Method for deuterating C (sp2)-H bond in benzene ring

Abstract

The invention discloses a method for deuterating a C (sp2)-H bond in a benzene ring. The invention provides a method for deuterating a C (sp2)-H bond in a benzene ring, which comprises the following steps: in a solvent, under the illumination conditions of phenol, alkali and visible light, carrying out deuteration reaction on a substance A and a deuterium source to obtain a substance B; the photocatalytic benzene ring deuteration method provided by the invention is easy to operate and wide in application prospect.

Description

[0001] This application claims the priority of Chinese Patent Application No. 2023116045622 with an application date of November 28, 2023. This application incorporates the entire text of the above-mentioned Chinese patent application by reference. Technical Field

[0002] The present invention relates to a method for deuterating C(sp 2 )-H bonds in a benzene ring. Background Art

[0003] Isotope labeling technology plays an important role in the development of products such as new drugs and pesticides. Deuterium atom (D) is a stable isotope of hydrogen atom (H), without radioactivity, and its natural abundance is about 0.0156%. Compared with other isotopes, D and H show a relatively large weight ratio. The mass of H atom is 1.008u, and the mass of D atom is 2.014u. The two-fold weight ratio makes the C-D bond have a lower vibration frequency and zero-point energy, so that the cleavage of C-D requires a higher activation energy compared with C-H. Therefore, H and D show obvious kinetic isotope effects (KIEs) in biochemical reactions. Pharmacologists utilize this effect. By deuterating drugs, it is possible to extend the action time of drugs in the body, reduce the dosage, improve the efficacy, and reduce toxic reactions, etc. Currently, deuterated drugs have become a hot research field in new drug research and development. Many pharmaceutical companies at home and abroad are actively researching and developing new deuterated drugs. In April 2017, the US Food and Drug Administration (FDA) approved the world's first deuterated drug - Deuterabenazine tablets (An Taitan) for marketing. In addition, Donafenib mesylate was approved for marketing in China in June 2022, becoming the first deuterated anti-tumor drug approved for marketing in China. The successful development of deuterated drugs has also attracted great attention from global pharmacologists and pharmaceutical companies to the deuteration technology related to drugs.

[0004] Traditional methods for deuterating C(sp 2 )-H bonds in a benzene ring require pre-halogenation pre-activation or introduction of a directing group in the substrate, and also require 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, visible light reaction strategies have developed rapidly due to mild reaction conditions, environmental friendliness, etc. However, current research mainly focuses on the deuteration of C(sp 3 )-H bonds, and there is no research report on achieving the deuteration of C(sp 2 )-H bonds in a benzene ring through visible light reaction strategies. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to overcome the lack of a photocatalytic reaction to achieve the deuteration of C(sp2 ) - H direct hydrogen-deuterium exchange defects, thus providing a method for deuterating C(sp 2 ) - H bonds in the benzene ring. Under the action of phenol, base, deuterium source and light, the deuteration of C(sp 2 ) - H bonds in the benzene ring is achieved in a one-step reaction. The preparation method of this application has high yield, few by-products, wide substrate scope, good functional group compatibility and mild reaction conditions.

[0006] The present invention provides a method for deuterating C(sp 2 ) - H bonds in the benzene ring, which comprises the following steps: in a solvent, under the conditions of phenol, base and visible light irradiation, subjecting substance A to a deuteration reaction with a deuterium source to obtain substance B;

[0007] The said substance A contains an aromatic group, and the said aromatic group contains one or more fragments I, and the said fragment I is The H in the said fragment I is H with natural abundance;

[0008] The said aromatic group is an aryl group,

[0009] X and Y are each independently NH, O or S; Z is N or CH;

[0010] Part or all of the said fragment I is converted into the said fragment II, and the said fragment II is Among the H in the said fragment II, the abundance of D is greater than the natural abundance of D;

[0011] The said aromatic group is not directly connected to a halogen;

[0012] The said phenol is

[0013] Ring A is C 6-14 An aryl group or a 5-10 membered heteroaryl group; the heteroatoms in the said 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1-4;

[0014] R 1 Are each independently H, C 1-10 An alkyl group, -OR 1a 、-NO 2 、-(C=O)R 1b 、-NR 1c R 1d 、C 6-14 An aryl group, a 5-10 membered heteroaryl group, a C 1e Substituted by one or more R 1-10 An alkyl group, a C 1f Substituted by one or more R 6-14 An aryl group, or a C substituted by one or more R1g Substituted 5- to 10-membered heteroaryl; the 5- to 10-membered heteroaryl and one or more R 1g The heteroatoms in the substituted 5- to 10-membered heteroaryl are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4;

[0015] m is 1, 2, 3, 4, or 5;

[0016] R 1a and R 1b are independently H or C 1-10 alkyl;

[0017] R 1c and R 1d are independently H, C 6-14 aryl, or C 1a-1 aryl substituted with one or more substituted R 6-14 ;

[0018] R 1e 、R 1f and R 1g are each independently -OH, C 1-10 alkyl, NR 1a-2 R 1a-3 、-(C=O)R 1a-4 or -CN;

[0019] R 1a-1 、R 1a-2 、R 1a-3 and R 1a-4 are independently H or C 1-10 alkyl.

[0020] 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 remaining group (i.e., the substituents other than the above aromatic groups) fragment of the substance A remains unchanged.

[0021] In the present invention, the above H is the H connected to the sp2 hybridized carbon.

[0022] In one embodiment, the substance A contains one or more of the above 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 fragment.

[0023] In one embodiment, in the substance A, the fragment I is a fragment of the following groups: the aryl, wherein the aryl, optionally attached to C 3-15Cycloalkyl or C 3-15 fused with heteroalkyl, wherein the C 3-15 in the heteroalkyl has one or more heteroatoms selected from N, O, and S, and the number of heteroatoms is 1 - 4.

[0024] In one embodiment, the solvent is a conventional solvent for such reactions in the art. Preferably, the solvent is an organic solvent or an inorganic solvent. Examples of the inorganic solvent include water, and examples of the organic solvent include one or more of alkane solvents, ether solvents, nitrile solvents, amine solvents, and sulfoxide solvents. Preferably, the solvent is an ether solvent (such as tetrahydrofuran).

[0025] Examples of the alkane solvents include n - hexane, cyclohexane, n - heptane, n - pentane, or petroleum ether.

[0026] Examples of the ether solvents include tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, isopropyl ether, 1,4 - dioxane, or methyl tert - butyl ether. Preferably, the ether solvents are tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, 1,4 - dioxane, or methyl tert - butyl ether.

[0027] Examples of the nitrile solvents include acetonitrile.

[0028] Examples of the amine solvents include ethylenediamine, N,N - dimethylformamide, or N,N - dimethylacetamide. Preferably, the amine solvents are ethylenediamine or N,N - dimethylformamide.

[0029] The sulfoxide solvent is preferably dimethyl sulfoxide.

[0030] 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.

[0031] In one embodiment, in the phenol, R 1 are each independently H, C 1-10 alkyl, - OR 1a , - NO 2 , -(C = O)R 1b , - NR 1c R 1d , C 6-14 aryl, 5 - 10 - membered heteroaryl, C 1e alkyl substituted by one or more R 1-10 or C 1f aryl substituted by one or more R 6-14 , 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.

[0032] In one embodiment, in the phenol, m is 1, 2, or 3.

[0033] In one embodiment, R 1c and R 1d are independently H or a C 1a-1 aryl substituted with one or more R 6-14 groups.

[0034] In one embodiment, in ring A, the C 6-14 aryl is phenyl, naphthyl, anthracenyl or phenanthryl.

[0035] In one embodiment, in ring A, the 5- to 10-membered heteroaryl is a 5- to 6-membered heteroaryl. In the 5- to 10-membered heteroaryl, the heteroatom is preferably N, and the number of heteroatoms is preferably 1. For example, the 5- to 10-membered heteroaryl is

[0036] In one embodiment, in R 1 , the C 1-10 alkyl and the C 1e alkyl substituted with one or more R 1-10 groups are each independently a C 1-10 straight-chain or branched-chain alkyl or a C 1-6 straight-chain alkyl. The C 7-10 straight-chain or branched-chain alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl (e.g., methyl, tert-butyl). The C 1-6 straight-chain alkyl is, for example, n-heptyl, n-octyl, n-nonyl or n-decyl (e.g., n-heptyl). 7-10 The C

[0037] In one embodiment, in R 1 , the C 6-14 aryl and the C 1f aryl substituted with one or more R 6-14 groups are each independently phenyl, naphthyl, anthracenyl or phenanthryl, for example, phenyl or anthracenyl. 6-14 In one embodiment, in R

[0038] , the 5- to 10-membered heteroaryl and the 5- to 10-membered heteroaryl substituted with one or more R 1 groups are each independently a 5- to 9-membered heteroaryl. In the 5- to 10-membered heteroaryl, the heteroatom is preferably N, and the number of heteroatoms is preferably 1 or 2. For example, 1g In one embodiment, R

[0039] In one embodiment, 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 alkyl groups are each independently a C 1-6 linear or branched alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl (such as methyl, tert-butyl).

[0040] In one embodiment, R 1c and R 1d In, the C 6-14 aryl group and the C 1a-1 aryl group substituted by one or more substituents R 6-14 are each independently phenyl, naphthyl, anthryl or phenanthryl, such as phenyl. 6-14 For example, the aryl group is phenyl, naphthyl, anthryl or phenanthryl, such as phenyl.

[0041] In one embodiment, the phenol is any of the following compounds:

[0042]

[0043]

[0044]

[0045] 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-phenanthrol, 9,10-anthracenediol, 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'-biphenyldiol, 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.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, triethylmethylmethylammonium carbonate, tributylmethylmethylammonium 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-dimethylpyridine, 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 (DBU), tetramethylguanidine, tetramethylethylenediamine, N-methylmorpholine, N,N,N',N'',N''-pentamethyldiethylenetriamine or phosphazene base, such as 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.

[0046] In one embodiment, the base is an organic base or an inorganic base. The cation in the inorganic base can be an alkali metal (such as Na + , Li + , K + or Cs + ), and the anion is carbonate, bicarbonate, hydroxide or phosphate. The organic base can be an alkoxide, quaternary ammonium salt, phosphazene-based basic compound or amidine-based basic compound of an alkali metal (such as Na + , Li + , K + or Cs + ), preferably an alkoxide of an alkali metal (such as Na + , Li + , K + or Cs + ), a carbonate of an alkali metal (such as Na + , Li + , K + or Cs + ), a bicarbonate of an alkali metal (such as Na + , Li + , K + or Cs + ) or a bicarbonate of an alkali metal (such as Na + , Li + , K + or Cs +) Hydroxide. Further preferably, the inorganic base can be potassium tert-butoxide, potassium carbonate, cesium carbonate, potassium hydroxide, sodium carbonate, potassium phosphate or cesium hydroxide; the organic base can 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.

[0047] In one embodiment, the light intensity of the visible light is the conventional light intensity for such reactions in the art, for example, 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.

[0048] In one embodiment, the light intensity of the visible light is the conventional light intensity for such reactions in the art, for example, 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 220 lux.

[0049] In one embodiment, the light intensity per unit volume ratio of the light intensity and the solvent volume is conventional for such reactions in the art. Those skilled in the art can select an appropriate light intensity according to the reaction scale, preferably 20 - 1500 lux / mL, such as 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, 105 lux / mL, 35 lux / mL, 160 / 3 lux / mL, 60 lux / mL, 650 / 6 lux / mL, 130 lux / mL, 175 lux / mL, 750 lux / mL, 70 / 4 lux / mL, 44 lux / mL, 90 lux / mL, 210 / 4 lux / mL, 350 / 4 lux / mL, 175 lux / mL, 225 lux / mL, 250 lux / mL, 150 lux / mL, 275 lux / mL or 44 lux / mL.

[0050] In one embodiment, the light source of the visible light 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).

[0051] In one embodiment, the visible light source is an incandescent lamp or an energy-saving lamp (e.g., an LED lamp).

[0052] In one embodiment, 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, 525 nm.

[0053] In one embodiment, the deuterium source is conventional in the art. For example, the deuterium source is R D -OD, where R D is H, D, C 3-10 cycloalkyl, C 1-6 alkyl or C 1-6 alkyl substituted by one or more (e.g., 2 - 13) D.

[0054] In one embodiment, in the deuterium source, the C 1-6 alkyl and the C 1-6 alkyl substituted by one or more D in the C 1-6 alkyl are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl.

[0055] In one embodiment, in the deuterium source, the C 3-10 cycloalkyl is C 3-6 cycloalkyl, such as cyclopropyl, cyclobutyl or cyclopentyl.

[0056] In one embodiment, the deuterium source is EtOD, MeOD, iPrOD, tBuOD, CD 3 OD, D 2 O or CD 3 CD 2 OD.

[0057] In one embodiment, the phenol and the base are used in the form of a phenolate. The base can be an inorganic base, and the phenolate can be the sodium salt of the phenol.

[0058] In one embodiment, the raw materials for the deuteration reaction are (under the light irradiation condition) the solvent, the phenol, the base, the substance A and the deuterium source.

[0059] In one embodiment, the substance A is a compound represented by Formula I;

[0060]

[0061] Among them, n is an integer from 0 to 10;

[0062] Ring B is a C 6-20 aryl or heteroaryl, and the C 6-20 aryl and heteroaryl are optionally fused with one or both of a C 3-15 heterocycloalkyl and a C 3-15 cycloalkyl; wherein, the C 3-15 heteroatoms in the heterocycloalkyl are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4;

[0063] In ring B, the heteroaryl is

[0064] X and Y are each independently NH, O, or S; Z is N or CH;

[0065] R 2 are each independently a C 1 -C 15 alkyl, a C 2-1 alkyl substituted with one or more R 1 -C 15 alkyl, a C 1 -C 15 alkoxy, a C 2-4 alkoxy substituted with one or more R 1 -C 15 alkoxy, a C 3-10 heterocycloalkyl, or a C 2-11 heterocycloalkyl substituted with one or more R 3-10 heterocycloalkyl, or ring C; the C 3-10 heteroatoms in the heterocycloalkyl are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4;

[0066] Ring C is a C 6-20 aryl,

[0067] X 1 and Y 1 are each independently NH, O, or S; Z 1 is N or CH;

[0068] R 2-1 and R 2-4 are each independently a hydroxyl group, a C 3-10 heterocycloalkyl, -NR 2-1-1 R 2-1-2 、a carboxyl group, an amide group (-CONH 2 ), -S-C 1 -C 15 alkyl, -O-C 1 -C 15An alkyl group, ring D, or a C 2-1-5 substituted by one or more Rs 3-10 heterocycloalkyl group, wherein the C 3-10 in the heterocycloalkyl group has one or more heteroatoms selected from N, O, and S, and the number of heteroatoms is 1-4;

[0069] Ring D is a C 6-20 aryl group,

[0070] X 2 and Y 2 are each independently NH, O, or S; Z 2 is N or CH;

[0071] R 2-11 are each independently a C 1 -C 15 alkyl group or a C 2-11-1 substituted by one or more Rs 1 -C 15 alkyl group;

[0072] R 2-1-1 and R 2-1-2 are each independently H, a C 1 -C 15 alkyl group, or -C 1 -C 15 alkyl group - O - R 2-1-1a ;

[0073] R 2-1-1a is a C 6-20 aryl group or a C 2-1-1b substituted by one or more Rs 6-20 aryl group;

[0074] R 2-1-1b are each independently -S-C 1 -C 15 alkyl group or -O-C 1 -C 15 alkyl group;

[0075] R 2-11-1 are each independently a hydroxyl group or -O-R 2-11-1a ;

[0076] R 2-11-1a is a 5-15 membered heteroaryl group or a 5-15 membered heteroaryl group substituted by one or more Rs 2-11-1b ;

[0077] R 2-11-1b are each independently an oxo group (=O) or a C 1 -C 6 alkyl group;

[0078] R2-1-5 Each independently is C 1 -C 6 alkyl or C 2-1-6a alkyl substituted by one or more R 1 -C 6 alkyl;

[0079] R 2-1-6a Each independently is an amide group, a carboxyl group or ring E;

[0080] Ring E is C 6-20 aryl,

[0081] X 3 and Y 3 Each independently is NH, O or S; Z 3 is N or CH;

[0082] Said fragment I is a fragment in the aryl or heteroaryl in ring B, ring C, ring D or ring E.

[0083] In one embodiment, said substance A is a compound represented by formula I;

[0084]

[0085] wherein, n is an integer from 0 to 10;

[0086] Ring B is C 6-20 aryl or heteroaryl, and said C 6-20 aryl and heteroaryl are optionally fused with one or two of C 3-15 heterocycloalkyl and C 3-15 cycloalkyl; wherein, said C 3-15 the heteroatoms in the heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4;

[0087] In ring B, said heteroaryl is

[0088] X and Y each independently are NH, O or S; Z is N or CH;

[0089] R 2 Each independently is C 1 -C 15 alkyl, C 2-1 alkyl substituted by one or more R 1 -C 15 alkyl, C 2-4 alkyl substituted by one or more R 1 -C 15 alkoxy or C 2-11 heterocycloalkyl substituted by one or more R 3-10 said C3-10 The heteroatom in the heterocycloalkyl is selected from one or more of N, O, and S, and the number of heteroatoms is 1 - 4;

[0090] R 2-1 and R 2-4 are each independently a hydroxyl group, C 3-10 heterocycloalkyl, -NR 2-1-1 R 2-1-2 , an amide group (-CONH 2 ), -S-C 1 -C 15 alkyl, ring D, or a C 2-1-5 heterocycloalkyl substituted with one or more R 3-10 , wherein the heteroatom in the C 3-10 heterocycloalkyl is selected from one or more of N, O, and S, and the number of heteroatoms is 1 - 4;

[0091] Ring D is a C 6-20 aryl;

[0092] R 2-11 are each independently a C 2-11-1 alkyl substituted with one or more R 1 -C 15 alkyl;

[0093] R 2-1-1 and R 2-1-2 are each independently H, C 1 -C 15 alkyl, or -C 1 -C 15 alkyl - O - R 2-1-1a ;

[0094] R 2-1-1a are each independently a C 2-1-1b aryl substituted with one or more R 6-20 ;

[0095] R 2-1-1b are each independently -O - C 1 -C 15 alkyl;

[0096] R 2-11-1 are each independently -O - R 2-11-1a ;

[0097] R 2-11-1a is a 5 - 15 - membered heteroaryl substituted with one or more R 2-11-1b ;

[0098] R 2-11-1b are each independently an oxo group (=O);

[0099] R2-1-5 Each independently is a C 2-1-6a alkyl group substituted by one or more R 1 -C 6 alkyl;

[0100] R 2-1-6a Each independently is an amide group, a carboxyl group or ring E;

[0101] Ring E is a C 6-20 aryl;

[0102] Said fragment I is a fragment in the aryl or heteroaryl in ring B, ring D or ring E.

[0103] In one embodiment, said substance A is a compound represented by formula I;

[0104]

[0105] wherein, n is an integer from 0 to 10;

[0106] Ring B is a C 6-20 aryl or heteroaryl, and said C 6-20 aryl and heteroaryl are optionally fused with one or two of C 3-15 heterocycloalkyl and C 3-15 cycloalkyl; wherein, said C 3-15 the heteroatoms in the heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 - 4;

[0107] In ring B, said heteroaryl is

[0108] X is NH, O or S; Z is N or CH;

[0109] R 2 Each independently is a C 2-1 alkyl group substituted by one or more R 1 -C 15 alkyl or a C 2-4 alkyl group substituted by one or more R 1 -C 15 alkoxy;

[0110] R 2-1 and R 2-4 Each independently is a hydroxyl group, a C 3-10 heterocycloalkyl, -NR 2-1-1 R 2-1-2 、ring D or a C 2 -1-5 heterocycloalkyl group substituted by one or more R 3-10 wherein, said C 3-10 the heteroatoms in the heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 - 4;

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

[0112] R 2-1-1 and R 2-1-2 are each independently H or C 1 -C 15 alkyl;

[0113] R 2-1-5 are each independently C 2-1-6a substituted by one or more R 1 -C 6 alkyl;

[0114] R 2-1-6a are each independently an amide group or ring E;

[0115] Ring E is C 6-20 aryl;

[0116] Said fragment I is a fragment in the aryl or heteroaryl in ring B, ring D or ring E.

[0117] In one embodiment, said substance A is a compound of formula I;

[0118]

[0119] wherein, n is an integer from 0 to 10;

[0120] Ring B is C 6-20 aryl or heteroaryl, and said C 6-20 aryl and heteroaryl are optionally fused with one or two of C 3-15 heterocycloalkyl and C 3-15 cycloalkyl; wherein, said C 3-15 the heteroatoms in the heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4;

[0121] Said heteroaryl is

[0122] X and Y are each independently NH, O or S; Z is N or CH;

[0123] R 2 are each independently C 1 -C 15 alkyl, C 3-10 cycloalkyl, C 2-1 substituted by one or more R 1 -C 15 alkyl, C 1 -C 15 alkoxy, -NR 2-2 R 2-3, by one or more R 2-4 Substituted C 1 -C 15 Alkoxy, C 3-10 Heterocycloalkyl, C 1 -C 15 Alkylthio, substituted by 1 or more R 2-7 Substituted C 1 -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;

[0124] 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, C 1 -C 15 Alkyl, -SC 1 -C 15 Alkyl, -OC 1 -C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or 1 or more R 2-1-4 Substituted C 1 -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;

[0125] R 2-2 and R 2-3 Each independently is H or C 1 -C 15 alkyl;

[0126] R 2-5 , R 2-6 , R 2-8 , R 2-9 and R 2-10 Each independently is H or C 1 -C 15 alkyl;

[0127] R 2-11 Each independently is C 1 -C 15 Alkyl or 1 or more R 2-11-1 Substituted C1 -C 15 alkyl;

[0128] R 2-1-1 and R 2-1-2 are each independently H, C 1 -C 15 alkyl, carbonyl-C 1 -C 15 alkyl or carbonyl-C 1 -C 15 alkoxy;

[0129] R 2-1-3 , R 2-11-1 and R 2-1-4 are each independently -NH 2 , hydroxy or cyano;

[0130] Said fragment I is a fragment in the aryl or heteroaryl in Ring B.

[0131] In one embodiment, said Substance A is a compound of Formula I;

[0132]

[0133] wherein, n is an integer from 0 to 10;

[0134] Ring B is a C 6-20 aryl or heteroaryl, and said C 6-20 aryl and heteroaryl are optionally fused with one or two of a C 3-15 heterocycloalkyl and a C 3-15 cycloalkyl; wherein, the heteroatom in said C 3-15 heterocycloalkyl is selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4;

[0135] Said heteroaryl is

[0136] X and Y are each independently NH, O or S; Z is N or CH;

[0137] R 2 are each independently C 1 -C 15 alkyl, C 3-10 cycloalkyl, C 2-1 -C 1 alkyl substituted with one or more R 15 -C 1 alkoxy, -NR 15 R 2-2 R 2-3 , C 2-4 -C 1 alkyl substituted with one or more R 15Alkoxy, C 3-10 heterocycloalkyl, C 1 -C 15 alkylthio, substituted by one or more R 2-11 substituted C 3-10 heterocycloalkyl or said C 3-10 The heteroatoms of the heterocycloalkyl are selected from one or more of N, O, and S, and the number of heteroatoms is 1-4;

[0138] R 2-1 and R 2-4 are each independently hydroxy, C 3-10 cycloalkyl, 5-15-membered heteroaryl, -NR 2-1-1 R 2-1-2 、carboxyl, C 1 -C 15 alkyl, -S-C 1 -C 15 alkyl, -O-C 1 -C 15 alkyl, substituted by one or more R 2-1-3 substituted C 3-10 cycloalkyl or substituted by one or more R 2-1-4 substituted C 1 -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;

[0139] R 2-2 and R 2-3 are each independently H;

[0140] R 2-5 、R 2-6 、R 2-8 、R 2-9 and R 2-10 are each independently C 1 -C 15 alkyl;

[0141] R 2-11 are each independently substituted by one or more R 2-11-1 substituted C 1 -C 15 alkyl;

[0142] R 2-1-1 and R 2-1-2 are each independently H, C 1 -C 15 alkyl, carbonyl-C 1 -C 15 alkyl or carbonyl-C 1 -C 15Alkoxy group;

[0143] R 2-1-3 and R 2-1-4 are each independently a hydroxyl group;

[0144] Said fragment I is a fragment in the aryl or heteroaryl in ring B.

[0145] In one embodiment, substance A does not contain an electron-withdrawing substituent, for example, said electron-withdrawing substituent is a halogen or an ester group.

[0146] In one embodiment, substance A is not said phenol.

[0147] In one embodiment, in substance A, said aromatic group is not directly connected to a halogen and / or a hydroxyl group, for example, said aryl group is not directly connected to a halogen and / or a hydroxyl group.

[0148] In one embodiment, in said aromatic group, said aryl group is a C 6-20 aryl group, for example, a C 6-14 aryl group (such as phenyl, naphthyl, anthryl or phenanthryl).

[0149] 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%.

[0150] In one embodiment, in substance B, the abundance of D in fragment II is 0.5%-100%, for example, 97%, 95%, 96%, 90%, 85%, 70%, 56%, 31%, 42%, 5%, 10% or 19%.

[0151] In one embodiment, in the compound shown in formula I, n is an integer from 0 to 6, for example, 1, 2, 3, 4 or 5.

[0152] In one embodiment, in the compound shown in formula I, R 2 are each independently a C 1 -C 15 alkyl group, a C 3-10 cycloalkyl group, a C 2-1 -C 1 alkyl group substituted by one or more R 15 groups, a C 1 -C 15 alkoxy group, -NR 2-2 R 2-3 group, a C 2-4 -C 1 alkoxy group substituted by one or more R 15 groups, a C 3-10 heterocycloalkyl group, substituted by one or more R2-7 Substituted C 1 -C 15 alkylthio, C substituted by one or more R 2-11 Substituted C 3-10 heterocycloalkyl or said C 3-10 The heteroatoms of the heterocycloalkyl are selected from one or more of N, O, and S, and the number of heteroatoms is 1-4.

[0153] In one embodiment, in ring B, the heteroaryl is

[0154] In one embodiment, R 2 are each independently C 1 -C 15 alkyl, C 3-10 cycloalkyl, C substituted by one or more R 2-1 Substituted C 1 -C 15 alkyl, C 1 -C 15 alkoxy, -NR 2-2 R 2-3 , C substituted by one or more R 2-4 Substituted C 1 -C 15 alkoxy, C 3-10 heterocycloalkyl, C 1 -C 15 alkylthio, C substituted by one or more R 2-11 Substituted C 3-10 heterocycloalkyl or said C 3-10 The heteroatoms of the heterocycloalkyl are selected from one or more of N, O, and S, and the number of heteroatoms is 1-4.

[0155] In one embodiment, R 2 are each independently C 1 -C 15 alkyl, C substituted by one or more R 2-1 Substituted C 1 -C 15 alkyl, C substituted by one or more R 2-4 Substituted C 1 -C 15 alkoxy or C substituted by one or more R 2-11 Substituted C 3-10 heterocycloalkyl; said C 3-10 The heteroatoms of the heterocycloalkyl are selected from one or more of N, O, and S, and the number of heteroatoms is 1-4.

[0156] In one embodiment, R 2 are each independently C substituted by one or more R2-1 Substituted C 1 -C 15 alkyl or C 2 -4 substituted by one or more R 1 -C 15 alkoxy.

[0157] In one embodiment, n is an integer from 0 to 10, and ring B is C 6-20 aryl;

[0158] R 2 are each independently C 1 -C 15 alkyl, C 1 -C 15 alkoxy or C 1 -C 15 alkylthio.

[0159] In one embodiment, R 2-1 , R 2-4 and R 2-7 are each independently hydroxy, C 3-10 cycloalkyl, 5- to 15-membered heteroaryl, -NR 2 -1-1 R 2-1-2 , carboxyl, C 1 -C 15 alkyl, -S-C 1 -C 15 alkyl, C 2-1-3 substituted by one or more R 3-10 cycloalkyl or C 2-1-4 substituted by one or more R 1 -C 15 alkyl; the heteroatoms in the 5- to 15-membered heteroaryl are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4.

[0160] In one embodiment, R 2-1 and R 2-4 are each independently hydroxy, C 3-10 heterocycloalkyl, -NR 2-1-1 R 2-1-2 , amido (-CONH 2 ), -S-C 1 -C 15 alkyl, ring D or C 2-1-5 substituted by one or more R 3-10 heterocycloalkyl, wherein the C 3-10 heterocycloalkyl has heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4.

[0161] In one embodiment, R2-1 and R 2-4 are each independently a hydroxyl group, C 3-10 heterocycloalkyl, -NR 2-1-1 R 2-1-2 , ring D or C 2-1-5 heterocycloalkyl substituted by one or more R 3-10 wherein, in the C 3-10 heterocycloalkyl, the heteroatoms are selected from one or more of N, O, and S, and the number of heteroatoms is 1 - 4.

[0162] In one embodiment, ring D is C 6-20 aryl.

[0163] In one embodiment, R 2-2 and R 2-3 are each independently H.

[0164] In one embodiment, R 2-5 , R 2-6 , R 2-8 , R 2-9 and R 2-10 are each independently C 1 -C 15 alkyl.

[0165] In one embodiment, R 2-11 are each independently C 2-11-1 alkyl substituted by one or more R 1 -C 15 alkyl.

[0166] In one embodiment, R 2-1-1 and R 2-1-2 are each independently H or C 1 -C 15 alkyl.

[0167] In one embodiment, R 2-1-3 , R 2-11-1 and R 2-1-4 are each independently a hydroxyl group.

[0168] In one embodiment, R 2-1-1a is C 2-1-1b aryl substituted by one or more R 6-20 aryl.

[0169] In one embodiment, R 2-1-1b are each independently -O-C 1 -C 15 alkyl.

[0170] In one embodiment, R 2-11-1 are each independently -O-R 2-11-1a .

[0171] In one embodiment, R 2-11-1a is a 5- to 15-membered heteroaryl group substituted by one or more R 2-11-1b groups.

[0172] In one embodiment, R 2-11-1b are each independently an oxo group (=O).

[0173] In one embodiment, R 2-1-5 are each independently a C 2-1-6a -C 1 alkyl group substituted by one or more R 6 groups.

[0174] In one embodiment, R 2-1-6a are each independently an amide group or ring E.

[0175] In one embodiment, ring E is a C 6-20 aryl group.

[0176] In one embodiment, in ring B, the C 6-20 aryl group is a C 6-14 aryl group; preferably phenyl, naphthyl, anthracenyl or phenanthryl, such as phenyl, naphthyl or anthracenyl.

[0177] In one embodiment, the C 3-15 cycloalkyl group is a C 3-6 monocyclic cycloalkyl group or a C 9-15 polycyclic cycloalkyl group, the C 3-6 monocyclic cycloalkyl group such as cyclopropyl, cyclobutyl, cyclohexyl (such as ) or cyclopentyl (such as ), the C 9-15 polycyclic cycloalkyl group such as dodecahydro-1H-cyclopenta[a]naphthyl (such as ).

[0178] In one embodiment, the C 3-15 heterocycloalkyl group is a C 3-6 monocyclic heterocycloalkyl group or a C 9-15 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 monocyclic heterocycloalkyl group is oxetanyl, oxolanyl (such as ) or oxanyl, the C 9-15 polycyclic cycloalkyl group such as decahydroquinolinyl (such as )

[0179]

[0180] In one embodiment, in R 2 , the C 1-C 15 alkyl and C substituted by one or more R 2-1 -C 1 -C 15 In the alkyl, C 1 -C 15 Each of the alkyls is independently a straight-chain or branched-chain C 1 -C 15 alkyl, such as 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, or again such as 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.

[0181] In one embodiment, R 2 、R 2-1 、R 2-4 and R 2-7 In, the C 3-10 cycloalkyl and C substituted by one or more R 2-1-3 -C 3-10 In the cycloalkyl, C 3-10 Each of the cycloalkyls is independently a C 3-6 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or again such as cyclohexyl.

[0182] In one embodiment, R 2 、R 2-1-1 and R 2-1-2 In, the C 1 -C 15 alkoxy, C substituted by one or more R 2-4 -C 1 -C 15 alkoxy, carbonyl-C 1 -C 15 In the alkoxy, C 1 -C 15 Each of the alkoxys is independently a C 1 -C 6 alkoxy, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentyloxy or n-hexyloxy, or again such as methoxy, ethoxy, n-propoxy, n-butoxy or tert-butoxy.

[0183] In one embodiment, R 2 In, the C 3-10 heterocycloalkyl and C substituted by one or more R 2-11 -C 3-10 In the heterocycloalkyl, C 3-10 Each of the heterocycloalkyls is independently a C3-6 heterocycloalkyl, wherein the C 3-10 In the heterocycloalkyl, the heteroatom is preferably N, and the number of heteroatoms is preferably 1 or 2. For example, it is

[0184] In one embodiment, R 2 wherein the C 1 -C 15 alkylthio, C substituted with one or more R 2-7 In the substituted C 1 -C 15 In the alkylthio, the C 1 -C 15 alkylthios are each independently C 1 -C 6 alkylthio, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio, n-pentylthio or n-hexylthio, and again such as tert-butylthio.

[0185] In one embodiment, R 2-1 , R 2-4 and R 2-7 wherein the 5- to 15-membered heteroaryl is a 5- to 6-membered heteroaryl. In the 5- to 15-membered heteroaryl, the heteroatom is preferably N, and the number of heteroatoms is preferably 1. For example, the 5- to 15-membered heteroaryl is pyridyl (for example ).

[0186] In one embodiment, R 2-1 and R 2-4 wherein the C 3-10 heterocycloalkyl and the C substituted with one or more R 2-1-5 In the substituted C 3-10 heterocycloalkyl, the C 3-10 heterocycloalkyls are each independently C 3-6 heterocycloalkyl, wherein the C 3-10 heterocycloalkyl has a heteroatom preferably being N, and the number of heteroatoms is preferably 1 or 2. For example, it is

[0187] In one embodiment, 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 wherein the C 1 -C 15 alkyl, C substituted with one or more R2-1-4 Substituted C 1 -C 15 -alkyl, C-alkyl substituted by one or more R 2-11-1 -C 1 -alkyl, -S-C 15 -C 1 -alkyl, -O-C 15 -C 1 -alkyl and carbonyl-C 15 -C 1 -alkyl, the C in 15 -C 1 -alkyl, the C in 15 -alkyl are each independently C 1 -C 6 -alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, or methyl, ethyl, n-propyl, isopropyl, tert-butyl or n-pentyl.

[0188] In one embodiment, R 2-1-1 , R 2-1-2 and R 2-1-1b , the C in 1 -C 15 -alkyl, C 1 -C 15 -alkyl -O-R 2-1-1a , -S-C 1 -C 15 -alkyl and -O-C 1 -C 15 -alkyl, the C in 1 -C 15 -alkyl are each independently C 1 -C 6 -alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, or methyl or ethyl.

[0189] In one embodiment, R 2-1-1a , the C in 6-20 aryl and aryl substituted by one or more R 2-1-1b are each independently C 6-20 aryl, such as phenyl. 6-20 aryl 6-14 In one embodiment, R

[0190] , the 5-15 membered heteroaryl and 5-15 membered heteroaryl substituted by one or more R 2-11-1a in 5-15 membered heteroaryl are each independently 5-10 membered heteroaryl. In the 5-15 membered heteroaryl, the heteroatom is preferably N, and the number of heteroatoms is preferably 1. For example, the 5-15 membered heteroaryl is 2-11-1b ​

[0191] In one embodiment, R 2-11-1b and R 2-1-5 in which the C 1 -C 6 alkyl, C 2-1-6a -C 1 alkyl substituted by one or more R 6 in C 1 -C 6 alkyl are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl, such as methyl.

[0192] In one embodiment, the R 2 is methyl, -NH 2 ,

[0193] n-propyl,

[0194] In one embodiment, the R 2 is methyl, -NH 2 ,

[0195] n-propyl,

[0196] Alternatively, the R 2 is n-propyl, n-ethyl,

[0197] In one embodiment, the ring B is

[0198]

[0199] In one embodiment, the ring B is

[0200] In one embodiment, the substance A is any one of the following compounds:

[0201]

[0202]

[0203]

[0204] In one embodiment, the substance B is

[0205]

[0206] Among them, the percentage of each site (%) is independently the deuteration ratio of each site.

[0207] In one embodiment, the substance B is

[0208]

[0209]

[0210]

[0211] Among them, the percentage of each site (%) is independently the deuteration ratio of each site.

[0212] In one embodiment, in the deuteration reaction, the amount of the solvent used may not be specifically limited as long as it does not affect the progress of the reaction. The concentration of the substance A in the solvent may be a conventional concentration in this type of reaction in the art, preferably 0.05 - 0.75 mol / L, such as 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.

[0213] 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, such as 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.

[0214] 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, such as 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.

[0215] 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, such as 100:1, 150:1, 400:3, 500:3, 700:3, 800:3, 200:1, 250:1 or 300:1.

[0216] In one embodiment, the progress of the deuteration reaction can be detected by conventional methods in the art, such as monitoring by HNMR. Preferably, the disappearance of the signal of the C(sp 2 )-H bond in the substance A or the cessation of the reaction is taken as the end point of the reaction. 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.

[0217] In one embodiment, the deuteration reaction is carried out at the conventional reaction temperature for such reactions in the art, such as -20°C - 80°C, preferably 0°C - 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.

[0218] In one embodiment, the deuteration reaction preferably further includes the following post-treatment steps: after the reaction is completed, quench the reaction (such as adding water to quench the reaction), extract with an organic solvent (such as ethyl acetate), wash (such as washing with water and saturated sodium chloride solution in sequence), dry (preferably drying with anhydrous sodium sulfate), and purify (such as column chromatography) to obtain substance B.

[0219] In one embodiment, the deuteration reaction is carried out in a protective gas, such as nitrogen.

[0220] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere, mix the phenol, the substance A, the deuterium source, the base and the solvent, and carry out the deuteration reaction under light irradiation conditions; preferably, after the reaction is completed, quench the reaction (such as adding water to quench the reaction), extract with an organic solvent (such as ethyl acetate), wash (such as washing with water and saturated sodium chloride solution in sequence), dry (preferably drying with anhydrous sodium sulfate), and purify (such as column chromatography) to obtain substance B.

[0221] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere, in the above-mentioned ether solvents (such as diethyl ether, tetrahydrofuran, 1,4-dioxane or methyl tert-butyl ether), in the presence of 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 irradiation with a wavelength of 380 - 600 nm, carry out the deuteration reaction of substance A with the above-mentioned deuterium source (such as EtOD) to obtain substance B.

[0222] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere, under visible light irradiation with an intensity of 350 lux to 420 lux, mix tetrahydrofuran, 2,6-di-tert-butyl-4-phenylphenol, phosphazene base, substance A and MeOD, and carry out the deuteration reaction to obtain substance B.

[0223] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation 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.

[0224] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation with an illumination intensity of 200 lux, 1,4-dioxane, 3-hydroxy-2-phenylpyridine, cesium carbonate, substance A and CD 3 OD are mixed to carry out a deuteration reaction to obtain substance B.

[0225] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation with an illumination intensity of 2000 lux, tetrahydrofuran, 3-((2,6-dimethylphenyl)amino)phenol, potassium hydroxide, substance A and CD 3 CD 2 OD are mixed to carry out a deuteration reaction to obtain substance B.

[0226] In one embodiment, the deuteration reaction comprises the following steps: under a nitrogen atmosphere and under visible light irradiation with an illumination intensity of 420 lux, diethyl ether, 2,6-di-tert-butyl-4-phenylphenol, potassium methoxide, substance A and CD 3 CD 2 OD are mixed to carry out a deuteration reaction to obtain substance B.

[0227] In one embodiment, the deuteration reaction comprises the following steps: in a solvent, under the conditions of a phenol, a base and visible light irradiation, substance A and a deuterium source are subjected to a deuteration reaction to obtain substance B;

[0228] Substance A contains an aromatic group, the aromatic group contains one or more fragments I, and the fragment I is The H in the fragment I is H with natural abundance;

[0229] The aromatic group is an aryl group,

[0230] X and Y are each independently NH, O or S; Z is N or CH;

[0231] Part or all of the fragment I is converted into the fragment II, and the fragment II is Among the H in the fragment II, the abundance of D is greater than the natural abundance of D;

[0232] The substance A does not contain the phenol; the aromatic group is not directly connected to a halogen and / or a hydroxyl group;

[0233] The phenol is

[0234] Ring A is a C 6-14 aryl or a 5- to 10-membered heteroaryl; the heteroatoms in the 5- to 10-membered heteroaryl are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4;

[0235] R 1 are each independently H, C 1-10 alkyl, -OR 1a , -NO 2 , -(C═O)R 1b , -NR 1c R 1d , C 6-14 aryl, 5- to 10-membered heteroaryl, C 1e alkyl substituted by one or more R 1-10 , C 1f aryl substituted by one or more R 6-14 , or 5- to 10-membered heteroaryl substituted by one or more R 1g ; the heteroatoms in the 5- to 10-membered heteroaryl and the 5- to 10-membered heteroaryl substituted by one or more R 1g are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4;

[0236] m is 1, 2, 3, 4, or 5;

[0237] R 1a and R 1b are independently H or C 1-10 alkyl;

[0238] R 1c and R 1d are independently H, C 6-14 aryl, or C 1a-1 aryl substituted by one or more substituted R 6-14 ;

[0239] R 1e , R 1f and R 1g are each independently -OH, C 1-10 alkyl, NR 1a-2 R 1a-3 , -(C═O)R 1a-4 or -CN;

[0240] R 1a-1 , R 1a-2 , R 1a-3 and R1a-4 Independently H or C 1-10 Alkyl group

[0241] In one embodiment, the deuteration reaction comprises the following steps: in a solvent, in the presence of a phenol, a base and visible light irradiation, subjecting substance A to a deuteration reaction with a deuterium source to obtain substance B;

[0242] The solvent is one or more of water, alkane solvents, ether solvents, nitrile solvents, amine solvents and sulfoxide solvents;

[0243] The base is an organic base or an inorganic base;

[0244] The said substance A contains an aromatic group, and the said aromatic group contains one or more fragments I, and the said fragment I is The H in the said fragment I is H with natural abundance;

[0245] The said substance A is a compound represented by formula I;

[0246]

[0247] Wherein, n is an integer from 0 to 10;

[0248] Ring B is C 6-20 Aryl or heteroaryl, and the said C 6-20 Aryl and heteroaryl are optionally fused with one or two of C 3-15 Heterocycloalkyl and C 3-15 Cycloalkyl; wherein, the said C 3-15 The heteroatoms in the heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4;

[0249] The said heteroaryl is

[0250] X and Y are each independently NH, O or S; Z is N or CH;

[0251] R 2 Each independently is C 1 -C 15 Alkyl group, C 3-10 Cycloalkyl, C substituted with one or more R 2-1 -C 1 Alkyl group, C 15 -C 1 Alkoxy group, -NR 15 R 2-2 R 2-3 、C substituted with one or more R 2-4 -C 1 Alkoxy group, C 15 Heterocycloalkyl, 3-10 ​ C 1 -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;

[0252] 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, C 1 -C 15 Alkyl, -SC 1 -C 15 Alkyl, -OC 1 -C 15 Alkyl, 1 or more R 2-1-3 Substituted C 3-10 Cycloalkyl or 1 or more R 2-1-4 Substituted C 1 -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;

[0253] R 2-2 and R 2-3 Each independently is H;

[0254] R 2-5 , R 2-6 , R 2-8 , R 2-9 and R 2-10 Each independently is C 1 -C 15 alkyl;

[0255] R 2-11 Each is independently controlled by one or more R 2-11-1 Substituted C 1 -C 15 alkyl;

[0256] R 2-1-1 and R 2-1-2 Each independently is H, C 1 -C 15 Alkyl, Carbonyl-C 1 -C 15 Alkyl or carbonyl-C 1 -C 15 Alkoxy;

[0257] R 2-1-3 and R 2-1-4 are each independently a hydroxyl group;

[0258] Said fragment I is a fragment in the aryl or heteroaryl in ring B;

[0259] Part or all of said fragment I is converted to said fragment II, and said fragment II is In the H of said fragment II, the abundance of D is greater than the natural abundance of D;

[0260] Said aromatic group is not directly connected to a halogen;

[0261] Said phenol is

[0262] Ring A is a C 6-14 aryl or a 5- to 10-membered heteroaryl; the heteroatoms in said 5- to 10-membered heteroaryl are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4;

[0263] R 1 are each independently H, C 1-10 alkyl, -OR 1a , -NO 2 , -(C=O)R 1b , -NR 1c R 1d C 6-14 aryl, 5- to 10-membered heteroaryl, C 1e substituted by one or more R 1-10 alkyl, C 1f substituted by one or more R 6-14 aryl, or 5- to 10-membered heteroaryl substituted by one or more R 1g ; the heteroatoms in said 5- to 10-membered heteroaryl and the 5- to 10-membered heteroaryl substituted by one or more R 1g are selected from one or more of N, O, and S, and the number of heteroatoms is 1 to 4;

[0264] m is 1, 2, 3, 4, or 5;

[0265] R 1a and R 1b are independently H or C 1-10 alkyl;

[0266] R 1c and R 1d are independently H, C 6-14 aryl, or C 1a-1 aryl substituted by one or more substituted R 6-14 ;

[0267] R1e , R 1f and R 1g are each independently -OH, C 1-10 alkyl, NR 1a-2 R 1a-3 , -(C=O)R 1a-4 or -CN;

[0268] R 1a-1 , R 1a-2 , R 1a-3 and R 1a-4 are independently H or C 1-10 alkyl;

[0269] The deuterium source is R D -OD, and R D is H, D, C 3-10 cycloalkyl, C 1-6 alkyl or C 1-6 alkyl substituted with one or more D.

[0270] In one embodiment, the deuteration reaction is carried out in a protective gas and an ether solvent, with 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%;

[0271] The phenol is Ring A is C 6-14 aryl, and R 1 are each independently C 1-10 alkyl or C 6-14 aryl;

[0272] The deuterium source is R D -OD, and the R D is C 1-6 alkyl;

[0273] The base is an organic base. The present invention provides a method for deuterating the C(sp 2 )-H bond in a benzene ring. The deuteration method comprises the following steps:

[0274] (1) Performing the above deuteration reaction on the substance A to obtain the substance B;

[0275] (2) Repeating the above deuteration reaction on the substance B.

[0276] In one embodiment, the number of repetitions is conventional in the art and can be adjusted by those skilled in the art according to the experimental purpose. For example, 1 - 3 times. Preferably, the deuteration method comprises the following steps: after the previous deuteration reaction is completed, under the above phenol, the above base, and the above visible light illumination conditions, reacting the substance B with the deuterium source in a deuteration reaction, and the experimental conditions and operations of the deuteration reaction can be as described in any one of the present invention.

[0277] Further preferably, in the repeated deuteration reaction process, the substance B undergoes deuteration reaction with or without purification. Without purification, it may include the following steps: after the previous deuteration reaction is completed, quench the reaction (such as adding water to quench the reaction), extract with an organic solvent (such as ethyl acetate), wash (such as washing with water and saturated sodium chloride solution in sequence), dry (preferably drying with anhydrous sodium sulfate), and then carry out the above deuteration reaction.

[0278] The present invention provides an application of a phenol as a photocatalyst for deuteration reaction;

[0279] The phenol is

[0280] wherein, ring A, R 1 and m are each independently as described in any one of the present invention; preferably, in the above application, the photocatalytic deuteration reaction is carried out under the action of the above base.

[0281] The present invention provides a substance X or a pharmaceutically acceptable salt thereof, and the substance X is wherein, the percentage of each site (%) is independently the deuteration ratio of each site.

[0282] Glossary:

[0283] Unless otherwise specified, the terms used in the present invention have the following meanings:

[0284] When a numerical range is listed, it is intended to include each value and sub-ranges within the range. For example, "C 1 ~C 15 " includes C 1 、C 2 、C 3 、C 4 、C 5 、C 6 、C 7 、C 8 、C 9 、C 10 、C 1 -C 6 、C 1 -C 5 、C 1 -C 4 、C 1 -C 3 、C 1 -C 2 、C 2 -C 6 、C 2 -C 5 、C 2-C 4 、 C 2 -C 3 、 C 3 -C 6 、 C 3 -C 5 、 C 3 -C 4 、 C 4 -C 6 、 C 4 -C 5 and C 5 -C 6 alkyl group.

[0285] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0286] The term "alkyl group" refers to a straight-chain or branched-chain alkyl group having a specified number of carbon atoms (e.g., C 1 ~ C 15 、 C 1 ~ C 10 or C 1 ~ C 6 ). The alkyl group 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.

[0287] The term "alkoxy group" refers to the group R X -O-, where R X is the alkyl group as defined above.

[0288] The term "alkylthio group" refers to the group R X -S-, where R X is the alkyl group as defined above.

[0289] The term "cycloalkyl group" refers to a saturated monocyclic group consisting only of carbon atoms and having a specified number of carbon atoms (e.g., C 3 ~ C 15 、 C 3 ~ C 10 or C 3 ~ C 6 ). The cycloalkyl group includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0290] The term "heterocycloalkyl" refers to a cyclic group having a specified number of ring atoms (e.g., 3 to 15-membered, 3 to 10-membered, or 3 to 6-membered), a specified number of heteroatoms (e.g., 1, 2, 3, or 4), and a specified type of heteroatoms (one or more of N, O, and S), which is monocyclic, bridged, or spiro, 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 spiro ring refers to a polycyclic ring in which one atom is shared between monocyclic rings. Heterocycloalkyl includes, but is not limited to, azetidinyl, azacyclohexyl, pyrrolidinyl, tetrahydrofuryl, morpholinyl, piperidinyl, etc.

[0291] The term "aryl" refers to a cyclic group having a specified number of carbon atoms (e.g., C 6 ~C 14 or C 6 ~C 20 ), which is composed only of carbon atoms, is monocyclic or polycyclic, and at least one ring has aromaticity (complies with Hückel's rule). An aryl is connected to other fragments in the molecule through an aromatic ring or a non-aromatic ring. Aryl includes, but is not limited to, phenyl, naphthyl, or etc.

[0292] The term "heteroaryl" refers to a cyclic group having a specified number of ring atoms (e.g., 5 to 20-membered or 5 - 10-membered), a specified number of heteroatoms (e.g., 1, 2, 3, or 4), and a specified type of heteroatoms (one or more of N, O, and S), which is monocyclic or polycyclic, and at least one ring has aromaticity (complies with Hückel's rule). A heteroaryl is connected to other fragments in the molecule through an aromatic ring or a non-aromatic ring. Heteroaryl includes, but is not limited to, furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, etc.

[0293] The "-" at the end of a group means that the group is connected to other fragments in the molecule through this site. For example, CH 3 -C(=O)- means acetyl.

[0294] In the structural fragment means that the structural fragment is connected to other fragments in the molecule through this site. For example, is cyclohexyl.

[0295] The term "plural" means 2, 3, 4, or 5.

[0296] The term "C 3 -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.

[0297] The term "ester group" is, for example, -C(=O)-O-alkyl, where alkyl is defined as the alkyl defined above.

[0298] When any variable (e.g., 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, a C 1-1 substituted by 3 R 6 ~C 10 aryl refers to C 6 ~C 10 aryl will be substituted by 3 R 1-1 , and the definitions of the 3 R 1-1 are independent of each other and do not affect each other.

[0299] The term "pharmaceutical excipient" refers to excipients and additives used in the production of drugs and the preparation of prescriptions, and is all substances contained in pharmaceutical preparations except for the active ingredients. For details, see the Pharmacopoeia of the People's Republic of China (2020 Edition) or Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009).

[0300] The term "pharmaceutically acceptable" means relatively non-toxic, safe, and suitable for use by patients.

[0301] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When a 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).

[0302] On the basis of not violating the common knowledge in the art, the above preferred conditions can be arbitrarily combined to obtain various preferred examples of the present invention.

[0303] The reagents and raw materials used in the present invention are all commercially available.

[0304] The positive and progressive effects of the present invention are as follows: The method for deuterating the C(sp 2 )-H bond in the aryl group provided by the present invention has a wide scope of application, mild reaction conditions, high deuteration efficiency, and broad application prospects. Detailed implementation manners

[0305] The present invention will be further described below by way of examples, but the present invention is not limited to the scope of the described examples. For the experimental methods without specific conditions in the following examples, they are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0306] Example 1

[0307]

[0308] Under a nitrogen atmosphere, the substrate 1 (0.30 mmol), a phenolic catalyst (using 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-anthracenediol or 2-tert-butyl-3,5-dimethylphenol, 10.0 mol%), and a base (potassium tert-butoxide, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 6.0 mL) and a deuterium source (EtOD, 60 mmol). After adding, the reaction mixture was placed at 45 °C and irradiated with a 405 nm LED (420 lux) lamp at a distance of 5 cm from the reaction device 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 combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 2 (the yield was 100% when using 2,6-di-tert-butyl-4-phenylphenol as the phenolic catalyst, 100% when using 2,6-di-tert-butyl-4-(9-anthryl)phenol as the phenolic catalyst, 99% when using 6-di-tert-butyl-4-heptylphenol as the phenolic catalyst, 98% when using 2,4,6-triphenylphenol as the phenolic catalyst, 95% when using 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol as the phenolic catalyst, 95% when using 9-phenanthrol as the phenolic catalyst, 98% when using 9,10-anthracenediol as the phenolic catalyst, 96% when using 2-tert-butyl-3,5-dimethylphenol as the phenolic catalyst, and the product purity was greater than 95%). 1 HNMR (400 MHz, CDCl 3 ): δ 7.30–7.26 (m, 0.12H (C 3 -H, C 5-H, deuterium substitution rate 94%), 0.18H (C) when using 2,6-di-tert-butyl-4-(9-anthryl)phenol as the phenolic catalyst 3 -H, C 5 -H, deuterium substitution rate 91%), 0.24H (C) when using 6-di-tert-butyl-4-heptylphenol as the phenolic catalyst 3 -H, C 5 -H, deuterium substitution rate 88%), 0.14H (C) when using 2,4,6-triphenylphenol as the phenolic catalyst 3 -H, C 5 -H, deuterium substitution rate 93%), 0.16H (C) when using 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol as the phenolic catalyst 3 -H, C 5 -H, deuterium substitution rate 92%), 0.24H (C) when using 9-phenanthrol as the phenolic catalyst 3 -H, C 5 -H, deuterium substitution rate 88%), 0.34H (C) when using 9,10-anthracenediol as the phenolic catalyst 3 -H, C 5 -H, deuterium substitution rate 83%), 0.30H (C) when using 2-tert-butyl-3,5-xylenol as the phenolic catalyst 3 -H, C 5 -H, deuterium substitution rate 85%)), 7.25–7.22 (m, 0.10H (C) when using 2,6-di-tert-butyl-4-phenylphenol as the phenolic catalyst 4 -H, deuterium substitution rate 90%), 0.13H (C) when using 2,6-di-tert-butyl-4-(9-anthryl)phenol as the phenolic catalyst 4 -H, deuterium substitution rate 87%), 0.16H (C) when using 6-di-tert-butyl-4-heptylphenol as the phenolic catalyst 4 -H, deuterium substitution rate 84%), 0.12H (C) when using 2,4,6-triphenylphenol as the phenolic catalyst 4 -H, deuterium substitution rate 88%), 0.14H (C) when using 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol as the phenolic catalyst 4 -H, deuterium substitution rate 86%), 0.17H (C) when using 9-phenanthrol as the phenolic catalyst 4 -H, deuterium substitution rate 83%), 0.22H (C) when using 9,10-anthracenediol as the phenolic catalyst 4 -H, deuterium substitution rate 78%), 0.20H (C) when using 2-tert-butyl-3,5-xylenol as the phenolic catalyst 4 -H, deuterium substitution rate 80%)), 7.20–7.16 (m, 0.16H (C) when using 2,6-di-tert-butyl-4-phenylphenol as the phenolic catalyst 2-H, C 6 -H, deuterium substitution rate 92%), 0.20H(C when using 2,6-di-tert-butyl-4-(9-anthryl)phenol as the phenolic catalyst 2 -H, C 6 -H, deuterium substitution rate 90%), 0.24H(C when using 6-di-tert-butyl-4-heptylphenol as the phenolic catalyst 2 -H, C 6 -H, deuterium substitution rate 88%), 0.18H(C when using 2,4,6-triphenylphenol as the phenolic catalyst 2 -H, C 6 -H, deuterium substitution rate 91%), 0.20H(C when using 2,6-di-tert-butyl-4-(1H-indol-3-yl)phenol as the phenolic catalyst 2 -H, C 6 -H, deuterium substitution rate 90%), 0.24H(C when using 9-phenanthrol as the phenolic catalyst 2 -H, C 6 -H, deuterium substitution rate 88%), 0.36H(C when using 9,10-anthracenediol as the phenolic catalyst 2 -H, C 6 -H, deuterium substitution rate 82%), 0.32H(C when using 2-tert-butyl-3,5-xylenol as the phenolic catalyst 2 -H, C 6 -H, deuterium substitution 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, CDCl 3 ) δ 143.1, 128.4 (m, marked), 125.7 (m, marked), 36.2, 32.0, 31.7, 29.6, 29.5, 29.4, 22.8, 14.2; HRMS (ESI) calculated value: C 14 H 18 D 5 + [M + H] + 196.2108, measured value: 196.2110.

[0309] Example 2

[0310]

[0311] Under a nitrogen atmosphere, substrate 3 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-(4-tert-butylphenyl)phenol, 2.0 mol%), base (using 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 solvent (tetrahydrofuran, 3.0 mL) and deuterium source (MeOD, 30 mmol). After addition, the reaction mixture was placed at 15 °C and irradiated with a 395 nm LED (350 lux) lamp at a distance of 7 cm from the reaction apparatus for 48 hours. The reaction was quenched with water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 4 (yield: 100% when using potassium tert-butoxide as the base, 100% when using phosphazene base (CAS: 111324-04-0) as the base, 99% when using potassium carbonate as the base, 97% when using cesium carbonate as the base, 98% when using potassium phosphate as the base, 97% when using potassium hydroxide as the base, 96% when using tetrabutylammonium hydroxide as the base, 99% when using potassium methoxide as the base, 99% when using sodium tert-butoxide as the base, and purity > 95%). 1 H NMR(500MHz,CDCl 3 ):δ7.34–7.30(m, 0.12H (C 3 -H, C 5 -H, deuteration rate 94% when using potassium tert-butoxide as the base), 0.10H (C 3 -H, C 5 -H, deuteration rate 95% when using phosphazene base (CAS: 111324-04-0) as the base), 0.36H (C 3 -H, C 5 -H, deuteration rate 82% when using potassium carbonate as the base), 0.28H (C 3 -H, C 5 -H, deuteration rate 86% when using cesium carbonate as the base), 0.38H (C 3 -H, C 5 -H, deuteration rate 81% when using potassium phosphate as the base), 0.26H (C 3 -H, C 5 -H, deuteration rate 87% when using potassium hydroxide as the base), 0.30H (C 3 -H, C 5 -H, deuteration rate 85% when using tetrabutylammonium hydroxide as the base), 0.12H (C 3 -H, C5 -H, deuterium substitution rate 94%), 0.16H (C when using sodium tert-butoxide as the base 3 -H, C 5 -H, deuterium substitution rate 92%)), 7.30–7.27 (m, 0.18H (C when using potassium tert-butoxide as the base 2 -H, C 6 -H, deuterium substitution rate 91%), 0.16H (C when using phosphazene base (CAS: 111324-04-0) as the base 2 -H, C 6 -H, deuterium substitution rate 92%), 0.40H (C when using potassium carbonate as the base 2 -H, C 6 -H, deuterium substitution rate 80%), 0.30H (C when using cesium carbonate as the base 2 -H, C 6 -H, deuterium substitution rate 85%), 0.40H (C when using potassium phosphate as the base 2 -H, C 6 -H, deuterium substitution rate 80%), 0.30H (C when using potassium hydroxide as the base 2 -H, C 6 -H, deuterium substitution rate 85%), 0.30H (C when using tetrabutylammonium hydroxide as the base 2 -H, C 6 -H, deuterium substitution rate 85%), 0.16H (C when using potassium methoxide as the base 2 -H, C 6 -H, deuterium substitution rate 92%), 0.20H (C when using sodium tert-butoxide as the base 2 -H, C 6 -H, deuterium substitution rate 90%)), 7.24–7.19 (m, 0.10H (C when using potassium tert-butoxide as the base 4 -H, deuterium substitution rate 90%), 0.08H (C when using phosphazene base (CAS: 111324-04-0) as the base 4 -H, deuterium substitution rate 92%), 0.19H (C when using potassium carbonate as the base 4 -H, deuterium substitution rate 81%), 0.17H (C when using cesium carbonate as the base 4 -H, deuterium substitution rate 83%), 0.22H (C when using potassium phosphate as the base 4 -H, deuterium substitution rate 78%), 0.14H (C when using potassium hydroxide as the base 4 -H, deuterium substitution rate 86%), 0.14H (C when using tetrabutylammonium hydroxide as the base 4 -H, deuterium substitution rate 86%), 0.09H (C when using potassium methoxide as the base 4-H, deuterium substitution rate 91%), when using sodium tert-butoxide as the base, 0.09H (C 4 -H, deuterium substitution 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, CDCl 3 ): δ 145.8, 128.4 (m, marked), 127.4 (m, marked), 126.7 (m, marked), 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 D 5 + [M + H] + 252.2734, measured value: 252.2736.

[0312] Example 3

[0313]

[0314] Under a nitrogen atmosphere, the substrate 5 (0.30 mmol), the phenolic catalyst (3-phenyl-1-naphthol, 5.0 mol%), and the 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 each) and a deuterium source (iPrOD, 40 mmol). After addition, the reaction mixture was placed at 5 °C and irradiated with a 455 nm LED (600 lux) lamp at a distance of 3 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 × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 6 (yield: 100% when using tetrahydrofuran as the reaction solvent, 99% when using diethyl ether, 100% when using 1,4-dioxane, 98% when using methyl tert-butyl ether, 99% when using n-hexane, 98% when using cyclohexane, 97% when using n-heptane, 99% when using n-pentane, 98% when using petroleum ether, 99% when using N,N-dimethylformamide as the reaction solvent, and the purity was greater than 95%). 11H NMR (500 MHz, C 6 D 6 ): δ 7.34–7.29 (m, 0.10 H (C 3 -H, C 5 -H, deuteration rate 95%) when using tetrahydrofuran as the reaction solvent, 0.16 H (C 3 -H, C 5 -H, deuteration rate 92%) when using diethyl ether as the reaction solvent, 0.16 H (C 3 -H, C 5 -H, deuteration rate 92%) when using 1,4-dioxane as the reaction solvent, 0.18 H (C 3 -H, C 5 -H, deuteration rate 91%) when using methyl tert-butyl ether as the reaction solvent, 0.30 H (C 3 -H, C 5 -H, deuteration rate 85%) when using n-hexane as the reaction solvent, 0.34 H (C 3 -H, C 5 -H, deuteration rate 83%) when using cyclohexane as the reaction solvent, 0.30 H (C 3 -H, C 5 -H, deuteration rate 85%) when using n-heptane as the reaction solvent, 0.30 H (C 3 -H, C 5 -H, deuteration rate 85%) when using n-pentane as the reaction solvent, 0.26 H (C 3 -H, C 5 -H, deuteration rate 87%) when using petroleum ether as the reaction solvent, 0.36 H (C 3 -H, C 5 -H, deuteration rate 82%)), 7.29–7.26 (m, 0.16 H (C 2 -H, C 6 -H, deuteration rate 92%) when using tetrahydrofuran as the reaction solvent, 0.20 H (C 2 -H, C 6 -H, deuteration rate 90%) when using diethyl ether as the reaction solvent, 0.18 H (C 2 -H, C 6 -H, deuteration rate 91%) when using 1,4-dioxane as the reaction solvent, 0.20 H (C 2 -H, C 6 -H, deuteration rate 90%) when using methyl tert-butyl ether as the reaction solvent, 0.34 H (C 2 -H, C 6-H, deuterium incorporation rate 83%), 0.36H (C when using cyclohexane as the reaction solvent 2 -H, C 6 -H, deuterium incorporation rate 82%), 0.34H (C when using n-heptane as the reaction solvent 2 -H, C 6 -H, deuterium incorporation rate 83%), 0.36H (C when using n-pentane as the reaction solvent 2 -H, C 6 -H, deuterium incorporation rate 82%), 0.28H (C when using petroleum ether as the reaction solvent 2 -H, C 6 -H, deuterium incorporation rate 86%), 0.38H (C when using N,N-dimethylformamide as the reaction solvent 2 -H, C 6 -H, deuterium incorporation rate 81%)), 7.25–7.21 (m, 0.06H (C when using tetrahydrofuran as the reaction solvent 4 -H, deuterium incorporation rate 94%), 0.10H (C when using diethyl ether as the reaction solvent 4 -H, deuterium incorporation rate 90%), 0.08H (C when using 1,4-dioxane as the reaction solvent 4 -H, deuterium incorporation rate 92%), 0.10H (C when using methyl tert-butyl ether as the reaction solvent 4 -H, deuterium incorporation rate 90%), 0.16H (C when using n-hexane as the reaction solvent 4 -H, deuterium incorporation rate 84%), 0.20H (C when using cyclohexane as the reaction solvent 4 -H, deuterium incorporation rate 80%), 0.17H (C when using n-heptane as the reaction solvent 4 -H, deuterium incorporation rate 83%), 0.16H (C when using n-pentane as the reaction solvent 4 -H, deuterium incorporation rate 84%), 0.13H (C when using petroleum ether as the reaction solvent 4 -H, deuterium incorporation rate 87%), 0.21H (C when using N,N-dimethylformamide as the reaction solvent 4 -H, deuterium incorporation 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, C 6 D 6 ): δ 148.2, 128.7 (m, marked), 127.2 (m, marked), 126.2 (m, marked), 45.0, 34.9, 27.3, 26.6; HRMS (ESI) calculated value: C12 H 12 D 5 + [M+H] + 166.1639, Measured value: 166.1640.

[0315] Example 4

[0316]

[0317] Under a nitrogen atmosphere, the substrate 7 (0.30 mmol), the phenolic catalyst (2-phenylphenol, 20.0 mol%), and the base (potassium carbonate, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 1.0 mL) and a deuterium source (tBuOD, 80 mmol). After completion of the addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 8 (99% yield, purity > 95%). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.28–7.24 (m, 0.10H, C 5 -H, deuteration rate 90%), 7.19–7.15 (m, 0.11H, C 4 -H, deuteration rate 89%), 7.12–7.09 (m, 0.09H, C 3 -H, deuteration rate 91%), 7.09–7.07 (m, 0.08H, C 6 -H, deuteration rate 92%), 3.85 (t, J = 6.9 Hz, 2H), 2.93 (t, J = 6.9 Hz, 2H), 2.38 (s, 3H), 1.92 (br s, 1H); 13 C NMR (100 MHz, CDCl 3 ): δ 136.5, 130.4, 129.7 (m, labeled), 126.6 (m, labeled), 126.1 (m, labeled), 62.6, 36.4, 19.5; HRMS (ESI) calculated value: C 9 H 9 D 4 O + [M+H] + 141.1212, Measured value: 141.1216.

[0318] Example 5:

[0319]

[0320] Under a nitrogen atmosphere, substrate 9 (0.30 mmol), phenolic catalyst (3-hydroxy-2-phenylpyridine, 10.0 mol%), base (cesium carbonate, 0.90 mmol) were dissolved in solvent (1,4-dioxane, 3.0 mL) and deuterium source (CD 3 OD, 60 mmol). After addition, the reaction mixture was placed at 25 °C and irradiated with light from a 405 nm LED (420 lux) at a distance of 7 cm for 48 h. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 10 (99% yield, purity > 95%). 1 HNMR (500 MHz, CDCl 3 ): δ 7.25–7.21 (m, 0.06H, C 6 -H, deuteration rate 94%), 7.20–7.17 (m, 0.04H, C 3 -H, deuteration rate 96%), 7.17–7.12 (m, 0.12H, C 2 -H, C 4 -H, deuteration rate 94%), 2.93–2.81 (m, 2H), 1.28 (d, J = 6.8 Hz, 12H); 13 C NMR (125 MHz, CDCl 3 ): δ 147.8, 128.1 (m, labeled), 125.7 (m, labeled), 125.4 (m, labeled), 34.1, 24.1; HRMS (ESI) calcd for C 12 H 15 D 4 + [M + H] + 167.1732, found: 167.1735.

[0321] Example 6:

[0322]

[0323] Under a nitrogen atmosphere, substrate 11 (0.30 mmol), phenolic 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 sources (EtOD, D 2 O, MeOD, iPrOD, tBuOD, CD 3 OD or CD 3 CD 2In OD (60 mmol), after the addition was completed, the reaction mixture was placed at 45 °C and irradiated with a 435 nm LED (2000 lux) lamp at a distance of 10 cm from the reaction device for 48 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The organic phases were combined, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 12 (yield: 100% when using EtOD as the deuterium source, 99% when using D 2 O as the deuterium source, 99% when using MeOD as the deuterium source, 100% when using iPrOD as the deuterium source, 98% when using tBuOD as the deuterium source, 99% when using CD 3 OD as the deuterium source, 100% when using CD 3 CD 2 OD as the deuterium source, and the purity was greater than 95%). 1 1H NMR (500 MHz, CDCl 3 ): δ 7.19–7.15 (m, 0.12H (C 2 -H, C 6 -H, deuteration rate 94%) when using EtOD as the deuterium source, 0.30H (C 2 -H, C 2 -H, deuteration rate 85%) when using D 6 O as the deuterium source, 0.18H (C 2 -H, C 6 -H, deuteration rate 91%) when using MeOD as the deuterium source, 0.16H (C 2 -H, C 6 -H, deuteration rate 92%) when using iPrOD as the deuterium source, 0.20H (C 2 -H, C 6 -H, deuteration rate 90%) when using tBuOD as the deuterium source, 0.18H (C 3 -H, C 2 -H, deuteration rate 91%) when using CD 6 -H, C 3 CD 2 OD as the deuterium source, 0.12H (C 2 -H, C 6 -H, deuteration rate 94%))), 7.14–7.10 (m, 0.14H (C 3 -H, C 5 -H, deuteration rate 93%) when using EtOD as the deuterium source, 0.30H (C 2 -H, C 3 -H, C 5-H, deuteration rate 85%), 0.20H (C when using MeOD as the deuterium source 3 -H, C 5 -H, deuteration rate 90%), 0.16H (C when using iPrOD as the deuterium source 3 -H, C 5 -H, deuteration rate 92%), 0.18H (C when using tBuOD as the deuterium source 3 -H, C 5 -H, deuteration rate 91%), when using CD 3 OD as the deuterium source 0.18H (C 3 -H, C 5 -H, deuteration rate 91%), when using CD 3 CD 2 OD as the deuterium source 0.12H (C 3 -H, C 5 -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, CDCl 3 ): δ 141.5, 140.4, 128.4 (m, marked), 127.9 (m, marked), 41.1, 33.5, 28.6, 27.9, 22.7, 15.8; HRMS (ESI) calculated value: C 13 H 17 D 4 + [M + H] + 181.1889, measured value: 181.1887.

[0324] Example 7:

[0325]

[0326] Under the atmosphere of nitrogen, the substrate 13 (0.30 mmol), phenolic catalyst (4'-aminophenyl-3-phenol, 15.0 mol%), 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 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 device for 72 hours. The reaction was quenched with water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The organic phases were combined, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 14 (100% yield, purity > 95%).1 H NMR (500 MHz, CDCl 3 ): δ 7.40 (s, 0.21H, C 2 -H, C 4 -H, C 6 -H, deuterium incorporation rate 93%), 1.32 (d, J = 0.8 Hz, 27H); 13 C NMR (125 MHz, CDCl 3 ): δ 149.4, 122.8 (m, labeled), 34.9, 31.6, 31.5; HRMS (ESI) calculated value: C 18 H 28 D 3 + [M + H] + 250.2609, measured value: 250.2610.

[0327] Example 8:

[0328]

[0329] Under a nitrogen atmosphere, substrate 15 (0.30 mmol), phenolic catalyst (2,6 - di - tert - butyl - 4 - phenylphenol, 10.0 mol%), base (potassium methoxide, 0.60 mmol) were dissolved in solvent (diethyl ether, 1.0 mL) and deuterium source (CD 3 CD 2 OD, 30 mmol). After addition, the reaction mixture was placed at 25 °C and irradiated with a 395 nm LED (210 lux), 405 nm LED (420 lux), 455 nm LED (650 lux), white LED (1380 lux), incandescent lamp (450 lux) or white energy - saving lamp (1250 lux) at a distance of 5 cm from the reaction apparatus for 48 h. The reaction was quenched with water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 16 (yield was 99% when using a 395 nm LED lamp as the light source, 100% when using a 405 nm LED lamp as the light source, 100% when using a 455 nm LED lamp as the light source, 99% when using a white LED as the light source, 99% when using an incandescent lamp as the light source, and 100% when using a white energy - saving lamp as the light source). 1 H NMR (400 MHz, CDCl 3 ): δ 7.00–6.95 (m, when using a 395 nm LED lamp as the light source 0.05H (C 5-H, deuterium substitution rate 95%), 0.04H (C when using a 405 nm LED lamp as the light source 5 -H, deuterium substitution rate 96%), 0.05H (C when using a 455 nm LED lamp as the light source 5 -H, deuterium substitution rate 95%), 0.07H (C when using a white LED lamp as the light source 5 -H, deuterium substitution rate 93%), 0.10H (C when using an incandescent lamp as the light source 5 -H, deuterium substitution rate 90%), 0.12H (C when using a white energy-saving lamp as the light source 5 -H, deuterium substitution rate 88%)), 6.70–6.64 (m, 0.07H (C when using a 395 nm LED lamp as the light source 6 -H, deuterium substitution rate 93%), 0.07H (C when using a 405 nm LED lamp as the light source 6 -H, deuterium substitution rate 93%), 0.08H (C when using a 455 nm LED lamp as the light source 6 -H, deuterium substitution rate 92%), 0.10H (C when using a white LED lamp as the light source 6 -H, deuterium substitution rate 90%), 0.11H (C when using an incandescent lamp as the light source 6 -H, deuterium substitution rate 89%), 0.20H (C when using a white energy-saving lamp as the light source 6 -H, deuterium substitution rate 80%)), 6.62–6.58 (m, 0.07H (C when using a 395 nm LED lamp as the light source 2 -H, deuterium substitution rate 93%), 0.07H (C when using a 405 nm LED lamp as the light source 2 -H, deuterium substitution rate 93%), 0.07H (C when using a 455 nm LED lamp as the light source 2 -H, deuterium substitution rate 93%), 0.10H (C when using a white LED lamp as the light source 2 -H, deuterium substitution rate 90%), 0.12H (C when using an incandescent lamp as the light source 2 -H, deuterium substitution rate 88%), 0.20H (C when using a white energy-saving lamp as the light source 2 -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, CDCl 3): δ 157.5, 138.3, 130.1, 129.4 (m, labeled), 113.8 (m, labeled), 111.9 (m, labeled), 55.4, 29.9, 28.7, 23.6, 23.3; HRMS (ESI) calcd for C 11 H 12 D 3 O + [M + H] + 166.1306, found: 166.1310.

[0330] Example 9:

[0331]

[0332] Under a nitrogen atmosphere, substrate 17 (0.30 mmol), phenolic catalyst (cyanobiphenol, 5.0 mol%), base (potassium ethoxide, 0.05 mmol) were dissolved in solvent (tetrahydrofuran, 5.0 mL) and deuterium source (EtOD, 60 mmol). After addition, the reaction mixture was placed at 55 °C and irradiated with a 405 nm LED (700 lux) lamp at a distance of 10 cm from the reaction device for 60 h. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 18 (99% yield, purity > 95%). 1 H NMR (500 MHz, CDCl 3 ): δ 7.07 (s, 0.05H, C 3 -H, deuterium incorporation 95%), 6.78 (s, 0.05H, C 6 -H, deuterium incorporation 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, CDCl 3 ) δ 156.8, 138.9, 135.4, 127.6, 127.5 (m, labeled), 109.1 (m, labeled), 55.7, 52.7, 39.8, 39.8, 16.2; HRMS (ESI) calcd for C 11 H 14 D 2 NO + [M + H] +180.1352, Measured value: 180.1355.

[0333] Example 10:

[0334]

[0335] Under a nitrogen atmosphere, substrate 19 (0.30 mmol), phenolic catalyst (2,6 - di - tert - butyl - 4 - (4 - acetylphenyl)phenol, 10.0 mol%), base (potassium tert - butoxide, 0.20 mmol) were dissolved in solvent (ethylenediamine, 2.0 mL) and deuterium source (EtOD, 60 mmol). After addition, the reaction mixture was placed at 25 °C and irradiated with a 455 nm LED (650 lux) lamp at a distance of 7 cm from the reaction device for 72 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 20 (99% yield). 1 HNMR (400 MHz, CDCl 3 ): δ 6.83 (s, 0.06H, C 6 - H, deuterium incorporation rate 94%), 2.24 (s, 6H), 2.21 (s, 3H), 2.17 (s, 6H); 13 C NMR (100 MHz, CDCl 3 ): δ 134.9, 133.3, 132.3, 129.0 (m, labeled), 20.5, 16.3, 15.9; HRMS (ESI) calculated value: C 11 H 16 D + [M + H] + 150.1388, Measured value: 150.1389.

[0336] Example 11:

[0337]

[0338] Under a nitrogen atmosphere, substrate 21 (0.30 mmol), phenolic catalyst (2,4,6 - tri - tert - butylphenol, 1.0 mol%), base (potassium tert - butoxide, 0.10 mmol) were dissolved in solvent (diethyl ether, 3.0 mL) and deuterium source (EtOD, 60 mmol). After addition, the reaction mixture was placed at 65 °C and irradiated with a 7 W 405 nm LED (420 lux) lamp at a distance of 5 cm from the reaction device for 48 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 22 (98% yield, purity > 95%). 1HNMR(400MHz,CDCl 3 ):δ7.32–7.25(m,0.16H,C 3 -H,C 5 -H, deuteration rate 92%), 6.99–6.95(m,0.10H,C 4 -H, deuteration rate 90%), 6.94–6.88(m,0.14H,C 2 -H,C 6 -H, deuteration rate 93%), 3.98(t, J = 6.7Hz, 2H), 1.78–1.63(m, 7H), 1.53–1.48(m, 1H), 1.31–1.14(m, 3H), 1.01–0.92(m, 2H); 13 C NMR(100MHz,CDCl 3 ):δ159.2, 129.4(m, labeled), 120.5(m, labeled), 114.5(m, labeled), 65.8, 36.7, 34.6, 33.4, 26.6, 26.3; HRMS(ESI) calculated value: C 14 H 16 D 5 O + [M + H] + 210.1901, measured value: 210.1903.

[0339] Example 12:

[0340]

[0341] Under a nitrogen atmosphere, the substrate 23(0.30 mmol), phenol catalyst (2-tert-butyl-3,5-dimethylphenol, 10.0 mol%), base (potassium tert-butoxide, 0.02 mmol) were dissolved in a solvent (cyclohexane, 6.0 mL) and a deuterium source (EtOD, 50 mmol). After addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 24(99% yield). 1 H NMR(500MHz,CDCl 3 ):δ7.33–7.21(m,0.12H,C 3 -H,C 5 -H, deuteration rate 94%), 6.99–6.92(m,0.10H,C 4 -H, deuteration rate 90%), 6.91–6.83(m,0.10H,C2 -H, C 6 -H, deuterium substitution rate 95%), 3.39 (t, J = 7.0 Hz, 4H), 1.69 (pd, J = 7.0, 1.1 Hz, 4H), 1.65–1.54 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ): δ 150.5, 129.1 (m, labeled), 118.6 (m, labeled), 115.5 (m, labeled), 115.5 (m, labeled), 50.6, 25.8, 24.4; HRMS (ESI) calculated value: C 11 H 11 D 5 N + [M + H] + 167.1591, measured value: 167.1593.

[0342] Example 13:

[0343]

[0344] Under a nitrogen atmosphere, the substrate 25 (0.30 mmol), the phenolic catalyst (1-anthrol, 0.5 mol%), and the base (tetrabutylammonium hydroxide, 0.20 mmol) were dissolved in a solvent (tetrahydrofuran, 4.0 mL) and a deuterium source (MeOD, 70 mmol). After addition, the reaction mixture was placed at 75 °C and irradiated with a 405 nm LED (420 lux) lamp at a distance of 7 cm from the reaction device for 60 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The organic phases were combined, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 26 (95% yield, purity > 95%). 1 H NMR (400 MHz, C 6 D 6 ): δ 7.58–7.52 (m, 0.16H, C 3 -H, C 5 -H, deuterium substitution rate 92%), 7.30–7.21 (m, 0.10H, C 4 -H, deuterium substitution rate 90%), 7.20–7.10 (m, 0.12H, C 2 -H, C 6 -H, deuterium substitution rate 94%), 1.65–1.55 (m, 4H), 1.05 (dt, J = 7.6, 7.2 Hz, 6H); 13 C NMR (100 MHz, C 6 D 6): δ 139.1, 132.4 (m, marker), 128.4 (m, marker), 128.2 (m, marker), 20.3, 9.7. 31 P NMR (162 MHz, C 6 D 6 ): δ –16.59 (s); HRMS (ESI) calcd for C 10 H 11 D 5 P + [M + H] + 172.1298, found 172.1296.

[0345] Example 14:

[0346]

[0347] Under a nitrogen atmosphere, substrate 27 (0.30 mmol), phenolic catalyst (5,5'-di-tert-butyl-2,2'-biphenyldiol, 2.0 mol%), base (phosphazene base (CAS: 111324-04-0), 0.02 mmol) were dissolved in solvent (ethylene glycol dimethyl ether, 3.0 mL) and deuterium source (iPrOD, 80 mmol). After addition, the reaction mixture was placed at 25 °C and irradiated with a 415 nm LED (350 lux) lamp at a distance of 5 cm from the reaction device for 72 h. The reaction was quenched with water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 28 (99% yield, purity > 95%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.34–7.30 (m, 0.12H, C 3 -H, C 5 -H, deuteration rate 94%), 7.29–7.24 (m, 0.08H, C 2 -H, C 6 -H, deuteration rate 96%), 7.17–7.12 (m, 0.10H, C 4 -H, deuteration rate 90%), 2.81 (d, J = 6.9 Hz, 2H), 1.89–1.82 (m, 1H), 1.03 (d, J = 6.7 Hz, 6H); 13 C NMR (100 MHz, CDCl 3 ): δ 137.4, 128.8 (m, marker), 128.7 (m, marker), 125.6 (m, marker), 42.6, 28.3, 22.1; HRMS (ESI) calcd for C 10 H 10 D5 S + [M+H] + 172.1203, Measured value: 172.1205.

[0348] Example 15:

[0349]

[0350] Under a nitrogen atmosphere, substrate 29 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-acetylphenol, 10.0 mol%), base (phosphazene base (CAS: 111324-04-0), 0.05 mmol) were dissolved in solvent (n-heptane, 3.0 mL) and deuterium source (iPrOD, 60 mmol). After addition, the reaction mixture was placed at 25 °C and irradiated with a 405 nm LED (210 lux) lamp at a distance of 7 cm from the reaction device for 90 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 30 (100% yield, purity > 95%). 1 H NMR (400 MHz, CDCl 3 ): δ: 7.49–7.44 (m, 0.14H, C 3 -H, C 5 -H, deuteration rate 93%), 6.94–6.90 (m, 0.10H, C 2 -H, C 6 -H, deuteration rate 95%), 3.82 (s, 3H), 0.26 (s, 9H); 13 C NMR (100 MHz, CDCl 3 ): δ 160.4, 134.9, 131.5 (m, marked), 113.7 (m, marked), 55.2, –0.78; HRMS (ESI) calculated value: C 10 H 13 D 4 OSi + [M+H] + 185.1294, Measured value: 185.1296.

[0351] Example 16:

[0352]

[0353] Under a nitrogen atmosphere, the substrate 31 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-methoxyphenol, 5.0 mol%), base (potassium tert-butoxide, 0.40 mmol) were dissolved in a solvent (1,4-dioxane, 6.0 mL) and deuterium source (tBuOD, 90 mmol). After addition, the reaction mixture was 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 adding water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 32 (99% yield, purity > 95%). 1 H NMR(400MHz,CDCl 3 ):δ8.48(d,J=5.6Hz,2H),7.30–7.26(m,0.08H,C 2 -H,C 6 -H, deuterium incorporation rate 96%),7.25–7.19(m,0.10H,C 3 -H,C 5 -H, deuterium incorporation rate 95%),7.16–7.13(m,0.08H,C 4 -H, deuterium incorporation rate 92%),7.08(d,J=5.6Hz,2H),2.93(br s,4H); 13 C NMR(75MHz,CDCl 3 ):δ150.4,149.7,140.6,128.4(m, labeled),128.3(m, labeled),126.2(m, labeled),123.9,37.0,36.5;HRMS(ESI) calculated value: C 13 H 9 D 5 N + [M+H] + 189.1435, measured value: 189.1437.

[0354] Example 17:

[0355]

[0356] Under a nitrogen atmosphere, the substrate 33 (0.30 mmol), phenolic catalyst (6-tert-butyl-2,4-dimethylphenol, 10.0 mol%), base (sodium carbonate, 0.60 mmol) were dissolved in a solvent (petroleum ether, 3.0 mL) and deuterium source (D 2To (O, 40 mmol), after the addition, the reactants were placed under the condition of 45 °C, irradiated with a 390 nm LED (160 lux) lamp at a distance of 5 cm from the reaction device for 24 hours, quenched with water, the aqueous phase was extracted three times with ethyl acetate (15 mL × 3), the organic phases were combined, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 34 (99% yield, purity > 95%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.92–7.89 (m, 0.07H, C 5 -H, deuteration rate 93%), 7.77–7.73 (m, 0.07H, C 4 -H, deuteration rate 93%), 7.71–7.67 (m, 0.07H, C 8 -H, deuteration rate 93%), 7.64 (s, 0.05H, C 1 -H, deuteration rate 95%), 7.52–7.48 (m, 0.45H, C 7 -H, deuteration rate 55%), 7.47–7.42 (m, 0.40H, C 6 -H, deuteration rate 60%), 7.36–7.32 (m, 0.46H, C 3 -H, deuteration rate 54%), 3.07 (septet, J = 6.8 Hz, 1H), 1.34 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 146.3, 133.7, 132.1, 127.8 (m, labeled), 127.6 (m, labeled), 127.5 (m, labeled), 125.8 (m, labeled), 125.7 (m, labeled), 125.0 (m, labeled), 124.1 (m, labeled), 34.2, 23.9; HRMS (ESI) calculated value: C 13 H 11 D 4 + [M + H] + 175.1419, measured value: 175.1420.

[0357] Example 18:

[0358]

[0359] Under a nitrogen atmosphere, the substrate 35 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-nitrophenol, 15.0 mol%), and the base (potassium hydroxide, 0.60 mmol) were dissolved in a solvent (dimethyl sulfoxide, 2.0 mL) and a deuterium source (EtOD, 70 mmol). After addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 36 (100% yield, purity > 95%). 1 H NMR(400MHz,CDCl 3 ):δ8.40(s,0.08H,C 10 -H, deuterium incorporation rate 92%), 8.29(s,0.09H,C 9 -H, deuterium incorporation rate 91%), 8.02–7.98(m,0.10H,C 5 -H, deuterium incorporation rate 90%), 7.97–7.92(m,0.10H,C 8 -H, deuterium incorporation rate 90%), 7.56–7.52(m,0.10H,C 4 -H, deuterium incorporation rate 90%), 7.51–7.48(m,0.45H,C 6 -H, deuterium incorporation rate 55%), 7.47–7.42(m,0.40H,C 7 -H, deuterium incorporation rate 60%), 7.35–7.28(m,0.40H,C 3 -H, deuterium incorporation rate 60%), 6.78–6.74(m,0.35H,C 2 -H, deuterium incorporation rate 65%), 4.27(s,2H); 13 C NMR(100MHz,CDCl 3 ):δ141.8,132.5,131.6,130.9,128.4(m, labeled),127.8,126.6(m, labeled),125.8(m, labeled),125.5(m, labeled),125.1(m, labeled),123.7(m, labeled),119.6(m, labeled),119.2(m, labeled),107.5(m, labeled); HRMS(ESI) calcd for C 14 H 7 D 5 N + [M+H] + 199.1278, found: 199.1280.

[0360] Example 19:

[0361]

[0362] Under a nitrogen atmosphere, the substrate 37 (0.30 mmol), the phenolic catalyst (3,5-di-tert-butylcatechol, 20.0 mol%), and the base (phosphazene base (CAS: 111324-04-0), 0.10 mmol) were dissolved in a solvent (water, 1.0 mL) and a deuterium source (D 2 O, 90 mmol). After addition, the reaction mixture was placed at 25 °C and irradiated with a 405 nm LED (420 lux) lamp at a distance of 5 cm from the reaction device for 36 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 38 (98% yield, purity > 95%). 1 H NMR (400 MHz, CDCl 3 ): δ 8.39 (br s, 1H), 7.64–7.60 (m, 0.07H, C 4 -H, deuteration rate 93%), 7.42–7.38 (m, 0.07H, C 7 -H, deuteration rate 93%), 7.25–7.21 (m, 0.31H, C 6 -H, deuteration rate 69%), 7.17–7.13 (m, 0.31H, C 5 -H, deuteration rate 69%), 7.04 (s, 0.05H, C 2 -H, deuteration rate 95%), 5.67 (br s, 1H), 3.62 (q, J = 6.6 Hz, 2H), 3.00 (td, J = 6.8, 0.9 Hz, 2H), 1.94 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ 170.3, 136.4, 127.3, 122.1, 119.4 (m, labeled), 118.6 (m, labeled), 112.8 (m, labeled), 111.3 (m, labeled), 39.9, 25.2, 23.3; HRMS (ESI) calcd for C 12 H 10 D 5 N 2 O + [M+H] + 208.1493, found: 208.1495.

[0363] Example 20:

[0364]

[0365] Under a nitrogen atmosphere, the substrate 39 (0.30 mmol), phenolic catalyst (4-phenylphenol, 10.0 mol%), base (potassium tert-butoxide, 0.20 mmol) were dissolved in a solvent (cyclohexane, 5.0 mL) and a deuterium source (EtOD, 60 mmol). After addition, the reaction mixture was 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 adding water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 40 (96% yield, purity > 95%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.60 (s, 0.05H, C 4 -H, deuterium incorporation rate 95%), 7.41–7.38 (m, 0.07H, C 7 -H, deuterium incorporation rate 93%), 7.09–7.05 (m, 0.05H, C 2 -H, deuterium incorporation rate 95%), 6.92–6.88 (m, 0.10H, C 6 -H, deuterium incorporation rate 90%), 6.73–6.69 (m, 0.07H, C 3 -H, deuterium incorporation rate 93%), 3.85 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ): δ 156.0, 150.0, 145.8, 127.9 (m, labeled), 113.1 (m, labeled), 111.9 (m, labeled), 106.8 (m, labeled), 103.6 (m, labeled), 29.8; HRMS (ESI) calcd for C 9 H 4 D 5 O 2 + [M + H] + 154.0911, found: 154.0913.

[0366] Example 21:

[0367]

[0368] Under a nitrogen atmosphere, the substrate 41 (0.30 mmol), the phenolic catalyst (2-amino-4-tert-butylphenol, 2.0 mol%), and the base (sodium tert-butoxide, 0.10 mmol) were dissolved in a solvent (tetrahydrofuran, 6.0 mL) and a deuterium source (EtOD, 60 mmol). After addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 42 (96% yield, purity > 95%). 1 H NMR(300MHz,CDCl 3 ):8.18–8.14(m,0.18H,C 4 -H,C 5 -H, deuterium incorporation rate 91%),7.59–7.55(m,0.14H,C 1 -H,C 8 -H, deuterium incorporation rate 93%),7.29–7.25(m,0.88H,C 2 -H,C 7 -H, deuterium incorporation rate 56%),7.26–7.22(m,0.88H,C 3 -H,C 6 -H, deuterium incorporation rate 56%),5.05–5.01(m,1H),1.75(d,J=6.9Hz,6H); 13 C NMR(75MHz,CDCl3):139.5,125.4,123.3(m, labeled),120.4(m, labeled),118.6(m, labeled),110.0(m, labeled),46.7,20.8;HRMS(ESI) calculated value: C 15 H 8 D 8 N + [M+H] + 218.1779, measured value: 218.1777.

[0369] Example 22:

[0370]

[0371] Under a nitrogen atmosphere, substrate 43 (0.30 mmol), phenolic catalyst (2,6-diphenylphenol, 10.0 mol%), base (sodium tert-butoxide, 0.20 mmol) were dissolved in solvent (n-hexane, 3.0 mL) and deuterium source (EtOD, 60 mmol). After addition, the reaction mixture was placed at 45 °C and irradiated with a 405 nm LED (650 lux) lamp at a distance of 15 cm from the reaction device for 36 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 44 (99% yield, purity > 95%). 1 HNMR(400MHz,DMSO-d6):δ12.56(br s,1H)7.72(s,0.44H,C 3 -H, deuterium incorporation rate 56%), 7.26–7.24(m,0.08H,C 7 -H, deuterium incorporation rate 92%), 6.79–6.76(m,0.30H,C 6 -H, deuterium incorporation rate 70%), 6.75(s,0.07H,C 4 -H, deuterium incorporation rate 93%), 4.75(br s,2H); 13 C NMR(100MHz,DMSO-d6):δ142.1,131.3,123.8,117.9(m, labeled),110.1(m, labeled),100.3(m, labeled); HRMS(ESI) calcd for C 7 H 5 D 3 N 3 + [M+H] + 137.0901, found: 137.0903.

[0372] Example 23:

[0373]

[0374] Under a nitrogen atmosphere, the substrate 45 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-methylphenol, 1.0 mol%), and the base (sodium tert-butoxide, 0.30 mmol) were dissolved in the solvent (methyl tert-butyl ether, 5.0 mL) and the deuterium source (EtOD, 60 mmol). After the addition was complete, the reaction mixture was 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 with water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 46 (99% yield, purity > 95%). 1 H NMR(400MHz,CDCl 3 ):δ8.03–7.99(m,0.18H,C 4 -H,C 5 -H, deuterium incorporation rate 91%), 7.43–7.39(m,0.20H,C 3 -H,C 6 -H, deuterium incorporation rate 90%), 7.29–7.25(m,0.30H,C 2 -H,C 7 -H, deuterium incorporation rate 85%), 2.63(s,6H); 13 C NMR(100MHz,CDCl 3 ):δ139.5,136.2,132.4,127.0(m, labeled),124.9(m, labeled),119.4(m, labeled),20.7; HRMS(ESI) calculated value: C 14 H 7 D 6 S + [M+H] + 219.1109, measured value: 219.1110.

[0375] Example 24:

[0376]

[0377] Under a nitrogen atmosphere, the substrate 47 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-hydroxymethylphenol, 10.0 mol%), and the 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 placed at 65 °C and irradiated with a 405 nm LED (350 lux) lamp at a distance of 3 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 × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 48 (99% yield, purity > 95%). 1 H NMR(500MHz,(CD 3 ) 2 CO):δ7.75–7.71(m,0.10H,C 5 -H, deuterium incorporation rate 90%), 7.69–7.65(m,0.10H,C 4 -H, deuterium incorporation rate 90%), 7.37–7.34(m,0.07H,C 8 -H, deuterium incorporation rate 93%), 7.29–7.25(m,0.38H,C 7 -H, deuterium incorporation rate 62%), 7.24–7.20(m,0.38H,C 6 -H, deuterium incorporation rate 62%), 6.89–6.85(m,0.38H,C 2 -H, deuterium incorporation rate 62%), 6.81–6.77(m,0.38H,C 3 -H, deuterium incorporation rate 62%), 2.31(3H,s); 13 C NMR(125MHz,(CD 3 ) 2 CO):δ155.1, 139.9, 131.5, 130.4(m, labeled), 128.6(m, labeled), 127.5(m, labeled), 124.9(m, labeled), 123.4(m, labeled), 123.2(m, labeled), 121.8(m, labeled), 120.4(m, labeled), 117.8(m, labeled), 68.2, 20.7; HRMS(ESI) calcd for C 13 H 4 D 7 O + [M+H] + 190.1244, found: 190.1245.

[0378] Example 25:

[0379]

[0380] Under a nitrogen atmosphere, the substrate 49 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), and the 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 addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 50 (99% yield, purity > 95%). 1 H NMR (400 MHz, CDCl 3 ): 7.32 - 7.29 (m, 0.12H, C 3 -H, C 5 -H, deuteration rate 94%), 7.29 - 7.25 (m, 0.10H, C 4 -H, deuteration rate 90%), 7.25 - 7.19 (m, 0.14H C 2 -H, C 6 -H, deuteration rate 93%), 6.61 (br s, 1H), 4.92 (br s, 1H), 3.22 - 3.18 (m, 2H), 1.43 - 1.32 (m, 9H); 13C NMR (100 MHz, CDCl3): 176.2, 155.5, 146.9, 136.0 (m, labeled), 129.5 (m, labeled), 128.7 (m, labeled), 127.1 (m, labeled), 85.3, 80.3, 54.4, 40.0, 28.4, 27.5; HRMS (ESI) calculated value: C 14 H 13 D 5 NO 4 - [M - H] - 269.1555, measured value: 269.1557.

[0381] Example 26:

[0382]

[0383] Under a nitrogen atmosphere, substrate 51 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 10.0 mol%), base (cesium carbonate, 0.40 mmol) were dissolved in a solvent (acetonitrile, 4.0 mL) and a deuterium source (tBuOD, 70 mmol). After addition, the reaction mixture was placed at 50 °C and irradiated with a 405 nm LED (70 lux) lamp at a distance of 2 cm from the reaction device for 24 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 52 (100% yield, purity > 95%). 1 HNMR(400MHz,DMSO-d6):δ12.53(br s,1H),10.82(br s,1H),7.53–7.50(m,0.05H,C 4 -H, deuterium incorporation rate 95%),7.35–7.31(m,0.06H,C 7 -H, deuterium incorporation rate 94%),7.16–7.14(m,0.08H,C 2 -H, deuterium incorporation rate 92%),7.08–7.04(m,0.29H,C 6 -H, deuterium incorporation rate 71%),7.00–6.95(m,0.29H,C 6 -H, deuterium incorporation 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(100MHz,DMSO-d6):δ174.0,155.4,136.1,127.2,123.6(m, labeled),120.9(m, labeled),118.3(m, labeled),118.1(m, labeled),111.4(m, labeled),110.16,78.0,54.50,28.2,26.8;HRMS(ESI) calculated value: C 16 H 14 D 5 N 2 O 4 - [M-H] - 308.1664, measured value: 308.1666.

[0384] Example 27:

[0385]

[0386] Under a nitrogen atmosphere, the substrate 53 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 2.0 mol%), and the 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 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 54 (100% yield, purity > 95%). 1 H NMR(400MHz,CDCl 3 ):δ7.03(s,0.04H,C 5 -H, deuterium incorporation rate 96%), 6.80(s,0.07H,C 6 -H, deuterium incorporation rate 93%), 6.70(s,0.07H,C 2 -H, deuterium incorporation rate 93%), 3.79(s,3H), 2.99(d,J=18.1Hz,1H), 2.81(dd,J=5.9,3.2Hz,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(100MHz,CDCl 3 ):δ158.2, 141.7, 129.8, 128.5(m, labeled), 111.1(m, labeled), 110.7(m, labeled), 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) calcd for C 18 H 23 D 3 NO + [M+H] + 275.2197, found: 275.2195.

[0387] Example 28:

[0388]

[0389] Under a nitrogen atmosphere, the substrate 55 (0.30 mmol), phenolic catalyst (2,4,6-triphenylphenol, 5.0 mol%), 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 addition, the reaction mixture was placed at 55 °C and irradiated with a 455 nm LED (650 lux) lamp at a distance of 5 cm from the reaction device for 60 h. The reaction was quenched with water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 56 (98% yield, purity > 95%). 1 HNMR(400MHz,CD 3 OD):δ7.20(s,0.14H,C 2 -H,C 6 -H, deuterium incorporation rate 93%), 7.08(s,0.14H,C 3 -H,C 5 -H, deuterium incorporation rate 93%), 3.66(q,J=7.1Hz,1H), 2.44(d,J=7.2Hz,2H), 1.83(p,J=6.8Hz,1H), 1.42(d,J=7.1Hz,3H), 0.88(d,J=6.6Hz,6H); 13 C NMR(100MHz,CD 3 OD)δ177.2, 140.1, 138.4, 128.9(m, labeled), 126.9(m, labeled), 30.1, 21.5, 21.3, 17.7; HRMS(ESI) calcd for C 13 H 13 D 4 O 2 - [M-H] - 209.1485, found: 209.1487.

[0390] Example 29:

[0391]

[0392] Under a nitrogen atmosphere, substrate 57 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 10.0 mol%), base (phosphazene base (CAS: 111324-04-0), 0.20 mmol) were dissolved in a solvent (cyclohexane, 3.0 mL) and deuterium source (MeOD, 90 mmol). After addition, the reaction mixture was placed at 45 °C and irradiated 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 by adding water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 58 (99% yield, purity > 95%). 1 H NMR(400MHz,CD 3 CN):δ6.93–6.88(m,0.25H,C 3 -H, deuterium incorporation rate 75%), 6.62(s,0.07H,C 6 -H, deuterium incorporation rate 93%), 6.59–6.55(m,0.86H,C 4 -H, deuterium incorporation rate 14%), 4.11–3.10(m,2.03H), 2.19(t,J=0.7Hz,3H), 2.04(s,3H), 1.71–1.51(m,4H), 1.10(s,6H); 13 C NMR(100MHz,CD 3 CN)δ179.3, 157.5, 137.1, 130.7(m, labeled), 123.7(m, labeled), 121.2(m, labeled), 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) calculated value: C 15 H 18 D 3 O 3 - [M-H] - 252.1684, measured value: 252.1686.

[0393] Example 30:

[0394]

[0395] Under a nitrogen atmosphere, the substrate 59 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-(9-anthryl)phenol, 10.0 mol%), and the 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 was complete, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 60 (100% yield, purity > 95%). 1 H NMR(400MHz,CDCl 3 ):δ6.95(s,0.07H,C 5 -H, deuterium incorporation rate 93%), 6.61(s,0.10H,C 6 -H, deuterium incorporation rate 90%), 4.80–4.34(m,2H), 3.41–3.30(m,2H), 3.30–3.04(m,3H), 2.89(ddd,J=14.9,8.4,6.3Hz,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 C NMR(400MHz,CDCl 3 ):δ173.7, 159.3, 143.1, 135.7, 123.3(m, labeled), 122.2(m, labeled), 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 D 2 NO 2 + [M+H] + 262.1771, measured value: 262.1778.

[0396] Example 31:

[0397]

[0398] Under a nitrogen atmosphere, substrate 61 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-(4-tert-butylphenyl)phenol, 15.0 mol%), base (phosphazene base (CAS: 111324-04-0), 0.10 mmol) were dissolved in solvent (petroleum ether, 4.0 mL) and deuterium source (EtOD, 80 mmol). After addition, the reaction mixture was placed at 45 °C and irradiated with a 405 nm LED (210 lux) lamp at a distance of 3 cm from the reaction device for 24 hours. The reaction was quenched with water, and the aqueous phase was extracted with ethyl acetate three times (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 62 (99% yield, purity > 95%). 1 H NMR(400MHz,CDCl 3 ):δ7.21–7.17(m,0.32H,C 5 -H, deuteration rate 68%),6.74–6.66(m,0.49H,C 6 -H, deuteration rate 51%),6.63(s,0.04H,C 2 -H, deuteration rate 96%),3.88(t,J=6.6Hz,1H),3.38(s,3H),3.31(t,J=8.3Hz,1H),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(101MHz,CDCl 3 )δ156.9,137.8,132.5(m, labeled),126.3(m, labeled),112.0(m, labeled),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 D 3 O 2 + [M+H] + 332.2663, measured value: 332.2665.

[0399] Example 32:

[0400]

[0401] Under a nitrogen atmosphere, the substrate 63 (0.30 mmol), the phenolic catalyst (2,4,6-triphenylphenol, 10.0 mol%), and the base (potassium tert-butoxide, 0.20 mmol) were dissolved in the solvent (diethyl ether, 3.0 mL) and the deuterium source (D 2 O, 40 mmol). After addition, the reaction mixture was placed at 50 °C and irradiated with a 455 nm LED (600 lux) lamp 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 × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 64 (98% yield, purity > 95%). 1 H NMR (400 MHz, CDCl 3 ): δ 7.95 (s, 1H), 7.19–7.15 (m, 0.44H, C 7 -H, deuterium incorporation rate 56%), 7.14–7.10 (m, 0.44H, C 6 -H, deuterium incorporation rate 56%), 6.97–6.93 (m, 0.84H, C 5 -H, deuterium incorporation rate 16%), 6.90 (s, 0.05H, C 2 -H, deuterium incorporation rate 95%), 3.38 (dd, J = 14.7, 4.1 Hz, 1H), 3.25 (d, J = 7.7 Hz, 1H), 2.98 (s, 1H), 2.82 (d, J = 10.2 Hz, 3H), 2.73 (t, J = 12.7 Hz, 1H), 2.63–2.40 (m, 3H), 2.16 (d, J = 1.5 Hz, 4H), 1.65–1.46 (m, 2H), 1.28 (d, J = 21.9 Hz, 1H), 1.14 (q, J = 11.8 Hz, 1H), 0.91 (t, J = 7.3 Hz, 3H); 13 C NMR (400 MHz, CDCl 3 ): δ 133.6, 133.3, 126.2, 123.1, 117.7 (m, labeled), 113.3 (m, labeled), 112.2 (m, labeled), 108.5 (m, labeled), 63.6, 58.7, 55.6, 41.0, 39.2, 35.2, 34.3, 26.8, 16.7, 16.1, 12.0; HRMS (ESI) calcd for C 19 H 23 D 4 N 2 S + [M+H] + 319.2141, found: 319.2143.

[0402] Example 33:

[0403]

[0404] Under a nitrogen atmosphere, the substrate 65 (0.30 mmol), a phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), and a base (potassium carbonate, 0.30 mmol) were dissolved in a solvent (tetrahydrofuran, 6.0 mL) and a deuterium source (tBuOD, 40 mmol). After addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 66 (100% yield, purity > 95%). 1 HNMR(400MHz,(CD 3 ) 2 CO)δ7.14–7.10(m,0.64H,C 3 -H,C 5 -H, deuterium incorporation rate 68%), 6.93–6.71(m,0.10H,C 2 -H,C 6 -H, deuterium incorporation rate 95%), 3.76(s,3H), 3.31(dd,J=12.7,11.5Hz,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 CNMR(100MHz,(CD 3 ) 2 CO)δ158.3, 133.2(m, labeled), 130.1, 113.1(m, labeled), 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 D 4 NO 2 + [M+H] + 282.2366, measured value: 282.2368.

[0405] Example 34:

[0406]

[0407] Under a nitrogen atmosphere, the substrate 67 (0.30 mmol), a phenolic catalyst (2,6-di-tert-butyl-4-(9-anthryl)phenol, 10.0 mol%), a 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 addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 68 (98% yield, purity > 95%). 1 H NMR (400 MHz, CD 3 CN) δ 7.28–7.24 (m, 0.52H, C 3 -H, C 5 -H, deuterium incorporation rate 74%), 7.03–6.90 (m, 0.14H, C 2 -H, C 6 -H, deuterium incorporation rate 93%), 6.85–6.81 (m, 0.72H, C 4 -H, deuterium incorporation rate 28%), 3.83 (dq, J = 7.5, 5.2 Hz, 1H), 3.61–3.48 (m, 1H), 3.51–3.43 (m, 1H), 3.21 (t, J = 5.1 Hz, 4H), 2.78 (dt, J = 10.4, 5.1 Hz, 2H), 2.68 (dt, J = 11.1, 5.1 Hz, 2H), 2.53 (dd, J = 6.4, 3.2 Hz, 2H); 13 C NMR (400 MHz, CD 3 CN) δ 151.9, 129.5 (m, labeled), 119.8,, 116.2 (m, labeled), 116.0 (m, labeled), 68.1, 65.5, 61.7, 53.9, 49.1; HRMS (ESI) calcd for C 13 H 16 D 5 N 2 O 2 + [M + H] + 242.1911, found: 242.1913.

[0408] Example 35:

[0409]

[0410] Under a nitrogen atmosphere, the substrate 69 (0.30 mmol), a phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 10.0 mol%), a 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 addition, the reaction mixture was placed under the condition of 55 °C. A 405 nm LED (350 lux) lamp was placed 4 cm away from the reaction device and the organic phase was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 70 (96% yield, purity > 95%). 1 H NMR (400 MHz, CD 3 CN): δ 7.13 (s, 0.44H, C 3 -H, C 5 -H, deuteration rate 78%), 6.88–6.79 (m, 0.10H, C 2 -H, C 6 -H, deuteration rate 95%), 4.00–3.76 (m, 3H), 3.51 (t, J = 6.9 Hz, 2H), 3.26 (s, 3H), 2.90–2.70 (m, 4H), 2.67–2.59 (m, 1H), 1.04 (d, J = 6.3 Hz, 6H); 13 C NMR (400 MHz, CD 3 CN): δ 157.9, 132.1, 130.3 (m, labeled), 114.8 (m, labeled), 73.9, 71.3, 68.8, 58.1, 50.0, 49.3, 35.3, 22.5; HRMS (ESI) calculated value: C 15 H 22 D 4 NO 3 + [M+H] + 272.2158, measured value: 272.2155.

[0411] Example 36:

[0412]

[0413] Under a nitrogen atmosphere, the substrate 71 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 20.0 mol%), base (potassium tert-butoxide, 0.30 mmol) were dissolved in a solvent (tetrahydrofuran, 3.0 mL) and deuterium source (MeOD, 80 mmol). After addition, the reaction mixture was 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 h. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 72 (97% yield, purity > 95%). 1 H NMR(400MHz,CD 3 OD):δ7.03–6.98(m,0.20H,C 2 -H,C 6 -H, deuterium incorporation rate 90%), 6.97–6.94(m,0.78H,C 3 -H,C 5 -H, deuterium incorporation rate 61%), 3.43(q,J=11.0Hz,4H), 2.65–2.32(m,4H), 1.69–1.56(m,2H), 1.51–1.41(m,2H), 1.20(dt,J=10.4,3.5Hz,10H), 0.79(t,J=6.8Hz,3H); 13 C NMR(400MHz,CD 3 OD):δ139.9, 139.8, 128.0(m, labeled), 127.8(m, labeled), 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) calcd for C 19 H 30 D 4 NO 2 + [M+H] + 312.2835, found: 312.2836.

[0414] Example 37:

[0415]

[0416] Under a nitrogen atmosphere, the substrate 73 (0.30 mmol), a phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), a 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 addition, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 74 (99% yield, purity > 95%). 1 H NMR(400MHz,CD 3 OD):δ7.86–7.82(m,0.58H,C 4 -H, deuterium incorporation rate 42%), 7.77–7.72(m,0.69H,C 5 -H, deuterium incorporation rate 31%), 7.64–7.60(m,0.08H,C 1 -H, deuterium incorporation rate 92%), 7.42–7.38(m,0.50H,C 6 -H, deuterium incorporation rate 50%), 7.36–7.30(m,0.60H,C 7 -H, deuterium incorporation rate 40%), 7.25–7.18(m,0.40H,C 3 -H, deuterium incorporation 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(400MHz,MeOD)δ172.1, 157.9, 133.7, 133.1, 129.8(m, labeled), 129.4(m, labeled), 126.8(m, labeled), 126.5(m, labeled), 122.8(m, labeled), 122.7(m, labeled), 117.9(m, labeled), 101.9, 54.5, 40.0, 39.6, 32.8; HRMS(ESI) calculated value: C 15 H 15 D 3 NO 2 + [M+H] + 247.1520, measured value: 247.1522.

[0417] Example 38:

[0418]

[0419] Under a nitrogen atmosphere, the substrate 79 (0.30 mmol), the phenolic catalyst (2-phenylphenol, 5.0 mol%), and the base (phosphazene base, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 2.0 mL) and a deuterium source (EtOD, 50 mmol). After addition, the reaction mixture was placed at 45 °C and irradiated with a 425 nm LED (350 lux) lamp at a distance of 3 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 × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 80 (95% yield, purity > 95%). 1 H NMR(400MHz,Acetone-d 6 ):δ7.42–7.05(m,4.65H,C 3 -H,C 5 -H,C 2′, -H,C 3′, -H,C 4′, -H,C 5′, -H,C 6′, -H, deuteration rate 34%), 7.04–6.92(m,0.39H,C 6 -H, deuteration rate 61%), 6.88–6.78(m,0.85H,C 4 -H, deuteration rate 15%), 4.19–4.00(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=6.8Hz,3H). 13 C NMR(100MHz,Acetone-d 6 ):δ156.8,141.4,130.3(m, marked), 129.5, 128.8(m, marked), 128.1(m, marked), 127.5(m, marked), 125.6(m, marked), 120.2(m, marked), 111.4(m, marked), 69.9, 58.9, 50.2, 35.8, 26.6, 24.8, 12.2; HRMS(ESI) calculated value: C 21 H 19 D 9 NO + [M+H] + 319.2658, measured value: 319.2655.

[0420] Example 39:

[0421]

[0422] Under a nitrogen atmosphere, the substrate 81 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-methoxyphenol, 5.0 mol%), and the base (potassium tert-butoxide, 0.60 mmol) were dissolved in a solvent (tetrahydrofuran, 2.0 mL) and a deuterium source (EtOD, 50 mmol). After addition, the reaction mixture was placed at 50 °C and irradiated with a 415 nm LED (500 lux) lamp at a distance of 7 cm from the reaction device for 48 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 82 (90% yield, purity > 95%). 1 H NMR (400 MHz, Acetone-d 6 ): δ 7.52–7.23 (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, deuterium substitution rate 20%), 7.06 (m, 0.20H, C 3 -H, deuterium substitution rate 80%), 6.92 (m, 0.82H, C 5 -H, deuterium substitution rate 18%), 6.37 (m, 0.19H, C 6 -H, deuterium substitution 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-d 6 ): δ 175.1, 159.0, 145.0, 144.6, 132.8, 130.4, 130.3 (m, marked), 128.4 (m, marked), 128.2, 128.1 (m, marked), 127.8 (m, marked), 127.0, 126.9 (m, marked), 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 N 2O 2 + [M+H] + 440.3123, measured value: 440.3124.

[0423] Example 40:

[0424]

[0425] Under a nitrogen atmosphere, the substrate 83 (0.30 mmol), phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 5.0 mol%), 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 addition, the reaction mixture was placed at 55 °C and irradiated with a 400 nm LED (300 lux) lamp at a distance of 10 cm from the reaction device for 48 hours. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The organic phases were combined, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 84 (89% yield, purity > 95%). 1 H NMR (400 MHz, CD 3 OD): δ 7.16–7.11 (m, 0.39H, C 2 -H, deuteration rate 61%), 7.05–7.00 (m, 1.68H, C 6 -H, C 7 -H, deuteration rate 32%), 6.59–6.54 (m, 0.08H, C 3 -H, deuteration rate 92%), 6.55–6.50 (m, 1H), 4.23–4.07 (m, 3H), 3.05–2.98 (m, 1H), 2.98–2.88 (m, 1H), 2.83–2.75 (m, 1H), 1.18–1.13 (m, 6H). 13 C NMR (150 MHz, CD 3 OD): δ 153.6, 139.2, 123.8, 122.9 (m, labeled), 120.2, 106.1, 101.1, 99.4 (m, labeled), 71.9, 69.7, 51.1, 50.0, 22.4, 22.2; HRMS (ESI) calculated value: C 14 H 16 D 5 N 2 O 2 + [M+H] + 254.1839, measured value: 254.1840.

[0426] Example 41:

[0427]

[0428] Under a nitrogen atmosphere, the substrate 53 (0.30 mmol), the phenolic catalyst (2,6-di-tert-butyl-4-phenylphenol, 2.0 mol%), and the 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 was complete, the reaction mixture was 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 with water, and the aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The combined organic phases were washed successively 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 for the above operation without purification. After completion, the crude product was subjected to column chromatography to obtain 54 (97% yield, purity > 95%). 1 HNMR(400MHz,CDCl 3 ):δ7.03(s,0.03H,C 5 -H, deuterium incorporation rate 97%), 6.80(s,0.04H,C 6 -H, deuterium incorporation rate 96%), 6.70(s,0.04H,C 2 -H, deuterium incorporation rate 96%), 3.79(s,3H), 2.99(d,J=18.1Hz,1H), 2.81(dd,J=5.9,3.2Hz,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(100MHz,CDCl 3 ):δ158.2, 141.7, 129.8, 128.5(m, labeled), 111.1(m, labeled), 110.7(m, labeled), 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 D 3 NO + [M+H] + 275.2197, measured value: 275.2195.

[0429] Example 42:

[0430]

[0431] Under a nitrogen atmosphere, the substrate 55 (0.30 mmol), the phenolic catalyst (2,4,6-triphenylphenol, 5.0 mol%), and the 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 reaction mixture was placed at 55 °C and irradiated with a 455 nm LED (650 lux) lamp at a distance of 5 cm from the reaction device for 60 hours. Then, the heating was stopped, and the solvent was removed by concentration under reduced pressure to obtain a crude product. Without purification, the crude product was redissolved in a solvent (n-heptane, 6.0 mL) and a deuterium source (EtOD, 60 mmol), and the above operation was repeated. After the irradiation was completed, the reaction was quenched with water. The aqueous phase was extracted three times with ethyl acetate (15 mL × 3). The organic phases were combined, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 56 (95% yield, purity > 95%). 1 H NMR (400 MHz, CD 3 OD): δ 7.20 (s, 0.0.4H, C 2 -H, C 6 -H, deuterium incorporation rate 98%), 7.08 (s, 0.04H, C 3 -H, C 5 -H, deuterium incorporation 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, CD 3 OD) δ 177.2, 140.1, 138.4, 128.9 (m, labeled), 126.9 (m, labeled), 30.1, 21.5, 21.3, 17.7; HRMS (ESI) calculated value: C 13 H 13 D 4 O 2 - [M - H] - 209.1485, measured value: 209.1487.

[0432] Example 38:

[0433] Test the improvement effects of the two deuterium-labeled drugs prepared in Test Examples 30 and 37 on the pharmacokinetic characteristics in rats.

[0434] Sixteen male Sprague-Dawley rats (source: Experimental Animal Center of Yunnan University) were randomly divided into 2 groups according to body weight, namely the deuterated drug (10 mg / kg) experimental group (for 3 days) and the non-deuterated drug (10 mg / kg) as the control group (for 3 days), with 8 rats in each group. The drug solutions for intragastric administration were all prepared with 0.5% sodium carboxymethylcellulose solution. All experimental animals were fasted for 12 h before administration, and were allowed free access to water during this period. Blood samples (0.5 ml) were collected from the medial canthus veins of the eyes at 0 h (before administration), 0.25, 0.5, 0.75, 1, 1.33, 1.66, 2, 3, 4, 6, 8, and 12 h after administration, and placed in 1.5 ml heparinized centrifuge tubes. Plasma was separated after low-speed centrifugation (5000 rpm) for 10 min and stored in a -80 °C freezer for further analysis. Each analytical batch included blank samples, zero-concentration samples, a freshly prepared standard curve (preparation method: accurately weigh the samples into blank rat plasma to prepare calibration standards with concentrations of 5, 10, 25, 50, 100, 250, 500, and 1000 ng / ml), and quality control samples at three concentrations (10 ng / mL, 90 ng / mL, 900 ng / mL, not less than 5% of the total number of experimental samples). The drug concentration in the plasma of rats after administration was calculated according to the standard curve of the analytical batch. After deuteration, the drug showed a significant improvement in the pharmacokinetic characteristics of the drug in compound rats. Compared with the non-deuterated drug, it had a significant effect of prolonging the half-life (t 1 / 2 ) and increasing the maximum plasma drug concentration (C max ). The results are shown in the following table.

[0435]

[0436]

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 in 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 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 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, 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, ethyl acetate, Sodium alkoxide, 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 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 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 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 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 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 phenanthryl; (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 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 phenanthrenyl, 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, cyclopropyl, cyclobutyl, cyclohexyl or cyclopentyl, wherein the cyclohexyl 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, substituted by 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, 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; (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 a light 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, -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 in 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 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 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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