Method for c(sp 2)-h bond deuteration in benzene ring

Abstract

A method for C(sp2)-H bond deuteration in a benzene ring, comprising the following step: in a solvent and under phenol, alkali, and visible light conditions, subjecting a substance A to a deuteration reaction with a deuterium source to obtain a substance B. The photocatalytic benzene ring deuteration method is easy to operate and has wide application prospects.

Description

A C(sp 2 )-H bond deuteration method

[0001] This application claims the benefit of Chinese Patent Application No. 2023116045622, filed on November 28, 2023. This application incorporates the entirety of the aforementioned Chinese Patent Application. Technical Field

[0002] The present invention relates to a C(sp 2 )-H bond deuteration method. Background Art

[0003] Isotope labeling technology plays a vital role in the development of new drugs, pesticides, and other products. Deuterium (D) is a stable, non-radioactive isotope of hydrogen (H), with a natural abundance of approximately 0.0156%. Compared to other isotopes, D exhibits a larger weight ratio to H, with the atomic mass of H being 1.008u and that of D being 2.014u. This double weight ratio results in a lower vibrational frequency and zero-point energy for the CD bond, resulting in a higher activation energy for CD breakage than for CH. Consequently, H and D exhibit significant kinetic isotope effects (KIEs) in biochemical reactions. Pharmacologists exploit this effect by deuterating drugs to prolong their duration of action in the body, reduce dosage, improve efficacy, and reduce toxic reactions. Currently, deuterated drugs have become a hot research area in new drug development, with numerous pharmaceutical companies both domestically and internationally actively developing new deuterated drugs. In April 2017, the U.S. Food and Drug Administration (FDA) approved the world's first deuterated drug, deuterabenazine tablets (Antaitan). Furthermore, donafenib mesylate was approved for marketing in China in June 2022, becoming the country's first deuterated anti-cancer drug. The successful development of deuterated drugs has garnered significant attention from pharmacists and pharmaceutical companies worldwide regarding drug-related deuteration technology.

[0004] In traditional benzene rings, C(sp 2 The deuteration method of )-H bonds requires pre-halogenation pre-activation or introduction of directing groups in the substrate, and requires strong acidic conditions or the participation of transition metals, which limits the application of related methods in the deuteration reaction of complex drug molecules. In recent years, the visible light reaction strategy has developed rapidly due to its mild reaction conditions and green environmental protection. However, current research mainly focuses on the deuteration of C(sp 3 )-H bond deuteration, there is no research on the C(sp 2 )-H bond deuteration research report.

[0005] Summary of the Invention

[0006] The technical problem to be solved by the present invention is to overcome the problem that there is no photocatalytic reaction in the prior art to realize the C (sp 2 )-H direct hydrogen-deuterium exchange defect, thus providing a C(sp 2 )-H bond deuteration method. Under the action of phenol, base, deuterium source and light, a single-step reaction is achieved to deuterate C(sp 2 The deuterated )-H bond of the present invention has a high yield, few by-products, a wide range of substrate applications, good functional group compatibility, and mild reaction conditions.

[0007] The present invention provides a C(sp 2 A method for deuterating a )-H bond, comprising the following steps: reacting a substance A with a deuterium source in a solvent under the conditions of phenol, a base and visible light irradiation to obtain a substance B;

[0008] The substance A contains an aromatic group, and the aromatic group contains one or more fragments I, and the fragment I is The H in the fragment I is the naturally abundant H;

[0009] The aromatic group is aryl,

[0010] X and Y are each independently NH, O or S; Z is N or CH;

[0011] Part or all of the fragment I is converted into the fragment II, and the fragment II is In H in the fragment II, the abundance of D is greater than the natural abundance of D;

[0012] The aromatic group is not directly connected to the halogen;

[0013] The phenol is

[0014] Ring A is C 6-14 Aryl or 5-10 membered heteroaryl; the heteroatoms in the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0015] R 1 Each independently is H, C 1-10 Alkyl, -OR 1a 、-NO2、-(C=O)R 1b 、-NR 1c R 1d 、C 6-14 Aryl, 5-10 membered heteroaryl, substituted by one or more R 1e Substituted C 1-10 Alkyl, one or more R1f Substituted C 6-14 Aryl, or one or more R 1 g substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1g The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0016] m is 1, 2, 3, 4 or 5;

[0017] R 1a and R 1b are independently H or C 1-10 alkyl;

[0018] R 1c and R 1d Independently H, C 6-14 Aryl, or substituted by one or more R 1a-1 C 6-14 aryl;

[0019] R 1e 、R 1f and R 1g Each independently is -OH, C 1-10 Alkyl, NR 1a-2 R 1a-3 、-(C=O)R 1a-4 or -CN;

[0020] R 1a-1 、R 1a-2 、R 1a-3 and R 1a-4 are independently H or C 1-10 alkyl.

[0021] In the present invention, preferably, the substance A is subjected to a deuteration reaction to obtain the substance B, and the abundance of H in the fragments of the remaining groups in the substance A (ie, substituents other than the aromatic groups) remains unchanged.

[0022] In the present invention, the above The H in is the H connected to the sp2 hybridized carbon.

[0023] In one embodiment, the substance A contains one or more aromatic groups, such as 1, 2, 3 or 4 (preferably 1), and the aromatic groups are the same or different. Preferably, when the aromatic fragments are different, the fragment I is the above Fragments in .

[0024] In one embodiment, in the substance A, the fragment I is a fragment of the following groups: the aromatic group, wherein the aryl group, Optionally with C 3-15 Cycloalkyl or C 3-15 Heterocycloalkyl fused, the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4.

[0025] In one embodiment, the solvent is a conventional solvent for this type of reaction in the art. Preferably, the solvent is an organic solvent or an inorganic solvent. The inorganic solvent is, for example, water. The organic solvent is, for example, one or more of an alkane solvent, an ether solvent, a nitrile solvent, an amine solvent and a sulfoxide solvent, preferably an ether solvent (e.g., tetrahydrofuran).

[0026] The alkane solvent is, for example, n-hexane, cyclohexane, n-heptane, n-pentane or petroleum ether.

[0027] The ether solvent is, for example, tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, 1,4-dioxane or methyl tert-butyl ether, preferably tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, 1,4-dioxane or methyl tert-butyl ether.

[0028] The nitrile solvent is, for example, acetonitrile.

[0029] The amine solvent is, for example, ethylenediamine, N,N-dimethylformamide or N,N-dimethylacetamide, preferably ethylenediamine or N,N-dimethylformamide.

[0030] The sulfoxide solvent is preferably dimethyl sulfoxide.

[0031] In one embodiment, the solvent is dimethyl sulfoxide, tetrahydrofuran, diethyl ether, 1,4-dioxane, methyl tert-butyl ether, n-hexane, cyclohexane, n-heptane, n-pentane, petroleum ether or N,N-dimethylformamide, ethylenediamine, ethylene glycol dimethyl ether or acetonitrile.

[0032] In one embodiment, in the phenol, R 1 Each independently is H, C 1-10 Alkyl, -OR 1a 、-NO2、-(C=O)R 1b 、-NR 1c R 1d 、C 6-14 Aryl, 5-10 membered heteroaryl, substituted by one or more R 1e Substituted C 1-10 Alkyl or one or more R 1f Substituted C 6-14 Aryl, the heteroatoms in the 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4.

[0033] In one embodiment, in the phenol, m is 1, 2 or 3.

[0034] In one scenario, R 1c and R 1d are independently H or substituted by one or more R 1a-1 C 6-14 Aryl.

[0035] In one embodiment, in ring A, the C 6-14 Aryl is phenyl, naphthyl, anthracenyl or phenanthrenyl.

[0036] In one embodiment, in ring A, the 5-10 membered heteroaryl is a 5-6 membered heteroaryl, wherein the heteroatom in the 5-10 membered heteroaryl is preferably N, and the number of heteroatoms is preferably 1. For example, the 5-10 membered heteroaryl is

[0037] In one scenario, R 1 In the C 1-10 Alkyl and one or more R 1e Substituted C 1-10 C in alkyl 1-10 The alkyl groups are each independently C 1-6 Straight chain or branched chain alkyl or C 7-10 Straight chain alkyl, the C 1-6 The straight chain or branched chain alkyl group is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl (for example, methyl, tert-butyl), and the C 7-10 Straight-chain alkyl groups include, for example, n-heptyl, n-octyl, n-nonyl or n-decyl (eg, n-heptyl).

[0038] In one scenario, R 1 In the C 6-14 Aryl and one or more R 1f Substituted C 6-14 C in aromatic group 6-14 Each aryl group is independently phenyl, naphthyl, anthracenyl or phenanthrenyl, for example phenyl or anthracenyl.

[0039] In one scenario, R 1 wherein the 5-10 membered heteroaryl group and one or more R 1g The 5-10 membered heteroaryl groups in the substituted 5-10 membered heteroaryl groups are each independently a 5-9 membered heteroaryl group, wherein the heteroatom in the 5-10 membered heteroaryl group is preferably N, and the number of heteroatoms is preferably 1 or 2, for example

[0040] In one scenario, R 1a 、R 1b 、R1e 、R 1f 、R 1g 、R 1a-1 、R 1a-2 、R 1a-3 and R 1a-4 In the C 1-10 The alkyl groups are each independently C 1-6 The straight-chain or branched alkyl group is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl (eg, methyl, tert-butyl).

[0041] In one scenario, R 1c and R 1d In the C 6-14 Aryl and substituted by one or more R 1a-1 C 6-14 C in aromatic group 6-14 Each aryl group is independently phenyl, naphthyl, anthracenyl or phenanthrenyl, for example phenyl.

[0042] In a certain embodiment, the phenol is any of the following compounds:

[0043] For example, the phenol is any of the following compounds: 2,6-di-tert-butyl-4-phenylphenol, 2,6-di-tert-butyl-4-(9-anthryl)phenol, 2,6-di-tert-butyl-4-heptylphenol, 2,4,6-triphenylphenol, 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol, 9-phenanthroline, 9,10-anthraquinone, 2-tert-butyl-3,5-xylenol, 2,6-di-tert-butyl-4-(4-tert-butylphenyl)phenol, 3-phenyl-1-naphthol, 2-phenylphenol, 3-hydroxy-2-phenylpyridine, 3-((2,6-dimethylphenyl)amino)phenol, 4′-aminophenyl-3-phenol, cyano Biphenol, 2,6-di-tert-butyl-4-(4-acetylphenyl)phenol, 2,4,6-tri-tert-butylphenol, 2-tert-butyl-3,5-xylenol, 1-anthrol, 5,5′-di-tert-butyl-2,2′-biphenol, 2,6-di-tert-butyl-4-acetylphenol, 2,6-di-tert-butyl-4-methoxyphenol, 6-tert-butyl-2,4-xylenol, 2,6-di-tert-butyl-4-nitrophenol, 3,5-di-tert-butylcatechol, 4-phenylphenol, 2-amino-4-tert-butylphenol, 2,6-diphenylphenol, 2,6-di-tert-butyl-4-methylphenol or 2,6-di-tert-butyl-4-hydroxymethylphenol.

[0044] In one embodiment, the base is sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, ammonium bicarbonate, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, rubidium carbonate, ammonium carbonate, triethylmethylammonium carbonate, tributylmethylammonium carbonate, potassium phosphate, sodium phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, ammonium hydroxide, tetrapropylammonium hydroxide, tetrabutylammonium hydroxide, tributylbenzylammonium hydroxide, sodium methoxide, potassium methoxide, potassium ethoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, pyridine, 2,6-lutidine, 2,6-di-tert-butylpyridine, 2,4,6 -collidine, 4-dimethylaminopyridine, triethylamine, trimethylamine, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), tetramethylguanidine, tetramethylethylenediamine, N-methylmorpholine, N,N,N′,N″,N″-pentamethyldiethylenetriamine or a phosphazene base, for example potassium tert-butoxide, a phosphazene base, potassium carbonate, cesium carbonate, potassium hydroxide, tetrabutylammonium hydroxide, potassium methoxide, sodium tert-butoxide, potassium ethoxide, sodium carbonate, 1,8-diazabicyclo[5.4.0]undec-7-ene, potassium phosphate or cesium hydroxide.

[0045] In one embodiment, the base is an organic base or an inorganic base, wherein the cation in the inorganic base can be an alkali metal (e.g., Na + 、Li + , K + or Cs + ), the anion is carbonate, bicarbonate, hydroxide or phosphate. The organic base can be an alkali metal (such as Na + 、Li + , K + or Cs + ) of an alkoxide, a quaternary ammonium salt, a phosphazene basic compound or an amidine basic compound, preferably an alkali metal (such as Na + 、Li + , K + or Cs + ) alkoxides, alkali metals (such as Na + 、Li + , K + or Cs + ) carbonates, alkali metals (such as Na + 、Li + , K + or Cs + ) bicarbonate or alkali metal (such as Na + 、Li + , K + or Cs +) hydroxide, further preferably, the inorganic base may be potassium tert-butoxide, potassium carbonate, cesium carbonate, potassium hydroxide, sodium carbonate, potassium phosphate or cesium hydroxide; the organic base may be potassium tert-butoxide, phosphazene base, tetrabutylammonium hydroxide, potassium methoxide, sodium tert-butoxide, potassium ethoxide or 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0046] In one embodiment, the intensity of the visible light is the conventional intensity for this type of reaction in the art, for example, 50-2500 lux, for example, 420 lux, 350 lux, 600 lux, 200 lux, 2000 lux, 650 lux, 210 lux, 1380 lux, 450 lux, 1250 lux, 700 lux, 160 lux, 300 lux, 750 lux, 70 lux or 200 lux.

[0047] In one embodiment, the intensity of the visible light is the conventional intensity for this type of reaction in the art, for example, 50-2500 lux, for example, 420 lux, 350 lux, 600 lux, 200 lux, 2000 lux, 650 lux, 210 lux, 1380 lux, 450 lux, 1250 lux, 700 lux, 160 lux, 300 lux, 750 lux, 70 lux or 220 lux.

[0048] In a certain embodiment, the ratio of illumination intensity per unit volume to solvent volume is conventional in this field for such reactions. Those skilled in the art can select an appropriate illumination intensity according to the scale of the reaction, preferably 20-1500 lux / mL, for example 70 lux / mL, 350 / 3 lux / mL, 300 lux / mL, 200 lux / mL, 140 lux / mL, 500 lux / mL, 650 / 3 lux / mL, 210 lux / mL, 420 lux / mL, 650 lux / mL, 1380 lux / mL, 450 lux / mL, 1250 lux / mL, 140 lux / mL, 325lux / mL, 100lux / mL, 105lux / mL, 35lux / mL, 160 / 3lux / mL, 60lux / mL, 650 / 6lux / mL, 130lux / mL, 175lux / mL, 750lux / mL, 7 0 / 4lux / mL, 44lux / mL, 90lux / mL, 210 / 4lux / mL, 350 / 4lux / mL, 175lux / mL, 225lux / mL, 250lux / mL, 150lux / mL, 275lux / mL or 44lux / mL.

[0049] In one embodiment, the visible light source is preferably 1-20 cm away from the reaction device, such as 1-15 cm (e.g., 2 cm, 3 cm, 4 cm, 5 cm, 7 cm, 10 cm, 15 cm).

[0050] In one embodiment, the visible light source is an incandescent lamp or an energy-saving lamp (such as an LED lamp).

[0051] In one embodiment, the wavelength of the visible light is 380-600 nm, preferably 380-560 nm, for example, 390 nm, 395 nm, 455 nm, 415 nm, 405 nm, 425 nm, 435 nm, 475 nm, 500 nm, 525 nm.

[0052] In one embodiment, the deuterium source is conventional in the art, for example, the deuterium source is R D -OD, the R D H, D, C 3-10 Cycloalkyl, C 1-6 Alkyl or C substituted with 1 or more (eg 2-13) D 1-6 alkyl.

[0053] In one embodiment, in the deuterium source, the C 1-6 Alkyl and C substituted with 1 or more D 1-6 C in alkyl 1-6 The alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0054] In one embodiment, in the deuterium source, the C 3-10 Cycloalkyl is C 3-6 Cycloalkyl, for example cyclopropyl, cyclobutane or cyclopentane.

[0055] In one embodiment, the deuterium source is EtOD, MeOD, iPrOD, tBuOD, CD3OD, D2O or CD3CD2OD.

[0056] In a certain embodiment, the phenol and the base are used in the form of phenolate, the base may be an inorganic base, and the phenolate may be a sodium salt of phenol.

[0057] In one embodiment, the raw materials for the deuteration reaction are (under the light irradiation conditions) the solvent, the phenol, the base, the substance A and the deuterium source.

[0058] In one embodiment, the substance A is a compound represented by formula I;

[0059] Wherein, n is an integer from 0 to 10;

[0060] Ring B is C6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally combined with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0061] In ring B, the heteroaryl group is

[0062] X and Y are each independently NH, O or S; Z is N or CH;

[0063] R 2 Each independently is C1-C 15 Alkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, 1 or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl or one or more R 2-11 Substituted C 3-10 Heterocycloalkyl or ring C; said C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0064] Ring C is C 6-20 Aryl,

[0065] X1 and Y1 are each independently NH, O or S; Z1 is N or CH;

[0066] R 2-1 and R 2-4 are each independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , carboxyl, amide (-CONH2), -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0067] Ring D is C 6-20 Aryl,

[0068] X2 and Y2 are each independently NH, O or S; Z2 is N or CH;

[0069] R 2-11 Each independently is C1-C 15 Alkyl or one or more R 2-11-1 Substituted C1-C 15 alkyl;

[0070] R 2-1-1 and R 2-1-2 Each independently represents H, C1-C 15 Alkyl or -C1-C 15 Alkyl-OR 2-1-1a ;

[0071] R 2-1-1a C 6-20 Aryl or one or more R 2-1-1b Substituted C 6-20 aryl;

[0072] R 2-1-1b Each is independently -S-C1-C 15 Alkyl or -O-C1-C 15 alkyl;

[0073] R 2-11-1 Each independently is hydroxyl or -OR 2-11-1a ;

[0074] R 2-11-1a is a 5-15 membered heteroaryl group or is substituted by one or more R 2-11-1b substituted 5-15 membered heteroaryl;

[0075] R 2-11-1b Each is independently an oxo group (═O) or a C1-C6 alkyl group;

[0076] R 2-1-5 Each independently is a C1-C6 alkyl group or is replaced by one or more R 2-1-6a Substituted C1-C6 alkyl;

[0077] R 2-1-6a Each is independently an amide group, a carboxyl group or a ring E;

[0078] Ring E is C 6-20 Aryl,

[0079] X3 and Y3 are each independently NH, O or S; Z3 is N or CH;

[0080] The fragment I is a fragment of an aryl or heteroaryl group in ring B, ring C, ring D or ring E.

[0081] In one embodiment, the substance A is a compound represented by formula I;

[0082] Wherein, n is an integer from 0 to 10;

[0083] Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally combined with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0084] In ring B, the heteroaryl group is

[0085] X and Y are each independently NH, O or S; Z is N or CH;

[0086] R 2 Each independently is C1-C 15 Alkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, 1 or more R 2-4 Substituted C1-C 15 Alkoxy or one or more R 2-11 Substituted C 3-10 Heterocycloalkyl; said C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0087] R 2-1 and R 2-4 are each independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 、amide (-CONH2), -S-C1-C 15 Alkyl, ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0088] Ring D is C 6-20 aryl;

[0089] R 2-11 Each is independently controlled by one or more R 2-11-1 Substituted C1-C 15 alkyl;

[0090] R2-1-1 and R 2-1-2 Each independently represents H, C1-C 15 Alkyl or -C1-C 15 Alkyl-OR 2-1-1a ;

[0091] R 2-1-1a Each independently is one or more R 2-1-1b Substituted C 6-20 aryl;

[0092] R 2-1-1b Each is independently -O-C1-C 15 alkyl;

[0093] R 2-11-1 Each independently is -OR 2-11-1a ;

[0094] R 2-11-1a For one or more R 2-11-1b substituted 5-15 membered heteroaryl;

[0095] R 2-11-1b are each independently oxo (=O);

[0096] R 2-1-5 Each independently is one or more R 2-1-6a Substituted C1-C6 alkyl;

[0097] R 2-1-6a Each is independently an amide group, a carboxyl group or a ring E;

[0098] Ring E is C 6-20 aryl;

[0099] The fragment I is a fragment of an aryl or heteroaryl group in ring B, ring D or ring E.

[0100] In one embodiment, the substance A is a compound represented by formula I;

[0101] Wherein, n is an integer from 0 to 10;

[0102] Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally combined with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0103] In ring B, the heteroaryl group is

[0104] X is NH, O or S; Z is N or CH;

[0105] R 2 Each independently is one or more R 2-1 Substituted C1-C 15 Alkyl or one or more R 2-4 Substituted C1-C 15 alkoxy;

[0106] R 2-1 and R 2-4 are each independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0107] Ring D is C 6-20 aryl;

[0108] R 2-1-1 and R 2-1-2 Each independently is H or C1-C 15 alkyl;

[0109] R 2-1-5 Each independently is one or more R 2-1-6a Substituted C1-C6 alkyl;

[0110] R 2-1-6a Each is independently an amide group or ring E;

[0111] Ring E is C 6-20 aryl;

[0112] The fragment I is a fragment of an aryl or heteroaryl group in ring B, ring D or ring E.

[0113] In one embodiment, the substance A is a compound represented by formula I;

[0114] Wherein, n is an integer from 0 to 10;

[0115] Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally combined with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0116] The heteroaryl group is

[0117] X and Y are each independently NH, O or S; Z is N or CH;

[0118] R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C 15 Alkylthio, 1 or more R 2-7 Substituted C1-C 15 Alkylthio, 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0119] R 2-1 、R 2-4 and R 2-7 are independently hydroxyl, cyano, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or one or more R 2 - 1-4 Substituted C1-C 15 Alkyl; the heteroatom in the 5-15 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0120] R 2-2 and R 2-3 Each independently is H or C1-C 15 alkyl;

[0121] R 2-5 、R 2-6 、R 2-8 、R 2-9 and R 2-10 Each independently is H or C1-C 15 alkyl;

[0122] R 2-11 Each independently is C1-C 15 Alkyl or one or more R 2-11-1 Substituted C1-C 15 alkyl;

[0123] R 2-1-1 and R 2-1-2 Each independently represents H, C1-C 15 Alkyl, carbonyl-C1-C 15 Alkyl or carbonyl-C1-C 15 alkoxy;

[0124] R 2-1-3 、R 2-11-1 and R 2-1-4 are each independently -NH2, hydroxyl or cyano;

[0125] The fragment I is a fragment of the aromatic or heteroaromatic group in ring B.

[0126] In one embodiment, the substance A is a compound represented by formula I;

[0127] Wherein, n is an integer from 0 to 10;

[0128] Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally combined with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0129] The heteroaryl group is

[0130] X and Y are each independently NH, O or S; Z is N or CH;

[0131] R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C 15 Alkylthio, 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0132] R 2-1 and R 2-4 are each independently hydroxyl, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or one or more R 2-1-4 Substituted C1-C 15 Alkyl; the heteroatom in the 5-15 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0133] R 2-2 and R 2-3 Each independently is H;

[0134] R 2-5 、R 2-6 、R 2-8 、R 2-9 and R 2-10 Each independently is C1-C 15 alkyl;

[0135] R 2-11 Each is independently controlled by one or more R 2-11-1 Substituted C1-C 15 alkyl;

[0136] R 2-1-1 and R 2-1-2 Each independently represents H, C1-C 15 Alkyl, carbonyl-C1-C 15 Alkyl or carbonyl-C1-C 15 alkoxy;

[0137] R 2-1-3and R 2-1-4 are each independently hydroxyl;

[0138] The fragment I is a fragment of the aromatic or heteroaromatic group in ring B.

[0139] In one embodiment, the substance A does not contain an electron-withdrawing substituent, for example, the electron-withdrawing substituent is a halogen or an ester group.

[0140] In one embodiment, the substance A is not the phenol.

[0141] In one embodiment, in the substance A, the aromatic group is not directly connected to the halogen and / or hydroxyl group, for example, the aryl group is not directly connected to the halogen and / or hydroxyl group.

[0142] In a certain embodiment, in the aromatic group, the aryl group is C 6-20 Aryl, such as C 6-14 Aryl (eg, phenyl, naphthyl, anthracenyl, or phenanthrenyl).

[0143] In one embodiment, in substance B, the abundance of D in fragment II is 20%-100%, for example, 97%, 95%, 96%, 90%, 85%, 70%, 56%, 31% or 42%.

[0144] In one embodiment, the abundance of D in fragment II of substance B is 0.5%-100%, for example, 97%, 95%, 96%, 90%, 85%, 70%, 56%, 31%, 42%, 5%, 10% or 19%.

[0145] In one embodiment, in the compound represented by formula I, n is an integer of 0-6, for example, 1, 2, 3, 4 or 5.

[0146] In one embodiment, in the compound represented by formula I, R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2- 1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, By one or more R 2-7 Substituted C1-C 15 Alkylthio, 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of the heteroatoms is 1-4.

[0147] In one embodiment, in ring B, the heteroaryl group is

[0148] In one scheme, R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C1 alkylthio, substituted by one or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4.

[0149] In one scheme, R 2 Each independently is C1-C 15 Alkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, 1 or more R 2-4 Substituted C1-C 15 Alkoxy or one or more R 2-11 Substituted C 3-10 Heterocycloalkyl; said C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4.

[0150] In one scheme, R 2 Each independently is one or more R 2-1 Substituted C1-C 15 Alkyl or one or more R 2-4 Substituted C1-C 15 Alkoxy.

[0151] In one embodiment, n is an integer from 0 to 10, and ring B is C 6-20 aryl;

[0152] R 2 Each independently is C1-C15 Alkyl, C1-C 15 Alkoxy or C1-C 15 Alkylthio.

[0153] In one scheme, R 2-1 、R 2-4 and R 2-7 are each independently hydroxyl, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or one or more R 2-1-4 Substituted C1-C 15 Alkyl; the heteroatoms in the 5-15 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1-4.

[0154] In one scheme, R 2-1 and R 2-4 are each independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 、amide (-CONH2), -S-C1-C 15 Alkyl, ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4.

[0155] In one scheme, R 2-1 and R 2-4 are each independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4.

[0156] In one scheme, ring D is C 6-20 Aryl.

[0157] In one scheme, R 2-2 and R 2-3 Each is independently H.

[0158] In one scheme, R2-5 、R 2-6 、R 2-8 、R 2-9 and R 2-10 Each independently is C1-C 15 alkyl.

[0159] In one scheme, R 2-11 Each independently is one or more R 2-11-1 Substituted C1-C 15 alkyl.

[0160] In one scheme, R 2-1-1 and R 2-1-2 Each independently is H or C1-C 15 alkyl.

[0161] In one scheme, R 2-1-3 、R 2-11-1 and R 2-1-4 are each independently a hydroxyl group.

[0162] In one scheme, R 2-1-1a For one or more R 2-1-1b Substituted C 6-20 Aryl.

[0163] In one scheme, R 2-1-1b Each is independently -O-C1-C 15 alkyl.

[0164] In one scheme, R 2-11-1 Each independently is -OR 2-11-1a .

[0165] In one scheme, R 2-11-1a For one or more R 2-11-1b Substituted 5-15 membered heteroaryl.

[0166] In one scheme, R 2-11-1b Each is independently an oxo group (=O).

[0167] In one scheme, R 2-1-5 Each independently is one or more R 2-1-6a Substituted C1-C6 alkyl.

[0168] In one scheme, R 2-1-6a Each is independently an amide group or ring E.

[0169] In one embodiment, ring E is C 6-20 Aryl.

[0170] In one embodiment, in ring B, the C 6-20 Aryl is C 6-14Aryl; preferably phenyl, naphthyl, anthracenyl or phenanthrenyl, for example phenyl, naphthyl or anthracenyl.

[0171] In one embodiment, the C 3-15 Cycloalkyl is C 3-6 Monocyclic cycloalkyl or C 9-15 Polycyclic cycloalkyl, the C 3-6 Monocyclic cycloalkyl groups are exemplified by cyclopropyl, cyclobutyl, cyclohexyl (e.g. ) or cyclopentyl (e.g. ), the C 9-15 Polycyclic cycloalkyl is exemplified by dodecahydro-1H-cyclopenta[a]naphthyl (e.g. ).

[0172] In one embodiment, the C 3-15 Heterocycloalkyl is C 3-6 Monocyclic heterocycloalkyl or C 9-15 Polycyclic heterocycloalkyl, wherein the heteroatom is, for example, N or O, and the number of heteroatoms is, for example, 1 or 2; for example, the C 3-6 Monocyclic heterocycloalkyl is oxetane, oxolane (e.g. ) or oxacyclohexane, said C 9-15 Polycyclic cycloalkyl is exemplified by decahydroquinolinyl (e.g. ) or

[0173] In one scheme, R 2 In the C1-C 15 Alkyl and one or more R 2-1 Substituted C1-C 15 C1-C 15 The alkyl groups are each independently a linear or branched C1-C 15 Alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, 2-methyl-n-butyl, 3-methyl-n-butyl, n-heptyl, n-octyl, n-nonyl, n-decyl or 2-n-pentyl-n-octyl, for example methyl, ethyl, n-propyl, isopropyl, 3-methyl-n-butyl, n-octyl or 2-n-pentyl-n-octyl, for example methyl, n-octyl, n-heptyl, ethyl, isopropyl, n-butyl, tert-butyl.

[0174] In one scheme, R 2 、R 2-1 、R 2-4 and R 2-7 In the C 3-10 Cycloalkyl and one or more R 2-1-3 Substituted C 3-10 C in cycloalkyl 3-10 The cycloalkyl groups are each independently C3-6 Cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclohexyl.

[0175] In one scheme, R 2 、R 2-1-1 and R 2-1-2 In the C1-C 15 Alkoxy, 1 or more R 2-4 Substituted C1-C 15 Alkoxy, carbonyl-C1-C 15 C1-C 15 The alkoxy groups are each independently C1-C6 alkoxy groups, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy or n-hexoxy, and also such as methoxy, ethoxy, n-propoxy, n-butoxy or tert-butoxy.

[0176] In one scheme, R 2 In the C 3-10 Heterocycloalkyl and one or more R 2-11 Substituted C 3-10 C in heterocycloalkyl 3-10 The heterocycloalkyl groups are each independently C 3-6 Heterocycloalkyl, the C 3-10 The heteroatom in the heterocycloalkyl group is preferably N, and the number of heteroatoms is preferably 1 or 2, for example

[0177] In one scheme, R 2 In the C1-C 15 Alkylthio, 1 or more R 2-7 Substituted C1-C 15 C1-C 15 Each alkylthio group is independently a C1-C6 alkylthio group, for example, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio, n-pentylthio or n-hexylthio, for example, tert-butylthio.

[0178] In one scheme, R 2-1 、R 2-4 and R 2-7 In the embodiment, the 5-15 membered heteroaryl group is a 5-6 membered heteroaryl group, wherein the heteroatom in the 5-15 membered heteroaryl group is preferably N, and the number of heteroatoms is preferably 1. For example, the 5-15 membered heteroaryl group is a pyridyl group (e.g. ).

[0179] In one scheme, R 2-1 and R 2-4 In the C 3-10 Heterocycloalkyl and one or more R 2-1-5Substituted C 3-10 C3- 10 The heterocycloalkyl groups are each independently C 3-6 Heterocycloalkyl, the C 3-10 The heteroatom in the heterocycloalkyl group is preferably N, and the number of heteroatoms is preferably 1 or 2, for example

[0180] In one scheme, R 2-1 、R 2-4 、R 2-7 、R 2-2 、R 2-3 、R 2-5 、R 2-6 、R 2-8 、R 2-8 、R 2-10 、R 2- 11. R 2-1-1 and R 2-1-2 In the C1-C 15 Alkyl, 1 or more R 2-1-4 Substituted C1-C 15 Alkyl, 1 or more R 2-11-1 Substituted C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl and carbonyl-C1-C 15 C1-C 15 The alkyl groups are each independently C1-C6 alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, for example methyl, ethyl, n-propyl, isopropyl, tert-butyl or n-pentyl.

[0181] In one scheme, R 2-1-1 、R 2-1-2 and R 2 - 1-1b In the C1-C 15 Alkyl, C1-C 15 Alkyl-OR 2-1-1a 、-S-C1-C 15 Alkyl and -O-C1-C 15 C1-C 15 The alkyl groups are each independently C1-C6 alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, for example methyl or ethyl.

[0182] In one scheme, R 2-1-1a In the C 6-20 Aryl and one or more R 2-1-1b Substituted C 6-20C in aromatic group 6-20 The aryl groups are each independently C 6-14 Aryl is, for example, phenyl.

[0183] In one scheme, R 2-11-1a wherein the 5-15 membered heteroaryl group is replaced by one or more R 2 - 11-1b The 5-15 membered heteroaryl groups in the substituted 5-15 membered heteroaryl groups are each independently a 5-10 membered heteroaryl group, wherein the heteroatom in the 5-15 membered heteroaryl group is preferably N, and the number of heteroatoms is preferably 1. For example, the 5-15 membered heteroaryl group is

[0184] In one scheme, R 2-11-1b and R 2-1-5 wherein the C1-C6 alkyl group is replaced by one or more R 2-1-6a The C1-C6 alkyl groups in the substituted C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, and are also such as methyl.

[0185] In one embodiment, the R 2 for Methyl, -NH2, n-propyl,

[0186] In one embodiment, the R 2 for Methyl, -NH2, n-propyl,

[0187] Alternatively, the R 2 For n-propyl, n-ethyl,

[0188] In one embodiment, the ring B is

[0189] In one embodiment, the ring B is

[0190] In one embodiment, substance A is any of the following compounds:

[0191] In one embodiment, the substance B is

[0192] The percentage (%) of each site is independently the deuterated ratio of each site.

[0193] In one embodiment, the substance B is

[0194] The percentage (%) of each site is independently the deuterated ratio of each site.

[0195] In one embodiment, in the deuteration reaction, the amount of the solvent used is not specifically limited, as long as it does not affect the reaction. The concentration of the substance A in the solvent can be a conventional concentration for such reactions in the art, preferably 0.05-0.75 mol / L, for example, 0.05 mol / L, 0.06 mol / L, 0.075 mol / L, 0.10 mol / L, 0.15 mol / L, or 0.30 mol / L.

[0196] In one embodiment, in the deuteration reaction, the molar ratio of the phenol to the substance A is (0.005-0.5):1, preferably (0.005-0.2):1, for example, 0.005:1, 0.01:1, 0.02:1, 0.05:1, 0.07:1, 0.09:1, 0.10:1, 0.15:1 or 0.20:1.

[0197] In one embodiment, in the deuteration reaction, the molar ratio of the base to the substance A is (0.01-5):1, preferably (0.05-3):1, for example, 0.2:3, 0.5:3, 1:3, 1:1, 2.0:1, 2.0:3, 1:6, 2:30, 3.0:1, 4:3 or 2.7:1.

[0198] In one embodiment, in the deuteration reaction, the molar ratio of the deuterium source to the substance A is (50.0-600.0):1, preferably (100.0-300.0):1, for example, 100:1, 150:1, 400:3, 500:3, 700:3, 800:3, 200:1, 250:1 or 300:1.

[0199] In one embodiment, the progress of the deuteration reaction can be detected by conventional methods in the art, such as monitoring by HNMR, preferably by monitoring the benzene ring C (sp 2The end point of the reaction is when the signal of the )-H bond disappears or no longer reacts. The reaction time can be 6-120 hours, preferably 18-90 hours, such as 24 hours, 72 hours, 30 hours, 36 hours, 40 hours, 45 hours, 48 ​​hours, 50 hours, 55 hours or 26 hours.

[0200] In one embodiment, the deuteration reaction is carried out at a conventional reaction temperature for such reactions in the art, such as -20°C to 80°C, preferably 0°C to 80°C, such as 0°C, 5°C, 15°C, 25°C, 22°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C or 75°C.

[0201] In one embodiment, the deuteration reaction preferably further includes the following post-treatment steps: after the reaction is completed, quenching the reaction (for example, adding water to quench the reaction), extracting with an organic solvent (for example, ethyl acetate), washing (for example, washing with water and saturated sodium chloride solution in sequence), drying (preferably drying with anhydrous sodium sulfate), and purification (for example, column chromatography) to obtain substance B.

[0202] In one embodiment, the deuteration reaction is carried out in a protective gas, such as nitrogen.

[0203] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere, mixing the phenol, the substance A, the deuterium source, the base and the solvent, and conducting the deuteration reaction under light conditions; preferably, after the reaction is completed, quenching the reaction (for example, adding water to quench the reaction), extracting with an organic solvent (for example, ethyl acetate), washing (for example, washing with water and saturated sodium chloride solution in sequence), drying (preferably drying with anhydrous sodium sulfate), and purifying (for example, column chromatography) to obtain substance B.

[0204] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere, in the above-mentioned ether solvent (such as diethyl ether, tetrahydrofuran, 1,4-dioxane or methyl tert-butyl ether), in the above-mentioned phenol (such as 2,6-di-tert-butyl-4-phenylphenol), an organic base (such as potassium tert-butoxide, phosphazene base, potassium methoxide or sodium tert-butoxide) and visible light illumination with a wavelength of 380-600 nm, reacting substance A with the above-mentioned deuterium source (such as EtOD) to obtain substance B.

[0205] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and visible light irradiation conditions with an intensity of 350 lux to 420 lux, tetrahydrofuran, 2,6-di-tert-butyl-4-phenylphenol, phosphazene base, substance A and MeOD are mixed to carry out a deuteration reaction to obtain substance B.

[0206] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and visible light irradiation conditions with an intensity of 350 lux to 420 lux, tetrahydrofuran, 2,6-di-tert-butyl-4-phenylphenol, potassium tert-butoxide, substance A and EtOD are mixed to carry out a deuteration reaction to obtain substance B.

[0207] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation conditions with an intensity of 200 lux, 1,4-dioxane, 3-hydroxy-2-phenylpyridine, cesium carbonate, substance A and CD3OD are mixed to carry out a deuteration reaction to obtain substance B.

[0208] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation with an intensity of 2000 lux, tetrahydrofuran, 3-((2,6-dimethylphenyl)amino)phenol, potassium hydroxide, substance A and CD3CD2OD are mixed to carry out a deuteration reaction to obtain substance B.

[0209] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation conditions with an illumination intensity of 420 lux, diethyl ether, 2,6-di-tert-butyl-4-phenylphenol, potassium methoxide, substance A and CD3CD2OD are mixed to carry out a deuteration reaction to obtain substance B.

[0210] In one embodiment, the deuteration reaction comprises the following steps: in a solvent, under the conditions of phenol, base and visible light, reacting substance A with a deuterium source to obtain substance B;

[0211] The substance A contains an aromatic group, and the aromatic group contains one or more fragments I, and the fragment I is The H in the fragment I is the naturally abundant H;

[0212] The aromatic group is aryl,

[0213] X and Y are each independently NH, O or S; Z is N or CH;

[0214] Part or all of the fragment I is converted into the fragment II, and the fragment II is In H in the fragment II, the abundance of D is greater than the natural abundance of D;

[0215] The substance A does not contain the phenol; the aromatic group is not directly connected to the halogen and / or hydroxyl group;

[0216] The phenol is

[0217] Ring A is C6-14 Aryl or 5-10 membered heteroaryl; the heteroatoms in the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0218] R 1 Each independently is H, C 1-10 Alkyl, -OR 1a 、-NO2、-(C=O)R 1b 、-NR 1c R 1d 、C 6-14 Aryl, 5-10 membered heteroaryl, substituted by one or more R 1e Substituted C 1-10 Alkyl, one or more R 1f Substituted C 6-14 Aryl, or one or more R 1g substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1g The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0219] m is 1, 2, 3, 4 or 5;

[0220] R 1a and R 1b are independently H or C 1-10 alkyl;

[0221] R 1c and R 1d Independently H, C 6-14 Aryl, or substituted by one or more R 1a-1 C 6-14 aryl;

[0222] R 1e 、R 1f and R 1 g are each independently -OH, C 1-10 Alkyl, NR 1a-2 R 1a-3 、-(C=O)R 1a-4 or -CN;

[0223] R 1a-1 、R 1a-2 、R 1a-3 and R 1a-4 are independently H or C 1-10 alkyl.

[0224] In one embodiment, the deuteration reaction comprises the following steps: in a solvent, under the conditions of phenol, base and visible light, reacting substance A with a deuterium source to obtain substance B;

[0225] The solvent is one or more of water, alkane solvents, ether solvents, nitrile solvents, amine solvents and sulfoxide solvents;

[0226] The base is an organic base or an inorganic base;

[0227] The substance A contains an aromatic group, and the aromatic group contains one or more fragments I, and the fragment I is The H in the fragment I is the naturally abundant H;

[0228] The substance A is a compound represented by formula I;

[0229] Wherein, n is an integer from 0 to 10;

[0230] Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally combined with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0231] The heteroaryl group is

[0232] X and Y are each independently NH, O or S; Z is N or CH;

[0233] R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C 15 Alkylthio, 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0234] R 2-1 and R 2-4are each independently hydroxyl, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or one or more R 2-1-4 Substituted C1-C 15 Alkyl; the heteroatom in the 5-15 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0235] R 2-2 and R 2-3 Each independently is H;

[0236] R 2-5 、R 2-6 、R 2-8 、R 2-9 and R 2-10 Each independently is C1-C 15 alkyl;

[0237] R 2-11 Each is independently controlled by one or more R 2-11-1 Replaced C1-C1 5 alkyl;

[0238] R 2-1-1 and R 2-1-2 Each independently represents H, C1-C 15 Alkyl, carbonyl-C1-C 15 Alkyl or carbonyl-C1-C 15 alkoxy;

[0239] R 2-1-3 and R 2-1-4 are each independently hydroxyl;

[0240] The fragment I is a fragment of an aryl or heteroaryl group in ring B;

[0241] Part or all of the fragment I is converted into the fragment II, and the fragment II is In H in the fragment II, the abundance of D is greater than the natural abundance of D;

[0242] The aromatic group is not directly connected to the halogen;

[0243] The phenol is

[0244] Ring A is C 6-14Aryl or 5-10 membered heteroaryl; the heteroatoms in the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0245] R 1 Each independently is H, C 1-10 Alkyl, -OR 1a 、-NO2、-(C=O)R 1b 、-NR 1c R 1d 、C 6-14 Aryl, 5-10 membered heteroaryl, substituted by one or more R 1e Substituted C 1-10 Alkyl, one or more R 1f Substituted C 6-14 Aryl, or one or more R 1g substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1g The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0246] m is 1, 2, 3, 4 or 5;

[0247] R 1a and R 1b are independently H or C 1-10 alkyl;

[0248] R 1c and R 1d Independently H, C 6-14 Aryl, or substituted by one or more R 1a-1 C 6-14 aryl;

[0249] R 1e 、R 1f and R 1g Each independently is -OH, C 1-10 Alkyl, NR 1a-2 R 1a-3 、-(C=O)R 1a-4 or -CN;

[0250] R 1a-1 、R 1a-2 、R 1a-3 and R 1a-4 are independently H or C 1-10 alkyl;

[0251] The deuterium source is R D -OD,R D H, D, C 3-10 Cycloalkyl, C 1-6Alkyl or C substituted by one or more D 1-6 alkyl.

[0252] In one embodiment, the deuteration reaction is carried out in a protective gas, an ether solvent, a light intensity of 50-2500 lux, and a temperature of 0° C.-80° C., and the abundance of D in fragment II is 20%-100%;

[0253] The phenol is Ring A is C 6-14 Aryl, R 1 Each independently is C 1-10 Alkyl or C 6-14 aryl;

[0254] The deuterium source is R D -OD, the R D C 1-6 alkyl;

[0255] The base is an organic base. The present invention provides a C (sp 2 )-H bond deuteration method, the deuteration method comprising the following steps:

[0256] (1) subjecting the substance A to the above-mentioned deuteration reaction to obtain substance B;

[0257] (2) Repeat the above deuteration reaction on the substance B.

[0258] In a certain scheme, the number of repetitions is conventional in the art and can be adjusted by those skilled in the art according to the purpose of the experiment, for example, 1-3 times. Preferably, the deuteration method comprises the following steps: after the last deuteration reaction is completed, the substance B is subjected to a deuterium source deuteration reaction under the above-mentioned phenol, the above-mentioned base and the above-mentioned visible light illumination conditions. The experimental conditions and operation of the deuteration reaction can be as described in any one of the present invention.

[0259] Further preferably, during the repeated deuteration reaction, the substance B is subjected to deuteration reaction with or without purification, and the deuteration reaction without purification, for example, comprises the following steps: after the previous deuteration reaction is completed, quenching the reaction (for example, adding water to quench the reaction), extracting with an organic solvent (for example, ethyl acetate), washing (for example, washing with water and saturated sodium chloride solution in sequence), drying (preferably drying with anhydrous sodium sulfate), and conducting the above-mentioned deuteration reaction.

[0260] The present invention provides an application of phenol as a deuterated reaction photocatalyst;

[0261] The phenol is

[0262] Among them, ring A, R 1and m are each independently as described in any one of the present invention; preferably, in the application, the photocatalytic deuteration reaction is carried out under the action of the above-mentioned base.

[0263] The present invention provides a substance X or a pharmaceutically acceptable salt thereof, wherein the substance X is The percentage (%) of each site is independently the deuterated ratio of each site.

[0264] Explanation of terms:

[0265] Unless otherwise specified, the terms used in this invention have the following meanings:

[0266] When a numerical range is listed, it is intended to include each value and sub-range within the stated range. For example, "C1 to C 15 "Including C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 , C1-C6, C1-C5, C1-C4, C1-C3, C1-C2, C2-C6, C2-C5, C2-C4, C2-C3, C3-C6, C3-C5, C3-C4, C4-C6, C4-C5 and C5-C6 alkyl.

[0267] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0268] The term "alkyl" refers to a group having a specified number of carbon atoms (e.g., C1 to C 15 、C1~C 10 or C1-C6) straight-chain or branched alkyl. Alkyl includes but is not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, etc.

[0269] The term "alkoxy" refers to a group R X -O-, where R X is an alkyl group as defined above.

[0270] The term "alkylthio" refers to a group R X -S-, where R X is an alkyl group as defined above.

[0271] The term "cycloalkyl" refers to a cycloalkyl group having a specified number of carbon atoms (e.g., C3 to C 15 、C3~C 10 or C3-C6), a saturated monocyclic ring group consisting only of carbon atoms. Cycloalkyl includes but is not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0272] The term "heterocycloalkyl" refers to a cyclic group having a specified number of ring atoms (e.g., 3 to 15 members, 3 to 10 members, or 3 to 6 members), a specified number of heteroatoms (e.g., 1, 2, 3, or 4 members), and a specified type of heteroatom (one or more of N, O, and S), which is a monocyclic, bridged, or spirocyclic ring, and each ring is saturated. A bridged ring refers to a polycyclic ring in which two or more atoms are shared between monocyclic rings. A spirocyclic ring refers to a polycyclic ring in which one atom is shared between monocyclic rings. Heterocycloalkyl includes, but is not limited to, azetidinyl, azetidinyl, tetrahydropyrrolyl, tetrahydrofuranyl, morpholinyl, piperidinyl, and the like.

[0273] The term "aryl" refers to a group having a specified number of carbon atoms (e.g., C6 to C 14 or C6~C 20 ) is a cyclic group consisting only of carbon atoms, which is monocyclic or polycyclic, and at least one ring is aromatic (in accordance with Huckel's rule). The aryl group is connected to other fragments in the molecule through an aromatic ring or a non-aromatic ring. Aryl groups include but are not limited to phenyl, naphthyl or wait.

[0274] The term "heteroaryl" refers to a cyclic group having a specified number of ring atoms (e.g., 5-20 members or 5-10 members), a specified number of heteroatoms (e.g., 1, 2, 3, or 4 members), a specified type of heteroatom (one or more of N, O, and S), which is monocyclic or polycyclic, and at least one ring is aromatic (in accordance with Huckel's rule). The heteroaryl group is connected to other fragments in the molecule through an aromatic ring or a non-aromatic ring. Heteroaryl includes, but is not limited to, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, wait.

[0275] The "-" at the end of a group means that the group is connected to other fragments in the molecule through this site. For example, CH3-C(=O)- refers to acetyl.

[0276] In the structure fragment It means that the structural fragment is connected to other fragments in the molecule through this site. For example, It refers to cyclohexyl.

[0277] The term "plurality" refers to 2, 3, 4 or 5.

[0278] The term "C3-C n"Cycloalkyl" refers to a non-aromatic cyclic hydrocarbon group having 3 to n ring carbon atoms and zero heteroatoms, where n is an integer greater than 3. Exemplary cycloalkyl groups include, but are not limited to, cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, cycloheptadienyl, cycloheptatrienyl, and the like.

[0279] The term "ester group" is exemplified by -C(=O)-O-alkyl, wherein alkyl is defined as an alkyl group as defined above.

[0280] When any variable (such as the group R 1-1 ) appears multiple times in the definition of a compound, their definitions are independent of each other and do not affect each other. For example, 1-1 Substituted C6~C 10 Aryl refers to C6~C 10 The aromatic group will be 3 R 1-1 Replacement, 3 R 1-1 The definitions are independent of each other and do not affect each other.

[0281] The term "pharmaceutical excipients" refers to excipients and additives used in the production of pharmaceuticals and the preparation of prescriptions. These excipients are all substances contained in pharmaceutical preparations, other than the active ingredient. For details, see the Pharmacopoeia of the People's Republic of China (2020 edition) or the Handbook of Pharmaceutical Excipients (Raymond C. Rowe, 2009).

[0282] The term "pharmaceutically acceptable" means relatively non-toxic, safe, and suitable for use by patients.

[0283] The term "pharmaceutically acceptable salt" refers to a salt formed by reacting a compound with a pharmaceutically acceptable acid or base. When the compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. For details, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0284] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0285] The reagents and raw materials used in the present invention are commercially available.

[0286] The positive progress of the present invention is that: the C (sp2 The method of deuteration of )-H bonds has a wide range of applications, mild reaction conditions, high deuteration efficiency, and broad application prospects. DETAILED DESCRIPTION

[0287] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0288] Example 1

[0289] Under a nitrogen atmosphere, substrate 1 (0.30 mmol), phenol catalyst (10.0 mol% of 2,6-di-tert-butyl-4-phenylphenol, 2,6-di-tert-butyl-4-(9-anthryl)phenol, 2,6-di-tert-butyl-4-heptylphenol, 2,4,6-triphenylphenol, 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol, 9-phenanthrol, 9,10-anthraquinone or 2-tert-butyl-3,5-xylenol), and base (potassium tert-butoxide, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 6.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 45° C. and chromatographed at 405 nm. The reaction was carried out for 48 hours with an LED (420 lux) lamp 5 cm away from the reaction apparatus, and water was added to quench the reaction. The aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 2 (the yield was 100% when 2,6-di-tert-butyl-4-phenylphenol was used as the phenol catalyst, the yield was 100% when 2,6-di-tert-butyl-4-(9-anthryl)phenol was used as the phenol catalyst, and the yield was 100% when 6-di-tert-butyl- When 4-heptylphenol is used as the phenol catalyst, the yield is 99%, when 2,4,6-triphenylphenol is used as the phenol catalyst, the yield is 98%, when 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol is used as the phenol catalyst, the yield is 95%, when 9-phenanthrol is used as the phenol catalyst, the yield is 95%, when 9,10-anthracenediol is used as the phenol catalyst, the yield is 98%, when 2-tert-butyl-3,5-xylenol is used as the phenol catalyst, the yield is 96%, and the product purity is greater than 95%). 1H NMR (400 MHz, CDCl3): δ 7.30-7.26 (m, when 2,6-di-tert-butyl-4-phenylphenol is used as the phenol catalyst, 0.12H (C3-H, C5-H, deuteration rate 94%), when 2,6-di-tert-butyl-4-(9-anthryl)phenol is used as the phenol catalyst, 0.18H (C3-H, C5-H, deuteration rate 91%), when 6-di-tert-butyl-4-heptylphenol is used as the phenol catalyst, 0.24H (C3-H, C5-H, deuteration rate 88%), when 2,4,6-triphenylphenol is used as the phenol catalyst, 0.14H (C3-H, C5-H, deuteration rate 93%), when 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol is used as the phenol catalyst. When phenol is used as the phenol catalyst, the reaction temperature is 0.16H (C3-H, C5-H, deuteration rate 92%), when 9-phenanthroline is used as the phenol catalyst, the reaction temperature is 0.24H (C3-H, C5-H, deuteration rate 88%), when 9,10-anthracenediphenol is used as the phenol catalyst, the reaction temperature is 0.34H (C3-H, C5-H, deuteration rate 83%), when 2-tert-butyl-3,5-xylenol is used as the phenol catalyst, the reaction temperature is 0.30H (C3-H, C5-H, deuteration rate 85%), 7.25-7.22 (m, when 2,6-di-tert-butyl-4-phenylphenol is used as the phenol catalyst, the reaction temperature is 0.10H (C4-H, deuteration rate 90%), when 2,6-di-tert-butyl-4-(9-anthryl)phenol is used as the phenol catalyst, the reaction temperature is 0.13H ( C4-H, deuteration rate 87%), when 6-di-tert-butyl-4-heptylphenol is used as the phenol catalyst, 0.16H (C4-H, deuteration rate 84%), when 2,4,6-triphenylphenol is used as the phenol catalyst, 0.12H (C4-H, deuteration rate 88%), when 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol is used as the phenol catalyst, 0.14H (C4-H, deuteration rate 86%), when 9-phenanthranol is used as the phenol catalyst, 0.17H (C4-H, deuteration rate 83%), when 9,10-anthracenediol is used as the phenol catalyst, 0.22H (C4-H, deuteration rate 78%), when 2-tert-butyl-3,5-xylenol is used as the phenol catalyst, 0.20H (C4-H , deuteration rate 80%)), 7.20-7.16 (m, when using 2,6-di-tert-butyl-4-phenylphenol as phenol catalyst 0.16H (C2-H, C6-H, deuteration rate 92%), when using 2,6-di-tert-butyl-4-(9-anthryl)phenol as phenol catalyst 0.20H (C2-H, C6-H, deuteration rate 90%), when using 6-di-tert-butyl-4-heptylphenol as phenol catalyst 0.24H (C2-H, C6-H, deuteration rate 88%), when using 2,4,6-triphenylphenol as phenol catalyst 0.18H (C2-H, C6-H, deuteration rate 91%), when using 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol as phenol catalyst 0.20H (C2-H, C6-H, deuteration rate 90%), when 9-phenanthrenol is used as the phenol catalyst, 0.24H (C2-H, C6-H, deuteration rate 88%), when 9,10-anthracenediol is used as the phenol catalyst, 0.36H (C2-H, C6-H, deuteration rate 82%), when 2-tert-butyl-3,5-xylenol is used as the phenol catalyst, 0.32H (C2-H, C6-H, deuteration rate 84%), 2.62 (t, J = 15.4, 2H), 1.68-1.58 (m, 2H), 1.39-1.24 (m, 10H), 0.90 (t, J = 13.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ 143.1, 128.4 (m, label), 125.7 (1n, label), 36.2, 32.0, 31.7, 29.6, 29.5, 29.4, 22.8, 14.2; HRMS (ESI) calculated value: C 14 H 18 D5 + [M+H] + 196.2108, measured value: 196.2110.

[0290] Example 2

[0291] Under a nitrogen atmosphere, substrate 3 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-(4-tert-butylphenyl)phenol, 2.0 mol%), and base (potassium tert-butoxide, phosphazene base (CAS: 111324-04-0), potassium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, tetrabutylammonium hydroxide, potassium methoxide, or sodium tert-butoxide, 0.30 mmol, respectively) were dissolved in a solvent (tetrahydrofuran, 3.0 ml) and a deuterium source (MeOD, 30 mmol). After the addition, the reactants were placed at 15° C. and heated at 395 nm. The reaction was carried out for 48 hours with an LED (350 lux) lamp irradiated at a distance of 7 cm from the reaction apparatus. Water was added to quench the reaction, and the aqueous phase was extracted three times with ethyl acetate (15 ml×3). The organic phases were combined, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 4 (the yield was 100% when potassium tert-butoxide was used as the base, the yield was 100% when phosphazene base (CAS: 111324-04-0) was used as the base, the yield was 99% when potassium carbonate was used as the base, the yield was 97% when cesium carbonate was used as the base, the yield was 98% when potassium phosphate was used as the base, the yield was 97% when potassium hydroxide was used as the base, the yield was 96% when tetrabutylammonium hydroxide was used as the base, the yield was 99% when potassium methoxide was used as the base, and the yield was 99% when sodium tert-butoxide was used as the base, all with a purity greater than 95%). 1H NMR (500 MHz, CDCl3): δ 7.34-7.30 (m, when potassium tert-butoxide is used as a base, 0.12H (C3-H, C5-H, deuteration rate 94%), when phosphazene base (CAS: 111324-04-0) is used as a base, 0.10H (C3-H, C5-H, deuteration rate 95%), when potassium carbonate is used as a base, 0.36H (C3-H, C5-H, deuteration rate 82%), when cesium carbonate is used as a base, 0.28H (C3-H, C5-H, deuteration rate 86%), when potassium phosphate is used as a base, 0.38H (C3-H, C5-H, deuteration rate 81%), when potassium hydroxide is used as a base, 0.26H (C3-H, C5-H, When tetrabutylammonium hydroxide is used as a base, 0.30H (C3-H, C5-H, deuteration rate 85%), when potassium methoxide is used as a base, 0.12H (C3-H, C5-H, deuteration rate 94%), when sodium tert-butoxide is used as a base, 0.16H (C3-H, C5-H, deuteration rate 92%), 7.30-7.27 (m, when potassium tert-butoxide is used as a base, 0.18H (C2-H, C6-H, deuteration rate 91%), when phosphazene base (CAS: 111324-04-0) is used as a base, 0.16H (C2-H, C6-H, deuteration rate 92%), when potassium carbonate is used as a base, 0.40H (C2-H, C6-H, deuteration rate 80%) ), when cesium carbonate is used as a base, 0.30H (C2-H, C6-H, deuteration rate 85%), when potassium phosphate is used as a base, 0.40H (C2-H, C6-H, deuteration rate 80%), when potassium hydroxide is used as a base, 0.30H (C2-H, C6-H, deuteration rate 85%), when tetrabutylammonium hydroxide is used as a base, 0.30H (C2-H, C6-H, deuteration rate 85%), when potassium methoxide is used as a base, 0.16H (C2-H, C6-H, deuteration rate 92%), when sodium tert-butoxide is used as a base, 0.20H (C2-H, C6-H, deuteration rate 90%), 7.24-7.19 (m, when potassium tert-butoxide is used as a base, 0.10H (C4-H , deuteration rate 90%), when phosphazene base (CAS: 111324-04-0) is used as a base, 0.08H (C4-H, deuteration rate 92%), when potassium carbonate is used as a base, 0.19H (C4-H, deuteration rate 81%), when cesium carbonate is used as a base, 0.17H (C4-H, deuteration rate 83%), when potassium phosphate is used as a base, 0.22H (C4-H, deuteration rate 78%), when potassium hydroxide is used as a base, 0.14H (C4-H, deuteration rate 86%), when tetrabutylammonium hydroxide is used as a base, 0.14H (C4-H, deuteration rate 86%), when potassium methoxide is used as a base, 0.09H (C4-H, deuteration rate 91%), when sodium tert-butoxide is used as a base, 0.09H (C4-H, deuteration rate 91%), 2.57 (p, J = 7.0 Hz, 1H), 1.89-1.63 (m, 4H), 1.56-1.36 (m, 4H), 1.36-1.22 (m, 10H), 0.99-0.73 (m, 6H);. 13 C NMR (125 MHz, CDCl3): δ 145.8, 128.4 (m, mark), 127.4 (m, mark), 126.7 (m, mark), 46.3, 34.9, 34.8, 31.8, 31.6, 29.2, 27.3, 27.2, 22.7, 22.6, 14.1; HRMS (ESI) calculated value: C 18 H 26 D5 + [M+H] + 252.2734, measured value: 252.2736.

[0292] Example 3

[0293] Under a nitrogen atmosphere, substrate 5 (0.30 mmol), phenol catalyst (3-phenyl-1-naphthol, 5.0 mol%), base (potassium tert-butoxide, 0.10 mmol) were dissolved in a solvent (tetrahydrofuran, diethyl ether, 1,4-dioxane, methyl tert-butyl ether, n-hexane, cyclohexane, n-heptane, n-pentane, petroleum ether or N,N-dimethylformamide, 2.0 ml) and a deuterium source (iPrOD, 40 mmol). After the addition, the reactants were placed at 5°C and chromatographed at 455 nm. The reaction was carried out for 48 hours with an LED (600 lux) lamp irradiated at a distance of 3 cm from the reaction apparatus, and water was added to quench the reaction. The aqueous phase was extracted three times with ethyl acetate (15 ml×3). The organic phases were combined, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 6 (the yield was 100% when tetrahydrofuran was used as the reaction solvent, the yield was 99% when diethyl ether was used as the reaction solvent, the yield was 100% when 1,4-dioxane was used as the reaction solvent, the yield was 98% when methyl tert-butyl ether was used as the reaction solvent, the yield was 99% when n-hexane was used as the reaction solvent, the yield was 98% when cyclohexane was used as the reaction solvent, the yield was 97% when n-heptane was used as the reaction solvent, the yield was 99% when n-pentane was used as the reaction solvent, the yield was 98% when petroleum ether was used as the reaction solvent, and the yield was 99% when N,N-dimethylformamide was used as the reaction solvent, and the purity was greater than 95%). 1H NMR (500 MHz, C6D6): δ7.34-7.29 (m, when tetrahydrofuran was used as the reaction solvent, 0.10H (C3-H, C5-H, deuteration rate 95%), when diethyl ether was used as the reaction solvent, 0.16H (C3-H, C5-H, deuteration rate 92%), when 1,4-dioxane was used as the reaction solvent, 0.16H (C3-H, C5-H, deuteration rate 92%). When methyl tert-butyl ether was used as the reaction solvent, the deuteration rate was 0.18H (C3-H, C5-H, deuteration rate 91%), when n-hexane was used as the reaction solvent, the deuteration rate was 0.30H (C3-H, C5-H, deuteration rate 85%), when cyclohexane was used as the reaction solvent, the deuteration rate was 0.34H (C3-H, C5-H, deuteration rate 83%), and when n-heptane was used as the reaction solvent, the deuteration rate was 0.30H. (C3-H, C5-H, deuteration rate 85%), when n-pentane is used as the reaction solvent 0.30H (C3-H, C5-H, deuteration rate 85%), when petroleum ether is used as the reaction solvent 0.26H (C3-H, C5-H, deuteration rate 87%), when N,N-dimethylformamide is used as the reaction solvent 0.36H (C3-H, C5-H, deuteration rate 82%), 7.29-7.26 (m, when tetrahydrofuran is used as the reaction solvent 0.16H (C2-H , C6-H, deuteration rate 92%), when using ether as the reaction solvent 0.20H (C2-H, C6-H, deuteration rate 90%), when using 1,4-dioxane as the reaction solvent 0.18H (C2-H, C6-H, deuteration rate 91%), when using methyl tert-butyl ether as the reaction solvent 0.20H (C2-H, C6-H, deuteration rate 90%), when using n-hexane as the reaction solvent 0.34H (C2-H, C6-H, deuteration rate 83%), when using cyclohexane When used as the reaction solvent, the deuteration rate was 0.36H (C2-H, C6-H, 82%), when n-heptane was used as the reaction solvent, the deuteration rate was 0.34H (C2-H, C6-H, 83%), when n-pentane was used as the reaction solvent, the deuteration rate was 0.36H (C2-H, C6-H, 82%), when petroleum ether was used as the reaction solvent, the deuteration rate was 0.28H (C2-H, C6-H, 86%), when N,N-dimethylformamide was used as the reaction solvent, the deuteration rate was 0.38H (C2-H, C6 -H, deuteration rate 81%)), 7.25-7.21 (m, when tetrahydrofuran is used as the reaction solvent 0.06H (C4-H, deuteration rate 94%), when diethyl ether is used as the reaction solvent 0.10H (C4-H, deuteration rate 90%), when 1,4-dioxane is used as the reaction solvent 0.08H (C4-H, deuteration rate 92%), when methyl tert-butyl ether is used as the reaction solvent 0.10H (C4-H, deuteration rate 90%), when n-hexane is used as the reaction solvent 0.16H (C4-H, deuteration rate 84%), when cyclohexane is used as the reaction solvent, 0.20H (C4-H, deuteration rate 80%), when n-heptane is used as the reaction solvent, 0.17H (C4-H, deuteration rate 83%), when n-pentane is used as the reaction solvent, 0.16H (C4-H, deuteration rate 84%), when petroleum ether is used as the reaction solvent, 0.13H (C4-H, deuteration rate 87%), when N,N-dimethylformamide is used as the reaction solvent, 0.21H (C4-H, deuteration rate 79%), 2.39-2.35 (m, 1H), 1.81-1.70 (m, 4H), 1.64 (d, J = 12.6 Hz, 1H), 1.37-1.23 (m, 5H); 13 C NMR (125 MHz, C6D6): δ 148.2, 128.7 (m, mark), 127.2 (m, mark), 126.2 (m, mark), 45.0, 34.9, 27.3, 26.6; HRMS (ESI) calculated value: C 12 H 12 D5 + [M+H] + 166.1639, measured value: 166.1640.

[0294] Example 4

[0295] Under a nitrogen atmosphere, substrate 7 (0.30 mmol), phenol catalyst (2-phenylphenol, 20.0 mol%), and base (potassium carbonate, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 1.0 ml) and a deuterium source (tBuOD, 80 mmol). After the addition, the reactants were placed at 35° C. and irradiated with a 415 nm LED (200 lux) lamp at a distance of 5 cm from the reaction apparatus for 36 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 8 (99% yield, purity greater than 95%). 1 H-NMR (400 MHz, CDCl3): δ 7.28-7.24 (m, 0.10 H, C5-H, deuteration rate 90%), 7.19-7.15 (m, 0.11 H, C4-H, deuteration rate 89%), 7.12-7.09 (m, 0.09 H, C3-H, deuteration rate 91%), 7.09-7.07 (m, 0.08 H, C6-H, deuteration rate 92%), 3.85 (t, J = 6.9 Hz, 2 H), 2.93 (t, J = 6.9 Hz, 2 H), 2.38 (s, 3 H), 1.92 (br s, 1 H); 13C NMR (100 MHz, CDCl3): δ 136.5, 130.4, 129.7 (m, mark), 126.6 (m, mark), 126.1 (m, mark), 62.6, 36.4, 19.5; HRMS (ESI) calculated value: C9H9D4O + [M+H] + 141.1212, measured value: 141.1216.

[0296] Example 5:

[0297] Under a nitrogen atmosphere, substrate 9 (0.30 mmol), phenol catalyst (3-hydroxy-2-phenylpyridine, 10.0 mol%), and base (cesium carbonate, 0.90 mmol) were dissolved in a solvent (1,4-dioxane, 3.0 ml) and a deuterium source (CD3OD, 60 mmol). After the addition, the reactants were placed at 25°C and irradiated with a 405 nm LED (420 lux) at a distance of 7 cm for 48 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 10 (99% yield, purity greater than 95%). 1 H NMR (500 MHz, CDCl3): δ 7.25-7.21 (m, 0.06 H, C6-H, deuteration rate 94%), 7.20-7.17 (m, 0.04 H, C3-H, deuteration rate 96%), 7.17-7.12 (m, 0.12 H, C2-H, C4-H, deuteration rate 94%), 2.93-2.81 (m, 2 H), 1.28 (d, J = 6.8 Hz, 12 H); 13 C NMR (125 MHz, CDCl3): δ 147.8, 128.1 (m, mark), 125.7 (m, mark), 125.4 (m, mark), 34.1, 24.1; HRMS (ESI) calculated value: C 12 H 15 D4 + [M+H] + 167.1732, measured value: 167.1735.

[0298] Example 6:

[0299] Under nitrogen atmosphere, substrate 11 (0.30 mmol), phenol catalyst (3-((2,6-dimethylphenyl)amino)phenol, 10.0 mol%), base (potassium hydroxide, 0.30 mmol) were dissolved in solvent (tetrahydrofuran, 4.0 ml) and deuterium source (EtOD, D2O, MeOD, iPrOD, tBuOD, CD3OD or CD3CD2OD, 60 mmol, respectively). After the addition, the reactants were placed at 45°C and chromatographed at 435 nm. The reaction was carried out for 48 hours with an LED (2000 lux) lamp irradiated at a distance of 10 cm from the reaction apparatus, and water was added to quench the reaction. The aqueous phase was extracted three times with ethyl acetate (15 ml × 3), and the organic phases were combined, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 12 (the yield was 100% when EtOD was used as the deuterium source, the yield was 99% when D2O was used as the deuterium source, the yield was 99% when MeOD was used as the deuterium source, the yield was 100% when iPrOD was used as the deuterium source, the yield was 98% when tBuOD was used as the deuterium source, the yield was 99% when CD3OD was used as the deuterium source, and the yield was 100% when CD3CD2OD was used as the deuterium source, and the purity was greater than 95%). 1H NMR (500 MHz, CDCl3): δ 7.19-7.15 (m, when EtOD was used as a deuterium source, 0.12 H (C2-H, C6-H, deuteration rate 94%), when D2O was used as a deuterium source, 0.30 H (C2-H, C6-H, deuteration rate 85%), when MeOD was used as a deuterium source, 0.18 H (C2-H, C6-H, deuteration rate 91%), when iPrOD was used as a deuterium source, 0.16 H (C2-H , C6-H, deuterium substitution rate 92%), when tBuOD was used as a deuterium source 0.20H (C2-H, C6-H, deuterium substitution rate 90%), when CD3OD was used as a deuterium source 0.18H (C2-H, C6-H, deuterium substitution rate 91%), when CD3CD2OD was used as a deuterium source 0.12H (C2-H, C6-H, deuterium substitution rate 94%), 7.14-7.10 (m, when EtOD was used as a deuterium source 0.14H (C3- H, C5-H, deuterium substitution rate 93%), when D2O was used as the deuterium source 0.30H (C3-H, C5-H, deuterium substitution rate 85%), when MeOD was used as the deuterium source 0.20H (C3-H, C5-H, deuterium substitution rate 90%), when iPrOD was used as the deuterium source 0.16H (C3-H, C5-H, deuterium substitution rate 92%), when tBuOD was used as the deuterium source 0.18H (C3-H, C5-H, deuterium substitution rate 91%), when When CD3OD was used as a deuterium source, the m / z value was 0.18H (C3-H, C5-H, deuteration rate 91%); when CD3CD2OD was used as a deuterium source, the m / z value was 0.12H (C3-H, C5-H, deuteration rate 94%); 2.56-2.63 (m, 4H); 1.62-1.54 (m, 1H); 1.51-1.45 (m, 2H); 1.22 (t, J = 7.6 Hz, 3H); 0.93 (d, J = 6.6 Hz, 6H); 13 C NMR (125 MHz, CDCl3): δ 141.5, 140.4, 128.4 (m, mark), 127.9 (m, mark), 41.1, 33.5, 28.6, 27.9, 22.7, 15.8; HRMS (ESI) calculated value: C 13 H 17 D4 + [M+H] + 181.1889, measured value: 181.1887.

[0300] Example 7:

[0301] Under a nitrogen atmosphere, substrate 13 (0.30 mmol), phenol catalyst (4′-aminophenyl-3-phenol, 15.0 mol%), and base (cesium hydroxide, 0.10 mmol) were dissolved in a solvent (1,4-dioxane, 3.0 ml) and a deuterium source (EtOD, 70 mmol). After the addition, the reactants were placed at 50°C and irradiated with a 475 nm LED (650 lux) lamp at a distance of 7 cm from the reaction apparatus for 72 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 14 (100% yield, purity greater than 95%). 1 H NMR (500 MHz, CDCl 3 ): δ 7.40 (s, 0.21 H, C 2 -H, C 4 -H, C 6 -H, deuteration rate 93%), 1.32 (d, J = 0.8 Hz, 27 H); 13 C NMR (125 MHz, CDCl3): δ 149.4, 122.8 (m, marker), 34.9, 31.6, 31.5; HRMS (ESI) calculated value: C 18 H 28 D3 + [M+H] + 250.2609, measured value: 250.2610.

[0302] Example 8:

[0303] Under nitrogen atmosphere, substrate 15 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 10.0 mol%), and base (potassium methoxide, 0.60 mmol) were dissolved in a solvent (diethyl ether, 1.0 ml) and a deuterium source (CD3CD2OD, 30 mmol). After the addition, the reactants were placed at 25°C and irradiated with a 395 nm LED (210 lux), a 405 nm LED (420 lux), a 455 nm LED (650 lux), a white LED (1380 lux), an incandescent lamp (450 lux), or a white energy-saving lamp (1250 lux) at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatographed to obtain 16 (when using 395 nm The yield was 99% when an LED lamp was used as the light source, 100% when a 405nm LED lamp was used as the light source, 100% when a 455nm LED lamp was used as the light source, 99% when a white LED was used as the light source, 99% when an incandescent lamp was used as the light source, and 100% when a white energy-saving lamp was used as the light source).1 H NMR (400 MHz, CDCl3): δ 7.00-6.95 (m, when using a 395 nm LED lamp as a light source, 0.05 H (C5-H, deuteration rate 95%), when using a 405 nm LED lamp as a light source, 0.04 H (C5-H, deuteration rate 96%), when using a 455 nm LED lamp as a light source, 0.05 H (C5-H, deuteration rate 95%), when using a white LED lamp as a light source, 0.07 H (C5-H, deuteration rate 93%), when using an incandescent lamp as a light source, 0.10 H (C5-H, deuteration rate 90%), when using a white energy-saving lamp as a light source, 0.12 H (C5-H, deuteration rate 88%)), 6.70-6.64 (m, when using a 395 nm LED lamp as a light source, 0.05 H (C5-H, deuteration rate 96%), when using a 455 nm LED lamp as a light source, 0.07 H (C5-H, deuteration rate 93%), when using an incandescent lamp as a light source, 0.10 H (C5-H, deuteration rate 90%), when using a white energy-saving lamp as a light source, 0.12 H (C5-H, deuteration rate 88%). When LED lamp is used as light source, 0.07H (C6-H, deuterium substitution rate 93%), when 405nm LED lamp is used as light source, 0.07H (C6-H, deuterium substitution rate 93%), when 455nm LED lamp is used as light source, 0.08H (C6-H, deuterium substitution rate 92%), when white LED lamp is used as light source, 0.10H (C6-H, deuterium substitution rate 90%), when incandescent lamp is used as light source, 0.11H (C6-H, deuterium substitution rate 89%), when white energy-saving lamp is used as light source, 0.20H (C6-H, deuterium substitution rate 80%), 6.62-6.58 (m, when 395nm LED lamp is used as light source, 0.07H (C2-H, deuterium substitution rate 93%), when 405nm When an LED lamp is used as the light source, the wavelength is 0.07H (C2-H, deuterium substitution rate 93%); when a 455nm LED lamp is used as the light source, the wavelength is 0.07H (C2-H, deuterium substitution rate 93%); when a white LED lamp is used as the light source, the wavelength is 0.10H (C2-H, deuterium substitution rate 90%); when an incandescent lamp is used as the light source, the wavelength is 0.12H (C2-H, deuterium substitution rate 88%); when a white energy-saving lamp is used as the light source, the wavelength is 0.20H (C2-H, deuterium substitution rate 80%); 3.75 (s, 3H); 2.68-2.78 (m, 4H); 1.76-1.80 (m, 4H); 13 C NMR (100 MHz, CDCl3): δ 157.5, 138.3, 130.1, 129.4 (m, mark), 113.8 (m, mark), 111.9 (m, mark), 55.4, 29.9, 28.7, 23.6, 23.3; HRMS (ESI) calculated value: C 11 H12D3O + [M+H] + 166.1306, measured value: 166.1310.

[0304] Example 9:

[0305] Under a nitrogen atmosphere, substrate 17 (0.30 mmol), phenol catalyst (cyanobiphenol, 5.0 mol%), and base (potassium ethoxide, 0.05 mmol) were dissolved in a solvent (tetrahydrofuran, 5.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 55°C and irradiated with a 405 nm LED (700 lux) lamp at a distance of 10 cm from the reaction apparatus for 60 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 18 (99% yield, purity greater than 95%). 1 H NMR (500 MHz, CDCl3): δ 7.07 (s, 0.05H, C3-H, deuterated rate 95%), 6.78 (s, 0.05H, C6-H, deuterated rate 95%), 3.82 (s, 3H), 3.70 (t, J = 7.2 Hz, 1H), 3.62 (t, J = 7.2 Hz, 1H), 3.59-3.46 (m, 1H), 2.73 (ddd, J = 12.3, 8.8, 7.0 Hz, 2H), 2.65 (dd, J = 12.4, 6.9 Hz, 1H), 2.55 (dd, J = 12.3, 6.9 Hz, 1H), 2.19 (s, 3H); 13 C NMR (125 MHz, CDCl3) δ 156.8, 138.9, 135.4, 127.6, 127.5 (m, mark), 109.1 (m, mark), 55.7, 52.7, 39.8, 39.8, 16.2; HRMS (ESI) calculated value: C 11 H 14 D2NO + [M+H] + 180.1352, measured value: 180.1355.

[0306] Example 10:

[0307] Under a nitrogen atmosphere, substrate 19 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-(4-acetylphenyl)phenol, 10.0 mol%), and base (potassium tert-butoxide, 0.20 mmol) were dissolved in a solvent (ethylenediamine, 2.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 25°C and irradiated with a 455 nm LED (650 lux) lamp at a distance of 7 cm from the reaction apparatus for 72 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain 20 (99% yield). 1H NMR (400 MHz, CDCl3): δ 6.83 (s, 0.06H, C6-H, deuteration rate 94%), 2.24 (s, 6H), 2.21 (s, 3H), 2.17 (s, 6H); 13 C NMR (100 MHz, CDCl3): δ 134.9, 133.3, 132.3, 129.0 (m, marker), 20.5, 16.3, 15.9; HRMS (ESI) calculated value: C 11 H16D + [M+H] + 150.1388, measured value: 150.1389.

[0308] Example 11:

[0309] Under a nitrogen atmosphere, substrate 21 (0.30 mmol), phenol catalyst (2,4,6-tri-tert-butylphenol, 1.0 mol%), and base (potassium tert-butoxide, 0.10 mmol) were dissolved in a solvent (ether, 3.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 65°C and irradiated with a 7-watt 405 nm LED (420 lux) lamp at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain 22 (98% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): δ 7.32-7.25 (m, 0.16 H, C3-H, C5-H, deuteration rate 92%), 6.99-6.95 (m, 0.10 H, C4-H, deuteration rate 90%), 6.94-6.88 (m, 0.14 H, C2-H, C6-H, deuteration rate 93%), 3.98 (t, J = 6.7 Hz, 2 H), 1.78-1.63 (m, 7 H), 1.53-1.48 (m, 1 H), 1.31-1.14 (m, 3 H), 1.010.92 (m, 2 H); 13 C NMR (100 MHz, CDCl3): δ 159.2, 129.4 (m, mark), 120.5 (m, mark), 114.5 (m, mark), 65.8, 36.7, 34.6, 33.4, 26.6, 26.3; HRMS (ESI) calculated value: C 14 H 16 D5O + [M+H] + 210.1901, measurement: 210.1903.

[0310] Example 12:

[0311] Under a nitrogen atmosphere, substrate 23 (0.30 mmol), phenol catalyst (2-tert-butyl-3,5-xylenol, 10.0 mol%), and base (potassium tert-butoxide, 0.02 mmol) were dissolved in a solvent (cyclohexane, 6.0 ml) and a deuterium source (EtOD, 50 mmol). After the addition, the reactants were placed at 25°C and irradiated with a 500 nm LED (600 lux) lamp at a distance of 3 cm from the reaction apparatus for 48 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 24 (99% yield). 1 H NMR (500 MHz, CDCl3): δ 7.33-7.21 (m, 0.12 H, C3-H, C5-H, deuteration rate 94%), 6.99-6.92 (m, 0.10 H, C4-H, deuteration rate 90%), 6.91-6.83 (m, 0.10 H, C2-H, C6-H, deuteration rate 95%), 3.39 (t, J = 7.0 Hz, 4 H), 1.69 (pd, J = 7.0, 1.1 Hz, 4 H), 1.65-1.54 (m, 2 H); 13 C NMR (125 MHz, CDCl3): δ 150.5, 129.1 (m, mark), 118.6 (m, mark), 115.5 (m, mark), 115.5 (m, mark), 50.6, 25.8, 24.4; HRMS (ESI) calculated value: C 11 H 11 D5N + [M+H] + 167.1591, measured value: 167.1593.

[0312] Example 13:

[0313] Under a nitrogen atmosphere, substrate 25 (0.30 mmol), phenol catalyst (1-anthraquinone, 0.5 mol%), and base (tetrabutylammonium hydroxide, 0.20 mmol) were dissolved in a solvent (tetrahydrofuran, 4.0 ml) and a deuterium source (MeOD, 70 mmol). After the addition, the reactants were placed at 75°C and irradiated with a 405 nm LED (420 lux) lamp at a distance of 7 cm from the reaction apparatus for 60 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 26 (95% yield, purity greater than 95%). 1H NMR (400 MHz, C6D6): δ 7.58-7.52 (m, 0.16 H, C3-H, C5-H, deuteration rate 92%), 7.30-7.21 (m, 0.10 H, C4-H, deuteration rate 90%), 7.20-7.10 (m, 0.12 H, C2-H, C6-H, deuteration rate 94%), 1.65-1.55 (m, 4 H), 1.05 (dt, J = 7.6, 7.2 Hz, 6 H); 13 C NMR (100 MHz, C6D6): δ 139.1, 132.4 (m, mark), 128.4 (m, mark), 128.2 (m, mark), 20.3, 9.7. 31 P NMR (162 MHz, C6D6): δ-16.59 (s); HRMS (ESI) calculated value: C 10 H 11 D5P + [M+H] + 172.1298, measured value: 172.1296.

[0314] Example 14:

[0315] Under a nitrogen atmosphere, substrate 27 (0.30 mmol), phenol catalyst (5,51-di-tert-butyl-2,2′-biphenyldiphenol, 2.0 mol%), and base (phosphazene base (CAS: 111324-04-0), 0.02 mmol) were dissolved in a solvent (ethylene glycol dimethyl ether, 3.0 mL) and a deuterium source (iPrOD, 80 mmol). After addition, the reaction mixture was incubated at 25°C under irradiation with a 415 nm LED (350 lux) at a distance of 5 cm from the reaction apparatus for 72 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then purified by column chromatography to obtain 28 (99% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): δ 7.34-7.30 (m, 0.12 H, C3-H, C5-H, deuteration rate 94%), 7.29-7.24 (m, 0.08 H, C2-H, C6-H, deuteration rate 96%), 7.17-7.12 (m, 0.10 H, C4-H, deuteration rate 90%), 2.81 (d, J = 6.9 Hz, 2 H), 1.89-1.82 (m, 1 H), 1.03 (d, J = 6.7 Hz, 6 H); 13C NMR (100 MHz, CDCl3): δ 137.4, 128.8 (m, mark), 128.7 (m, mark), 125.6 (m, mark), 42.6, 28.3, 22.1; HRMS (ESI) calculated value: C 10 H 10 D5S + [M+H] + 172.1203, measured value: 172.1205.

[0316] Example 15:

[0317] Under a nitrogen atmosphere, substrate 29 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-acetylphenol, 10.0 mol%), and base (phosphazene base (CAS: 111324-04-0), 0.05 mmol) were dissolved in a solvent (n-heptane, 3.0 mL) and a deuterium source (iPrOD, 60 mmol). After the addition, the reactants were incubated at 25°C under irradiation with a 405 nm LED (210 lux) lamp at a distance of 7 cm from the reaction apparatus for 90 h. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 30 (100% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): δ: 7.49-7.44 (m, 0.14 H, C3-H, C5-H, deuteration rate 93%), 6.94-6.90 (m, 0.10 H, C2-H, C6-H, deuteration rate 95%), 3.82 (s, 3 H), 0.26 (s, 9 H); 13 C NMR (100 MHz, CDCl3): δ 160.4, 134.9, 131.5 (m, mark), 113.7 (m, mark), 55.2, -0.78; HRMS (ESI) calculated value: C 10 H 13 D4OSi + [M+H] + 185.1294, measured value: 185.1296.

[0318] Example 16:

[0319] Under a nitrogen atmosphere, substrate 31 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-methoxyphenol, 5.0 mol%), and base (potassium tert-butoxide, 0.40 mmol) were dissolved in a solvent (1,4-dioxane, 6.0 ml) and a deuterium source (tBuOD, 90 mmol). After the addition, the reactants were placed at 25°C and irradiated with a 405 nm LED (210 lux) lamp at a distance of 3 cm from the reaction apparatus for 36 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 32 (99% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): δ 8.48 (d, J = 5.6 Hz, 2H), 7.30-7.26 (m, 0.08 H, C2-H, C6-H, deuteration rate 96%), 7.25-7.19 (m, 0.10 H, C3-H, C5-H, deuteration rate 95%), 7.16-7.13 (m, 0.08 H, C4-H, deuteration rate 92%), 7.08 (d, J = 5.6 Hz, 2H), 2.93 (br s, 4H); 13 C NMR (75 MHz, CDCl3): δ 150.4, 149.7, 140.6, 128.4 (m, mark), 128.3 (m, mark), 126.2 (m, mark), 123.9, 37.0, 36.5; HRMS (ESI) calculated value: C 13 H9D5N + [M+H] + 189.1435, measured value: 189.1437.

[0320] Example 17:

[0321] Under a nitrogen atmosphere, substrate 33 (0.30 mmol), phenol catalyst (6-tert-butyl-2,4-xylenol, 10.0 mol%), and base (sodium carbonate, 0.60 mmol) were dissolved in a solvent (petroleum ether, 3.0 ml) and a deuterium source (D2O, 40 mmol). After the addition, the reactants were placed at 45°C and irradiated with a 390 nm LED (160 lux) lamp at a distance of 5 cm from the reaction apparatus for 24 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 34 (99% yield, purity greater than 95%). 1H NMR (400 MHz, CDCl3): δ 7.92-7.89 (m, 0.07H, C5-H, deuterated rate 93%), 7.77-7.73 (m, 0.07H, C4-H, deuterated rate 93%), 7.71-7.67 (m, 0.07H, C8-H, deuterated rate 93%), 7.64 (s, 0.05H, C1-H, deuterated rate 93%). deuteration rate 95%), 7.52-7.48 (m, 0.45H, C7-H, deuteration rate 55%), 7.47-7.42 (m, 0.40H, C6-H, deuteration rate 60%), 7.36-7.32 (m, 0.46H, C3-H, deuteration rate 54%), 3.07 (septet, J = 6.8 Hz, 1H), 1.34 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl 3 ) δ 146.3, 133.7, 132.1, 127.8 (m, mark), 127.6 (m, mark), 127.5 (m, mark), 125.8 (m, mark), 125.7 (m, mark), 125.0 (m, mark), 124.1 (m, mark), 34.2, 23.9; HRMS (ESI) calculated value: C 13 H 11 D4 + [M+H] + 175.1419, measured value: 175.1420.

[0322] Example 18:

[0323] Under a nitrogen atmosphere, substrate 35 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-nitrophenol, 15.0 mol%), and base (potassium hydroxide, 0.60 mmol) were dissolved in a solvent (dimethyl sulfoxide, 2.0 ml) and a deuterium source (EtOD, 70 mmol). After the addition, the reactants were placed at 50°C and irradiated with a 455 nm LED (650 lux) lamp at a distance of 3 cm from the reaction apparatus for 18 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 36 (100% yield, purity greater than 95%). 1 H NMR (400MHz, CDCl3): δ8.40 (s, 0.08H, C 10-H, deuterated rate 92%), 8.29 (s, 0.09H, C9-H, deuterated rate 91%), 8.02-7.98 (m, 0.10H, C5-H, deuterated rate 90%), 7.97-7.92 (m, 0.10H, C8-H, deuterated rate 90%), 7.56-7.52 (m, 0.10H, C4-H, deuterated rate 90%), 7. 51-7.48 (m, 0.45H, C6-H, deuteration rate 55%), 7.47-7.42 (m, 0.40H, C7-H, deuteration rate 60%), 7.35-7.28 (m, 0.40H, C3-H, deuteration rate 60%), 6.78-6.74 (m, 0.35H, C2-H, deuteration rate 65%), 4.27 (s, 2H); 13 C NMR (100 MHz, CDCl3): δ 141.8, 132.5, 131.6, 130.9, 128.4 (m, label), 127.8, 126.6 (m, label), 125.8 (m, label), 125.5 (m, label), 125.1 (m, label), 123.7 (m, label), 119.6 (m, label), 119.2 (m, label), 107.5 (m, label); HRMS (ESI) calculated value: C 14 H7D5N + [M+H] + 199.1278, measured value: 199.1280.

[0324] Example 19:

[0325] Under a nitrogen atmosphere, substrate 37 (0.30 mmol), phenol catalyst (3,5-di-tert-butylcatechol, 20.0 mol%), and base (phosphazene base (CAS: 111324-04-0), 0.10 mmol) were dissolved in a solvent (water, 1.0 mL) and a deuterium source (D2O, 90 mmol). After the addition, the reactants were incubated at 25°C under irradiation with a 405 nm LED (420 lux) at a distance of 5 cm from the reaction apparatus for 36 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 38 (98% yield, purity greater than 95%). 1H NMR (400 MHz, CDCl3): δ 8.39 (br s, 1H), 7.64-7.60 (m, 0.07H, C4-H, deuterated rate 93%), 7.42-7.38 (m, 0.07H, C7-H, deuterated rate 93%), 7.25-7.21 (m, 0.31H, C6-H, deuterated rate 69%), 7.17-7.13 (m, 0.31H, C5-H, deuterated rate 69%), 7.04 (s, 0.05H, C2-H, deuterated rate 95%), 5.67 (br s, 1H), 3.62 (q, J=6.6Hz, 2H), 3.00 (td, J=6.8, 0.9Hz, 2H), 1.94 (s, 3H); 13 C NMR (100 MHz, CDCl3): δ 170.3, 136.4, 127.3, 122.1, 119.4 (m, mark), 118.6 (m, mark), 112.8 (m, mark), 111.3 (m, mark), 39.9, 25.2, 23.3; HRMS (ESI) calculated value: C 12 H 10 D5N2O + [M+H] + 208.1493, measured value: 208.1495.

[0326] Example 20:

[0327] Under a nitrogen atmosphere, substrate 39 (0.30 mmol), phenol catalyst (4-phenylphenol, 10.0 mol%), and base (potassium tert-butoxide, 0.20 mmol) were dissolved in a solvent (cyclohexane, 5.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 35°C and irradiated with a 405 nm LED (300 lux) lamp at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 40 (96% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): δ 7.60 (s, 0.05H, C4-H, deuteration rate 95%), 7.41-7.38 (m, 0.07H, C7-H, deuteration rate 93%), 7.09-7.05 (m, 0.05H, C2-H, deuteration rate 95%), 6.92-6.88 (m, 0.10H, C6-H, deuteration rate 90%), 6.73-6.69 (m, 0.07H, C3-H, deuteration rate 93%), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 156.0, 150.0, 145.8, 127.9 (m, mark), 113.1 (m, mark), 111.9 (m, mark), 106.8 (m, mark), 103.6 (m, mark), 29.8; HRMS (ESI) calculated value: C9H4D5O2 + [M+H] + 154.0911, measured value: 154.0913.

[0328] Example 21:

[0329] Under a nitrogen atmosphere, substrate 41 (0.30 mmol), phenol catalyst (2-amino-4-tert-butylphenol, 2.0 mol%), and base (sodium tert-butoxide, 0.10 mmol) were dissolved in a solvent (tetrahydrofuran, 6.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 25°C and irradiated with a 425 nm LED (650 lux) lamp at a distance of 7 cm from the reaction apparatus for 48 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 42 (96% yield, purity greater than 95%). 1 H NMR (300 MHz, CDCl3): 8.18-8.14 (m, 0.18 H, C4-H, C5-H, deuteration rate 91%), 7.59-7.55 (m, 0.14 H, C1-H, C8-H, deuteration rate 93%), 7.29-7.25 (m, 0.88 H, C2-H, C7-H, deuteration rate 56%), 7.26-7.22 (m, 0.88 H, C3-H, C6-H, deuteration rate 56%), 5.05-5.01 (m, 1 H), 1.75 (d, J = 6.9 Hz, 6 H); 13 C NMR (75 MHz, CDCl3): 139.5, 125.4, 123.3 (m, mark), 120.4 (m, mark), 118.6 (m, mark), 110.0 (m, mark), 46.7, 20.8; HRMS (ESI) calculated value: C 15 H8D8N + [M+H] + 218.1779, measured value: 218.1777.

[0330] Example 22:

[0331] Under a nitrogen atmosphere, substrate 43 (0.30 mmol), phenol catalyst (2,6-diphenylphenol, 10.0 mol%), and base (sodium tert-butoxide, 0.20 mmol) were dissolved in a solvent (n-hexane, 3.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 45°C and irradiated with a 405 nm LED (650 lux) lamp at a distance of 15 cm from the reaction apparatus for 36 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain 44 (99% yield, purity greater than 95%). 1 H NMR (400 MHz, DMSO-d6): δ 12.56 (br s, 1H) 7.72 (s, 0.44 H, C3-H, deuteration rate 56%), 7.26-7.24 (m, 0.08 H, C7-H, deuteration rate 92%), 6.79-6.76 (m, 0.30 H, C6-H, deuteration rate 70%), 6.75 (s, 0.07 H, C4-H, deuteration rate 93%), 4.75 (br s, 2H); 13 C NMR (100 MHz, DMSO-d6): δ 142.1, 131.3, 123.8, 117.9 (m, mark), 110.1 (m, mark), 100.3 (m, mark); HRMS (ESI) calculated value: C7H5D3N3 + [M+H] + 137.0901, measured value: 137.0903.

[0332] Example 23:

[0333] Under a nitrogen atmosphere, substrate 45 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-methylphenol, 1.0 mol%), and base (sodium tert-butoxide, 0.30 mmol) were dissolved in a solvent (methyl tert-butyl ether, 5.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 25°C and irradiated with a 475 nm LED (650 lux) lamp at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 46 (99% yield, purity greater than 95%). 1H NMR (400 MHz, CDCl3): δ 8.03-7.99 (m, 0.18 H, C4-H, C5-H, deuteration rate 91%), 7.43-7.39 (m, 0.20 H, C3-H, C6-H, deuteration rate 90%), 7.29-7.25 (m, 0.30 H, C2-H, C7-H, deuteration rate 85%), 2.63 (s, 6 H); 13 C NMR (100 MHz, CDCl3): δ 139.5, 136.2, 132.4, 127.0 (m, mark), 124.9 (m, mark), 119.4 (m, mark), 20.7; HRMS (ESI) calculated value: C 14 H7D6S + [M+H] + 219.1109, measured value: 219.1110.

[0334] Example 24:

[0335] Under a nitrogen atmosphere, substrate 47 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-hydroxymethylphenol, 10.0 mol%), and base (1,8-diazabicyclo[5.4.0]undec-7-ene, 0.60 mmol) were dissolved in a solvent (diethyl ether, 2.0 mL) and a deuterium source (tBuOD 50 mmol). After the addition, the reaction mixture was incubated at 65°C under irradiation with a 405 nm LED (350 lux) at a distance of 3 cm from the reaction vessel for 36 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 48 (99% yield, purity greater than 95%). 1 H NMR (500 MHz, (CD3)2CO): δ7.75-7.71 (m, 0.10H, C5-H, deuterated rate 90%), 7.69-7.65 (m, 0.10H, C4-H, deuterated rate 90%), 7.37-7.34 (m, 0.07H, C8-H, deuterated rate 93%), 7.29-7.25 ... m, 0.38H, C7-H, deuterated rate 62%), 7.24-7.20 (m, 0.38H, C6-H, deuterated rate 62%), 6.89-6.85 (m, 0.38H, C2-H, deuterated rate 62%), 6.81-6.77 (m, 0.38H, C3-H, deuterated rate 62%), 2.31 (3H, s); 13CNMR (125 MHz, (CD3)2CO): δ 155.1, 139.9, 131.5, 130.4 (m, label), 128.6 (m, label), 127.5 (m, label), 124.9 (m, label), 123.4 (m, label), 123.2 (m, label), 121.8 (m, label), 120.4 (m, label), 117.8 (m, label), 68.2, 20.7; HRMS (ESI) calculated value: C 13 H4D7O + [M+H] + 190.1244, measured value: 190.1245.

[0336] Example 25:

[0337] Under a nitrogen atmosphere, substrate 49 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), and base (potassium phosphate, 0.20 mmol) were dissolved in a solvent (methyl tert-butyl ether, 1.0 ml) and a deuterium source (MeOD, 60 mmol). After the addition, the reactants were placed at 50°C and irradiated with a 525 nm LED (750 lux) lamp at a distance of 2 cm from the reaction apparatus for 48 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 50 (99% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): 7.32-7.29 (m, 0.12 H, C3-H, C5-H, deuterated rate 94%), 7.29-7.25 (m, 0.10 H, C4-H, deuterated rate 90%), 7.25-7.19 (m, 0.14 HC2-H, C6-H, deuterated rate 93%), 6.61 (br s, 1 H), 4.92 (br s, 1 H), 3.22-3.18 (m, 2 H), 1.43-1.32 (m, 9 H); 13C NMR (100 MHz, CDCl3): 176.2, 155.5, 146.9, 136.0 (m, mark), 129.5 (m, mark), 128.7 (m, mark), 127.1 (m, mark), 85.3, 80.3, 54.4, 40.0, 28.4, 27.5; HRMS (ESI) calculated value: C 14 H 13 D5NO4 - [MH] - 269.1555, measured value: 269.1557.

[0338] Example 26:

[0339] Under a nitrogen atmosphere, substrate 51 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 10.0 mol%), and base (cesium carbonate, 0.40 mmol) were dissolved in a solvent (acetonitrile, 4.0 mL) and a deuterium source (tBuOD, 70 mmol). After the addition, the reactants were incubated at 50°C under irradiation with a 405 nm LED (70 lux) at a distance of 2 cm from the reaction apparatus for 24 h. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 52 (100% yield, purity greater than 95%). 1 H NMR (400 MHz, DMSO-d6): δ 12.53 (br s, 1H), 10.82 (br s, 1H), 7.53-7.50 (m, 0.05H, C4-H, deuteration rate 95%), 7.35-7.31 (m, 0.06H, C7-H, deuteration rate 94%), 7.16-7.14 (m, 0.08H, C2-H, deuteration rate 92%), 7.08-7.04 (m, 0.29H, C6-H, deuteration rate 71%), 7.00-6.95 (m, 0.29H, C6-H, deuteration rate 71%), 6.50 (br s, 1H), 4.17-4.11 (m, 1H), 3.13 (dd, J=14.6, 4.8Hz, 1H), 2.97 (dd, J=14.6, 9.3Hz, 1H), 1.33 (s, 9H); 13 C NMR (100 MHz, DMSO-d6): δ 174.0, 155.4, 136.1, 127.2, 123.6 (m, label), 120.9 (m, label), 118.3 (m, label), 118.1 (m, label), 111.4 (m, label), 110.16, 78.0, 54.50, 28.2, 26.8; HRMS (ESI) calculated value: C 16 H 14 D5N2O4 - [MH] - 308.1664, measured value: 308.1666.

[0340] Example 27:

[0341] Under a nitrogen atmosphere, substrate 53 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 2.0 mol%), and base (potassium tert-butoxide, 0.10 mmol) were dissolved in a solvent (tetrahydrofuran, 5.0 ml) and a deuterium source (EtOD, 80 mmol). After the addition, the reactants were placed at 45°C and irradiated with a 395 nm LED (220 lux) lamp at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 54 (100% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): δ 7.03 (s, 0.04H, C5-H, deuterated rate 96%), 6.80 (s, 0.07H, C6-H, deuterated rate 93%), 6.70 (s, 0.07H, C2-H, deuterated rate 93%), 3.79 (s, 3H), 2.99 (d, J = 18.1 Hz, 1H), 2.81 (dd, J = 5.9, 3.2 Hz, 1H), 2.59 (dd, J = 18.1 , 5.8Hz, 1H), 2.51-2.26 (m, 5H), 2.08 (td, J=12.3, 3.3Hz, 1H), 1.91-1.69 (m, 2H), 1. 67-1.58(m, 1H), 1.58-1.47(m, 1H), 1.46-1.21(m, 6H), 1.13(qd, J=12.2, 3.6Hz, 1H); 13 C NMR (100 MHz, CDCl3): δ 158.2, 141.7, 129.8, 128.5 (m, mark), 111.1 (m, mark), 110.7 (m, mark), 58.0, 55.2, 47.3, 45.4, 42.8, 42.1, 37.2, 36.7, 26.8, 26.6, 23.3, 22.7, 22.3; HRMS (ESI) calculated value: C 18 H 23 D3NO + [M+H] + 275.2197, measured value: 275.2195.

[0342] Example 28:

[0343] Under a nitrogen atmosphere, substrate 55 (0.30 mmol), phenol catalyst (2,4,6-triphenylphenol, 5.0 mol%), and base (potassium tert-butoxide, 0.60 mmol) were dissolved in a solvent (n-heptane, 6.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 55°C and irradiated with a 455 nm LED (650 lux) lamp at a distance of 5 cm from the reaction apparatus for 60 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain 56 (98% yield, purity greater than 95%). 1 H NMR (400 MHz, CD3OD): δ 7.20 (s, 0.14 H, C2-H, C6-H, deuteration rate 93%), 7.08 (s, 0.14 H, C3-H, C5-H, deuteration rate 93%), 3.66 (q, J = 7.1 Hz, 1 H), 2.44 (d, J = 7.2 Hz, 2 H), 1.83 (p, J = 6.8 Hz, 1 H), 1.42 (d, J = 7.1 Hz, 3 H), 0.88 (d, J = 6.6 Hz, 6 H); 13 C NMR (100 MHz, CD3OD) δ 177.2, 140.1, 138.4, 128.9 (m, marker), 126.9 (m, marker), 30.1, 21.5, 21.3, 17.7; HRMS (ESI) calculated value: C 13 H 13 D4O2 - [MH] - 209.1485, measured value: 209.1487.

[0344] Example 29:

[0345] Under a nitrogen atmosphere, substrate 57 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 10.0 mol%), and base (phosphazene base (CAS: 111324-04-0), 0.20 mmol) were dissolved in a solvent (cyclohexane, 3.0 mL) and a deuterium source (MeOD, 90 mmol). After the addition, the reaction was incubated at 45°C under irradiation with a 405 nm LED lamp (420 lux) at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 58 (99% yield, purity greater than 95%). 1H NMR (400 MHz, CD3CN): δ 6.93-6.88 (m, 0.25H, C3-H, deuteration rate 75%), 6.62 (s, 0.07H, C6-H, deuteration rate 93%), 6.59-6.55 (m, 0.86H, C4-H, deuteration rate 14%), 4.11-3.10 (m, 2.03H), 2.19 (t, J=0.7 Hz, 3H), 2.04 (s, 3H), 1.71-1.51 (m, 4H), 1.10 (s, 6H); 13 C NMR (100 MHz, CD3CN) δ 179.3, 157.5, 137.1, 130.7 (m, mark), 123.7 (m, mark), 121.2 (m, mark), 68.5, 41.9, 37.2, 25.5, 25.00, 20.97, 20.90, 15.46, 15.39, 1.52, 1.31, 1.11, 0.90, 0.69, 0.49, 0.28; HRMS (ESI) calcd: C 15 H 18 D3O3 - [MH] - 252.1684, measured value: 252.1686.

[0346] Example 30:

[0347] Under a nitrogen atmosphere, substrate 59 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-(9-anthryl)phenol, 10.0 mol%), and base (potassium tert-butoxide, 0.30 mmol) were dissolved in a solvent (tetrahydrofuran, 5.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 35°C and irradiated with a 415 nm LED (450 lux) lamp at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 60 (100% yield, purity greater than 95%). 1H NMR (400 MHz, CDCl3): δ 6.95 (s, 0.07 H, C5-H, deuterated rate 93%), 6.61 (s, 0.10 H, C6-H, deuterated rate 90%), 4.80-4.34 (m, 2H), 3.41-3.30 (m, 2H), 3.30-3.04 (m, 3H), 2.89 (ddd, J = 14.9, 8.4, 6.3 Hz, 1H), 2.76 (ddd, J = 15 .3, 8.6, 6.0Hz, 1H), 2.28 (dtd, J=12.6, 8.3, 6.4Hz, 1H), 2.17 (q, J=7.6Hz, 2H), 2.08-1.95 (m, 1H) , 1.82 (ddt, J=12.7, 8.4, 5.8Hz, 1H), 1.63 (dddd, J=13.3, 9.7, 8.1, 6.3Hz, 1H), 1.21-1.09 (m, 3H); 13 CNMR (400 MHz, CDCl3): δ 173.7, 159.3, 143.1, 135.7, 123.3 (m, label), 122.2 (m, label), 107.3, 71.2, 71.1, 42.2, 38.0, 33.5, 31.7, 30.6, 29.7, 28.6, 9.8; HRMS (ESI) calculated value: C 16 H 19 D2NO2 + [M+H] + 262.1771, measured value: 262.1778.

[0348] Example 31:

[0349] Under a nitrogen atmosphere, substrate 61 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-(4-tert-butylphenyl)phenol, 15.0 mol%), and base (phosphazene base (CAS: 111324-04-0), 0.10 mmol) were dissolved in a solvent (petroleum ether, 4.0 mL) and a deuterium source (EtOD, 80 mmol). After the addition, the reactants were incubated at 45°C under irradiation with a 405 nm LED (210 lux) at a distance of 3 cm from the reaction vessel for 24 h. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 62 (99% yield, purity greater than 95%). 1H NMR (400 MHz, CDCl3): δ 7.21-7.17 (m, 0.32 H, C5-H, deuteration rate 68%), 6.74-6.66 (m, 0.49 H, C6-H, deuteration rate 51%), 6.63 (s, 0.04 H, C2-H, deuteration rate 96%), 3.88 (t, J = 6.6 Hz, 1 H), 3.38 (s, 3 H), 3.31 (t, J = 8.3 Hz, 1 H), 2.84 (td, J = 7.4, 3.8Hz, 2H), 2.36-2.22 (m, 1H), 2.18 (td, J=11.0, 4.3Hz, 1H), 2.06 (ddt, J=15.8, 7.4, 5.0Hz, 1H), 1.94-1.62 (m, 4H), 1.58-1.14 (m, 7H), 1.02 (t, J=7.4Hz, 3H), 0.78 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 156.9, 137.8, 132.5 (m, mark), 126.3 (m, mark), 112.0 (m, mark), 69.4, 57.9, 50.3, 43.9, 43.3, 38.6, 38.1, 29.8, 27.8, 27.3, 26.5, 23.1, 22.7, 11.6, 10.6; HRMS (ESI) calculated value: C 22 H 30 D3O2 + [M+H] + 332.2663, measured value: 332.2665.

[0350] Example 32:

[0351] Under a nitrogen atmosphere, substrate 63 (0.30 mmol), phenol catalyst (2,4,6-triphenylphenol, 10.0 mol%), and base (potassium tert-butoxide, 0.20 mmol) were dissolved in a solvent (ether, 3.0 ml) and a deuterium source (D2O, 40 mmol). After the addition, the reactants were placed at 50°C and irradiated with a 455 nm LED (600 lux) lamp 5 cm away from the reaction apparatus for 36 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine in sequence, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain 64 (98% yield, purity greater than 95%). 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.19-7.15 (m, 0.44H, C7-H, deuteration rate 56%), 7.14-7.10 (m, 0.44H, C6-H, deuteration rate 56%), 6.97-6.93 (m, 0.84H, C5-H, deuteration rate 16%), 6.90 (s, 0.05H, C2-H, deuteration rate 95%), 3.38 (dd, J = 14.7, 4.1 Hz, 1H), 3.2 5 (d, J=7.7Hz, 1H), 2.98 (s, 1H), 2.82 (d, J=10.2Hz, 3H), 2.73 (t, J=12.7Hz, 1H), 2.63-2.40 (m, 3H), 2.16 ( d, J=1.5Hz, 4H), 1.65-1.46 (m, 2H), 1.28 (d, J=21.9Hz, 1H), 1.14 (q, J=11.8Hz, 1H), 0.91 (t, J=7.3Hz, 3H); 13 C NMR (400 MHz, CDCl3): δ 133.6, 133.3, 126.2, 123.1, 117.7 (m, mark), 113.3 (m, mark), 112.2 (m, mark), 108.5 (m, mark), 63.6, 58.7, 55.6, 41.0, 39.2, 35.2, 34.3, 26.8, 16.7, 16.1, 12.0; HRMS (ESI) calculated value: C 19 H 23 D4N2S + [M+H] + 319.2141, measured value: 319.2143.

[0352] Example 33:

[0353] Under a nitrogen atmosphere, substrate 65 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), and base (potassium carbonate, 0.30 mmol) were dissolved in a solvent (tetrahydrofuran, 6.0 ml) and a deuterium source (tBuOD, 40 mmol). After the addition, the reactants were placed at 50°C and irradiated with a 405 nm LED (420 lux) lamp at a distance of 5 cm from the reaction apparatus for 50 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 66 (100% yield, purity greater than 95%). 1H NMR (400 MHz, (CD3)2CO) δ7.14-7.10 (m, 0.64H, C3-H, C5-H, deuteration rate 68%), 6.93-6.71 (m, 0.10H, C2-H, C6-H, deuteration rate 95%), 3.76 (s, 3H), 3.31 (dd, J = 12.7, 11.5 Hz, 1H), 2.92 (dd, J = 11. 5, 4.1Hz, 1H), 2.27 (d, J=2.3Hz, 7H), 1.70 (tt, J=13.0, 3.6Hz, 3H), 1.58-1.39 (m, 3H) , 1.29 (ddd, J=12.2, 7.9, 3.9Hz, 2H), 0.96 (td, J=13.2, 4.2Hz, 1H), 0.91-0.76 (m, 1H); 13 C NMR (100 MHz, (CD3)2CO) δ 158.3, 133.2 (m, mark), 130.1, 113.1 (m, mark), 73.3, 61.2, 54.5, 51.8, 51.8, 51.7, 44.8, 38.0, 31.6, 26.1, 21.5, 21.2; HRMS (ESI) calculated value: C 17 H 24 D4NO2 + [M+H] + 282.2366, measured value: 282.2368.

[0354] Example 34:

[0355] Under a nitrogen atmosphere, substrate 67 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-(9-anthryl)phenol, 10.0 mol%), and base (cesium hydroxide, 0.20 mmol) were dissolved in a solvent (methyl tert-butyl ether, 3.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 45°C and irradiated with a 475 nm LED (650 lux) lamp at a distance of 5 cm from the reaction apparatus for 36 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 68 (98% yield, purity greater than 95%). 1H NMR (400 MHz, CD3CN) δ7.28-7.24 (m, 0.52H, C3-H, C5-H, deuteration rate 74%), 7.03-6.90 (m, 0.14H, C2-H, C6-H, deuteration rate 93%), 6.85-6.81 (m, 0.72H, C4-H, deuteration rate 28%), 3.83 (dq, J = 7.5, 5.2Hz, 1H), 3.61-3.48(m, 1H), 3.51-3.43(m, 1H), 3.21(t, J=5.1Hz, 4H), 2.78(d t, J=10.4, 5.1Hz, 2H), 2.68 (dt, J=11.1, 5.1Hz, 2H), 2.53 (dd, J=6.4, 3.2Hz, 2H); 13 C NMR (400 MHz, CD3CN) δ 151.9, 129.5 (m, mark), 119.8, , 116.2 (m, mark), 116.0 (m, mark), 68.1, 65.5, 61.7, 53.9, 49.1; HRMS (ESI) calculated value: C 13 H 16 D5N2O2 + [M+H] + 242.1911, measured value: 242.1913.

[0356] Example 35:

[0357] Under a nitrogen atmosphere, substrate 69 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 10.0 mol%), and base (phosphazene base (CAS: 111324-04-0), 0.60 mmol) were dissolved in a solvent (1,4-dioxane, 4.0 ml) and a deuterium source (tBuOD, 60 mmol). After the addition, the reactants were placed at 55°C under a 405 nm LED (350 lux) lamp at a distance of 4 cm from the reaction apparatus. The organic phase was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 70 (96% yield, purity greater than 95%). 1 H NMR (400 MHz, CD3CN): δ 7.13 (s, 0.44 H, C3-H, C5-H, deuteration rate 78%), 6.88-6.79 (m, 0.10 H, C2-H, C6-H, deuteration rate 95%), 4.00-3.76 (m, 3 H), 3.51 (t, J = 6.9 Hz, 2 H), 3.26 (s, 3 H), 2.90-2.70 (m, 4 H), 2.67-2.59 (m, 1 H), 1.04 (d, J = 6.3 Hz, 6 H); 13C NMR (400 MHz, CD3CN): δ 157.9, 132.1, 130.3 (m, label), 114.8 (m, label), 73.9, 71.3, 68.8, 58.1, 50.0, 49.3, 35.3, 22.5; HRMS (ESI) calculated value: C 15 H 22 D4NO3 + [M+H] + 272.2158, measured value: 272.2155.

[0358] Example 36:

[0359] Under a nitrogen atmosphere, substrate 71 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 20.0 mol%), and base (potassium tert-butoxide, 0.30 mmol) were dissolved in a solvent (tetrahydrofuran, 3.0 ml) and a deuterium source (MeOD, 80 mmol). After the addition, the reactants were placed at 50°C and irradiated with a 405 nm LED (350 lux) lamp at a distance of 5 cm from the reaction apparatus for 60 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 72 (97% yield, purity greater than 95%). 1 H NMR (400 MHz, CD3OD): δ 7.03-6.98 (m, 0.20 H, C2-H, C6-H, deuteration rate 90%), 6.97-6.94 (m, 0.78 H, C3-H, C5-H, deuteration rate 61%), 3.43 (q, J = 11.0 Hz, 4 H), 2.65-2.32 (m, 4 H), 1.69-1.56 (m, 2 H), 1.51-1.41 (m, 2 H), 1.20 (dt, J = 10.4, 3.5 Hz, 10 H), 0.79 (t, J = 6.8 Hz, 3 H); 13 C NMR (400 MHz, CD3OD): δ 139.9, 139.8, 128.0 (m, label), 127.8 (m, label), 65.1, 55.4, 36.3, 35.1, 31.6, 31.4, 29.2, 29.0, 28.9, 28.6, 22.3, 13.0; HRMS (ESI) calculated value: C 19 H 30 D4NO2 + [M+H] + 312.2835, measured value: 312.2836.

[0360] Example 37:

[0361] Under a nitrogen atmosphere, substrate 73 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), and base (potassium tert-butoxide, 0.60 mmol) were dissolved in a solvent (N,N-dimethylformamide, 2.0 ml) and a deuterium source (tBuOD, 50 mmol). After the addition, the reactants were placed at 45°C and irradiated with a 425 nm LED (350 lux) lamp at a distance of 5 cm from the reaction apparatus for 48 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 74 (99% yield, purity greater than 95%). 1 H NMR (400 MHz, CD3OD): δ 7.86-7.82 (m, 0.58H, C4-H, deuteration rate 42%), 7.77-7.72 (m, 0.69H, C5-H, deuteration rate 31%), 7.64-7.60 (m, 0.08H, C1-H, deuteration rate 92%), 7.42-7.38 (m, 0.50H, C6-H, deuteration rate 50%), 7.36-7.30 (m, 0.60H, C7-H, deuteration rate 40%), 7.25-7.18 (m, 0.40H, C3-H, deuteration rate 60%), 4.06 (s, 3H), 3.63-3.53 (m, 2H), 3.38-3.24 (m, 2H), 2.01 (s, 3H); 13 C NMR (400 MHz, MeOD) δ 172.1, 157.9, 133.7, 133.1, 129.8 (m, label), 129.4 (m, label), 126.8 (m, label), 126.5 (m, label), 122.8 (m, label), 122.7 (m, label), 117.9 (m, label), 101.9, 54.5, 40.0, 39.6, 32.8; HRMS (ESI) calcd: C 15 H 15 D3NO2 + [M+H] + 247.1520, measured value: 247.1522.

[0362] Example 38:

[0363] Under a nitrogen atmosphere, substrate 79 (0.30 mmol), phenol catalyst (2-phenylphenol, 5.0 mol%), and base (phosphazene base, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 2.0 ml) and a deuterium source (EtOD, 50 mmol). After the addition, the reactants were incubated at 45°C under irradiation with a 425 nm LED (350 lux) at a distance of 3 cm from the reaction apparatus for 48 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 80 (95% yield, purity greater than 95%). 1 H NMR (400MHz, Acetone-d6): δ7.42-7.05(m, 4.65H, C3-H, C5-H, C 2′ ,-H,C 3′ ,-H,C 4′ ,-H,C 5′ ,-H,C 6′ δ 4.77-5.11 (m, 1H), 4.11-4.00 (m, 1H), 3.98 (s, 2H), 3.90-3.79 (m, 1H), 3.11-2.92 (m, 1H), 2.68-2.39 (m, 4H), 1.61-1.44 (m, 4H), 1.44-1.29 (m, 2H), 1.08 (d, J = 6.8 Hz, 3H). 13 C NMR (100 MHz, Acetone-d6): δ 156.8, 141.4, 130.3 (m, label), 129.5, 128.8 (m, label), 128.1 (m, label), 127.5 (m, label), 125.6 (m, label), 120.2 (m, label), 111.4 (m, label), 69.9, 58.9, 50.2, 35.8, 26.6, 24.8, 12.2; HRMS (ESI) calculated value: C 21 H 19 D9NO + [M+H] + 319.2658, measured value: 319.2655.

[0364] Example 39:

[0365] Under a nitrogen atmosphere, substrate 81 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-methoxyphenol, 5.0 mol%), and base (potassium tert-butoxide, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 2.0 ml) and a deuterium source (EtOD, 50 mmol). After the addition, the reactants were placed at 50°C and irradiated with a 415 nm LED (500 lux) lamp at a distance of 7 cm from the reaction apparatus for 48 hours. The reaction was quenched by adding water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain 82 (90% yield, purity greater than 95%). 1 H NMR (400MHz, Acetone-d6): δ7.52-7.23 (m, 8H, C 2′ -H, C 3′ -H, C 4′ -H, C 5′ -H, C 6′ -H, C 2″ -H, C 3″ -H, C 4″ -H, C 5″ -H, C 6″ -H, deuterated rate 20%), 7.06 (m, 0.20H, C3-H, deuterated rate 80%), 6.92 (m, 0.82H, C5-H, deuterated rate 18%), 6.37 (m, 0.19H, C6-H, deuterated rate 81%), 4.52 (t, J = 8.6 Hz, 2H), 3.63-3.55 (m, 1H), 3.18 (t, J = 8.7 Hz, 2H), 2.81 (d, J = 7.5 Hz, 2H), 2.69-2.42 (m, 6H), 1.95-1.75 (m, 2H). 13 C NMR (150 MHz, Acetone-d6): δ 175.1, 159.0, 145.0, 144.6, 132.8, 130.4, 130.3 (m, label), 128.4 (m, label), 128.2, 128.1 (m, label), 127.8 (m, label), 127.0, 126.9 (m, label), 125.6, 109.0, 71.3, 64.7, 58.2, 57.8, 54.3, 44.2, 34.6; HRMS (ESI) calculated value: C 28 H 18 D 13 N2O2 + [M+H] + 440.3123, measured value: 440.3124.

[0366] Example 40:

[0367] Under a nitrogen atmosphere, substrate 83 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), and base (potassium carbonate, 0.60 mmol) were dissolved in a solvent (N,N-dimethylformamide, 2.0 ml) and a deuterium source (EtOD, 50 mmol). After the addition, the reactants were placed at 55°C and irradiated with a 400 nm LED (300 lux) lamp at a distance of 10 cm from the reaction apparatus for 48 hours. The reaction was quenched by water, and the aqueous phase was extracted three times with ethyl acetate (15 ml x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and then column chromatography to obtain 84 (89% yield, purity greater than 95%). 1 H NMR (400 MHz, CD3OD): δ 7.16-7.11 (m, 0.39 H, C2-H, deuterated rate 61%), 7.05-7.00 (m, 1.68 H, C6-H, C7-H, deuterated rate 32%), 6.59-6.54 (m, 0.08 H, C3-H, deuterated rate 92%), 6.55-6.50 (m, 1 H), 4.23-4.07 (m, 3 H), 3.05-2.98 (m, 1 H), 2.98-2.88 (m, 1 H), 2.83-2.75 (m, 1 H), 1.18-1.13 (m, 6 H). 13 C NMR (150 MHz, CD3OD): δ 153.6, 139.2, 123.8, 122.9 (m, label), 120.2, 106.1, 101.1, 99.4 (m, label), 71.9, 69.7, 51.1, 50.0, 22.4, 22.2; HRMS (ESI) calculated value: C14H 16 D5N2O2 + [M+H] + 254.1839, measured value: 254.1840.

[0368] Example 41:

[0369] Under a nitrogen atmosphere, substrate 53 (0.30 mmol), phenol catalyst (2,6-di-tert-butyl-4-phenylphenol, 2.0 mol%), and base (potassium tert-butoxide, 0.10 mmol) were dissolved in a solvent (tetrahydrofuran, 5.0 mL) and a deuterium source (EtOD, 80 mmol). After addition, the reaction mixture was incubated at 45°C under irradiation with a 395 nm LED (220 lux) at a distance of 5 cm from the reactor for 48 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL x 3). The organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was used directly as the reaction substrate in the above process without purification. After completion, the crude product was purified by column chromatography to obtain 54 (97% yield, purity greater than 95%). 1 H NMR (400 MHz, CDCl3): δ 7.03 (s, 0.03H, C5-H, deuteration rate 97%), 6.80 (s, 0.04H, C6-H, deuteration rate 96%), 6.70 (s, 0.04H, C2-H, deuteration rate 96%), 3.79 (s, 3H), 2.99 (d, J = 18.1 Hz, 1H), 2.81 (dd, J = 5.9, 3.2 Hz, 1H), 2 .59 (dd, J=18.1, 5.8Hz, 1H), 2.51-2.26 (m, 5H), 2.08 (td, J=12.3, 3.3Hz, 1H), 1.91-1.69 (m, 2H), 1.67-1.58(m, 1H), 1.58-1.47(m, 1H), 1.46-1.21(m, 6H), 1.13(qd, J=12.2, 3.6Hz, 1H); 13 C NMR (100 MHz, CDCl3): δ 158.2, 141.7, 129.8, 128.5 (m, mark), 111.1 (m, mark), 110.7 (m, mark), 58.0, 55.2, 47.3, 45.4, 42.8, 42.1, 37.2, 36.7, 26.8, 26.6, 23.3, 22.7, 22.3; HRMS (ESI) calculated value: C 18 H 23 D3NO + [M+H] + 275.2197, measured value: 275.2195.

[0370] Example 42:

[0371] Under a nitrogen atmosphere, substrate 55 (0.30 mmol), phenol catalyst (2,4,6-triphenylphenol, 5.0 mol%), and base (potassium tert-butoxide, 0.60 mmol) were dissolved in a solvent (n-heptane, 6.0 ml) and a deuterium source (EtOD, 60 mmol). After the addition, the reactants were placed at 55°C and irradiated with a 455 nm LED (650 lux) lamp 5 cm away from the reaction apparatus for 60 hours. Then, heating was stopped and the solvent was removed under reduced pressure to obtain a crude product. The crude product was not purified and the solvent (n-heptane, 6.0 ml) and a deuterium source (EtOD, 60 mmol) were added again and the above steps were repeated. After irradiation, water was added to quench the reaction. The aqueous phase was extracted three times with ethyl acetate (15 ml × 3). The organic phases were combined, washed with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatography to obtain 56 (95% yield, purity greater than 95%). 1 H NMR (400 MHz, CD3OD): δ 7.20 (s, 0.0.4H, C2-H, C6-H, deuteration rate 98%), 7.08 (s, 0.04H, C3-H, C5-H, deuteration rate 98%), 3.66 (q, J = 7.1 Hz, 1H), 2.44 (d, J = 7.2 Hz, 2H), 1.83 (p, J = 6.8 Hz, 1H), 1.42 (d, J = 7.1 Hz, 3H), 0.88 (d, J = 6.6 Hz, 6H); 13 C NMR (100 MHz, CD3OD) δ 177.2, 140.1, 138.4, 128.9 (m, marker), 126.9 (m, marker), 30.1, 21.5, 21.3, 17.7; HRMS (ESI) calculated value: C 13 H 13 D4O2 - [MH] - 209.1485, measured value: 209.1487.

[0372] Example 38:

[0373] The two deuterium-labeled drugs prepared in Examples 30 and 37 were tested for their improving effects on the pharmacokinetic characteristics in rats.

[0374] Sixteen male SD rats (source: Experimental Animal Center of Yunnan University) were randomly divided into two groups according to body weight: a deuterated drug (10 mg / kg) experimental group (3 days) and a non-deuterated drug (10 mg / kg) control group (3 days), with 8 rats in each group. Drug solutions for oral administration were prepared with 0.5% sodium carboxymethyl cellulose solution. All experimental animals were fasted for 12 hours before administration and had free access to water during this period. 0.5 ml of blood was collected from the medial canthal vein before administration (0 h) and at 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 3, 4, 6, 8, and 12 h after administration and placed in a 1.5 ml heparinized centrifuge tube. Plasma was separated after low-speed centrifugation (5000 rpm) for 10 min and stored in a -80°C freezer for testing. Each analytical batch contains blank samples and zero-concentration samples, a freshly prepared standard curve (preparation method: accurately weigh the samples into rat blank plasma to prepare calibration standards with concentrations of 5, 10, 25, 50, 100, 250, 500, and 1000 ng / ml), and accompanying quality control samples with low, medium, and high concentrations (the concentrations are 10 ng / mL, 90 ng / mL, and 900 ng / mL, respectively, not less than 5% of the total number of experimental samples). The concentration of the drug in rat plasma after administration is calculated based on the standard curve of the analytical batch. Deuterium substitution of the drug shows a significant improvement in the pharmacokinetic characteristics of the drug in compound rats, and has a significantly prolonged half-life (t 1 / 2 ) and increase the maximum blood concentration (C max The results are shown in the following table.

Claims

1. A C(sp 2 )-H bond deuteration method, characterized in that, The method comprises the following steps: in a solvent, under the conditions of phenol, alkali and visible light illumination, subjecting substance A to a deuterium source for a deuterium substitution reaction to obtain substance B; The substance A contains an aromatic group, and the aromatic group contains one or more fragments I, and the fragment I is The H in the fragment I is the naturally abundant H; The aromatic group is aryl, X and Y are each independently NH, O or S; Z is N or CH; Part or all of the fragment I is converted into the fragment II, wherein the fragment II is In H of the fragment II, the abundance of D is greater than the natural abundance of D; The aromatic group is not directly connected to the halogen; The phenol is Ring A is C 6-14 Aryl or 5-10 membered heteroaryl; the heteroatom in the 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 1 Each independently is H, C 1-10 Alkyl, -OR 1a 、-NO2、-(C=O)R 1b 、-NR 1c R 1d , C 6-14 Aryl, 5-10 membered heteroaryl, substituted by one or more R 1e Substituted C 1-10 Alkyl, with one or more R 1f Substituted C 6-14 Aryl, or one or more R 1g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1g The heteroatom in the substituted 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of the heteroatoms is 1-4; m is 1, 2, 3, 4 or 5; R 1a and R 1b are independently H or C 1-10 alkyl; R 1c and R 1d Independently H, C 6-14 Aryl, or substituted by one or more R 1a-1 C 6-14 Aryl; R 1e , R 1f and R 1g Each independently is -OH, C 1-10 Alkyl, NR 1a-2 R 1a-3 、-(C=O)R 1a-4 or -CN; R 1a-1 , R 1a-2 , R 1a-3 and R 1a-4 are independently H or C 1-10 alkyl.

2. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) The solvent is an organic solvent or an inorganic solvent, the inorganic solvent is, for example, water, and the organic solvent is, for example, one or more of an alkane solvent, an ether solvent, a nitrile solvent, an amine solvent, and a sulfoxide solvent; (2) The base is sodium bicarbonate, potassium bicarbonate, cesium bicarbonate, ammonium bicarbonate, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, rubidium carbonate, ammonium carbonate, triethylmethyl methyl ammonium carbonate, tributylmethyl methyl ammonium carbonate, potassium phosphate, sodium phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide, ammonium hydroxide, tetrapropylammonium hydroxide, tetrabutylammonium hydroxide, tributylbenzylammonium hydroxide, sodium methoxide, potassium methoxide, potassium ethoxide, sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, pyridine, 2,6-lutidine, 2,6-di-tert-butylpyridine, 2,4,6-trimethylpyridine, 4-dimethylaminopyridine, triethylamine, trimethylamine, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane, 1,8-diazabicyclo[5.4.0]undec-7-ene, tetramethylguanidine, tetramethylethylenediamine, N-methylmorpholine, N,N,N′,N″,N″-pentamethyldiethylenetriamine or a phosphazene base; (3) The visible light source is preferably 1-20 cm away from the reaction device, such as 1-15 cm. Preferably, the visible light source is preferably 2 cm, 3 cm, 4 cm, 5 cm, 7 cm, 10 cm, or 15 cm away from the reaction device. Further preferably, the illumination intensity of the visible light is 50-2500 lux, such as 420 lux, 350 lux, 600 lux, 200 lux, 2000 lux, 650 lux, 210 lux, 1380 lux, 450 lux, 1250 lux, 700 lux, 160 lux, 300 lux, 750 lux, 70 lux, or 200 lux. (4) The wavelength of the visible light is 380-600 nm, preferably 380-560 nm, such as 390 nm, 395 nm, 455 nm, 415 nm, 405 nm, 425 nm, 435 nm, 475 nm, 500 nm or 525 nm; (5) The deuterium source is R D -OD, R D H, D, C 3-10 Cycloalkyl, C 1-6 Alkyl or C substituted with 1 or more D 1- 6 alkyl; (6) The substance A is a compound represented by formula I; Wherein, n is an integer from 0 to 10; Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; The heteroaryl group is X and Y are each independently NH, O or S; Z is N or CH; R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C 15 Alkylthio, substituted by 1 or more R 2-7 Substituted C1-C 15 Alkylthio, substituted by 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 2-1 , R 2-4 and R 2-7 are independently hydroxyl, cyano, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or 1 or more R 2-1-4 Substituted C1-C 15 The heteroatoms in the 5-15 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 2-2 and R 2-3 Each independently is H or C1-C 15 alkyl; R 2-5 , R 2-6 , R 2-8 , R 2-9 and R 2-10 Each independently is H or C1-C 15 alkyl; R 2-11 Each is independent of C1-C 15 Alkyl or 1 or more R 2-11-1 Substituted C1-C 15 alkyl; R 2-1-1 and R 2-1-2 Each independently is H, C1-C 15 Alkyl, carbonyl-C1-C 15 Alkyl or carbonyl-C1-C 15 Alkoxy; R 2-1-3 , R 2-11-1 and R 2-1-4 Each is independently -NH2, hydroxyl or cyano; The fragment I is a fragment of an aryl or heteroaryl group in ring B; and (7) In the substance B, the abundance of D in fragment II is 20%-100%, for example, 97%, 95%, 96%, 90%, 85%, 70%, 56%, 31% or 42%.

3. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) The substance A undergoes a deuterated reaction to obtain the substance B, and the abundance of H in the remaining radical fragments in the substance A remains unchanged; (2) The substance A contains one or more aromatic groups, such as 1, 2, 3 or 4, and the aromatic groups are the same or different. Preferably, when the aromatic fragments are different, the fragment I is the above Fragments in; (3) In the substance A, the fragment I is a fragment of the following groups: aromatic group, wherein the aryl group, Optionally with C 3-15 Cycloalkyl or C 3-15 Heterocycloalkyl fused, the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; (4) The base is an organic base or an inorganic base, wherein the cation in the inorganic base may be an alkali metal, and the anion may be a carbonate, bicarbonate, hydroxide or phosphate. The organic base may be an alkali metal alkoxide, a quaternary ammonium salt, a phosphazene basic compound or an amidine basic compound. Preferably, the organic base is an alkali metal alkoxide, an alkali metal carbonate, an alkali metal bicarbonate or an alkali metal hydroxide, wherein the alkali metal is, for example, Na + , Li + , K + or Cs + ; (5) The ratio of the light intensity to the solvent volume is 20-1500 lux / mL, for example 70 lux / mL, 350 / 3 lux / mL, 300 lux / mL, 200 lux / mL, 140 lux / mL, 500 lux / mL, 650 / 3 lux / mL, 210 lux / mL, 420 lux / mL, 650 lux / mL, 1380 lux / mL, 450 lux / mL, 1250 lux / mL, 140 lux / mL, 325 lux / mL, 100 lux / mL L, 105lux / mL, 35lux / mL, 160 / 3lux / mL, 60lux / mL, 650 / 6lux / mL, 130lux / mL, 175lux / mL, 750lux / mL, 70 / 4lux / mL, 44l ux / mL, 90lux / mL, 210 / 4lux / mL, 350 / 4lux / mL, 175lux / mL, 225lux / mL, 250lux / mL, 150lux / mL, 275lux / mL or 44lux / mL; (6) The visible light source is an incandescent lamp or an energy-saving lamp; (7) the abundance of D in fragment II is 0.5%-100%, such as 97%, 95%, 96%, 90%, 85%, 70%, 56%, 31%, 42%, 5%, 10% or 19%; (8) the phenol and the base are used in the form of phenolate, the base may be an inorganic base, and the phenolate may be a sodium salt of phenol; and (9) The substance A is the following scheme A, scheme B, scheme C or scheme D: Option A: n is an integer from 0 to 10; Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; In ring B, the heteroaryl group is X and Y are each independently NH, O or S; Z is N or CH; R 2 Each independently is C1-C 15 Alkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, with 1 or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl or one or more R 2-11 Substituted C 3-10 Heterocycloalkyl or ring C; said C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; Ring C is C 6-20 Aryl, X1 and Y1 are each independently NH, O or S; Z1 is N or CH; R 2-1 and R 2-4 are independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , carboxyl, amide, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; Ring D is C 6-20 Aryl, X2 and Y2 are each independently NH, O or S; Z2 is N or CH; R 2-11 Each independently is C1-C 15 Alkyl or 1 or more R 2-11-1 Substituted C1-C 15 alkyl; R 2-1-1 and R 2-1-2 Each independently is H, C1-C 15 Alkyl or -C1-C 15 Alkyl-OR 2-1-1a ; R 2-1-1a C 6-20 Aryl or one or more R 2-1-1b Substituted C 6-20 Aryl; R 2-1-1b Each independently is -S-C1-C 15 Alkyl or -O-C1-C 15 alkyl; R 2-11-1 Each independently is hydroxyl or -OR 2-11-1a ; R 2-11-1a is a 5-15 membered heteroaryl group or is substituted by one or more R 2-11-1b substituted 5-15 membered heteroaryl; R 2-11-1b Each is independently oxo or C1-C6 alkyl; R 2-1-5 Each independently is a C1-C6 alkyl group or is substituted by one or more R 2-1-6a Substituted C1-C6 alkyl; R 2-1-6a Each is independently an amide group, a carboxyl group or a ring E; Ring E is C 6-20 Aryl, X3 and Y3 are each independently NH, O or S; Z3 is N or CH; The fragment I is a fragment of an aryl or heteroaryl group in ring B, ring C, ring D or ring E; Option B: n is an integer from 0 to 10; Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; In ring B, the heteroaryl group is X and Y are each independently NH, O or S; Z is N or CH; R 2 Each independently is C1-C 15 Alkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, 1 or more R 2-4 Substituted C1-C 15 Alkoxy or 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl; said C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 2-1 and R 2-4 are independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , amide, -S-C1-C 15 Alkyl, ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; Ring D is C 6-20 Aryl; R 2-11 Each is independently controlled by one or more R 2-11-1 Substituted C1-C 15 alkyl; R 2-1-1 and R 2-1-2 Each independently is H, C1-C 15 Alkyl or -C1-C 15 Alkyl-OR 2-1-1a ; R 2-1-1a Each independently is one or more R 2-1-1b Substituted C 6-20 Aryl; R 2-1-1b Each is independently -O-C1-C 15 alkyl; R 2-11-1 Each independently is -OR 2-11-1a ; R 2-11-1a For one or more R 2-11-1b substituted 5-15 membered heteroaryl; R 2-11-1b each independently is oxo; R 2-1-5 Each independently is one or more R 2-1-6a Substituted C1-C6 alkyl; R 2-1-6a Each is independently an amide group, a carboxyl group or a ring E; Ring E is C 6-20 Aryl; The fragment I is a fragment of an aryl or heteroaryl group in ring B, ring D or ring E; Option C: n is an integer from 0 to 10; Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatom in the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4 indivual; In ring B, the heteroaryl group is X is NH, O or S; Z is N or CH; R 2 Each independently is one or more R 2-1 Substituted C1-C 15 Alkyl or 1 or more R 2-4 Substituted C1-C 15 Alkoxy; R 2-1 and R 2-4 are independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; Ring D is C 6-20 Aryl; R 2-1-1 and R 2-1-2 Each independently is H or C1-C 15 alkyl; R 2-1-5 Each independently is one or more R 2-1-6a Substituted C1-C6 alkyl; R 2-1-6a Each is independently an amide group or ring E; Ring E is C 6-20 Aryl; The fragment I is a fragment of an aryl or heteroaryl group in ring B, ring D or ring E; Plan D: n is an integer from 0 to 10; Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; The heteroaryl group is X and Y are each independently NH, O or S; Z is N or CH; R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C 15 Alkylthio, substituted by 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 2-1 and R 2-4 are independently hydroxyl, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or 1 or more R 2-1-4 Substituted C1-C 15 Alkyl; the heteroatom in the 5-15 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 2-2 and R 2-3 Each independently is H; R 2-5 , R 2-6 , R 2-8 , R 2-9 and R 2-10 Each independently is C1-C 15 alkyl; R 2-11 Each is independently controlled by one or more R 2-11-1 Substituted C1-C 15 alkyl; R 2-1-1 and R 2-1-2 Each independently is H, C1-C 15 Alkyl, carbonyl-C1-C 15 Alkyl or carbonyl-C1-C 15 Alkoxy; R 2-1-3 and R 2-1-4 are each independently hydroxyl; The fragment I is a fragment of the aromatic or heteroaromatic group in ring B.

4. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) The alkane solvent is n-hexane, cyclohexane, n-heptane, n-pentane or petroleum ether; (2) The ether solvent is tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, 1,4-dioxane or methyl tert-butyl ether, preferably tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, 1,4-dioxane or methyl tert-butyl ether; (3) The nitrile solvent is acetonitrile; (4) The amine solvent is ethylenediamine, N,N-dimethylformamide or N,N-dimethylacetamide, preferably ethylenediamine or N,N-dimethylformamide; (5) The sulfoxide solvent is dimethyl sulfoxide; (6) In ring A, the C 6-14 Aryl is phenyl, naphthyl, anthracenyl or phenanthrenyl; (7) In ring A, the 5-10 membered heteroaryl group is a 5-6 membered heteroaryl group, in which the heteroatom is preferably N, and the number of heteroatoms is preferably 1. For example, the 5-10 membered heteroaryl group is (8)R 1 In the C 1-10 Alkyl and one or more R 1e Substituted C 1-10 C in alkyl 1-10 The alkyl groups are each independently C 1-6 Straight or branched chain alkyl or C 7-10 Straight chain alkyl, the C 1-6 The straight chain or branched chain alkyl group is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl. 7-10 A straight chain alkyl group such as n-heptyl, n-octyl, n-nonyl or n-decyl, wherein the C 1-6 The straight chain or branched chain alkyl group is preferably a methyl group or a tert-butyl group. 7-10 The straight-chain alkyl group is preferably n-heptyl; (9)R 1 In the C 6-14 Aryl and one or more R 1f Substituted C 6-14 C in aromatic group 6-14 Aryl is each independently phenyl, naphthyl, anthracenyl or phenanthryl, for example phenyl or anthracenyl; (10)R 1 wherein the 5-10 membered heteroaryl group and one or more R 1g The 5-10-membered heteroaryl groups in the substituted 5-10-membered heteroaryl groups are each independently a 5-9-membered heteroaryl group, wherein the heteroatom in the 5-10-membered heteroaryl group is preferably N, and the number of heteroatoms is preferably 1 or 2, for example (11)R 1a , R 1b , R 1e , R 1f , R 1g , R 1a-1 , R 1a-2 , R 1a-3 and R 1a-4 In the C 1-10 The alkyl groups are each independently C 1-6 Straight-chain or branched alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, for example methyl or tert-butyl; (12)R 1c and R 1d In the C 6-14 Aryl and substituted by one or more R 1a-1 C 6-14 C in aromatic group 6-14 Aryl is each independently phenyl, naphthyl, anthracenyl or phenanthryl, for example phenyl; (13) In the deuterium source, the C 1-6 Alkyl and C substituted with 1 or more D 1-6 C in alkyl 1-6 The alkyl groups are each independently a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl; (14) In the deuterium source, the C 3-10 Cycloalkyl is C 3-6 Cycloalkyl, for example cyclopropyl, cyclobutyl or cyclopentyl; (15) In ring B, the C 6-20 Aryl is C 6-14 Aryl; preferably phenyl, naphthyl, anthracenyl or phenanthryl, for example phenyl, naphthyl or anthracenyl; (16) C 3-15 Cycloalkyl is C 3-6 Monocyclic cycloalkyl or C 9-15 Polycyclic cycloalkyl, the C 3-6 Monocyclic cycloalkyl is, for example, cyclopropane, cyclobutane, cyclohexane or cyclopentane. The cyclohexane is preferably The cyclopentyl group is preferably The C 9-15 The polycyclic cycloalkyl group is exemplified by dodecahydro-1H-cyclopenta[a]naphthyl, wherein the dodecahydro-1H-cyclopenta[a]naphthyl group is preferably (17) C 3-15 Heterocycloalkyl is C 3-6 Monocyclic heterocycloalkyl or C 9-15 A polycyclic heterocycloalkyl group, wherein The heteroatom is, for example, N or O, and the number of heteroatoms is, for example, 1 or 2; for example, the C 3-6 The monocyclic heterocycloalkyl group is oxetane, oxolane or oxhexane, wherein the C 9-15 Polycyclic cycloalkyl is, for example, decahydroquinolinyl; preferably, the C 3-15 Heterocycloalkyl is (18)R 2 In the above, C1-C 15 Alkyl and 1 or more R 2-1 Substituted C1-C 15 C1-C 15 The alkyl groups are each independently a linear or branched C1-C 15 Alkyl, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, 2-methyl-n-butyl, 3-methyl-n-butyl, n-heptyl, n-octyl, n-nonyl, n-decyl or 2-n-pentyl-n-octyl, for example methyl, ethyl, n-propyl, isopropyl, 3-methyl-n-butyl, n-octyl or 2-n-pentyl-n-octyl, for example methyl, n-octyl, n-heptyl, ethyl, isopropyl, n-butyl, tert-butyl; (19)R 2 , R 2-1 , R 2-4 and R 2-7 In the C 3-10 Cycloalkyl and 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl C 3- 10 The cycloalkyl groups are each independently C 3-6 Cycloalkyl, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclohexyl; (20)R 2 , R 2-1-1 and R 2-1-2 In the above, C1-C 15 Alkoxy, with 1 or more R 2-4 Substituted C1-C 15 Alkoxy, carbonyl-C1-C 15 C1-C 15 The alkoxy groups are each independently C1-C6 alkoxy groups, for example methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy or n-hexoxy, for example methoxy, ethoxy, n-propoxy, n-butoxy or tert-butoxy; (21)R 2 In the C 3-10 Heterocycloalkyl and one or more R 2-11 Substituted C 3-10 Heterocycloalkyl C 3-10 The heterocycloalkyl groups are each independently C 3-6 Heterocycloalkyl, the C 3-10 The heteroatom in the heterocycloalkyl group is preferably N, and the number of heteroatoms is preferably 1 or 2, for example (22)R 2 In the above, C1-C 15 Alkylthio, substituted by 1 or more R 2-7 Substituted C1-C 15 C1-C 15 Each alkylthio group is independently a C1-C6 alkylthio group, for example, methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio, n-pentylthio or n-hexylthio, for example, tert-butylthio; (23)R 2-1 , R 2-4 and R 2-7 In the above, the 5-15 membered heteroaryl is a 5-6 membered heteroaryl, in which the heteroatom is preferably N, and the number of heteroatoms is preferably 1. For example, the 5-15 membered heteroaryl is a pyridyl, and the pyridyl is, for example, and (24)R 2-1 , R 2-4 , R 2-7 , R 2-2 , R 2-3 , R 2-5 , R 2-6 , R 2-8 , R 2-9 , R 2-10 , R 2-11 , R 2-1-1 and R 2-1-2 In the above, C1-C 15 Alkyl, 1 or more R 2-1-4 Substituted C1-C 15 Alkyl, 1 or more R 2-11-1 Substituted C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl and carbonyl -C1-C 15 C1-C 15 The alkyl groups are each independently C1-C6 alkyl groups, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, for example methyl, ethyl, n-propyl, isopropyl, tert-butyl or n-pentyl.

5. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1)R 2-1 and R 2-4 In the C 3-10 Heterocycloalkyl and 1 or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl C 3-10 The heterocycloalkyl groups are each independently C 3-6 Heterocycloalkyl, the C 3-10 The heteroatom in the heterocycloalkyl group is preferably N, and the number of heteroatoms is preferably 1 or 2, for example (2)R 2-1-1 , R 2-1-2 and R 2-1-1b In the above, C1-C 15 Alkyl, C1-C 15 Alkyl-OR 2-1-1a 、-S-C1-C 15 Alkyl and -O-C1-C 15 C1-C 15 The alkyl groups are each independently C1-C6 alkyl, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, for example, methyl or ethyl; (3)R 2-1-1a In the C 6-20 Aryl and one or more R 2-1-1b Substituted C 6-20 C in aromatic group 6-20 The aryl groups are each independently C 6-14 Aryl, for example, phenyl; (4)R 2-11-1a wherein the 5-15 membered heteroaryl group and one or more R 2-11-1b The 5-15-membered heteroaryl groups in the substituted 5-15-membered heteroaryl groups are each independently a 5-10-membered heteroaryl group, wherein the heteroatom in the 5-15-membered heteroaryl group is preferably N, and the number of heteroatoms is preferably 1. For example, the 5-15-membered heteroaryl group is and (5)R 2-11-1b and R 2-1-5 wherein the C1-C6 alkyl group is replaced by one or more R 2-1-6a The C1-C6 alkyl groups in the substituted C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, such as methyl.

6. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) In the phenol, R 1 Each independently is H, C 1-10 Alkyl, -OR 1a 、-NO2、-(C=O)R 1b 、-NR 1c R 1d , C 6-14 Aryl, 5-10 membered heteroaryl, substituted by one or more R 1e Substituted C 1-10 Alkyl or one or more R 1f Substituted C 6-14 Aryl, wherein the heteroatoms in the 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; (2) In the phenol, m is 1, 2 or 3; (3)R 1c and R 1d is independently H or substituted by one or more R 1a-1 C 6-14 Aryl; (4) In the aromatic group, the aromatic group is C 6-20 Aryl, such as C 6-14 aryl, for example phenyl, naphthyl, anthracenyl or phenanthrenyl; (5) In the compound represented by formula I, n is an integer of 0-6, for example, 1, 2, 3, 4 or 5; (6) In the compound represented by formula I, R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, By one or more R 2-7 Substituted C1-C 15 Alkylthio, substituted by 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; (7)R 2-1 , R 2-4 and R 2-7 are independently hydroxyl, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or 1 or more R 2-1-4 Substituted C1-C 15 Alkyl; the heteroatom in the 5-15 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; (8)R 2-2 and R 2-3 Each independently is H; (9)R 2-5 , R 2-6 , R 2-8 , R 2-9 and R 2-10 Each independently is C1-C 15 alkyl; (10)R 2-11 Each is independently controlled by one or more R 2-11-1 Substituted C1-C 15 Alkyl; and (11)R 2-1-3 , R 2-11-1 and R 2-1-4 are each independently hydroxyl.

7. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) In ring B, the heteroaryl group is (2)R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C 15 Alkylthio Base, 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; Preferably, R 2 Each independently is C1-C 15 Alkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, 1 or more R 2- 4 Substituted C1-C 15 Alkoxy or 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl; said C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; For example, R 2 Each independently is one or more R 2-1 Substituted C1-C 15 Alkyl or 1 or more R 2-4 Substituted C1-C 15 Alkoxy; (3)R 2-1 and R 2-4 are independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , amide, -S-C1-C 15 Alkyl, ring D or one or more R 2-1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; Preferably, R 2-1 and R 2-4 are independently hydroxyl, C 3-10 Heterocycloalkyl, -NR 2-1-1 R 2-1-2 , ring D or one or more R 2- 1-5 Substituted C 3-10 Heterocycloalkyl, wherein the C 3-10 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; (4) Ring D is C 6-20 Aryl; (5)R 2-1-1 and R 2-1-2 Each independently is H or C1-C 15 alkyl; (6)R 2-1-1a For one or more R 2-1-1b Substituted C 6-20 Aryl; (7)R 2-1-1b Each is independently -O-C1-C 15 alkyl; (8)R 2-11-1 Each independently is -OR 2-11-1a ; (9)R 2-11-1a For one or more R 2-11-1b substituted 5-15 membered heteroaryl; (10)R 2-11-1b each independently is oxo; (11)R 2-1-5 Each independently is one or more R 2-1-6a Substituted C1-C6 alkyl; (12)R 2-1-6a Each is independently an amide group or ring E; (13) The substance A is not the phenol; (14) In the substance A, the aromatic group is not directly connected to the halogen and / or hydroxyl group, for example, the aromatic group is not directly connected to the halogen and / or hydroxyl group; and (15) Ring E is C 6-20 Aryl.

8. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) R 2 for Methyl, -NH2, n-propyl, Preferably, the R 2 for Methyl, -NH2, n-propyl, Alternatively, the R 2 For n-propyl, n-ethyl, and (2) The ring B is Preferably, the ring B is 9. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) The solvent is dimethyl sulfoxide, tetrahydrofuran, diethyl ether, 1,4-dioxane, methyl tert-butyl ether, n-hexane, cyclohexane, n-heptane, n-pentane, petroleum ether, N,N-dimethylformamide, ethylenediamine, ethylene glycol dimethyl ether or acetonitrile; (2) The phenol is any of the following compounds: For example, the phenol is Any of the following compounds: 2,6-di-tert-butyl-4-phenylphenol, 2,6-di-tert-butyl-4-(9-anthryl)phenol, 2,6-di-tert-butyl-4-heptylphenol, 2,4,6-triphenylphenol, 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol, 9-phenanthroline, 9,10-anthraquinone, 2-tert-butyl-3,5-xylenol, 2,6-di-tert-butyl-4-(4-tert-butylphenyl)phenol, 3-phenyl-1-naphthol, 2-phenylphenol, 3-hydroxy-2-phenylpyridine, 3-((2,6-dimethylphenyl)amino)phenol, 4′-aminophenyl-3-phenol, cyanobiphenol, 2,6-di-tert-butyl-4-(4-acetylphenyl)phenol, 2,4,6-tri-tert-butylphenol, 2-tert-butyl-3,5-xylenol, 1-anthrol, 5,5′-di-tert-butyl-2,2′-biphenol, 2,6-di-tert-butyl-4-acetylphenol, 2,6-di-tert-butyl-4-methoxyphenol, 6-tert-butyl-2,4-xylenol, 2,6-di-tert-butyl-4-shylphenol, 3,5-di-tert-butylcatechol, 4-phenylphenol, 2-amino-4-tert-butylphenol, 2,6-diphenylphenol, 2,6-di-tert-butyl-4-methylphenol or 2,6-di-tert-butyl-4-hydroxymethylphenol; (3) The base is potassium tert-butoxide, phosphazene base, potassium carbonate, cesium carbonate, potassium hydroxide, tetrabutylammonium hydroxide, potassium methoxide, sodium tert-butoxide, potassium ethoxide, sodium carbonate, 1,8-diazabicyclo[5.4.0]undec-7-ene, potassium phosphate or cesium hydroxide; (4) the deuterium source is EtOD, MeOD, iPrOD, tBuOD, CD3OD, D2O or CD3CD2OD; and (5) The substance A is any of the following compounds:

10. C(sp 2 )-H bond deuteration method, characterized in that, The substance B is any of the following compounds: Here, the percentage (%) of each site is independently the deuterated ratio of each site.

11. C(sp 2 )-H bond deuteration method, characterized in that, It meets one or more of the following conditions: (1) The concentration of the substance A in the solvent is 0.05-0.75 mol / L, for example, 0.05 mol / L, 0.06 mol / L, 0.075 mol / L, 0.10 mol / L, 0.15 mol / L or 0.30 mol / L; (2) the molar ratio of the phenol to the substance A is (0.005-0.5):1, preferably (0.005-0.2):1, for example, 0.005:1, 0.01:1, 0.02:1, 0.05:1, 0.07:1, 0.09:1, 0.10:1, 0.15:1 or 0.20:1; (3) the molar ratio of the base to the substance A is (0.01-5):1, preferably (0.05-3):1, for example 0.2:3, 0.5:3, 1:3, 1:1, 2.0:1, 2.0:3, 1:6, 2:30, 3.0:1, 4:3 or 2.7:1; (4) The molar ratio of the deuterium source to the substance A is (50.0-600.0):1, preferably (100.0-300.0):1, for example, 100:1, 150:1, 400:3, 500:3, 700:3, 800:3, 200:1, 250:1 or 300:1; (5) The reaction temperature of the deuteration reaction is -20°C to 80°C, preferably 0°C to 80°C, for example 0°C, 5°C, 15°C, 25°C, 22°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, 65°C or 75°C (6) The deuteration reaction is carried out in a protective gas, such as nitrogen; (7) The substance A does not contain an electron-withdrawing substituent, for example, the electron-withdrawing substituent is a halogen or ester group; (8) The raw materials for the deuteration reaction are the solvent, the phenol, the base, the substance A and the deuterium source; (9) The deuterated reaction comprises the following post-treatment steps: after the reaction is completed, quenching the reaction, extracting with an organic solvent, washing, drying, and purifying to obtain substance B; Preferably, the deuteration reaction comprises the following steps: under a nitrogen atmosphere, the phenol, the substance A, the deuterium source, the base and the solvent are mixed, and the deuteration reaction is carried out under light conditions; preferably, after the reaction is completed, the reaction is quenched, organic solvent extraction is performed, washing, drying and purification are performed to obtain substance B; further preferably, the deuteration reaction comprises the following steps: under a nitrogen atmosphere, in the above-mentioned ether solvent, under the conditions of the above-mentioned phenol, organic base and visible light with a wavelength of 380-600nm, substance A is subjected to a deuteration reaction with the above-mentioned deuterium source to obtain substance B; Further preferably, the deuteration reaction is any of the following schemes: Scheme 1: The deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation conditions with an illumination intensity of 350 lux to 420 lux, tetrahydrofuran, 2,6-di-tert-butyl-4-phenylphenol, phosphazene base, substance A and MeOD are mixed to carry out a deuteration reaction to obtain substance B; Scheme 2: The deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation conditions with an illumination intensity of 350 lux to 420 lux, tetrahydrofuran, 2,6-di-tert-butyl-4-phenylphenol, potassium tert-butoxide, substance A and EtOD are mixed to carry out a deuteration reaction to obtain substance B; Scheme 3: The deuteration reaction comprises the following steps: in a nitrogen atmosphere, under visible light irradiation conditions with an illumination intensity of 200 lux, 1,4-dioxane, 3-hydroxy-2-phenylpyridine, cesium carbonate, substance A and CD3OD are mixed to carry out a deuteration reaction to obtain substance B; Scheme 4: The deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation conditions with an illumination intensity of 2000 lux, tetrahydrofuran, 3-((2,6-dimethylphenyl)amino)phenol, potassium hydroxide, substance A and CD3CD2OD are mixed to carry out a deuteration reaction to obtain substance B; Scheme 5: The deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation conditions with an illumination intensity of 420 lux, ether, 2,6-di-tert-butyl-4-phenylphenol, potassium methoxide, substance A and CD3CD2OD are mixed to carry out a deuteration reaction to obtain substance B.

12. C(sp 2 )-H bond deuteration method, characterized in that, The method comprises the following steps: in a solvent, under the conditions of phenol, alkali and visible light illumination, subjecting substance A to a deuterium source for a deuterium substitution reaction to obtain substance B; The solvent is one or more of water, alkane solvents, ether solvents, nitrile solvents, amine solvents and sulfoxide solvents; The base is an organic base or an inorganic base; The substance A contains an aromatic group, and the aromatic group contains one or more fragments I, and the fragment I is The H in the fragment I is the naturally abundant H; The substance A is a compound represented by formula I; Wherein, n is an integer from 0 to 10; Ring B is C 6-20 Aryl or heteroaryl, the C 6-20 Aryl and heteroaryl are optionally with C 3-15 Heterocycloalkyl and C 3-15 One or two of the cycloalkyl groups are fused; wherein the C 3-15 The heteroatoms in the heterocycloalkyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4; The heteroaryl group is X and Y are each independently NH, O or S; Z is N or CH; R 2 Each independently is C1-C 15 Alkyl, C 3-10 Cycloalkyl, 1 or more R 2-1 Substituted C1-C 15 Alkyl, C1-C 15 Alkoxy Base, -NR 2-2 R 2-3 , by one or more R 2-4 Substituted C1-C 15 Alkoxy, C 3-10 Heterocycloalkyl, C1-C 15 Alkylthio, substituted by 1 or more R 2-11 Substituted C 3-10 Heterocycloalkyl or The C 3-10 The heteroatom of the heterocycloalkyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 2-1 and R 2-4 are independently hydroxyl, C 3-10 Cycloalkyl, 5-15 membered heteroaryl, -NR 2-1-1 R 2-1-2 , carboxyl, C1-C 15 Alkyl, -S-C1-C 15 Alkyl, -O-C1-C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or 1 or more R 2-1-4 Substituted C1-C 15 Alkyl; the heteroatom in the 5-15 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 2-2 and R 2-3 Each independently is H; R 2-5 , R 2-6 , R 2-8 , R 2-9 and R 2-10 Each independently is C1-C 15 alkyl; R 2-11 Each is independently controlled by one or more R 2-11-1 Substituted C1-C 15 alkyl; R 2-1-1 and R 2-1-2 Each independently is H, C1-C 15 Alkyl, carbonyl-C1-C 15 Alkyl or carbonyl-C1-C 15 Alkoxy; R 2-1-3 and R 2-1-4 are each independently hydroxyl; The fragment I is a fragment of an aryl or heteroaryl group in ring B; Part or all of the fragment I is converted into the fragment II, wherein the fragment II is In H of the fragment II, the abundance of D is greater than the natural abundance of D; The aromatic group is not directly connected to the halogen; The phenol is Ring A is C 6-14 Aryl or 5-10 membered heteroaryl; the heteroatom in the 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of heteroatoms is 1-4; R 1 Each independently is H, C 1-10 Alkyl, -OR 1a 、-NO2、-(C=O)R 1b 、-NR 1c R 1d , C 6-14 Aryl, 5-10 membered heteroaryl, substituted by one or more R 1e Substituted C 1-10 Alkyl, with one or more R 1f Substituted C 6-14 Aryl, or one or more R 1g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1g The heteroatom in the substituted 5-10 membered heteroaryl is selected from one or more of N, O and S, and the number of the heteroatoms is 1-4; m is 1, 2, 3, 4 or 5; R 1a and R 1b are independently H or C 1-10 alkyl; R 1c and R 1d Independently H, C 6-14 Aryl, or substituted by one or more R 1a-1 C 6-14 Aryl; R 1e , R 1f and R 1g Each independently is -OH, C 1-10 Alkyl, NR 1a-2 R 1a-3 、-(C=O)R 1a-4 or -CN; R 1a-1 , R 1a-2 , R 1a-3 and R 1a-4 are independently H or C 1-10 alkyl; The deuterium source is R D -OD, R D H, D, C 3-10 Cycloalkyl, C 1-6 Alkyl or C substituted with 1 or more D 1-6 alkyl; Preferably, the deuteration reaction is carried out in a protective gas, an ether solvent, a light intensity of 50-2500 lux, and a temperature of 0°C-80°C, and the abundance of D in fragment II is 20%-100%; The phenol is Ring A is C 6-14 Aryl, R 1 Each independently is C 1-10 Alkyl or C 6-14 Aryl; The deuterium source is R D -OD, R D C 1-6 alkyl; The base is an organic base.

13. A use of phenol as a deuterated reaction photocatalyst, characterized in that: The phenol is Among them, ring A, R 1 and m are each independently as described in any one of claims 1-12; preferably, in the application, the deuteration reaction is carried out under the action of a base as described in any one of claims 1-12.

14. A substance X or a pharmaceutically acceptable salt thereof, wherein the substance X is any of the following compounds: in, The percentage (%) of each site is independently the deuterated ratio of each site.

15. A C(sp 2 )-H bond deuteration method, characterized in that, It includes the following steps: (1) Substance A as described in any one of claims 1 to 12 is subjected to a deuteration reaction as described in any one of claims 1 to 12 to obtain substance B; (2) repeating the deuteration reaction of any one of claims 1 to 12 on the substance B; Preferably, the C(sp 2 The method of deuterating the )-H bond satisfies one or more of the following conditions: (1) The number of repetitions is 1 to 3 times; (2) The deuteration method comprises the following steps: after the last deuteration reaction is completed, subjecting the substance B to a deuterium source under the conditions of the phenol, the base and the visible light illumination; Preferably, during the deuteration reaction, the substance B is subjected to deuteration reaction with or without purification, and the deuteration reaction without purification, for example, comprises the following steps: after the last deuteration reaction is completed, quenching the reaction, extracting with an organic solvent, washing, drying, and conducting a deuteration reaction.

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