33 mL) and cool to 0 °C. Then add triethylamine (2.5 g, 3.48 mL, 25 mmol), followed by... (4.5 g, 2.70 mL, 15 mmol). The reaction mixture was heated to room temperature and stirred for 2 h, then quenched with saturated ammonium chloride solution (20 mL) and water (20 mL), and extracted with dichloromethane (20 mL × 3). The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was further purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to give compound II. R2, m, and R3 are as defined above.

[0116] General preparation method 4:

[0117]

[0118] A dried, sealed tube fitted with a magnetic stirrer was purged three times with nitrogen. Then, the following were added sequentially: Formula I (0.5 mmol, 1 equivalent), Formula II (1.5 mmol, 3 equivalent), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), B2(OH)4 (0.0672 g, 0.75 mmol, 1.5 equivalent), and Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalent). Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at 60 °C for 6 hours. After the reaction was complete, saturated NH4Cl solution (10 mL) and water (20 mL) were added sequentially to quench the reaction, and the mixture was extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed successively with saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product. Finally, the product was purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to obtain product formula III. R2, m, R1, n, and R3 are as defined above.

[0119] Example 1 Synthesis of thiaanthracene-S-oxide

[0120]

[0121] In a 100 mL round-bottom flask equipped with a magnetic stirrer, dichloromethane (DCM, 50 mL), thiamethoxam (5.0 g, 23 mmol, 1.0 equivalent), sodium bromide (0.10 g, 0.97 mmol, 4.2 mol%), ferric nitrate (III) 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 sequentially. The reaction mixture was stirred at room temperature for 3 hours. After the reaction was confirmed to be complete by TLC analysis, water (50 mL) was added to the 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 (Na₂SO₄), filtered, and the solvent was removed under reduced pressure. The resulting solid was recrystallized from ethyl acetate (EtOAc). The crystals were collected, washed with diethyl ether (Et2O, 20 mL), and dried under vacuum to give colorless needle-like thiathracene-S-oxide (4.38 g, yield 82%).

[0122] Example 2

[0123] Synthesize compounds 1a, 1c–1n according to general preparation method 1: (1a) (1c) (1d) (1e) (1f) (1g) (1h) (1i) (1j) (1k) (1l) (1m) (1n).

[0124] Synthesize compound 1b according to general preparation method 2: .

[0125] Example 3

[0126] Compound 3a was prepared using the catalysts shown in Table 1, following the general preparation method 4.

[0127]

[0128] Table 1. Preparation of Compound 3 using different catalysts a

[0129]

[0130] a. Reaction conditions: The reaction was carried out in anhydrous methanol (2 mL) at 60 °C for 12 h under a nitrogen atmosphere using 1a (0.5 mmol), 2a (0.75 mmol), catalyst (10 mol%), SPhos (10 mol%), B2Pin2 (0.75 mmol), and K3PO4 (1.5 mmol) as starting materials. b. Yield was determined by NMR analysis of the post-treated crude reaction mixture, using 1,3,5-trimethoxybenzene as an internal standard. c. 5 mol% catalyst was used. d. 3 equivalents of 2a were used. e. B2(OH)4 was used instead of B2Pin2. f. Na2CO3 was used instead of K3PO4. g. Reaction time: 6 h. Yield separation. i. No catalyst added. j. No boron reducing agent added. k. No alkali added.

[0131] Compound 3a (serial number 15) was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. The product was a white solid, 97.5 mg, in 98% yield. 1H NMR (400 MHz, CDCl3): δ 7.53–7.48 (m, 2H), 7.44 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 7.9 Hz, 2H), 6.98–6.93 (m, 2H), 3.83 (s, 3H), 2.37 (s, 3H)ppm. 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, 21.0ppm. IR (KBr, neat): 2958, 2839, 1607, 1501, 1289, 1182, 1038, 842, 808, 498cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 14 H 15 O + : 199.1117, found: 199.1121.

[0132] Example 4

[0133] Referring to general preparation method 4, the compound shown in Formula I (1b) (1c) (1d) (1e) (1f) (1j) (1k) (1l) (1m) (1n), respectively with compounds (2a) The reaction prepared the following: (3b) (3c) (3d) (3e) (3f) (3j) (3k) (3l) (3m) (3n). The compound shown in Formula I is (1g) (1h) (1i), respectively with (2b) The reaction prepared the following: (3g) (3h) (3i). The reaction was carried out under a nitrogen atmosphere using 1b-n (0.5 mmol), 2a or 2b (1.5 mmol), Pd(PPh3)2Cl2 (5 mol%), SPhos (10 mol%), B2(OH)4 (0.75 mmol) and Na2CO3 (1.5 mmol) in anhydrous MeOH (2 mL) as solvent, and at 60 °C for 6 hours.

[0134] Compound 3b was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as eluent. The product was a white solid, 57.3 mg, in 48% yield. 1 H NMR (400 MHz, CDCl3): δ7.74 (d, J = 2.4 Hz, 1H), 7.70 (dd, J = 8.7, 2.4 Hz, 1H), 7.39 (d, J = 8.2Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.7 Hz, 1H), 4.18 (q, J = 7.0Hz, 2H), 2.39 (s, 3H), 1.50 (t, J = 7.0 Hz, 3H) ppm. 13 IR (KBr, neat): 3047, 2224, 1469, 1269, 1129,1034, 809, 765, 496 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 16 H 16 NO + : 238.1226, found: 238.1227.

[0135] Compound 3c was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as eluent. The product was a white solid, 71.5 mg, in 56% yield.1 H NMR (400 MHz, CDCl3): δ8.03 (d, J = 2.4 Hz, 1H), 7.68 (dd, J = 8.7, 2.5 Hz, 1H), 7.47 (d, J = 8.2Hz, 2H), 7.26–7.22 (m, 2H), 7.04 (d, J = 8.7 Hz, 1H), 3.94 (s, 3H), 3.92 (s, 3H), 2.39 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ 166.7, 158.3, 136.9, 136.8,133.2, 131.7, 130.0, 129.5, 126.5, 120.1, 112.4, 56.1, 52.1, 21.0 ppm. IR(KBr, neat): 3037, 2846, 1727, 1580, 1495, 1307, 1226, 1012, 811, 503 cm -1 .HRMS (ESI, m / z): [M+H] + calcd for C 16 H 17 O3 + : 257.1172, found: 257.1176.

[0136] Compound 3d was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 200:1). 82.7 mg of a white solid was given, with a yield of 77%. 1 H NMR (400 MHz, CDCl3): δ7.46–7.42 (m, 2H), 7.35–7.28 (m, 2H), 7.24 (d, J = 7.7 Hz, 2H), 7.02 (t, J =8.7 Hz, 1H), 3.93 (s, 3H), 2.40 (s, 3H)ppm. 19 F NMR (376 MHz, CDCl3): δ -135.13 (s, 1F) ppm. 13C NMR (100 MHz, CDCl3): δ 152.7 (d, J = 245.2 Hz), 146.9(d, J = 10.7 Hz), 137.1, 136.9, 134.5 (d, J = 6.6 Hz), 129.7, 126.6, 122.5(d, J = 3.4 Hz), 114.7 (d, J = 18.9 Hz), 113.7 (d, J = 2.3 Hz), 56.4, 21.2ppm. IR (KBr, neat): 3051, 2570, 1506, 1276, 1135, 1018, 876, 804, 765, 506cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 14 H 14 FO + : 217.1023, found: 217.1029.

[0137] Compound 3e was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 100:1). The product was a white solid, weighing 92.5 mg, in 81% yield. 1 H NMR (400 MHz, CDCl3): δ7.45 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 7.6 Hz, 2H), 7.14–7.08 (m, 2H), 6.92(d, J = 8.2 Hz, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 2.38 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ 149.2, 148.5, 138.3, 136.7, 134.3, 129.6, 126.8, 119.3,111.6, 110.4, 56.1, 56.0, 21.2 ppm. IR (KBr, neat): 3053, 2834, 1504, 1250,1172, 1144, 1023, 859, 801, 746, 512 cm -1 HRMS (ESI, m / z): [M+H] + calcd forC 15 H 17 O2+ : 229.1223, found: 229.1218.

[0138] Compound 3f was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 200:1). 92.0 mg was obtained in 87% yield as a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.43(d, J = 8.1 Hz, 2H), 7.24 (d, J = 7.9 Hz, 2H), 7.09–7.04 (m, 2H), 6.89 (d, J= 7.9 Hz, 1H), 6.00 (s, 2H), 2.40 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ148.0, 146.8, 138.0, 136.6, 135.6, 129.4, 126.7, 120.3, 108.5, 107.5, 101.1,21.0 ppm. IR (KBr, neat): 3028, 2888, 2781, 1503, 1482, 1437, 1246, 1225,1034, 932, 808, 520 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 14 H 13 O2 + : 213.0910, found: 213.0905.

[0139] 3 g of the compound was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as the eluent. The yield was 91% (94.3 mg), and the product was a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.74–7.64(m, 4H), 7.55–7.50 (m, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.72 (q, J = 7.6 Hz,2H), 1.29 (t, J = 7.6 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 145.6, 145.0,136.4, 132.5, 128.6, 127.4, 127.1, 119.0, 110.4, 28.5, 15.5 ppm. IR (KBr,neat): 3059, 2931, 2857, 2228, 1603, 1496, 1182, 821, 542, 492 cm -1 HRMS(ESI, m / z): [M+H] + calcd for C 15 H 14 N + : 208.1121, found: 208.1118.

[0140] The compound was purified by silica gel column chromatography after 3 hours, using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as the eluent. The product was a white solid, weighing 85.7 mg, with a yield of 83%. 1 H NMR (400 MHz, CDCl3): δ7.71–7.66 (m, 2H), 7.44–7.39 (m, 2H), 7.12 (s, 1H), 7.09 (d, J = 1.1 Hz, 2H), 2.37 (s, 3H), 2.23 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ 146.8, 138.1,137.1, 134.8, 131.9, 131.4, 130.0, 129.3, 126.8, 119.0, 110.4, 21.0, 20.2ppm. IR (KBr, neat): 3018, 2917, 2227, 1603, 1489, 1447, 1035, 854, 819, 583,545 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 15 H 14 N + : 208.1121, found: 208.1120.

[0141] Compound 3i was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 100:1). The yield was 55% (57.3 mg), and it was a white solid.1 H NMR (400 MHz, CDCl3): δ 7.72–7.65 (m, 4H), 7.37 (s, 1H), 7.34 (dd, J = 7.7, 2.0 Hz, 1H), 7.25 (d, J = 7.9Hz, 1H), 2.35 (s, 3H), 2.33 (s, 3H)ppm. 13 IR (KBr, neat): 2965, 2924, 2227, 1605, 1492, 1454, 1180, 816, 559,543 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 15 H 14 N + : 208.1121, found: 208.1125.

[0142] Compound 3j was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. The yield was 62% (80.7 mg), and the product was a yellow oil. 1 H NMR (400 MHz, CDCl3): δ7.55–7.51 (m, 2H), 7.48–7.43 (m, 2H), 7.38–7.31 (m, 2H), 7.25–7.21 (m, 2H),7.14–7.08 (m, 1H), 7.07–7.02 (m, 4H), 2.38 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ 157.2, 156.5, 137.6, 136.8, 136.2, 129.8, 129.5, 128.2, 126.7,123.3, 119.0, 118.9, 21.1 ppm. IR (KBr, neat): 3057, 1590, 1491, 1281, 1172,812, 781, 748, 692, 484 cm -1HRMS (ESI, m / z): [M+H] + calcd for C 19 H 17 O + :261.1274, found: 261.1271.

[0143] Compound 3k was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as eluent. The yield was 50% (63.7 mg), and the product was a yellow oil. 1 H NMR (400 MHz, CDCl3): δ7.55–7.50 (m, 2H), 7.50–7.45 (m, 2H), 7.24 (d, J = 7.9 Hz, 2H), 6.99 (d, J =8.7 Hz, 2H), 3.92–3.86 (m, 4H), 3.25–3.18 (m, 4H), 2.40 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ 150.3, 137.9, 136.2, 132.7, 129.4, 127.6, 126.4, 115.8,66.9, 49.2, 21.0 ppm. IR (KBr, neat): 2964, 2856, 1607, 1502, 1448, 1229,1122, 1067, 924, 808, 507, 419 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 17 H 20 NO + : 254.1539, found: 254.1541.

[0144] Compound 3l was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 50:1). The yield was 73% (120.1 mg), and the product was a white solid. 1H NMR (400 MHz, CDCl3): δ 7.86 (dd, J = 5.5, 3.1 Hz, 2H), 7.70 (dd, J = 5.5, 3.0 Hz, 2H), 7.57–7.49 (m, 4H), 7.46 (d, J = 8.2 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 4.89 (s, 2H), 2.39 (s,3H) ppm. 13 IR (KBr, neat):3028, 1769, 1703, 1449, 1397, 1352, 1086, 937, 797, 716, 529 cm -1 HRMS (ESI,m / z): [M+H] + calcd for C 22 H 18 NO2 + : 328.1332, found: 328.1335.

[0145] Compound 3m was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 50:1) as eluent. The yield was 62% (88.8 mg) as a white solid. 1 H NMR (400 MHz, CDCl3): δ 8.51(d, J = 2.4 Hz, 1H), 8.37–8.31 (m, 1H), 7.94–7.89 (m, 1H), 7.70 (ddt, J =8.5, 7.1, 1.6 Hz, 1H), 7.58–7.53 (m, 2H), 7.53–7.45 (m, 2H), 7.39–7.33 (m,1H), 7.26 (d, J = 8.4 Hz, 2H), 2.39 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ177.2, 156.1, 155.3, 137.5, 136.9, 136.4, 134.7, 133.4, 129.6, 126.8, 126.7,124.1, 123.9, 121.8, 121.7, 118.4, 117.9, 21.1 ppm. IR (KBr, neat): 2919,1667, 1616, 1482, 1464, 1338, 1148, 882, 811, 756, 509 cm -1 HRMS (ESI, m / z):[M+H] + calcd for C 20 H 15 O2 + : 287.1067, found: 287.1072.

[0146] Compound 3n was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 50:1) as eluent. The yield was 45% (92.7 mg), and the product was a white solid. 1 H NMR (400 MHz, CDCl3): δ 8.17 (dd, J= 4.2, 2.1 Hz, 1H), 7.61–7.55 (m, 1H), 7.54–7.50 (m, 2H), 7.48–7.45 (m, 2H), 7.24 (d, J = 8.5 Hz, 2H), 7.04–6.99 (m, 4H), 6.98–6.94 (m, 2H), 6.90–6.85 (m,1H), 6.77 (d, J = 8.4 Hz, 1H), 5.66–5.58 (m, 1H), 4.22 (dd, J = 9.9, 5.3 Hz,1H), 4.10 (dd, J = 9.8, 4.8 Hz, 1H), 2.40 (s, 3H), 1.51 (d, J = 6.4 Hz, 3H)ppm. 13C NMR (100 MHz, CDCl3): δ 163.1, 157.8, 155.3, 150.2, 146.7, 138.7,137.7, 136.6, 135.5, 129.4, 128.1, 126.7, 120.8, 117.8, 116.7, 115.8, 111.7,71.0, 69.3, 21.0, 17.0 ppm. IR (KBr, neat): 2831, 1610, 1529, 1491, 1360,1230, 1167, 948, 819, 758 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 27 H 26 NO3 + :412.1907, found: 412.1903.

[0147] Example 5

[0148] Referring to general preparation method 4, the compound shown in Formula I is (1a), respectively with the compound shown in Formula II (2b) (2c) (2d) (2e) (2f) (2g) (2h) (2i) (2j) (2k) (2l) (2m) (2n) (2o) (2p) reaction prepared to obtain (4b) (4c) (4d) (4e) (4f) (4g) (4h) (4i) (4j) (4k) (4l) (4m) (4n) (4o) (4p) The reaction was carried out under a nitrogen atmosphere using 1a (0.5 mmol), 2b-p (1.5 mmol), Pd(PPh3)2Cl2 (5 mol%), SPhos (10 mol%), B2(OH)4 (0.75 mmol) and Na2CO3 (1.5 mmol) in anhydrous methanol (2 mL) as solvent, and at 60 °C for 6 hours.

[0149] Compound 4b was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 100:1). The product was a white solid, weighing 73.3 mg, in 70% yield. 1 H NMR (400 MHz, CDCl3): δ7.71–7.67 (m, 2H), 7.64 (d, J = 8.6 Hz, 2H), 7.56–7.52 (m, 2H), 7.03–6.98 (m,2H), 3.86 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ 160.1, 145.1, 132.5, 131.4,128.3, 127.1, 119.1, 114.5, 110.0, 55.3 ppm. IR (KBr, neat): 3069, 2223,1605, 1494, 1294, 1176, 854, 824, 536, 452 cm -1 HRMS (ESI, m / z): [M+H] + calcdfor C 14 H 12 NO + : 210.0913, found: 210.0912.

[0150] Compound 4c was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as eluent. Yield: 51% (58.9 mg), as a yellow solid. 1 H NMR (400 MHz, CDCl3): δ 8.29–8.23 (m,2H), 7.71–7.66 (m, 2H), 7.60–7.56 (m, 2H), 7.04–7.00 (m, 2H), 3.87 (s, 3H)ppm. 13C NMR (100 MHz, CDCl3): δ 160.4, 147.2, 146.5, 131.0, 128.5, 127.0,124.1, 114.6, 55.4 ppm. IR (KBr, neat): 3061, 2836, 1601, 1509, 1487, 1343,1251, 1186, 1033, 1015, 757, 492 cm -1 HRMS (ESI, m / z): [M+H] + calcd forC 13 H 12 NO3 + : 230.0812, found: 230.0814.

[0151] Compound 4d was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as eluent. The product was a yellow solid, weighing 55.0 mg, in 45% yield. 1 H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.60–7.55 (m, 2H), 7.02–6.97 (m, 2H), 3.93 (s, 3H), 3.86 (s, 3H)ppm. 13 C NMR (100 MHz, CDCl3): δ167.0, 159.8, 145.1, 132.3, 130.1, 128.3, 128.2, 126.4, 114.3, 55.3, 52.0ppm. IR (KBr, neat): 3079, 2842, 1717, 1601, 1530, 1433, 1290, 1198, 1112,960, 833, 772, 505 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 15 H 15 O3 + : 243.1016,found: 243.1017.

[0152] Compound 4e was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. The product was a yellow solid, weighing 91.6 mg, in 68% yield. 1 H NMR (400 MHz, CDCl3): δ 7.56–7.52 (m, 2H), 7.51–7.46 (m, 2H), 7.26 (s, 1H), 7.24 (s, 1H), 7.00–6.95(m, 2H), 3.84 (s, 3H) ppm. 19 F NMR (376 MHz, CDCl3): δ -57.72 (s, 3F) ppm. 13 CNMR (100 MHz, CDCl3): δ 159.4, 148.2, 139.6, 132.3, 128.1, 127.9, 121.2,120.5 (q, J = 255.3 Hz), 114.3, 55.3. ppm. IR (KBr, neat): 2967, 2845, 1609,1499, 1465, 1292, 1210, 1158, 1036, 828, 795, 508 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 14 H 12 F3O2 + : 269.0784, found: 269.0787.

[0153] Compound 4f was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. 77.3 mg of a white solid was obtained, with a yield of 61%. 1 H NMR (400 MHz, CDCl3): δ 7.70–7.64(m, 4H), 7.58–7.53 (m, 2H), 7.04–6.99 (m, 2H), 3.87 (s, 3H) ppm. 19 F NMR (376MHz, CDCl3): δ -62.16 (s, 3F) ppm. 13C NMR (100 MHz, CDCl3): δ 159.8, 144.2,132.1, 128.6 (q, J = 32.4 Hz), 128.3, 126.8, 125.6 (q, J = 3.8 Hz), 124.4 (q,J = 271.8 Hz), 114.4, 55.3 ppm. IR (KBr, neat): 2966, 2845, 1604, 1533, 1502,1402, 1335, 1276, 1173, 1122, 1075, 1034, 825, 704 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 14 H 12 F3O + : 253.0835, found: 253.0838.

[0154] 4 g of the compound was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as the eluent. The product was a white solid, weighing 70.3 mg, with a yield of 70%. 1 H NMR (400 MHz, CDCl3): δ 7.52–7.45 (m, 4H), 7.13–7.07 (m, 2H), 7.00–6.95 (m, 2H), 3.85 (s, 3H) ppm. 19 F NMR (376 MHz, CDCl3): δ -116.60 (s, 1F) ppm. 13 C NMR (100 MHz, CDCl3): δ162.1 (d, J = 245.4 Hz), 159.1, 136.9 (d, J = 3.2 Hz), 132.8, 128.2 (d, J =8.0 Hz), 128.0, 115.5 (d, J = 21.2 Hz), 114.2, 55.3 ppm. IR (KBr, neat):2967, 2843, 1607, 1496, 1456, 1291, 1236, 1181, 1038, 1012, 827, 817, 540,511 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 13 H12 FO + : 203.0867, found:203.0866.

[0155] The compound was purified by silica gel column chromatography after 4 hours, using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. The yield was 76% (82.6 mg), and the product was a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.53–7.46 (m, 4H), 7.41–7.37 (m, 2H), 7.01–6.96 (m, 2H), 3.86 (s, 3H) ppm. 13 C NMR(100 MHz, CDCl3): δ 159.3, 139.2, 132.6, 132.4, 128.8, 128.0, 127.9, 114.3,55.3 ppm. IR (KBr, neat): 3061, 2839, 1606, 1523, 1485, 1290, 1263, 1179,1011, 821, 736, 499 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 13 H 12 ClO + :219.0571, found: 219.0570.

[0156] Compound 4i was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as eluent. The yield was 77% (93.5 mg), and it was a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.52–7.47(m, 2H), 7.10 (dd, J = 8.2, 2.1 Hz, 1H), 7.07 (d, J = 2.1 Hz, 1H), 6.99–6.95(m, 2H), 6.93 (d, J = 8.2 Hz, 1H), 3.95 (s, 3H), 3.92 (s, 3H), 3.85 (s, 3H)ppm. 13C NMR (100 MHz, CDCl3): δ 158.7, 149.0, 148.1, 133.9, 133.6, 127.8,118.8, 114.1, 111.4, 110.1, 55.9, 55.8, 55.3 ppm. IR (KBr, neat): 2970, 2928,1604, 1507, 1439, 1281, 1243, 1145, 1051, 837, 569 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 15 H 17 O3 + : 245.1172, found: 245.1173.

[0157] Compound 4j was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 50:1). The yield was 79% (108.8 mg), and the product was a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 8.5 Hz, 2H), 6.97 (d, J = 8.6 Hz, 2H), 6.74 (s, 2H), 3.92 (s, 6H), 3.89 (s, 3H), 3.85 (s, 3H) ppm. 13 C NMR (100 MHz, CDCl3): δ 159.1, 153.4,137.1 136.9, 133.9, 128.1, 114.1, 104.0, 60.9, 56.1, 55.3 ppm. IR (KBr,neat): 3065, 2833, 1608, 1588, 1502, 1462, 1244, 1180, 1130, 816, 591 cm -1 .HRMS (ESI, m / z): [M+H] + calcd for C 16 H 19 O4 + : 275.1278, found: 275.1276.

[0158] Compound 4k was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. The product was a white solid, weighing 82.9 mg, in 84% yield. 1 H NMR (400 MHz, CDCl3): δ 7.56–7.51 (m, 2H), 7.39–7.29 (m, 3H), 7.14 (d, J = 7.3 Hz, 1H), 6.98 (d, J= 6.7 Hz, 2H), 3.86 (s, 3H), 2.42 (s, 3H)ppm. 13 C NMR (100 MHz, CDCl3): δ159.0, 140.8, 138.3, 133.9, 128.6, 128.1, 127.5, 127.4, 123.8, 114.1, 55.3,21.5 ppm. IR (KBr, neat): 2955, 2838, 1606, 1516, 1486, 1286, 1252, 1185,1029, 837, 786, 696, 577, 438 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 14 H 15 O + :199.1117, found: 199.1120.

[0159] Compound 4l was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. The product was a white solid, weighing 79.5 mg, in 66% yield. 1 H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 2.2 Hz, 1H), 7.52 (dd, J = 9.7, 2.1 Hz, 3H), 7.46 (d, J = 8.4Hz, 2H), 7.01–6.96 (m, 2H), 3.86 (s, 3H), 1.38 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ 158.9, 149.6, 137.9, 133.6, 128.0, 126.3, 125.7, 114.1, 55.3, 34.4, 31.4 ppm. IR (KBr, neat): 2959, 2835, 1604, 1517, 1499, 1363, 1289, 1248,1184, 1038, 822, 528 cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 17 H 21 O + : 241.1587, found: 241.1580.

[0160] Compound 4m was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 200:1). The yield was 93% (105.1 mg) as a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.59–7.54 (m, 2H), 7.32 (t, J = 7.4 Hz, 1H), 7.02–6.97 (m, 2H), 6.97–6.91 (m, 2H), 6.74 (dd, J = 8.3, 2.6 Hz, 1H), 3.87 (s, 3H), 3.02 (s, 6H) ppm. 13 C NMR (100MHz, CDCl3): δ 159.0, 150.9, 141.8, 134.7, 129.3, 128.3, 115.5, 114.0, 111.2,111.1, 55.3, 40.7 ppm. IR (KBr, neat): 2925, 2800, 1601, 1568, 1496, 1350,1275, 1243, 1178, 1027, 990, 824, 575 cm -1 HRMS (ESI, m / z): [M+H] + calcd forC 15 H 18 NO + : 228.1383, found: 228.1388.

[0161] Compound 4n was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 200:1) as eluent. The product was a white solid, weighing 87.4 mg, with a yield of 75%. 1 H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 2.2 Hz, 1H), 7.93–7.84 (m, 3H), 7.73 (dd, J = 8.5, 1.9 Hz, 1H), 7.70–7.65 (m, 2H), 7.53–7.44 (m, 2H), 7.07–7.01 (m, 2H), 3.88 (s, 3H)ppm. 13 C NMR (100 MHz, CDCl3): δ 159.2, 138.2, 133.8, 133.6, 132.3, 128.4,128.3, 128.0, 127.6, 126.2, 125.6, 125.4, 125.0, 114.3, 55.4 ppm. IR (KBr,neat): 3050, 2838, 1607, 1521, 1282, 1254, 1184, 1038, 814, 741, 476 cm -1 .HRMS (ESI, m / z): [M+H] + calcd for C 17 H 15 O + : 235.1117, found: 235.1120.

[0162] Compound 4o was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluent (petroleum ether / EtOAc = 200:1). The yield was 79% (108.8 mg), and the product was a white solid. 1 H NMR (400 MHz, CDCl3): δ 8.10(dd, J = 1.9, 0.7 Hz, 1H), 8.00 (m, 1H), 7.67–7.58 (m, 5H), 7.49 (m, 1H),7.37 (td, J = 7.5, 1.0 Hz, 1H), 7.06–7.01 (m, 2H), 3.88 (s, 3H) ppm. 13C NMR(100 MHz, CDCl3): δ 159.0, 156.6, 155.4, 136.1, 133.9, 128.4, 127.2, 126.3,124.6, 124.3, 122.7, 120.6, 118.7, 114.2, 111.71, 111.66, 55.3 ppm. IR (KBr,neat): 3052, 2836, 1607, 1519, 1472, 1447, 1273, 1207, 1183, 811, 744, 526cm -1 HRMS (ESI, m / z): [M+H] + calcd for C 19 H 15 O2 + : 275.1067, found: 275.1068.

[0163] Compound 4p was purified by silica gel column chromatography using petroleum ether / ethyl acetate (petroleum ether / EtOAc = 100:1) as eluent. The yield was 56% (96.3 mg), and it was a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.60–7.54(m, 6H), 7.16–7.04 (m, 2H), 7.02–6.96 (m, 2H), 6.71 (d, J = 2.2 Hz, 2H), 6.42(t, J = 2.2 Hz, 1H), 3.86 (s, 3H), 3.85 (s, 6H) ppm. 13 C NMR (100 MHz, CDCl3): δ 160.9, 159.2, 140.0, 139.4, 135.5, 133.1, 128.7, 128.3, 127.9, 127.0,126.8, 114.2, 104.5, 99.9, 55.34, 50.30 ppm. IR (KBr, neat): 2987, 2901,1406, 1394, 1242, 1074, 892, 689, 433 cm -1 HRMS (ESI, m / z): [M+H] + calcd forC 23 H 23 O3 + : 347.1642, found: 347.1643.

[0164] Example 6

[0165] Compound 3a was prepared using the ligands listed in Table 2, following general preparation method 4.

[0166]

[0167] Table 2 Using different ligands a

[0168]

[0169]

[0170] a. The reaction was carried out under a nitrogen atmosphere, using 1a (0.5 mmol), 2a (0.75 mmol), Pd(PPh3)2Cl2 (5 mol%), ligand (10 mol%), B2Pin2 (0.75 mmol), and K3PO4 (1.5 mmol) as reagents, and anhydrous methanol (2 mL) as solvent, at 60 °C for 12 h. b. The yield was determined by NMR analysis of the post-treated crude reaction mixture, using 1,3,5-trimethoxybenzene as an internal standard.

[0171] Example 7

[0172] Referring to the general preparation method 4, compound 3a was prepared by reacting compound 1a with different equivalents of compound 2a in Table 3.

[0173]

[0174] Table 2. Compound 2a with different equivalents a

[0175]

[0176] a) The reaction was carried out under a nitrogen atmosphere using 1a (0.5 mmol), 2a (X mmol), Pd(PPh3)2Cl2 (5 mol%), SPhos (10 mol%), B2Pin2 (0.75 mmol), and K3PO4 (1.5 mmol) in anhydrous methanol (2 mL) at 60 °C for 12 h. b) The yield was determined by NMR analysis of the post-treated crude reaction mixture, using 1,3,5-trimethoxybenzene as an internal standard.

[0177] Example 8

[0178] Compound 3a was prepared using different solvents listed in Table 4, following the general preparation method 4.

[0179]

[0180] Table 4 Different solvents a

[0181]

[0182] a) The reaction was carried out under a nitrogen atmosphere using 1a (0.5 mmol), 2a (1.5 mmol), Pd(PPh3)2Cl2 (5 mol%), SPhos (10 mol%), B2Pin2 (0.75 mmol), and K3PO4 (1.5 mmol) in anhydrous solvent (2 mL) at 60 °C for 12 h. b) The yield was determined by NMR analysis of the post-treated crude reaction mixture, using 1,3,5-trimethoxybenzene as an internal standard.

[0183] Example 9

[0184] Compound 3a was prepared using different reducing agents listed in Table 5, following the general preparation method 4.

[0185]

[0186] Table 5. Using different reducing agents a

[0187]

[0188] a) The reaction was carried out under a nitrogen atmosphere using 1a (0.5 mmol), 2a (1.5 mmol), Pd(PPh3)2Cl2 (5 mol%), SPhos (10 mol%), reducing agent (0.75 mmol), and K3PO4 (1.5 mmol) in anhydrous methanol (2 mL) at 60 °C for 12 h. b) The yield was determined by NMR analysis of the post-treated crude reaction mixture, using 1,3,5-trimethoxybenzene as an internal standard.

[0189] Example 10

[0190] Compound 3a was prepared using different basic reagents as shown in Table 6, following the general preparation method 4.

[0191]

[0192] Table 6 Different alkaline reagents a

[0193]

[0194] a) The reaction was carried out under a nitrogen atmosphere using 1a (0.5 mmol), 2a (1.5 mmol), Pd(PPh3)2Cl2 (5 mol%), SPhos (10 mol%), B2(OH)4 (0.75 mmol), and base (1.5 mmol) in anhydrous methanol (2 mL) at 60 °C for 12 h. b) The yield was determined by NMR analysis of the post-treated crude reaction mixture, using 1,3,5-trimethoxybenzene as an internal standard.

[0195] Example 11

[0196]

[0197] In a 50 mL single-necked round-bottom flask, p-cresol (0.5407 g, 5 mmol, 1 equivalent) was dissolved in dichloromethane (20 mL) and cooled to 0 °C under nitrogen protection. Triethylamine (1.5179 g, 15 mmol, 3.0 equivalent) and p-toluenesulfonyl chloride (TsCl, 0.9533 g, 5 mmol, 1.0 equivalent) were then added. The reaction mixture was heated to room temperature and stirred for 12 hours. The reaction was then quenched by adding saturated ammonium chloride solution (10 mL) and water (20 mL) sequentially, followed by extraction with dichloromethane (20 mL × 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. This crude product was purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to give product 2a'.

[0198] Example 12

[0199]

[0200] In a 50 mL single-necked round-bottom flask, p-cresol (0.5407 g, 5 mmol, 1 equivalent) was dissolved in dichloromethane (DCM, 20 mL), cooled to 0 °C under nitrogen protection, and then triethylamine (Et3N, 1.5179 g, 15 mmol, 3.0 equivalent) and methanesulfonic anhydride (1.0451 g, 6 mmol, 1.2 equivalent) were added. The reaction mixture was heated to room temperature and stirred for 12 hours, followed by quenching the reaction with saturated ammonium chloride solution (10 mL) and water (20 mL), and extraction with dichloromethane (20 mL × 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to give product 2a''.

[0201] Example 13

[0202]

[0203] In a 50 mL single-necked round-bottom flask, p-cresol (0.5407 g, 5 mmol, 1 equivalent) was dissolved in anhydrous dichloromethane (10 mL) and cooled to 0 °C. Pyridine (0.7910 g, 10 mmol, 2.0 equivalent) was then added, followed by trifluoromethanesulfonic anhydride (1.6928 g, 6 mmol, 1.2 equivalent). The reaction mixture was heated to room temperature and stirred for 2 hours, then quenched successively with saturated ammonium chloride solution (10 mL) and water (20 mL), and extracted with dichloromethane (20 mL × 3). The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. This crude product was purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to give product 2a'''.

[0204] Example 14

[0205]

[0206] In a dried 50 mL flask equipped with a magnetic stirrer, the air inside the flask was purged three times with nitrogen. Then, the following solutions were added sequentially: 1a (1.1815 g, 2.5 mmol, 1.0 equivalent), 2a (2.9265 g, 7.5 mmol, 3.0 equivalent), Pd(PPh3)2Cl2 (0.0875 g, 0.125 mmol, 5 mol%), SPhos (0.1025 g, 0.25 mmol, 10 mol%), B2(OH)4 (0.3375 g, 3.75 mmol, 1.5 equivalent), and Na2CO3 (0.7950 g, 7.5 mmol, 3.0 equivalent). Anhydrous methanol (10 mL) was then added, and the reaction mixture was stirred at 60 °C for 6 hours. After the reaction was completed, 20 mL of saturated NH4Cl solution and 50 mL of water were added sequentially to quench the reaction, and the mixture was extracted with ethyl acetate (60 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether) to finally obtain product 3a (0.4562 g, yield 92%).

[0207] Example 15

[0208]

[0209] Under a nitrogen atmosphere, 5a (0.5 mmol, 1 equivalent), thiaanthracene-S-oxide (TTSO, 0.13 g, 0.55 mmol, 1.1 equivalent), and anhydrous dichloromethane (DCM, 2.0 mL) were added sequentially to a dried Schlenk tube equipped with a magnetic stirrer. The reaction mixture was cooled to -40 °C, and trifluoromethanesulfonic anhydride (Tf₂O, 0.1692 g, 0.6 mmol, 1.2 equivalent) was added dropwise. The reaction mixture was stirred at -40 °C for 30 min, followed by stirring at room temperature for 12 h, and the solvent was removed under reduced pressure. Next, aryl nonafluorobutyrate sulfonate 2a (0.5853 g, 1.5 mmol, 3 equivalents), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), B2(OH)4 (0.0672 g, 0.75 mmol, 1.5 equivalents), and Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalents) were added to the tube. Anhydrous methanol (MeOH, 2 mL) was then added, and the reaction mixture was stirred at 60 °C for 6 hours. The reaction was then quenched with saturated ammonium chloride solution (10 mL) and water (20 mL), and extracted with ethyl acetate (EtOAc, 20 mL × 3). The organic layers were combined, washed successively with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product; then purified by silica gel column chromatography (using ethyl acetate / petroleum ether as eluent) to obtain product 3a (80.1 mg, yield 81%).

[0210] Following this method, the following preparations were obtained respectively. (68.2 mg, yield 53%) (94.9 mg, yield 88%) (111.8 mg, yield 68%).

[0211] Example 16

[0212]

[0213] In a dried Schlenk tube equipped with a magnetic stir bar, phenolic compound 6a (1.5 mmol, 3 equivalents) and anhydrous dichloromethane (2 mL) were added sequentially, and the system was cooled to 0 °C. Triethylamine (0.3795 g, 3.75 mmol, 7.5 equivalents) and nonafluorobutyryl fluoride (0.6797 g, 2.25 mmol, 4.5 equivalents) were then added. The reaction mixture was heated to room temperature and stirred for 2 hours, followed by removal of the solvent under reduced pressure. Next, thiaanthracite 1a (0.2363 g, 0.5 mmol, 1 equivalent), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), B2(OH)4 (0.0672 g, 0.75 mmol, 1.5 equivalent), and Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalent) were added to the tube. Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at 60 °C for 6 hours. After the reaction was complete, a saturated ammonium chloride solution (10 mL) and water (20 mL) were added sequentially to quench the reaction, and extraction was performed with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluting with ethyl acetate / petroleum ether) to finally obtain product 3a (82.1 mg, yield 83%).

[0214] Following this method, the following preparations were obtained respectively. (4b: 80.9 mg, yield 77%) (81.9 mg, yield 75%).

[0215] Example 17

[0216]

[0217] In a dried, sealed tube equipped with a magnetic stirrer, nitrogen purging is performed three times. Arylthiazine anthracene salt 1a (0.2363 g, 0.5 mmol, 1 equivalent), aryl pseudohalides (p-toluenesulfonate 2a', 0.3935 g, 1.5 mmol, 3 equivalents; methyl p-toluenesulfonate 2a'', 0.2793 g, 1.5 mmol, 3 equivalents; trifluoromethyl p-toluenesulfonate 2a''', 0.3603 g, 1.5 mmol, 3 equivalents; aryl nonafluorobutyrate 2a, 0.5853 g, 1.5 mmol, 3 equivalents), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), B2(OH)4 (0.0672 g, ... 0.75 mmol (1.5 equivalents) and Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalents). Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at 60 °C for 6 hours. After the reaction was complete, saturated NH4Cl solution (10 mL) and water (20 mL) were added sequentially to quench the reaction, and extraction was performed with ethyl acetate (20 mL × 3). The combined organic phases were washed with saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether) to finally obtain product 3a [For substrates 2a' and 2a'', the crude product was purified using 1,3,5-trimethoxybenzene as an internal standard]. 1 1H NMR analysis showed that the yield of product 3a was less than 5%; for substrate 2a''', the yield of product 3a was 91% (90.5 mg); for substrate 2a, product 3a was obtained in 98% yield (97.5 mg).

[0218] Example 18

[0219]

[0220] Nitrogen gas was introduced into a dried, sealed tube equipped with a magnetic stir bar (replaced three times). Subsequently, arylthianonium salt 1a (0.2363 g, 0.5 mmol, 1 equivalent), aryl nonafluorobutyrate sulfonate 2a (0.5853 g, 1.5 mmol, 3 equivalents), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), B2(OH)4 (0.0672 g, 0.75 mmol, 1.5 equivalents), free radical scavengers (BHT: 0.3305 g, 1.5 mmol, 3 equivalents; 1,1-diphenylethylene: 0.2704 g, 1.5 mmol, 3 equivalents) and Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalents) were added to the tube. Next, anhydrous methanol (2 mL) was added, and the reaction mixture was stirred at 60 °C for 6 hours. The reaction was then quenched with saturated NH₄Cl solution (10 mL) and water (20 mL), and extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed successively with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to obtain the crude product. This crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether) to finally obtain product 3a (BHT system: 83.8 mg, 85%; 1,1-diphenylethylene system: 82.8 mg, 83%).

[0221] Example 19

[0222]

[0223] Nitrogen gas was purged (three times) into a dried, sealed tube equipped with a magnetic stirrer. Then, (4-methoxyphenyl)boronic acid 7 (0.0760 g, 0.5 mmol, 1 equivalent), aryl nonafluorobutyrate sulfonate 2a (0.5853 g, 1.5 mmol, 3 equivalents), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), and Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalents) were added sequentially. Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at 60 °C for 6 hours. After the reaction was complete, the reaction was quenched sequentially with saturated NH4Cl solution (10 mL) and water (20 mL), and extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether) to finally obtain product 3a (96.2 mg, yield 97%).

[0224] Example 20

[0225]

[0226] In a dried, sealed tube equipped with a magnetic stirrer, nitrogen purging was performed three times. Then, arylthianonium salt 1a (0.2363 g, 0.5 mmol, 1 equivalent), p-tolueneboronic acid 8 (0.2039 g, 1.5 mmol, 3 equivalents), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), and Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalents) were added sequentially. Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at 60 °C for 6 hours. After the reaction was complete, saturated NH4Cl solution (10 mL) and water (20 mL) were added sequentially to quench the reaction, and extraction was performed with ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluting with ethyl acetate / petroleum ether) to finally obtain product 3a (83.3 mg, yield 84%).

[0227] Example 21

[0228]

[0229] Nitrogen gas was purged (three times) into a dried, sealed tube fitted with a magnetic stirrer. Then, arylthianthaneonium salt 1a (0.2363 g, 0.5 mmol, 1 equivalent), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalents), and B2(OH)4 (0.0672 g, 0.75 mmol, 1.5 equivalents) were added sequentially. Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at room temperature for 30 minutes. Pinarol (0.2954 g, 2.5 mmol, 5 equivalents) was then added, and the mixture was stirred for 10 minutes at room temperature. After the reaction was complete, water (20 mL) was added to quench the reaction, and the mixture was extracted with ethyl acetate (20 mL × 3). The organic phases were combined, washed successively with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether) to finally obtain product 9 (93.5 mg, yield 80%).

[0230] Compound 9, 1 H NMR (400 MHz, CDCl3): δ 7.79–7.70 (m, 2H), 6.95–6.85 (m,2H), 3.83 (s, 3H), 1.33 (s, 12H) ppm. 13 C NMR (100 MHz, CDCl3): δ 162.1,136.5, 113.3, 83.5, 55.1, 24.8 ppm. IR (KBr, neat): ν = 2980, 1592, 1359,1248, 1143, 1089, 1030, 862, 652cm -1 HRMS (ESI, m / z): [M+H] + calcd forC 13 H 20 BO3 + : 235.1500, found: 235.1504.

[0231] Example 22

[0232]

[0233] Nitrogen gas was purged (three times) into a dried, sealed tube fitted with a magnetic stirrer. Then, arylnonafluorobutyrate sulfonate 2a (0.5853 g, 1.5 mmol, 1 equivalent), Pd(PPh3)2Cl2 (0.0179 g, 0.0255 mmol, 1.7 mol%), SPhos (0.0203 g, 0.0495 mmol, 3.3 mol%), Na2CO3 (0.1590 g, 1.5 mmol, 1 equivalent), and B2(OH)4 (0.0672 g, 0.75 mmol, 0.5 equivalent) were added sequentially. Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at room temperature for 30 minutes. Pinarol (0.3013 g, 2.55 mmol, 1.7 equivalents) was then added, and the mixture was stirred for 10 minutes at room temperature. After the reaction was complete, water (20 mL) was added to quench the reaction, and the mixture was extracted with ethyl acetate (20 mL × 3). The combined organic phases were washed successively with saturated brine, dried over anhydrous sodium sulfate, and finally concentrated under reduced pressure. The crude product was analyzed using 1,3,5-trimethoxybenzene as an internal standard. 1 1H NMR analysis showed that the yield of product 10 was less than 5%.

[0234] Example 23

[0235]

[0236] Nitrogen gas was purged (three times) into a dried, sealed tube equipped with a magnetic stirrer. Then, arylthianonium salt 1a (0.2363 g, 0.5 mmol, 1 equivalent), arylnonafluorobutyrate sulfonate 2a (0.5853 g, 1.5 mmol, 3 equivalents), Pd(PPh3)2Cl2 (0.0175 g, 0.025 mmol, 5 mol%), SPhos (0.0205 g, 0.05 mmol, 10 mol%), Na2CO3 (0.1590 g, 1.5 mmol, 3 equivalents), and B2(OH)4 (0.0672 g, 0.75 mmol, 1.5 equivalents) were added sequentially. Anhydrous methanol (2 mL) was then added, and the reaction mixture was stirred at 60 °C for 1 minute. Pinarol (0.2954 g, 2.5 mmol, 5 equivalents) was then added, and the mixture was stirred at 60 °C for 1 minute. The reaction was then quenched with water (20 mL) and extracted with ethyl acetate (20 mL × 3). The combined organic phases were washed successively with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. This crude product was purified by silica gel column chromatography (eluent: ethyl acetate / petroleum ether) to give product 9 (86.1 mg, 74% yield). Furthermore, the crude product was analyzed using 1,3,5-trimethoxybenzene as an internal standard. 1 1H NMR analysis showed that (before silica gel column chromatography purification) the yield of product 10 in the reaction was less than 5%.

Claims

1. A method for preparing a biaryl compound, namely, 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 catalyst, a ligand, a reducing agent, and a basic reagent to form a compound of formula III. ， in, R1 and R2 are each independently selected from C 1-6 Alkyl, halogen, -CN, -NO2, -OR4, -COOR4, -SR4, -NR5R6, 6- to 10-membered aryl, 5- to 10-membered heterocyclic, C2-C6 alkenyl, or two adjacent R1 or two adjacent R2 together with the attached carbon atom to form a 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 cycloalkyl, 5- to 10-membered heterocyclic groups, wherein the C 1-6 Alkyl, 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 The cycloalkyl group, the 5- to 10-membered heterocyclic group, and the C2-C6 alkenyl group are each optionally surrounded by one or more groups selected from oxo, halogen, cyano, amino, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Substituted by alkoxy groups or R7 substituents; R3 is selected from halogenated C 1-6 alkyl; R4 is selected from H and C. 1-6 Alkyl, 6- to 8-membered aryl, 5- to 8-membered heteroaryl, C 3-8 cycloalkyl, 5- to 8-membered heterocyclic groups, wherein the C 1-6 Alkyl, 6- to 8-membered aryl, 5- to 8-membered heteroaryl, C 3-8 The cycloalkyl group and the 5- to 8-membered heterocyclic group are each optionally surrounded by one or more groups selected from halogen, cyano, amino, C 1-6 Alkyl, Halogenated C 1-6 Alkyl groups and R8 substituents are used to replace them; R5 and R6 are each independently selected from H and C. 1-6 Alkyl, 6 to 10 aryl; R7 is selected from 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 Cycloalkyl, 5- to 10-membered heterocyclic groups, said 6- to 10-membered aryl, 5- to 10-membered heteroaryl, C 3-10 Cycloalkyl groups, 5 to 10-membered heterocyclic groups optionally surrounded by one or more groups selected from oxo, halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Substituted with alkoxy or 6- to 8-membered aryl groups; R8 is selected from C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, the C 1-6 Alkoxy, halogenated C 1-6 Alkyl groups are optionally surrounded by one or more C16 groups. 1-6 Alkyl, Halogenated C 1-6 Alkyl groups and -OR7 substituents are used; n and m are each independently selected from 0, 1, 2, 3, 4, and 5.

2. The method according to claim 1, wherein the catalyst is selected from Pd(OAc)2, Pd(PPh3)4, Pd2(dba)3, Pd(P t Bu3)2, Pd(CH3CN)2Cl2, Pd(PPh3)2Cl2, preferably Pd(PPh3)2Cl2; further, the amount of the catalyst is 1% to 15% of the molar amount of the compound of formula I, preferably 10%.

3. The method according to claims 1 and 2, wherein the ligand is selected from... , , , , , , , , , Preferred Furthermore, the amount of the ligand used is 1% to 15% of the molar amount of the compound of Formula I, preferably 10%.

4. The method according to any one of claims 1 to 3, wherein the reducing agent is selected from B2Pin2 and B2(OH)4, preferably B2(OH)4; further, the amount of the reducing agent is 1-5 equivalents of the molar amount of the compound of formula I, preferably 1.5 equivalents.

5. The method according to any one of claims 1 to 4, wherein the alkaline reagent is selected from K3PO4, K2CO3, KOH, Cs2CO3, Na2CO3, t BuOK, CsF, Et3N, preferably Na2CO3; further, the amount of alkaline reagent is 1-5 equivalents of the molar amount of compound I, preferably 3.0 equivalents.

6. The method according to any one of claims 1 to 5, further comprising a solvent selected from MeOH, DMF, DMA, DMSO, NMP, THF, 1,4-dioxane, ... t BuOMe, MeCN, and EtOH are preferred, with MeOH being the preferred choice.

7. The method according to any one of claims 1-6, wherein the method is carried out at 0-80°C, preferably 60°C.

8. The method according to any one of claims 1-7, further comprising the step of converting formula I' into formula I. , where R1 and n are as defined in claim 1.

9. The method according to any one of claims 1-7, further comprising the step of converting formula II' into formula II. , where R2 and m are as defined in claim 1.

10. The method according to any one of claims 1-9, wherein the compound represented by formula III is selected from: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。

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