A photocatalytic benzylic C(sp) 3 Methods and applications of )-Cl bond functionalization

Abstract

The application provides a method for photocatalytic functionalization of C(sp 3 )‑Cl bond at the benzyl position and application thereof. The method comprises the following steps: adding a photocatalyst, a benzyl chloride compound and a functionalization reagent into a solvent, and then adding or not adding a base to obtain solution A; irradiating solution A with light under an inert atmosphere to obtain a functionalization product at the benzyl position; wherein the photocatalyst is selected from copper-n-heterocyclic carbene complexes; the functionalization comprises trifluoromethylation, cyanation or amination. The method can be carried out under normal temperature and pressure in an inert atmosphere, and uses a cheap transition metal copper-n-heterocyclic carbene complex as a catalyst, and cooperates with a functionalization reagent to capture the chlorine atom of the C(sp 3 )‑Cl bond at the benzyl position of the benzyl chloride compound under light irradiation to obtain a benzyl radical, the benzyl radical is captured by the copper-n-heterocyclic carbene complex, and the benzyl radical is reduced and eliminated to obtain the functionalization product at the benzyl position. The reaction has the advantages of mild conditions, no need of additional precursors or reducing agents, wide application range of substrates and high reaction efficiency.

Description

Technical Field

[0001] This invention belongs to the field of photocatalysis technology, specifically comprising a photocatalytic benzylic C(sp) site. 3 Methods and applications of functionalization of )-Cl bonds. Background Technology

[0002] Photocatalytic organic synthesis boasts advantages such as being green, clean, efficient, and energy-saving. Typically, photocatalysis is coupled with transition metal complex catalysis or small molecule catalysis to precisely activate chemical bonds and efficiently synthesize target molecules (Nat. Rev. Chem. 2017, 1, 2397-3358). Compared to traditional photocatalysis and transition metal synergistic photocatalysis, single transition metal complex photocatalysis offers significant advantages. In single transition metal complex photocatalysis, the photoresponsive transition metal complex synergistically interacts with the substrate, lowering the threshold for substrate photo-redox and activating inert chemical bonds (ACS Catal. 2020, 10, 9170-9196). Therefore, the development of novel photocatalysts integrating photosensitizer and catalyst functions has attracted widespread attention.

[0003] Copper complexes, as photocatalysts, possess advantages such as tunable excited-state redox capabilities, flexible ligand environments, allowing for stereoinduction during reactions, the ability to transform into multiple oxidation states, rapid free radical capture, and strong reductive elimination capabilities (Chem. Rev. 2022, 122, 16365-16609). The selection of strong-field ligands can significantly enhance the excited-state performance of copper complexes (Science 2019, 363, 484–488). Nitrogen heterocyclic carbenes, with their strong σ-electron-donating ability and relatively weak π-electron-accepting ability, endow copper-nitrogen heterocyclic carbene complexes with abundant electronic effects and excellent photophysical properties, enabling them to exhibit superior catalytic activity in photocatalytic organic reactions and achieving the functionalization of inert chemical bonds (Appl OrganometChem. 2022, e6746). Benzyl chlorides, compared to bromides and iodides, are readily available, have low toxicity, and are inexpensive. They are also multifunctional intermediates in organic synthesis and ideal alkyl reagents. However, the low reduction potential of benzyl chlorides makes their direct activation and functionalization under mild conditions challenging. Introducing trifluoromethyl groups into organic compounds can effectively control molecular polarity, dipole moment, stability, and lipophilicity. Therefore, trifluoromethyl-containing organic compounds have significant applications in pharmaceuticals, pesticides, and functional materials. For copper-catalyzed trifluoromethylation of benzyl chloride, the system requires excess base and heating, and the functional groups exhibit poor tolerance (Org. Biomol. Chem. 2014, 12, 5594–5596). Phenylacetonitrile is an important building block of many natural products and bioactive substances, and these compounds can be further converted into high-value-added products; therefore, cyanation reactions have always been a focus of attention in organic synthesis. The copper-catalyzed cyanidation of benzyl chloride requires a high temperature of 180°C, and these stringent conditions limit the substrate range (Tetrahedron Lett. 2012, 53, 2825–2827). Currently, although copper photocatalyzed C(sp) cyanidation of chloramides... 3 The )-Cl bond amination reaction, but the introduction of the amide increases the C(sp) bond. 3 The reduction potential of the β-Cl bond facilitates the reaction (J. Am. Chem. Soc. 2022, 144, 4550-4558). Benzyl C(sp) 3 The catalytic activation of the )-Cl bond to construct the CN bond still faces insurmountable barriers.

[0004] Therefore, a strategy for copper-catalyzed activation of benzyl chloride without additional additives and under mild conditions is urgently needed. Summary of the Invention

[0005] In view of the above-mentioned problems existing in the prior art, the first object of the present invention is to provide a photocatalytic benzylic C(sp) 3A method for functionalizing the )-Cl bond. This method can be carried out in an inert atmosphere at room temperature and pressure, using inexpensive transition metal copper-nitrogen heterocyclic carbene complexes as catalysts, and in conjunction with functionalizing reagents (trifluoromethyl reagents, cyano reagents, or amine reagents), under ultraviolet to visible light irradiation to functionalize the benzyl C(sp) bond of benzyl chloride compounds. 3 The activation of the )-Cl bond yields benzylic functionalized products, which have the advantages of mild reaction conditions, no need for additional precursors or external reducing agents, wide substrate applicability, and high reaction efficiency.

[0006] Another object of the present invention is to provide a method for catalyzing benzylic C(sp) using the method described above. 3 Applications of )-Cl bonds in the preparation of functionalized products.

[0007] To achieve the first objective mentioned above, the technical solution adopted by this invention includes:

[0008] This invention discloses a photocatalytic benzylic C(sp) 3 The method for functionalizing the )-Cl bond includes the following steps:

[0009] A solution A is obtained by adding a photocatalyst, a benzyl chloride compound, and a functionalizing agent to a solvent, and then adding or not adding an alkali.

[0010] Under an inert atmosphere, solution A was irradiated with light to obtain a benzylic functionalized product;

[0011] The photocatalyst is selected from copper-nitrogen heterocyclic carbene complexes;

[0012] The functionalization includes trifluoromethylation, cyanation, or amination.

[0013] This invention reports for the first time a photocatalytic method for benzylic C(sp) sites using a copper-nitrogen heterocyclic carbene complex. 3 The method of functionalizing the β-Cl bond involves using inexpensive transition metal copper-nitrogen heterocyclic carbene complexes as catalysts in an inert atmosphere at room temperature and pressure, along with functionalizing reagents (trifluoromethyl reagents, cyano reagents, or amine reagents), and then irradiating with ultraviolet to visible light to functionalize the benzyl C(sp) bond of benzyl chloride compounds. 3 The activation of the )-Cl bond yields benzylic functionalized products, which have the advantages of mild reaction conditions, no need for additional precursors or external reducing agents, wide substrate applicability, and high reaction efficiency.

[0014] The synthetic process involved in the reaction is as follows: Under light irradiation, the active photocatalyst generated in situ from the copper-nitrogen heterocyclic carbene complex and the functional reagent is photoexcited to an excited state. The benzyl chloride compound is then subjected to a chlorine atom capture by the excited-state copper-nitrogen heterocyclic carbene active photocatalyst, generating a Bn radical and producing a divalent copper-nitrogen heterocyclic carbene complex. The divalent copper-nitrogen heterocyclic carbene complex undergoes ligand-to-metal charge transfer, the free radical is captured and then combines with the Bn radical, undergoing a reductive elimination process to yield the benzyl (sp) group. 3 The )-Cl bond is functionalized into the product and the catalytic cycle is completed.

[0015] Furthermore, in the trifluoromethylation, cyanation, or amination reactions, the photocatalysts used can all be copper-nitrogen heterocyclic carbene complexes, which include one or more of Cu(IPr)I, Cu(SIPr)I, Cu(CAAC)I, Cu(IPr)Br, Cu(IPr)Cl, Cu(IPr)Br2, Cu(IPr)Cl2, Cu(IPr)F2, Cu(IPr)OAc, Cu(IPr)(OAc)2, Cu(IPr)CN, Cu(IPr)SCN, Cu(IPr)OTf, and Cu(IPr)SO4; preferably, the copper-nitrogen heterocyclic carbene complex is selected from Cu(IPr)I. These copper-nitrogen heterocyclic carbene complexes are usually prepared on demand. The preparation method is as follows: under stirring conditions, copper salt and nitrogen heterocyclic carbene ligand are fed in a molar ratio of 1:1, a small amount of THF is added for dispersion, and after stirring for 30 min, the solution is dried to obtain the target copper-nitrogen heterocyclic carbene complex. Subsequently, the solvent, benzyl chloride compound, functionalizing reagent and base used for the functionalization reaction can be added to carry out the reaction.

[0016] Furthermore, the molar concentration of the copper-nitrogen heterocyclic carbene complex in solution A is between zero and the saturation molar concentration, but does not include zero; preferably, the molar concentration of the copper-nitrogen heterocyclic carbene complex in solution A is 1 × 10⁻⁶. -3 M~1×10 -2 M.

[0017] In this invention, the functionalizing reagents and solvents used differ for different reaction types, as further explained below:

[0018] When photocatalysis is performed at the benzylic C(sp) site 3 During the trifluoromethylation reaction of the )-Cl bond, no base is required in the reaction; the functionalizing reagents selected include, but are not limited to, one or more of CF3SO2Na, CF3SO3Na, CF3CO2Na and TMSCF3.

[0019] Furthermore, the molar concentration of the functionalizing agent (trifluoromethyl reagent) in solution A is between zero and the saturation molar concentration, excluding zero; preferably, the molar concentration of the functionalizing agent in solution A is 0.1M to 0.3M.

[0020] Furthermore, the solvent in this invention is merely to provide a solution environment for the substrate; those skilled in the art are capable of selecting suitable solvents, and this invention does not limit this selection. For example, when performing photocatalytic benzylic C(sp...)... 3 When performing trifluoromethylation of the )-Cl bond, the solvents used include, but are not limited to, one or more of N,N-dimethylformamide, tetrahydrofuran, acetone, N,N-dimethylacetamide, dimethyl adipate, acetonitrile, dichloroethane, dichloromethane, benzene, and toluene.

[0021] Furthermore, when N,N-dimethylformamide is used as the solvent, the molar ratio of benzyl chloride compound to functionalizing reagent is 1:0.33-3.

[0022] When photocatalysis is performed at the benzylic C(sp) site 3 During the cyanation reaction of the )-Cl bond, no base is required in the reaction; the functionalizing reagents include, but are not limited to, TMSCN and / or TBACN.

[0023] Furthermore, the molar concentration of the functionalizing reagent (cyano reagent) in solution A is between zero and the saturation molar concentration, excluding zero; preferably, the molar concentration of the functionalizing reagent in solution A is 0.1M to 0.3M.

[0024] Furthermore, the solvent in this invention is merely to provide a solution environment for the substrate; those skilled in the art are capable of selecting suitable solvents, and this invention does not limit this selection. For example, when performing photocatalytic benzylic C(sp...)... 3 During the cyanation reaction of the )-Cl bond, the solvent includes, but is not limited to, one or more of tetrahydrofuran, acetone, N,N-dimethylformamide, dimethyl adipate, acetonitrile, dichloroethane, benzene, toluene, dimethyl sulfoxide, dichloromethane, diethyl ether, 1,4-dioxane, n-hexane, cyclohexane, and methylcyclohexane.

[0025] Furthermore, when the solvent used is tetrahydrofuran or acetonitrile, the molar ratio of benzyl chloride compound to functionalizing reagent is 1:0.33 to 3.

[0026] When photocatalysis is performed at the benzylic C(sp) site 3 During the amination reaction of the )-Cl bond, a base should be added to the reaction; the functionalizing reagents include, but are not limited to, one or more of morpholine, piperidine and carbazole.

[0027] Furthermore, the molar concentration of the functionalizing reagent (amine reagent) in solution A is between zero and the saturation molar concentration, and does not include zero; preferably, the molar concentration of the functionalizing reagent in solution A is 0.1M to 0.3M.

[0028] Furthermore, the base includes, but is not limited to, potassium tert-butoxide and / or sodium tert-butoxide.

[0029] Furthermore, the molar concentration of the alkali in solution A is between zero and the saturation molar concentration, excluding zero; preferably, the molar concentration of the alkali in solution A is 0.1M to 0.3M.

[0030] Furthermore, the solvent in this invention is merely to provide a solution environment for the substrate; those skilled in the art are capable of selecting suitable solvents, and this invention does not limit this selection. For example, when performing photocatalytic benzylic C(sp...)... 3 During the )-Cl bond amination reaction, the solvent includes, but is not limited to, one or more of N,N-dimethylacetamide, N,N-dimethylformamide, acetonitrile, tetrahydrofuran, acetone and dichloromethane.

[0031] Furthermore, when the solvent used is N,N-dimethylacetamide, the molar ratio of benzyl chloride compound to functionalizing reagent is 1:0.33-3.

[0032] Furthermore, when the solvent used is N,N-dimethylacetamide, the molar ratio of the functionalizing agent to the base is 1:1.

[0033] Furthermore, for trifluoromethylation, cyanation, or amination reactions, the substrate benzyl chloride compound can be selected from one of the following structures:

[0034]

[0035] In Formula I, R1 represents one of H, CH3, CN, COOCH2CH3, COOC(CH3)3, and CF3.

[0036] R2 represents one of H, CH3, OCH3, and CF3;

[0037] R3 represents one of H, CH3, OCH3, CH=CH2, Ph, F, Cl, CN, COOCH3, COOCH2CH3, COOC(CH3)3, and CF3;

[0038] R4 represents H or OCH3.

[0039] Furthermore, when selecting groups R1 to R4, at least two groups represent H; for example, R1, R2, R3, and R4 are independently H; or R1 is CH3, and R2, R3, and R4 are independently H; or R2 is CH3, and R1, R3, and R4 are independently H; or R3 is CH3, and R1, R2, and R4 are independently H; or R3 is CH=CH2, and R1, R2, and R4 are independently H; or R3 is Ph, and R1, R2, and R4 are independently H; or R3 is OCH3, and R1, R2, and R4 are independently H; or R2 and R4 are independently OCH3, and R1 and R3 are independently H; or R3 is Cl, and R1, R2, and R4 are independently H; or R1 is CN, and R1, R2, and R4 are independently H. H; or R3 is CN, and R1, R2, and R4 are independently H; or R3 is COOCH3, and R1, R2, and R4 are independently H; or R1 is COOCH2CH3, and R1, R2, and R4 are independently H; or R3 is COOCH2CH3, and R1, R2, and R4 are independently H; or R1 is COOC(CH3)3, and R1, R2, and R4 are independently H; or R3 is COOC(CH3)3, and R1, R2, and R4 are independently H; or R1 is CF3, and R2, R3, and R4 are independently H; or R2 is CF3, and R1, R3, and R4 are independently H; or R3 is CF3, and R1, R2, and R4 are independently H; or R3 is F, and R1, R2, and R4 are independently H.

[0040] Furthermore, the molar concentration of the benzyl chloride compound in solution A is between zero and the saturation molar concentration, excluding zero; preferably, the molar concentration of the benzyl chloride compound in solution A is 0.1M to 0.3M.

[0041] Furthermore, in the trifluoromethylation, cyanation, or amination reactions, the light is selected from ultraviolet to visible light;

[0042] Furthermore, the light source is selected from LED lights.

[0043] Furthermore, the irradiation wavelength of the LED lamp is 360-460nm; the irradiation time is 18h-24h.

[0044] Furthermore, the inert atmosphere includes, but is not limited to, a nitrogen atmosphere or an argon atmosphere.

[0045] To achieve the second objective mentioned above, the technical solution adopted by the present invention includes:

[0046] This invention discloses a method for catalytically catalyzing C(sp) at the benzylic position using the method described above. 3 Applications of )-Cl bond in the preparation of trifluoromethylated products.

[0047] This invention discloses a method for catalytically catalyzing C(sp) at the benzylic position using the method described above. 3 Applications of )-Cl bond in the preparation of cyanide products.

[0048] This invention discloses a method for catalytically catalyzing C(sp) at the benzylic position using the method described above. 3 Applications of )-Cl bond in the preparation of amination products.

[0049] Beneficial effects of this invention:

[0050] This invention uses inexpensive transition metal copper-nitrogen heterocyclic carbene complexes as catalysts, combined with functionalizing agents, to extract the benzyl C(sp) site of benzyl chloride compounds under ultraviolet-visible light irradiation. 3 The chlorine atom in the )-Cl bond yields a benzyl radical, which is then captured by a copper-nitrogen heterocyclic carbene complex and reductively eliminated to obtain the benzyl-functionalized product. Compared to existing preparation methods, this method has the following advantages:

[0051] 1. This invention is the first to report a photocatalytic benzylic C(sp) group using a copper-nitrogen heterocyclic carbene complex. 3 The method of functionalizing the )-Cl bond (trifluoromethylation, cyanation or amination) demonstrates the potential application of this method in the photocatalysis of single inexpensive metal complexes to achieve the activation and functionalization of inert bonds.

[0052] 2. This invention proposes a photocatalytic method using copper-nitrogen heterocyclic carbene complexes to generate Bn radicals from benzyl chloride compounds. These Bn radicals are then captured by the divalent copper-nitrogen heterocyclic carbene complexes, and the product is generated through a reductive elimination process. This provides a universal method for achieving benzyl C(sp) oxidation without the need for precursors or external reducing agents. 3 Methods for functionalizing )-Cl bonds.

[0053] 3. The method provided by this invention can be achieved by light irradiation at room temperature, without requiring harsh reaction conditions such as high temperature and pressure, additional precursors, or external reducing agents. The entire reaction process is green, efficient, and the reaction conditions are very mild.

[0054] 4. The method of the present invention is applicable to the functionalization reactions of many benzyl chloride compounds, has a wide range of applicable substrates, and has high reaction efficiency. Attached Figure Description

[0055] Figure 1 Photocatalytic benzylic C(sp) site of copper-nitrogen heterocyclic carbene complex 3 The reaction process of trifluoromethylation of the )-Cl bond;

[0056] Figure 2 Photocatalytic benzylic C(sp) site of copper-nitrogen heterocyclic carbene complex 3 The reaction process of cyanidation of the )-Cl bond;

[0057] Figure 3 2-(2,2,2-trifluoroethyl)-toluene prepared in Example 1 1 H NMR spectrum;

[0058] Figure 4 2-(2,2,2-trifluoroethyl)-toluene prepared in Example 1 13 C NMR spectrum;

[0059] Figure 5 2-(2,2,2-trifluoroethyl)-toluene prepared in Example 1 19 F NMR spectrum;

[0060] Figure 6 1-(2,2,2-trifluoroethyl)-3,5-dimethoxybenzene prepared in Example 6 1 H NMR spectrum;

[0061] Figure 7 1-(2,2,2-trifluoroethyl)-3,5-dimethoxybenzene prepared in Example 6 13 C NMR spectrum;

[0062] Figure 8 1-(2,2,2-trifluoroethyl)-3,5-dimethoxybenzene prepared in Example 6 19 F NMR spectrum;

[0063] Figure 9 4-(2,2,2-trifluoroethyl)-benzonitrile prepared in Example 8 1 H NMR spectrum;

[0064] Figure 10 4-(2,2,2-trifluoroethyl)-benzonitrile prepared in Example 8 13 C NMR spectrum;

[0065] Figure 11 4-(2,2,2-trifluoroethyl)-benzonitrile prepared in Example 8 19 F NMR spectrum;

[0066] Figure 12 Ethyl 3-(2,2,2-trifluoroethyl)-benzoate prepared in Example 10 1 H NMR spectrum;

[0067] Figure 13 Ethyl 3-(2,2,2-trifluoroethyl)-benzoate prepared in Example 10 13 C NMR spectrum;

[0068] Figure 14 Ethyl 3-(2,2,2-trifluoroethyl)-benzoate prepared in Example 1019 F NMR spectrum;

[0069] Figure 15 4-(2,2,2-trifluoroethyl)-chlorobenzene prepared in Example 14 1 H NMR spectrum;

[0070] Figure 16 4-(2,2,2-trifluoroethyl)-chlorobenzene prepared in Example 14 13 C NMR spectrum;

[0071] Figure 17 4-(2,2,2-trifluoroethyl)-chlorobenzene prepared in Example 14 19 F NMR spectrum;

[0072] Figure 18 4-Trifluoromethylphenylacetonitrile prepared in Example 30 1 H NMR spectrum;

[0073] Figure 19 4-Trifluoromethylphenylacetonitrile prepared in Example 30 13 C NMR spectrum;

[0074] Figure 20 4-Trifluoromethylphenylacetonitrile prepared in Example 30 19 F NMR spectrum;

[0075] Figure 21 4-Fluorophenylacetonitrile prepared in Example 33 1 H NMR spectrum;

[0076] Figure 22 4-Fluorophenylacetonitrile prepared in Example 33 13 C NMR spectrum;

[0077] Figure 23 4-Fluorophenylacetonitrile prepared in Example 33 19 F NMR spectrum;

[0078] Figure 24 4,4'-Diphenylacetonitrile prepared in Example 38 1 H NMR spectrum;

[0079] Figure 25 4,4'-Diphenylacetonitrile prepared in Example 38 13 C NMR spectrum;

[0080] Figure 26 4,4'-Diphenylacetonitrile prepared in Example 38 19 F NMR spectrum. Detailed Implementation

[0081] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and accompanying drawings, further clarifies the invention. It should be understood that the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0082] Preparation Example

[0083] The catalyst Cu(IPr)I used in the examples is usually prepared on demand. Its preparation method is as follows: under stirring conditions, CuI and IPr are fed in a molar ratio of 1:1, a small amount of THF is added for dispersion, and after stirring for 30 min, the solution is dried to obtain Cu(IPr)I; other catalysts can be prepared by referring to this method.

[0084] Example 1

[0085]

[0086] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R1 being CH3, and R2, R3, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at 385 ± 5 nm under an LED for 18 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 2-(2,2,2-trifluoroethyl)toluene, with a yield of 47%.

[0087] 1 H NMR (400MHz, CDCl3) δ7.27–7.17 (m, 4H), 3.40 (q, J = 10.8Hz, 2H), 2.36 (s, 3H).

[0088] HRMS(EI)m / z Calcd for C9H9F3[M] + :174.0656,found:174.0648.

[0089] Example 2

[0090]

[0091] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 being CH3, and R1, R3, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 3-(2,2,2-trifluoroethyl)toluene, with a yield of 82%.

[0092] 1 H NMR (400MHz, CDCl3) δ7.24(t,J=7.4Hz,1H),7.15(d,J=7.7Hz,1H),7.12–7.06(m,2H),3.32(q,J=10.9Hz,2H),2.35(s,3H).

[0093] HRMS(EI)m / z Calcd for C9H9F3[M] + :174.0656,found:174.0648.

[0094] Example 3

[0095]

[0096] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being CH3, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-(2,2,2-trifluoroethyl)toluene, with a yield of 66%.

[0097] 1 H NMR (400MHz, CDCl3) δ7.22–7.11 (m, 4H), 3.32 (q, J = 10.9Hz, 2H), 2.35 (s, 3H).

[0098] HRMS(EI)m / z Calcd for C9H9F3[M] + :174.0656,found:174.0647.

[0099] Example 4

[0100]

[0101] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being Ph, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-(2,2,2-trifluoroethyl)-1,1'-biphenyl, with a yield of 33%.

[0102] 1 H NMR (400MHz, CDCl3) δ7.58(d,J=7.6Hz,4H),7.44(t,J=7.4Hz,2H),7.36(d,J=7.7Hz,4H),3.40(q,J=10.8Hz,2H).

[0103] HRMS(EI)m / z Calcd for C 14 H 11 F3[M] + :236.0813,found:236.0808.

[0104] Example 5

[0105]

[0106] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 is OCH3, and R1, R2, and R4 are H, respectively), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-(2,2,2-trifluoroethyl)-anisole, with a yield of 52%.

[0107] 1 H NMR (400MHz, CDCl3) δ7.23–7.16(m,2H),6.92–6.82(m,2H),3.79(s,3H),3.29(q,J=10.9Hz,2H).

[0108] HRMS(EI)m / z Calcd for C9H9F3O[M] + :190.0605,found:190.0618.

[0109] Example 6

[0110]

[0111] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 and R4 are OCH3, and R1 and R3 are H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 1,3-dimethoxy-5-(2,2,2-trifluoroethyl)-benzene, with a yield of 58%.

[0112] 1 H NMR (600MHz, CDCl3) 6.47 (s, 1H), 3.80 (s, 3H), 3.31 (q, J = 10.8Hz, 1H).

[0113] HRMS(EI)m / z Calcd for C 10 H 11 F3O2[M] + :220.0711,found:220.0703.

[0114] Example 7

[0115]

[0116] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 being CN, and R1, R3, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The reaction was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 3-(2,2,2-trifluoroethyl)-benzonitrile, with a yield of 67%.

[0117] 1 H NMR (400MHz, CDCl3) δ7.66(dt,J=7.5,1.5Hz,1H),7.61(s,1H),7.56(d,J=7.9Hz,1H),7.50(t,J=7.7Hz,1H),3.42(q,J=10.5Hz,2H).

[0118] HRMS(EI)m / z Calcd for C9H6F3N[M] +:185.0452,found:185.0482.

[0119] Example 8

[0120]

[0121] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being CN, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-(2,2,2-trifluoroethyl)-benzonitrile, with a yield of 74%.

[0122] 1 H NMR (400MHz, CDCl3) δδ7.69–7.64 (m, 2H), 7.43 (d, J = 8.0Hz, 2H), 3.45 (q, J = 10.5Hz, 2H).

[0123] HRMS(EI)m / z Calcd for C9H6F3N[M] + :185.0452,found:185.0445.

[0124] Example 9

[0125]

[0126] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being COOCH3, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as methyl 4-(2,2,2-trifluoroethyl)benzoate, with a yield of 61%.

[0127] 1 H NMR (400MHz, CDCl3) δ8.06–8.01(m,2H),7.38(d,J=8.1Hz,3H),3.92(s,3H),3.43(q,J=10.7Hz,2H).

[0128] HRMS(EI)m / z Calcd for C 10H9F3O2[M] + :218.0555,found:218.0548.

[0129] Example 10

[0130]

[0131] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 is COOCH2CH3, and R1, R3, and R4 are H, respectively), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as ethyl 3-(2,2,2-trifluoroethyl)benzoate, with a yield of 71%.

[0132] 1 H NMR (400MHz, CDCl3) δ8.03(dt,J=7.5,1.6Hz,1H),7.99(s,1H),7.49(d,J=7.6Hz,1H),7. 44(t,J=7.6Hz,1H), 4.39(q,J=7.1Hz,2H), 3.42(q,J=10.7Hz,2H), 1.40(t,J=7.1Hz,3H).

[0133] HRMS(EI)m / z Calcd for C 11 H 11 F3O2[M] + :232.0711,found:232.0706.

[0134] Example 11

[0135]

[0136] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 is COOCH2CH3, and R1, R2, and R4 are H, respectively), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as ethyl 4-(2,2,2-trifluoroethyl)benzoate, with a yield of 66%.

[0137] 1H NMR (600MHz, CDCl3) δ8.05–8.02(m,2H),7.37(d,J=8.0Hz,2H),4.38(q,J=7.1Hz,2H),3.42(q,J=10.7Hz,2H),1.39(t,J=7.1Hz,3H).

[0138] HRMS(ESI)m / z Calcd for C 11 H 12 F3O2[M+H] + :233.0784,found:233.0782.

[0139] Example 12

[0140]

[0141] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 is COO(CH3)3, and R1, R3, and R4 are H, respectively), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The reaction was carried out at room temperature under an LED at 385 ± 5 nm for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as tert-butyl 3-(2,2,2-trifluoroethyl)benzoate, with a yield of 53%.

[0142] 1 H NMR (600MHz, CDCl3) δ7.97(dt,J=7.7,1.5Hz,1H),7.93(s,1H),7.46(d,J=7.7Hz,1H),7.41(td,J=7.7,1.3Hz,1H),3.41(q,J=10.8Hz,2H),1.60(s,9H).

[0143] 13 C NMR (101MHz, CDCl3) δ165.38, 134.16, 132.72, 131.29, 130.45 (q, J = 3.0Hz), 129.33,128.74,125.74(q,J=276.9Hz),81.47,40.17(q,J=29.9Hz),28.28.

[0144] 19 F NMR (565MHz, CDCl3) δ -65.88.

[0145] Example 13

[0146]

[0147] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R1 is COO(CH3)3, and R1, R2, and R4 are independently H), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The reaction was carried out at room temperature under an LED at 385 ± 5 nm for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as tert-butyl 4-(2,2,2-trifluoroethyl)benzoate, with a yield of 74%.

[0148] 1 H NMR (400MHz, CDCl3) δ8.00–7.96 (m, 2H), 7.35 (d, J = 8.1Hz, 2H), 3.42 (q, J = 10.7Hz, 2H), 1.59 (s, 9H).

[0149] HRMS(ESI)m / z Calcd for C 13 H 16 F3O2[M+H] + :261.1097,found:261.1097.

[0150] Example 14

[0151]

[0152] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being Cl, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at 385 ± 5 nm under an LED for 18 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-(2,2,2-trifluoroethyl)-chlorobenzene, with a yield of 89%.

[0153] 1 H NMR (600MHz, CDCl3) δ7.34 (m, 2H), 7.23 (d, J = 8.2Hz, 2H), 3.34 (q, J = 10.7Hz, 2H).

[0154] HRMS(EI)m / z Calcd for C8H6ClF3[M] + :194.0110,found:194.0101.

[0155] Example 15

[0156]

[0157] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (a compound containing a naphthalene ring), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 1-(2,2,2-trifluoroethyl)-naphthalene, with a yield of 30%.

[0158] 1 H NMR (400MHz, CDCl3) δ8.01 (d, J = 8.4Hz, 1H), 7.87 (t, J = 8.5Hz, 2H), 7.63–7.41 (m, 4H), 3.86 (q, J = 10.6Hz, 2H).

[0159] HRMS(EI)m / z Calcd for C 12 H9F3[M] + :210.0656,found:210.0644.

[0160] Example 16

[0161]

[0162] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R1, R2, R3, and R4 are H-based independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction was complete, column chromatography was used for separation. 1H NMR, 1C NMR, and mass spectrometry identified the product as phenylacetonitrile, with a yield of 76%.

[0163] 1 H NMR (400MHz, CDCl3) δ7.41–7.29(m,5H),3.72(s,2H).

[0164] HRMS(EI)m / z Calcd for C8H7N[M] + :117.0578,found:117.0570.

[0165] Example 17

[0166]

[0167] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R1 being CH3, R2, R3, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 2-methylphenylacetonitrile, with a yield of 56%.

[0168] 1 H NMR (400MHz, CDCl3) δ7.37–7.32(m,1H),7.26–7.18(m,3H),3.64(s,2H),2.33(s,3H).

[0169] HRMS(EI)m / z Calcd for C9H9N[M] + :131.0735,found:131.0727.

[0170] Example 18

[0171]

[0172] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 being CH3, and R1, R3, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction was complete, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 3-methylphenylacetonitrile, with a yield of 76%.

[0173] 1 H NMR (400MHz, CDCl3) δ7.26 (t, J = 7.5Hz, 1H), 7.17–7.08 (m, 3H), 3.70 (s, 2H), 2.36 (s, 3H).

[0174] HRMS(EI)m / z Calcd for C9H9N[M] + :131.0735,found:131.0729.

[0175] Example 19

[0176]

[0177] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being CH3, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (tetra-n-butylammonium cyanide) were added to 1 mL of MeCN. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction was complete, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 4-methylphenylacetonitrile, with a yield of 91%.

[0178] 1 H NMR (400MHz, CDCl3) δ7.24–7.16(m,4H),3.70(s,2H),2.36(s,3H).

[0179] HRMS(EI)m / z Calcd for C9H9N[M] + :131.0735,found:131.0727.

[0180] Example 20

[0181]

[0182] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being CHCH2, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of MeCN. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 4-(cyanomethyl)styrene, with a yield of 35%.

[0183] 1 H NMR (400MHz, CDCl3) δ7.44–7.38(m,2H),7.28(d,J=8.3Hz,2H),6.71(dd,J=17.6,10 .9Hz,1H),5.77(dd,J=17.6,0.8Hz,1H),5.29(dd,J=10.9,0.8Hz,1H),3.73(s,2H).

[0184] HRMS(EI)m / z Calcd for C 10 H9N[M] + :143.0735,found:143.0727.

[0185] Example 21

[0186]

[0187] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being Ph, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of MeCN. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 4-(cyanomethyl)1-1'-biphenyl, with a yield of 60%.

[0188] 1 H NMR (400MHz, CDCl3) δ7.63–7.56(m,4H),7.49–7.34(m,5H),3.80(s,2H).

[0189] HRMS(EI)m / z Calcd for C 14 H 11 N[M] + :193.0891,found:193.0884.

[0190] Example 22

[0191]

[0192] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 is OCH3, and R1, R2, and R4 are H independently), and 0.15 mmol of functionalizing reagent (tetra-n-butylammonium cyanide) were added to 1 mL of MeCN. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction was complete, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 4-cyanomethyl anisole, with a yield of 99%.

[0193] 1 H NMR (400MHz, CDCl3) δ7.26–7.21(m,2H),6.92–6.87(m,2H),3.81(s,3H),3.68(s,2H).

[0194] HRMS(EI)m / z Calcd for C9H9NO[M] + :147.0684,found:147.0678.

[0195] Example 23

[0196]

[0197] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 and R4 are OCH3, R1 and R3 are H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 1,3-dimethoxyphenylacetonitrile, with a yield of 75%.

[0198] 1 H NMR (400MHz, CDCl3) δ6.46 (d, J = 2.2Hz, 2H), 6.40 (t, J = 2.3Hz, 1H), 3.79 (s, 6H), 3.68 (s, 2H).

[0199] HRMS(EI)m / z Calcd for C 10 H 11 NO2[M] + :177.0790,found:177.0784.

[0200] Example 24

[0201]

[0202] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being CN, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 4-cyanomethylbenzonitrile, with a yield of 96%.

[0203] 1 H NMR (400MHz, CDCl3) δ7.69 (dt, J=8.4, 2.0Hz, 2H), 7.48 (dp, J=7.4, 0.9Hz, 2H), 3.84 (s, 2H).

[0204] HRMS(EI)m / z Calcd for C9H6N2[M] + :142.0531,found:142.0527.

[0205] Example 25

[0206]

[0207] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being COOMe, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as methyl 4-cyanomethylbenzoate, with a yield of 73%.

[0208] 1 H NMR (400MHz, CDCl3) δ8.05 (dt, J = 8.4Hz, 2.0Hz, 2H), 7.42 (d, J = 8.7Hz, 2H), 3.93 (s, 3H), 3.82 (s, 2H).

[0209] HRMS(EI)m / z Calcd for C 10 H9NO2[M]+:175.0633,found:175.0623.

[0210] Example 26

[0211]

[0212] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 is COOCH2CH3, and R1, R3, and R4 are H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as ethyl 3-cyanomethylbenzoate, with a yield of 84%.

[0213] 1 H NMR (400MHz, CDCl3) δ8.05–7.97(m,2H),7.55(d,J=7.8Hz,1H),7.47(t,J=7.6Hz,1H),4.39(q,J=6.9Hz,2H),3.80(s,2H),1.40(t,J=7.0Hz,3H).

[0214] HRMS(EI)m / z Calcd for C 11 H 11 NO2[M] + :189.0790,found:189.0783.

[0215] Example 27

[0216]

[0217] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being COOCH2CH3, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction was complete, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as ethyl 4-cyanomethylbenzoate, with a yield of 67%.

[0218] 1 H NMR (400MHz, CDCl3) δ8.05(dt,J=8.4,2.0Hz,2H),7.41(ddt,J=7.7,1.9,1.0Hz,2H),4.38(q,J=7.1Hz,2H),3.81(s,2H),1.39(t,J=7.1Hz,3H).

[0219] HRMS(EI)m / z Calcd for C 11 H 11 NO2[M] + :189.0790,found:189.0784.

[0220] Example 28

[0221]

[0222] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 is COOC(CH3)3, and R1, R3, and R4 are each H), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction was complete, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as tert-butyl 3-cyanomethylbenzoate, with a yield of 77%.

[0223] 1 H NMR (400MHz, CDCl3) δ7.95(dt,J=7.6,1.5Hz,1H),7.93–7.90(m,1H),7.54–7.49(m,1H),7.44(t,J=7.7Hz,1H),3.79(s,2H),1.59(s,9H).

[0224] HRMS(ESI)m / z Calcd for C 13 H 16 NO2[M+H] + :218.1176,found:218.1176.

[0225] Example 29

[0226]

[0227] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being COOC(CH3)3, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as tert-butyl 4-cyanomethylbenzoate, with a yield of 79%.

[0228] 1 H NMR (400MHz, CDCl3) δ8.00 (dt, J=8.4, 2.0Hz, 2H), 7.38 (d, J=8.4Hz, 2H), 3.80 (s, 2H), 1.60 (s, 9H).

[0229] 13 C NMR (101MHz, CDCl3) δ165.17,134.35,132.12,130.38,127.92,117.35,81.57,28.31,23.78.

[0230] Example 30

[0231]

[0232] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R1 being CF3, R2, R3, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 2-trifluoromethylphenylacetonitrile, with a yield of 54%.

[0233] 1H NMR (600MHz, CDCl3) δ7.67(t,J=7.9Hz,2H),7.59(t,J=7.6Hz,1H),7.45(t,J=7.7Hz,1H),3.94(s,2H).

[0234] HRMS(EI)m / z Calcd for C9H6F3N[M] + :185.0452,found:185.0446.

[0235] Example 31

[0236]

[0237] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R2 is CF3, R1, R3, and R4 are H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 3-trifluoromethylphenylacetonitrile, with a yield of 68%.

[0238] 1 H NMR (600MHz, CDCl3) δ7.61 (d, J = 7.5Hz, 1H), 7.59 (s, 1H), 7.57–7.51 (m, 2H), 3.83 (s, 2H).

[0239] HRMS(EI)m / z Calcd for C9H6F3N[M] + :185.0452,found:185.0445.

[0240] Example 32

[0241]

[0242] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being CF3, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-trifluoromethylphenylacetonitrile, with a yield of 74%.

[0243] 1H NMR (600MHz, CDCl3) δ7.64 (d, J = 7.8 Hz, 2H), 7.46 (d, J = 7.9 Hz, 2H), 3.82 (s, 2H).

[0244] HRMS(EI)m / z Calcd for C9H6F3N[M] + :185.0452,found:185.0448.

[0245] Example 33

[0246]

[0247] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being F, R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-fluorophenylacetonitrile, with a yield of 83%.

[0248] 1 H NMR (400MHz, CDCl3) δ7.33–7.27(m,2H),7.11–7.03(m,2H),3.72(s,2H).

[0249] HRMS(EI)m / z Calcd for C8H6FN[M] + :135.0484,found:135.0479.

[0250] Example 34

[0251]

[0252] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being Cl, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 4-chlorophenylacetonitrile, with a yield of 56%.

[0253] 1H NMR (400MHz, CDCl3) δ7.36 (dt, J = 8.8, 2.4Hz, 2H), 7.30–7.24 (m, 2H), 3.73 (s, 2H).

[0254] HRMS(EI)m / z Calcd for C8H6ClN[M] + :151.0189,found:151.0182.

[0255] Example 35

[0256]

[0257] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (a compound containing a naphthalene ring), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of MeCN. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 1-cyanomethylnaphthalene, with a yield of 92%.

[0258] 1 H NMR (400MHz, CDCl3)7.92(dd,J=8.0,1.5Hz,1H),7.87(dd,J=8.4,3.4Hz,2H),7.65–7.54(m,3H),7.48(dd,J=8.3,7.1Hz,1H),4.14(s,2H).

[0259] HRMS(EI)m / z Calcd for C 12 H9N[M] + :167.0735,found:167.0726.

[0260] Example 36

[0261]

[0262] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (a heterocyclic compound), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 2-cyanomethyl-4,6-dimethylpyrimidine, with a yield of 51%.

[0263] 1H NMR(400MHz, CDCl3)6.99(s,1H),4.01(s,2H),2.50(s,6H).

[0264] HRMS(EI)m / z Calcd for C8H9N3[M] + :147.0796,found:147.0790.

[0265] Example 37

[0266]

[0267] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (compound 1 containing two aromatic rings), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of MeCN. The mixture was irradiated at 385 ± 5 nm under an LED for 24 hours at room temperature. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as diphenylacetonitrile, with a yield of 68%.

[0268] 1 H NMR (600MHz, CDCl3) δ7.39–7.29(m,10H),5.15(s,1H).

[0269] HRMS(EI)m / z Calcd for C 14 H 11 N[M] + :193.0891,found:193.0883.

[0270] Example 38

[0271]

[0272] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (compound 2 containing two aromatic rings), and 0.15 mmol of functionalizing reagent (trimethylcyanosilane) were added to 1 mL of THF. The mixture was irradiated at room temperature under a 385±5 nm LED for 24 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4,4'-difluorodiphenylacetonitrile, with a yield of 60%.

[0273] 1 H NMR (600MHz, CDCl3)7.07–7.02(m,4H),6.86–6.80(m,4H),4.62(s,1H).

[0274] HRMS(EI)m / z Calcd for C 14 H9F2N[M] + :229.0703,found:229.0698.

[0275] Example 39

[0276]

[0277] Using Cu(SIPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R3 being CN, and R1, R2, and R4 being H independently), and 0.15 mmol of functionalizing reagent (sodium trifluoromethyl sulfinate) were added to 1 mL of DMF. The mixture was irradiated at room temperature under a 385 ± 5 nm LED for 18 hours. After the reaction, column chromatography was performed. 1H NMR, 1C NMR, fluorine NMR, and mass spectrometry identified the product as 4-(2,2,2-trifluoroethyl)-benzonitrile, with a yield of 67%.

[0278] 1 H NMR (400MHz, CDCl3) δ7.69–7.64(m,2H),7.43(d,J=8.0Hz,2H),3.45(q,J=10.5Hz,2H).

[0279] HRMS(EI)m / z Calcd for C9H6F3N[M] + :185.0452,found:185.0445.

[0280] Example 40

[0281]

[0282] Using Cu(IPr)I as a catalyst, under an Ar atmosphere, 0.01 mmol of Cu(IPr)I catalyst, 0.1 mmol of benzyl chloride compound (R1, R2, R3, and R4 are H-based independently), 0.15 mmol of functionalizing reagent (morpholine), and 0.15 mmol of base (sodium tert-butoxide) were added to 1 mL of DCM. The mixture was irradiated at 385 ± 5 nm under an LED for 18 hours at room temperature. After the reaction was complete, column chromatography was performed. 1H NMR, 1C NMR, and mass spectrometry identified the product as 4-benzylmorpholine, with a yield of 86%.

[0283] 1H NMR (600MHz, CDCl3) δ7.36–7.29(m,4H),7.28–7.23(m,1H),3.71(t,J=4.9Hz,4H),3.51(s,2H),2.46(s,4H).

[0284] 13 C NMR (151MHz, CDCl3) δ137.58,129.31,128.32,127.25,66.98,63.45,53.61.

[0285] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A photocatalytic benzylic C( sp 3 The method for functionalizing the )-Cl bond is characterized by, Includes the following steps: A solution A is obtained by adding a photocatalyst, a benzyl chloride compound, and a functionalizing agent to a solvent, and then adding or not adding an alkali. Under an inert atmosphere, solution A was irradiated with light to obtain a benzylic functionalized product; The photocatalyst is selected from copper-nitrogen heterocyclic carbene complexes; The functionalization includes trifluoromethylation, cyanation, or amination; The copper-nitrogen heterocyclic carbene complexes include one or more of Cu(IPr)I, Cu(SIPr)I, Cu(CAAC)I, Cu(IPr)Br, Cu(IPr)Cl, Cu(IPr)Br2, Cu(IPr)Cl2, Cu(IPr)F2, Cu(IPr)OAc, Cu(IPr)(OAc)2, Cu(IPr)CN, Cu(IPr)SCN, Cu(IPr)OTf, and Cu(IPr)SO4; The benzyl chloride compound has one of the following structures: Ⅰ; II: III: IV: V: In Formula I, R1 represents one of H, CH3, CN, COOCH2CH3, COOC(CH3)3, and CF3; R2 represents one of H, CH3, OCH3, and CF3; R3 represents one of H, CH3, OCH3, CH=CH2, Ph, F, Cl, CN, COOCH3, COOCH2CH3, COOC(CH3)3, and CF3; R4 represents H or OCH3.

2. The method according to claim 1, characterized in that, The copper-nitrogen heterocyclic carbene complex is selected from Cu(IPr)I.

3. The method according to claim 1, characterized in that, The molar concentration of the copper-nitrogen heterocyclic carbene complex in solution A is 1 × 10⁻⁶. -3 M~1×10 -2 M.

4. The method according to claim 1, characterized in that, When photocatalysis is performed at the benzylic C ( sp 3 During the trifluoromethylation reaction of the )-Cl bond, the functionalizing agent includes one or more of CF3SO2Na, CF3SO3Na, CF3CO2Na, and TMSCF3.

5. The method according to claim 1, characterized in that, The molar concentration of the functionalizing agent in solution A is 0.1 M to 0.3 M.

6. The method according to claim 1, characterized in that, The solvent includes one or more of N,N-dimethylformamide, tetrahydrofuran, acetone, N,N-dimethylacetamide, dimethyl adipate, acetonitrile, dichloroethane, dichloromethane, benzene, and toluene.

7. The method according to claim 1, characterized in that, When the solvent is N,N-dimethylformamide, the molar ratio of benzyl chloride compound to functionalizing reagent is 1:0.33~3.

8. The method according to claim 1, characterized in that, When photocatalysis is performed at the benzylic C ( sp 3 During the cyanidation reaction of the )-Cl bond, the functionalizing agent includes TMSCN and / or TBACN.

9. The method according to claim 1, characterized in that, The molar concentration of the functionalizing agent in solution A is 0.1 M to 0.3 M.

10. The method according to claim 1, characterized in that, The solvent includes one or more of tetrahydrofuran, acetone, N,N-dimethylformamide, dimethyl adipate, acetonitrile, dichloroethane, benzene, toluene, dimethyl sulfoxide, dichloromethane, diethyl ether, 1,4-dioxane, n-hexane, cyclohexane, and methylcyclohexane.

11. The method according to claim 1, characterized in that, When the solvent is tetrahydrofuran or acetonitrile, the molar ratio of benzyl chloride compound to functionalizing reagent is 1:0.33~3.

12. The method according to claim 1, characterized in that, When photocatalysis is performed at the benzylic C ( sp 3 In the )-Cl bond amination reaction, the functionalizing agent includes one or more of morpholine, piperidine, and carbazole.

13. The method according to claim 1, characterized in that, The molar concentration of the functionalizing agent in solution A is 0.1 M to 0.3 M.

14. The method according to claim 1, characterized in that, The base includes potassium tert-butoxide and / or sodium tert-butoxide.

15. The method according to claim 1, characterized in that, The molar concentration of the alkali in solution A is 0.1 M to 0.3 M.

16. The method according to claim 1, characterized in that, The solvent includes one or more of N,N-dimethylacetamide, N,N-dimethylformamide, acetonitrile, tetrahydrofuran, acetone, and dichloromethane.

17. The method according to claim 1, characterized in that, When the solvent is N,N-dimethylacetamide, the molar ratio of benzyl chloride compound to functionalizing reagent is 1:0.33~3.

18. The method according to claim 1, characterized in that, When the solvent is N,N-dimethylacetamide, the molar ratio of the functionalizing agent to the base is 1:

1.

19. The method according to claim 1, characterized in that, The molar concentration of the benzyl chloride compound in solution A is 0.1 M to 0.3 M.

20. The method according to claim 1, characterized in that, The method according to claim 1, wherein the light is selected from ultraviolet to visible light.

21. The method according to claim 1, characterized in that, The light source is selected from LED lights.

22. The method according to claim 21, characterized in that, The LED lamp has an irradiation wavelength of 360-460 nm and an irradiation time of 18 h-24 h.

23. The method according to any one of claims 1-22 at the catalytic benzyl C ( sp 3 Applications of )-Cl bond in the preparation of trifluoromethylated products.

24. The method according to any one of claims 1-22 at the catalytic benzyl C ( sp 3 Applications of )-Cl bond in the preparation of cyanide products.

25. The method according to any one of claims 1-22 at the catalytic benzyl C ( sp 3 Applications of )-Cl bond in the preparation of amination products.

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