CN113563147B - Method for selectively deuterating aromatic ring benzyl hydrocarbon bond - Google Patents
Method for selectively deuterating aromatic ring benzyl hydrocarbon bond Download PDFInfo
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- CN113563147B CN113563147B CN202110863225.XA CN202110863225A CN113563147B CN 113563147 B CN113563147 B CN 113563147B CN 202110863225 A CN202110863225 A CN 202110863225A CN 113563147 B CN113563147 B CN 113563147B
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- 238000000034 method Methods 0.000 title claims abstract description 21
- 229930195733 hydrocarbon Natural products 0.000 title abstract description 9
- 239000004215 Carbon black (E152) Substances 0.000 title abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 239000001257 hydrogen Substances 0.000 claims abstract description 41
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- 239000010948 rhodium Substances 0.000 claims abstract description 21
- 229910052751 metal Inorganic materials 0.000 claims abstract description 17
- 239000002184 metal Substances 0.000 claims abstract description 17
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 17
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 8
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims description 60
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 39
- 238000004440 column chromatography Methods 0.000 claims description 35
- CSCPPACGZOOCGX-WFGJKAKNSA-N deuterated acetone Substances [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 claims description 30
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical group [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 claims description 28
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 11
- 239000011903 deuterated solvents Substances 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 150000007529 inorganic bases Chemical class 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 4
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical group CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 claims description 3
- 229910001386 lithium phosphate Inorganic materials 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- TWQULNDIKKJZPH-UHFFFAOYSA-K trilithium;phosphate Chemical compound [Li+].[Li+].[Li+].[O-]P([O-])([O-])=O TWQULNDIKKJZPH-UHFFFAOYSA-K 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000001492 aromatic hydrocarbon derivatives Chemical class 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- MCVFFRWZNYZUIJ-UHFFFAOYSA-M lithium;trifluoromethanesulfonate Chemical compound [Li+].[O-]S(=O)(=O)C(F)(F)F MCVFFRWZNYZUIJ-UHFFFAOYSA-M 0.000 claims description 2
- FJOLTQXXWSRAIX-UHFFFAOYSA-K silver phosphate Chemical compound [Ag+].[Ag+].[Ag+].[O-]P([O-])([O-])=O FJOLTQXXWSRAIX-UHFFFAOYSA-K 0.000 claims description 2
- 229940019931 silver phosphate Drugs 0.000 claims description 2
- 229910000161 silver phosphate Inorganic materials 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 37
- 229910052805 deuterium Inorganic materials 0.000 abstract description 6
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 230000004913 activation Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000002253 acid Substances 0.000 abstract 1
- 239000003513 alkali Substances 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 169
- 229910052799 carbon Inorganic materials 0.000 description 169
- 125000001743 benzylic group Chemical group 0.000 description 102
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 97
- 238000005481 NMR spectroscopy Methods 0.000 description 95
- 238000006243 chemical reaction Methods 0.000 description 84
- 238000004611 spectroscopical analysis Methods 0.000 description 35
- 229910018119 Li 3 PO 4 Inorganic materials 0.000 description 20
- 239000000758 substrate Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 2
- 125000004431 deuterium atom Chemical group 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 230000035502 ADME Effects 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003378 silver Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
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- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
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- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
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- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
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Abstract
The invention discloses a method for selectively deuterating aromatic ring benzyl hydrocarbon bond. The method utilizes a rhodium metal catalyst to carry out eta on an aromatic ring 6 Coordination activation enables selective exchange of hydrogen and deuterium with deuterated reagents at the benzyl position. The method of the invention does not need to add strong acid or strong alkali, and is low in cost and easy to obtainThe deuteration reagent is used as a deuterium source, has good universality for various aromatic hydrocarbons with different functional groups, can be applied to selective deuteration of the later stage of complex drug molecules, and has high application value.
Description
Technical Field
The invention relates to the technical field of hydrogen-deuterium exchange, in particular to a method for selectively deuterating a benzyl hydrocarbon bond from common aromatic hydrocarbon.
Background
The C-D bonds are more stable in the living body than the C-H bonds due to the kinetic isotopic effect of the deuterium atoms. In drug development, the introduction of deuterium atoms to specific sites of a target molecule, such as the benzyl position of an aryl group, can significantly alter its pharmacokinetic properties (ADME). In addition, deuterated compounds have also found wide application in reaction mechanism studies.
Currently, there are mainly the following methods for synthesizing deuterated compounds with benzylic hydrocarbon bonds:
(1) Starting from commercially available deuterated starting materials, it is obtained by a multi-step synthesis. The process is generally cumbersome and does not give high overall yields.
(2) Starting from the raw material which is not marked by deuterium, the raw material is directly subjected to hydrogen deuterium exchange at the benzyl position to synthesize the raw material, and the steps are simple and direct. However, the current methods for realizing deuteration of the benzyl hydrocarbon bond have few reports and have great limitations. One such method is to grab the benzyl position of the substrate molecule with a strong base (e.g., potassium t-butoxide/DMSO) and then hydrogen deuterium exchange with a deuterated reagent (Hu, y.; liang, l.; wei, w.; sun, x.; zhang, x.; yan, m. tetrahedron 2015,71,1425; tie, l.; shan, x.; h.; qu, j.; p.; kang, y.; B.Org.Chem.Front.2021, DOI:10.1039/d1qo00265 a). The method has poor compatibility of substrate functional groups and is only suitable for simpler molecules. Another class of methods is the use of transition metal catalysts such as Pd/C, ru, ni, co, rh, ir, etc. (Sajiki, h.; aoki, f; esaki, h.; maegawa, t., hirota, K.Org.Lett.2004,6,1485;Neubert,L, michalik, d., bahn, s., imm, s.neumann, h., atzrodt, j., derdau, v., holla, w., beller, m.j.am.chem.soc.2012,134,12239, heys, j.r.j.label compd.radiopharm 2010,53 716;Palmer,W.N, chirik, p.j.acs catalyst.7, 7,5674, rhinehart, j.l., manbeck, k.a., buzak, s.k., lippa, g.m., brennessel, w., goldberg, k.i., jones, w.d.organometal, 2012,31, d.labelcompd.radiopharm, 2010,53 716;Palmer,W.N, chik, p.j.acs.c.7, 7,5674, rhinehart, j.l., manbeck, k.k.a., buzak, s.k., lippa, g.m., brennessel, w., goldberg, k.i., w., j.j.j.m., g., g.d.d.d.m., d.metal, d.d.m., c., 35, g., g.g.g., g. But due to other hydrocarbons in the moleculeThe influence of bonds, the use of transition metal catalysis for benzylic deuteration often presents selectivity problems, e.g. sp on the aromatic ring 2 The carbon hydrogen bond may also be deuterated.
In conclusion, although the aromatic ring benzyl hydrocarbon bond selective deuteration has important significance in organic chemistry and pharmaceutical chemistry, the existing method has the problems of narrow substrate applicability, poor deuteration selectivity and the like, and limits the application of the method in the late selective deuteration of complex molecules.
Disclosure of Invention
Aiming at the defects of narrow applicability, poor deuteration selectivity and the like of the existing substrate, the invention provides a method for selectively deuterating hydrocarbon bonds at the benzyl positions of aromatic rings. The method comprises the steps of 6 The coordination activation is realized, and the specific mechanism is as follows: aromatic ring and rhodium metal ([ Rh)]) Generating eta 6 After coordination, the acidity of the benzyl C-H bond is greatly enhanced. This allows easier H/D exchange of the benzylic C-H bond than other C-H bonds, providing a basis for benzylic selective deuteration.
The aim of the invention is achieved by the following technical scheme:
a method for selectively deuterating aromatic ring at benzyl position comprises the steps of preparing raw material S in nitrogen atmosphere 1 Rhodium metal catalyst ([ Rh)]) Silver salts ([ Ag)]) Mixing uniformly, adding deuterated solvent (solvent), stirring at 80-140 deg.C to make them react completely, cooling to room temperature, concentrating, column chromatography separating to obtain compound S 1 D, the benzyldeuterated product, is specifically of the formula:
wherein, raw material S 1 Is aromatic hydrocarbon or aromatic hydrocarbon derivative;
the metal rhodium catalyst is a derivative of pentamethyl cyclopentadienyl rhodium dichloride dimer;
the silver salt is silver salt with weak coordination counter silver ion;
the deuterated solvent is deuterated methanol or deuterated acetone, and when the deuterated solvent is deuterated acetone, phosphate is required to be added as inorganic Base (Base); at this time the raw material S 1 The ratio of the metal rhodium catalyst, the silver salt, the inorganic base and the deuterated acetone is 1: (5-10 mol%): (10-40 mol%): (10-100 mol%): (0.5-4 mol/L);
when the deuterated solvent is deuterated methanol, the raw material S is 1 The ratio of the metal rhodium catalyst to the silver salt to the deuterated solvent is 1: (5-10 mol%): (10-40 mol%): (0.5-4 mol/L);
the silver salt and the rhodium metal catalyst satisfy the molar ratio of [ Ag ]/[ Rh ] =2: 1.
preferably, the raw material S 1 The R group in (a) is a hydrogen atom, an alkyl group, an aryl group or a heteroatom, but is not limited to these groups.
Preferably, the metal rhodium catalyst is a derivative of pentamethyl cyclopentadienyl rhodium dichloride dimer, as shown below:
of these, catalyst10 (cat.10) works best.
Preferably, the silver salt is AgNTf 2 、AgOTf、AgSbF 6 、AgBF 4 、AgPF 6 Any one or a combination of a plurality of the components according to any proportion, wherein AgNTf 2 The effect is optimal.
Preferably, the inorganic base is selected from any one or a combination of a plurality of phosphates such as lithium phosphate, sodium phosphate and silver phosphate according to any proportion, wherein the lithium phosphate is optimal.
Preferably, an inorganic salt with a weakly coordinating counter silver ion is also added as an additive to the reaction.
Preferably, the additive is LiNTf 2 、NaNTf 2 、KNTf 2 Any of LiOTf, naOTf, KOTfOne or a combination of a plurality of the components according to arbitrary proportion, wherein NaNTf 2 The effect is optimal.
Preferably, raw material S 1 The proportion of the metal rhodium catalyst, the silver salt, the inorganic base and the deuterated acetone is as follows: 1:2.5mol%:10mol%:10mol%:1mol/L.
Preferably, raw material S 1 The ratio of the metal rhodium catalyst to the silver salt to the deuterated methanol is as follows: 1:2.5mol%:10mol%:1mol/L.
The beneficial effects of the invention are as follows:
(1) Most of the raw materials used in the invention are commercially available, and the operation and treatment are convenient without special purification treatment.
(2) The method is simple and convenient to operate, and the target compound can be obtained in one step with high yield, high deuteration rate and high selectivity only by mixing and heating all reactants.
(3) The substrate functional group of the invention has wide compatibility, and can be applied to the late deuteration reaction of complex bioactive molecules and drug molecules.
Detailed Description
The objects and effects of the present invention will become more apparent from the following detailed description of the preferred embodiments, it being understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to be limiting.
The following examples are given to select different kinds of substrates, and to illustrate the specific operation of the reaction and the specific conditions of the reaction, and to better illustrate the present invention from different structural ranges. The products were identified by nuclear magnetic resonance and chiral products were detected by supercritical liquid chromatography (SFC).
Example 1
Raw material 1 (0.2 mmol,30.0 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). After stirring the reaction at 120℃for 24 hours, it was cooled to room temperature, and 1, 2-tetrachloroethane (0.2 mmol,33.6 mg) and deuterated chloroform (0.5 mL) were added thereto, and the target product was found to have a benzyldeuteration rate of 86% and a nuclear magnetic resonance yield of 99% by nuclear magnetic resonance spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.16(d,J＝8.7Hz,2H),6.85(d,J＝8.7Hz,2H),3.80(s,3H),2.92–2.80(m,0.14H,86％ D),1.28–1.16(m,6H). 13 C NMR(126MHz,Chloroform-d)δ157.6,127.2,141.0,113.7,55.2,33.2(benzylic carbon of remaining 1),32.8(t,J＝19.5Hz,benzylic carbon of deuterated 1),24.19–24.08(m,–CH 3 carbon).
Example 2
Raw material 22 (0.2 mmol,24.0 mg), catalyst1 (0.005 mmol,3.1 mg), agOTf (0.02 mmol,5.1 mg), naOTf (0.2 mmol,34.4 mg) and finally methanol-d were added sequentially to a reaction flask under nitrogen atmosphere 4 (0.2 mL). After stirring the reaction at 120℃for 24 hours, it was cooled to room temperature, and 1, 2-tetrachloroethane (0.2 mmol,33.6 mg) and deuterated chloroform (0.5 mL) were added thereto, whereby the target product was found to have a benzyldeuteration ratio of 50% and a magnetonuclear yield of 99% by nuclear magnetic resonance spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.30–7.26(m,2H),7.23–7.21(m,2H),7.19–7.15(m,1H),2.95–2.86(m,0.50H,50％ D),1.26–1.21(m,6H). 13 C NMR(126MHz,Chloroform-d)δ148.74–148.71(m,aromatic carbon adjacent to benzylic carbon),128.2,126.3,125.6,34.0(benzylic carbon of remaining 2),33.53(t,J＝19.5Hz,benzylic carbon of deuterated 2),23.81–23.70(m,–CH 3 carbon).
Example 3
Raw material 3 (0.2 mmol,29.7 mg), catalyst 11 (0.005 mmol,3.7 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). After stirring the reaction at 120℃for 24 hours, it was cooled to room temperature, and 1, 2-tetrachloroethane (0.2 mmol,33.6 mg) and deuterated chloroform (0.5 mL) were added thereto, and the target product was found to have a benzyldeuteration ratio of 83% and a nuclear magnetic resonance yield of 99% by nuclear magnetic resonance spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.31(d,J＝8.3Hz,2H),7.14(d,J＝8.3Hz,2H),2.38–2.31(m,0.51H,83％ D),1.34(s,6H). 13 C NMR(126MHz,Chloroform-d)δ148.2,134.8–134.7(m,aromatic carbon adjacent to benzylic methyl carbon),128.7,125.1,34.3,31.4,20.8–19.4(m,benzylic methyl carbon).
Example 4
Raw material 4 (0.2 mmol,26.8 mg), catalyst 12 (0.01 mmol,7.4 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.04mmol,15.6mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the target product in 85% yield. The target product was determined to have a benzyldeuteration rate of 72% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.28–7.27(m,2H),7.18–7.13(m,3H),2.48–2.44(m,0.56H,72％ D),1.90–1.81(m,1H),0.90(d,J＝6.5Hz,6H). 13 C NMR(126MHz,Chloroform-d)δ141.7–141.6(m,aromatic carbon adjacent to benzylic carbon),129.1,128.0,125.6,45.5(benzylic carbon of remaining 4),45.2–44.3(m,benzylic carbon of deuterated 4),30.28–29.99(m,–CH carbon),22.38–22.24(m,–CH 3 carbon).
Example 5
Raw material 5 (0.2 mmol,33.6 mg), cat, was added sequentially to the reaction flask under nitrogen atmospherealyst 10(0.005mmol,3.5mg)，AgNTf 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 81% yield. The target product was found to have a benzyldeuteration rate of 88% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.33–7.30(m,4H),7.24–7.22(m,6H),4.02–4.00(m,0.23H,88％ D). 13 C NMR(126MHz,Chloroform-d)δ141.07–141.04(m,aromatic carbon adjacent to benzylic carbon),128.9,128.4,126.1,41.9–40.9(m,benzylic carbon).
Example 6
Raw material 6 (0.2 mmol,36.4 mg), catalyst 26 (0.01 mmol,8.6 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 140 ℃ for 48 hours, cooled to room temperature and subjected to direct column chromatography to give the target product in 92% yield. The target product was 90% benzyldeuterated as determined by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.28–7.25(m,4H),7.22–7.20(m,4H),7.18–7.16(m,2H),4.16–4.12(m,0.10H,90％ D),1.64–1.62(m,3H). 13 C NMR(126MHz,Chloroform-d)δ146.34–146.30(m,aromatic carbon adjacent to benzylic carbon),128.3,127.6,126.0,44.7(benzylic carbon of remaining 6),44.3(t,J＝19.5Hz,benzylic carbon of deuterated 6),21.83–21.71(m,–CH 3 carbon).
Example 7
Raw material 7 (0.2 mmol,39.3 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.4 mmol,121.2 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 140 ℃ for 48 hours, cooled to room temperature and subjected to direct column chromatography to give the target product in 92% yield. The target product was found to have a benzyldeuteration rate of 87% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.62–7.61(m,2H),7.57–7.55(m,2H),7.47–7.44(m,2H),7.37–7.32(m,3H),3.03–2.95(m,0.13H,87％ D),1.33–1.32(m,6H). 13 C NMR(126MHz,Chloroform-d)δ147.98–147.96(m,aromatic carbon adjacent to benzylic carbon),141.2,138.7,128.7,127.1,127.0,126.9,126.8,33.8(benzylic carbon of remaining 7),33.4(t,J＝19.5Hz,benzylic carbon of deuterated 7),24.00–23.90(m,–CH 3 carbon).
Example 8
Raw material 8 (0.2 mmol,26.8 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.4 mL). After stirring the reaction at 120℃for 24 hours, it was cooled to room temperature, and 1, 2-tetrachloroethane (0.2 mmol,33.6 mg) and deuterated chloroform (0.5 mL) were added thereto, whereby the target product was 80% in terms of benzyldeuteration and 99% in terms of nuclear magnetic resonance yield, as determined by nuclear magnetic resonance hydrogen spectrometry. 1 H NMR(500MHz,Chloroform-d)δ7.32–7.27(m,2H),7.19–7.16(m,3H),2.62–2.56(m,0.2H,80％ D),1.61–1.57(m,2H),1.25–1.23(m,3H),0.82(t,J＝7.4Hz,3H). 13 C NMR(126MHz,Chloroform-d)δ147.54–147.52(m,aromatic carbon adjacent to benzylic carbon),128.1,126.9,125.6,41.5(benzylic carbon of remaining 8),41.0(t,J＝19.5Hz,benzylic carbon of deuterated 8),31.00–30.89(m,–CH 2 carbon),21.62–21.51(m,–CH 3 carbon),12.00–11.98(m,–CH 3 carbon).
Example 9
Raw material 9 (0.2 mmol,32.5 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.4 mmol,121.2 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature, and subjected to direct column chromatography to give the desired product in 87% yield. The target product was determined to have a benzyldeuteration rate of 66% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.33–7.30(m,2H),7.24–7.23(m,2H),7.21–7.18(m,1H),2.55–2.49(m,0.34H,68％ D),1.91–1.85(m,4H),1.79–1.76(m,1H),1.50–1.38(m,4H),1.33–1.24(m,1H). 13 C NMR(126MHz,Chloroform-d)δ148.09–148.07(m,aromatic carbon adjacent to benzylic carbon),128.3,126.82–126.80(m),125.8,44.6(benzylic carbon of remaining 9),44.1(t,J＝19.3Hz,benzylic carbon of deuterated 9),34.47–34.37(m,–CH 2 carbon),26.93–26.92(m,–CH 2 carbon),26.2.
Example 10
Raw material 10 (0.2 mmol,26.4 mmg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially charged into a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). After stirring the reaction at 120℃for 24 hours, it was cooled to room temperature, and 1, 2-tetrachloroethane (0.2 mmol,33.6 mg) and deuterated chloroform (0.5 mL) were added to determine the target product, namely, the benzyldeuteration ratio was 87% and 48% and the nuclear magnetic yield was 99% by nuclear magnetic resonance hydrogen spectrometry. 1 H NMR(500MHz,Chloroform-d)δ7.22–7.12(m,4H),3.21–3.116(m,0.13H,87％ D),2.94–2.80(m,1.04H,48％ D),2.32–2.27(m,1H),1.63–1.57(m,1H),1.30–1.28(m,3H). 13 C NMR(126MHz,Chloroform-d)δ148.51–148.43(m,aromatic carbon adjacent to benzylic carbon),143.65–143.54(m,aromatic carbon adjacent to benzylic carbon),125.8,124.08–124.05(m),122.9,39.14–38.55(m,benzylic–CH carbon),34.33–34.12(m,benzylic–CH 2 carbon),31.11–30.60(m,–CH 2 carbon),19.49–19.40(m,–CH 3 carbon).
Example 11
Raw material 11 (0.2 mmol,26.4 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.1 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature, and subjected to direct column chromatography to give the target product in a yield of 72%. The target product was found to have a benzyldeuteration rate of 81% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.09–7.04(m,4H),2.77–2.72(m,0.76H,81％ D),1.79–1.77(m,4H). 13 C NMR(126MHz,Chloroform-d)δ137.11–137.06(m,aromatic carbon adjacent to benzylic carbon),129.1,125.4,29.36–28.29(m,benzylic carbon),23.15–22.94(m,–CH 2 carbon).
Example 12
Raw material 12 (0.2 mmol,33.2 mg), catalyst 21 (0.005 mmol,4.4 mg) and AgSbF were sequentially added to a reaction flask under nitrogen atmosphere 6 (0.02mmol,6.9mg)，KNTf 2 (0.4 mmol,127.7 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 80 ℃ for 48 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 86% yield. The target product was found to have a benzyldeuteration rate of 88% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.78–7.76(m,2H),7.53–7.51(m,2H),7.38–7.34(m,2H),7.30–7.27(m,2H),3.88–3.85(m,0.24H,88％ D). 13 C NMR(126MHz,Chloroform-d)δ143.14–143.11(m),141.75–141.71(m),126.71,126.66,125.02–125.00(m),119.8,36.89–35.96(m,benzylic carbon).
Example 13
Raw material 13 (0.2 mmol,36.1 mg), catalyst 23 (0.005 mmol,4.5 mg), agOTf (0.02 mmol,5.1 mg) and LiNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.2 mmol,57.4 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 83% yield. The target product was determined to have a benzyldeuteration rate of 92% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.75–7.74(m,2H),7.50–7.48(m,2H),7.36–7.29(m,4H),3.95–3.91(m,0.08H,92％ D),1.50–1.48(m,3H). 13 C NMR(126MHz,Chloroform-d)δ148.96–148.94(m),140.55–140.49(m),126.9,124.0,119.8,42.4(benzylic carbon of remaining 14),42.0(t,J＝19.8Hz,benzylic carbon of deuterated 14),18.1.
Example 14
Raw material 14 (0.2 mmol,36.1 mg), catalyst10 (0.01 mmol,7.0 mg) and AgPF were sequentially charged to a reaction flask under nitrogen atmosphere 6 (0.04 mmol,10.1 mg), KOTF (0.2 mmol,37.6 mg), and finally methanol-d were added 4 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 83% yield. The target product was found to have a benzyldeuteration rate of 76% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.75(d,J＝7.7Hz,2H),7.32–7.28(m,2H),7.24–7.22(m,4H),2.87–2.84(m,0.96H,76％D). 13 C NMR(126MHz,Chloroform-d)δ137.37–137.27(m,aromatic carbon adjacent to benzylic carbon),134.5,128.1,127.4,126.9,123.7,28.93–28.31(m,benzylic carbon).
Example 15
Raw material 15 (0.2 mmol,30.4 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature, and subjected to direct column chromatography to give the desired product in 87% yield. The target product was determined to have a benzyldeuteration rate of 64% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.22–7.20(m,1H),7.18–7.14(m,1H),6.94–6.91(m,1H),6.86–6.84(m,1H),3.83(s,3H),3.36–3.28(m,0.36H,64％ D),1.22–1.20(m,6H). 13 C NMR(126MHz,Chloroform-d)δ156.74–156.72(m),136.99–136.96(m,aromatic carbon adjacent to benzylic carbon),126.5,125.98–125.96(m),120.5,110.3,55.3,26.6(s,benzylic carbon of remaining 17),26.2(t,J＝19.8Hz,benzylic carbon of deuterated 17),22.66–22.57(m,–CH 3 carbon).
Example 16
Raw material 16 (0.2 mmol,27.2 mg), catalyst10 (0.01 mmol,7.0 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.04mmol,15.6mg)，Li 3 PO 4 (0.2 mmol,23 mg) and finally acetone-d 6 (0.2 mL). After stirring the reaction at 120℃for 24 hours, it was cooled to room temperature, and 1, 2-tetrachloroethane (0.2 mmol,33.6 mg) and deuterated chloroform (0.5 mL) were added thereto, and the target product was determined to have a benzyldeuteration rate of 70% and a nuclear magnetic resonance yield of 99% by nuclear magnetic resonance spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.12–7.10(m,2H),6.85–6.82(m,2H),3.79(s,3H),2.62–2.57(m,0.60H,70％ D),1.21–1.19(m,3H). 13 C NMR(126MHz,Chloroform-d)δ157.1,135.65–135.60(m,aromatic carbon adjacent to benzylic carbon),128.1,113.1,54.5,27.34–26.33(m,benzylic carbon),15.28–15.11(m,–CH 3 carbon).
Example 17
Raw material 17 (0.2 mmol,26.8 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). After stirring the reaction at 120℃for 24 hours, it was cooled to room temperature, and 1, 2-tetrachloroethane (0.2 mmol,33.6 mg) and deuterated chloroform (0.5 mL) were added thereto, and the target product was found to have a benzyldeuteration rate of 74% and a nuclear magnetic resonance yield of 99% by nuclear magnetic resonance spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.09–7.06(m,1H),7.04–7.02(m,1H),6.84–6.81(m,1H),6.79–6.78(m,1H),4.20–4.16(t,J＝5.0Hz,2H),2.80–2.75(m,0.53H,74％ D),2.03–1.98(m,2H). 13 C NMR(126MHz,Chloroform-d)δ154.91–154.87(m),129.8,127.2,122.19–122.08(m,aromatic carbon adjacent to benzylic carbon),120.1,116.7,66.4,24.85–23.98(m,benzylic carbon),22.35–22.15(m,–CH 2 carbon).
Example 18
Raw material 18 (0.2 mmol,36.4 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature, and subjected to direct column chromatography to give the desired product in 97% yield. The target product was found to have a benzyldeuteration rate of 63% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.21–7.13(m,4H),7.04–6.99(m,4H),4.03–4.00(m,0.75H,63％ D). 13 C NMR(126MHz,Chloroform-d)δ151.94–151.91(m),128.9,127.6,122.9,120.53–120.41(m,aromatic carbon adjacent to benzylic carbon),116.4,27.83–26.96(m,benzylic carbon).
Example 19
Raw material 19 (0.2 mmol,32.6 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Na 3 PO 4 (0.02mmol，3.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature, and subjected to direct column chromatography to give the target product in 55% yield. The target product was 52% benzyldeuterated as determined by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.11–7.06(m,2H),6.71(d,J＝9.1Hz,0.13H,93％ D),2.91(s,6H),2.85–2.80(m,0.48H,52％ D),1.23–1.21(m,3H). 13 C NMR(126MHz,Chloroform-d)δ148.95–148.90(m),137.21–137.17(m,aromatic carbon adjacent to benzylic carbon),126.79–126.78(m),112.99–112.52(m,aromatic carbon at ortho position of NMe 2 ),40.9,33.0(s,benzylic carbon of remaining 22),32.7(t,J＝19.2Hz,benzylic carbon of deuterated 22),24.21–24.10(m,–CH 3 carbon).
Example 20
Raw material 23 (0.2 mmol,40.5 mg), catalyst 11 (0.005 mmol,3.7 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature, and directly purifiedChromatography gave the target product in 77% yield. The target product was found to have a benzyldeuteration rate of 76% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.28(t,J＝7.4Hz,2H),7.23(t,J＝7.7Hz,2H),7.19(d,J＝7.3Hz,1H),7.15(d,J＝7.4Hz,2H),7.10(d,J＝8.3Hz,2H),3.93–3.91(m,0.48H,76％ D). 13 C NMR(126MHz,Chloroform-d)δ140.53–140.46(m,aromatic carbon adjacent to benzylic carbon),139.56–139.49(m,aromatic carbon adjacent to benzylic carbon),131.9,130.2,128.8,128.55,128.54,126.3,41.22–40.38(m,benzylic carbon).
Example 21
Raw material 21 (0.2 mmol,49.0 mg), catalyst10 (0.005 mmol,3.5 mg) and AgBF were sequentially charged into a reaction flask under nitrogen atmosphere 4 (0.02 mmol,3.8 mg), liOTf (0.2 mmol,31.2 mg), finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 98% yield. The target product was found to have a benzyldeuteration rate of 87% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.71(d,J＝7.5Hz,1H),7.63(d,J＝1.9Hz,1H),7.58(d,J＝8.1Hz,1H),7.50–7.45(m,2H),7.37–7.34(m,1H),7.31–7.28(m,1H),3.83–3.80(m,0.26H,87％D). 13 C NMR(126MHz,Chloroform-d)δ145.11–145.08(m),142.76–142.72(m,aromatic carbon adjacent to benzylic carbon),140.72–140.67(m,aromatic carbon adjacent to benzylic carbon),129.8,128.22–128.20(m),127.1,126.9,125.0,121.0,120.4,119.9,36.69–35.93(m,benzylic carbon).
Example 22
Raw material 22 (0.2 mmol,48.5 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 90% yield. The target product was found to have a benzylic deuteration of 83% and 59% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.71(d,J＝7.5Hz,1H),7.63(d,J＝1.9Hz,1H),7.58(d,J＝8.1Hz,1H),7.50–7.45(m,2H),7.37–7.34(m,1H),7.31–7.28(m,1H),3.83–3.80(m,0.26H,87％ D). 13 C NMR(126MHz,Chloroform-d)δ145.11–145.08(m),142.76–142.72(m,aromatic carbon adjacent to benzylic carbon),140.72–140.67(m,aromatic carbon adjacent to benzylic carbon),129.8,128.22–128.20(m),127.1,126.9,125.0,121.0,120.4,119.9,36.69–35.93(m,benzylic carbon).
Example 23
Raw material 23 (0.2 mmol,30.0 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature, and subjected to direct column chromatography to give the objective product in 59% yield. The target product was determined to have a benzyldeuteration rate of 64% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.30–7.27(m,2H),7.20–7.175(m,3H),3.39(t,J＝6.4Hz,2H),3.35(s,3H),2.70–2.65(m,0.72H,64％ D),1.91–1.86(m,2H). 13 C NMR(126MHz,Chloroform-d)δ141.97–141.90(m,aromatic carbon adjacent to benzylic carbon),128.5,128.3,125.8,71.93–71.90(m),58.6,32.31–31.43(m,benzylic carbon),31.26–31.10(m).
Example 24
In the atmosphere of nitrogen gas, the air is heated,to the reaction flask was then added raw material 24 (0.2 mmol,40.5 mg), catalyst10 (0.01 mmol,7.0 mg), agNTf 2 (0.04mmol,15.6mg)，Ag 3 PO 4 (0.02mmol，8.4mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 99% yield. The target product was determined to have a benzyldeuteration rate of 70% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.82–7.78(m,4H),7.50–7.48(m,2H),7.44–7.41(m,4H),7.25–7.24(m,2H),7.17–7.13(m,3H),4.06–4.02(m,2H),2.74–2.69(m,0.60H,70％ D),2.04–2.00(m,2H). 13 C NMR(126MHz,Chloroform-d)δ140.95–140.88(m,aromatic carbon adjacent to benzylic carbon),132.1(d,J＝2.9Hz),131.9,131.5(d,J＝10.2Hz),130.8,128.4(d,J＝13.2Hz),128.3,125.9,64.1(d,J＝6.0Hz),32.01–30.90(m,benzylic carbon).
Example 25
Raw material 25 (0.2 mmol,44.0 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 95% yield. The benzyl deuteration rate of the target product is 77% and 85% determined by nuclear magnetic hydrogen spectrum. 1 H NMR(500MHz,Chloroform-d)δ7.19(d,J＝7.9Hz,2H),7.09(d,J＝8.0Hz,2H),3.72–3.67(m,0.15H,85％ D),3.65(s,3H),2.45–2.41(m,0.47H,77％ D),1.87–1.79(m,1H),1.49–1.48(m,3H),0.89(d,J＝6.7Hz,6H). 13 C NMR(126MHz,Chloroform-d)δ175.2,140.49–140.42(m,aromatic carbon adjacent to benzylic carbon),137.71–137.65(m,aromatic carbon adjacent to benzylic carbon),129.3,127.1,51.9,44.99–44.04(m,containing two benzylic carbons),30.12–29.96(m),22.32–22.29(m),18.57–18.46(m).
Example 26
Raw material 26 (0.2 mmol,38.8 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 91% yield. The target product was determined to have a benzyldeuteration rate of 85% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.21–7.17(m,1H),7.15–7.13(m,1H),6.89–6.83(m,2H),3.81(s,3H),3.66(s,3H),2.95–2.90(m,0.31H,85％ D),2.61–2.60(m,2H). 13 C NMR(126MHz,Chloroform-d)δ173.8,157.4,129.9,128.74–128.67(m,aromatic carbon adjacent to benzylic carbon),127.6,120.4,110.1,55.1,51.4,33.95–33.82(m),26.07–25.14(m,benzylic carbon).
Example 27
Raw material 27 (0.2 mmol,44.0 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 93% yield. The target product was found to have a benzyldeuteration rate of 76% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.28–7.25(m,2H),7.20–7.15(m,3H),5.73(s,1H),3.05(t,J＝7.0Hz,2H),2.66–2.60(m,0.48H,76％ D),2.17(t,J＝7.6Hz,2H),1.97–1.93(m,2H),1.80–1.69(m,1H),0.89(d,J＝6.8Hz,6H). 13 C NMR(126MHz,Chloroform-d)δ172.8,141.43–141.37(m,aromatic carbon adjacent to benzylic carbon),128.4,128.3,125.9,46.7,35.90–35.85(m),35.12–34.39(m,benzylic carbon),28.4,27.19–27.03(m),20.00.
Example 28
Raw material 28 (0.2 mmol,35.0 mg), catalyst10 (0.01 mmol,7.0 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.04mmol,15.6mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature, and subjected to direct column chromatography to give the target product in 77% yield. The target product was determined to have a benzyldeuteration rate of 91% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.35–7.32(m,2H),7.27–7.25(m,1H),7.25–7.21(m,2H),3.74(d,J＝9.7Hz,1H),3.62–3.52(m,0.09H,91％ D),3.40(d,J＝9.7Hz,1H),2.90(s,3H),2.80(d,J＝16.8Hz,1H),2.54(d,J＝16.8Hz,1H). 13 C NMR(126MHz,Chloroform-d)δ173.9,142.42–142.38(m,aromatic carbon adjacent to benzylic carbon),128.8,127.0,126.6,56.62–56.56(m),38.73–38.66(m),37.0(s,benzylic carbon of remaining 33),36.7(t,J＝20.3Hz,benzylic carbon of deuterated 33),29.5.
Example 29
Raw material 29 (0.2 mmol,55.1 mg), catalyst10 (0.01 mmol,7.0 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.04mmol,15.6mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120 ℃ for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 79% yield. The target product was found to have a benzyldeuteration rate of 60% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.69(d,J＝8.2Hz,2H),7.28–7.24(m,4H),7.21–7.18(m,1H),7.08–7.07(m,2H),4.66(t,J＝6.1Hz,1H),3.20–3.17(m,2H),2.76–2.72(m,0.81H,60％ D),2.41(s,3H). 13 C NMR(126MHz,Chloroform-d)δ143.3,137.67–137.60(m,aromatic carbon adjacent to benzylic carbon),136.8,129.6,128.7,128.6,127.0,126.7,44.17–44.06(m),35.72–34.88(m,benzylic carbon),21.5.
Example 30
Raw material 30 (0.2 mmol,50.2 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 94% yield. The target product was determined to have a benzyldeuteration rate of 72% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.83–7.80(m,2H),7.71–7.68(m,2H),7.29–7.24(m,4H),7.22–7.19(m,1H),3.92–3.91(m,2H),3.00–2.95(m,0.56H,72％ D). 13 C NMR(126MHz,Chloroform-d)δ168.1,137.93–137.85(m,aromatic carbon adjacent to benzylic carbon),133.8,132.0,128.8,128.5,126.6,123.1,39.20–39.07(m),34.53–33.54(m,benzylic carbon).
Example 31
Raw material 31 (0.2 mmol,29.8 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，NaNTf 2 (0.2 mmol,60.6 mg), HOTf (0.24 mmol,36.0 mg), and finally methanol-d were added 4 (0.2 mL). Stirring the reaction at 120 ℃ for 24 hours, cooling to room temperature, and directly performing column chromatography to obtainThe yield to the target product was 85%. The target product was found to have a benzyldeuteration rate of 68% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(600MHz,Chloroform-d)δ7.28–7.25(m,2H),7.21–7.18(m,1H),7.15–7.13(m,2H),5.96(s,3H),3.37–3.31(m,1H),2.66–2.59(m,0.65H,68％ D),2.02–1.97(m,1H),1.85–1.80(m,1H),1.31(d,J＝6.6Hz,3H). 13 CNMR(126MHz,Chloroform-d)δ139.58–139.42(m,aromatic carbon adjacent to benzylic carbon),128.7,128.1,126.5,119.4(q,J＝320.4Hz),49.3,35.92–35.77(m),31.37–30.53(m,benzylic carbon),18.1.
Example 32
Raw material 32 (0.2 mmol,54.6 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 83% yield. The target product was found to have a benzyldeuteration rate of 78% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.68–7.63(m,3H),7.22–7.17(m,3H),7.07(d,J＝6.2Hz,1H),6.96(t,J＝7.4Hz,1H),3.91–3.89(m,2H),2.89–2.84(m,0.45H,78％ D),2.36(s,3H). 13 C NMR(126MHz,Chloroform-d)δ144.0,142.00–141.94(m,aromatic carbon adjacent to benzylic carbon),134.0,131.71–131.58(m),129.6,127.7,127.3,125.09–125.07(m),123.6,114.9,49.88–49.73(m),27.81–27.03(m,benzylic carbon),21.5.
Example 33
Raw material 333 (0.2 mmol,50.5 mg), catalyst10 (0.01 mmol,7.0 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.04mmol,15.6mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally adding methanol-d 4 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 82% yield. The target product was determined to have a benzyldeuteration rate of 72% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.54(d,J＝8.0Hz,2H),7.32–7.27(m,4H),7.24–7.21(m,1H),7.18–7.16(m,2H),3.00–2.98(m,2H),2.96–2.91(m,0.57H,72％ D).Quantitative 13 C NMR(151MHz,Chloroform-d)δ145.7(s,1C),141.02–140.95(m,1C),128.8(s,2C),128.4(s,5C),126.1(s,1C),125.26–125.18(m,2C),124.4(m,J＝271.8Hz,1C,–CF 3 carbon),37.63–37.49(m,1C,benzylic carbon adjacent to 4-CF 3 C 6 H 4 –group),37.25–36.49(m,benzylic carbon adjacent to phenyl group,containing 0.07undeuterated C,0.47mono-deuterated C,0.46di-deuterated C,70％D). 19 F NMR(471MHz,Chloroform-d)δ-62.3.
Example 34
Raw material 34 (0.2 mmol,32.8mg,>99/1e.r.)，catalyst 10(0.005mmol,3.5mg)，AgNTf 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 90% yield. The target product was 62% benzyldeuterated as determined by nuclear magnetic hydrogen spectroscopy. The product e.r. value was 97/3 as determined by SFC under the following conditions: OD-3column, meOH/CO 2 ＝5:95,1.5mL/min,210nm,t major ＝0.914min,t minor ＝1.103min； 1 H NMR(500MHz,Chloroform-d)δ7.31–7.28(m,2H),7.24–7.19(m,3H),3.30–3.23(m,0.38H,62％ D),2.69–2.64(m,1H),2.60–2.55(m,1H),1.34–1.28(m,3H). 13 C NMR(126MHz,Chloroform-d)δ178.4,145.44–145.40(m,aromatic carbon adjacent to benzylic carbon),128.5,126.69–126.67(m),126.5,42.57–42.48(m),36.13–35.58(m,benzylic carbon),21.83–21.72(m).
Example 35
Raw material 35 (0.2 mmol,32.8mg,>99/1e.r.)，catalyst 10(0.005mmol,3.5mg)，AgNTf 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 90% yield. The target product was determined to have a benzyldeuteration rate of 70% by nuclear magnetic hydrogen spectroscopy. The product e.r. value was 98.6/1.4 as determined by SFC under the following conditions: OD-3column, meOH/CO 2 ＝1:99to 5:95,1.0mL/min,215nm,t major ＝1.686min,t minor ＝2.442min； 1 H NMR(500MHz,Chloroform-d)δ7.31–7.28(m,2H),7.20–7.17(m,3H),3.28(s,3H),3.31–3.20(m,2H),2.90–2.83(m,0.30H,70％ D),1.88–1.80(m,2H),1.27–1.26(m,3H). 13 C NMR(126MHz,Chloroform-d)δ146.95–146.91(m,aromatic carbon adjacent to benzylic carbon),128.3,126.96–126.94(m),125.9,70.8,58.5,37.95–37.85(m),36.4(s,benzylic carbon of remaining 41),35.97(t,J＝19.5Hz,benzylic carbon of deuterated 41),22.25–22.13(m).
Example 36
Raw material 36 (0.2 mmol,50.2mg,97.5/2.5 e.r.) and catalyst10 (0.005 mmol,3.5 mg) AgNTf were added sequentially to the flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). Stirring the reaction at 120 ℃ for 24 hours, cooling to room temperature, and directly carrying out column chromatography to obtain the target product with the yield92%. The target product was determined to have a benzyldeuteration rate of 70% by nuclear magnetic hydrogen spectroscopy. The product e.r. value was determined to be 95/5 by SFC under the following conditions: OD-3column, meOH/CO 2 ＝3:97,1.5mL/min,210nm,t minor ＝1.690min,t major ＝1.903min； 1 H NMR(500MHz,Chloroform-d)δ7.80–7.78(m,2H),7.68–7.66(m,2H),7.52–7.50(m,2H),7.34–7.31(m,2H),7.27–7.25(m,1H),5.59–5.55(m,0.25H,75％ D),1.94–1.92(m,3H). 13 C NMR(126MHz,Chloroform-d)δ168.1,140.24–140.18(m,aromatic carbon adjacent to benzylic carbon),133.8,131.9,128.4,127.62–127.60(m),127.40–127.38(m),123.1,49.6(s,benzylic carbon of remaining 42),49.3(t,J＝21.3Hz,benzylic carbon of deuterated 42),17.46–17.36(m).
Example 37
Raw material 37 (0.2 mmol,44.2 mg), catalyst10 (0.02 mmol,14.0 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.08mmol,31.2mg)，Li 3 PO 4 (0.02 mmol,2.3 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 90% yield. The target product was determined to have a benzyldeuteration rate of 57% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ6.60(s,0.11H,89％ D),6.49(s,2H,89％ D),6.16(s,1H),4.95–4.86(m,1H),4.06–3.97(m,2H),3.68(t,J＝9.0Hz,1H),3.49(t,J＝8.4Hz,1H),2.26–2.19(m,2.60H,57％ D). 13 C NMR(126MHz,Chloroform-d)δ160.5,157.98–157.94(m),139.30–139.11(m),123.36–122.86(m),112.30–111.80(m),74.9,67.8,42.5,21.20–20.28(m).
Example 38
In nitrogen atmosphere, the mixture is sequentially introduced into a reaction flaskRaw material 38 (0.2 mmol,86.7 mg), catalyst10 (0.005 mmol,3.5 mg) AgNTf was added 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 50% yield. The target product was determined to have a benzyldeuteration rate of 79% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.09(s,4H),5.67(s,1H),4.35(s,4H),2.60–2.52(m,0.86H,79％ D),2.19–2.17(m,2H),2.08(s,6H),1.94(s,3H),1.56(t,J＝7.0Hz,1H),1.31–1.26(m,10H),0.88(t,J＝6.9Hz,3H). 13 C NMR(126MHz,Chloroform-d)δ170.8,170.1,140.72–140.69(m,aromatic carbon adjacent to benzylic carbon),138.30–138.26(m,aromatic carbon adjacent to benzylic carbon),128.5,128.2,64.6,58.2,35.50–34.98(m,benzylic carbon),33.68–33.54(m),31.9,31.55–31.39(m),29.5,29.29–29.22(m),29.02–28.39(m,benzylic carbon),24.1,22.6,20.8,14.1.
Example 39
Raw material 39 (0.2 mmol,65.5 mg), catalyst10 (0.01 mmol,7.0 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.04mmol,15.6mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 88% yield. The target product was 52% benzyldeuterated as determined by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.17(d,J＝8.2Hz,1H),7.00(d,J＝8.1Hz,1H),6.90(s,1H),5.44(s,0.5H,50％ D),3.25–3.21(m,1H),3.11–3.07(m,1H),2.93–2.80(m,1H),2.29(d,J＝13.0Hz,1H),1.96(s,3H),1.89–1.64(m,4H),1.42–1.35(m,4H),1.23–1.21(m,9H),0.93(s,3H). 13 C NMR(126MHz,Chloroform-d)δ170.06–169.98(m),147.19–147.13(m,aromatic carbon adjacent to benzylic carbon),145.66–145.62(m,aromatic carbon adjacent to benzylic carbon),134.76–134.67(m,aromatic carbon adjacent to benzylic carbon),126.93–126.91(m),124.12–123.84(m),123.8,49.76–49.65(m),45.11–45.08(m),38.3,37.4,37.2,36.1,33.39–32.80(m,benzylic–CH carbon),30.13–29.29(m,benzylic–CH 2 carbon),25.24–25.22(m),23.96–23.81(m),23.55–23.50(m),18.9,18.78–18.68(m),18.6.
Example 40
Raw material 40 (0.2 mmol,56.8 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 93% yield. The target product was determined to have a benzylic deuteration rate of 66% and 53% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(500MHz,Chloroform-d)δ7.20(d,J＝8.6Hz,1H),6.71(d,J＝8.5Hz,0.90H,10％ D),6.64–6.61(m,0.82H,18％ D),3.77(s,3H),2.90–2.86(m,0.94H,53％ D),2.50–2.47(m,1H),2.39–2.37(m,1H),2.27–2.22(m,0.34H,66％ D),2.17–2.10(m,0.89H,11％ D),2.06–1.93(m,3H),1.62–1.41(m,6H),0.90(s,3H). 13 C NMR(126MHz,Chloroform-d)δ220.82–220.78(m),157.51–157.47(m),137.69–137.59(m,aromatic carbon adjacent to benzylic carbon),131.97–131.86(m,aromatic carbon adjacent to benzylic carbon),127.33–126.15(m),113.8,111.91–111.47(m),55.10–55.04(m),50.3,47.90–47.80(m),43.87–43.20(m,benzylic–CH carbon),38.27–38.18(m),35.77–35.24(m,-deuterated carbon of carbonyl group),31.5,29.58–29.08(m,benzylic–CH 2 carbon),26.46–26.25(m),25.84–25.73(m),21.67–21.39(m),13.76–13.31(m).
Example 41
Raw material 41 (0.2 mmol,115.4 mg), catalyst10 (0.005 mmol,3.5 mg) and AgNTf were sequentially added to a reaction flask under nitrogen atmosphere 2 (0.02mmol,7.8mg)，Li 3 PO 4 (0.02mmol，2.3mg)，NaNTf 2 (0.2 mmol,60.6 mg) and finally acetone-d 6 (0.2 mL). The reaction was stirred at 120℃for 24 hours, cooled to room temperature and subjected to direct column chromatography to give the desired product in 90% yield. The target product was determined to have a benzyldeuteration rate of 70% by nuclear magnetic hydrogen spectroscopy. 1 H NMR(600MHz,Chloroform-d)δ7.35(d,J＝8.2Hz,1H),7.18(dd,J＝8.3,2.2Hz,1H),7.07–7.05(m,3H),6.82–6.81(m,2H),5.28(t,J＝9.4Hz,1H),5.20(t,J＝9.7Hz,1H),5.05(t,J＝9.6Hz,1H),4.32–4.25(m,2H),4.14(dd,J＝12.4,2.3Hz,1H),4.03–3.96(m,2.60H,70％ D),3.81–3.78(m,1H),2.07(s,3H),2.05(s,3H),1.99(s,3H),1.70(s,3H),1.39(t,J＝7.0 Hz,3H). 13 C NMR(126 MHz,Chloroform-d)δ170.7,170.3,169.4,168.7,157.5,139.02–138.95(m,aromatic carbon adjacent to benzylic carbon),135.1,134.5,130.98–130.92(m,aromatic carbon adjacent to benzylic carbon),129.8,125.9,114.5,79.4,76.1,74.1,72.5,68.4,63.3,62.2,38.20–37.24(m,benzylic carbon),20.7,20.59,20.58,20.2,14.8.
Claims (3)
1. A process for selectively deuterating aromatic ring at benzyl position, which is characterized in that raw material S is prepared in nitrogen atmosphere 1 Mixing with rhodium catalyst and silver salt, adding deuterated solvent, adding additive, stirring at 80-140 deg.C to make them react completely, cooling to room temperature, concentrating, column chromatography separating to obtain compound S 1 D, the benzyldeuterated product, is specifically of the formula:
wherein, raw material S 1 Is aromatic hydrocarbon or aromatic hydrocarbon derivative;the raw material S 1 Wherein R is hydrogen, alkyl, aryl or heteroatom;
the metal rhodium catalyst is a derivative of pentamethyl cyclopentadienyl rhodium dichloride dimer, and is shown as follows:
the silver salt is AgNTf 2 、AgOTf、AgSbF 6 、AgBF 4 、AgPF 6 Any one or a combination of a plurality of the components according to any proportion;
the additive is LiNTf 2 、NaNTf 2 、KNTf 2 Any one or a plurality of inorganic salts in any proportion in LiOTf, naOTf, KOTf;
the deuterated solvent is deuterated methanol or deuterated acetone, and when the deuterated solvent is deuterated acetone, phosphate is required to be added as inorganic base; at this time the raw material S 1 The proportion of the metal rhodium catalyst, the silver salt and the inorganic base is 1mol: (0.05 to 0.1 mol): (0.1 to 0.4 mol): (0.1 to 1 mol); the raw material S 1 The concentration of the deuterated acetone is 0.5 to 4mol/L;
the phosphate is any one or the combination of a plurality of lithium phosphate, sodium phosphate and silver phosphate according to any proportion;
when the deuterated solvent is deuterated methanol, the raw material S is 1 The proportion of the metal rhodium catalyst and the silver salt is 1mol: (0.05 to 0.1 mol): (0.1 to 0.4 mol); the raw material S 1 The concentration of the deuterated solvent is 0.5 to 4mol/L;
the silver salt and the rhodium metal catalyst satisfy the molar ratio of [ Ag ]/[ Rh ] =2: 1.
2. the method of aromatic ring benzyl site selective deuteration according to claim 1 wherein starting material S 1 The proportion of the metal rhodium catalyst, the silver salt, the inorganic base and the deuterated acetone is 1mol:0.025mol:0.1mol:0.1mol; the raw material S 1 Concentration after addition of deuterated acetoneIs 1mol/L.
3. The method of aromatic ring benzyl site selective deuteration according to claim 1 wherein starting material S 1 The proportion of the metal rhodium catalyst and the silver salt is 1mol:0.025mol:0.1mol; the raw material S 1 The concentration after adding deuterated methanol is 1mol/L.
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