A steroid-derived chiral monoboron Lewis acid catalyst, its synthesis method and application

Abstract

The present invention provides a steroid-derived chiral monoboron Lewis acid catalyst and a synthesis method and application thereof, and belongs to the technical field of chemical synthesis. The chiral monoboron Lewis acid catalyst of the present invention is a compound shown in Formula I, or a salt thereof. The catalyst of the present invention has high catalytic efficiency, high product enantioselectivity, and excellent catalytic effect. At the same time, in the synthesis method of the present invention, the raw materials used are cheap and easy to obtain, the amount of borane used is relatively small, the synthesis steps are short, and the cost is low. In addition, the synthesis method of the present invention has the potential for industrial scale-up production. Therefore, the present invention has good application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a steroid-derived chiral monoboron Lewis acid catalyst and a synthesis method and application thereof. Background Art

[0002] In the past two decades, boron-based catalysis has gradually attracted attention in the field of organic synthesis. Lewis acid catalysts with halogenated triarylborane as the main group are an effective way to increase the rate of chemical conversion. After years of research and improvement, their performance is now comparable to or even better than standard catalysts. Professor Armando Carlone and others from the University of L'Aquila in Italy published an article in Catalysts, which reviewed the synthesis methods of boranes and the research progress of boron-based Lewis acid catalysis, especially tri(pentafluorophenyl)borane (B(C6F5)3) and other halogenated triarylboranes, highlighting the advantages of boron Lewis acids as catalysts in chemical conversion and improving reaction efficiency. Therefore, the synthesis of efficient boron-based Lewis catalysts has become a hot topic in current research.

[0003] Among the several chiral boron catalysts reported so far, many boron catalysts have many problems such as difficulty in synthesis, separation and purification, difficulty in structural modification, low catalytic efficiency, and low product enantioselectivity. For example, Klankermaymer.J.etal, Chem.Commun.2008, 2130. Therefore, providing a chiral boron-based Lewis acid catalyst with high catalytic efficiency and a method for efficiently synthesizing a chiral boron-based Lewis acid catalyst is helpful for practical application. The patent with announcement number CN109046447B provides a method for synthesizing a chiral boron catalyst, which synthesizes a BAr F 2 chiral bicyclic biboron catalyst, used in the asymmetric hydrogenation of aromatic ketone imines. The five-membered bicyclic chiral biboron catalyst in this patent is described by the author in his article (Synthesis 2022, 54, 1527-1536 ) The specific synthetic route reported is as follows:

[0004] a)Preparation of the fused bicyclic dienes

[0005]

[0006] b)Generation of the fused bicyclic bisborane catalysts byhydroboration

[0007]

[0008] The synthesis route is long, has many steps, requires splitting, and is costly, which greatly limits the application of this type of catalyst. According to the reaction principle, a single boron catalyst can also have a similar catalytic effect, and the precursor of the synthetic boron catalyst, Piers borane, is expensive. A single boron catalyst can reduce the amount of the corresponding borane used, which can reduce its cost and greatly improve the practicality of this type of catalyst.

[0009] Therefore, developing cheap, readily available, efficient and novel chiral monoboron catalysts and expanding their applications in the synthesis of chiral drugs has high scientific value and practical significance. Summary of the invention

[0010] The invention aims to provide a steroid-derived chiral monoboron Lewis acid catalyst and a synthesis method and application thereof.

[0011] The present invention provides a compound represented by formula I, or a salt thereof:

[0012]

[0013] in,

[0014] R is selected from C1-C6 alkyl, benzyl, phenyl;

[0015] R1 is a substituent on the benzene ring, n1 is the number of R1, n1 is an integer from 0 to 5, and each R1 is independently selected from substituted or unsubstituted C1 to C6 alkyl, halogen, and phenyl; the substituent of the alkyl is halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, and trifluoromethoxy;

[0016] R2 and R3 are substituents on the benzene ring, n2 is the number of R2, n3 is the number of R3, n2 and n3 are integers of 0 to 5, R2 and R3 are selected from halogen or trifluoromethyl;

[0017] Ring A is selected from 6-membered cycloalkyl or phenyl;

[0018] When ring A is selected from a 6-membered cycloalkyl group, R4 is selected from a C1-C6 alkyl group, and R5 is selected from hydrogen;

[0019] When the A ring is selected from phenyl, R4 is selected from hydrogen and R5 is selected from hydrogen.

[0020] Furthermore, the compound is represented by Formula II:

[0021]

[0022] in,

[0023] R is selected from C1-C6 alkyl, benzyl, phenyl;

[0024] R1 is a substituent on the benzene ring, n1 is the number of R1, n1 is an integer from 0 to 5, and each R1 is independently selected from substituted or unsubstituted C1 to C6 alkyl, halogen, and phenyl; the substituent of the alkyl is halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, and trifluoromethoxy;

[0025] R2 and R3 are substituents on the benzene ring respectively, n2 is the number of R2, n3 is the number of R3, n2 and n3 are integers of 0 to 5 respectively, and R2 and R3 are selected from halogen or trifluoromethyl.

[0026] Further,

[0027] R is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, benzyl, phenyl;

[0028] R1 is a substituent on the benzene ring, n1 is the number of R1, n1 is 0, 1, 2, 3, 4 or 5, and each R1 is independently selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, fluorine, chlorine, bromine, iodine, and phenyl;

[0029] R2 and R3 are substituents on the benzene ring, n2 is the number of R2, n3 is the number of R3, n2 and n3 are 0, 1, 2, 3, 4 or 5, R2 and R3 are selected from fluorine or trifluoromethyl;

[0030] Preferably, R2 and R3 have the same number and position of substitutions on the benzene ring;

[0031] More preferably, the Selected from

[0032] and / or, Selected from

[0033] Furthermore, the compound is represented by formula III:

[0034]

[0035] in,

[0036] R1 is a substituent on the benzene ring, n1 is the number of R1, n1 is 0, 1, 2, 3, 4 or 5, and each R1 is independently selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, fluorine, chlorine, bromine, iodine, and phenyl;

[0037] R2 and R3 are substituents on the benzene ring, n2 is the number of R2, n3 is the number of R3, n2 and n3 are 0, 1, 2, 3, 4 or 5, R2 and R3 are selected from fluorine or trifluoromethyl;

[0038] Preferably, R2 and R3 have the same number and position of substitutions on the benzene ring;

[0039] More preferably, the Selected from

[0040] and / or, Selected from

[0041] Furthermore, the compound is represented by formula IV:

[0042]

[0043] in,

[0044] R1 is a substituent on the benzene ring, n1 is the number of R1, n1 is 0, 1, 2, 3, 4 or 5, and each R1 is independently selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, trifluoromethyl, fluorine, chlorine, bromine, iodine, and phenyl;

[0045] Preferably, the Selected from

[0046] Furthermore, the compound is one of the following structures:

[0047]

[0048] The present invention also provides a method for preparing the aforementioned compound, which comprises the following steps:

[0049]

[0050] The olefin ligand L1 and the boron hydride compound are reacted in a solvent to obtain;

[0051] Wherein, R, R1, R2, R3, R4, R5, n1, n2, n3 are as described above;

[0052] Preferably,

[0053] The molar ratio of the olefin ligand L1 to the boron hydride compound is 1:1 to 2:1;

[0054] And / or, the solvent is one or more of toluene, dichloromethane, and n-hexane;

[0055] And / or, the reaction temperature is 25 to 80°C;

[0056] And / or, the reaction time is 5 to 60 minutes.

[0057] Furthermore, the preparation method of L1 comprises the following steps:

[0058]

[0059] (1) Compound a reacts with an iodinated alkyl group IR in a solvent to undergo an alkyl protection reaction under alkaline conditions to obtain compound b;

[0060] (2) Compound b, mesitylpyridine and trifluoromethanesulfonic anhydride are subjected to an esterification reaction in a solvent to obtain compound c;

[0061] (3) In a solvent, compound c, palladium catalyst, tricyclohexylphosphine, base and After coupling reaction, olefin ligand L1 is obtained;

[0062] Wherein, R, R1, R4, R5, and n1 are as described above;

[0063] Preferably,

[0064] In step (1), the molar ratio of compound a, iodinated alkyl IR and base is 1:2.4:2.4 to 1:5:5;

[0065] And / or, in step (1), the reaction temperature is 20 to 30°C;

[0066] And / or, in step (2), the molar ratio of compound b, mesitylpyridine and trifluoromethanesulfonic anhydride is 1:2:2 to 1:5:5;

[0067] And / or, in step (2), the reaction temperature is 20 to 30°C;

[0068] And / or, in step (3), the compound c, palladium catalyst, tricyclohexylphosphine, base and The molar ratio is 1:0.01:0.5:2.5:1.5 to 1:0.1:0.5:2.5:1.5;

[0069] And / or, in step (3), the reaction temperature is 80-100°C;

[0070] More preferably,

[0071] In step (1), the solvent is N,N-dimethylformamide;

[0072] And / or, in step (1), the base is potassium hydroxide;

[0073] And / or, in step (2), the solvent is dichloromethane;

[0074] And / or, in step (3), the solvent is N,N-dimethylformamide;

[0075] And / or, in step (3), the palladium catalyst is palladium acetate;

[0076] And / or, in step (3), the base is a combination of one or more of sodium carbonate, potassium carbonate, cesium fluoride, and sodium hydroxide;

[0077] More preferably, in step (3), the base is cesium fluoride and sodium carbonate; the molar ratio of cesium fluoride to sodium carbonate is 1:1.5.

[0078] The present invention also provides the use of the aforementioned compound or its salt as a chiral boron Lewis acid catalyst;

[0079] Preferably, the catalyst is a catalyst used in the hydrosilylation reaction of imines;

[0080] More preferably, the catalyst is a catalyst used in the asymmetric hydrosilylation reaction of imine.

[0081] The present invention also provides a hydrosilylation reaction of imine, wherein the reaction uses the aforementioned compound or a salt thereof as a catalyst;

[0082] Preferably, the hydrosilylation reaction of imine is an asymmetric hydrosilylation reaction of imine.

[0083] The invention uses cheap commercially available estrone as a starting material, obtains a catalyst precursor through alkyl protection, esterification, and coupling reaction, and then reacts with a boron hydride compound in situ to obtain a corresponding steroid-derived chiral monoboron catalyst.

[0084] Compared with the prior art, the present invention has the following beneficial effects:

[0085] (1) The chiral steroid compound used in the present invention is cheap and readily available;

[0086] (2) The chiral monoboron Lewis acid catalyst synthesized by the present invention has short synthesis steps and low cost;

[0087] (3) The chiral monoboron Lewis acid catalyst synthesized by the present invention is easy to modify in structure and does not have diastereoselectivity;

[0088] (4) The chiral boron Lewis acid catalyst synthesized by the present invention has high activity and enantioselectivity in the asymmetric hydrosilylation reaction of imines and the desymmetrization reaction of aryl pyrroles to construct axial chiral compounds;

[0089] (5) The present invention has been tested on a gram scale and has the potential for industrial expansion.

[0090] In summary, the present invention provides a new chiral monoboron Lewis acid catalyst and a synthesis method thereof. The catalyst of the present invention has high catalytic efficiency, high product enantioselectivity, and excellent catalytic effect. At the same time, in the synthesis method of the present invention, the raw materials used are cheap and easy to obtain, the amount of borane used is relatively small, the synthesis steps are short, and the cost is low. In addition, the synthesis method of the present invention has the potential for industrial scale-up production. Therefore, the present invention has good application prospects.

[0091] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0092] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0093] Figure 1 This is the hydrogen spectrum of the chiral monoboron catalyst Cat1-A.

[0094] Figure 2 This is the carbon spectrum of chiral monoboron catalyst Cat1-A.

[0095] Figure 3 This is the fluorine spectrum of the chiral monoboron catalyst Cat1-A.

[0096] Figure 4 This is the hydrogen spectrum of the chiral monoboron catalyst Cat1-B.

[0097] Figure 5 This is the carbon spectrum of the chiral monoboron catalyst Cat1-B.

[0098] Figure 6 This is the fluorine spectrum of the chiral monoboron catalyst Cat1-B.

[0099] Figure 7 This is the hydrogen spectrum of the chiral monoboron catalyst Cat1-C.

[0100] Figure 8 This is the carbon spectrum of the chiral monoboron catalyst Cat1-C.

[0101] Fig. 9 This is the fluorine spectrum of the chiral monoboron catalyst Cat1-C. DETAILED DESCRIPTION

[0102] Unless otherwise specified, the raw materials and equipment used in the present invention are all known products obtained by purchasing commercially available products.

[0103] Example 1: Synthesis of the chiral monoboron Lewis acid catalyst of the present invention

[0104] The synthetic route is:

[0105]

[0106] The specific preparation method is:

[0107] Take a 300mL flask, dissolve estrone (5.41g, 20.0mmol) in N,N-dimethylformamide (40mL), add potassium hydroxide (1.35g, 24mmol), place in a 0℃ ice bath, then dissolve iodomethane (1.5mL, 24mmol) in N,N-dimethylformamide (40mL), and add dropwise at 0℃ (process about 5 minutes). The reaction was stirred at room temperature for 30 minutes, and then potassium hydroxide (1.35g, 24.0mmol) was added, placed in a 0℃ ice bath, and iodomethane (1.5mL, 24.0mmol) was dissolved in N,N-dimethylformamide (40mL), and added dropwise (process about 5 minutes). After the addition was complete, the temperature was raised to room temperature and reacted for more than 3 hours. Add water to quench, precipitate the material, and obtain product 2, which is 5.35g of white solid, with a yield of 98%. NMR data of product 2 1 HNMR(500MHz, CDCl3)δ:7.21(d,J=8.5Hz,1H),6.72(dd,J=8.5Hz,2.5Hz,1H),6.65(d,J=3.0Hz,1H),3.78(s,3H),2.96–2.86(m,2H),2.54–2.47(m,1H ),2.42–2.38(m,1H),2.29–2.23(m,1H),2.18–2.09(m,1H),2.08–1.99(m, 2H),1.97–1.91(m,1H),1.67–1.62(m,1H),1.60–1.39(m,5H),0.91(s,3H). 13 C{ 1H}NMR(126MHz, CDCl3)δ:157.57,137.73,132.01,126.32,113.86,111.55,55.1 9,50.39,47.99,43.95,38.36,35.85,31.56,29.65,26.53,25.91,21.57,13.83.

[0108] Take a 300mL flask, under nitrogen protection, dissolve product 2 (2.84g, 10.0mmol) in 35mL dichloromethane. Add isotrimethylpyridine (2.8mL, 20.0mmol) in an ice bath at 0℃, dissolve trifluoromethanesulfonic anhydride (3.4mL, 21.0mmol) in 15mL dichloromethane, add dropwise, and after the addition is complete, heat the reaction to room temperature for more than 6 hours. After the reaction is completed, add saturated sodium bicarbonate aqueous solution, extract with water and dichloromethane, add anhydrous sodium sulfate to the organic layer and dry it, filter with silica gel, wash with ethyl acetate, spin dry, column chromatography (petroleum ether: ethyl acetate = 20:1), and obtain product 3 as a colorless oily liquid 3.47g, with a yield of 83%. NMR data of product 3 1 HNMR(500MHz, CDCl3)δ:7.20(d,J=8.5Hz,1H),6.75(dd,J=8.5Hz,3.0Hz,1H), 6.67(d,J=2.5Hz,1H),5.65(dd,J=3.5Hz,2.0Hz,1H),3.80(s,3H),2.98–2.87 (m,2H),2.44–2.39(m,1H),2.38–2.30(m,2H),2.16–2.09(m,1H),1.97–1.89( m,2H),1.86–1.79(m,1H),1.72–1.55(m,3H),1.51–1.41(m,1H),1.03(s,3H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ:159.30,157.60,137.62,132.09,125.92,118.59(q,J C-F =321.0),114.45,113.89,111.47,55.14,53.53,45.06,44.17,36.68,32.71,29.41,28.33,26.72,25.80,15.29. 19 F{ 1 H}NMR (471MHz,CDCl3)δ:-73.56.

[0109] Palladium acetate (188.2 mg, 0.84 mmol) and tricyclohexylphosphine (1.32 g, 4.2 mmol) were weighed into a 100 mL three-necked flask, nitrogen was replaced 3 times, and deoxygenated N,N-dimethylformamide (10 mL) was added. The oily product 3 (3.50 g, 8.4 mmol) was dissolved in N,N-dimethylformamide (10 mL) and added to the reaction system. Phenylboric acid (12.6 mmol) was dissolved in N,N-dimethylformamide (10 mL), added to the reaction system, and then sodium carbonate (1.34 g, 12.7 mmol), cesium fluoride (1.28 g, 8.4 mmol) and 5 mL of water were added under nitrogen protection. The reaction was heated to 90 ° C and refluxed for 4 hours. The metal and inorganic salts were filtered out with silica gel, washed with ethyl acetate for several times, and the filtrate was extracted with ethyl acetate, water, and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and spin-dried by column chromatography (petroleum ether: ethyl acetate = 50:1) to obtain olefin ligand L1-A as a white solid of 2.45 g, with a yield of 85%. The NMR data of product L1-A 1 HNMR(500MHz, CDCl3)δ:7.43–7.39(m,2H),7.34–7.29(m,2H),7.26–7.20(m,2H),6.72 (dd,J=8.5Hz,2.5Hz,1H),6.66(d,J=2.5Hz,1H),5.95(dd,J=3.5Hz,2.0Hz,1H),3.79( s,3H),2.96–2.90(m,2H),2.41–2.29(m,3H),2.23–2.20(m,1H),2.16–2.09(m,1H),2. 01–1.95(m,1H),1.84–1.78(m,1H),1.73–1.63(m,3H),1.54–1.43(m,1H),1.07(s,3H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ:157.45,154.96,138.01,137.30,132.91,128.11,127.07,126.74,126.69,126 .04,113.84,111.40,56.83,55.20,47.58,44.11,37.36,35.50,31.31,29.76,27.74,26.62,16.73.DEPT 135NMR(126MHz, CDCl3)δ:128.11,127.07,126.74,126.69,126.04,113.84,111 .40,56.83,55.21,44.11,37.36,35.50,31.31,29.76,27.74,26.62,16.73.

[0110] Under argon or nitrogen protection, take a 25mL reaction tube, weigh the olefin ligand L1-A (1mmol), and dissolve it in 1mL toluene, dissolve di(pentafluorophenyl)borane (345.9mg, 1mmol) in 1mL toluene and add it, stir at 35°C for 1 hour, and dry under argon or nitrogen protection to obtain an equivalent amount of chiral monoboron catalyst Cat1-A as a white solid with a yield of 100%. It can be used directly without further purification. The NMR data of the product Cat1-A 1 HNMR(500MHz,d8-Toluene)δ:7.07(d,J=9.0Hz,1H),7.03–6.99(m,2H),6.96–6.92(m,3 H),6.03(dd,J=9.0Hz,3.0Hz,1H),6.61(d,J=3.0Hz,1H),3.43(s,3H),3.24–3.18(m,1H) ,2.82(d,J=12.0Hz,1H),2.79–2.64(m,2H),2.10–1.99(m,3H),1.84(q,J=12.5Hz,1H),1 .80–1.74(m,1H),1.46–1.41(m,1H),1.36–1.21(m,4H),1.16–1.09(m,1H),0.53(s,3H). 13 C{ 1 H}NMR(126MHz,d8-Toluene),δ:158.33,146.98–146.78(m),145.03–144.82(m),144.04–14 3.74(m),142.00–141.70(m),139.24,138.75–138.46(m),137.69–137.23(m),137.57,136.7 4–136.45(m),132.39,129.17,128.24–127.86(m),128.01,126.91,126.51,114.21,111.90, 60.32,55.45,54.63,45.84,44.15,42.91,39.54,37.70,30.02,28.21,27.75,26.61,12.94. 19 F{ 1H}NMR(471MHz,d8-Toluene),δ:-130.47,-130.49,-130.52,-130.54,-149.2 2,-149.26,-149.30,-161.13,-161.15,-161.18,-161.19,-161.22,-161.24.

[0111] Example 2: Synthesis of the chiral monoboron Lewis acid catalyst of the present invention

[0112] The synthetic route is:

[0113]

[0114] The specific preparation method is:

[0115] Take a 300mL flask, dissolve estrone (5.41g, 20.0mmol) in N,N-dimethylformamide (40mL), add potassium hydroxide (1.35g, 24mmol), place in an ice bath at 0℃, then dissolve iodomethane (1.5mL, 24mmol) in N,N-dimethylformamide (40mL), add dropwise at 0℃ (process about 5 minutes). The reaction is stirred at room temperature for 30 minutes, then potassium hydroxide (1.35g, 24.0mmol) is added, placed in an ice bath at 0℃, iodomethane (1.5mL, 24.0mmol) is dissolved in N,N-dimethylformamide (40mL), and added dropwise (process about 5 minutes), and after the addition is complete, warm to room temperature and react for more than 3 hours. Add ice water to quench, precipitate the material, and obtain product 2, which is 5.35g of white solid, with a yield of 98%.

[0116] Take a 300mL flask, under nitrogen protection, dissolve the product 2 (2.84g, 10.0mmol) in 35mL dichloromethane. Add mesitylpyridine (2.8mL, 20.0mmol) in an ice bath at 0℃, dissolve trifluoromethanesulfonic anhydride (3.4mL, 21.0mmol) in 15mL dichloromethane, add dropwise, and after the addition is complete, warm the reaction temperature to room temperature for more than 6 hours. After the reaction is complete, add saturated sodium bicarbonate aqueous solution, extract with water and dichloromethane, add anhydrous sodium sulfate to the organic layer, dry it, filter it with silica gel, wash it with ethyl acetate, spin dry it, and column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain product 3 as a colorless oily liquid 3.47g, with a yield of 83%.

[0117] Palladium acetate (188.2 mg, 0.84 mmol) and tricyclohexylphosphine (1.32 g, 4.2 mmol) were weighed into a 100 mL three-necked flask, nitrogen was replaced 3 times, and deoxygenated N,N-dimethylformamide (10 mL) was added. The oily product 3 (3.50 g, 8.4 mmol) was dissolved in N,N-dimethylformamide (10 mL) and added to the reaction system. 3,5-di(tert-butyl)phenylboronic acid (12.6 mmol) was dissolved in N,N-dimethylformamide (10 mL) and added to the reaction system, and then sodium carbonate (1.34 g, 12.7 mmol), cesium fluoride (1.28 g, 8.4 mmol) and 5 mL of water were added under nitrogen protection. The reaction was heated to 90°C and refluxed for 4 hours. The metal and inorganic salts were filtered out with silica gel, washed with ethyl acetate for several times, and the filtrate was extracted with ethyl acetate, water, and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and spin-dried by column chromatography (petroleum ether: ethyl acetate = 50:1) to obtain olefin ligand L1-B as a white solid of 3.10 g, with a yield of 81%. The NMR data of product L1-B 1 HNMR(500MHz, CDCl3)δ:7.33(t,J=1.5Hz,1H),7.27(d,J=2.0Hz,1H),7.22(d,J=8.0Hz,1H),6.73 (dd,J=8.5Hz,3.0Hz,1H),6.66(d,J=3.0Hz,1H),5.95(dd,J=3.5Hz,2.0Hz,1H),3.79(s,3H),2.9 6–2.87(m,2H),2.42–2.37(m,1H),2.35–2.29(m,2H),2.24–2.20(m,1H),2.17–2.10(m,1H),2.02 –1.96(m,1H),1.85–1.79(m,1H),1.75–1.65(m,3H),1.54–1.45(m,1H),1.35(s,9H),1.09(s,3H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ:157.46,155.78,150.25,138.05,136.28,133.00,126.42,126.04,120.95,120.88,11 3.87,111.41,56.85,55.21,47.56,44.15,37.39,35.69,34.83,31.52,31.31,29.78,27.76,26.75,16.90.DEPT 135NMR(126MHz, CDCl3)δ:126.42,126.04,120.95,120.88,113.87,111.41,56 .85,55.21,44.15,37.39,35.69,31.51,31.31,29.78,27.76,26.75,16.90.

[0118] Under argon or nitrogen protection, take a 25mL reaction tube, weigh the olefin ligand L1-B (1mmol), and dissolve it in 1mL toluene, dissolve di(pentafluorophenyl)borane (345.9mg, 1mmol) in 1mL toluene and add it, stir at 35°C for 1 hour, and dry under argon or nitrogen protection to obtain an equivalent amount of chiral monoboron catalyst Cat1-B as a white solid with a yield of 100%. It can be used directly without further purification. The NMR data of the product Cat1-B 1 HNMR(500MHz,d8-Toluene)δ:7.28(t,J=1.5Hz,1H),7.08(d,J=6.5Hz,1H),6.96(s,2H),6. 93(dd,J=8.5Hz,3.0Hz,1H),6.61(d,J=2.5Hz,1H),3.43(s,3H),3.29–3.23(m,1H),2.96(d ,J=12.5Hz,1H),2.80–2.65(m,2H),2.11–2.02(m,3H),1.89(q,J=12.0Hz,1H),1.81–1.75( m,1H),1.53–1.49(m,1H),1.44–1.35(m,2H),1.31(s,18H),1.28–1.19(m,2H),0.63(s,3H). 13 C{ 1H}NMR(126MHz,d8-Toluene),δ:158.32,150.37,146.62–146.42(m),144.68–144.48(m),143.80– 143.57(m),141.77–141.47(m),138.64–138.38(m),138.06,137.69–137.24(m),137.61,136.63–1 36.37(m),132.46,129.17,128.50–127.53(m),126.51,122.90,120.86,114.26,111.93,60.47,5 5.43,54.63,45.59,44.25,44.05,39.60,37.65,34.79,31.49,30.10,28.46,28.28,26.70,12.97. 19 F{ 1 H}NMR(471MHz,d8-Toluene),δ:-130.80,-130.82,-130.86,-130.88,-149.4 8,-149.52,-149.57,-160.98,-161.00,-161.03,-161.05,-161.08,-161.09.

[0119] Example 3: Synthesis of the chiral monoboron Lewis acid catalyst of the present invention

[0120] The synthetic route is:

[0121]

[0122] The specific preparation method is:

[0123] Take a 300mL flask, dissolve estrone (5.41g, 20.0mmol) in N, N-dimethylformamide (40mL), add potassium hydroxide (1.35g, 24mmol), place in a 0℃ ice bath, then dissolve iodomethane (1.5mL, 24mmol) in N, N-dimethylformamide (40mL), add dropwise at 0℃ (process about 5 minutes). The reaction is stirred at room temperature for 30 minutes, then potassium hydroxide (1.35g, 24.0mmol) is added, placed in a 0℃ ice bath, iodomethane (1.5mL, 24.0mmol) is dissolved in N, N-dimethylformamide (40mL), and added dropwise (process about 5 minutes), and after the addition is complete, warm to room temperature and react for more than 3 hours. Add water to quench, precipitate the material, and obtain product 2, which is 5.35g of white solid, with a yield of 98%.

[0124] Take a 300mL flask, under nitrogen protection, dissolve the product 2 (2.84g, 10.0mmol) in 35mL dichloromethane. Add mesitylpyridine (2.8mL, 20.0mmol) in an ice bath at 0℃, dissolve trifluoromethanesulfonic anhydride (3.4mL, 21.0mmol) in 15mL dichloromethane, add dropwise, and after the addition is complete, warm the reaction temperature to room temperature for more than 6 hours. After the reaction is complete, add saturated sodium bicarbonate aqueous solution, extract with water and dichloromethane, add anhydrous sodium sulfate to the organic layer, dry it, filter it with silica gel, wash it with ethyl acetate, spin dry it, and column chromatography (petroleum ether: ethyl acetate = 20:1) to obtain product 3 as a colorless oily liquid 3.47g, with a yield of 83%.

[0125] Palladium acetate (188.2 mg, 0.84 mmol) and tricyclohexylphosphine (1.32 g, 4.2 mmol) were weighed into a 100 mL three-necked flask, nitrogen was replaced 3 times, and deoxygenated N,N-dimethylformamide (10 mL) was added. The oily product 3 (3.50 g, 8.4 mmol) was dissolved in N,N-dimethylformamide (10 mL) and added to the reaction system. 3,5-bis(trifluoromethyl)phenylboronic acid (12.6 mmol) was dissolved in N,N-dimethylformamide (10 mL) and added to the reaction system, and then sodium carbonate (1.34 g, 12.7 mmol), cesium fluoride (1.28 g, 8.4 mmol) and 5 mL of water were added under nitrogen protection. The reaction was heated to 90°C and refluxed for 4 hours. The metal and inorganic salts were filtered out with silica gel, washed with ethyl acetate for several times, and the filtrate was extracted with ethyl acetate, water, and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and spin-dried by column chromatography (petroleum ether: ethyl acetate = 50:1) to obtain olefin ligand L1-C as a white solid of 3.45 g, with a yield of 85%. The NMR data of product L1-C 1 HNMR(500MHz, CDCl3)δ:7.82(s,2H),7.75(s,1H),7.21(d,J=8.5Hz,1H),6.74(dd,J =8.5Hz,3.0Hz,1H),6.67(d,J=3.0Hz,1H),6.74(dd,J=3.5Hz,1.5Hz,1H),3.78(s,3H ),3.01–2.88(m,2H),2.45–2.40(m,2H),2.37–2.30(m,2H),2.22–2.14(m,2H),2.01 –1.96(m,1H),1.88–1.82(m,1H),1.75–1.63(m,3H),1.56–1.46(m,1H),1.09(s,3H). 13 C{ 1H}NMR (126MHz, CDCl3) δ: 157.58, 152.59, 139.30, 137.88, 132.48, 131.45 (q, J=33.1Hz), 126.49, 126.47, 126.01, 123.45 (q, J= 273.5Hz), 120.31 (t, J = 3.8Hz), 113.93, 111.48, 56.82, 55.20, 47.79, 44.01, 37.26, 35.26, 31.54, 29.67, 27.67, 26.49, 16.81. 19 F{ 1 H}NMR (471MHz,CDCl3)δ:-62.90.

[0126] Under argon or nitrogen protection, take a 25mL reaction tube, weigh the olefin ligand L1-C (1mmol), and dissolve it in 1mL toluene, dissolve di(pentafluorophenyl)borane (345.9mg, 1mmol) in 1mL toluene, add it, stir at 35°C for 1 hour, and dry it under argon protection to obtain an equivalent amount of chiral monoboron catalyst Cat1-C as a white solid with a yield of 100%. It can be used directly without further purification. The NMR data of the product Cat1-C 1 HNMR(500MHz,d8-Toluene)δ:7.68(s,1H),7.52(s,2H),7.08(d,J=8.5Hz,1H),6.72( dd,J=8.5Hz,3.0Hz,1H),6.62(d,J=2.5Hz,1H),3.44(s,3H),3.15–3.08(m,1H),2.78 (d,J=12.0Hz,1H),2.76–2.64(m,2H),2.03–1.94(m,3H),1.79(q,J=12.5Hz,1H),1.7 5–1.71(m,1H),1.30–1.19(m,3H),1.18–1.11(m,2H),0.88–0.82(m,1H),0.38(s,3H). 13 C{ 1H}NMR(126MHz,d8-Toluene),δ:158.46,146.98–146.73(m),145.04–144.81(m),144.39–144.08(m),142.87 ,142.31–142.03(m),138.82–138.54(m),137.69–137.24(m),136.81–136.53(m),131.93,131.79(q,J=33.4 Hz),129.17,128.48–127.46(m),126.42,123.88(q,J=273.0Hz),120.79–120.67(m),114.34,113.80(t,J=2 6.3Hz),112.00,60.28,55.43,54.65,46.13,43.97,42.45,39.42,36.92,29.92,28.10,27.45,26.38,12.46. 19 F{ 1 H}NMR(471MHz,d8-Toluene),δ:-62.94,-130.46,-130.48,-130.52,-130.53,-14 7.58,-147.62,-147.66,-160.38,-160.40,-160.43,-160.45,-160.48,-160.49.

[0127] Example 4: Application of the chiral monoboron Lewis acid catalyst of the present invention in the asymmetric hydrosilylation of imines

[0128]

[0129] Under nitrogen atmosphere, take a 300mL flask, dissolve di(pentafluorophenyl)borane (0.035g, 1mol%, 0.1mmol) and olefin ligand L1-B (0.046g, 1mol%, 0.1mmol) in 100mL toluene, and stir at room temperature for 1 hour. Then dissolve the p-methoxyphenyl protected ketimine (1a, 2.55g, 10mmol) in 95mL toluene and add it to the reaction system, and place it at -40°C for activation for 1 hour. Dissolve diphenylsilane (Ph2SiH2, 1.84g, 12mmol) in 5mL toluene and add it dropwise to the reaction system. After adding, react at -40°C for 2 days. After the reaction is complete, remove the solvent under reduced pressure, column chromatography, and obtain product 2a, which is 2.57g of white solid, with a yield greater than 99%. After high performance liquid chromatography and ODH column analysis, the enantioselectivity of product 2a is 98%ee. NMR data of product 2a 1HNMR(500MHz, CDCl3)δ:7.31–7.27(m,2H),6.88–6.85(m,2H),6.73–6.69(m,2H),6.51 –6.47(m,2H),4.38(q,J=6.5Hz,1H),3.79(s,3H),3.71(s,3H),1.49(d,J=7.0Hz,3H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ:158.41,151.87,141.54,137.43,126.90,114.71,114.61,113.93,55.70,55.20,53.65,25.05.

[0130] Comparative Example 1: Catalytic Effects of Other Boron Catalysts

[0131]

[0132] As reported in the literature (Org. Biomol. Chem., 2015, 13, 1013–1016), the axial chiral diene derived from binaphthyl reacts with di(pentafluorophenyl)borane to form a biboron catalyst in situ to catalyze the hydrosilylation reaction of imine 1a (0.5 mmol, 0.1275 g) with silane (PhMe2SiH, 0.55 mmol). Under the optimal conditions, only 2a with an enantioselectivity of 65% ee was obtained, and the reaction was only conducted on a small amount of 0.5 mmol.

[0133] It can be seen that in the hydrosilylation reaction of imines, compared with the existing biboron-based catalysts, the chiral monoboron Lewis acid catalyst prepared by the present invention has excellent catalytic effect, high catalytic efficiency, and high product enantioselectivity.

[0134] In summary, the present invention provides a new chiral monoboron Lewis acid catalyst and a synthesis method thereof. The catalyst of the present invention has high catalytic efficiency, high product enantioselectivity, and excellent catalytic effect. At the same time, in the synthesis method of the present invention, the raw materials used are cheap and easy to obtain, the amount of borane used is relatively small, the synthesis steps are short, and the cost is low. In addition, the synthesis method of the present invention has the potential for industrial scale-up production. Therefore, the present invention has good application prospects.

Claims

1. A compound or a salt thereof, characterized in that: The compound is one of the following structures: 。 2. The method for preparing the compound or its salt according to claim 1, characterized in that: It includes the following steps: or or ; The olefin ligand and di(pentafluorophenyl)borane are reacted in a solvent to obtain the compound; the olefin ligand is any one of the olefin ligand L1-A, the olefin ligand L1-B and the olefin ligand L1-C.

3. The preparation method according to claim 2, characterized in that: The molar ratio of the olefin ligand to di(pentafluorophenyl)borane is 1:1 to 2:1; And / or, the solvent is one or more of toluene, dichloromethane, and n-hexane; And / or, the reaction temperature is 25-80°C; And / or, the reaction time is 5 to 60 minutes.

4. The preparation method according to claim 2 or 3, characterized in that: The preparation method of the olefin ligand comprises the following steps: or or (1) N , N - In dimethylformamide solvent, compound 1 undergoes alkyl protection reaction with methyl iodide under alkaline conditions of potassium hydroxide to obtain compound 2; (2) Compound 2, mesitylpyridine and trifluoromethanesulfonic anhydride are subjected to esterification reaction in dichloromethane solvent to obtain compound 3; (3) Perform one of the following operations: a. N , N -In dimethylformamide solvent, compound 3, palladium acetate, tricyclohexylphosphine, sodium carbonate, cesium fluoride and phenylboronic acid undergo coupling reaction to obtain olefin ligand L1-A; or, b. in N , N -In dimethylformamide solvent, compound 3, palladium acetate, tricyclohexylphosphine, sodium carbonate, cesium fluoride and 3,5-di(tert-butyl)phenylboronic acid undergo coupling reaction to obtain olefin ligand L1-B; or, c. N , N -In dimethylformamide solvent, compound 3, palladium acetate, tricyclohexylphosphine, sodium carbonate, cesium fluoride and 3,5-bis(trifluoromethyl)phenylboronic acid undergo coupling reaction to obtain olefin ligand L1-C.

5. The preparation method according to claim 4, characterized in that: In step (1), the molar ratio of compound 1, methyl iodide and potassium hydroxide is 1:2.4:2.4~1:5:5; And / or, in step (1), the reaction temperature is 20-30°C; And / or, in step (2), the molar ratio of compound 2, mesitylpyridine and trifluoromethanesulfonic anhydride is 1:2:2 to 1:5:5; And / or, in step (2), the reaction temperature is 20-30°C; And / or, in step (3) a, the molar ratio of the compound 3, palladium acetate, tricyclohexylphosphine, base and phenylboric acid is 1:0.01:0.5:2.5:1.5~1:0.1:0.5:2.5:1.5, and the base is sodium carbonate or cesium fluoride; in step (3) b, the molar ratio of the compound 3, palladium acetate, tricyclohexylphosphine, base and 3,5-di(tert-butyl)phenylboric acid is 1:0.0 1:0.5:2.5:1.5~1:0.1:0.5:2.5:1.5, the base is sodium carbonate, cesium fluoride; in step (3) c, the molar ratio of the compound 3, palladium acetate, tricyclohexylphosphine, base and 3,5-bis(trifluoromethyl)phenylboronic acid is 1:0.01:0.5:2.5:1.5~1:0.1:0.5:2.5:1.5, the base is sodium carbonate, cesium fluoride; And / or, in step (3), the reaction temperature is 80-100°C.

6. The preparation method according to claim 4, characterized in that: In step (3), the molar ratio of sodium carbonate to cesium fluoride is 1.5:

1.

7. Use of the compound according to claim 1 or a salt thereof as a chiral boron Lewis acid catalyst, characterized in that: The catalyst is a catalyst used in the asymmetric hydrosilylation reaction of imine; the asymmetric hydrosilylation reaction of imine is: .

8. An asymmetric hydrosilylation reaction of imines, characterized in that: The reaction uses the compound described in claim 1 or its salt as a catalyst; the asymmetric hydrosilylation reaction of the imine is as follows: 。

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