A free radical amino group migration method from alkyl carbon to aryl carbon

Abstract

The present invention discloses a radical-type amino migration method from alkyl carbon to aryl carbon, and further provides a one-pot synthesis strategy for benzolactam and primary arylamine based on this migration method. The radical-type amino migration method from alkyl carbon to aryl carbon in the present invention is carried out under light irradiation. Under the action of a photocatalyst, an additive, and a small molecule catalyst, the compound of formula (I) undergoes a photocatalytic reaction in an organic solvent to obtain the amino migration product of formula (II), realizing the 1,4- or 1,5-migration of amino group from C(sp<supgt;3< / supgt;) to C(sp<supgt;2< / supgt>). The method of the present invention has the advantages of simple and easily available raw materials, mild reaction conditions, wide substrate applicability, etc., meets the requirements of the development of green and environmentally friendly chemistry, and is expected to be widely applied in the synthesis and modification of pharmaceutical molecules.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a free radical amino group migration method from an alkyl carbon to an aryl carbon. Background Art

[0002] The rapid development of free radical chemistry over the past decade has brought more diverse platforms for the construction and reorganization of molecules. Hydrogen atom transfer (HAT) has attracted great attention, based on which C(sp 3 )-H bonds are then functionalized by C–H functionalization. Many reactive radical species (such as radicals centered on O-, S-, N-, Cl-, and Br) and photocatalysts (such as aromatic ketones, decatungstate anions, and neutral eosin Y) have been developed and utilized, which can abstract hydrogen and promote intermolecular HAT. At the same time, intramolecular HAT has also made great progress, especially for aromatic-mediated intramolecular HAT, which is a highly active intermediate with strong hydrogen abstraction ability for aliphatic C–H bonds.

[0003] Based on this intramolecular HAT pattern, can other atoms or functional groups (FG) also undergo C(sp 3 ) to C(sp 3 ) is a similar transfer process. However, this is relatively more difficult. First, the radius of other atoms is larger than that of hydrogen atoms, and aromatic groups can preferentially capture hydrogen atoms in the reaction system. In addition, for atoms with multiple empty orbitals, the intramolecular cyclization process is also a highly competitive reaction process.

[0004] Traditional FG migration mainly focuses on C(sp 3 )-C(sp 3 ) framework, i.e., a given FG is transferred from one site on the alkyl chain to another, and the second site may need to be activated or directly CH functionalized. 3 )-C(sp 3 ) framework has been widely reported. 3 ) migration variants have also been proposed and studied, including nitrogen, boron and sulfur. Recently, the ester and hydroxyl groups have been synthesized in C(sp 2 )-C(sp 2 ) framework has also been found. However, C(sp 2 )-C(sp 2 ) framework is extremely rare, and the sporadic early reaction studies were not chemically selective and lacked methodological significance.

[0005] Amino group migration also has important research value because alkylamines and amino acids have a wide range of sources, but for a long time, the migration reaction of amino groups in alkyl chains or aromatic rings has received less attention in the synthesis community.

[0006] Han Bing's research group at Lanzhou University reported a remote amino migration reaction based on a readily available oxime ether model, achieving a mild and efficient synthesis of a series of functionalized β(γ)-primary amino ketones under non-metallic conditions (DOI: 10.1002 / anie.202110583). In addition to polyfluoroalkyl radicals, fluorine-free electron-deficient alkyl radicals, electron-rich alkyl radicals, and azide radicals are also applicable to the remote amino migration.

[0007] The electronegativity of nitrogen makes the dissociation energy of C–N bond very high, which may make the migration of amino group relatively difficult. 2 )-C(sp 2 ) framework has important research significance. Summary of the invention

[0008] The present invention provides a method for free radical amino group migration from alkyl carbon to aryl carbon. The reaction is efficient and has mild conditions, and can quickly realize the migration reaction of amino groups on carbons with different properties.

[0009] The technical solution of the present invention is as follows:

[0010] A method for free radical amino group migration from alkyl carbon to aryl carbon, comprising:

[0011] Under light conditions, the compound of formula (I) undergoes a photocatalytic reaction in an organic solvent under the action of a photocatalyst, an additive, and a small molecule catalyst to obtain an amino migration product of formula (II);

[0012] ;

[0013] Wherein, the Ar ring is a benzene ring, a heteroaromatic ring, a condensed aromatic ring or a condensed heteroaromatic ring;

[0014] [N] is ;

[0015] EWG is an electron withdrawing group; LG is a leaving group; n is 1 or 2;

[0016] R is selected from substituted or unsubstituted alkyl, aryl, alkenyl, alkynyl, alkoxy, benzyl, ester, and halide.

[0017] The present invention also provides a method for preparing a benzolactam compound, comprising:

[0018] Under light conditions, the compound of formula (III) undergoes a photocatalytic reaction in an organic solvent under the action of a photocatalyst, an additive, and a small molecule catalyst, and is then further acidified to obtain a benzolactam compound of formula (IV);

[0019] ;

[0020] Wherein, the Ar ring is a benzene ring, a heteroaromatic ring, a condensed aromatic ring or a condensed heteroaromatic ring;

[0021] [N] is ;

[0022] LG is a leaving group; n is 1 or 2;

[0023] R 1 is selected from substituted or unsubstituted alkyl, aryl, alkenyl, alkynyl, alkoxy, benzyl, ester, and halide; R 2 Selected from substituted or unsubstituted alkyl and aryl.

[0024] The present invention also provides a method for preparing a primary aromatic amine compound, comprising:

[0025] Under light conditions, the compound of formula (V) undergoes a photocatalytic reaction in an organic solvent under the action of a photocatalyst, an additive, and a small molecule catalyst, and is then further acidified to obtain a primary aromatic amine compound of formula (VI);

[0026] ;

[0027] Wherein, the Ar ring is a benzene ring, a heteroaromatic ring, a condensed aromatic ring or a condensed heteroaromatic ring;

[0028] [N] is ;

[0029] LG is a leaving group; n is 1 or 2;

[0030] R 1 is selected from substituted or unsubstituted alkyl, aryl, alkenyl, alkynyl, alkoxy, benzyl, ester, and halide; R 2 and R 3 Independently selected from substituted or unsubstituted alkyl, aryl, and tert-butyloxycarbonyl.

[0031] Preferably, the LG is a halogen group.

[0032] Preferably, the photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate (Ir(ppy) 2 (dtbbpy)PF 6), bis[2-(2,4-difluorophenyl)-5-trifluoromethylpyridine][2-2'-bi(4-tert-butylpyridine)]iridium hexafluorophosphate (Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 )、Tris(2,2'-bipyridyl)ruthenium di(hexafluorophosphate)(Ru(bpy) 3 (PF 6 ) 2 ) at least one of the following.

[0033] Preferably, the additive is N -(1-adamantyl)-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane-2-amine, N -Isopropyl-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane-2-amine, N -tert-butyl-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane-2-amine.

[0034] Preferably, the small molecule catalyst is at least one of tetrabutylammonium salt, tetrapropylammonium salt, tetraethylammonium salt, tetrabutylphosphonium salt, tetrapropylphosphonium salt and tetraethylphosphonium salt.

[0035] Preferably, the organic solvent is at least one of toluene, 1,4-dioxane, tetrahydrofuran, acetonitrile, ether, ethyl acetate, 1,2-dichloroethane and chloroform.

[0036] Preferably, the reagent used for acidification is hydrochloric acid and the solvent is tetrahydrofuran.

[0037] Preferably, based on the molar amount of the compound of formula (I), formula (III) or formula (V), the molar amount of the photocatalyst is 1-10%; the molar amount of the additive is 100-200%; the molar amount of the small molecule catalyst is 10-50%; and the concentration of the compound of formula (I), formula (III) or formula (V) in the reaction solution is 0.1-0.5 mol / L.

[0038] Furthermore, during the acidification process, the molar amount of the acid is 300% based on the molar amount of the compound of formula (III) or formula (V).

[0039] Preferably, an inert gas is used as a protective gas, and the photocatalytic reaction is carried out at room temperature. The wavelength of light for the photocatalytic reaction is 370-467 nm; the photocatalytic reaction time is 9-36 h; and the acidification reaction is 2 h.

[0040] Preferably, the compound of formula (I) is selected from:

[0041] .

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] The present invention provides a new type of amino group migration reaction method from alkyl carbon to aryl carbon, which can smoothly realize C(sp 3 ) to C(sp 2 ) free radical amino migration; at the same time, a series of substituted benzolactams and primary aromatic amines were synthesized in a one-pot method. In particular, there is currently no general method for synthesizing mono-substituted or poly-substituted benzolactams.

[0044] The method of the present invention has the advantages of readily available raw materials, mild reaction conditions, wide substrate applicability, etc., and meets the requirements for developing green and environmentally friendly chemistry; the method of the present invention is novel and simple, and is expected to be widely used in the synthesis and modification of drug molecules. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 is a diagram of the free radical amino group migration mechanism from the alkyl carbon to the aryl carbon in an embodiment of the present invention;

[0046] Figure 2 is the H NMR spectrum of Example 1 of the present invention;

[0047] Figure 3 is the NMR carbon spectrum of Example 1 of the present invention;

[0048] Figure 4 is the H NMR spectrum of Example 4 of the present invention;

[0049] Figure 5 is the NMR carbon spectrum of Example 4 of the present invention;

[0050] Figure 6 is the H NMR spectrum of Example 8 of the present invention;

[0051] Figure 7 is the NMR carbon spectrum of Example 8 of the present invention;

[0052] Figure 8 is the H NMR spectrum of Example 11 of the present invention;

[0053] Fig. 9 is the NMR carbon spectrum of Example 11 of the present invention;

[0054] Fig.10 is the H NMR spectrum of Example 15 of the present invention;

[0055] Fig.11 is the NMR carbon spectrum of Example 15 of the present invention;

[0056] Fig.12 is the H NMR spectrum of Example 18 of the present invention;

[0057] Fig.13 is the NMR carbon spectrum of Example 18 of the present invention;

[0058] Fig.14 is the H NMR spectrum of Example 19 of the present invention;

[0059] Fig.15 is the NMR carbon spectrum of Example 19 of the present invention;

[0060] Fig.16 is the H NMR spectrum of Example 20 of the present invention;

[0061] Fig.17 This is the NMR carbon spectrum of Example 20 of the present invention. DETAILED DESCRIPTION

[0062] The present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be pointed out that the embodiments described below are intended to facilitate the understanding of the present invention and do not have any limiting effect on the present invention.

[0063] In the embodiment, the migration precursor is selected from any one of the following:

[0064] .

[0065] In the embodiment, the migration product is selected from any one of the following:

[0066] .

[0067] The benzolactam synthesized in the embodiment is any one of the following:

[0068] .

[0069] The primary aromatic amine synthesized in the embodiment is any one of the following:

[0070] .

[0071] General Procedure A:

[0072]

[0073] Using nitrogen as protective gas, the migration precursor (0.2 mmol), 4CzIPN (8 mg, 0.01 mmol), (TMS) were added in sequence into a dry reaction bottle (8 mL) equipped with a magnetic stirrer. 3 SiNHAd (119 mg, 0.3 mmol) and TBAB (16 mg, 0.05 mmol) were added, and then the reaction bottle was placed in a glove box, and solvent toluene (1.0 mL) was added. The reaction was irradiated by a 40 W 440 nm blue LED lamp at room temperature and stirred for an appropriate time. The reaction was monitored by TLC. After the reaction was completed, the reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the product.

[0074] General Procedure B:

[0075]

[0076] In a dry reaction bottle (8 mL) equipped with a magnetic stirrer, the migration precursor (0.2 mmol), 4CzIPN (8 mg, 0.01 mmol), (TMS) 3 SiNHAd (119 mg, 0.3 mmol) and TBAB (16 mg, 0.05 mmol) were added, and then the reaction bottle was placed in a glove box, and solvent toluene (1.0 mL) was added. The reaction was irradiated by a 40 W 440 nm blue LED lamp at room temperature and stirred for an appropriate time. TLC was used to monitor the reaction. After the reaction was completed, the reaction solution was concentrated under reduced pressure without post-treatment. 3 M HCl (0.6 mmol) and THF (1.0 mL) were then added to the residue and stirred at room temperature for 2 h. Saturated NaHCO was then added to the reaction solution. 3 (2.0 mL), ethyl acetate (3 mL 3) Extraction. The organic phases were combined, dried and concentrated, and purified by silica gel column chromatography to obtain the product.

[0077] General Procedure C:

[0078]

[0079] In a dry reaction bottle (8 mL) equipped with a magnetic stirrer, the migration precursor (0.2 mmol), 4CzIPN (8 mg, 0.01 mmol), (TMS) 3 SiNHAd (119 mg, 0.3 mmol) and TBAB (16 mg, 0.05 mmol) were added, and then the reaction bottle was placed in a glove box, and solvent toluene (1.0 mL) was added. The reaction was irradiated by a 40 W 440 nm blue LED lamp at room temperature and stirred for an appropriate time. TLC was used to monitor the reaction. After the reaction was completed, the reaction solution was concentrated under reduced pressure without post-treatment. 3 M HCl (0.6 mmol) and THF (1.0 mL) were then added to the residue and stirred at room temperature for 2 h. Saturated NaHCO was then added to the reaction solution. 3 (2.0 mL), chloroform (3 mL 3) Extraction. The organic phases were combined, dried and concentrated, and purified by silica gel column chromatography to obtain the product.

[0080] In order to make the purpose, technical scheme and advantages of the present invention more clearly understood, the free radical amino migration reaction from alkyl carbon to aryl carbon of the present invention is further described in conjunction with the following specific examples.

[0081] Example 1: Methyl 3-(2-((benzhydryl)amino)phenyl)-2-methylpropanoate

[0082]

[0083] Using S1 as the starting material, the reaction was carried out according to the general procedure A for 9 h to obtain a light yellow oil (61 mg, yield 86%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.84 – 7.76 (m, 2H), 7.51 – 7.38 (m, 3H), 7.27 (d, J =5.1 Hz, 3H), 7.12 (dd, J = 7.4, 2.2 Hz, 2H), 7.05 (dd, J = 7.3, 1.7 Hz, 1H), 6.88(ddd, J = 12.4, 7.4, 1.6 Hz, 2H), 6.38 (dd, J = 7.6, 1.5 Hz, 1H), 3.59 (s, 3H), 3.06 – 2.91 (m, 2H), 2.70 – 2.65 (m, 1H), 1.18 (d, J= 6.8 Hz, 3H). 13 C NMR (100MHz, CDCl 3 ) δ 177.19, 167.00, 149.64, 139.57, 136.33, 130.74, 130.61, 129.86,129.45, 129.12, 128.72, 128.27, 128.04, 126.60, 123.46, 120.10, 51.60, 39.25,36.36, 17.25.HRMS (ESI-TOF) m / z calcd. for C 24 H 24 NO 2 + ([M+H] + ) 358.1802, found:358.1800.

[0084] Example 2: Methyl 3-(2-((benzhydryl)amino)-5-methoxyphenyl)-2-methylpropanoate

[0085]

[0086] Using S3 as the starting material, the reaction was carried out according to the general procedure A for 36 h to obtain a light yellow oil (59 mg, yield 76%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.83 – 7.73 (m, 2H), 7.48 – 7.43 (m, 1H), 7.40 (dd, J = 8.2, 6.4 Hz, 2H), 7.29 (dd, J = 5.2, 2.0 Hz, 3H), 7.17 – 7.08 (m, 2H), 6.65(d, J = 2.9 Hz, 1H), 6.42 (d, J = 2.9 Hz, 1H), 6.25 (d, J = 8.7 Hz, 1H), 3.70 (s,3H), 3.60 (s, 3H), 3.04 – 2.92 (m, 2H), 2.80 – 2.69 (m, 1H), 1.19 (d, J = 6.4Hz, 3H). 13 C NMR (100 MHz, CDCl 3) δ 177.15, 166.45, 155.95, 142.73, 139.86,136.64, 133.12, 130.53, 129.32, 129.22, 128.58, 128.22, 128.18, 121.16,115.31, 111.68, 55.38, 51.66, 39.54, 36.65, 17.29. HRMS (ESI-TOF) m / z calcd.for C 25 H 26 NO 3 + ([M+H] + ) 388.1907, found: 388.1904.

[0087] Example 3: Methyl 3-(2-((benzhydryl)amino)-4-fluorophenyl)-2-methylpropanoate

[0088]

[0089] Using S6 as the starting material, the reaction was carried out according to the general procedure A for 9 h to obtain a light yellow oil (64 mg, yield 85%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.82 – 7.76 (m, 2H), 7.52 – 7.47 (m, 1H), 7.42 (dd, J =8.3, 6.8 Hz, 2H), 7.33 – 7.27 (m, 3H), 7.15 – 7.09 (m, 2H), 6.99 (dd, J = 8.5,6.2 Hz, 1H), 6.59 – 6.53 (m, 1H), 6.11 (dd, J = 10.1, 2.7 Hz, 1H), 3.59 (s,3H), 3.00 – 2.84 (m, 2H), 2.65 – 2.60 (m, 1H), 1.17 (d, J = 6.9 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 177.02, 167.90, 161.47 (d, J = 244.1 Hz), 150.97 (d, J= 3.6Hz), 139.13, 135.77, 131.08, 130.86 (d, J = 9.1 Hz), 129.54, 129.08, 128.93,128.35, 128.24, 126.31 (d, J = 3.2 Hz), 109.90 (d, J = 21.1 Hz), 107.16 (d, J =23.1 Hz), 51.66, 39.28, 35.71, 17.28. HRMS (ESI-TOF) m / z calcd. for C 24 H 23 FNO 2 + ([M+H] + ) 376.1707, found: 376.1702.

[0090] Example 4: Methyl 3-(2-((benzhydryl)amino)-4-chlorophenyl)-2-methylpropanoate

[0091]

[0092] Using S7 as the starting material, the reaction was carried out according to the general procedure A for 12 h to obtain a light yellow oil (56 mg, yield 70%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.82 – 7.76 (m, 2H), 7.52 – 7.46 (m, 1H), 7.42 (dd, J =8.2, 6.6 Hz, 2H), 7.33 – 7.28 (m, 3H), 7.12 (dd, J = 7.6, 2.0 Hz, 2H), 6.98 (d, J = 8.2 Hz, 1H), 6.83 (dd, J = 8.1, 2.2 Hz, 1H), 6.39 (d, J = 2.1 Hz, 1H), 3.60(s, 3H), 3.02 – 2.86 (m, 2H), 2.65 – 2.61 (m, 1H), 1.18 (d, J = 6.9 Hz, 3H). 13 CNMR (100 MHz, CDCl 3) δ 176.88, 168.04, 150.74, 139.10, 135.74, 131.89,131.09, 130.88, 129.54, 129.10, 129.08, 128.91, 128.35, 128.23, 123.25,120.03, 51.66, 39.10, 35.77, 17.29. HRMS (ESI-TOF) m / z calcd. for C 24 H 23 ClNO 2 + ([M+H] + ) 392.1412, found: 392.1407.

[0093] Example 5: Methyl 3-(2-((benzhydryl)amino)-4-bromophenyl)-2-methylpropanoate

[0094]

[0095] Using S9 as the starting material, the reaction was carried out according to the general procedure A for 24 h to obtain a light yellow oil (39 mg, yield 45%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.78 (d, J = 7.2 Hz, 2H), 7.51 – 7.38 (m, 3H), 7.32 –7.28 (m, 3H), 7.14 – 7.09 (m, 2H), 6.99 – 6.89 (m, 2H), 6.53 (d, J = 2.0 Hz,1H), 3.60 (s, 3H), 2.98– 2.84 (m, 2H), 2.64 – 2.58 (m, 1H), 1.17 (d, J = 6.9Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) 176.87, 168.10, 150.97, 139.12, 135.76,131.22, 131.11, 129.66, 129.57, 129.13, 128.95, 128.37, 128.25, 126.20,122.93, 119.85, 51.68, 39.06, 35.85, 17.31. HRMS (ESI-TOF) m / z calcd. forC 24H 23 BrNO 2 + ([M+H] + ) 436.0907, found: 436.0905.

[0096] Example 6: Methyl 3-(2-((benzhydryl)amino)-4-cyanophenyl)-2-methylpropanoate

[0097]

[0098] Using S11 as the starting material, the reaction was carried out according to the general procedure A for 12 h to obtain a light yellow oil (54 mg, yield 71%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.79 (d, J = 7.3 Hz, 2H), 7.54 – 7.48 (m, 1H), 7.43 (dd, J = 8.3, 6.8 Hz, 2H), 7.31 (dd, J = 8.9, 7.0 Hz, 3H), 7.18 – 7.12 (m, 2H), 7.08(dd, J = 7.8, 1.7 Hz, 2H), 6.62 (d, J = 1.4 Hz, 1H), 3.60 (s, 3H), 3.05 – 2.95 (m, 2H), 2.78 – 2.69 (m, 1H), 1.19 (d, J = 6.7 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 )δ 176.48, 169.05, 150.46, 138.70, 136.61, 135.33, 131.44, 130.59, 129.65,129.41, 128.79, 128.44, 126.98, 123.22, 119.00, 110.32, 51.79, 38.77, 36.34,17.48. HRMS (ESI-TOF) m / z calcd. for C 25 H 26 N 2 O 2 + ([M+H] + ) 383.1754, found:383.1750.

[0099] Example 7: Methyl 3-(2-((benzhydryl)amino)-3-pyridyl)-2-methylpropanoate

[0100]

[0101] Using S14 as the starting material, the reaction was carried out according to the general procedure A for 12 h to obtain a light yellow oil (34 mg, yield 47%). 1 HNMR (400 MHz, CDCl 3 ) δ 8.12 (dd, J = 4.8, 1.6 Hz, 1H), 7.83 – 7.78 (m, 2H), 7.53 – 7.47 (m, 1H), 7.43 (dd, J = 8.2, 6.6 Hz, 2H), 7.28 (dd, J = 8.2, 2.1 Hz,3H), 7.13 – 7.07 (m, 2H), 6.83 (dd, J = 7.9, 4.8 Hz, 1H), 6.64 (dd, J = 8.0, 1.6Hz, 1H), 3.64 (s, 3H), 3.27 – 3.12 (m, 2H), 2.91 – 2.86 (m, 1H), 1.23 (d, J =7.0 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 177.28, 169.00 150.62, 145.56, 144.16,139.02, 135.76, 131.23, 129.58, 129.08, 128.98, 128.40, 128.30, 126.78,121.22, 51.72, 37.78, 37.45, 17.26. HRMS (ESI-TOF) m / z calcd. for C 23 H 23 N 2 O 2 + ([M+H] + ) 359.1754, found: 359.1750.

[0102] Example 8: Methyl 3-(2-((benzhydryl)amino)phenyl)propanoate

[0103]

[0104] Using S15 as the starting material, the reaction was carried out according to the general procedure A for 12 h to obtain a light yellow oil (36 mg, yield 52%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.83 – 7.74 (m, 2H), 7.50 – 7.45 (m, 1H), 7.41 (dd, J =8.2, 6.5 Hz, 2H), 7.27 – 7.26 (m, 3H), 7.11 (ddd, J = 8.9, 4.3, 1.8 Hz, 3H), 6.94 – 6.84 (m, 2H), 6.37 (dd, J = 7.3, 1.8 Hz, 1H), 3.64 (s, 3H), 2.94 – 2.88(m, 2H), 2.74 – 2.66 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ) δ 173.96, 167.30,149.60, 139.56, 136.28, 131.36, 130.80, 129.50, 129.15, 128.95, 128.79,128.30, 128.07, 126.61, 123.64, 120.02, 51.68, 33.66, 27.57. HRMS (ESI-TOF)m / z calcd. for C 23 H 22 NO 2 + ([M+H] + ) 344.1645, found: 344.1640.

[0105] Example 9: Methyl 3-cyclopropyl-2-(2-((benzhydryl)amino)benzyl)propanoate

[0106]

[0107] Using S15 as the starting material, the reaction was carried out according to the general procedure A for 12 h to obtain a light yellow oil (48 mg, yield 60%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.80 (d, J= 7.4 Hz, 2H), 7.49 – 7.44 (m, 1H), 7.40 (dd, J = 8.2, 6.9 Hz, 2H), 7.30 – 7.26 (m, 3H), 7.14 (dd, J = 7.3, 2.2 Hz, 2H), 7.06(d, J = 7.2 Hz, 1H), 6.94 – 6.78 (m, 2H), 6.36 (d, J = 7.6 Hz, 1H), 3.58 (s, 3H), 3.06 – 2.99 (m, 1H), 2.94 – 2.77 (m, 2H), 1.52 – 1.37 (m, 2H), 0.68 – 0.62(m, 1H), 0.40 – 0.23 (m, 2H), -0.03 – -0.08 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ) δ176.73, 166.86, 149.48, 139.62, 136.24, 130.89, 130.72, 129.72, 129.44,129.17, 128.73, 128.22, 128.04, 126.56, 123.50, 119.99, 51.44, 45.89, 37.70,35.00, 9.23, 4.53. HRMS (ESI-TOF) m / z calcd. for C 27 H 28 NO 2 + ([M+H] + ) 398.2115,found: 398.211.

[0108] Example 10: Methyl 2-benzyl-3-(2-((benzhydryl)amino)phenyl)propanoate

[0109]

[0110] Using S19 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (67 mg, yield 77%). 1 HNMR (400 MHz, CDCl 3) δ 7.81 – 7.77 (m, 2H), 7.53 – 7.50 (m, 1H), 7.47 – 7.43(m, 2H), 7.26 – 7.21 (m, 3H), 7.10 – 7.03 (m, 8H), 6.94 – 6.84 (m, 2H), 6.38(dd, J = 7.6, 1.5 Hz, 1H), 3.49 (s, 3H), 3.34 – 3.29 (m, 1H), 3.07 – 2.99(m,1H), 2.89 – 2.77 (m, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 175.98, 166.95, 149.55,139.55, 139.22, 136.18, 130.74, 130.28, 129.94, 129.56, 129.14, 128.94,128.71, 128.35, 128.24, 127.97, 126.71, 126.27, 123.48, 120.06, 51.44, 46.87,38.67, 35.21. HRMS (ESI-TOF) m / z calcd. for C 30 H 28 NO 2 + ([M+H] + ) 434.2115, found:434.2111.

[0111] Example 11: Methyl 3-tert-butoxy-2-(2-((benzhydryl)amino)benzyl)propanoate

[0112]

[0113] Using S21 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (64 mg, yield 74%). 1 HNMR (400 MHz, CDCl 3 ) ) δ 7.84 – 7.78 (m, 2H), 7.49 – 7.45 (m, 1H), 7.41 (dd, J = 8.2, 6.4 Hz, 2H), 7.28 – 7.26 (m, 3H), 7.15 (dd, J = 7.6, 2.1 Hz, 2H), 7.10(dd, J= 7.3, 1.8 Hz, 1H), 6.92 – 6.83 (m, 2H), 6.36 (dd, J = 7.5, 1.6 Hz, 1H),3.59 (s, 3H), 3.55 (d, J = 8.0 Hz, 1H), 3.49 (dd, J = 8.7, 5.1 Hz, 1H), 3.17 –3.11 (m, 1H), 2.95 – 2.80 (m, 2H), 1.10 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ) δ175.23, 167.00, 149.55, 139.57, 136.29, 130.70, 130.48, 129.84, 129.52,129.18, 128.70, 128.21, 128.02, 126.59, 123.47, 120.03, 73.03, 62.82, 51.49,46.46, 31.60, 27.52. HRMS (ESI-TOF) m / z calcd. for C 28 H 32 NO 3 + ([M+H] + ) 430.2377,found: 430.2373.

[0114] Example 12: 2-(2-(((diphenylmethylene)amino)benzyl)-3-methoxy-3-oxopropyl)-1 H -Indole-1-carboxylic acid tert-butyl ester

[0115]

[0116] Using S23 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (65 mg, yield 57%). 1 HNMR (400 MHz, CDCl 3 ) ) δ 7.78 – 7.74 (m, 2H), 7.47 (d, J = 7.4 Hz, 1H), 7.42 –7.38 (m, 2H), 7.33 (dd, J = 6.0, 3.4 Hz, 2H), 7.29 (d, J= 7.4 Hz, 2H), 7.24 –7.21 (m, 3H), 7.10 – 7.04 (m, 4H), 6.95 – 6.85 (m, 2H), 6.39 (dd, J = 7.6, 1.5Hz, 1H), 3.47 (s, 3H), 3.36 – 3.30 (m, 1H), 3.11 – 3.05 (m, 1H), 3.02 – 2.87(m, 3H), 1.64 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ) δ 176.02, 167.10, 149.51,139.44, 136.20, 130.86, 130.78, 130.33, 129.77, 129.39, 129.13, 128.71,128.41, 128.28, 128.01, 127.71, 126.79, 124.28, 123.58, 123.41, 122.48,120.24, 119.01, 118.37, 115.26, 83.43, 51.53, 45.96, 35.81, 28.36, 27.93.HRMS (ESI-TOF) m / z calcd. for C 37 H 37 N 2 O 4 + ([M+H] + ) 573.2748, found: 573.2745.

[0117] Example 13: Diethyl 2-(2-((benzhydryl)amino)benzyl)malonate

[0118]

[0119] Using S25 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (71 mg, yield 82%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.84 – 7.77 (m, 2H), 7.50 – 7.45 (m, 1H), 7.41 (dd, J =8.2, 6.5 Hz, 2H), 7.29 – 7.26 (m, 3H), 7.17 – 7.13 (m, 2H), 7.11 (dd,J = 7.5,1.6 Hz, 1H), 6.93 – 6.88 (m, 1H), 6.86 – 6.82 (m, 1H), 6.35 (dd, J = 7.6, 1.4Hz, 1H), 4.12 (dq, J = 7.1, 1.7 Hz, 4H), 4.04 (t, J = 7.7 Hz, 1H), 3.20 (d, J = 7.7Hz, 2H), 1.15 (t, J = 7.1 Hz, 6H). 13 C NMR (100 MHz, CDCl 3 ) δ 169.48, 167.26,149.48, 139.43, 136.20, 130.82, 130.10, 129.54, 129.28, 129.14, 128.80,128.24, 128.09, 127.06, 123.60, 120.08, 61.39, 51.13, 32.00, 14.12. HRMS(ESI-TOF) m / z calcd. for C 27 H 28 NO 4 + ([M+H] + ) 430.2013, found: 430.2009.

[0120] Example 14: Methyl 2-(2-((benzhydryl)amino)benzyl)-4-pentynoate

[0121]

[0122] Using S30 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (28 mg, yield 37%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.82 – 7.78 (m, 2H), 7.49 – 7.45 (m, 1H), 7.41 (dd, J =8.2, 6.5 Hz, 2H), 7.29 – 7.26 (m, 3H), 7.15 – 7.11 (m, 2H), 7.09 (dd, J= 7.5,1.6 Hz, 1H), 6.95 – 6.85 (m, 2H), 6.38 (dd, J = 7.7, 1.4 Hz, 1H), 3.62 (s, 3H), 3.21 – 3.15 (m, 1H), 2.94 (dd, J = 7.4, 3.0 Hz, 2H), 2.50 – 2.45 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ) δ 174.78, 167.20, 149.65, 139.46, 136.25, 130.78, 130.04,129.76, 129.54, 129.08, 128.75, 128.22, 128.06, 126.92, 123.57, 120.16,81.60, 70.10, 51.82, 44.09, 34.01, 21.14. HRMS (ESI-TOF) m / z calcd. forC 26 H 24 NO 2 + ([M+H] + ) 382.1802, found: 382.1798.

[0123] Example 15: Methyl 3-(2-((benzhydryl)amino)phenyl)butyrate

[0124]

[0125] Using S31 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (58 mg, yield 81%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.80 (d, J = 8.1 Hz, 2H), 7.47 (t, J = 7.2 Hz, 1H), 7.41(t, J = 7.4 Hz, 2H), 7.26 – 7.22 (m, 3H), 7.18 – 7.11 (m, 3H), 6.94 – 6.87 (m,2H), 6.41 (d, J = 7.5 Hz, 1H), 3.61 (s, 3H), 3.53 (q, J= 7.1 Hz, 1H), 2.74 –2.63 (m, 1H), 2.56 – 2.48 (m, 1H), 1.25 (dd, J = 6.9, 1.9 Hz, 3H). 13 C NMR (100MHz, CDCl 3 ) δ 173.27, 166.96, 148.64, 139.69, 136.27, 136.20, 130.70, 129.50,129.34, 128.71, 128.26, 127.99, 126.24, 125.97, 123.79, 120.38, 51.54, 41.14,31.37, 20.50. HRMS (ESI-TOF) m / z calcd. for C 24 H 24 NO 2 + ([M+H] + ) 358.1802, found:358.1798.

[0126] Example 16: 3-(2-((Benzhydryl)amino)benzyl)dihydrofuran-2(3 H )-ketone

[0127]

[0128] Using S32 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (56 mg, yield 77%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.79 – 7.71 (m, 2H), 7.51 – 7.46 (m, 1H), 7.44 – 7.40 (m, 2H), 7.28 – 7.26 (m, 3H), 7.13 – 7.07 (m 3H), 6.98 – 6.87 (m, 2H), 6.40(dd, J = 7.7, 1.5 Hz, 1H), 4.31 (td, J = 8.6, 3.2 Hz, 1H), 4.23 – 4.17 (m, 1H), 3.25 – 3.11 (m, 2H), 2.67 (dd, J = 13.7, 10.1 Hz, 1H), 2.33 – 2.25 (m, 1H), 2.20 – 2.10 (m, 1H).13 C NMR (100 MHz, CDCl 3 ) δ 179.45, 167.83, 150.01, 139.28,136.16, 130.98, 129.55, 129.47, 129.38, 129.00, 128.85, 128.37, 128.17,128.09, 127.02, 123.70, 66.90, 39.48, 32.46, 28.60. HRMS (ESI-TOF) m / z calcd.for C 24 H 22 NO 2 + ([M+H] + ) 356.1645, found: 356.1640.

[0129] Example 17: Dimethyl 2-(2-((benzhydryl)amino)benzyl)succinate

[0130]

[0131] Using S33 as the starting material, the reaction was carried out according to the general procedure A for 15 h to obtain a light yellow oil (51 mg, yield 61%). 1 HNMR (400 MHz, CDCl 3 ) δ 7.80 (d, J = 6.9 Hz, 2H), 7.50 – 7.45 (m, 1H), 7.42 (dd, J = 8.2, 6.5 Hz, 2H), 7.27 (d, J = 4.8 Hz, 3H), 7.12 (dd, J = 7.7, 1.8 Hz, 2H),7.04 (dd, J = 7.4, 1.7 Hz, 1H), 6.94 – 6.84 (m, 2H), 6.38 (dd, J = 7.6, 1.5 Hz,1H), 3.61 (s, 3H), 3.57 (s, 3H), 3.40 – 3.31 (m, 1H), 2.99 (dd, J = 13.6, 6.3Hz, 1H), 2.81 – 2.69 (m, 2H), 2.52 (dd, J = 16.8, 4.6 Hz, 1H). 13C NMR (125 MHz, CDCl 3 ) 175.37, 172.66, 167.38, 149.73, 139.42, 136.24, 130.84, 129.91,129.56, 129.53, 129.09, 128.77, 128.28, 128.07, 127.00, 123.63, 120.30,51.95, 51.78, 41.22, 35.35, 34.25. HRMS (ESI-TOF) m / z calcd. for C 26 H 26 NO 4 + ([M+H] + ) 416.1856, found: 416.1852.

[0132] Example 18: 3-Methyl-3,4-dihydroquinoline-2(1 H )-ketone

[0133]

[0134] Using S1 as the starting material, the reaction was carried out according to the general procedure B for 11 h to obtain a white solid (24 mg, yield 75%). 1 H NMR (400 MHz, CDCl 3 ) δ 8.83 (s, 1H), 7.20 – 7.12 (m, 2H), 7.01 – 6.95 (m, 1H), 6.83 (s, 1H), 3.00 (dd, J = 14.8, 5.2 Hz, 1H), 2.79 – 2.61 (m, 2H), 1.29 (d, J =6.6 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 174.86, 137.31, 128.16, 127.56, 123.66,123.02, 115.29, 35.04, 33.52, 15.47. HRMS (ESI-TOF) m / z calcd. for C 10 H 12 NO + ([M+H] + ) 162.0913, found: 162.0912.

[0135] Example 19: 2-Oxo-2,3,4-5-tetrahydro-1H-benzo[b]azepane-4-carboxylic acid methyl ester

[0136]

[0137] Using S33 as the starting material, the reaction was carried out according to the general procedure B for 17 h to obtain a white solid (21 mg, yield 48%). 1 H NMR (400 MHz, CDCl 3 ) δ 8.39 (s, 1H), 7.21 – 7.13 (m, 2H), 7.01 – 6.97 (m, 1H), 6.78 (dd, J = 7.8, 1.2 Hz, 1H), 3.73 (s, 3H), 3.14 – 2.97 (m, 3H), 2.88 (dd, J =15.3, 13.1 Hz, 1H), 2.51 (dd, J = 16.3, 7.4 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ172.61, 172.22, 137.05, 128.20, 127.82, 123.44, 123.29, 115.33, 52.01, 36.89,34.31, 31.26. HRMS (ESI-TOF) m / z calcd. for C 12 H 14 NO 3 + ([M+H] + ) 220.0968, found:220.0967.

[0138] Example 20: 3-(2-aminophenyl)-2-methyl-1-(1-pyrrolidinyl)propan-1-one

[0139]

[0140] Starting from S38, the reaction was carried out according to the general procedure C to give a light yellow oil (20 mg, 43%) after 26 h. 1 H NMR (400 MHz, CDCl 3 ) δ 7.07 – 6.92 (m, 2H), 6.73 – 6.56 (m, 2H), 3.97 (s, 2H), 3.36 (dddd, J= 18.2, 13.4, 6.8, 5.4 Hz, 2H), 3.29 – 3.22 (m, 1H), 3.06 – 2.95(m, 2H), 2.94 – 2.83 (m, 1H), 2.51 (dd, J = 13.6, 4.5 Hz, 1H), 1.81 – 1.63 (m,4H), 1.23 (d, J = 6.7 Hz, 3H). 13 C NMR (100 MHz, CDCl 3 ) δ 175.16, 145.17, 130.77,127.39, 125.08, 118.58, 116.07, 46.48, 45.92, 39.38, 35.92, 26.06, 24.34,18.42. HRMS (ESI-TOF) m / z calcd. for C 14 H 21 NO 2 + ([M+H] + ) 233.1648, found:233.1652.

[0141] The embodiments described above provide a detailed description of the technical solutions and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements and equivalent substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for free radical amino group migration from alkyl carbon to aryl carbon, characterized in that: include: Under light conditions, the compound of formula (I) undergoes a photocatalytic reaction in an organic solvent under the action of a photocatalyst, an additive, or a small molecule catalyst to obtain an amino migration product of formula (II); Among them, Ar ring is a benzene ring or a heteroaromatic ring; [N] is EWG R 2 and R 3 are independently selected from alkyl and aryl; LG is a halogen group; n is 1 or 2; R is selected from alkyl, aryl, alkenyl, alkynyl, alkoxy, benzyl, ester, and halide; The photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile; The additive is N-(1-adamantyl)-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane-2-amine; The small molecule catalyst is tetrabutylammonium salt, tetrapropylammonium salt, tetraethylammonium salt; The wavelength of light for photocatalytic reaction is 370-467nm.

2. The method for free radical amino group migration from alkyl carbon to aryl carbon according to claim 1, characterized in that: Based on the molar dosage of the compound of formula (I), the molar dosage of the photocatalyst is 1-10%; the molar dosage of the additive is 100-200%; the molar dosage of the small molecule catalyst is 10-50%; and the concentration of the compound of formula (I) in the reaction solution is 0.1-0.5 mol / L.

3. The method for free radical amino group migration from alkyl carbon to aryl carbon according to claim 1, characterized in that: The photocatalytic reaction is carried out at room temperature using an inert gas as a protective gas; the photocatalytic reaction time is 9 to 36 hours.

4. The method for free radical amino group migration from alkyl carbon to aryl carbon according to claim 1, characterized in that: The compound of formula (I) is selected from:

5. A method for preparing a benzolactam compound, characterized in that: include: Under light conditions, the compound of formula (III) undergoes a photocatalytic reaction in an organic solvent under the action of a photocatalyst, an additive, and a small molecule catalyst, and is then further acidified to obtain a benzolactam compound of formula (IV); Among them, Ar ring is a benzene ring or a heteroaromatic ring; [N] is LG is a halogen group; n is 1 or 2; R 1 is selected from alkyl, aryl, alkenyl, alkynyl, alkoxy, benzyl, ester, and halide; R 2 is selected from alkyl and aryl; The photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile; The additive is N-(1-adamantyl)-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane-2-amine; The small molecule catalyst is tetrabutylammonium salt, tetrapropylammonium salt, tetraethylammonium salt; The wavelength of light for photocatalytic reaction is 370-467nm.

6. A method for preparing a primary aromatic amine compound, characterized in that: include: Under light conditions, the compound of formula (V) undergoes a photocatalytic reaction in an organic solvent under the action of a photocatalyst, an additive, and a small molecule catalyst, and is then further acidified to obtain a primary aromatic amine compound of formula (VI); Among them, Ar ring is a benzene ring or a heteroaromatic ring; [N] is LG is a halogen group; n is 1 or 2; R 1 is selected from alkyl, aryl, alkenyl, alkynyl, alkoxy, benzyl, ester, and halide; R 2 and R 3 Independently selected from alkyl, aryl, tert-butyloxycarbonyl; The photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile; The additive is N-(1-adamantyl)-1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane-2-amine; The small molecule catalyst is tetrabutylammonium salt, tetrapropylammonium salt, tetraethylammonium salt; The wavelength of light for photocatalytic reaction is 370-467nm.

7. The method for preparing a benzolactam compound according to claim 5 or the method for preparing a primary aromatic amine compound according to claim 6, characterized in that: The reagent used for acidification is hydrochloric acid and the solvent is tetrahydrofuran.

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