Method for synthesizing 1, 4-diketone by photooxidation reduction catalysis of alkenyl amide and alpha-carbonyl oxidation sulfonium ylide

Abstract

The invention relates to the fields of medicine, organic chemical industry and fine chemical industry, in particular to a method for synthesizing 1, 4-diketone by catalyzing alkenyl amide and alpha-carbonyl oxidized sulfonium ylide through photooxidation reduction. The preparation method comprises the following steps: under the protection of inert gas, reacting alkenyl amide and alpha-carbonyl oxidized sulfonium ylide serving as substrates in an organic solvent by taking a photosensitizer as a catalyst under the action of blue light irradiation and alkali at 30 DEG C for 18 hours to obtain an alkenyl amide alpha-carbonyl alkylate, and then hydrolyzing under an acidic condition to synthesize various asymmetric 1, 4-diketone compounds. The 1, 4-diketone compound is synthesized by a two-step method by taking alkenyl amide and alpha-carbonyl oxidized sulfonium ylide as initial raw materials, and the method has the remarkable advantages of wide substrate raw material sources, simplicity and convenience in operation, mild reaction conditions, high reaction efficiency, good universality, excellent functional group compatibility and the like.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceuticals, organic chemicals, and fine chemicals, and specifically to a method for synthesizing 1,4-diones by photo-oxidation-reduction catalysis of enamides and α-carbonyl oxysulfonium ylide. Background Technology

[0002] Ketones are among the most common structural motifs in various bioactive natural products and drug molecules, and are also important starting materials for the rapid assembly of complex molecular structures. 1,4-Diketone molecules contain two carbonyl groups and are ubiquitous structural groups in agrochemicals, pharmaceutical molecules, and dye materials. Furthermore, using 1,4-diketones as starting materials, important heterocyclic compounds such as furans, thiophenes, pyrroles, and pyridazines can be easily synthesized via the Paal-Knorr synthesis method. These heterocycles are useful pharmacophores and are widely found in antitumor, antibacterial, and antiviral active molecules, such as lophotoxin, the non-natural amino acid Fmoc-D-3-Ala(2-thienyl)-OH, and Liptor. (J.Mu, al.,Mol.Divers(2024),11030-11083;H.Dong,M.Liang,C.Zhang etal.,Phys.Chem.C 120(2016),22822-22830)

[0003]

[0004] Traditional methods for preparing 1,4-diketones typically involve constructing a new chemical bond connecting two segments containing a ketone carbonyl group. Two main strategies exist: C2,C3- and C3,C4- bonding pathways, including classical nucleophilic substitution reactions, oxidative cross-coupling of metal enols, and Stetter-type addition reactions, respectively. Therefore, the synthesis of 1,4-diketones is more challenging than that of other dicarbonyl compounds, as they are obtained through coupling reactions with multifunctional substrates. These coupling reactions either utilize multiple synthons or require multiple steps to functionalize a single structural donor. Stetter-type addition reactions, in particular, catalyze the synthesis of 1,4-dicarbonyl compounds using highly toxic sodium cyanide, demanding high operator skill, causing significant environmental pollution, and posing difficulties in post-processing. Therefore, the development of novel catalytic systems for the synthesis of 1,4-diketones is urgently needed. Summary of the Invention

[0005] The purpose of this invention is to provide a green and simple method for synthesizing various asymmetric 1,4-diketone compounds by reacting enamides and α-carbonylsulfonium ylides under nitrogen protection, in an organic solvent medium, with an organic photocatalyst, in the presence of a base, and under blue light irradiation, to obtain the α-carbonylalkylated product of the enamide. Subsequent hydrolysis under acidic conditions further facilitates the simple and efficient synthesis of these compounds. This method utilizes light energy to drive the reaction, offering unique and sustainable advantages compared to traditional thermocatalysis. It features mild reaction conditions (avoiding molecular degradation caused by strong acids and high temperatures in traditional methods), fewer byproducts, good functional group compatibility, and avoidance of highly toxic reagents.

[0006] The specific process of this reaction is shown below:

[0007]

[0008] The specific reaction conditions of this invention are as follows: synthesis is carried out under nitrogen protection, at 30°C, and irradiated with blue light (45W) for 18 hours.

[0009] The photocatalyst used in the reaction was tris(2-phenylpyridine)iridium fac - Ir(ppy)3, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile 4CzIPN, ruthenium tripyridine chloride Ru(bpy)3Cl2, the amount of photocatalyst is 2 mol% of the number of moles of enamide.

[0010] The bases used in the reaction are hexamethylphosphoramide (HMPA), sodium dihydrogen phosphate dihydrate, and potassium phosphate, and the amount used is 0.2-1 times that of the amide.

[0011] The reaction solvents are: N,N-dimethylformamide (DMF), acetonitrile (MeCN), dichloromethane (DCM), N,N-dimethylacetamide (DMA), and methanol (MeOH).

[0012] The molar ratio of the amide and α-carbonyl oxysulfonium ylide reaction is 1:2.

[0013] The structural formula of the 1,4-dione compound is: Ar 1 It is phenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-biyl, 3-fluorophenyl, 3,4-dichlorophenyl. 2 It is phenyl, 4-isopropylphenyl, 4-methoxyphenyl, 2-thienyl.

[0014] The 1,4-dione compounds synthesized in this invention are used to synthesize furans or pyrroles.

[0015] The post-reaction processing of this invention is simple, requiring only basic thin-layer chromatography (TLC) for separation and purification. Using petroleum ether:ethyl acetate (3:1) as the eluent, TLC separation yields the α-carbonylalkylated product of the enamide. This product is then hydrolyzed in anhydrous tetrahydrofuran solution with 2M hydrochloric acid at 50°C for 12 hours. After the reaction, the product is washed with saturated NaHCO3 solution, extracted with ethyl acetate, and the solvent is removed by rotary evaporation. The crude product is then separated by TLC using petroleum ether:ethyl acetate (12:1) as the eluent to obtain the 1,4-diketone product.

[0016] Beneficial effects:

[0017] 1. This invention avoids the use of high temperatures, strong acids, and highly toxic substances (sodium cyanide). Its synthesis process is simple and has high catalytic efficiency. It uses green and clean light energy as the reaction driving force, in the presence of the metal photosensitizer fac - Under the action of Ir(ppy)3, highly selective α-carbonyl alkylation of enamines is achieved, followed by hydrolysis with dilute hydrochloric acid to obtain 1,4-dione compounds.

[0018] 2. The synthesized product of this invention is an important motif for the synthesis of heterocycles (such as furan, thiophene, pyrrole and pyridazine), and can be used to synthesize agrochemicals, pharmaceutical molecules and organic dyes. Therefore, the 1,4-dione synthesized by the two-step method using enamide and α-carbonyl sulfonium ylide as substrates has important application value. Detailed Implementation

[0019] The reactants in this invention are α-carbonyl sulfonium oxide ylides, which were synthesized according to literature (Q. Sun, YZ Peng, YJ Wang, et al., Organic Letters, 2023, 25(36): 6613-6617.); another reactant, an enamide, was synthesized according to literature (X. Li, J. Liu, R. Song, et al., Organic Letters, 26(17), 3673-3678.); and the photocatalyst is tris(2-phenylpyridine)iridium fac - Ir(ppy)3, 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile 4CzIPN, ruthenium tripyridine chloride Ru(bpy)3Cl3, reaction solvents N,N-dimethylformamide (DMF), acetonitrile (MeCN), dichloromethane (DCM), N,N-dimethylacetamide (DMA), methanol (MeOH), and additives hexamethylphosphoramide (HMPA), sodium dihydrogen phosphate dihydrate, and potassium phosphate are all commercially available products.

[0020] The invention will now be described in detail with specific examples, and the reactions are shown in the following formulas:

[0021]

[0022] Example 1

[0023] N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), DMF (1 mL), HMPA (0.04 mmol), fac - Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ7.98 (d, J = 7.7Hz, 4H), 7.51 (t, J = 7.4Hz, 2H), 7.42 (t, J = 7.6Hz, 4H), 3.40 (s, 4H). 13 C NMR (101MHz, CDCl3) δ198.7,136.8,133.2,128.6,128.1,32.6.

[0024] Example 2

[0025] N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeCN (1 mL), HMPA (0.04 mmol), fac - Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 65%.

[0026] Example 3

[0027] N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), DCM (1 mL), HMPA (0.04 mmol), fac - Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 72%.

[0028] Example 4

[0029] N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), DMA (1 mL), HMPA (0.04 mmol), fac - Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 66%.

[0030] Example 5

[0031] N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeOH (1 mL), HMPA (0.04 mmol), fac -Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 40%.

[0032] Example 6

[0033] N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeCN (1 mL), HMPA (0.2 mmol), fac - Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 68%.

[0034] Example 7

[0035] The following ingredients were added: N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeCN (1 mL), sodium dihydrogen phosphate dihydrate (0.04 mmol), and fac -Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 66%.

[0036] Example 8

[0037] N-benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeCN (1 mL), potassium phosphate (0.04 mmol), fac - Ir(ppy)3 (2 mmol%) was added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 25%.

[0038] Example 9

[0039] N-Benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium ylide (2a, 0.4 mmol), MeCN (1 mL), HMPA (0.04 mmol), and 4CzIPN (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 32%.

[0040] Example 10

[0041] N-Benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium ylide (2a, 0.4 mmol), MeCN (1 mL), HMPA (0.04 mmol), and Ru(bpy)3Cl2 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 17%.

[0042] Example 11

[0043] N-Benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), benzoylsulfonium ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3a, with a yield of 84%.

[0044] Example 12

[0045] N-Benzyl-N-(1-(4-methylphenyl)vinyl)acetamide (1b, 0.2 mmol), benzoylsulfonium ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3b, with a yield of 82%. 1 H NMR (400MHz, CDCl3) δ8.03(t,J=8.0Hz,4H),7.58(t,J=7.3Hz,1H),7.48(t,J=7.5Hz,2H),6.95(d,J=8.4Hz,2H),3.88(s,3H),3.49–3.38(m,4H). 13 C NMR (101MHz, CDCl3) δ199.1,197.4,163.7,137.0,133.3,130.5,130.0,128.7,128.3,113.9,77.5,77.2,76.8,55.6,32.8,32.4.

[0046] Example 13

[0047] N-Benzyl-N-(1-(3-fluorophenyl)vinyl)acetamide (1c, 0.2 mmol), benzoylsulfonium ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3c, with a yield of 62%. 1 H NMR(400MHz, CDCl3)δ7.99(d,J=7.6Hz,2H),7.79(d,J=7.5Hz,1H),7.73–7.64(m, 1H),7.57–7.51(m,1H),7.54–7.44(m,3H),7.32–7.26(m,1H),3.46–3.36(m,4H). 13 C NMR (101MHz, CDCl3) δ198.6, 197.7, 163.0 (d, J = 248.5Hz), 139.0 (d, J = 5.1Hz), 136.8, 133.4, 130.4 (d ,J=8.1Hz),128.8,128.3,124.1(d,J=4.1Hz),120.3(d,J=21.2Hz),115.0(d,J=22.2Hz),32.8,32.7.

[0048] Example 14

[0049] N-Benzyl-N-(1-(4-chlorophenyl)vinyl)acetamide (1d, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3d, with a yield of 72%. 1 H NMR (400MHz, CDCl3) δ8.04–7.96 (m, 4H), 7.52 (t, J = 7.4Hz, 1H), 7.42 (t, J = 7. 5Hz, 2H), 7.09 (t, J = 8.4Hz, 2H), 3.40 (d, J = 4.8Hz, 2H), 3.37 (d, J = 4.7Hz, 2H). 13 C NMR (101MHz, CDCl3) δ198.6,197.1,136.7,133.2,130.8,130.7,128.6,128.1,115.8,115.6,32.6,32.5.

[0050] Example 15

[0051] N-Benzyl-N-(1-(4-bromophenyl)vinyl)acetamide (1e, 0.2 mmol), benzoylsulfonium ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3e, with a yield of 76%. 1H NMR (400MHz, CDCl3) δ8.07–8.00(m,2H),7.95–7.87(m,2H),7.66–7.60(m,2H),7.60–7.55(m,1H),7.48(t,J=7.7Hz,2H),3.50–3.38(m,4H). 13 C NMR (101MHz, CDCl3) δ198.7,197.9,136.8,135.6,133.4,132.1,129.8,128.8,128.5,128.3,32.7,32.6.

[0052] Example 16

[0053] N-Benzyl-N-(1-(4-iodophenyl)vinyl)acetamide (1f, 0.2 mmol), benzoylsulfonium ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3f, with a yield of 78%. 1 H NMR (400MHz, CDCl3) δ8.07–8.00(m,2H),7.85(d,J=8.4Hz,2H),7.75(d,J=8.3Hz,2H) ,7.59(t,J=7.3Hz,1H),7.48(t,J=7.6Hz,2H),3.50–3.44(m,2H),3.44–4.38(m,2H). 13 C NMR (101MHz, CDCl3) δ198.7,198.2,138.1,136.8,136.2,133.4,129.7,128.8,128.3,101.3,32.7,32.6.

[0054] Example 17

[0055] N-Benzyl-N-(1-(4-trifluoromethylphenyl)vinyl)acetamide (1 g, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain 3 g of solid product, with a yield of 60%. 1 HNMR (400MHz, CDCl3) δ8.15(d,J=8.1Hz,2H),8.04(d,J=7.7Hz,2H),7.75(d,J=8.1 Hz,2H),7.59(t,J=7.4Hz,1H),7.49(t,J=7.5Hz,2H),3.55–3.41(m,J=3.5Hz,4H). 13 C NMR (101MHz, CDCl3) δ198.5, 198.0, 139.6, 136.7, 134.9 (q, J = 33.3Hz), 133. 5,128.8,128.6,128.3,125.8(q,J=4.0Hz),123.7(q,J=273.3Hz)32.9,32.7.

[0056] Example 18

[0057] N-Benzyl-N-(1-(3,4-dichlorophenyl)vinyl)acetamide (1 h, 0.2 mmol), benzoylsulfonium oxide ylide (2 a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain the solid product 3 h, with a yield of 47%. 1 HNMR (400MHz, CDCl3) δ8.22–7.95(m,3H),7.87(d,J=8.3Hz,1H),7.64–6.54(m,2H),7.49(t,J=7.7Hz,2H),3.58–3.34(m,4H). 13 C NMR (101MHz, CDCl3) δ198.9,196.9,151.9,148.3,136.9,133.3,131.8,128.7,128.3,124.5,108.1,102.0,32.8,32.5.

[0058] Example 19

[0059] N-Benzyl-N-(1-(naphth-2-yl)vinyl)acetamide (1i, 0.2 mmol), benzoylsulfonium oxide ylide (2a, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the enamide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3i, with a yield of 77%. 1H NMR(400MHz, CDCl3)δ8.60(s,1H),8.13–8.04(m,3H),7.99(d,J=8.0Hz,1H),7.93–7.87(m, 2H),7.64–7.55(m,3H),7.50(t,J=7.6Hz,2H),3.62(t,J=6.5Hz,2H),3.53(t,J=6.2Hz,2H). 13 C NMR (101MHz, CDCl3) δ199.0,198.8,136.9,135.8,134.2,133.3,132.7,130 .0,129.8,128.8,128.60,128.58,128.3,127.9,126.9,124.0,32.9,32.8.

[0060] Example 20

[0061] N-Benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), 4-isopropylbenzoylsulfonium oxide ylide (2b, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3j, with a yield of 62%. 1 HNMR (400MHz, CDCl3) δ8.04(d,J=7.8Hz,2H),7.98(d,J=7.9Hz,2H),7.58(t,J=7.4Hz,1H),7.48(t,J= 7.5Hz,2H),7.33(d,J=7.9Hz,2H),3.46(d,J=1.7Hz,4H),3.02–2.93(m,1H),1.29(s,3H),1.27(s,3H). 13 C NMR (101MHz, CDCl3) δ198.8,198.4,154.7,146.8,136.8,133.1,128.6,128.4,128.1,126.7,34.3,32.7,32.5,23.7.

[0062] Example 21

[0063] N-Benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), 4-methoxybenzoylsulfonium ylide (2c, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain solid product 3k, with a yield of 75%. 1 HNMR (400MHz, CDCl3) δ7.97(t,J=7.6Hz,4H),7.51(t,J=7.4Hz,1H),7.41(t,J=7.5Hz,2H),6.88(d,J=8.4Hz,2H),3.81(s,3H),3.42–3.31(m,4H). 13 C NMR (101MHz, CDCl3) δ199.1,197.4,163.7,139.4,137.0,133.3,130.5,128.7,128.3,113.9,55.6,32.8,32.4.

[0064] Example 22

[0065] N-Benzyl-N-(1-(phenyl)vinyl)acetamide (1a, 0.2 mmol), 2-thienylbenzoylsulfonium oxide ylide (2d, 0.4 mmol), MeCN (2 mL), HMPA (0.04 mmol), and fac-Ir(ppy)3 (2 mmol%) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed under blue light (45 W) irradiation, and the reaction temperature was controlled at 30 °C for 18 hours. After the reaction, the product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 3:1 as the eluent to obtain the α-carbonylalkylated product of the amide. This product was then hydrolyzed in anhydrous tetrahydrofuran solvent with 2 M hydrochloric acid at 50 °C for 12 hours. After the reaction, a saturated aqueous solution of NaHCO3 was added, and the product was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was separated by thin-layer chromatography using petroleum ether:ethyl acetate = 12:1 as the eluent to obtain 3 μL of solid product, with a yield of 54%. 1 HNMR (400MHz, CDCl3) δ7.96(d,J=7.7Hz,2H),7.77(d,J=3.8Hz,1H),7.58(d,J=5.0Hz,1H),7.51(t,J= 7.4Hz, 1H), 7.41 (t, J = 7.6Hz, 2H), 7.10 (d, J = 4.5Hz, 1H), 3.39 (d, J = 5.7Hz, 2H), 3.35 (d, J = 5.8Hz, 2H). 13 C NMR (125MHz, CDCl3) δ199.3,192.6,143.9,138.0,133.9,133.2,132.0,128.8,128.3,128.1,39.3,39.0.

[0066] Example 23

[0067] The obtained diketone product 3k (0.2 mmol), trifluoromethanesulfonic acid (0.3 mmol), and anhydrous acetonitrile (2 mL) were added to a Schlenk reaction tube under nitrogen protection. The reaction tube was placed in an oil bath at 85 °C for 1 hour. After the reaction was completed, a saturated aqueous solution of NaHCO3 was added, and the mixture was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was purified by thin-layer chromatography using petroleum ether:ethyl acetate = 20:1 as the eluent to obtain the furan product in 82% yield. 1H NMR (CDCl3, 400MHz): δ8.47 (s, 1H), 7.51 (d, J = 8.0Hz, 2H), 7.45 (d, J = 8.4Hz, 2H), 7.37 (t, J = 7.8Hz 2H),7.24–7.18(m,1H),6.93(d,J=8.4Hz,2H),6.56(m,1H),6.46(s,1H),3.82(s,3H); 13 C NMR (CDCl3, 101MHz) δ158.4,133.2,132.6,132.4,128.9,126.1,125.5,125.2,123.6,114.4,107.7,106.8,55.3.

[0068] Example 24

[0069] The obtained diketone product 3k (0.2 mmol), ammonium acetate (0.5 mmol), and anhydrous methanol (5 mL) were added to a 25 mL round-bottom flask and refluxed for 12 hours. After the reaction was completed, a saturated NaCl solution was added, and the mixture was extracted with ethyl acetate. After removing the solvent by rotary evaporation, the crude product was purified by thin-layer chromatography using petroleum ether:ethyl acetate = 16:1 as the eluent to obtain the pyrrole product, with a yield of 88%. 1 H NMR (CDCl3, 400MHz): δ7.73(d,J=7.6Hz,2H),7.68(d,J=8.8Hz,2H),7.42–7.38(m,2H),7.27– 7.24(m,1H),6.95(d,J=8.8Hz,2H),6.72(d,J=3.6Hz,1H),6.61(d,J=3.6Hz,1H),3.85(s,3H); 13 C NMR (CDCl3, 101MHz): δ159.0,153.4,152.6,130.9,128.7,127.1,125.2,123.9,123.5,114.1,107.2,105.6,55.3.

Claims

1. A method for synthesizing 1,4-dione from enamide and α-carbonyl oxysulfonium ylide via photoredox catalysis, characterized in that, The method is as follows: under nitrogen protection, irradiated with blue light, and under the action of a photocatalyst and a base, an enamide and an α-carbonylsulfonium ylide react in a solvent to obtain an enamide α-carbonylalkylated product, which is then hydrolyzed under acidic conditions to synthesize 1,4-dione in two steps.

2. The method for synthesizing 1,4-dione as described in claim 1, characterized in that, The photocatalyst is tris(2-phenylpyridine)iridium fac - Ir(ppy)3, 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile 4CzIPN, and ruthenium tripyridine chloride Ru(bpy)3Cl2 were used in amounts equal to 2% of the molar amount of the enamide.

3. The method for synthesizing 1,4-dione as described in claim 1, characterized in that, The alkali is: hexamethylphosphoramide, sodium dihydrogen phosphate dihydrate, and potassium phosphate, and its amount is 0.2-1 times that of the amide.

4. The method for synthesizing 1,4-dione as described in claim 1, characterized in that, The reaction solvents are: N,N-dimethylformamide, acetonitrile, dichloromethane, N,N-dimethylacetamide, and methanol.

5. The method for synthesizing 1,4-dione as described in claim 1, characterized in that, The molar ratio of enamide to α-carbonyl sulfonium oxide ylide was 1:2; the reaction conditions were: reaction temperature 30℃, duration 18 hours.

6. The method for synthesizing 1,4-dione as described in claim 1, characterized in that, The structural formula of the amide is Ar 1 It can be phenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-bi-, 3-fluorophenyl, or 3,4-dichlorophenyl.

7. The method for synthesizing 1,4-dione according to claim 1, characterized in that, The structural formula of α-carbonyl oxysulfonium ylide is as follows: Ar 2 It is phenyl, 4-isopropylphenyl, 4-methoxyphenyl or 2-thienyl.

8. The method for synthesizing 1,4-dione as described in claim 1, characterized in that, The hydrolysis conditions under acidic conditions are: reaction at 50°C for 12 hours in an anhydrous tetrahydrofuran solution of 2M hydrochloric acid.

9. The method for synthesizing 1,4-dione as described in claim 1, characterized in that, The structural formula of the synthesized 1,4-dione compound is as follows: Ar 1 It is phenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 4-biyl, 3-fluorophenyl, or 3,4-dichlorophenyl; Ar 2 It is phenyl, 4-isopropylphenyl, 4-methoxyphenyl or 2-thienyl.

10. An application of a 1,4-diketone compound synthesized by the method of claim 1, characterized in that, The 1,4-dione compound is used to synthesize furan or pyrrole.

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