A triarylboron compound, a preparation method thereof, and an application thereof in catalytic reductive amination reaction

Abstract

The present invention relates to a class of triarylboron compounds, their preparation methods and applications in catalytic reductive amination reactions, belonging to the technical field of organic chemical synthesis. The triarylboron compound is a compound represented by Formula I, which can be prepared by reacting a polyfluoro-substituted phenyl Grignard reagent with a substituted phenyl potassium trifluoroborate. Its main structural feature is that three polysubstituted phenyl groups are connected to a boron atom. This class of compounds can be used as highly efficient catalysts to catalyze the reductive amination reactions of aldehyde or ketone compounds in aqueous phase to prepare organic amine compounds.

Description

Technical Field

[0001] The present invention relates to the technical field of organic chemical synthesis, and relates to a triarylboron compound, a preparation method thereof and an application thereof. Specifically, it relates to a preparation method of a class of trifluorinated phenylboron compounds and their application in the reductive amination reaction of aldehyde or ketone compounds in an aqueous phase to prepare organic amine compounds. Background Art

[0002] In the 1960s, Massey et al. first synthesized the organoboron reagent B(C 6 F 5 ) 3 , which was only used as an initiator in some polymerization reactions at that time and had few other applications. In 1996, Piers first reported that B(C 6 F 5 ) 3 could be used as a catalyst in the hydrosilylation reaction of carbonyl groups. A decade later, Stephan et al. discovered the reversible hydrogen activation of the phosphine-borane complex formed by B(C 6 F 5 ) 3 with a phosphorus ligand, and first proposed the concept of "Frustrated Lewis pairs (FLPs)" a year later. Stephan's work has attracted great attention from chemists, not only starting the field of FLP chemistry, but also arousing people's interest in the application of B(C 6 F 5 ) 3 and other halogenated triarylboranes in catalysis and the activation of small molecules (hydrogen H 2 , carbon dioxide CO 2 , nitrous oxide N 2 O, isocyanate MesCNO, etc.).

[0003] In recent years, the research on halogenated triarylboranes has attracted extensive attention. Compared with B(C 6 F 5 ) 3 , subtle changes in the functional group structure on the aromatic ring will affect the accessibility and energy of the empty p-orbitals on the central boron atom, thereby regulating its Lewis acidity and chemical reactivity. Because nucleophiles can easily access the empty p-orbitals on the central boron atom, boranes can act as Lewis acid catalysts. It is the attack and subsequent release of this empty p-orbital that constitutes the theoretical basis for the catalysis of organic chemical reactions by boranes as Lewis acids.

[0004] Currently, based on B(C 6 F 5 ) 3Although some progress has been made in the structural modification of triarylboron catalysts, B(C 6 F 5 ) 3 is still the mainstream catalyst. Obviously, by optimizing the Lewis acidity or steric requirements of the boron center, the catalytic activity can be adjusted and improved. However, since the Lewis acidity of triarylboron compounds is subtly affected by the electronic effects and steric hindrance of aryl functional groups, developing more efficient triarylboron catalysts and applying them to more valuable metal-free organic chemical reactions is a very meaningful challenge.

[0005] Due to the sensitivity of most halogenated triarylboranes to air and moisture, Schlenk techniques are required for compound storage and chemical synthesis applications. Therefore, this defect contributes to one of the key limitations in the development of FLP chemistry, namely the enhanced sensitivity to water. Summary of the Invention

[0006] The object of the present invention is to provide a class of triarylboron compounds, their preparation methods, and their applications in catalytic reductive amination reactions. Compared with the triarylboron compounds reported in the literature, these novel triarylboron compounds have Lewis acidity and at the same time have stability to air and water. When stored and used as catalysts in organic chemical synthesis reactions, anhydrous and anaerobic operation technical requirements are not needed.

[0007] To solve the technical problems of the present invention, the technical solution proposed is: a triarylboron compound, whose structure is shown as formula I below:

[0008]

[0009] In formula I, R 1 is hydrogen, fluorine, or trifluoromethyl, and R 2 is hydrogen, fluorine, or trifluoromethyl; a is the substitution number of the non-hydrogen substituent R 1 , a = 1 - 5; b is the substitution number of the non-hydrogen substituent R 2 , b = 1 - 5.

[0010] Preferably, it is selected from one of the following 5 compounds:

[0011]

[0012] To solve the technical problems of the present invention, another technical solution proposed is: using polyfluoro-substituted bromobenzene as the starting material, the reaction route is as follows:

[0013]

[0014] wherein R 1 is hydrogen, fluorine, or trifluoromethyl, R2 is hydrogen, fluorine or trifluoromethyl; a is a non-hydrogen substituent R 1 The substitution number a of is 1 to 5; b is a non-hydrogen substituent R 2 The substitution number b of is 1 to 5;

[0015] Under an inert gas atmosphere and in the presence of an organic solvent, a Grignard reagent or magnesium chips, the compound represented by Formula 1 reacts in a reactor for 1 to 2 hours to prepare the compound represented by Formula 2;

[0016] Under an inert gas atmosphere, the compound represented by Formula 2 reacts with the compound represented by Formula 3 in an organic solvent in a reactor for 12 to 24 hours to prepare the compound represented by Formula 4.

[0017] In the above synthesis method, the organic solvent is one or a mixed solvent of several of toluene, tetrahydrofuran, cyclopentyl methyl ether, and diethyl ether.

[0018] To solve the technical problems of the present invention, another technical solution is proposed: for the reductive amination reaction of aldehyde or ketone compounds catalyzed by a metal-free boron catalyst to prepare organic amine compounds:

[0019]

[0020] R in Formulas (I), (II), and (III) 1 is any one of hydrogen, alkyl or substituted alkyl, aryl or substituted aryl;

[0021] R 2 is any one of hydrogen, alkyl or substituted alkyl, aryl or substituted aryl;

[0022] R 3 is any one of hydrogen, methyl, methoxy, fluorine, chlorine, bromine, hydroxyl, methoxycarbonyl, amino, cyano, nitro, acetyl.

[0023] Preferably, in the aqueous phase, using the triarylboron compound as a catalyst, the reductive amination reaction of aromatic aldehyde or aromatic ketone compounds is catalyzed to prepare organic amine compounds:

[0024]

[0025] R in Formulas (I), (II), and (III) 1 is any one of hydrogen, alkyl or substituted alkyl, aryl or substituted aryl;

[0026] R 2 is any one of hydrogen, alkyl or substituted alkyl, aryl or substituted aryl;

[0027] R3 is any one of hydrogen, methyl, methoxy, fluorine, chlorine, bromine, hydroxyl, methoxycarbonyl, amino, cyano, nitro, and acetyl.

[0028] Preferably, using 5 mol% of Cat 1 and 1.5 chemical equivalents of phenyldimethylsilane, in an aqueous phase under an argon atmosphere at 80 °C for 12 hours, the reductive amination reaction of aromatic aldehydes or aromatic ketones is catalyzed to prepare a series of organic amine compounds.

[0029]

[0030]

[0031] In an aqueous phase, using the novel triarylboron compound Cat 1 as a catalyst and silane as a reducing agent, the reductive amination reaction of aromatic aldehydes or aromatic ketones is catalyzed to prepare organic amine compounds.

[0032] The ratio of the aromatic aldehyde or aromatic ketone substrate to the catalyst is 100:1 to 10:1.

[0033] The novel triarylboron compound provided by the present invention has the main performance characteristics that while maintaining Lewis acidity, it also has a certain stability in air and water, and can use water as a green solvent to catalyze the reductive amination reaction of aromatic aldehydes or aromatic ketones to prepare organic amine compounds in high yields (up to 99%). Using 5 mol% of Cat 1 and 1.5 equivalents of phenyldimethylsilane, in an aqueous phase under an argon atmosphere at 80 °C for 12 hours, the reductive amination reaction of aromatic aldehydes or aromatic ketones is catalyzed to prepare a series of organic amine compounds.

[0034] BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 is the 1H NMR spectrum of catalyst Cat 1 1 H NMR(400MHz,Benzene-d 6 )

[0036] Figure 2 is the 19F NMR spectrum of catalyst Cat 1 19 F NMR(376MHz,Benzene-d 6 )

[0037] Figure 3 is the 11B NMR spectrum of catalyst Cat 1 11 B NMR(160MHz,Benzene-d 6 )

[0038] Figure 4 It is the high-resolution mass spectrometry data of catalyst Cat 1

[0039] Figure 5 It is the 1H NMR spectrum of the products 1-7 of reductive amination 1 H NMR(400MHz,CDCl 3 )

[0040] Figure 6 It is the 13C NMR spectrum of the products 1-7 of reductive amination 13 C NMR(101MHz,CDCl 3 ) Detailed implementation mode

[0041] The present invention will be further described in detail and completely below in combination with the implementation examples. The listed implementation examples will help to understand the present invention, but this should not be understood that the scope of the above-mentioned subject matter of the present invention is limited to the following examples. All technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0042] General description:

[0043] Abbreviations are used in the implementation examples, and their meanings are as follows:

[0044] NMR is nuclear magnetic resonance, and HRMS is high-resolution mass spectrometry.

[0045] The solvents used were purified and dried by standard methods before use; all reagents used were commercially available or synthesized according to the methods in the existing literature and purified before use.

[0046] Example 1:

[0047] Preparation of boron reagent Cat 1:

[0048]

[0049] Potassium trifluoro(2-(trifluoromethyl)phenyl)borate: Take a 100 mL plastic reaction flask, dissolve 3.0 g (2-trifluoromethyl)phenylboronic acid (15.81 mmol) in methanol (30 mL), and then add 5 mL of KHF 2 (1.64 g, 21.2 mmol, 4 equiv.) distilled aqueous solution to the reaction system. The reaction solution becomes turbid and a white precipitate is formed. The resulting suspension is continuously stirred and reacted for 12 h. Then, it is extracted with an appropriate amount of acetone, and all volatiles are removed by concentration under reduced pressure to obtain a white solid. It is extracted with acetone again, filtered and evaporated to obtain a solid, washed with hexane, and then dried in vacuo to obtain the target product as a white solid product (3.99 g, 15.81 mmol, yield 99%).

[0050] The 1H NMR data of this product are as follows: 1 1H NMR (400 MHz, DMSO-d 6 ) δ 6.95 (dd, J=9.2, 7.3 Hz, 2H). 19 19F NMR (376 MHz, DMSO-d 6 ) δ -138.95 (d, J=30.2 Hz, 2F), -140.43 (d, J=47.5 Hz, 3F), -167.86 (s, 1F).

[0051] B(3,4,5-C 6 H 2 F 3 )(C 6 F 5 ) 2 Preparation of (Cat 1): Take a 250 mL Schlenk reaction flask, add 500 mg of magnesium chips (24 mmol) activated by dilute hydrochloric acid, and introduce 50 mL of ultra-dry diethyl ether under nitrogen. At room temperature, 2.8 mL of C 6 F 5 Br (24 mmol) was added dropwise to the reaction system within 30 min. There was heat release during the addition. Ensure that the reaction solution did not reach the reflux state, and stir rapidly at the same time. After reacting at room temperature for 0.5 h, the Grignard reagent was transferred to a diethyl ether solution of 10 mL of (3,4,5-trifluorophenyl) potassium trifluoroborate (3.0 g, 11.90 mmol) through a double-headed syringe. Stir and react at 0 °C for 12 h. The organic solvent was recovered under reduced pressure. Under nitrogen, it was extracted with 50 mL of hot toluene, filtered through filter paper, and the organic solvent was recovered under reduced pressure to obtain a pale yellow solid product. The product was recrystallized from toluene / n-hexane (1:1) to obtain 1.26 g of white crystals (2.65 mmol, yield 22%).

[0052] The 1H NMR data of this product are as follows: 1 1H NMR (400 MHz, Benzene-d 6 ) δ 6.90 - 6.75 (m, 2H), 3.62 (s, 4H). 19 19F NMR (376 MHz, Benzene-d 6 ) δ -133.17 (s, 4F), -136.68 (s, 2F), -156.33 (s, 2F), -163.32 (s, 4F), -163.80 (s, 1F). 11 11B NMR (160 MHz, Benzene-d 6 ) δ 0.40. HRMS (EI) Calcd for C 18 H 2 BF13 :[M+H] + 477.0120.Found: m / z 477.0111.

[0053] Example 2:

[0054] Preparation of boron reagent Cat 2:

[0055]

[0056] B(3,4,5-C 6 H 2 F 3 )(C 6 HF 4 ) 2 (Preparation of Cat 2): Take a 250 mL Schlenk reaction flask, add 500 mg of magnesium chips (24 mmol) activated by dilute hydrochloric acid, introduce 50 mL of ultra-dry ether under nitrogen. At room temperature, add 2.8 mL of C 6 HF 4 Br (24 mmol) dropwise to the reaction system within 30 min. There is heat release during the dropping process. Ensure that the reaction solution does not reach the reflux state, and stir rapidly at the same time. After reacting at room temperature for 0.5 h, transfer the Grignard reagent to an ether solution of 10 mL of (3,4,5-trifluorophenyl) potassium trifluoroborate (3.0 g, 11.90 mmol) through a double-headed syringe. Stir and react at 0 °C for 12 h. Recover the organic solvent under reduced pressure. Under nitrogen, extract with 50 mL of hot toluene, filter through filter paper, and recover the organic solvent under reduced pressure to obtain a pale yellow solid product. The product is recrystallized from toluene / n-hexane (1:1) to obtain 1.92 g (4.37 mmol, yield 37%) of white crystals.

[0057] The 1H NMR data of this product are as follows: 1 1H NMR (400 MHz, Benzene-d 6 ) δ 7.38 (m, 2H), 6.87–6.81 (m, 2H). 19 19F NMR (376 MHz, Benzene-d 6 ) δ -134.83, -134.95, -135.06, -135.24, -135.28, -143.93, -161.50. 11 11B NMR (160 MHz, Benzene-d 6 ) δ 48.88.

[0058] Example 3:

[0059] Preparation of boron reagent Cat 3:

[0060]

[0061] B(3,5-C 6 H 3 F 2 )(C 6 HF 4 ) 2 (Preparation of (Cat 3): Take a 250 mL Schlenk reaction flask, add 500 mg of magnesium chips (24 mmol) activated by dilute hydrochloric acid, introduce 50 mL of ultra-dry diethyl ether under nitrogen. At room temperature, add 2.8 mL of C 6 HF 4 Br (24 mmol) dropwise to the reaction system. There is heat release during the dropping process. Ensure that the reaction solution does not reach the reflux state, and stir rapidly at the same time. After reacting at room temperature for 0.5 h, transfer the Grignard reagent to an ether solution of 10 mL of (3,5-difluorophenyl) potassium trifluoroborate (2.80 g, 11.90 mmol) by a double-headed syringe. Stir and react at 0 °C for 12 h. Recover the organic solvent under reduced pressure. Under nitrogen, extract with 50 mL of hot toluene, filter through filter paper, and recover the organic solvent under reduced pressure to obtain a pale yellow solid product. The product is recrystallized from toluene / n-hexane (1:1) to obtain 1.61 g of white crystals (3.81 mmol, yield 32%).

[0062] The 1H NMR data of this product are as follows: 1 1H NMR (400 MHz, Benzene-d 6 ) δ 7.68 (m, 2H), 7.37 (tt, J = 8.0, 4.9 Hz, 2H), 6.99 (s, 1H). 19 19F NMR (376 MHz, Benzene-d 6 ) δ -134.83, -134.95, -135.06, -135.24, -135.28, -143.93, -161.50. 11 11B NMR (160 MHz, Benzene-d 6 ) δ 45.86.

[0063] Example 4:

[0064] Preparation of boron reagent Cat 4:

[0065]

[0066] B(2-CF 3 -C 6 H 4 )(C 6 F 5) 2 (Preparation of Cat 4): Take a 250 mL Schlenk reaction flask, add 500 mg of magnesium chips (24 mmol) activated by dilute hydrochloric acid, introduce 50 mL of ultra-dry diethyl ether under nitrogen. At room temperature, add 2.8 mL of C 6 F 5 Br (24 mmol) dropwise to the reaction system within 30 min. There is a heat release during the dropping process. Ensure that the reaction solution does not reach the reflux state, and stir rapidly at the same time. After reacting at room temperature for 0.5 h, transfer the Grignard reagent to an ether solution of 10 mL of potassium (2-trifluoromethyl)trifluoroborate (3.2 g, 11.90 mmol) through a double-headed syringe. Stir and react at 0 °C for 12 h. Recover the organic solvent under reduced pressure. Under nitrogen, extract with 50 mL of hot toluene, filter through filter paper, and recover the organic solvent under reduced pressure to obtain a pale yellow solid product. The product is recrystallized from toluene / n-hexane (1:1) to obtain 1.63 g (3.33 mmol, yield 28%) of white crystals.

[0067] The 1H NMR data of this product are as follows: 1 H NMR (400 MHz, Benzene-d 6 ) δ 7.69 (s, 1H), 7.48 (s, 1H), 7.44–7.33 (m, 2H). 19 F NMR (376 MHz, Benzene-d 6 ) δ -59.52, -129.32, -153.96, -161.72. 11 B NMR (160 MHz, Benzene-d 6 ) δ 71.25.

[0068] Example 5:

[0069] Preparation of boron reagent Cat 5:

[0070]

[0071] B(3,5-CF 3 -C 6 H 4 )(C 6 HF 4 ) 2 (Preparation of Cat 5): Take a 250 mL Schlenk reaction flask, add 500 mg of magnesium chips (24 mmol) activated by dilute hydrochloric acid, introduce 50 mL of ultra-dry diethyl ether under nitrogen. At room temperature, add 2.8 mL of C 6 HF 4Br (24 mmol) was added dropwise to the reaction system. There was an exothermic phenomenon during the addition. Ensure that the reaction solution did not reach the reflux state, and at the same time, stir rapidly. After reacting at room temperature for 0.5 h, the Grignard reagent was transferred to an ether solution of 10 mL of potassium tris(3,5-bis(trifluoromethyl)phenyl)borate (3.5 g, 11.90 mmol) through a double-headed syringe. Under the condition of 0 °C, stir and react for 12 h. The organic solvent was recovered under reduced pressure. Under nitrogen conditions, it was extracted with 50 mL of hot toluene, filtered through filter paper, and the organic solvent was recovered under reduced pressure to obtain a pale yellow solid product. The product was recrystallized from toluene / n-hexane (1:1) to obtain 1.61 g (3.09 mmol, yield 26%) of white crystals.

[0072] The 1H NMR data of this product are as follows: 1 H NMR (400 MHz, DMSO-d 6 ) δ 7.88 (s, 1H), 7.63 (s, 2H), 7.37 (tt, J = 8.1, 4.9 Hz, 2H). 19 F NMR (376 MHz, DMSO-d 6 ) δ -63.55, -135.26, -143.93. 11 B NMR (160 MHz, Benzene-d 6 ) δ 47.85.

[0073] Example 6:

[0074]

[0075] Take a 10 mL Schlenk reaction tube, and sequentially weigh and add S1-2 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl(dimethyl)silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring reaction for 12 h. After the reaction, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain 112.2 mg of the target product 1-2, with a yield of 79%.

[0076] N-(4-(((2S,3R,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)oxy)benzyl)aniline (1-2)

[0077]

[0078] As a white solid; TLC: R f = 0.35 (silica gel, PE / EA, 5:1).

[0079] 1 H NMR (400 MHz, CDCl 3 ) δ 7.45–7.14 (m, 24H), 7.13–7.05 (m, 2H), 6.82–6.62 (m, 4H), 5.54 (d, J = 7.9 Hz, 1H), 4.94 (t, J = 12.3 Hz, 2H), 4.84 (d, J = 11.9 Hz, 1H), 4.76 (d, J = 12.1 Hz, 1H), 4.62 (d, J = 12.1 Hz, 1H), 4.57–4.49 (m, 2H), 4.42 (d, J = 11.5 Hz, 1H), 4.32–4.22 (m, 3H), 4.21 (t, J = 2.6 Hz, 1H), 3.83 (dd, J = 10.8, 1.9 Hz, 1H), 3.73 (dd, J = 10.8, 4.8 Hz, 1H), 3.63–3.52 (m, 2H).

[0080] 13 C NMR (101 MHz, CDCl 3 ) δ 156.97, 148.28, 138.99, 138.65, 138.46, 137.93, 133.21, 129.40, 128.80, 128.55, 128.52, 128.42, 128.32, 128.10, 127.91, 127.84, 127.77, 127.63, 127.57, 118.66, 117.63, 117.12, 115.23, 112.98, 99.51, 78.79, 75.55, 74.87, 74.64, 73.55, 73.27, 72.82, 71.73, 69.24, 47.93.

[0081] HRMS (EI) Calcd for C 47 H 47 NO 6 :[M+H] + 722.3482. Found: m / z 722.3488.

[0082] Example 7:

[0083]

[0084] Take a 10 mL Schlenk reaction tube, and sequentially weigh and add S1-3 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, using a Schlenk inert gas protection device, displace nitrogen three times, inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring reaction for 12 h. After the reaction, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-3, 72.4 mg, with a yield of 77%.

[0085] ((5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-5H-bis([1,3]dioxolo)[4,5-b:4',5'-d]pyran-5-yl)methyl 4-((phenylamino)methyl)benzoate(1-3)

[0086]

[0087] As a white solid;TLC:R f =0.40(silica gel,PE / EA,5:1).

[0088] 1 H NMR(400MHz,CDCl 3 )δ8.05–7.99(m,2H),7.43(d,J=8.2Hz,2H),7.16(ddd,J=8.4,7.3,3.7Hz,3H),6.80–6.66(m,2H),6.64–6.57(m,2H),5.57(d,J=4.9Hz,1H),4.65(dd,J=7.9,2.5Hz,1H),4.52(dd,J=11.5,4.9Hz,1H),4.46–4.39(m,3H),4.34(ddd,J=9.8,6.4,2.2Hz,2H),4.18(ddd,J=7.1,4.9,1.9Hz,1H),1.50(d,J=14.2Hz,6H),1.35(d,J=9.4Hz,6H).

[0089] 13 C NMR(101MHz,CDCl 3)δ166.37,147.82,145.15,130.20,129.41,127.21,117.94,112.99,109.79,108.92,96.42,71.22,70.80,70.60,66.21,63.93,48.07,26.13,25.08,24.58.

[0090] HRMS(EI)Calcd for C 26 H 31 NO 7 :[M+H] + 470.2179.Found:m / z 470.2186.

[0091] Example 8:

[0092]

[0093] Take a 10 mL Schlenk reaction tube, and successively weigh and add S1-4 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-4, 41.6 mg, with a yield of 52%.

[0094] (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-(4-(3-(phenylamino)butyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol(1-4)

[0095]

[0096] As a white solid; TLC: R f =0.30(silica gel, DCM / MeOH, 10:1).

[0097] 1 H NMR(400MHz,CDCl 3)δ 7.10 (t, J = 7.7 Hz, 2H), 6.93 (d, J = 8.1 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 6.63 (t, J = 7.3 Hz, 1H), 6.48 (d, J = 7.8 Hz, 2H), 5.65 (s, 1H), 5.14 (d, J = 57.1 Hz, 2H), 4.79 (s, 1H), 3.68 (s, 6H), 3.37 (m, J = 6.2 Hz, 1H), 3.27 (s, 1H), 2.52 (s, 2H), 1.65 (ddt, J = 48.4, 15.0, 7.5 Hz, 2H), 1.13–1.03 (m, 3H).

[0098] 13 C NMR (101 MHz, CDCl 3 )δ 155.29, 147.50, 136.61, 129.42, 117.10, 113.46, 100.87, 76.40, 75.30, 73.26, 69.15, 62.43, 49.37, 48.16, 40.32, 31.78, 21.78.

[0099] HRMS (EI) Calcd for C 22 H 29 NO 6 :[M + H] + 404.2073. Found: m / z 404.2078.

[0100] Example 9:

[0101]

[0102] Take a 10 mL Schlenk reaction tube, and successively weigh and add S1-5 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times, inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-5, 48.1 mg, with a yield of 89%.

[0103] N-(4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-yl)aniline (1-5)

[0104]

[0105] As a white solid;TLC:R f =0.45(silica gel,PE / EA,20:1).

[0106] 1 H NMR(400MHz,CDCl 3 )δ7.20–7.12(m,2H),6.66(tt,J=7.3,1.1Hz,1H),6.61–6.56(m,2H),3.44(m,J=6.3Hz,1H),2.05(m,J=13.5,5.3Hz,2H),1.88(t,J=6.3Hz,2H),1.70–1.44(m,7H),1.42–1.37(m,2H),1.21(d,J=6.3Hz,3H),0.97(d,J=8.8Hz,6H).

[0107] 13 C NMR(101MHz,CDCl 3 )δ147.69,136.93,129.37,127.09,116.97,113.30,49.35,39.88,37.55,35.03,32.83,28.74,25.28,20.68,19.93,19.61.

[0108] HRMS(EI)Calcd for C 19 H 29 N:[M+H] + 272.2378.Found:m / z 272.2387.

[0109] Example 10:

[0110]

[0111] Take a 10 mL Schlenk reaction tube, and sequentially weigh and add S1-6 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring reaction for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-6, 58.5 mg, with a yield of 79%.

[0112] (5S,8S,9S,10S,13S,14R,17S)-10,13-dimethyl-3-(phenylamino)hexadecahydro-1H-cyclopenta[a]phenanthren-17-ol(1-6)

[0113]

[0114] As a white solid;TLC:R f =0.45(silica gel,PE / EA,2:1).

[0115] 1 H NMR(400MHz,CDCl 3 )δ7.21–7.13(m,2H),6.66(t,J=7.3Hz,1H),6.60(d,J=8.0Hz,2H),3.69–3.59(m,2H),2.06(dtd,J=13.3,9.3,5.8Hz,1H),1.86–1.15(m,19H),1.10–0.92(m,2H),0.85(s,4H),0.74(s,4H).

[0116] 13 C NMR(101MHz,CDCl 3 )δ147.45,129.40,116.73,112.99,82.06,54.70,51.18,47.44,43.09,40.48,36.84,36.28,35.61,33.08,32.69,31.66,30.60,28.53,25.94,23.45,20.48,11.64,11.27.

[0117] HRMS(EI)Calcd for C25 H 37 NO: [M+H] + 368.2953. Found: m / z 368.2958.

[0118] Example 11:

[0119]

[0120] Take a 10 mL Schlenk reaction tube, and sequentially weigh and add S1-7 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring reaction for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-7, 69.9 mg, with a yield of 76%.

[0121] (5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-N-phenylhexadecahydro-1H-cyclopenta[a]phenanthren-3-amine (1-7)

[0122]

[0123] As a colorless solid; TLC: R f = 0.35 (silica gel, PE / EA, 20:1).

[0124] 1 H NMR (400 MHz, CDCl 3 ) δ 7.21–7.12 (m, 2H), 6.65 (t, J = 7.3 Hz, 1H), 6.60 (d, J = 8.0 Hz, 2H), 3.92 (s, 1H), 3.67 (m, J = 3.1 Hz, 1H), 1.98 (dt, J = 12.5, 3.4 Hz, 1H), 1.76–0.99 (m, 29H), 0.91 (d, J = 6.5 Hz, 3H), 0.87 (dd, J = 6.6, 1.9 Hz, 6H), 0.83 (s, 3H), 0.73 (td, J = 11.7, 4.0 Hz, 1H), 0.66 (s, 3H).

[0125] 13 C NMR(101MHz,CDCl 3 )δ147.48,129.39,116.68,112.98,56.67,56.38,54.58,47.48,42.70,40.43,40.14,39.63,36.18,35.94,35.58,33.06,32.73,32.12,28.71,28.37,28.13,25.93,24.28,23.97,22.97,22.70,20.91,18.79,12.20,11.63.

[0126] HRMS(EI)Calcd for C 33 H 53 N:[M+H] + 464.4256.Found:m / z 464.4248.

[0127] Example 12:

[0128]

[0129] Take a 10 mL Schlenk reaction tube, and successively weigh and add S1-8 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-8, 63.6 mg, with a yield of 74%.

[0130] (2S,5S,8R,9S,10S,13S,14S)-10,13-dimethyl-17-(1-(phenylamino)ethyl)hexadecahydro-1H-cyclopenta[a]phenanthren-2-yl acetate(1-8)

[0131]

[0132] As a white solid; TLC: R f =0.45(silica gel,PE / EA,5:1).

[0133] 1 H NMR(400MHz,CDCl 3 )δ7.20–7.11(m,2H),6.63(t,J=7.4Hz,1H),6.54(d,J=7.9Hz,2H),5.40–5.35(m,1H),4.60(tdd,J=10.7,6.7,4.0Hz,1H),3.42–3.33(m,2H),2.35–2.29(m,2H),2.13(dt,J=12.1,3.4Hz,1H),2.04(d,J=2.1Hz,3H),2.01–1.94(m,1H),1.85(ttd,J=11.4,8.5,7.0,4.2Hz,3H),1.70–1.07(m,17H),1.01(d,J=17.0Hz,4H),0.76(s,1H),0.68(s,2H).

[0134] 13 C NMR(101MHz,CDCl 3 )δ170.70,139.83,129.45,122.55,116.36,112.58,74.03,57.26,56.25,50.56,50.10,42.56,41.94,39.60,39.21,38.19,37.04,36.67,31.97,31.91,31.86,31.80,27.83,27.60,27.08,24.38,21.57,21.03,20.51,19.38,12.35.

[0135] HRMS(EI)Calcd for C 29 H 41 NO 2 :[M+H] + 436.3216.Found:m / z 436.3218.

[0136] Example 13:

[0137]

[0138] Take a 10 mL Schlenk reaction tube and successively weigh and add S1-9 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethylsilane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-9, 68.6 mg, with a yield of 73%.

[0139] N-((6-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)naphthalen-2-yl)methyl)aniline(1-9)

[0140]

[0141] As a white solid;TLC:R f =0.40(silica gel,PE / EA,20:1).

[0142] 1 H NMR(400MHz,CDCl 3 )δ7.98(d,J=1.8Hz,1H),7.91–7.81(m,3H),7.74(dd,J=8.5,1.8Hz,1H),7.60(d,J=2.4Hz,1H),7.52(ddd,J=10.6,8.4,2.0Hz,2H),7.25–7.15(m,2H),7.00(d,J=8.4Hz,1H),6.79–6.68(m,3H),4.51(s,2H),3.91(s,3H),2.20(d,J=2.9Hz,6H),2.12(s,3H),1.82(s,6H),1.27(s,1H).

[0143] 13 C NMR(101MHz,CDCl 3)δ158.66,148.11,138.97,136.56,133.21,132.36,129.41,128.64,128.21,126.19,126.12,125.98,125.85,125.68,124.94,117.87,113.18,112.16,55.28,48.74,40.70,37.28,37.24,29.22.

[0144] HRMS(EI)Calcd for C 34 H 35 NO:[M+H] + 474.2797.Found:m / z 474.2795.

[0145] Example 14:

[0146]

[0147] Take a 10 mL Schlenk reaction tube, and successively weigh and add S1-10 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe. After sealing, transfer it to an 80 °C oil bath and heat with stirring for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-10, 35.1 mg, with a yield of 65%.

[0148] (E)-N-(6,10-dimethylundeca-5,9-dien-2-yl)aniline(1-10)

[0149]

[0150] As a colorless solid; TLC: R f =0.50 (silica gel, PE / EA, 20:1).

[0151] 1 H NMR(400MHz,CDCl 3)δ 7.20–7.12 (m, 2H), 6.66 (tt, J = 7.3, 1.1 Hz, 1H), 6.61–6.56 (m, 2H), 3.44 (m, J = 6.3 Hz, 1H), 2.05 (m, J = 13.5, 5.3 Hz, 2H), 1.88 (t, J = 6.3 Hz, 2H), 1.70–1.44 (m, 7H), 1.42–1.37 (m, 2H), 1.21 (d, J = 6.3 Hz, 3H), 0.97 (d, J = 8.8 Hz, 6H).

[0152] 13 C NMR (101 MHz, CDCl 3 )δ 147.69, 136.93, 129.37, 127.09, 116.97, 113.30, 49.35, 39.88, 37.55, 35.03, 32.83, 28.74, 25.28, 20.68, 19.93, 19.61.

[0153] HRMS (EI) Calcd for C 19 H 29 N: [M + H] + 272.2378. Found: m / z 272.2371.

[0154] Example 15:

[0155]

[0156] Take a 10 mL Schlenk reaction tube, and successively weigh and add S1-11 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times, inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-11, 61.6 mg, with a yield of 88%.

[0157] 3,7-dimethyl-1-(5-(phenylamino)hexyl)-3,4,5,7-tetrahydro-1H-purine-2,6-dione (1-11)

[0158]

[0159] As a white solid; TLC: R f = 0.35 (silica gel, PE / EA, 5:1).

[0160] 1 H NMR (400 MHz, CDCl 3 ) δ 7.49 (s, 1H), 7.17–7.08 (m, 2H), 6.63 (tt, J = 7.3, 1.1 Hz, 1H), 6.56 (dt, J = 8.4, 1.5 Hz, 2H), 4.04–3.95 (m, 5H), 3.56 (s, 3H), 3.44 (p, J = 6.1 Hz, 1H), 1.79–1.57 (m, 3H), 1.54–1.39 (m, 3H), 1.16 (d, J = 6.3 Hz, 3H).

[0161] 13 C NMR (101 MHz, CDCl 3 ) δ 155.41, 151.60, 148.83, 147.67, 141.52, 129.34, 116.80, 113.13, 107.76, 48.47, 41.24, 36.82, 33.69, 29.80, 28.11, 23.61, 20.88.

[0162] HRMS (EI) Calcd for C 19 H 27 N 5 O 2 : [M + H] + 358.2243. Found: m / z 358.2245.

[0163] Example 16:

[0164]

[0165] Take a 10 mL Schlenk reaction tube, and successively weigh and add S1-12 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring reaction for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-12, 41.4 mg, with a yield of 69%.

[0166] N-(4-(6-methoxynaphthalen-2-yl)butan-2-yl)aniline (1-12)

[0167]

[0168] As a white solid; TLC: R f = 0.45 (silica gel, PE / EA, 10:1).

[0169] 1 H NMR (400 MHz, CDCl 3 ) δ 7.69–7.64 (m, 2H), 7.58–7.52 (m, 1H), 7.29 (dd, J = 8.4, 1.8 Hz, 1H), 7.19–7.08 (m, 4H), 6.68 (t, J = 7.3 Hz, 1H), 6.56 (d, J = 7.9 Hz, 2H), 3.92 (s, 3H), 3.52 (h, J = 6.3 Hz, 1H), 2.86 (t, J = 7.8 Hz, 2H), 2.05–1.79 (m, 2H), 1.24 (d, J = 6.3 Hz, 3H).

[0170] 13 C NMR (101 MHz, CDCl 3 ) δ 157.27, 151.41, 137.16, 133.08, 129.41, 129.18, 129.01, 127.92, 126.90, 126.42, 118.82, 117.19, 113.41, 105.70, 55.39, 48.09, 38.80, 32.48, 20.94.

[0171] HRMS (EI) Calcd for C 21 H 23 NO: [M + H] + 306.1858. Found: m / z 306.1866.

[0172] Example 17:

[0173]

[0174] Take a 10 mL Schlenk reaction tube and sequentially weigh and add S1-13 (0.2 mmol, 1.0 equiv.), aniline (0.3 mmol, 1.5 equiv.), Cat 1 (0.01 mmol, 5 mol%), phenyl dimethyl silane (0.3 mmol, 1.5 equiv.). Then, use a Schlenk inert gas protection device to displace nitrogen three times. Inject 1.0 mL of ultrapure water with a syringe, seal it, and transfer it to an 80 °C oil bath for heating and stirring reaction for 12 h. After the reaction is completed, detect the reaction solution by TLC, and then use silica gel column chromatography to separate and purify the reaction solution with a PE / EA mobile phase system to obtain the target product 1-13, 57.6 mg, with a yield of 64%.

[0175] (E)-N-(4-(octadec-9-en-1-yloxy)benzyl)aniline(1-13)

[0176]

[0177] As a colorless solid;TLC:R f =0.38(silica gel,PE / EA,20:1).

[0178] 1 H NMR(400 MHz,CDCl 3 )δ7.31–7.27(m,2H),7.22–7.15(m,2H),6.93–6.83(m,2H),6.73(td,J=7.3,1.2 Hz,1H),6.67–6.63(m,2H),5.53–5.28(m,1H),4.25(s,2H),3.95(t,J=6.6 Hz,3H),2.03(q,J=7.2,6.6 Hz,3H),1.84–1.75(m,2H),1.50–1.24(m,24H),0.94–0.86(m,3H).

[0179] 13 C NMR(101 MHz,CDCl 3)δ158.54,148.31,131.22,130.09,129.94,129.36,128.91,117.59,114.69,112.93,68.13,47.93,32.03,29.89,29.86,29.82,29.78,29.71,29.65,29.59,29.53,29.50,29.45,29.39,29.35,27.33,27.31,26.16,22.81,14.25.

[0180] HRMS(EI)Calcd for C 31 H 47 NO:[M+H] + 450.3736.Found:m / z 450.3743.

[0181] Comparative Example 1:

[0182]

[0183] Table 1

[0184]

[0185] General conditions for carrying out the comparative example: Benzaldehyde (0.2 mmol) and aniline (0.3 mmol) were used as template substrates for reductive amination, phenyl dimethylsilane was used as the reducing agent (0.3 mmol), 5% boron catalyst, in 1 mL H 2 O, under a nitrogen atmosphere, reacted at 80 °C for 12 hours. a NMR yield using nitromethane as an internal standard; b Isolated yield.

[0186] First, benzaldehyde and aniline were selected as the template substrates for reductive amination, and phenyl dimethyl silane was used as the reducing agent to attempt the reductive amination reaction in aqueous phase. The boron catalyst library constructed by the research group was screened. Since triphenyl borane is extremely unstable in water, the experimental results showed that catalyst Cat 1 had the best catalytic effect, and the reductive amination product 1-15 was obtained with a yield of 97%. Secondly, the yields of catalysts Cat 2, Cat 3, Cat 4 and Cat 5 were 27%, 85%, 56% and 79% respectively, and no product was formed without adding a catalyst (Table 1, entries 1-6). Subsequently, various silanes were screened as reducing agents. The experimental results showed that no reductive amination product was obtained when fatty alkyl silanes were used as reducing agents. Silanes containing phenyl structures could all achieve the reductive amination reaction to varying degrees in aqueous phase, but still phenyl dimethyl silane had the highest efficiency with a yield of 97%. Obviously, without silane participating in the catalytic process as a reducing agent, the reductive amination reaction could not proceed normally (Table 1, entries 7-16). The aprotic solvent toluene was used to replace water as the reaction medium, and the result showed that the reductive amination effect decreased slightly (Table 1, entry 17).

[0187] The present invention is not limited to the specific technical solutions described in the above embodiments. Any technical solutions formed by equivalent substitution are within the scope of protection required by the present invention.

Claims

1. Application of a triarylboron compound, characterized in that: 5 mol% of Cat 1 1.5 chemical equivalents of phenyldimethylsilane, in the aqueous phase, under an argon atmosphere, at 80 °C, react for 12 hours to achieve the reductive amination of aromatic aldehyde or aromatic ketone compounds to prepare a series of organic amine compounds:

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