A visible light-stimulated method for disassembling and synthesizing aryl ketone building blocks

Abstract

The present invention discloses a method for synthesizing aryl ketone building blocks by disassembling aryl ketones under visible light, wherein the OPC catalyst is 4CzIPN, 4CzTPN, 4CzPN, 3DPAFIPN, t-Bu-4CzIPN, Ph-4CzIPN, [Acr-Mes-Ph] + BF4 ‑ , [Acr‑Mes‑Me] + BF4 ‑ , Riboflavin. This invention utilizes OPC catalysts to achieve increased molecular value in a greener, low-carbon manner. The reaction utilizes widely available substrates, mild reaction conditions, simple and efficient operation, and inexpensive, readily available reagents. No additional additives are required, and there is no metal residue contamination. The reaction exhibits high chemo- and regio-selectivity. This reaction will provide a reference for research on the functionalization of carbon skeletons of carboxylic acid derivatives and is suitable for industrial production and large-scale market applications.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing aryl ketone building blocks by disassembling them under the influence of visible light. Background Art

[0002] For a long time, research in organic chemistry has focused on developing efficient, green, and low-carbon synthetic methods to construct molecular carbon-carbon bond skeletons and ultimately achieve molecular value-added (e.g., Chem. Rev. 2020, 120, 1788–1887; Chem. Rev. 2011, 111, 1215–1292). However, relatively little research has been conducted on achieving molecular value-added through disassembly functionalization of molecular skeletons. In recent years, methods for achieving molecular value-added through carbon-carbon bond activation have emerged. However, these research strategies primarily focus on transition metal catalysis (e.g., Chem. Rev. 2017, 117, 8864–8907; Chem. Rev. 2023, 123, 12313–12370). These research strategies struggle to achieve green and low-carbon goals and are therefore not easily commercialized, primarily due to disadvantages such as expensive transition metal catalysts, high metal residues, and harsh reaction conditions. Therefore, how to achieve the disassembly and functionalization of carbon skeletons in a green and low-carbon manner remains a challenging scientific problem that needs to be solved urgently.

[0003] With the development of photocatalytic research, a relatively green and low-carbon synthesis methodology has also emerged, that is, through photoinduced decarboxylation functionalization, the Csp 3 -Csp 2 The bond breaks, the reaction principle is as follows:

[0004]

[0005] The non-strained carbon skeleton functionalization of carboxylic acid derivatives, which are widely found in nature, is limited to cleavage at the α-position of the carboxyl group. However, functionalization of the carbon skeleton distal to the carboxyl group, such as at the β, γ, δ, and ε positions, to achieve value-added molecular structures, remains a challenging problem. This is primarily due to the physical distance between the carboxyl group and the distal reaction site, making it difficult to achieve with existing synthetic techniques. Furthermore, functionalization of the carbon skeleton distal to the carboxyl group can construct high-value-added aryl ketone building blocks. These aryl ketone-containing molecules are often found in bioactive molecules such as pharmaceuticals, such as Raloxifene, HDAC inhibitors, IDO inhibitors, and COX-2 inhibitors. Therefore, developing new synthetic technologies to overcome this challenge and achieve green and low-carbon construction of aryl ketone building blocks through a novel synthetic strategy is of great significance. Summary of the Invention

[0006] In order to solve the above technical problems, the present invention provides a method for synthesizing aryl ketone building blocks by disassembly induced by visible light. The method is a synthesis method based on the functionalization of the carboxylic acid distal carbon skeleton catalyzed by organic photocatalysis.

[0007] The present invention is achieved through the following technical solution: a method for disassembling and synthesizing aryl ketone building blocks promoted by visible light, characterized in that the reaction formula is:

[0008]

[0009] The OPC catalysts are 4CzIPN, 4CzTPN, 4CzPN, 3DPAFIPN, t-Bu-4CzIPN, Ph-4CzIPN, [Acr-Mes-Ph] + BF4 - 、[Acr-Mes-Me] + BF4 - , one of the Riboflavins.

[0010] The reaction principle of the present invention is as follows:

[0011]

[0012] The structural formula of OPC catalyst is:

[0013]

[0014] In the above scheme: the base is an organic base or an inorganic base.

[0015] In the above scheme: the base is one of triethylamine (TEA), TMG (tetramethylguanidine), NMM (N-methylmorpholine), lithium acetate (LiOAc), lithium carbonate (Li2CO3), sodium acetate (NaOAc), potassium bicarbonate (KHCO3), sodium hydroxide (NaOH), sodium phosphate (Na3PO4), sodium carbonate (Na2CO3), potassium tert-butoxide (t-BuK), potassium carbonate (K2CO3), potassium acetate (KOAc), potassium hydroxide (KOH), potassium thiocyanate (KSCN), cesium acetate (CsOAc), cesium hydroxide (CsOH), cesium carbonate (Cs2CO3), and cesium bicarbonate (CsHCO3).

[0016] In the above scheme, the solvent is one of acetone, N,N-dimethylformamide (DMF), 1,4-dioxane, N,N-dimethylacetamide (DMAc), trimethylacetonitrile (t-BuCN), dimethyl sulfoxide (DMSO), trifluorotoluene (PhCF3), ethanol (EtOH), n-hexane (Hexane), acetonitrile (MeCN), n-butanol ((1-BuOH), diethylene glycol dimethyl ether (Diglyme), and ethyl acetate.

[0017] In the above scheme: the R 1 One selected from cycloalkyl, aliphatic alkyl, alcohol, ester, aryl, heterocyclic aromatic, drug molecule, pesticide molecule or important fragment of natural product molecule;

[0018] The Ar fragment is selected from aromatic rings with different electrical groups, wherein the electrical group is one of hydrogen, cyano, alkoxy, halogen, chain alkyl, aryl, and heterocyclic aromatic groups;

[0019] n represents the number of atoms between the carboxyl group and the tertiary carbon atom;

[0020] R 2 is selected from one of amine fragments, carbon chain alkane fragments, aromatic hydrocarbon fragments or other heteroatom fragments. 2 、R 1 Other groups may also be used.

[0021] The specific operation steps are: dissolving the carboxylic acid substrate a, OPC catalyst and alkali in a solvent, mixing them evenly under oxygen protection, and then reacting them under visible light. After the reaction is completed, the mixture is diluted with ethyl acetate, filtered, and the solvent is evaporated to obtain the product.

[0022] In the above scheme, the wavelength of light can be set to 360nm-600nm.

[0023] In the above scheme, after evaporating the solvent, the target product is obtained by flash column chromatography using an ethyl acetate / petroleum ether (volume ratio) of 1:1 as the eluent. The OPC catalyst is added in an amount of 2%-5% of the molar amount of the substrate, and the base is added in a molar ratio of 1:2:1 to the substrate.

[0024] The present invention realizes the remote inert carbon skeleton Csp through a free radical migration mechanism. 3 -Csp 3 Bond rupture (the inert Csp 3 -Csp 3 The bond energy is large and it is almost difficult to break in the absence of tension. ), and then functionalization is carried out to achieve the green and low-carbon construction of aryl ketone building blocks.

[0025] This invention leverages OPC catalysts to achieve increased molecular value in a green and low-carbon manner. The reaction utilizes widely available substrates, mild reaction conditions, simple and efficient operation, and inexpensive, readily available reagents. No additional additives are required, and there is no metal residue contamination. The reaction exhibits high chemo- and regio-selectivity. This reaction will provide insights into the functionalization of carbon skeletons and is suitable for industrial production and large-scale market applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the NMR spectrum (partial) of b1.

[0027] Figure 2 This is the NMR spectrum of b1 (the other part).

[0028] Figure 3 This is the NMR spectrum (partial) of b2.

[0029] Figure 4 This is the NMR spectrum of b2 (the other part).

[0030] Figure 5 This is the NMR spectrum (partial) of b3.

[0031] Figure 6 This is the NMR spectrum of b3 (another part).

[0032] Figure 7 This is the NMR spectrum (partial) of b4.

[0033] Figure 8 This is the NMR spectrum of b4 (another part).

[0034] Figure 9 This is the NMR spectrum (partial) of b5.

[0035] Figure 10 This is the NMR spectrum of b5 (another part). DETAILED DESCRIPTION

[0036] The present invention will be further described below with reference to the embodiments.

[0037] Example 1:

[0038]

[0039] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 4CzIPN (2.0% of the substrate molar weight, 3.2 mg), and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio: 1:20) to obtain the target product, benzophenone (b1, 84% yield).

[0040] NMR characterization data:

[0041] 1 H NMR (500MHz, Chloroform-d) δ7.85–7.77(m,2H),7.62–7.56(m,1H),7.52–7.45(m,2H).

[0042] 13 C NMR (126MHz, Chloroform-d) δ196.79,137.62,132.43,130.07,128.29.

[0043] Example 2:

[0044]

[0045] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 4CzTPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio: 1:20) to obtain the target product, benzophenone (b1, 69% yield).

[0046] Example 3:

[0047]

[0048] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 4CzPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product, benzophenone (b1, 28% yield).

[0049] Example 4:

[0050]

[0051] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst t-Bu-4CzIPN (5.0% of the substrate molar weight, 12.4 mg), and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the crude product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product, benzophenone (b1, 75% yield).

[0052] Example 5:

[0053]

[0054] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst Ph-4CzIPN (5.0% of the substrate molar weight, 14 mg), and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product, benzophenone (b1, 40% yield).

[0055] Example 6:

[0056]

[0057] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst Riboflavin (5.0% of the substrate molar weight, 3.8 mg), and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product, benzophenone (b1, 23% yield).

[0058] Example 7:

[0059]

[0060] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst [Acr-Mes-Me] + (BF4) - (5.0% of the substrate molar weight, 5.1 mg) and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product. Subsequently, flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) was performed to obtain the target product, benzophenone (b1, 32% yield).

[0061] Example 8:

[0062]

[0063] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst [Acr-Mes-Ph] + (BF4) - (5.0% of the substrate molar weight, 5.7 mg) and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product. Subsequently, flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) was performed to obtain the target product, benzophenone (b1, 51% yield).

[0064] Example 9:

[0065]

[0066] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst TPT (5.0% of the substrate molar weight, 4.0 mg), and cesium carbonate (0.4 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product, benzophenone b1 (trace yield).

[0067] Example 10:

[0068]

[0069] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 3DPAFIPN (5.0% of the substrate molar weight, 6.5 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the crude product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio: 1:20) to obtain the desired product, benzophenone (b1, 86% yield).

[0070] Example 11:

[0071]

[0072] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 360 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio: 1:20) to obtain the target product, benzophenone (b1, 60% yield).

[0073] Example 12:

[0074]

[0075] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and potassium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio: 1:20) to obtain the desired product, benzophenone (b1, 88% yield).

[0076] Example 13:

[0077]

[0078] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and potassium carbonate (0.3 mmol) were placed in N,N-dimethylacetamide (DMAc, 1 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product, benzophenone (b1, 68% yield).

[0079] Example 14:

[0080]

[0081] Compound a1 (0.20 mmol, 45.2 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.2 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio: 1:20) to obtain the target product, benzophenone (b1, 80% yield).

[0082] Example 15:

[0083]

[0084] Compound a2 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b2 (92% yield).

[0085] NMR characterization data:

[0086] 1 H NMR (500MHz, Chloroform-d) δ7.78(d,J=6.9Hz,2H),7.72(d,J=8.2Hz,2H),7.60–7.55(m,1H),7.48(t,J=7.7Hz,2H),7.28(d,J=7.9Hz,2H),2.44(s,3H).

[0087] 13 C NMR (126MHz, Chloroform-d) δ196.55,143.26,137.97,134.90,132.17,130.33,129.95,128.99,128.22,21.66.

[0088] Example 16:

[0089]

[0090] Compound a3 (0.20 mmol, 48.8 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b3 (86% yield).

[0091] NMR characterization data:

[0092] 1H NMR (500MHz, Chloroform-d) δ7.85(dd,J=8.6,5.5Hz,2H),7.80–7.74(m,2H),7.59(t,J=7.5Hz,1H),7.49(t,J=7.6Hz,2H),7.16(t,J=8.6Hz,2H).

[0093] 13 C NMR(126MHz,Chloroform-d)δ195.29,166.41(J C-F =253.26Hz),137.52,133.82(J C-F =3.78Hz),132.68(J C-F =10.08Hz),132.49,129.89,128.37,115.47(J C-F =22.68Hz).

[0094] Example 17:

[0095]

[0096] Compound a4 (0.20 mmol, 55.2 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b4 (78% yield).

[0097] NMR characterization data:

[0098] 1 H NMR(500MHz,Chloroform-d)δ8.12–8.07(m,1H),8.01(dt,J=8.1,1.0Hz,1H) ,7.95–7.91(m,1H),7.89–7.85(m,2H),7.62–7.57(m,2H),7.56–7.44(m,5H).

[0099] 13C NMR(126MHz,Chloroform-d)δ198.05,138.34,136.37,133.73,133.23,131.2 7,130.97,130.42,128.45,128.41,127.77,127.26,126.46,125.71,124.34.

[0100] Example 18:

[0101]

[0102] Compound a5 (0.20 mmol, 48.9 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated and stirred under 460 nm light. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b5 (89% yield).

[0103] NMR characterization data:

[0104] 1 H NMR(500MHz,Chloroform-d)δ7.84(d,J=8.4Hz,2H),7.63–7.50(m,3H),7.50–7.45(m,2H),7.29–7.24(m,1H),7.16(ddd,J=9.6,8.3,1.0Hz,1H).

[0105] 13 C NMR(126MHz,Chloroform-d)δ193.50,161.11(J C-F =253.26Hz),137.41,133.42,133.07(J C-F =8.82Hz),130.77(J C-F =3.78Hz),129.83,128.47,127.06(J C-F =15.12Hz),124.29(J C-F =3.78Hz),116.29(J C-F =21.42Hz).

[0106] Example 19:

[0107]

[0108] Compound a6 (0.20 mmol, 68.2 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (97% yield).

[0109] Example 20:

[0110]

[0111] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (90% yield).

[0112] Example 21

[0113]

[0114] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and triethylamine (TEA, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (25% yield).

[0115] Example 22

[0116]

[0117] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and NMM (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (trace yield).

[0118] Example 23

[0119]

[0120] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and lithium carbonate (Li2CO3, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (45% yield).

[0121] Example 24

[0122]

[0123] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and sodium acetate (NaOAc, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (61% yield).

[0124] Example 25

[0125]

[0126] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and sodium phosphate (Na3PO4, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated and stirred under 460 nm light. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (52% yield).

[0127] Example 26

[0128]

[0129] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and potassium bicarbonate (KHCO3, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was protected with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (44% yield).

[0130] Example 27

[0131]

[0132] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and potassium carbonate (K2CO3, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (88% yield).

[0133] Example 28

[0134]

[0135] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and potassium tert-butoxide (t-BuOK, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (57% yield).

[0136] Example 29

[0137]

[0138] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and potassium hydroxide (KOH, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (36% yield).

[0139] Example 30

[0140]

[0141] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium hydroxide (CsOH, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b1 (46% yield).

[0142] Example 31

[0143]

[0144] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium acetate (CsOAc, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the crude product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (50% yield).

[0145] Example 32

[0146]

[0147] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium bicarbonate (CsHCO3, 0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (84% yield).

[0148] Example 33

[0149]

[0150] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in dichloromethane (DCM, 2 mL). After the addition, the reaction vessel was protected with 1 atm of oxygen, and the reaction mixture was then irradiated and stirred under 460 nm light. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b1 (trace yield).

[0151] Example 34

[0152]

[0153] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetone (2 ml). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b1 (75% yield).

[0154] Example 35

[0155]

[0156] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in N,N-dimethylformamide (DMF, 2 ml). After the addition, the reaction vessel was protected with 1 atm of oxygen. The reaction mixture was then irradiated with 460 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b1 (85% yield).

[0157] Example 36

[0158]

[0159] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in trimethylacetonitrile (t-BuCN, 2 ml) as solvent. After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b1 (57% yield).

[0160] Example 37

[0161]

[0162] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in dimethyl sulfoxide (DMSO, 2 ml) as solvent. After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated and stirred under 460 nm light. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b1 (70% yield).

[0163] Example 38

[0164]

[0165] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in diethylene glycol dimethyl ether (Diglyme, 2 ml) as solvent. After the addition, the reaction vessel was protected with 1 atm of oxygen, and the reaction mixture was then irradiated and stirred under 460 nm light. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The filtrate was desolventized on a rotary evaporator to obtain the initial product, which was then subjected to flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b1 (70% yield).

[0166] Example 39

[0167]

[0168] Compound a7 (0.20 mmol, 48.0 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in aqueous solution (H2O, 2 ml). After the addition, the reaction vessel was shielded with 1 atm of oxygen, and the reaction mixture was then irradiated with 460 nm light with stirring. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then subjected to flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the target product b1 (trace yield).

[0169] Example 40:

[0170]

[0171] Compound a3 (0.20 mmol, 48.8 mg), OPC catalyst 4CzIPN (5.0% of the substrate molar weight, 7.9 mg), and cesium carbonate (0.3 mmol) were placed in acetonitrile (2 mL). After the addition, the reaction vessel was shielded with 1 atm of oxygen. The reaction mixture was then irradiated with 600 nm light and stirred. After 24 hours, the reaction mixture was diluted with ethyl acetate and filtered through celite, and the filtrate was collected. The solvent was removed from the filtrate by rotary evaporation to obtain the initial product, which was then purified by flash column chromatography (eluent: ethyl acetate / petroleum ether, volume ratio, 1:20) to obtain the desired product b3 (50% yield).

[0172] NMR characterization data:

[0173] 1 H NMR (500MHz, Chloroform-d) δ7.85(dd,J=8.6,5.5Hz,2H),7.80–7.74(m,2H),7.59(t,J=7.5Hz,1H),7.49(t,J=7.6Hz,2H),7.16(t,J=8.6Hz,2H).

[0174] 13 C NMR(126MHz,Chloroform-d)δ195.29,166.41(J C-F =253.26Hz),137.52,133.82(J C-F =3.78Hz),132.68(J C-F =10.08Hz),132.49,129.89,128.37,115.47(J C-F =22.68Hz).

[0175] It will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing aryl ketone building blocks by disassembly assisted by visible light, characterized in that: The reaction formula is: The OPC catalysts are 4CzIPN, 4CzTPN, 4CzPN, 3DPAFIPN, t-Bu-4CzIPN, Ph-4CzIPN, [Acr-Mes-Ph] + BF4 - 、[Acr-Mes-Me] + BF4 - , one of Riboflavin; a compound is: The base is one of triethylamine, TMG, lithium acetate, lithium carbonate, sodium acetate, potassium bicarbonate, sodium hydroxide, sodium phosphate, sodium carbonate, potassium tert-butoxide, potassium carbonate, potassium acetate, potassium hydroxide, cesium acetate, cesium hydroxide, cesium carbonate, and cesium bicarbonate; The solvent is one of acetone, N,N-dimethylformamide, N,N-dimethylacetamide, trimethylacetonitrile, dimethyl sulfoxide, ethanol, acetonitrile, n-butanol, and diethylene glycol dimethyl ether.

2. The method for synthesizing aryl ketone building blocks by visible light disassembly according to claim 1, characterized in that: The specific operation steps are: dissolving the carboxylic acid substrate a, OPC catalyst and alkali in a solvent, mixing them evenly under oxygen protection, and then reacting them under visible light. After the reaction is completed, the mixture is diluted with ethyl acetate, filtered, and the solvent is evaporated to obtain the product.

3. The method of claim 2 wherein: The wavelength of visible light is 360nm-600nm.

4. The method of claim 3 wherein: After evaporating the solvent, the target product was obtained by flash column chromatography. The eluent used for column chromatography was ethyl acetate / petroleum ether in a volume ratio of 1:

1.

5. The method of claim 4 , wherein: The amount of the OPC catalyst added is 2%-5% of the molar amount of the substrate, and the molar ratio of the base added to the substrate is 1-2:1.

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