Double-chiral element rotation-resistant aryl tertiary amide compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of rotation-resistant aryl tertiary amide compounds, in particular to a double-chiral element rotation-resistant aryl tertiary amide compound, a preparation method and application. The chiral element rotation-resistant aryl tertiary amide compound disclosed by the invention contains two important homoallylic alcohol and aryl amide functional groups, double bonds and hydroxyl can be subjected to abundant chemical conversion to obtain different axial chiral skeletons, and the chiral element rotation-resistant aryl tertiary amide compound has potential application value in the fields of asymmetric catalysis and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of atroparyl tertiary amide compounds, and in particular to a chiral element atroparyl tertiary amide compound, a preparation method and an application thereof. Background Art

[0002] At present, the catalytic asymmetric synthesis of atropisomers of aromatic tertiary amides has made certain research progress, but compared with the typical synthesis strategy of biaryl atropisomers, it is still relatively limited. The asymmetric synthesis of atropisomers of aromatic tertiary amides containing chiral elements based on organic catalysis is even rarer.

[0003] So far, there are only two reports on the construction of aromatic amide atropisomers containing both a carbon center chirality and a CC chiral axis through organic catalytic asymmetric dynamic kinetic transformation based on aldehyde groups. Therefore, the single reaction type and narrow product structure and functional group range greatly limit the research and application of this type of chiral skeleton. Therefore, the invention of a new chiral element atropisomer aromatic tertiary amide compound is a technical problem that needs to be solved urgently. Summary of the invention

[0004] The purpose of the present invention is to provide a chiral element atroparyl tertiary amide compound, a preparation method and an application thereof, and to prepare a new type of atroparyl tertiary amide compound containing a point-axis chiral element by asymmetric allylation catalyzed by chiral phosphoric acid using achiral o-formyl substituted aromatic tertiary amide as a starting material.

[0005] To achieve the above object, the present invention provides a chiral element atroparyl tertiary amide compound, the structure of which is as follows:

[0006]

[0007] Among them, R 1 is selected from the following groups: -H, alkyl, alkoxy, aryl; R 2 Selected from the following groups: alkyl.

[0008] The present invention also provides a method for preparing a chiral element atroparyl tertiary amide compound, comprising:

[0009] The reactants 2-formyl-N,N-dialkyl-1-naphthylamide and 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborane are dissolved in a solvent and reacted to obtain a chiral element-retarded aromatic tertiary amide compound.

[0010] The present invention also provides an application of a chiral element atropytic aromatic tertiary amide compound, and an application of the chiral element atropytic aromatic tertiary amide compound in asymmetric catalysis.

[0011] Technical effects and advantages of the present invention:

[0012] 1. The starting materials required in the present invention are cheap and readily available, and the preparation method is simple.

[0013] 2. The reaction conditions in the present invention are mild and easy to operate.

[0014] 3. The present invention constructs two easily separable aromatic amide diastereomers containing two different chiral elements in one step, and has good enantioselectivity.

[0015] 4. The chiral element-restricted aromatic tertiary amide compound prepared by the method of the present invention contains two important homoallyl alcohol and aromatic amide functional groups. The double bonds and hydroxyl groups can undergo a variety of chemical transformations to obtain different axial chiral skeletons, which has potential application value in the fields of asymmetric catalysis and the like.

[0016] Other features and advantages of the present invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is the HPLC spectrum of 3a;

[0018] Figure 2 is the HPLC spectrum of the racemic compound corresponding to 3a;

[0019] Figure 3 For 3a 1 H NMR spectrum;

[0020] Figure 4 For 3a 13 C NMR spectrum;

[0021] Figure 5 is the HPLC spectrum of 4a;

[0022] Figure 6 is the HPLC spectrum of the racemic compound corresponding to 4a;

[0023] Figure 7 For 4a 1 H NMR spectrum;

[0024] Figure 8 For 4a 13 C NMR spectrum;

[0025] Fig. 9 is the HPLC spectrum of 3b;

[0026] Fig.10 is the HPLC spectrum of the racemic compound corresponding to 3b;

[0027] Fig.11 For 3b 1 H NMR spectrum;

[0028] Fig.12 For 3b 13 C NMR spectrum;

[0029] Fig.13 is the HPLC spectrum of 4b;

[0030] Fig.14 is the HPLC spectrum of the racemic compound corresponding to 4b;

[0031] Fig.15 For 4b 1 H NMR spectrum;

[0032] Fig.16 For 4b 13 C NMR spectrum;

[0033] Fig.17 is the HPLC spectrum of 3c;

[0034] Fig.18 is the HPLC spectrum of the racemic compound corresponding to 3c;

[0035] Fig.19 For 3c 1 H NMR spectrum;

[0036] Fig. 20 For 3c 13 C NMR spectrum;

[0037] Fig.21 is the HPLC spectrum of 4c;

[0038] Fig. 22 is the HPLC spectrum of the racemic compound corresponding to 4c;

[0039] Fig.23 For 4c 1 H NMR spectrum;

[0040] Fig.24 For 4c 13 C NMR spectrum;

[0041] Fig.25 is the HPLC spectrum of 3d;

[0042] Fig.26 is the HPLC spectrum of the corresponding racemic compound of 3d;

[0043] Fig. 27 For 3D 1 H NMR spectrum;

[0044] Fig.28 For 3D 13 C NMR spectrum;

[0045] Fig.29 is the HPLC spectrum of 4d;

[0046] Fig.30 is the HPLC spectrum of the racemic compound corresponding to 4d;

[0047] Fig.31 For 4D 1 H NMR spectrum;

[0048] Fig.32 For 4D 13 C NMR spectrum;

[0049] Fig.33 is the HPLC spectrum of 3e;

[0050] Fig.34 is the HPLC spectrum of the racemic compound corresponding to 3e;

[0051] Fig.35 For 3e 1 H NMR spectrum;

[0052] Fig.36 For 3e 13 C NMR spectrum;

[0053] Fig.37 is the HPLC spectrum of 3f;

[0054] Fig.38 is the HPLC spectrum of the corresponding racemic compound of 3f;

[0055] Fig.39 For 3f 1 H NMR spectrum;

[0056] Fig.40 For 3f 13 C NMR spectrum;

[0057] Fig.41 is the HPLC spectrum of 4f;

[0058] Fig.42 is the HPLC spectrum of the racemic compound corresponding to 4f;

[0059] Fig.43 For 4f 1 H NMR spectrum;

[0060] Fig.44 For 4f 13 C NMR spectrum;

[0061] Fig.45 HPLC spectrum of 3g;

[0062] Fig.46 is the HPLC spectrum of 3 g of the corresponding racemic compound;

[0063] Fig.47 For 3g 1 HNMR spectrum;

[0064] Fig.48 For 3g 13 C NMR spectrum;

[0065] Fig.49 HPLC spectrum of 4g;

[0066] Fig.50 is the HPLC spectrum of 4 g of the corresponding racemic compound;

[0067] Fig.51 For 4G 1 HNMR spectrum;

[0068] Fig.52 For 4G 13 C NMR spectrum;

[0069] Fig.53 HPLC spectrum of 3h;

[0070] Fig.54 is the HPLC spectrum of the racemic compound corresponding to 3h;

[0071] Fig.55 For 3h 1 HNMR spectrum;

[0072] Fig.56 For 3h 13 C NMR spectrum;

[0073] Fig.57 HPLC spectrum of 4h;

[0074] Fig.58 is the HPLC spectrum of the racemic compound corresponding to 4h;

[0075] Fig.59 For 4 hours 1 HNMR spectrum;

[0076] Fig.60 For 4 hours 13 C NMR spectrum;

[0077] Fig.61 is the HPLC spectrum of 3i;

[0078] Fig.62 is the HPLC spectrum of the racemic compound corresponding to 3i;

[0079] Fig.63 For 3i 1 HNMR spectrum;

[0080] Fig.64 For 3i 13 C NMR spectrum. DETAILED DESCRIPTION

[0081] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0082] The present invention discloses a chiral element atroparyl tertiary amide compound, the structure of which is as follows:

[0083]

[0084] Among them, R 1 is selected from the following groups: -H, alkyl, alkoxy, aryl; R 2 Selected from the following groups: alkyl

[0085] Specifically, R 1 Includes the following groups: -H, -CH3, -CH2CH3, -OCH3, -Ph; R 2 Includes the following groups: -CH(CH3)2, -cyclohexyl.

[0086] The present invention also provides a method for preparing a chiral element atropytic aromatic tertiary amide compound, comprising: dissolving reactants 2-formyl-N,N-dialkyl-1-naphthylamide and 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborane in a solvent and reacting to obtain a chiral element atropytic aromatic tertiary amide compound.

[0087] The specific steps are as follows: in a nitrogen atmosphere, the substrate 2-formyl-N,N-dialkyl-1-naphthylamide 1 and the substrate 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborane 2 are dissolved in a solvent, and chiral phosphoric acid (CPA) is added as a catalyst and Molecular sieve( MS) as an additive, and then stirred at a temperature of 40 to -40°C for 10 to 36 hours to obtain the corresponding diastereoisomer products 3 and 4. The reaction is shown below:

[0088]

[0089] Specifically, the molar ratio of the 2-formyl-N,N-dialkyl-1-naphthylamide, the 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, and the chiral phosphoric acid catalyst is 1:1-3:0.05-0.25. The mass ratio of the 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and the molecular sieve additive is 279:20-93:400.

[0090] Specifically, the solvent includes at least one of the following: anhydrous chlorobenzene (Chlorobenzene, simplified as MCB), anhydrous toluene, anhydrous mesitylene, anhydrous ethyl acetate, anhydrous tetrahydrofuran, anhydrous ethyl acetate, anhydrous dichloromethane, anhydrous chloroform.

[0091] Specifically, the structural formula of the chiral phosphoric acid catalyst is as follows:

[0092]

[0093] Among them, G=2,4,6-(i-Pr)3C6H2.

[0094] Specifically, the enantiomeric excess (EE) of compound 3 obtained in the above reaction reaches 63% to 97%, and the ee of compound 4 reaches 72% to 98%. The enantiomeric excess can measure the optical purity of chiral molecules, and the optical purity can be measured on a high performance liquid chromatography (HPLC) instrument using a chiral stationary phase chromatographic column (Daicel Co. CHIRALPAK), and the HPLC separation conditions are established using the corresponding racemic product. The preparation method of the racemic product is the same as the preparation method of the chiral product, and non-chiral phosphoric acid is used instead of chiral phosphoric acid as a catalyst.

[0095] The present invention also provides an application of a chiral element ablation aromatic tertiary amide compound. Preferably, the chiral element ablation aromatic tertiary amide compound is used in asymmetric catalysis. For example, the prepared ablation aromatic tertiary amide compound can be converted into an axially chiral phosphine ligand, which has important application prospects in asymmetric allylic substitution reaction, Heck coupling reaction, Suzuki-Miyaura coupling reaction and cycloaddition reaction.

[0096] In order to better understand the present invention, the following examples are provided below.

[0097] Embodiment 1:

[0098] R in substrate 11 =-H, R 2 =-CH(CH3)2. The specific steps are as follows:

[0099] In a nitrogen atmosphere, the substrate 2-formyl-N,N-diisopropyl-1-naphthamide 1a (28.3 mg, 0.10 mmol) and the substrate 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 2 (25.2 mg, 0.887 g / cm, 29 μL, 0.15 mmol) were dissolved in anhydrous chlorobenzene (MCB) (2.5 mL) as solvent, and chiral phosphoric acid catalyst CPA (7.5 mg, 10 mol%) and Molecular sieve( MS) (40 mg), and stirred at -40°C for 24 hours.

[0100] After the reaction was completed, the mixed solution was extracted with ethyl acetate and saturated ammonium chloride solution, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed by reduced pressure distillation using a rotary evaporator. Column chromatography was then performed and gradient elution (petroleum ether / ethyl acetate = 20 / 1 to 5 / 1) was used to obtain products 3a and 4a.

[0101]

[0102] 3a is a white powdery solid with a yield of 47% and 96% ee. The yield was measured by chromatography, where the chromatographic conditions were: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A was n-hexane, B was isopropanol; A:B = 0.9:0.1; flow rate was 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 21.449 min, tr (minor) = 24.879 min, and the corresponding peak area ratio was: 97.95:2.05. The HPLC spectrum of 3a and the HPLC spectrum of the corresponding racemic compound are shown in Figure 1 and 2 As shown, and the data in the figure are shown in Tables 1 and 2.

[0103] Table 1 HPLC spectrum data table of 3a

[0104]

[0105] Table 2 HPLC spectrum data table of 3a corresponding to the racemic compound

[0106]

[0107] To verify the structure of 3a, nuclear magnetic resonance spectroscopy (NMR) was also performed, such as Figure 3-4 As shown, the details are as follows: 1HNMR(600 MHz, CDCl3)δ7.85–7.80(m,2H),7.80–7.76(m,1H),7.65(d,J=8.4 Hz,1H),7.51–7.43(m,2H),5.92–5.84(m,1H),5.26–5.18(m,2H),4.91(dd,J=9.6,3.0 Hz,1H),3.65–3.54(m,2H),2.74–2.69(m,1H),2.46–2.40(m,1H),2.38(br.,s,1H),1.75(d,J=6.6Hz,3H),1.67(d,J=7.2 Hz,3H),1.09(d,J=6.6 Hz,3H),0.99(d,J=6.6 Hz,3H); 13 C NMR (150MHz, CDCl3) δ168.9,136.3,134.7,133.1,132.9,129.3,128.5,128.1,12 6.7,126.2,125.0,123.3,119.0,70.5,51.2,46.1,43.9,21.0,20.7,20.6,20.4.

[0108]

[0109] 4a is a white powdery solid with a yield of 46% and 88% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.9:0.1; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 10.081 min, tr (minor) = 7.676 min, and the corresponding peak area ratio is: 93.98:6.02. The HPLC spectrum of 4a and the HPLC spectrum of the corresponding racemic compound are shown in Figure 5 and 6 As shown, and the data in the figure are shown in Tables 3 and 4.

[0110] Table 3 HPLC spectrum data table of 4a

[0111]

[0112] Table 4 HPLC spectrum data table of 4a corresponding to the racemic compound

[0113]

[0114] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 7-8 As shown, the details are as follows: 1H NMR (600 MHz, CDCl3) δ7.85–7.81(m,2H),7.80–7.77(m,1H),7.66(d,J=8.4 Hz,1H),7.51–7.45(m,2H),5.92–5.84(m,1H),5.26–5.18(m,2H),4.91(dd,J=9.6,3.6Hz,1H),3.65–3.55(m,2H),2.75–2.69(m,1H ),2.47–2.40(m,1H),2.21(br.,s,1H),1.75(d,J=6.6Hz,3H),1.66(d,J=7.2Hz,3H),1.09(d,J=6.6Hz,3H),0.99(d,J=7.2Hz,3H); 13 C NMR (150MHz, CDCl3) δ168.9,136.3,134.7,133.1,132.9,129.3,128.5,128.1,12 6.8,126.2,125.0,123.3,119.1,70.5,51.2,46.2,44.0,21.0,20.7,20.6,20.4.

[0115] Embodiment 2:

[0116] Replace substrate 1 with R 1 =-CH3, and the rest of the experimental procedures refer to Example 1.

[0117]

[0118] 3b is a white powdery solid with a yield of 43% and 88% ee. Chromatographic conditions: OD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.9:0.1; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 12.466 min, tr (minor) = 10.163 min, and the corresponding peak area ratio is: 93.96:6.04. The HPLC spectrum of 3b and the HPLC spectrum of the corresponding racemic compound are shown in Fig. 9 and 10 As shown, and the data in the figure are shown in Tables 5 and 6.

[0119] Table 5 HPLC spectrum data table of 3b

[0120]

[0121] Table 6 HPLC spectrum data table of 3b corresponding to the racemic compound

[0122]

[0123] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 11-12 As shown, the details are as follows: 1 H NMR(600MHz, CDCl3)δ8.25(d,J=7.8Hz,1H),7.72(d,J=8.4Hz,1H),7.54–7.41(m, 2H),6.99(s,1H),5.95–5.83(m,1H),5.28–5.17(m,2H),4.90(dd,J=12.0,6.0Hz,1 H),4.03(s,3H),3.68–3.53(m,2H),2.79–2.71(m,1H),2.47–2.39(m,1H),1.74(d, J=7.2Hz,3H),1.65(d,J=5.4Hz,3H),1.09(d,J=6.6Hz,3H),0.99(d,J=6.6Hz,3H); 13 C NMR (150MHz, CDCl3) δ169.2,135.8,135.0,134.9,132.2,131.6,129.5,126.4,126. 1,125.6,124.3,123.8,118.9,70.5,51.1,46.1,43.9,20.9,20.7,20.6,20.4,19.7.

[0124]

[0125] 4b is a white powdery solid with a yield of 37% and 87% ee. Chromatographic conditions: OD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.9:0.1; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 5.841 min, tr (minor) = 7.297 min, and the corresponding peak area ratio is: 93.46:6.54. The HPLC spectrum of 4b and the HPLC spectrum of the corresponding racemic compound are shown in Fig.13 and 14 As shown, and the data in the figure are shown in Tables 7 and 8.

[0126] Table 7 HPLC spectrum data of 4b

[0127]

[0128] Table 8 HPLC spectrum data of 4b corresponding to the racemic compound

[0129]

[0130] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 15-16 As shown, the details are as follows: 1 H NMR (600MHz, CDCl3) δ8.03–7.93(m,1H),7.83–7.70(m,1H),7.57–7.45(m,3H ),5.95–5.81(m,1H),5.29–5.15(m,2H),4.88(dd,J=9.6,3.6Hz,1H),3.64–3 .54(m,2H),2.75–2.71(m,1H),2.70(s,3H),2.48–2.39(m,1H),1.75(d,J=6. 6Hz, 3H), 1.66 (d, J = 6.6Hz, 3H), 1.09 (d, J = 6.6Hz, 3H), 0.98 (d, J = 6.6Hz, 3H); 13 C NMR (150MHz, CDCl3) δ169.2,135.8,135.0,134.9,132.2,131.6,129.5,126.4,126. 1,125.6,124.3,123.8,118.9,70.5,51.1,46.1,43.9,20.9,20.7,20.6,20.4,19.7.

[0131] Embodiment 3:

[0132] Replace substrate 1 with R 1 =-CH2CH3, and the rest of the experimental operations refer to Example 1.

[0133]

[0134] 3c is a white powdery solid with a yield of 51% and 73% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B=0.95:0.05; flow rate is 1.0 mL / min, wavelength λ=254 nm, tr(major)=12.983 min, tr(minor)=8.851 min, and the corresponding peak area ratio is: 86.33:13.67. The HPLC spectrum of 3c and the HPLC spectrum of the corresponding racemic compound are shown in Fig.17 and 18 As shown, and the data in the figure are shown in Tables 9 and 10.

[0135] Table 9 HPLC spectrum data table of 3c

[0136]

[0137] Table 10 HPLC spectrum of the racemic compound corresponding to 3c

[0138]

[0139] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 19-20 As shown, the details are as follows: 1 H NMR(600MHz, CDCl3)δ8.04(d,J=7.2Hz,1H),7.80(d,J=6.6Hz,1H),7.55–7.42(m,3H),5.9 4–5.83(m,1H),5.27–5.17(m,2H),4.89(dd,J=9.6,3.6Hz,1H),3.67–3.54(m,2H),3.18–3. 04(m,2H),2.76–2.68(m,1H),2.48–2.40(m,1H),2.37(br.,s,1H),1.75(d,J=7.2Hz,3H), 1.66(d,J=7.2Hz,3H), 1.40(t,J=7.2Hz,3H), 1.09(d,J=7.2Hz,3H), 0.99(d,J=6.6Hz,3H); 13 CNMR (150MHz, CDCl3) δ169.2,140.9,135.9,134.9,131.6,131.4,129.7,126.3,126. 0,125.8,124.0,122.1,118.9,70.6,51.1,46.1,43.9,26.1,20.9,20.6,20.4,14.9.

[0140]

[0141] 4c is a white powdery solid with a yield of 43% and 71% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B=0.95:0.05; flow rate is 1.0 mL / min, wavelength λ=254 nm, tr(major)=5.131 min, tr(minor)=7.186 min, and the corresponding peak area ratio is: 85.56:14.44. The HPLC spectrum of 4c and the HPLC spectrum of the corresponding racemic compound are shown in Fig.21 and 22 As shown, and the data in the figure are shown in Tables 11 and 12.

[0142] Table 11 HPLC spectrum data table of 4c

[0143]

[0144] Table 12 HPLC spectrum of the racemic compound corresponding to 4c

[0145]

[0146] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 23-24 As shown, the details are as follows: 1 H NMR(600MHz, CDCl3)δ8.08–8.00(m,1H),7.83–7.75(m,1H),7.55–7.44(m,3H),5.95–5.8 2(m,1H),5.28–5.17(m,2H),4.89(dd,J=9.6,3.6Hz,1H),3.66–3.54(m,2H),3.19–3.04( m,2H),2.77–2.69(m,1H),2.48–2.39(m,1H),2.32(br.,s,1H),1.75(d,J=6.6Hz,3H),1. 66(d,J=7.2Hz,3H),1.40(t,J=7.2Hz,3H),1.10(d,J=6.6Hz,3H),1.00(d,J=6.6Hz,3H); 13 C NMR (150MHz, CDCl3) δ169.2,140.9,135.9,134.9,131.6,131.4,129.7,126.2,126. 0,125.8,124.0,122.1,118.9,70.6,51.1,46.1,43.9,26.1,20.9,20.6,20.4,14.9.

[0147] Embodiment 4:

[0148] Replace substrate 1 with R 1 =-OCH3, and the rest of the experimental operations refer to Example 1.

[0149]

[0150] 3d is a colorless powder solid with a yield of 44% and 93% ee. Chromatographic conditions: IC column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B=0.97:0.03; flow rate is 1.0 mL / min, wavelength λ=254 nm, tr(major)=18.822 min, tr(minor)=15.004 min, and the corresponding peak area ratio is: 96.68:3.32. The HPLC spectrum of 3d and the HPLC spectrum of the corresponding racemic compound are shown in Fig.25 and 26 As shown, and the data in the figure are shown in Tables 13 and 14.

[0151] Table 13 HPLC spectrum data table of 3d

[0152]

[0153] Table 14 HPLC spectrum data table of 3d corresponding racemic compound

[0154]

[0155] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 27-28 As shown, the details are as follows: 1 H NMR (600MHz, CDCl3) δ8.26–8.20(m,1H),7.75–7.70(m,1H),7.53–7.40(m,2H),6.99 (s,1H),5.95–5.83(m,1H),5.27–5.15(m,2H),4.89(dd,J=9.6,3.6Hz,1H),4.02(s,3 H),3.69–3.50(m,2H),2.77–2.69(m,1H),2.56(br.,s,1H),2.47–2.37(m,1H),1.73( d,J=6.6Hz,3H),1.64(d,J=6.6Hz,3H),1.07(d,J=7.2Hz,3H),0.98(d,J=6.6Hz,3H); 13 C NMR (150MHz, CDCl3) δ169.2,155.5,136.9,134.9,130.5,127.3,125.8,125.6,125. 1,124.7,122.2,118.9,100.8,70.8,55.6,51.1,46.1,43.9,20.9,20.7,20.6,20.4.

[0156]

[0157] 4d is a white powdery solid with a yield of 47% and 87% ee. Chromatographic conditions: IC column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.97:0.03; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 16.983, tr (minor) = 15.710 minmin, and the corresponding peak area ratio is: 93.50:6.50. The HPLC spectrum of 4d and the HPLC spectrum of the corresponding racemic compound are shown in Fig.29 and 30 As shown, and the data in the figure are shown in Tables 15 and 16.

[0158] Table 15 HPLC spectrum data table of 4d

[0159]

[0160] Table 16 HPLC spectrum of the racemic compound corresponding to 4d

[0161]

[0162] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 31-32 As shown, the details are as follows: 1 H NMR(600MHz, CDCl3)δ8.14–8.09(m,1H),7.92–7.88(m,1H),7.53–7.46(m,2H) ,7.43(s,1H),5.87–5.78(m,1H),5.27–5.23(m,1H),5.08–4.98(m,2H),3.83( s,3H),3.66–3.54(m,2H),2.60–2.54(m,1H),2.53–2.47(m,1H),1.70(d,J=6. 6Hz,3H),1.65(d,J=6.6Hz,3H),1.09(d,J=7.2Hz,3H),1.03(d,J=6.6Hz,3H); 13 C NMR (150MHz, CDCl3) δ170.1,152.4,134.5,133.3,131.6,130.6,127.9,126.8,125. 3,122.5,120.9,118.6,117.8,67.6,62.7,51.1,46.1,42.8,20.9,20.8,20.7,20.6.

[0163] Embodiment 5:

[0164] Replace substrate 1 with R 1 =-Ph, and the rest of the experimental procedures refer to Example 1.

[0165]

[0166] 3e is a white powdery solid with a yield of 46% and 84% ee. Chromatographic conditions: OD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B=0.96:0.04; flow rate is 1.0 mL / min, wavelength λ=254 nm, tr(major)=10.817 min, tr(minor)=13.316 min, and the corresponding peak area ratio is: 92.19:7.81. The HPLC spectrum of 3e and the HPLC spectrum of the corresponding racemic compound are shown in Fig.33 and 34 As shown, and the data in the figure are shown in Tables 17 and 18.

[0167] Table 17 HPLC spectrum data table of 3e

[0168]

[0169] Table 18 HPLC spectrum data table of 3e corresponding to the racemic compound

[0170]

[0171] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 35-36 As shown, the details are as follows: 1 H NMR(600MHz, CDCl3)δ7.88(d,J=8.4Hz,1H),7.84(d,J=8.4Hz,1H),7.61(s,1H),7.53–7 .44(m,5H),7.44–7.36(m,2H),5.95–5.80(m,1H),5.26–5.13(m,2H),4.94(dd,J=9.6,3. 6Hz,1H),3.76–3.57(m,2H),2.81–2.71(m,1H),2.50–2.41(m,1H),2.33(br.,s,1H),1. 77(d,J=6.6Hz,3H),1.68(d,J=6.6Hz,3H),1.13(d,J=7.2Hz,3H),1.03(d,J=6.6Hz,3H); 13 C NMR (150MHz, CDCl3) δ169.0,140.8,140.5,135.8,135.8,134.8,132.6,131.3,130.1,129.7,128.3 ,127.4,126.6,126.4,126.3,125.3,124.5,119.1,119.0,70.5,51.3,46.2,44.0,21.1,20.7,20.4.

[0172] It should be noted that in this example, the main product is 3e, and the corresponding diastereoisomer product 4e has a small yield and is therefore not separated.

[0173] Embodiment 6:

[0174] Replace substrate 1 with R 1 =-CH3, R 2 =-cyclohexyl The rest of the experimental procedures refer to Example 1.

[0175]

[0176] 3f is a white powdery solid with a yield of 47% and 97% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.9:0.1; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 8.606 min, tr (minor) = 10.481 min, and the corresponding peak area ratio is: 98.54:1.46. The HPLC spectrum of 3f and the HPLC spectrum of the corresponding racemic compound are shown in Fig.37 and 38 As shown, and the data in the figure are shown in Tables 19 and 20.

[0177] Table 19 HPLC spectrum data table of 3f

[0178]

[0179] Table 20 HPLC spectrum data table of 3f corresponding to racemic compound

[0180]

[0181] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 39-40 As shown, the details are as follows: 1 H NMR(600MHz, CDCl3) δ7.97(d,J=9.0Hz,1H),7.80(d,J=7.8Hz,1H),7.53–7.42( m,3H),5.94–5.80(m,1H),5.27–5.14(m,2H),4.89(dd,J=9.6,3.0Hz,1H),3.22– 3.05(m,2H),2.98–2.77(m,2H),2.70(s,3H),2.47–2.38(m,1H),1.95–1.79(m,3 H),1.78–1.53(m,5H),1.51–1.30(m,7H),0.99–0.78(m,3H),0.66–0.52(m,1H); 13 C NMR (150MHz, CDCl3) δ168.3,134.6,133.9,133.8,131.0,130.7,128.4,125.2,124.9,124.7,123.2,1 22.8,117.7,69.5,58.9,55.2,42.8,30.3,30.0,29.0,28.7,25.7,25.6,24.5,24.3,24.3,24.0,18.7.

[0182]

[0183] 4f is a white powdery solid with a yield of 48% and 98% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.95:0.05; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 14.972 min, tr (minor) = 25.428 min, and the corresponding peak area ratio is: 99.02:0.98. The HPLC spectrum of 4f and the HPLC spectrum of the corresponding racemic compound are shown in Fig.41 and 42 As shown, and the data in the figure are shown in Tables 21 and 22.

[0184] Table 21 HPLC spectrum data table of 4f

[0185]

[0186]

[0187] Table 22 HPLC spectrum of the racemic compound corresponding to 4f

[0188]

[0189] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 43-44 As shown, the details are as follows: 1 H NMR (600MHz, CDCl3) δ7.97(d,J=7.8Hz,1H),7.80(d,J=7.8Hz,1H),7.50–7.45(m,3H ),5.90–5.84(m,1H),5.24–5.16(m,2H),4.88(dd,J=9.6,3.6Hz,1H),3.16–3.10(m,2 H),2.93–2.82(m,2H),2.70(s,3H),2.46–2.40(m,1H),2.28(br.,s,1H),1.95–1.79 (m,3H),1.78–1.54(m,5H),1.51–1.29(m,7H),0.97–0.82(m,3H),0.65–0.53(m,1H); 13 C NMR (150MHz, CDCl3) δ169.3,135.7,135.0,134.8,132.1,131.7,129.4,126.2,125.9,125.7,124.2,1 23.8,118.7,70.5,59.9,56.3,43.8,31.3,31.0,30.0,29.7,26.7,26.7,25.5,25.4,25.3,25.0,19.6.

[0190] Embodiment 7:

[0191] Replace substrate 1 with R 1 =-CH2CH3, R 2 =-cyclohexyl The rest of the experimental procedures refer to Example 1.

[0192]

[0193] 3g is a white powdery solid with a yield of 45% and 74% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B=0.9:0.1; flow rate is 1.0 mL / min, wavelength λ=254 nm, tr (main)=8.554 min, tr (secondary)=5.809 min, and the corresponding peak area ratio is: 87.01:12.99. The HPLC spectrum of 3g and the HPLC spectrum of the corresponding racemic compound are shown in Fig.45 and 46 As shown, and the data in the figure are shown in Tables 23 and 24.

[0194] Table 23 HPLC spectrum data table of 3g

[0195]

[0196] Table 24 HPLC spectrum data table of 3g corresponding racemic compound

[0197]

[0198] Nuclear magnetic resonance spectroscopy (NMR), such as Figures 47-48 As shown, the details are as follows: 1 H NMR (600MHz, CDCl3) δ8.03(d,J=7.8Hz,1H),7.81(d,J=8.4Hz,1H),7.53–7.39(m,3H ),5.94–5.81(m,1H),5.27–5.13(m,2H),4.94–4.83(m,1H),3.22–3.01(m,4H),2.98 –2.76(m,2H),2.74–2.65(m,1H),2.48–2.38(m,1H),2.26(br.,s,1H),1.98–1.79(m ,3H),1.78–1.54(m,5H),1.52–1.29(m,10H),0.98–0.81(m,3H),0.68–0.51(m,1H); 13C NMR (150MHz, CDCl3) δ169.4,140.7,135.7,135.0,131.7,131.3,129.7,126.1,125.9,125.8,123.9,122. 0,118.7,70.7,59.9,56.3,43.9,31.3,31.0,30.0,29.7,26.7,26.7,26.1,25.5,25.4,25.3,25.0,14.9.

[0199]

[0200] 4g is a white powdery solid with a yield of 47% and 95% ee. Chromatographic conditions: OD-H column; injection volume: 2μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B=0.96:0.04; flow rate is 1.0mL / min, wavelength λ=254nm, tr(main)=8.430min, tr(secondary)=9.571min, and the corresponding peak area ratio is: 97.22:2.78. The HPLC spectrum of 4g and the HPLC spectrum of the corresponding racemic compound are shown in Fig.49 and 50 As shown, and the data in the figure are shown in Tables 25 and 26.

[0201] Table 25 HPLC spectrum data table of 4g

[0202]

[0203] Table 26 HPLC spectrum data table of 4g corresponding racemic compound

[0204]

[0205] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 51-52 As shown, the details are as follows: 1H NMR(600MHz, CDCl3)δ8.03(d,J=8.4Hz,1H),7.81(d,J=7.2Hz,1H),7.53–7.40(m,3H), 5.94–5.82(m,1H),5.28–5.13(m,2H),4.90(dd,J=9.6,3.6Hz,1H),3.21–3.02(m,4H), 2.97–2.78(m,2H),2.74–2.65(m,1H),2.48–2.38(m,1H),2.22(br.,s,1H),1.97–1.79 (m,3H),1.78–1.54(m,5H),1.52–1.29(m,10H),1.00–0.81(m,3H),0.66–0.53(m,1H); 13 C NMR (150MHz, CDCl3) δ169.4,140.7,135.7,135.0,131.7,131.3,129.7,126.1,125.9,123.9,122.0,118. 7,118.7,70.7,59.9,56.3,43.9,31.3,31.0,30.0,29.7,26.7,26.7,26.1,25.5,25.4,25.3,25.0,14.9.

[0206] Embodiment 8:

[0207] Replace substrate 1 with R 1 =-OCH3, R 2 =-cyclohexyl, and the rest of the experimental procedures refer to Example 1.

[0208]

[0209] 3h is a white powdery solid with a yield of 46% and 63% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.9:0.1; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 8.866 min, tr (minor) = 7.397 min, and the corresponding peak area ratio is: 81.41:18.59. The HPLC spectrum of 3h and the HPLC spectrum of the corresponding racemic compound are shown in Fig.53 and 54 As shown, and the data in the figure are shown in Tables 27 and 28.

[0210] Table 27 HPLC spectrum data table of 3h

[0211]

[0212] Table 28 HPLC spectrum data table of racemic compound corresponding to 3h

[0213]

[0214] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 55-56 As shown, the details are as follows: 1 H NMR (600MHz, CDCl3) δ8.19–8.12(m,1H),7.70–7.60(m,1H),7.46–7.33(m,2H), 6.90(s,1H),5.87–5.75(m,1H),5.20–5.07(m,2H),4.88–4.76(m,1H),3.96(s, 3H),3.11–2.98(m,2H),2.88–2.59(m,3H),2.39–2.30(m,1H),1.87–1.78(m,2H ),1.66–1.48(m,5H),1.42–1.25(m,7H),0.87–0.75(m,4H),0.60–0.46(m,1H); 13 C NMR (150MHz, CDCl3) δ169.5,155.4,136.9,135.0,130.5,127.2,125.5,125.1,124.8,122.1,118. 8,100.8,70.8,60.0,56.4,55.6,43.9,31.3,31.1,30.0,29.7,26.7,26.6,25.6,25.4,25.3,25.1.

[0215]

[0216] 4h is a white powdery solid with a yield of 46% and 96% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B = 0.95:0.05; flow rate is 1.0 mL / min, wavelength λ = 254 nm, tr (major) = 9.791 min, tr (minor) = 6.478 min, and the corresponding peak area ratio is: 98.18:1.82. The HPLC spectrum of 4h and the HPLC spectrum of the corresponding racemic compound are shown in Fig.57 and 58 As shown, and the data in the figure are shown in Tables 29 and 30.

[0217] Table 29 HPLC spectrum data table of 4h

[0218]

[0219] Table 30 HPLC spectrum data table of racemic compound corresponding to 4h

[0220]

[0221] Nuclear magnetic resonance spectroscopy (NMR), such as Figures 59-60 As shown, the details are as follows: 1 H NMR (600MHz, CDCl3) δ8.29–8.18(m,1H),7.77–7.67(m,1H),7.52–7.41(m,2H),6.97(s,1H),5.98 –5.83(m,1H),5.28–5.16(m,2H),4.96–4.86(m,1H),4.05(s,3H),3.22–3.04(m,2H),2.94–2.67(m ,3H),2.47–2.37(m,1H),2.26(br.,s,1H),1.94–1.86(m,2H),1.84–1.77(m,1H),1.75–1.60(m,4H ),1.60–1.53(m,1H),1.52–1.37(m,4H),1.37–1.29(m,3H),1.00–0.78(m,3H),0.68–0.55(m,1H); 13 C NMR (150MHz, CDCl3) δ168.3,154.3,135.8,134.0,129.4,126.1,124.9,124.4,124.0,123.8,121.1,1 17.7,99.8,69.8,58.9,55.2,54.5,42.9,30.3,30.1,29.0,28.7,25.7,25.7,24.5,24.4,24.3,24.0.

[0222] Embodiment 9:

[0223] Replace substrate 1 with R 1 =-Ph, R 2 =-cyclohexyl, and the rest of the experimental procedures refer to Example 1.

[0224]

[0225] 3i is a white powdery solid with a yield of 49% and 90% ee. Chromatographic conditions: AD-H column; injection volume: 2 μL; column temperature: 25°C; mobile phase A is n-hexane, B is isopropanol; A:B=0.95:0.05; flow rate is 1.0 mL / min, wavelength λ=254 nm, tr(major)=13.293 min, tr(minor)=9.290 min, and the corresponding peak area ratio is: 94.81:5.19. The HPLC spectrum of 3i and the HPLC spectrum of the corresponding racemic compound are shown in Fig.61 and 62 As shown, and the data in the figure are shown in Tables 31 and 32.

[0226] Table 31 HPLC spectrum data table of 3i

[0227]

[0228] Table 32 HPLC spectrum data table of 3i corresponding to racemic compound

[0229]

[0230] Nuclear magnetic resonance spectroscopy (NMR), such as Figure 63-64 As shown, the details are as follows: 1 H NMR (600MHz, CDCl3) δ7.95–7.81(m,2H),7.59(s,1H),7.55–7.36(m,7H),5.95–5.82(m,1H), 5.26–5.14(m,2H),4.96(dd,J=9.6,3.0Hz,1H),3.30–3.10(m,2H),3.00–2.80(m,2H),2.79– 2.69(m,1H),2.50–2.39(m,1H),2.17(br.,s,1H),1.97–1.84(m,3H),1.83–1.76(m,1H),1.7 6–1.58(m,4H),1.56–1.38(m,5H),1.29–1.21(m,2H),1.00–0.90(m,2H),0.74–0.60(m,1H); 13 C NMR (150MHz, CDCl3) δ169.1,140.6,140.5,135.6,134.9,132.8,131.2,130.2,129.7,128.3,127.4,126.5,12 6.3,126.2,125.4,124.4,119.0,70.5,60.1,56.4,43.9,31.4,31.1,30.1,29.8,26.7,25.5,25.4,25.3,25.1.

[0231] It should be noted that in this example, the main product is 3i, and the corresponding diastereoisomer product 4i has a small yield and is therefore not separated.

[0232] Finally, it should be noted that the above is only a preferred embodiment of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A chiral element atroparyl tertiary amide compound, characterized in that: The structure of the compound is as follows: Among them, R 1 is selected from the following groups: -H, alkyl, alkoxy, aryl; R 2 Selected from the following groups: alkyl.

2. The compound according to claim 1, characterized in that R 1 The alkyl groups in include: -CH3, -CH2CH3; R 2 The alkyl groups in include: -CH(CH3)2, cyclohexyl; R 1 The alkoxy group in is -OCH3; R 1 The aryl group in is -Ph.

3. A method for preparing the chiral element atroparyl tertiary amide compound as claimed in claim 1, characterized in that: include: The reactants 2-formyl-N,N-dialkyl-1-naphthylamide and 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborane are dissolved in a solvent and reacted to obtain a chiral element-retarded aromatic tertiary amide compound.

4. The method according to claim 3, characterized in that The method further comprises: Add chiral phosphoric acid catalyst and Molecular sieve additives, through the reaction to obtain chiral element atroparyl tertiary amide compounds.

5. The method according to claim 4, characterized in that The structural formula of the chiral phosphoric acid catalyst is as follows: Among them, G=2,4,6-(i-Pr)3C6H2.

6. The method according to claim 4, characterized in that The molar ratio of the 2-formyl-N,N-dialkyl-1-naphthylamide, the 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and the chiral phosphoric acid catalyst is 1:1-3:0.05-0.

25.

7. The method according to claim 4, characterized in that The mass ratio of the 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane to the molecular sieve additive is in the range of 279:20-93:

400.

8. The method according to claim 3, characterized in that The reaction conditions include: a nitrogen atmosphere, a reaction temperature of 40 to -40°C, and a reaction time of 10 to 36 hours.

9. The method according to claim 4, characterized in that The solvent comprises at least one of the following: anhydrous chlorobenzene, anhydrous toluene, anhydrous mesitylene, anhydrous ethyl acetate, anhydrous tetrahydrofuran, anhydrous ethyl acetate, anhydrous dichloromethane, and anhydrous chloroform.

10. The method according to claim 3, characterized in that The method further comprises: Extracting the solution after the reaction and removing the solvent in the extract by a rotary evaporator; The extract after the solvent is removed is subjected to column chromatography separation to obtain a chiral element-attractive aromatic tertiary amide compound.

11. The method according to claim 10, characterized in that The extractant used in the extraction is a solution formed by ethyl acetate and saturated ammonium chloride.

12. An application of the chiral element atroparyl tertiary amide compound as claimed in claim 1, characterized in that: The application of the chiral element atroparyl tertiary amide compound in asymmetric catalysis.

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