A method for synthesizing conjugated dienyl ester compounds with high regioselectivity

Abstract

The application discloses a method for synthesizing conjugated dienyl ester compounds with high regioselectivity. Specifically, the method is a method for preparing a series of conjugated dienyl ester compounds by catalyzing C5-regioselective esterification reaction of 1,4-dienyl alcohol and free carboxylic acid through combination of an iridium catalyst and a phosphoramidite ligand, and belongs to the field of organic synthesis. The specific operation steps are as follows: an iridium catalyst and a phosphoramidite ligand are added into a reaction tube, a solvent is added, and the iridium and the ligand are fully combined through stirring, then 1,4-dienyl alcohol, a carboxylic acid compound and an additive are added, and then the reaction is carried out at room temperature; after the reaction is completed, quenching and purification are carried out to obtain the conjugated dienyl ester compound. The method has the advantages of good substrate applicability, mild reaction condition, high regioselectivity and high E-selectivity.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing conjugated dienyl ester compounds with high regioselectivity. Background Technology

[0002] Conjugated dienyl esters are a common organic synthesis unit structure, widely found in natural products, various bioactive molecules, and pharmaceutical intermediates. Natural products such as Anguinomycins C / D, Reveromycin B, and Zooxanthellactone all possess conjugated dienyl ester structural units. However, to date, there is still no efficient and concise synthetic method. Traditional methods for synthesizing conjugated dienyl esters typically use conjugated dienes (1,3-dienal or 1,3-dienyl chloride) as starting materials, employing nucleophilic addition and esterification steps (see: a) P. Zhang, JP Morken, J. Am. Chem. Soc. 2009, 131, 12550; b) JL Jat, SR De, G.Kumar, AM Adebesin, SK Gandham, JR Falck, Org. Lett. 2015, 17, 1058;c) N. Nakanishi, S. Matsubara, K. Utimoto, S. Kozima, R. Yamaguchi, J. Org. Chem. 1991, 56, 3278; d) P. Stamm, F. Etl, ACD Maia, S. Dötterl, S.Schulz, J. Org. Chem. 2021, 86, 5245.); In particular, the esterification process requires the use of environmentally unfriendly esterification reagents such as acid anhydrides or acyl chlorides. The complex structures of acid anhydrides and acyl chlorides are both unstable and difficult to prepare. Therefore, the types of conjugated dienyl ester skeletons synthesized by traditional methods are very limited, which to some extent restricts the development and application of conjugated dienyl ester compounds.

[0003] Building upon previous research, we have been seeking simpler and more efficient methods to construct conjugated dienyl esters using readily available substrates. Therefore, through catalytic system design and screening of reaction conditions, we achieved iridium-catalyzed C5-regioselective esterification of 1,4-dienyl alcohols and carboxylic acids, conveniently preparing a series of conjugated dienyl esters. This method offers advantages such as good substrate applicability, mild reaction conditions, and high regioselectivity and E-selectivity. Summary of the Invention

[0004] Given the limitations of traditional methods for synthesizing conjugated dienyl esters, this invention utilizes a transition metal-catalyzed esterification strategy to achieve a novel method for synthesizing conjugated dienyl ester compounds with high regio and E-selectivity, using readily available 1,4-dienyl alcohols and commercially available carboxylic acid compounds as raw materials.

[0005] To achieve the objectives of this invention, the technical solution adopted is as follows:

[0006] A method for highly regioselective synthesis of conjugated dienyl ester compounds, characterized in that: under the catalysis of an iridium catalyst, 1,4-dienyl alcohol and a carboxylic acid compound undergo a C5-regioselective esterification reaction to prepare a series of conjugated dienyl ester compounds. The structural formula of the 1,4-dienyl alcohol 1 is as follows:

[0007]

[0008] In this context, R and R′ represent different alkyl substituents.

[0009] Furthermore, R can be a straight-chain or branched alkane group from C1 to C8, a substituted alkane group, a cycloalkane group, an aromatic group, or a substituted aromatic group;

[0010] R′ can be H, methyl, or ethyl;

[0011] Further, the method is carried out according to the following steps: the iridium catalyst and phosphoramide ligand are dissolved in a solvent and stirred, then 1,4-dienyl alcohols, carboxylic acids and additives are added, and the reaction is carried out at 0~40℃ for 12 h~48 h, followed by quenching and purification to obtain conjugated dienyl esters.

[0012] Furthermore, the structural formula of the carboxylic acid compound is as follows:

[0013]

[0014] Among them, R 1 It can be alkyl or aryl.

[0015] Further R 1 It can be methyl, phenyl, 2-bromophenyl, 4-methylphenyl, 1-naphthylmethyl, 4-biphenylmethyl, 4-nitrophenylmethyl, 4-methoxyphenylmethyl, benzyloxymethyl, etc. It is not limited to these; aryl carboxylic acids and aryl acetic acids can also react.

[0016] The specific reaction equation is as follows (Scheme 1):

[0017]

[0018] Scheme 1. Reaction Equation

[0019] Furthermore, the molar ratio of the 1,4-dienyl alcohol compound and the carboxylic acid compound is 1.2:1 to 2:1, with a preferred molar ratio of 1.5:1, which yields the highest yield.

[0020] Furthermore, the iridium catalyst is a 1,5-cyclooctadiene iridium chloride dimer, and the amount of iridium catalyst used is 2-5% of the carboxylic acid compound equivalent. Preferably, the amount of iridium catalyst used is 3% of the carboxylic acid compound equivalent.

[0021] Furthermore, the phosphoramidite ligand L is:

[0022]

[0023] The amount of phosphoramide ligand L used is 200-400% of the molar amount of 1,5-cyclooctadiene iridium chloride dimer.

[0024] Furthermore, the additive is acetic acid, trifluoroacetic acid, or Zn(OTf)₂. Acetic acid is the most effective. The additive equivalent can be 50-200% of the carboxylic acid equivalent. The highest yield is achieved when the additive dosage is 100%.

[0025] Furthermore, the reaction solvent is dichloromethane, dichloroethane, tetrahydrofuran, toluene, or trichloromethane, with dichloromethane being more preferred.

[0026] Furthermore, the reaction temperature is 0~40℃, the reaction time is 12 h~48 h, the preferred reaction temperature is room temperature, and the highest yield is achieved when the reaction time is 24 h.

[0027] Beneficial effects:

[0028] This invention utilizes a transition metal-catalyzed esterification strategy to synthesize conjugated dienyl ester compounds from readily available 1,4-dienyl alcohols and commercially available carboxylic acid compounds with high regioselectivity and E-selectivity. This method offers advantages such as good substrate applicability, mild reaction conditions, and high regioselectivity and E-selectivity. Attached Figure Description

[0029] Figure 1 The NMR spectrum of compound 3aa is a proton NMR spectrum.

[0030] Figure 2 The NMR spectrum of compound 3aa is shown in carbon NMR. Detailed Implementation

[0031] The following carboxylic acid compounds 2a-2h are commercially available and can be used directly without further purification. 1,4-dienyl alcohols 1a-1e, 1g, and 1i are known compounds and prepared according to literature reports. The specific preparation methods for 1,4-dienyl alcohols 1f, 1h, and 1j are as follows:

[0032] Synthesis of raw material (1f):

[0033]

[0034] Aldehyde I (5 mmol) was added to a dry round-bottom flask and dissolved in dry THF. The flask was cooled to 0°C and filled with argon gas. Then, vinyl magnesium chloride (1.0 M THF solution, 15.0 mmol) was slowly added dropwise to the flask. The mixture was stirred at 0°C for 1 h and monitored by TLC. The mixture was quenched with saturated NH4Cl solution (30 mL), the aqueous phase was extracted with EtOAc, the organic phase was dried over Na2SO4, and the mixture was concentrated by vacuum filtration. The crude product was purified by silica gel column chromatography to give compound 1f (694.0 mg, yield: 90%, E / Z = 6:1), which was a yellow oil. 1 H NMR (300 MHz, CDCl3) δ 6.00-5.83 (m, 1H), 5.78-5.61 (m,1H), 5.56-5.42 (m, 1H), 5.26 (d, J = 17.3 Hz, 1H), 5.13 (d, J = 10.6 Hz, 1H), 4.95 (t, J = 7.2 Hz, 0.15H), 4.61 (t, J = 6.3 Hz, 0.86H), 2.02 (d, J = 7.9Hz, 0.33 H), 1.93 (d, J = 7.5 Hz, 1.74 H), 0.92 (s, 1.27 H), 0.89 (s, 8.10H). 13 C NMR (75 MHz, CDCl3) δ 140.0, 133.3, 130.1, 114.8, 74.0, 46.8, 31.1,29.4. HRMS (ESI) m / z calculated for C 10 H 19 O3 [M+H] + Found: 155.1430; Found: 155.1435.

[0035] Synthesis of raw materials (1h):

[0036]

[0037] Aldehyde I (5 mmol) was added to a dry round-bottom flask and dissolved in dry THF. The flask was cooled to 0°C and filled with argon gas. Then, vinyl magnesium chloride (1.0 M THF solution, 15.0 mmol) was slowly added dropwise to the flask. The mixture was stirred at 0°C for 1 h and monitored by TLC. The mixture was quenched with saturated NH4Cl solution (30 mL), the aqueous phase was extracted with EtOAc, the organic phase was dried over Na2SO4, and the mixture was concentrated by vacuum filtration. The crude product was purified by silica gel column chromatography to give compound 1h (760.1 mg, yield: 87%, E / Z = 1:1), which was a colorless oil. 1 H NMR (300 MHz, CDCl3) δ 5.92-5.78 (m, 1H), 5.66 (dt, J =15.5, 6.6 Hz, 0.53H), 5.50 (dd, J = 15.5, 6.5 Hz, 0.51H), 5.21 (dd, J = 17.2,6.4 Hz, 1H), 5.14-5.05 (m, 1H), 4.56 (t, J = 6.3 Hz, 0.48H), 4.08 (q, J = 5.9Hz, 0.49H), 3.52 (t, J = 6.7 Hz, 2H), 2.06 (q, J = 7.1 Hz, 1H), 1.94 (d, J =15.3 Hz, 1H), 1.82-1.71 (q, J = 6.9 Hz, 2H), 1.59-1.42 (m, 2H). 13 C NMR (75MHz, CDCl3) δ 141.0, 139.8, 114.9, 114.8, 73.7, 73.0, 44.99, 44.96, 36.1,32.5, 32.0, 31.4, 26.3, 22.8. HRMS (ESI) m / z calculated for C9H 16 ClO [M+H] + 175.0884 found: 175.0886.

[0038] Synthesis of raw material (1j):

[0039]

[0040] Aldehyde I (5 mmol) was added to a dry round-bottom flask and dissolved in dry THF. The flask was cooled to 0°C and filled with argon gas. Then, vinyl magnesium chloride (1.0 M THF solution, 15.0 mmol) was slowly added dropwise to the flask. The mixture was stirred at 0°C for 1 h and monitored by TLC. The mixture was quenched with saturated NH4Cl solution (30 mL), the aqueous phase was extracted with EtOAc, the organic phase was dried over Na2SO4, and the mixture was concentrated by vacuum filtration. The crude product was purified by silica gel column chromatography to give the compound dienyl alcohol 1j (700.3 mg, yield: 92%) as a colorless oil.

[0041] 1 H NMR (300 MHz, CDCl3) δ 5.89 (ddd, J = 16.6, 10.4, 5.7 Hz, 1H), 5.67(dd, J = 15.4, 7.5 Hz, 1H), 5.47 (dd, J = 15.4, 6.6 Hz, 1H), 5.24 (d, J =17.1 Hz, 1H), 5.11 (d, J = 10.4 Hz, 1H), 4.57 (t, J = 6.3 Hz, 1H), 2.49-2.36(m, 1H), 1.83-1.47 (m, 6H), 1.36-1.20 (m, 2H). 13 C NMR (75 MHz, CDCl3) δ140.0, 137.6, 129.1, 114.8, 74.0, 43.0, 33.0, 25.2. HRMS (ESI) m / z calculated for C 10 H 17 O [M+H] + 153.1274 found: 153.1277.

[0042] The present invention will be further described below with reference to embodiments, but is not limited thereto.

[0043] Implementation Example 1:

[0044] Synthesis of (3aa):

[0045]

[0046] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and dichloromethane (1.5 mL) were added to the reaction tube, and the mixture was stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 equiv.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3aa (29.6 mg, yield: 81%). 1 H NMR (300MHz, CDCl3) δ 7.77 (dd, J = 7.4, 2.1 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.41-7.27 (m, 2H), 6.41-6.25 (m, 2H), 5.73 (dd, J = 14.2, 7.3 Hz, 1H), 5.53 (q, J = 6.8 Hz, 1H), 5.32-5.21 (m, 1H), 5.15 (d, J = 8.5 Hz, 1H), 1.87-1.66 (m,2H), 1.46-1.19 (m, 10H), 0.87 (t, J = 6.3 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ165.7, 136.2, 134.4, 133.8, 132.8, 132.5, 131.4, 131.3, 127.3, 121.7, 118.8,76.2, 34.6, 31.9, 29.5, 29.3, 25.3, 22.8, 14.2. HRMS (ESI) m / z calculated forC 19 H 26 BrO2 [M+H] + 365.1111 found: 365.1114.

[0047] Implementation Example 2:

[0048] Synthesis of (3ab):

[0049]

[0050] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and dichloromethane (1.5 mL) were added to the reaction tube and stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2b (0.1 mmol, 12.2 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ab (21.5 mg, yield: 75%). 1 H NMR (300MHz, CDCl3) δ 8.06 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 6.39-6.25 (m, 2H), 5.74 (dd, J = 14.0, 7.0 Hz, 1H), 5.53 (q, J = 6.8 Hz, 1H), 5.31-5.17 (m, 1H), 5.12 (d, J = 9.0 Hz, 1H), 1.85-1.66 (m,2H), 1.45-1.24 (m, 10H), 0.87 (t, J = 6.3 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ166.0, 136.3, 133.1, 133.0, 132.0, 130.8, 129.7, 128.5, 118.5, 75.0, 34.7,31.9, 29.5, 29.3, 25.3, 22.8, 14.2. HRMS (ESI) m / z calculated for C 19 H 27 O2 [M+H] + Found: 287.2006; Found: 287.2008.

[0051] Implementation Example 3:

[0052] Synthesis of (3ac):

[0053]

[0054] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2c (0.1 mmol, 13.6 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ac (23.1 mg, yield: 77%). 1 H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 7.8 Hz, 2H), 7.24 (d, J = 7.9 Hz, 2H), 6.41-6.24 (m, 2H), 5.74 (dd, J = 14.2, 6.9 Hz, 1H), 5.51 (q, J = 6.7 Hz, 1H), 5.25 (dd, J = 17.2, 11.7 Hz, 1H), 5.11 (d, J = 8.7 Hz, 1H), 2.41 (s, 3H), 1.84-1.65 (m, 2H), 1.45-1.22 (m, 10H), 0.87 (t, J = 6.6 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ 166.1, 143.6, 136.3, 132.9, 132.2, 129.8, 129.2, 128.0, 118.4, 74.7,34.7, 31.9, 29.5, 29.3, 25.3, 22.8, 21.8, 14.2. HRMS (ESI) m / z calculated forC 20 H 29 O2 [M+H] + 301.2162 found: 301.2166.

[0055] Implementation Example 4:

[0056] Synthesis of (3ad):

[0057]

[0058] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2d (0.1 mmol, 21.2 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ad (25.3 mg, yield: 67%). 1 H NMR (300MHz, CDCl3) δ 7.56 (t, J = 7.9 Hz, 4H), 7.45-7.30 (m, 5H), 6.28 (dt, J =16.4, 10.1 Hz, 1H), 6.15 (dd, J = 15.0, 10.5 Hz, 1H), 5.61 (dd, J = 14.9, 6.9Hz, 1H), 5.30 (q, J = 6.8 Hz, 1H), 5.17 (d, J = 16.4 Hz, 1H), 5.09 (d, J =9.8 Hz, 1H), 3.66 (s, 2H), 1.69-1.51 (m, 2H), 1.33-1.23 (m, 10H), 0.86 (t, J = 6.5 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ 171.0, 140.9, 140.1, 136.2, 133.3,133.0, 131.8, 129.8, 128.9, 127.4, 127.3, 127.2, 118.4, 74.9, 41.5, 34.5,31.9, 29.4, 29.3, 25.2, 22.7, 14.2. HRMS (ESI) m / z calculated for C 26 H 33 O2 [M+H] + 377.2475 found: 377.2480.

[0059] Implementation Example 5:

[0060] Synthesis of (3ae):

[0061]

[0062] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2e (0.1 mmol, 16.5 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ae (21.2 mg, yield: 64%). 1 H NMR (300MHz, CDCl3) δ 7.20 (d, J = 8.2 Hz, 2H), 6.85 (d, J = 8.2 Hz, 2H), 6.28 (dt, J = 16.6, 10.2 Hz, 1H), 6.13 (dd, J = 15.1, 10.5 Hz, 1H), 5.60 (dd, J = 15.1, 6.9 Hz, 1H), 5.27 (q, J = 6.8 Hz, 1H), 5.17 (d, J = 16.6 Hz, 1H), 5.09 (d, J = 9.8 Hz, 1H), 3.79 (s, 3H), 3.55 (s, 2H), 1.66-1.51 (m, 2H), 1.32-1.23 (m,10H), 0.87 (t, J = 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 171.3, 158.7, 136.2,132.9, 131.9, 130.4, 126.4, 118.3, 114.0, 74.63, 55.3, 40.9, 34.5, 31.9,29.4, 29.3, 25.2, 22.7, 14.2. HRMS (ESI) m / z calculated for C21H31O3 [M+H]+:331.2268 found: 331.2270.

[0063] Implementation Example 6:

[0064] Synthesis of (3af):

[0065] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2f (0.1 mmol, 18.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3af (25.6 mg, yield: 74%). 1 H NMR (300 MHz, CDCl3) δ 8.19 (d, J = 8.3 Hz, 2H), 7.46 (d, J = 8.3 Hz, 2H), 6.37-6.10 (m, 2H), 5.58 (dd, J = 14.7, 7.3 Hz, 1H), 5.28 (q, J = 7.4 Hz, 1H), 5.21(d, J = 15.8 Hz, 1H), 5.13 (d, J = 8.5 Hz, 1H), 3.73 (s, 2H), 1.68-1.53 ​​(m,2H), 1.31-1.23 (m, 10H), 0.87 (t, J = 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ169.6, 147.3, 141.6, 136.0, 133.7, 131.2, 130.4, 123.9, 118.9, 75.7, 41.5,34.4, 31.8, 29.4, 29.3, 25.2, 22.7, 14.2. HRMS (ESI) m / z calculated forC 20 H 28 NO4 [M+H] + 346.2013 found: 346.2014.

[0066] Implementation Example 7:

[0067] Synthesis of (3ag):

[0068]

[0069] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2g (0.1 mmol, 18.6 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to 3ag (24.8 mg, yield: 71%). 1 H NMR (300 MHz, CDCl3) δ 8.00 (d, J = 7.9 Hz, 1H), 7.89-7.83 (m, 1H), 7.82-7.76 (m,1H), 7.56-7.39 (m, 4H), 6.24 (dt, J = 16.8, 10.2 Hz, 1H), 6.06 (dd, J = 15.2,10.5 Hz, 1H), 5.57 (dd, J = 15.2, 6.8 Hz, 1H), 5.28 (q, J = 6.7 Hz, 1H),5.15-5.01 (m, 2H), 4.07 (s, 2H), 1.61-1.47 (m, 2H), 1.26-1.11(m, 10H), 0.86(t,J = 6.9 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ 171.1, 136.2, 133.9, 132.9,132.2, 131.7, 130.9, 128.8, 128.1, 126.4, 125.9, 125.6, 124.0, 118.3, 74.8,39.7, 34.5, 31.8, 29.4, 29.2, 25.1, 22.8, 14.2. HRMS (ESI) m / z calculated forC 24 H 31 O2 [M+H] + 351.2319 found: 351.2324.

[0070] Implementation Example 8:

[0071] Synthesis of (3ah):

[0072]

[0073] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2h (0.1 mmol, 16.6 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to 3ah (23.5 mg, yield: 71%). 1 H NMR (300 MHz, CDCl3) δ 7.41-7.26 (m, 5H), 6.38-6.18 (m, 2H), 5.62 (dd, J = 14.1, 7.4 Hz, 1H), 5.38 (q, J = 6.9 Hz, 1H), 5.24 (d, J = 15.7 Hz, 1H), 5.14 (d, J = 8.9 Hz, 1H), 4.64 (s, 2H), 4.09 (s, 2H), 1.72-1.56 (m, 2H), 1.35-1.24 (m,10H), 0.87 (t,J = 6.4 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ 169.8, 137.2, 136.1,133.6, 131.4, 128.6, 128.2, 128.1, 118.8, 75.1, 73.4, 67.4, 34.5, 31.8, 29.4,29.2, 25.2, 22.7, 14.2. HRMS (ESI) m / z calculated for C 21 H 31 O3 [M+H] + 331.2268 found: 331.2270.

[0074] Implementation Example 9:

[0075] Synthesis of (3ba):

[0076]

[0077] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1b (0.15 mmol, 25.0 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ba (27.1 mg, yield: 77%). 1 H NMR (300 MHz, CDCl3) δ 7.77 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.39-7.29 (m, 2H), 6.40-6.27 (m, 2H), 5.73 (dd, J = 14.0, 7.3 Hz, 1H), 5.53 (q, J = 6.9 Hz, 1H), 5.36-5.20 (m, 1H), 5.14 (d, J = 8.5 Hz, 1H), 1.89-1.66 (m,2H), 1.50-1.23 (m, 8H), 0.88 (t, J= 6.6 Hz, 3H). 13 C NMR (75 MHz, CDCl3) δ165.7, 136.2, 134.4, 133.8, 132.8, 132.5, 131.4, 131.3, 127.3, 121.7, 118.7,76.2, 34.6, 31.8, 29.2, 25.3, 22.7, 14.2. HRMS (ESI) m / z calculated forC 18 H 24 BrO2 [M+H] + 351.0954 found: 351.0956.

[0078] Implementation Example 10:

[0079] Synthesis of (3ca):

[0080]

[0081] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1c (0.15 mmol, 20.8 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ca (23.6 mg, yield: 74%). 1 H NMR (300 MHz, CDCl3) δ 7.78 (dd, J = 7.3, 2.2 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H),7.39-7.23 (m, 2H), 6.41-6.26 (m, 2H), 5.74 (dd, J = 14.1, 7.4 Hz, 1H), 5.54(q, J = 6.8 Hz, 1H), 5.24 (dd, J = 13.5, 9.0 Hz, 1H), 5.14 (d, J= 8.6 Hz,1H), 1.88-1.63 (m, 2H), 1.41-1.33 (m, 4H), 0.91 (t, J = 6.6 Hz, 3H). 13 C NMR(75 MHz, CDCl3) δ 165.6, 136.1, 134.4, 133.7, 132.7, 132.5, 131.4, 131.3,127.2, 121.7, 118.7, 76.1, 34.3, 27.4, 22.6, 14.1. HRMS (ESI) m / z calculated for C 16 H 20 BrO2 [M+H] + 323.0641 found: 323.0644.

[0082] Implementation Example 11:

[0083] Synthesis of (3da):

[0084]

[0085] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Subsequently, 1d (0.15 mmol, 16.8 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was then purified by TLC to give 3da (20.0 mg, yield: 68%). 1 H NMR (300 MHz, CDCl3) δ 7.78 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.41-7.24 (m, 2H), 6.42-6.26 (m, 2H), 5.79-5.68 (m, 1H), 5.48 (q, J = 6.8 Hz, 1H),5.33-5.20 (m, 1H), 5.14 (d, J = 9.0 Hz, 1H), 1.92-1.71 (m, 2H), 0.99 (t,J =7.4 Hz, 3H). 13 HRMS (ESI) m / zcalculated for C 14 H 16 BrO2 [M+H] + Found: 295.0328; Found: 295.0332.

[0086] Implementation Example 12:

[0087] Synthesis of (3ea):

[0088]

[0089] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1e (0.15 mmol, 14.6 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ea (18.0 mg, yield: 64%). 1 H NMR (300 MHz, CDCl3) δ 7.77 (dd, J = 7.4, 2.1 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H),7.39-7.29 (m, 2H), 6.42-6.26 (m, 2H), 5.81 (dd, J = 14.2, 6.8 Hz, 1H), 5.66(p, J = 6.6 Hz, 1H), 5.33-5.22 (m, 1H), 5.15 (d, J = 8.8 Hz, 1H), 1.49 (d, J = 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 165.5, 136.0, 134.3, 132.8, 132.7,132.4, 132.3, 131.2, 127.1, 121.6, 118.8, 72.2, 20.2. HRMS (ESI) m / zcalculated for C 13 H 14 BrO2 [M+H] + : 281.0172 found: 281.0176.

[0090] Implementation Example 13:

[0091] Synthesis of (3fa):

[0092]

[0093] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1f (0.15 mmol, 23.1 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3fa (24.6 mg, yield: 73%). 1 H NMR (300 MHz, CDCl3) δ 7.78 (d, J = 7.4 Hz, 1H), 7.65 (d, J = 7.4 Hz, 1H), 7.40-7.26 (m, 2H), 6.46-6.23 (m, 2H), 5.84-5.63 (m, 2H), 5.26 (d, J = 15.8 Hz, 1H), 5.13 (d, J = 9.0 Hz, 1H), 1.86 (dd, J = 14.7, 7.1 Hz, 1H), 1.64-1.57 (m,1H), 0.98 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 165.3, 136.2, 134.5, 133.2,132.8, 132.6, 132.5, 131.2, 127.3, 121.9, 118.8, 74.0, 47.9, 30.4, 30.1. HRMS(ESI) m / z calculated for C 17 H 22 BrO2 [M+H] + 337.0798 found: 337.0799.

[0094] Implementation Example 14:

[0095] Synthesis of (3ga):

[0096]

[0097] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1 g (0.15 mmol, 28.2 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ga (24.7 mg, yield: 67%). 1 H NMR (300 MHz, CDCl3) δ 7.76 (dd, J = 7.2, 2.2 Hz, 1H), 7.66 (dd, J = 7.2, 1.9 Hz,1H), 7.40-7.17 (m, 7H), 6.36 (dt, J = 13.1, 9.6 Hz, 2H), 5.77 (dd, J = 14.3, 7.2 Hz, 1H), 5.58 (q, J = 6.8 Hz, 1H), 5.35 – 5.20 (m, 1H), 5.16 (d, J = 9.2Hz, 1H), 2.85-2.64 (m, 2H), 2.24-1.95 (m, 2H). 13C NMR (75 MHz, CDCl3) δ165.6, 141.3, 136.0, 134.5, 134.2, 132.63, 132.60, 131.4, 130.9, 128.6,128.5, 127.3, 126.2, 121.7, 119.0, 75.6, 36.2, 31.7. HRMS (ESI) m / zcalculated for C 20 H 20 BrO2 [M+H] + 371.0641 found: 371.0644.

[0098] Implementation Example 15:

[0099] Synthesis of (3ha):

[0100]

[0101] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1 g (0.15 mmol, 26.0 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to 3 ha (23.8 mg, yield: 67%). 1 H NMR (300 MHz, CDCl3) δ 7.77 (d, J = 7.4 Hz, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.40-7.28 (m, 2H), 6.42-6.27 (m, 2H), 5.73 (dd, J = 14.1, 7.4 Hz, 1H), 5.55 (q, J = 6.8 Hz, 1H), 5.28 (d, J = 15.5 Hz, 1H), 5.16 (d, J = 8.6 Hz, 1H), 3.54 (t, J= 6.6 Hz, 2H), 1.93-1.73 (m, 4H), 1.65-1.50 (m, 2H). 13 C NMR (75 MHz, CDCl3)δ 165.6, 136.0, 134.4, 134.1, 132.61, 132.59, 131.3, 130.9, 127.3, 121.7,119.1, 75.7, 44.8, 33.8, 32.3, 22.7. HRMS (ESI) m / z calculated for C 16 H 19 ClBrO2[M+H] + 357.0251 found: 357.0255.

[0102] Implementation Example 16:

[0103] Synthesis of (3ia):

[0104]

[0105] Add 4.0 mg (3 mol%) of 1,5-cyclooctadiene iridium chloride dimer to the reaction tube. L (12.2 mg, 12 mol%) and dichloromethane (1.5 mL) were added and stirred at room temperature for 10 min. Then, 1i (0.15 mmol, 25.0 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ia (27.6 mg, yield: 80%). 1 H NMR (300 MHz, CDCl3) δ 7.79 (dd, J = 7.4, 2.1 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H),7.40-7.28 (m, 2H), 6.40-6.27 (m, 2H), 5.72 (dd, J = 13.9, 7.8 Hz, 1H), 5.36(t, J = 7.1 Hz, 1H), 5.25 (d, J = 14.9 Hz, 1H), 5.13 (d, J= 9.2 Hz, 1H), 1.89-1.61 (m, 6H), 1.32-1.06 (m, 5H). 13 C NMR (75 MHz, CDCl3) δ 165.6, 136.2,134.6, 134.5, 132.7, 132.5, 131.3, 130.0, 127.3, 121.7, 118.6, 80.2, 42.0,28.80, 28.77, 26.4, 26.1, 26.0. HRMS (ESI) m / z calculated for C 18 H 22 BrO2 [M+H] + 349.0798 found: 349.0799.

[0106] Implementation Example 17:

[0107] Synthesis of (3ja):

[0108]

[0109] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and dichloromethane (1.5 mL) were added to a reaction tube and stirred at room temperature for 10 min. Subsequently, 1j (0.15 mmol, 22.6 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 eq.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3ja (25.4 mg, yield: 76%). 1 H NMR (300 MHz, CDCl3) δ 7.77 (d, J = 7.4 Hz, 1H), 7.65 (d, J = 7.5 Hz, 1H), 7.40-7.28 (m, 2H), 6.44-6.24 (m, 2H), 5.73 (dd, J = 14.2, 7.6 Hz, 1H), 5.42 (t, J = 7.7 Hz, 1H), 5.25 (d, J = 16.3 Hz, 1H), 5.13 (d, J= 9.3 Hz, 1H), 2.34-2.21(m, 1H), 1.87-1.25 (m, 8H). 13 C NMR (75 MHz, CDCl3) δ 165.7, 136.2, 134.4,134.2, 132.8, 132.5, 131.3, 130.7, 127.3, 121.7, 118.7, 79.6, 43.9, 29.2,28.9, 25.7, 25.5. HRMS (ESI) m / z calculated for C 17 H 20 BrO2 [M+H] + 335.0641 found: 335.0644.

[0110] The following examples 18-22 are experiments with controlled variables:

[0111] Implementation Example 18:

[0112] Synthesis of (3aa):

[0113] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and dichloroethane (1.5 mL) were added to the reaction tube, and the mixture was stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 equiv.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3aa (28.9 mg, yield: 79%).

[0114] Implementation Example 19:

[0115] Synthesis of (3aa):

[0116] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and toluene (1.5 mL) were added to a reaction tube and stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 equiv.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3aa (15.4 mg, yield: 42%).

[0117] Implementation Example 20:

[0118] Synthesis of (3aa):

[0119] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and dichloromethane (1.5 mL) were added to a reaction tube and stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and TFA (1 equiv.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3aa (16.4 mg, yield: 45%).

[0120] Implementation Example 21:

[0121] Synthesis of (3aa):

[0122] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and dichloromethane (1.5 mL) were added to the reaction tube, and the mixture was stirred at room temperature for 10 min. Subsequently, 1a (0.15 mmol, 27.5 mg, 1.5 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and Zn(OTf)₂ (1 equiv.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3aa (8.0 mg, yield: 22%).

[0123] Implementation Example 22:

[0124] Synthesis of (3aa):

[0125] 1,5-cyclooctadiene iridium chloride dimer (4.0 mg, 3 mol%), L (12.2 mg, 12 mol%), and dichloromethane (1.5 mL) were added to a reaction tube and stirred at room temperature for 10 min. Subsequently, 1a (0.1 mmol, 18.3 mg, 1 equiv.), 2a (0.1 mmol, 20.1 mg, 1 equiv.), and AcOH (1 equiv.) were added. The tube was then sealed, and the reaction was allowed to proceed at room temperature for 24 h. The crude product was purified by TLC to give 3aa (24.5 mg, yield: 67%).

[0126] The embodiments described above are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments. Any obvious improvements, substitutions or modifications that can be made by those skilled in the art without departing from the essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. A method for synthesizing a conjugated dienyl ester compound with high regioselectivity, characterized by: Under the action of iridium catalyst, phosphoramidite ligand and additive, 1,4-dienyl alcohol compound and carboxylic acid compound undergo high C5-regioselective esterification reaction to prepare conjugated dienyl ester compound; ； wherein R is a linear alkyl group, a branched alkyl group, a substituted alkyl group, a cycloalkyl group, an arene group or a substituted arene group having 8 carbons or less, and R' is H; R 1 is an alkyl group or an aryl group; the iridium catalyst is 1,5-cyclooctadiene iridium chloride dimer; the additive is acetic acid, trifluoroacetic acid, Zn(OTf)2; and the phosphoramidite ligand used is: 。 2. The method according to claim 1, wherein the conjugated dienyl ester compound is synthesized with high regioselectivity. The method is performed according to the following steps: the iridium catalyst and the phosphoramidite ligand are dissolved in a reaction solvent and stirred, then the 1,4-dienyl alcohol compound, the carboxylic acid compound and the additive are added, and the reaction is carried out at 0-40℃ for 12-48h, and then the conjugated dienyl ester compound is obtained after quenching and purification.

3. The method for synthesizing a conjugated dienyl ester compound with high regioselectivity according to claim 1 or 2, characterized in that: The molar ratio of the 1,4-dienyl alcohol compound to the carboxylic acid compound is 1.2:1-2:

1.

4. The method for synthesizing conjugated dienyl ester compounds with high regioselectivity according to claim 2, characterized in that: The reaction solvent is dichloromethane, dichloroethane, tetrahydrofuran, toluene or trichloromethane.

5. The method for synthesizing a conjugated dienyl ester compound with high regioselectivity according to claim 1 or 2, characterized in that: The amount of the iridium catalyst is 2-5% of the amount of substance of the carboxylic acid compound.

6. The method according to claim 1 or 2, wherein the equivalent of the additive is 50-200% of the equivalent of the carboxylic acid compound.

7. The method according to claim 2, wherein the molar ratio of the 1,4-dienyl alcohol compound to the carboxylic acid compound is 1.5:1, the reaction solvent is dichloromethane, and the amount of the iridium catalyst is 3% of the amount of substance of the carboxylic acid compound.

8. The method according to claim 1 or 2, wherein the additive is acetic acid, and the equivalent of the additive is 100% of the equivalent of the carboxylic acid compound.

9. The method for synthesizing a conjugated dienyl ester compound with high regioselectivity according to claim 1 or 2, characterized in that: The amount of the phosphoramidite ligand is 200-400% of the equivalent of the 1,5-cyclooctadiene iridium chloride dimer.

10. The method of claim 9, wherein the method is characterized by: The amount of the phosphoramidite ligand is 400% of the equivalent of the 1,5-cyclooctadiene iridium chloride dimer.

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