CN114478351A - Method for synthesizing alpha-alkyl substituted indole-3-formaldehyde compound - Google Patents

Abstract

The invention discloses a novel method for synthesizing an alpha-alkyl substituted indole-3-formaldehyde compound, which is characterized in that under the existence of magnesium chips, an iron (III) complex containing 1, 3-di (2, 4, 6-trimethylphenyl) imidazole cation is used as a catalyst, and the alpha-alkyl substituted indole-3-formaldehyde compound is synthesized through the hydrogen heteroaromatic reaction of aryl ethylene and indole-3-formaldehyde imine. Compared with the prior art, the method avoids using sensitive and flammable Grignard reagent and additive TMEDA, thereby having higher safety and atom economy, and simultaneously having higher applicability of the substrate, which is the first example of the hydrogen heteroaromatic reaction realized by the iron catalyst under the action of magnesium chips.

Description

A kind of method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds

technical field

The invention belongs to the technical field of organic synthesis and preparation, and particularly relates to a new method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds.

Background technique

α-Alkyl-substituted indole-3-carbaldehydes are a class of important structural fragments, which widely exist in natural products, drugs and bioactive molecules, and have important synthetic value. Over the past decade, transition metal-catalyzed hydroheteroarylation of arylethenes with indoles has gradually developed into a promising method for the synthesis of α-alkyl-substituted indoles due to its 100% atom economy. new method. However, there are only two reports in the literature involving iron-based catalysts. In 2015, Yoshikai's research group used iron acetylacetonate in the presence of sensitive and flammable Grignard reagent cyclohexyl magnesium chloride (CyMgCl) and excess additive N,N,N',N'-tetramethylethylenediamine (TMEDA). (Fe(acca) ₃ ) and imidazolium salt SIXyl∙HCl (SIXyl is 1,3-bis(2,6-dimethylphenyl)imidazoline cation) as the catalytic system to realize the arylethene and indole-3 - Hydrogenheteroarylation of formaldehyde imines. In 2017, Ackermann's research group realized arylethene and indole-3-carbaldehyde in the presence of sensitive and flammable Grignard reagent CyMgCl and excess additive TMEDA, using Fe(acca) ₃ and chiral imidazolium salt as catalytic system. Enantioselective hydroheteroarylation of imines. It can be seen that the hydrogen-heteroarylation of arylethenes and indole compounds catalyzed by iron-based catalysts all require the use of sensitive and flammable Grignard reagents and excess additive TMEDA to make the reaction proceed. Limits its functional group tolerance (e.g., p-trifluoromethylstyrene, p-trimethylsilylstyrene, p-morpholinestyrene, 2-vinylpyridine and 2-vinylbenzofuran, etc., which cannot be tolerated ), while also reducing the atom economy of the reaction. Therefore, it is necessary to develop new preparation methods to improve the safety and industrial applicability of synthesizing α-alkyl-substituted indole-3-carbaldehydes.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a new method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds. base) iron(III) complexes of imidazolium cations as catalysts to synthesize α-alkyl-substituted indole-3-carboxaldehydes through the hydroheteroarylation of arylethene and indole-3-carboxaldehyde imines. The invention does not require Grignard reagents and TMEDA necessary in the prior art, and the catalyst is an iron(III) complex that is easy to obtain, has a well-defined structure and is air-stable.

The present invention adopts following technical scheme:

A method for synthesizing α-alkyl-substituted indole-3-carboxaldehyde compounds, comprising the following steps, in an inert gas atmosphere, a catalyst, magnesium, indole-3-carboxaldehyde imine, aryl vinyl and a solvent, and then carrying out Reaction and acidification to obtain α-alkyl substituted indole-3-carbaldehyde compounds; specifically, acidification with dilute hydrochloric acid after the reaction, extraction with ethyl acetate, separation and purification by column chromatography to obtain α-alkyl Substituted indole-3-carbaldehyde compounds can be quantitatively analyzed. The catalyst is an iron(III) complex containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation.

Application of iron(III) complexes containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cations in the synthesis of α-alkyl-substituted indole-3-carbaldehyde compounds.

In the present invention, the iron(III) complex containing 1,3-bis(2,4,6-trimethylphenyl)imidazolium cation is [HIMes][FeBr ₄ ], and its chemical structural formula is as follows:

In the present invention, indole-3-carboxaldehyde imine is expressed by the following chemical structural formula:

R ¹ is one of hydrogen, methyl, methoxy and fluorine; R ² is methyl or benzyl.

In the present invention, aryl vinyl is expressed by the following chemical structural formula:

Ar is aryl, substituted aryl, heterocyclic aryl; preferably, aryl vinyl includes styrene, o-methoxystyrene, m-methoxystyrene, p-methoxystyrene, p-methylstyrene , p-trifluoromethyl styrene, p-trimethylsilyl styrene, p-dianilino styrene, p-morpholine styrene, 2-vinylnaphthalene, 2-vinylpyridine or 2-vinylbenzofuran .

In the present invention, α-alkyl-substituted indole-3-carbaldehyde compounds are expressed by the following chemical structural formula:

The substituents in the formula are derived from indole-3-carboxaldehyde imine, aryl vinyl.

In the above technical scheme, the temperature of the reaction is 25-80° C., and the time is 16-48 hours.

In the above technical solution, the inert gas is argon or nitrogen; the solvent is tetrahydrofuran, 2-methyltetrahydrofuran, and the like.

In the above technical scheme, the molar ratio of catalyst, magnesium, indole-3-formaldehyde imine, and arylethene is 0.03-0.08:0.8-1:1:1.2-1.6. In a preferred technical solution, the amount of arylethene is 1.5 times that of the indole compounds, the amount of magnesium is 1 times that of the indole compounds, and the amount of the catalyst is 5 times the molar amount of the indole compounds. %; the reaction temperature was 40°C, and the reaction time was 24 hours.

The reaction process of the present invention for preparing α-alkyl-substituted indole-3-carbaldehyde compounds can be expressed as follows:

Due to the application of the above-mentioned technical solutions, the present invention has the following advantages:

1. In the present invention, in the presence of magnesium scraps, the iron (III) complex containing 1,3-bis(2,4,6-trimethylphenyl) imidazolium cation is used as a catalyst to realize arylethene and indole. The hydrogen-heteroarylation of -3-formaldehyde imine provides a new method for the synthesis of α-alkyl-substituted indole-3-carbaldehyde compounds.

2. The preparation method disclosed in the present invention has mild conditions, does not require the use of sensitive and flammable Grignard reagents and excessive additives, has good substrate applicability, and is not only suitable for aryl vinyls containing electron-donating substituents, but also suitable for For aryl vinyls and heterocyclic alkenes containing electron withdrawing substituents.

Detailed ways

The raw material of the present invention is a commercially available product, the specific operation method and testing method are conventional methods in the field, and the yield is the separation yield (except in the table).

Below in conjunction with embodiment, the present invention is further described:

Example 1: Containing 1,3-bis(2,4,6-trimethylphenyl) imidazolium cation (molecular formula is [HIMes][FeBr ₄ ]), ([HIMes] is 1,3-bis(2, Synthesis of iron(III) complexes of 4,6-trimethylphenyl)imidazolium cation).

1,3-Bis(2,4,6-trimethylphenyl)imidazolium bromide (0.38 g, 1.0 mmol) was added to a solution of iron tribromide (0.27 g, 0.9 mmol) in tetrahydrofuran, 60 The reaction was carried out at ^oC for 24 hours, the solvent was removed in vacuo, washed with hexane, dried by suction, extracted with tetrahydrofuran, transferred to the clear liquid by centrifugation, recrystallized by adding hexane to the clear liquid, and a reddish-brown solid powder was precipitated at room temperature with a yield of 85%. The chemical structural formula is as follows:

Elemental analysis of the product showed the following results:

Elemental analysis

Since the iron complexes are paramagnetic, NMR characterizations were not performed.

The complex [HIMes][FeBr ₄ ] exists in the form of an ion pair, and the anion [FeBr ₄ ] ^- was characterized by Raman spectroscopy, and it was found to have a characteristic peak at 204 cm ^-1 , which is similar to the phase reported in the literature. Conforms to (Melissa, SS; Eric, RS; Eric, VP; Freeman, RG, Inorg. Chem. , 2001, 40 , 2298). The cationic part [HIMes] ⁺ of the complex was characterized by mass spectrometry, and it was found that it has a molecular ion peak at 305.2011, which is theoretically at 305.2012, which is consistent with the theory. The obtained compound was proved to be the target compound.

Embodiment 2 [HIMes][FeBr ₄ ] is a catalyst to catalyze the hydrogen heteroarylation reaction of N-benzyl indole-3-carboximine and styrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), styrene (86 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvents, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/L) , 1.5 ml) was acidified, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 93%.

The product was dissolved in CDCl ₃ (approximately 0.4 mL), sealed, and measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.23 (s, 1H), 8.42 ( d, J = 7.6 Hz, 1H), 7.31 – 7.21 (m, 10H), 7.14 (d, J = 8.1 Hz, 1H), 6.95 – 6.86 (m, 2H), 5.22 (s, 2H), 5.05 (q , J = 7.3, 6.8 Hz, 1H), 1.74 (d, J = 7.3 Hz, 3H).

On the basis of the above reaction of styrene and N -benzylindole-3-carboximine, a single factor change was made, and the results were as follows.

^a Reaction conditions: N -benzylindole-3-carbaldehydeimine (0.5 mmol), styrene (0.75 mmol), iron catalyst (5 mol%), additives (0.5 mmol), tetrahydrofuran (1.5 mL), 24 h , the yield of the product was determined by gas phase with n-dodecane as the internal standard. ^bIsolation yield.

The chemical structure of [HItBu][FeBr ₄ ] is as follows:

Example 3 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzyl indole-3-carboximine and o-methoxystyrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), o-methoxystyrene (100 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 25 ^o C for 48 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 96% .

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.21 (s, 1H), 8.44 ( d, J = 7.7 Hz, 1H), 7.42(d, J = 7.5 Hz, 1H), 7.28 (d, J = 3.7 Hz, 2H), 7.24 (d, J = 4.6 Hz, 3H), 7.02– 6.97 ( m, 3H), 6.76 (d, J = 8.2 Hz, 1H), 5.48 (s, 2H), 4.93 (q, J = 7.4 Hz, 1H), 3.61 (s, 3H), 1.66 (d, J = 7.4 Hz, 3H).

Example 4 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzyl indole-3-formaldehyde imine and m-methoxystyrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), m-methoxystyrene (100 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 25 ^o C for 48 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 92% .

The product was dissolved in CDCl ₃ (approximately 0.4 mL), sealed, and measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.23 (s, 1H), 8.42 ( d, J = 7.8 Hz, 1H), 7.31(t, J = 7.8 Hz, 1H), 7.26 – 7.13 (m, 6H), 6.93 – 6.89 (m, 2H), 6.80 (d, J =7.8 Hz, 1H) ), 6.77 – 6.72 (m, 2H), 5.24 (s, 2H), 5.02 (q, J = 7.4 Hz, 1H), 3.72 (s, 3H), 1.73 (d, J = 7.4 Hz, 3H).

Example 5 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydroheteroarylation of N-benzyl indole-3-carboximine and p-methoxystyrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), p-methoxystyrene (104 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 92% .

The product was dissolved in CDCl ₃ (about 0.4 mL), sealed, and measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.23 (s, 1H), 8.44 ( d, J = 7.8 Hz, 1H), 7.31(t, J = 7.5 Hz, 1H), 7.27 – 7.25 (m, 3H), 7.24 – 7.21 (m, 1H), 7.14 (dd, J =12.3, 8.3 Hz , 3H), 6.94 – 6.90 (m, 2H), 6.81 (d, J = 8.8 Hz, 2H), 5.24 (s, 2H), 5.00 (q, J = 7.4 Hz, 1H), 3.77 (s, 3H) , 1.72 (d, J = 7.4 Hz, 3H).

Example 6 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydroheteroarylation of N-benzyl indole-3-carboxaldehyde imine with p-methylstyrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), p-methylstyrene (99 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 40 ^o C for 16 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol /L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 95%.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and it was measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.26 (s, 1H), 8.52 – 8.46 (m, 1H), 7.33 (t, J= 7.5 Hz, 1H), 7.27 (dt, J = 5.6, 2.6 Hz, 3H), 7.23 (d, J = 8.3 Hz, 1H), 7.17(d, J = 8.2 Hz, 1H), 7.12 (s, 4H), 6.97 – 6.92 (m, 2H), 5.26 (s, 2H), 5.03(q, J = 7.4 Hz, 1H), 2.33 (s, 3H), 1.75 (d, J = 7.4 Hz, 3H).

Example 7 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen heteroarylation of N-benzyl indole-3-carboximine and p-trifluoromethyl styrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), p-trifluoromethylstyrene (111 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 60 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid ( 2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 68 %.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.23 (s, 1H), 8.41 ( d, J = 7.8 Hz, 1H), 7.50(d, J = 8.2 Hz, 2H), 7.32 (t, J = 8.5 Hz, 3H), 7.27 – 7.23 (m, 4H), 7.20 (d, J = 8.2 Hz, 1H), 6.89 – 6.84 (m, 2H), 5.24 (s, 2H), 5.13 (d, J = 7.4 Hz, 1H), 1.79 (d, J = 7.3 Hz, 3H).

Example 8 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzylindole-3-carboximine and p-trimethylsilylstyrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), trimethylsilylstyrene (154 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid ( 2 mol/L, 1.5 mL) was acidified, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 92 %.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.26 (s, 1H), 8.47 ( d, J = 7.9 Hz, 1H), 7.45(d, J = 7.7 Hz, 2H), 7.34 (t, J = 7.5 Hz, 1H), 7.27 – 7.22 (m, 6H), 7.18 (d, J = 8.1 Hz, 1H), 6.95 – 6.91 (m, 2H), 5.29 (s, 2H), 5.05 (q, J = 7.4 Hz, 1H), 1.78 (d, J = 7.4 Hz, 3H), 0.28 (s, 9H ).

Example 9 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzyl indole-3-carboximine and p-diphenylaminostyrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), p-diphenylaminostyrene (271.0 mg, 0.75 mmol), tetrahydrofuran (1.5 mL) as solvent, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol) /L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 93%.

The product was dissolved in CDCl ₃ (about 0.4 mL), sealed, and measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.46 (s, 1H), 8.63 ( d, J = 7.8 Hz, 1H), 7.48(d, J = 7.7 Hz, 1H), 7.44 (dt, J = 5.9, 3.2 Hz, 4H), 7.39 (d, J = 7.3 Hz, 3H), 7.32 – 7.26 (m, 3H), 7.23 – 7.14 (m, 9H), 7.12 – 7.09 (m, 2H), 5.57 –5.45 (m, 2H), 5.19 (q, J = 7.3 Hz, 1H), 1.93 (d, J = 7.3 Hz, 3H).

Example 10 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzyl indole-3-carboximine and p-morpholine styrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), p-morpholine styrene (142.0 mg, 0.75 mmol), tetrahydrofuran (1.5 mL) as solvent, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/ liter, 1.5 ml) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 92%.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.24 (s, 1H), 8.45 ( d, J = 7.8 Hz, 1H), 7.34 –7.25 (m, 4H), 7.22 (d, J = 7.2 Hz, 1H), 7.13 (dd, J = 15.1, 8.4 Hz, 3H), 6.92(d, J = 5.0 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 5.25 (s, 2H), 4.98 (q, J = 7.3Hz, 1H), 3.86 (s, 4H), 3.12 (s, 4H) ), 1.72 (d, J = 7.3 Hz, 3H).

Example 11 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydroheteroarylation of N-benzyl indole-3-carboximine and 2-vinylnaphthalene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), 2-vinylnaphthalene (154 mg, 0.75 mmol), tetrahydrofuran (1.5 mL) as solvent, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/ liter, 1.5 ml) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 88%.

The product was dissolved in CDCl ₃ (about 0.4 mL), sealed, and measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.30 (s, 1H), 8.47 ( d, J = 7.9 Hz, 1H), 7.90 – 7.72 (m, 5H), 7.50 (dd, J = 6.7, 3.1 Hz, 2H), 7.36 (s, 1H), 7.28 – 7.23 (m, 4H), 7.19 (s, 1H), 6.92 (d, J = 7.8 Hz, 2H), 5.26 (d, J = 7.9 Hz, 3H), 1.89(s, 3H).

Example 12 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzylindole-3-carboximine and 2-vinylpyridine

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), 2-vinylpyridine (81 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 50 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol /L, 1.5 ml) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 72%.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.24 (s, 1H), 8.45 ( d, J = 7.9 Hz, 1H), 7.33 – 7.26 (m, 3H), 7.25 – 7.19 (m, 6H), 7.14 (d, J = 8.2 Hz, 1H), 6.91 (dd, J =6.9, 2.4 Hz , 2H), 5.23 (s, 2H), 5.05 (q, J = 7.4 Hz, 1H), 1.75 (d, J = 7.4 Hz, 3H).

Example 13 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydroheteroarylation of N-benzyl indole-3-carboximide and 2-vinylbenzofuran

Under the protection of argon, catalyst (33.8 mg, 0.05 mmol, 10 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzylindole-3-carboximide (169.6 mol%) were added to the reaction flask in sequence. mg, 0.5 mmol), 2-vinylbenzofuran (102 μl, 0.75 mmol), and tetrahydrofuran (1.5 ml) as solvents, react at 50 ^o C for 48 hours, quench the reaction with water, add dilute hydrochloric acid ( 2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 54 %.

The product was dissolved in CDCl ₃ (about 0.4 mL), sealed, and measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ δ 10.31 (s, 1H), 8.41 (d , J = 7.8 Hz, 1H), 7.48(d, J = 6.7 Hz, 1H), 7.31 (dt, J = 13.3, 6.4 Hz, 3H), 7.24 – 7.18 (m, 6H), 6.96 (d, J = 6.3 Hz, 2H), 6.57 (s, 1H), 5.44 (s, 2H), 5.13 (q, J = 7.1 Hz, 1H).

Example 14 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-methylindole-3-carbaldehyde imine and styrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-methylindole-3-carboximide (132.2 mol%) were added to the reaction flask in sequence mg, 0.5 mmol), styrene (86 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/l, 1.5 ml) was acidified, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 90%.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and it was measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.26 (s, 1H), 8.42 – 8.37 (m, 1H), 7.34 – 7.23(m, 8H), 5.20 (q, J = 7.4 Hz, 1H), 3.44 (s, 3H), 1.87 (d, J = 7.4 Hz, 3H).

Example 15 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzyl-5-methoxyindole-3-carboxaldehyde imine with styrene

Under the protection of argon, catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-methyl-5-methoxyindole-3 were sequentially added to the reaction flask. -formaldehyde imine (185.1 mg, 0.5 mmol), styrene (86 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) as solvent, react at 40 ^o C for 24 hours, quench the reaction with water, add dilute hydrochloric acid (2 mol/L, 1.5 mL) was acidified, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), and the yield was 91%.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.18 (s, 1H), 7.97 ( d, J = 2.5 Hz, 1H), 7.31 – 7.26 (m, 5H), 7.22 (d, J = 7.6 Hz, 3H), 7.04 (d, J = 8.9 Hz, 1H), 6.94 – 6.90(m, 2H ), 6.86 (dd, J = 8.9, 2.6 Hz, 1H), 5.21 (s, 2H), 4.98 (q, J = 7.4 Hz, 1H), 3.91 (s, 3H), 1.75 (d, J = 7.4 Hz , 3H).

Example 16 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydroheteroarylation of N-benzyl-5-fluoro-indole-3-carboxaldehyde imine with styrene

Under the protection of argon, catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-methyl-5-fluoro-indole-3- Formaldehyde imine (179.1 mg, 0.5 mmol), styrene (86 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) were used as solvents, and the reaction was carried out at 40 ^o C for 24 hours. The reaction was quenched with water, and diluted hydrochloric acid ( 2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 87 %.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.17 (s, 1H), 8.10 ( dd, J = 9.4, 2.6 Hz, 1H), 7.28 (d, J = 7.5 Hz, 5H), 7.25 – 7.19 (m, 3H), 7.07 – 7.03 (m, 1H), 6.95 (td, J = 9.0, 2.6 Hz, 1H), 6.91 – 6.87 (m, 2H), 5.21 (d, J = 1.3 Hz, 2H), 5.00 (q, J = 7.4 Hz, 1H), 1.75 (d, J = 7.4 Hz, 3H) .

Example 17 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzyl-6-chloro-indole-3-carboxaldehyde imine with styrene

Under the protection of argon, catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-methyl-6-chloro-indole-3- Formaldehyde imine (187.1 mg, 0.5 mmol), styrene (86 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) were used as solvents, and the reaction was carried out at 50 ^o C for 24 hours. The reaction was quenched with water, and diluted hydrochloric acid ( 2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 80 %.

The product was dissolved in CDCl ₃ (about 0.4 mL), the tube was sealed, and the characterization was performed on a Unity Inova-400 NMR instrument at room temperature: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.18 (s, 1H), 8.34 ( d, J = 8.4 Hz, 1H), 7.31 –7.27 (m, 5H), 7.21 (dd, J = 16.9, 7.5 Hz, 4H), 7.14 (d, J = 1.7 Hz, 1H), 6.89(dd, J = 7.2, 2.4 Hz, 2H), 5.20 – 5.17 (m, 2H), 4.98 (q, J = 7.4 Hz, 1H), 1.74 (d, J = 7.4 Hz, 3H).

Example 18 Using [HIMes][FeBr ₄ ] as a catalyst to catalyze the hydrogen-heteroarylation of N-benzyl-7-methylindole-3-carboxaldehyde imine with styrene

Under the protection of argon, the catalyst (16.9 mg, 0.025 mmol, 5 mol%), magnesium turnings (12.0 mg, 0.5 mmol), N-benzyl-7-methylindole-3- Formaldehyde imine (177.1 mg, 0.5 mmol), styrene (86 μl, 0.75 mmol), tetrahydrofuran (1.5 ml) were used as solvents, and the reaction was carried out at 80 ^o C for 16 hours. The reaction was quenched with water, and diluted hydrochloric acid ( 2 mol/L, 1.5 mL) for acidification, the reaction product was extracted with ethyl acetate, separated and purified by column chromatography (using a mixed solvent with a volume ratio of ethyl acetate/petroleum ether of 1:5 as the developing solvent), the yield was 86 %.

The product was dissolved in CDCl ₃ (about 0.4 mL), sealed, and measured on a Unity Inova-400 NMR instrument at room temperature. Characterization: ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.21 (s, 1H), 8.36 ( d, J = 7.9 Hz, 1H), 7.31 –7.26 (m, 5H), 7.20 (t, J = 7.6 Hz, 4H), 6.98 (d, J = 7.2 Hz, 1H), 6.85 (d, J= 6.1 Hz, 2H), 5.48 (d, J = 5.7 Hz, 2H), 4.97 (q, J = 7.4 Hz, 1H), 2.44 (s, 3H), 1.69 (d, J = 7.3 Hz, 3H).

In the prior art, the iron-based catalyst-catalyzed hydrogen-heteroarylation of arylethylene and indole-3-formaldehyde imine requires the use of sensitive and flammable Grignard reagents and excess additive TMEDA to make the reaction proceed. This limits its functional group tolerance and potential application value. Therefore, in the present invention, α-alkane is constructed by the hydrogen heteroarylation reaction of arylethene and indole-3-formaldehyde imine under mild conditions with iron(III) complex as catalyst in the presence of magnesium scraps The substituted indole-3-carbaldehyde compounds have obvious innovation, safety and better potential application value.

Claims (10)

1. a method for synthesizing α-alkyl-substituted indole-3-formaldehyde compounds, is characterized in that, comprises the following steps, in inert gas atmosphere, mixed catalyst, magnesium, indole-3-carboxaldehyde imine, aromatic base ethylene and a solvent, then react and acidify to obtain α-alkyl-substituted indole-3-carbaldehyde compounds; the catalyst is an iron (III) complex containing imidazolium cations. 2. The method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds according to claim 1, characterized in that, acidifying with hydrochloric acid. 3. The method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds according to claim 1, wherein the catalyst is [HIMes][FeBr ₄ ]. 4. the method for synthesizing α-alkyl-substituted indole-3-carboxaldehyde compounds according to claim 1, is characterized in that, indole-3-carboxaldehyde imine is expressed by following chemical structural formula:

R ¹ is one of hydrogen, methyl, methoxy and fluorine; R ² is methyl or benzyl; Aryl vinyls are represented by the following chemical structural formulas:

Ar is an aryl group, a substituted aryl group, or a heterocyclic aryl group. 5. the method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds according to claim 4, is characterized in that, aryl vinyl comprises styrene, o-methoxystyrene, m-methoxystyrene, p-methoxystyrene, p-methylstyrene, p-trifluoromethylstyrene, p-trimethylsilylstyrene, p-dianilinostyrene, p-morpholine styrene, 2-vinylnaphthalene, 2 - vinylpyridine or 2-vinylbenzofuran. 6 . The method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds according to claim 1 , wherein the temperature of the reaction is 25-80° C. and the time is 16-48 hours. 7 . 7. the method for synthesizing α-alkyl-substituted indole-3-carboxaldehyde compounds according to claim 1, is characterized in that, the mol ratio of catalyst, magnesium, indole-3-carboxaldehyde imine, arylethene is 0.03 ~0.08:0.8~1:1:1.2~1.6. 8. The α-alkyl-substituted indole-3-carbaldehyde compounds prepared by the method for synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds according to claim 1. 9. The application of the iron (III) complex containing imidazolium cation in the reaction of synthesizing α-alkyl-substituted indole-3-carbaldehyde compounds, wherein the iron (III) complex containing imidazolium cation is [HIMes] [FeBr ₄ ]. 10. The use according to claim 9, wherein the reaction is carried out in the presence of magnesium.