Method for reducing alpha, beta-unsaturated ester, nitrile and amide

Abstract

The invention provides a method for reducing alpha, beta-unsaturated ester, nitrile and amide, which comprises the following steps: dissolving a substrate in MeOD and MeCN, adding an additive, stirring, and adding magnesium chips to obtain a mixture; stirring the mixture in a water bath, and then stirring at room temperature; after the reaction is finished, adding an organic solvent into the mixture, performing suction filtration, washing filtrate after suction filtration, drying an organic phase, performing suction filtration, performing vacuum concentration, and purifying residues to obtain a product; the additive is I2. The Mg / CH3OD system can be used for reduction deuterization of alpha, beta-unsaturated ester, amide and nitrile, the reaction system is mild in condition and easy to post-treat, can be compatible with various functional groups and has high yield and deuteration rate, a deuterium source is cheap, dissolved metal and transition metal are not contained, and reagents are easy to treat.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for reducing α,β-unsaturated esters, nitrites and amides. Background Art

[0002] The application of isotope D-labeled molecules in medicine, food safety, physics, materials science, ecology, etc. has promoted the development of deuteration reaction systems and methods. At present, there are many synthetic methods based on hydrogen-deuterium exchange (HIE), reductive deuteration, and defunctionalization. Some commonly used isotope labeling reactions provide convenient and regioselective methods to introduce one or more deuterium atoms into various molecular frameworks with high deuteration rates. Among all these deuteration reactions, the reductive deuteration of unsaturated CC bonds via free radical pathways mediated by single-electron reductants (Li, Na, and SmI2) or involving transition metal deuterides (M-Ds) has attracted considerable attention due to its mild conditions, excellent regioselectivity, and the use of inexpensive deuterium sources. M-Ds are produced by transition metal catalysts and deuterium sources through electrochemical and photochemical methods. Lin and co-workers reported electron-initiated deuteration and hydroarylation of olefins. In their work, Mg powder or C cathode acted as a terminal reductant to trigger the generation of Co(III)-H, which is a key transition metal hydride in various hydrogen atom transfer reactions (HATs) with olefins. Based on the HAT process in organic reactions, Matsunaga and co-workers developed a photocatalytic deuterium atom transfer (DAT) method for the deuteration of electron-deficient olefins. Dissolved metal system reduction is a traditional reduction reaction in which aromatic and conjugated polyunsaturated hydrocarbons are reduced by alkali metals in liquid ammonia through a single electron transfer process. The reaction occurs through two consecutive electron transfer and protonation steps, and alcohols are often used as proton sources. However, dissolved metal systems are incompatible with some sensitive functional groups and lack selectivity due to their strong reduction activity. Compared with the Li / NH3(l) system, the Na dispersion system in mineral oil is safer and milder. An Jie and colleagues developed a series of sodium dispersion-mediated reductive deuteration of activated unsaturated bonds. The deuteration reaction uses EtOD as a deuterium source and can selectively synthesize α,β-dideuterated compounds. Similar to the mechanism of dissolved metal reduction, methanol and magnesium (Mg / MeOH) were found to reduce some functional groups through a single electron transfer process in the 1920s. Compared with lithium or sodium / liquid ammonia systems, the magnesium / methanol system has the advantages of good versatility, good selectivity, easy handling, low cost and mild conditions. However, there are few studies on Mg / CD3OD or Mg / CH3OD in the synthesis of D-containing organic molecules. Therefore, a method for deuterating alkenes and alkynes to the corresponding di-deuterated and tetra-deuterated compounds using inexpensive deuterated reagents under transition metal-free, mild and environmentally friendly conditions is urgently needed. Summary of the invention

[0003] In view of this, the present invention aims to propose a method for the reduction of α,β-unsaturated esters, nitriles and amides, so as to provide a reaction system having the advantages of mild conditions, easy post-treatment, compatibility with multiple functional groups, high yield and deuteration rate, and cheap deuterium source.

[0004] To achieve the above object, the technical solution of the present invention is achieved as follows:

[0005] A method for reducing α,β-unsaturated esters, nitriles and amides, comprising the following steps:

[0006] The substrate is dissolved in MeOD and MeCN, an additive is added, the mixture is stirred, and magnesium chips are added to obtain a mixture; the mixture is first stirred in a water bath and then stirred at room temperature; after the reaction is completed, an organic solvent is added to the mixture and then filtered, the filtrate is washed after filtration, the organic phase is dried, filtered, and concentrated under reduced pressure, and the residue is purified to obtain a product;

[0007] The additive is I2;

[0008] The chemical formula is as follows:

[0009]

[0010] Furthermore, the step also includes: adding a co-solvent while adding the additive.

[0011] Further, the co-solvent is toluene and TBAI;

[0012] The chemical formula is as follows:

[0013]

[0014] Furthermore, in the chemical formula, EWG is an ester group, an amide bond, or a cyano group.

[0015] Furthermore, in the chemical formula, R 1 , R 2 , R 3 Selected from alkyl, aromatic ring, aromatic heterocycle, chlorine, cyano, ester, methoxy, methylthio, amide bond, hydroxyl, cycloalkyl.

[0016] Furthermore, the equivalent ratio of the substrate, I2, and magnesium chips is 1:3-6:10-15.

[0017] Furthermore, the organic solvent is ethyl acetate.

[0018] Furthermore, the filtrate is washed with a saturated sodium thiosulfate solution, and the organic phase is dried with anhydrous magnesium sulfate.

[0019] Furthermore, the residue is purified by silica gel column chromatography.

[0020] Compared with the prior art, the method for reducing α,β-unsaturated esters, nitriles and amides described in the present invention has the following advantages:

[0021] The Mg / CH3OD system of the present invention can be used for the reductive deuteration of α,β-unsaturated esters, amides and nitriles. The reaction system has mild conditions, is easy to post-process, is compatible with various functional groups, has a high yield and deuteration rate, has a cheap deuterium source, does not contain dissolved metals and transition metals, and the reagents are easy to handle. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention. In the accompanying drawings:

[0023] Figure 1 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2a described in Example 1 of the present invention;

[0024] Figure 2 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2i described in Example 9 of the present invention;

[0025] Figure 3 The hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum of compounds 2o and 2o' described in Example 15 of the present invention;

[0026] Figure 4 is a high-resolution mass spectrum of compound 2o described in Example 15 of the present invention;

[0027] Figure 5 is a high-resolution mass spectrum of compound 2o' described in Example 15 of the present invention;

[0028] Figure 6 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum and high-resolution mass spectrum of the compound 2q described in Example 17 of the present invention;

[0029] Figure 7 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2r described in Example 18 of the present invention;

[0030] Figure 8 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2u described in Example 21 of the present invention;

[0031] Fig. 9The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2v described in Example 22 of the present invention;

[0032] Fig.10 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2z described in Example 26 of the present invention;

[0033] Fig.11 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2ae described in Example 31 of the present invention;

[0034] Fig.12 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2ah described in Example 34 of the present invention;

[0035] Fig.13 The hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum, and high-resolution mass spectrum of the compound 2ai described in Example 35 of the present invention;

[0036] Fig.14 It is the hydrogen nuclear magnetic resonance spectrum, carbon nuclear magnetic resonance spectrum and high-resolution mass spectrum of compound 2aj described in Example 36 of the present invention. DETAILED DESCRIPTION

[0037] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments may be combined with each other.

[0038] The present invention will be described in detail below with reference to the accompanying drawings and in conjunction with embodiments.

[0039] Experimental Example Screening of Deuteration Reaction Conditions

[0040] When Mg / CH3OH was replaced by Mg / CH3OD with methyl cinnamate (1a) as the initial substrate, 1a did not undergo the recognized reduction hydrogenation reaction (Table 1, entry 1). It was inferred that the activity of CH3OD was insufficient for the reaction due to the kinetic isotope effect (KIE). The combination of heavy water and deuterated methanol / heavy water (1 / 2, v / v) was further explored, and no reaction occurred (Table 1, entries 2-3). Ac2O was subsequently added to the reaction mixture to activate the Mg / CH3OD system by the in situ generated AcOD. Although the deuteration rate was 88 / 91 (α / β), the yield of 2a was very low (Table 1, entry 4). When AcOD was used instead of CH3OD in THF, the yield and deuteration rate increased slightly (Table 1, entry 5). When the CH3OD / ND4Cl combination was used as the deuterium source, both the yield and deuteration rate were significantly improved (Table 1, entry 6). However, deuterated ammonium chloride is not an economical deuterium source, and it is well known that initiators play a key role in the preparation of Grignard reagents. The surface of activated magnesium may facilitate the deuteration of 1a, which inspired us to add 1,2-dibromoethane (EDB) or I2 to the reaction mixture. EDB improved the yield and deuteration rate (Table 1, entry 7). Compared with EDB, I2 promoted the deuteration reaction of 1a, resulting in a lower yield of 2a (Table 1, entry 8). We further found that a co-solvent was required in the case of using I2 as an initiator. When THF was used as a co-solvent, it provided similar results to EDB (Table 1, entry 9). The use of 3 equivalents of I2 on the basis of MeCN as a co-solvent achieved high yield and deuterium incorporation of 2a (Table 1, entry 10). Further addition of TBAI and toluene to the reaction also gave satisfactory results (Table 1, entry 11). When CD3OD was used instead of CH3OD under the optimal conditions, 2a and 2a′ were obtained in a 1:2 ratio with an overall yield of 88% (Table 1, entry 12). This clearly indicates that concomitant transesterification occurred during the reductive deuteration of 1a.

[0041]

[0042] Table 1 Deuteration reaction conditions screening a

[0043]

[0044] a . Conditions: 1a (0.77 mmol, 1.0 equiv), magnesium turnings (7.7 mmol, 10.0 equiv), MeOD (3 mL), rt, 30 min; b . Isolated yield; c . Depend on1 H-NMR shows that D% = deuteration rate, α-D% is the deuteration rate of the α position of the ester group, and β-D% is the deuteration rate of the β position of the ester group; d . Deuterium source (2 mL), solvent (1 mL); e . AcOD(3.85mmol,5.0equiv),THF(3mL); f . MeOD(3mL),ND4Cl(3.85mmol,5.0equiv); g . MeOD (2mL), MeCN (0.5mL), toluene (0.5mL), TBAI (0.077mmol, 0.1equiv), rt, 1h.

[0045] Example 1

[0046]

[0047] Compound 1a (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2a with a yield of 91%.

[0048] The characterization data of the target product methyl 3-phenylpropanoate-2,3-d2 (2a) obtained by the above-mentioned synthesis method are: 115.6 mg colorless liquid; α-D%: 97%; β-D%: 98%; yield: 91%; 1 H-NMR (400MHz, CDCl3) δ7.32-7.28(m,2H),7.24-7.20(m,3H),3.68(s,3H),2.93(d,J=8.0Hz,1H),2.61(d,J=8.0Hz,1H). 13 C-NMR(101MHz, CDCl3)δ173.4,140.5,128.5,128.3,126.3,51.6,35.6,35.4,35.2,30.8,30.6,30.4; HRMS(ESI)m / z calcd for C 10 H 10 D2O2Na +[M+Na] + :189.0855,found 189.0860.

[0049] Example 2

[0050]

[0051] Compound 1b (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2b with a yield of 90%.

[0052] The characterization data of the target product methyl 3-(p-tolyl) prpranoate-2,3-d2 (2b) obtained by the above-mentioned synthesis method are as follows: 82.4 mg colorless liquid; α-D%: 97%; β-D%: 99%; yield: 90%; 1 H-NMR (400MHz, CDCl3) δ7.12-7.07(m,4H),3.67(s,3H),2.89(d,J=8.0Hz,1H),2.61(d,J=8.0Hz,1H),2.32(s,3H). 13 C-NMR(101MHz, CDCl3)δ173.5,137.4,135.7,129.2,128.1,51.6,35.7,35.5,35.3,30.3,30.1,29.9,21.0; HRMS(ESI)m / z calcd for C 11 H 12 D2O2Na + [M+Na] + :203.1012, found 203.1017.

[0053] Example 3

[0054]

[0055] Compound 1c (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2c with a yield of 71%.

[0056] The characterization data of the target product methyl 3-(4-methoxyphenyl)propanoate-2,3-d2(2c) obtained by the above-mentioned synthesis method are: 89.2 mg colorless liquid; α-D%: 94%; β-D%: 97%; yield: 71%; 1 H NMR (400MHz, CDCl3) δ7.12(d,J=8.4Hz,2H),6.83(d,J=8.8Hz,2H),3.78(s,3H),3.66(s,3H),2.87(d,J=8.0Hz,1H),2.58(d,J=6.8Hz,1H). 13 C NMR(101MHz, CDCl3)δ173.5,158.0,132.5,129.2,113.9,55.2,51.6,35.8,35.6,35.4,29.9,29.7,29.5; HRMS(ESI)m / z calcdfor C 11 H 12 D2O3Na + [M+Na] + :219.0961,found 219.0969.

[0057] Example 4

[0058]

[0059] Compound 1d (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2d with a yield of 77%.

[0060] The characterization data of the target product methyl 3-(4-(methylthio)phenyl)propanoate-2,3-d2(2d) obtained by the above synthesis method are: 117.1 mg colorless liquid; α-D%: 98%; β-D%: 99%; yield: 77%; 1 H-NMR (400MHz, CDCl3) δ7.21-7.18(m,2H),7.14-7.11(m,2H),3.66(s,3H),2.89(d,J=6.8Hz,1H),2.59(d,J=6.4Hz,1H),2.46(s,3H); 13 C-NMR(101MHz, CDCl3)δ173.2,137.4,135.9,128.8,127.1,51.6,35.4,35.2,35.0,30.1,30.0,29.8,16.1.HRMS(ESI)m / z calcdfor C 11 H 12 D2SO2Na + [M+Na] + :235.0732,found235.0730.

[0061] Example 5

[0062]

[0063] Compound 1e (1 eq) was dissolved in a mixed solution of 2 mL MeOD, 1 mL MeCN and 1 mL toluene, I2 (3 eq) and TBAI (0.1 eq) were added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2e with a yield of 90%.

[0064] The characterization data of the target product methyl 3-(naphthalen-2-yl)propanoate-2,3-d2(2e) obtained by the above-mentioned synthesis method are as follows: 111.3 mg white powder; α-D%: 98%; β-D%: 96%; yield: 90%; 1H-NMR (400MHz, CDCl3) δ7.83-7.78(m,3H),7.65(s,1H),7.49-7.42(m,2H),7.3 5(d,J=10.0Hz,1H),3.69(s,3H),3.11(d,J=7.6Hz,1H),2.72(d,J=6.8Hz,1H). 13 C-NMR (101MHz, CDCl3) δ173.3,137.9,133.6,132.1,128.1,127.6,127.5,126.9,1 26.4,126.0,125.4,51.6,35.4,35.2,35.0,30.9,30.7,30.5; HRMS(ESI)m / zcalcd for C 10 H 10 D2O3Na + [M+Na] + :205.0804,found 205.0813.

[0065] Example 6

[0066]

[0067] Compound 1f (1 eq) was dissolved in a mixed solution of 2 mL MeOD, 1 mL MeCN and 1 mL toluene, I2 (3 eq) and TBAI (0.1 eq) were added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2f with a yield of 88%.

[0068] The characterization data of the target product methyl 3-(6-methoxynaphthalen-2-yl)propanoate-2,3-d2(2f) obtained by the above-mentioned synthesis method are as follows: 165.2 mg white solid; α-D%: 99%; β-D%: 97%; yield: 88%; 1 H-NMR(400MHz, CDCl3)δ7.68(m,2H),7.57(s,1H),7.31-7.29(m,1H),7.15-7.11 (m,2H),3.91(s,3H),3.68(s,3H),3.06(d,J=8.0Hz,1H),2.68(d,J=9.2Hz,1H); 13C-NMR (101MHz, CDCl3) δ173.4,157.3,135.6,133.2,129.0,129.0,127.4,127.0,1 26.3,118.8,105.6,55.3,51.6,35.6,35.4,35.2,30.7,30.5,30.3; HRMS(ESI)m / z calcd forC 15 H 14 D2O3Na + [M+Na] + :269.1117, found 269.1124.

[0069] Example 7

[0070]

[0071] 161 mg of compound 1g (0.82 mmol, 1 eq) was dissolved in a mixed solution of 2 mL of MeOD, 1 mL of MeCN and 1 mL of toluene, 30.4 mg of TBAI (0.082 mmol, 0.1 eq) and 1.04 g of I2 (4.1 mmol, 5 eq) were added, and after stirring for 5 minutes, 299 mg of magnesium chips (12.3 mmol, 15 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and the eluent was petroleum ether: ethyl acetate = 75:1 (v / v), and 43.2 mg of light yellow liquid 2g was obtained, with a yield of 26% (2g).

[0072] The characterization data of the target product methyl 3-(2-chlorophenyl)propanoate-2,3-d2 (2 g) obtained by the above synthesis method are: 43.2 mg light yellow liquid; α-D%: 96%; β-D%: 97%; yield: 26%; 1 H-NMR (400MHz, CDCl3) δ7.34(dd,J=7.2,2.0Hz,1H),7.27-7.23(m,1H),7.21-7.13(m,2H),3.68(s,3H),3.04(d,J=7.6Hz,1H),2.63(d,J=7.2Hz,1H); 13C-NMR(101MHz, CDCl3)δ173.1,138.0,134.0,130.4,129.6,127.9,126.9,51.6,33.6,33.4,33.2,28.8,28.6,28.4; HRMS(ESI)m / z calcd for C 10 H 10 D2ClO2 + :[M+H] + :201.0646,found 201.0644.

[0073] Example 8

[0074]

[0075] 161 mg of compound 1h (0.82 mmol, 1 eq) was dissolved in a mixed solution of 2 mL of MeOD and 2 mL of MeCN, and I2 (3 eq) was added. After stirring for 5 minutes, 299 mg of magnesium chips (12.3 mmol, 15 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and the eluent was petroleum ether: ethyl acetate = 50:1 (v / v), and 144.1 mg of colorless liquid 2h was obtained, with a yield of 88%.

[0076] The characterization data of the target product methyl 3-(3-chlorophenyl)propanoate-2,3-d2(2h) obtained by the above synthesis method are: 144.1 mg colorless liquid; α-D%: 95%; β-D%: 97%; yield: 88%; 1 H-NMR (400MHz, CDCl3) δ7.24-7.16(m,3H),7.09-7.06(m,1H),3.67(s,3H),2.90(d,J=7.6Hz,1H),2.59(d,J=8.4Hz,1H); 13 C-NMR(101MHz, CDCl3)δ173.0,142.4,134.2,129.7,128.4,126.5,51.6,35.1,34.9,34.7,30.3,30.1,29.9; HRMS(ESI)m / z calcd for C 10 H9D2ClO2Na + :[M+Na] +:223.0465,found 223.0462.

[0077] Example 9

[0078]

[0079] 161 mg of compound 1i (0.82 mmol, 1 eq) was dissolved in a mixed solution of 2 mL of MeOD, 1 mL of MeCN and 1 mL of toluene, 30.4 mg of TBAI (0.082 mmol, 0.1 eq) and 1.04 g of I2 (4.1 mmol, 5 eq) were added, and after stirring for 5 minutes, 299 mg of magnesium chips (12.3 mmol, 15 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and the eluent was petroleum ether: ethyl acetate = 75:1 (v / v), and 103.7 mg of colorless liquid 2i was obtained, with a yield of 63% (2i).

[0080] The characterization data of the target product methyl 3-(4-chlorophenyl)propanoate-2,3-d2(2i) obtained by the above-mentioned synthesis method are: 103.7 mg colorless liquid; α-D%: 96%; β-D%: 97%; yield: 63%; 1 H-NMR (400MHz, CDCl3) δ7.25 (d, J = 8.4Hz, 2H), 7.13 (d, J = 8.0Hz, 2H), 3.67 (s, 3H), 2.90 (d, J = 7.6Hz, 1H), 2.59 (d, J = 8.0Hz, 1H); 13 C-NMR(101MHz, CDCl3)δ173.0,138.9,132.1,129.7,128.6,51.7,35.3,35.1,34.9,30.1,29.9,29.7; HRMS(ESI)m / z calcd for C 10 H 10 D2ClO2 + :[M+H] + :201.0646,found 201.0655.

[0081] Example 10

[0082]

[0083] Compound 1j (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2j with a yield of 79%.

[0084] The characterization data of the target product methyl 3-(3-cyanophenyl)propanoate-2,3-d2(2j) obtained by the above-mentioned synthesis method are: 109.3 mg colorless viscous liquid; α-D%: 97%; β-D%: 98%; yield: 79%; 1 H-NMR (400MHz, CDCl3) δ7.52-7.50(m,2H),7.47-7.44(m,1H),7.42-7.38(m,1H),3.68(s,3H),2.97(d,J=7.6Hz,1H),2.62(d,J=8.4Hz,1H). 13 C-NMR(101MHz, CDCl3)δ172.6,141.8,132.9,131.9,130.1,129.3,118.8,112.5,51.7,34.8,34.6,34.4,30.1,29.9,29.7; HRMS(ESI)m / z calcd for C 11 H 10 ND2O2 + [M+H] + :192.0988,found 192.0990.

[0085] Embodiment 11

[0086]

[0087] Compound 1k (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2k with a yield of 88%.

[0088] The characterization data of the target product methyl 2-phenylpropanoate-2,3-d2 (2k) obtained by the above-mentioned synthesis method are: 161.0 mg colorless liquid; α-D%:>95%; β-D%:98%; yield: 88%; 1 H-NMR (400MHz, CDCl3) δ7.35-7.24(m,5H),3.66(s,3H),1.48(s,2H); 13 C-NMR(101MHz, CDCl3)δ175.0,140.5,128.6,127.4,127.1,52.0,45.2,45.0,18.4,18.2,18.0; HRMS(ESI)m / z calcd forC 10 H 10 D2O2Na + [M+Na] + :189.0855,found 189.0854.

[0089] Example 12

[0090]

[0091] Compound 11 (1 eq) was dissolved in a mixed solution of 2 mL MeOD, 1 mL MeCN and 1 mL toluene, I2 (3 eq) and TBAI (0.1 eq) were added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 21 with a yield of 68%.

[0092] The characterization data of the target product methyl 2-(1,2,3,4-tetrahydronaphthalen-1-yl-1-d)acetate-2-d(2l) obtained by the above synthesis method are: 79.7 mg colorless liquid. α-D%: 98%; β-D%: 96%; yield: 68%; 1 H-NMR (400MHz, CDCl3) δ7.17-7.06(m,4H),3.72(s,3H),2.84-2.75(m,2H),2.70(s ,0.66H),2.53(s,0.36H),1.94-1.88(m,1H),1.86-1.74(m,2H),1.72-1.67(m,1H); 13C-NMR (101MHz, CDCl3) δ173.3,139.1,137.1,129.3,128.2,126.0,125.8,51 .6,41.6,41.4,41.2,34.2,34.0,33.8,29.5,27.9,27.9,19.4; HRMS(ESI)m / z calcd for C 13 H 14 D2O2Na + [M+Na] + :229.1168,found 229.1180.

[0093] Embodiment 13

[0094]

[0095] Compound 1m (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2m with a yield of 87%.

[0096] The characterization data of the target product methyl 3-phenylbutanoate-2,3-d2(2m) obtained by the above-mentioned synthesis method are: 87.3 mg colorless liquid; α-D%: 99%; β-D%: 97%; yield: 87%; 1 H-NMR (400MHz, CDCl3) δ7.33-7.29(m,2H),7.24-7.19(m,3H),3.63(s,1.75H),3.62(s,1.25H),2.61(s,0.6H),2.54(s,0.4H),1.29(s,3H); 13 C-NMR(101MHz, CDCl3)δ172.9,145.6,128.5,126.7,126.4,51.5,42.5,42.3,42.1,36.1,35.9,35.7,21.6,21.6; HRMS(ESI)m / z calcd for C 11 H 12 D2O3Na + [M+Na] + :203.1012, found 203.1016.

[0097] Embodiment 14

[0098]

[0099] Compound 1n (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2n with a yield of 92%.

[0100] The characterization data of the target product methyl 2-methyl-3-phenylpropanoate-2,3-d2(2n) obtained by the above synthesis method are: 130.8 mg colorless liquid; α-D%: 69%; β-D%: 98%; yield: 92%; 1 H NMR (400MHz, CDCl3) δ7.31-7.26(m,3H),7.23-7.15(m,3H),3.64(s,1.4H),3.64( s,1.6H),3.01(s,0.5H),2.65(s,0.52H),2.13(d,J=1.6Hz,0.31H),1.15(s,3H); 13 C NMR (101MHz, CDCl3) δ176.6,139.3,128.9,128.3,126.3,52.0,51.5,41.3,41.1 ,40.9,40.7,39.5,39.4,39.3,39.2,39.1,39.0,16.6,14.0; HRMS(ESI)m / zcalcd for C 11 H 12 D2O2Na + [M+Na] + :203.1012,found 203.1010.

[0101] Embodiment 15

[0102]

[0103] Compound 1o (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2o with a yield of 31%.

[0104] The characterization data of the target product methyl 2,3-dimethyl-3-phenylpropanoate-2,3-d2ðyl 2,3-dimethyl-3-phenyl propanoate-2,3-d2(2o&2o') obtained by the above-mentioned synthesis method are as follows: 74.3 mg light yellow liquid; 2o:2o'=6:11(n / n); α-D%:79%; β-D%:98%; yield (2o):31%; yield (2o'):58%; 1 H NMR(400MHz, CDCl3)δ7.30(td,J=7.6,2.0Hz,2H),7.21-7.15(m,3H),4.21-4.15(m,1.1H),3.72(s, 0.64H), 3.71 (s, 0.26H), 3.47 (s, 0.21H), 1.28 (td, J = 7.2, 2.4Hz, 2.2H), 1.24 (s, 3H), 0.92 (s, 3H); 13 C NMR (101MHz, CDCl3) δ176.9,176.4,144.4,144.3,128.5,128.4,128.2,127.5,127.3,126.5,1 26.4,126.3,60.2,51.5,51.3,46.8,42.9,20.5,17.3,16.1,16.1,14.3,13.9..HRMS(ESI)m / z calcd for C 12 H 14 D2O2Na + [M+Na] + :217.1168,found 217.1171.HRMS(ESI)m / zcalcd for C 13 H 16 D2O2Na + [M+Na] + :231.1325, found 231.1329.

[0105] Example 16

[0106]

[0107] Compound 1p (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2p with a yield of 37%.

[0108] The characterization data of the target product methyl 3-(2-hydroxyphenyl)propanoate-2,3-d2(2p) obtained by the above synthesis method are: 78.8 mg light yellow liquid. α-D%: 99%; β-D%: 94%; yield: 37%; 1 H-NMR (400MHz, CDCl3) δ7.14-7.07(m,2H),6.89-6.85(m,2H),3.69(s,3H),2.89(d,J=6.4Hz,1H),2.70(d,J=8.4Hz,1H). 13 C-NMR(101MHz, CDCl3)δ176.0,154.3,130.5,128.0,127.2,120.9,117.2,52.2,34.8,34.6,34.4,24.4,24.2,24.0; HRMS(ESI)m / z calcd forC 10 H 10 D2O3Na + [M+Na] + :205.0804,found205.0813.

[0109] Embodiment 17

[0110]

[0111] Compound 1q (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2q with a yield of 81%.

[0112] The characterization data of the target product methyl 3-cyclohexylpropanoate-2,3-d2(2q) obtained by the above synthesis method are: 96.4 mg light yellow liquid; α-D%: 99%; β-D%: 94%; yield: 81%; 1 H-NMR (400MHz, CDCl3) δ3.66(s,3H),2.29(d,J=7.6Hz,1H),1.71-1.62(m,5H),1.50(d,J=8.0Hz,1H),1.28-1.14(m,6H); 13 C-NMR(101MHz, CDCl3)δ175.7,51.4,37.1,32.9,32.1,31.9,31.7,31.5,31.4,31.3,31.1,26.5,26.2; HRMS(ESI)m / z calcd for C 10 H 16 D2O2Na + [M+H] + :173.1505, found 173.1517.

[0113] Embodiment 18

[0114]

[0115] Compound 1r (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2r with a yield of 57%.

[0116] The characterization data of the target product dimethyl succinate-2,3-d2(2r) obtained by the above-mentioned synthesis method are: 73.2 mg colorless liquid; D%: 99%, yield: 57%; 1 H-NMR (400MHz, CDCl3) δ3.67 (s, 3H), 2.59 (d, J = 1.6Hz, 1H); 13 C-NMR(101MHz, CDCl3)δ172.7,51.8,28.8,28.5,28.3; HRMS(ESI)m / z calcdfor C6H8D2O4Na + [M+Na] + :171.0597,found 171.0600.

[0117] Embodiment 19

[0118]

[0119] Compound 1s (1 eq) was dissolved in a mixed solution of 2 mL MeOD, 1 mL MeCN and 1 mL toluene, I2 (3 eq) and TBAI (0.1 eq) were added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the product 2s with a yield of 47%.

[0120] The characterization data of the target product 2-(cyclohept-1-en-1-yl)acetate-2-d(2s&2s') obtained by the above-mentioned synthesis method are as follows: 124.2 mg of colorless liquid; a mixture of methyl 2-(cycloheptyl-1-d)acetate-2-d(2s) and methyl 2-(cyclohept-1-en-1-yl)acetate-2-d(2s') which cannot be separated, 2s:2s'=7:2(n / n); yield: 47%(2s); yield: 13%(2s'); α-D%(2s):97%; β-D%(2s):98%; D%(2s'):98%; 1H-NMR (400MHz, CDCl3) δ5.69 (t, J = 6.0Hz, 0.24H), 3.68 (s, 0.67H), 3.66 (s, 2.33H), 2.99 (s, 0.23H), 2 .22-2.16(m,1.25H),2.13-2.09(m,0.49H),1.74-1.52(m,5H),1.58-1.43(m,4H),1.26-1.18(m,2H); 13 C-NMR (101MHz, CDCl3) δ173.8,137.4,130.8,51.6,51.3,45.2,45.0,44.8,42.4,42.3,42.2,42.1,42.0,41 .9,36.4,36.1,35.7,34.5,34.4,34.3,34.3,32.8,32.3,28.4,28.2,26.9,26.4,26.2,26.1; HRMS(ESI)m / z calcd forC 10 H 17 D2O2 + [M+H] + :173.1505, found 173.1512; HRMS(ESI)m / z calcd for C 10 H 16 DO2 + [M+H] + :170.1286,found 170.1286.

[0121] Embodiment 20

[0122]

[0123] Compound 1t (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2t with a yield of 48%.

[0124] The characterization data of the target product methyl 4-phenylbutanoate-2,3-d2&methyl4-phenylbut-3-enoate-2,2-d2(2t&2t') obtained by the above-mentioned synthesis method are as follows: 101.8 mg colorless liquid; a mixture of methyl 4-phenylbutanoate-2,3-d2(2t) and methyl 4-phenylbut-3-enoate-2-d(2t') which cannot be separated, 2t:2t'=4:3(n / n); yield: 48%(2t); yield: 36%(2t'); α-D%(2t):93%; β-D%(2t):93%; D%(2t'):95%; 1 H-NMR (400MHz, CDCl3) δ7.39-7.36(m,1H),7.34-7.27(m,2H),7.24-7.16(m,2H),6.52-6.48(m,0.45H),6.31-6.27 (m,0.45H),3.72(s,1.3H),3.67(s,1.7H),2.65(d,J=7.6Hz,1.2H),2.31(d,J=9.2Hz,0.6H),1.97-1.91(m,0.6H); 13 C-NMR (101MHz, CDCl3) δ174.0,141.4,136.8,133.5,128.5,128.5,128.4,127.6, 126.3,121.5,51.9,51.5,35.0,33.2,33.0,32.8,26.2,26.0,25.8; HRMS(ESI)m / z calcd for C 11 H 12 D2O2Na + [M+Na] + :203.1012, found 203.1015; HRMS(ESI)m / z calcd for C 11 H 11 D2O2 + [M+H] + :179.1036,found179.1037.

[0125] Embodiment 21

[0126]

[0127] Compound 1u (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2u with a yield of 75%.

[0128] The characterization data of the target product methyl 3-(thiophen-2-yl)propanoate-2,3-d2(2u) obtained by the above synthesis method are: 116.2 mg colorless liquid; α-D%: 117%; β-D%: 95%; the deuteration rate of thiophene 5-position is 17%; yield: 75%; 1 H-NMR (400MHz, CDCl3) δ7.13 (d, J=5.2Hz, 1H), 6.92 (dd, J=2.8, 8.4Hz, 1H), 6. 82(d,J=3.6Hz,1H),3.69(s,3H),3.15(d,J=7.4Hz,1H),2.67(d,J=6.0Hz,1H); 13 C-NMR(101MHz, CDCl3)δ172.8,142.9,126.8,126.7,124.6,123.5,51.7,35.8,35.6,35.4,25.0,24.8,24.6; HRMS(ESI)m / z calcd for C8H8D2O2SNa + [M+Na] + :195.0419,found195.0417.

[0129] Embodiment 22

[0130]

[0131] Compound 1v (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2v with a yield of 52%.

[0132] The characterization data of the target product methyl 3-(quinolin-2-yl-4-d)propanoate2,3-d2(2v) obtained by the above-mentioned synthesis method are as follows: 106.0 mg of light yellow liquid; α-D%: 104%; β-D%: 85%; the deuteration rate of the quinoline 4-position is 59%; the yield: 52%; 1 H-NMR (400MHz, CDCl3) δ8.07(d,J=8.4Hz,0.41H),8.03(d,J=8.4Hz,1H),7.81-7.76(m,1H),7.70-7.66(m,1H ),7.51-7.47(m,1H),7.33(dd,J=8.4,4.0Hz,1H),3.69(s,3H),3.29(d,J=7.2Hz,1H),2.92(d,J=8.0Hz,1H); 13 C-NMR (101MHz, CDCl3) δ173.6,160.4,129.4,128.8,127.51,127.46,126.9,126 .8,125.9,121.5,121.4,51.6,33.2,33.0,32.8,32.8,32.6,32.4; HRMS(ESI)m / z calcd for C 13 H 11 D3O2N + [M+H] + :219.1207, found 219.1214; HRMS(ESI)m / z calcd for C 13 H 12 D2O2N + [M+H] + :218.1145, found 218.1154; HRMS(ESI)m / z calcd for C 13 H 10 D3O2NNa + [M+Na] + :241.1027,found241.1034; HRMS(ESI)m / z calcd for C 13 H 11 D2O2NNa + [M+Na] + :240.0964,found 240.0972.

[0133] Embodiment 23

[0134]

[0135] Compound 1w (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2w with a yield of 61%.

[0136] The characterization data of the target product methyl 3-(1-methyl-1H-pyrrol-2-yl-3,4,5-d3)propanoate-2,3-d2(2w) obtained by the above-mentioned synthesis method are as follows: 91.2 mg brown liquid; α-D%: 98%; β-D%: 99%; the deuteration rate of the 3, 4, and 5 positions of pyrrole is 44%; yield: 61%; 1 H-NMR (400MHz, CDCl3) δ6.56 (s, 0.56H), 6.07-6.05 (m, 0.56H), 5.88 (d, J = 2.4H z,1H),3.70(s,3H),3.55(s,3H),2.86(d,J=7.6Hz,1H),2.64(d,J=8.4Hz,1H); 13 C-NMR (101MHz, CDCl3) δ173.3,131.3,121.5,121.4,106.6,106.5,106.5,106.4, 105.4,105.3,51.7,33.5,33.4,33.0,32.8,32.6,21.4,21.2,21.0; HRMS(ESI)m / z calcd for C9H 11 D2O2NNa + [M+Na] + :192.0964, found 192.0961; HRMS(ESI)m / zcalcd for C9H 10 D3O2NNa + [M+Na] + :193.1027, found 193.1023; HRMS(ESI)m / z calcd forC9H9D4O2NNa + [M+Na] + :194.1090, found 194.1083; HRMS(ESI)m / z calcd for C9H8D5O2NNa + [M+Na] +:195.1152, found 195.1138.

[0137] Embodiment 24

[0138]

[0139] Compound 1x (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2x with a yield of 64%.

[0140] The characterization data of the target product methyl 3-(furan-2-yl-5-d)propanoate-2,3-d2 (2x) obtained by the above synthesis method are: 108.8 mg of light yellow liquid; α-D%: 99%; β-D%: 96%; the deuteration rate of furan 5 is 12%; yield: 64%; 1 H-NMR (400MHz, CDCl3) δ7.30 (d, J=1.2Hz, 0.88H), 6.27 (dd, J=3.2, 2.0Hz, 1H), 6 .02(d,J=3.2Hz,1H),3.69(s,3H),2.95(d,J=7.6Hz,1H),2.63(d,J=8.0Hz,1H); 13 C-NMR(101MHz, CDCl3)δ173.0,154.1,141.2,110.2,105.3,51.7,32.3,32.1,31.9,23.2,23.1,22.9; HRMS(ESI)m / zcalcd for C8H8D2O2Na + [M+Na] + :179.0648,found179.0644; HRMS(ESI)m / z calcd for C8H7D3O2Na + [M+Na] + :180.0710,found 180.0682.

[0141] Embodiment 25

[0142]

[0143] Compound 1y (1 eq) was dissolved in a mixed solution of 2 mL MeOD, 1 mL MeCN and 1 mL toluene, I2 (3 eq) and TBAI (0.1 eq) were added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2y with a yield of 84%.

[0144] The characterization data of the target product methyl 2-(4-isobutylphenyl)propanoate-2,3-d2(2y) obtained by the above synthesis method are: 195.5 mg colorless liquid; α-D%: 98%; β-D%: 97%; yield: 84%; 1 H-NMR (400MHz, CDCl3) δ7.20(d,J=8.0Hz,2H),7.10(d,J=8.0Hz,2H),3.66(s,3H),2.45 (d,J=7.2Hz,2H),1.85(qt,J=13.6,6.8Hz,1H),1.47(s,2H),0.91(s,3H),0.90(s,3H); 13 C-NMR(101MHz, CDCl3)δ175.2,140.6,137.7,129.3,127.1,51.9,45.0,44.8,44.6,30.2,22.4,18.4,18.2,18.0.HRMS(ESI)m / z calcd for C 14 H 18 D2O2Na + [M+Na] + :245.1481,found245.1485.

[0145] Embodiment 26

[0146]

[0147] 167.5 mg 2y (0.753 mmol, 1 eq) was dissolved in 5 mL THF, 10 mL 3 mol / L KOH solution was added, and the mixture was stirred at 65°C overnight. The solution was concentrated under reduced pressure, and the pH was adjusted to 1 with concentrated hydrochloric acid. The mixture was extracted with ethyl acetate three times, separated, and the organic phase was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to obtain 145.8 mg colorless viscous liquid 2z. The liquid solidified rapidly after cooling. Yield: 93%.

[0148] The characterization data of the target product 2-(4-isobutylphenyl)propanoic-2,3-d2acid(2z) obtained by the above-mentioned synthesis method are as follows: 145.8 mg white solid; α-D%: 98%; β-D%: 97%; yield: 93%; 1 H-NMR (400MHz, CDCl3) δ7.23(d,J=8.0Hz,2H),7.11(d,J=8.0Hz,2H),2.45(d,J= 7.2Hz,2H),1.84(qt,J=13.6,6.8Hz,1H),1.48(s,2H),0.91(s,3H),0.89(s,3H); 13 C-NMR(101MHz, CDCl3)δ180.8,140.8,136.9,129.4,127.2,45.0,44.7,44.5,44.3,30.1,22.4,17.9,17.7,17.5.HRMS(ESI)m / z calcd for C 13 H 16 D2O2Na + [M+Na] + :231.1325, found 231.1322.

[0149] Embodiment 27

[0150]

[0151] Compound 1aa (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2aa with a yield of 81%.

[0152] The characterization data of the target product 3-phenyl-1-(piperidin-1-yl)propan-1-one-2,3-d2(2aa) obtained by the above-mentioned synthesis method are: 127.9 mg colorless viscous liquid; α-D%: 98%; β-D%: 97%; yield: 81%; 1H-NMR (400MHz, CDCl3) δ7.32-7.27(m,2H),7.23-7.18(m,3H),3.56(t,J=5.6Hz,2H),3.33(t,J=5 .6Hz,2H),2.94(d,J=8.0Hz,1H),2.59(d,J=7.2Hz,1H),1.6(q,J=6.0Hz,2H),1.55-1.44(m,4H); 13 C-NMR (101MHz, CDCl3) δ170.4,141.4,128.42,128.39,126.1,46.6,42.7,34.9,34.7,34.5,31.4,31.2,31.0,26.3,25.5,24.5; HRMS(ESI)m / z calcd forC 14 H 17 D2ON + [M+Na] + :242.1484, found 242.1495; HRMS(ESI)m / z calcd for C 14 H 18 D2ON + [M+H] + :220.1665,found 220.1673.

[0153] Embodiment 28

[0154]

[0155] Compound 1ab (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2ab with a yield of 85%.

[0156] The characterization data of the target product 1-morpholino-3-phenylpropan-1-one-2,3-d2(2ab) obtained by the above-mentioned synthesis method are: 136.5 mg colorless viscous liquid; α-D%: 96%; β-D%: 98%; yield: 85%; 1H-NMR (400MHz, CDCl3) δ7.33-7.27(m,2H),7.24-7.17(m,3H),3.62(s,4H),3.50(t ,J=4.8Hz,2H),3.35(t,J=4.8Hz,2H),2.96(d,J=6.6Hz,1H),2.59(d,J=7.2Hz,1H); 13 C-NMR(101MHz, CDCl3)δ170.9,141.0,128.5,128.4,126.3,66.8,66.4,45.9,41.9,34.6,34.4,34.2,31.2,31.1,30.9; HRMS(ESI)m / z calcd for C 13 H 15 D2O2NNa + [M+Na] + :244.1277,found244.1276.

[0157] Embodiment 29

[0158]

[0159] Compound 1ac (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20° C. for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2ac with a yield of 83%.

[0160] The characterization data of the target product N-methyl-N,3-diphenylpropanamide-2,3-d2(2ac) obtained by the above synthesis method are: 187.2 mg colorless viscous liquid; α-D%: 96%; β-D%: 98%; yield: 83%; 1 H-NMR (400MHz, CDCl3) δ7.38-7.34(m,2H),7.30(d,J=7.2Hz,1H),7.24-7.21(m,2H),7.16(d ,J=7.2Hz,1H),7.07-7.01(m,4H),3.25(s,3H),2.89(d,J=7.6Hz,1H),2.35(d,J=8.0Hz,1H); 13C-NMR (101MHz, CDCl3) δ172.2,144.0,141.2,129.7,128.4,128.3,127.7,127.3,126.0,37.3,35.8,35.6,35.4,31.5,31.3,31.1; HRMS(ESI)m / z calcd for C 16 H 15 D2ON + [M+Na] + :264.1328, found 264.1335; HRMS(ESI)m / z calcd for C 16 H 16 D2ON + [M+H] + :242.1508,found242.1510.

[0161] Embodiment 30

[0162]

[0163] Compound 1ad (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the product 2ad with a yield of 76%.

[0164] The characterization data of the target product N,N-diphenylpropanamide-2,3-d2 (2ad) obtained by the above synthesis method are: 102.2 mg white solid; α-D%: 97%; β-D%: 98%; yield: 76%; 1 H-NMR (400MHz, CDCl3) δ7.38-7.35(m,4H),7.26-7.23(m,6H),2.25(t,J=8.4Hz,1H),1.11(d,J=5.2Hz,2H); 13 C-NMR(101MHz, CDCl3)δ174.0,142.9,129.3-126.0(m),28.6,28.4,28.2,9.5,9.3,9.1; HRMS(ESI)m / z calcd for C 15 H 14 D2ON +[M+H] + :228.1352, found 228.1356; HRMS(ESI)m / z calcdfor C 15 H 13 D2ON + [M+Na] + :250.1171, found 250.1176.

[0165] Embodiment 31

[0166]

[0167] Compound 1ae (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2ae with a yield of 86%.

[0168] The characterization data of the target product N-methyl-N-phenylbutanamide-2,3-d2(2ae) obtained by the above-mentioned synthesis method are: 167.8 mg colorless viscous liquid; α-D%: 96%; β-D%: 98%; yield: 86%; 1 H-NMR (400MHz, CDCl3) δ7.42-7.38(m,2H),7.34-7.30(m,1H),7.16(d,J=7.6Hz,2 H),3.25(s,3H),2.01(d,J=6.8Hz,1H),1.59-1.54(m,1H),0.80(d,J=7.6Hz,3H); 13 C-NMR(101MHz, CDCl3)δ173.1,144.3,129.7,127.6,127.3,37.2,35.7,35.5,35.3,18.7,18.5,18.3,13.7; HRMS(ESI)m / z calcd for C 11 H 13 D2ON + [M+Na] + :202.1171, found 202.1168; HRMS(ESI)m / z calcd for C 11 H 14 D2ON+ [M+H] + :180.1352,found 180.1349.

[0169] Embodiment 32

[0170]

[0171] Compound 1af (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2af with a yield of 84%.

[0172] The characterization data of the target product N,2-dimethyl-N-phenylpropanamide-2,3-d2(2af) obtained by the above-mentioned synthesis method are as follows: 241.6 mg white solid; α-D%: 97%; β-D%: 95%; yield: 84%; 1 H-NMR (400MHz, CDCl3) δ7.43-7.39(m,2H),7.36-7.32(m,1H),7.20-7.17(m,2H),3.25(s,3H),1.01(s,3H),1.00(s,2H); 13 C-NMR(101MHz, CDCl3)δ177.4,144.3,129.7,127.7,127.3,37.4,30.7,30.5,30.3,19.5,19.4,19.2,19.1; HRMS(ESI)m / z calcd for C 11 H 13 D2ON + [M+Na] + :202.1171, found 202.1170; HRMS(ESI)m / z calcd for C 11 H 14 D2ON + [M+H] + :180.1352,found 180.1356.

[0173] Embodiment 33

[0174]

[0175] Compound 1ag (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the product 2ag with a yield of 87%.

[0176] The characterization data of the target product N,2-dimethyl-N-(p-tolyl)propanamide-2,3-d2(2ag) obtained by the above-mentioned synthesis method are as follows: 263.3 mg of light yellow viscous liquid; α-D%: 98%; β-D%: 96%; yield: 87%; 1 H-NMR (400MHz, CDCl3) δ7.20(d,J=8.0Hz,2H),7.06(d,J=8.0Hz,2H),3.21(s,3H),2.37(s,3H),1.01(s,3H),0.99(s,2H); 13 C-NMR(101MHz, CDCl3)δ177.6,141.7,137.6,130.3,127.0,37.4,30.4,21.0,19.5,19.4,19.2,19.0; HRMS(ESI)m / z calcd for C 12 H 16 D2ON + [M+H] + :194.1508, found 194.1505; HRMS(ESI)m / z calcd for C 12 H 15 D2ON + [M+Na] + :216.1328,found 216.1323.

[0177] Embodiment 34

[0178]

[0179] Compound 1ah (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the product 2ah with a yield of 57%.

[0180] The characterization data of the target product 1-benzylpyrrolidine-2,5-dione-3,4-d2 (2ah) obtained by the above-mentioned synthesis method are: 73.2 mg of light yellow solid; D%: 144%, yield: 57%; 1 H-NMR (400MHz, CDCl3) δ7.40-7.36(m,2H),7.33-7.25(m,3H),4.66(s,2H),2.68(s,1.12H); 13 C-NMR(101MHz, CDCl3)δ177.4,51.8,28.8,28.5,28.3; HRMS(ESI)m / z calcd for C 11 H9D2O2NNa + [M+Na] + :214.0808, found 214.0809; HRMS(ESI)m / z calcd for C 11 H8D3O2NNa + [M+Na] + :215.0870, found 215.0858; HRMS(ESI)m / z calcd for C 11 H7D4O2NNa + [M+Na] + :216.0933,found216.0923.

[0181] Embodiment 35

[0182]

[0183] Compound 1ai (1 eq) was dissolved in a mixed solution of 2 mL MeOD and 2 mL MeCN, I2 (3 eq) was added, and after stirring for 5 minutes, magnesium chips (10 eq) were added. The mixture was first stirred in a water bath at 15-20 ° C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10 mL of ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2ai with a yield of 85%.

[0184] The characterization data of the target product 3-phenylpropanenitrile-2,3-d2(2ai) obtained by the above synthesis method are: 134.1 mg colorless liquid; α-D%: 98%; β-D%: 94%, yield: 85%; 1 H-NMR (400MHz, CDCl3) δ7.37-7.33(m,2H),7.30-7.22(m,3H),2.94(d,J=5.2Hz,1H),2.62(d,J=5.6Hz,1H); 13 C-NMR(101MHz, CDCl3)δ138.0,128.8,128.2,127.2,119.1,31.3,31.1,30.9,19.2,19.0,18.8; HRMS(ESI)m / z calcd for C9H8D2N + [M+H] + :134.0933,found 134.0932.

[0185] Embodiment 36

[0186]

[0187] 128mg 1aj (0.80mmol, 1eq) was dissolved in a mixed solution of 2mL MeOD and 2mL MeCN, 1.22g I2 (4.8mmol, 6eq) was added, and after stirring for 5 minutes, 292mg magnesium chips (12.0mmol, 15eq) were added. The mixture was first stirred in a water bath at 15-20°C for 2 minutes, and then continued to stir at room temperature for half an hour. After the reaction was completed, 10mL ethyl acetate was added to the mixture and filtered. The filtrate was washed twice with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, and the eluent was petroleum ether: ethyl acetate = 50:1 (v / v), and 124.1mg colorless liquid 2aj was obtained, with a yield of 92%.

[0188] The characterization data of the target product methyl 3-phenylpropanoate-2,2,3,3-d4 (2aj) obtained by the above-mentioned synthesis method are: 124.1 mg colorless liquid; α-D%: 97%; β-D%: 99%; yield: 92%; 1 H-NMR (400MHz, CDCl3) δ7.32-7.28(m,2H),7.23-7.19(m,3H),3.67(s,3H); 13 C-NMR(101MHz, CDCl3)δ173.4,140.4,128.5,128.2,126.3,51.4,35.2,35.0 34.7,30.3,30.1,29.9; HRMS(ESI)m / zcalcd for C 10 H8D4O2Na + [M+Na] + :191.0981,found 191.0988.

[0189] As described in the above experimental examples and embodiments, 1 H NMR and 13 C NMR was measured using an AVANCE AV400 NMR instrument. NMR chemical shifts were referenced to TMS as an internal standard. The NMR spectrum produced using CDCl3 as the NMR solvent contained a CHCl3 peak. 1 H is 7.26ppm, 13 C is 77.0ppm. The peak shape is as follows: s: single peak; d: double peak; bs: broad single peak; dd: double peak; t: triplet; m: multiple peak; q: quartet. The coupling constant J is in Hertz (Hz). The data are as follows: chemical shift, peak shape, coupling constant and integration. High-resolution mass spectrometry (HRMS) was measured using Q-TOF LC-MS and ESI-FTICR (electron spray ionization-Fourier transform ion cyclotron resonance) techniques. The reaction was monitored by thin layer chromatography (TLC) on a 0.25mm silica gel glass plate coated with 60F254. A mixture of petroleum ether (60-90°C) / ethyl acetate was used as an eluent and column chromatography was performed on silica gel (200-300 mesh). The deuteration rate is expressed as D%, α-D% is the deuteration rate of the α position of the ester group, β-D% is the deuteration rate of the β position of the ester group, and the magnesium chips are washed with 5% hydrochloric acid before being added to the reaction system. All reactants were used without additional purification steps unless otherwise described.

[0190] Deuterium substitution rate calculation formula:

[0191]

[0192] 1a-1c, 1p and 1ah-1aj were purchased from official channels, and 1d-1o, 1q, 1s-1z, 1aa-1ag and 1ak-1am were prepared by known methods.

[0193] In summary, under the reaction conditions of entries 10 and 11 of Table 1, the scope of synthetic substrates for Mg / CH3OD-mediated deuteration was investigated, and this deuteration was applicable to various α,β-unsaturated esters, compatible with a range of substituents including Me, MeO, SMe, Cl and CN, and well tolerated on the benzene ring, resulting in good yields and high deuterium incorporation rates (Examples 2-23). ​​In this reaction system, the chlorine atom remains unchanged regardless of the ortho-meta-para position (Examples 7-9). The substrate scope is not limited to disubstituted olefins, and the deuteration reaction conditions are also compatible with tri- and tetra-substituted olefins (Examples 11-15). The common transesterification reaction occurs when the substrate 1o is reduced, and a mixture of methyl and ethyl esters 2o and 2o' is obtained in a ratio of 6:11. Similarly, coumarin 1p underwent complete transesterification to afford methyl o-hydroxyphenylpropionate-2,3-d2 (2p) in 37% yield and high deuteration rate (α / β, 99 / 94). In addition to β-aromatic olefins, β-cyclohexyl substrate 1q was also evaluated under deuterated conditions to afford the desired product 2q in 81% yield and 94 / 99 deuteration rate. Dimethyl fumarate 1r was converted to dimethyl dideuterated succinate 2r in 57% yield and high deuteration rate. Reduction of exocyclic olefin 1s afforded the desired product 2s in 47% yield, while partial rearrangement occurred to afford product 2s' in 13% yield, introducing a deuterium atom label at the α position. Rearrangement was also observed in the reaction of 1t, affording 2t' in 36% yield. We infer that the reactive benzylic CH bond promotes the formation of product 2t'. Partial HIE phenomena were observed in the case of heterocyclic substituted α,β-unsaturated esters (Examples 21-24). For example, deuterium was introduced into one position of thiophene, quinoline and furan, and three positions of pyrrole were labeled with deuterium atoms (Example 23). This method is also applicable to the synthesis of deuterated ibuprofen 2z, which was produced by hydrolysis of the corresponding 2-(4-isobutylphenyl) propionic acid methyl ester-2,3-d2 (2y).

[0194] According to Examples 27-34, we explored α,β-unsaturated amides under this deuteration condition. Olefins with phenyl or methyl groups were also suitable substrates to give the desired products 2aa-ah in good yields and high deuteration rates. The deuteration rate of 2ah was higher than 100% (144%), and we believe that the HIE process also occurred during the reduction process, which led to overdeuteration at the α position.

[0195] According to Examples 35-36, the substrate scope was further expanded to cinnamonitrile 1ai and 3-phenylpropiolic acid methyl ester 1aj to generate the corresponding products 2ai and 2aj in high yields and good deuterium incorporation rates.

[0196] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for reducing α,β-unsaturated esters, nitriles and amides, characterized in that: The following steps are involved: The substrate is dissolved in MeOD and MeCN, an additive is added, the mixture is stirred, and magnesium chips are added to obtain a mixture; the mixture is first stirred in a water bath and then stirred at room temperature; after the reaction is completed, an organic solvent is added to the mixture and then filtered, the filtrate is washed after filtration, the organic phase is dried, filtered, and concentrated under reduced pressure, and the residue is purified to obtain a product; The additive is I2; The chemical formula is as follows:

2. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 1, characterized in that: The step further includes: adding a co-solvent while adding the additive.

3. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 2, characterized in that: The co-solvents are toluene and TBAI; The chemical formula is as follows:

4. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 1, characterized in that: In the chemical formula, EWG represents an ester group, an amide bond, or a cyano group.

5. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 1, characterized in that: In the chemical formula, R 1 , R 2 , R 3 Selected from alkyl, aromatic ring, aromatic heterocycle, chlorine, cyano, ester, methoxy, methylthio, amide bond, hydroxyl, cycloalkyl.

6. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 1, characterized in that: The equivalent ratio of the substrate, I2 and magnesium chips is 1:3-6:10-15.

7. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 1, characterized in that: The organic solvent is ethyl acetate.

8. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 1, characterized in that: The filtrate was washed with a saturated sodium thiosulfate solution, and the organic phase was dried over anhydrous magnesium sulfate.

9. A method for reducing α,β-unsaturated esters, nitriles and amides according to claim 1, characterized in that: The residue is purified by silica gel column chromatography.

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