Novel chiral aminoamide-selenoether ligand and preparation method thereof

Abstract

The present invention discloses a novel chiral aminoamide-selenoether ligand having a chemical structure shown in Formula 1: wherein X represents selenium; R 1 represents any one of hydrogen, methyl, and benzyl; R 2 represents an aryl or alkyl group. The complex formed by the ligand and copper trifluoromethanesulfonate has good catalytic activity for asymmetric Friedel-Crafts alkylation reactions. A method for preparing the novel chiral aminoamide-selenoether ligand is provided, comprising reacting phenylselenol with chiral 2,3-diphenylaziridine under nitrogen protection to obtain an aminoselenoether intermediate, and then dehydrating and condensing the aminoselenoether intermediate with an amino acid to obtain the target ligand. The preparation method is simple and has a high ligand yield.

Description

Technical Field

[0001] The present invention relates to the field of chemistry, and more particularly to a novel chiral aminoamide-selenoether ligand and a preparation method thereof. Background Art

[0002] Chiral ligands play a crucial role in metal-catalyzed asymmetric syntheses. In recent decades, scientists have developed a series of chiral ligands with novel structures and broad applicability. Among them, chiral selenoether compounds exhibit excellent stereocontrol in both metal and organocatalysis, but their research and application in the synthesis of bioactive compounds remains limited. Therefore, the rational design and application of efficient, novel chiral selenoether ligands is of great significance.

[0003] Selenium atoms coordinate with metals to form stable metal complexes, which can catalyze reactions with high efficiency and high enantioselectivity. Therefore, we rapidly constructed chiral aminoamide-selenoether ligands using phenylselenol, chiral aziridine, and chiral nitrogen-substituted amino acids as raw materials, providing a new path for the development and application of ligands. Summary of the Invention

[0004] An object of the present invention is to solve at least the above problems and to provide at least the advantages which will be described hereinafter.

[0005] In order to achieve these purposes and other advantages according to the present invention, a novel chiral aminoamide-selenoether ligand is provided, having a chemical structure shown in Formula 1:

[0006]

[0007] Wherein, X represents selenium; R 1 represents any one of hydrogen, methyl, and benzyl; R 2 represents an aryl group or an alkyl group.

[0008] Provided is a method for preparing a novel chiral aminoamide-selenoether ligand, further comprising the following steps:

[0009] Under nitrogen protection, phenylselenol and chiral 2,3-diphenylaziridine react to obtain an aminoselenoether intermediate, which is then dehydrated and condensed with an amino acid to obtain the target ligand, which is a novel chiral aminoamide-selenoether ligand. The chemical reaction equation is shown below:

[0010]

[0011] Among them, the chemical structures of phenylselenol, chiral 2,3-diphenylaziridine, aminoselenoether intermediate, and amino acid are structures 2, 3, 4, and 5, respectively; EDCI is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; DMAP is 4-dimethylaminopyridine; reflux means reflux; and MeOH means methanol.

[0012] Preferably, the specific method includes:

[0013] Step 1: Under nitrogen protection, 1.2 to 2.0 equivalents of phenylselenol and 1 equivalent of chiral 2,3-diphenylaziridine are refluxed in methanol. After the reaction is completed, the reaction solution is separated by column chromatography using petroleum ether-ethyl acetate as eluent, and the chromatographic liquid is removed under reduced pressure to obtain an aminoselenoether intermediate;

[0014] Step 2: 2.0 to 3.0 equivalents of a nitrogen-substituted amino acid, 2.0 to 3.0 equivalents of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and 0.1 equivalent of 4-dimethylaminopyridine are stirred in anhydrous dichloromethane, and then 1.0 equivalent of an aminoselenoether intermediate is added to react at room temperature for 3 to 24 hours. After the reaction is completed, the reaction solution is separated by column chromatography using petroleum ether-ethyl acetate as an eluent to obtain the novel chiral aminoamide-selenoether ligand.

[0015] Preferably, the volume ratio of petroleum ether to ethyl acetate in the eluent in steps 1 and 2 is 1 to 5:1.

[0016] Preferably, the complex formed by the complexation reaction of the novel chiral aminoamide-selenoether ligand with copper trifluoromethanesulfonate can be used as a catalyst for the asymmetric Friedel-Crafts alkylation reaction of the indole carbon 3 position.

[0017] The present invention has at least the following beneficial effects:

[0018] First, the complex formed by the compound of the general formula 1 (a novel chiral aminoamide-selenoether ligand) and copper trifluoromethanesulfonate has good catalytic activity for catalyzing asymmetric Friedel-Crafts alkylation reactions, among which the compound of formula 1-7 has the best effect.

[0019] Second, the compound of formula 1 of the present invention (a novel chiral aminoamide-selenoether ligand) can be used as a ligand for the copper-catalyzed asymmetric indole Friedel-Crafts alkylation reaction and can be directly used to prepare various compounds functionalized at the 3-position of the indole carbon.

[0020] Other advantages, objectives and features of the present invention will be reflected in part from the following description and will be understood by those skilled in the art through study and practice of the present invention. DETAILED DESCRIPTION

[0021] The present invention is further described in detail below with reference to the embodiments so that those skilled in the art can implement the invention with reference to the description.

[0022] It should be noted that the experimental methods described in the following embodiments are conventional methods unless otherwise specified, and the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0023] <Example 1>

[0024] Under nitrogen protection, (2S,3S)-2,3-diphenylaziridine 3-1 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until (2S,3S)-2,3-diphenylaziridine 3-1 disappeared. Silica gel powder was added to the reaction solution and stirred evenly. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 2.92 g of aminoselenoether intermediate 4-1 was obtained as a white solid in a yield of 83%.

[0025] N-methyl-L-proline 5-1 (0.52 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.86 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-1 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution with stirring, and then the solution was concentrated under reduced pressure and passed through a silica gel column. Column chromatography was performed using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-1 as a white solid in an 80% yield.

[0026]

[0027] NMR data of target compound 1-1:

[0028] 1H NMR (400MHz, CDCl3) δ7.97 (d, J=12.8Hz, 1H), 7.30-7.26k (m, 5H), 7.21-7.06 (m, 10H), 5.53 (d, J=6.4Hz, 1H), 4.57 (d, J=7.8Hz, 1H), 3.01 (t, J=6.0Hz, 1H), 2.75 (dd, J=10.2, 4.8Hz, 1H), 2.25 (d, J=12.5Hz, 1H), 2.06 (m, 4H), 1.63 (m, 3H). 13 CNMR (100MHz, CDCl3) δ173.15, 140.24, 138.87, 135.37, 129.21, 128.74, 128.25, 1 27.83, 127.55, 127.29, 127.07, 68.72, 56.56, 56.03, 54.63, 41.27, 30.69, 24.27.

[0029] <Example 2>

[0030] Under nitrogen protection, (2S,3S)-2,3-diphenylaziridine 3-1 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until the (2S,3S)-2,3-diphenylaziridine disappeared. Silica gel powder was added to the reaction solution and stirred. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 2.92 g of aminoselenoether intermediate 4-1 was obtained as a white solid in a yield of 83%.

[0031] N-benzyl-L-proline 5-2 (0.82 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.86 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-1 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution with stirring, and then the solution was concentrated under reduced pressure and passed through a silica gel column. Column chromatography was performed using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-2 as a white solid in a yield of 85%.

[0032]

[0033] NMR data of target compound 1-2:

[0034] 1 H NMR (400MHz, CDCl3) δ7.82–7.72 (m, 1H), 7.31-7.26 (m, 1H), 7.18-7.09 (m, 14H), 6.93-6.85 (m, 2H), 5.34 (t, J=8.0Hz, 1H), 4.64 (d, J=8Hz, 1H), 3.52(dd, J=16, 20.0Hz, 2H), 3.12-3.03(m, 1H), 2.78-2.65(m, 1H), 2.41 -2.32(m, 1H), 2.11-2.06(m, 1H), 1.75-1.55(m, 3H), 1.51-1.38(m, 1H). 13 C NMR (100MHz, CDCl3) δ173.34, 139.57, 139.22, 137.35, 134.97, 134.50, 129.46, 128.98, 128.63, 128.44, 128. 25, 127.99, 127.77, 127.45, 127.28, 127.14, 127.09, 68.09, 57.27, 53.82, 53.49, 53.08, 30.25, 23.90, 20.70.

[0035] <Example 3>

[0036] Under nitrogen protection, (2S,3S)-2,3-diphenylaziridine 3-1 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until (2S,3S)-2,3-diphenylaziridine 3-1 disappeared. Silica gel powder was added to the reaction solution and stirred evenly. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 2.92 g of aminoselenoether intermediate 4-1 was obtained as a white solid in a yield of 83%.

[0037] (S)-N-Benzylindolecarboxylic acid 5-3 (1.0 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.86 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-1 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution with stirring, and then the solution was concentrated under reduced pressure and passed through a silica gel column. Column chromatography was performed using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-3 as a white solid in a yield of 81%.

[0038]

[0039] NMR data of target compounds 1-3:

[0040] 1 H NMR (400MHz, CDCl3) δ8.03-7.87(m, 2H), 7.82-7.74(m, 2H), 7.65-7.55(m, 3H) 7.54-7.01(m, 13H), 6.95-6.80( m, 2H), 6.21 (d, J=8Hz, 1H), 4.30-4.16 (m, 1H) 3.74 (q, J=12Hz, 2H) 2.04 (d, J=2.8Hz, 6H), 1.85 (d, J=3.1Hz, 3H). 13 CNMR (100MHz, CDCl3) δ150.16, 150.11, 149.51, 143.89, 143.24, 136.15, 135.01, 132 .79, 132.43, 131.34, 130.77, 130.22, 130.15, 130.10, 129.05, 128.45, 128.27, 128.1 8, 127.66, 127.55, 127.01, 126.80, 125.98, 125.89, 124.73, 124.43, 124.35, 124.18, 124.12, 122.31, 122.24, 121.62, 58.41 (d, J=23Hz), 45.69, 22.81 (d, J=27Hz), 21.42.

[0041] <Example 4>

[0042] Under nitrogen protection, (2S,3S)-2,3-diphenylaziridine 3-1 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until (2S,3S)-2,3-diphenylaziridine 3-1 disappeared. Silica gel powder was added to the reaction solution and stirred evenly. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 2.92 g of aminoselenoether intermediate 4-1 was obtained as a white solid in a yield of 83%.

[0043] (2S,3aS,7aS)-N-benzyloctahydroindole-2-carboxylic acid 5-4 (1.02 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.86 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-1 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution with stirring, and then the solution was concentrated under reduced pressure and passed through a silica gel column. Column chromatography was performed using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-4 as a white solid in a yield of 78%.

[0044]

[0045] NMR data of target compounds 1-4:

[0046] 1 H NMR (400MHz, CDCl3) δ8.25 (d, J=9.1Hz, 1H), 7.34-6.99 (m, 22H), 5.44 (s, 1H), 4.49 (d, J=8.3Hz, 1H), 3.56 (d, J=13.6Hz, 1H) , 3.40 (d, J=13.8Hz, 1H), 2.78 (s, 1H), 2.01-1.80 (m, 2H), 1.71 (d, J=11.8Hz, 1H), 1.49-1.22 (m, 7H), 1.13 (t, J=9.4Hz, 2H). 13CNMR (100MHz, CDCl3) δ173.47, 139.72, 139.21, 136.50, 135.04, 129.81, 129.30, 128.93, 128.72, 128.22, 128.10 , 127.74, 127.67, 127.29, 127.21, 64.93, 60.62, 56.84, 55.67, 54.64, 36.74, 34.53, 27.88, 27.20, 24.14, 21.31.

[0047] <Example 5>

[0048] Under nitrogen protection, (2S,3S)-2,3-diphenylaziridine 3-1 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until (2S,3S)-2,3-diphenylaziridine 3-1 disappeared. Silica gel powder was added to the reaction solution and stirred evenly. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 2.92 g of aminoselenoether intermediate 4-1 was obtained as a white solid in a yield of 83%.

[0049] (S)-N-Benzylpiperidine-2-carboxylic acid 5-5 (0.87 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.86 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-1 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution and stirred. The solution was then concentrated under reduced pressure and passed through a silica gel column. Column chromatography was performed using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-5 as a white solid in a yield of 75%.

[0050]

[0051] NMR data of target compounds 1-5:

[0052] 1H NMR (400MHz, CDCl3) δ7.40-7.31 (m, 2H), 7.31 (s, 8H), 7.16 (d, J=7.4Hz, 1H), 7.10 (d, J =7.4Hz, 4H), 7.05 (d, J = 7.4Hz, 2H), 6.97 (s, 5H), 5.64 (t, J = 9.0Hz, 1H), 4.58 (d, J = 8.7 Hz, 1H), 3.42 (d, J=13.8Hz, 1H), 2.94 (d, J=13.8Hz, 1H), 2.74 (dd, J=31.8, 11.8Hz, 2H) , 1.86 (d, J=10.8Hz, 1H), 1.75 (d, J=13.5Hz, 1H), 1.61-1.44 (m, 2H), 1.36-1.23 (m, 4H). 13 C NMR (100MHz, CDCl3) δ172.95, 139.97, 138.72, 137.83, 135.33, 128.99, 128.61, 128.45, 128.41, 128.14, 1 28.02, 127.80, 127.71, 127.26, 127.13, 126.87, 67.08, 60.11, 56.36, 53.94, 51.26, 29.66, 24.36, 23.25.

[0053] <Example 6>

[0054] Under nitrogen protection, (2S,3S)-2,3-diphenylaziridine 3-1 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until (2S,3S)-2,3-diphenylaziridine 3-1 disappeared. Silica gel powder was added to the reaction solution and stirred evenly. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 2.92 g of aminoselenoether intermediate 4-1 was obtained as a white solid in a yield of 83%.

[0055] N-(4-Methylbenzyl)-L-proline 5-6 (0.82 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.87 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-1 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution with stirring, and then the solution was concentrated under reduced pressure and passed through a silica gel column. Column chromatography was performed using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-6 as a white solid in a yield of 88%.

[0056]

[0057] NMR data of target compounds 1-6:

[0058] 1 H NMR (400MHz, CDCl3) δ8.28 (t, J=7.2Hz, 1H), 7.32-7.27 (m, 5H), 7.26-7.23)m, 3H), 7.15 -7.05(m, 8H), 7.03-6.98(m, 2H), 6.95-6.90(m, 2H), 5.47(dd, J=9.0, 6.4Hz, 1H), 4.56( d, J=4Hz, 1H), 3.81 (d, J=13.1Hz, 1H), 3.33 (d, J=13.1Hz, 1H), 3.22-3.12 (m, 1H), 3.02- 2.93 (m, 1H), 2.27 (d, J=3.8Hz,, 1H), 2.23 (S, 3H), 2.14-2.03 (m, 1H), 1.75-1.55 (m, 3H). 13 C NMR (100MHz, CDCl3) δ173.40, 138.96, 138.44, 138.33, 137.16, 132.62, 132.22, 130.63, 129.49, 129.44, 128.93, 128.73, 128. 71, 128.30, 128.07, 127.57, 127.38, 127.34, 127.22, 127.08, 67.27, 59.56, 59.45, 56.42, 53.44, 30.36, 30.13, 23.95, 21.01.

[0059] <Example 7>

[0060] Under nitrogen protection, (2R,3R)-2,3-diphenylaziridine 3-2 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until (2R,3R)-2,3-diphenylaziridine 3-2 disappeared. Silica gel powder was added to the reaction solution and stirred. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 3.23 g of aminoselenoether intermediate 4-2 was obtained as a white solid in a yield of 92%.

[0061] N-methyl-L-proline 5-1 (0.52 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.86 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-2 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution, which was then desolvated and concentrated under reduced pressure. The solution was then passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-7 as a white solid in a yield of 86%.

[0062]

[0063] NMR data of target compounds 1-7:

[0064] 1 H NMR (400MHz, CDCl3) δ8.02 (d, J=9.9Hz, 1H)), 7.27-7.26 (m, 5H), 7.22-7.15 (m, 6H), 7.14-7.07 (m, 4H), 5.57 (d, J=10.9Hz, 1H), 4.53 ( d, J=13.6Hz, 1H), 3.06-2.91 (m, 1H), 2.80-2.67 (m, 1H), 2.30-2.20 (m, 4H), 2.12-2.03 (m, 1H), 1.75-1.52 (m, 1H), 1.38-1.43 (m, 2H). 13 C NMR (100MHz, CDCl3) δ140.30, 139.06, 135.40, 129.31, 128.72, 128.32, 128.04, 1 27.81, 127.62, 127.27, 127.14, 68.59, 56.61, 55.77, 54.94, 41.50, 30.76, 24.29.

[0065] <Example 8>

[0066] Under nitrogen protection, (2R,3R)-2,3-diphenylaziridine 3-2 (1.95 g, 10 mmol) was dissolved in 10 mL of methanol, and then phenylselenol 2-1 (1.88 g, 12 mmol) was added. The reaction was refluxed until (2R,3R)-2,3-diphenylaziridine 3-2 disappeared. Silica gel powder was added to the reaction solution and stirred. After the solvent was removed under reduced pressure, the reaction solution was passed through a silica gel column and separated by column chromatography using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent. After removing the chromatographic liquid under reduced pressure, 3.23 g of aminoselenoether intermediate 4-2 was obtained as a white solid in a yield of 92%.

[0067] N-benzyl-L-proline 5-2 (0.82 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (0.86 g, 4 mmol), and 4-dimethylaminopyridine (DMAP) (12 mg, 0.1 mmol) were dissolved in 10 mL of dichloromethane, and then the aminoselenoether intermediate 4-2 (0.7 g, 2 mmol) was added to the reaction system. The reaction was continued at room temperature. After the reaction was completed, silica gel powder was directly added to the reaction solution with stirring, and then the solution was concentrated under reduced pressure and passed through a silica gel column. Column chromatography was performed using petroleum ether-ethyl acetate (the volume ratio of petroleum ether to ethyl acetate was 5:1) as the eluent to obtain the target compound represented by formula 1-8 as a white solid in a yield of 76%.

[0068]

[0069] NMR data of target compound 1-8:

[0070] 1 H NMR (400MHz, CDCl3) δ8.16 (d, J=9.9Hz, 1H), 7.35-7.30 (m, 2H), 7.27-7.25 (m, 1H), 7.24-7. 14(m, 10H), 7.16-7.12(m, 2H), 7.11-7.07(m, 2H), 7.06-7.02(m, 1H), 5.58(d, J=8.0Hz, 1H) , 4.56 (d, J = 7.6Hz, 1H), 3.71 (d, J = 13.0Hz, 1H), 3.33 (d, J = 13.0Hz, 1H), 3.12 (q, J = 8.0Hz, 4 .0Hz, 1H), 2.94 (q, J=8.0Hz, 1H), 2.35-2.20 (m, 1H), 2.13-2.00 (m, 1H), 1.62-1.75 (m, 4H). 13C NMR (100MHz, CDCl3) δ173.26, 140.07, 138.63, 138.58, 135.32, 135.31, 128.90, 128.89, 128.80, 128.47, 128.45, 128.3 7, 128.35, 128.28, 128.12, 127.86, 127.58, 127.33, 127.10, 127.08, 67.35, 59.82, 55.87, 54.85, 53.90, 30.46, 24.24.

[0071] <Example 9>

[0072] Asymmetric indole Friedel-Crafts alkylation reaction:

[0073] Under nitrogen, 0.01 mmol of copper trifluoromethanesulfonate (Cu(OTf)2) and 0.01 mmol of the target compound (ligand) prepared in Examples 1-8 were dissolved in 2 mL of dichloromethane (DCM) and stirred at room temperature for 1 hour. 0.2 mmol of Michael acceptor (Michael acceptor) was then added to the system and stirred for 10 minutes. Then, 0.3 mmol of indole was added and stirred until the reaction was complete. The reaction solution was directly added to silica gel powder, desolventized and concentrated, and then separated by column chromatography using petroleum ether-ethyl acetate (petroleum ether:ethyl acetate volume ratio of 2:1) as the eluent. The chromatographic solution was removed under reduced pressure to obtain the target product. Table 1 shows the results of the copper-catalyzed asymmetric Friedel-Crafts alkylation reaction of the ligand. As can be seen from the experimental data below, the complex formed by the target compound prepared in Examples 1-8 of the present invention and copper trifluoromethanesulfonate has good catalytic activity for catalyzing the asymmetric Friedel-Crafts alkylation reaction. Among them, the compound of Formula 1-7 has the best effect. The target compounds prepared in Examples 1 to 8 of the present invention can be used as ligands for copper-catalyzed asymmetric indole Friedel-Crafts alkylation reaction and can be directly used to prepare various compounds functionalized at the 3-position of indole carbon.

[0074]

[0075] Table 1 Influence of ligand effect on allylation reaction a

[0076]

[0077] Although the embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the description and implementation methods. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and embodiments shown and described herein.

Claims

1. A novel chiral aminoamide-selenoether ligand, characterized in that: It has the chemical structure shown in Formula 1: Wherein, X represents selenium; R 1 represents either a methyl group or a benzyl group; R 2 Represents phenyl.

2. The method for preparing the novel chiral aminoamide-selenoether ligand according to claim 1, wherein: The following steps are also included: Under nitrogen protection, phenylselenol and chiral 2,3-diphenylaziridine react to obtain an aminoselenoether intermediate, which is then dehydrated and condensed with an amino acid to obtain the target ligand, which is a novel chiral aminoamide-selenoether ligand. The chemical reaction equation is shown below: Among them, the chemical structures of phenylselenol, chiral 2,3-diphenylaziridine, aminoselenoether intermediate, and amino acid are structures 2, 3, 4, and 5, respectively; EDCI is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; DMAP is 4-dimethylaminopyridine; reflux means reflux; and MeOH means methanol.

3. The method for preparing the novel chiral aminoamide-selenoether ligand according to claim 2, wherein: Specific methods include: Step 1: Under nitrogen protection, 1.2 to 2.0 equivalents of phenylselenol and 1 equivalent of chiral 2,3-diphenylaziridine are refluxed in methanol. After the reaction is completed, the reaction solution is separated by column chromatography using petroleum ether-ethyl acetate as eluent, and the chromatographic liquid is removed under reduced pressure to obtain an aminoselenoether intermediate; Step 2: 2.0 to 3.0 equivalents of an amino acid, 2.0 to 3.0 equivalents of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and 0.1 equivalent of 4-dimethylaminopyridine are stirred in anhydrous dichloromethane, and then 1.0 equivalent of an aminoselenoether intermediate is added and reacted at room temperature for 3 to 24 hours. After the reaction is completed, the reaction solution is separated by column chromatography using petroleum ether-ethyl acetate as an eluent to obtain the novel chiral aminoamide-selenoether ligand.

4. The method for preparing the novel chiral aminoamide-selenoether ligand according to claim 3, wherein: The volume ratio of petroleum ether to ethyl acetate in the eluent in steps 1 and 2 is 1-5:

1.

5. The use of the novel chiral aminoamide-selenoether ligand according to claim 1, characterized in that: The complex formed by the complexation reaction of the novel chiral aminoamide-selenoether ligand and copper trifluoromethanesulfonate can be used as a catalyst for the asymmetric Friedel-Crafts alkylation reaction of the indole carbon 3 position.

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