A method for direct decarboxylative hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts

Abstract

The application relates to a method for directly decarboxylating and hydrogenating alkyl carboxylic acid without transition metal and photocatalyst, and relates to the field of organic compound synthesis. The method is as follows: under an argon atmosphere, alkyl carboxylic acid, N-hydroxy phthalimide compound, phosphine catalyst, hydrogen atom transfer reagent and alkaline substance are placed in a solvent, and under visible light driving, radical-mediated decarboxylation and hydrogenation are carried out to synthesize a series of alkane compounds. The reaction condition is mild, the operation is simple, the method has wide substrate range and good functional group tolerance. In addition, the method can realize the late-stage modification of complex natural products and drug molecules, and further proves the practicability of the method. More importantly, the application innovatively uses stable, low-toxicity and cheap alkyl carboxylic acid to directly realize the synthesis of hydrocarbon products, and the alkyl carboxylic acid does not need to be pre-activated by additional steps, and the method does not need the participation of transition metal and photocatalyst, and is more in line with the concept of modern green chemistry.

Description

Technical Field

[0001] This invention relates to the field of organic compound synthesis, and in particular to a method for the direct decarboxylation and hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts. Background Technology

[0002] Alkanes are not only intermediates in organic synthesis but also essential raw materials in chemical synthesis. They also have significant applications in fuels, chemical feedstocks, and pharmaceuticals (Chem. Commun., 2021, 57, 9956–9967). Therefore, developing efficient methods for synthesizing alkanes has always been a research hotspot in the field of organic chemistry.

[0003] Alkyl carboxylic acids possess advantages such as stability, low cost, non-toxicity, and abundance, making them important synthetic raw materials in the field of organic synthesis (ACS Catal., 2021, 11, 1640-1683; ACS Med. Chem. Lett., 2022, 13, 1413-1420). Therefore, decarboxylation hydrogenation based on alkyl carboxylic acids is one of the important strategies for synthesizing alkanes. Currently, decarboxylation hydrogenation strategies can be divided into indirect decarboxylation and direct decarboxylation. Indirect decarboxylation strategies require the pre-activation of the carboxylic acid to thiohydroxamic esters, N-hydroxyphthalimide esters, etc., followed by free radical-mediated decarboxylation hydrogenation (Chem. Soc. Chem. Commun. 1983, 939-941; Angew. Chem. Int. Ed. 2016, 55, 1–7). Direct decarboxylation strategies primarily rely on single-electron oxidation via photocatalysis and photo-induced transition metal-catalyzed ligand-to-metal charge transfer (Am. Chem. Soc. 2015, 137, 11340-11348; Angew. Chem. Int. Ed. 2023, 62, e202213055). However, these strategies require pre-activation of the carboxylic acid, highly toxic reagents, and photocatalysts or transition metal catalysts, significantly increasing production costs. Therefore, to align with modern green chemistry principles and enhance product economics, developing hydrogenation methods for the direct decarboxylation of alkyl carboxylic acids without the involvement of transition metals and photocatalysts is of paramount importance. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a method for the direct decarboxylation hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts in order to solve the above-mentioned technical problems.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] A method for the direct decarboxylation hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts, wherein the molar amount of the alkyl carboxylic acid is 50% to 200%. The method involves placing the alkyl carboxylic acid, an N-hydroxyphthalimide compound, a phosphine catalyst, a hydrogen atom transfer reagent, and a basic substance in a solvent under an argon atmosphere, and then, under visible light irradiation, undergoing radical-mediated decarboxylation hydrogenation to obtain an alkane compound having the following general formula (II).

[0007]

[0008] Wherein, R is a substituted or unsubstituted C1-C20 alkyl or a substituted or unsubstituted C3-C20 cycloalkyl;

[0009] When the substituted or unsubstituted groups have substituents, the substituents are ester groups, halogens, methoxy groups, amides, or natural product molecular fragments, and the natural product molecular fragments are any one of ibuprofen, isocolic acid, and lithocholic acid.

[0010] The photocatalyst is at least one of 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, basic methylene blue trihydrate, bis[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(tetra-tert-butylpyridine)]iridium di(hexafluorophosphate), fac-tris(2-phenylpyridine)iridium, tris(2,2'-bipyridine)ruthenium di(hexafluorophosphate), and disodium eosin Y.

[0011] The phosphine catalyst is at least one selected from 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene), 1,4-bis(diphenylphosphine)butane, 1,3-bis(diphenylphosphine)propane, 1,2-bis(diphenylphosphine)ethane, and triphenylphosphine, with 1,3-bis(diphenylphosphine)propane being preferred.

[0012] The hydrogen atom transfer reagent is selected from at least one of diphenyl disulfide, p-toluene disulfide, p-methylbenzylthiophenol, 2,4,6-triisopropylbenzylthiophenol, methyl mercaptoacetate, and triisopropylsilanethiol, with diphenyl disulfide being preferred.

[0013] The alkaline substance is at least one selected from sodium bicarbonate, potassium carbonate, dipotassium hydrogen phosphate, 4-dimethylaminopyridine, 2,6-dimethylpyridine, and triethylamine, with sodium bicarbonate being preferred.

[0014] The solvent is at least one selected from N,N-dimethylacetamide, acetonitrile, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, ethyl acetate, trifluorotoluene, and dimethyl sulfoxide, with N,N-dimethylacetamide being preferred.

[0015] The N-hydroxyphthalimide compound is at least one of N-hydroxyphthalimide, N-hydroxytetrachlorophthalimide, 2-hydroxy-5-methylisoindoline-1,3-dione, and 4-bromo-2-hydroxy-1(H)-phthalimide, with N-hydroxyphthalimide being preferred.

[0016] The wavelength range of the visible light irradiation includes 390–520 nm; the reaction temperature range includes 15–60 °C; and the reaction time range includes 12–48 hours, wherein the wavelength of the visible light irradiation is preferably 450–455 nm, the reaction temperature is preferably 30 °C, and the reaction time is preferably 24 hours.

[0017] This method provides a direct synthesis of alkane compounds from alkyl carboxylic acids. The reaction conditions are mild, the operation is simple, and it exhibits a broad substrate range and good functional group tolerance. Furthermore, this method can achieve late-stage modification of complex natural products and drug molecules, further demonstrating its practicality. More importantly, this invention innovatively uses stable, low-toxicity, inexpensive, and readily available alkyl carboxylic acids to directly synthesize alkane compounds without requiring additional pre-activation steps, and without the involvement of transition metals or photocatalysts, thus aligning more closely with the principles of modern green chemistry. Attached Figure Description

[0018] Figure 1 The image shows the 1H NMR spectrum of N-propylphthalimide prepared in Example 1 of this invention.

[0019] Figure 2 The image shows the carbon NMR spectrum of N-propylphthalimide prepared in Example 1 of this invention.

[0020] Figure 3 The 1H NMR spectrum of 2-(cyclohexylmethyl)isoindoline-1,3-dione prepared in Example 10 of the present invention.

[0021] Figure 4 The carbon NMR spectrum of 2-(cyclohexylmethyl)isoindoline-1,3-dione prepared in Example 10 of the present invention.

[0022] Figure 5 The 1H NMR spectrum of 4-bromocyclopropylbenzene prepared in Example 13 of this invention is shown.

[0023] Figure 6 The image shows the carbon NMR spectrum of 4-bromocyclopropylbenzene prepared in Example 13 of this invention.

[0024] Figure 7The proton NMR spectrum of (3R,8R,9S,10S,13R,14S,17R)-17-[(R)-sec-butyl]-10,13-dimethyl-hexadecylhydro-1H-cyclopenta[a]phenanthrene-3-ol prepared in Example 18 of the present invention.

[0025] Figure 8 The carbon NMR spectrum of (3R,8R,9S,10S,13R,14S,17R)-17-[(R)-sec-butyl]-10,13-dimethyl-hexadecylhydro-1H-cyclopenta[a]phenanthrene-3-ol prepared in Example 18 of the present invention. Detailed Implementation

[0026] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0027] Example 1:

[0028]

[0029] Compound 1a (0.2 mmol, 47 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. (The product was a white solid, totaling 32.2 mg, with a yield of 85%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0030] The target product 2a obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1H NMR (400MHz, CDCl3): δ7.82-7.78(m,2H),7.70-7.65(m,2H),3.63-3.60(m,2H),1.72-1.63(m,2H),0.91(t,J=7.4Hz,3H); 13 C{ 1 ¹H NMR (100MHz, CDCl₃): δ 168.4, 133.7, 132.1, 123.0, 39.5, 21.8, 11.2 ppm. Its ¹H NMR and ¹³C NMR spectra are attached. Figure 1 and 2 As shown.

[0031] Example 2:

[0032]

[0033] Compound 1b (0.2 mmol, 36 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2b. (The product was a colorless oil, totaling 22.9 mg, with a yield of 84%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0034] The target product 2b obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.16-7.14(m,2H),6.88-6.85(m,2H),3.81(s,3H),2.63(q,J=7.6Hz,2H),1.24(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ157.6,136.4,128.7,113.7,55.2,27.9,15.9ppm.

[0035] Example 3:

[0036]

[0037] Compound 1c (0.2 mmol, 33 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2c. (The product was a white solid, totaling 18.9 mg, with a yield of 77%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0038] The target product 2c obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.10-7.06(m,2H),6.80-6.76(m,2H),4.98(s,1H),2.60(q,J=7.6Hz,2H),1.22(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ153.3, 136.6, 128.9, 115.1, 27.9, 15.8ppm.

[0039] Example 4:

[0040]

[0041] Compound 1d (0.2 mmol, 48 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2d. (The product was a colorless oil, totaling 33.2 mg, with a yield of 84%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0042] The target product obtained by the above synthesis method was subjected to 1H and 1C NMR spectra on 2d, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.36-7.28(m,4H),7.25-7.21(m,1H),7.00(d,J=8.0Hz,2H),6.80(d,J=8.1Hz,2H),4.95(s,2H),2.21(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ156.9,137.3,130.1,129.9,128.5,127.8,127.4,114.7,70.1,20.5ppm.

[0043] Example 5:

[0044]

[0045] Compound 1e (0.2 mmol, 50 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2e. (The product was a white solid, totaling 35.4 mg, with a yield of 85%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0046] The target product 2e obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.15 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.1 Hz, 2H), 6.41 (s, 1H), 2.20 (s, 3H), 1.43 (s, 9H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ152.9,135.7,132.4,129.4,118.7,80.2,28.3,20.6ppm.

[0047] Example 6:

[0048]

[0049] Compound 1f (0.2 mmol, 44 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2f. (The product was a colorless oil, totaling 29.6 mg, with a yield of 83%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0050] The target product 2f obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.39-7.30(m,5H),5.13(s,2H),2.35(t,J=7.4Hz,2H),1.73-1.64(m,2H),0.96(t,J=7.4Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ173.5,136.1,128.5,128.1,66.0,36.2,18.4,13.6ppm.

[0051] Example 7:

[0052]

[0053] In a 10 mL Schlenk reaction tube (capacity 10 mL, ground joint 14 / 20), 1 g (0.2 mmol, 67 mg) of compound, N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added. The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain 2 g of product. (The product was a white solid, totaling 43.5 mg, with a yield of 74%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0054] The target product (2g) obtained by the above synthesis method was subjected to proton and carbon NMR spectra. The test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.38-7.30(m,5H),5.22-5.07(m,3H),4.33-4.28(m,1 H),1.89-1.82(m,1H),1.72-1.65(m,1H),1.43(s,9H),0.90(t,J=7.5Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ172.6,155.3,135.4,128.5,128.3,128.2,79.7,66.8,54.6,28.2,25.8,9.5ppm.

[0055] Example 8:

[0056]

[0057] In a 10 mL Schlenk reaction tube (capacity 10 mL, ground joint 14 / 20), compound 1h (0.2 mmol, 38 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added. The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2h. (The product was a white solid, totaling 25.2 mg, with a yield of 87%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0058] The target product obtained by the above synthesis method was subjected to 1H and 1C NMR spectra after 2 hours. The test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.69(m,1H),7.53(d,J=7.8Hz,1H),7.24-7.22(m,1H),7.12-7.08( m,1H),7.05-7.01(m,1H),6.85-6.84(m,1H),2.71(q,J=7.5Hz,2H),1.25(t,J=7.5Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ136.4,127.4,121.8,120.4,119.0,118.9,118.8,111.0,18.3,14.4ppm.

[0059] Example 9:

[0060]

[0061] Compound 1i (0.2 mmol, 46 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2i. (The product was a colorless oil, totaling 27.1 mg, with a yield of 73%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0062] The target product 2i obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ3.36-3.33(m,4H),1.58-1.53(m,2H),1.50-1.48(m,4H),1.45(s,9H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ154.9,79.0,44.6,28.4,25.7,24.5ppm.

[0063] Example 10:

[0064]

[0065] Compound 1j (0.2 mmol, 57 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2j. (The product was a white solid, totaling 44.7 mg, with a yield of 92%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0066] The target product 2j obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.82-7.79(m,2H),7.69-7.67(m,2H),3.50(d,J=7.3Hz,2H),1.78-1.62(m,6H),1.20-1.14(m,3H),1.04-0.94(m,2H); 13 C{ 1 ¹H NMR (100MHz, CDCl₃): δ 168.6, 133.8, 132.0, 123.1, 44.0, 36.9, 30.7, 26.2, 25.6 ppm. Its ¹H NMR and ¹³C NMR spectra are attached. Figure 3 and 4 As shown.

[0067] Example 11:

[0068]

[0069] Compound 1k (0.2 mmol, 46 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2k. (The product was a white solid, totaling 29.1 mg, with a yield of 78%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0070] The target product 2k obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.71-7.68(m,2H),7.57(s,1H),7.34(d,J=8.4Hz,1H), 7.16-7.13(m,2H),3.93(s,3H),2.80(q,J=7.6Hz,2H),1.33(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ157.1,139.4,132.9,129.2,128.9,127.5,126.7,125.4,118.6,105.6,55.3,28.8,15.6ppm.

[0071] Example 12:

[0072]

[0073] Compound 1L (0.2 mmol, 49 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2L. (The product was a colorless oil, totaling 22.1 mg, with a yield of 55%, and petroleum ether was used as the eluent.)

[0074] The target product 2l obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.57(d,J=7.7Hz,2H),7.46(t,J=7.6Hz,2H),7.37(t,J =7.7Hz,2H),7.08-7.01(m,2H),2.71(q,J=7.7Hz,2H),1.30(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ160.9,158.5,145.92,145.85,135.94,135.93,130.5,130.4,128. 94,128.92,128.4,127.4,126.3,126.1,123.84,123.81,115.5,115.2,28.4,28.3,15.2ppm.

[0075] Example 13:

[0076]

[0077] In a 10 mL Schlenk reaction tube (capacity 10 mL, ground joint 14 / 20), compound 1m (0.2 mmol, 39 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added. The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2m. (The product was a white solid, totaling 25.2 mg, with a yield of 84%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0078] The target product 2m obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ2.52 (s, 2H), 2.07-1.91 (m, 12H); 13 C{ 1 ¹H NMR (100MHz, CDCl₃): δ 218.4, 46.9, 39.2, 36.2, 27.4 ppm. Its ¹H NMR spectrum and ¹H NMR spectrum are attached. Figure 5 and 6 As shown.

[0079] Example 14:

[0080]

[0081] Compound 1n (0.2 mmol, 48 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2n. (The product was a colorless oil, totaling 17.4 mg, with a yield of 44%. The eluent was petroleum ether.)

[0082] The target product 2n obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.36 (d, J = 8.1Hz, 2H), 6.94 (d, J = 8.1Hz, 2H), 1.89-1.82 (m, 1H), 0.99-0.94 (m, 2H), 0.68-0.64 (m, 2H); 13 C{ 1 H} NMR (100MHz, CDCl3): δ143.0, 131.2, 127.4, 118.8, 15.0, 9.3ppm.

[0083] Example 15:

[0084]

[0085] Compound 1o (0.2 mmol, 49 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2o. (The product was a colorless oil, totaling 20.6 mg, with a yield of 52%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0086] The target product 2o obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ4.03 (s, 2H), 2.66 (t, J = 12.9Hz, 2H), 1.58 (d, J = 13.7Hz, 2H),1.51-1.47(m,1H),1.44(s,9H),1.11-1.02(m,2H),0.92(d,J=6.5Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ154.9,79.1,44.0,34.0,30.9,28.4,21.9ppm.

[0087] Example 16:

[0088]

[0089] Compound 1p (0.2 mmol, 41 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2p. (The product was a colorless oil, totaling 16 mg, with a yield of 49%, and petroleum ether was used as the eluent.)

[0090] The target product 2p obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.13-7.11(m,2H),7.08-7.06(m,2H),2.64(q,J=7.6Hz,2H),2 .46(d,J=7.1Hz,2H),1.91-1.81(m,1H),1.24(t,J=7.6Hz,3H),0.92(d,J=6.6Hz,6H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ141.4,138.9,129.0,127.5,45.0,30.3,28.4,22.4,15.6ppm.

[0091] Example 17:

[0092]

[0093] Compound 1q (0.2 mmol, 54 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2q. (The product was a white solid, totaling 30.6 mg, with a yield of 68%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0094] The target product 2q obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ8.03-8.02(m,1H),7.90(dd,J=7.6,1.4Hz,1H),7.55-7.51(m,1H),7.47-7.43(m ,1H),7.34(dd,J=7.5,1.3Hz,1H),7.29-7.25(m,1H),6.94(d,J=8.3Hz,1H),5.15(s,2H),2.34(s,3H); 13 C{ 1 H}NMR (100MHz, DMSO): δ191.1,159.3,140.5,136.4,135.7,132.6,131.5,131.4,129.4,129.1,127.7,125.0,120.4,73.6,20.4ppm.

[0095] Example 18:

[0096]

[0097] Compound 1r (0.2 mmol, 75 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2r. (The product was a white solid, totaling 45.4 mg, with a yield of 68%. The eluent was ethyl acetate:petroleum ether = 1:1).

[0098] The target product 2r obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, DMSO): δ3.65-3.57(m,1H),1.98-1.94(m,1H),1.87-1.74(m,4H),1.68-1.47(m,5H) ),1.44-1.21(m,12H),1.13-0.99(m,6H),0.91-0.88(m,5H),0.81(t,J=7.4Hz,3H),0.63(s,3H); 13 C{ 1 ¹H NMR (100MHz, DMSO): δ 71.8, 56.5, 55.8, 42.6, 42.1, 40.5, 40.2, 37.0, 36.4, 35.8, 35.4, 34.6, 30.5, 28.3, 28.2, 27.2, 26.4, 24.2, 23.4, 20.8, 18.0, 12.0, 10.3 ppm. Its ¹H NMR and ¹³C NMR spectra are attached. Figure 7 and 8 As shown.

[0099] Example 19:

[0100]

[0101] Compound 1S (0.2 mmol, 72 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2S. (The product was a yellow oil, totaling 51.6 mg, with a yield of 82%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0102] The target product 2s obtained by the above synthesis method was subjected to proton and carbon NMR spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.65-7.63(m,2H),7.47-7.45(m,2H),6.93-6.90(m,2H),6.68-6.65(m,1H),3.85(s,3H),2.32(s,3H),2.20(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ168.1,155.9,138.8,134.3,133.7,131.9,131.0,130.8,128.9,115.3,114.9,111.1,101.2,55.6,13.2,8.7ppm.

[0103] Conditional optimization

[0104] Reaction

[0105]

[0106] Examples 20-27

[0107] Compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (0.16 mmol, 93 mg), 4-dimethylaminopyridine (0.24 mmol, 29 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground glass joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of the corresponding solvent was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific solvents used in the reaction and the yields are shown in Table 4, numbered 20–27.

[0108] Table 1: Effect of different types of solvents on the decarboxylation hydrogenation yield of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a.

[0109]

[0110] By comparing the test results of each embodiment in Table 1, it can be seen that when N,N-dimethylacetamide is used as a solvent, the yield of the decarboxylation product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, reaching 40%.

[0111] Examples 28-33

[0112] In a 10 mL Schlenk reaction tube (capacity 10 mL, ground glass joint 14 / 20), compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (0.16 mmol, 93 mg), a basic substance (0.24 mmol), and diphenyl disulfide (0.02 mmol, 4 mg) were added. The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The different types of basic substances and their yields in the specific reactions are shown in Table 2, numbered 28–33.

[0113] Table 2: Effects of different types of bases on the decarboxylation hydrogenation yield of 1a of 4-(1,3-dioxoisoindol-2-yl)butyric acid.

[0114]

[0115] By comparing the test results of each embodiment in Table 2, it can be seen that when sodium bicarbonate is used as the base, the yield of the decarboxylation product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, reaching 62%.

[0116] Examples 34-38

[0117] Compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), phosphine catalyst (0.16 mmol or 0.32 mmol), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The different types of phosphine catalysts and yields for the specific reactions are shown in Table 3, numbered 34–38.

[0118] Table 3: Effect of different types of phosphine catalysts on the decarboxylation hydrogenation yield of 1a of 4-(1,3-dioxoisoindol-2-yl)butyric acid.

[0119]

[0120] By comparing the test results of each example in Table 3, it can be seen that when 1,3-bis(diphenylphosphine)propane is used as a phosphine catalyst, the yield of the decarboxylation hydrogenation product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, reaching 69%.

[0121] Examples 39-44

[0122] Compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and hydrogen transfer reagent (0.02 mmol) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The different types of hydrogen atom transfer reagents and yields for the specific reactions are shown in Table 4, numbered 39–44.

[0123] Table 4: Effect of different types of hydrogen atom transfer reagents on the decarboxylation hydrogenation yield of 1a of 4-(1,3-dioxoisoindol-2-yl)butyric acid.

[0124]

[0125] By comparing the test results of each embodiment in Table 4, it can be seen that when diphenyl disulfide is used as the hydrogen atom transfer reagent, the yield of the decarboxylation hydrogen product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, reaching 69%.

[0126] Examples 45-50

[0127] Compound 1a (0.2 mmol, 47 mg), photocatalyst (0.012 mmol or 0.002 mmol), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific photocatalysts and yields for the reactions are shown in Table 5, with the corresponding numbers 45–50.

[0128] Table 5: Effects of different types of photocatalysts on the decarboxylation hydrogenation yield of 1a of 4-(1,3-dioxoisoindol-2-yl)butyric acid.

[0129]

[0130] By comparing the test results of each embodiment in Table 5, it can be seen that when basic methylene blue trihydrate is used as the photocatalyst, the yield of the decarboxylation product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, reaching 81%.

[0131] Examples 51-56

[0132] Compound 1a (0.2 mmol, 47 mg), basic methylene blue trihydrate (0.012 mmol, 5 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (wavelength) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific wavelengths and yields of different types of reactions are shown in Table 6, with corresponding numbers 51 to 56.

[0133] Table 6: Effect of different wavelengths on the decarboxylation hydrogenation yield of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a.

[0134]

[0135] By comparing the detection results of each embodiment in Table 6, it can be seen that when a wavelength of 450-455 nm is used, the yield of the decarboxylation product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, reaching 81%.

[0136] Examples 57-61

[0137] Compound 1a (0.2 mmol, 47 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphine)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 2 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 10 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific control and yield of different species are shown in Table 7, corresponding to numbers 57–61.

[0138] Table 7: Effects of different types of control experiments on the decarboxylation hydrogenation yield of 1a of 4-(1,3-dioxoisoindol-2-yl)butyric acid.

[0139]

[0140] By comparing the test results of each embodiment in Table 7, it can be seen that the yield of the decarboxylation product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a without photocatalyst is the highest, reaching 85%, which is equal to the yield with photocatalyst. Therefore, the product without photocatalyst is selected.

[0141] Example 63, Preparation of N-propylphthalimide (2a, 1 mmol reaction)

[0142]

[0143] Compound 1a (1 mmol, 233 mg), N-hydroxyphthalimide (1 mmol, 163 mg), 1,3-bis(diphenylphosphine)propane (0.8 mmol, 330 mg), sodium bicarbonate (1.2 mmol, 101 mg), and diphenyl disulfide (0.1 mmol, 21.8 mg) were added to a 50 mL Schlenk reaction tube (10 mL capacity, ground joint 14 / 20). The air in the tube was completely purged three times with argon, and then 10 mL of N,N-dimethylacetamide was added under an argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450–455 nm) illumination. After the reaction was complete, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3 × 15 mL). The combined organic phases were then concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. (The product was a white solid, totaling 153.5 mg, with a yield of 81%. The eluent was ethyl acetate:petroleum ether = 1:10).

[0144] Example 64

[0145]

[0146] In Example 64, 2.0 equivalents of tetramethylpiperidine nitride were added as a free radical scavenger, and the yield of the target product 2a was 0%. Experiments showed that the reaction did indeed involve a free radical reaction process.

[0147] Example 65

[0148]

[0149] In Example 64, 1.0 equivalent of N-tert-butoxycarbonyl-cyclopropylglycine was added to the reaction, and the yield of the radical-induced ring-opening product was 32%. Experiments further demonstrate that the reaction indeed proceeds via a radical reaction process.

[0150] Based on the above embodiments, this invention provides a method for the direct decarboxylation hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts. This method involves placing alkyl carboxylic acids, N-hydroxyphthalimide compounds, a phosphine catalyst, a hydrogen transfer reagent, and a basic substance in a solvent under an argon atmosphere. Under visible light, free radical-mediated decarboxylation hydrogenation occurs, synthesizing a series of alkane compounds. Specific examples verify the effects of different phosphine catalysts, hydrogen transfer reagents, basic substances, organic solvents, and different wavelengths of light on the yield of the reaction products. While achieving the objectives of this invention and obtaining the technical solution, this invention also reveals the optimal selection of the phosphine catalyst, hydrogen transfer reagent, basic substance, organic solvent, and different wavelengths of light, possessing strong theoretical and practical value. This invention innovatively uses stable, low-toxicity, inexpensive, and readily available alkyl carboxylic acids to directly synthesize hydrocarbon products without additional pre-activation steps, and without the participation of transition metals and photocatalysts, thus better aligning with the principles of modern green chemistry.

[0151] It should be further noted that the specific embodiments described above provide a more detailed explanation of the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A process for the direct decarboxylative hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts, characterized in that, Under an argon atmosphere, the alkyl carboxylic acid, the N-hydroxy phthalimide compound, the phosphine catalyst, the hydrogen atom transfer reagent and the basic substance are placed in a solvent, and under visible light irradiation, an alkane compound as shown in formula 2a-2s is obtained through radical-mediated decarboxylative hydrogenation; The phosphine catalyst is 1,3-bis(diphenylphosphino)propane; The hydrogen atom transfer reagent is diphenyl disulfide; The basic substance is sodium bicarbonate; The solvent is N,N-dimethylacetamide; The N-hydroxy phthalimide compound is N-hydroxy phthalimide; The wavelength range of the visible light irradiation is 450-455 nm; Specifically includes: ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； ； 。 2. The method of claim 1, wherein, The molar amount of the phosphine catalyst is 50%-200% of the molar amount of the alkyl carboxylic acid.

3. The method of claim 1, wherein, The molar amount of the hydrogen atom transfer reagent is 5%-25% of the molar amount of the alkyl carboxylic acid.

4. The method of claim 1, wherein, The molar amount of the basic substance is 50%-200% of the molar amount of the alkyl carboxylic acid.

5. The method of claim 1, wherein, The molar amount of the N-hydroxy phthalimide compound is 50%-150% of the molar amount of the alkyl carboxylic acid.

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