A method for constructing carbon-carbon axial chiral indole-anisole biaryl compounds

Abstract

The present invention belongs to the field of asymmetric organic synthesis and discloses a method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound. A chiral gold-catalyzed asymmetric C-H bond insertion reaction of anisole derivatives and 3-diazoindole derivatives is provided to efficiently and selectively synthesize optically active axially chiral indole-anisole biaryl compounds, with an enantioselectivity of up to 98% ee. The advantages of the method of the present invention include: rapid and efficient construction of novel carbon-carbon axial chiral indole-anisole biaryl compounds, mild reaction conditions, simple operation, good substrate universality, high reaction yield, high atom economy, and good enantioselectivity.

Description

Technical Field

[0001] The invention belongs to the field of asymmetric catalysis, and specifically is a method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound by inserting the CH bond of anisole derivative into 3-diazoindole gold carbene using chiral gold catalysis. Background Art

[0002] Axially chiral ligands and catalysts are very common and have important applications in asymmetric catalysis. For example, BINAP has achieved industrial application in multiple asymmetric catalytic reactions. Axially chiral phosphoric acid has demonstrated excellent catalytic performance and application prospects in organic small molecule catalysis. Research on the construction of axially chiral frameworks is receiving increasing attention.

[0003] Axially chiral compounds containing indole structures are widely present in the frameworks of biopharmaceutical molecules, natural product active molecules, and chiral ligands and catalysts. Therefore, the development of compounds with axially chiral indole skeletons has broad application prospects and practical significance. The methods reported for constructing axially chiral compounds with indole skeletons include: constructing axially chiral compounds at the 2-position of indole through an asymmetric Cacchi reaction between N-arylalkyl-2-alkynylaniline and arylboronic acid (YPHe, H.Wu, Q.Wang, et al.Angew.Chem.Int.Ed.2020,59(5):2105-2109.); using transition metal palladium and chiral ligands to catalyze the synthesis of axially chiral compounds at the 3-position of indole (CSWang, L.Wei, CJWang, et al.Org.Lett.2021,23(19):7401-7406.); using chiral rhodium to achieve carbon-hydrogen insertion of naphthalene ring diazo into the 2-position of indole to construct axially chiral compounds (J.Liu, Q.Li, Y.Shao, et al.Org.Lett.2022,24(25):4670-4674.).

[0004] The C-H bond insertion reaction of carbenes is an efficient method for constructing C-H bonds. If carbenes can be inserted into the C-H bonds of aromatic rings using a suitable chiral catalyst to construct C-H axial chirality, it would be a very direct and effective method. This invention provides a new method for synthesizing carbon-carbon axial chiral indole-anisole biaryl compounds by chiral gold-catalyzed C-H bond insertion of anisole derivatives into 3-diazoindole. Summary of the Invention

[0005] The present invention discloses a method for synthesizing a carbon-carbon axially chiral indole-anisole biaryl compound by inserting a chiral gold-catalyzed anisole derivative into a 3-diazoindole C-H bond. This method produces the indole-anisole biaryl compound with good yield and corresponding selectivity. A possible reaction process is proposed: first, the diazonium compound and the gold catalyst form a gold carbene intermediate, which then undergoes selective carbon-hydrogen insertion dearomatization of the electron-rich aromatic hydrocarbon; the resulting metal-bonded zwitterion further aromatizes the intermediate through proton migration, releasing the gold catalyst and achieving a conversion from central chirality to axial chirality; and finally, protonation achieves the establishment of the target axially chiral skeleton.

[0006] The specific reaction formula of the present invention is as follows:

[0007]

[0008] Among them, A 1 = one of methyl, ethyl, and allyl; A 2 = one of benzenesulfonyl, p-toluenesulfonyl, p-methoxybenzenesulfonyl, and 2-naphthalenesulfonyl; A 3 = methyl, methoxy, halogen or hydrogen; A 4 = methyl, halogen or hydrogen; A 5 = one of methyl and hydrogen; B 1 = one of methyl, ethyl, and tert-butyldimethylsilyl; R = one of hydrogen, phenyl, acetylmethyl, (4-tert-butyl)phenyl, (4-methoxycarbonyl)phenyl, (4-methoxy)phenyl, and (3-methoxy)phenyl.

[0009] The 3-diazoindole derivatives (1) are as follows:

[0010]

[0011]

[0012] The anisole derivative (2) has the following structure:

[0013]

[0014] The specific description of the present invention is as follows:

[0015] The chiral gold catalysts used are: Au1, Au2, Au3, Au4, Au5, Au6, Au7, Au8, and the best catalyst is: Au3. The structure of the chiral gold catalyst is:

[0016]

[0017] The silver salt used is one of silver bis(trifluorosulfonyl)imide (AgNTf2), silver tetrafluoroborate (AgBF4), and silver hexafluoroantimonate (AgSbF6), among which the best additive is silver bis(trifluorosulfonyl)imide (AgNTf2).

[0018] The reaction solvents include dichloromethane, 1,2-dichloroethane, tetrahydrofuran, acetonitrile, etc., among which the best solvent is 1,2-dichloroethane.

[0019] The molar ratio of the chiral gold catalyst to 3-indolediazonium (1) in the reaction is 0.01-0.1:1; the optimal molar ratio of the chiral gold catalyst to 3-indolediazonium (1) in the reaction is 0.02:1.

[0020] The molar ratio of 3-indolediazide (1) and anisole derivative (2) is 1:1.2-1.2:1, and the optimal molar ratio is 1:1.2.

[0021] The concentration of the reaction solution is: the concentration of the indole derivative (1) is 0.025-0.2 mol / L, and the optimal reaction concentration is 0.07 mol / L.

[0022] The reaction temperature is: 0℃ to -10℃, with the optimal temperature being -5℃.

[0023] The reaction time is 2 to 5 hours, and the more preferred reaction time is 2.5 hours.

[0024] Beneficial effects

[0025] This invention discloses a method for constructing carbon-carbon axially chiral 3-indole-anisole biaryl compounds by inserting a metal carbene into the C-H bond of an anisole derivative using chiral gold. This method efficiently completes the construction of axial chirality in a single step through a carbene transfer strategy. Advantages of the method include mild reaction conditions, simple operation, good substrate universality, high reaction yield, and good enantioselectivity. This is the first gold-catalyzed synthesis of axially chiral compounds at the indole 3 position, adding a new approach to the synthesis of axially chiral indole compounds.

[0026] The carbon-carbon axially chiral compounds of this invention can also serve as precursors for the development of novel catalysts and ligands. The compatibility of substituent positions and electrical properties within their structures also facilitates structural modification of the derived axially chiral ligands. The present invention provides a carbon-carbon axially chiral phosphine ligand through simple derivatization, which exhibits moderate catalytic activity in palladium-catalyzed asymmetric allylation reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 3aa obtained in Example 1 1 H-NMR (nuclear magnetic hydrogen spectrum);

[0028] Figure 2 3aa obtained in Example 1 13 C-NMR (nuclear magnetic carbon spectroscopy);

[0029] Figure 3 HRMS (high resolution mass spectrometry) of 3aa obtained in Example 1;

[0030] Figure 4 This is the HPLC (high performance liquid chromatography) of 3aa obtained in Example 1. DETAILED DESCRIPTION

[0031] The present invention will be further described below by means of specific examples, but the present invention is not limited to the following examples:

[0032] Example 1:

[0033]

[0034] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and 1,2-dichloroethane (DCE) (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. Then, 1a (65.2 mg, 0.2 mmol) was added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The product was then isolated and purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (82.9 mg, 81% yield, 97% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0035] Example 2:

[0036]

[0037] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au1 (2.8 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (59.4 mg, 58% yield, 37% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0038] Example 3:

[0039]

[0040] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au4 (3.7 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (49.1 mg, 48% yield, 20% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0041] Example 4:

[0042]

[0043] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgSbF6 (1.4 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The product was then isolated and purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (57.3 mg, 56% yield, 95% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0044] Example 5:

[0045]

[0046] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and dichloromethane (DCM) (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The product was then isolated and purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (63.5 mg, 62% yield, 53% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0047] Example 6:

[0048]

[0049] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (4 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (56.3 mg, 55% yield, 76% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0050] Example 7:

[0051]

[0052] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (2 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (47.1 mg, 55% yield, 68% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0053] Example 8:

[0054]

[0055] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at 0°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at 0°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (67.6 mg, 66% yield, 77% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0056] Example 9:

[0057]

[0058] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at -10°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -10°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (74.8 mg, 73% yield, 97% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0059] Example 10:

[0060]

[0061] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.0 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (78.9 mg, 77% yield, 95% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0062] Example 11:

[0063]

[0064] Under argon, compound 2a (51.4 mg, 0.24 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (65.2 mg, 0.2 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The mixture was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (80.9 mg, 79% yield, 96% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0065] Example 12:

[0066]

[0067] Under argon, compound 2a (42.8 mg, 0.2 mmol), gold catalyst Au3 (3.0 mg, 0.004 mmol), AgNTf2 (1.1 mg, 0.004 mmol), and DCE (3 mL) were added to a dry reaction tube and stirred at -5°C for 10 minutes. 1a (78.2 mg, 0.24 mmol) was then added all at once. The reaction tube was placed in a cooler at -5°C for 2.5 hours. The reaction was monitored by thin-layer chromatography. Upon completion, the solvent was removed by rotary evaporation. The product was then purified by column chromatography (eluent: PE / EA = 20:1-5:1) to afford compound 3aa (72.7 mg, 71% yield, 87% ee) as a white solid with a melting point of 235-236°C. The structural characterization of 3aa is shown in Table 1.

[0068] Example 13:

[0069]

[0070] 1b (68.8 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted for 2.5 hours using the method of Example 1 to obtain a white solid product 3ab (75.5 mg, 71% yield, 93% ee). The structural characterization of 3ab is shown in Table 1.

[0071] Example 14:

[0072]

[0073] 1c (72.0 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3ac (72.1 mg, 66% yield, 96% ee), a white solid product with a melting point of 217-218°C. The structural characterization of 3ac is shown in Table 1.

[0074] Example 15:

[0075]

[0076] 1d (80.7 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3ad (82.7 mg, 70% yield, 98% ee), a white solid product with a melting point of 237-238°C. The structural characterization of 3ad is shown in Table 1.

[0077] Example 16:

[0078]

[0079] 1e (71.2 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3ae (93.2 mg, 86% yield, 67% ee), a white solid product with a melting point of 203-204°C. The structural characterization of 3ae is shown in Table 1.

[0080] Example 17:

[0081]

[0082] 1f (68.0 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3af (71.5 mg, 68% yield, 94% ee), a white solid product with a melting point of 232-233°C. The structural characterization of 3af is shown in Table 1.

[0083] Example 18:

[0084]

[0085] 1g (68.0 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3ag (54.7 mg, 52% yield, 90% ee), a white solid product with a melting point of 237-238°C. The structural characterization of 3ag is shown in Table 1.

[0086] Example 19:

[0087]

[0088] 1h (68.0 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted by the method of Example 1 to give 3ah (76.8 mg, 73% yield, 84% ee), a white solid product with a melting point of 220-221°C. The structural characterization of 3ah is shown in Table 1.

[0089] Example 20:

[0090]

[0091] 1i (72.0 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3ai (74.3 mg, 68% yield, 88% ee), a white solid product with a melting point of 231-232°C. The structural characterization of 3ai is shown in Table 1.

[0092] Example 21:

[0093]

[0094] 1j (68.0 mg, 0.2 mmol) and 2a (51.4 mg, 0.2 mmol) were reacted with the method of Example 1 to afford 3aj (49.4 mg, 47% yield, 76% ee) as a white solid, melting point 194-195°C. The structural characterization of 3aj is shown in Table 1.

[0095] Example 22:

[0096]

[0097] 1k (70.4 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3ak (49.5 mg, 46% yield, 60% ee), a white solid product with a melting point of 191-192°C. The structural characterization of 3ak is shown in Table 1.

[0098] Example 23:

[0099]

[0100] 1l (50.0 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3al (58.4 mg, 67% yield, 94% ee), a white solid product with a melting point of 242-243°C. The structural characterization of 3al is shown in Table 1.

[0101] Example 24:

[0102]

[0103] 1m (62.4 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3am (55.8 mg, 56% yield, 84% ee), a white solid product with a melting point of 194-195°C. The structural characterization of 3am is shown in Table 1.

[0104] Example 25:

[0105]

[0106] 1n (68.4 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3an (77.1 mg, 73% yield, 90% ee), a white solid product with a melting point of 199-200°C. The structural characterization of 3an is shown in Table 1.

[0107] Example 26:

[0108]

[0109] 1o (72.4 mg, 0.2 mmol) and 2a (51.4 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3ao (47.1 mg, 43% yield, 61% ee), a white solid product with a melting point of 207-208°C. The structural characterization of 3da is shown in Table 1.

[0110] Example 27:

[0111]

[0112] 1a (65.2 mg, 0.2 mmol) and 2b (46.6 mg, 0.24 mmol) were reacted by the method of Example 1 to give 3ba (84.6 mg, 86% yield, 0% ee), a white solid product with a melting point of 197-198°C. The structural characterization of 3ba is shown in Table 1.

[0113] Example 28:

[0114]

[0115] 1a (65.2 mg, 0.2 mmol) and 2c (99.4 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3ca (92.6 mg, 65% yield, 77% ee), a white solid product with a melting point of 164-165°C. The structural characterization of 3ca is shown in Table 1.

[0116] Example 29:

[0117]

[0118] 1a (65.2 mg, 0.2 mmol) and 2d (64.8 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3da (77.2 mg, 68% yield, 87% ee), a white solid product with a melting point of 257-258°C. The structural characterization of 3da is shown in Table 1.

[0119] Example 30:

[0120]

[0121] 1a (65.2 mg, 0.2 mmol) and 2e (58.1 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3ea (82.1 mg, 76% yield, 86% ee), a white solid product with a melting point of 194-195°C. The structural characterization of 3ea is shown in Table 1.

[0122] Example 31:

[0123]

[0124] 1a (65.2 mg, 0.2 mmol) and 2f (72.0 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3fa (61.6 mg, 54% yield, 66% ee) as a white oil with a melting point of 197-198°C. The structural characterization of 3fa is shown in Table 1.

[0125] Example 32:

[0126]

[0127] 1a (65.2 mg, 0.2 mmol) and 2g (33.1 mg, 0.24 mmol) were reacted using the method of Example 1 to afford 3ga (65.4 mg, 75% yield, 0% ee), a white solid product with a melting point of 185-186°C. The structural characterization of 3ga is shown in Table 1.

[0128] Example 33:

[0129]

[0130] 1a (65.2 mg, 0.2 mmol) and 2h (58.4 mg, 0.24 mmol) were reacted using the method of Example 1 to afford 3ha (70.5 mg, 65% yield, 99% ee), a white solid product with a melting point of 186-187°C. The structural characterization of 3ha is shown in Table 1.

[0131] Example 34:

[0132]

[0133] 1a (65.2 mg, 0.2 mmol) and 2i (58.4 mg, 0.24 mmol) were reacted by the method of Example 1 to afford 3ia (68.3 mg, 63% yield, 64% ee), a white solid product with a melting point of 180-181°C. The structural characterization of 3ia is shown in Table 1.

[0134] Example 35:

[0135]

[0136] 1d (80.6 mg, 0.2 mmol) and 2f (58.6 mg, 0.24 mmol) were reacted with the method of Example 1 to afford 3fd (85.4 mg, 68% yield, 47% ee), a white solid product with a melting point of 258-259°C. The structural characterization of 3fd is shown in Table 1.

[0137] Example 36:

[0138]

[0139] 1c (72.0 mg, 0.2 mmol) and 2f (58.4 mg, 0.24 mmol) were reacted using the method of Example 1 to afford 3fc (83.1 mg, 72% yield, 36% ee), a white solid product with a melting point of 216-217°C. The structural characterization of 3fc is shown in Table 1.

[0140] Table 1 Structural characterization data of product 3 in Example

[0141]

[0142]

[0143]

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

Claims

1. A method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound, characterized in that: The construction method comprises the following steps: adding a chiral gold catalyst, a silver salt, an anisole derivative, and a solvent to a reaction vessel under argon protection, stirring, adding a 3-diazoindole derivative, and stirring the reaction for a certain period of time to obtain an indole-anisole biaryl compound with carbon-carbon chirality; ； Among them, A 1 = one of methyl, ethyl, and allyl; A 2 = one of benzenesulfonyl, p-toluenesulfonyl, p-methoxybenzenesulfonyl, and 2-naphthalenesulfonyl; A 3 = methyl, methoxy, halogen or hydrogen; A 4 = methyl, halogen or hydrogen; A 5 = one of methyl and hydrogen; B 1 = methyl, ethyl, tert-butyldimethylsilyl; R = hydrogen, phenyl, acetylmethyl, (4-tert-butyl) phenyl, (4-methoxycarbonyl) phenyl, (4-methoxy) phenyl, (3-methoxy) phenyl; The chiral gold catalyst is one or two of Au1, Au2, Au3, and Au4; the structure is as follows: ； The silver salt is one or two of bis(trifluorosulfonyl)imide silver, silver tetrafluoroborate, and silver hexafluoroantimonate; and the solvent is one of dichloromethane, dichloroethane, tetrahydrofuran, and acetonitrile.

2. The method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound according to claim 1, wherein The 3-diazoindole derivatives include the following structural formula: ； ； 。 3. The method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound according to claim 1, wherein: The anisole derivatives include the following structural formula: 。 4. The method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound according to claim 1, wherein: In the reaction, the molar ratio of the chiral gold catalyst to the 3-diazoindole derivative is 0.01-0.1:1; the molar ratio of the 3-diazoindole derivative to the anisole derivative is 1:1.2-1.2:

1.

5. The method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound according to claim 1, wherein: The concentration of 3-diazoindole derivatives is: 0.025~0.2 mol / L.

6. The method for constructing a carbon-carbon axial chiral indole-anisole biaryl compound according to claim 1, wherein: The reaction temperature is 0°C to -10°C, and the reaction time is 2 to 5 hours.

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