An enantiopure planar chiral dibenzodiazocinone compound, its preparation method and applications

Abstract

The present invention discloses an enantiopure planar chiral dibenzo diazocin dione compound, which has the characteristics of novel structure and provides a novel skeleton for planar chiral compounds. The present invention also provides a preparation method of the above compound. This planar chiral compound can be obtained by catalytic asymmetric kinetic resolution of readily available racemic dibenzo diazocin dione. The operation is simple and the structure is easy to modify. The present invention further provides the application of the above compound. This planar chiral compound is used as a chiral acylation reagent to resolve racemic 3,3-dimethylbutan-2-amine. The reaction conditions are mild, the yield is high, and the enantioselectivity is moderate.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemical synthesis, and relates to an enantiopure planar chiral dibenzo diazocin dione compound, a preparation method thereof, and an application thereof. Background Art

[0002] In the field of asymmetric catalytic synthesis, the research on central chiral, axial chiral, and helical chiral compounds has been relatively mature. In sharp contrast, the exploration of catalytic asymmetric synthesis of planar chiral compounds is relatively scarce. Planar chiral compounds widely exist in natural products and have important applications in host-guest chemistry and materials science. Typical planar chiral structures include metallocenes, cyclophanes, rigid cycloolefins, etc. Planar chiral compounds can be used as efficient catalysts or ligands in asymmetric catalytic reactions. For example, planar chiral phosphoric acids, thioureas, N-heterocyclic carbenes (NHCs), and pyridine-N-oxides have successfully achieved multiple examples of catalytic asymmetric synthesis. In addition, planar chiral cyclophane-derived phosphine ligands have also been proven to be a class of classical and efficient ligands, which can be combined with various Lewis acids to develop new catalytic asymmetric synthesis methodologies. Therefore, the synthesis of planar chiral compounds has always attracted the attention of chemists. It has been reported that a series of ferrocene compounds with planar chirality have been constructed through a C-H activation strategy. However, the known conformationally stable planar chiral compounds are single in type and have cumbersome synthesis steps, which greatly limits their application scope. Therefore, it is still necessary to explore new catalytic asymmetric synthesis methods for novel planar chiral compounds. Summary of the Invention

[0003] In order to overcome the deficiencies of the prior art, one of the objectives of the present invention is to provide an enantiopure planar chiral dibenzo diazocin dione compound.

[0004] Another objective of the present invention is to provide a preparation method for the enantiopure planar chiral dibenzo diazocin dione compound.

[0005] A further objective of the present invention is to provide the application of the enantiopure planar chiral dibenzo diazocin dione compound as a chiral acylation reagent in the kinetic resolution of 3,3-dimethylbutan-2-amine.

[0006] One of the objectives of the present invention is achieved by adopting the following technical solution:

[0007] An enantiopure planar chiral dibenzo diazocin dione compound has a general structural formula S

[0008]

[0009] Wherein, R 1It is one of benzyl, alkyl-substituted benzyl, alkoxy-substituted benzyl, halogen-substituted benzyl, unsaturated alkyl, and ester group; Ar is an unsaturated six-membered ring, halogenated unsaturated six-membered ring, alkoxy unsaturated six-membered ring, or naphthyl group.

[0010] In some embodiments, the R 1 is one of Bn, 4-CH3C6H4CH2, 4-CH3OC6H4CH2, 3-BrC6H4CH2, allyl, and 2-ethoxy-2-oxoethyl; Ar is one of C6H5, 4-CH3OC6H4, 4-ClC6H4, 5-ClC6H4, 5-IC6H4, and naphthyl group.

[0011] The second object of the present invention is achieved by the following technical solution:

[0012] A method for preparing an enantiopure planar chiral dibenzoazepinedione compound, comprising the following steps:

[0013]

[0014] (1) Dissolve compound I and compound II in an organic solvent, then add an inorganic base, and react to obtain a racemic product, compound III;

[0015] (2) Dissolve the compound III obtained in step (1) in an organic solvent, and react with compound IV under the action of a catalyst to obtain an enantiopure compound S.

[0016] In some embodiments, the organic solvent in step (1) and step (2) is CH3CN.

[0017] In some embodiments, the inorganic base in step (1) is potassium carbonate.

[0018] In some embodiments, the reaction temperature of step (1) is 85 °C and the time is 4 h.

[0019] In some embodiments, the catalyst in step (2) is quinidine.

[0020] In some embodiments, the reaction temperature of step (2) is room temperature and the time is 6 h.

[0021] In some embodiments, the molar ratio of compound I, compound II, and inorganic base in step (1) is 1:1:0.5; the molar ratio of compound III, compound IV, and catalyst in step (2) is 1:0.6:0.1.

[0022] The third object of the present invention is achieved by the following technical solution:

[0023] Use of an enantiopure planar chiral dibenzodiazocinone compound as described in the foregoing technical solution, or an enantiopure planar chiral dibenzodiazocinone compound prepared by the foregoing technical solution, as a chiral acylation reagent in the kinetic resolution of 3,3-dimethylbutan-2-amine.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0025] The present invention provides an enantiopure planar chiral dibenzodiazocinone compound, which has the characteristics of novel structure and provides a new skeleton for planar chiral compounds.

[0026] The present invention also provides a preparation method of the above compound. The planar chiral compound can be synthesized by catalytic asymmetric kinetic resolution reaction from readily available racemic dibenzodiazocinone. The operation is simple and the structure is easy to modify. Dibenzodiazocinone and benzyl bromide as starting reaction materials have the advantages of being cheap and readily available, reducing the cost of the reaction. The preparation method of the present invention has simple operation, excellent yield of the obtained enantiopure planar chiral dibenzodiazocinone, and good enantioselectivity. The obtained enantiopure planar chiral dibenzodiazocinone derivative has a novel structure skeleton, which forms a complement with the existing types of planar chiral compounds. The obtained enantiopure planar chiral dibenzodiazocinone structure prepared by the preparation method of the present invention is easy to modify, and different products can be modularly obtained by simply selecting different substrates.

[0027] The present invention further provides an application of the above compound. The planar chiral compound is used as a chiral acylation reagent to resolve racemic 3,3-dimethylbutan-2-amine, and the reaction conditions are mild, the yield is high, and the enantioselectivity is moderate. Description of the Drawings

[0028] Figure 1 For the compound S-1 obtained in Example 1 of the present invention 1 H NMR result diagram;

[0029] Figure 2 For the compound S-1 obtained in Example 1 of the present invention 13 C NMR result diagram;

[0030] Figure 3 For the compound S-2 obtained in Example 2 of the present invention 1 H NMR result diagram;

[0031] Figure 4 For the compound S-2 obtained in Example 2 of the present invention 13 C NMR result diagram;

[0032] Figure 51H NMR spectra of compound S-3 obtained in Example 3 of the present invention 1 ;

[0033] Figure 6 1H NMR spectra of compound S-3 obtained in Example 3 of the present invention 13 ;

[0034] Figure 7 1H NMR spectra of compound S-4 obtained in Example 4 of the present invention 1 ;

[0035] Figure 8 1H NMR spectra of compound S-4 obtained in Example 4 of the present invention 13 ;

[0036] Figure 9 1H NMR spectra of compound S-5 obtained in Example 5 of the present invention 1 ;

[0037] Figure 10 1H NMR spectra of compound S-5 obtained in Example 5 of the present invention 13 ;

[0038] Figure 11 1H NMR spectra of compound S-6 obtained in Example 6 of the present invention 1 ;

[0039] Figure 12 1H NMR spectra of compound S-6 obtained in Example 6 of the present invention 13 ;

[0040] Figure 13 1H NMR spectra of compound S-7 obtained in Example 7 of the present invention 1 ;

[0041] Figure 14 1H NMR spectra of compound S-7 obtained in Example 7 of the present invention 13 ;

[0042] Figure 15 1H NMR spectra of compound S-8 obtained in Example 8 of the present invention 1 ;

[0043] Figure 16 1H NMR spectra of compound S-8 obtained in Example 8 of the present invention 13 ;

[0044] Figure 17 1H NMR spectra of compound S-9 obtained in Example 9 of the present invention 1 ;

[0045] Figure 18 13C NMR result diagram of compound S-9 obtained in Example 9 of the present invention 13 ;

[0046] Figure 19 1H NMR result diagram of compound S-10 obtained in Example 10 of the present invention 1 ;

[0047] Figure 20 13C NMR result diagram of compound S-10 obtained in Example 10 of the present invention 13 ;

[0048] Figure 21 1H NMR result diagram of compound S-11 obtained in Example 11 of the present invention 1 ;

[0049] Figure 22 13C NMR result diagram of compound S-11 obtained in Example 11 of the present invention 13 ; Detailed implementation mode

[0050] Next, in combination with the accompanying drawings and specific implementation modes, the present invention will be further described. It should be noted that, on the premise of no conflict, the following-described embodiments or technical features can be arbitrarily combined to form new embodiments. Unless otherwise defined, the technical terms used in the following embodiments have the same meaning as commonly understood by those skilled in the art to which the present invention belongs. The test reagents used in the following embodiments are all conventional biochemical reagents unless otherwise specified; the experimental methods are all conventional methods unless otherwise specified. The room temperature mentioned in the present invention generally refers to 20-35°C.

[0051] The preparation methods of Examples 1 to 11 can refer to the following reaction flow chart.

[0052]

[0053] Example 1

[0054] An enantiopure planar chiral dibenzo diazocin dione compound S-1 Its preparation process includes:

[0055] (1) Take a 100 mL round-bottom flask, add compound I-1 (Ar = Ph) (2.3 g, 10 mmol, 1.0 equiv), anhydrous potassium carbonate (0.69 g, 5 mmol), add 25 mL of anhydrous acetonitrile, and then slowly add compound II-1 (R 1= Bn) (1.18 mL, 10 mmol), after reacting at 85 °C for 4 h, 20 mL of saturated ammonium chloride solution was added to the reaction system to terminate the reaction, and the mixture was extracted with ethyl acetate (3 × 25 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography with ethyl acetate / petroleum ether = 1 / 1 as the eluent to obtain 1.64 g of compound Ⅲ-1 (R 1 = Bn). The yield was 50%, and the product was a white solid.

[0056] (2) A dry reaction tube equipped with a magnetic stir bar was charged with compound Ⅲ-1 (32.8 mg, 0.1 mmol), quinidine (3.2 mg, 0.01 mmol), and anhydrous acetonitrile (2.0 mL), and then Ⅳ (13.8 mg, 0.06 mmol) was added. The resulting mixture was reacted at room temperature for 6 h. After completion of the reaction, saturated brine was added to stop the reaction, and the mixture was washed with ethyl acetate and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by column chromatography to obtain 15.4 mg of compound S-1. The yield was 47%, and the product was a white solid.

[0057] M.p.: 137.3 - 138.9 °C; 7.51 - 7.41 (m, 1H), 7.37 - 7.31 (m, 1H), 7.29 - 7.16 (m, 9H), 7.03 - 6.94 (m, 2H), 5.43 - 5.15 (m, 1H), 4.98 - 4.74 (m, 1H); 13 C NMR (100 MHz, CDCl3) δ 170.3, 170.3, 168.2, 168.1, 139.19, 136.4, 134.7, 134.1, 133.3, 131.2, 130.6, 128.9, 128.7, 128.3, 127.9, 127.9, 126.6, 126.6, 125.5, 53.5. HRMS (ESI) m / z calcd for C 21 H 16 N2O2 [M + H] + = 329.1285, found = 329.1292. HPLC (IC column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 16.95 min (minor), t2 = 18.32 min (major), ee = 91%.

[0058] Example 2

[0059] An enantiopure planar chiral dibenzo diazocin dione compound S-2 Its preparation process includes:

[0060] Adjust I-1 in step (1) of Example 1 to I-2 (Ar = 4-CH3OC6H4), and the remaining steps are the same as those in Example 1. Compound S-2 (R 1 = Bn, Ar = 4-CH3OC6H4) 17.8 mg was obtained. The yield was 46%, and the state was a white solid.

[0061] M.p.: 97.5 - 99.9 °C; 1 H NMR (400 MHz, CDCl3) δ 8.04 (s,

[0062] 1H), 7.40 (d, J = 8.6 Hz, 1H), 7.31 - 7.21 (m, 6H), 6.81 - 6.69 (m, 2H), 6.55 - 6.34 (m, 2H), 5.15 (d, J = 14.3 Hz, 1H), 4.92 (d, J = 14.3 Hz, 1H), 3.72 (s, 3H), 3.62 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 170.2, 168.2, 161.5, 161.1, 140.9, 136.8, 135.8, 129.9, 129.8, 129.0, 128.0, 127.8, 127.1, 125.4, 114.3, 113.7, 112.0, 110.6, 55.5, 55.4. HRMS (ESI) m / z calcdfor C 23 H 20 N2O4[M + H] + = 389.1496, found = 389.1497; HPLC (IB column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 8.18 min (minor), t2 = 8.84 min (major), ee = 90%.

[0063] Example 3

[0064] An enantiopure planar chiral dibenzo diazocin dione compound S-3 Its preparation process includes:

[0065] Adjust I-1 in step (1) of Example 1 to I-3 (Ar = 4-ClC6H4), and the remaining steps are the same as those in Example 1. Compound S-3 (R 1= Bn, Ar = 4-ClC6H4) 19.0 mg. The yield was 48%, and the state was a white solid.

[0066] M.p.: 265.8 - 267.2 °C; 7.40 (d, J = 8.3 Hz, 1H), 7.31 - 7.18 (m, 8H), 7.09 - 6.82 (m, 2H), 5.33 (t, J = 14.7 Hz, 1H), 4.77 (t, J = 14.2 Hz, 1H); 13 C NMR (100 MHz, CDCl3) δ 169.0, 166.9, 140.0, 137.1, 136.4, 135.6, 135.0, 132.8, 131.4, 129.7, 129.6, 129.3, 128.9, 128.8, 128.6, 128.2, 127.0, 125.7, 53.6. HRMS (ESI) m / z calcd for C 21 H 14 Cl2N2O2 [M+H] + = 397.0506, found = 397.0504; HPLC (IC column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 7.01 min (major), t2 = 8.51 min (minor), ee = 94%.

[0067] Example 4

[0068] An enantiopure planar chiral dibenzodiazocinone compound S-4 Its preparation process includes:

[0069] Adjust I-1 in step (1) of Example 1 to I-4 (Ar = 5-ClC6H4), and the remaining steps are the same as those in Example 1. Compound S-4 (R 1 = Bn, Ar = 5-ClC6H4) 19.0 mg. The yield was 48%, and the state was a white solid.

[0070] M.p.: 137.2 - 138.6 °C; 1 H NMR (400 MHz, CDCl3) δ 7.98 (s,

[0071] 1H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.74 (d, J = 1.9 Hz, 1H), 7.67 - 7.51 (m, 3H), 7.30 - 7.27 (m, 2H), 7.27 - 7.22 (m, 3H), 6.72 (dd, J = 17.3, 8.4 Hz, 2H), 5.16 (d, J = 14.3 Hz, 1H), 4.87 (d, J = 14.3 Hz, 1H); 13 13C NMR (100 MHz, CDCl3) δ 168.2, 166.4, 137.2, 135.9, 135.8, 134.0, 134.4, 134.1, 132.1, 131.6, 130.9, 128.9, 128.8, 128.39, 128.4, 128.2, 127.0, 53.5. HRMS (ESI) m / z calcd for C 21 H 14 Cl2N2O2 [M + H] + = 397.0506, found = 397.0503; HPLC (IC column, i - propanol / n - hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 4.98 min (minor), t2 = 5.83 min (major), ee => 99%.

[0072] Example 5

[0073] An enantiopure planar chiral dibenzodiazocinone compound S - 5 Its preparation process includes:

[0074] Adjust I - 1 in step (1) of Example 1 to I - 5 (Ar = 5 - IC6H4), and the remaining steps are the same as those in Example 1. Compound S - 5 (R 1 = Bn, Ar = 5 - IC6H4) 27.2 mg was obtained. The yield was 47%, and the state was a white solid.

[0075] M.p.: 272.1 - 272.9 °C; 1 1H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.74 (d, J = 2.4 Hz, 1H), 7.38 - 7.19 (m, 8H), 7.09 - 6.86 (m, 2H), 5.22 (d, J = 14.3 Hz, 1H), 4.85 (d, J = 14.3 Hz, 1H); 1313C NMR (100 MHz, CDCl3) δ 167.8, 166.1, 140.5, 139.8, 138.4, 137.1, 137.1, 136.2, 135.8, 133.2, 128.9, 128.8, 128.4, 128.2, 127.3, 94.0, 93.0, 53.4. HRMS (ESI) m / z calcd for C 21 H 14 I2N2O2 [M+Na] + = 602.9037, found = 602.9039 HPLC (IF column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 10.75 min (major), t2 = 14.89 min (minor), ee = 97%.

[0076] Example 6

[0077] An enantiopure planar chiral dibenzodiazocinone compound S-6 Its preparation process includes:

[0078] Adjust I-1 in step (1) of Example 1 to I-6 (Ar = napthyl), and the remaining steps are the same as in Example 1. Compound S-6 (R 1 = Bn, Ar = napthyl) 20.1 mg was obtained. The yield was 47%, and the state was a colorless liquid.

[0079] 1 1H NMR (400 MHz, CDCl3) δ 8.38 (s, 1H), 7.97 (s, 1H), 7.89 (s, 1H), 7.80 - 7.68 (m, 2H), 7.66 - 7.60 (m, 1H), 7.59 - 7.53 (m, 1H), 7.48 (s, 1H), 7.46 - 7.37 (m, 4H), 7.37 - 7.24 (m, 6H), 5.19 (s, 2H); 13 13C NMR (100 MHz, CDCl3) δ 170.5, 168.6, 136.7, 136.0, 133.8, 133.8, 133.6, 132.1, 132.0, 131.9, 130.9, 129.2, 128.9, 128.7, 128.4, 128.3, 128.1, 127.9, 127.9, 127.7, 127.7, 127.5, 127.4, 127.0, 126.3, 124.5, 54.2. HRMS (ESI) m / z calcd for C29 H 20 N2O2[M+H] + = 429.1598, found = 429.1607; HPLC (IC column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 22.24 min (major), t2 = 27.08 min (minor), ee => 99%.

[0080] Example 7

[0081] An enantiopure planar chiral dibenzodiazepinedione compound S-7 Its preparation process includes:

[0082] Adjust II-1 in step (1) of Example 1 to II-2 (R 1 = 4-CH3C6H4CH2), and the remaining steps are the same as those in Example 1. Obtain 16.8 mg of compound S-7 (R 1 = 4-CH3C6H4CH2, Ar = Ph). The yield is 49%, and the state is a white solid.

[0083] M.p.: 166.7-167.3 °C; 1 H NMR (400 MHz, CDCl3) δ 9.12 (s, 1H), 7.44 (dd, J = 7.0, 2.0 Hz, 1H), 7.35-7.30 (m, 1H), 7.27-7.15 (m, 6H), 7.06 (d, J = 7.9 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 5.28 (d, J = 14.3 Hz, 1H), 4.83 (d, J = 14.3 Hz, 1H), 2.16 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 170.7, 168.1, 139.2, 137.6, 134.7, 134.3, 133.4, 133.3, 131.1, 130.5, 129.3, 128.8, 128.6, 128.3, 128.2, 127.8, 126.6, 125.4, 53.2, 21.0. HRMS (ESI) m / z calcd for C 22 H 18 N2O2[M+H] += 343.1442, found = 343.1449; HPLC (IK column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 10.48 min (minor), t2 = 12.05 min (major), ee = 98%.

[0084] Example 8

[0085] An enantiopure planar chiral dibenzodiazocinone compound S-8 Its preparation process includes:

[0086] Adjust II-1 in step (1) of Example 1 to II-3 (R 1 = 4-CH3OC6H4CH2), and the remaining steps are the same as those in Example 1. Compound S-8 (R 1 = 4-CH3OC6H4CH2, Ar = Ph) 15.8 mg was obtained. The yield was 47%, and the state was a white solid.

[0087] M.p.: 198.5 - 199.9 °C; 1 H NMR (400 MHz, CDCl3) δ 8.37 (s, 1H), 7.42 (dd, J = 7.2, 1.9 Hz, 1H), 7.38 - 7.31 (m, 1H), 7.28 - 7.19 (m, 6H), 7.04 - 6.98 (m, 1H), 6.96 - 6.90 (m, 1H), 6.81 (d, J = 8.6 Hz, 2H), 5.11 (d, J = 14.3 Hz, 1H), 4.91 (d, J = 14.3 Hz, 1H), 3.73 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 170.2, 168.1, 159.2, 139.2, 134.8, 134.0, 133.3, 131.1, 130.5, 130.3, 128.6, 128.6, 128.3, 128.3, 127.9, 126.7, 125.5, 114.0, 55.2, 52.8. HRMS (ESI) m / z calcd for C 22 H 18 N2O3[M + H] += 359.1391, found = 359.1398; HPLC (IF column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 23.12 min (major), t2 = 29.72 min (minor), ee => 99%.

[0088] Example 9

[0089] An enantiopure planar chiral dibenzodiazocinone compound S-9 Its preparation process includes:

[0090] Adjust II-1 in step (1) of Example 1 to II-4 (R 1 = 3-BrC6H4CH2), and the remaining steps are the same as those in Example 1. Compound S-9 (R 1 = 3-BrC6H4CH2, Ar = Ph) 19.1 mg was obtained. The yield was 47%, and the state was a white solid.

[0091] M.p.: 106.8 - 107.9 °C; 1 H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.50 - 7.43 (m, 2H), 7.41 - 7.34 (m, 2H), 7.32 - 7.20 (m, 5H), 7.18 - 7.13 (m, 1H), 7.05 - 6.96 (m, 2H), 5.24 (d, J = 14.5 Hz, 1H), 4.84 (d, J = 14.5 Hz, 1H); 13 C NMR (100 MHz, CDCl3) δ 169.9, 168.2, 139.0, 138.6, 134.5, 133.9, 133.2, 131.8, 131.4, 131.0, 130.7, 130.2, 128.8, 128.5, 128.4, 128.1, 127.3, 126.4, 125.5, 122.7, 52.9. HRMS (ESI) m / z calcd for C 21 H 15 BrN2O2 [M + H] + = 407.0390, found = 407.0389 HPLC (IF column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 13.72 min (minor), t2 = 14.59 min (major), ee = 96%.

[0092] Example 10

[0093] An enantiopure planar chiral dibenzo[b,f][1,4]diazepine-2,5-dione compound S-10 Its preparation process includes:

[0094] Adjust II-1 in step (1) of Example 1 to II-5 (R 1 =allyl), and the remaining steps are the same as in Example 1. 12.3 mg of compound S-10 (R 1 =allyl, Ar = Ph) was obtained. The yield was 48%, and the state was a colorless liquid.

[0095] 1 1H NMR (400 MHz, DMSO) δ 10.26 (s, 1H), 7.46 - 7.25 (m, 6H), 7.23 - 7.18 (m, 1H), 7.03 (d, J = 7.8 Hz, 1H), 5.81 - 5.65 (m, 1H), 5.25 - 5.14 (m, 1H), 5.10 (d, J = 10.2 Hz, 1H), 4.84 (dd, J = 15.3, 5.4 Hz, 1H), 4.13 (dd, J = 15.3, 6.7 Hz, 1H); 13 13C NMR (100 MHz, CDCl3) δ 174.3, 172.3, 143.8, 140.0, 139.7, 139.4, 137.9, 136.1, 135.5, 133.5, 133.0, 132.7, 132.3, 131.4, 130.6, 3.5, 56.3. HRMS (ESI) m / z calcd for C 17 H 14 N2O2 [M + H] + = 279.1129, found = 279.1136; HPLC (IF column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 9.11 min (minor), t2 = 12.33 min (major), ee = 95%.

[0096] Example 11

[0097] An enantiopure planar chiral dibenzo[b,f][1,4]diazepine-2,5-dione compound S-11 Its preparation process includes:

[0098] Adjust II-1 in step (1) of Example 1 to II-6 (R 1= 2-ethoxy-2-oxoethyl), and the remaining steps were the same as in Example 1. Compound S-11 (R 1 = 2-ethoxy-2-oxoethyl, Ar = Ph) 14.9 mg was obtained. The yield was 46%, and the state was a white solid.

[0099] M.p.: 194.1 - 195.5 °C; 1 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.50 - 7.40 (m, 2H), 7.40 - 7.32 (m, 2H), 7.30 - 7.22 (m, 3H), 7.04 (d, J = 7.4 Hz, 1H), 4.60 (d, J = 17.1 Hz, 1H), 4.44 (d, J = 17.1 Hz, 1H), 4.34 - 4.21 (m, 2H), 1.32 (t, J = 7.1 Hz, 3H); 13 13C NMR (100 MHz, CDCl3) δ 169.9, 168.6, 168.3, 139.7, 134.1, 133.8, 132.9, 131.7, 130.8, 128.9, 128.6, 128.2, 125.8, 125.5, 61.7, 51.9, 14.2. HRMS (ESI) m / z calcd for C 18 H 16 N2O4 [M + H] + = 325.1183, found = 325.1191; HPLC (IF column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 20.42 min (major), t2 = 26.02 min (minor), ee = 90%.

[0100] Experimental Example 1

[0101]

[0102] (a) Take a 50 mL round-bottom flask, add 10 mL of dichloromethane, add compound S-1 (R 1 = Bn) (328 mg, 1 mmol, 1.0 equiv) and triethylamine (138 μL, 1 mmol), and then slowly add compound V-1 (R 3=Ph)(0.59 mL, 1.2 mmol). After reacting at room temperature for 2 hours, 10 mL of saturated ammonium chloride solution was added to the reaction system to terminate the reaction. The mixture was extracted with ethyl acetate (3 × 25 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography with the eluent ratio of ethyl acetate / petroleum ether = 1 / 5 to obtain 419 mg of compound VI-1 (R 1 =Bn, R 3 =Ph). The yield was 97%, and the product was a white solid.

[0103] M.p.: 162.1 - 162.9 °C; 1 1H NMR (400 MHz, CDCl3) δ 7.74 - 7.60 (m, 2H), 7.54 - 7.46 (m, 1H), 7.43 - 7.26 (m, 12H), 7.22 - 7.16 (m, 2H), 6.86 - 6.77 (m, 1H), 5.48 (d, J = 14.2 Hz, 1H), 4.94 (d, J = 14.2 Hz, 1H); 13 13C NMR (100 MHz, CDCl3) δ 171.2, 169.1, 168.0, 139.1, 136.7, 135.0, 134.7, 134.6, 134.0, 132.4, 131.8, 130.3, 129.5, 129.3, 129.0, 129.0, 128.9, 128.8, 128.7, 128.5, 128.2, 127.5, 126.8, 53.1. HRMS (ESI) m / z calcd for C 28 H 20 N2O3 [M + H] + = 433.1547, found = 433.1559; HPLC (IB column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 8.14 min (major), t2 = 11.88 min (minor), ee = 98%.

[0104] (b) A dry reaction tube equipped with a magnetic stir bar was charged with compound VI-1 (43.2 mg, 0.1 mmol) and dry toluene (2.0 mL), and then VII (20.2 mg, 0.2 mmol) was added. The resulting mixture was reacted at 0 °C for 12 hours. After the reaction was completed, saturated brine was added to stop the reaction. The mixture was washed with ethyl acetate, and the solvent was removed by distillation under reduced pressure. The product was purified by column chromatography to obtain compound VIII-1 (R 3=Ph) 19.7 mg. The yield was 48%, and the state was a colorless liquid.

[0105] 1 1H NMR (400 MHz, CDCl3) δ 7.90 - 7.67 (m, 2H), 7.61 - 7.34 (m, 3H), 5.99 (d, J = 7.6 Hz, 1H), 4.22 - 3.97 (m, 1H), 1.16 (d, J = 6.8 Hz, 3H), 0.97 (s, 9H); 13 13C NMR (100 MHz, CDCl3) δ 166.9, 135.3, 131.3, 128.6, 126.8, 53.1, 34.5, 26.3, 16.2. HRMS (ESI) m / z calcd for C 13 H 19 NO[M + H] + = 206.1540, found = 206.1543; HPLC (IB column, i - propanol / n - hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 3.73 min (major), t2 = 4.24 min (minor), ee = 46%.

[0106] Experimental Example 2

[0107] The difference between this experimental example and Experimental Example 1 is that Compound V - 1 was adjusted to V - 2 (R 3 = furyl), and Compound VI - 2 (R 1 = Bn, R 3 = furyl) 405 mg was obtained. The yield was 96%, and the state was a white solid.

[0108] M.p.: 176.5 - 177.9 °C; 1 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 0.9 Hz, 1H), 7.45 - 7.26 (m, 10H), 7.25 - 7.18 (m, 2H), 7.09 - 7.00 (m, 1H), 6.86 - 6.76 (m, 1H), 6.45 (dd, J = 3.6, 1.7 Hz, 1H), 5.40 (d, J = 14.3 Hz, 1H), 4.89 (d, J = 14.3 Hz, 1H); 1313C NMR (100 MHz, CDCl3) δ 168.7, 167.9, 159.7, 147.3, 146.9, 139.2, 136.7, 135.0, 134.6, 133.5, 131.8, 130.5, 129.6, 129.3, 129.1, 128.8, 128.7, 128.0, 127.6, 127.1, 120.6, 112.8, 53.2. HRMS (ESI) m / z calcd for C 26 H 18 N2O4 [M + H] + = 423.1340, found = 423.1342; HPLC (IB column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 10.97 min (major), t2 = 23.02 min (minor), ee = 97%.

[0109] Compound VIII-2 (R 3 = furyl) 18 mg was obtained. The yield was 46% and the state was a white solid.

[0110] M.p.: 75.0 - 78.5 °C; 1 1H NMR (400 MHz, CDCl3) δ 7.43 (dd, J =

[0111] 1.6, 0.7 Hz, 1H), 7.10 (dd, J = 3.5, 0.7 Hz, 1H), 6.50 (dd, J = 3.5, 1.8 Hz, 1H), 6.21 (d, J = 7.2 Hz, 1H), 4.12 - 3.97 (m, 1H), 1.15 (d, J = 6.8 Hz, 3H), 0.96 (s, 9H); 13 13C NMR (100 MHz, CDCl3) δ 157.8, 148.3, 143.6, 114.0, 112.2, 52.4, 34.4, 26.2, 16.2. HRMS (ESI) m / z calcd for C 11 H 17 NO2 [M + H] + = 196.133, found = 196.1334; HPLC (IB column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 3.91 min (major), t2 = 4.45 min (minor), ee = 38%.

[0112] Experimental Example 3

[0113] The difference between this experimental example and Experimental Example 1 is that compound V-1 was adjusted to V-3 (R 3 = napthyl), and 443 mg of compound VI-3 (R 1 = Bn, R 3 = napthyl) was obtained. The yield was 92%, and the state was a white solid.

[0114] M.p.: 182.3 - 183.7 °C; 1 H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.88 - 7.81 (m, 2H), 7.80 - 7.70 (m, 1H), 7.60 - 7.49 (m, 2H), 7.46 - 7.40 (m, 3H), 7.38 - 7.33 (m, 4H), 7.29 - 7.26 (m, 2H), 7.22 - 7.11 (m, 3H), 6.82 - 6.74 (m, 1H), 5.68 (d, J = 14.2 Hz, 1H), 4.90 (d, J = 14.2 Hz, 1H); 13 C NMR (100 MHz, CDCl3) δ 171.3, 169.2, 168.2, 138.9, 136.8, 135.3, 135.2, 134.8, 134.0, 132.5, 131.7, 131.6, 130.7, 130.4, 129.5, 129.4, 129.2, 129.0, 128.9, 128.9, 128.8, 128.7, 128.6, 128.4, 128.4, 128.2, 127.8, 127.6, 126.8, 126.8, 124.8, 53.1. HRMS (ESI) m / z calcd for C 32 H 22 N2O3 [M + H] + = 483.1704, found = 483.1710; HPLC (IB column, i-propanol / n-hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 9.33 min (major), t2 = 10.42 min (minor), ee => 99%.

[0115] 23.4 mg of compound VIII-3 (R 3 = napthyl) was obtained. The yield was 46%, and the state was a colorless liquid.

[0116] 1 1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1H), 7.98 - 7.77 (m, 4H), 7.63 - 7.48 (m, 2H), 6.07 (d, J = 9.3 Hz, 1H), 4.24 - 4.11 (m, 1H), 1.21 (d, J = 6.8 Hz, 3H), 1.02 (s, 9H); 13 13C NMR (100 MHz, CDCl3) δ 167.0, 128.9, 128.5, 127.8, 127.6, 127.1, 126.8, 3.6, 53.3, 34.6, 26.3, 16.3. HRMS (ESI) m / z calcd for C 17 H 21 NO[[M + H]] + = 256.1696, found = 256.1694; HPLC (IB column, i - propanol / n - hexane = 30 / 70, flow rate 1.0 mL / min, λ = 254 nm), t1 = 4.48 min (major), t2 = 5.00 min (minor), ee = 50%.

[0117] The above - mentioned embodiments are only the preferred embodiments of the present invention, and the scope of protection of the present invention cannot be limited thereby. Any non - substantial changes and substitutions made by those skilled in the art based on the present invention fall within the scope of protection required by the present invention.

Claims

1. An enantiopure planar chiral dibenzodiazocinone compound, characterized in that, Having the structural general formula S Among them, the R 1 is one of 4-CH3C6H4CH2, 4-CH3OC6H4CH2, 3-BrC6H4CH2, allyl, 2-ethoxy-2-oxoethyl; Ar is one of C6H5, 4-CH3OC6H4, 4-ClC6H4, 5-ClC6H4, 5-IC6H4, naphthyl.

2. The preparation method of an enantiopure planar chiral dibenzodiazocinone compound as described in claim 1, characterized in that, Comprising the following steps: (1) Dissolve Compound I and Compound II in an organic solvent, then add an inorganic base and react to obtain a racemic product, Compound III; (2) Dissolve the Compound III obtained in step (1) in an organic solvent and react with Compound IV under the action of a catalyst to obtain an enantiopure Compound S, and the catalyst is quinidine; The reaction temperature of step (1) is 85 °C and the time is 4 h; The reaction temperature of step (2) is room temperature and the time is 6 h.

3. The method according to claim 2, characterized in that, The organic solvent in step (1) and step (2) is CH3CN.

4. The method according to claim 2, wherein The inorganic base in step (1) is potassium carbonate.

5. The method according to claim 2, wherein The molar ratio of Compound I, Compound II and the inorganic base in step (1) is 1:1:0.5; The molar ratio of Compound III, Compound IV and the catalyst in step (2) is 1:0.6:0.

1.

6. Use of an enantiopure planar chiral dibenzodiazepinoctadione compound as claimed in claim 1 as a chiral acylation reagent in the kinetic resolution of 3,3-dimethylbutan-2-amine.

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