CN116041129A - Method for dehalogenation/deuteration of halides - Google Patents
Method for dehalogenation/deuteration of halides Download PDFInfo
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- CN116041129A CN116041129A CN202310008779.0A CN202310008779A CN116041129A CN 116041129 A CN116041129 A CN 116041129A CN 202310008779 A CN202310008779 A CN 202310008779A CN 116041129 A CN116041129 A CN 116041129A
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- dehalogenation
- deuteration
- halide
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- 238000005695 dehalogenation reaction Methods 0.000 title claims abstract description 89
- 150000004820 halides Chemical class 0.000 title claims abstract description 69
- 238000000034 method Methods 0.000 title claims abstract description 47
- 238000006243 chemical reaction Methods 0.000 claims abstract description 83
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 38
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 24
- 239000002841 Lewis acid Substances 0.000 claims abstract description 19
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 18
- NFHRNKANAAGQOH-UHFFFAOYSA-N triphenylstannane Chemical group C1=CC=CC=C1[SnH](C=1C=CC=CC=1)C1=CC=CC=C1 NFHRNKANAAGQOH-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002879 Lewis base Substances 0.000 claims abstract description 16
- 150000007527 lewis bases Chemical class 0.000 claims abstract description 15
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- NFHRNKANAAGQOH-RCUQKECRSA-N deuterio(triphenyl)stannane Chemical compound C1(=CC=CC=C1)[Sn](C1=CC=CC=C1)(C1=CC=CC=C1)[2H] NFHRNKANAAGQOH-RCUQKECRSA-N 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052782 aluminium Inorganic materials 0.000 claims abstract description 5
- WHAFDJWJDDPMDO-UHFFFAOYSA-N trimethyl(phenyl)phosphanium Chemical group C[P+](C)(C)C1=CC=CC=C1 WHAFDJWJDDPMDO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims description 12
- 229910052805 deuterium Inorganic materials 0.000 claims description 9
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 5
- 150000001347 alkyl bromides Chemical class 0.000 claims description 3
- 150000001348 alkyl chlorides Chemical class 0.000 claims description 3
- 150000001349 alkyl fluorides Chemical class 0.000 claims description 3
- 150000001351 alkyl iodides Chemical class 0.000 claims description 3
- 150000001499 aryl bromides Chemical class 0.000 claims description 3
- 150000001503 aryl iodides Chemical class 0.000 claims description 3
- 239000012298 atmosphere Substances 0.000 claims description 3
- 230000001681 protective effect Effects 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 13
- 150000003254 radicals Chemical class 0.000 abstract description 12
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 7
- -1 tin free radical Chemical class 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 4
- 239000003999 initiator Substances 0.000 abstract description 3
- 238000006467 substitution reaction Methods 0.000 abstract description 2
- 238000010505 homolytic fission reaction Methods 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 description 34
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 18
- 229910052786 argon Inorganic materials 0.000 description 16
- 238000005259 measurement Methods 0.000 description 16
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000000758 substrate Substances 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005286 illumination Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- QPUYECUOLPXSFR-UHFFFAOYSA-N 1-methylnaphthalene Chemical compound C1=CC=C2C(C)=CC=CC2=C1 QPUYECUOLPXSFR-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001723 carbon free-radicals Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- NRXWFTYEJYEOGW-UHFFFAOYSA-N 1-methyl-4-(4-methylphenyl)sulfanylbenzene Chemical compound C1=CC(C)=CC=C1SC1=CC=C(C)C=C1 NRXWFTYEJYEOGW-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 150000005838 radical anions Chemical class 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/26—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only halogen atoms as hetero-atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B35/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving a change in the type of bonding between two carbon atoms already directly linked
- C07B35/06—Decomposition, e.g. elimination of halogens, water or hydrogen halides
-
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
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- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/24—Preparation of ethers by reactions not forming ether-oxygen bonds by elimination of halogens, e.g. elimination of HCl
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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- C07D209/04—Indoles; Hydrogenated indoles
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- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
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Abstract
The invention relates to the technical field of dehalogenation and hydrogenation, in particular to a method for dehalogenation and hydrogen/deuteration of halides. The method provided by the invention comprises the following steps: mixing Lewis acid, lewis base, halide, dehalogenation reagent, mesitylene and organic solvent for dehalogenation/deuteration reaction; the Lewis acid is aluminum trifluorophenyl, and the Lewis base is trimethylphenyl phosphine; the dehalogenation reagent is triphenyltin hydride or triphenyltin deuteride. The invention combines the specific Lewis acid and Lewis base, can be used as a mild and efficient initiator to trigger the homolytic cleavage of tin-hydrogen bonds in dehalogenation reagents, and the homolytic tin free radical can be used as a high-activity dehalogenation free radical to complete dehalogenation hydrogenation of various carbon-halogen bonds; the substitution of triphenyltin hydride for high deuteration triphenyltin deuteride can preserve the high deuteration rate to obtain dehalogenation deuteration products.
Description
Technical Field
The invention relates to the technical field of dehalogenation and hydrogenation, in particular to a method for dehalogenation and hydrogen/deuteration of halides.
Background
Organic halides are widely used in the fields of nature and synthetic chemistry, and the reduction reaction to obtain dehalogenated hydrides is also an important class of organic reactions. The free radical reaction is a very efficient process in the dehalogenation of halides. There are currently three methods for this type of reaction: 1. the earliest reactions developed required the choice of specific wavelength illumination conditions depending on the type of substrate-halogen bond. For example, C-I bonds typically require illumination below 320nm, while cleavage of C-Br bonds requires illumination below 280 nm. The method has very limited applicable substrate range and more severe reaction conditions; 2. reduction reactions based on a single electron transfer mechanism. Such reactions require a strongly reducing photocatalyst or additive (the catalyst has a relatively high redox potential) such that the halide is reduced to a radical anion, after which the halide group leaves as a halide anion, and the resulting carbon-centered radical reacts with a hydrogen source (typically silane, amine, water, etc.) in the system to give a dehalogenated product. 3. Reduction reactions based on halogen atom transfer. In such reactions, the substrate halide may be polarized by a dehalogenation reagent and then directly cleaved to form a carbon radical, which is then reacted with a hydrogen source to yield the dehalogenated hydride. The advantage of such reactions is the broad range of suitable substrate halides: it is easier to consider the redox potential of the substrate and the catalyst as long as the bond energy of the dehalogenation reagent-halogen bond is greater than the bond energy of the carbon-halogen bond of the substrate halide; in addition, the various substituents on the substrate have little effect on the reactivity and the dehalogenation reagent will act exclusively on carbon-halogen bonds. This has led to the rapid development of halide dehydrohalogenation reactions of this halogen atom transfer mechanism in recent years.
The dehalogenation of halides based on a halogen atom transfer mechanism requires the selection of an appropriate dehalogenation reagent, one of the most commonly used being an organotin reagent. Tin-halogen bond can be greater than carbon-halogen bonds in most alkyl or aryl halides. The formation of triphenyltin radicals is usually carried out by irradiation with light of a specific wavelength (wavelength of about 276 nm) or by adding a radical initiator AIBN at a high temperature of 100℃under severe reaction conditions. In addition, dehalogenation and deuteration are reactions that have practical value. Deuterium labeled compounds are commonly used in chemical reaction mechanism studies to study the reactive sites or reaction kinetics; deuterium-labeled drugs are often used to track the absorption, catabolism, and excretion properties of the drug due to their radioactivity. In the prior art, organometal reagents, such as organolithium and organomagnesium reagents, are generally required to complete dehalogenation and deuteration of halides, but the reaction has a certain danger, and the selectivity of the reaction is difficult to ensure.
Disclosure of Invention
The object of the present invention is to provide a method for dehalogenation/deuteration of halides, which method has a high selectivity.
In order to achieve the above object, the present invention provides the following technical solutions:
the present invention provides a method for dehalogenation/deuteration of a halide comprising the steps of:
mixing Lewis acid, lewis base, halide, dehalogenation reagent, mesitylene and organic solvent for dehalogenation/deuteration reaction;
the Lewis acid is aluminum trifluorophenyl, and the Lewis base is trimethylphenyl phosphine;
the dehalogenation reagent is triphenyltin hydride or triphenyltin deuteride.
Preferably, the molar ratio of the Lewis acid to the Lewis base is 1 (1-1.5).
Preferably, the halide comprises one or more of alkyl iodide, alkyl bromide, alkyl chloride, alkyl fluoride, aryl iodide and aryl bromide.
Preferably, the halide comprises
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Preferably, the molar ratio of halide to dehalogenation agent is 1: (1-1.2).
Preferably, the molar ratio of the halide, mesitylene and lewis acid is 1:1:0.1.
Preferably, the organic solvent comprises C 6 D 6 、CD 3 CN and (CD) 3 ) 2 One or more of SO.
Preferably, the mixing is performed in a protective atmosphere.
Preferably, the dehalogenation/deuteration reaction is performed under conditions of visible light irradiation;
the dehalogenation hydrogen/deuterium reaction temperature is room temperature and the time is 3-24 h.
The present invention provides a method for dehalogenation/deuteration of a halide comprising the steps of: mixing Lewis acid, lewis base, halide, dehalogenation reagent, mesitylene and organic solvent for dehalogenation/deuteration reaction; the Lewis acid is aluminum trifluorophenyl, and the Lewis base is trimethylphenyl phosphine; the dehalogenation reagent is triphenyltin hydride or triphenyltin deuteride. The invention has the efficient single-electron transfer function between the specific Lewis acid and the Lewis base, and the generated Lewis acid free radical anions and Lewis base free radical cations form hindered free radical pairs, and the free radicals can be used as a mild and efficient initiator and can carry out Sn-H homolytic activation on the dehalogenation reagent triphenyltin hydride, and the generated tin free radicals are efficient dehalogenation free radicals; the tin free radical can be used as a high-activity dehalogenation free radical to complete dehalogenation hydrogenation of various carbon-halogen bonds, the reaction process condition is mild, and the dehalogenation hydrogenation can be completed under the condition of mild and visible light; the substitution of triphenyltin hydride for high deuteration triphenyltin deuteride can preserve the high deuteration rate to obtain dehalogenation deuteration products. The halide substrate applicable to the method disclosed by the invention has a wide range, the hindered free radical has high activity on the generated triphenyltin free radical, and can be subjected to an activation dehalogenation reaction with various carbon-halogen bonds, the mechanism is a halogen atom transfer mechanism, the dehalogenation reaction is easy to occur, the generated dehalogenation reagent-halogen bond can be required to be larger than carbon-halogen bonds in halides, and the tin-halogen bond can be larger than carbon-halogen bonds in most halides, so that the method is one of the reasons of wide reaction applicability. When the triphenyldeuterated tin with high deuteration rate is used as a dehalogenation reagent, other hydrogen sources are not in the reaction system, so that the carbon free radical generated by dehalogenation of the halide can only react with a tin-deuterium bond to generate deuterated products. Since the route of product formation is unique, the deuteration rate of the product is well preserved.
Detailed Description
The present invention provides a method for dehalogenation/deuteration of a halide comprising the steps of:
mixing Lewis acid, lewis base, halide, dehalogenation reagent, mesitylene and organic solvent for dehalogenation/deuteration reaction;
the lewis acid is aluminum trifluorophenyl (Al (C) 6 F 5 ) 3 ) The Lewis base is tricresylphosphine (Mes 3 P)；
The dehalogenation reagent is triphenyltin hydride (Ph 3 SnH) or triphenyltin deuteride (Ph) 3 SnD)。
In the present invention, all the preparation materials are commercially available products well known to those skilled in the art unless specified otherwise.
In the present invention, the Al (C) 6 F 5 ) 3 The structural formula is as follows:
in the present invention, the Mes 3 The structural formula of P is:
in the present invention, the molar ratio of the lewis acid to lewis base is preferably 1: (1 to 1.5), more preferably 1: (1-1.2).
In the present invention, the halide preferably includes one or more of alkyl iodide, alkyl bromide, alkyl chloride, alkyl fluoride, aryl iodide and aryl bromide, more preferably includes
In the present invention, the dehalogenation reagent is preferably triphenyltin hydride (Ph 3 SnH) or triphenyltin deuteride (Ph) 3 SnD); the triphenyltin hydride is preferably a commercially available product; the triphenyldeuterated tin is preferably prepared by a preparation method of the triphenyldeuterated tin, which is preferably as follows: in a 50mL Schlenk flask filled with nitrogen, a solution of Calvanoxy radical (galvinoxy) (24.5 mg,0.06 mmol) and phenylmagnesium bromide in diethyl ether (1.1 eq,3.7mL,3.0M in diethyl ether) was added. A solution of triphenyltin hydride (3.5 g,10 mmol) in diethyl ether (5 mL) was added dropwise under nitrogen. After stirring at room temperature for 1 hour, D was slowly added to the above mixture at 0 ℃ 2 O (0.6 mL,33 mmol). After stirring at room temperature for 2 hours, the organic phase is extracted three times with diethyl ether, dried over anhydrous magnesium sulfate and the solvent is evaporated under reduced pressure to give Ph 3 SnD was 65% yield with 99% deuteration.
In the present invention, the molar ratio of halide to dehalogenation agent is preferably 1: (1 to 1.2), more preferably 1:1.2.
In the present invention, the molar ratio of the halide, mesitylene and lewis acid is preferably 1:1:0.1.
In the present invention, the organic solvent preferably includes C 6 D 6 、CD 3 CN and (CD) 3 ) 2 One or more of SO, more preferably C 6 D 6 。
In the present invention, the ratio of the halide to the organic solvent is preferably (0.05 to 0.1) mmol: 500. Mu.L, more preferably (0.08-0.1) mmol: 500. Mu.L, most preferably 0.1mmol: 500. Mu.L.
In the present invention, the mixing is preferably performed in a protective atmosphere, preferably an argon atmosphere. In the present invention, the mixing was performed in a glove box filled with argon.
In the present invention, the dehalogenation/deuteration reaction is preferably performed under conditions of visible light irradiation; the temperature of the dehalogenation/deuterium reaction is preferably room temperature, and the time is preferably 3-24 hours.
The methods of dehalogenation/deuteration of halides provided herein are described in detail below with reference to the examples, but they should not be construed as limiting the scope of the invention.
Dehalogenation deuteration reagent (Ph) 3 Preparation of SnD):
in a 50mL Schlenk flask filled with nitrogen, a solution of Calvanoxy radical (galvinoxy) (24.5 mg,0.06 mmol) and phenylmagnesium bromide in diethyl ether (1.1 eq,3.7mL,3.0M in diethyl ether) was added. A solution of triphenyltin hydride (3.5 g,10 mmol) in diethyl ether (5 mL) was added dropwise under nitrogen. After stirring at room temperature for 1 hour, D was slowly added to the above mixture at 0 ℃ 2 O (0.6 mL,33 mmol). After stirring at room temperature for 2 hours, the organic phase is extracted three times with diethyl ether, dried over anhydrous magnesium sulfate and the solvent is evaporated under reduced pressure to give Ph 3 SnD was 65% yield with 99% deuteration.
Example 1
The specific process of the dehalogenation and hydrogenation reaction method of the halide 1a comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1a (21.0 mg,0.10 mmol), dehalogenation reagent triphenyltin hydride Ph 3 SnH (42.0 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then taken out of the glove box and left to stand at room temperature under visible light for 3 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 2a is 95%;
examples 2 to 30
Reference example 1, except that the starting materials and end products were different, and the starting materials and end products of examples 2 to 30 are shown in Table 1:
TABLE 1 raw materials, products and yields for examples 1-30
Example 31
The specific process of the dehalogenation and hydrogenation reaction method of the halide 3a comprises the following steps:
into a 2mL nuclear magnetic reaction tube in a glove box filled with argonAdding the catalyst Al (C) in sequence 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 3a (21.8 mg,0.10 mmol), dehalogenation reagent triphenyltin hydride Ph 3 SnH (42.0 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 24 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 4a is 63%;
examples 32 to 48
Reference example 31 differs in that the starting materials and end products are different, and the starting materials and end products of examples 2 to 30 are shown in table 2:
TABLE 2 raw materials, products and yields for examples 31-48
Example 49
The specific process of the method for preparing 5e (1-ethyl-2-deuterium-naphthalene) by dehalogenation and deuteration of halide 1e comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1e (28.2 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuteration tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out to obtain the nuclear magnetic of the product 5eThe yield was 95% and the deuteration rate was 95%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give an isolated yield of 5e of 90%;
1 H NMR(500MHz,C 6 D 6 )δ7.90(d,J＝8.2Hz,1H,H Ar ),7.70(dd,J＝7.8,1.6Hz,1H,H Ar ),7.57(d,J＝8.1Hz,1H,H Ar ),7.37–7.21(m,3H,H Ar ),7.16(1H,H Ar ),2.86(t,J＝7.5Hz,2H,CH 2 ),1.20–1.15(m,2H,CH 2 D). 13 C NMR(126MHz,C 6 D 6 ) Delta 140.07,134.15,132.03,128.79,126.50,125.56,125.27,124.82,123.70,25.72,14.74-14.32 (m) structural formula is as follows:
example 50
The specific process of the reaction method for preparing 5H (3-ethyl-2-deuterium-1H-indole) by dehalogenation and deuteration of halide for 1H comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1h (27.1 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuterated tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product for 5h is 95%, and the deuteration rate is 92%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give a separation yield of 90% for 5 h;
1 H NMR(500MHz,C 6 D 6 )δ7.66(d,J＝7.7Hz,1H,HAr),7.27–7.22(m,1H,HAr),7.22–7.18(m,1H,HAr),7.07(d,J＝7.9Hz,1H,HAr),6.56(s,1H,HAr),6.43(d,J＝2.2Hz,1H,NH),2.72(q,J＝7.4Hz,2H,CH2),1.29–1.23(m,2H,CH 2 D).13C NMR(126MHz,C6D6)delta 136.93,122.12,120.44,119.36,118.55,111.30,18.71,14.86 the structural formula is as follows:
example 51
The specific process of the reaction method for preparing 5i (2, 3-dihydro-2-deuterium-1-hydroindene) by dehalogenation and deuteration of the halide 1i comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1i (24.4 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuterated tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 5i is 99%, and the deuteration rate is 95%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give an isolated yield of 5i of 93%;
1 H NMR(500MHz,C 6 D 6 )δ7.14(d,J＝8.7Hz,2H,H Ar ),7.11–7.05(m,2H,H Ar ),2.69(d,J＝7.3Hz,4H,CH 2 ),1.81–1.72(m,1H,CHD). 13 C NMR(126MHz,C 6 D 6 ) Delta 143.79,126.05,124.29,32.64,25.48-24.61 (m) structural formula is as follows:
example 52
The specific process of the reaction method for preparing 5t (1-ethoxy-3-deuterium-4-methylbenzene) by dehalogenation and deuteration of halide 1t comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1t (21.4 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuterated tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 5t is 94%, and the deuteration rate is 99%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give an isolated yield of 85% of 5 t;
1 H NMR(500MHz,C 6 D 6 )δ6.97(d,J＝8.3Hz,1H),6.82(d,J＝8.5Hz,1H),3.58(t,J＝6.5Hz,1H),2.14(s,2H),1.63–1.54(m,1H),0.87–0.82(m,1H). 13 C NMR(126MHz,C 6 D 6 ) Delta 129.81,129.19,114.39,68.99,52.94,22.52,20.18 the structural formula is as follows:
example 53
The specific process of the reaction method for preparing 5u (ethyl-3-deuterium p-tolyl sulfide) by dehalogenation and deuteration of halide 1u comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1u (23.0 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuterated tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 5u is 92% and the deuteration rate is 99%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give a separation yield of 86% of 5 u;
1 H NMR(500MHz,C 6 D 6 )δ6.97(d,J＝8.3Hz,1H),6.82(d,J＝8.5Hz,1H),3.58(t,J＝6.5Hz,1H),2.14(s,2H),1.63–1.54(m,1H),0.87–0.82(m,1H). 13 C NMR(126MHz,C 6 D 6 ) Delta 129.81,129.19,114.39,68.99,52.94,22.52,20.18 the structural formula is as follows:
example 54
The reaction method for preparing 5x (8-deuterium methyl quinoline) by dehalogenation and deuteration of halide 1x comprises the following specific steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1X (22.1 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuteration tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 5x is 61%, and the deuteration rate is 95%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give an isolated yield of 52% 5×;
1 H NMR(500MHz,C 6 D 6 )δ8.80(dd,J＝4.1,1.8Hz,1H,H Ar ),7.57(dd,J＝8.3,1.8Hz,1H,H Ar ),7.32(dd,J＝11.9,7.6Hz,2H,H Ar ),7.18(s,1H,H Ar ),6.81(dd,J＝8.2,4.1Hz,1H,H Ar ),2.97–2.86(m,2H,CH 2 D). 13 C NMR(126MHz,C 6 D 6 ) Delta 149.06,135.43,129.24,126.01,125.60,120.58,17.99-17.40 (m) structural formula is as follows:
example 55
The specific process of the reaction method for preparing 5z (1, 4-dideutomethylbenzene) by dehalogenation and deuteration of halide 1z comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1z (26.2 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuterated tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 5z is 85%, and the deuteration rate is 97%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give a separation yield of 78% of 5 z;
1 H NMR(500MHz,C 6 D 6 )δ6.97(d,J＝8.0Hz,2H,H Ar ),6.81(d,J＝7.8Hz,2H,H Ar ),2.03–1.95(m,2H,CH 2 D). 13 C NMR(126MHz,C 6 D 6 ) Delta 136.08,129.55,125.86,19.32 the structural formula is as follows:
example 56
The specific process of the reaction method for preparing 6o (1-methyl-1-hydrogen-6-deuterium-indole) by dehalogenation and deuteration of halide 3o comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 3o (20.9 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuteration tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out to obtain a product 6o with a nuclear magnetic yield of 31% and a deuteration rate of 99%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give an isolated yield of 21% of 6 o;
1 H NMR(500MHz,C 6 D 6 )δ7.73(s,1H,H Ar ),7.25(d,J＝8.3Hz,1H,H Ar ),7.06(d,J＝8.2Hz,1H,H Ar ),6.56(d,J＝3.1Hz,1H,H Ar ),6.51(d,J＝3.1Hz,1H,H Ar ),2.93(s,3H,N-CH 3 ). 13 C NMR(126MHz,C 6 D 6 ) Delta 136.90,128.94,128.21,121.41,120.98,119.40,109.10,101.03,31.60 the structural formula is as follows:
example 57
The reaction method for preparing 5ac (1-deuterium methyl naphthalene) by dehalogenation and deuteration of halide 1ac comprises the following specific steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 5ac (17.6 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuterated tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 5ac is 43%, and the deuteration rate is 99%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give an isolated yield of 5ac of 29%;
1 H NMR(500MHz,C 6 D 6 )δ7.85–7.78(m,1H,H Ar ),7.68(dd,J＝7.5,1.9Hz,1H,H Ar ),7.57(d,J＝8.2Hz,1H,H Ar ),7.31(pd,J＝6.9,1.6Hz,2H,H Ar ),7.24–7.20(m,1H,H Ar ),7.12(d,J＝7.6Hz,1H,H Ar ),2.44–2.33(m,2H,CH 2 D). 13 C NMR(126MHz,C 6 D 6 )δ134.00,133.86,132.87,128.54,126.51,126.47,125.55,125.48,125.41,124.09,18.94 the structural formula is as follows:
example 58
The specific process of the reaction method for preparing 5ad (triphenyldeuterium methane) by dehalogenation and deuteration of halide 1ad comprises the following steps:
in a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 5ad (27.8 mg,0.10 mmol), dehalogenation deuteration reagent triphenyldeuteration tin Ph 3 SnD (42.1 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 12 hours. After the reaction is finished, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product 5ad is 98%, and the deuteration rate is 99%. The reaction mixture was further purified by silica gel column chromatography using hexane as eluent to give an isolated yield of 5ad of 91%;
1 H NMR(500MHz,C 6 D 6 )δ7.85–7.78(m,1H,H Ar ),7.68(dd,J＝7.5,1.9Hz,1H,H Ar ),7.57(d,J＝8.2Hz,1H,H Ar ),7.31(pd,J＝6.9,1.6Hz,2H,H Ar ),7.24–7.20(m,1H,H Ar ),7.12(d,J＝7.6Hz,1H,H Ar ),2.44–2.33(m,2H,CH 2 D). 13 C NMR(126MHz,C 6 D 6 ) Delta 134.00,133.86,132.87,128.54,126.51,126.47,125.55,125.48,125.41,124.09,18.94 the structural formula is as follows:
comparative example 1
In a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1q (17.0 mg,0.10 mmol), dehalogenation reagent triphenyltin hydride Ph 3 SnH (42.0 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then taken out of the glove box and left to stand at room temperature for 3 hours in the dark. After the reaction is finished, nuclear magnetic measurement is carried out to obtain the nuclear magnetic yield of the product toluene 2c of 0%;
comparative example 2
Catalyst B (C) was added sequentially to a 2mL nuclear magnetic reaction tube in a glove box filled with argon 6 F 5 ) 3 (5.1 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1q (17.0 mg,0.10 mmol), dehalogenation reagent triphenyltin hydride Ph 3 SnH (42.0 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 3 hours. After the reaction, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product toluene 2c is 77%.
Comparative example 3
In a glove box filled with argon, 2mL of a nuclear magnetic reaction tube was sequentially charged with catalyst Al (C 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent C 6 D 6 (500. Mu.L), catalyst Ph 3 P (2.6 mg,0.01 mol), halide 1q (17.0 mg,0.10 mmol), dehalogenation reagent triphenyltin hydride Ph 3 SnH (42.0 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 3 hours. After the reaction, nuclear magnetic measurement is carried out, and the nuclear magnetic yield of the product toluene 2c is 0%.
Comparative example 4
In a glove box filled with argon, 2mL of nuclear magnetic reaction tube was sequentially added withInto a catalyst Al (C) 6 F 5 ) 3 (5.3 mg,0.01 mmol), solvent CD 3 CN (500. Mu.L), catalyst Mes 3 P (3.9 mg,0.01 mol), halide 1q (17.0 mg,0.10 mmol), dehalogenation reagent triphenyltin hydride Ph 3 SnH (42.0 mg,0.12 mmol) and internal standard mesitylene (12.0 mg,0.10 mmol). The nuclear magnetic reaction tube was then removed from the glove box and left to stand at room temperature under visible light for 3 hours. After the reaction, nuclear magnetic measurement was performed to obtain a product toluene 2c having a nuclear magnetic yield of 62%.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (9)
1. A method for dehalogenation/deuteration of a halide comprising the steps of:
mixing Lewis acid, lewis base, halide, dehalogenation reagent, mesitylene and organic solvent for dehalogenation/deuteration reaction;
the Lewis acid is aluminum trifluorophenyl, and the Lewis base is trimethylphenyl phosphine;
the dehalogenation reagent is triphenyltin hydride or triphenyltin deuteride.
2. The process of claim 1, wherein the molar ratio of Lewis acid to Lewis base is 1 (1) to 1.5.
3. The method of claim 1, wherein the halide comprises one or more of an alkyl iodide, an alkyl bromide, an alkyl chloride, an alkyl fluoride, an aryl iodide, and an aryl bromide.
4. The method of claim 3, wherein the halide comprises
/>
5. The method of any one of claims 1 to 4, wherein the molar ratio of halide to dehalogenation reagent is 1: (1-1.2).
6. The method of claim 5, wherein the molar ratio of halide, mesitylene, and lewis acid is 1:1:0.1.
7. The method of claim 1, wherein the organic solvent comprises C 6 D 6 、CD 3 CN and (CD) 3 ) 2 One or more of SO.
8. The method of claim 1, wherein the mixing is performed in a protective atmosphere.
9. The method of claim 1, wherein the dehalogenation/deuteration reaction is performed under conditions of visible light irradiation;
the dehalogenation hydrogen/deuterium reaction temperature is room temperature and the time is 3-24 h.
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