A method for site-selective carbonylation of remote b-h bonds in carboranes

Abstract

The application discloses a method for site-selective carbonylation of remote B-H bond of carborane without a guiding group, which realizes efficient carbonylation conversion of carborane by a palladium catalytic system under mild reaction conditions with carbon monoxide as a carbonyl source, and carboxylic acid ester derivatives of carborane are obtained by one-step construction. The compound can be used as a multifunctional synthon to continue downstream conversion, and a series of carborane molecule libraries with various structures are obtained.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis, specifically relating to a method for selective carbonylation of the distal B–H bond sites of carboranes. Background Technology

[0002] Carboxylic acids and their derivatives are indispensable structural units in living systems and are also the most prevalent functional groups in modern drug molecules and functional materials. Developing novel carboxylic acid cores with unique three-dimensional structures is of paramount importance for expanding the research boundaries of organic synthetic chemistry and promoting innovative development in biomedicine and materials science.

[0003] Currently, the field of medicinal chemistry is undergoing a paradigm shift from "planar molecules" to "three-dimensional molecules." To address the problems of poor metabolic stability and significant off-target effects inherent in traditional planar aromatic ring drug molecules, researchers are dedicated to developing three-dimensional bioisosteres that can precisely mimic the spatial configuration of aromatic hydrocarbons. Against this backdrop, carboranes, as a class of cage-like boron cluster compounds with three-dimensional σ-aromaticity, have become ideal candidates to replace traditional aromatic rings due to their perfect spherical structure, excellent chemical stability, and unique biocompatibility. Crucially, the multiple modifiable sites on the carborane skeleton allow for precise functionalization, providing a rich platform for constructing structurally diverse functional molecules. However, existing synthetic methods for boron-site carborane carboxylic acids generally suffer from inherent drawbacks such as lengthy steps and low atom economy. Traditional synthetic routes rely on a three-step reaction of iodination, alkylation, and oxidation, requiring harsh conditions such as strong acidity and strong oxidizing properties throughout, and necessitating the use of water- and oxygen-sensitive Grignard reagents and highly toxic chromium trioxide oxidants, severely limiting their widespread application in the biopharmaceutical and materials fields. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a palladium-catalyzed selective carbonylation method for distal B–H bonds of carboranes without the need for a directing group. The method uses carbon monoxide as the carbonyl source and can efficiently construct a series of carborane carboxylic acid ester derivatives in one step. These ester derivatives exhibit excellent stability and are easily separated and purified. Carborane carboxylic acids can be quantitatively obtained through mild hydrolysis, and further diverse downstream derivatization reactions can rapidly prepare a library of structurally rich functionalized carborane molecules.

[0005] The specific technical solution of this invention is as follows:

[0006] A method for preparing a carborane carboxylic acid ester, wherein the hydrogen atom on the distal B atom of the carborane is replaced by -COOC(CF3)2, and the carborane is an ortho-carborane, meta-carborane, or para-carborane. One or more carbon atoms and / or boron atoms in the carborane structure are substituted by one or more of the following: hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, 5-10 member oxygen-containing spirocyclic heterocycle, C2-C6 alkoxyalkyl, silyl group substituted with 1-3 C1-C6 alkyl groups, phenyl, and pinacol boronic acid ester group. The phenyl group is substituted by one or more of the following: hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, and five- or six-membered heteroaryl.

[0007] The method involves reacting carborane with a palladium catalyst, CO, an oxidant, hexafluoroisopropanol, and an organic acid at 0–100 °C for 24–48 hours.

[0008] Preferably, the palladium catalyst is selected from one or more of Pd(AcO)2, Pd(TFA)2, Pd(CH3CN)4(BF4)2, and Pd(CH3CN)4(OTf)2. Pd(CH3CN)4(BF4)2 is preferred. 2。

[0009] The method of the present invention uses an oxidant that is an organic peroxide or an inorganic peroxide, selected from one or more of tBuOOtBu, K2S2O8, and (NH4)2S2O8. (NH4)2S2O8 is preferred. 8。

[0010] The organic acid in the method of this invention is selected from one or more of AcOH, Cl3CCOOH, TFAH, and TfOH. TFAH is preferred.

[0011] The method described in this invention further includes an additive in the reaction system, selected from one or more of AgOAc, NaOAc, CuOAc, and Cu(OAc)2. Cu(OAc)2 is preferred. 2。

[0012] The method described in this invention is preferably carried out at room temperature - 80°C for 24-48 hours.

[0013] In a preferred method of this invention, Pd(CH3CN)4(BF4)2 is used as a catalyst, carbon monoxide (CO) as a carbonyl source, trifluoroacetic acid as an organic acid, and hexafluoroisopropanol (HFIP) as a solvent, at room temperature -40°C. o C (preferably room temperature, 10-30°C) oThe reaction is carried out under the conditions of C) for 24-48 hours. The molar ratio of carborane to catalyst is 10:0.5-2 (preferably 10:1), and the molar ratio of carborane to trifluoroacetic acid is 1:2-4 (preferably 1:3).

[0014] A preferred method of the present invention, based on the above method, adds the additive copper acetate (Cu(OAc)2, wherein the molar ratio of carborane to copper acetate is 10:1-3 (preferably 10:2), and is heated at 40-80 °C. o C (preferred 60) o The reaction is carried out under the conditions of C) for 24-48 hours.

[0015] The carborane described in this invention has the following general formula:

[0016]

[0017] Among them, R 1 -R 4 The same or different can represent hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, 5-10 hydroxyspirocyclic heterocycle, C2-C6 alkoxyalkyl, silyl substituted with 1 to 3 C1-C6 alkyl groups, phenyl, pinacol boronic acid ester group, wherein the phenyl group is replaced by hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, five- or six-membered heteroaryl.

[0018] Preferred, R 1 -R 4 The same or different, representing hydrogen, methyl, ethyl, n-butyl, methoxy, ethoxy, cyclopentyl, 5-10 member oxygen-containing spirocyclic heterocycle, methoxyethyl, trimethylsilyl, phenyl, pinacol boronic acid ester group, wherein the phenyl is replaced by hydrogen, methyl, ethyl, n-butyl, methoxy, ethoxy, phenoxy, F, Cl, Br, I, trifluoromethyl, trifluoromethoxy, methoxycarbonyl, thiophene.

[0019] Preferred, R 1 and R 2 Same, R 3 and R 4 same.

[0020] The method described in this invention further includes the steps of extracting the reaction product with saturated brine and ethyl acetate, taking the organic phase, removing the solvent, and then purifying it by column chromatography.

[0021] Another object of the present invention is to provide a method for preparing carborane carboxylic acid, characterized in that carborane carboxylic acid ester is prepared by the method according to any one of claims 1-9, and then hydrolyzed to obtain carborane carboxylic acid.

[0022] Another objective of this invention is to provide a diversified derivatization method for carborane carboxylic acids based on the boron site. After preparing carborane carboxylic acids using the method described in this invention, efficient conversion can be achieved through the following four pathways:

[0023] 1. Esterification and amidation reactions: React with alcohols (4-hydroxypyridine, borneol, furanose, pyranose), amines (phenylalanine, methyl 7-aminoheptanoate hydrochloride, and 2-(4-(aminomethyl)phenoxy)-N,N-dimethylethane-1-amine) and other reagents to construct carborane esters and carborane amide derivatives with diverse structures;

[0024] 2. Lossen rearrangement reaction: It undergoes a metal-free Lossen rearrangement reaction with dioxazolone to generate isocyanate-substituted carborane, providing highly active reaction sites for subsequent bioconjugation and functionalization;

[0025] 3. Free radical oxidative decarboxylation functionalization reaction: In the silver salt / peroxide oxidation system, carborane boron center free radicals are generated in situ, which then undergo coupling reactions with various free radical acceptors to achieve arylation, fluorination, and azidation transformation of carboranes;

[0026] 4. Free radical reduction decarboxylation and borylation reaction: The carborane carboxylic acid is converted into N-hydroxyphthalimide (NHPI) ester as a free radical precursor, which reacts with bis(catechol) borate ester (B2cat2) to efficiently prepare borated carborane derivatives.

[0027] The present invention aims to simplify the preparation process of carborane carboxylic acid derivatives and expand the application scope of carborane molecules in medicinal chemistry, organic light-emitting materials, biomedical materials, polymer materials, nanomaterials and magnetic materials.

[0028] Advantages of this invention:

[0029] This invention features mild reaction conditions, excellent atom economy and step economy, a wide range of applicable substrates, and the reaction can be successfully scaled up. In contrast, existing technologies suffer from drawbacks such as lengthy synthesis steps, harsh reaction conditions, and poor substrate compatibility. They typically require stoichiometric amounts of metal reagents or additives and generate large amounts of difficult-to-handle metal salt byproducts, which does not align with the development principles of green and sustainable chemistry. Attached Figure Description

[0030] Figure 1 This is a schematic diagram illustrating the mechanism of the method described in this invention. Detailed Implementation

[0031] The present invention will now be described in detail with reference to specific embodiments and exemplary examples, but these descriptions should not be construed as limiting the present invention in any way. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and implementation methods of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention.

[0032] Example 1: Preparation of carborane carboxylic acid ester.

[0033]

[0034] Standard Method A: A dried Schlenk flask equipped with a magnetic stir bar was filled with carborane 1a (0.1 mmol), Pd(CH3CN)4(BF4)2 (10%, 4.5 mg, 0.01 mmol), and (NH4)2S2O8 (23 mg, 0.1 mmol). The flask was then evacuated and refilled with CO three times, followed by the addition of HFIP (1 mL, 0.1 M) and TFAH (3.0 equivalent, 23 μL, 0.3 mmol). The mixture was stirred at room temperature for 24 hours. After the reaction was complete, the resulting mixture was diluted with ethyl acetate and extracted (10 mL × 3 times). After removing volatiles under vacuum, the product was purified through 200-300 mesh silica gel to give the target product 2a in 82% yield.

[0035] The preparation was carried out by modifying a single reaction condition, following the standard method described above.

[0036]

[0037] Yield% represents the total yield of the products substituted at the B9 and B8 positions, where B(9 / 8) indicates the mass ratio of the product substituted at the B9 position to the product substituted at the B8 position.

[0038] Standard Method B: In a dried Schlenk flask equipped with a magnetic stir bar, add carborane (0.1 mmol), Pd(CH3CN)4(BF4)2 (10%, 4.5 mg, 0.01 mmol), and (NH4)2S2O8 (23 mg, 0.1 mmol), Cu(AcO)2 (20 mol%, 4.0 mg, 0.02 mmol). Then, evacuate the flask and refill it with CO three times, followed by the addition of HFIP (1 mL, 0.1 M) and TFAH (3.0 equivalent, 23 μL, 0.3 mmol). The mixture is kept at 40–80 °C. o Stirring at C for 36-48 hours. After the reaction is complete, the resulting mixture is diluted with ethyl acetate and extracted (10 mL × 3 times). After removing volatiles under vacuum, the product is purified by passing through 200-300 mesh silica gel to obtain the target product 2a.

[0039] Following the above method and using standard conditions, a series of carborane carboxylic esters 2a-2z were prepared by reacting with carboranes of different substitutions as raw materials (where a is the yield prepared by standard method A; b is the yield prepared by standard method B at 60°C; and c is the yield prepared by standard method B at 80°C).

[0040]

[0041]

[0042]

[0043]

[0044]

[0045]

[0046]

[0047] The structural identification results of the above compounds (using a 400MHz NMR spectrometer) are as follows:

[0048] 2a: White solid. Yield: 82%.

[0049] 1 H NMR (400 MHz, CDCl3) δ 5.76, (hept, J = 8.0 Hz, 1H), 3.66 (s, 1H), 3.69 (s, 1H).

[0050] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 120.8 (q, J = 283.0 Hz), 64.5 (hept, J= 34.0 Hz), 53.7, 53.6.

[0051] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.6 (1B), –2.2 (1B), –9.0 (2B), –13.9(4B), –15.1 (2B).

[0052] 19 F NMR (376 MHz, CDCl3) δ – 73.5.

[0053] HRMS (ESI + ): m / z calcd for C2H 11 B 10 F6O2 [M−H] − : 327.1661, Found:327.1656.

[0054] 2b: White solid. Yield: 86%.

[0055] 1 H NMR (400 MHz, CDCl3) δ 5.77 (hept, J = 8.0 Hz, 1H), 2.09 (s, 3H),2.04 (s, 3H).

[0056] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 120.8 (q, J = 284.0 Hz), 73.2, 73.0,64.4 (hept, J = 34.0 Hz), 23.3, 23.0.

[0057] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –3.8 (1B), –5.0(1B), –8.5 (2B), –10.0(6B).

[0058] 19 F NMR (376 MHz, CDCl3) δ –73.5.

[0059] 2c: Colorless oil. Yield: 80%.

[0060] 1 H NMR (400 MHz, CDCl3) δ 5.77 (hept, J = 6.0 Hz, 1H), 2.58 – 2.50 (m,4H), 2.48 – 2.41 (m, 2H),

[0061] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 120.8 (q, J = 282.0 Hz), 83.9, 64.4(hept, J = 34.0 Hz), 34.6, 34.3, 32.3.

[0062] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –5.1 (1B), –6.6 (1B), –7.9 (2B), –9.3(2B), –12.0 (4B).

[0063] 19 F NMR (376 MHz, CDCl3) δ –73.46, –73.48.

[0064] 2d: Colorless oil. Yield: 75%.

[0065] 1 H NMR (400 MHz, CDCl3) δ 5.76 (hept, J = 6.0 Hz, 1H), 4.62 (m, 4H),2.96 (s, 2H), 2.93 (s, 2H).

[0066] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 120.8 (q, J = 281.0 Hz), 84.3, 81.4,64.5 (hept, J = 34.0 Hz), 55.1, 47.0, 46.8.

[0067] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –4.7 (1B), –6.0 (1B), –7.8 (2B), –9.4(2B), –11.9 (4B).

[0068] 19 F NMR (376 MHz, CDCl3) δ –73.46, –73.48.

[0069] 2e: Colorless oil. Yield: 85%.

[0070] 1H NMR (400 MHz, CDCl3) δ 5.78 (hept, J = 8.0 Hz, 1H), 2.19 – 2.11 (m,4H), 1.59 – 1.47 (m, 4H), 1.40 – 1.29 (m, 4H), 0.96 – 0.91 (m, 6H).

[0071] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 120.8 (q, J = 282 Hz), 79.5, 64.4(hept, J = 35.0 Hz), 34.8, 34.6, 31.93, 31.88, 22.5, 13.8.

[0072] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –3.6 (1B), –4.7(1B), –10.4 (4B), –11.3(4B).

[0073] 19 F NMR (376 MHz, CDCl3) δ –73.4.

[0074] 2f: Colorless oil. Yield: 81%.

[0075] 1 H NMR (400 MHz, CDCl3) δ 5.77 (hept, J = 8.0 Hz, 1H), 3.95 (s, 2H),3.91 (s, 2H), 3.41 (s, 3H), 3.39 (s, 3H).

[0076] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 120.8 (q, J = 284 Hz), 75.9, 72.6,72.5, 64.5 (hept, J = 34.0 Hz), 59.8.

[0077] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –2.2 (1B), –3.2 (1B), –11.2 (8B).

[0078] 19 F NMR (376 MHz, CDCl3) δ –73.5.

[0079] 2h: White solid. Yield: 83%.

[0080] 1 H NMR (400 MHz, CDCl3) δ 7.42 – 7.39 (m, 4H), 7.29 – 7.24 (m, 2H),7.18 – 7.13 (m, 4H), 5.82 (hept, J = 8.0 Hz, 1H).

[0081] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 130.8, 130.73, 130.67, 129.7, 128.7,128.6, 120.8 (q, J = 284.0 Hz), 85.0, 84.9, 64.5 (hept, J = 34 Hz).

[0082] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.3 (1B), –2.4 (1B), –9.5 – –11.6(8B).

[0083] 19 F NMR (376 MHz, CDCl3) δ –73.4.

[0084] 2i: White solid. Yield: 83%.

[0085] 1 H NMR (400 MHz, CDCl3) δ 7.30 – 7.26 (m, 4H), 6.97 – 6.94 (m, 4H),5.81 (hept, J = 8.0 Hz, 1H), 2.23 (s, 6H).

[0086] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 141.19, 141.15, 130.64, 130.58, 129.4,129.3, 127.2, 127.1, 120.9 (q, J = 284.0 Hz), 85.4, 85.3, 64.5 (hept, J =34.0 Hz), 21.1.

[0087] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.5 (1B), –2.6 (1B), –9.5 – –11.7(8B).

[0088] 19 F NMR (376 MHz, CDCl3) δ –73.4.

[0089] 2j: White solid. Yield: 80%.

[0090] 1 H NMR (400 MHz, CDCl3) δ 7.33 – 7.28 (m, 4H), 6.66 – 6.61 (m, 4H),5.82 (hept, J = 8.0 Hz, 1H), 1.18 (s, 9H), 1.17 (s, 9H).

[0091] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 154.18, 154.15, 130.51, 130.45, 126.89,126.87 125.4, 125.3, 120.9 (q, J = 283.0 Hz), 85.23, 85.19, 64.5 (hept, J =34.0 Hz), 34.7, 31.0.

[0092] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.6 (1B), –2.6 (1B), –10.4 (8B).

[0093] 19 F NMR (376 MHz, CDCl3) δ –73.39, –73.41.

[0094] 2k: White solid. Yield: 89%.

[0095] 1 H NMR (400 MHz, CDCl3) δ 7.34 – 7.31 (m, 4H), 6.67 – 6.64 (m, 4H),5.82 (hept, J = 8.0 Hz, 1H), 3.73 (s, 6H).

[0096] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 161.38, 161.37, 132.3, 132.2, 120.9 (q,J = 285.0 Hz), 122.22, 122.18, 113.91, 113.86, 85.91, 85.85, 64.5 (hept, J =34.0 Hz), 55.47, 55.45.

[0097] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.6 (1B), –2.7 (1B), –9.6 – –10.7(8B).

[0098] 19 F NMR (376 MHz, CDCl3) δ –73.4.

[0099] 2l: White solid. Yield: 88%.

[0100] 1 H NMR (400 MHz, CDCl3) δ 7.33 – 7.28 (m, 4H), 6.66 – 6.61 (m, 4H),5.82 (hept, J = 8.0 Hz, 1H), 3.94 (q, J = 6.8 Hz, 2H), 3.93 (q, J = 6.8 Hz,2H), 1.36 (t, J = 7.2 Hz, 6H).

[0101] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 160.78, 160.77, 132.3, 132.2, 120.9 (q,J = 283.0 Hz) 122.03, 121.98, 114.32, 114.27, 86.04, 85.97, 64.4 (hept, J =34.0 Hz), 63.77, 63.76, 14.7.

[0102] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.7 (1B), –2.8 (1B), –9.7 – –10.6(8B).

[0103] 19 F NMR (376 MHz, CDCl3) δ –73.4.

[0104] 2m: White solid. Yield: 82%.

[0105] 1 H NMR (400 MHz, CDCl3) δ 7.38 – 7.33 (m, 8H), 7.19 – 7.16 (m, 2H),6.97 – 6.94 (m, 4H), 6.78 – 6.75 (m, 4H), 5.82 (hept, J = 8.0 Hz, 1H).

[0106] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 159.99, 159.96, 155.6, 132.5, 132.4,130.2, 124.7, 124.01, 123.99, 120.9 (q, J = 284.0 Hz),120.0, 119.4, 117.7,117.6, 85.3, 85.2, 64.5 (hept, J = 34.0 Hz).

[0107] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.4 (1B), –2.4 (1B), –10.2 (8B).

[0108] 19F NMR (376 MHz, CDCl3) δ –73.4.

[0109] 2n: White solid. Yield: 80%.

[0110] 1 H NMR (400 MHz, CDCl3) δ 7.37 – 7.32 (m, 4H), 7.20 – 7.16 (m, 4H),5.81 (hept, J = 8.0 Hz, 1H).

[0111] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 137.82, 137.78, 131.93, 131.88, 129.2,129.1, 128.2, 120.8 (q, J = 283.0 Hz), 83.98, 83.92, 64.5 (hept, J = 34.0Hz).

[0112] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.0 (1B), –2.1 (1B), – 10.0 – –11.7(8B).

[0113] 19 F NMR (376 MHz, CDCl3) δ –73.41, –73.42.

[0114] 2o: White solid. Yield: 82%.

[0115] 1 H NMR (400 MHz, CDCl3) δ 7.44 – 7.37 (m, 4H), 6.92 – 6.85 (m, 4H),5.82 (hept, J = 8.0 Hz, 1H).

[0116] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 164.1 (J = 254.5 Hz), 132.9 (d, J = 6.1Hz), 132.9 (d, J = 6.1 Hz), 132.8 (d, J = 6.1 Hz), 125.7 (m), 120.8 (q, J =283.0 Hz), 116.0 (d, J = 21.2 Hz), 115.95 (d, J = 22.2 Hz), 84.2, 84.2, 64.5(hept, J = 34.0 Hz).

[0117] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.1 (1B), –2.2 (1B), –10.2 (8B).

[0118] 19 F NMR (376 MHz, CDCl3) δ –73.4, –108.4, –108.5.

[0119] 2p: White solid. Yield: 87%.

[0120] 1 H NMR (400 MHz, CDCl3) δ 7.25 – 7.12 (m, 6H), 7.05 – 6.99 (m, 2H),5.81 (hept, J = 8.0 Hz, 1H).

[0121] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 162.28 (J = 249.5 Hz), 162.26 (J =250.5 Hz) 131.67 (d, J = 8.1Hz), 131.65 (d, J = 8.1 Hz), 130.5 (d, J = 8.1Hz), 130.4 (d, J = 8.1 Hz), 126.52 (d, J = 3.0 Hz), 126.45 (d, J = 3.0 Hz),120.8 (q, J = 284.0 Hz), 118.34 (d, J = 20.2 Hz), 118.30 (d, J = 20.2 Hz),118.12 (d, J = 24.2 Hz), 118.07 (d, J = 25.3 Hz), 83.5, 83.4, 64.6 (hept, J =34.3 Hz).

[0122] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.0 (1B), –1.9 (1B), –9.9 (6B), –11.8(2B).

[0123] 19 F NMR (376 MHz, CDCl3) δ 73.4, –110.8, –110.9.

[0124] 2q: White solid. Yield: 60%.

[0125] 1 H NMR (400 MHz, CDCl3) δ 7.04 – 6.96 (m, 4H), 6.87 – 6.80 (m, 2H),5.81 (hept, J = 8.0 Hz, 1H).

[0126] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 162.73 (d, J = 253.5 Hz), 162.70 (d, J= 252.5 Hz), 162.60 (d, J = 253.5 Hz), 162.58 (d, J = 253.5 Hz), 132.6 (m),120.8 (q, J = 284.0 Hz), 114.3 (m), 107.5 (d, J = 5.1 Hz), 107.2 (m), 82.4,82.3, 64.6 (hept, J = 34.0 Hz).

[0127] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –0.7 (1B), –1.8 (1B), –9.8 (6B), –12.0(2B).

[0128] 19 F NMR (376 MHz, CDCl3) δ –73.4, –106.3, –106.4.

[0129] 2r: White solid. Yield: 89%.

[0130] 1 H NMR (400 MHz, CDCl3) δ 7.58 – 7.55 (m, 4H), 7.49 – 7.46 (m, 4H),5.82 (hept, J = 8.0 Hz, 1H).

[0131] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 133.29 (q, J = 34.0 Hz), 133.26 (q, J =34.0 Hz), 133.00 (d, J = 1.0 Hz), 132.97 (d, J = 1.0 Hz), 131.1 (d, J = 5.0Hz), 126.0 (m), 123.2 (q, J = 274.0 Hz), 120.8 (q, J = 282.8 Hz), 120.77 (q,J = 282.8 Hz), 83.2, 83.1, 64.6 (hept, J = 34.0 Hz).

[0132] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –0.7 (1B), –1.7 (1B), –9.6 (6B), –11.9(2B).

[0133] 19 F NMR (376 MHz, CDCl3) δ –63.36, –63.37, –73.4.

[0134] 2s: White solid. Yield: 92%.

[0135] 1 H NMR (400 MHz, CDCl3) δ 7.46 – 7.42 (m, 4H), 7.05 – 7.01(m, 4H),5.82 (hept, J = 8.0 Hz, 1H).

[0136] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 151.2, 132.44, 132.39, 127.9, 120.8 (d,J = 282.3 Hz), 120.7, 120.6, 120.3 (q, J = 260.6 Hz), 83.6, 83.5, 64.6 (hept,J = 34.0 Hz).

[0137] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.0 (1B), –2.0 (1B), –9.9 (8B).

[0138] 19 F NMR (376 MHz, CDCl3) δ –58.0, –73.5.

[0139] 2t: White solid. Yield: 86%.

[0140] 1 H NMR (400 MHz, CDCl3) δ 7.83 – 7.80 (m, 4H), 7.51 – 7.46 (m, 4H),5.82 (hept, J = 8.0 Hz, 1H), 3.86 (s, 6H).

[0141] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 165.6, 133.60, 133.55, 132.5, 130.8,130.7, 129.9, 129.8, 120.8 (q, J = 283.0 Hz), 83.7, 83.6, 64.5 (hept, J =34.0 Hz), 52.6.

[0142] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –0.8 (2B), –9.7 (8B).

[0143] 19 F NMR (376 MHz, CDCl3) δ –73.4.

[0144] 2u: White solid. Yield: 80%.

[0145] 1 H NMR (400 MHz, CDCl3) δ 7.24 – 7.22 (m, 2H), 7.20 – 7.17 (m, 2H),6.85 – 6.82 (m, 2H), 5.81 (hept, J = 8.0 Hz, 1H).

[0146] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ133.4, 133.2, 130.5, 130.4, 130.3,127.5, 127.4, 120.8 (q, J = 284.0 Hz), 80.8, 80.7, 64.5 (hept, J = 34.0 Hz).

[0147] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.6 (1B), –2.6 (1B), –9.3 (6B), –10.7(2B).

[0148] 19 F NMR (376 MHz, CDCl3) δ –73.39, –73.41.

[0149] 2v: White solid. Yield: 90%.

[0150] 1 H NMR (400 MHz, CDCl3) δ 7.64 – 7.62 (m, 4H), 7.49 – 7.45 (m, 2H),7.43 – 7.38 (m, 4H), 5.83 (hept, J = 8.0 Hz, 1H), 3.96 (s, 2H).

[0151] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 133.3, 130.5, 128.6, 120.9 (q, J =284.0 Hz), 64.7 (hept, J = 34.0 Hz), 58.4, 58.2.

[0152] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –1.6 – –3.8 (4B), –11.4 (2B), –13.3(2B).

[0153] 19 F NMR (376 MHz, CDCl3) δ –73.36, –73.37.

[0154] 2w: White solid. Yield: 80%.

[0155] 1 H NMR (400 MHz, CDCl3) δ 5.77 (hept, J = 8.0 Hz, 1H), 3.64 (s, 1H),3.61 (s, 1H), 1.28 (s, 24H).

[0156] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 120.9 (q, J = 285.0 Hz), 84.7, 64.4(hept, J = 34.0 Hz), 56.8.

[0157] 11 B{ 1H} NMR (128 MHz, CDCl3) δ 33.8 (2B), –0.1 (2B), –6.5 (2B), –12.1(6B).

[0158] 19 F NMR (376 MHz, CDCl3) δ –73.4.

[0159] 2x: White solid. Yield: 78%.

[0160] 1 H NMR (400 MHz, CDCl3) δ 5.84 (hept, J = 8.0 Hz, 1H), 3.07 (s, 2H).

[0161] 13 C NMR (101 MHz, CDCl3) δ 120.8 (q, J = 284.0 Hz), 64.5 (hept, J =34.0 Hz), 55.1.

[0162] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –6.4 (2B), –8.4 (1B), –9.8 (1B), –13.1(4B), –16.9(2B).

[0163] 19 F NMR (376 MHz, CDCl3) δ –73.5.

[0164] 2y: White solid. Yield: 75%.

[0165] 1 H NMR (400 MHz, CDCl3) δ 5.84 (hept, J = 8.0 Hz, 1H), 1.76 (s, 6H).

[0166] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ120.8 (q, J = 283.0 Hz), 71.5, 64.5(hept, J = 34.0 Hz), 24.4.

[0167] 11 B{ 1H} NMR (128 MHz, CDCl3) δ –7.2 (2B), –8.3 (1B), –10.0 (5B), –12.1(2B).

[0168] 19 F NMR (376 MHz, CDCl3) δ –73.42, –73.44.

[0169] 2z: White solid. Yield: 70%.

[0170] 1 H NMR (400 MHz, CDCl3) δ 5.87 (hept, J = 8.0 Hz, 1H), 3.22 (s, 1H), 2.93 (s, 1H).

[0171] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 120.8 (q, J = 283.0 Hz), 64.8 (hept, J = 34.0 Hz) 64.4, 63.9.

[0172] Example 2: Preparation of carborane carboxylic acid

[0173] Taking carborane carboxylic acid ester 2x as an example, carborane carboxylic acid ester 2x is hydrolyzed overnight at 60°C in lithium hydroxide isopropanol / water solution to quantitatively obtain carborane carboxylic acid 2x-1.

[0174]

[0175] 2x-1: White solid. Yield: 98%.

[0176] 1 H NMR (400 MHz, CDCl3) δ 10.52 (br, 1H), 3.02 (s, 2H).

[0177] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 54.8.

[0178] 11 B{ 1H} NMR (128 MHz, CDCl3) δ –6.4 (2B), –7.6 (1B), –9.8 (1B), –13.0– –13.4 (4B), –17.1(2B).

[0179] HRMS (ESI + m / z calcd for C3B 10 H 11 O2 – , [M–H] – : 187.1757, Found:187.1758.

[0180] Example 3: Preparation of carborane carboxylic acid derivatives

[0181] Taking carborane carboxylic acid 2x-1 as an example, downstream conversion of carboxylic acid yields a series of functionalized carborane molecules.

[0182] 1. Esterification and amidation reactions

[0183]

[0184]

[0185]

[0186] Under ambient air and a magnetic stirrer, 2x-1 carborane carboxylic acid (19 mg, 0.10 mmol), the corresponding base, the nucleophilic substrate HXR (alcohol / amine / thioglycolate), and dichloromethane (DCM, 1.0 mL) were added to a 10 mL oven-dried Schlenk flask, followed by the addition of 4-dimethylaminopyridinium trifluoromethanesulfonate (DMAP-Tf) condensing agent. The reaction mixture was stirred for 5–30 minutes, quenched with water, and extracted with dichloromethane (3 × 3 mL). The combined organic phases were dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was separated by rapid silica gel column chromatography using petroleum ether / ethyl acetate as eluent to give the target ester or amide product.

[0187] Among them, 3a-3d uses triethylamine (Et3N) as a base, and the specific reaction conditions are as follows:

[0188] Esterification reaction: In a flask containing 2x-1 dissolved in dichloromethane, triethylamine (Et3N, 0.15 mmol) and alcohol substrate (0.12 mmol, including 4-pyridinemethanol, borneol, and diacetone-α-D-mannofuranose) were added, followed by DMAP-Tf (0.12 mmol).

[0189] In this reaction, 4-dimethylaminopyridine (DMAP) is used as the base for 3e-3g. The specific reaction conditions are as follows:

[0190] Amide reaction: In a flask containing 2x-1 solutions dissolved in dichloromethane, add 4-dimethylaminopyridine (DMAP, 33 mg, 0.27 mmol) and nucleophilic substrates (0.12 mmol, including 2,3,4,6-tetra-O-acetyl-1-thio-β-D-pyranose, 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-D-pyranose hydrochloride, L-phenylalanine methyl ester hydrochloride), 7-aminoheptanoate methyl ester hydrochloride, and then add DMAP-Tf (53 mg, 0.13 mmol).

[0191] Note: For the 3h synthesis, potassium hydroxide (168 mg, 3 mmol) and methanol (5 mL) were added to a 10 mL Schlenk flask equipped with a magnetic stirrer and stirred until the solid was completely dissolved. Hydroxylamine hydrochloride (140 mg, 2 mmol) was added in one go, and the mixture was stirred at 40°C for 30 minutes and then cooled to room temperature. The supernatant was transferred to a methanol solution of product 3h, and the mixture was stirred at 70°C for 12 hours. After the reaction was complete as detected by TLC, the crude product was purified by silica gel rapid column chromatography to obtain a white solid product 3h.

[0192] 2. Amine-ester exchange reaction

[0193]

[0194] Hexafluoroisopropanol carborane carboxylate (2x, 34 mg, 0.1 mmol), 4-dimethylaminoethoxybenzylamine (58 mg, 0.3 mmol), and acetonitrile (CH3CN, 0.5 mL) were added to a reaction flask and heated to 100 °C for 24 hours. After the reaction was completed, the reaction was quenched with water and extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography to give a white solid product 3i (15.4 mg, yield 41%).

[0195] 3. Lossen rearrangement reaction

[0196]

[0197] Under argon protection, carborane carboxylic acid (2x-1, 19 mg, 0.1 mmol), methyl dioxazolone (14 μL, 0.2 mmol), and ethyl acetate (EA, 0.2 mL) were added to an oven-dried Schlenk flask equipped with a magnetic stirrer, followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 23 μL, 0.15 mmol). The reaction mixture was stirred at room temperature for 4 hours. After the reaction was complete, water (5 mL) was added for dilution, and the mixture was extracted with ethyl acetate (3 × 5 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure to remove volatile solvents, and the crude product was purified by silica gel through a 200-300 mesh screen to give a white solid product 3j (15.1 mg, 87% yield).

[0198] 4. Free radical oxidative decarboxylation functionalization reaction

[0199]

[0200] Decarboxylation arylation reaction: Silver trifluoroacetate (AgTFA, 4.4 mg, 0.02 mmol, 20 mol%) and potassium persulfate (81 mg, 0.3 mmol) were added to a Schlenk flask containing 2x-1 carborane carboxylic acid. The mixture was used as a mixed solvent of benzene / acetonitrile (0.5 mL / 0.1 mL) and reacted at 120 °C for 24 hours to give a white solid product 3k (17.6 mg, yield 80%).

[0201]

[0202] Decarboxylation and fluorination reaction: Selectfluor (36 mg, 0.2 mmol), potassium persulfate (54 mg, 0.2 mmol), and silver nitrate (AgNO3, 3.4 mg, 0.02 mmol, 20 mol%) were added to a Schlenk flask containing 2x-1 carborane carboxylic acid. The reaction was carried out at 50 °C for 12 hours with deionized water (2 mL) as solvent, yielding 3 l of white solid product (14.6 mg, 90% yield).

[0203]

[0204] Decarboxylation and azidation reaction: p-Toluenesulfonyl azide (TsN3, 59 mg, 0.3 mmol), potassium persulfate (54 mg, 0.2 mmol), and silver nitrate (3.4 mg, 0.02 mmol, 20 mol%) were added to a Schlenk flask containing 2x-1 carborane carboxylic acid. The mixture was prepared in deionized water / acetonitrile (0.5 mL / 0.5 mL) and reacted at 50 °C for 10 hours to give a white solid product 3m (15.7 mg, yield 85%).

[0205] 5. Free radical reductive decarboxylation-boronization reaction

[0206]

[0207] Under argon protection, carborane carboxylic acid-N-hydroxyphthalimide ester (3n, 34 mg, 0.1 mmol) and bis(catechol borate) ester (B2cat2, 48 mg, 0.2 mmol) were added to an oven-dried Schlenk flask equipped with a magnetic stirrer, followed by the addition of N,N-dimethylacetamide (DMAc, 0.5 mL). The reaction flask was sealed and stirred under 450 nm blue light for 14 hours. Pinarol (63 mg, 0.53 mmol, 4.0 equivalents) was dissolved in triethylamine (0.45 mL), added to the reaction mixture, and stirring continued for 1 hour. After the reaction was complete, the mixture was diluted with water (5 mL) and extracted with ethyl acetate (3 × 5 mL). The combined organic phases were dried over anhydrous sodium sulfate and filtered. The filtrate was evaporated under reduced pressure to remove volatile solvents. The crude product was purified by rapid column chromatography to give a white solid product 3o (25.6 mg, 95% yield).

[0208] The structural identification results of the above compounds (using a 400MHz NMR spectrometer) are as follows:

[0209] 3a: White solid. Yield: 90%.

[0210] 1 H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 4.0 Hz, 2H), 7.23 (d, J = 4.0Hz, 2H), 5.13 (s, 2H), 3.04 (s, 2H).

[0211] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 149.7, 146.1, 121.5, 62.4, 54.7.

[0212] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –6.5 (2B), –7.4 (1B), –9.9 (1B), –13.3(4B), –17.1 (2B).

[0213] 3b: White solid. Yield: 95%.

[0214] 1 H NMR (400 MHz, CDCl3) δ 4.97 – 4.93 (m, 1H), 2.99 (s, 2H), 2.37 –2.29 (m, 1H), 2.08 – 2.01 (m, 1H), 1.78 – 1.68 (m, 1H), 1.66 – 1.64 (m, 1H),1.31 – 1.20 (m, 2H), 0.94 (dd, J = 13.6 Hz, J = 3.6 Hz, 1H), 0.90 (s, 3H),0.86 (s, 3H), 0.81 (s, 3H).

[0215] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 80.0, 54.5, 49.1, 47.8, 45.2, 37.3,28.2, 27.3, 19.9, 19.1, 13.6.

[0216] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –6.6 (3B), –9.9 (1B), –13.1 – –13.6(4B), –17.2 (1B), –18.0 (1B).

[0217] 3c: White solid. Yield: 78%.

[0218] 1 H NMR (400 MHz, CDCl3) δ 6.16 (s, 1H), 4.84 – 4.82 (m, 1H), 4.65 (d,J = 8.0 Hz, 1H), 4.36 (m, 1H), 4.07(m, 1H), 3.99 – 3.94 (m, 2H), 3.01 (s,2H), 1.46 (s, 3H), 1.42 (s, 3H), 1.35 (s, 3H), 1.31 (s, 3H).

[0219] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 113.1, 109.3, 99.0, 85.3, 82.3, 79.5,72.9, 67.2, 54.7, 27.0, 26.0, 25.2, 24.8.

[0220] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –6.5 (2B), –7.5 (1B), –9.9 (B), –13.3(4B), –17.1 (2B).

[0221] 3d: White solid. Yield: 60%.

[0222] 1 H NMR (400 MHz, CDCl3) δ 5.32 – 5.22 (m, 2H), 5.13 – 5.07 (m, 2H),4.26 (dd, J = 12.1 Hz, J = 4.4 Hz, 1H), 4.06 (dd, J = 12.1 Hz, J = 2.4 Hz,1H), 3.84 – 3.79 (m, 1H), 3.04 (s, 2H), 2.05 (s, 3H), 2.00 (s, 3H), 1.97 (s,3H), 1.96 (s, 3H).

[0223] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 170.8, 170.2, 169.5, 169.4, 78.4, 76.5,74.2, 69.7, 68.2, 61.9, 54.8, 20.8, 20.69, 20.67, 20.6.

[0224] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –5.2 (1B), –6.7 (2B), –10.0 (1B), –13.4(4B), –17.0 (2B).

[0225] 3e: White solid. Yield: 82%.

[0226] 1H NMR (400 MHz, CDCl3) δ 6.10 (d, 1H, J = 12.0 Hz), 5.67 (d, 1H, J =8.0 Hz), 5.25 – 5.20 (m, 1H), 5.10 – 5.05 (m, 1H), 4.53 – 4.45 (m, 1H), 4.22– 4.18 (m, 1H), 4.10 – 4.06 (m, 1H), 3.83 – 3.79 (m, 1H), 3.00 (s, 2H), 2.03(s, 6H), 2.00 (s, 3H), 1.97 (s, 3H).

[0227] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 171.1, 170.7, 169.5, 169.4, 92.8, 73.1,72.3, 68.1, 62.0, 54.7, 51.4, 20.74, 20.72, 20.6, 20.5.

[0228] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –6.8 (3B), –10.4 (1B), –13.4 (4B), –17.0 (2B).

[0229] 3f: White solid. Yield: 86%.

[0230] 1 H NMR (400 MHz, CDCl3) δ 7.29 – 7.20 (m, 3H), 7.10 – 7.07 (m, 2H),6.29 (d, J = 8.0 Hz, 1H), 5.03 – 4.98 (m, 1H), 3.71 (s, 3H), 3.17(dd, J =13.6 Hz, J = 8.0 Hz, 1H), 3.09 (dd, J = 13.6 Hz, J = 8.0 Hz, 1H), 3.01 (s,2H).

[0231] 13 C{ 1H} NMR (101 MHz, CDCl3) δ 172.2, 136.2, 129.5, 128.5, 127.1,54.7, 52.28, 52.25, 38.0.

[0232] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –5.8 (1B), –6.8 (2B), –10.3 (1B), –13.5(4B), –17.1 (1B), –18.1 (1B).

[0233] 3g: Colorless oil. Yield: 78%.

[0234] 1 H NMR (400 MHz, CDCl3) δ 5.81 (s, 1H), 3.62 (s, 3H), 3.25 – 3.20 (m,2H), 3.00 (s, 2H), 2.26 (t, J= 7.6 Hz, 2H), 1.62 – 1.54 (m, 2H), 1.49 – 1.42(m, 2H), 1.31 – 1.27 (m, 4H).

[0235] 13 C{1H} NMR (101 MHz, CDCl3) δ 174.2, 54.7, 51.5, 38.6, 34.0, 29.5,28.8, 26.6, 24.9.

[0236] 11 B{1H} NMR (128 MHz, CDCl3) δ –5.4 (1B), –6.8 (2B), –10.4 (1B), –13.5(4B), –17.1 (1B), –18.3 (1B).

[0237] 3h: White solid. Yield: 67%.

[0238] 1H NMR (400 MHz, CDCl3) δ 5.81 (s, 1H), 3.62 (s, 3H), 3.25 – 3.20 (m,2H), 3.00 (s, 2H), 2.26 (t, J = 7.6 Hz, 2H), 1.62 – 1.54 (m, 2H), 1.49 – 1.42(m, 2H), 1.31 – 1.27 (m, 4H).

[0239] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 174.2, 54.7, 51.5, 38.6, 34.0, 29.5,28.8, 26.6, 24.9.

[0240] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –5.4 (1B), –6.8 (2B), –10.4 (1B), –13.5(4B), –17.1 (1B), –18.3 (1B).

[0241] 3i: White solid. Yield: 41%.

[0242] 1 H NMR (500 MHz, CDCl3) δ 7.17 – 7.16 (m, 2H), 6.87 – 6.85 (m, 2H),6.05 (t, J = 6.0 Hz, 1H), 4.39 (d, J = 5.5 Hz, 2H), 4.05 (t, J = 5.5 Hz, 2H),3.01 (s, 2H), 2.74 (t, J = 5.5 Hz, 2H), 2.34 (s, 6H).

[0243] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 157.9, 131.5, 129.1, 114.9, 65.5, 58.1,54.6, 45.6, 42.3.

[0244] 11B NMR (160 MHz, CDCl3) δ –0.24 (1B), –1.51(2B), –5.07(1B), –7.83 – –8.30 (4B), –11.84 (1B), –13.05 (1B).

[0245] 3j: White solid. Yield: 87%.

[0246] 1 H NMR (400 MHz, CDCl3) δ 2.87 (s, 2H).

[0247] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 51.8.

[0248] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –2.5 (1B), –7.1 (2B), –10.6 (1B), –13.9(2B), –15.4 (2B), –19.1 (1B), –23.1 (1B).

[0249] 3k: White solid. Yield: 85%.

[0250] 1 H NMR (400 MHz, CDCl3) δ 7.53 – 7.51 (m, 2H), 7.27 – 7.25 (m, 3H),3.00 (s, 2H).

[0251] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 133.3, 127.7, 127.6, 54.4.

[0252] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ 0.5 (1B), –6.5 (2B), –9.5 (1B), –13.0 ––13.8 (2B), –17.4 (1B), –19.7 (1B).

[0253] 3l: White solid. Yield: 90%.

[0254] 1 H NMR (400 MHz, CDCl3) δ 2.76 (s, 2H).

[0255] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 49.6.

[0256] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ 10.4 (1B), –8.3 (2B), –12.3 (1B), –15.2(2B), –16.9 (2B), –20.6 (1B), –26.6 (1B).

[0257] 19 F NMR (376 MHz, CDCl3) δ –204.7 (m).

[0258] 3m: White solid. Yield: 85%.

[0259] 1 H NMR (400 MHz, CDCl3) δ 2.90 (s, 2H).

[0260] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 52.0.

[0261] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ 2.0 (1B), –7.6 (2B), –11.2 (1B), –14.3(2B), –15.2 (2B), –18.9 (1B), –22.9 (1B).

[0262] 3n: White solid. Yield: 80%.

[0263] 1 H NMR (400 MHz, CDCl3) δ 7.85 – 7.83 (m, 2H), 7.76 – 7.74 (m, 2H),3.13 (2H).

[0264] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 162.4, 134.6, 129.2, 123.8, 55.2.

[0265] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ –6.2 (2B), –9.2 (2B), –13.0 (4B), –16.7(2B).

[0266] 3o: White solid. Yield: 95%.

[0267] 1 H NMR (400 MHz, CDCl3) δ 2.97 (s, 2H), 1.23 (s, 12H).

[0268] 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 83.1, 57.0, 25.0.

[0269] 11 B{ 1 H} NMR (128 MHz, CDCl3) δ 35.2 (1B), –5.9 (2B), –9.2 (1B), –12.3(4B), –15.2 (1B), –16.0 (1B)。

Claims

1. A method for preparing a carborane carboxylic acid ester, characterized in that... The hydrogen atom on the distal B atom of the carborane is replaced by -COOC(CF3)2, and the carborane is an ortho-carborane, meta-carborane, or para-carborane. One or more carbon atoms and / or boron atoms in the carborane structure are substituted by one or more of the following: hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, 5-10 member oxygen-containing spirocyclic heterocycle, C2-C6 alkoxyalkyl, silyl group substituted with 1 to 3 C1-C6 alkyl groups, phenyl, and pinacol boronic acid ester group. The phenyl group is substituted by one or more of the following: hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, and five- or six-membered heteroaryl. The method involves reacting carborane with a palladium catalyst, CO, an oxidant, hexafluoroisopropanol, and an organic acid at 0–100 °C for 6–72 hours.

2. The method according to claim 1, characterized in that... The palladium catalyst is selected from one or more of Pd(AcO)2, Pd(TFA)2, Pd(CH3CN)4(BF4)2, and Pd(CH3CN)4(OTf)2.

3. The method according to claim 1, characterized in that... The oxidant is an organic peroxide or an inorganic peroxide.

4. The method according to claim 3, characterized in that... The oxidant is selected from one or more of tBuOOtBu, K2S2O8, and (NH4)2S2O8.

5. The method according to claim 1, characterized in that... The organic acid is selected from one or more of AcOH, Cl3CCOOH, TFAH, and TfOH.

6. The method according to claim 1, characterized in that... The reaction system also contains additives, selected from one or more of AgOAc, NaOAc, CuOAc, and Cu(OAc)2.

7. The method according to claim 1, characterized in that... The reaction was carried out at room temperature to 80°C for 24-48 hours.

8. The method according to claim 1, characterized in that... The carborane has the following general formula: Among them, R 1 -R 4 The same or different, representing one or more of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, 5-10 member oxygen-containing spirocyclic heterocycle, C2-C6 alkoxyalkyl, silyl substituted with 1 to 3 C1-C6 alkyl, phenyl, pinacol boronic acid ester group, wherein the phenyl is substituted with hydrogen, C1-C6 alkyl, C1-C6 alkoxy, phenoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxycarbonyl, five- or six-membered heteroaryl.

9. The method according to any one of claims 1-8, characterized in that... The method further includes the steps of extracting the reaction product with saturated brine and ethyl acetate, taking the organic phase, removing the solvent, and then purifying it by column chromatography.

10. A method for preparing carborane carboxylic acid, characterized in that... Carborane carboxylic acid esters are prepared by the method according to any one of claims 1-9, and then hydrolyzed to obtain carborane carboxylic acid.

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