A method for the synthesis of photoinduced chromium-catalyzed beta-deuterated alcohols
By employing a photocatalytic and chromium salt synergistic catalytic reaction strategy, β-deuterated alcohols are synthesized using α-deuterated alkyl sulfonium salts and aldehydes. This approach addresses the shortcomings of existing β-deuterated alcohol synthesis methods, achieving mild reaction conditions and simple operation, and possesses potential for industrial application.
Patent Information
- Application Number
- CN202411976260.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-30
- Publication Date
- 2025-11-28
- Estimated Expiration
- 2044-12-30
AI Technical Summary
There are few existing methods for synthesizing β-deuterated alcohols, making it difficult to achieve regioselective deuteration reactions, and the reaction conditions are quite harsh.
A photocatalytic and chromium salt co-catalytic reaction strategy was adopted, using readily available α-deuterated alkyl sulfonate salts and aldehydes as raw materials. Under light irradiation, electron donor-acceptor complexes were formed with Hantzsch esters, and the addition reaction of deuterated alkyl fragments with aldehydes was achieved by combining chromium salt catalysis to synthesize β-deuterated alcohols.
The efficient synthesis of β-deuterated alcohols was achieved under mild reaction conditions and simple operation, showing promising prospects for industrial application.
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Figure QLYQS_1 
Figure QLYQS_2 
Figure QLYQS_3
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the field of synthesis of deuterated organic compounds, and particularly relates to a synthesis method of photo-induced chromium-catalyzed β-deuterated alcohol. BACKGROUND
[0002] Deuterium, as a stable non-radioactive isotope, has been widely used in nuclear magnetic resonance analysis, mechanism research, pharmaceutical and biochemical research and development, etc. Since the first deuterated drug Austedo (deutertrabenazine) for treating "chorea symptoms" related to Huntington's disease was approved by the US Food and Drug Administration (FDA) in 2017, the synthesis of deuterated organic molecules has attracted much attention, and more and more reaction strategies for synthesizing deuterated organic molecules have been successfully developed. However, how to achieve the deuterium substitution reaction of alkyl groups in a region-selective manner has always been a difficulty in organic synthesis.
[0003] The synthesis of α-deuterated alcohol can be carried out by deuterium substitution reduction of carbonyl compounds (Chem. Rev. 2022, 122, 6634-6718) or by means of oxygen atom activation reaction strategy for ortho carbon-hydrogen bond (Chem. Sci. 2022, 13, 8744-8751). However, there are few reports on the synthesis method of β-deuterated alcohol. Therefore, it is of great practical value to develop a synthesis method for preparing β-deuterated alcohol compounds. We have developed a reaction system with mild reaction conditions and simple system, which uses simple and readily available α-deuterated alkyl sulfonium salt (Angew. Chem. Int. Ed. 2024, 63, e202409862) and aldehyde compound as raw materials, and rapidly synthesizes β-deuterated alcohol under the condition of co-catalysis of photo-catalysis and chromium metal. SUMMARY
[0004] The purpose of the present application is to provide a reaction strategy utilizing photo-catalysis and chromium salt co-catalysis to realize the synthesis of β-deuterated alcohol. The reaction uses simple and readily available α-deuterated alkyl sulfonium salt and aldehyde compound as raw materials, activates the electron donor-acceptor (EDA) complex formed by Hantzsch ester (HE) and α-deuterated alkyl sulfonium salt through light, and combines chromium salt catalysis to realize the addition reaction of deuterated alkyl fragment and aldehyde, thereby synthesizing a series of β-deuterated alcohol with high deuterium substitution rate. The reaction has mild reaction conditions, simple operation and good industrial application prospect.
[0005] A synthesis method of photo-induced chromium-catalyzed β-deuterated alcohol, the method comprising the following process:
[0006] The alpha-deuterated alkylsulfonium salt, aldehyde, Hantzsch ester and CrCl2 catalyst are dispersed in an organic solvent, and the reaction is carried out at room temperature under light irradiation of a certain wavelength, and after the reaction is completed, a beta-deuterated alcohol is obtained.
[0007] The alpha-deuterated alkylsulfonium salt has the following structural formula: The aldehyde has the following structural formula: The Hantzsch ester has the following structural formula: The beta-deuterated alcohol has the following structural formula:
[0008] The alpha-deuterated alkylsulfonium salt is selected from any one or more of the following:
[0009]
[0010] The aldehyde is selected from any one or more of the following:
[0011]
[0012] In an embodiment of the present application, the wavelength is selected from any one or more of the following: 400-410 nm, 410-420 nm, 440-450 nm. Specifically, 400-410 nm can be preferred.
[0013] In an embodiment of the present application, the reaction time is 12 h.
[0014] In an embodiment of the present application, the molar ratio of the alpha-deuterated alkylsulfonium salt, aldehyde and Hantzsch ester is 1.5:1.
[0015] In an embodiment of the present application, the amount of chromium catalyst used is 20 mol% relative to the aldehyde.
[0016] In an embodiment of the present application, the molar ratio of Hantzsch ester to aldehyde is 3:1.
[0017] In an embodiment of the present application, the organic solvent is selected from any one or more of the following: tetrahydrofuran, acetonitrile, ethylene glycol dimethyl ether, dioxane and acetone, and tetrahydrofuran is preferred. Specifically, tetrahydrofuran can be preferred.
[0018] In an embodiment of the present application, the reaction is carried out under N2 atmosphere.
[0019] In an embodiment of the present application, the reaction has the following synthetic route:
[0020]
[0021] In an embodiment of the present application, the beta-deuterated alcohol compound specifically comprises the following structure:
[0022]
[0023] In an embodiment of the present application, the method specifically comprises the following steps:
[0024] A reaction tube equipped with a stirrer is added with CrCl2 in a glove box, the reaction tube is taken out of the glove box, and under N2 atmosphere, an alpha-deuterated alkyl sulfonium salt, a Hantzsch ester, an aldehyde and a solvent tetrahydrofuran are sequentially added, and under irradiation of blue light at 400-410 nm, the reaction is stirred at room temperature for 12 h. After the reaction is completed, the reaction mixture is filtered with silica gel, washed with ethyl acetate, and the organic phases are combined, and the solvent is removed by a rotary evaporator to obtain a crude product, and the crude product is separated by silica gel column chromatography, and petroleum ether and ethyl acetate are used as eluents to finally obtain the target compound.
[0025] Advantages:
[0026] The present application uses an alpha-deuterated alkyl sulfonium salt and an aldehyde compound as raw materials, a chromium salt as a catalyst, a Hantzsch ester as a reducing agent, and tetrahydrofuran as a reaction solvent, and under irradiation of blue light at 400-410 nm, the reaction is carried out at room temperature for 12 h, and after the reaction is completed, a beta-deuterated alcohol compound is obtained. The synthesis method of the present application has simple catalyst and reaction raw materials, mild reaction conditions, good functional group compatibility, convenient operation, and good industrial application prospect. BRIEF DESCRIPTION OF DRAWINGS
[0027] Figure 1 The present application is a schematic diagram of the synthesis method. DETAILED DESCRIPTION
[0028] In order to make the content described in the present application more convenient to understand, the technical solutions described in the present application are further described in combination with specific embodiments, but the present application is not limited in the scope of the described embodiments.
[0029] Example 1
[0030] In a reaction tube with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by the addition of the α-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 1 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 1 was obtained (separation yield 82%).
[0031]
[0032] 1 H NMR (600 MHz, CDC13) δ 7.28 (td, J = 7.5, 2.8 Hz, 4H), 7.22-7.15 (m, 6H), 3.64 (dd, J = 8.2, 4.1 Hz, 1H), 2.78 (ddd, J = 13.7, 9.8, 5.6 Hz, 1H), 2.65 (dddd, J = 14.8, 13.5, 9.8, 6.7 Hz, 3H), 1.82-1.70 (m, 3H), 1.66 (dt, 1 = 14.0, 7.6 Hz, 1H), 1.36 (s, 1H). 13 C NMR (151 MHz, CDC13) δ 142.29, 142.07, 128.38, 128.29, 125.80, 125.73, 71.07, 38.99, 36.50, 36.38, 36.26, 36.13, 35.78, 32.00, 27.18.
[0033] Example 2
[0034] In a reaction tube with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by the addition of the α-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 2 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 2 was obtained (separation yield 65%).
[0035]
[0036] 1 H NMR (600 MHz, CDC13) δ 7.28 (dd, J = 8.3, 7.0 Hz, 2H), 7.19 (dd, J = 7.9, 1.8 Hz, 3H), 3.37 (d, J = 5.4 Hz, 1H), 2.69 - 2.58 (m, 2H), 1.84 - 1.71 (m, 4H), 1.69 - 1.60 (m, 3H), 1.34 - 1.19 (m, 4H), 1.18 - 0.96 (m, 3H). 13 C NMR (151 MHz, CDC13) δ 142.49, 128.38, 128.26, 125.67, 75.94, 43.55, 35.89, 32.87 (dd, J = 37.6, 18.8 Hz), 29.26, 27.65, 27.55, 26.52, 26.34, 26.17.
[0037] Example 3
[0038] In a reaction tube equipped with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by α-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 3 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 3 was obtained (separation yield 78%).
[0039]
[0040] 1 H NMR (600 MHz, CDC13) δ 7.38 - 7.30 (m, 4H), 7.30 - 7.25 (m, 3H), 7.21 - 7.11 (m, 3H), 4.68 (s, 1H), 2.64 (t, J = 7.7 Hz, 2H), 1.81 (s, 1H), 1.76 (dt, J = 13.4, 7.8 Hz, 1H), 1.61 (dt, J = 13.4, 7.8 Hz, 1H). 13C NMR (151 MHz, CDCI3) δ 144.67, 142.23, 128.46, 128.39, 128.27, 127.55, 125.87, 125.72, 74.42, 37.81 (dd, J = 38.5, 19.1 Hz), 35.67, 27.36.
[0041] Example 4
[0042] In a reaction tube equipped with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by α-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), para-aldehyde 4 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, and finally the compound of formula 4 was obtained (separation yield 83%).
[0043]
[0044] 1 H NMR (600 MHz, CDCI3) δ 7.28 (ddd, J = 15.6, 7.9, 4.8 Hz, 4H), 7.21 - 7.12 (m, 3H), 7.05 - 6.98 (m, 2H), 4.66 (s, 1H), 2.63 (t, J = 7.7 Hz, 2H), 1.85 (s, 1H), 1.73 (dt, J = 13.4, 7.8 Hz, 1H), 1.59 (dd, J = 14.4, 6.7 Hz, 1H). 13 C NMR (151 MHz, CDCI3) δ 162.14 (d, J = 245.2 Hz), 142.10, 140.36 (d, J = 3.1 Hz), 128.36, 128.30, 127.49 (d, J = 8.2 Hz), 125.77, 115.23 (d, J = 21.3 Hz), 73.74, 37.75 (dd, J = 38.3, 20.1 Hz), 35.61, 27.27. 19 F NMR (565 MHz, CDCI3) δ -115.11.
[0045] Example 5
[0046] In a reaction tube equipped with a stir bar, under N2atmosphere, the catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by the addition of the a-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), the Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), the aldehyde 5 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, the organic phases were combined, the solvent was removed using a rotary evaporator to obtain the crude product, which was separated by column chromatography on silica gel using petroleum ether and ethyl acetate as eluents, obtaining the compound of formula 5 (isolated yield 76%).
[0047]
[0048] 1 H NMR (600 MHz, CDC13) δ 7.30-7.25 (m, 4H), 7.20-7.13 (m, 4H), 7.06 (dd, J = 5.0, 1.3 Hz, 1H), 4.78 (s, 1H), 2.64 (t, J = 7.7 Hz, 2H), 1.80-1.73 (m, 2H), 1.63 (dd, J = 14.1, 7.1 Hz, 1H). 13 C NMR (151 MHz, CDC13) δ 146.17, 142.19, 128.39, 128.29, 126.14, 125.75, 125.59, 120.73, 70.41, 37.13 (dd, J = 39.2, 20.4 Hz), 35.62, 27.21.
[0049] Example 6
[0050] In a reaction tube equipped with a stir bar, under N2atmosphere, the catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by the addition of the a-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), the Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), the aldehyde 5 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, the organic phases were combined, the solvent was removed using a rotary evaporator to obtain the crude product, which was separated by column chromatography on silica gel using petroleum ether and ethyl acetate as eluents, obtaining the compound of formula 5 (isolated yield 76%).
[0051]
[0052] 1 H NMR (600 MHz, CDCI3) δ 7.31 - 7.26 (m, 2H), 7.21 - 7.17 (m, 3H), 4.37 (d, J = 5.1 Hz, 1H), 2.67 (t, J = 7.7 Hz, 2H), 1.85 - 1.73 (m, 3H), 0.17 (s, 9H). 13 C NMR (151 MHz, CDCI3) δ 142.07, 128.39, 128.31, 125.78, 106.63, 89.55, 62.63, 36.38 (dd, J = 37.8, 19.0 Hz), 35.31, 26.58, -0.14.
[0053] Example 7
[0054] In a reaction tube equipped with a stir bar, under N2atmosphere, catalyst CrCI2(0.04 mmol, 20 mol%) was added, followed by the addition of the α-deuterated sulfoxonium salt 1 (0.3 mmol, 1.5 equiV), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 7 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the end of the reaction, the reaction mixture was filtered on silica gel, eluted with ethyl acetate, the organic phases were combined and the solvent was removed using a rotary evaporator to obtain the crude product, which was separated by column chromatography on silica gel using petroleum ether and ethyl acetate as eluents, obtaining the compound of formula 7 (42% isolated yield).
[0055]
[0056] 1 H NMR (600 MHz, CDCI3) δ 7.34 (t, J = 7.6 Hz, 2H), 7.31 - 7.25 (m, 4H), 7.25 - 7.16 (m, 4H), 6.49 (s, 1H), 4.19 (s, 1H), 2.68 (t, J = 7.7 Hz, 2H), 1.84 (d, J = 1.4 Hz, 3H), 1.76 (dt, J = 14.9, 7.7 Hz, 1H), 1.65 (dd, J = 14.5, 6.7 Hz, 1H). 13 C NMR (151 MHz, CDCI3) δ 142.29, 140.19, 137.49, 128.95, 128.40, 128.30, 128.10, 126.44, 125.90, 125.74, 77.92, 35.73, 33.82 (dd, J = 37.9, 19.7 Hz), 27.37, 13.09.
[0057] Example 8
[0058] In a reaction tube equipped with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by α-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 8 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, and the organic phase was combined. The solvent was removed by rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluent, and finally the compound of formula 8 was obtained (separation yield 58%).
[0059]
[0060] 1 H NMR (600 MHz, CDC13) δ 7.67 (dd, J = 8.6, 1.9 Hz, 2H), 7.47 (dt, J = 8.9, 2.2 Hz, 2H), 7.32 - 7.23 (m, 4H), 7.16 (ddd, J = 19.1, 7.4, 4.0 Hz, 3H), 7.09 - 7.01 (m, 3H), 6.91 (dd, J = 9.0, 3.1 Hz, 1H), 6.71 (dd, J = 9.0, 2.6 Hz, 1H), 4.64 (s, 1H), 3.91 (d, J = 2.3 Hz, 2H), 3.84 (d, J = 2.0 Hz, 3H), 2.62 (t, J = 7.8 Hz, 2H), 2.46 (d, J = 2.1 Hz, 3H), 2.04 (s, 1H), 1.73 (dt, J = 13.1, 7.8 Hz, 1H), 1.59 (dt, J = 13.2, 7.8 Hz, 1H). 13 C NMR (151 MHz, CDC13) δ 169.29, 168.26, 156.06, 149.83, 142.44, 142.08, 139.28, 136.15, 133.75, 131.14, 130.79, 130.44, 129.09, 128.33, 128.24, 126.86, 125.70, 121.25, 114.97, 111.94, 111.73, 101.19, 73.66, 55.67, 37.79 (dd, J = 38.4, 18.5 Hz), 35.57, 30.48, 27.22, 13.37.
[0061] Example 9
[0062] In a reaction tube equipped with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by the addition of a-deuterated alkylsulfonium salt 2 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 1 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, rinsed with ethyl acetate, and the organic phases were combined. The solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents to obtain the compound of formula 9 (separation yield 76%).
[0063]
[0064] 1 H NMR (600 MHz, CDC13) δ 7.29 (t, J = 7.6 Hz, 2H), 7.24 - 7.16 (m, 3H), 3.62 (dd, J = 8.1, 4.1 Hz, 1H), 2.74 (dddd, J = 74.5, 13.7, 9.9, 6.1 Hz, 2H), 1.85 - 1.69 (m, 2H), 1.42 (p, J = 7.6 Hz, 1H), 1.38 - 1.23 (m, 6H), 0.89 (t, J = 6.9 Hz, 3H). 13 C NMR (151 MHz, CDC13) δ 142.22, 128.39, 128.37, 125.76, 71.31, 39.02, 36.66 (dd, J = 37.9, 19.0 Hz), 32.05, 31.81, 25.06, 22.62, 14.01.
[0065] Example 10
[0066] In a reaction tube equipped with a stir bar, under N2atmosphere, the catalyst CrCl2(0.04 mmol, 20 mol%), the a-deuterated alkylsulfonium salt 3 (0.3 mmol, 1.5 equiv), the Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), the aldehyde 1 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL) were added successively, irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, the organic phases were combined, the solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluent, finally obtaining the compound of formula 10 (separation yield 61%).
[0067]
[0068] 1 H NMR (600 MHz, CDC13) δ 7.42-7.38 (m, 2H), 7.29 (t, J = 7.6 Hz, 2H), 7.22-7.17 (m, 3H), 7.08-7.04 (m, 2H), 3.64 (dd, J = 7.9, 4.4 Hz, 1H), 2.83-2.59 (m, 4H), 1.87-1.74 (m, 2H), 1.41 (s, 1H). 13 C NMR (151 MHz ， CDC13) δ 141.85, 140.98, 131.42, 130.15, 128.44, 128.36, 125.89, 119.52, 70.46, 39.15, 38.09 (dd, J = 38.3, 19.6 Hz), 32.00, 31.20.
[0069] Example 11
[0070] In a reaction tube equipped with a stir bar, under N2atmosphere, the catalyst CrCl2(0.04 mmol, 20 mol%), the a-deuterated alkylsulfonium salt 3 (0.3 mmol, 1.5 equiv), the Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), the aldehyde 1 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL) were added successively, irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, washed with ethyl acetate, the organic phases were combined, the solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluent, finally obtaining the compound of formula 10 (separation yield 61%).
[0071]
[0072] 1 H NMR (600 MHz, CDC13) δ 7.33 - 7.27 (m, 2H), 7.23 - 7.18 (m, 3H), 7.13 (dd, J = 5.1, 1.2 Hz, 1H), 6.93 (dd, J = 5.2, 3.4 Hz, 1H), 6.80 (dd, J = 3.3, 1.3 Hz, 1H), 3.70 (dt, J = 8.0, 3.7 Hz, 1H), 3.04 - 2.89 (m, 2H), 2.80 (ddd, J = 13.8, 9.6, 6.0 Hz, 1H), 2.69 (ddd, J = 13.8, 9.6, 6.7 Hz, 1H), 1.87 - 1.76 (m, 2H), 1.46 (d, J = 4.2 Hz, 1H). 13 C NMR (151 MHz, CDC13) δ 144.83, 141.90, 128.42, 128.36, 126.76, 125.86, 124.20, 123.04, 70.42, 39.12, 38.61 (dd, J = 38.5, 19.7 Hz), 32.00, 25.92.
[0073] Example 12
[0074] In a reaction tube equipped with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by α-deuterated alkylsulfonium salt 5 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 1 (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. After the reaction was completed, the reaction mixture was filtered with silica gel, rinsed with ethyl acetate, the organic phases were combined, and the solvent was removed using a rotary evaporator to obtain the crude product, which was separated by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, to finally obtain compound of formula 12 (isolated yield 65%).
[0075]
[0076] 1H NMR (600 MHz, CDC13) δ 7.29 (t, J = 7.6 Hz, 2H), 7.22-7.17 (m, 3H), 3.82 (t, J = 6.2 Hz, 1H), 2.76 (ddd, J = 13.7, 9.5, 6.1 Hz, 1H), 2.68 (ddd, J = 13.8, 9.4, 6.9 Hz, 1H), 1.84-1.71 (m, 2H), 1.36 (s, 1H). 13 C NMR (151 MHz, CDC13) δ 142.04, 128.39, 128.38, 125.81, 67.38, 40.77, 32.11, 29.68.
[0077] Example 13 Synthesis of target product with different solvents
[0078] In a reaction tube with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by α-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), aldehyde 1 (0.2 mmol, 1 equiv), solvent (1.0 mL), irradiation under blue light at 400-410 nm, stirring at room temperature for 12 h. The reaction results are shown in Table 1.
[0079] Table 1 Synthesis results with different solvents
[0080] Solvent NMR yield of compound of formula 1 Tetrahydrofuran 90％ Acetonitrile 53％ Ethylene glycol dimethyl ether 71％ Dioxane 60％ Acetone 70％
[0081] Example 14 Synthesis of target product with different wavelengths of light
[0082] In a reaction tube with a stir bar, under N2atmosphere, catalyst CrCl2(0.04 mmol, 20 mol%) was added, followed by α-deuterated alkylsulfonium salt 1 (0.3 mmol, 1.5 equiv), Hantzsch ester (HE) (0.6 mmol, 3.0 equiv), phenylpropyl aldehyde (0.2 mmol, 1 equiv), tetrahydrofuran solvent (1.0 mL), irradiation under blue light at different wavelengths, stirring at room temperature for 12 h. The reaction results are shown in Table 2.
[0083] Table 2 Synthesis results with different wavelengths of light
[0084] Wavelength NMR yield of compound of formula 1 400-410 nm 90％ 410-420 nm 83％ 440-450 nm 70％ 490-500 am 0 No light 0
[0085] While the application has been illustrated by a description of the previous specific embodiments, it is not the intention to restrict it to that detail; rather, the application is construed as covering all the features and embodiments falling within the spirit and scope of the application. Various modifications and embodiments can occur to those skilled in the art upon reading the preceding specification and accompanying drawings.
Claims
1. A method for the photo-induced chromium-catalyzed synthesis of β-deuterated alcohols, characterized in that, The method includes the following procedures: An α-deuterated alkyl sulfonate, an aldehyde, a Hantzsch ester, and a CrCl2 catalyst were dispersed in an organic solvent and reacted at room temperature under light of a certain wavelength. After the reaction was completed, a β-deuterated alcohol was obtained. The structural formula of the α-deuterated alkyl sulfonium salt is as follows: The structural formula of the aldehyde is: The structural formula of the Hantzsch ester is: The structural formula of the β-deuterol is: The α-deuterated alkyl sulfonate salt mentioned above is selected from any one or more of the following: The aldehyde is selected from any one or more of the following: The organic solvent is selected from any one or more of the following: tetrahydrofuran, acetonitrile, ethylene glycol dimethyl ether, dioxane, and acetone; The wavelength is selected from any one or more of the following: 400-410nm, 410-420nm, 440-450nm.
2. The method for synthesizing β-deuterated alcohols by photoinduced chromium catalysis according to claim 1, characterized in that, The molar ratio of the α-deuterated alkyl sulfonium salt reagent to the aldehyde is 1.5:
1.
3. The method for synthesizing β-deuterated alcohols by photoinduced chromium catalysis according to claim 1, characterized in that, The amount of CrCl2 relative to the aldehyde reagent is 20 mol%.
4. The method for synthesizing β-deuterated alcohols by photoinduced chromium catalysis according to claim 1, characterized in that, The molar ratio of the Hantzsch ester to the aldehyde is 3:1.