A method for the synthesis of non-protected 1,2-amino esters and oxazoline derivatives

Abstract

The application discloses a synthesis method of unprotected 1,2-amino ester and oxazoline derivative. Aryl alkene is used as raw material, and selective oxidative amination is carried out on the aryl alkene in the presence of an aminating agent, an iron catalyst and a base to obtain an unprotected 1,2-amino ester compound; or a one-pot two-step method is used to obtain an oxazoline derivative in the presence of an aminating agent, an iron catalyst, a base and an acid. The method has the advantages of high efficiency, mild reaction condition, convenient operation, short reaction time, less by-products and the like, and is suitable for large-scale production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a synthesis method of non-protected 1,2-amino ester and oxazoline derivative. BACKGROUND

[0002] 1,2-amino ester, as an important synthetic intermediate, plays an important role in drug chemistry, material science and synthesis of natural products. Similarly, the oxazoline ring, as a five-membered heterocyclic compound, is widely used in the development of new drugs and functional materials due to its unique electronic properties and biological activity. For example, the oxazoline structure is an important component of drug molecules Deflazacort and Tucatinib. At the same time, the oxazoline ring is also a widely used chiral ligand in the field of asymmetric synthesis, and plays an important role in asymmetric catalytic conversion.

[0003] 1,2-amino ester is converted from 1,2-amino alcohol by chemical synthesis method, which usually involves acylation of 1,2-amino alcohol using suitable acylating reagents to introduce ester group into the molecule. However, this often requires protection of the amino group first, and then acylation of the hydroxyl group. Therefore, the synthesis of 1,2-amino ester compounds usually requires multi-step reactions, especially the process of synthesizing non-protected 1,2-amino ester compounds is particularly cumbersome. As for oxazoline, generally speaking, the common synthesis methods of oxazoline include reaction of carboxylic acid and its ester with β-amino alcohol, cyclization and dehydration reaction of β-hydroxy amide. For example, using carboxylic acid or carboxylic acid ester and chiral amino alcohol as raw materials, β-hydroxy amide is generated as an intermediate, and then intramolecular cyclization is carried out to synthesize oxazoline compounds. However, these traditional synthesis methods usually require multi-step reactions, use excessive reagents, produce difficult-to-handle byproducts, and have poor functional group compatibility. Therefore, it is still one of the important problems in synthetic chemistry to develop a synthesis method with wide raw material sources, high atom economy and good functional group compatibility to selectively, rapidly and efficiently prepare non-protected 1,2-amino ester and oxazoline compounds. SUMMARY

[0004] The present application provides a synthesis method of non-protected 1,2-amino ester and oxazoline derivative aiming at the shortcomings of the existing synthesis route. The present application realizes selective oxidative amination and cyclization reaction of olefins by using iron catalyst and in the presence of amination reagent, to generate non-protected 1,2-amino ester and oxazoline derivative, respectively. The method of the present application has the advantages of easy availability of raw materials, simple process, mild conditions, high yield, wide substrate range, and less byproducts.

[0005] The application discloses a synthesis method of non-protected 1,2-amino ester, which is prepared from aryl olefin in the presence of an amination reagent, an iron catalyst and a base, and the non-protected 1,2-amino ester compound is obtained after separation and purification.

[0006] Specifically, the aryl olefin is dissolved in a solvent under an air atmosphere, and the reaction is carried out at room temperature in the presence of an amination reagent, an iron catalyst and a base, and the non-protected 1,2-amino ester compound is obtained after separation and purification.

[0007] The aryl olefin has the following structural formula:

[0008] ;

[0009] R1 is selected from substituent groups such as an alkyl group, an alkoxy group, an ester group and a halogen.

[0010] For example, R1 is a substituent group such as a tert-butyl group, an acetoxy group or a Br atom.

[0011] The reaction temperature of the synthesis method is 10-40 DEG C, preferably 28 DEG C, and the reaction time is 6-12 h, preferably 12 h.

[0012] The iron catalyst is selected from ferrous triflate, ferrous acetate, ferrous sulfate, ferrous chloride or ferrous acetylacetone, and the amount of the iron catalyst is 1-20 mol% (calculated based on the olefin).

[0013] The base is at least one of potassium fluoride, potassium carbonate, sodium carbonate and potassium phosphate, and the addition amount is 1-5 equivalents (calculated based on the olefin).

[0014] The amination reagent has the following structural formula:

[0015] ;

[0016] R2 is a substituent group such as a hydrogen atom, a halogen, an alkoxy group (such as a methoxy group) and an ester group, - OTf is triflate, and the addition amount of the amination reagent is 2.0-3.0 equivalents (calculated based on the olefin).

[0017] The solvent is dichloromethane, ethyl acetate, 1,2-dichloroethane, chloroform or acetone.

[0018] The synthesis method of the non-protected 1,2-amino ester has the following synthesis route:

[0019] .

[0020] The synthesis method of the oxazoline derivative of the present application is to react aryl olefin as raw material in the presence of amination reagent, iron catalyst, base and acid by one-pot two-step method, and the oxazoline derivative is obtained after separation and purification.

[0021] Specifically, the aryl olefin is dissolved in a solvent under air atmosphere, and the first step reaction is carried out at room temperature in the presence of amination reagent, iron catalyst and base. After the reaction is completed, no post-treatment is needed, and then the second step reaction is carried out by adding acid to the system. After the reaction is completed, the oxazoline derivative is obtained after separation and purification.

[0022] The structural formula of the aryl olefin is as follows:

[0023] ;

[0024] R1 is selected from substituent groups such as alkyl, alkoxy, ester, halogen, etc.

[0025] For example, R1 is a substituent group such as tert-butyl, acetoxy or Br atom, etc.

[0026] The reaction temperature of the synthesis method is 10-40°C, preferably 28°C.

[0027] The reaction time of the first step is 6-12 h, preferably 12 h; and the reaction time of the second step is 12 h.

[0028] The iron catalyst is selected from ferrous triflate, ferrous acetate, ferrous sulfate, ferrous chloride or ferrous acetylacetone, and the amount of the iron catalyst is 1-20 mol% (based on the olefin).

[0029] The base is at least one of potassium fluoride, potassium carbonate, sodium carbonate and potassium phosphate, and the addition amount is 1-5 equivalents (based on the olefin).

[0030] The structural formula of the amination reagent is as follows:

[0031] ;

[0032] R2 is a substituent group such as hydrogen atom, halogen, alkoxy (such as methoxy), ester, etc. - OTf is triflate. The addition amount of the amination reagent is 2.0-3.0 equivalents (based on the olefin).

[0033] The acid is a strong acid such as trifluoromethanesulfonic acid, hydrochloric acid or hypochlorous acid, and the amount is 1-5 eq (based on the olefin).

[0034] The solvent is dichloromethane, ethyl acetate, 1,2-dichloroethane, chloroform or acetone.

[0035] The separation and purification step involves adding a saturated aqueous sodium bicarbonate solution to the reaction solution, extracting with ethyl acetate, drying over anhydrous sodium sulfate, and finally removing the solvent by rotary evaporation. Purification by column chromatography yields the target product. The eluent for column chromatography separation and purification of unprotected 1,2-amino esters is a ratio of petroleum ether:ethyl acetate (v / v) of 2:1; for column chromatography separation and purification of oxazoline derivatives, the eluent is a ratio of petroleum ether:ethyl acetate (v / v) of 10:1.

[0036] The synthetic method of the oxazoline derivative of the present invention, the synthetic route is as follows:

[0037]

[0038] The beneficial effects of the present invention are embodied in:

[0039] 1. The synthesis method of the present invention uses iron to catalyze the oxidative amination and cyclization reactions of aromatic olefins, which has the characteristics of low price, low toxicity, and green environmental protection.

[0040] 2. The synthetic method of the present invention has wide substrate applicability, high atom utilization rate, compatibility with various functional groups, and is applicable to aryl halides with various substituents. DETAILED DESCRIPTION

[0041] To further illustrate the features and advantages of the present invention, the technical solutions of the present invention are described below in conjunction with specific embodiments. However, the following embodiments are only intended to further illustrate the present invention, rather than to limit the present invention.

[0042] During the synthesis process of the present invention, some reaction conditions were optimized and screened as follows:

[0043]

[0044]

[0045] For the above reaction, we used p-tert-butylstyrene (1a) and benzoylhydroxylamine amination reagent (2a) as model substrates, ferrous trifluoromethanesulfonate as a catalyst, potassium carbonate as a base, and 1,10-phenanthroline as a ligand. We synthesized the target compound using different solvents. Screening of different solvents revealed that dichloromethane (DCM) produced the best reaction results. Therefore, DCM is the optimal solvent for this reaction.

[0046]

[0047]

[0048] For the above reaction, we take p-tert-butyl styrene (1a) and benzoyl hydroxylamine reagent (2a) as model substrates, dichloromethane as solvent, ferrous triflate as catalyst and 1,10-phenanthroline as ligand, and the synthesis of target compounds is realized by adding different bases. Through the screening of different kinds of bases, potassium carbonate as the base, the reaction effect is the best.

[0049]

[0050]

[0051] For the above reaction, we take p-tert-butyl styrene (1a) and benzoyl hydroxylamine reagent (2a) as model substrates, dichloromethane as solvent, potassium carbonate as base, 1,10-phenanthroline as ligand, and the synthesis of target compounds is realized by adding different metal catalysts. Through the screening of different catalysts, ferrous triflate as the catalyst, the reaction effect is the best, so ferrous triflate is the best catalyst for the reaction.

[0052]

[0053]

[0054] For the above reaction, we take p-tert-butyl styrene (1a) and benzoyl hydroxylamine reagent (2a) as model substrates, ferrous triflate as catalyst, dichloromethane as solvent, potassium carbonate as base, 1,10-phenanthroline as ligand to complete the first step of the reaction, and then the synthesis of target compounds is realized by adding different acid additives. Through the screening of different kinds of acids, trifluoromethanesulfonic acid as the additive, the reaction effect is the best, so it is the best acid additive for the reaction.

[0055] The technical scheme of the present application is further described below through specific examples.

[0056] Example 1:

[0057]

[0058] Into a 25 mL clear Schlenk tube equipped with a magnetic stir bar, was placed the starting material 4-tert-butylstyrene (la) (0.2 mmol), benzoyl hydroxylamine reagent (2a) (0.5 mmol, 2.5 eq), potassium carbonate (0.4 mmol, 2 eq), iron (II) triflate catalyst (0.04 mmol, 20 mol%) and ligand 1,10-phenanthroline (0.04 mmol, 20 mol%). Dichloromethane solvent (2 ml) was added under air atmosphere, the reaction tube was fixed on a stirrer and the reaction was carried out at room temperature for 6-12 h. The reaction mixture was extracted with water and ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate and concentrated in vacuo. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) to give white solid (3a) (47 mg, 80%). The NMR data of this compound are: 1 H NMR (400 MHz, Chloroform-d) δ 7.76 (d, J = 7.0 Hz, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.45 - 7.37 (m, 4H), 7.33 (d, J = 8.3 Hz, 2H), 6.69 (s, 1H), 4.92 (dd, J = 8.2, 3.4 Hz, 1H), 3.91 (ddd, J = 14.0, 7.1, 3.4 Hz, 1H), 3.51 (ddd, J = 14.1, 8.2, 4.7 Hz, 1H), 2.92 (s, 1H), 1.32 (s, 9H); 13 C NMR (101 MHz, Chloroform-d) δ 168.58, 151.02, 138.74, 134.16, 131.69, 128.62, 127.03, 125.64, 125.55, 73.55, 47.70, 34.59, 31.36.

[0059]

[0060] Into a 25 mL clear Schlenk tube equipped with a magnetic stir bar, was placed the starting material 4-tert-butylstyrene (1a) (0.2 mmol), benzoyl hydroxylamine reagent (2a) (0.5 mmol, 2.5 eq), potassium carbonate (0.4 mmol, 2 eq), iron (II) triflate catalyst (0.04 mmol, 20 mol%) and ligand 1,10-phenanthroline (0.04 mmol, 20 mol%). Dichloromethane solvent (2 ml) was added under air atmosphere, the reaction tube was fixed on a stirrer, after reaction at room temperature for 6-12 h, trifluoromethanesulfonic acid (0.4 mmol, 2.0 eq) was added to the reaction solution, after stirring at room temperature overnight, the reaction solution was extracted with water and ethyl acetate, the organic phase was combined, dried over anhydrous sodium sulfate, then concentrated in vacuum, the product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to give yellow oily liquid (4a) (42 mg, 76%). The NMR data of this compound are: 1 H NMR (400 MHz, Chloroform-d) δ: 8.03-8.00 (m, 2H), 7.51-7.47 (m, 1H), 7.44-7.39 (m, 4H), 7.31-7.28 (m, 2H), 5.63 (dd, J = 8.1, 10.1 Hz, 1H), 4.45 (dd, J = 10.1, 14.8 Hz, 1H), 4.01 (dd, J = 8.0, 14.8 Hz, 1H), 1.32 (s, 9H); 13 C NMR (100 MHz, Chloroform-d) δ: 164.0, 151.4, 137.8, 131.4, 128.3, 128.3, 127.6, 125.69, 125.66, 81.0, 62.9, 34.6, 31.3.

[0061] Example 2:

[0062]

[0063] Example 2: 1HNMR (400 MHz, DMSO-d6) δ 8.57 (t, J = 5.7 Hz, 1H), 7.89 (d, J = 8.5 Hz, 4H),7.83 (d, J = 7.4 Hz, 2H), 7.57 - 7.42 (m, 6H), 5.68 (d, J = 4.3 Hz, 1H), 4.96 (dt, J = 8.7, 4.9 Hz, 1H), 3.69 - 3.53 (m, 1H), 3.49 - 3.38 (m, 1H). 13 C NMR(101 MHz, DMSO-d6) δ 166.99, 141.82, 134.97, 133.26, 132.85, 131.60, 128.71,128.22, 128.02, 127.97, 127.66, 126.50, 126.09, 125.10, 124.88, 71.77, 48.00.

[0064]

[0065] Example 1 using naphthalene (1b) instead of 4-tert-butylstyrene (1a). The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1) to give a yellow oily liquid (4b) (30 mg, 55%). The NMR data of this compound are: 1 H NMR (400 MHz, Chloroform-d) δ 8.07 (d, J = 8.0 Hz, 2H), 7.94 - 7.80 (m, 4H), 7.58 - 7.40 (m, 6H), 5.84 (dd, J = 10.2, 8.0 Hz, 1H), 4.56 (dd, J = 14.8, 10.2 Hz, 1H), 4.09 (dd, J = 14.8, 7.8 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 164.21, 138.24, 133.26, 133.19, 131.58, 129.06, 128.52, 128.42, 128.06, 127.82, 127.66, 126.54, 126.36, 124.98, 123.39, 81.34, 63.15.

[0066] Example 3:

[0067]

[0068] Example 1 using 4-acetyloxy styrene (1c) instead of 4-tert-butyl styrene (1a). The product was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 1:1) to give a yellow solid (3c) (39 mg, 68 %). The NMR data for this compound are: 1 H NMR (600 MHz, DMSO-d6) δ 8.53 (t, J = 5.7 Hz, 1H), 7.84 (d, J = 7.0 Hz, 2H), 7.51 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.40 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 5.57 (d, J = 4.4 Hz, 1H), 4.80 (dt, J = 7.8, 4.7 Hz, 1H), 3.49 (ddd, J = 13.2, 6.1, 4.9 Hz, 1H), 3.37 – 3.31 (m, 1H), 2.26 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 169.77, 166.96, 149.91, 141.71, 134.93, 131.60, 128.71, 127.66, 127.49, 121.86, 71.12, 48.00, 21.31.

[0069]

[0070] Example 1 using 4-acetyloxy styrene (1c) instead of 4-tert-butyl styrene (1a). The product was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 5:1) to give a yellow oil liquid (4c) (37 mg, 65 %). The NMR data for this compound are: 1H NMR (400 MHz, Chloroform-d) δ: 8.02-7.99 (m, 2H), 7.52-7.48 (m,1H), 7.45-7.41 (m, 2H), 7.38-7.35 (m, 2H), 7.12-7.08 (m, 2H), 5.65 (dd, J=7.92, 10.1 Hz, 1H), 4.47 (dd, J= 10.1, 14.8 Hz, 1H), 3.98 (dd, J= 7.9, 14.8Hz, 1H), 2.29 (s, 3H); 13 CNMR (100 MHz, Chloroform-d) δ: 169.3, 163.9, 150.5,138.6, 131.4, 128.4, 128.2, 127.5, 126.9, 121.9, 80.4, 63.1, 21.1.

[0071] Example 4:

[0072]

[0073] Example 4: with 3-bromostyrene (1d) instead of 4-tert-butylstyrene (1a), otherwise as in Example 1. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) to give white solid (3d) (33 mg, 52%). The NMR data of this compound are: 1 H NMR (400 MHz, Chloroform-d) δ 7.76 (d, J = 7.2 Hz, 2H), 7.59 (s, 1H),7.53 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.8 Hz, 3H), 7.34 (d, J = 7.7 Hz, 1H),7.23 (d, J = 7.8 Hz, 1H), 6.57 (s, 1H), 4.96 (dd, J = 7.7, 3.1 Hz, 1H), 3.91(ddd, J = 14.3, 6.9, 3.1 Hz, 1H), 3.51 (ddd, J = 13.6, 7.7, 5.1 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) δ 163.93, 143.44, 131.66, 131.40, 130.50, 128.77, 128.53, 128.38, 127.41, 124.28, 122.96, 80.11, 63.25.

[0074]

[0075] Using 3-bromostyrene (1d) instead of 4-tert-butylstyrene (1a), and following Example 1. The product was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 10: 1) to give a yellow oil liquid (4d) (30 mg, 50%). The NMR data of this compound are: 1 H NMR (400 MHz, Chloroform-d) δ 8.06 (d, J = 8.0 Hz, 2H), 7.54 (d, J= 7.7 Hz, 2H), 7.48 (t, J = 7.6 Hz, 3H), 7.30 (d, J = 14.6 Hz, 2H), 5.65 (dd, J = 10.2, 7.9 Hz, 1H), 4.52 (dd, J = 14.9, 10.2 Hz, 1H), 4.00 (dd, J = 14.8, 7.8 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 163.93, 143.44, 131.66, 131.40, 130.50, 128.77, 128.53, 128.38, 127.41, 124.28, 122.96, 80.11, 63.25.

[0076] Example 5:

[0077]

[0078] Using 4-methoxy-benzoyl hydroxylamine reagent (2b) instead of benzoyl hydroxylamine reagent (2a), and following Example 1. The product was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 2: 1) to give a white solid (3e) (51 mg, 79%). The NMR data of this compound are: 1H NMR (400 MHz, DMSO-d6) δ 8.39 (t, J = 5.6 Hz,1H), 7.84 (d, J = 8.6 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.1 Hz,2H), 6.99 (d, J = 8.7 Hz, 2H), 5.43 (d, J = 4.2 Hz, 1H), 4.74 (dt, J = 8.5,4.5 Hz, 1H), 3.80 (s, 3H), 3.51 – 3.40 (m, 1H), 3.33 – 3.22 (m, 1H), 1.27 (s,9H). 13 C NMR (101 MHz, DMSO-d6) δ 166.40, 161.94, 149.76, 141.39, 129.51,127.22, 126.17, 125.24, 113.88, 71.48, 55.78, 48.18, 34.65, 31.67.

[0079]

[0080] Using 4-methoxy-benzoyl hydroxylamine reagent (2b) instead of benzoyl hydroxylamine reagent (2a), otherwise as in Example 1. The product was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 10:1) to give yellow oily liquid (4e) (42 mg, 68%). The NMR data of this compound are: 1 H NMR (600 MHz, Chloroform-d) δ: 7.96 (d, J = 8.7Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 6.93 (d, J = 8.8Hz, 2H), 5.66 – 5.57 (m, 1H), 3.99 (dd, J = 14.6, 8.0 Hz, 1H), 3.85 (s, 3H),1.32 (s, 9H); 13 C NMR (100 MHz, Chloroform-d) δ: 163.89, 162.18, 151.41,138.08, 130.09, 125.77, 125.76, 120.25, 113.78, 81.00, 62.97, 55.41, 34.66,31.36.

[0081] Example 6:

[0082]

[0083] Example 1 using 4-chlorobenzoyl hydroxylamine reagent (2c) instead of benzoyl hydroxylamine reagent (2a). The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) to give white solid (3f) (36 mg, 55%). The NMR data of this compound are: 1 H NMR (600 MHz, DMSO-d6) δ 8.63 (t, J = 5.7 Hz, 1H), 7.88(d, J = 8.6 Hz, 2H), 7.53 (d, J = 8.6 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.29(d, J = 8.3 Hz, 2H), 5.43 (d, J = 4.3 Hz, 1H), 4.75 (dt, J = 8.5, 4.4 Hz,1H), 3.47 (ddd, J = 13.3, 6.0, 4.6 Hz, 1H), 3.30 (ddd, J = 13.4, 8.2, 5.3 Hz,1H), 1.27 (s, 9H). 13 C NMR (151 MHz, DMSO-d6) δ 170.59, 154.59, 146.00, 141.13,138.54, 134.41, 133.53, 130.94, 130.01, 76.04, 52.97, 39.40, 36.42.

[0084]

[0085] Example 1 using 4-chlorobenzoyl hydroxylamine reagent (2c) instead of benzoyl hydroxylamine reagent (2a). The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) to give yellow oily liquid (4f) (31 mg, 50%). The NMR data of this compound are: 1H NMR (600 MHz, Chloroform-d) δ: 7.94 (d, J = 8.3 Hz,2H), 7.40 (dd, J = 8.3, 5.9 Hz, 4H), 7.28 (d, J = 8.1 Hz, 2H), 5.63 (dd, J =10.1, 8.0 Hz, 1H), 4.44 (dd, J = 14.9, 10.1 Hz, 1H), 4.01 (dd, J = 14.9, 8.1Hz, 1H), 1.32 (s, 9H); 13 C NMR (100 MHz, Chloroform-d) δ: 163.18, 151.61,137.71, 137.63, 129.70, 128.75, 126.30, 125.84, 125.77, 81.34, 34.68, 31.36.

[0086] Example 7:

[0087]

[0088] Example 1 using 4-ester benzoyl hydroxylamine reagent (2d) instead of benzoyl hydroxylamine reagent (2a). The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give white solid (3g) (41 mg, 57%). The NMR data of this compound are: 1 H NMR (600 MHz, Chloroform-d) δ 8.73 (t, J = 5.7 Hz, 1H),8.03 (d, J = 8.5 Hz, 2H), 7.96 (d, J = 8.7 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H),7.30 (d, J = 8.3 Hz, 2H), 5.44 (d, J = 4.3 Hz, 1H), 4.76 (dt, J = 8.6, 4.5Hz, 1H), 3.88 (s, 3H), 3.51 – 3.44 (m, 1H), 3.36 – 3.30 (m, 1H), 1.27 (s,9H). 13C NMR (151 MHz, Chloroform-d) δ 170.97, 170.80, 154.61, 145.96, 143.94, 136.89, 134.31, 132.87, 130.95, 130.03, 57.58, 52.97, 39.41, 36.42.

[0089]

[0090] Using 4-ester benzoyl hydroxylamine reagent (2d) instead of benzoyl hydroxylamine reagent (2a), otherwise as in Example 1. The product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to give yellow oily liquid (4g) (34 mg, 50%). The NMR data of this compound are: 1 H NMR (600 MHz, Chloroform-d) δ: 8.08 (d, J = 2.6Hz, 4H), 7.41 (d, J = 8.1 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 5.66 (dd, J =10.1, 8.2 Hz, 1H), 4.48 (dd, J = 15.1, 10.1 Hz, 1H), 4.05 (dd, J = 15.1, 8.2Hz, 1H), 3.94 (s, 3H), 1.32 (s, 9H); 13 C NMR (100 MHz, Chloroform-d) δ: 166.52, 163.29, 151.66, 137.59, 132.56, 131.78, 129.65, 128.33, 125.85, 125.79, 81.42, 63.10, 52.39, 34.68, 31.34.

Claims

1. A method for synthesizing a compound of formula 3, comprising: dissolving an aryl alkene 1 in a solvent under an air atmosphere, in the presence of an amination reagent 2, an iron catalyst, a base, and a ligand, and reacting at room temperature, and separating and purifying a compound of formula 3 after the reaction is completed; and wherein: R1 is selected from an alkyl group, an alkoxy group, or a halogen; the iron catalyst is selected from ferrous triflate, ferrous acetate, ferrous sulfate, ferrous chloride, or ferrous acetylacetonate; and the ligand is 1,10-phenanthroline.

2. The method of claim 1, wherein: the base is at least one of potassium fluoride, potassium carbonate, sodium carbonate, or potassium phosphate, and is added in an amount of 1-5 equivalents.

3. The method of claim 1, wherein: the solvent is dichloromethane, ethyl acetate, 1,2-dichloroethane, chloroform, or acetone. ； 4. A method for synthesizing an oxazoline derivative, comprising: dissolving an aryl alkene 1 in a solvent under an air atmosphere, in the presence of an amination reagent 2, an iron catalyst, a base, and a ligand, and reacting at room temperature in a first step, and then adding an acid to the system without post-treatment to perform a second step, and separating and purifying an oxazoline derivative 4 after the reaction is completed; and wherein: R1 is selected from an alkyl group, an alkoxy group, or a halogen; the iron catalyst is selected from ferrous triflate, ferrous acetate, ferrous sulfate, ferrous chloride, or ferrous acetylacetonate; the ligand is 1,10-phenanthroline; and the acid is trifluoromethanesulfonic acid, hydrochloric acid, or hypochlorous acid.

5. The method of claim 4, wherein: the base is at least one of potassium fluoride, potassium carbonate, sodium carbonate, or potassium phosphate, and is added in an amount of 1-5 equivalents. R2is a hydrogen atom, a halogen or an alkoxy group, - OTf is triflate; 6. The method of claim 5, wherein: the solvent is dichloromethane, ethyl acetate, 1,2-dichloroethane, chloroform, or acetone. ​ ​ ​ ​ ​ ​ ​ ​ ； ​ ​ R2is a hydrogen atom, a halogen or an alkoxy group, - OTf is triflate; ​ ​ ​ ​ ​ ​ ​

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