Process for the asymmetric catalytic synthesis of tetra-deuterated 1-(n-methylimidazole)-4-nitro-3-phenylbutan-1-one derivatives

Abstract

The application provides a method for asymmetrically catalyzing synthesis of tetra-deuterated 1-(N-methyl imidazole)-4-nitro-3-phenyl butan-1-one derivative. The asymmetric Michael reaction of 1-(N-methyl imidazole)-3-phenyl propyl-2-en-1-one and nitromethane is catalyzed by a chiral ligand-nickel triflate complex, so that 1-(N-methyl imidazole)-4-nitro-3-phenyl butan-1-one derivative is constructed in one step with high yield, high enantioselectivity, high deuterium realization rate and high enantioselectivity, and the substrate has good universality. The product is easy to separate from the catalyst and the raw material; the catalytic system has the advantages of simple operation, no need to exclude air and moisture, convenient product purification and the like, and has great application prospect.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry technology and relates to asymmetric catalysis, specifically to a method for asymmetric catalytic synthesis of tetradeuterated 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivatives. Background Technology

[0002] α,β-Unsaturated ketones (enones) are a key functional group widely used by chemists because they can undergo a series of transformations, such as 1,2-addition, conjugate addition, and Diels-Alder reactions. In 2022, Jian et al. used water as a medium and Lewis acid catalysis to complete the Michael conjugate addition of enone substrates with nucleophiles, obtaining excellent yields (Catal Lett 152, 3338–3346 (2022)).

[0003]

[0004] In 2018, Kang et al. performed conjugated addition of nitroolefins and simple α-ketone nucleophiles, using a rhodium complex as a catalyst, and obtained products with high yield and high enantioselectivity at a catalyst loading of 1 mol% (Advanced Synthesis & Catalysis, 2018, 360(6):1094-8.).

[0005] Summary of the Invention

[0006] This invention provides a method for the asymmetric catalytic synthesis of tetradeuterated 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivatives, which uses readily available raw materials, involves few steps, and has a simple process.

[0007] The objective of this invention is achieved through the following technical solution:

[0008] A method for asymmetric catalytic synthesis of tetradeuterated 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivatives, using compounds 1 and 2 as raw materials, and a complex formed by a ligand and a metal compound as a catalyst, to asymmetrically catalytically synthesize tetradeuterated 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivative compound 3 under alkaline conditions;

[0009] The reaction formula is as follows:

[0010]

[0011] Wherein, R is selected from methyl, ethyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 4-phenylphenyl, 2-pyridyl, 2-furanyl, 2-thienyl, 1-naphthyl, 2-naphthyl; the ligand is a pyridine imidazoline compound.

[0012]

[0013] The metal compound is nickel trifluoromethanesulfonate; the catalyst is obtained by in-situ complexation of nickel trifluoromethanesulfonate and chiral ligand pyridine imidazoline, wherein the amount of nickel trifluoromethanesulfonate is 5-40% of the molar amount of 1-(N-methylimidazolium)-3-phenylpropyl-2-en-1-one, preferably 20%.

[0014] The amount of the chiral ligand pyridine imidazoline is 5-20% of the molar amount of 1-(N-methylimidazolium)-3-phenylpropyl-2-en-1-one, preferably 10%.

[0015] The base is selected from at least one of triethylamine, N,N-diisopropylethylamine, dibutylamine, N,N-dimethylmethylamine, piperidine, N-methylmorpholine, 2,2,6,6-tetramethylpiperidine, N,N-diisopropylamine, pyridine, and dicyclohexylmethylamine, preferably triethylamine. The amount of the base used is 50% of the molar amount of 1-(N-methylimidazolium)-3-phenylpropyl-2-en-1-one.

[0016] The solvent is selected from at least one of toluene, ethanol, ethyl acetate, acetonitrile, dichloromethane, tetrahydrofuran, 1,2-dichloroethane, trichloromethane, 1,4-dioxane, and heavy water. 1,4-dioxane and heavy water are preferred.

[0017] The beneficial effects of this invention are:

[0018] This invention utilizes a chiral ligand-nickel trifluoromethanesulfonate complex to catalyze an asymmetric Michael reaction of 1-(N-methylimidazolium)-3-phenylpropyl-2-en-1-one with nitromethane in the presence of heavy water, achieving a one-step construction of tetradeuterated 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivatives with high yield, high enantioselectivity, and high deuteration rate, exhibiting good substrate versatility.

[0019] This invention provides a novel asymmetric catalytic synthesis method for tetradeuterated 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivatives. The product of this invention is easily separated from the catalyst and starting materials; the catalytic system has advantages such as simple operation, mild reaction conditions, no need to remove air and moisture, and convenient product purification, and has great application potential. Detailed Implementation

[0020] To better understand the content of this invention, further explanation is provided below with reference to specific examples, but the specific embodiments are not intended to limit the content of this invention. Unless otherwise stated, all figures representing quantities of ingredients, proportions, conditions, etc., used in this specification (including the claims) should be understood to be modified by the term "about" under all conditions. Therefore, unless otherwise stated, numerical parameters are approximate values ​​and can vary according to the desired characteristics of the invention. Those skilled in the art will recognize many equivalents of the specific embodiments of the invention described herein, and many modifications and variations of the invention can be made without departing from its spirit and scope, which are covered within the scope of the appended claims. The specific embodiments described herein are provided by way of example only and are not intended to limit in any way. The true scope and spirit of the invention are shown by the appended claims, and the specification and examples are merely exemplary. The raw materials and reagents described in this invention are all commercially available products.

[0021] The present invention will now be described in detail with reference to specific embodiments:

[0022] Example 1

[0023] Synthesis of 2,2,4,4-tetradeuterated 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one

[0024]

[0025] Detailed operation steps:

[0026] Nickel trifluoromethanesulfonate (0.02 mmol), chiral pyridine imidazoline ligand (0.01 mmol), 1,4-dioxane (0.5 mL), and a stir bar were added to a reaction vessel, and the mixture was stirred at 35 °C for 0.5 h. Then, nitromethane 1 (0.25 mmol), 1-(N-methylimidazolium)-3-phenylpropyl-2-en-1-one 2 (0.1 mmol), triethylamine (0.05 mmol), D2O (0.2 mL), and 1,4-dioxane (0.5 mL) were added, and the mixture was stirred at 80 °C for 24 h. The reaction was monitored by TLC. The target compound 3 (92% yield, 96% ee) was obtained by column chromatography in petroleum ether / ethyl acetate. The enantiomeric excess of the product was determined by high performance liquid chromatography (Daicel Chiralpak IA, V hexane:V ethanol = 85:15, flow rate 1.0 mL / min; tminor = 16.2 min, tmajor = 19.4 min). 1 HNMR(600MHz,CHCl3)δ7.39–7.20(m,5H),7.12(s,1H),7.02(s,1H),4.68(dd,J=52.9 ,7.4Hz,0.12H,94%D2),4.19(d,J=7.2Hz,1H),3.93(s,3H),3.71–3.45(m,0.14H,93%

[0027] D1).

[0028] Table 1. Effect of different solvents on the catalytic preparation of compound 3

[0029]

[0030] Table 1 shows that the solvent 1,4-dioxane has the best catalytic and deuteration effects, achieving a yield of 74%, an ee value of 98%, and a deuteration rate of 42% / 90%, while other solvents yielded relatively poor results.

[0031] Table 2. Effects of different metal compounds on the catalytic preparation of compound 3

[0032]

[0033] As shown in Table 2, the combination of catalytic and deuteration effects is the best when nickel trifluoromethanesulfonate forms a metal complex with the ligand, achieving a yield of 88%, an ee value of 98%, and a deuteration rate of 66% / 88%, while the results for other metal salts are relatively poor.

[0034] Table 3. Effect of different ligand and metal salt addition ratios on the catalytic preparation of compound 3

[0035]

[0036] As shown in Table 3, the catalytic and deuteration effects are best when the ratio of ligand to metal salt is 1:2, achieving a yield of 93%, an ee value of 97%, and a deuteration rate of 80% / 88%, while the results of the ratio are relatively poor.

[0037] Table 4. Effect of different D2O addition amounts on the catalytic preparation of compound 3

[0038]

[0039] As shown in Table 4, the addition of D2O at a rate of 0.2 mL yields the best overall catalytic and deuteration effects, and is the most economical, achieving a yield of 93%, an ee value of 97%, and a deuteration rate of 80% / 93%.

[0040] Table 5. Effect of different temperatures on the catalytic preparation of compound 3

[0041]

[0042] As shown in Table 5, the catalytic and deuteration effects are best at a temperature of 80℃, achieving a yield of 86%, an ee value of 97%, and a deuteration rate of 85% / 90%, while the ratio results are relatively poor.

[0043] Table 6. Effect of different amounts of base on the catalytic preparation of compound 3

[0044]

[0045] As shown in Table 6, the catalytic and deuteration effects are best when the alkali dosage is 0.05 mmol.

[0046] Table 7. Examination of substrate universality

[0047]

[0048] From the perspective of substrate versatility, good results can be obtained regardless of whether the substituents of the substrate are electron-withdrawing groups, electron-donating groups, or alkyl groups. The specific structure and structural analysis data of compound 4-24 prepared according to Example 1 are as follows.

[0049]

[0050] The structural analysis data is as follows:

[0051] Compound 4: 11H NMR (600 MHz, Chloroform-d) δ 7.39–7.20 (m, 5H), 7.12 (s, 1H), 7.02 (s, 1H), 4.68 (dd, J = 52.8, 7.2 Hz, 0.12H, 94% D2), 4.19 (d, J = 7.2 Hz, 1H), 3.93 (s, 3H), 3.71–3.45 (m, 0.14H, 93% D1). 13 13C NMR (151 MHz, Chloroform-d) δ 189.18, 142.58, 138.92, 129.31, 128.91, 127.71, 127.52, 127.33, 39.07, 36.07, 29.66. Compound 5: 1 1H NMR (600 MHz, Chloroform-d) δ 7.17 (d, J = 7.8 Hz, 2H), 7.10 (d, J = 7.8 Hz, 3H), 7.01 (s, 1H), 4.64 (dd, J = 54.6, 7.5 Hz, 0.1H, 95% D2), 4.14 (d, J = 7.8 Hz, 1H), 3.92 (s, 3H), 3.55 (dd, J = 127.8, 7.3 Hz, 0.19H, 91% D1). 13 13C NMR (151 MHz, CDCl3) δ 189.19, 189.15, 142.51, 137.27, 135.78, 129.53, 129.49, 129.18, 129.17, 127.29, 127.27, 38.69, 38.65, 35.98, 20.93.

[0052] Compound 6: 1 1H NMR (600 MHz, Chloroform-d) δ 7.18 (t, J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.11–7.03 (m, 3H), 7.02 (s, 1H), 4.65 (dd, J = 52.8, 7.5 Hz, 0.12H, 94% D2), 4.14 (d, J = 7.8 Hz, 1H), 3.93 (s, 3H), 3.56 (dd, J = 117.6, 7.2 Hz, 0.15H, 93% D1), 2.31 (s, 3H). 13C NMR(151MHz,Chloroform-d)δ189.17(d,J=6.9Hz),142.53,138.83,138.48,129.55,129 .20,128.68,128.42,128.19,127.29,126.28,124.44,38.92(d,J=6.4Hz),36.00,21.31.

[0053] Compound 7: 1 H NMR(600MHz,Chloroform-d)δ7.23(d,J=7.8Hz,1H),7.17–7.09(m,4H),7.01(s,1H),4.65(dd,J=42.0,7.8Hz,0.13H,94% D2),4.49(d,J=7.8Hz,1H),3.91(s,3H),3.55(dd,J=147.0,6.6Hz,0.18H,91% D1),2.46(s,3H). 13 C NMR(151MHz,Chloroform-d)δ189.24(d,J=7.1Hz),142.51,137.16,136.36,130.88, 129.56,129.21,127.29,126.46,126.29,125.62,35.98,34.18(d,J=5.6Hz),19.45.

[0054] Compound 8: 1 H NMR(600MHz,Chloroform-d)δ7.20(d,J=9.0Hz,2H),7.11(s,1H),7.02(s,1H),6.83(d,J=9.0Hz,2H),4.63(dd,J=60.6,7.2Hz,0.14H,93% D2),4.14(d,J=7.7Hz,1H),3.92(s,3H),3.75(s,3H),3.54(dd,J=136.8,7.2Hz,0.31H,85% D1). 13 CNMR(151MHz,Chloroform-d)δ189.21(d,J=7.2Hz),158.88,142.55,130.76,1 29.20(d,J=1.7Hz),128.52,127.29,114.19,55.11,38.39(t,J=5.5Hz),36.00.

[0055] Compound 9: 1H NMR(600MHz,Chloroform-d)δ7.22(t,J=8.4Hz,2H),7.11(s,1H),7.01(s,1H),6.92–6.82(m,3H),4.78(dd,J=36.0,7.2Hz,0.13H,94% D2),4.37(d,J=7.8Hz,1H),3.92(s,3H),3.85(s,3H),3.65(dd,J=96.6,6.6Hz,0.2H,90% D1). 13 C NMR (151MHz, CDCl3) δ189.95,189.91,157.19,142.62,129.42,129.08,128.76,127.08,126.56,120.65,110.84,55.30,36.00,35.52,35.46.

[0056] Compound 10: 1 H NMR(600MHz,Chloroform-d)δ7.57–7.48(m,4H),7.40(t,J=7.2Hz,2H),7.36(d,J=7.8Hz, 2H),7.31(t,J=7.2Hz,1H),7.11(s,1H),7.00(s,1H),4.70(dd,J=48.6,7.2Hz,0.14H,93% D2), 4.23 (d, J=7.8Hz, 1H), 3.91 (s, 3H), 3.76–3.43 (m, 0.47H, 77% D1). 13 C NMR(151MHz,Chloroform-d)δ188.99(d,J=6.2Hz),142.48,140.46,140.33,137.90(d,J=4.4Hz), 129.23,128.66,127.90,127.50,127.33,127.28,126.89,41.69,38.73(q,J=6.6,6.2Hz),36.00.

[0057] Compound 11: 11H NMR (600 MHz, Chloroform-d) δ 7.18 (d, J = 7.8 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.09 (s, 1H), 6.96 (s, 1H), 4.65 (dd, J = 50.2, 7.2 Hz, 0.13H, 94% D2), 4.14 (d, J = 7.8 Hz, 1H), 3.91 (s, 3H), 3.54 (dd, J = 103.2, 7.2 Hz, 0.29H, 86% D1), 2.85 (p, J = 7.2 Hz, 1H), 1.20 (d, J = 7.2 Hz, 6H). 13 13C NMR (151 MHz, Chloroform-d) δ 189.28 (d, J = 7.2 Hz), 148.17, 142.56, 136.17, 129.20 (d, J = 1.7 Hz), 127.34, 127.25, 126.89, 39.09–38.26 (m), 36.01, 33.60, 23.79 (d, J = 2.0 Hz).

[0058] Compound 12: 1 1H NMR (600 MHz, Chloroform-d) δ 7.24 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 1.2 Hz, 1H), 6.94 (s, 1H), 4.58 (dd, J = 50.4, 7.2 Hz, 0.11H, 95%D2), 4.09 (d, J = 7.8 Hz, 1H), 3.85 (s, 3H), 3.48 (dd, J = 120.0, 7.2 Hz, 0.19H, 91%D1), 1.20 (s, 9H). 13 13C NMR (151 MHz, Chloroform-d) δ 189.30 (d, J = 7.3 Hz), 150.44, 142.58, 135.82, 129.21 (d, J = 1.7 Hz), 127.25, 127.07, 125.76, 38.80–38.20 (m), 36.03, 34.39, 31.20.

[0059] Compound 13: 11H NMR (600 MHz, Chloroform-d) δ 7.27 (dt, J = 7.8, 3.6 Hz, 2H), 7.12 (s, 1H), 7.03 (s, 1H), 6.99 (t, J = 8.4 Hz, 2H), 4.66 (dd, J = 67.8, 7.2 Hz, 0.12H, 94% D2), 4.18 (d, J = 7.8 Hz, 1H), 3.94 (s, 3H), 3.55 (dd, J = 136.2, 7.2 Hz, 0.22H, 89% D1). 13 13C NMR (151 MHz, Chloroform-d) δ 188.89 (d, J = 7.2 Hz), 162.89, 161.26, 142.48, 134.59 (d, J = 3.3 Hz), 129.34, 129.33, 129.18, 129.13, 127.44, 115.85, 115.71, 38.42 (d, J = 6.8 Hz), 36.04.

[0060] Compound 14: 1 1H NMR (600 MHz, Chloroform-d) δ 7.28 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 7.13 (s, 1H), 7.03 (s, 1H), 4.65 (dd, J = 63.0, 7.8 Hz, 0.14H, 93% D1), 4.17 (d, J = 7.8 Hz, 1H), 3.94 (s, 3H), 3.55 (dd, J = 141.0, 7.2 Hz, 0.14H, 93% D2). 13 13C NMR (151 MHz, Chloroform-d) δ 188.79, 142.47, 137.37, 133.57, 129.40, 129.08, 128.95, 127.48, 38.54 (d, J = 10.8 Hz), 36.09.

[0061] Compound 15: 1 1H NMR (600 MHz, Chloroform-d) δ 7.42 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.11 (s, 1H), 7.02 (s, 1H), 4.64 (dd, J = 61.8, 7.8 Hz, 0.1H, 95% D2), 4.15 (d, J = 7.6 Hz, 1H), 3.93 (s, 3H), 3.53 (dd, J = 143.4, 7.2 Hz, 0.15H, 93% D1). 13C NMR (151MHz, Chloroform-d) δ188.75,142.45,137.90,132.03,129.40,129.29,127.49,121.68,38.56,36.08.

[0062] Compound 16: 1 H NMR(600MHz,Chloroform-d)δ7.57(d,J=7.8Hz,2H),7.43(d,J=7.8Hz,2H),7.12(d,J=1.2Hz,1H),7.03(s,1H),4 .70(dd,J=57.6,7.8Hz,0.14H,93%D2),4.26(d,J=7.7Hz,1H),3.93(s,3H),3.58(dd,J=138.0,7.2Hz,0.19H,91% D1). 13 CNMR(151MHz,Chloroform-d)δ188.55,143.02,142.40,129.46,128.06,127.56,125.89(q,J=3.8Hz),124.77,122.97,38.81,36.07.

[0063] Compound 17: 1 H NMR(600MHz,Chloroform-d)δ8.19(d,J=7.8Hz,2H),7.51(d,J=7.8Hz,2H),7.14(s,1H),7.06(s,1H),4.81–4.66(m,0.48H,76% D2), 4.32 (d, J=7.8Hz, 1H), 3.95 (s, 3H), 3.61 (dd, J=136.6, 7.2Hz, 0.45H, 78% D1). 13 C NMR(151MHz,Chloroform-d)δ188.12(t,J=6.1Hz),147.43,146.39(d,J=3.5Hz ),142.26,129.55,128.70,127.71,124.11,38.91(td,J=10.5,6.1Hz),36.08.

[0064] Compound 18: 11H NMR (600 MHz, Chloroform-d) δ 7.29 (s, 1H), 7.28–7.21 (m, 2H), 7.20–7.18 (m, 1H), 7.13 (s, 1H), 7.04 (s, 1H), 4.67 (dd, J = 61.2, 7.8 Hz, 0.11H, 95% D2), 4.17 (d, J = 7.8 Hz, 1H), 3.95 (s, 3H), 3.56 (dd, J = 115.2, 7.2 Hz, 0.12H, 94% D1). 13 13C NMR (151 MHz, Chloroform-d) δ 188.68 (d, J = 6.9 Hz), 142.44, 140.99, 134.70, 130.18, 129.42, 128.01, 127.81, 127.48, 125.79, 38.71 (d, J = 6.6 Hz), 36.08, 29.66.

[0065] Compound 19: 1 1H NMR (600 MHz, Chloroform-d) δ 7.39 (dd, J = 7.8, 1.8 Hz, 1H), 7.32 (dd, J = 7.8, 1.8 Hz, 1H), 7.26–7.18 (m, 2H), 7.14 (s, 1H), 7.04 (s, 1H), 4.77 (dd, J = 16.8, 7.2 Hz, 0.12H, 94% D2), 4.67 (d, J = 7.8 Hz, 1H), 3.95 (s, 3H), 3.75–3.60 (m, 0.13H, 94% D1). 13 13C NMR (151 MHz, Chloroform-d) δ 188.99 (d, J = 6.1 Hz), 142.49, 136.15, 133.88, 130.27, 129.37, 128.85, 128.32, 127.37, 127.30, 36.08, 35.56. Compound 20: 1 1H NMR (600 MHz, Chloroform-d) δ 7.61–7.57 (m, 1H), 7.36–7.23 (m, 2H), 7.13 (d, J = 7.8 Hz, 2H), 7.04 (s, 1H), 4.79–4.71 (m, 0.15H, 93% D2), 4.67 (d, J = 7.2 Hz, 1H), 3.95 (s, 3H), 3.66 (dd, J = 59.3, 7.2 Hz, 0.1H, 95% D1). 13C NMR (151MHz, Chloroform-d) δ188.93,142.48,137.78,133.59,129.36,129.12,128.08,127.93,127.38,124.55,37.78,36.08.

[0066] Compound 21: 1 H NMR(600MHz,Chloroform-d)δ8.26(d,J=8.4Hz,1H),7.84(d,J=8.4Hz,1H),7.74(d,J=8.4Hz,1H),7.66–7.53(m,1H),7.52–7.43(m,2H),7.3 9(t,J=7.8Hz,1H),7.11(s,1H),6.97(s,1H),5.13(s,1H),4.79(dd,J=17.4,7.2Hz,0.12H,94%D2),3.85(s,3H),3.63(d,J=6.6Hz,0.16H,92% D1). 13 C NMR(151MHz,Chloroform-d)δ189.22(d,J=6.8Hz),142.52,134.82,134.01,130.99,129.44– 129.13(m),129.04,128.25,127.32,126.73,125.87,125.25,123.72,122.44,35.93,33.44.

[0067] Compound 22: 1 H NMR(600MHz,Chloroform-d)δ7.85–7.67(m,4H),7.53–7.36(m,3H),7.11(s,1H),6.97(s,1H),4.75(dd,J=36.6,7.2Hz,0.14H,93% D2), 4.36 (d, J = 7.7Hz, 1H), 3.88 (s, 3H), 3.54 (d, J = 6.6Hz, 0.24H, 88% D1). 13 C NMR(151MHz,Chloroform-d)δ188.98(t,J=6.7Hz),142.50,136.25,133.28,132.71,129.25 ,128.74,127.77,127.55,127.35,126.61,126.25,126.01,125.23,39.61–38.47(m),35.99.

[0068] Compound 23: 11H NMR (600 MHz, Chloroform-d) δ 8.51 (d, J = 4.2 Hz, 1H), 7.62 (td, J = 7.8, 1.8 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.15–7.11 (m, 1H), 7.11 (s, 1H), 7.03 (s, 1H), 4.89 (dd, J = 138.0, 7.2 Hz, 0.18H, 91% D2), 4.27 (d, J = 7.2 Hz, 1H), 3.95 (s, 3H), 3.61 (dd, J = 182.4, 6.6 Hz, 0.28H, 86% D1). 13 13C NMR (151 MHz, Chloroform-d) δ 188.45 (d, J = 6.6 Hz), 157.69, 148.53, 141.49, 135.68, 128.35, 126.26, 122.60, 121.36, 39.22 (dd, J = 10.1, 5.3 Hz), 35.06.

[0069] Compound 24: 1 1H NMR (600 MHz, Chloroform-d) δ 7.33 (dd, J = 1.8, 0.6 Hz, 1H), 7.14 (s, 1H), 7.06 (s, 1H), 6.27 (dd, J = 3.6, 1.8 Hz, 1H), 6.19 (d, J = 3.0 Hz, 1H), 4.71 (t, J = 7.8 Hz, 0.13H, 94% D2), 4.29 (d, J = 7.8 Hz, 1H), 3.98 (s, 3H), 3.58 (dd, J = 136.8, 7.2 Hz, 0.2H, 90% D1). 13 13C NMR (151 MHz, Chloroform-d) δ 188.77 (d, J = 6.2 Hz), 151.85, 142.40, 142.22, 129.37, 127.41, 110.31, 107.03, 36.05, 32.89 (d, J = 6.7 Hz). Compound 25: 1 1H NMR (600 MHz, Chloroform-d) δ 7.18 (dd, J = 5.4, 1.2 Hz, 1H), 7.14 (d, J = 1.2 Hz, 1H), 7.04 (s, 1H), 6.96 (d, J = 3.6 Hz, 1H), 6.91 (dd, J = 5.4, 3.6 Hz, 1H), 4.69 (dd, J = 54.0, 7.2 Hz, 0.11H, 95% D2), 4.51 (d, J = 7.8 Hz, 1H), 3.62 (dd, J = 123.0, 7.2 Hz, 0.2H, 90% D1). 1313C NMR (151 MHz, Chloroform-d) δ 188.58 (d, J = 6.7 Hz), 142.43, 141.68, 129.38, 127.43, 126.96, 125.44, 124.61, 36.04, 34.44 (d, J = 6.9 Hz).

[0070] Compound 26: 1 1H NMR (600 MHz, Chloroform-d) δ 7.14 (s, 1H), 7.06 (s, 1H), 4.42 (dd,

[0071] J = 104.4, 6.6 Hz, 0.1H, 95% D2), 4.01 (s, 3H), 3.16 (dt, J = 6.6, 2.4 Hz, 0.26H, 87%

[0072] D1), 3.04–2.90 (m, 1H), 1.13 (dd, J = 6.6, 1.8 Hz, 3H). 13 13C NMR (151 MHz,

[0073] Chloroform-d) δ 190.23 (d, J = 7.3 Hz), 142.70, 129.23, 127.33, 36.14, 28.55 (d, J = 6.1 Hz), 17.51 (d, J = 2.5 Hz).

[0074] Compound 27: 1 1H NMR (600 MHz, Chloroform-d) δ 7.14 (s, 1H), 7.06 (s, 1H), 4.48 (dd, J = 37.8, 6.6 Hz, 0.09H, 96% D2), 4.00 (s, 3H), 3.22 (dd, J = 51.0, 5.4 Hz, 0.26H, 87%D1), 2.78 (q, J = 7.2, 6.6 Hz, 1H), 1.63–1.45 (m, 2H), 0.99 (t, J = 7.2 Hz, 3H).

[0075] 13 13C NMR (151 MHz, Chloroform-d) δ 190.59 (d, J = 7.4 Hz), 142.72, 129.19, 127.28, 36.14, 34.55 (d, J = 5.7 Hz), 24.52 (d, J = 2.2 Hz), 10.72.

[0076] The above description is merely a preferred embodiment of the present invention. It should be understood that the present invention is not limited to the forms disclosed herein and should not be construed as excluding other embodiments. It can be used in various other combinations, modifications, and environments, and can be altered within the scope of the concept described herein through the above teachings or related technologies or knowledge. Modifications and variations made by those skilled in the art that do not depart from the spirit and scope of the present invention should be within the protection scope of the appended claims.

Claims

1. A method for the asymmetric catalytic synthesis of a 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivative, comprising using compound 1, heavy water, and compound 2 as raw materials, and a complex formed by a ligand and a metal compound as a catalyst, to asymmetricly synthesize 1-(N-methylimidazolium)-4-nitro-3-phenylbut-1-one derivative compound 3 under alkaline conditions; the reaction solvent is selected from at least one of ethanol, ethyl acetate, acetonitrile, and 1,4-dioxane; the reaction formula is as follows: ， in, R is selected from phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 4-bromophenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-nitrophenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 2-pyridyl, 2-furanyl, 2-thienyl, 1-naphthyl, 2-naphthyl; The metal compound is selected from one of Ni(CH3COO)2·4H2O, Ni(acac)2, NiCl2, NiCl2(PPh3)2, and nickel trifluoromethanesulfonate; the ligand is a pyridine imidazoline compound. 。 2. The method as described in claim 1, characterized in that: The metal compound is nickel trifluoromethanesulfonate.

3. The method as described in claim 2, characterized in that: The catalyst is obtained by in-situ complexation of nickel trifluoromethanesulfonate and the ligand.

4. The method as described in claim 3, characterized in that: The amount of nickel trifluoromethanesulfonate used is 5-40% of 2 moles of the compound.

5. The method as described in claim 3, characterized in that: The amount of the ligand used is 5-20% of 2 moles of the compound.

6. The method as described in claim 1, characterized in that: The base is at least one of triethylamine, N,N-diisopropylethylamine, dibutylamine, N,N-dimethylmethylamine, piperidine, N-methylmorpholine, 2,2,6,6-tetramethylpiperidine, N,N-diisopropylamine, pyridine, and dicyclohexylmethylamine.

7. The method as described in claim 6, characterized in that: The base is triethylamine.

8. The method as described in claim 6 or 7, characterized in that: The amount of alkali used is 5% of 2 moles of the compound.

9. The method as described in claim 1, characterized in that: The reaction solvent is 1,4-dioxane.

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