A process for the preparation of alkyl acid phenyl esters from alkyl olefins

Abstract

The application belongs to the technical field of organic medicine synthesis, and particularly relates to a method for preparing alkyl acid phenyl ester from alkyl olefin, wherein alkyl olefin, phenyl formate, a palladium catalyst, a biphosphine ligand dtbpx and / or a monophosphine ligand TFPP are dispersed in an organic solvent in a molar ratio of 1:3:0.05:0.1-0.2 under a protective atmosphere, and then reacted at 50-110 DEG C to obtain alkyl acid phenyl ester; after the reaction is completed, the target product alkyl acid phenyl ester is separated out. The corresponding terminal alkyl carboxylic acid ester and its derivative can be obtained under mild conditions of low temperature and non-high pressure by taking the metal palladium salt, the biphosphine ligand or the monophosphine ligand as the catalyst, the generation of toxic pollutants is avoided, no additional strong acid needs to be added, the steps are simple and convenient to operate, and the yield is high.

Description

Technical Field

[0001] This invention belongs to the field of organic drug synthesis technology, and specifically relates to a method for preparing alkyl phenyl esters from alkyl olefins. Background Technology

[0002] Terminal alkyl carboxylic acids and their derivatives are a very important class of synthetic intermediates in organic synthesis, and their applications in fine chemicals, medicinal chemistry, and other disciplines are extremely wide. In addition, they play a significant role in industry as pharmaceuticals, fragrances, and synthetic building blocks.

[0003] Currently, the industrial synthesis of these compounds generally uses toxic, flammable, and explosive carbon monoxide gas in high-temperature and high-pressure reactions. These methods mostly suffer from the problems of using toxic carbon monoxide gas reagents, high reaction temperatures, and high reaction pressures, which places high demands on the pressure resistance of the reaction equipment. In addition, some reports have used carbon monoxide substitutes as carbonyl sources, but their reactions all require the addition of strong acids to the system, such as formic acid and p-toluenesulfonic acid, which limits the application scenarios of these compounds in the pharmaceutical or industrial sectors. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a method for preparing alkyl phenyl esters from alkyl olefins under mild conditions without involving carbon monoxide, without adding strong acids, and solely through the use of a catalyst:

[0005] Under a protective atmosphere, alkyl olefins, phenyl formate, palladium catalyst, bisphosphine ligand dtbpx and / or monophosphine ligand TFPP are dispersed in an organic solvent at a molar ratio of 1:3:0.05:0.1 to 0.2, and then reacted at 50 to 110 °C to obtain alkyl phenyl acid esters. After the reaction is completed, the target product alkyl phenyl acid esters are separated.

[0006] The reaction formula for this preparation method is:

[0007]

[0008] Among them, bisphosphine ligand d t The structure of bpx is

[0009]

[0010] The structural formula of the monophosphine ligand TFPP is as follows:

[0011]

[0012] R 1 R 2 Each can be an alkyl group or a hydrogen atom.

[0013] Compared to other esters, phenyl formate can directly undergo a palladium insertion reaction with metallic palladium, thus directly initiating the hydrogen palladiumization of olefins. This avoids the pathway that requires prior decomposition into carbon monoxide before the reaction. The specific reaction mechanism is as follows:

[0014]

[0015] First, palladium acetate combines with the ligand to form Pd(0)L n ; then Pd(0)L n An oxidative addition reaction occurs with phenyl formate to give H-Pd-substituted species M1, which then rearranges to intermediate M2. Intermediate M2 undergoes a hydrogen-palladiumation reaction with an alkene to generate intermediates M3 (major) and M4 (minor). Intermediates M3 and M4 undergo a migration insertion reaction to generate acylpalladium species M5 (major) and M6 (minor). M5 and M6 then undergo a reductive elimination reaction to generate products 2a (major) and 3a (minor), while simultaneously generating Pd(0)L. n Implement a loop.

[0016] Furthermore: R 2 For H, R 1 These are groups that do not have a conjugation effect with the double bond, such as octyl, cyclohexyl, tert-butyl, dodecyl, acetoxy, ester, amide, cyano, phosphonate, phthalamide, 8-aminoquinoline substituent, indole, glycosyl, nucleotide, steroidal, and non-conjugated olefinic groups.

[0017] Preferably, the alkyl olefin is a cyclic olefin, including cyclohexene, cycloheptene, norbornene, etc.

[0018] Preferably, the alkyl olefin is α-methylstyrene, methylenecyclohexane, or 2-(3-methylbut-3-en-1-yl)isoindoline-1,3-dione.

[0019] Preferred organic solvents include toluene, benzene, acetonitrile, 1,2-dichloroethane, and n-hexane.

[0020] As a preferred method, the target product, alkyl phenyl acid ester, is separated by column chromatography.

[0021] The beneficial results of this invention are as follows: By using palladium salts, bisphosphine ligands, or monophosphine ligands as catalysts, the reaction of olefins with phenyl formate can yield the corresponding terminal alkyl carboxylic acid esters and their derivatives under mild conditions of low temperature and non-high pressure. Under the mild reaction temperature of this scheme, no carbon monoxide intermediate is generated on phenyl formate, thus avoiding the generation of toxic pollutants. Furthermore, the synthesis method of this scheme does not require the addition of additional strong acids, the steps are simple and easy to operate, the yield is high, and it can greatly save energy and improve the synthesis efficiency. Attached Figure Description

[0022] Figure 1 The phenyl nonanoate (structural formula 2a) synthesized in Example 1 1 H NMR spectrum;

[0023] Figure 2 The phenyl nonanoate (structural formula 2a) synthesized in Example 1 13 C NMR spectrum;

[0024] Figure 3 The phenyl 7-acetoxyheptanoate (structural formula 2g) synthesized in Example 7 1 H NMR spectrum;

[0025] Figure 4 The phenyl 7-acetoxyheptanoate (structural formula 2g) synthesized in Example 7 13 C NMR spectrum;

[0026] Figure 5 For the methyl phenyl adipate (structural formula 2h) synthesized in Example 8 1 H NMR spectrum;

[0027] Figure 6 For the methyl phenyl adipate (structural formula 2h) synthesized in Example 8 13 C NMR spectrum;

[0028] Figure 7 The phenyl 5-oxo-5-(quinoline-8-amino)pentanoic acid ester (structural formula 2m) synthesized in Example 13. 1 H NMR spectrum;

[0029] Figure 8 The phenyl 5-oxo-5-(quinoline-8-amino)pentanoic acid ester (structural formula 2m) synthesized in Example 13. 13 C NMR spectrum;

[0030] Figure 9 The phenyl 4,4-dimethylpentanoate (structural formula 2p) synthesized in Example 16 1 H NMR spectrum;

[0031] Figure 10 The phenyl 4,4-dimethylpentanoate (structural formula 2p) synthesized in Example 16 13 C NMR spectrum;

[0032] Figure 11 The phenyl 5-(1,3-dioxoisoindoline-2-yl)-3-methylpentanoate (structural formula 2t) synthesized in Example 20 1 H NMR spectrum;

[0033] Figure 12 The phenyl 5-(1,3-dioxoisoindoline-2-yl)-3-methylpentanoate (structural formula 2t) synthesized in Example 20 13 C NMR spectrum;

[0034] Figure 13 The 8-(((3aR,5R,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolane-4-yl)-2,22-dimethyltetrahydrofurfuryl[2,3-d][1,3]dioxolane-6-yl)oxy)octanoic acid phenyl ester (structural formula 2u) synthesized in Example 21 1 HNMR spectrum;

[0035] Figure 14 The 8-(((3aR,5R,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolane-4-yl)-2,22-dimethyltetrahydrofurfuryl[2,3-d][1,3]dioxolane-6-yl)oxy)octanoic acid phenyl ester (structural formula 2u) synthesized in Example 21 13 CNMR spectrum;

[0036] Figure 15 The 8-(3-((3aR,4R,6R,6aR)-6-(methoxymethyl)-2,2-dimethyltetrahydrofurfuryl[3,4-d][1,3]dioxacyclopentan-4-yl)-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl) octanoic acid phenyl ester (structural formula 2v) synthesized in Example 22 1 H NMR spectrum;

[0037] Figure 16 The 8-(3-((3aR,4R,6R,6aR)-6-(methoxymethyl)-2,2-dimethyltetrahydrofurfuryl[3,4-d][1,3]dioxacyclopentan-4-yl)-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl) octanoic acid phenyl ester (structural formula 2v) synthesized in Example 22 13 C NMR spectrum;

[0038] Figure 17 The 4-((8R,9S,13S,14S,17S)-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-17-yl)butyrate phenyl ester (structural formula 2w) synthesized in Example 23 is... 1 H NMR spectrum;

[0039] Figure 18The 4-((8R,9S,13S,14S,17S)-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-17-yl)butyrate phenyl ester (structural formula 2w) synthesized in Example 23 is... 13 C NMR spectrum;

[0040] Figure 19 The phenyl(1S,4R)-bicyclo[2.2.1]heptane-2-carboxylic acid ester (structural formula 2z) synthesized in Example 26 is used for... 1 H NMR spectrum;

[0041] Figure 20 The phenyl(1S,4R)-bicyclo[2.2.1]heptane-2-carboxylic acid ester (structural formula 2z) synthesized in Example 26 is used for... 13 C10 NMR spectrum. Detailed Implementation

[0042] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the scope of protection of the invention.

[0043] Example 1

[0044] Synthesis of phenyl nonanoate (structural formula 2a):

[0045] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0561 g (0.5 mmol) of 1-octene (structural formula 1a), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature (25 °C). Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 100:1) was used to separate the product into a colorless oil, the target product (0.1078 g, yield 92%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0046]

[0047] The results of the product structure confirmation are as follows: 1H NMR (400MHz, CDCl3) δ7.31-7.24(m,2H),7.15-7.09(m,1H),7.01-6.95(m,2H),2. 46(t,J=7.6Hz,2H),1.72-1.62(m,2H),1.35-1.15(m,10H),0.81(t,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ172.5,150.9,129.5,125.8,121.7,34.6,32.0,29.4,29.31,29.28,25.1,22.8,14.3.

[0048] Comparative Example 1

[0049] Replace "phenyl formate" with an equimolar amount of "methyl formate", and perform the remaining operations as in Example 1:

[0050] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0561 g (0.5 mmol) of 1-octene (structural formula 1a), and methyl formate (0.09 g, 1.5 mmol) were mixed thoroughly and sealed. The mixture in the reactor was heated to 70 °C and reacted for 48 hours using a heating plate. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography was then used to separate the product (the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate in a volume ratio of 100:1). No synthetic product was collected.

[0051] Comparative Example 2

[0052] Replace "phenyl formate" with an equimolar amount of "butyl formate", and perform the remaining operations as in Example 1:

[0053] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 1-octene (0.0561 g, 0.5 mmol) of structural formula 1a, and butyl formate (0.1532 g, 1.5 mmol) were mixed thoroughly and sealed. The mixture in the reactor was heated to 70 °C and reacted for 48 hours using a heating plate. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography was then used to separate the product (the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate in a volume ratio of 100:1). No synthetic product was collected.

[0054] Comparative Example 3

[0055] Replace "phenyl formate" with an equimolar amount of "benzyl formate", and perform the remaining operations as in Example 1:

[0056] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0561 g (0.5 mmol) of 1-octene (structural formula 1a), and 0.20 g (1.5 mmol) of benzyl formate were mixed thoroughly and sealed. The mixture in the reactor was heated to 70 °C and reacted for 48 hours using a heating plate. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography was then used to separate the product (the column was packed with petroleum ether, and the eluent was petroleum ether:ethyl acetate in a volume ratio of 100:1). No synthetic product was collected.

[0057] In the above comparative examples 1 to 3, the different reactants resulted in different molecular structural environments for the ester groups on the reactants, which prevented the ester groups from directly undergoing palladium insertion reaction with metallic palladium. Therefore, synthesis could not be achieved at a mild reaction temperature of 70°C without external additives such as oxygen and carbon monoxide. Even if the reaction temperature was further increased to allow the reactants to decompose and release carbon monoxide, the target product could not be synthesized through the carbon monoxide because there were no acidic additives in the entire reaction system of this scheme.

[0058] Example 2

[0059] Synthesis of phenyl tridecanoate (structural formula 2b):

[0060] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.0842 g (0.5 mmol) of dodecyl-1-ene (structural formula 1b), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl petroleum ether:ethyl acetate volume ratio 100:1) was then used to separate the product into a colorless oil, the target product (0.1113 g, yield 77%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0061]

[0062] The results of the product structure confirmation are as follows:1 H NMR (400MHz, CDCl3) δ7.31-7.24(m,2H),7.15-7.09(m,1H),7.01-6.96(m,2H),2. 46(t,J=7.2Hz,2H),1.72-1.62(m,2H),1.38-1.15(m,18H),0.80(t,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ172.4; 150.9, 129.5, 125.8, 121.7, 34.6, 32.1, 29.84, 29.83, 29.79, 29.7, 29.5, 29.4, 29.3, 25.1, 22.9, 14.3.

[0063] Example 3

[0064] Synthesis of phenyl 4-cyclohexylbutyrate (structural formula 2c):

[0065] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of BPX, 0.1 mL of 1,2-dichloroethane, 0.0621 g (0.5 mmol) of allylcyclohexane (structural formula 1C), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl acetate volume ratio 50:1) was then used to separate the product into a colorless oily substance, the target product (0.1004 g, yield 82%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0066]

[0067] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.31-7.24(m,2H),7.15-7.09(m,1H),7.01-6.95(m,2H), 2.44(t,J=7.2Hz,2H),1.74-1.53(m,7H),1.25-1.03(m,6H),0.88-0.75(m,2H); 13 C NMR (100MHz, CDCl3) δ172.5,150.9,129.5,125.8,121.7,37.5,37.0,34.8,33.4,26.8,26.5,22.5.

[0068] Example 4

[0069] Synthesis of phenyl 5,5-dimethylhexanoate (structural formula 2d):

[0070] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0491 g (0.5 mmol) of 4,4-dimethylpent-1-ene (Structure 1d), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly and sealed. The mixture was then heated to 70 °C using a heating plate and reacted for 48 hours. Heating was stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 50:1) was used to separate the product into a colorless oil, the target product (0.0791 g, yield 72%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0071]

[0072] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.31-7.24(m,2H),7.15-7.09(m,1H),7.02-6.96(m,2H ),2.44(t,J=7.6Hz,2H),1.69-1.58(m,2H),1.24-1.16(m,2H),0.83(s,3H); 13 C NMR (100MHz, CDCl3) δ172.4,150.9,129.5,125.8,121.7,43.7,35.2,30.5,29.5,20.4.

[0073] Example 5

[0074] Synthesis of phenyl 5-phenylpentanoate (structural formula 2e):

[0075] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.0661 g (0.5 mmol) of but-3-en-1-ylbenzene (structural formula 1e), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl acetate volume ratio 40:1) was then used to separate the product into a white solid, the target product (0.1084 g, yield 85%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0076]

[0077] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.28-7.21(m,2H),7.21-7.15(m,2H),7.13-7.05(m,4H),6. 99-6.94(m,2H);2.56(t,J=7.2Hz,2H),2.45(t,J=6.8Hz,2H),1.74-1.58(m,4H); 13 C NMR (100MHz, CDCl3) δ172.1,150.8,142.1,129.5,128.49,128.45,125.9,125.8,121.7,35.6,34.3,30.9,24.6.

[0078] Example 6

[0079] Synthesis of phenyl 4-phenylbutyrate (structural formula 2f):

[0080] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.0591 g (0.5 mmol) of allylbenzene (structural formula 1f), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl petroleum ether:ethyl acetate volume ratio 50:1) was used to separate the product into a white solid, the target product (0.100 g, yield 83%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0081]

[0082] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.28-7.15(m,4H),7.13-7.06(m,4H),6.97-6.93(m,2H),2.62(t,J=7.2Hz,2H),2.45(t,J=7.2Hz,2H),2.01-1.92(m,2H); 13 C NMR (100MHz, CDCl3) δ172.1,150.8,141.3,129.5,128.7,128.6,126.2,125.9,121.7,35.2,33.8,26.6.

[0083] Example 7

[0084] Synthesis of phenyl 7-acetoxyheptanoate (structural formula 2g):

[0085] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 1 g of 5-en-1-ylhexyl acetate (0.0711 g, 0.5 mmol), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl acetate, volume ratio 5:1) was then used to separate the product into a colorless oil, the target product (0.1097 g, yield 83%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0086]

[0087] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.41-7.33(m,2H),7.25-7.19(m,1H),7.09-7.04(m,2H),4.07(t,J=6.4Hz, 2H),2.56(t,J=7.2Hz,2H),2.04(s,3H),1.81-1.71(m,2H),1.71-1.61(m,2H),1.51-1.36(m,4H); 13C NMR (100MHz, CDCl3) δ172.3,171.4,150.9,129.6,125.9,121.7,64.6,34.4,28.9,28.6,25.8,24.9,21.2.

[0088] Example 8

[0089] Synthesis of methyl phenyl adipate (structural formula 2h):

[0090] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, methyl pent-4-enoate (0.0571 g, 0.5 mmol) with structural formula 1h, and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl petroleum ether:ethyl acetate volume ratio 20:1) was used to separate the product into a colorless oily substance, the target product (0.1099 g, yield 93%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0091]

[0092] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.41-7.34(m,2H),7.25-7.19(m,1H),7.10-7.05(m,2H) ,3.68(s,3H),2.59(t,J=7.2Hz,2H),2.39(t,J=7.2Hz,2H),1.84-1.72(m,4H); 13 C NMR (100MHz, CDCl3) δ173.9,172.0,150.8,129.6,126.0,121.7,51.8,34.2,33.8,24.54,24.51.

[0093] Example 9

[0094] Synthesis of phenyl 5-(methoxy(methyl)amino)-5-oxopentanoic acid ester (structural formula 2i):

[0095] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, N-methoxy-N-methylbut-3-enamide (0.0646 g, 0.5 mmol) with structural formula 1i, and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl petroleum ether:ethyl acetate volume ratio 8:1) was used to separate the product into a colorless oil, the target product (0.1014 g, yield 81%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0096]

[0097] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.38-7.31(m,2H),7.19(t,J=7.2Hz,1H),7.08-7.04(m,2H),3.6 5(s,3H),3.16(s,3H),2.64(t,J=7.2Hz,2H),2.56(t,J=6.8Hz,2H),2.11-2.02(m,2H); 13 C NMR (100MHz, CDCl3) δ171.8,150.7,129.4,125.8,121.6,61.3,33.6,32.2,30.8,19.8.

[0098] Example 10

[0099] Synthesis of phenyl 4-cyanobutyrate (structural formula 2j):

[0100] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.0335 g (0.5 mmol) of butyronitrile (Structure 1J), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 5:1) was then used to separate the product into a colorless oil, the target product (0.0584 g, yield 62%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0101]

[0102] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.42-7.35(m,2H),7.27-7.21(m,1H),7.11-7.06(m,2H),2.74(t,J=7.2Hz,2H),2.51(t,J=7.0Hz,2H),2.11-2.02(m,2H); 13 C NMR (100MHz, CDCl3) δ170.7,150.5,129.6,126.1,121.5,119.1,32.5,20.7,16.6.

[0103] Example 11

[0104] Synthesis of 4-(diethoxyphosphoryl)butyrate phenyl ester (structural formula 2k)

[0105] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of BPX, 0.1 mL of 1,2-dichloroethane, 0.0891 g (0.5 mmol) of allylphosphonate (Structure 1K), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 1:1) was then used to separate the product into a colorless oil, the target product (0.1104 g, yield 74%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0106]

[0107] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.35-7.27(m,2H),7.18-7.12(m,1H),7.04-6.98(m,2H),4.13-3.96( m,4H),2.63(t,J=7.2Hz,2H),2.05-1.92(m,2H),1.88-1.76(m,2H),1.26(t,J=7.2Hz,6H); 13C NMR (100MHz, CDCl3) δ171.2,150.5,129.4,125.8,121.5,61.62,61.55,34.4,34.2,25.4,24.0,18.1,18.0,16.5,16.4.

[0108] Example 12

[0109] Synthesis of phenyl 3-(1,3-dioxoisoindoline-2-yl)propionate (structural formula 2l):

[0110] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0866 g (0.5 mmol) of 2-vinylisoindoline-1,3-dione (Structure 1L), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly and sealed. The mixture was then heated to 70 °C using a heating plate and reacted for 48 hours. Heating was stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 5:1) was used to separate the product into a white solid, the target product (0.1233 g, yield 84%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0111]

[0112] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.87-7.80(m,2H),7.73-7.66(m,2H),7.40-7.32(m,2H),7. 23-7.17(m,1H),7.13-7.06(m,2H),4.11(t,J=7.2Hz,2H),2.97(t,J=8.0Hz,2H); 13 C NMR (100MHz, CDCl3) δ169.5,168.1,150.5,134.2,132.0,129.5,126.0,123.5,121.6,33.8,33.3.

[0113] Example 13

[0114] Synthesis of phenyl 5-oxo-5-(quinoline-8-amino)pentanoic acid ester (structural formula 2m):

[0115] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor.t 0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.1061 g (0.5 mmol) of N-(quinolin-8-yl)but-3-enamide (0.1061 g, 0.5 mmol) and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly and sealed. The mixture was then heated to 70 °C using a heating plate and reacted for 48 hours. Heating was stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 5:1) was used to separate the product into a white solid, the target product (0.1157 g, yield 69%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0116]

[0117] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ9.85 (s, 1H), 8.80 (dd, J1 = 0.8Hz, J2 = 7.2Hz, 1H), 8.76 (dd, J1 = 1.6Hz, J2 = 4.0Hz, 1H), 8.11 (dd, J1 = 1.2Hz, J2 = 8 .0Hz,1H),7.55-7.45(m,2H),7.43-7.33(m,3H),7.21(t,J=7.2Hz,1H),7.11(d,J=7.6Hz,2H),2.78-2.68(m,4H),2.31-2.21(m,2H); 13 C NMR (100MHz, CDCl3) δ171.7,170.7,150.7,148.2,138.3,136.4,134.4,12 9.4,128.0,127.4,125.8,121.7,121.64,121.60,116.5,36.7,33.5,20.7.

[0118] Example 14

[0119] Synthesis of phenyl 6-oxo-6-(quinoline-8-amino)hexanoate (structural formula 2n):

[0120] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.1131 g (0.5 mmol) of N-(quinolin-8-yl)pentyl-4-enamide (structural formula 1n), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl petroleum ether:ethyl acetate volume ratio 8:1) was used to separate the product into a white solid, the target product (0.1375 g, yield 79%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0121]

[0122] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ9.83 (s, 1H), 8.81-8.77 (m, 2H), 8.15 (dd, J1 = 1.6Hz, J2 = 8.0Hz, 1H), 7.56-7.47 (m, 2H), 7.46- 7.42(m,1H),7.39-7.33(m,2H),7.24-7.18(m,1H),7.11-7.06(m,2H),2.66(d,J=7.2Hz,2H),2.63(d,J=7.2Hz,2H); 13 CNMR (100MHz, CDCl3) δ172.0,171.3,150.8,148.3,138.4,136.5,134.6,129 .5,128.1,127.6,125.9,121.8,121.7,121.6,116.6,37.8,34.3,25.1,24.7.

[0123] Example 15

[0124] Synthesis of phenyl 3-cyclohexylpropionate (structural formula 2o):

[0125] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0551 g (0.5 mmol) of vinylcyclohexane (Structure 1O), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 40:1) was then used to separate the product into a colorless oil, the target product (0.0975 g, yield 84%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0126]

[0127] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl) 3 )δ7.31-7.24(m,2H),7.15-7.09(m,1H),7.01-6.96(m,2H),2.50-2.44(m,2H),1.73-1.53(m,7H),1.31-1.04(m,4H),0.93-0.80(m,2H); 13 C NMR (100MHz, CDCl3) δ172.7,150.9,129.5,125.8,121.7,37.4,33.1,32.4,32.1,26.7,26.4.

[0128] Example 16

[0129] Synthesis of 4,4-dimethylpentanoic acid phenyl (structural formula 2p):

[0130] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.0421 g (0.5 mmol) of 3,3-dimethylbut-1-ene (1p) (0.0421 g, 0.5 mmol), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 100:1) was then used to separate the product into a colorless oily substance, the target product (0.0885 g, yield 86%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0131]

[0132] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.31-7.24(m,2H),7.15-7.09(m,1H),7.01-6.96(m,2H),2.48-2.41(m,2H),1.63-1.57(m,2H),0.87(s,9H); 13 C NMR (100MHz, CDCl3) δ173.0,150.9,129.5,125.9,121.7,38.7,30.4,30.3,29.2.

[0133] Example 17

[0134] Synthesis of 3-(triethylsilyl)propionic acid phenyl (structural formula 2q):

[0135] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of bpx, 0.1 mL of 1,2-dichloroethane, 0.0712 g (0.5 mmol) of triethyl(vinyl)silane (structural formula 1q), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl petroleum ether:ethyl acetate volume ratio 100:1) was then used to separate the product into a colorless oily substance, the target product (0.1242 g, yield 94%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0136]

[0137] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.42-7.35(m,2H),7.26-7.20(m,1H),7.12-7.07(m,2H),2. 58-2.52(m,2H),1.03-0.95(m,2H),0.99(t,J=8.0Hz,9H),0.59(q,J=8.0Hz,6H); 13 C NMR (100MHz, CDCl3) δ173.9,151.1,129.6,125.8,121.7,29.3,7.6,6.8,3.3.

[0138] Example 18

[0139] Synthesis of phenyl 3-phenylbutyrate (structural formula 2r):

[0140] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of BPX, 0.1 mL of 1,2-dichloroethane, 0.0591 g (0.5 mmol) of propen-1-en-2-ylbenzene (Structure 1R), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate eluent ratio of 50:1) was then used to separate the product into a colorless oily substance, the target product (0.098 g, yield 82%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0141]

[0142] The results of the product structure confirmation are as follows: 1 H NMR(400MHz, CDCl3)δ7.29-7.16(m,6H),7.16-7.10(m,1H),7.10-7.04(m,1H), 6.82-6.77(m,2H),3.36-3.25(m,1H),2.79-2.65(m,2H),1.30(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ171.0,150.7,145.3,129.5,128.7,127.0,126.8,125.9,121.7,43.1,36.9,22.1.

[0143] Example 19

[0144] Synthesis of 2-cyclohexylacetic acid phenyl ester (structural formula 2S):

[0145] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0481 g (0.5 mmol) of methylenecyclohexane (1S structural formula), and phenyl formate (0.1832 g, 1.5 mmol) were thoroughly mixed. After sealing, the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed column, eluent: ethyl petroleum ether:ethyl acetate volume ratio 50:1) was then used to separate the product into a colorless oily substance, the target product (0.0472 g, yield 43%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0146]

[0147] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.41-7.35(m,2H),7.25-7.19(m,1H),7.10-7.06(m,2H),2.44(d,J=7.2Hz,2H),2.00- 1.89(m,1H),1.88-1.80(m,2H),1.80-1.65(m,3H),1.39-1.25(m,2H),1.25-1.16(m,1H),1.16-1.02(m,2H); 13 C NMR (100MHz, CDCl3)δ

[0148] 171.8,150.9,129.6,125.9,121.8,42.3,35.3,33.2,26.3,26.2.

[0149] Example 20

[0150] Synthesis of phenyl 5-(1,3-dioxoisoindoline-2-yl)-3-methylpentanoate (structural formula 2t):

[0151] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t0.0197 g (0.050 mmol) of BPX, 0.1 mL of 1,2-dichloroethane, 0.1076 g (0.5 mmol) of 2-(3-methylbut-3-en-1-yl)isoindoline-1,3-dione (0.1076 g, 0.5 mmol) and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly and sealed. The mixture was then heated to 70 °C using a heating plate and reacted for 48 hours. Heating was stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 10:1) was used to separate the product into a colorless oil, the target product (0.0887 g, yield 53%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0152]

[0153] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.83-7.78(m,2H),7.69-7.64(m,2H),7.38-7.31(m ,2H),7.22-7.16(m,1H),7.07-7.03(m,2H),3.76(t,J=7.2Hz,2H),2.63(d d, J1=6.0Hz, J2=15.2Hz, 1H), 2.44 (dd, J1=8.0Hz, J2=15.2Hz, 1H), 2.20- 2.05(m,1H),1.93-1.80(m,1H),1.70-1.58(m,1H),1.15(d,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ171.2,168.4,150.7,134.0,132.1,129.5,125.8,123.3,121.7,41.4,35.9,35.1,28.2,19.5.

[0154] Example 21

[0155] Synthesis of 8-(((3aR,5R,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolane-4-yl)-2,22-dimethyltetrahydrofurfuryl[2,3-d][1,3]dioxolane-6-yl)oxy)phenyl octanoate (structural formula 2u):

[0156] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. tbpx (0.0197 g, 0.050 mmol), 0.1 mL of 1,2-dichloroethane, (3aR,5R,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolane-4-yl)-6-(hept-6-en-1-oxy)-2,2-dimethyltetrahydrofuran[2,3-d][1,3]dioxane (0.1772 g, 0.5 mmol) with the structural formula 1u, and formic acid Phenyl ester (0.1832 g, 1.5 mmol) was mixed thoroughly and sealed. The mixture was then heated to 70°C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing material and petroleum ether:ethyl acetate as the eluent in a 3:1 volume ratio) was used to separate the product into a colorless oil, the target product (0.143 g, 60% yield, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0157]

[0158] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.40-7.32(m,2H),7.23-7.17(m,1H),7.08-7.02(m,2H) ,5.76(d,J=4.0Hz,1H),4.68-4.58(m,2H),4.13-4.01(m,2H),4.00-3.94(m,1 H),3.70-3.62(m,1H),3.56-3.50(m,1H),3.40-3.32(m,1H),2.54(t,J=7.6Hz ,2H),1.78-1.68(m,2H),1.63-1.54(m,5H),1.42(s,3H),1.40-1.29(m,12H); 13 C NMR (100MHz, CDCl3)δ

[0159] 172.3,150.8,129.5,125.8,121.6,113.9,108.5,105.1,82.8,78.8,78.0,75.5,71.0,67.1,34.4,29.6,29.1,26.89,26.87,26.4,25.9,25.3,24.9.

[0160] Example 22

[0161] Synthesis of 8-(3-((3aR,4R,6R,6aR)-6-(methoxymethyl)-2,2-dimethyltetrahydrofurfuryl[3,4-d][1,3]dioxacyclopentan-4-yl)-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl) phenyl octanoate (structural formula 2v):

[0162] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t bpx (0.0197 g, 0.050 mmol), 0.1 mL of 1,2-dichloroethane, 3-(hept-6-en-1-yl)-1-((3aR,4R,6R,6aR)-6-(methoxymethyl)-2,2-dimethyltetrahydrofurfuryl[3,4-d][1,3]dihydroxy-4-yl)pyrimidine-2,4(1H,3H)-dione (0.1972 g, 0.5 mmol) with the structural formula 1V, and methyl Phenyl ethyl acetate (0.1832 g, 1.5 mmol) was mixed thoroughly and sealed. The mixture was then heated to 70°C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing material and petroleum ether:ethyl acetate eluent in a 5:1 volume ratio) was used to separate the product into a colorless oil, the target product (0.1324 g, 51% yield, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0163]

[0164] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.41 (d, J = 8.0Hz, 1H), 7.36-7.29 (m, 2H), 7.20-7.14 (m, 1H), 7.05-7.00 (m ,2H),5.80(d,J=1.6Hz,1H),5.68(d,J=8.0Hz,1H),4.76-4.70(m,2H),4.38-4.33(m,1H),II3.93 -3.80(m,2H),3.59(dd,J=2.8,10.4Hz,1H),3.52(dd,J=4.4,10.4Hz,1H),3.32(s,3H),2.50(t,J =7.2Hz,2H),1.75-1.65(m,2H),1.65-1.57(m,2H),1.55(s,3H),1.42-1.32(m,6H),1.32(s,3H); 13C NMR (100MHz, CDCl3) δ172.3,162.7,150.79,150.75,138.7,129.4,125.7,121.6,113.9,101. 4,94.4,I85.8,85.5,81.2,72.8,59.2,41.1,34.3,29.0,28.9,27.5,27.2,26.8,25.3,24.9.

[0165] Example 23

[0166] Synthesis of 4-((8R,9S,13S,14S,17S)-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-17-yl)butyrate (structural formula 2w):

[0167] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t bpx (0.0197 g, 0.050 mmol), 0.1 mL of 1,2-dichloroethane, and (8R, 9S, 13S, 14S, 17R)-17-allyl-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentadiene[a]phenanthrene with the structural formula 1w

[0168] (0.1703 g, 0.5 mmol) and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly, sealed, and the mixture in the reactor was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column, with a petroleum ether:ethyl acetate volume ratio of 30:1) was then used to separate the product into a colorless oil, i.e., the target product (0.1643 g, yield 71%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0169]

[0170] The results of the product structure confirmation are as follows: 1H NMR (400MHz, CDCl3) δ7.41-7.33(m,2H),7.24-7.15(m,2H),7.11-7.06(m,2H),6.70(dd,J=8.4,2.8Hz,1H)6.62(d,J=2.8Hz,1H),3.75(s,3H),3 .24(s,3H),2.92-2.76(m,2H),2.63(t,J=6.8Hz,2H),2.31-2.22(m,1H) ,2.19-2.06(m,2H),2.00-1.57(m,8H),1.57-1.21(m,6H),0.95(s,3H); 13 C NMR (100MHz, CDCl3) δ172.3,157.5,150.8,138.0,132.6,129.5,126.3,125.9,121.6,113.8,111.6,8 7.6,55.2,51.4,50.9,47.1,43.6,39.4,34.74,34.70,34.0,30.1,29.9,27.5,26.7,23.3,18.9,13.9.

[0171] Example 24

[0172] Synthesis of 2,4,6-trichlorophenyl-4-((8R,9S,13S,14S,17S)-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-17-yl)butyrate (structural formula 2x):

[0173] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t bpx (0.0197 g, 0.050 mmol), 0.1 mL of 1,2-dichloroethane, (8R, 9S, 13S, 14S, 17R)-17-allyl-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentadiene[a]phenanthrene (0.1703 g, 0.5 mmol) and trichlorobenzene formate. The ester (0.3382 g, 1.5 mmol) was thoroughly mixed and sealed. The mixture was then heated to 70°C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing material and petroleum ether:ethyl acetate as the eluent in a 30:1 volume ratio) was used to separate the product into a white solid, the target product (0.2128 g, 75% yield, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0174]

[0175] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.40(s,2H),7.22(d,J=8.4Hz,1H),6.74(dd,J=8.4,2.8Hz,1H),6.66(d,J=2.8Hz,1H)3.80(s,3H),3.28(s,3 H),2.96-2.83(m,2H),2.83-2.71(m,2H),2.36-2.27(m,1H),2.25-2.11(m,2H),2.05-1.80(m,5H),1.80-1.25(m,9H),1.00(s,3H); 13 C NMR (100MHz, CDCl3) δ170.1,157.6,143.1,138.0,132.6,132.1,129.6,128.7,126.3,113.9,111.6, 87.6,55.3,51.4,51.0,47.2,43.7,39.5,34.8,34.1,34.0,30.2,29.9,27.6,26.7,23.4,18.9,14.0.

[0176] Example 25

[0177] Synthesis of 2,2,2-trifluoroethyl-4-((8R,9S,13S,14S,17S)-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-17-yl)butyrate (structural formula 2y):

[0178] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. tbpx (0.0197 g, 0.050 mmol), 0.1 mL of 1,2-dichloroethane, (8R, 9S, 13S, 14S, 17R)-17-allyl-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentadiene[a]phenanthrene (0.1703 g, 0.5 mmol) and trifluoroethyl formate. The alcohol ester (0.1921 g, 1.5 mmol) was thoroughly mixed, sealed, and the mixture in the reactor was heated to 70 °C using a heating plate. After reacting for 48 hours, heating was stopped, and the mixture was allowed to cool naturally to room temperature. The product was then separated by column chromatography (column packed with petroleum ether, eluent: ethyl acetate, volume ratio 30:1) to obtain a colorless oily substance, the target product (0.127 g, yield 54%, straight-chain to branched-chain ratio greater than 20:1). The reaction formula is:

[0179]

[0180] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.20(d,J=8.8Hz,1H),6.72(dd,J=8.8,2.8Hz,1H),6.64(d,J=2.8Hz,1H),4.52(q,J=8.4Hz,2H),3.79(s,3H),3.24(s,3H),2. 94-2.78(m,2H),2.52(t,J=7.2Hz,2H),2.34-2.23(m,1H),2.20-2.11(m,1 H),2.10-1.99(m,1H),1.96-1.60(m,8H),1.58-1.25(m,6H),0.97(s,3H); 13 C NMR (100MHz, CDCl3) δ172.2,157.6,138.1,132.7,126.4,123.2(q,J=275.8Hz),113.9,111.6,87.6,60.3(q ,J=36.2Hz),55.3,51.3,51.0,47.2,43.7,39.5,34.7,34.1,34.0,30.1,30.0,27.5,26.7,23.3,18.7,14.0.

[0181] Example 26

[0182] Synthesis of phenyl-bicyclo[2.2.1]heptane-2-carboxylic acid ester (structural formula 2z):

[0183] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol), 0.1 mL of 1,2-dichloroethane, 0.0471 g (0.5 mmol) of bicyclo[2.2.1]hept-2-ene (0.0471 g, 0.5 mmol), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly and sealed. The mixture was then heated to 70 °C using a heating plate and reacted for 48 hours. Heating was stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing material and petroleum ether:ethyl acetate as the eluent in a volume ratio of 50:1) was used to separate the product into a colorless oil, the target product (0.0749 g, 69% yield). The reaction formula is:

[0184]

[0185] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.32-7.24(m,2H),7.19-7.09(m,1H),7.01-6.95(m,2H),2.60(d,J=3.6Hz,1H),2.49(dd,J1=5 .2Hz, J2=8.8Hz,1H),2.30-2.25(m,1H),1.94-1.85(m,1H),1.60-1.43(m,4H),1.29-1.21(m,1H),1.20-1.12(m,2H); 13 CNMR (100MHz, CDCl3) δ174.7,151.1,129.5,125.7,121.7,46.7,41.3,36.6,36.3,34.3,29.6,28.8.

[0186] Example 27

[0187] Synthesis of cyclohexane phenyl carboxylate (structural formula 2aa):

[0188] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.0411 g (0.5 mmol) of cyclohexene (1aa), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column and petroleum ether:ethyl acetate as the eluent in a 50:1 volume ratio) was then used to separate the product into a colorless oil, the target product (0.0466 g, 46% yield). The reaction formula is as follows:

[0189]

[0190] The results of the product structure confirmation are as follows: 1 HNMR(400MHz, CDCl3)δ7.41-7.34(m,2H),7.24-7.18(m,1H),7.09-7.03(m,2H),2.61-2 .51(m,1H),2.12-2.02(m,2H),1.88-1.78(m,2H),1.73-1.53(m,3H),1.43-1.23(m,3H); 13 C NMR (100MHz, CDCl3) δ174.8,151.1,129.5,125.8,121.8,43.4,29.2,25.9,25.6.

[0191] Example 28

[0192] Synthesis of cyclooctylcarboxylic acid phenyl ester (structural formula 2ab):

[0193] Under argon protection, palladium acetate (0.0056 g, 0.025 mmol) and bisphosphine ligand d were added sequentially to the reactor. t 0.0197 g (0.050 mmol) of β-px, 0.1 mL of 1,2-dichloroethane, 0.0551 g (0.5 mmol) of cyclooctene (1ab), and phenyl formate (0.1832 g, 1.5 mmol) were mixed thoroughly. After sealing, the mixture was heated to 70 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether as the packing column and petroleum ether:ethyl acetate as the eluent in a 50:1 volume ratio) was then used to separate the product into a colorless oil, the target product (0.0431 g, 37% yield). The reaction formula is as follows:

[0194]

[0195] The results of the product structure confirmation are as follows: 1H NMR (400MHz, CDCl3) δ7.41-7.34(m,2H),7.22(t,J=7.2Hz,1H),7.09-7.04(m,2 H),2.83-2.74(m,1H),2.12-2.00(m,2H),1.92-1.74(m,4H),1.68-1.51(m,8H); 13 C NMR (100MHz, CDCl3) δ175.9,151.1,129.5,125.8,121.7,43.8,28.9,27.0,26.3,25.4.

[0196] Example 29

[0197] Synthesis of phenyl 4-(1H-indol-3-yl)butyrate (structural formula 2ac):

[0198] Under argon protection, tetrakis(triphenylphosphine)palladium (0.0289 g, 0.025 mmol), monophosphine ligand TFPP (0.0316 g, 0.100 mmol), 0.1 mL toluene, 3-allyl-1H-indole (0.0786 g, 0.5 mmol) with the structural formula 1ac, and phenyl formate (0.1832 g, 1.5 mmol) were added sequentially to a reactor and mixed thoroughly. After sealing, the mixture in the reactor was heated to 90 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed columns and a petroleum ether:ethyl acetate eluent ratio of 10:1) was then used to separate the product into a colorless oily substance, the target product (0.1019 g, yield 73%, straight-chain to branched-chain ratio 7:1). The reaction formula is as follows:

[0199]

[0200] The results of the product structure confirmation are as follows: 1 H NMR (400MHz, CDCl3) δ7.92(s,1H),7.62(d,J=8.0Hz,1H),7.38-7.30(m,2H),7.27(d,J=8.0Hz,1H),7.23-7.14(m,2H),7.1 4-7.09(m,1H),7.06-7.01(m,2H),6.89(d,J=2.4Hz,1H),2.87(t,J=7.6Hz,2H),2.61(t,J=7.2Hz,2H),2.20-2.10(m,2H); 13C NMR (100 MHz, CDCl3) δ172.6,150.8,136.5,129.6,127.5,125.9,122.0,121.8,121.7,119.3,119.0,115.2,111.4,34.0,25.5,24.6.

[0201] Example 30

[0202] Synthesis of phenyl 6-methylhept-6-enoic acid ester (structural formula 2ad):

[0203] Under argon protection, tetrakis(triphenylphosphine)palladium (0.0289 g, 0.025 mmol), monophosphine ligand TFPP (0.0316 g, 0.100 mmol), 0.1 mL toluene, 2-methylhexa-1,5-diene (0.0481 g, 0.5 mmol) with the structural formula 1ad, and phenyl formate (0.1832 g, 1.5 mmol) were added sequentially to a reactor and mixed thoroughly. After sealing, the mixture was heated to 90 °C using a heating plate and reacted for 48 hours. Heating was then stopped, and the mixture was allowed to cool naturally to room temperature. Column chromatography (using petroleum ether-packed columns and a petroleum ether:ethyl acetate eluent ratio of 50:1) was then used to separate the product into a colorless oily substance, the target product (0.0713 g, yield 65%, straight-chain to branched-chain ratio 7:1). The reaction formula is as follows:

[0204]

[0205] The results of the product structure confirmation are as follows: 1 H NMR (400 MHz, CDCl3) δ7.30-7.25(m,2H),7.15-7.09(m,1H),7.01-6.96(m,2H),4.63(d,J=10.0 Hz,2H),2.48(t,J=7.6 Hz,2H),1.99(t,J=7.6 Hz,2H),

[0206] 1.71-1.61(m,2H),1.64(s,3H),1.52-1.42(m,2H); 13 C NMR (100 MHz, CDCl3) δ172.3,150.9,145.5,129.6,125.9,121.7,110.4,37.5,34.4,27.1,24.7,22.5.

[0207] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing alkyl phenyl esters from alkyl olefins, characterized in that: The method is as follows: Under a protective atmosphere, alkyl olefins, phenyl formate, palladium acetate, and bisphosphine ligand dtbpx were dispersed in an organic solvent at a molar ratio of 1:3:0.05:0.1–0.

2. The mixture was then reacted at 50–110 °C without the addition of any additional strong acid to yield alkyl phenyl acid esters. After the reaction was complete, the target product, alkyl phenyl acid esters, was separated. The alkyl olefins have the following structural formulas: 1-octene, dodecyl-1-ene, allylcyclohexane, 4,4-dimethylpent-1-ene, but-3-en-1-ylbenzene, allylbenzene, 5-en-1-ylacetate hexyl ester, methyl pent-4-enoate, N-methoxy-N-methylbut-3-enamide, but-3-enonitrile, diethyl allylphosphonate, 2-vinylisoindoline-1,3-dione. N -(quinolin-8-yl)but-3-enamide, N -(quinolin-8-yl)pentyl-4-enamide, vinylcyclohexane, 3,3-dimethylbut-1-ene, triethyl(vinyl)silane, prop-1-en-2-ylbenzene, methylenecyclohexane, 2-(3-methylbut-3-en-1-yl)isoindoline-1,3-dione, (3aR,5R,6S,6aR)-5-((R)-2,2-dimethyl-1,3-dioxolane-4-yl)-6-(hept-6-en-1-oxy)-2,2-dimethyl-tetrahydrofurano[2,3-d][1,3]dioxacyclopentane, 3-(hept-6-en- The following is a list of the following: 1-yl)-1-((3aR,4R,6R,6aR)-6-(methoxymethyl)-2,2-dimethyltetrahydrofurano[3,4-d][1,3]dioxane-4-yl)pyrimidine-2,4(1H,3H)-dione, (8R,9S,13S,14S,17S)-17-allyl-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentano[a]phenanthrene, bicyclo[2.2.1]hept-2-ene, cyclohexene, and cyclooctene. The alkyl phenyl esters mentioned are: phenyl nonanoate, phenyl tridecanoate, phenyl 4-cyclohexylbutyrate, phenyl 5,5-dimethylhexanoate, phenyl 5-phenylpentanoate, phenyl 4-phenylbutyrate, phenyl 7-acetoxyheptanoate, methyl phenyl adipate, phenyl 5-(methoxy(methyl)amino)-5-oxopentanoate, phenyl 4-cyanobutyrate, phenyl 4-(diethoxyphosphono)butyrate, phenyl 3-(1,3-dioxoisoindoline-2-yl) Phenyl propionate, 5-oxo-5-(quinoline-8-amino)pentanoic acid phenyl ester, 6-oxo-6-(quinoline-8-amino)hexanoic acid phenyl ester, 3-cyclohexylpropionate phenyl ester, 4,4-dimethylpentanoic acid phenyl ester, 3-(triethylsilyl)propionate phenyl ester, 3-phenylbutyrate phenyl ester, 2-cyclohexylacetic acid phenyl ester, 5-(1,3-dioxoisoindoline-2-yl)-3-methylpentanoic acid phenyl ester, 8-(((3aR,5R,6S,6a) R)-5-((R)-2,2-dimethyl-1,3-dioxacyclopentan-4-yl)-2,2-dimethyltetrahydrofurano[2,3-d][1,3]dioxacyclopentan-6-yl)oxy) octanoic acid phenyl ester, 8-(3-((3aR,4R,6R,6aR)-6-(methoxymethyl)-2,2-dimethyltetrahydrofurano[3,4-d][1,3]dioxacyclopentan-4-yl)-2,6-dioxo- The following are all of the following: 3,6-dihydropyrimidin-1(2H)-yl) phenyl octanoate, 4-((8R,9S,13S,14S,17S)-3,17-dimethoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopentyl[a]phenanthrene-17-yl) phenyl butyrate, bicyclo[2.2.1]heptane-2-carboxylic acid phenyl ester, cyclohexanecarboxylate phenyl ester, and cyclooctanecarboxylate phenyl ester. The structural formula of the bisphosphine ligand dtbpx is: .

2. A method for preparing alkyl phenyl esters from alkyl olefins, characterized in that: The method is as follows: Under a protective atmosphere, alkyl olefins, phenyl formate, tetraphenylphosphine palladium, and monophosphine ligand TFPP were dispersed in an organic solvent at a molar ratio of 1:3:0.05:0.1–0.

2. The mixture was then reacted at 50–110 °C without the addition of any additional strong acid to yield alkyl phenyl acid esters. After the reaction was complete, the target product, alkyl phenyl acid esters, was separated. The alkyl olefin has the structural formula of 3-allyl-1H-indole or 2-methylhexa-1,5-diene. The alkyl phenyl ester is either phenyl 4-(1H-indol-3-yl)butyrate or phenyl 6-methylhept-6-enoic acid. The molecular formula of the monophosphine ligand TFPP is: .

3. The method for preparing alkyl phenyl esters from alkyl olefins as described in claim 1 or 2, characterized in that: The organic solvent is toluene, benzene, acetonitrile, 1,2-dichloroethane, or n-hexane.

4. The method for preparing alkyl phenyl esters from alkyl olefins as described in claim 1 or 2, characterized in that: The target product, alkyl phenyl acid ester, was separated by column chromatography.

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