Ligand as well as preparation method and application thereof

Abstract

The invention discloses a ligand as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. The ligand provided by the invention has a structural formula shown in the specification, in the structural formula, R is the same or different and independently represents one of phenyl, p-methoxyphenyl, cyclohexyl and 3, 5-bis (trifluoromethyl) phenyl; r'are the same or different and independently represent one of C1-4 alkyl, phenyl and tolyl. The ligand provided by the invention can be matched with Ir to form a catalyst with a catalytic boronation effect on C-H, and the catalyst is wide in substrate range, mild in reaction condition and high in product yield. The invention also provides a preparation method and application of the ligand.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a ligand, its preparation method, and its application. Background Technology

[0002] Organoboron compounds in pharmaceuticals (related drug structures such as...) Figure 1 Organoboron compounds have been widely applied in fields such as materials science and synthetic chemistry. The research on hydroboration based on unsaturated carbon-carbon bonds (Brown, 1979) and the Suzuki-miyaura cross-coupling reaction (Suzuki, 2010) were awarded the Nobel Prizes, directly demonstrating the crucial role of organoboron compounds in advancing chemical synthesis and emphasizing the importance of developing new and efficient strategies for preparing organoboron compounds.

[0003] Among various methods for synthesizing organoboron compounds, the transition metal-catalyzed borylation reaction via the CH bond is a highly attractive and atom-economical strategy, capable of directly converting abundant hydrocarbon feedstocks into valuable boron-containing organic compounds. Although conventional techniques often involve C(sp...) 2 Significant progress has been made in the Ir-catalyzed borylation of C(sp)-H bonds, but C(sp) 3 Selective boronization of the C(sp)-H bond remains highly challenging. This is primarily due to the lack of a π-electron system in alkanes, which makes the C(sp)-H bond highly susceptible to π-electrons. 3 The C(sp)-H bond exhibits poor reactivity to metal-mediated activation. To address this challenge, suitable catalytic systems must be developed to achieve precise regioselectivity and realize the C(sp)-H bond activation. 3 Borylation reactions of )-H. A representative example developed by Hartwig's group shows that Ir(I) precursors coordinated with N,N-bident ligands can catalyze C(sp)-H induced hydride-directed reactions. 3 The 1H-bond boronization reaction occurs. In this system, the silyl group on the substrate undergoes ligand exchange with a boron-based ligand to generate the Ir(III)(N,N)Si(Bpin) structure, which serves as a highly efficient catalytic species. Besides L,L-type ligands, L,X-type bidentate ligands have also been developed for binding with Ir(I) catalytic precursors to form C(sp) catalytically active ligands. 3 The )-H borylation reaction catalyst can form two vacancy coordination sites at the iridium center to promote regioselective activation. For example, researchers such as Li and Xu reported a catalyst using Ir to catalyze C(sp) 3The )-H boronized system employs a nitrogen-boron-(N,B) bidentate ligand and an Ir precursor to form a specific catalyst. Researchers such as Smith and Clark introduced a nitrogen-silicon bidentate ligand to generate an intermediate species similar to bis(boron)Ir; thereby enabling the C(sp) of N,N-dicarboxamide to... 3 )-H borylation becomes possible. Furthermore, Chattopadhyay's group demonstrated that Ir complexes carrying pyridine-thiophene ligands can also promote the C(sp) of various aliphatic substrates directed by pyridine. 3 Boration of C(sp)-H bonds. Although various ligand systems have been developed to promote C(sp)-H bond boration. 3 While the β-H borylation reaction is a common target for catalytic reactions, existing catalytic schemes still have inherent limitations, such as high reaction temperatures (typically 60-120 °C), narrow substrate range, and the use of complex ligands (and Ir complexations) that are difficult to obtain and modify. Furthermore, the limited mechanistic understanding of these systems hinders further improvements to the catalytic system. It is noteworthy that existing catalytic systems have emphasized the crucial role of X-type ligands in promoting the β-H borylation reaction; therefore, the question arises whether the rational design of L-X-type ligands can facilitate efficient and selective β-H borylation of C(sp)-H. 3 The L-H borylation reaction offers new opportunities. Among the X-type ligands, silicon-based ligands exhibit strong σ-electron-donating ability and significant trans influence, which weakens the metal-ligand bond opposite the silicon coordination site. This unique property promotes the formation of empty coordination sites, thereby enhancing catalyst-substrate binding, activation efficiency, and overall catalytic efficiency. Furthermore, silicon sources for preparing silicon-based ligands are inexpensive and generally commercially available, and the substituents of silicon-based ligands are easily tuned to adjust steric and electronic effects. These combined characteristics endow silicon-based ligands with unparalleled advantages in promoting transition metal-catalyzed CH borylation reactions. Representative structures of the L,L-type and L,X-type ligands mentioned above are shown below. Figure 2 As shown.

[0004] In summary, existing methods for catalyzing C(sp) 3 )-H or C(sp 2 Catalysts with 1-H boronization often exhibit low catalytic efficiency, require high temperatures, or can only act on a limited range of substrates. Therefore, it is crucial to provide a new ligand that can coordinate with transition metal compounds such as Ir to form catalysts that are either highly efficient, operate at room temperature, or have a wide range of applications. Summary of the Invention

[0005] This invention aims to address at least one of the technical problems existing in the prior art. To this end, this invention proposes a ligand capable of coordinating with Ir compounds to form a catalyst that catalyzes the boration of CH bonds. This catalyst has a broad substrate range, mild reaction conditions (e.g., it can react at room temperature), and high product yield.

[0006] The present invention also provides a method for preparing the above-mentioned ligands.

[0007] The present invention also provides catalysts comprising the above-described ligands.

[0008] The present invention also provides a method for synthesizing the above-mentioned catalysis.

[0009] The present invention also provides a borylation reaction using the above-described catalyst.

[0010] According to an embodiment of a first aspect of the present invention, a ligand is provided having the following structural formula:

[0011]

[0012] Where R is the same or different, and independently represents one of phenyl, p-methoxyphenyl, cyclohexyl, or 3,5-di(trifluoromethyl)phenyl;

[0013] R' means the same or different, and independently represents one of C1-4 alkyl, phenyl, or tolyl.

[0014] The ligands according to embodiments of the present invention have at least the following beneficial effects:

[0015] The ligand provided by this invention consists of three parts: (i) an L-type phosphine unit, which acts as a strong σ-electron donor and has extensive tunability in spatial and electronic properties; (ii) an X-type silicon group with strong electron-donating ability and significant anti-site effect; and (iii) a rigid linker (phenyl) that covalently connects the phosphine unit and the silicon group, thereby forming a stable five-membered metal ring (e.g., phenyl group) during coordination. Figure 3 (As shown); the use of rigid linkers further enhances the stability and pre-organization of the ligand scaffold. Notably, this modular design allows for the efficient synthesis of structurally diverse and electronically tunable P,Si ligands via a simple two-step nucleophilic substitution process (through the selection and combination of R and R' groups). Commercially available phosphine chlorosilanes (which are both inexpensive and structurally diverse) are ideal precursors for constructing phosphine units and silicon-based modules, respectively. By systematically tuning the spatial and electronic characteristics of each module, the catalytic performance of the resulting catalyst can be optimized, enabling efficient and regioselective C(sp) catalysis under mild conditions. 3 )-H and C(sp 2The boronization reaction of )-H; and the resulting catalyst is applicable to a wide range of nitrogen heterocycles, cyclopropanes, and phenyl-containing structures, that is, it has a wide range of applicable substrates.

[0016] The ligands provided by this invention not only expand the structural diversity of X-type silicon-based ligands, but also inject new vitality into their application in transition metal catalysis.

[0017] According to some embodiments of the present invention, in the ligand, the C1-4 alkyl group of R' includes at least one of methyl and isopropyl.

[0018] According to some embodiments of the present invention, the ligand is a compound with the following structure:

[0019]

[0020] In the chemical formula provided by this invention, R2 represents two R groups; similarly, R'2 represents two R' groups (see L9 for details).

[0021] According to an embodiment of a second aspect of the present invention, a method for preparing the ligand described in the first aspect of the present invention is provided, the method comprising: reacting an intermediate product of formula I with a chlorosilane of chemical formula R'SiHCl under the action of n-butyllithium (nBuli) to obtain the ligand.

[0022]

[0023] Where X represents one of Br, Cl and F.

[0024] Since the preparation method employs all the technical solutions of the ligands in the above embodiments, it possesses at least all the beneficial effects brought about by the technical solutions in the above embodiments. Furthermore,

[0025] The preparation method provided by this invention can rapidly and flexibly construct P and Si bidentate ligands with a wide range of structural diversity, laying a solid foundation for their application in the catalytic CH borylation reaction.

[0026] According to some embodiments of the present invention, the molar ratio of the intermediate product to nBuli is 1:1 to 1.5; specifically, it can be about 1:1.2.

[0027] The intermediate product is used in the form of a solution, wherein the solvent includes at least one of tetrahydrofuran and diethyl ether; the ratio of intermediate product to solvent is 1 to 2 mmol / mL; specifically, it can be about 1.5 mmol / mL.

[0028] The nBuli is used in the form of a solution, wherein the solvent includes n-hexane; the concentration is 2 to 3 M; specifically, it can be about 2.5 M.

[0029] According to some embodiments of the present invention, the molar ratio of the intermediate product to the chlorosilane is 1:1.2 to 1.8; specifically, it may be about 1:1.5.

[0030] According to some embodiments of the present invention, in the reaction of the intermediate product and the chlorosilane, the feeding sequence in the batching stage is as follows: add nBuli to the intermediate product, stir, and then add the chlorosilane. The stirring time is 0.5–1.5 h; specifically, it can be about 1.0 h.

[0031] According to some embodiments of the present invention, in the reaction of the intermediate product and the chlorosilane, the temperature during the feeding stage is ≤-75°C; specifically, it can be about -78°C.

[0032] According to some embodiments of the present invention, in the reaction of the intermediate product and the chlorosilane, the temperature of the reaction stage is room temperature (about 25°C);

[0033] The reaction phase is carried out under stirring.

[0034] The reaction phase lasts 8–15 hours; usually overnight is sufficient. A reaction duration of ≥8 hours has little impact on the results.

[0035] According to some embodiments of the present invention, the preparation method further includes a purification process after the intermediate product and chlorosilane have reacted.

[0036] The purification process includes sequential quenching reaction, extraction, drying, solvent removal, and flash chromatographic purification. The quenching reaction uses a saturated ammonium chloride solution; the extraction uses ethyl acetate; the drying uses anhydrous sodium sulfate; the solvent removal includes vacuum distillation; and the eluent used in the flash chromatographic purification is a mixture of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is 1–30:1; specifically, it can be approximately 5:1, 10:1, 15:1, 20:1, or approximately 25:1.

[0037] According to some embodiments of the present invention, the method for obtaining the intermediate product shown in Formula I includes the following steps:

[0038] The ortho-dihalobenzene is reacted with R2PCl in the presence of n-butyllithium. The halogenated group in the ortho-dihalobenzene includes at least one of bromine, fluorine, and chlorine.

[0039] Therefore, when the o-dihalobenzene is o-dibromobenzene, the preparation method is illustrated below;

[0040]

[0041] This streamlined two-step technique allows for the rapid assembly of ligands with different alkyl and / or aryl substituents at phosphorus and silicon centers to achieve the modulation of spatial and electronic structures.

[0042] According to some embodiments of the present invention, the method for obtaining the intermediate product shown in Formula I includes the following steps:

[0043] 2-Halophenylphosphine dichloride is reacted with Grignard reagent ArMgBr. Here, "halogenated" indicates bromo, chloro, or fluorinated.

[0044] Therefore, when the 2-halophenylphosphine dichloride is 2-bromophenylphosphine dichloride, the preparation method is illustrated as follows:

[0045]

[0046] This allows for further expansion of the electronic diversity of phosphine groups. This modular approach provides a convenient method for controlling the electronic structure of ligands without requiring laborious purification steps.

[0047] According to some embodiments of the present invention, the molar ratio of 2-bromophenylphosphine dichloride to Grignard reagent is 1:1.8 to 2.2; for example, it can be about 1:2.

[0048] According to some embodiments of the present invention, the 2-bromophenyl dichloride is used in the form of a solution, wherein the solvent includes diethyl ether; the ratio of the 2-bromophenyl dichloride to the solvent is 1 mmol: 3.5 to 4.5 mL; specifically, it may be about 1 mmol: 4 mL.

[0049] According to some embodiments of the present invention, the Grignard reagent is used in the form of a solution, wherein the solvent includes diethyl ether; the concentration is 0.8 to 1.2 M; specifically, it may be about 1.0 M.

[0050] According to some embodiments of the present invention, the temperature during the reaction of 2-bromophenylphosphine dichloride and Grignard reagent ArMgBr is ≤2°C; specifically, it can be about 0°C.

[0051] According to some embodiments of the present invention, the reaction stage of the reaction between 2-bromophenylphosphine dichloride and Grignard reagent ArMgBr is carried out at room temperature for a duration of ≥8 hours (usually overnight is sufficient).

[0052] According to some embodiments of the present invention, the preparation of the intermediate product further includes a purification stage. The purification includes sequential quenching reaction, extraction, drying, solvent removal, and flash chromatography purification. The quenching reaction uses water; the extraction uses ethyl acetate; the drying is performed using anhydrous sodium sulfate; the solvent removal includes vacuum distillation; and the eluent used in the flash chromatography purification is a mixture of petroleum ether and ethyl acetate. The volume ratio of petroleum ether to ethyl acetate is 1–30:1; specifically, it can be about 5:1, 10:1, 15:1, 20:1, or about 25:1.

[0053] According to some embodiments of the present invention, the preparation method is carried out under argon protection.

[0054] Both of the above methods for preparing intermediate compounds were carried out under mild conditions using readily available reagents, and the scalability of the preparation methods provided by the present invention was verified by gram-scale synthesis of L5 and L8, with separation yields of 60% and 56%, respectively.

[0055] In actual production, if the intermediate product shown in Formula I is commercially available, the commercially available intermediate product can be used directly to prepare the ligand.

[0056] According to an embodiment of a third aspect of the present invention, a catalyst is provided, said catalyst being a complex formed by the ligand shown in the first aspect of the present invention and [Ir(COD)OMe]2; the structure of said catalyst is shown below:

[0057]

[0058] Since the catalyst adopts all the technical solutions of the ligands in the above embodiments, it has at least all the beneficial effects brought about by the technical solutions in the above embodiments.

[0059] According to an embodiment of a fourth aspect of the present invention, a method for synthesizing a catalyst provided in an embodiment of a third aspect of the present invention is provided, the method comprising the following steps: mixing and reacting [Ir(COD)OMe]2 with the ligand shown in an embodiment of a first aspect of the present invention.

[0060] Since the synthesis method adopts all the technical solutions of the catalysts in the above embodiments, it has at least all the beneficial effects brought about by the technical solutions in the above embodiments.

[0061] According to some embodiments of the present invention, the synthesis method is carried out in argon gas.

[0062] According to some embodiments of the present invention, the synthesis method includes the following steps:

[0063] Mix [Ir(COD)OMe]2 with the solvent;

[0064] The resulting mixture is then reacted with the ligand.

[0065] Remove the solvent from the resulting mixture and wash and dry it.

[0066] The solvent used in the synthesis method includes dichloromethane.

[0067] In the synthesis method described, the ratio of [Ir(COD)OMe]2 to solvent is 1–1.5 mmol: 40 mL. For example, it can be approximately 1.4 mmol: 40 mL.

[0068] In the synthesis method, the molar ratio of [Ir(COD)OMe]2 to the ligand is 1:1 to 4; for example, it can be about 1:2 or about 1:3.

[0069] In the synthesis method, the duration of the mixed reaction is 5 to 25 minutes; for example, it can be about 5 minutes, 10 minutes, 15 minutes, 20 minutes or about 25 minutes.

[0070] The washing process includes sequential n-pentane washing and methanol washing.

[0071] According to an embodiment of the fifth aspect of the present invention, an application of the catalyst provided in the third aspect of the present invention in an organoboron compound is provided, wherein the method for preparing the organoboron compound comprises reacting a substrate with pinacol diboronate (CAS: 73183-34-3, abbreviated as B2pin2) under the catalytic conditions;

[0072] The substrate has C(sp) 2 )-H or C(sp 3 )-H.

[0073] Since the application employs all the technical solutions of the catalysts described in the above embodiments, it possesses at least all the beneficial effects brought about by the technical solutions of the above embodiments.

[0074] According to some embodiments of the present invention, the molar ratio of the substrate to B2pin2 is 1:0.8 to 1.2; for example, it can be about 1:1.

[0075] According to some embodiments of the present invention, the catalyst is used in the form of a solution, and the solvent used includes at least one selected from tetrahydrofuran, diethyl ether, toluene, n-hexane or cyclohexane; the catalyst accounts for 0.5 to 3% of the molar percentage of the substrate; specifically, it may be about 1%, 2% or about 2.5%; the ratio of the substrate to the solvent is 2 mmol: 2 to 3 mL, specifically, it may be about 2 mmol: 2.5 mL.

[0076] According to some embodiments of the present invention, the reaction time of the substrate and phenazine diboronate is 6 to 24 hours; specifically, it can be about 10 hours, 12 hours, 15 hours or about 20 hours.

[0077] According to some embodiments of the present invention, the reaction temperature between the substrate and phenazine diboronate is 20–65°C. Specifically, it can be room temperature or about 60°C.

[0078] According to some embodiments of the present invention, the preparation of the organoboron compound further includes purification. The purification includes sequential filtration, solvent removal, and flash chromatography purification, wherein the solvent removal includes vacuum evaporation; the eluent used in the flash chromatography purification is petroleum ether and ethyl acetate; the volume ratio of the two is 1 to 30:1; specifically, it can be about 3:1, 5:1, 10:1, 15:1, 20:1, or about 25:1.

[0079] According to some embodiments of the present invention, the preparation of the organoboron compound is carried out in an argon protective atmosphere.

[0080] According to some embodiments of the present invention, having C(sp) 2 The substrates of )-H are at least one of the compounds shown in the following structural formulas:

[0081]

[0082] According to some embodiments of the present invention, having C(sp) 3 The substrates of )-H are at least one of the compounds shown in the following structural formulas:

[0083]

[0084] According to an embodiment of a sixth aspect of the present invention, an application of a ligand provided in a first aspect of the present invention in the preparation of an organoboron compound is provided, the preparation of the organoboron compound comprising reacting a substrate with phenazine diboronate under the conditions of the ligand and [Ir(COD)OMe]2.

[0085] The substrate has C(sp) 2 )-H or C(sp 3 )-H.

[0086] Since the application adopts all the technical solutions of the ligands in the above embodiments, it has at least all the beneficial effects brought about by the technical solutions in the above embodiments.

[0087] The preparation processes of the organoboron compounds in the sixth aspect embodiment and the fifth aspect embodiment of the present invention have the same range of choices in terms of material ratio, reagent selection and reaction conditions.

[0088] Compared with the preparation of organoboron compounds in the sixth aspect embodiment of the present invention, the former does not require the synthesis and purification steps of the catalyst, making it more convenient and easier to operate; however, since the induction time for catalyst synthesis is saved, the actual effect of the catalyst may be affected, and the yield of the organoboron compound is slightly lower in the end.

[0089] According to an embodiment of the seventh aspect of the present invention, an application of the application provided in the fifth or sixth aspect of the present invention is provided in drug preparation, synthetic chemistry and materials preparation.

[0090] Since the application adopts all the technical solutions for the preparation of organoboron compounds in the above embodiments, it has at least all the beneficial effects brought about by the technical solutions in the above embodiments.

[0091] Unless otherwise specified, the term "about" in this invention actually means that the error is allowed to be within ±2%, for example, about 100 is actually 100 ± 2% × 100.

[0092] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0093] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0094] Figure 1 This is a common example of boron-containing organic pharmaceuticals.

[0095] Figure 2 It is a common ligand used in traditional techniques to combine with transition metal compounds such as Ir to form borylation catalysts; the temperature represents the temperature required for catalytic borylation of CH bonds after catalyst formation.

[0096] Figure 3 This is a structural breakdown diagram of the ligand in this invention and a schematic diagram of the principle of coordination with transition metals to form a five-membered ring.

[0097] Figure 4 This invention C(sp) 3 Fitting results of the kinetic isotope effect of the )-H boronization process.

[0098] Figure 5 This is a schematic diagram of the catalytic mechanism of the catalyst in this invention.

[0099] Figure 6 This is a cell structure diagram of Complex A in this invention.

[0100] Figure 7 This is a cell structure diagram of Complex B in this invention.

[0101] Figure 8 This is a cell structure diagram of product 2a in this invention. Detailed Implementation

[0102] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0103] Unless otherwise specified, all reagents used in the specific implementation methods are commercially available, and the specific purchase channels include pharmaceutical companies such as Bider, Leyan and Anaiji.

[0104] Example 1

[0105] This example demonstrates the preparation of a ligand, with the specific process illustrated below:

[0106]

[0107] Where R represents phenyl (-Ph) and R' represents tolyl (-PhMe); and the intermediate product in this example is commercially available, so only the second step is performed in this example.

[0108] The specific preparation steps are as follows:

[0109] In a 100 mL Schlenk flask equipped with a magnetic stirrer, 1.5 mmol of (2-bromophenyl)diphenylphosphine (CAS: 62336-24-7, intermediate product) was introduced and purged with argon for 2-3 cycles.

[0110] Then, 10 mL of THF was added, and the resulting mixture was cooled to -78 °C.

[0111] Slowly add a hexane solution of nBuli (1.2 molar amounts of the intermediate, 2.5 M) to the resulting mixture and stir at -78°C for 1 h.

[0112] Chlorosilane (1.5 equivalents of the intermediate product, by molar weight) was gradually added to the resulting mixture; the CAS of the chlorosilane used in this example is 18551-61-6.

[0113] The resulting mixture was then slowly heated to room temperature and stirred overnight.

[0114] After the reaction was complete, the reaction was quenched with saturated NH4Cl (10 mL) aqueous solution, and extracted three times with EtOAc (10 mL × 3), collecting the organic phase. The organic phase was dried on anhydrous Na2SO4, concentrated under reduced pressure, and purified by flash chromatography on silica gel (GENERAL-REAGENT silica gel (200-300 mesh), the same in other examples) (eluent: petroleum ether / ethyl acetate = 10 / 1, v / v) to obtain the target compound.

[0115] The ligand obtained in this example is L2.

[0116] The calculated yield of L2 is 67%.

[0117] The test results for the ligands obtained in this example are as follows:

[0118] 1 H NMR(600MHz,Chloroform-d)δ7.49-7.45(m,4H),7.38-7.34(m,1H),7.34-7.29(m ,3H),7.29-7.17(m,12H),7.00(td,J=7.6,7.1,1.5Hz,4H),1.00(d,J=2.4Hz,3H).

[0119] 13 C NMR(151MHz,Chloroform-d)δ144.8,144.5,144.4,144.3,138.2,138.1,137.7,137.6(3),137.6(1), 137.5(7),136.0,135.5,133.4,133.2,129.9,129.1,128.5,128.3,128.2,128.1,127.8,-0.3,-0.4.

[0120] 31 P NMR(243MHz,Chloroform-d)δ-11.2.

[0121] HRMS(ESI,m / z)[M+H] + calcd for[C 31 H 28 PSi] + :459.1692; found:459.1691.

[0122] Example 2

[0123] This example prepares a ligand, which differs from Example 1 in that:

[0124] In this example, R' represents methyl; the chlorosilane used is dimethylchlorosilane (CAS: 1066-35-9); and the ligand obtained is L3.

[0125] The calculated yield of L3 is 80%.

[0126] The test results of the product obtained in this example are as follows:

[0127] 1 H NMR(600MHz,Chloroform-d)δ7.66-7.60(m,1H),7.36-7.28(m,8H),7.27-7.23(m,4H),7.10-7.06(m,1H),4.75-4.68(m,1H),0.35(dd,J=3.7,1.1Hz,6H).

[0128] 13 C NMR(151MHz,Chloroform-d)δ145.5,145.2,143.6,143.5,137.8,137.7,135.4,135.3, 134.2,133.8,133.7,129.7,128.6,128.5(4),128.5(3),128.4(5),-2.1(3),-2.1(8).

[0129] 31 P NMR(243MHz,Chloroform-d)δ-10.6.

[0130] HRMS(ESI,m / z)[M+H] + calcd for[C 20 H 22 PSi] + :321.1223; found:321.1222.

[0131] Example 3

[0132] This example prepares a ligand, which differs from Example 1 in that:

[0133] In this example, R' represents isopropyl; the chlorosilane used is diisopropylchlorosilane (CAS: 2227-29-4); and the ligand obtained is L4.

[0134] The calculated yield of L4 is 75%.

[0135] The test results for the ligands obtained in this example are as follows:

[0136] 1H NMR(600MHz,Chloroform-d)δ7.62-7.58(m,1H),7.34-7.27(m,8H),7.26-7.21(m,4H),7.10–7.06(m,1H) ), 4.23 (dt, J = 5.4, 4.1Hz, 1H), 1.35 (pd, J = 7.3, 3.9Hz, 2H), 1.08 (d, J = 7.3Hz, 6H), 0.86 (d, J = 7.4Hz, 6H).

[0137] 13 C NMR(151MHz,Chloroform-d)δ143.9,143.8,143.6,143.2,138.0,137.9,136.9,136.8,134.3,133.8 ,133.7,129.4,128.5,128.5,128.4,128.1,19.4(7),19.4(5),19.4(0),19.3(9),12.2(9),12.2(5).

[0138] 31 P NMR(243MHz,Chloroform-d)δ-8.5.

[0139] HRMS(ESI,m / z)[M+H] + calcd for[C 24 H 30 PSi] + :377.1849; found:377.1849.

[0140] Example 4

[0141] This example prepares a ligand, which differs from Example 1 in that:

[0142] In this example, R' represents phenyl; the chlorosilane used is diphenylchlorosilane (CAS: 1631-83-0); and the ligand obtained is L5.

[0143] Calculations show that the yield of L5 is ≥60%, and it can be prepared in gram-scale.

[0144] The test results for the ligands obtained in this example are as follows:

[0145] L5: 1 H NMR(600MHz,Chloroform-d)δ7.52-7.46(m,5H),7.34(dq,J=10.0,8.6,7.9Hz,

[0146] 4H),7.30-7.20(m,12H),7.19(dd,J=7.6,3.9Hz,1H),7.13-7.08(m,4H),5.87(d,J=6.8Hz,1H).

[0147] 13 C NMR(151MHz,Chloroform-d)δ144.7,144.6,141.7,141.4,137.6,137.5(2),137.4(8),137.4,136.1,13 4.6,134.5,134.1(9),134.1(7),133.7,133.6,130.3,129.6,128.6,128.4(1),128.38,128.36,127.95.

[0148] 31 P NMR(243MHz,Chloroform-d)δ-10.5.

[0149] HRMS(ESI,m / z)[M+H] + calcd for[C 30 H 26 PSi] + :445.1536; found:445.1536.

[0150] Example 5

[0151] This example prepares a ligand, which differs from Example 1 in that:

[0152] In this example, R represents cyclohexyl and R' represents phenyl.

[0153] The intermediate product used in this example is (2-bromophenyl)dicyclohexylphosphine (CAS: 757958-40-0);

[0154] The chlorosilane used in this example is diphenylchlorosilane (CAS: 1631-83-0); the ligand obtained is L6.

[0155] Example 6

[0156] This example demonstrates the preparation of a ligand, with the specific process illustrated below:

[0157]

[0158] Where R represents p-methoxyphenyl and R' represents phenyl.

[0159] The specific preparation steps are as follows:

[0160] S1. In a 100 mL Schlenk flask equipped with a magnetic stirrer, purge with argon for 2-3 cycles, then add 2-bromophenylphosphine dichloride (1.29 g, 5 mmol, CAS: 5274-51-1) and EtO (20 mL, diethyl ether).

[0161] The resulting mixture was cooled to 0°C, and a solution of aryl Grignard reagent ArMgBr in diethyl ether (2 molar amounts of 2-bromophenylphosphine dichloride, 1M) was slowly added dropwise. The Ar group in the Grignard reagent is p-methoxyphenyl (CAS: 13139-86-1). The mixture was then heated to room temperature and stirred overnight.

[0162] After the reaction was complete, the mixture was quenched with water (10 mL), extracted three times with EtOAc (10 mL × 3), and the organic phase was collected. The mixed organic layers were dried over anhydrous Na2SO4, concentrated under reduced pressure, and purified by flash chromatography on silica gel to obtain the intermediate shown below:

[0163]

[0164] The yield for this step is 75%.

[0165] S2. In a 100 mL Schlenk flask equipped with a magnetic stirrer, introduce 1.5 mmol of the intermediate product obtained in step S1, and degas by purging with argon gas for 2-3 cycles; then, add 10 mL of Et2O (diethyl ether), cool the system to -78 °C, and slowly add a hexane solution of n-Buli (1.2 equivalents, based on the molar amount of the intermediate product, 2.5 M). Stir the resulting mixture at -78 °C for 1 h.

[0166] Add diphenylchlorosilane (CAS: 1631-83-0) (1.5 equivalents, based on the amount of the intermediate product) dropwise to the resulting mixture; then slowly heat the mixture to room temperature and stir overnight.

[0167] After the reaction was completed, the reaction was quenched with saturated NH4Cl (10 mL) aqueous solution (10 mL), and extracted three times with EtOAc (10 mL × 3) to collect the organic phase.

[0168] The mixed organic layer was dried on anhydrous sodium sulfate, concentrated under reduced pressure, and then purified by flash chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 10 / 1, volume ratio) to obtain the target compound.

[0169] The ligand obtained in this example is L7.

[0170] The yield in this example is calculated to be 65%.

[0171] Recordings were made on the Bruker DRX-400 and DPX-600 spectrometers, respectively.1 H NMR 400MHz, 13 C NMR 101MHz, 31 P NMR 162MHz and 19 The NMR spectrum at 376 MHz was obtained using the following NMR standards: (¹H NMR) TMS = 0 ppm; (¹³C NMR) CDCl₃ = 77.16 ppm. Chemical shifts (δ) are expressed in ppm, and coupling constants (J) are expressed in Hz. ¹H NMR data are recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet; D = doublet; Dd = multiplet of multiplet; T = triplet; Td = quartet; m = multiplet), coupling constant (Hz), and integral. 13 C10 NMR data are expressed as chemical shifts (δ, ppm). High-resolution mass spectrometry analysis was performed using electrospray ionization (ESI) on an Agilent Technologies 6230 TOFLC / MS spectrometer. (The same applies to other examples regarding product characterization methods).

[0172] The test results of the product are as follows:

[0173] 1 H NMR (400MHz, CDCl3): δ7.50-7.42(m,5H),7.37-7.30(m,3H),7.29-7.23(m,5H),7.18-7.13(m ,1H),7.05(dd,J=8.8,7.1Hz,4H),6.80-6.73(m,4H),5.86(d,J=6.5Hz,1H),3.76(s,6H)ppm.

[0174] 13 C NMR (101MHz, CDCl3): δ160.0, 146.0 (d, J = 11.2Hz), 140.7 (d, J = 44.1Hz), 137.5 (d, J = 13.7Hz), 136.10 (d, J = 1.2Hz), 135.2 (d, J = 20.3Hz), 134.3 (d, J = 4.0Hz), 133.8, 130.2, 129.5, 128.5 (d, J = 8.1Hz), 128.2, 127.9, 114.1 (d, J = 7.6Hz), 55.3ppm.

[0175] 31 P NMR (162MHz, CDCl3): δ-13.3ppm.

[0176] HRMS(ESI,m / z)[M+H]+ calcd for[C 32 H 30 O2PSi] + :505.1747; found:505.1747.

[0177] Therefore, it can be concluded that the target ligand L7 was indeed successfully prepared in this case.

[0178] Example 7

[0179] This example prepared a ligand, which differs from Example 6 in that:

[0180] In step S2, the amount of intermediate product used is 4.5 mmol, and the amount of other raw materials used is scaled up proportionally; the proportion of raw materials used is the same as in Example 6.

[0181] In step S2, the chlorosilane used is diisopropylchlorosilane (CAS: 2227-29-4); the ligand obtained is L8.

[0182] In step S2, during chromatographic purification, the eluent used is petroleum ether / ethyl acetate = 15 / 1, by volume.

[0183] The yield of L8 was calculated to be 56%; and it can be prepared in gram-scale, specifically, in this example, 1.1g of product can be obtained.

[0184] The product test results are shown below:

[0185] 1 H NMR (400MHz, CDCl3): δ7.51-7.46(m,1H),7.20-7.15(m,2H),7.11-7.04(m,4H),7.01-6.96(m,1H),6.78-6.73(m, 4H), 4.14(dt,J=5.7,4.0Hz,1H),3.67(s,6H),1.29-1.19(m,2H),0.99(d,J=7.4Hz,6H),0.76(d,J=7.4Hz,6H)ppm.

[0186] 13 C NMR (101MHz, CDCl3): δ160.0, 144.9 (d, J = 10.5Hz), 142.8 (d, J = 45.9Hz), 136.8 (d, J = 14.2Hz), 135.2 (d, J = 20.1Hz), 133.8, 129.2, 129.0 (d, J = 8.4Hz), 127.8, 114.2 (d, J = 7.5Hz), 55.2, 19.4 (dd, J = 7.8, 1.6Hz), 12.2 (d, J = 6.1Hz) ppm.

[0187] 31 P NMR (162MHz, CDCl3): δ-11.7ppm.

[0188] HRMS(ESI,m / z)[M+H] + calcd for[C 26 H 34 O2PSi] + :437.2060; found:437.2060.

[0189] Example 8

[0190] This example prepared a ligand, which differs from Example 6 in that:

[0191] In step S1, the CAS number of the Grignard reagent used is 112981-69-8; the ligand obtained in this example is L9.

[0192] In step S2, during chromatographic purification, the eluent used is petroleum ether / ethyl acetate = 15 / 1, by volume.

[0193] The calculated yield of L9 was 78%.

[0194] The product test results are shown below:

[0195] 1 H NMR (400MHz, CDCl3): δ7.78(s,2H),7.65(dt,J=6.8,3.0Hz,1H),7.54-7.46(m,6H),7.41(d,J=6.5Hz,4H), 7.31(t,J=7.2Hz,2H),7.25(t,J=6.6Hz,4H),7.10(dt,J=7.4,2.5Hz,1H),5.86(dd,J=5.9,1.3Hz,1H)ppm.

[0196] 13 C NMR (101MHz, CDCl3): δ143.2(d,J=48.9Hz), 139.7(d,J=17.7Hz), 138.6(d,J=16.0Hz), 136.0(d,J=1.5Hz), 134.7(d,J=1.5Hz), 133.2-1 32.6(m,3C),132.0(qd,J=33.4,6.1Hz),131.4,130.5(d,J=1.4Hz),130.1,128.2,123.1(1)(q,J=273.2Hz),123.0(6)(p,J=3.8Hz)ppm.

[0197] 19 F NMR (376MHz, CDCl3): δ-63.1ppm.

[0198] 31 P NMR (162MHz, CDCl3): δ-10.0ppm.

[0199] HRMS(ESI,m / z)[M+H] + calcd for[C 34 H 22 F 12 PSi] + :717.1031; found:717.1019.

[0200] Application Example 1

[0201] This example demonstrates the synthesis of a catalyst, with the specific process illustrated below:

[0202]

[0203] The specific synthesis process is as follows:

[0204] In an argon-filled glove box, add [Ir(COD)OMe]2 (91.7 mg, 0.14 mmol, CAS: 12148-71-9) and anhydrous dichloromethane (4.0 mL) to a 10 mL dry microwave reaction tube.

[0205] Then, add 2 molar equivalents of the ligand (from Examples 1-8) to the microwave reaction tube and stir for 20 min.

[0206] The solvent was then removed by vacuum drying, and the resulting solid was washed sequentially with 5 mL of n-pentane and 5 mL of methanol and then vacuum dried.

[0207] The final product is a yellow solid.

[0208] When the ligand is L4 obtained in Example 3, the yield in this example is 72%. The catalyst is denoted as Complex A, which has a 16-electron structure.

[0209] This example also tested the X-ray single-crystal diffraction of Complex A; sample preparation involved obtaining a hexane solution of Complex A at 0°C; diffraction data and refinement were acquired on a Bruker D8 instrument using copper-potassium X-ray diffraction. Experiments were conducted. The test results have been stored in the Cambridge Crystallography Data Centre (CCDC 2449659). The unit cell structure diagram of Complex A is shown below. Figure 6 (As shown).

[0210] The refined results of the above XRD results are shown in Table 1.

[0211] Table 1. XRD refinement results of Complex A

[0212]

[0213] In addition, this example also characterized other ligands and the catalyst formed by [Ir(COD)OMe]2 by XRD, proving that it did indeed obtain the correct structure. To avoid redundancy, they are not shown one by one.

[0214] Comparative Application Example 1

[0215] This example demonstrates the preparation of a catalyst, and the reaction process is as follows:

[0216]

[0217] The difference between the specific example and application example 1 is:

[0218] (1) The reaction was carried out using only ligand L3. The metal-ligand ratio was 1:2.

[0219] (2) Replace [Ir(COD)OMe]2 with an equal amount of [Rh(COD)Cl]2 (CAS No.: 12092-47-6).

[0220] In this example, the product yield was 85%, and the product color was light yellow. The obtained product is denoted as Complex B, which has a 16-electron structure.

[0221] Using a method similar to that in Application Example 1, XRD data for Complex B were acquired. The sample was a chloroform solution of Complex B, data numbered CCDC 2442532 (the cell structure diagram of Complex B is shown below). Figure 7 (As shown).

[0222] The refined results of the above XRD results are shown in Table 2.

[0223] Table 2 XRD refinement results of Complex B

[0224]

[0225]

[0226] The NMR results of the product in this example are as follows:

[0227] 1H NMR (400MHz, CDCl3): δ8.03-7.95(m,4H),7.68-7.60(m,2H),7.57-7.45(m, 12H),7.41-7.31(m,4H),7.28-7.20(m,6H),-0.06(s,6H),-0.42(s,6H)ppm.

[0228] 13 C NMR (101MHz, CDCl3): δ159.3 (t, J = 29.3Hz), 138.1 (t, J = 30.3Hz), 135.5 (t, J = 23.2Hz), 134.1 (t, J = 6.3Hz), 133.6 (t, J = 5.4Hz), 1 32.4,132.2,132.1,132.0,131.8,130.4,130.2,129.7,128.7(t,J=4.5Hz),128.4(t,J=3.0Hz),127.9(t,J=5.2Hz),7.1,2.3ppm.

[0229] 31 P NMR (162MHz, CDCl3): δ55.8, 55.0ppm.

[0230] Comparative Application Example 2

[0231] This example prepares a catalyst, which differs from application example 1 in that:

[0232] (1) The reaction was carried out using only ligand L3. The metal-ligand ratio was 1:2.

[0233] (2) Replace [Ir(COD)OMe]2 with an equal amount of nickel compound NiCl(dme) (CAS: 29046-78-4), the product is called Complex C, which has a 16-electron structure.

[0234] Comparing the results of Complex A through Complex C reveals that all three exhibit similar metal-ligand chelation behavior, and each catalyst forms a five-membered P,Si chelate ring. This highlights the strong bidentate coordination ability of the ligands prepared in this invention and indicates that structural changes in the ligands significantly affect the coordination geometry of the central metal and the electronic environment. These results are crucial for understanding the catalytic behavior of the ligands prepared in this invention during borylation reactions.

[0235] Application Example 2

[0236] This example uses the catalysts obtained from Application Example 1 and Comparative Application Examples 1-2 to perform C(sp) 3The borylation reaction was catalyzed by H, using substrate 1a (CAS number 157646-95-2). The specific conditions and simplified procedure for the borylation reaction are as follows:

[0237]

[0238] The specific reaction steps are as follows:

[0239] In an argon-filled glove box, [Ir(COD)OMe]2, a ligand (from the example or as shown in L1 below), and cyclohexane were added to a 10 mL dry microwave reaction tube in a 1:2 molar ratio. The amount of [Ir(COD)OMe]2 was 2.5 mol% of the substrate, and the ratio of substrate to cyclohexane was 2 mmol: 5 mL. After stirring at a specific temperature (room temperature rt) for 10 min, substrate 1a was added, and after stirring for 10 min, B2pin2 was added. The molar ratio of substrate 1a to B2pin2 was 1:1. In this example, the amount of substrate used was 0.2 mmol.

[0240]

[0241] Then, seal the microwave reaction tube and remove it from the glove box, and continue stirring at the corresponding temperature (room temperature or 60°C) for the corresponding duration (12h or 24h).

[0242] After the reaction was completed, the product was filtered using a short silica gel pad, and the solvent was removed by vacuum evaporation. Finally, the product was purified by flash chromatography on silica gel or preparative chromatography (eluent: petroleum ether / ethyl acetate = 5:1, volume ratio) to obtain the target product (colorless oily substance).

[0243] When the catalyst used comes from Comparative Application Examples 1 to 2, it is only necessary to replace the catalyst with an equal amount of the catalyst obtained from Comparative Application Examples 1 to 2.

[0244] In actual production, the process of separately adding the ligand and [Ir(COD)OMe]2 can be omitted, and the catalyst obtained in Example 1 (in the same amount) can be added directly. Adding the separated catalyst saves the induction period of the catalyst reaction, thus improving the yield of the borylation reaction to some extent. However, for convenience in actual production, the ligand and [Ir(COD)OMe]2 are added directly. Therefore, it can be seen that by optimizing the reaction conditions, the catalyst provided by this invention can further improve the yield of the borylation reaction.

[0245] The test results of the product obtained in this example are as follows:

[0246] 1H NMR (400MHz, CDCl3): δ3.43-3.36(m,1H),3.32(q,J=7.1Hz,4H),3.11(td,J=9.5,7.2Hz,1H),2.83(dd,J=11.6,6.4Hz ,1H),2.18-2.09(m,1H),2.04-1.92(m,1H),1.79-1.70(m,1H),1.66(dd,J=12.0,6.7Hz,1H),1.20-1.13(m,18H)ppm.

[0247] 13 C NMR (101MHz, CDCl3): δ165.3,79.5,49.0,42.6,30.2,26.9,25.3,24.9,13.4ppm.

[0248] 11 B NMR (128MHz, CDCl3): 11.4δppm.

[0249] Therefore, it can be concluded that the corresponding product was indeed obtained through catalytic borylation reaction in this example.

[0250] The yield of product 2a was calculated based on NMR data from different reactions, and the specific test results are shown in Table 3:

[0251] Table 3 C(sp) values ​​of different ligands under different conditions 3 Performance in the )–H borylation reaction

[0252]

[0253] In Table 3, Complex A, Complex B, and Complex C represent the direct addition of catalysts to the reaction system, while the other groups represent the in-situ addition of ligands and [Ir(COD)OMe]2 during the reaction process, with the proportion of added [Ir(COD)OMe]2 controlled to be the same. Furthermore, when the ligands in Complex B and Complex C are replaced with L4, they still essentially lack catalytic activity for the borylation reaction.

[0254] In Table 3, in the yield of group 12, 88(80) indicates that the NMR yield is 88% and the separation yield is 80%; the yields of the other groups are all NMR yields.

[0255] The data in Table 5 are explained in the same way.

[0256] Table 3 shows that catalyst Complex A effectively catalyzed the monoboration of substrate 1a, achieving an NMR yield of 86%, while Complex B and Complex C showed no catalytic activity under the same conditions. In the screening of ligands, ligands L1 and L2 were found to be inactive, possibly due to their inability to form catalytically active substances or due to their spatial or electronic structures. Ligand L3, with minimal steric hindrance on silicon atoms, also failed to promote the reaction, indicating that insufficient steric volume hindered catalytic activity. Introducing bulky substituents on silicon, such as L4 (isopropyl) and L5 (phenyl), restored the activity of the catalyst formed by the combination of the ligand and Ir, with L4 providing a 60% yield. However, L5 exhibited lower efficiency, possibly due to the reduced electron-donating ability of the phenyl group. To elucidate the electronic effects of substituents on catalytic activity, ligands L7 and L9, with electron-donating and electron-withdrawing properties respectively, were evaluated. Compared to L5, the ligand L7, containing p-methoxyphenyl, showed slightly improved reactivity, indicating that an electron-rich phosphine environment can enhance catalytic performance. In contrast, ligand L9, with its strongly electron-withdrawing 3,5-bis(trifluoromethyl)phenyl, exhibited negligible catalytic activity. This significant difference highlights the importance of electron-deficient phosphine ligands for C(sp...) 3 The adverse effects of )-H borylation process efficiency. Notably, ligand L8, combining an electron-rich phosphine moiety with a large isopropylsilyl group, provided the highest catalytic activity among the tested ligands, achieving a yield of 88% at 60 °C. It is also noteworthy that the reaction proceeded efficiently at room temperature, with a yield of 62% after 12 hours and 88% after 24 hours, indicating that these ligands possess regioselectivity for C(sp)-H. 3 The potential for )-H boronization.

[0257] Application Example 3

[0258] In this example, when ligand L8 is used, the catalyst (Application Example 1) is effective for catalysts with C(sp...) 3 The efficiency of catalytic borylation reactions of different substrates of )–H differs from that in application example 2 in the following ways:

[0259] The substrates vary, specifically any one of 1b to 1p; the reaction temperature is limited to room temperature, and the reaction time is 24 hours; the purification process is slightly different in some reactions, which will be described in detail later.

[0260] The corresponding product structures and yields are shown below:

[0261]

[0262] The products of the different reactions described above were tested, and the yields were calculated based on the following test results:

[0263] Product 2b, a colorless oily substance:

[0264] 1 H NMR (400MHz, CDCl3): δ3.53 (dd, J=10.1, 6.1Hz, 1H), 3.37-3.16 (m, 5H), 2.77 (d, J=1.9Hz, 1H),1.88-1.75(m,2H),1.23-1.13(m,18H),0.99-0.91(m,1H),0.30(q,J=4.4Hz,1H)ppm.

[0265] 13 C NMR (101MHz, CDCl3): δ166.5,79.7,54.2,42.6,25.4,25.2,22.6,20.2,19.9,13.3ppm.

[0266] 11 B NMR (128MHz, CDCl3): δ12.1ppm.

[0267] Following the XRD testing method in Application Example 1, the XRD data of product 2b were tested; the obtained data number is CCDC2449474, and the unit cell structure diagram of product 2b is shown below. Figure 8 As shown.

[0268] The refined results of the above XRD results are shown in Table 4.

[0269] Table 4. XRD refinement results of product 2b

[0270]

[0271]

[0272] Product 2d: a colorless, oily substance.

[0273] 1 H NMR (400MHz, CDCl3): δ3.51 (dd, J=10.4, 7.9Hz, 1H), 3.29 (q, J=7.1Hz, 4H), 3.05 (dd, J=10.5, 4.0Hz, 1H), 2.80-2.69 (m, 2H) ,2.51(d,J=8.6Hz,1H),1.78-1.68(m,2H),1.68-1.57(m,2H),1.56-1.48(m,1H),1.48-1.40(m,1H),1.21-1.13(m,18H)ppm.

[0274] 13C NMR (101MHz, CDCl3): δ164.3,79.6,55.4,47.8,44.1,42.5,32.9,31.0,25.6,25.4,24.9,13.4ppm.

[0275] 11 B NMR (128MHz, CDCl3): δ11.4ppm.

[0276] Product 2e, a colorless oily substance:

[0277] 1 H NMR (400MHz, CDCl3): δ3.38-3.26(m,4H),3.26-3.17(m,1H),3.02-2.93(m,2H),2.29-2.18(m,1H),2.16-2.0 6(m,1H),1.99-1.86(m,2H),1.70-1.63(m,1H),1.59-1.50(m,2H),1.46-1.40(m,2H),1.22-1.09(m,18H)ppm.

[0278] 13 C NMR (101MHz, CDCl3): δ166.7,79.5,56.2,42.7,42.0,38.4,28.5,25.6,25.5,25.4,24.9,21.0,13.4ppm.

[0279] 11 B NMR (128MHz, CDCl3): δ11.4ppm.

[0280] Product 2f, a colorless oily substance:

[0281] 1 H NMR (400MHz, CDCl3): δ3.52(d,J=7.8Hz,2H),3.46-3.35(m,3H),3.14(td,J=9.6,7.2Hz,1H),2.79(dd,J=11.7,6.2Hz,1H),2.16-2.05( m,1H),2.00-1.88(m,3H),1.77(d,J=4.5Hz,2H),1.74(td,J=6.3,1.4Hz,1H),1.65(dd,J=12.1,6.6Hz,1H),1.17(d,J=2.1Hz,12H)ppm.

[0282] 13C NMR (101MHz, CDCl3): δ164.0,79.5,48.1,29.8,29.3,27.1,25.3,24.8ppm.

[0283] 11 B NMR (128MHz, CDCl3): δ 9.8ppm.

[0284] Product 2g, colorless oily substance:

[0285] Unlike other products, the stability of 2g of this product is slightly worse, requiring the following special purification and drying steps:

[0286] The solution was concentrated under reduced pressure after filtration through diatomaceous earth using dichloromethane as solvent. Anhydrous THF (2 mL) was then added to the concentrate at room temperature, followed by the gradual addition of vinyl Grignard reagent (0.30 mL, 1 M, THF solvent, 1.5 molar equivalent of the substrate, CAS: 1826-67-1), and the mixture was stirred for 0.5 h. A methanol solution of I₂ (5 molar equivalents of the substrate, 1.0 mmol, 3 mL MeOH) was then slowly added to the reaction mixture at -78 °C. The mixture was stirred at this temperature for another 0.5 h. A methanol solution of NaOMe (sodium methoxide) (5 molar equivalents of the substrate; 1.0 mmol, 3 mL MeOH) was then slowly added at -78 °C. The resulting mixture was then heated to room temperature and stirred for 1 h. A saturated aqueous solution of Na₂S₂O₃ (5 mL) was then added to quench the reaction. After dilution with H₂O (20 mL), the mixture was extracted three times with ethyl acetate (3 × 20 mL). The mixed organic phase was dried over anhydrous Na₂SO₄. After removing the solvent, the product was purified by column chromatography on silica gel using petroleum ether / ethyl acetate (10:1, volume ratio) as the eluent to obtain the corresponding 2f product.

[0287] The test results for product 2f are as follows:

[0288] 1 H NMR (400MHz, CDCl3): δ6.07-5.94(m,1H),5.23(dt,J=17.1,1.4Hz,1H),5.10(dt,J=10.3,1.4Hz,1H),4.80(q,J=7.2Hz,1H),3.9 8-3.87(m,1H),3.78(dt,J=9.0,7.3Hz,1H),3.30-3.10(m,4H),2.42-2.31(m,1H),2.06-1.97(m,1H),1.11(t,J=7.1Hz,6H)ppm.

[0289] 13C NMR (126MHz, CDCl3): δ162.7,139.5,115.0,62.9,49.8,40.9,23.1,13.7ppm.

[0290] The product, after 2 hours, is a yellow oily substance.

[0291] 1 H NMR (400MHz, CDCl3): δ7.34-7.23(m,4H),7.20(d,J=6.5Hz,1H),3.48-3.31(m,2H),3.23(q,J=7.1Hz,2H),1.67(dd,J=9.9,3.9Hz,1H ),1.42(dd,J=7.5,3.9Hz,1H),1.25(d,J=8.0Hz,12H),1.17(t,J=7.1Hz,3H),0.72(t,J=7.1Hz,3H),0.66(dd,J=9.9,7.5Hz,1H)ppm.

[0292] 13 C NMR (101MHz, CDCl3): δ175.4, 140.2, 128.7, 127.6, 126.8, 81.5, 43.1, 42.1, 36.1, 25.1 (d, J = 4.9Hz), 19.5, 12.6 (d, J = 7.3Hz) ppm.

[0293] 11 B NMR (128MHz, CDCl3): δ22.7ppm.

[0294] Product 2i, a yellow oily substance:

[0295] 1 H NMR (400MHz, CDCl3): δ7.23(d,J=8.7Hz,2H),6.80(d,J=8.7Hz,2H),3.78(d,J =2.1Hz,3H),3.46-3.30(m,2H),3.24(q,J=7.1Hz,2H),1.59(dd,J=9.8,3.8Hz, 1H),1.39(dt,J=7.2,3.6Hz,1H),1.26(d,J=2.1Hz,6H),1.24(d,J=1.9Hz,6H), 1.16(t,J=7.1Hz,3H),0.73(t,J=7.1Hz,3H),0.61(dd,J=9.8,7.4Hz,1H).ppm.

[0296] 13C NMR (101MHz, CDCl3): δ175.9,158.6,132.3,129.23,129.21,114.1,81.4,55.4,43.0,42.3,35.4,25.2(d,J=2.2Hz),19.7,12.7(d,J=15.6Hz)ppm.

[0297] 11 B NMR (128MHz, CDCl3): δ20.6ppm.

[0298] Product 2j, a yellow oily substance:

[0299] 1 H NMR (400MHz, CDCl3): δ7.18(d,J=7.9Hz,2H),7.07(d,J=7.9Hz,2H),3.48-3.30(m,2H),3.23(p,J=7.0Hz,2H),2.30(s,3H),1.62(dd,J=9.9,3 .9Hz,1H),1.40(dd,J=7.5,3.8Hz,1H),1.24(d,J=8.0Hz,12H),1.16(t,J=7.1Hz,3H),0.74(t,J=7.1Hz,3H),0.63(dd,J=9.8,7.4Hz,1H)ppm.

[0300] 13 C NMR (101MHz, CDCl3): δ175.8,137.1,136.5,129.4,127.7,81.3,43.0,42.2,35.7,25.1(d,J=2.6Hz),21.1,19.6,21.0,19.5,12.7(d,J=12.4Hz)ppm.

[0301] 11 B NMR (128MHz, CDCl3): δ21.3ppm.

[0302] Product 2K is a yellow oily substance. During purification, the eluent used was petroleum ether:ethyl acetate in a 3:1 volume ratio.

[0303] 1H NMR (400MHz, CDCl3): δ7.30-7.24(m,2H),6.96(t,J=8.6Hz,2H),3.42-3.31(m,2H),3.24(q,J=7.1Hz,2H),1.60(dd,J=9.9,4.0Hz,1H ),1.44(dd,J=7.5,3.9Hz,1H),1.25(d,J=8.6Hz,12H),1.16(t,J=7.1Hz,3H),0.74(t,J=7.1Hz,3H),0.62(dd,J=9.8,7.5Hz,1H).ppm.

[0304] 13 C NMR (101MHz, CDCl3): δ174.9,161.8(d,J=245.9Hz), 136.2(d,J=3.2Hz), 129.3(dd,J=7.9,1.7Hz ), 115.6 (d, J = 21.4Hz), 81.7, 42.9, 42.0, 35.5, 25.1 (d, J = 3.5Hz), 19.6, 12.7 (d, J = 16.4Hz) ppm.

[0305] 11 B NMR (128MHz, CDCl3): δ22.6ppm.

[0306] 19 F NMR (376MHz, CDCl3): δ-115.6ppm.

[0307] Product 2L, a yellow oily substance, was purified using petroleum ether:ethyl acetate in a volume ratio of 3:1.

[0308] 1 H NMR (400MHz, CDCl3): δ7.53(d,J=8.2Hz,2H),7.38(d,J=8.1Hz,2H),3.46-3.33(m,2H),3.31-3.14(m,2H),1.66(dd,J=9.9,4.2Hz,1H ),1.53(dd,J=7.7,4.1Hz,1H),1.25(d,J=10.0Hz,12H),1.17(t,J=7.1Hz,3H),0.78(t,J=7.1Hz,3H),0.68(dd,J=9.9,7.7Hz,1H)ppm.

[0309] 13C NMR (101MHz, CDCl3): δ173.4, 144.9, 129.0 (q, J = 32.5Hz), 125.7 (q, J = 3.7Hz), 124.2 (q ,J=271.8Hz),82.2,42.9,41.5,36.1,25.1(d,J=6.9Hz),19.6,12.8(d,J=24.1Hz)ppm.

[0310] 11 B NMR (128MHz, CDCl3): δ23.9ppm.

[0311] 19 F NMR (376MHz, CDCl3): δ-62.46ppm.

[0312] Product 2m, a white solid, was purified using petroleum ether:ethyl acetate in a volume ratio of 3:1.

[0313] 1 H NMR (400MHz, CDCl3): δ7.40(d,J=8.5Hz,2H),7.16(d,J=8.6Hz,2H),3.44-3.32(m,2H),3.31-3.16(m,2H),1.59(dd,J=9.9,4.0Hz,1H ),1.46(dd,J=7.6,4.0Hz,1H),1.25(d,J=9.2Hz,12H),1.15(d,J=7.1Hz,3H),0.78(t,J=7.1Hz,3H),0.63(dd,J=9.9,7.6Hz,1H)ppm.

[0314] 13 C NMR (101MHz, CDCl3): δ174.2, 139.6, 131.9, 129.1, 120.6, 81.9, 42.9, 41.8, 35.7, 25.1 (d, J = 4.4Hz), 19.5, 12.8 (d, J = 27.2Hz) ppm.

[0315] 11 B NMR (128MHz, CDCl3): δ23.4ppm.

[0316] Product 2n is a yellow oily substance. During purification, the eluent used was petroleum ether:ethyl acetate in a volume ratio of 3:1.

[0317] 1H NMR (400MHz, CDCl3): δ7.28-7.25(m,1H),7.24-7.14(m,3H),3.44-3.33(m,2H),3.31-3.18(m,2H),1.63(dd,J=9.8,4.1Hz,1H),1 .46(dd,J=7.7,4.1Hz,1H),1.25(d,J=9.3Hz,12H),1.17(t,J=7.1Hz,3H),0.79(t,J=7.1Hz,3H),0.66(dd,J=9.9,7.6Hz,1H)ppm.

[0318] 13 C NMR (101MHz, CDCl3): δ174.0,142.6,134.7,130.0,127.3,127.0,125.5,81.9,42.9,41.7,35.9,25.1(d,J=6.2Hz),19.4,12.7(d,J=20.6Hz)ppm.

[0319] 11 B NMR (128MHz, CDCl3): δ22.9ppm.

[0320] Product 2O is a yellow oily substance. During purification, the eluent used was petroleum ether:ethyl acetate in a volume ratio of 3:1.

[0321] 1 H NMR (400MHz, CDCl3): δ7.82-7.69(m,4H),7.49-7.40(m,3H),3.50-3.33(m,2H),3.33-3.16(m,2H),1.83-1.76(m,1H),1.52( dd,J=7.6,4.0Hz,1H),1.27(d,J=9.3Hz,12H),1.19(t,J=7.1Hz,3H),0.76(dd,J=9.8,7.5Hz,1H),0.69(t,J=7.1Hz,3H)ppm.

[0322] 13 C NMR (101MHz, CDCl3): δ175.2,137.8,133.5,132.4,128.5,127.8,127.7,126.4,126.3, 125.9, 125.6, 81.6, 43.0, 42.1, 36.4, 25.2 (d, J = 3.2Hz), 19.6, 12.7 (d, J = 18.6Hz) ppm.

[0323] 11B NMR (128MHz, CDCl3): δ22.0ppm.

[0324] Product 2p is a white solid. During purification, the eluent used was petroleum ether:ethyl acetate in a volume ratio of 3:1.

[0325] 1 H NMR (400MHz, CDCl3): δ7.60-7.54(m,2H),7.51(d,J=8.3Hz,2H),7.42(t,J= 7.6Hz,2H),7.37-7.30(m,3H),3.53-3.20(m,2H),3.30-3.20(m,2H),1.69(d d,J=9.8,3.9Hz,1H),1.47(dd,J=7.5,3.9Hz,1H),1.26(d,J=8.5Hz,12H),1 .19(t,J=7.1Hz,3H),0.78(t,J=7.1Hz,3H),0.70(dd,J=9.8,7.5Hz,1H)ppm.

[0326] 13 C NMR (101MHz, CDCl3): δ175.1,140.6,139.6,139.4,128.9,127.9,127.43,127.36 ,127.0,81.6,43.1,42.0,35.9,25.2(d,J=3.6Hz),19.6,12.7(d,J=15.2Hz)ppm.

[0327] 11 B NMR (128MHz, CDCl3): δ21.8ppm.

[0328] Based on the above results, it can be concluded that for C(sp) 3 The 1-H borylation reaction exhibits broad compatibility with saturated nitrogen heterocycles and cyclopropane derivatives of varying ring sizes. Notably, five-membered nitrogen heterocycles fused with three, five, or six-membered rings show good tolerance, providing the corresponding borylated products (2b-2e) in moderate to high yields. Furthermore, bis(pyrrolidine-1-acyl)methane (2f) is given up to 95% yield via selective monoboronation. Substrate tolerance extends to α-aryl-substituted N,N-diethylcyclopropane amides with different electron-donating groups, including electron-donating methoxy (2i) and methyl (2j), and electron-withdrawing fluoro (2k), trifluoromethyl (2l), bromo (2m), and chloro (2n), in moderate to high yields. α-naphthyl-substituted N,N-diethylcyclopropane amides (20) and α-biphenyl-substituted N,N-diethylcyclopropane amides (2p) are also compatible.

[0329] Application Example 4

[0330] This example uses the catalysts obtained from Application Example 1 and Comparative Application Examples 1-2 to perform C(sp) 2 The borylation reaction was catalyzed by H, using substrate 3a (CAS number 2133859-08-0). The specific conditions and simplified procedure for the borylation reaction are as follows:

[0331]

[0332] The specific reaction steps are as follows:

[0333] In an argon-filled glove box, [Ir(COD)OMe]2, a ligand (from the example or as shown in L1 below), and a solvent (tetrahydrofuran (THF), diethyl ether (Et2O), toluene, hexane, or cyclohexane)) were added to a 10 mL dry microwave reaction tube at a molar ratio of 1:2. The substrate to solvent ratio was 1 mmol: 1 mL. The amount of [Ir(COD)OMe]2 was 0.5 mol% of the substrate. After stirring at a specific room temperature (rt) for 10 min, substrate 1a was added sequentially, followed by stirring for 10 min, and then B2pin2 was added. The molar ratio of substrate 3a to B2pin2 was 1:1. The microwave reaction tube was then sealed and removed from the glove box, and stirring was continued at the corresponding temperature (room temperature (rt) or 60 °C) for the corresponding duration (6 h or 12 h).

[0334] After the reaction was completed, the product was filtered using a short silica gel pad and the solvent was removed by vacuum evaporation. Finally, the product was purified by flash chromatography on silica gel or preparative chromatography (eluent: petroleum ether / ethyl acetate = 30:1, volume ratio) to obtain the target product.

[0335] When the catalyst used comes from Comparative Application Examples 1 to 2, it is only necessary to replace the catalyst with an equal amount of the catalyst obtained from Comparative Application Examples 1 to 2.

[0336] In this example, product 4a was a colorless oily substance, and the test results are as follows:

[0337] 1 H NMR (400MHz, CDCl3): δ7.42(d,J=2.4Hz,1H),7.37(d,J=8.1Hz,1H),7.02(dd,J=8.0, 2.4Hz,1H),3.89(s,3H),1.40(s,12H),1.28-1.21(m,3H),1.08(d,J=7.4Hz,18H)ppm.

[0338] 1313C NMR (101 MHz, CDCl3): δ 168.5, 157.1, 135.6, 133.9, 123.5, 120.5, 84.0, 52.4, 25.0, 18.0, 12.8 ppm.

[0339] 11 11B NMR (128 MHz, CDCl3): δ 32.1 ppm.

[0340] It can be seen from this that in this example, the corresponding product was indeed obtained through the catalytic borylation reaction.

[0341] The yields of product 4a were calculated based on the NMR data of different reactions, and the specific test results are shown in Table 5.

[0342] Table 5 Effects of ligand type, solvent type and reaction duration on the C(sp 2 )–H borylation reaction

[0343]

[0344] The results in Table 5 show that compared with Complex B and C, only Complex A has catalytic activity; this reflects its excellent performance in C(sp 2 )-H activation. Subsequently, we used [Ir(cod)OMe]2 as the precatalyst to further evaluate the catalytic activity of various ligands in the C( sp2 )-H borylation reaction; similar to the rule of the C(sp 3 )-H borylation reaction, ligands L1-L3 did not show catalytic activity. Different from the C(sp 3 )-H system, ligands L7 and L9 showed considerable activity, indicating a reduced sensitivity to the electronic effect of the phosphine substituent in C(sp 2 )-H activation. It is noteworthy that L9 achieved nearly quantitative conversion, producing 89% of the isolated product 4a.

[0345] Combining the results of Application Example 2 and Application Example 4, it can be seen that reasonable adjustment of the steric and electronic properties of P and Si ligands can achieve efficient C(sp 3 )-H and C(sp 2 )-H borylation reactions at room temperature. The successful realization of C-H borylation under mild conditions highlights the synthetic practicability of this type of ligand and further demonstrates the potential of P and Si ligands as a versatile platform for expanding the scope of transition metal-catalyzed C-H functionalization.

[0346] Application Example 5

[0347] When ligand L9 was used in this example, the catalyst (Application Example 1) for the C(sp 2The efficiency of catalytic borylation reactions of different substrates of )–H differs from that in application example 4 in the following ways:

[0348] The substrates vary, specifically any one of 3b to 3k, and the solvent is limited to tetrahydrofuran, with a reaction time of 6 hours. The eluent ratios used in the purification process also vary, which will be described in detail later.

[0349] The corresponding product structures and yields are shown below:

[0350]

[0351] The products of the different reactions described above were tested, and the yields were calculated based on the following test results:

[0352] Product 4b is a colorless oily substance. The eluent used for purification was petroleum ether / ethyl acetate at a volume ratio of 10 / 1.

[0353] 1 H NMR (400MHz, CDCl3): δ7.94 (d, J = 7.8Hz, 1H), 7.54-7.48 (m, 2H), 7.46-7.38 (m, 1H), 3.91 (s, 3H), 1.42 (s, 12H) ppm.

[0354] 13 C NMR (101MHz, CDCl3): δ168.6,133.5,132.3,132.0,129.1,128.9,84.2,52.4,25.0ppm.

[0355] 11 B NMR (128MHz, CDCl3): δ32.4ppm.

[0356] Product 4c is a colorless oily substance. The eluent used for purification was petroleum ether / ethyl acetate at a volume ratio of 10 / 1.

[0357] 1 H NMR (400MHz, CDCl3): δ7.81(d,J=7.2Hz,1H),7.42(td,J=7.5,1.1Hz,1H),7.36(t,J=7.0Hz,1H),7.29–7.25( m,1H),3.58(q,J=7.1Hz,2H),3.22(q,J=7.1Hz,2H),1.31(s,12H),1.27–1.25(m,3H),1.07(t,J=7.1Hz,3H).

[0358] 13C NMR (101MHz, CDCl3): δ171.84,135.18,130.62,128.35,125.55,83.56,43.16,39.92,25.03,24.69,13.82,12.62ppm.

[0359] The product, 4 days after extraction, was a white solid. The eluent used for purification was petroleum ether / ethyl acetate at a volume ratio of 20 / 1.

[0360] 1 H NMR (400MHz, CDCl3): δ7.87(dd,J=7.3,1.6Hz,1H),7.64(dd,J=5.8,3.4Hz,1H),7.58(dd,J=7.8,1.2Hz,1H),7.54-7.48(m,1H),7.45(dd,J=6.0, 3.2Hz,1H),7.34-7.29(m,1H),7.26-7.21(m,2H),3.20-3.09(m,2H),2. 84-2.73(m,2H),2.42-2.29(m,1H),2.05-1.90(m,1H),1.01(s,12H)ppm.

[0361] 13 C NMR (101MHz, CDCl3): δ172.8,150.8,149.4,142.0,136.9,130.7,126.4,126.3,124.0,123.8,119.7,110.2,83.4,48.8,35.2,24.7,16.7ppm.

[0362] 11 B NMR (128MHz, CDCl3): δ 2.0ppm.

[0363] Product 4e, a colorless oily substance:

[0364] 1 H NMR (600MHz, CDCl3): δ7.84 (dd, J=8.6, 1.7Hz, 1H), 6.92 (t, J=2.1Hz, 1H), 6.86-6.82 (m, 1H),3.86(s,3H),1.41(d,J=1.9Hz,12H),1.30-1.23(m,3H),1.09(d,J=8.4Hz,18H)ppm.

[0365] 13C NMR (151MHz, CDCl3): δ168.2,159.6,131.1,125.8,123.4,119.7,84.0,52.1,24.9,18.0,12.8ppm.

[0366] 11 B NMR (128MHz, CDCl3): δ30.8ppm.

[0367] Product 4f, a colorless oily substance:

[0368] 1 H NMR (600MHz, CDCl3): δ7.17 (d, J = 3.6Hz, 1H), 7.08 (d, J = 3.5Hz, 1H), 4.37 (q, J = 7.1Hz, 3H), 1.35 (s, 12H) ppm.

[0369] 13 C NMR (151MHz, CDCl3): δ158.9,148.9,124.2,117.8,84.8,61.2,24.9,14.5ppm.

[0370] 11 B NMR (128MHz, CDCl3): δ22.4ppm.

[0371] 4g of product, a colorless oily substance, was purified using a petroleum ether / ethyl acetate ratio of 1 / 1 (v / v).

[0372] 1 H NMR (400MHz, CDCl3): δ9.47(brs,1H),6.20(dd,J=2.6,1.0Hz,1H),4.32(q,J=7.1Hz,2H),2.27(s,3H),1.38(d,J=7.1Hz,3H),1.35(s,12H)ppm.

[0373] 13 C NMR (101MHz, CDCl3): δ161.8,133.3,125.7,115.6,83.5,60.4,24.9,14.6,12.8ppm.

[0374] 11 B NMR (128MHz, CDCl3): δ32.1ppm.

[0375] The product was a colorless oily substance after 4 hours. The eluent used for purification was petroleum ether / ethyl acetate in a 1 / 1 volume ratio.

[0376] 1H NMR (600MHz, CDCl3): δ8.87(brs,1H),7.68(d,J=8.2Hz,1H),7.61(d,J=8.2Hz,1H) ,7.36(t,J=2.9Hz,1H),6.57(dd,J=3.3,1.9Hz,1H),3.91(s,3H),1.45(s,12H)ppm.

[0377] 13 C NMR (151MHz, CDCl3): δ170.3,139.8,129.9,129.8,127.2,122.1,120.5,102.7,84.2,52.2,25.2ppm.

[0378] 11 B NMR (128MHz, CDCl3): δ31.1ppm.

[0379] Product 4i, a white solid, was purified using a petroleum ether / ethyl acetate ratio of 10 / 1 (v / v).

[0380] 1 H NMR (600MHz, CDCl3): δ7.91-7.85(m,1H),7.50-7.46(m,2H),7.41-7.32(m,1H),4.97-4.87(m,1H),2.19-2.11(m,1H),2.00-1.89(m, 1H),1.75-1.67(m,2H),1.58-1.48(m,2H),1.41(s,12H),1.17-1.05(m,2H),0.91(dd,J=10.7,6.7Hz,7H),0.79(d,J=7.0Hz,3H)ppm.

[0381] 13 C NMR (151MHz, CDCl3): δ167.7,134.7,132.1,131.6,128.8,128.3,84.0,75.2,47.5,41.0,34.5,31.6,26.4,25.0,24.9,23.6,22.2,21.0,16.5ppm.

[0382] 11 B NMR (128MHz, CDCl3): δ33.2ppm.

[0383] Product 4j, a white solid, was purified using a petroleum ether / ethyl acetate ratio of 10 / 1 (v / v).

[0384] 1H NMR (400MHz, CDCl3): δ8.11(d,J=7.8Hz,1H),7.56(d,J=4.3Hz,2H),7.51-7.44(m,1H),7.31(d,J= 8.5Hz,1H),6.98(dd,J=8.5,2.5Hz,1H),6.93(d,J=2.5Hz,1H),3.82(t,J=8.2Hz,1H),2.91-2.82( m,2H),2.36-2.27(m,1H),2.27-2.18(m,1H),2.06-1.95(m,2H),1.93-1.84(m,1H),1.74-1.61(m, 1H),1.61-1.41(m,4H),1.35(s,12H),1.29-1.12(m,3H),1.08(d,J=1.9Hz,21H),0.79(s,3H)ppm.

[0385] 13 C NMR (101MHz, CDCl3): δ166.7,148.8,138.3,138.3,133.4,132.6,132.3,129.6,129.3,126.4,121.8,118. 9,84.3,82.1,49.8,44.4,44.2,38.7,37.6,31.6,29.7,27.2,26.5,25.0,23.5,18.3,18.2,12.6,11.5ppm.

[0386] 11 B NMR (128MHz, CDCl3): δ32.0ppm.

[0387] Product 4K, a white solid, was purified using a petroleum ether / ethyl acetate ratio of 10 / 1 (v / v).

[0388] 1 H NMR (400MHz, CDCl3): δ7.90(d,J=7.8Hz,1H),7.48(d,J=4.3Hz,2H),7.40- 7.34(m,1H),5.01-4.84(m,1H),2.01-1.89(m,2H),1.80-1.61(m,5H),1.6 0-1.46(m,5H),1.42(s,12H),1.38-1.20(m,11H),1.16-1.05(m,6H),1.05 -0.96(m,3H),0.90(d,J=6.5Hz,4H),0.89-0.83(m,10H),0.66(s,4H)ppm.

[0389] 13 C NMR (101MHz, CDCl3): δ167.7,134.5,132.0,131.7,128.8,128.5,84.0,56.6,56.4,54.4,44.8,42.7,40.1,39.6,3 6.9,36.3,35.9,35.6,34.2,32.2,28.8,28.4,28.1,27.6,25.0,24.3,23.9,23.0,22.7,21.4,18.8,12.4,12.2ppm.

[0390] 11 B NMR (128MHz, CDCl3): δ 2.7ppm.

[0391] The above results show that for C(sp) 2 The )-H borylation reaction exhibits compatibility with various directing groups (groups adjacent to the substitution site), various heterocycles, and natural product frameworks, providing moderate to excellent yields. Acyl and amide groups on the benzene ring are both directing groups, showing good regioselectivity for the ortho-boronation reaction, with yields of approximately 90%. When oxazoline is used as the directing group in compounds containing C(sp...) 2 )-H and C(sp 3 In substrates with )-H activation sites, selective C(sp) occurs. 2 The )-H borylation reaction yielded 81%. When the relative positions of the substituents on the benzene ring of the standard substrate (3a) changed from 1,3- to 1,4-, only the ortho-boronized product (4e) oriented by the ester group was obtained, indicating that the ester group in this system is aligned with C(sp... 2 The )-H borylation reaction exhibits strong directing ability. Attempts to use methoxy groups as directing groups failed to achieve the expected borylation substitution results. We then evaluated the compatibility of the system with other heteroaryl rings. Furan (4f) and pyrrole (4g) both yielded ideal isolated yields. Furthermore, we investigated the directing groups at different substitution positions of indole derivatives. Only when the directing group was located at position 6 did the reaction produce C(sp) at position 7. 2 The )-H boronized product was isolated in 50% yield. Other positional isomers exhibited poor regioselectivity, leading to different reaction results. To further broaden the generality of the reaction, we evaluated its compatibility with natural product derivatives, including menthol derivatives (3j), β-estradiol derivatives (3k), and dihydrocholesterol derivatives (3l). All reactions yielded desirable products in good yields (4j-4l).

[0392] Application Example 6

[0393] In this example, the experimental conditions in the last row of Table 1 were used to conduct a scale-up experiment of the synthesized product 2a. The difference between this example and application example 2 is that the substrate amount used in this example is 4.5 mmol.

[0394] The results showed that the yield of product 2a in this case was 79%. After the scale-up experiment, the precision of the instrument used was relatively poor, and there were losses in purification and other steps, so the separation yield would be slightly lower.

[0395] Application Example 7

[0396] This example demonstrates an application of product 2a, with the specific process shown below:

[0397]

[0398] The specific steps are as follows:

[0399] Add reactant 2a (59.3 mg, 0.2 mmol) and THF (2.0 mL) to a 25 mL flame-dried Schlenk tube, followed by dropwise addition of Grignard reagent in THF solution (0.3 mL, 1 M, 0.3 mmol, 1.5 substrate equivalent, CAS: 1826-67-1), and stir the mixture for 0.5 h.

[0400] The temperature of the resulting mixture was controlled at -78℃, and a methanol solution of I2 (254 mg, 1.0 mmol, 3.0 mL methanol) was slowly added dropwise; the temperature was maintained, and stirring was continued for 0.5 h.

[0401] While maintaining the temperature, slowly add a methanol solution of sodium methoxide (54.1 mg, 1.0 mmol, 3.0 mL methanol) to the resulting mixture; heat the resulting mixture to room temperature and then stir for 1 hour while maintaining room temperature.

[0402] Add 5.0 mL of saturated aqueous solution of Na2S2O3 to the resulting mixture to quench the reaction;

[0403] The resulting mixture was diluted with 20 mL of H₂O and extracted three times (3 × 20 mL) with ethyl acetate. The mixed organic phase was dried over anhydrous Na₂SO₄. The dried product was purified by column chromatography on silica gel using petroleum ether / ethyl acetate = 5 / 1 as the eluent, yielding a colorless oily product with a calculated yield of 55%. Product 5 is a precursor to a five-membered nitrogen heterocyclic compound, and a series of chemical substances can be synthesized through further derivatization of its double bonds. This demonstrates that the borylation reaction provided by this invention has wide applications in chemical synthesis.

[0404] The test results of the product obtained in this example are as follows:

[0405] 1H NMR (400MHz, CDCl3): δ5.78-5.66(m,1H),5.21-5.12(m,1H),5.04-5.00(m,1H),4.51-4.42(m,1H),3.41-3.28(m,4H),3 .18-3.06(m,2H),2.12-2.03(m,1H),1.91-1.82(m,1H),1.82-1.69(m,1H),1.64-1.54(m,1H),1.12(t,J=7.1Hz,6H)ppm.

[0406] 13 C NMR (101MHz, CDCl3): δ163.1,139.9,114.3,60.8,50.4,41.7,32.4,25.2,13.6ppm.

[0407] Application Example 8

[0408] This example demonstrates an application of product 2a, with the specific process as follows:

[0409]

[0410] The specific process is as follows:

[0411] In an argon atmosphere at -78°C, add a hexane solution (0.2 mL, 2.5 M, 0.5 mmol) of n-BuLi to a 25 mL Schlenk tube containing thiophene (42.2 mg, 0.5 mmol) and THF (1.0 mL); the Schlenk tube was flame-dried before use.

[0412] Maintain the temperature and stir the resulting mixture for 2 hours;

[0413] While maintaining the temperature, add 1.0 mL of a THF solution containing product 2a (59.3 mg, 0.2 mmol) to the resulting mixture; and stir the mixture for 2 h.

[0414] The mixture was heated to room temperature, and a THF (1.0 mL) solution of NBS (89.0 mg, 0.5 mmol, N-bromosuccinimide, CAS: 128-08-5) was added to it, and the mixture was stirred for 2.5 h.

[0415] The resulting mixture was diluted with 10 mL of H₂O, and the resulting two-phase mixture was extracted three times with dichloromethane (3 × 10 mL). The organic phases were then combined. The combined organic phases were dried over Na₂SO₄ and then removed from the initial solvent. Finally, the remaining product was purified by column chromatography on silica gel using petroleum ether / ethyl acetate = 8 / 1 as the eluent. A yellow oily product was obtained, and the calculated yield was 68%. Similar to Application Example 8, this example also demonstrates that the borylation reaction provided by this invention can be widely applied in synthetic chemistry.

[0416] The test results of the product obtained in this example are as follows:

[0417] 1 H NMR (400MHz, CDCl3): δ7.10(dd,J=5.0,1.3Hz,1H),6.93(d,J=3.3Hz,1H),6.90(dd,J=5.0,3.4Hz,1H),5.39(t,J=7.1Hz,1H),3.55(td ,J=9.2,6.4Hz,1H),3.47-3.28(m,3H),3.122-3.07(m,2H),2.35(td,J=6.6,3.1Hz,1H),2.03-1.83(m,3H),1.11(t,J=7.1Hz,6H)ppm.

[0418] 13 C NMR (101MHz, CDCl3): δ163.2,149.3,126.8,123.7,123.2,57.9,51.0,41.7,35.7,25.9,13.6ppm.

[0419] Application Example 9

[0420] This example provides a further application of product 2i, and a simplified flowchart is shown below:

[0421]

[0422] The specific process is as follows:

[0423] At -78°C, a Schlenk tube equipped with a magnetic stir bar and oven-dried was provided, containing 2h (0.2 mmol, 1.0 equiv.), ClCH2I (2.0 mmol, 10.0 equiv.), and THF (2.0 mL); a hexane solution of n-BuLi (1.6 M, 2.0 mmol, 10.0 equiv.) was added dropwise to the above tube.

[0424] Maintain the temperature, stir the resulting mixture for 10 minutes, then raise the temperature to room temperature and continue stirring for 16 hours; after completion, remove the residual solvent by vacuum distillation.

[0425] Finally, the remaining product was purified by column chromatography on silica gel using petroleum ether / ethyl acetate = 3 / 1 as the eluent; the product corresponding to the yellow color was obtained, and the product yield was calculated to be 66%.

[0426] The product obtained in this example can be converted in one step to produce milnacipran, a serotonin-norepinephrine reuptake inhibitor (SNRI) with antidepressant activity.

[0427] The test results of the product obtained in this example are as follows:

[0428] 1 H NMR (500MHz, CDCl3): δ7.28-7.20(m,4H),7.19-7.13(m,1H),3.63-3.49(m,2H),3.20-3.11(m,1H),3.08-3.00(m,1H),2.02-1.92(m,1H),1 .40(dd,J=6.4,4.4Hz,1H),1.28(s,12H),1.11(t,J=7.2Hz,4H),0.91(dd,J=8.9,4.7Hz,1H),0.61-0.54(m,1H),0.52(t,J=7.0Hz,3H)ppm.

[0429] 13 C NMR (126MHz, CDCl3): δ170.6,142.1,128.6,126.5,126.2,83.4,41.5,39.3,35.7,25.0,23.4,19.6,12.7,12.7ppm.

[0430] 11 B NMR (128MHz, CDCl3): δ33.7ppm.

[0431] Application Example 10

[0432] This example demonstrates an application of product 4a, with a brief flowchart as follows:

[0433]

[0434] The specific preparation process in this example is based on the reference (KNKumar, M.Mhate, V.Ravichandiran and S.P.Swain, Synthesis 2024, 56, 573-576.).

[0435] The product obtained in this example has a typical boron-containing pharmacophore group, which is expected to be further synthesized into boron-containing drugs; for example, functionalization can yield crisaborole (a PDE4 inhibitor approved by the U.S. Food and Drug Administration for the treatment of atopic dermatitis).

[0436] The characterization results of the product obtained in this example are as follows:

[0437] 1 H NMR (400MHz, DMSO-d6): δ9.74(s,1H),8.85(s,1H),7.51(d,J=8.7Hz,1H),6.78-6.66(m,2H),4.86(s,2H)ppm.

[0438] 13 C NMR (151MHz, DMSO-d6): δ160.0,156.4,131.8,115.0,107.6,69.5ppm.

[0439] 11 B NMR (128MHz, DMSO-d6): δ37.4ppm.

[0440] Application Example 11

[0441] This example demonstrates the application of product 4e, with a simplified process as follows:

[0442]

[0443] The specific preparation process in this example is based on the reference (KNKumar, M.Mhate, V.Ravichandiran and S.P.Swain, Synthesis 2024, 56, 573-576.).

[0444] The product obtained in this example possesses typical boron-containing pharmacophores and holds promise for further synthesis of boron-containing drugs. For instance, it could be converted into a TbLeuRS inhibitor with potent antibacterial activity against Mycobacterium tuberculosis.

[0445] The characterization results of the product obtained in this example are as follows:

[0446] 1 H NMR (400MHz, DMSO-d6): δ9.30(s,1H),9.05(s,1H),7.18(d,J=8.2Hz,1H),7.09(d,J=2.4Hz,1H),6.87(dd,J=8.2,2.4Hz,1H),4.86(s,2H)ppm.

[0447] 13C NMR (101MHz, DMSO-d6): δ156.4,144.2,122.1,118.6,115.9,69.6ppm.

[0448] 11 B NMR (128MHz, CDCl3): δ 7.0ppm.

[0449] As can be seen from Application Examples 7-11, the borylated products obtained by the borylation reaction provided by the present invention have significant effects in chemical synthesis, drug preparation, and other fields.

[0450] Theoretical calculation example

[0451] This example studies the mechanism of the borylation reaction, specifically using DFT (Gaussian 16) calculations.

[0452] The first aspect of this example explores C(sp) 3 The kinetic isotope effect of the )-H borylation process, and the corresponding chemical reaction process, are as follows:

[0453]

[0454] Where R = D indicates that R is deuterium.

[0455] In an argon-filled glove box, [Ir(COD)OMe]2, a ligand (from the example or as shown in L1 below), and cyclohexane were added to a 10 mL dry microwave reaction tube in a 1:2 molar ratio. The amount of [Ir(COD)OMe]2 was 5 mol% of the substrate, and the ratio of substrate to cyclohexane was 2 mmol: 2.5 mL. After stirring at a specific temperature (room temperature rt) for 10 min, substrate 1a (or 1a-D) was added sequentially, and after stirring for 10 min, B2pin2 was added. The molar ratio of substrate 1a to B2pin2 was 1:1. In this example, the amount of substrate used was 0.2 mmol.

[0456] The resulting mixture was continuously stirred at room temperature until analytical sampling was performed. At regular intervals, small samples were collected using a micropipette, transferred to gas chromatography tubes, and immediately quenched by adding 1 mL of dichloromethane (DCM). The quenched samples were then placed at room temperature and quantitatively analyzed by gas chromatography (GC).

[0457] Table 6 shows the decrease in product yield and reactant concentration at different time points.

[0458] Table 6. Statistics on the decrease in product yield and reactant concentration at different time periods.

[0459]

[0460]

[0461] In Table 6, C(2a) represents the concentration of product 2a.

[0462] Based on the time and reactant concentration decrease values ​​in the table above, curves were plotted and fitted. The results were obtained. Figure 4 The results are shown. Calculation Figure 4 The slopes of the two straight lines are kH / kD = KIE = 3.3.

[0463] Based on the above, we propose a mechanism in which [Ir(cod)OMe]2, ligands L8 and B2pin2 first generate a catalytically active species A with two empty coordination sites (e.g., Figure 5 (As shown). Species A then coordinates the directing group of the substrate (DG, commonly -CO-NEt2 in this invention) to form intermediate B, intermediate C (sp... 3 )-H activation generates intermediate C, which then undergoes reduction and elimination to generate borylated product and intermediate D. Finally, intermediate D reacts with B2pin2 to regenerate species A, completing the catalytic cycle.

[0464] In summary, this invention provides and prepares a series of ligands, which, when combined with Ir, form catalysts that, for (sp... 3 )-H and C(sp 2 The borylation reaction of )-H exhibits excellent catalytic performance, specifically enabling borylation reactions at high temperatures or room temperature. Through fine-tuning of the ligand structure, the catalyst prepared in this invention can perform highly efficient borylation reactions with precise positional selection on substrates with different functional groups, such as saturated nitrogen heterocycles, cyclopropanes, and aromatic compounds. Furthermore, the obtained borylated products are also of significant value as multifunctional synthetic intermediates for further functionalization.

[0465] The embodiments of the present invention have been described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments, and various changes can be made within the scope of knowledge possessed by those skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof can be combined with each other unless otherwise specified.

Claims

1. A ligand, characterized in that, The ligand has the following structural formula: Where R is the same or different, and independently represents one of phenyl, p-methoxyphenyl, cyclohexyl, or 3,5-di(trifluoromethyl)phenyl; R' means the same or different, and independently represents one of C1-4 alkyl, phenyl, or tolyl.

2. The ligand according to claim 1, characterized in that, In the ligand, the C1-4 alkyl group of R' includes at least one of methyl and isopropyl; And / or, the ligand is a compound with the following structure:

3. A method for preparing the ligand as described in claim 1 or 2, characterized in that, The preparation method includes reacting the intermediate product shown in Formula I with a chlorosilane with the chemical formula R'SiHCl under the action of n-butyllithium. Where X represents one of Br, Cl and F.

4. The preparation method according to claim 3, characterized in that, The method for obtaining the intermediate product shown in Formula I includes the following steps: The ortho-dihalobenzene and R2PCl are reacted under the action of n-butyllithium; or, 2-Halogenated phenylphosphine dichloride was reacted with Grignard reagent ArMgBr.

5. A catalyst, characterized in that, The catalyst is a complex formed by the ligand shown in claim 1 or 2 and [Ir(COD)OMe]2; the structure of the catalyst is shown below:

6. A method for synthesizing the catalyst as described in claim 5, characterized in that, The synthesis method includes the following steps: mixing and reacting [Ir(COD)OMe]2 with the ligand shown in claim 1 or 2.

7. The use of the catalyst according to claim 5 in the preparation of organoboron compounds, characterized in that, The method for preparing organoboron compounds includes reacting a substrate with phenazine diboronate under the catalytic conditions described above; The substrate has C(sp) 2 )-H or C(sp 3 )-H.

8. The application according to claim 7, characterized in that, With C(sp 2 The substrates of )-H are at least one of the compounds shown in the following structural formulas: And / or, having C(sp 3 The substrates of )-H are at least one of the compounds shown in the following structural formulas:

9. The use of the ligand according to any one of claims 1 to 2 in the preparation of organoboron compounds; characterized in that, The method for synthesizing the organoboron compound includes reacting the substrate with borane diboron ester under the conditions of the ligand and [Ir(COD)OMe]2. The substrate has C(sp) 2 )-H or C(sp 3 )-H.

10. The application as described in any one of claims 7 to 9 in pharmaceutical preparation, synthetic chemistry, and materials preparation.

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