9-site-azabicyclo [3, 1, 0] hexyl methyl substituted o-carborane compound and preparation method thereof

Abstract

The invention provides a 9-bit-azabicyclo [3, 1, 0] hexyl methyl substituted o-carborane compound and a preparation method thereof, and the 9-bit-azabicyclo [3, 1, 0] hexyl methyl substituted o-carborane compound is synthesized by one-step reaction of a 1, 6-enyne compound, an o-carborane compound and a reaction solvent under the action of a carbene gold catalyst. According to the invention, a 1, 6-enyne compound which is cheap and easy to obtain is used as a non-diazo carbene precursor, an o-carborane compound is used as a raw material, and under the action of a carbene gold catalyst, the 9-position-azabicyclo [3, 1, 0] hexyl methyl substituted o-carborane compound is highly selectively and rapidly obtained through a carbene regioselective boron-hydrogen bond insertion reaction route.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical synthesis, specifically relating to a 9-azadicyclo[3,1,0]hexylmethyl-substituted orthocarborane compound and its preparation method. Background Technology

[0002] Carborane derivatives have wide applications in boron neutron capture therapy (BNCT), supramolecular design, luminescent materials, and organometallic chemistry, making the synthesis of these compounds a hot research topic in organic chemistry. Figure 1 (a, b, and c). Functionalization of carboranes is the most direct and effective method for obtaining carborane derivatives, while the regioselective functionalization of ortho-carboranes is the most challenging. Currently reported functionalizations of ortho-carboranes mainly focus on the CH bond, while studies on the functionalization of the BH bond are relatively limited. The main reason is that the electron cloud distribution of the B atoms in ortho-carborane cages is relatively small, making regioselectivity difficult to control in BH bond functionalization reactions, often resulting in multi-substituted mixtures that are difficult to separate. However, BH bonds have a numerical advantage in ortho-carboranes, and their selective functionalization will greatly enrich the structural diversity of carborane derivatives, providing more possibilities for the application of ortho-carboranes in many fields. Therefore, the selective boron-hydrogen bond functionalization of ortho-carboranes is a highly attractive and challenging research topic. Although transition metal-catalyzed directed ortho-boron-hydrogen bond functionalization has made some progress, non-directed, non-ortho-selective functionalization reactions have not yet been reported. On the other hand, bicyclo[3,1,0]hexane is a bioactive structural unit that is ubiquitous in natural products and drug molecules ( Figure 1 (d, e, and f). Among them, the gold-catalyzed cyclization carbene insertion reaction using 1,6-enyne as a non-diazo carbene precursor is one of the important routes for constructing such units. However, there are no reports on the construction of carborane compounds with azabicyclic [3,1,0]hexane structural units by the boron-hydrogen bond insertion reaction of carboranes using such carbene precursors. Therefore, the development of synthetic methods for carborane compounds containing azabicyclic [3,1,0]hexane structures can not only promote the development of metal carbene reaction methodologies, but also contribute to the application research of novel carborane compounds. Summary of the Invention

[0003] The purpose of this invention is to provide a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound and its preparation method, in order to overcome the problems existing in the prior art. This invention uses inexpensive and readily available 1,6-enyne compounds as non-diazo carbene precursors and ortho-carborane compounds as raw materials. Under the action of a carbene gold catalyst, a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound is generated with high selectivity via a regioselective boron-hydrogen bond insertion reaction of carbene to carborane.

[0004] To achieve the above objectives, the present invention adopts the following technical solution: A 9-azadicyclo[3,1,0]hexylmethyl-substituted o-carborane compound, the structural formula of which is shown in formula (1):

[0005] Among them, R 1 For H, Me, or OMe; R 2 For H, Me, SiMe2Ph, Ph; R 3 It can be H or I.

[0006] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound involves adding a 1,6-enyne compound as shown in formula (2) and an ortho-carborane compound as shown in formula (3) to a reaction solvent, and synthesizing the 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound as shown in formula (1) in one step under the action of a carbenekin catalyst as shown in formula (4).

[0007] Further, the specific steps include: adding a carbene gold catalyst, an ortho-carborane compound, and a reaction solvent sequentially to a reaction vessel at 0°C and under an inert atmosphere, and stirring until homogeneous; then adding a 1,6-enyne compound to carry out the reaction; and finally separating the 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound by silica gel column chromatography.

[0008] Furthermore, the molar ratio of the 1,6-enyne compound, the ortho-carborane compound, and the carbene gold catalyst is 1:4:0.1.

[0009] Furthermore, the reaction solvent is dichloromethane, and 0.1~0.5 mmol of 1,6-enyne compound is added to every 1.0 mL of reaction solvent.

[0010] Furthermore, the reaction time is 8-20 hours.

[0011] Furthermore, after the reaction is complete, silica gel column chromatography is performed directly.

[0012] Furthermore, the inert atmosphere is nitrogen.

[0013] Furthermore, during separation by silica gel column chromatography, the eluents are petroleum ether and ethyl acetate.

[0014] Furthermore, the volume ratio of petroleum ether to ethyl acetate is 2:1 to 4:1.

[0015] Compared with the prior art, the present invention has the following beneficial technical effects: This invention represents the first time that a non-directed strategy has been used to achieve highly efficient and selective boron-hydrogen bond alkylation at the 9-position of o-carboranes. The synthesized compound is a novel o-carborane compound containing a azabicyclo[3,1,0]hexane skeleton. Not only is the azabicyclo[3,1,0]hexane structure an important structure in natural product medicinal chemistry, but o-carboranes also have enormous development potential in the biopharmaceutical field. This invention features readily available raw materials, simple operation steps, mild reaction conditions, excellent regioselectivity, and 100% atom economy. It is a unique method for preparing novel o-carborane derivatives, suitable for large-scale industrial production. Attached Figure Description

[0016] Figure 1 These are bioactive natural products and drug molecules containing o-carborane and bicyclo[3,1,0]hexane. Detailed Implementation

[0017] The present invention will now be described in further detail: A 9-azadicyclo[3,1,0]hexylmethyl-substituted o-carborane compound, as shown in formula (1), has the following structural formula: (1) The preparation process is as follows: 1,6-enyne compounds as shown in formula (2) and o-carborane compounds as shown in formula (3) are added to the reaction solvent, and under the action of the carbene gold catalyst as shown in formula (4), the 9-azabicyclo[3,1,0]hexylmethyl-substituted o-carborane compounds as shown in formula (1) are synthesized in one step.

[0019] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted o-carborane compound, specifically comprising: Under nitrogen conditions at 0°C, a carbenekin catalyst, an ortho-carborane compound, and a reaction solvent were added sequentially to a reaction vessel and stirred until homogeneous. Then, a 1,6-enyne compound was added to initiate the reaction. Finally, the mixture was directly separated by silica gel column chromatography. The eluent used for silica gel column chromatography was petroleum ether:ethyl acetate = 4:1 (volume ratio) to obtain a 9-azabicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound. The molar ratio of the 1,6-enyne compound, the ortho-carborane compound, and the carbenekin catalyst was 1:4:0.1. The reaction solvent was dichloromethane, and 0.1–0.5 mmol of the 1,6-enyne compound was added to every 1.0 mL of the reaction solvent. The reaction time was 8–20 hours.

[0020] The specific equation is as follows:

[0021] The present invention will now be described in detail with reference to embodiments and accompanying drawings to facilitate a more comprehensive understanding of the invention by those skilled in the art, but this does not limit the invention to all embodiments. All other embodiments obtained without inventive effort are within the scope of protection of the present invention.

[0022] Example 1 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1aa, the reaction equation of which is as follows:

[0023] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound 1aa, the implementation scheme is as follows: under 0℃ and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (8.8 mg, 0.01 mmol, 0.1 eq), o-carborane 3a (57.6 mg, 0.4 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2a (32.5 mg, 0.1 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 8 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1aa (38.6 mg, 82% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.71(d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.24 (t, J = 7.5 Hz, 2H), 7.15 (t, J =7.3 Hz, 1H), 6.95 (d, J = 7.4 Hz, 2H), 3.61 (d, J = 8.9 Hz, 1H), 3.50 (d, J = 9.4Hz, 1H), 3.43 (s, 2H), 3.30 (dd, J = 8.9, 3.9 Hz, 1H), 3.18 (d, J= 9.3 Hz, 1H), 2.45 (s, 3H), 1.99 (d, J = 4.1 Hz, 1H), 1.70 (t, J = 3.9 Hz, 1H), 0.80 (d, J = 15.8Hz, 1H), 0.62 (d, J = 15.7 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 143.5, 138.1, 132.8, 129.7, 128.2, 128.0, 127.8, 125.8, 54.9, 53.6, 51.8, 49.2, 36.6, 30.9, 26.6, 21.7, 14.2. 11 B NMR (160 MHz, CDCl3): d 7.1, -2.4, -9.0, -14.3. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 21 H 31 B 10 NO2S, M + H] + : 472.3079, found:472.3076. Example 2 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ba, the reaction equation of which is as follows:

[0024] A method for preparing 1ba, a 9-azabicyclo[3,1,0]hexylmethyl-substituted o-carborane compound, is described below: A dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel at 0°C under nitrogen atmosphere. i PrAuNTf2 (17.6 mg, 0.02 mmol, 0.1 eq), o-carborane 3a (115.2 mg, 0.8 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2b (67.8 mg, 0.2 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 12 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ba (63.1 mg, 65% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.73 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 7.8 Hz, 2H), 6.83(d, J = 7.7 Hz, 2H), 3.61 (d, J = 8.9 Hz, 1H), 3.48 (d, J = 9.4 Hz, 1H), 3.41 (s,2H), 3.29 (dd, J = 8.9, 3.9 Hz, 1H), 3.19 (d, J = 9.3 Hz, 1H), 2.45 (s, 3H), 2.30 (s, 3H), 1.94 (d, J = 3.9 Hz, 1H), 1.65 (t, J = 3.9 Hz, 1H), 0.79 (d, J = 15.8 Hz, 1H), 0.59 (d, J = 15.7 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 143.4, 135.3, 134.9, 133.0, 129.7, 137.9, 54.8, 53.5, 51.8, 49.1, 36.4, 30.7, 26.5, 21.7, 21.1, 14.1. 11 B NMR (160 MHz, CDCl3): d 7.4, -2.2, -9.0, -14.3, -15.4. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 22 H 33 B 10 NO2S, M + H] + : 486.3235, found:486.3237. Example 3 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ca, the reaction equation of which is as follows:

[0025] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound 1ca, the implementation scheme is as follows: under 0℃ and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (17.6 mg, 0.02 mmol, 0.1 eq), o-carborane 3a (115.2 mg, 0.8 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2c (71.8 mg, 0.2 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 12 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ca (71.6 mg, 71% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.72 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 6.87(d, J = 8.4 Hz, 2H), 3.61 (d, J = 9.1 Hz, 1H), 3.51 (d, J = 9.5 Hz, 1H), 3.40 (d, J =8.75 Hz, 2H), 3.27 (dd, J = 9.0, 3.9 Hz, 1H), 3.15 (d, J = 9.4 Hz, 1H), 2.45 (s, 3H), 1.98 (d, J = 4.2 Hz, 1H), 1.63 (t, J = 4.0 Hz, 1H), 0.80 (d, J = 15.9 Hz, 1H), 0.57 (d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 143.5, 136.8, 133.0, 129.8, 129.6, 128.2, 127.9, 54.8, 53.5, 51.6, 49.2, 36.7, 30.3, 26.9, 21.7, 13.9. 11BNMR (160 MHz, CDCl3): d 7.1, -2.3, -9.0, -14.3, -15.5. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 21 H 30 B 10 ClNO2S, M + H] + : 505.2748, found: 505.2748. Example 4 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1da, the reaction equation of which is as follows:

[0026] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound 1da, the implementation scheme is as follows: under 0°C and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (35.2 mg, 0.04 mmol, 0.1 eq), o-carborane 3a (230.4 mg, 1.6 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2d (141.2 mg, 0.4 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 18 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1da (103.8 mg, 52% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.72 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 6.78 (s, 1H), 6.54 (s, 2H), 3.60 (d, J = 8.9 Hz, 1H), 3.47 (d, J = 9.3 Hz, 1H), 3.40 (d, J = 11.5 Hz, 2H), 3.30(dd, J = 8.8, 3.8 Hz, 1H), 3.20 (d, J = 9.4 Hz, 1H), 2.46 (s, 3H), 2.25 (s, 6H), 1.86 (d,J = 4.1 Hz, 1H), 1.67 (t, J = 3.8 Hz, 1H), 0.78 (d, J = 16.0 Hz, 1H), 0.65(d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 143.4, 138.0, 137.4, 133.1, 139.7, 137.9, 127.5, 126.1, 54.9, 53.5, 51.9, 49.1, 36.6, 30.7, 26.6, 21.7, 21.4, 13.8. 11 B NMR (160 MHz, CDCl3): d 4.5, -5.0, 10.1. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 23 H 35 B 10 ClNO2S, M + H] + : 500.3392, found: 500.3395. Example 5 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ea, the reaction equation of which is as follows:

[0027] A method for preparing a 9-azabicyclic [3,1,0]hexylmethyl-substituted ortho-carborane compound 1ea, the implementation scheme is as follows: under nitrogen conditions at 0℃, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (17.6 mg, 0.02 mmol, 0.1 eq), o-carborane 3a (115.2 mg, 0.8 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2e (72.2 mg, 0.2 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 12 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ea (50.9 mg, 50% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.72 (d, J= 8.0 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 6.60 (t, J = 8.9 Hz, 1H), 6.47(d, J = 6.9 Hz, 2H), 3.61 (d, J = 9.2 Hz, 1H), 3.53 (d, J = 9.6 Hz, 1H), 3.41 (d, J =15.0 Hz, 2H), 3.26 (dd, J = 9.0, 3.7 Hz, 1H), 3.14 (d, J = 9.6 Hz, 1H), 2.46 (s, 3H), 1.96 (d, J = 4.1 Hz, 1H), 1.62 (t, J = 4.0 Hz, 1H), 0.84 (d, J = 16.0 Hz, 1H), 0.61 (d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 163.9, 162.0, 143.6, 142.6(d, J = 9.9 Hz), 133.1, 129.8, 127.9, 111.3(d, J = 5.7 Hz), 111.1(d, J = 5.8 Hz),101.6, 101.4, 101.2, 54.8, 53.5, 51.4, 49.3, 37.2, 30.7, 27.4, 21.7, 14.4. 11 BNMR (160 MHz, CDCl3): d 7.1, -2.2, -9.0, -14.2, -15.5. High-resolution data: HRMS(ESI, m / z) Calculated for [C 21 H 29 B 10 F2NO2S, M + H] + : 508.2890, found: 508.2882. Example 6 A method for preparing 1fa, a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound, is given by the following reaction equation:

[0028] A method for preparing 1fa, a 9-azabicyclic [3,1,0]hexylmethyl-substituted o-carborane compound, is described below: A dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel at 0°C under nitrogen atmosphere. i PrAuNTf2 (8.8 mg, 0.01 mmol, 0.1 eq), o-carborane 3a (57.6 mg, 0.4 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2f (35.9 mg, 0.1 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 8 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1fa (38.3 mg, 76% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.72(d, J = 7.7 Hz, 2H), 7.34 (d, J = 7.2 Hz, 2H), 7.32 (s, 1H), 7.17-7.08(m, 2H), 6.89 (d, J = 7.0 Hz, 1H), 3.62 (d, J = 8.8 Hz, 1H), 3.55 (d, J = 9.3 Hz, 1H), 3.38(d, J = 9.5 Hz, 3H), 3.30 (d, J = 9.2 Hz, 1H), 2.43 (s, 3H), 2.09 (d, J = 3.9 Hz,1H), 1.74 (s, 1H), 0.95 (d, J = 16.0 Hz, 1H), 0.15 (d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d143.4, 136.2, 136.2, 133.1, 129.8, 129.3, 129.1, 127.9, 127.4, 126.5, 54.1, 53.5, 51.9, 49.2, 36.2, 29.9, 25.7, 21.7, 14.3. 11 B NMR (160MHz, CDCl3): d 7.1, -2.3, -9.0, -14.3, -15.5. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 21 H 30 B 10 ClNO2S, M + H] + : 505.2748, found: 505.2753. Example 7 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ga, the reaction equation of which is as follows:

[0029] A method for preparing 1ga, a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound, is described below: A dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel at 0°C under nitrogen atmosphere. i PrAuNTf2 (17.6 mg, 0.02 mmol, 0.1 eq), o-carborane 3a (115.2 mg, 0.8 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 2 g of 1,6-enyne compound (62.2 mg, 0.2 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 12 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ga (69.3 mg, 76% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.85 (d, J = 7.3 Hz, 2H), 7.62 (d, J = 6.9 Hz, 1H), 7.57 (t, J = 7.3 Hz, 2H), 7.24(t, J = 8.2 Hz, 2H), 7.14 (t, J = 7.1 Hz, 1H), 6.94 (d,J = 7.3 Hz, 2H), 3.64 (d, J =8.9 Hz, 1H), 3.54 (d, J = 9.4 Hz, 1H), 3.29 (s, 2H), 3.32 (dd, J = 8.6, 3.2 Hz, 1H), 3.21 (d, J = 9.4 Hz, 1H), 1.97 (d, J = 3.4 Hz, 1H), 1.70 (s, 1H), 0.82 (d, J =15.9 Hz, 1H), 0.62 (d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 138.1, 136.1, 132.7, 129.1, 128.3, 128.1, 127.8, 125.8, 54.9, 53.5, 51.8, 49.1, 36.7, 31.0, 26.7, 14.3. 11 B NMR (160 MHz, CDCl3): d 7.1, -2.3, -9.0, -14.3. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 20 H 29 B 10 NO2S, M + H] + : 457.2975, found:457.2973. Example 8 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ha, the reaction equation of which is as follows:

[0030] A method for preparing 1 ha of a 9-azabicyclo[3,1,0]hexylmethyl-substituted o-carborane compound, the implementation scheme is as follows: under 0°C and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. iPrAuNTf2 (17.6 mg, 0.02 mmol, 0.1 eq), o-carborane 3a (115.2 mg, 0.8 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes; then, 1,6-enyne compound 2h (68.2 mg, 0.2 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 12 hours; the mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ha (77.8 mg, 80% yield). NMR analysis was performed, and the NMR data were as follows: 1 H NMR (500 MHz, CDCl3): d 7.77 (d, J = 8.7 Hz, 2H), 7.24 (t, J = 7.6 Hz, 2H), 7.15 (t, J = 7.4 Hz, 1H), 7.03(d, J = 8.8 Hz, 2H), 6.96 (d, J = 7.4 Hz, 2H), 3.88 (s, 3H), 3.60 (d, J = 8.9 Hz, 1H), 3.49 (d, J = 9.4 Hz, 1H), 3.43 (s, 2H), 3.29 (dd, J = 8.9, 3.8 Hz, 1H), 3.17(d, J = 9.4 Hz, 1H), 2.03 (d, J = 4.2 Hz, 1H), 1.70 (t, J = 4.0 Hz, 1H), 0.81 (d, J =15.9 Hz, 1H), 0.62 (d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 163.1, 138.1, 129.9, 128.3, 128.1, 127.6, 125.8, 114.3, 55.7, 54.9, 53.6, 51.8, 49.2, 36.6, 31.0, 26.7, 14.2. 11 B NMR (160 MHz, CDCl3): d7.0, -2.4, -9.1, -14.3, -15.4. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 21 H 31 B 10 NO3S, M + H] + : 487.3082, found: 487.3077. Example 9 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ab, the reaction equation of which is as follows:

[0031] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound 1ab, the implementation scheme is as follows: under 0℃ and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (26.4 mg, 0.03 mmol, 0.1 eq), o-carborane compound 3b (172.8 mg, 1.2 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes; then, 1,6-enyne compound 2a (97.5 mg, 0.3 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 14 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ab (122.6 mg, 82% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.73 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 7.9 Hz, 2H), 7.23 (t, J = 7.6 Hz, 2H), 7.14 (t, J = 7.4 Hz, 1H), 6.94 (d, J = 7.4 Hz, 2H), 3.61 (d, J = 8.9 Hz, 1H), 3.50 (d, J = 9.5 Hz, 1H), 3.29 (dd, J = 8.9, 3.9 Hz, 1H), 3.17 (d, J = 9.4 Hz, 1H), 2.45 (s, 3H), 1.99 (d,J = 4.2 Hz, 1H), 1.96 (s, 3H), 1.89 (s, 3H), 1.67 (t, J =4.0 Hz, 1H), 0.77 (d, J = 15.9 Hz, 1H), 0.58 (d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 143.3, 138.3, 133.2, 129.7, 128.3, 128.0, 127.9, 125.8, 72.3, 67.9, 54.9, 51.8, 36.8, 31.0, 26.7, 23.4, 22.4, 21.7, 13.4. 11 B NMR (160 MHz, CDCl3): d 4.5, -5.0, -10.1. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 23 H 35 B 10 NO2S,M + H] + : 499.3447, found: 499.3440. Example 10 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ac, the reaction equation of which is as follows:

[0032] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound 1ac, the implementation scheme is as follows: under 0℃ and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (44 mg, 0.05 mmol, 0.1 eq), o-carborane compound 3c (824.3 mg, 2.0 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2a (162.5 mg, 0.5 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 20 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ac (258.3 mg, 70% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.73 (d, J J = 7.8 Hz, 2H), 7.47 (t, J J = 7.2 Hz, 4H), 7.39 (q, J J = 8.5 Hz,8H), 7.21 (t, J J = 7.5 Hz, 2H), 7.13 (t, J J = 7.1 Hz, 1H), 6.86 (d, J J = 7.5 Hz, 2H),3.51 (d, J J = 9.1 Hz, 1H), 3.44 (d, J J = 9.4 Hz, 1H), 3.18 (d, J J = 9.3 Hz, 1H), 3.09(dd, J J = 8.9, 3.7 Hz, 1H), 2.45 (s, 3H), 1.94 (d, J J = 4.1 Hz, 1H), 1.43 (t, J J = 3.5Hz, 1H),0.72 (d, J J = 15.9 Hz, 1H), 0.50 (d, J J = 15.9 Hz, 1H), 0.30 (d, J J = 6.7 Hz,6H), 0.16 (d, J J = 3.9 Hz, 6H). 13 C NMR(125 MHz, CDCl3): d 143.2, 138.4, 135.5,135.4, 134.4, 134.1, 133.0, 130.8, 129.7, 128.2, 128.1, 128.0 (d, j J = 2.52 Hz),125.6, 73.8, 67.5, 54.9, 51.9, 36.7, 30.9, 26.4, 21.8, 14.4, 0.5, 0.3, -0.3,-0.4. 11 B NMR(160 MHz, CDCl3): d 11.9, 2.2 -5.7, -9.3. High resolution mass spectrometry data: HRMS(ESI,m / z) Calculated for [C 37 H 51 B 10NO2SSi2, M + H] + : 739.4249, found: 739.4245. Example 11 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ad, the reaction equation of which is as follows:

[0033] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound 1ad, the implementation scheme is as follows: under 0℃ and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (17.6 mg, 0.02 mmol, 0.1 eq), o-carborane compound 3d (214.4 mg, 0.8 mmol, 4.0 eq), and dichloromethane (DCM) (1 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2a (65.0 mg, 0.2 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 12 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ad (79.6 mg, 64% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.76 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 8.1 Hz, 4H), 7.30 (d, J = 7.7 Hz,2H), 7.26-7.20 (m, 4H), 7.13 (q, J = 7.3 Hz, 5H), 6.97 (d, J = 7.4 Hz, 2H), 3.65(d, J = 9.1 Hz, 1H), 3.57 (d, J = 9.4 Hz, 1H), 3.34 (dd, J = 8.9, 3.9 Hz, 1H), 3.29(d, J = 9.4 Hz, 1H), 2.47 (s, 3H), 2.03 (d, J = 4.1 Hz, 1H), 1.75 (t, J = 3.5 Hz, 1H), 0.93 (d, J= 15.9 Hz, 1H), 0.75 (d, J = 15.9 Hz, 1H). 13 C NMR (125 MHz, CDCl3): d 143.3, 138.2, 133.2, 128.3 (d, j =5.6 Hz), 128.1, 127.9, 128.8, 84.2, 79.7,54.9, 51.8, 36.8, 31.0, 26.7, 21.8, 13.5. 11 B NMR (160 MHz, CDCl3): d 7.2, -2.3, -10.0. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 33 H 39 B 10 NO2S, M + H] + :623.3766, found: 623.3758. Example 12 A method for preparing a 9-azadicyclic [3,1,0]hexylmethyl-substituted o-carborane compound 1ae, the reaction equation of which is as follows:

[0034] A method for preparing a 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound 1ae, the implementation scheme is as follows: under 0℃ and nitrogen conditions, a dried stir bar and a carbene gold catalyst are added sequentially to a reaction vessel. i PrAuNTf2 (35.2 mg, 0.04 mmol, 0.1 eq), o-carborane compound 3e (480.2 mg, 1.6 mmol, 4.0 eq), and dichloromethane (DCM) (2 mL) were stirred for 5 minutes. Then, 1,6-enyne compound 2a (130.2 mg, 0.4 mmol, 1.0 eq) was added, and the reaction was allowed to proceed for 8 hours. The mixture was then directly separated by silica gel column chromatography (petroleum ether:ethyl acetate = 4:1, v / v) to give o-carborane compound 1ae (74.8 mg, 30% yield). NMR analysis was performed. NMR data are as follows: 1 H NMR (500 MHz, CDCl3): d 7.75 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 7.9 Hz, 2H), 7.23 (t, J= 7.6 Hz, 2H), 7.15 (t, J = 7.4 Hz, 1H), 6.99 (d, J = 7.3 Hz, 2H), 3.65 (d, J = 9.0 Hz, 1H), 3.60 (d, J = 9.5 Hz, 1H), 3.29 (dd, J = 8.9, 3.9 Hz, 1H), 3.24 (d, J = 9.4 Hz, 1H), 2.45 (s, 3H), 2.03 (d, J = 4.2 Hz, 1H), 2.00 (s, 3H), 1.82 (t, J = 4.0 Hz, 1H),1.79 (s, 3H), 0.93 (d, J = 15.9 Hz, 1H), 0.80 (d, J = 15.9 Hz, 1H). 13 C NMR (125MHz, CDCl3): d 143.3, 137.9, 133.4, 129.8, 128.4, 128.1, 128.0, 125.9, 69.7, 69.6, 55.1, 51.5, 36.7, 31.1, 27.2, 23.3, 22.3, 21.7, 14.3. 11 B NMR (160 MHz, CDCl3): d 4.2, -1.1, -3.4, -8.4, -15.5. High-resolution mass spectrometry data: HRMS (ESI, m / z) Calculated for [C 23 H 34 B 10 INO2S, M + H] + : 625.2413, found: 625.2404. The 9-position-azabicyclic [3,1,0]hexylmethyl-substituted o-carborane compounds obtained in this invention can undergo deboronization to yield nested carboranes. These compounds have important applications in the fields of chemistry and materials. As shown in the following formula, 1aa can be efficiently converted to compound 5.

[0035]

[0036] The specific conversion process is as follows: 1aa (0.5 mmol, 1.0 eq) and potassium hydroxide (2 mmol, 4.0 eq) were dissolved in 5 mL of ethanol. The solution was then stirred under reflux for 1 day. After cooling to room temperature, hydrochloric acid (1 M) was added to adjust the pH to 6–7. After filtration and evaporation, the resulting white solid was dissolved in 5 mL of deionized water, and Et4NCl (0.55 mmol, 1.1 eq) was added. The resulting mixture was stirred overnight and filtered, and the filter cake was washed three times with n-hexane and DCM. Finally, it was dried under vacuum to give the corresponding product 5 (153.4 mg, yield 52%).

[0037] The embodiments described above are merely preferred technical solutions of the present invention and should not be considered as limitations on the present invention. The embodiments and features described in this application can be arbitrarily combined with each other without conflict. The scope of protection of the present invention should be limited to the technical solutions described in the claims, including equivalent substitutions of the technical features described in the claims. That is, equivalent substitutions and improvements within this scope are also within the scope of protection of the present invention.

Claims

1. A 9-azadicyclo[3,1,0]hexylmethyl-substituted o-carborane compound, characterized in that, The structural formula of the 9-azabicyclic [3,1,0]hexylmethyl-substituted orthocarborane compound is shown in formula (1): Among them, R 1 For H, Me, or OMe; R 2 For H, Me, SiMe2Ph, Ph; R 3 It can be H or I.

2. A method for preparing the 9-position-aziridine bicyclic [3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 1, characterized in that, The 1,6-enyne compound shown in formula (2) and the o-carborane compound shown in formula (3) were added to the reaction solvent and synthesized in one step by a carbene gold catalyst shown in formula (4) through a one-step reaction. 。 3. The method for preparing the 9-position-azabicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 2, characterized in that, The specific steps include: adding a carbene gold catalyst, an ortho-carborane compound, and a reaction solvent sequentially to a reaction vessel at 0°C and under an inert atmosphere, and stirring until homogeneous; then adding a 1,6-enyne compound to carry out the reaction; and finally separating the 9-azadicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound by silica gel column chromatography.

4. The method for preparing the 9-position-azabicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 2 or 3, characterized in that, The molar ratio of the 1,6-enyne compound, the ortho-carborane compound, and the carbene gold catalyst is 1:4:0.

1.

5. The method for preparing the 9-position-azabicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 2 or 3, characterized in that, The reaction solvent is dichloromethane, and 0.1~0.5 mmol of 1,6-enyne compound is added to every 1.0 mL of reaction solvent.

6. The method for preparing the 9-position-azabicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 2 or 3, characterized in that, The reaction time is 8-20 hours.

7. The method for preparing the 9-position-aziridine bicyclic [3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 2 or 3, characterized in that, After the reaction is complete, silica gel column chromatography is performed directly.

8. The method for preparing the 9-position-aziridine bicyclic [3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 3, characterized in that, The inert atmosphere is nitrogen.

9. The method for preparing the 9-position-azabicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 3, characterized in that, When separating by silica gel column chromatography, the eluents are petroleum ether and ethyl acetate.

10. The method for preparing the 9-position-azabicyclo[3,1,0]hexylmethyl-substituted ortho-carborane compound according to claim 9, characterized in that, The volume ratio of petroleum ether to ethyl acetate is 2:1 to 4:1.

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