Preparation method of chiral imidazolidine compound

Abstract

The invention provides a preparation method of a chiral imidazolidine compound, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: mixing an (S)-N-tert-butylimine compound # imgabs0 #, a dipole precursor # imgabs1 # and a photocatalyst such as tris (2-phenylpyridine) iridium in an organic solvent under the protection of inert gas, and carrying out asymmetric [3 + 2] cycloaddition reaction under illumination to obtain the chiral imidazolidine compound. The method for synthesizing the chiral imidazolidine compound through iridium / blue light concerted catalysis is constructed by taking a cheap photocatalyst as a catalyst, and has the advantages of mild conditions, wide substrate applicability, high economic benefits and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing novel chiral imidazolidine compounds through a photocatalytic asymmetric [3+2] cycloaddition reaction directed by a chiral sulfenamide. Background Art

[0002] Imidazolidines are saturated heterocyclic compounds with a cyclic aminal core, found widely in natural products and bioactive molecules. These compounds are not only important building blocks but also have extensive applications as chiral ligands, N-heterocyclic carbene (NHC) precursors, and catalysts for organic synthesis. The imidazolidine skeleton is ubiquitous in many natural alkaloids (e.g., (-)-chaetominine) and a variety of natural bioactive compounds (e.g., chaetominine, fumi-quinazolines A, tryptoquivalin G, and kifunensine). Furthermore, imidazolidines are used as chiral ligands, auxiliary agents, N-heterocyclic carbene precursors, and in organocatalysis (e.g., MacMillan catalysts). Due to their unique molecular properties and versatility, numerous methods have been devised to access a diverse range of imidazolidines.

[0003] In recent years, considerable progress has been made in the development of step-economical [3 + 2] cycloadditions, streamlining the catalytic synthesis of these heterocyclic compounds through organocatalytic, transition-metal-mediated, Lewis-acid-assisted, or thermally promoted pathways. A prominent strategy involves enantiocontrolled cycloadditions of azomethine imide (AYI) using glycine-derived acylate and imine counterparts, where the pre-intermediates are typically generated in situ from aldehyde and aminoester precursors. An alternative approach involves palladium-catalyzed asymmetric [3 + 2] cycloadditions between 5-vinyloxazolidinones and imines using chiral ammonium-phosphine hybrid ligands. Despite these achievements, several limitations remain, such as the use of expensive metal catalysts, complex starting materials, or tedious synthetic steps. Consequently, we are committed to developing green, mild, and simple methods for the synthesis of chiral imidazolidines and their derivatives. Summary of the Invention

[0004] In view of the above shortcomings of the prior art, the present invention provides a method for synthesizing novel chiral imidazolidine compounds via a chiral sulfenamide-directed photocatalytic asymmetric [3 + 2] cycloaddition reaction.

[0005] To achieve the above purpose, the specific technical solutions of the present invention are as follows:

[0006] The present invention provides a method for synthesizing novel chiral imidazolidine compounds through a chiral sulfenamide-directed photocatalytic asymmetric [3 + 2] cycloaddition reaction, comprising the following steps: under inert gas protection conditions, mixing a (S)-N-tert-butylimine compound represented by Formula I, a dipole precursor represented by Formula II, and a photocatalyst in an organic solvent, and subjecting the mixture to an asymmetric [3 + 2] cycloaddition reaction under light to obtain a novel chiral imidazolidine compound represented by Formula III. The reaction scheme is as follows:

[0007]

[0008] Wherein, R1 is selected from phenyl or substituted phenyl, , thienyl or substituted thienyl, thiazolyl, One of the following;

[0009] R2 is selected from benzyl or substituted benzyl, methoxy, and methyl.

[0010] Furthermore, the substituted phenyl group includes but is not limited to 4-cyanophenyl, 4-chlorophenyl, 4-methylphenyl, 4-nitrophenyl or 4-fluorophenyl.

[0011] Furthermore, the substituted thienyl group includes but is not limited to 5-cyanothiophene.

[0012] Furthermore, the substituted benzyl group includes but is not limited to 4-fluorobenzyl.

[0013] Furthermore, the photocatalyst includes but is not limited to at least one of tris(2-phenylpyridine)iridium, tris(4,4'-dimethyl-2,2'-bipyridyl)ruthenium hexafluorophosphate, tris(2,2'-bipyridyl)ruthenium di(hexafluorophosphate), and bis(2,3-diphenylquinoxaline-C2,N)iridium acetylacetonate.

[0014] Furthermore, the organic solvent includes but is not limited to at least one of tetrahydrofuran, methanol, toluene, and dichloromethane.

[0015] Furthermore, the molar ratio of the (S)-N-tert-butylimine compound represented by Formula I, the dipole precursor represented by Formula II, and the photocatalyst is 1:(2-4):(0.05-0.1).

[0016] Furthermore, the wavelength of the light is 450-465 nm.

[0017] Furthermore, the reaction temperature is room temperature.

[0018] Furthermore, the inert gas is argon or nitrogen.

[0019] The present invention also provides a novel chiral imidazolidine compound obtained by the method.

[0020] Furthermore, the novel chiral imidazolidine compound is selected from one of the following compounds:

[0021] ; ; ; ; ; ; ; ; ; .

[0022] Compared with the prior art, the present invention is beneficial in that:

[0023] (1) The method provided by the present invention adopts a one-step method to synthesize chiral imidazolidine compounds. The reaction raw materials are low in cost and readily available, the yield of chiral imidazolidine compounds is high, and the economic benefit is high.

[0024] (2) The photocatalyst used in the method provided by the present invention is low in cost, low in toxicity, and environmentally friendly.

[0025] (3) The method provided by the present invention is simple to operate and has relatively mild reaction conditions. The reaction can be carried out under normal temperature and pressure conditions, which is safe and convenient.

[0026] (4) The substituents in the raw materials of the method provided by the present invention can be selected from a variety of options, so the method has a wide range of applicability and can be used to synthesize various chiral imidazolidine compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 is the compound III-1 in Example 1 1 H NMR spectrum;

[0028] Figure 2 is the compound III-1 in Example 1 13 C NMR spectrum;

[0029] Figure 3 is the compound III-2 in Example 2 1 H NMR spectrum;

[0030] Figure 4 is the compound III-2 in Example 2 13 C NMR spectrum;

[0031] Figure 5 is the compound III-3 in Example 3 1 H NMR spectrum;

[0032] Figure 6 is the compound III-3 in Example 3 13 C NMR spectrum;

[0033] Figure 7 is the compound III-4 in Example 4 1 H NMR spectrum;

[0034] Figure 8 is the compound III-4 in Example 4 13 C NMR spectrum;

[0035] Figure 9 is the compound III-5 in Example 5 1 H NMR spectrum;

[0036] Figure 10 is the compound III-5 in Example 5 13 C NMR spectrum;

[0037] Figure 11 is the compound III-6 in Example 6 1 H NMR spectrum;

[0038] Figure 12 is the compound III-6 in Example 6 13 C NMR spectrum;

[0039] Figure 13 is the compound III-6 in Example 6 19 F NMR spectrum;

[0040] Figure 14 is the compound III-7 in Example 7 1 H NMR spectrum;

[0041] Figure 15 is the compound III-7 in Example 7 13 C NMR spectrum;

[0042] Figure 16 is the compound III-8 in Example 8 1 H NMR spectrum;

[0043] Figure 17 is the compound III-8 in Example 8 13 C NMR spectrum;

[0044] Figure 18 is the compound III-9 in Example 9 1 H NMR spectrum;

[0045] Figure 19is the compound III-9 in Example 9 13 C NMR spectrum;

[0046] Figure 20 is the compound III-10 in Example 10 1 H NMR spectrum;

[0047] Figure 21 is the compound III-10 in Example 10 13 C NMR spectrum;

[0048] Figure 22 is the compound III-10 in Example 10 19 F NMR spectrum. DETAILED DESCRIPTION

[0049] To facilitate understanding by those skilled in the art, the technical solutions of the present invention will be described clearly and completely below. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0050] The present invention provides a method for synthesizing novel chiral imidazolidine compounds through a chiral sulfenamide-directed photocatalytic asymmetric [3 + 2] cycloaddition reaction, comprising the following steps: under inert gas protection conditions, mixing a (S)-N-tert-butylimine compound represented by Formula I, a dipole precursor represented by Formula II, and a photocatalyst in an organic solvent, and subjecting the mixture to an asymmetric [3 + 2] cycloaddition reaction under light to obtain a novel chiral imidazolidine compound represented by Formula III. The reaction scheme is as follows:

[0051]

[0052] Wherein, R1 is selected from phenyl or substituted phenyl, , thienyl or substituted thienyl, thiazolyl, R2 is selected from one of benzyl or substituted benzyl, methoxy and methyl.

[0053] In some examples, the substituted phenyl group is selected from 4-cyanophenyl, 4-chlorophenyl, 4-methylphenyl, 4-nitrophenyl, or 4-fluorophenyl; the substituted thienyl group is 5-cyanothiophene; and the substituted benzyl group is 4-fluorobenzyl.

[0054] In some examples, the photocatalyst includes but is not limited to at least one of tris(2-phenylpyridine)iridium, tris(4,4'-dimethyl-2,2'-bipyridyl)ruthenium hexafluorophosphate, tris(2,2'-bipyridyl)ruthenium di(hexafluorophosphate), and bis(2,3-diphenylquinoxaline-C2,N)iridium acetylacetonate.

[0055] In some examples, the organic solvent is selected from at least one of tetrahydrofuran, methanol, toluene, and dichloromethane.

[0056] In some examples, the molar ratio of the (S)-N-tert-butylimine compound represented by Formula I, the dipole precursor represented by Formula II, and the photocatalyst is 1:(2-4):(0.05-0.1).

[0057] In some examples, the wavelength of the illumination is 450-465 nm. In the following specific embodiments, the wavelength of the illumination is 450 nm blue light.

[0058] In some examples, the inert gas is argon or nitrogen.

[0059] In the following specific examples, unless otherwise specified, all raw materials and reagents used were purchased conventionally.

[0060] Example 1

[0061] Preparation of novel chiral imidazolidine compound III-1:

[0062]

[0063] Under argon protection, I-1 (100 mg, 0.43 mmol) was dissolved in anhydrous tetrahydrofuran (2.2 mL), and tris(2-phenylpyridine)iridium (18.3 mg, 0.02 mmol) and II-1 (0.93 mL, 1.29 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. The mixture was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-1 as a white solid (145 mg, yield 93%). 1 H NMR spectra and 13 C NMR spectra are shown in Figure 1 and Figure 2 shown. 1 H NMR (400 MHz, Chloroform-d) δ 7.65 –7.60 (m, 2H), 7.42 (d,J = 8.0 Hz, 2H), 7.35 – 7.26 (m, 5H), 5.10 (t, J = 7.0Hz, 1H), 4.27 (d, J = 8.6 Hz, 1H), 4.21 (dd, J = 8.6, 0.9 Hz, 1H), 3.75 (d, J =13.1 Hz, 1H), 3.66 (d, J = 13.1 Hz, 1H), 3.34 (ddt, J = 10.2, 7.6, 1.2 Hz, 1H),2.62 (dd, J = 10.5, 6.5 Hz, 1H), 0.97 (d, J = 0.9 Hz, 9H). 13 C NMR (100 MHz, Chloroform- d ) δ 149.2, 138.0, 132.5, 128.7, 128.5, 127.8, 127.4, 118.7,111.1, 77.7, 62.4, 57.4, 56.9, 53.9, 22.8. HRMS (ESI) calculated for C 21 H 26 N3OS + [M+H] + : 368.1791, found 368.1794.

[0064] Example 2

[0065] Preparation of novel chiral imidazolidine compound III-2:

[0066]

[0067] Under argon protection, I-2 (100 mg, 0.48 mmol) was dissolved in anhydrous tetrahydrofuran (2.4 mL), and then tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-1 (0.4 mL, 1.44 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-2 as a yellow oil (139 mg, yield 85%). 1 H NMR spectra and 13 C NMR spectra are shown in Figure 3 and Figure 4 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 7.43 –7.39 (m, 2H), 7.37 – 7.31 (m, 6H), 7.28 (tdd, J = 10.0, 4.4, 2.6 Hz, 2H), 5.08(t, J = 7.4 Hz, 1H), 4.33 (dd, J = 9.0, 1.4 Hz, 1H), 4.25 (d, J = 9.0 Hz, 1H), 3.79(d, J = 13.1 Hz, 1H), 3.68 (d, J = 13.1 Hz, 1H), 3.41 (ddd, J = 10.7, 7.6, 1.5 Hz,1H), 2.70 (dd, J = 10.6, 7.1 Hz, 1H), 1.00 (s, 9H). 13 C NMR (100MHz, Chloroform- d ) δ 143.6, 138.4, 128.8, 128.6, 128.4, 127.3, 127.0, 78.1, 63.2, 57.4, 57.0,53.8, 22.9. HRMS (ESI) calculated for C 20 H 27 N2OS + [M+H] +: 343.1839, found343.1840.

[0068] Example 3

[0069] Preparation of novel chiral imidazolidine compound III-3:

[0070]

[0071] Under argon protection, I-3 (100 mg, 0.41 mmol) was dissolved in anhydrous tetrahydrofuran (2.0 mL), and tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-1 (0.3 mL, 1.23 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-3 (139 mg, 90% yield) as a yellow oil. 1 H NMR spectra and 13 C NMR spectra are shown in Figure 5 and Figure 6 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 7.39 –7.35 (m, 2H), 7.35 – 7.29 (m, 3H), 7.28 – 7.26 (m, 1H), 7.24 (d, J = 7.4 Hz,1H), 7.21 (dt, J = 8.0, 1.8 Hz, 1H), 7.17 (dt, J = 7.2, 1.7 Hz, 1H), 5.03 (t, J =7.2 Hz, 1H), 4.28 (dd, J = 8.9, 1.4 Hz, 1H), 4.20 (d, J = 8.9 Hz, 1H), 3.75 (d, J =13.1 Hz, 1H), 3.65 (d, J = 13.1 Hz, 1H), 3.35 (ddd, J = 10.5, 7.6, 1.4 Hz, 1H),2.63 (dd, J= 10.6, 6.8 Hz, 1H), 0.99 (s, 9H). 13 C NMR (100 MHz, Chloroform- d ) δ145.8, 138.2, 134.5, 130.0, 128.8, 128.5, 127.3, 127.2, 127.1, 125.2, 78.0,62.8, 57.4, 56.9, 53.5, 22.9. HRMS (ESI) calculated for C 20 H 26 ClN2OS + [M+H] + :377.1449, found 377.1451.

[0072] Example 4

[0073] Preparation of novel chiral imidazolidine compound III-4:

[0074]

[0075] Under argon protection, I-4 (100 mg, 0.45 mmol) was dissolved in anhydrous tetrahydrofuran (2.3 mL), and then tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-1 (0.4 mL, 1.34 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-4 (145 mg, yield 91%) as a yellow oil. 1 H NMR spectra and 13 C NMR spectra are shown in Figure 7 and Figure 8 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 7.46 (d, J = 7.5 Hz, 2H), 7.39 (dd, J = 8.2, 6.5 Hz, 2H), 7.33 (d, J = 1.8 Hz, 1H), 7.25 (d, J = 7.8 Hz, 2H), 7.19 (d,J = 7.8 Hz, 2H), 5.09 (t, J = 7.3 Hz, 1H), 4.36 (d, J =9.1 Hz, 1H), 4.30 (d, J = 9.1 Hz, 1H), 3.84 (d, J = 13.0 Hz, 1H), 3.74 (d, J = 13.1Hz, 1H), 3.44 (dd, J = 10.7, 7.6 Hz, 1H), 2.74 (dd, J = 10.7, 7.2 Hz, 1H), 2.40(s, 3H), 1.05 (d, J = 1.8 Hz, 9H). 13 C NMR (101 MHz, Chloroform- d ) δ 140.36,138.18, 136.69, 129.30, 128.90, 128.45, 127.31, 126.97, 77.78, 63.12, 57.40,57.02, 53.76, 22.95, 21.10. HRMS (ESI) calculated for C 21 H 29 N2OS + [M+H] + :357.1995, found 357.1998.

[0076] Example 5

[0077] Preparation of novel chiral imidazolidine compound III-5:

[0078]

[0079] Under argon protection, I-5 (100 mg, 0.39 mmol) was dissolved in anhydrous tetrahydrofuran (2.0 mL), and then tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-1 (0.3 mL, 1.18 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-5 as a white solid (132 mg, yield 86%). 1 H NMR spectra and 13 C NMR spectra are shown in Figure 9 and Figure 10 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 8.19(dd, J = 8.8, 2.1 Hz, 2H), 7.51 – 7.45 (m, 2H), 7.38 – 7.26 (m, 5H), 5.16 (t, J =7.0 Hz, 1H), 4.31 – 4.22 (m, 2H), 3.78 (d, J = 13.1 Hz, 1H), 3.68 (d, J = 13.0Hz, 1H), 3.36 (dd, J = 10.5, 7.6 Hz, 1H), 2.66 (dd, J = 10.6, 6.5 Hz, 1H), 0.97(d, J = 2.0 Hz, 9H). 13 C NMR (100 MHz, Chloroform- d ) δ 151.2, 147.1, 137.8,128.8, 128.6, 127.9, 127.5, 124.1, 77.6, 62.3, 57.6, 56.9, 53.7, 22.8. HRMS(ESI) calculated for C 20 H 26 N3O3S + [M+H] + : 388.1689, found 388.1692.

[0080] Example 6

[0081] Preparation of novel chiral imidazolidine compound III-6:

[0082]

[0083] Under argon protection, I-6 (100 mg, 0.44 mmol) was dissolved in anhydrous tetrahydrofuran (2.2 mL), and then tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-1 (0.6 mL, 1.32 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-6 as a white solid (147 mg, yield 92%). The target compound III-6 1 H NMR spectrum, 13 C NMR spectra and 19 The F NMR spectra are as follows Figure 11 、 Figure 12 and Figure 13 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 7.37 (d, J = 7.2 Hz, 2H), 7.32 (t, J = 7.4 Hz, 3H), 7.25 (q, J =4.1 Hz, 2H), 7.04 – 6.97 (m, 2H), 5.03 (t, J = 7.2 Hz, 1H), 4.26 (d, J = 8.8 Hz,1H), 4.21 (d, J = 8.8 Hz, 1H), 3.76 (d, J = 13.1 Hz, 1H), 3.65 (d, J = 13.1 Hz,1H), 3.37 – 3.30 (m, 1H), 2.64 (dd, J = 10.5, 6.9 Hz, 1H), 0.97 (s, 9H). 13 C NMR (100 MHz, Chloroform- d) δ 163.1, 139.4, 138.3, 128.8, 128.4, 127.3, 115.6,115.4, 77.7, 63.0, 57.4, 57.0, 53.4, 22.9. 19 F NMR (376 MHz, Chloroform- d ) δ -105.87. HRMS (ESI) calculated for C 20 H 26 FN2OS + [M+H] + : 361.1744, found 361.1745.

[0084] Example 7

[0085] Preparation of novel chiral imidazolidine compound III-7:

[0086]

[0087] Under argon protection, I-7 (100 mg, 0.29 mmol) was dissolved in anhydrous tetrahydrofuran (1.5 mL), and then tris(2-phenylpyridine)iridium (6.7 mg, 0.01 mmol) and II-1 (0.2 mL, 0.86 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-7 (79 mg, yield 58%) as a yellow oil. 1 H NMR spectra and 13 C NMR spectra are shown in Figure 14 and Figure 15 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 8.13 (d, J =8.2 Hz, 1H), 7.59 – 7.51 (m, 2H), 7.39 (d, J = 7.0 Hz, 2H), 7.32 (t, J = 7.3 Hz,3H), 7.27 (d, J = 7.1 Hz, 1H), 7.25 – 7.20 (m, 1H), 5.31 (t, J= 7.2 Hz, 1H), 4.28 (s, 2H), 3.80 (d, J = 13.1 Hz, 1H), 3.70 (d, J = 13.1 Hz, 1H), 3.37 (dd, J =10.2, 7.6 Hz, 1H), 2.78 (dd, J = 10.2, 6.9 Hz, 1H), 1.67 (s, 9H), 1.03 (s, 9H). 13 C NMR (100 MHz, Chloroform- d ) δ 149.7, 138.3, 135.9, 128.8, 128.6, 128.4,127.3, 124.6, 123.3, 122.6, 119.8, 115.4, 83.8, 76.5, 60.4, 57.4, 57.2, 47.9,28.2, 22.8. HRMS (ESI) calculated for C 27 H 36 N3O3S + [M+H] + : 482.2472, found482.2475.

[0088] Example 8

[0089] Preparation of novel chiral imidazolidine compound III-8:

[0090]

[0091] Under argon protection, I-8 (100 mg, 0.42 mmol) was dissolved in anhydrous tetrahydrofuran (2.1 mL), and tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-1 (0.4 mL, 1.25 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-8 as a yellow solid (80 mg, yield 82%). 1 H NMR spectra and 13 C NMR spectra are shown in Figure 16 and Figure 17 shown. 1H NMR (400 MHz, Chloroform- d ) δ 7.45(d, J = 3.8 Hz, 1H), 7.37 – 7.26 (m, 5H), 6.90 (d, J = 3.8 Hz, 1H), 5.30 (dd, J =7.0, 4.6 Hz, 1H), 4.22 (d, J = 7.6 Hz, 1H), 4.04 (d, J = 7.6 Hz, 1H), 3.78 (d, J =13.1 Hz, 1H), 3.69 (d, J = 13.1 Hz, 1H), 3.17 (dd, J = 10.0, 7.1 Hz, 1H), 2.78(dd, J = 10.0, 4.6 Hz, 1H), 1.06 (s, 9H). 13 C NMR (100 MHz, Chloroform- d ) δ156.6, 137.7, 137.3, 128.6, 128.6, 127.5, 124.9, 114.5, 108.8, 75.5, 61.6,57.7, 56.8, 51.2, 22.7. HRMS (ESI) calculated for C 19 H 24 N3OS2 + [M+H] + : 374.1355,found 374.1357.

[0092] Example 9

[0093] Preparation of novel chiral imidazolidine compound III-9:

[0094]

[0095] Under argon protection, I-9 (100 mg, 0.46 mmol) was dissolved in anhydrous tetrahydrofuran (2.3 mL), and then tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-1 (0.4 mL, 1.39 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-9 as a yellow solid (97 mg, yield 85%). 1 H NMR spectra and 13 C NMR spectra are shown in Figure 18 and Figure 19 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 7.71(d, J = 3.3 Hz, 1H), 7.38 – 7.35 (m, 2H), 7.34 – 7.31 (m, 2H), 7.27 – 7.24 (m,2H), 5.43 (dd, J = 7.4, 4.8 Hz, 1H), 4.27 (d, J = 8.1 Hz, 1H), 4.14 (d, J = 8.1 Hz,1H), 3.80 (d, J = 13.1 Hz, 1H), 3.69 (d, J = 13.1 Hz, 1H), 3.35 – 3.29 (m, 1H), 2.93 (dd, J = 10.3, 4.9 Hz, 1H), 1.09 (s, 9H). 13 C NMR (100 MHz, Chloroform- d ) δ173.9, 142.6, 138.1, 128.7, 128.5, 127.3, 119.1, 76.0, 60.7, 57.7, 57.0,53.4, 22.7. HRMS (ESI) calculated for C 17 H 24 N3OS2 + [M+H] + : 350.1355, found350.1357.

[0096] Example 10

[0097] Preparation of novel chiral imidazolidine compound III-10:

[0098]

[0099] Under argon protection, I-10 (100 mg, 0.33 mmol) was dissolved in anhydrous tetrahydrofuran (2.3 mL), and then tris(2-phenylpyridine)iridium (13.4 mg, 0.02 mmol) and II-2 (0.24 g, 1.00 mmol) were added. The reaction mixture was placed in an integrated photoreactor (20 W, 4 cm between the reaction tube and the light source) and stirred at room temperature for reaction until the reaction was complete as monitored by TLC. It was then extracted with ethyl acetate (3×50 mL), and the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified to obtain the target compound III-10 (115 mg, yield 82%) as a yellow oil. 1 HNMR spectrum, 13 C NMR spectra and 19 The F NMR spectra are as follows Figure 20 、 Figure 21 and Figure 22 shown. 1 H NMR (400 MHz, Chloroform- d ) δ 7.30 (d, J = 8.2 Hz, 2H), 7.22 (td, J = 8.2, 5.4 Hz, 4H), 6.98(t, J = 8.5 Hz, 2H), 6.90 (d, J = 6.2 Hz, 1H), 4.47 (dd, J = 8.0, 4.9 Hz, 1H), 4.41(t, J = 6.4 Hz, 2H), 4.03 (d, J = 7.8 Hz, 1H), 3.96 (d, J = 7.9 Hz, 1H), 3.66 (d, J =13.0 Hz, 1H), 3.56 (d, J = 13.0 Hz, 1H), 3.10 (dd, J = 10.2, 7.8 Hz, 1H), 2.93(dd, J= 10.2, 4.9 Hz, 1H), 1.10 (s, 9H). 13 C NMR (100 MHz, Chloroform- d ) δ171.8, 163.4, 161.0, 136.4, 133.5, 133.4, 133.4, 130.2, 130.1, 129.3, 128.9,115.5, 115.3, 75.3, 57.7, 57.3, 56.0, 55.5, 42.7, 22.6. 19 F NMR (376 MHz, Chloroform- d ) δ -114.94. HRMS (ESI) calculated for C 22 H 28 ClFN3O2S + [M+H] + :452.1569, found 452.1570.

[0100] The above specific embodiments describe the implementation of the present invention in detail, but the present invention is not limited to the specific details of the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a chiral imidazolidine compound, characterized in that: The following steps are involved: Under inert gas protection conditions, (S)-N-tert-butylimine compounds, dipole precursors, and photocatalysts are mixed in an organic solvent and placed under light for an asymmetric [3 + 2] cycloaddition reaction to obtain chiral imidazolidine compounds. The reaction scheme is shown below: ； Wherein, R1 is selected from phenyl or substituted phenyl, , thienyl or substituted thienyl, thiazolyl, One of the following; R2 is selected from benzyl or substituted benzyl, methoxy, and methyl.

2. The method for preparing a chiral imidazolidine compound according to claim 1, wherein The substituted phenyl includes but is not limited to 4-cyanophenyl, 4-chlorophenyl, 4-methylphenyl, 4-nitrophenyl or 4-fluorophenyl; the substituted thienyl includes but is not limited to 5-cyanothiophene; the substituted benzyl includes but is not limited to 4-fluorobenzyl.

3. The method for preparing a chiral imidazolidine compound according to claim 1, wherein The photocatalyst includes but is not limited to at least one of tris(2-phenylpyridine)iridium, tris(4,4'-dimethyl-2,2'-bipyridyl)ruthenium hexafluorophosphate, tris(2,2'-bipyridyl)ruthenium di(hexafluorophosphate), and bis(2,3-diphenylquinoxaline-C2,N)iridium acetylacetonate.

4. The method for preparing a chiral imidazolidine compound according to claim 1, wherein The molar ratio of the (S)-N-tert-butylimine compound, the dipole precursor and the photocatalyst is 1:(2-4):(0.05-0.1).

5. The method for preparing a chiral imidazolidine compound according to claim 1, wherein The wavelength of the light is 450-465 nm.

6. The method for preparing a chiral imidazolidine compound according to claim 1, wherein The reaction temperature is room temperature.

7. The method for preparing a chiral imidazolidine compound according to claim 1, wherein The inert gas includes but is not limited to argon or nitrogen.

8. The method for preparing a chiral imidazolidine compound according to claim 1, wherein: The organic solvent includes but is not limited to at least one of tetrahydrofuran, methanol, toluene, and dichloromethane.

9. A chiral imidazolidine compound prepared by the method according to any one of claims 1 to 8.

10. The chiral imidazolidine compound according to claim 9, characterized in that The chiral imidazolidine compound is selected from one of the following compounds: ； ； ； ； ； ； ； ； ； 。

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