A five-membered cyclic boronic acid skeleton and a method for preparing the same

Abstract

The application discloses a five-membered ring cyclic boronic acid skeleton and a preparation method thereof. The application constructs a novel five-membered ring boronic acid skeleton through adopting an allyl boron reagent with higher stereoselectivity and an allylation reaction of an aldehyde and an intramolecular cyclization reaction in series, and is a five-membered ring cyclic boronic acid skeleton synthesis method with simple operation, mild conditions, high yield and wide substrate application range, and has important research value and industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing a five-membered cyclic boric acid skeleton. Background Technology

[0002] Boron-containing compounds exhibit unique and significant applications in medicinal chemistry. The empty p-orbitals of boron atoms allow them to form reversible covalent bonds with functional groups such as hydroxyl and amino groups in biological targets, making them ideal scaffolds for enzyme inhibitor design. In recent years, several boron-containing drugs have been successfully marketed or entered clinical trials, such as the proteasome inhibitor bortezomib for the treatment of multiple myeloma, and the antifungal drug tavaborole, which works by inhibiting leucyl-tRNA synthetase. Furthermore, boron-containing compounds show great promise in the treatment of antibacterial, anti-inflammatory, antitumor, and metabolic diseases. Therefore, developing novel and efficiently synthesized boron-containing scaffolds is crucial for advancing the discovery of innovative boron-containing drugs.

[0003] In existing technologies, methods for constructing five-membered cyclic boric acid skeletons mainly include the following categories: 1. Condensation reaction method: Boric acid and vicinal diol undergo reversible dehydration condensation to generate cyclic boric acid esters, often using azeotropic dehydration or transesterification to drive equilibrium. 2. Organometallic reagent method: Five-membered cyclic organoboron heterocycles are synthesized using Grignard reagents or lithium reagents, and then reacted with Grignard reagents to generate four-coordinate organoboron derivatives. However, existing technologies suffer from problems such as limited reaction equilibrium, high requirements for reaction conditions, and unstable yields. Summary of the Invention

[0004] Purpose of the invention: To address the problems existing in the prior art, this invention provides a five-membered cyclic borate skeleton and its preparation method. By using a more stereoselective allylboron reagent to tandemly react with an allylation reaction of an aldehyde and an intramolecular cyclization reaction to construct a novel five-membered cyclic borate skeleton, this method is simple to operate, has mild conditions, high yield, and a wide range of applicable substrates, and has significant research value and industrial application prospects.

[0005] Technical solution: To achieve the above objectives, the present invention adopts the following technical solution: a five-membered cyclic boric acid framework having the following structure:

[0006]

[0007] In the formula, R is selected from substituted phenyl, heterocyclic or alkyl groups.

[0008] Preferably, the substituted phenyl group is selected from para-substituted phenyl, meta-substituted phenyl, or ortho-substituted phenyl, and the substituent on the benzene ring is an electron-donating group or an electron-withdrawing group.

[0009] The present invention also provides a method for preparing the above-mentioned five-membered cyclic borate skeleton, comprising the following steps:

[0010] S1, 1,3-dieneboron and borate ester reagent are added to the solvent, and the reaction is carried out under the conditions of platinum catalyst and protective gas to obtain allylboron product by stirring.

[0011] S2, in a solvent, the obtained allyl boron product is mixed with aldehyde reactants, and after stirring, a five-membered cyclic borate skeleton product is obtained.

[0012] Preferably, the molar ratio of 1,3-dieneboron and borate ester reagent in step S1 is 1:1.1~1.5.

[0013] Preferably, the allyl boron product obtained in step S1 needs to be separated and purified by column chromatography; the five-membered cyclic borate skeleton product obtained in step S2 also needs to be separated and purified by column chromatography.

[0014] Preferably, the reaction temperature in step S1 is 80±10℃ and the reaction time is 8-15h.

[0015] Preferably, the eluent used in the column chromatography is a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1.

[0016] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0017] 1. This invention efficiently constructs a series of five-membered cyclic borate skeleton compounds by allylating an allyl borate reagent with a molecule of aldehyde, followed by intramolecular transesterification of the borate ester group in the intermediate with the generated high-allyl alcohol hydroxyl group. This strategy achieves the synthesis of five-membered cyclic borate skeletons under mild reaction conditions, providing a green and efficient new synthetic method.

[0018] 2. The raw materials used in this invention are allyl boron reagent and inexpensive and readily available aldehydes. The operation is simple, requires no heating, effectively reduces the synthesis cost, and is conducive to industrial production.

[0019] 3. The synthesis method of this invention has broad substrate applicability and can be compatible with a variety of common functional groups, natural products and drug molecule skeletons. Attached Figure Description

[0020] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 It is the structural formula of the five-membered cyclic borate skeleton described in this invention.

[0022] Figure 2 This is the NMR spectrum of Embodiment 1 of the present invention, 400MHz.

[0023] Figure 3 This is the NMR spectrum of Embodiment 1 of the present invention, 101MHz. Detailed Implementation

[0024] The present invention will be further illustrated below with reference to the accompanying drawings and specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. After reading this invention, any modifications of the invention in various equivalent forms by those skilled in the art will fall within the scope defined by the appended claims.

[0025] Unless otherwise specified in the embodiments of this invention, the conditions shall be performed according to conventional conditions or the manufacturer's recommendations. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0026] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0027] Example:

[0028] In this embodiment, (Z)-2,2'-[1-(1,3,2-dioxaborane-2-yl)-3-methylbut-2-ene-1,4-diyl]bis(4,4,5,5-tetramethyl-1,3,2-dioxaborane) (1):

[0029] The reaction equation is:

[0030]

[0031] The synthesis steps and process are as follows:

[0032] 1,3-Dieneboron 4 (1 mmol, 194 mg), toluene (1.0 mL), and B2Pin 2 (1.1 mmol, 279 mg) were added sequentially to a 5 mL reaction tube equipped with a magnetic stirrer, followed by Pt(dba) 3 (0.02 mmol, 18 mg). The reaction flask was purged with argon gas and sealed with a cap lined with a PTFE-lined silicone septum. Under an argon atmosphere, the reaction tube was fixed to a magnetic stirrer and reacted at room temperature for 12 hours. The crude product was then directly purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain target product 1 (385 mg), with a yield of 86%.

[0033] The NMR data for compound (1) are as follows:

[0034] 1 H NMR (400 MHz, CDCl3) δ 5.33 (d, J = 9.3 Hz, 1H), 1.82 (d, J = 9.2Hz, 1H), 1.68 (s, 3H), 1.56 (s, 2H), 1.18 (s, 36H).

[0035] 13 C NMR (101 MHz, CDCl3) δ 130.5, 119.1, 83.22, 83.17, 27.2, 25.8,25.3, 25.0, 24.93, 24.91, 24.8.

[0036] HRMS (ESI+): m / z for C 23 H 43 B3O6 [M+H]+ calcd. 449.3417, found 449.3402.

[0037] Example 1:

[0038] In this embodiment, (3S,4R,5S / 3R,4S,5R)-5-phenyl-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-1,2-oxaborhecyclopentan-2-ol (3a) was prepared:

[0039] The reaction equation is:

[0040]

[0041] The synthesis steps and process were as follows: 1 (0.4 mmol, 179 mg) and 2a (0.6 mmol, 64 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3a (126 mg), with a yield of 96%.

[0042] The NMR data for compound (3a) are as follows:

[0043] 1 H NMR (400 MHz, CDCl3) δ 7.22 – 7.35 (m, 5H), 5.03 (d, J = 9.1 Hz,1H), 4.75 (s, 1H), 4.72 (s, 1H), 3.02 (dd, J = 10.2, 10.2 Hz, 1H), 1.72 (s,3H), 1.22 (s, 12H), 1.12 (d, J = 11.2 Hz, 1H).

[0044] 13 C NMR (101 MHz, CDCl3) δ 145.5, 142.5, 128.4, 127.8, 126.2, 112.3, 84.7, 83.7, 56.7, 25.3, 24.8, 20.7.

[0045] HRMS (ESI + ): m / z for C 18 H 27 B2O4 [M+H] + calcd. 329.2095, found: 329.2085.

[0046] Example 2:

[0047] In this embodiment, (3S,4R,5S / 3R,4S,5R)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-5-(p-tolyl)-1,2-oxaborhecyclopentan-2-ol (3b) is prepared:

[0048] The reaction equation is:

[0049]

[0050] The synthesis steps and process were as follows: 1 (0.4 mmol, 179 mg) and 2b (0.6 mmol, 72 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3b (129 mg), with a yield of 94%.

[0051] The NMR data for compound (3b) are as follows:

[0052] 1 H NMR (400 MHz, CDCl3) δ 7.21 – 7.26 (m, 2H), 7.09 – 7.13 (m, 2H), 4.99 (d, J = 9.2 Hz, 1H), 4.73 (s, 1H), 4.71 (s, 1H), 3.01 (dd, J = 11.5, 9.1Hz, 1H), 2.32 (s, 3H), 1.70 (s, 3H), 1.22 (s, 6H), 1.21 (s, 6H), 1.10 (d, J =11.3 Hz, 1H).

[0053] 13 C NMR (101 MHz, CDCl3) δ 145.6, 139.4, 137.4, 129.1, 126.3, 112.1, 84.7, 83.6, 56.6, 25.3, 24.8, 21.5, 20.8.

[0054] HRMS (ESI + ): m / z for C 19 H 29 B2O4 [M+H] + calcd. 343.2252, found: 343.2249.

[0055] Example 3:

[0056] In this embodiment, (3S,4R,5S / 3R,4S,5R)-5-(4-bromophenyl)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-1,2-oxaborhecyclopentan-2-ol (3c) was prepared:

[0057] The reaction equation is:

[0058]

[0059] The synthesis steps and process were as follows: 1 (0.4 mmol, 179 mg) and 2c (0.6 mmol, 111 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3c (155 mg), with a yield of 95%.

[0060] The NMR data for compound (3c) are as follows:

[0061] 1 H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.4Hz, 2H), 4.97 (d, J = 9.1 Hz, 1H), 4.76 (s, 1H), 4.71 (s, 1H), 2.92 (dd, J =11.2, 9.1 Hz, 1H), 1.72 (s, 3H), 1.22 (s, 6H), 1.21 (s, 6H), 1.11 (d, J =11.3 Hz, 1H).

[0062] 13 C NMR (101 MHz, CDCl3) δ 145.1, 141.7, 131.5, 127.9, 121.6, 112.7, 84.0, 83.8, 56.9, 25.3, 24.8, 20.6.

[0063] HRMS (ESI + ): m / z for C 18 H 26 B2BrO4 [M+H] + calcd. 407.1201, found:407.1189.

[0064] Example 4:

[0065] In this embodiment, (3S,4R,5S / 3R,4S,5R)-5-(3-bromophenyl)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-1,2-oxaborhecyclopentan-2-ol (3d) was prepared:

[0066] The reaction equation is:

[0067]

[0068] The synthesis steps and process were as follows: 1 (0.4 mmol, 179 mg) and 2d (0.6 mmol, 111 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3d (133 mg), with a yield of 82%.

[0069] The NMR data for compound (3d) are as follows:

[0070] 1 H NMR (400 MHz, CDCl3) δ 7.51 (s, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.15-7.23 (m, 2H), 4.99 (d, J = 8.9 Hz, 1H), 4.78 (s, 1H), 4.73 (s, 1H), 2.94(dd, J = 11.0, 8.9 Hz, 1H), 1.73 (s, 3H), 1.22 (s, 12H), 1.11 (d, J = 11.2Hz, 1H).

[0071] 13 C NMR (101 MHz, CDCl3) δ 145.1, 145.0, 130.8, 130.0, 129.0, 124.8,122.7, 112.7, 83.8(two overlapping carbon signals), 56.8, 25.35, 25.32,24.8, 20.5.

[0072] HRMS (ESI + ): m / z for C 18 H 26 B2BrO4 [M+H] + calcd. 407.1201, found:407.1186.

[0073] Example 5:

[0074] In this embodiment, (3S,4R,5S / 3R,4S,5R)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-5-(m-tolyl)-1,2-oxaborhecyclopentan-2-ol (3e) is prepared:

[0075] The reaction equation is:

[0076]

[0077] The synthesis steps and process are as follows: 1 (0.4 mmol, 179 mg) and 2e (0.6 mmol, 72 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; under air atmosphere, the reaction tube was fixed on the magnetic stirrer and reacted for 12 hours. The crude product was then directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3e (123 mg), with a yield of 90%.

[0078] The NMR data for compound (3e) are as follows:

[0079] 1 H NMR (400 MHz, CDCl3) δ 7.16-7.21 (m, 2H), 7.11 (d, J = 7.9 Hz, 1H), 7.06 (d, J = 7.5 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.74 (s, 1H), 4.72 (s,1H), 3.01 (dd, J = 11.2, 9.0 Hz, 1H), 2.34 (s, 3H), 1.72 (s, 3H), 1.22 (s,12H), 1.11 (d, J = 11.2 Hz, 1H).

[0080] 13 C NMR (101 MHz, CDCl3) δ 145.6, 142.4, 138.0, 128.5, 128.3, 126.8,123.4, 112.2, 84.8, 83.6, 56.5, 25.33, 25.30, 24.7, 21.8, 20.7.

[0081] HRMS (ESI + ): m / z for C 19 H 29 B2O4 [M+H] + calcd. 343.2252, found: 343.2244.

[0082] Example 6:

[0083] In this embodiment, (3S,4R,5S / 3R,4S,5R)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-5-(o-tolyl)-1,2-oxaborhecyclopentan-2-ol (3f) was prepared:

[0084] The reaction equation is:

[0085]

[0086] The synthesis steps and process were as follows: 1 (0.4 mmol, 179 mg) and 2f (0.6 mmol, 72 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3f (130 mg), with a yield of 95%.

[0087] The NMR data for compound (3f) are as follows:

[0088] 1 H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 7.4 Hz, 1H), 7.13 – 7.20 (m,2H), 7.09 – 7.13 (m, 1H), 5.24 (d, J = 8.3 Hz, 1H), 4.69 (s, 1H), 4.69 (s,1H), 3.14 (dd, J = 10.2, 8.3 Hz, 1H), 2.31 (s, 3H), 1.69 (s, 3H), 1.21 (s,6H), 1.21 (s, 6H), 1.10 (d, J = 10.3 Hz, 1H).

[0089] 13 C NMR (101 MHz, CDCl3) δ 145.8, 140.5, 135.9, 130.6, 127.7, 126.3,126.2, 112.0, 83.7 (two overlapping carbon signals), 55.8, 25.2, 24.8, 20.5,20.0.

[0090] HRMS (ESI + ): m / z for C 19 H 29 B2O4 [M+H] +calcd. 343.2252, found: 343.2243.

[0091] Example 7:

[0092] In this embodiment, (3S,4R,5S / 3R,4S,5R)-5-(2-chlorophenyl)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)-1,2-oxaborhexacyclopentan-2-ol (3g) was prepared:

[0093] The reaction equation is:

[0094]

[0095] The synthesis steps and process were as follows: 1 g (0.4 mmol, 141 mg) and 2 g (0.6 mmol, 84 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain 3 g (126 mg) of the target product, with a yield of 87%.

[0096] The NMR data for compound (3g) are as follows:

[0097] 1 H NMR (400 MHz, CDCl3) δ 7.46 (dd, J = 7.7, 1.8 Hz, 1H), 7.32 (dd, J= 7.9, 1.4 Hz, 1H), 7.24-7.28 (m, 1H), 7.20 (dd, J = 7.5, 1.8 Hz, 1H), 5.46(d, J = 7.9 Hz, 1H), 4.69 (s, 2H), 3.12 (dd, J = 9.8, 7.9 Hz, 1H), 1.74 (s,3H), 1.20 (s, 6H), 1.19 (s, 6H), 1.11 (d, J = 9.8 Hz, 1H).

[0098] 13 C NMR (101 MHz, CDCl3) δ 145.3, 140.0, 133.3, 129.7, 129.0, 128.1,127.1, 112.2, 83.7, 81.4, 56.4, 27.23, 25.3, 25.2, 24.8, 20.0.

[0099] HRMS (ESI + ): m / z for C 18 H 26 B2ClO4 [M+H] + calcd. 363.1706, found:363.1695.

[0100] Example 8:

[0101] In this embodiment, (3S,4R,5S / 3R,4S,5R)-5-(3,5-dichlorophenyl)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)-1,2-oxaborhexacyclopentan-2-ol was prepared (3h):

[0102] The reaction equation is:

[0103]

[0104] The synthesis steps and process were as follows: 1 (0.4 mmol, 162 mg) and 2h (0.6 mmol, 105 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; under an air atmosphere, the reaction tube was fixed on a magnetic stirrer and reacted for 12 hours. The crude product was then directly purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3h (132 mg), with a yield of 83%.

[0105] The NMR data for compound (3h) are as follows:

[0106] 1 H NMR (400 MHz, d 6 -acteone) δ 7.34-7.39 (m, 1H), 7.28-7.30 (m, 2H),5.04 (d, J = 8.4 Hz, 1H), 4.78 (s, 1H), 4.73 (s, 1H), 2.85 – 2.90 (m, 1H),1.79 (s, 3H), 1.18 (s, 12H), 1.05 (d, J = 10.4 Hz, 1H).

[0107] 13 C NMR (101 MHz, d 6 -actone) δ 148.6, 146.4, 135.2, 127.7, 125.0,112.5, 83.7, 82.4, 58.8, 25.2, 24.8, 19.9.

[0108] HRMS (ESI + ): m / z for C 18 H 25 B2Cl2O4 [M+H] + calcd. 397.1316, found:397.1307.

[0109] Example 9:

[0110] In this embodiment, (3S,4R,5S / 3R,4S,5R)-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhexacyclopentan-2-yl)-5-(thiophene-2-yl)-1,2-oxaborhexacyclopentan-2-ol (3i) was prepared:

[0111] The reaction equation is:

[0112]

[0113] The synthesis steps and process were as follows: 1 (0.4 mmol, 124 mg) and 2i (0.6 mmol, 67 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3i (112 mg), with a yield of 84%.

[0114] The NMR data for compound (3i) are as follows:

[0115] 1 H NMR (400 MHz, d 6 -acteone) δ 7.33-7.37 (m, 1H), 6.94 – 7.01 (m, 2H), 5.23 (d, J = 9.3 Hz, 1H), 4.77 (s, 1H), 4.75 (s, 1H), 3.07 (dd, J = 11.7, 9.5Hz, 1H),, 1.74 (s, 3H), 1.21 (s, 12H), 1.03 (d, J = 11.2 Hz, 1H).

[0116] 13 C NMR (101 MHz, d 6-acteone) δ 147.3, 146.4, 127.2, 125.2, 124.9,112.0, 83.6, 80.3, 58.6, 25.3, 24.8, 20.5.

[0117] HRMS (ESI + ): m / z for C 16 H 25 B2O4S [M+H] + calcd. 335.1660, found:335.1652.

[0118] Example 10:

[0119] In this embodiment, (3S,4R,5R / 3R,4S,5R)-5-cyclohexyl-4-(prop-1-en-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborhecyclopentan-2-yl)-1,2-oxaborhecyclopentan-2-ol (3j) was prepared:

[0120] The reaction equation is:

[0121]

[0122] The synthesis steps and process were as follows: 1 (0.4 mmol, 124 mg) and 2j (0.6 mmol, 67 mg) were added to a 5 mL reaction tube equipped with a magnetic stirrer, followed by 1.0 mL of toluene; the reaction tube was fixed on the magnetic stirrer under air atmosphere, and after reacting for 12 hours, the crude product was directly separated and purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 3j (100 mg), with a yield of 75%.

[0123] The NMR data for compound (3j) are as follows:

[0124] 1H NMR (400 MHz, CDCl3) δ 4.77 (s, 1H), 4.68 (s, 1H), 3.88 (dd, J =7.9, 5.7 Hz, 1H), 2.90 (dd, J = 9.6, 7.9 Hz, 1H), 1.88 (app. d, J = 13.0 Hz,1H), 1.70 (s, 3H), 1.62 – 1.75 (m, 3H), 1.35-1.45 (m, 1H), 1.23 (s, 12H), 1.14 – 1.27 (m, 4H), 1.02-1.11 (m, 2H), 0.90 (d, J = 9.5 Hz, 1H).

[0125] 13 C NMR (101 MHz, CDCl3) δ 148.1, 110.7, 87.6, 83.6, 50.4, 43.5, 29.8,28.3, 26.9, 26.7, 26.4, 25.3, 24.9, 20.4.

[0126] HRMS (ESI + ): m / z for C 18 H 33 B2O4 [M+H] + calcd. 335.2565, found: 335.2550.

[0127] Example 11:

[0128] In this embodiment, (3S,4R,5S / 3R,4S,5R)-3-(4-methoxyphenyl)-5-phenyl-4-(prop-1-en-2-yl)-1,2-oxaborane-2-ol (7) was prepared:

[0129]

[0130] The synthesized compound 3a (0.4 mmol, 131 mg), toluene (1.0 mL), and 4-bromomethoxybenzene (0.6 mmol, 112 mg) were added sequentially to a 5 mL reaction tube equipped with a magnetic stirrer. Pd(OAc)₂ (0.016 mmol, 4 mg), Sphos (0.032 mmol, 13 mg), and CsF (0.6 mmol, 91 mg) were then added. The reaction flask was purged with argon and sealed with a cap lined with a PTFE-lined silicone septum. Under an argon atmosphere, the reaction tube was fixed to a magnetic stirrer and reacted at room temperature for 12 hours. The crude product was then directly purified by column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain the target product 7 (89 mg), with a yield of 72%.

[0131] The NMR data for compound (7) are as follows:

[0132] 1 H NMR (400 MHz, d 6 -acteone) δ 7.45 (d, J = 6.9 Hz, 2H), 7.35 (dd, J =7.9, 7.2 Hz, 2H), 7.26 – 7.29 (m, 1H), 7.10 (d, J = 8.6 Hz, 2H), 6.81 (d, J =8.6 Hz, 2H), 5.45 (d, J = 8.1 Hz, 1H), 4.71 (s, 1H), 4.64 (s, 1H), 3.75 (s,3H), 3.12 (dd, J = 8.6, 8.2 Hz, 1H), 2.87 (d, J = 8.7 Hz, 1H), 1.44 (s, 3H),0.84 – 0.88 (m, 1H).

[0133] 13 C NMR (101 MHz, d 6 -acteone) δ158.6, 144.4, 143.9, 132.5, 131.6,129.0, 128.2, 127.0, 114.3, 112.8, 82.6, 59.9, 55.3, 23.2.

[0134] HRMS (ESI+): m / z for C 19 H 21 BNaO3 [M+Na]+ calcd. 331.1481, found331.1466.

[0135] The synthesized multi-substituted five-membered ring skeleton contains multiple functional groups, facilitating further modification. For example, the boric acid group on the ring can undergo a Suzuki coupling reaction with 4-bromomethoxybenzene, introducing a methoxyphenyl group and forming a new five-membered ring boric acid skeleton. After introducing the methoxyphenyl group, the Lewis acidity of the boric acid can be modulated through the electron-donating effect of the methoxy group, thereby enhancing the recognition ability of cis-diol molecules such as sugars. Simultaneously, the hydrophobic volume of the methoxybenzene helps improve membrane permeability, making it suitable for targeted drug delivery. Furthermore, its benzene ring can also serve as a secondary modification site for grafting functional molecules and provide aromatic stacking in supramolecular assembly. In summary, this structure has practical value in the fields of sensing and recognition, drug delivery, and smart materials.

[0136] The above embodiments detail the fabrication method, characterization techniques, and performance advantages of the wet power generation device of the present invention. By introducing a thermally induced covalent crosslinking strategy, the present invention successfully solves the core problem of weak bonding between carbon dots and the substrate interface, obtaining a high-output, highly stable, and highly flexible wet power generation device, and demonstrating its great potential for modular integration and practical applications.

Claims

1. A five-membered cyclic borate skeleton having the following structure: ， In the formula, R is selected from substituted phenyl, heterocyclic or alkyl groups.

2. The five-membered cyclic borate skeleton according to claim 1, characterized in that: The substituted phenyl group is selected from para-substituted phenyl, meta-substituted phenyl, ortho-substituted phenyl, and the substituent on the benzene ring is an electron-donating group or an electron-withdrawing group.

3. A method for preparing the five-membered cyclic borate skeleton according to claim 1 or 2, characterized in that, Includes the following steps: S1, 1,3-dieneboron and borate ester reagent are added to the solvent, and the reaction is carried out under the conditions of platinum catalyst and protective gas to obtain allylboron product by stirring. S2, in a solvent, the obtained allyl boron product is mixed with aldehyde reactants, and after stirring, a five-membered cyclic borate skeleton product is obtained.

4. The method for preparing the five-membered cyclic borate skeleton according to claim 3, characterized in that, The molar ratio of 1,3-dieneboron and borate ester reagent in step S1 is 1:1.1~1.

5.

5. The method for preparing the five-membered cyclic borate skeleton according to claim 3, characterized in that, The allyl boron product obtained in step S1 needs to be separated and purified by column chromatography; the five-membered cyclic boric acid skeleton product obtained in step S2 also needs to be separated and purified by column chromatography.

6. The method for preparing the five-membered cyclic borate skeleton according to claim 3, characterized in that, In step S1, the reaction temperature is 80±10℃ and the reaction time is 8-15h.

7. The method for preparing the five-membered cyclic borate skeleton according to claim 5, characterized in that, The column chromatography method uses a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 5:1 as the eluent.

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