A method for converting an amide into an alpha-substituted amine compound

Abstract

The application discloses a method for converting an amide into an alpha-substituted amine compound, and uses a mixed system of divalent metal samarium salt and / or metal ytterbium salt, metal element and metal additive to promote a direct deoxygenation functionalization reaction of the amide compound, and convert the amide compound into the alpha-substituted amine compound. The method of the application is simple in reaction operation and can be carried out under mild conditions.

Description

Technical Field

[0001] This invention relates to a method for converting amides into α-substituted amine compounds. Background Technology

[0002] Amides are common functional groups in organic chemistry and also represent a class of underdeveloped nitrogen-containing compounds, widely found in fine chemicals, agrochemicals, and pharmaceutical industries. The carbonyl carbon in amides exhibits low reactivity, and converting them into important amine compounds through carbonyl deoxygenation has long been a challenge for synthetic chemists. To date, methods involving electrophilic activation and controlled hydride reduction have been reported to achieve the deoxygenation of amides to construct new covalent bonds. Nevertheless, due to the weak electrophilicity of the carbonyl carbon in amides, strong acids / bases, special amides with directing groups, multi-step operations, and the use of water / air-sensitive organometallic reagents are typically required, which somewhat limits their applications.

[0003] In 1992, N. Sonoda's group reported the first deoxydimerization reaction of amides via the SmI2 / Sm system, suggesting that the reaction system might involve an α-aminocarbene intermediate (J. Am. Chem. Soc. 1992, 114, 8729). However, this reaction only yielded dimer products, which were a mixture of cis and trans isomers, and most substrate yields were at a moderate level. Summary of the Invention

[0004] The purpose of this invention is to provide a method for converting amides into α-substituted amine compounds and a method for synthesizing 1,1-diarylmethylamine compounds.

[0005] This invention provides a method for preparing α-substituted amine compounds, wherein the method uses a mixed system of divalent samarium salts and / or ytterbium salts, elemental metals, and metal additives to promote the reaction of the amide compound with organometallic reagents and C. 6-14 Aromatic hydrocarbons, 5-10 membered heterocyclic hydrocarbons, 5-15 membered heteroaromatic hydrocarbons, C 2-20 Alkenes or C 1-20 Alkanes undergo deoxyfunctionalization reactions to yield α-substituted amine compounds.

[0006] Wherein, the metallic element is one or a combination of two or more of the following: Sm, Mg, Zn, In, and Yb;

[0007] The metal additive is a metal salt and / or complex of one or more of Pd, Rh, Ir, Ru, Ni, Ag, Cu, Fe, Co, Mn, and Cr.

[0008] The organometallic reagents are selected from: organoboron reagents, Grignard reagents, organolithium reagents, and organosilicon reagents.

[0009] In another preferred embodiment, the method uses a mixture of divalent samarium salts and / or ytterbium salts, elemental metals, and metal additives to promote the reaction of amide compounds with organometallic reagents and C. 6-14 Aromatic hydrocarbons, 5-8 membered heterocyclic hydrocarbons, 5-15 membered heteroaromatic hydrocarbons, C 2-6 Alkenes or C 1-6 Alkanes undergo deoxyfunctionalization reactions to yield α-substituted amine compounds.

[0010] In another preferred embodiment, the method includes the following steps:

[0011] The method uses a mixed system of divalent samarium salts and / or ytterbium salts, elemental metals, and metal additives to promote the deoxyfunctionalization reaction of amide compound 1 with reactant 2, yielding α-substituted amine compound 3.

[0012]

[0013] In each formula, LG is selected from: boron groups in organoboron reagents (such as pinacol borate ester group), [MgBr] + [MgCl] + Li + Silicon-based and hydrogen;

[0014] R 1 F and G are each independently selected from: substituted or unsubstituted C. 6-14 aryl, substituted or unsubstituted 5-15 heteroaryl, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 2-20 alkenyl, substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted 5-10 membered heterocyclic groups; wherein the substitution refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkyl, C 2-4 alkenyl, halogen, C 1-4 Halogenated alkyl, cyano, C 1-4 Alkyl group, -(CH2) m -CN、-NR 6 R 7 -SiR 8 R 9 R 10 -O (5-8 membered heterocyclic group), -O (C 3-6 cycloalkyl), -S(C 1-4 Alkyl), 5-10 membered heteroaryl, C 6-14 Aryl group; or adjacent substituents forming a 5-10 membered heterocycle with the two connected carbon atoms; wherein, R 8 R9 R 10 Each independently is C 1-4 Alkyl, C 6-14 Aryl; R 6 R 7 Each independently is hydrogen, C 1-4 Alkyl, C 6-14 Aryl; the above 5-10 membered heteroaryl, C 6-14 The aryl group is optionally substituted by one or more substituents selected from the group consisting of: 5-10 membered heteroaryl groups, C 6-14 Aryl, C 1-4 Alkoxy, C 1-4 alkyl;

[0015] R 2 R 3 Each is independently selected from: substituted or unsubstituted C 1-4 Alkyl, substituted or unsubstituted C 1-4 alkoxy; the substitution refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkoxy, C 1-4 Alkyl, C 2-4 alkenyl, halogen, C 1-4 Halogenated alkyl groups, cyano groups;

[0016] Or R 2 R 3 Together with the connected N, it forms a substituted or unsubstituted 5-12 membered heterocycle (monocyclic, fused, bridged), wherein, in addition to N, the heterocycle optionally has 1, 2, or 3 heteroatoms selected from S, O, or N; substitution on the heterocycle refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, C 1-4 Haloalkyl, -(5-15-membered heteroaryl), =(5-15-membered heteroaryl), -(CH2) m -(C 6-14 Aryl)(R 4 ) n1 -C 2-4 alkenyl-(C 6-14 Aryl)(R 5 ) n2 Where m is 0, 1, 2, or 4; n1 and n2 are independently 1, 2, 3, or 4; each R 4 Each R 5 Independently for C 1-4 alkyl.

[0017] In another preferred embodiment, R 1 Selected from the following group: substituted or unsubstituted C 6-14aryl, substituted or unsubstituted 5-10 heteroaryl; wherein the substitution refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkyl, halogen, C 1-4 Halogenated alkyl, cyano, C 1-4 Alkoxy group; or adjacent substituents forming 5-10 membered heterocycles with the two connected carbon atoms.

[0018] In another preferred embodiment, R 1 Selected from the following group: substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-9 membered heteroaryl (e.g. furanyl, benzofuranyl, pyrroleyl, thiopheneyl, indolyl).

[0019] In another preferred embodiment, R 1 Substitution refers to the substitution of a carbon atom by one or more substituents selected from the group consisting of methyl, chlorine, fluorine, trifluoromethyl, cyano, methoxy, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, ethoxy, propoxy, and bromine; or the adjacent substituents form a 5-7 membered heterocycle with the two carbon atoms connected to it, the heterocycle having 1, 2, or 3 heteroatoms selected from S, O, or N.

[0020] In another preferred embodiment, R 2 R 3 Each is independently selected from: substituted or unsubstituted C 1-4 Alkyl; the substitution refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkoxy;

[0021] Or R 2 R 3 Together with the linked N, it forms a substituted or unsubstituted 5-12 membered heterocycle (monocyclic, fused, or bridged), wherein, in addition to N, the heterocycle optionally has one, two, or three heteroatoms selected from S, O, or N; substitution on the heterocycle refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkyl, -(5-15-membered heteroaryl), =(5-15-membered heteroaryl), -(CH2) m -(C 6-14 Aryl)(R 4 ) n1 -C 2-4 alkenyl-(C 6-14 Aryl)(R 5 ) n2 Where m is 0, 1, 2, or 4; n1 and n2 are independently 1, 2, 3, or 4; each R 4 Each R 5 Independently for C 1-4 alkyl.

[0022] In another preferred embodiment, FG-LG is FG-BPin.

[0023] In another preferred embodiment, the silicon group is selected from: trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, and diphenylmethylsilyl.

[0024] In another preferred embodiment, FG is selected from: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-15 membered heteroaryl;

[0025] The substitution mentioned therein refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkyl, C 2-4 alkenyl, C 1-4 Alkoxy, halogen, C 1-4 Haloalkyl, -(CH2) m -CN、-NR 6 R 7 -SiR 8 R 9 R 10 -O (5-8 membered heterocyclic group), -O (C 3-6 cycloalkyl), -S(C 1-4 Alkyl), 5-10 membered heteroaryl, C 6-14 aryl; or adjacent substituents forming a 5-10 membered heterocycle with the two connected carbon atoms; R 8 R 9 R 10 Each independently is C 1-4 Alkyl; R 6 R 7 Each independently is C 6-14 Aryl; the above 5-10 membered heteroaryl, C 6-14 The aryl group is optionally substituted by one or more substituents selected from the group consisting of: 5-10 membered heteroaryl groups, C 6-14 Aryl, C 1-4 Alkyl group.

[0026] In another preferred embodiment, the divalent samarium salt is one or a combination of two or more of SmI2, SmBr2, and SmCl2; the divalent ytterbium salt is one or a combination of two or more of YbI2, YbBr2, and YbCl2.

[0027] In another preferred embodiment, the amount of the metal additive is 0.001 mol% to 500 mol% of the amount of the amide compound.

[0028] In another preferred embodiment, the amount of the divalent samarium or ytterbium salt is 0.001 mol% to 500 mol% of the amount of the amide compound.

[0029] In another preferred embodiment, the amount of the elemental metal is 0.001 mol% to 500 mol% of the amount of the amide compound.

[0030] In another preferred embodiment, the amount of the metal additive is preferably 10 mol% to 50 mol% of the amide compound.

[0031] In another preferred embodiment, the amount of the divalent samarium salt or ytterbium salt is preferably 200 mol% to 300 mol% of the amide compound.

[0032] In another preferred embodiment, the amount of the elemental metal is preferably 200 mol% to 300 mol% of the amount of the amide compound.

[0033] In another preferred embodiment, the reaction temperature is from -80°C to 200°C, more preferably from 40°C to 100°C, and even more preferably from 70°C to 90°C.

[0034] In another preferred embodiment, the reaction is carried out in an organic solvent selected from: tetrahydrofuran, methanol, toluene, acetonitrile, carbon tetrachloride, chloroform, 1,4-dioxane, 1,2-dichloroethane, ethylene glycol dimethyl ether, dimethyl sulfoxide, N,N-dimethylformamide, and N-methylpyrrolidone.

[0035] In another preferred embodiment, the metal additive is selected from the group consisting of: FeCl3, Fe(OTf)3, Rh2(OAc)4, Rh2(OCt)4, Sc(OTf)3, NiI2, Ni(COD)2 / PPh3, Ni(COD)2, CoCl2, CuI, Pd(PPh3)4, Pd2(dba)3 / Xantphos, Pd2(dba)3 / PPh3, and Pd(OAc)2 / Xantphos.

[0036] This invention discloses for the first time a method for converting amides into α-substituted amine compounds using a mixture of divalent samarium (or ytterbium) salts, elemental metals, and metal additives. The use of metal additives is key to achieving efficient deoxygenation functionalization of amides.

[0037] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0038] Figure 1 The image shows the 1H NMR spectrum of compound 3aa obtained in Example 1.

[0039] Figure 2The image shows the carbon NMR spectrum of compound 3aa obtained in Example 1. Specific implementation methods

[0040] The inventors of this application, through extensive and in-depth research, have developed a method for the direct deoxyfunctionalization of amides using a mixed system of divalent samarium (or ytterbium) salts, elemental metals, and metal additives. The reaction is simple to operate, can be carried out under mild conditions, and can convert amides into α-substituted amine compounds. Based on this, the present invention was completed.

[0041] the term

[0042] Term "C" 1-6 "C3-C" refers to a carbon atom with 1, 2, 3, 4, 5, or 6 carbon atoms. 10 "" refers to having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, and so on.

[0043] The term "alkyl" refers to a saturated linear or branched hydrocarbon moiety, such as -CH3 or -CH(CH3)2. The term "alkoxy" refers to the group formed when an alkyl group is linked to an oxygen atom, such as -OCH3 or -OCH2CH3. The term "cycloalkyl" refers to a saturated cyclic hydrocarbon moiety, including monocyclic, fused, and bridged ring structures, such as cyclohexyl. The term "heterocyclic" refers to a cyclic hydrocarbon moiety having one, two, three, or four heteroatoms selected from O, N, and S, including monocyclic, fused, and bridged ring structures, such as morpholine. The term "aryl" refers to a hydrocarbon moiety containing one or more aromatic rings, including but not limited to phenyl, benzyl, phenylene, naphthyl, naphthylene, pyrene, anthracene, and phenanthrene. The term "heteroaryl" refers to an aryl group containing at least one cyclic heteroatom (e.g., having 1, 2, 3, or 4 heteroatoms selected from O, N, and S), including monocyclic and fused-ring structures, such as benzisothiazolyl, thiazolyl, thiophene, furanyl, pyrrole, indolyl, benzimidazolyl, etc.

[0044] Unless otherwise stated, the terms alkyl, alkoxy, cycloalkyl, heterocyclic, heteroaryl, and aryl as used herein include both substituted and unsubstituted portions. Possible substituents on alkyl, alkoxy, cycloalkyl, heterocyclic, heteroaryl, and aryl groups include, but are not limited to: C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkyne, and C4-C6 alkyne. 10 cycloalkyl, C3-C 10 Cycloalkenyl, C1-C6 alkoxy, aryl, hydroxyl, halogen, amino.

[0045] use

[0046] The α-aryl-substituted amine compounds involved in this invention can be used to treat diseases such as urticaria caused by allergens. Therefore, they can be used to prepare drugs for the prevention and treatment of tumors.

[0047] The α-aryl-substituted amine compounds involved in this invention can be administered alone or in combination with other pharmaceutically acceptable compounds (such as other antitumor drugs). Representative antitumor drugs include (but are not limited to): letrozole, solifenacin, cetirizine, cinnamirizine, chlorpheniramine, and bukelizine.

[0048] The advantages of this invention are:

[0049] (1) A method is provided for converting an amide into an α-substituted amine compound.

[0050] (2) A novel method for preparing 1,1-diarylmethylamine compounds is provided.

[0051] (3) The method of this invention develops a direct deoxyfunctionalization reaction of amides using a mixture of divalent samarium (or ytterbium) salts, elemental metals, and metal additives. The reaction is simple to operate, carried out under mild conditions, and can convert amides into α-substituted amine compounds. From a synthetic perspective, this conversion is an extremely simple method for carrying out challenging deoxyfunctionalization of amides, a long-standing goal of organic chemists.

[0052] The present invention will be specifically described below through embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above content of the present invention shall fall within the scope of protection of the present invention.

[0053] Example 1

[0054] In this embodiment, naphthalene-2-borate pinacol ester was used as the arylating agent, tetrahydrofuran was used as the solvent, and the deoxyarylation reaction of substrate 1a was catalyzed in the presence of SmI2 and Sm. The reaction formula is as follows:

[0055]

[0056] The reaction was as follows: Under a nitrogen atmosphere, 1a (17.5 mg, 0.1 mmol) and 2a (25.4 mg, 0.2 mmol) were added to separate sealed tubes, followed by the addition of Sm (30.0 mg, 0.2 mmol) and SmI2 (2.2 mL, 0.22 mmol). After stirring at 80 °C for 18 hours, the mixture was quenched with saturated sodium bicarbonate (4 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography packed with alkaline alumina. The deoxyarylated product 3aa was obtained in 56% yield.

[0057] The proton and carbon NMR spectra of 3aa are as follows: Figure 1 and Figure 2 As shown.

[0058] 1 H NMR (400MHz, CDCl3)7.89(s,1H),7.80(d,J=7.6Hz,1H),7.73(dd,J=8.4,2.8Hz,2H),7.62(d,J=8.4Hz,1H),7.52(d,J=7.6Hz ,2H),7.45–7.34(m,2H),7.25(t,J=7.6Hz,2H),7.14(t,J=7.2Hz,1H),4.32(s,1H),2.51–2.42(m,4H),1.83–1.74(m,4H)ppm.

[0059] Example 2

[0060] In this embodiment, pinacol ester of naphthalene-2-borate was used as the arylating agent and tetrahydrofuran as the solvent to catalyze the deoxyarylation reaction of substrate 1a at different temperatures. The reaction formula is as follows:

[0061]

[0062] The reaction was as follows: Under a nitrogen atmosphere, 1a (17.5 mg, 0.1 mmol) and 2a (25.4 mg, 0.2 mmol) were added to separate sealed tubes, followed by the addition of Sm (30.0 mg, 0.2 mmol) and SmI2 (2.2 mL, 0.22 mmol). After stirring at different temperatures for eighteen hours, the reaction was quenched with saturated sodium bicarbonate (4 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product.

[0063] Table 2: Effect of different temperature conditions on deoxyarylation results

[0064]

[0065] a GC yield.

[0066] Example 3

[0067] In this embodiment, naphthalene-2-borate pinacol ester was used as the arylating agent, tetrahydrofuran was used as the solvent, and the deoxyarylation reaction of substrate 1a was catalyzed by SmI2 and Sm under the catalysis of different metal additives. The reaction formula is as follows:

[0068]

[0069] The reaction was carried out as follows: Under a nitrogen atmosphere, 1a (17.5 mg, 0.1 mmol) and 2a (25.4 mg, 0.2 mmol) were added to separate sealed tubes, followed by Additive (5 mmol%), Sm (30.0 mg, 0.2 mmol), and SmI2 (2.2 mL, 0.22 mmol). After stirring at 80 °C for 18 hours, saturated sodium bicarbonate (4 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product.

[0070] Table 3: Effects of different additives on deoxyarylation results

[0071]

[0072]

[0073] b 0.2 mmol scale separation yield

[0074] Example 4

[0075] In this embodiment, arylboronic acid pinacol esters with different substitutions were used as arylating agents, tetrahydrofuran was used as solvent, and Pd(PPh3)4 was used as additive. The deoxyarylization reaction of substrate 1a was catalyzed by Sm and SmI2 (reaction formula is as follows):

[0076]

[0077] The reaction was as follows: Under a nitrogen atmosphere, 1a (35.0 mg, 0.2 mmol) and 2 (0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product 3. The experimental results are shown below:

[0078]

[0079] 3aa, yellow solid, 86% yield, MPa 78-79℃. 1H NMR (400MHz, CDCl3): δ7.89(s,1H),7.80(d,J=7.6Hz,1H),7.73(dd,J=8.4,2.8Hz,2H),7.62(d,J=8.4Hz,1H),7.52(d,J=7.6H z,2H),7.45–7.34(m,2H),7.25(t,J=7.6Hz,2H),7.14(t,J=7.2Hz,1H),4.32(s,1H),2.51–2.42(m,4H),1.83–1.74(m,4H)ppm; 13 C NMR (101MHz, CDCl3): δ144.0,141.8,133.4,132.6,128.4,128.1,127.8,127.6,127.5,126.8,125.9 ,125.8,125.7,125.4,76.6,53.7,23.6ppm;IR(neat)ν2962,2874,1598,1506,1359,1127,810,729cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 21 H 22 N 288.1750; found 288.1747.

[0080]

[0081] 3ab, yellow solid, 84% yield, MPa 70-71℃. 1 H NMR (400MHz, CDCl3) δ7.40(d,J=7.6Hz,4H),7.19(t,J=7.2Hz,4H),7.09(t,J=7.6Hz,2H),4.10(s,1H),2.42–2.33(m,4H),1.75–1.66(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ144.3,128.3,127.5,126.7,76.5,53.6,23.5ppm.

[0082]

[0083] 3ac, yellow oil, 88% yield. 1 H NMR (400MHz, CDCl3) 1HNMR (400 MHz, CDCl3) δ 7.40 (t, J = 7.2 Hz, 4H), 7.27–7.20 (m, 4H), 7.16 (t, J = 7.2 Hz, 1H), 4.13 (s, 1H), 2.45–2.33 (m, 4H), 1.80–1.69 (m, 4H) ppm; 13 13C NMR (101 MHz, CDCl3) δ 128.8, 128.6, 128.5, 127.4, 75.7, 53.6, 23.5 ppm (Four carbons are missing due to overlapping); IR (neat) ν 2960, 2873, 1599, 1487, 1268, 1088, 756, 698 cm -1 -1. HRMS (ESI) m / z: [M+H] + + calcd for C 17 16 19 ClN2 272.1192; found: 272.1201.

[0084]

[0085] 3ad, yellow oil, 65% yield, 1 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 7.6 Hz, 2H), 7.27 (t, J = 8.0 Hz, 2H), 7.18 (t, J = 7.6 Hz, 1H), 4.45–7.34 (s, 1H), 2.46–2.39 (m, 4H), 1.82–1.73 (m, 4H) ppm; 13 13C NMR (151 MHz, CDCl3) δ 148.3, 143.3, 129.0 (q, J = 31.7 Hz), 128.6, 127.7, 127.5, 127.2, 125.4 (q, J = 3.0 Hz), 124.2 (q, J = 271.8 Hz), 76.0, 53.5, 23.5 ppm; 19 19F NMR (376 MHz, CDCl3) δ -62.4 (s, 3F) ppm; HRMS (ESI) m / z: [M+H] + + calcd for C 18 18 19 F3N2 306.1474; found: 306.1464.

[0086]

[0087] 3ae, yellow oil, 80% yield. 1 H NMR (400MHz, CDCl3) δ7.47(d,J=6.8Hz,2H),7.37(d,J=7.2Hz,2H),7.26(t,J=7.2Hz,2H),7.15(t,J=7 .2Hz,1H),7.08(d,J=7.6Hz,2H),4.17(s,1H),2.52–2.43(m,4H),2.27(s,3H),1.85–1.74(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ129.1,128.4,127.40,127.36,126.8,76.3,53.7,23.5,21.0ppm(Three carbons is missing because of overlapping); IR(neat)ν2922,2854,1602,1510,1361,1126,799,697cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 18 H 22 N 252.1752; found: 252.1747.

[0088]

[0089] 3af, yellow solid, 66% yield, MPa 58-59℃. 1 H NMR (400MHz, CDCl3) δ7.48–7.38(m,6H),7.25(t,J=7.2Hz,2H),7.15(t,J=7. 2Hz,1H),4.13(s,1H),2.46–2.38(m,4H),1.80–1.73(m,4H),0.21(s,9H)ppm; 13 C NMR (101MHz, CDCl3) δ144.8,144.2,138.5,133.4,128.3,127.5,126.80,126.77,7 6.6,53.7,23.5,-1.1ppm; IR(neat)ν2965,1596,1450,1361,1247,1131,831,722cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 20 H 28NSi 310.1991; found:310.1986.

[0090]

[0091] 3ag, yellow solid, 77% yield, MPa 50-51℃. 1 H NMR (400MHz, CDCl3) δ7.44(d,J=7.6Hz,2H),7.36(d,J=8.4Hz,2H),7.25–7.23(m,2H),7.15(t,J=7. 2Hz,1H),6.80(d,J=8.4Hz,2H),4.11(s,1H),3.74(s,3H),2.46–2.37(m,4H),1.82–1.72(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ158.3,144.5,136.5,128.4,128.3,127.3,126.6,113.7,75. 8,55.1,53.7,23.5ppm;IR(neat)ν2928,2853,1603,1509,1452,1360,1147,698cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 18 H 22 NO 268.1702; found: 268.1696.

[0092]

[0093] 3ah, yellow solid, 80% yield, MPa 84-85℃. 1 H NMR (400MHz, CDCl3) δ7.46(d,J=7.6Hz,2H),7.38(d,J=8.4Hz,2H),7.27(t,J =7.6Hz,2H),7.17(t,J=7.6Hz,1H),6.97(d,J=8.8Hz,2H),5.37(q,J=3.2Hz,1 H),4.13(s,1H),3.94–3.87(m,1H),3.57–3.61(m,1H),2.49–2.38(m,4H),2. 05–1.93(m,1H),1.86–1.81(m,2H),1.73–1.80(m,4H),1.69–1.55(m,3H)ppm; 13C NMR (101MHz, CDCl3) δ155.9,144.5,137.4,128.34,128.31,128.2,127.3,126.6,116.16,116.12,96.3,75.84,7 5.79,61.99,61.97,53.6,30.4,25.2,23.5,18.8ppm;IR(neat)ν2938,2873,1608,1509,1453,1356,1073,699cm -1 .HRMS(ESI)m / z:[M+H] + calcdfor C 22 H 28 NO2 338.2118; found:338.2115.

[0094]

[0095] 3ai, white solid, 80% yield, MPa 40-41℃. 1 H NMR (400MHz, CDCl3) δ7.45(d,J=7.6Hz,2H),7.28(dd,J=17.6,8.4Hz,4H),7.18(t,J=7.2Hz,5H), 7.03(d,J=7.6Hz,4H),6.95–6.89(m,4H),4.09(s,1H),2.46–2.37(m,4H),1.81–1.72(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ147.8,146.2,144.4,138.6,129.1,128.3,128.2,127.5,126.7,124.1,123.8,122.5,76.0,53.7,23.5ppm IR(neat)ν2963,1587,1488,1311,1271,1028,750,694cm -1 .;HRMS(ESI)m / z:[M+H] + calcd for C 29 H 29 N2 405.2328; found: 405.2325.

[0096]

[0097] 3aj, yellow solid, 67% yield, Mp 52-53℃. 1¹H NMR (400 MHz, CDCl₃) δ 7.50–7.37 (m, 4H), 7.31 (d, J = 8.0 Hz, 2H), 7.25 (t, J = 7.6 Hz, 2H), 7.15 (t, J = 7.2 Hz, 1H), 6.64 (dd, J = 17.6, 10.8 Hz, 1H), 5.69 (d, J = 17.2 Hz, 1H), 5.16 (d, J = 10.8 Hz, 1H), 4.15 (s, 1H), 2.47–2.36 (m, 4H), 1.82–1.72 (m, 4H) ppm; 13 ¹³C NMR (101 MHz, CDCl₃) δ 144.1, 144.0, 136.5, 136.1, 128.4, 127.6, 127.4, 126.8, 126.3, 113.3, 76.2, 53.6, 23.5 ppm; IR (neat) ν 2956, 2874, 1597, 1486, 1451, 1362, 899, 697 cm -1 ⁻¹. HRMS (ESI) m / z: [M+H] + ⁺ calcd for C 19 ₁₉ 22 N 264.1755; found: 264.1747.

[0098]

[0099] 3ak, white solid, 55% yield, Mp 97-98°C. 1 ¹H NMR (400 MHz, CDCl₃) δ 7.47 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 7.2 Hz, 2H), 7.25 (t, J = 8.0 Hz, 2H), 7.23–7.12 (m, 3H), 4.17 (s, 1H), 3.62 (s, 2H), 2.34–2.48 (m, 4H), 1.82–1.72 (m, 4H) ppm; 13 ¹³C NMR (101 MHz, CDCl₃) δ 144.3, 143.8, 128.4, 128.2, 128.1, 127.9, 127.3, 126.9, 117.9, 75.9, 53.5, 23.5, 23.1 ppm; IR (neat) ν 2974, 2857, 2086, 1598, 1486, 1024, 823, 792 cm -1 ⁻¹. HRMS (ESI) m / z: [M+H] + ⁺ calcd for C 19 ₁₉ 21 N₂ 277.1701; found: 277.1699.

[0100]

[0101] 3al, yellow oil, 91% yield. 1 H NMR (400MHz, CDCl3) δ7.45(d,J=7.6Hz,2H),7.24(t,J=7.2Hz,2H),7.19–7.10(m,3H),7.05(d,J=7.6Hz,1H),6.87(dd ,J=8.4,2.4Hz,1H),4.11(s,1H),3.73–3.65(m,1H),2.42(d,J=6.4Hz,4H),1.79–1.71(m,4H),0.76–0.68(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ158.9,145.8,144.2,129.1,128.3,127.5,126.7,120.1,114.4,112.9,76 .4,53.6,50.6,23.5,6.14,6.13ppm;IR(neat)ν2965,2874,1584,1443,1357,1255,1018,775cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 20 H 24 NO 294.1861; found: 294.1852.

[0102]

[0103] 3am, colorless oil, 59% yield. 1 H NMR(400MHz, CDCl3)δ7.43(d,J=6.8Hz,2H),7.37(s,1H),7.28–7.21(m,3H),7.20–7.12(m, 2H),7.08–7.01(m,1H),4.11(s,1H),2.44(s,3H),2.43–2.36(m,4H),1.72–1.79(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ145.0,143.9,138.2,128.8,128.3,127.5,126.8,125.7,124.8,12 4.3,76.3,53.6,23.5,15.8ppm; IR(neat)ν2964,2872,1587,1492,1361,1128,779,703cm -1.HRMS(ESI)m / z:[M+H] + calcd for C 18 H 22 NS284.1478; found: 284.1468.

[0104]

[0105] 3an, yellow oil, 77% yield. 1 H NMR (400MHz, CDCl3) δ7.48(d,J=7.2Hz,2H),7.27(t,J=7.2Hz,2H),7.18(t,J=7.2Hz,1H),6.68(d,J=2 .0Hz,2H),6.29(t,J=2.4Hz,1H),4.09(s,1H),3.77(s,6H),2.51–2.37(m,4H),1.82–1.75(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ160.6,146.8,144.0,128.3,127.4,126.8,105.4,98.5,76. 6,55.2,53.6,23.5ppm;IR(neat)ν2960,2835,1593,1454,1201,1151,827,706cm -1 .HRMS(ESI)m / z:[M+H] + calcd forC 19 H 24 NO2 298.1802; found:298.1802.

[0106]

[0107] 3ao, white solid, 72% yield, MPa 73-74℃. 1 H NMR (400MHz, CDCl3) δ7.45(d,J=7.2Hz,2H),7.28(t,J=7.2Hz,2H),7.18(t,J=7.2Hz,1H),7.02(d,J=1.6Hz,1H),6.91(dd,J =8.0,1.2Hz,1H),6.70(d,J=8.0Hz,1H),5.88(dd,J=9.2,1.2Hz,2H),4.09(s,1H),2.48–2.37(m,4H),1.83–1.76(m,4H)ppm; 1313C NMR (101 MHz, CDCl3) δ 147.6, 146.2, 144.4, 138.5, 128.3, 127.3, 126.7, 120.4, 107.9, 107.7, 100.8, 76.0, 53.6, 23.5 ppm; IR (neat) ν 2917, 2874, 1486, 1373, 1245, 1107, 1039, 693 cm -1 . HRMS (ESI) m / z: [M+H] + calcd for C 18 H 20 NO2 282.1496; found: 282.1489.

[0108]

[0109] 3ap, yellow oil, 67% yield, 1 1H NMR (400 MHz, CDCl3) δ 7.92 (t, J=7.6 Hz, 1H), 7.46 (d, J=7.6 Hz, 2H), 7.40 (d, J=8.0 Hz, 1H), 7.29 (t, J=7.4 Hz, 2H), 7.25–7.17 (m, 2H), 4.65 (s, 1H), 2.52–2.38 (m, 4H), 1.84–1.76 (m, 4H) ppm; 13 13C NMR (151 MHz, CDCl3) δ 159.5 (d, J=249.2 Hz), 142.2, 135.3 (d, J=12.1 Hz), 130.3 (qd, J=33.2, 9.1 Hz), 129.5 (d, J=4.5 Hz), 128.5, 127.7, 127.4, 123.4 (q, J=271.8 Hz), 121.3–121.1 (m), 112.9 (dq, J=25.7, 4.5 Hz), 67.0, 53.4, 23.5 ppm; 19 19F NMR (376 MHz, CDCl3) δ -62.6 (s, 3F), -116.5 (m, 1F) ppm; IR (neat) ν 2976, 1585, 1454, 1367, 1328, 1126, 742, 698 cm -1 . HRMS (ESI) m / z: [M+H] + calcd for C 18 H 18 F4N 324.1367; found: 324.1370.

[0110]

[0111] 3aq, white solid, 68% yield, Mp 135-136℃. 1 H NMR (400MHz, CDCl3) δ8.18(d,J=8.0Hz,2H),7.80–7.72(m,1H),7.65(d,J=8.4Hz,2H),7.60–7.54(m,1H),7.49(d ,J=7.6Hz,2H),7.38–7.27(m,4H),7.20(t,J=7.6Hz,1H),4.26(s,1H),2.53–2.43(m,4H),1.86–1.75(m,4H)ppm; 13 CNMR (101MHz, CDCl3) δ163.0,150.6,148.1,143.4,142.1,128.5,128.0,127.8,127.5,127.1,125.6,124 .9,124.4,119.8,110.5,76.2,53.5,23.5ppm; IR(neat)ν2957,1617,1452,1361,1242,1053,1014,740cm -1 .HRMS(ESI)m / z:[M+H] + calcd forC 24 H 23 N2O 355.1815; found:355.1805.

[0112]

[0113] 3ar, colorless solid, 83% yield, MPa 44-45℃. 1 H NMR(400MHz, CDCl3) δ7.45(d,J=7.2Hz,2H),7.39(s,1H),7.31(t,J=7.2Hz,3H),7.22 (t,J=7.2Hz,1H),6.46(s,1H),4.18(s,1H),2.51–2.43(m,4H),1.83–1.74(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ143.4,142.9,139.2,128.4,128.3,127.6,126.9,109.8, 66.8,53.4,23.4ppm;IR(neat)ν2967,2920,1598,1499,1450,1125,1020,727cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C15 H 18 NO 228.1387; found: 228.1383.

[0114]

[0115] 3as, colorless solid, 91% yield, Mp 50-51℃. 1 H NMR(400MHz, CDCl3)δ7.48(d,J=7.2Hz,2H),7.31(t,J=7.6Hz,2H),7.25–7.17(m,3H) ,7.16(dd,J=4.4,1.2Hz,1H),4.35(s,1H),2.49–2.43(m,4H),1.82–1.75(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ145.3,143.5,128.3,127.6,127.1,126.9,125.4,120.9, 71.5,53.5,23.5ppm;IR(neat)ν2927,2873,1600,1493,1451,1362,1027,698cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 15 H 18 NS 244.1162; found: 244.1155.

[0116]

[0117] 3 at, yellow solid, 89% yield, Mp 126-127℃. 1 H NMR (400MHz, CDCl3) δ7.48(d,J=7.6Hz,2H),7.30(t,J=7.6Hz,2H),7.21(t,J=7.6Hz,1H),7.16(d,J=4.8Hz,1H),7.12(d,J=3.2Hz,1H),7.01 (d,J=3.6Hz,1H),6.97(t,J=3.6Hz,2H),6.90(d,J=3.6Hz,1H),6.84(d,J=3.6Hz,1H),4.43(s,1H),2.56–2.42(m,4H),1.84–1.72(m,4H)ppm; 13<13>C NMR (101 MHz, CDCl<3>) δ 148.2, 143.0, 137.2, 136.6, 136.2, 135.7, 128.4, 127.8, 127.5, 127.3, 124.5, 124.24, 124.19, 123.7, 123.5, 122.6, 71.3, 53.4, 23.5 ppm; IR (neat) ν 2951, 2850, 1599, 1452, 1354, 1249, 831, 697 cm -1 . HRMS (ESI) m / z: [M+H] + calcd for C 23 H 22 NS<3> 408.0909; found: 408.0909.

[0118]

[0119] 3au, white solid, 86% yield, Mp 75-76 °C. 1 <1>H NMR (400 MHz, CDCl<3>) δ 8.23 (s, 1H), 8.14 (d, J=7.6 Hz, 1H), 7.72 (d, J=8.0 Hz, 2H), 7.62 (d, J=7.2 Hz, 2H), 7.58–7.49 (m, 5H), 7.47–7.38 (m, 3H), 7.37–7.30 (m, 3H), 7.25 (t, J=7.2 Hz, 3H), 7.13 (t, J=7.6 Hz, 1H), 4.35 (s, 1H), 2.55–2.46 (m, 4H), 1.86–1.77 (m, 4H) ppm; 13 <13>C NMR (101 MHz, CDCl<3>) δ 144.8, 141.0, 140.2, 140.0, 139.9, 136.8, 136.3, 128.9, 128.3, 127.5, 127.4, 127.1, 127.0, 126.6, 125.80, 125.77, 123.44, 123.37, 120.3, 119.8, 119.0, 109.73, 109.70, 76.7, 53.9, 23.6 ppm (One carbon is missing because of overlapping); IR (neat) ν 2962, 1599, 1487, 1452, 1230, 1027, 763, 696 cm -1 . HRMS (ESI) m / z: [M+H] + calcd for C 35 H 31N2479.2472; found: 479.2482.

[0120]

[0121] 3av, yellow solid, 83% yield, MPa 74-75℃. 1 H NMR (400MHz, CDCl3) δ7.85–7.79(m,1H),7.70–7.63(m,1H),7.59–7.47(m,4H),7.31–7.19(m,5H),7.14–7 .05(m,4H),6.91–6.83(m,4H),4.33(s,1H),3.87–3.77(m,6H),2.60–2.47(m,4H),1.88–1.79(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ155.6,146.2,144.2,141.1,139.7,133.6,129.0,128.4,128.3,1 27.4,126.8,126.7,126.2,125.4,122.8,116.5,114.6,76.5,55.4,53.7,23.5ppm(One carbonis missing because of overlapping); IR(neat)ν2951,1600,1501,1487,1380,1237,1072,736cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 35 H 35 N2O2 515.2704; found:515.2693.

[0122]

[0123] 3aw, white solid, 72% yield, Mp 194-195℃. 1 H NMR (400MHz, CDCl3) δ8.71(d,J=6.4Hz,4H),8.63(d,J=8.4Hz,2H),7.65(d,J=8.4Hz,2H),7.57–7.47(m, 8H),7.27(t,J=7.2Hz,2H),7.17(t,J=7.6Hz,1H),4.26(s,1H),2.53–2.43(m,4H),1.83–1.14(m,4H)ppm; 13C NMR (101MHz, CDCl3) δ171.44,171.40,149.0,143.6,136.2,134.8,132.4,129.2,128.9,128.5,128.4 ,127.7,127.5,127.0,76.3,53.6,23.5ppm; IR(neat)ν2964,1588,1517,1445,1367,1023,764,687cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 32 H 29 N4 469.2393; found: 469.2387.

[0124] Example 5

[0125] In this embodiment, 2a is used as the arylating agent, tetrahydrofuran as the solvent, and Pd(PPh3)4 as the additive. Under the catalysis of Sm and SmI2, the deoxyarylation reactions of various substrates 1 are catalyzed (reaction formulas are as follows):

[0126]

[0127] The reaction was as follows: Under a nitrogen atmosphere, 1 (xx mg, 0.2 mmol) and 2a (102.0 mg, 0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product 3. The experimental results are shown below:

[0128]

[0129] 3ba, colorless solid, 94% yield, MPa 98-99℃. 11H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.76–7.72 (m, 2H), 7.58 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 7.6 Hz, 2H), 7.44–7.35 (m, 2H), 7.29–7.23 (m, 2H), 7.15 (t, J = 7.2 Hz, 1H), 4.38 (s, 1H), 2.36 (s, 4H), 1.62-1.53 (m, 4H), 1.48-1.39 (m, 2H) ppm; 13 13C NMR (101 MHz, CDCl3) δ 143.1, 140.8, 133.4, 132.6, 128.3, 128.0, 127.8, 127.5, 126.7, 126.5, 126.1, 125.8, 125.4, 76.9, 53.3, 26.2, 24.7 ppm (One carbon is missing because of overlapping); IR (neat) ν 2964, 2854, 1598, 1492, 1442, 1360, 1147, 733 cm -1 . HRMS (ESI) m / z: [M+H] + calcd for C 22 H 24 N 302.1907; found: 302.1903.

[0130]

[0131] 3ca, colorless oil, 71% yield, 1 1H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), δ 7.79–7.71 (m, 3H), 7.63 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 7.6 Hz, 2H), 7.45–7.36 (m, 2H), 7.26–7.23 (m, 2H), 7.15 (t, J = 7.2 Hz, 1H), 4.76 (s, 1H), 2.63 (t, J = 5.6 Hz, 4H), 1.69–1.58 (m, 8H) ppm; 13C NMR (101MHz, CDCl3) δ144.0,141.8,133.4,132.6,128.3,127.99,127.96,127.8,127.5,126.7,126.4,12 6.2,125.8,125.4,75.6,54.0,29.1,26.9ppm; IR(neat)ν2921,2851,1598,1491,1450,1361,1148,742cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 23 H 26 N 316.2071; found: 316.2060.

[0132]

[0133] 3 da, colorless solid, 92% yield, Mp 125-126℃. 1 H NMR (400MHz, CDCl3) δ7.83(s,1H),7.78(d,J=7.6Hz,1H),7.73(d,J=8.4Hz,2H),7.59(dd,J=8.8,1.6Hz,1H),7.48(d,J=7.2Hz,2H ),7.45–7.34(m,2H),7.26(t,J=7.2Hz,2H),7.15(t,J=7.2Hz,1H),4.35(s,1H),3.72(t,J=4.4Hz,4H),2.42(d,J=4.8Hz,4H)ppm; 13 C NMR (101MHz, CDCl3) δ142.1,139.8,133.4,132.7,128.5,128.3,127.9,127.7,127.5,127.1,126.6,1 26.0,125.73,125.65,76.8,67.2,52.7ppm;IR(neat)ν2970,2856,1488,1285,1109,1066,1031,754cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 21 H 22 NO 304.1698; found: 304.1696.

[0134]

[0135] 3ea, yellow solid, 58% yield, Mp 97-98℃.1 1H NMR (400 MHz, CDCl3) major isomer: δ 7.93 (s, 1H), 7.85 (s, 1H), 7.76–7.81 (m, 2H), 7.75–7.70 (m, 3H), 7.55 (d, J = 7.6 Hz, 1H), 7.42–7.37 (m, 2H), 7.24–7.22 (m, 1H), 7.12 (t, J = 7.2 Hz, 1H), 5.12 (s, 1H), 3.25–3.11 (m, 2H), 1.84–1.70 (m, 3H), 1.38–1.46 (m, 3H), 1.06 (d, J = 7.2 Hz, 3H), 1.01 (d, J = 7.6 Hz, 3H) ppm; minor isomer: δ 7.93 (s, 1H), 7.85 (s, 1H), 7.76–7.81 (m, 2H), 7.75–7.70 (m, 3H), 7.55 (d, J = 7.6 Hz, 1H), 7.42–7.37 (m, 2H), 7.24–7.22 (m, 1H), 7.12 (t, J = 7.2 Hz, 1H), 5.31 (s, 1H), 3.25–3.11 (m, 2H), 1.84–1.70 (m, 3H), 1.38–1.46 (m, 3H), 1.06 (d, J = 7.2 Hz, 3H), 1.01 (d, J = 7.6 Hz, 3H) ppm; 13 13C NMR (101 MHz, CDCl3) δ 143.7, 141.6, 141.4, 133.50, 133.48, 132.62, 132.59, 128.3, 128.0, 127.68, 127.67, 127.5, 126.6, 126.5, 126.4, 126.11, 126.09, 125.74, 125.72, 125.40, 125.37, 70.4, 70.3, 48.0, 47.7, 31.4, 16.2, 16.1, 14.6 ppm; IR (neat) ν 2923, 2849, 1597, 1504, 1364, 1144, 742, 699 cm -1 -1. HRMS (ESI) m / z: [M+H] + + calcd for C 21 20H< 22 23NO 304.1698; found: 304.1696.

[0136]

[0137] 3fa, yellow oil, 72% yield, 1H NMR(400MHz,CDCl3)major isomer:δ7.90–7.71(m,3H),7.63(s,1H),7.56(d,J=8.4Hz,1H),7.48–7.40(m,3H),7.35(dd,J=14.0,6.8Hz,1H),7.27(dd,J=15.6,8.0Hz,1H),7.19(t,J=7.2Hz,1H),5.74(s,1H),2.92(dd,J=22.4,10.8Hz,1H),2.55(dd,J=23.6,11.2Hz,1H),1.94–1.77(m,3H),1.73–1.47(m,5H),1.37–1.18(m,4H),1.06–0.78(m,2H)ppm;minor isomer:δ7.90–7.71(m,3H),7.63(s,1H),7.56(d,J=8.4Hz,1H),7.48–7.40(m,3H),7.35(dd,J=14.0,6.8Hz,1H),7.27(dd,J=15.6,8.0Hz,1H),7.19(t,J=7.2Hz,1H),5.71(s,1H),2.92(dd,J=22.4,10.8Hz,1H),2.55(dd,J=23.6,11.2Hz,1H),1.94–1.77(m,3H),1.73–1.47(m,5H),1.37–1.18(m,4H),1.06–0.78(m,2H)ppm; 13 C NMR(101MHz,CDCl3)δ143.4,141.0,138.3,136.1,133.2,133.0,132.4,132.3,130.5,129.2,128.7,128.3,128.0,127.7,127.5,127.4,127.1,127.0,126.9,126.8,126.7,126.1,125.8,125.7,125.6,125.3,64.0,63.8,63.3,63.2,49.0,43.54,43.51,33.3,33.2,33.0,32.9,30.74,30.71,26.39,26.37,26.1,25.86,25.85ppm;IR(neat)ν2918,2850,1598,1505,1444,1239,1030,701cm -1 .HRMS(ESI)m / z:[M+H] + calcd forC 21 H 22NO 304.1698; found: 304.1696.

[0138]

[0139] 3ga, white solid, 77% yield, Mp 108-109℃. 1 H NMR (400MHz, CDCl3) δ7.80 (s, 1H), 7.77 (d, J = 7.6Hz, 1H), 7.73 (d, J = 8.4Hz, 2H), 7.6 0(dd,J=8.8,1.2Hz,1H),7.47(d,J=7.6Hz,2H),7.44–7.34(m,2H),7.25(t,J=7.6Hz ,2H),7.14(t,J=7.2Hz,1H),4.36(s,1H),4.22(dd,J=17.6,4.4Hz,2H),2.59(dd,J= 27.6,11.2Hz,2H),2.23(d,J=11.2Hz,2H),2.17–2.08(m,2H),1.94–1.84(m,2H)ppm; 13 C NMR (101MHz, CDCl3) δ142.43,140.1,133.4,132.7,128.5,128.3,127.8,127.7,127.5,127.0,126.6,125.9,125. 6,125.5,76.2,74.88,74.86,57.6,57.4,28.7,28.6ppm;IR(neat)ν2960,1598,1504,1450,1327,1133,992,877cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 23 H 24 NO330.1851; found: 330.1852.

[0140]

[0141] 3ha, white solid, 45.3mg, 52% yield, MP 158-159℃. 1¹H NMR (400 MHz, CDCl₃) δ 7.91 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.80 (d, J=8.4 Hz, 3H), 7.67 (d, J=8.8 Hz, 1H), 7.56 (d, J=7.2 Hz, 2H), 7.50–7.41 (m, 3H), 7.32 (t, J=7.6 Hz, 3H), 7.22 (t, J=7.6 Hz, 1H), 4.54 (s, 1H), 3.60 (t, J=4.4 Hz, 4H), 2.78–2.63 (m, 4H) ppm; 13 ¹³C NMR (101 MHz, CDCl₃) δ 164.0, 152.7, 142.3, 140.0, 133.4, 132.7, 128.6, 128.4, 128.04, 128.00, 127.8, 127.6, 127.4, 127.1, 126.6, 126.0, 125.8, 125.7, 123.9, 123.8, 120.5, 76.3, 51.9, 50.3 ppm; IR (neat) ν 2953, 1593, 1486, 1420, 1379, 1257, 1003, 733 cm -1 . HRMS (ESI) m / z: [M+H] + calcd for C 28 H 26 N₃S 436.1844; found: 436.1842.

[0142]

[0143] 3ia, yellow oil, 83% yield, 1 ¹H NMR (400 MHz, CDCl₃) δ 7.81 (s, 1H), 7.78–7.71 (m, 3H), 7.56 (dd, J=8.8, 1.2 Hz, 1H), 7.46–7.38 (m, 4H), 7.27 (t, J=7.6 Hz, 2H), 7.21–7.16 (m, 1H), 5.08 (s, 1H), 3.48 (t, J=6.4 Hz, 4H), 3.27 (s, 6H), 2.83 (t, J=6.4 Hz, 4H) ppm; 1313C NMR (101 MHz, CDCl3) δ 142.2, 140.0, 133.3, 132.6, 128.5, 128.2, 127.9, 127.8, 127.5, 127.1, 126.9, 126.6, 125.8, 125.6, 72.2, 71.5, 58.7, 50.9 ppm; IR (neat) ν 2872, 1598, 1491, 1450, 1363, 1114, 814, 701 cm -1 −1. HRMS (ESI) m / z: [M+H] + + calcd for C 23 22 28 H26NO2 350.2119; found: 350.2115.

[0144]

[0145] 3ja, colorless solid, 87% yield, Mp 65-66 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.85 (d, J=7.6 Hz, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.66 (dd, J=8.4, 1.2 Hz, 1H), 7.54 (d, J=7.6 Hz, 2H), 7.51–7.41 (m, 2H), 7.32 (t, J=7.2 Hz, 2H), 7.21 (t, J=7.2 Hz, 1H), 4.29 (s, 1H), 2.30 (s, 6H) ppm; 13 13C NMR (101 MHz, CDCl3) δ 143.2, 141.0, 133.4, 132.6, 128.5, 128.2, 127.8, 127.5, 126.9, 126.2, 125.9, 125.8, 125.5, 78.1, 44.8 ppm (One carbon is missing because of overlapping); IR (neat) ν 2989, 2857, 1597, 1494, 1362, 1250, 812, 734 cm - 1 −1. HRMS (ESI) m / z: [M+H] + + calcd for C 19 H 20 20N 262.1597; found: 262.1590.

[0146]

[0147] 3 kDa, white solid, 73% yield, MPa 95-96℃. 1 H NMR (400MHz, CDCl3) δ7.91 (s, 1H), 7.85 (d, J = 7.6Hz, 1H), 7.80 (d, J = 8.4Hz, 2H), 7.65 (dd, J = 8.4, 1.2Hz,1H),7.43–7.38(m,4H),7.14(d,J=7.6Hz,2H),4.26(s,1H),2.32(s,3H),2.30(s,6H)ppm; 13 C NMR (101MHz, CDCl3) δ141.2,140.2,136.5,133.5,132.6,129.2,128.2,127.8,127.6,127.5,126.0,1 25.83,125.75,125.5,77.8,,44.8,21.0ppm;IR(neat)ν2990,2857,1597,1509,1362,1250,858,742cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 20 H 22 N 276.1738; found: 276.1747.

[0148]

[0149] 3la, white solid, 66% yield, MPa 89-90℃. 1 H NMR (400MHz, CDCl3) δ7.82(s,1H),7.79(d,J=8.0Hz,1H),7.75(d,J=8.8Hz,2H),7.53(dd, J=8.8,1.6Hz,1H),7.48–7.35(m,4H),7.24(d,J=8.4Hz,2H),4.21(s,1H),2.22(s,6H)ppm; 13 C NMR (101MHz, CDCl3) δ141.8,140.4,133.4,132.7,132.5,129.1,128.6,128.4,127.8,127.6,126. 2,126.0,125.7,125.5,77.3,44.7ppm;IR(neat)ν2951,2819,1591,1503,1462,1363,1026,743cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 19H 19 NCl296.1206; found: 296.1201.

[0150]

[0151] 3ma, white solid, 91% yield, MPa 58-59℃. 1 H NMR (400MHz, CDCl3) δ7.82(s,1H),7.78(d,J=8.0Hz,1H),7.74(d,J=8.4Hz,2H),7.54(d ,J=8.4Hz,1H),7.49–7.31(m,4H),6.94(t,J=8.4Hz,2H),4.19(s,1H),2.21(s,6H)ppm; 13 C NMR (101MHz, CDCl3) δ161.7 (d, J = 246.4Hz), 140.7, 139.0 (d, J = 3.0Hz), 133.4, 132.6, 129.1 (d, J =8.1Hz),128.3,127.7,127.6,126.1,126.0,125.6,125.5,115.2(d,J=20.2Hz),77.1,44.7ppm; 19 F NMR(376MHz, CDCl3)δ-115.7(m,1F)ppm; IR(neat)ν2976,2856,1601,1481,1235,1094,1039,775cm - 1 .HRMS(ESI)m / z:[M+H] + calcd for C 19 H 19 NF 280.1504; found: 280.1496.

[0152]

[0153] 3na, white solid, 77% yield, Mp 70-71℃. 1 H NMR (400MHz, CDCl3) δ7.84(s,1H),7.79(d,J=8.0Hz,1H),7.76(d,J=8.4Hz,2H),7.62(d ,J=8.0Hz,2H),7.54(t,J=8.9Hz,3H),7.47–7.37(m,2H),4.28(s,1H),2.23(s,6H)ppm; 1313C NMR (151 MHz, CDCl3) δ 147.4, 140.0, 133.4, 132.8, 130.1, 129.1 (q, J = 33.2 Hz), 128.5, 128.0, 127.8, 127.6, 126.5, 126.1, 125.9, 125.5 (q, J = 3.0 Hz), 124.2 (q, J = 271.8 Hz), 77.6, 44.6 ppm; 19 19F NMR (376 MHz, CDCl3) δ -62.4 (s, 3F) ppm; IR (neat) ν 2953, 1617, 1507, 1323, 1265, 1121, 1016, 733 cm -1 -1. HRMS (ESI) m / z: [M+H] + + calcd for C 20 20H 19 16NF3 330.1475; found: 330.1464.

[0154]

[0155] 3oa, white solid, 50% yield, Mp 115-116 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 9.6 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.52 (dd, J = 8.4, 1.2 Hz, 1H), 7.50–7.41 (m, 2H), 4.31 (s, 1H), 2.25 (s, 6H) ppm; 13 13C NMR (101 MHz, CDCl3) δ 148.9, 139.4, 133.4, 132.8, 132.4, 128.6, 128.4, 127.8, 127.6, 126.6, 126.2, 126.0, 125.3, 118.8, 110.7, 77.6, 44.6 ppm; IR (neat) ν 2956, 2851, 2223, 1605, 1502, 1361, 1025, 752 cm -1 -1. HRMS (ESI) m / z: [M+H] + + calcd for C 20 20H 19 19N2 287.1550; found: 287.1543.

[0156]

[0157] 3 Pa, yellow solid, 81% yield, MPa 62-63℃. 1 H NMR (400MHz, CDCl3) δ7.87–7.83(m,2H),7.81(d,J=8.4Hz,2H),7.60(dd,J=7.2,2.0Hz,1H),7.56(dd,J=8 .8,1.6Hz,1H),7.53–7.43(m,2H),7.42–7.36(m,1H),7.02(t,J=8.8Hz,1H),4.23(s,1H),2.26(s,6H)ppm; 13 CNMR(101MHz, CDCl3)δ156.9(d,J=248.5Hz),140.5(d,J=4.0Hz),139.9,133.3,132.7,129.6,128.5,127.8,12 7.6, 127.2 (d, J = 7.1Hz), 126.3, 126.1, 125.8, 125.4, 120.8 (d, J = 17.2Hz), 116.5 (d, J = 20.2Hz), 76.7, 44.6ppm; 19 F NMR(376MHz, CDCl3)δ-118.0(m,1F)ppm; IR(neat)ν2975,2862,1598,1494,1253,1023,828,745cm -1 .HRMS(ESI)m / z:[M+H] + calcdfor C 19 H 18 NFCl 314.1106; found:314.1106.

[0158]

[0159] 3qa, colorless oil, 41% yield. 1 H NMR (400MHz, CDCl3) δ7.86–7.76(m,4H),7.53–7.42(m,3H),7.21–7.11(m,2H),4.19(s,1H),2.24(s,6H)ppm; 13<13>C NMR (151 MHz, CDCl<3>) δ 151.2 (ddd, J=251.0, 9.1, 3.0 Hz), 140.1–139.8 (m), 139.2, 138.5 (dt, J=251.0, 15.1 Hz), 133.4, 132.9, 128.6, 127.8, 127.6, 126.6, 126.3, 126.0, 125.2, 111.4 (dd, J=18.1, 3.0 Hz), 76.6, 44.4 ppm; 19 <19>F NMR (376 MHz, CDCl<3>) δ -134.0 (dd, J=18.8, 7.5 Hz, 2F), -162.5 (m, 1F) ppm; IR (neat) ν 2953, 2865, 1617, 1524, 1345, 1030, 744, 701 cm -1 <-><1>. HRMS (EI) m / z: [M] + calcd for C 19 H 16 NF<3> 315.1224; found: 315.1229.

[0160]

[0161] 3ra, white solid, 73% yield, Mp 73-74°C. 1 <1>H NMR (400 MHz, CDCl<3>) δ 7.90 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.79 (d, J=8.0 Hz, 2H), 7.63 (d, J=8.4 Hz, 1H), 7.50–7.37 (m, 4H), 6.86 (d, J=8.4 Hz, 2H), 4.24 (s, 1H), 3.76 (s, 3H), 2.29 (s, 6H) ppm; 13 <13>C NMR (101 MHz, CDCl<3>) δ 158.4, 141.3, 135.3, 133.4, 132.5, 128.7, 128.2, 127.7, 127.5, 125.9, 125.7, 125.4, 113.7, 77.3, 55.1, 44.8 ppm (One carbon is missing because of overlapping); IR (neat) ν 2936, 1604, 1504, 1301, 1277, 1172, 1020, 820 cm -1 <-><1>. HRMS (ESI) m / z: [M+H] + calcd for C 20 H 22NO 292.1704; found: 292.1696.

[0162]

[0163] 3sa, colorless oil, 76% yield. 1 H NMR (400MHz, CDCl3) δ7.86(s,1H),7.81(d,J=8.0Hz,1H),7.77(d,J=8.4Hz,2H),7.61(d,J=8.4Hz,1H),7.47–7.39(m,2 H),7.07(s,1H),7.01(d,J=8.0Hz,1H),6.78(d,J=8.4Hz,1H),4.19(s,1H),3.88(s,3H),3.82(s,3H),2.26(s,6H)ppm; 13 C NMR (101MHz, CDCl3) δ149.0,147.9,141.1,135.9,133.5,132.6,128.2,127.8,127.5,126.0,125.9,125.7,125 .5,120.0,110.9,110.5,77.7,55.9,55.8,44.8ppm; IR(neat)ν2983,2817,1589,1510,1464,1230,1024,786cm -1 .HRMS(ESI)m / z:[M+H] + calcd forC 21 H 24 NO2 322.1802; found:322.1802.

[0164]

[0165] 3ta, white solid, 71% yield, Mp 114-115℃. 1 H NMR (400MHz, CDCl3) δ7.88(s,1H),7.84(d,J=8.0Hz,1H),7.80(d,J=8.4Hz,2H),7.61(d,J=8.4Hz,1H),7.51–7.40(m,2H ),7.11–7.04(m,1H),6.96(d,J=8.0Hz,1H),6.74(d,J=8.0Hz,1H),5.90(d,J=11.6Hz,2H),4.18(s,1H),2.28(s,6H)ppm; 13C NMR (101MHz, CDCl3) δ147.7,146.4,141.1,137.4,133.4,132.6,128.2,127.8,127.5,125.92,125.91,125.6, 125.5,120.9,108.0,107.8,100.8,77.7,44.7ppm;IR(neat)ν2975,2855,1599,1482,1436,1236,1022,774cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 20 H 20 NO2 306.1488; found:306.1489.

[0166]

[0167] 3ua, yellow oil, 83% yield. 1 H NMR(400MHz, CDCl3)δ7.90(s,1H),7.85(d,J=8.0Hz,1H),7.82–7.77(m,2H),7.66(d,J= 8.8Hz,1H),7.51–7.40(m,2H),7.17(s,2H),4.14(s,1H),3.67(s,3H),2.28(s,12H)ppm; 13 C NMR (101MHz, CDCl3) δ155.7,141.2,138.4,133.4,132.6,130.6,128.2,127.8,127.7,127.5,126.0,12 5.9,125.7,125.5,77.8,59.5,44.9,16.2ppm;IR(neat)ν2946,2859,1599,1481,1220,1011,907,732cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 22 H 26 NO320.2019; found: 320.2009.

[0168]

[0169] 3va, white solid, 93% yield, Mp 137-138℃. 11H NMR (400 MHz, CDCl3) δ 8.01 (s, 2H), 7.88 (d, J=8.0 Hz, 2H), 7.84–7.82 (m, 1H), 7.81 (t, J=4.0 Hz, 3H), 7.73 (dd, J=8.8, 1.2 Hz, 2H), 7.52–7.42 (m, 4H), 4.48 (s, 1H), 2.37 (s, 6H) ppm; 13 13C NMR (101 MHz, CDCl3) δ 140.7, 133.4, 132.7, 128.3, 127.8, 127.5, 126.3, 125.91, 125.85, 125.6, 78.1, 44.9 ppm; IR (neat) ν 2925, 2854, 1598, 1503, 1361, 1268, 834, 764 cm -1 -1. HRMS (ESI) m / z: [M+H] + + calcd for C 23 21H 22 19N 312.1750; found: 312.1747.

[0170]

[0171] 3wa, colorless solid, 76% yield, Mp 87-88 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.86–7.82 (m, 3H), 7.75 (dd, J=8.8, 1.6 Hz, 1H), 7.52 (t, J=6.4 Hz, 2H), 7.50–7.44 (m, 2H), 7.28–7.23 (m, 1H), 7.20 (td, J=7.6, 0.8 Hz, 1H), 6.72 (s, 1H), 4.63 (s, 1H), 2.36 (s, 6H) ppm; 13 13C NMR (101 MHz, CDCl3) δ 157.6, 154.9, 137.0, 133.2, 133.0, 128.2, 127.9, 127.6, 127.3, 126.2, 126.0, 125.9, 123.8, 122.6, 120.7, 111.4, 104.7, 70.4, 44.0 ppm (One carbon is missing because of overlapping); IR (neat) ν 2976, 2858, 1598, 1505, 1452, 1362, 1148, 739 cm -1 -1. HRMS (ESI) m / z: [M+H] + + calcd for C21 H 20 NO302.1547; found: 302.1539.

[0172]

[0173] 3xa, yellow oil, 51% yield. 1 H NMR (400MHz, CDCl3) δ7.88 (s, 1H), 7.85–7.80 (m, 3H), 7.67 (d, J = 8.4Hz, 1H), 7. 49–7.43(m,2H),7.39(s,1H),6.35–6.25(m,2H),4.49(s,1H),2.27(s,6H)ppm; 13 C NMR (101MHz, CDCl3) δ154.7,141.9,137.6,133.3,132.9,128.0,127.9,127.5,127.0,126.3,125. 9,125.8,110.0,107.9,69.8,43.9ppm;IR(neat)ν2946,2861,1598,1503,1457,1361,1011,733cm -1 .HRMS(EI)m / z:[M] + calcd for C 17 H 17 NO 251.1310; found: 251.1305.

[0174]

[0175] 3ya, yellow oil, 67% yield. 1 H NMR(400MHz, CDCl3)δ7.88(s,1H),7.86–7.80(m,3H),7.69(dd,J=8.4,1.6Hz,1H),7.52–7.43(m,2H),7.2 3(dd,J=5.2,1.2Hz,1H),7.01(d,J=3.6Hz,1H),6.91(dd,J=5.2,3.6Hz,1H),4.68(s,1H),2.31(s,6H)ppm; 13C NMR (101MHz, CDCl3) δ147.3,139.4,133.3,132.8,128.2,127.9,127.6,126.7,126.2,126.0,125. 9,125.8,125.1,124.9,72.5,44.2ppm;IR(neat)ν2947,2859,1599,1505,1454,1359,1017,695cm -1 .HRMS(EI)m / z:[M] + calcd for C 17 H 17 NS 267.1082; found: 267.1085.

[0176] Example 6

[0177] In this embodiment, 2n is used as the arylating agent, tetrahydrofuran as the solvent, and Pd(PPh3)4 as the additive. The deoxyarylation reaction of substrate 4 is catalyzed by Sm and SmI2 (reaction formula is as follows):

[0178]

[0179] The reaction was as follows: Under a nitrogen atmosphere, 4 (79.8 mg, 0.2 mmol) and 2n (102.0 mg, 0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product. The experimental results are shown below:

[0180]

[0181] 5. White solid, 62% yield, MPa 96-97℃. 1 H NMR (400MHz, CDCl3) δ7.50–7.34(m,4H),7.30–7.11(m,7H),7.05(d,J=7.6Hz,1H),6.85(t,J=7.6Hz,1H),6.63(d, J=9.6Hz,2H),6.32–6.20(m,1H),4.18(s,1H),3.73(s,3H),3.72(s,3H),3.66–3.10(m,4H),2.66–2.27(m,4H)ppm; 13CNMR(101MHz,CDCl3)δ160.9,160.8,160.72,160.70,148.9,145.00,144.96,14 2.0,139.8,134.0,132.1,132.0,130.6,128.98,128.95,128.44,128.42,128.1 ,127.9,127.82,127.80,127.0,125.3,122.6,105.8,105.7,98.6,98.5,76.22, 76.17,55.2,51.7ppm;IR(neat)ν2805,1594,1574,1452,1246,1149,1004,741cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 32 H 32 N3O2S 522.2208; found:522.2210.

[0182] Example 7

[0183] In this embodiment, 2a is used as the arylating agent, tetrahydrofuran as the solvent, and Pd(PPh3)4 as the additive. The deoxyarylation reaction of substrate 6 is catalyzed by Sm and SmI2 (reaction formula is as follows):

[0184]

[0185] The reaction was as follows: Under a nitrogen atmosphere, 6 (82.8 mg, 0.2 mmol) and 2a (102.0 mg, 0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product. The experimental results are shown below:

[0186]

[0187] 7. Orange solid, 90% yield, MPa 108-109℃ 1H NMR(400MHz, CDCl3)δ8.34(s,1H),7.81(s,1H),7.78–7.68(m,3H),7.59(d,J=8.4 Hz,1H),7.46(d,J=7.2Hz,2H),7.43–7.36(m,2H),7.34(d,J=7.6Hz,1H),7.23(t,J =7.2Hz,2H),7.17–7.04(m,4H),7.03–6.95(m,1H),4.42(s,1H),3.41–3.23(m,2H ),2.84–2.67(m,4H),2.61–2.42(m,2H),2.38–2.26(m,2H),2.12–2.02(m,2H)ppm; 13 C NMR(101MHz, CDCl3)157.51,157.48,146.4,142.7,142.6,140.40,140.39,139.44,139.40,1 39.38,137.68,137.65,137.1,133.3,132.5,132.4,132.1,130.8,128.8,128.3,128.1,127.8 ,127.64,127.63,127.4,126.8,126.4,126.3,125.8,125.4,121.9,75.89,75.86,53.5,31.7 ,31.3,31.11,31.09,30.9ppm;IR(neat)ν2897,1635,1585,1477,1437,1242,1173,813,731cm -1 .HRMS(ESI)m / z:[M+H] + calcd forC 36 H 32 N2Cl 527.2251; found:527.2249.

[0188] Example 8

[0189] In this embodiment, 2a is used as the arylating agent, tetrahydrofuran as the solvent, and Pd(PPh3)4 as the additive. The deoxyarylation reaction of substrate 8 is catalyzed by Sm and SmI2 (reaction formula is as follows):

[0190]

[0191] The reaction was as follows: Under a nitrogen atmosphere, 8 (49.4 mg, 0.2 mmol) and 2a (102.0 mg, 0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product. The experimental results are shown below:

[0192]

[0193] 11. Yellow oil, 51% yield. 1 H NMR (400MHz, CDCl3) δ7.84–7.73(m,4H),7.59(d,J=8.4Hz,1H),7.47–7.38(m,2H),7.01(s,1H),6.94(d,J=7.6Hz,1H) ,6.77(d,J=8.4Hz,1H),4.29(s,1H),4.22–4.17(m,4H),2.48–2.29(m,4H),1.64–1.56(m,4H),1.49–1.41(m,2H)ppm; 13 C NMR (101MHz, CDCl3) δ143.3,142.3,141.1,136.6,133.4,132.6,128.0,127.8,127.5,126.3,126.1,125.8,125.4,1 20.9,117.0,116.6,76.2,64.3,64.2,53.2,26.2,24.7ppm;IR(neat)ν2928,1589,1501,1361,1280,1106,811,734cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 24 H 26 NO2 360.1959; found:360.1958.

[0194] Example 9

[0195] In this embodiment, 2a is used as the arylating agent, tetrahydrofuran as the solvent, and Pd(PPh3)4 as the additive. The deoxyarylation reaction of substrate 9 is catalyzed by Sm and SmI2 (reaction formula is as follows):

[0196]

[0197] The reaction was as follows: Under a nitrogen atmosphere, 9 (61.4 mg, 0.2 mmol) and 2a (102.0 mg, 0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product. The experimental results are shown below:

[0198]

[0199] 12. Colorless oil, 75% yield. 1 H NMR (400MHz, CDCl3) δ6.95 (s, 1H), 6.84 (d, J = 7.6Hz, 1H), 6.70 (d, J = 8.0Hz, 1H), 6.67 (s, 2H), 5.91 (d, J = 8.0Hz, 2H), 4.3 1(s,1H),3.84(s,6H),3.80(s,3H),2.51(t,J=5.6Hz,4H),1.85–1.75(m,2H),1.69–1.63(m,4H),1.55–1.46(m,4H)ppm; 13 C NMR (101MHz, CDCl3) δ152.9,147.5,146.2,140.4,138.1,136.3,121.3,108.2,107.8,104.4,100.8,7 6.8,60.8,55.9,52.9,28.1,27.8,25.5ppm; IR(neat)ν2919,1589,1502,1417,1233,1123,1036,731cm -1 .HRMS(ESI)m / z:[M+H] + calcd for C 24 H 32 NO5414.2274; found: 414.2275.

[0200] Example 10

[0201] In this embodiment, 2a is used as the arylating agent, tetrahydrofuran as the solvent, and Pd(PPh3)4 as the additive. The deoxyarylation reaction of substrate 10 is catalyzed by Sm and SmI2 (reaction formula is as follows):

[0202]

[0203] The reaction was as follows: Under a nitrogen atmosphere, 10 (56.2 mg, 0.2 mmol) and 2a (102.0 mg, 0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product. The experimental results are shown below:

[0204]

[0205] 13, yellow oil, 59% yield. 1 H NMR (400MHz, CDCl3) δ8.16(d,J=6.0Hz,2H),7.78(d,J=8.4Hz,2H),7.66(d,J=7.2Hz,2H),7.59(d,J=8.0Hz,2H),7.53–7.37( m,7H),7.29(t,J=7.2Hz,1H),6.80(s,2H),4.31(s,1H),3.87(s,6H),3.78(s,3H),3.77–3.69(m,4H),2.56–2.38(m,4H)ppm; 13 CNMR(101MHz, CDCl3)δ153.2,141.0,140.2,140.1,140.0,138.8,136.7,136.6,133.8,128.9,128.4,127.6,127.1,127.0,126.0,125.8,123.4 ,123.2,120.2,119.9,119.6,110.0,109.9,104.4,77.1,67.2,60.7,56.1,52.8ppm;IR(neat)ν2952,2832,1589,1489,1453,1229,1117,746cm -1 .HRMS(ESI)m / z:[M+Na] + calcd for C 38 H 36 N2O4Na607.2577; found:607.2567.

[0206] Example 11

[0207] In this embodiment, 2a is used as the arylating agent, tetrahydrofuran as the solvent, and Pd(PPh3)4 as the additive. The deoxyarylation reaction of substrate 1 is catalyzed by Sm and SmI2 (reaction formula is as follows):

[0208]

[0209] The reaction was as follows: Under a nitrogen atmosphere, 1 (xx mg, 0.2 mmol) and 2a (102.0 mg, 0.4 mmol) were added to separate sealed tubes, followed by the addition of Pd(PPh3)4 (11.6 mg, 5 mmol%), Sm (60.0 mg, 0.4 mmol), and SmI2 (4.4 mL, 0.44 mmol). After stirring at 80 °C for 18 hours, the reaction was quenched with saturated sodium bicarbonate (8 mL), extracted with ethyl acetate (3 × 10 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography using alkaline alumina as the packing material to obtain the deoxyarylated product. The experimental results are shown below:

[0210]

[0211] 14. Yellow oil, 74% yield. 1 H NMR (400MHz, CDCl3) δ7.37–7.28(m,6H),7.27–7.21(m,6H),7.20–7.15(m,1H),4.20(s,1H),3.48(s,2H),2.63–2.20(m,8H),1.29(s,9H)ppm; 13 CNMR(101MHz,CDCl3)δ149.8,142.2,141.4,134.8,132.4,129.2,128.9,12 8.54,128.48,127.9,127.0,125.0,75.4,62.6,53.2,51.8,34.4,31.4ppm.

[0212]

[0213] 15. Yellow oil, 73% yield. 1 H NMR (400MHz, CDCl3) δ7.38–7.28(m,4H),7.27–7.19(m,4H),7.19–7.12(m,2H),7 .12–6.98(m,3H),4.20(s,1H),3.47(s,2H),2.99–2.32(m,8H),2.31(s,3H)ppm; 13C NMR (101MHz, CDCl3) δ142.1,141.3,137.7,137.6,132.4,130.0,129.2,128.54, 128.48,128.0,127.81,127.75,127.0,126.4,75.4,63.0,53.2,51.7,21.4ppm.

[0214]

[0215] 16. White solid, 80% yield. 1 H NMR (400MHz, CDCl3) δ7.43–7.37(m,4H),7.34(d,J=7.6Hz,2H),7.31–7.21(m,6H),7.21–7.18(m,1H),7.17–7.11(m, 2H),6.49(d,J=15.6Hz,1H),6.26(dt,J=15.6,6.8Hz,1H),4.23(s,1H),3.15(d,J=6.4Hz,2H),2.70–2.25(m,8H)ppm; 13 C NMR (101MHz, CDCl3) δ142.7,136.9,132.9,128.5,128.4,127.9,127.4,126.8,126.5,126.2,76.1,61.0,53.4,51.8ppm.

[0216] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A method for preparing an α-substituted amine compound, characterized in that, The method includes the following steps: A mixture of divalent samarium salt, elemental metal, and metal additives was used to promote the deoxyfunctionalization reaction between amide compound 1 and reactant 2, yielding α-substituted amine compound 3. Among them, FG-LG is FG-BPin; FG is selected from: substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-membered heteroaryl; wherein the substitution refers to being substituted by one or more substituents selected from the group consisting of: C 1-4 Alkyl, C 2-4 alkenyl, C 1-4 Alkoxy, halogen, C 1-4 Halogenated alkyl groups, -NR 6 R 7 -SiR 8 R 9 R 10 -O(C 3-6 cycloalkyl), -S(C 1-4 Alkyl), 5-membered heteroaryl, phenyl, naphthyl; R 8 R 9 R 10 C 1-4 Alkyl; R 6 R 7 It is a phenyl group; wherein the heteroaryl group is selected from: furanyl or thiophene; R 1 Selected from the group consisting of: substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, and substituted or unsubstituted 5-9 membered heteroaryl groups, wherein the heteroaryl group is selected from: furanyl, benzofuranyl, and thiopheneyl; R 1 Substitution refers to the substitution of a carbon atom by one or more substituents selected from the group consisting of methyl, chlorine, fluorine, trifluoromethyl, methoxy, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, ethoxy, propoxy, bromine; or the adjacent substituents form a 5-7 membered heterocycle with the two carbon atoms attached to it, the heterocycle having one or two oxygen atoms. R 2 R 3 Each is independently either substituted or unsubstituted C 1-4 Alkyl; the substitution refers to substitution by one or more substituents selected from the group consisting of: C 1-4 Alkoxy; Or R 2 R 3 Together with the connected N, they form substituted or unsubstituted 5-12-membered heterocycles, which are monocyclic, fused, or bridged rings, except with R. 2 R 3 The linked N, the heterocycle optionally having one or two heteroatoms selected from O or N; substitution on the heterocycle refers to substitution by one or more substituents selected from the group consisting of: C 1-4 alkyl; The divalent samarium salt is SmI2, SmBr2, or SmCl2; The metallic element is Sm; The metal additives are selected from the group consisting of: Rh2(OAc)4, Rh2(OCt)4, NiI2, Ni(COD)2 / PPh3, Ni(COD)2, CuI, Pd(PPh3)4, Pd2(dba)3 / Xantphos, and Pd2(dba)3 / PPh3. The amount of the metal additive is 0.001 mol% to 500 mol% of the amount of the amide compound. The amount of the divalent samarium salt is 0.001 mol% to 500 mol% of the amount of the amide compound. The amount of the elemental metal used is 0.001 mol% to 500 mol% of the amount of the amide compound used. The reaction is carried out in an organic solvent selected from: tetrahydrofuran, methanol, toluene, acetonitrile, carbon tetrachloride, chloroform, 1,4-dioxane, 1,2-dichloroethane, ethylene glycol dimethyl ether, dimethyl sulfoxide, N,N-dimethylformamide, and N-methylpyrrolidone. The reaction temperature is 70-90 ℃.

2. The preparation method according to claim 1, characterized in that, R 1 Selected from the following group: substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl; R 1 Substitution refers to substitution by one or more substituents selected from the group consisting of: methyl, chlorine, fluorine, trifluoromethyl, methoxy, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, ethoxy, propoxy, and bromine.

3. The preparation method according to claim 1, characterized in that, R 2 R 3 Together with the connected N, they form substituted or unsubstituted 5-membered heterocycles.

4. The preparation method according to claim 1, characterized in that, FG is selected from: phenyl, naphthyl.

5. The preparation method according to claim 1, characterized in that, The divalent samarium salt is SmI2.

6. The preparation method according to claim 1, characterized in that, The amount of the metal additive is 10 mol%-50 mol% of the amount of the amide compound.

7. The preparation method according to claim 1, characterized in that, The amount of the divalent samarium salt is 200 mol% - 300 mol% of the amount of the amide compound.

8. The preparation method according to claim 1, characterized in that, The amount of the elemental metal used is 200 mol% to 300 mol% of the amount of the amide compound used.

9. The preparation method according to claim 1, characterized in that, The organic solvent is selected from: tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, and N-methylpyrrolidone.

10. The preparation method according to claim 1, characterized in that, The metal additives are selected from the following group: NiI2, Ni(COD)2 / PPh3, Pd(PPh3)4, Pd2(dba)3 / Xantphos, Pd2(dba)3 / PPh3.

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