Chiral bipyridine-octahydroindoloimidazolone-nitrogen oxide ligands, methods for their preparation and use in asymmetric catalytic reactions

Abstract

The application discloses a kind of chiral bipyridine-octahydroindole and imidazolone-nitrogen oxygen ligand.The present application is generated intermediate 3 by condensation reaction with corresponding octahydroindole arylamide 1 and bipyridine-formaldehyde 2 first, then tertiary amine nitrogen atom of octahydroindole and imidazolone group in intermediate 3 occurs nitrogen oxidation reaction under the action of 1.5 equivalent oxidant m-chloroperbenzoic acid, generates final product chiral bipyridine-octahydroindole and imidazolone-mononitrogen oxygen ligand;With corresponding octahydroindole arylamide 1 and bipyridine-formaldehyde 2 first condensation reaction, generate intermediate 3, then intermediate 3 and bipyridine occur nitrogen oxidation reaction under the action of oxidant, generate final product chiral bipyridine-octahydroindole and imidazolone-dinitrogen oxygen ligand.This kind of ligand includes bipyridine group and nitrogen oxygen group, can form ring coordination with metal, to generate chiral ligand metal complex, as chiral ligand application in asymmetric catalytic reaction.

Description

Technical Field

[0001] This invention relates to the fields of chiral chemistry and asymmetric catalytic synthesis, and in particular to a chiral bipyridine-octahydroindole zimidazolone-nitrogen oxide ligand (BPy-OPI-NO and BPy-OPI-2NO), its preparation method, and its application in asymmetric catalytic indole-indole-in Friedel-Crafts alkylation reactions. Background Technology

[0002] Chiral pharmaceuticals are a cutting-edge field in the pharmaceutical industry. The Nobel Prizes in Chemistry in 2001 and 2021 were awarded to major contributors to chiral catalysis. Currently, there are approximately 2,000 drugs in use worldwide, with chiral drugs accounting for more than 50%. Among the 250 commonly used drugs in clinical practice, as many as 200 are chiral.

[0003] Key technologies for the preparation of chiral drugs have been selected as one of the "Top Ten Chemical Inventions That Change the World" by IUPAC. Asymmetric catalysis is the most efficient and environmentally friendly approach to obtaining chiral molecules, and one of its core scientific challenges is the creation of dominant chiral ligands and catalysts. The design and synthesis of original dominant chiral ligands play a crucial role in the development of asymmetric catalytic reactions and are among the most attractive and challenging goals in asymmetric catalysis, providing core technologies for the efficient and environmentally friendly synthesis of chiral drugs and drug candidates. Furthermore, economically feasible synthetic routes are also essential for dominant chiral ligands, enabling their widespread application. In particular, N-oxides of amines are highly polar substances, and they can be readily prepared through the N-oxidation of pyridine compounds or tertiary amines. The oxygen atoms generated in N-oxides belong to electron-rich coordination sites. Therefore, the unique properties of the electron pairs in N-oxides provide opportunities for complex formation with various metals. Some research focuses on developing novel chiral amine N-oxide ligands for metal-catalyzed reactions.

[0004] In tertiary amine-derived N-oxides, if the parent tertiary amine contains three distinct groups, the nitrogen center on the corresponding N-oxy group will generate a stable chiral center. Against this backdrop, we designed and developed novel types of chiral bipyridine-octahydroindole-imidazolone-nitrogen oxide ligands (BPy-OPI-NO and BPy-OPI-2NO) and tested their application in indole asymmetric Friedel-Crafts alkylation reactions. Based on the design and synthesis of these novel types of chiral bipyridine-octahydroindole-imidazolone-nitrogen oxide ligands, our design concept is inspired by the biomimetic model of a "mantis catching a cicada": the octahydroindole-imidazolone group represents the "mantis's" body, the bipyridine group and nitrogen oxide group represent the "mantis's" claws, and the complexed metal represents the "cicada" (e.g., the mantis catching the cicada). Figure 1 (As shown). Summary of the Invention

[0005] The purpose of this invention is to provide a chiral bipyridine-octahydroindoleimidazole-nitrogen oxide ligand (BPy-OPI-NO and BPy-OPI-2NO), its preparation method, and its applications. This type of ligand contains a bipyridine group and a nitrogen oxide group (the nitrogen atom of the bipyridine and the oxygen atom of the nitrogen oxide group are electron-rich coordination sites), which can form cyclic coordination with metals to generate chiral ligand-metal complexes. These complexes can be used as chiral ligands in asymmetric catalytic reactions. Therefore, they have significant application value in the field of asymmetric catalytic synthesis, and their synthesis method is very economical and simple. They also exhibit good air stability, wide applicability, and good compatibility with various substituents.

[0006] The present invention is achieved as follows: a chiral bipyridine-octahydroindole-imidazolone-nitrogen oxide ligand (BPy-OPI-NO and BPy-OPI-2NO), characterized in that: the chiral bipyridine-octahydroindole-imidazolone-mononitrogen oxide ligand BPy-OPI-NO has the structure shown in general formula (I), and the chiral bipyridine-octahydroindole-imidazolone-bisonitrogen oxide ligand BPy-OPI-2NO has the structure shown in general formula (II);

[0007] ;

[0008] In the formula, R is a halogen, ethyl, tert-butyl, isopropyl, methyl, or hydrogen group.

[0009] A method for preparing chiral bipyridine-octahydroindole-imidazolone-monooxy ligand BPy-OPI-NO is characterized by: a condensation reaction first between the corresponding octahydroindole aromatic amide 1 and bipyridine-formaldehyde 2 to generate intermediate 3; then, the tertiary amine nitrogen atom of the octahydroindole-imidazolone group in intermediate 3 undergoes a nitrogen oxidation reaction under the action of 1.5 equivalents of the oxidant m-chloroperoxybenzoic acid to generate the final product chiral bipyridine-octahydroindole-imidazolone-monooxy ligand BPy-OPI-NO.

[0010] The synthesis route is as follows:

[0011] ;

[0012] A method for preparing chiral bipyridine-octahydroindole-imidazolone-bis(nitroxide) ligand BPy-OPI-2NO is characterized by: a condensation reaction first between the corresponding octahydroindole aromatic amide 1 and bipyridine-formaldehyde 2 to generate intermediate 3; then, the tertiary amine nitrogen atom of the octahydroindole-imidazolone group and a nitrogen atom of bipyridine in intermediate 3 undergo a nitrogen oxidation reaction under the action of 3.0 equivalents of the oxidant m-chloroperoxybenzoic acid to generate the final product chiral bipyridine-octahydroindole-imidazolone-bis(nitroxide) ligand BPy-OPI-2NO.

[0013] The synthesis route is as follows:

[0014] ;

[0015] This invention also discovers the application of chiral bipyridine-octahydroindole zimidazolone-monooxy ligand BPy-OPI-NO as a ligand in asymmetric catalytic Friedel-Crafts alkylation reactions involving indole.

[0016] This invention also discovers the application of chiral bipyridine-octahydroindole-imidazolone-bis(oxo) ligand BPy-OPI-2NO in asymmetric catalytic Friedel-Crafts alkylation reactions involving indole.

[0017] Our design concept is as follows: Figure 7 As shown.

[0018] An example of the Friedel-Crafts alkylation reaction mechanism involving indole catalysis by chiral bipyridine-octahydroindole zimidazolone-bis(oxo) ligand BPy-OPI-2NO is as follows:

[0019] ;

[0020] By adopting the above technical solution, the corresponding octahydroindole aromatic amide 1 and bipyridine-formaldehyde 2 first undergo a condensation reaction to generate intermediate 3. Then, the tertiary amine nitrogen atom of the octahydroindole-imidazolone group in intermediate 3 undergoes a nitrogen oxidation reaction under the action of 1.5 equivalents of the oxidant m-chloroperoxybenzoic acid to generate the final product chiral bipyridine-octahydroindole-imidazolone-mono-nitrogen oxide ligand BPy-OPI-NO. Alternatively, the corresponding octahydroindole aromatic amide 1 and bipyridine-formaldehyde 2 first undergo a condensation reaction to generate intermediate 3. Then, the tertiary amine nitrogen atom of the octahydroindole-imidazolone group and one nitrogen atom of bipyridine in intermediate 3 undergo a nitrogen oxidation reaction under the action of 3.0 equivalents of the oxidant m-chloroperoxybenzoic acid to generate the final product chiral bipyridine-octahydroindole-imidazolone-bis-nitrogen oxide ligand BPy-OPI-2NO. These ligands contain a bipyridine group and a nitroxide group (the nitrogen atom of the bipyridine and the oxygen atom of the nitroxide group are electron-rich coordination sites), and can form cyclic coordination with metals to generate chiral ligand-metal complexes, which are used as chiral ligands in asymmetric catalytic reactions. Therefore, they have important application value in the field of asymmetric catalytic synthesis, and their synthetic methods are very economical and simple. They also have good air stability, wide applicability, and good compatibility with various substituents. Attached Figure Description

[0021] Figure 1The biomimetic model diagram of "Mantis Stalking Cicada" referenced in this invention: the octahydroindole-imidazolone group is a metaphor for the body of the "mantis", the bipyridine group and nitroxy group are metaphors for the claws of the "mantis", and the complexed metal is a metaphor for the "cicada".

[0022] Figure 2 This is a single crystal image of the chiral ligand BPy-OPI-NO-1g synthesized in this invention;

[0023] Figure 3 and Figure 4 The spectral data of the chiral ligand BPy-OPI-NO-1a in this embodiment of the invention;

[0024] Figure 5 and Figure 6 The spectral data of the chiral ligand BPy-OPI-2NO-2a in this embodiment of the invention;

[0025] Figure 7 This is the design concept of the present invention. Detailed Implementation

[0026] (I) Preparation of bipyridine-octahydroindole-imidazolone-mononitroxide ligand BPy-OPI-NO

[0027]

[0028] Chiral ligand BPy-OPI-NO-1a: Octahydroindole aromatic amide 1a (2.5 eq) and bipyridine-formaldehyde (1 eq, 0.78 mmol) 2 were dissolved in an appropriate amount of anhydrous ethanol and refluxed for 12 h. After treatment of the reaction solution, the mixture was purified by column chromatography to obtain a white solid intermediate 3. Intermediate 3 (100 mg, 1 eq) from the second step reaction was dissolved in an appropriate amount of dichloromethane and reacted at room temperature for 10 min. After treatment of the reaction solution, the mixture was purified by column chromatography to obtain a white solid BPy-OPI-NO-1a; melting point: 153.0-153.7℃. o C; Total yield 45%, 17:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz) δ: 1.16-1.20 (m, 1H), 1.29-1.36 (m, 1H), 1.45-1.50 (m, 2H), 1.67-1.73 (m, 1H), 1.77-1.82 (m, 2H), 2.29-2.32 (m, 2H), 2.40-2.46 (m, 1H), 3.28-3.33 (m, 1H), 3.85-3.89 (m, 1H), 4.71-4.74 (m, 1H), 6.87 (s, 1H), 7.04-7.06 (m, 1H), 7.17-7.20 (m, 2H), 7.29-7.31(m, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 7.2 Hz, 1H), 7.79-7.82 (m,1H), 7.85-7.87 (m, 1H), 8.25 (d, J = 7.8 Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H), 8.51 (d, J = 4.8 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.8, 23.8, 24.1, 24.5,27.3, 35.7, 75.9, 84.3, 84.4, 121.0, 122.1, 124.2, 126.5, 128.0, 129.0,129.4, 135.0, 137.4, 137.7, 148.8, 151.0, 155.1, 155.8, 169.7; HRMS (ESI-TOF)m / z: Calcd. for C 26 H 27 N4O2[M+H] + : 427.2129; Found: 427.2131.

[0029] The chiral ligands BPy-OPI-NO-1b to BPy-OPI-NO-1h prepared by the examples were prepared using the same method as chiral ligand BPy-OPI-NO-1a, with the same feed ratio. The reaction yields of ligands BPy-OPI-NO-1b to BPy-OPI-NO-1h were obtained. However, it should be emphasized that the examples are intended to illustrate, not limit, the scope of the invention. The compounds of the present invention are not limited to those shown in Table 1.

[0030] Table 1 shows the chemical structure of the bipyridine-octahydroindopimidazolone-monooxy ligand BPy-OPI-NO.

[0031]

[0032] This embodiment prepares the chiral ligand BPy-OPI-NO-1b: a white solid with a melting point of 148.1-148.9°C. o C; Total yield 43%, 17:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR (CD3OD, 600 MHz)δ: 1.16-1.20 (m, 1H), 1.29-1.36 (m, 1H), 1.39-1.43 (m, 1H), 1.49 (d, J = 13.2Hz, 1H), 1.67-1.72 (m, 1H), 1.77-1.81 (m, 2H), 2.26-2.30 (m, 2H), 2.41-2.46(m, 1H), 3.28-3.31 (m, 1H), 3.85-3.89 (m, 1H), 4.70-4.72 (m, 1H), 6.87 (s,1H), 7.19 (d, J = 8.4 Hz, 2H), 7.28-7.32 (m, 1H), 7.39 (d, J = 9.0 Hz, 2H), 7.59 (d, J = 7.2 Hz, 1H), 7.79-7.82 (m, 1H), 7.86-7.89 (m, 1H), 8.21 (d, J =8.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.51 (d, J = 4.8 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.7, 23.8, 24.0, 24.5, 27.3, 35.7, 75.8, 84.0, 84.4,120.9, 121.5, 123.4, 124.2, 126.8, 128.4, 129.0, 133.7, 137.4, 137.8, 148.9,150.7, 155.1, 155.9, 169.6; HRMS (ESI-TOF) m / z: Calcd. for C 26 H 26 ClN4O2[M+H] + :461.1739; Found: 461.1736.

[0033] This embodiment prepares the chiral ligand BPy-OPI-NO-1c: a white solid with a melting point of 162.1-163.0°C. o C; Total yield 47%, 18:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR (CD3OD, 600 MHz)δ: 1.15-1.20 (m, 1H), 1.28-1.34 (m, 1H), 1.38-1.45 (m, 1H), 1.48 (d, J = 13.2Hz, 1H), 1.67-1.72 (m, 1H), 1.76-1.81 (m, 2H), 2.25-2.30 (m, 2H), 2.41-2.46(m, 1H), 3.28-3.31 (m, 1H), 3.85-3.88 (m, 1H), 4.69-4.72 (m, 1H), 6.87 (s,1H), 7.29-7.31 (m, 2H), 7.33 (s, 3H), 7.58-7.60 (m, 1H), 7.78-7.81 (m, 1H), 7.86-7.89 (m, 1H), 8.21 (d, J = 7.8 Hz, 1H), 8.29-8.30 (m, 1H), 8.50-8.51 (m,1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.7, 23.8, 24.0, 24.5, 27.3, 35.7, 75.8,83.9, 84.4, 119.4, 120.9, 121.5, 123.5, 124.2, 126.8, 132.0, 134.3, 137.4,137.8, 148.9, 150.7, 155.1, 155.9, 169.6; HRMS (ESI-TOF) m / z: Calcd. forC 26 H 26 BrN4O2[M+H] + Found: 505.1234 Found: 505.1237.

[0034] In this embodiment, the chiral ligand BPy-OPI-NO-1d was prepared as a white solid with a melting point of 144.1-144.8°C. o C; Total yield 44%, 20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 0.97-1.00 (m, 3H), 1.14-1.19 (m, 1H), 1.27-1.34 (m, 1H), 1.44-1.49 (m,2H), 1.66-1.71 (m, 1H), 1.76-1.80 (m, 2H), 2.24-2.32 (m, 2H), 2.38-2.42 (m,3H), 3.28-3.31 (m, 1H), 3.84-3.88 (m, 1H), 4.71-4.73 (m, 1H), 6.82 (s, 1H),7.00 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.27-7.29 (m, 1H), 7.56(d, J = 7.8 Hz, 1H), 7.76-7.79 (m, 1H), 7.83-7.86 (m, 1H), 8.24-8.28 (m, 2H),8.49-8.50 (m, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 14.5, 19.8, 23.8, 24.1, 24.5,27.2, 27.8, 35.8, 75.9, 84.3, 84.4, 121.0, 121.4, 122.3, 124.2, 126.7, 128.3,132.6, 137.4, 137.7, 143.1, 148.9, 151.0, 155.2, 155.8, 169.6; HRMS (ESI-TOF)m / z: Calcd. for C 28 H 31 N4O2[M+H] + : 455.2442; Found: 455.2447.

[0035] This embodiment prepares the chiral ligand BPy-OPI-NO-1e: a white solid with a melting point of 167.6-168.1°C. o C; Total yield 44%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.13-1.20 (m, 1H), 1.28-1.36 (m, 1H), 1.45-1.49 (m, 2H), 1.65-1.72 (m,1H), 1.77-1.81 (m, 2H), 2.10 (s, 3H), 2.24-2.33 (m, 2H), 2.39-2.44 (m, 1H), 3.28-3.31 (m, 1H), 3.84-3.88 (m, 1H), 4.70-4.73 (m, 1H), 6.81 (s, 1H), 6.98(d, J = 8.4 Hz, 2H), 7.21 (d, J = 9.0 Hz, 2H), 7.29-7.31 (m, 1H), 7.54-7.55(m, 1H), 7.78-7.81 (m, 1H), 7.83-7.86 (m, 1H), 8.25-8.29 (m, 2H), 8.50-8.51(m, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.5, 19.8, 23.8, 24.1, 24.5, 27.2, 35.7,75.9, 83.4, 84.5, 121.0, 121.3, 122.3, 124.2, 126.7, 129.5, 132.4, 136.8,137.4, 137.7, 148.9, 151.0, 155.2, 155.7, 169.6; HRMS (ESI-TOF) m / z: Calcd.For C 27 H 29 N4O2[M+H] + : 441.2285; Found: 441.2284.

[0036] This embodiment prepares the chiral ligand BPy-OPI-NO-1f: a white solid with a melting point of 158.1-158.6 degrees Celsius. o C; Total yield 42%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.23-1.27 (m, 1H), 1.30-1.36 (m, 1H), 1.49-1.52 (m, 2H), 1.68-1.73 (m,1H), 1.81 (d, J = 14.4 Hz, 1H), 1.87 (d, J = 17.4 Hz, 1H), 2.01 (s, 3H),2.26-2.31 (m, 1H), 2.38-2.44 (m, 1H), 2.66-2.68 (m, 1H), 3.34-3.37 (m, 1H),3.88-3.92 (m, 1H), 4.99-5.02 (m, 1H), 6.85 (s, 1H), 6.97 (d, J = 7.8 Hz, 1H), 7.03-7.10 (m, 2H), 7.31-7.35 (m, 2H), 7.38 (d, J = 7.8 Hz, 1H), 7.74-7.76 (m,1H), 7.84-7.87 (m, 1H), 8.28 (d, J = 7.8 Hz, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.54 (d, J = 4.2 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 18.0, 19.6, 23.8, 24.3,24.6, 26.4, 35.8, 76.0, 84.6, 86.3, 121.2, 121.6, 124.3, 125.1, 126.4, 126.5,128.3, 131.6, 132.8, 136.2, 137.3, 137.4, 148.9, 151.1, 155.0, 155.7, 168.2;HRMS (ESI-TOF) m / z: Calcd. for C 27 H 29 N4O2[M+H] + : 441.2285; Found: 441.2284.

[0037] In this embodiment, the chiral ligand BPy-OPI-NO-1g was prepared as a white solid with a melting point of 163.7-164.5°C. o C; Total yield 45%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.01 (s, 3H), 1.02 (s, 3H), 1.15-1.19 (m, 1H), 1.29-1.35 (m, 1H), 1.45-1.49 (m, 2H), 1.66-1.72 (m, 1H), 1.77-1.81 (m, 2H), 2.27-2.32 (m, 2H), 2.39-2.45 (m, 1H), 2.65-2.70 (m, 1H), 3.28-3.30 (m, 1H), 3.84-3.88 (m, 1H), 4.70-4.73 (m, 1H), 6.82 (s, 1H), 7.04 (d, J = 7.8 Hz, 2H), 7.25-7.30 (m, 3H), 7.56(d, J = 7.2 Hz, 1H), 7.77-7.80 (m, 1H), 7.84-7.87 (m, 1H), 8.25 (d, J = 7.8Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H), 8.50 (d, J = 4.8 Hz, 1H); 13 C NMR (CD3OD,150 MHz) δ: 19.8, 22.8, 23.8, 24.1, 24.5, 27.2, 33.5, 35.7, 75.9, 84.3, 84.4,121.0, 121.4, 122.3, 124.2, 126.7, 126.9, 132.6, 137.4, 137.7, 147.7, 148.8,151.0, 155.2, 155.8, 169.6; HRMS (ESI-TOF) m / z: Calcd. for C 29 H 33 N4O2[M+Na] + :469.2598; Found: 469.2603.

[0038] In this embodiment, the chiral ligand BPy-OPI-NO-1h was prepared as a white solid with a melting point of 174.7-175.4°C. o C; Total yield 46%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.08 (s, 9H), 1.15-1.19 (m, 1H), 1.28-1.35 (m, 1H), 1.44-1.49 (m, 2H), 1.65-1.72 (m, 1H), 1.76-1.81 (m, 2H), 2.25-2.31 (m, 2H), 2.39-2.45 (m, 1H), 3.27-3.32 (m, 1H), 3.84-3.88 (m, 1H), 4.70-4.73 (m, 1H), 6.83 (s, 1H), 7.20(d, J = 8.0 Hz, 2H), 7.26-7.29 (m, 3H), 7.57-7.58 (m, 1H), 7.75-7.78 (m, 1H), 7.84-7.87 (m, 1H), 8.24-8.29 (m, 2H), 8.49-8.50 (m, 1H); 13 C NMR (CD3OD, 150MHz) δ: 19.8, 23.8, 24.1, 24.5, 27.3, 30.2, 34.0, 35.7, 75.9, 84.3, 121.0,121.4, 121.8, 124.2, 125.9, 126.7, 132.3, 137.4, 137.7, 148.8, 149.7, 151.0,155.2, 155.8, 169.6; HRMS (ESI-TOF) m / z: Calcd. for C 30 H 35 N4O2[M+H] + : 483.2755;Found: 483.2759.

[0039] (II) Preparation of bipyridine-octahydroindopimidazolone-bis(oxo) ligand BPy-OPI-2NO

[0040]

[0041] Chiral ligand BPy-OPI-2NO-2a: Octahydroindole aromatic amide 1a (2.5 eq) and bipyridine-formaldehyde (1 eq, 0.78 mmol) 2 were dissolved in an appropriate amount of anhydrous ethanol and refluxed for 12 h. After treatment of the reaction solution, the mixture was purified by column chromatography to obtain a white solid intermediate 3. Intermediate 3 (100 mg, 1 eq) from the second step reaction was dissolved in an appropriate amount of dichloromethane and reacted at room temperature for 40 min. After treatment of the reaction solution, the mixture was purified by column chromatography to obtain a white solid BPy-OPI-2NO-2a with a melting point of 178.7-179.4 °C. o C; Total yield 42%, 18:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1 H NMR (CD3OD, 600 MHz) δ: 1.17-1.21 (m, 1H), 1.30-1.35 (m, 1H), 1.41-1.45 (m, 1H), 1.51 (d, J = 13.2 Hz, 1H), 1.69-1.73 (m,1H), 1.78-1.83 (m, 2H), 2.27-2.30 (m, 2H), 2.41-2.46 (m, 1H), 3.31-3.34 (m,1H), 3.86-3.90 (m, 1H), 4.68-4.70 (m, 1H), 6.92 (s, 1H), 7.06-7.08 (m, 1H),7.19-7.22 (m, 2H), 7.36 (d, J = 7.8 Hz, 2H), 7.42-7.45 (m, 1H), 7.55-7.58 (m,1H), 7.67 (d, J = 7.8 Hz, 1H), 7.89-7.92 (m, 1H), 8.07-8.09 (m, 1H), 8.28 (d,J = 6.6 Hz, 1H), 8.64 (d, J = 7.8 Hz, 1H); 13C NMR (CD3OD, 150 MHz) δ: 19.7,23.8, 24.0, 24.5, 27.2, 35.7, 75.8, 84.1, 84.4, 121.8, 126.3, 126.4, 126.4,126.5, 127.4, 128.1, 128.8, 129.0, 134.9, 136.9, 140.4, 146.8, 149.5, 151.6,169.3; HRMS (ESI-TOF) m / z: Calcd. for C 26 H 27 N4O3[M+H] + : 443.2078; Found:443.2085.

[0042] The chiral ligands BPy-OPI-2NO-2b to BPy-OPI-2NO-2j prepared by the examples were prepared using the same method as chiral ligand BPy-OPI-2NO-2a, with the same feed ratio. The reaction yields of ligands BPy-OPI-2NO-2b to BPy-OPI-2NO-2j are shown in Table 2. However, it should be emphasized that the examples are intended to illustrate, not limit, the scope of the invention. The compounds of the present invention are not limited to those shown in Table 2.

[0043] Table 2 shows the chemical structure of the bipyridine-octahydroindopimetazolone-bis(oxo) ligand BPy-OPI-2NO.

[0044]

[0045] This embodiment prepares the chiral ligand BPy-OPI-2NO-2b: a white solid with a melting point of 157.1-157.6 degrees Celsius. o C; Total yield 40%, 15:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.17-1.21 (m, 1H), 1.29-1.34 (m, 1H), 1.39-1.45 (m, 1H), 1.50 (d, J = 13.2Hz, 1H), 1.68-1.73 (m, 1H), 1.78-1.82 (m, 2H), 2.23-2.31 (m, 2H), 2.40-2.45(m, 1H), 3.30-3.35 (m, 1H), 3.86-3.90 (m, 1H), 4.67-4.70 (m, 1H), 6.88 (s,1H), 6.93-6.96 (m, 2H), 7.34-7.36 (m, 2H), 7.42-7.44 (m, 1H), 7.54-7.57 (m,1H), 7.64-7.65 (m, 1H), 7.89-7.91 (m, 1H), 8.06-8.07 (m, 1H), 8.28-8.29 (m,1H), 8.61-8.63 (m, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.7, 23.8, 24.0, 24.5,27.2, 35.8, 75.7, 84.2, 84.4, 115.7 (d, J CF = 22.5 Hz), 124.5 (d, J CF = 9.0Hz), 126.3, 126.5, 127.4, 128.1, 128.8, 131.0 (d, J CF = 3.3 Hz), 137.0, 140.4,146.8, 149.6, 151.4, 161.0 (d, J CF = 244.5 Hz), 169.4; HRMS (ESI-TOF) m / z:Calcd. for C 26 H 26 FN4O3[M+H] + : 461.1987; Found: 461.1996.

[0046] This embodiment prepares the chiral ligand BPy-OPI-2NO-2c: a white solid with a melting point of 150.4-150.9°C. o C; Total yield 47%, 20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.14-1.19 (m, 1H), 1.30-1.38 (m, 2H), 1.49 (d, J = 13.2 Hz, 1H), 1.69-1.82(m, 3H), 2.23-2.28 (m, 2H), 2.41-2.46 (m, 1H), 3.30-3.33 (m, 1H), 3.85-3.89(m, 1H), 4.66-4.69 (m, 1H), 6.92 (s, 1H), 7.18-7.20 (m, 2H), 7.41-7.43 (m,1H), 7.53-7.56 (m, 1H), 7.68 (d, J = 7.2 Hz, 1H), 7.90-7.92 (m, 1H), 8.03-8.04 (m, 1H), 8.27 (d, J = 6.0 Hz, 1H), 8.62 (d, J = 7.8 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.7, 23.8, 23.9, 24.5, 27.3, 35.7, 75.7, 83.8, 84.5,123.1, 126.4, 126.5, 127.4, 128.1, 128.8, 129.1, 131.6, 133.7, 137.0, 140.3,146.8, 149.6, 151.4, 169.3; HRMS (ESI-TOF) m / z: Calcd. for C 26 H 26 ClN4O3[M+H] + :477.1688; Found: 477.1692.

[0047] This embodiment prepares the chiral ligand BPy-OPI-2NO-2d: a white solid with a melting point of 171.2-171.6 degrees Celsius. o C; Total yield 42%, 16:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.12-1.19 (m, 1H), 1.30-1.36 (m, 2H), 1.48 (d, J = 13.2 Hz, 1H), 1.66-1.72(m, 1H), 1.75-1.82 (m, 2H), 2.22-2.29 (m, 2H), 2.41-2.46 (m, 1H), 3.29-3.33(m, 1H), 3.85-3.89 (m, 1H), 4.66-4.69 (m, 1H), 6.99 (s, 1H), 7.05-7.06 (m,1H), 7.15-7.18 (m, 1H), 7.26-7.27 (m, 1H), 7.40-7.43 (m, 1H), 7.53-7.56 (m,1H), 7.60-7.61 (m, 1H), 7.71 (d, J = 7.2 Hz, 1H), 7.91-7.94 (m, 1H), 8.02-8.04 (m, 1H), 8.27 (d, J = 6.6 Hz, 1H), 8.64 (d, J = 7.8 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.7, 23.8, 23.9, 24.5, 27.3, 35.7, 75.7, 83.5, 84.5,119.1, 121.2, 126.1, 126.4, 126.5, 127.5, 128.1, 128.7, 130.3, 134.6, 136.3,137.0, 140.4, 146.8, 149.6, 151.3, 169.4; HRMS (ESI-TOF) m / z: Calcd. forC 26 H 26 ClN4O3[M+H] + : 477.1688; Found: 477.1690.

[0048] This embodiment prepares the chiral ligand BPy-OPI-2NO-2e: a white solid with a melting point of 178.3-178.9°C. o C; Total yield 43%, 20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.16-1.20 (m, 1H), 1.29-1.35 (m, 1H), 1.38-1.45 (m, 1H), 1.49 (d, J = 13.2Hz, 1H), 1.67-1.73 (m, 1H), 1.77-1.82 (m, 2H), 2.13 (s, 3H), 2.23-2.32 (m,2H), 2.39-2.44 (m, 1H), 3.29-3.43 (m, 1H), 3.85-3.89 (m, 1H), 4.66-4.69 (m,1H), 6.86 (s, 1H), 7.00 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 9.0 Hz, 2H), 7.41-7.44 (m, 1H), 7.54-7.57 (m, 1H), 7.64-7.65 (m, 1H), 7.87-7.90 (m, 1H), 8.07-8.09 (m, 1H), 8.27-8.28 (m, 1H), 8.63-8.64 (m, 1H); 13 C NMR (CD3OD, 150 MHz)δ: 19.5, 19.7, 23.8, 24.0, 24.5, 27.2, 35.7, 75.9, 84.2, 84.4, 121.9, 126.2,126.4, 127.3, 128.1, 128.7, 129.5, 132.3, 136.7, 136.9, 140.4, 146.8, 149.5,151.7, 169.3; HRMS (ESI-TOF) m / z: Calcd. for C 27 H 29 N4O3 [M+H] + : 457.2239;Found: 457.2248.

[0049] This embodiment prepares the chiral ligand BPy-OPI-2NO-2f: a white solid with a melting point of 165.3-165.9°C. o C; Total yield 45%, 19:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.13-1.20 (m, 1H), 1.28-1.36 (m, 1H), 1.38-1.43 (m, 1H), 1.49 (d, J = 13.2Hz, 1H), 1.68-1.72 (m, 1H), 1.76-1.82 (m, 2H), 2.13 (s, 3H), 2.26-2.29 (m,2H), 2.40-2.45 (m, 1H), 3.29-3.33 (m, 1H), 3.85-3.89 (m, 1H), 4.67-4.69 (m,1H), 6.88 (d, J = 7.2 Hz, 1H), 6.91 (s, 1H), 7.04-7.07 (m, 1H), 7.12 (d, J =9.0 Hz, 1H), 7.23 (s, 1H), 7.40-7.43 (m, 1H), 7.53-7.56 (m, 1H), 7.66-7.68(m, 1H), 7.88-7.91 (m, 1H), 8.07-8.08 (m, 1H), 8.26-8.27 (m, 1H), 8.63-8.64(m, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.7, 20.0, 23.8, 24.0, 24.5, 27.2, 35.7,75.9, 84.1, 84.4, 118.7, 122.2, 126.3, 126.4, 127.1, 127.3, 128.1, 128.7,128.8, 134.9, 136.9, 139.3, 140.4, 146.8, 149.4, 151.7, 169.3; HRMS (ESI-TOF)m / z: Calcd. for C 27 H 29 N4O3[M+H] + : 457.2234; Found: 457.2236.

[0050] This embodiment prepares the chiral ligand BPy-OPI-2NO-2g: a white solid with a melting point of 168.1-168.8°C. o C; Total yield 44%, 19:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.00-1.03 (m, 3H), 1.15-1.18 (m, 1H), 1.28-1.34 (m, 1H), 1.37-1.44 (m,1H), 1.49 (d, J = 13.2 Hz, 1H), 1.67-1.73 (m, 1H), 1.76-1.82 (m, 2H), 2.23-2.30 (m, 2H), 2.41-2.45 (m, 3H), 3.30-3.33 (m, 1H), 3.85-3.89 (m, 1H), 4.67-4.70 (m, 1H), 6.87 (s, 1H), 7.02 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.40-7.43 (m, 1H), 7.53-7.55 (m, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.87-7.90 (m, 1H), 8.07-8.09 (m, 1H), 8.27 (d, J = 6.6 Hz, 1H), 8.63 (d, J = 7.8Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 14.5, 19.7, 23.8, 24.0, 24.5, 27.2, 27.8,35.7, 75.8, 84.2, 84.4, 122.0, 126.3, 126.4, 127.4, 128.1, 128.4, 128.7,132.5, 136.9, 140.4, 143.1, 146.8, 149.5, 151.7, 169.3; HRMS (ESI-TOF) m / z:Calcd. for C 28 H 31 N4O3[M+H] + : 471.2391; Found: 471.2390.

[0051] This embodiment prepares the chiral ligand BPy-OPI-2NO-2h: a white solid with a melting point of 163.5-164.4°C. o C; Total yield 46%, 20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.16-1.20 (m, 1H), 1.29-1.35 (m, 1H), 1.43-1.46 (m, 1H), 1.49 (d, J = 12.6Hz, 1H), 1.67-1.73 (m, 1H), 1.80 (d, J = 12.0 Hz, 2H), 2.22-2.27 (m, 1H), 2.33-2.34 (m, 1H), 2.38-2.43 (m, 1H), 3.30-3.33 (m, 1H), 3.59 (s, 3H), 3.85-3.89 (m, 1H), 4.67-4.69 (m, 1H), 6.71 (d, J = 9.0 Hz, 2H), 6.80 (s, 1H),7.18-7.19 (m, 2H), 7.41-7.44 (m, 1H), 7.54-7.56 (m, 1H), 7.61 (d, J = 7.8 Hz,1H), 7.86-7.89 (m, 1H), 8.09-8.11 (m, 1H), 8.28 (d, J = 6.6 Hz, 1H), 8.63 (d,J = 7.8 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.7, 23.8, 24.0, 24.5, 27.1,35.8, 54.5, 75.8, 84.4, 84.6, 114.2, 124.3, 126.3, 126.4, 127.4, 127.5,128.1, 128.7, 136.9, 140.4, 146.9, 149.5, 151.7, 158.5, 169.3; HRMS (ESI-TOF)m / z: Calcd. for C 27 H 29 N4O4[M+H] + : 473.2183; Found: 473.2190.

[0052] This embodiment prepares the chiral ligand BPy-OPI-2NO-2i: a white solid with a melting point of 176.2-176.7°C. o C; Total yield 47%, 20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.03 (s, 3H), 1.04 (s, 3H), 1.13-1.18 (m, 1H), 1.28-1.35 (m, 1H), 1.37-1.44 (m, 1H), 1.49 (d, J = 13.2 Hz, 1H), 1.67-1.73 (m, 1H), 1.76-1.82 (m,2H), 2.23-2.29 (m, 2H), 2.39-2.45 (m, 1H), 2.68-2.72 (m, 1H), 3.29-3.33 (m,1H), 3.85-3.89 (m, 1H), 4.67-4.70 (m, 1H), 6.88 (s, 1H), 7.05 (d, J = 8.4 Hz,2H), 7.25 (d, J = 9.0 Hz, 2H), 7.40-7.43 (m, 1H), 7.52-7.55 (m, 1H), 7.66 (d,J = 7.2 Hz, 1H), 7.88-7.90 (m, 1H), 8.07-8.09 (m, 1H), 8.27 (d, J = 6.0 Hz, 1H), 8.64 (d, J = 7.8 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ: 19.8, 22.8, 23.8,24.0, 24.5, 27.2, 33.5, 35.7, 75.8, 84.2, 84.4, 121.9, 126.3, 126.4, 126.9,127.4, 128.2, 128.8, 132.6, 136.9, 140.4, 146.9, 147.6, 149.5, 151.7, 169.3;HRMS (ESI-TOF) m / z: Calcd. for C 29 H 33 N4O3 [M+H] + : 485.2549; Found: 485.2556.

[0053] In this embodiment, the chiral ligand BPy-OPI-2NO-2j was prepared: a white solid with a melting point of 173.0-173.7°C. o C; Total yield 43%, >20:1 dr; The results of nuclear magnetic resonance and high-resolution mass spectrometry tests are as follows: 1H NMR (CD3OD, 600 MHz)δ: 1.11-1.13 (m, 10H), 1.30-1.35 (m, 1H), 1.38-1.44 (m, 1H), 1.49 (d, J =13.2 Hz, 1H), 1.68-1.73 (m, 1H), 1.76-1.82 (m, 2H), 2.26-2.29 (m, 2H), 2.40-2.45 (m, 1H), 3.29-3.33 (m, 1H), 3.85-3.89 (m, 1H), 4.67-4.70 (m, 1H), 6.88(s, 1H), 7.22-7.24 (m, 2H), 7.26-7.28 (m, 2H), 7.40-7.43 (m, 1H), 7.53-7.55(m, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.88-7.91 (m, 1H), 8.07-8.09 (m, 1H), 8.27(d, J = 6.0 Hz, 1H), 8.63 (d, J = 7.8 Hz, 1H); 13 C NMR (CD3OD, 150 MHz) δ:19.8, 23.8, 24.0, 24.5, 27.2, 30.2, 34.0, 35.7, 75.8, 84.1, 84.4, 121.5,125.9, 126.3, 126.4, 127.4, 128.2, 128.8, 132.3, 136.9, 140.3, 146.9, 149.5,149.7, 151.7, 169.3; HRMS (ESI-TOF) m / z: Calcd. for C 30 H 35 N4O3 [M+H] + :499.2704; Found: 499.2704.

[0054] (III) Application of chiral bipyridine-octahydroindole-imidazolone-nitrogen oxide ligands (BPy-OPI-NO and BPy-OPI-2NO) in asymmetric catalytic indole Friedel-Crafts alkylation reaction

[0055] The bipyridine-octahydroindole-imidazole ketone-nitrogen oxide ligands (BPy-OPI-NO and BPy-OPI-2NO) of formula (1) of the present invention contain a bipyridine group and a nitrogen oxide group (the nitrogen atom of the bipyridine and the oxygen atom of the nitrogen oxide group belong to electron-rich coordination sites), which can form cyclic coordination with metals to generate chiral ligand-metal complexes, and are used as dominant chiral ligands in asymmetric catalytic Friedel-Crafts alkylation reactions involving indole. However, it should be emphasized that the chiral ligands (BPy-OPI-NO and BPy-OPI-2NO) of the present invention are not limited to use as chiral ligands only in asymmetric catalytic Friedel-Crafts alkylation reactions of indole.

[0056] Example 1: Application of chiral ligands BPy-OPI-NO with various substituents in the asymmetric catalytic Friedel-Crafts alkylation reaction of indole 4a and enone lactam 5a

[0057] Table 3 shows the applications of chiral ligands BPy-OPI-NO with various substituents in asymmetric catalytic reactions.

[0058]

[0059] To demonstrate the application value of the developed chiral ligand BPy-OPI-NO in asymmetric catalytic systems, we selected the Friedel-Crafts alkylation reaction involving indole 4a and enone lactam 5a as the template reaction, and selected compounds BPy-OPI-NO-1a~BPy-OPI-NO-1h as chiral ligands to generate chiral complexes in situ with Lewis acid Ni(OTf)2, thus verifying the asymmetric catalytic effect of ligand BPy-OPI-NO (Table 3).

[0060] Experimental conclusions: The experimental results show that the chiral ligands BPy-OPI-NO-1a~BPy-OPI-NO-1h with various substituents shown in formula (1) generate chiral complexes in situ with Lewis acid Ni(OTf)2. They all show asymmetric catalytic effects in Friedel-Crafts alkylation reactions involving indole 4a and enone lactam 5a, and can be developed into new chiral ligands BPy-OPI-NO, which is worth further in-depth research.

[0061] Example 2: Application of chiral ligands BPy-OPI-2NO with various substituents in the asymmetric catalytic Friedel-Crafts alkylation reaction of indole 4a and enone lactam 5a

[0062] Table 4 shows the applications of chiral ligands BPy-OPI-2NO with various substituents in asymmetric catalytic reactions.

[0063]

[0064] To demonstrate the application value of the developed chiral ligand BPy-OPI-2NO in asymmetric catalytic systems, we selected the Friedel-Crafts alkylation reaction involving indole 4a and enone lactam 5a as the template reaction, and selected compounds BPy-OPI-2NO-2a to BPy-OPI-2NO-2j as chiral ligands to generate chiral complexes in situ with Lewis acid Ni(OTf)2, thus verifying the asymmetric catalytic effect of the chiral ligand BPy-OPI-2NO (Table 4).

[0065] Experimental conclusions: The experimental results show that the chiral ligands BPy-OPI-2NO-2a~BPy-OPI-2NO-2j with various substituents shown in formula (1) generate chiral complexes in situ with Lewis acid Ni(OTf)2. They all show asymmetric catalytic effects in Friedel-Crafts alkylation reactions involving indole 4a and enone lactam 5a, and can be developed into new chiral ligands BPy-OPI-2NO, which is worth further in-depth research.

[0066] Example 3: Application of chiral ligand BPy-OPI-2NO-2b in the asymmetric catalytic Friedel-Crafts alkylation reaction of various substituents of indole 4 and various substituents of enone lactam 5.

[0067] Table 5 shows the application of the chiral ligand BPy-OPI-2NO-2b in asymmetric catalytic reactions.

[0068]

[0069] To demonstrate the application value of the developed chiral ligand BPy-OPI-2NO-2b in asymmetric catalytic systems, we selected Friedel-Crafts alkylation reactions of various substituents of indole 4 and various substituents of enone lactam 5 as template reactions to verify the catalytic effect of chiral ligand BPy-OPI-2NO-2b (Table 5).

[0070] Experimental conclusions: The experimental results show that the chiral ligand BPy-OPI-2NO-2b shown in formula (1) forms a chiral complex in situ with Lewis acid Ni(OTf)2. It shows asymmetric catalytic effect in the Friedel-Crafts alkylation reaction of various substituents of indole 4 and various substituents of enone lactam 5. It can be developed into a new dominant chiral ligand and is worth further in-depth study.

Claims

1. A chiral bipyridine-octahydroindopimetazolone-nitrogen oxide ligand (BPy-OPI-NO and BPy-OPI-2NO), characterized in that: Chiral bipyridine-octahydroindole-imidazolone-mononitroxide ligand BPy-OPI-NO has the structure shown in general formula (Ⅰ), and chiral bipyridine-octahydroindole-imidazolone-bis(nitroxide) ligand BPy-OPI-2NO has the structure shown in general formula (Ⅱ). ； Specifically, the chiral bipyridine-octahydroindopimidazolone-mononitroxide ligand BPy-OPI-NO has one of the following structural formulas: ； The chiral bipyridine-octahydroindole-imidazolone-bis(oxo) ligand BPy-OPI-2NO has one of the following structural formulas: 。 2. A method for preparing the chiral bipyridine-octahydroindolimidazolone-mononitroxide ligand BPy-OPI-NO as described in claim 1, characterized in that: The corresponding octahydroindole aromatic amide 1 and bipyridine-formaldehyde 2 first undergo a condensation reaction to generate intermediate 3. Then, the tertiary amine nitrogen atom of the octahydroindole-imidazolone group in intermediate 3 undergoes a nitrogen oxidation reaction under the action of 1.5 equivalents of the oxidant m-chloroperoxybenzoic acid to generate the final product chiral bipyridine-octahydroindole-imidazolone-monooxy ligand BPy-OPI-NO.

3. The synthesis route is as follows: 。 4. A method for preparing the chiral bipyridine-octahydroindolimidazolone-bis(oxo) ligand BPy-OPI-2NO as described in claim 1, characterized in that: The corresponding octahydroindole aromatic amide 1 and bipyridine-formaldehyde 2 first undergo a condensation reaction to generate intermediate 3. Then, the tertiary amine nitrogen atom of the octahydroindole imidazolidinone group and one nitrogen atom of bipyridine in intermediate 3 undergo a nitrogen oxidation reaction under the action of 3.0 equivalents of the oxidant m-chloroperoxybenzoic acid to generate the final product chiral bipyridine-octahydroindole imidazolidinone-bis(nitroxide) ligand BPy-OPI-2NO. The synthesis route is as follows: 。 5. The application of the chiral bipyridine-octahydroindole zimidazolone-monooxy ligand BPy-OPI-NO as described in claim 1 as a ligand in asymmetric catalytic Friedel-Crafts alkylation reactions involving indole.

6. The application of the chiral bipyridine-octahydroindole zimidazolone-bis(oxo) ligand BPy-OPI-2NO as described in claim 1 in asymmetric catalytic Friedel-Crafts alkylation reactions involving indole.

Images