Method for catalyzing hydrogen dienation reaction of alpha, beta-unsaturated ketone and 1, 3-diene by nickel

Abstract

The invention relates to a method for catalyzing a hydrodienation reaction of alpha, beta-unsaturated ketone and 1, 3-diene by nickel. Specifically, an alpha, beta-unsaturated ketone compound reacts with 1, 3-diene under the action of a zero-valent nickel catalyst and a monophosphine ligand. According to the method, alpha, beta-unsaturated ketone and 1, 3-diene are used as raw materials to selectively react at a No.1 position or a No.4 position of olefin to generate two regioselective conjugated diene derivatives; wherein the alpha, beta-unsaturated ketone 1 comprises one or two of aryl alpha, beta-unsaturated ketone and alkyl alpha, beta-unsaturated ketone derivatives; the 1, 3-diene compound 2 comprises one or more than two of aryl olefin and alkyl olefin derivatives; a series of conjugated olefin derivatives are obtained through simple and safe steps. The reaction raw materials alpha, beta-unsaturated ketone compound and 1, 3-diene are simple and easy to obtain. Secondly, reaction conditions are mild and safe, and reaction steps are simple and efficient. Finally, the obtained product is a class of novel conjugated diene derivatives, and the yield and selectivity are excellent.

Description

Technical Field

[0001] The invention relates to a method for the hydrogen dienization reaction of α,β-unsaturated ketone catalyzed by nickel. Background Art

[0002] Conjugated dienes are versatile building blocks for the construction of natural products and synthetic polymer molecules. In the past few decades, the development of catalytic methods to achieve the synthesis and transformation of conjugated dienes has attracted much attention from organic chemists. Among them, adjusting the elementary steps of metal organic reactions is an important approach. For example, the coupling of two unsaturated compounds can be achieved by regulating the process of oxidative cyclometallation. α,β-Unsaturated ketones and 1,3-dienes can easily undergo oxidative cyclometallation with the assistance of low-valent ruthenium, cobalt and iron to form seven-membered metal rings, which can then undergo β-hydrogen elimination and reductive elimination to provide hydrodienylation products. On the other hand, zero-valent nickel has been widely studied for the functionalization of olefins through oxidative cyclometallation. However, to date, the strategy of catalyzing the selective hydrodienylation of α,β-Unsaturated ketones and 1,3-dienes has not been explored. Therefore, it is necessary to develop an efficient method to achieve the hydrodienylation of activated olefins. Based on this, we can obtain conjugated dienes with high regio- and stereoselectivity by regulating the oxidative cyclometallation step and using aryl-substituted dienes and alkyl-substituted dienes as dienes under nickel / tricyclohexylphosphine ligand catalysis. This method has good functional group tolerance. In addition, the conjugated diene products can undergo a series of complex transformations, further demonstrating that this strategy has broad application prospects.

[0003] The raw materials used in the present invention are cheap and easy to obtain, the conditions are mild and easy to operate, the target product can be obtained in one step, and the product has excellent regional and stereoselectivity. The synthesis method of complex conjugated dienes is enriched, and the product can undergo multiple transformations, providing a new method for the diversity of synthetic chemistry.

[0004] In summary, this paper describes a simple and easy-to-use method for the hydrodienylation of α,β-unsaturated ketones under mild conditions. Summary of the invention

[0005] The object of the present invention is to provide a method for the asymmetric bisallylation of alkynes catalyzed by nickel

[0006]

[0007] Reaction equation 1: Hydrodiolefination of α,β-unsaturated ketones

[0008] The specific steps are as follows:

[0009] The reaction is carried out in a reactor. Under the protection of an inert atmosphere, a nickel catalyst, a monophosphorus ligand, an additive, an α,β-unsaturated ketone 1, a solvent, a 1,3-diene 2a, and allylboronic acid pinacol ester 3a are added in sequence. The reaction is carried out at 80° C. for 24 hours. After the reaction is completed, a conjugated diene derivative 3 or 4 is separated.

[0010] The α,β-unsaturated ketone compound includes one or two of aryl alkyne α,β-unsaturated ketone and alkyl α,β-unsaturated ketone derivatives; its specific structure is:

[0011]

[0012] The 1,3-diene compound includes one or two of an aromatic 1,3-diene and an alkyl 1,3-diene; wherein the specific structure of the compound is one or more of the following structural formulas:

[0013]

[0014] The α,β-unsaturated ketone compound 1 and the 1,3-diene compound 2 shown in the following formula are used as raw materials to generate a tetrasubstituted olefin derivative 3 or 4, and the reaction formula is as follows:

[0015]

[0016] The molar ratio of the α,β-unsaturated ketone compound to the 1,3-diene compound 2 is 1:3-1:1, preferably 1:2-1:1.

[0017] The nickel catalyst used is bis(1,5-cyclooctadiene)nickel, and the amount of the nickel catalyst used is 1-10% molar equivalent (relative to the α,β-unsaturated ketone compound), preferably 5-10% molar equivalent.

[0018] The additive is one or more of benzoquinone, tetrachlorobenzoquinone, 2,6-dimethylbenzoquinone, 1,4-naphthoquinone, 1,2-naphthoquinone, 2,3-dichloro-1,4-naphthoquinone, 2,3-dichloro-5,6-dicyanobenzoquinone, menadione, anthraquinone, phenol, potassium peroxymonosulfonate, iodobenzene acetate, and methyl fumarate; preferably one or more of benzoquinone, 1,4-naphthoquinone, and 1,2-naphthoquinone; the amount of the additive is 5-50% molar equivalent (relative to the α, β-unsaturated ketone compound), preferably 5-20% molar equivalent.

[0019] The solvent is changed to one or more of toluene, n-hexane, dichloromethane, dichloroethane, nitrogen methyl pyrrolidone, acetonitrile, tetrahydrofuran, 1,4-dioxane, ethyl acetate, ethanol, tert-butanol, N,N-dimethylformamide; preferably one or more of N,N-dimethylformamide and tert-butanol. The amount of the solvent is 5-10 ml, preferably 5-6 ml, per mmol of the α,β-unsaturated ketone compound.

[0020] The ligand is a monophosphine ligand or a diphosphine ligand, one or more of the compounds shown in the following structures L1, L2, L3, L4, L5, L6, L7, L8, and L9. Preferably, one or more of L1 and L2; the amount of the nitrogen heterocyclic carbene ligand is 10-20% molar equivalent (relative to the α, β-unsaturated ketone compound), preferably 10-20% molar equivalent;

[0021]

[0022] The present invention has the following advantages:

[0023] First, the raw materials of the reaction, α,β-unsaturated ketone compounds and 1,3-dienes, are simple and easily available. Second, the reaction conditions are mild and safe, and the reaction steps are simple and efficient. Finally, the obtained product is a novel class of conjugated diene derivatives with excellent yield and selectivity. DETAILED DESCRIPTION

[0024] In order to better understand the present invention, the following examples are used for illustration. The reaction materials and results of Examples 1-15 are shown in Table 1.

[0025] Table 1 Reaction results of different α,β-unsaturated ketones and different 1,3-butadiene compounds

[0026]

[0027]

[0028]

[0029] It can be seen from the results in Table 1 that different α, β-unsaturated ketones can be converted into conjugated diene derivatives with medium to high yields, high regio- and stereoselectivity with aromatic or alkyl 1,3-butadiene under the action of nickel catalyst and monophosphine ligand.

[0030] Example 1

[0031] The reaction was carried out in a reactor, and bis(1,5-cyclooctadiene)nickel Ni(COD) was added in sequence under nitrogen protection. 2(0.01mmol), tricyclohexylphosphine L1 (0.02mmol), 1,4-naphthoquinone (0.05mmol), α,β-unsaturated ketone (0.20mmol), tert-butyl alcohol (1.0mL), 1-phenyl-1,3-butadiene 2a (0.24mmol), react at 80°C for 24 hours; after the reaction, the substituted conjugated olefin derivative 3aa was separated by column chromatography with a yield of 82%, and the compound was identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0032] The test data are as follows:

[0033]

[0034] (4E,6E)-1,3,7-Triphenylhepta-4,6-dien-1-one(3aa):Prepared according to the general procedure A,light yellow solid,mp 110-111℃,R f =0.4 (PE / EA=30 / 1), 55.5mg, 82% yield. 1 H NMR (400MHz, Chloroform-d) δ7.97-7.89(m,2H),7.53(t,J=7.3Hz,1H),7.43(t,J=7.6Hz,2H),7.34-7.14(m,10H),6.71(dd,J=15.7,10. 3Hz, 1H), 6.42 (d, J = 15.7Hz, 1H), 6.19 (dd, J = 15.3, 10.2Hz, 1H), 6.01 (dd, J = 15.2, 7.1Hz, 1H), 4.23 (q, J = 7.1Hz, 1H), 3.50-3.39 (m, 2H). 13 C NMR(100MHz,Chloroform-d)δ198.2,143.4,137.5,137.2,137.1,133.2,131.7,130 .8,128.9,128.8,128.7,128.6,128.2,127.9,127.4,126.7,126.3,44.6,43.9.HRMS calculated for C 25 H 23 O[M+H] + 339.1743, found 339.1742.

[0035] Example 2

[0036] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3bb is 95%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0037]

[0038] (4E,6E)-3,7-Bis(4-methoxyphenyl)-1-phenylhepta-4,6-dien-1-one(3bb):Prepared according to the general procedure A,yellow oil,R f =0.3 (PE / EA=20 / 1), 75.9mg, 95% yield. 1 H NMR(400MHz,Chloroform-d)δ7.98-7.88(m,2H),7.59-7.50(m,1H),7.45-7.41 (m,2H),7.28-7.24(m,2H),7.21-7.16(m,2H),6.88-6.78(m,4H),6.59(dd,J=1 5.6,10.2Hz,1H),6.37(d,J=15.6Hz,1H),6.20-6.09(m,1H),5.94(dd,J=15.2, 7.0Hz,1H),4.17(q,J=7.1Hz,1H),3.77(s,3H),3.76(s,3H),3.46-3.35(m,2H). 13 C NMR(100MHz,Chloroform-d)δ198.4,159.1,158.3,137.3,136.3,135.5,133.1,131.1,130. 7,130.3,128.8,128.7,128.2,127.5,127.0,114.1,55.4,55.3,44.8,43.1.HRMScalculated forC 27 H 27 O 2 [M+H] + 399.1955, found 399.1960.

[0039] Example 3

[0040] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3cb is 52%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0041]

[0042] (4E,6E)-3-(4-Isopropylphenyl)-7-(4-methoxyphenyl)-1-phenylhepta-4,6-dien-1-one(3cb):Prepared according to the general procedure A,yellow oil,R f =0.5(PE / EA=30 / 1), 42.4mg, 52% yield(EE / ZE=19:1), NMR date for main product EE-isomer was provided. 1 H NMR(400MHz,Chloroform-d)δ7.97-7.88(m,2H),7.57-7.49(m,1H),7.44(t,J=7.6Hz,2H) ,7.27-7.23(m,2H),7.21-7.15(m,4H),6.85-6.77(m,2H),6.58(dd,J=15.6,10.3Hz,1H),6 .38(d,J=15.6Hz,1H),6.17(dd,J=15.3,10.2Hz,1H),5.95(dd,J=15.2,7.3Hz,1H),4.19( q,J=7.1Hz,1H),3.78(s,3H),3.48-3.37(m,2H),2.95-2.79(m,1H),1.23(d,J=6.9Hz,6H). 13 C NMR(100MHz,Chloroform-d)δ198.5,159.1,147.2,140.9,137.3,136.1,133.1,131.1,130.8 ,130.4,128.7,128.2,127.7,127.5,127.1,126.8,114.1,55.4,44.8,43.6,33.8,24.1.HRMS calculated for C 29 H 31 O 2 [M+H] +411.2319,found 411.2327.found 341.1715.

[0043] Example 4

[0044] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3db is 89%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum and fluorine spectrum) and high-resolution mass spectrometry.

[0045]

[0046] (4E,6E)-3-(4-Fluorophenyl)-7-(4-methoxyphenyl)-1-phenylhepta-4,6-dien-1-one(3db):Prepared according to the general procedure A,yellow oil,R f =0.5(PE / EA=30 / 1), 69.0mg, 89% yield(EE / ZE=16:1), NMR date for main product EE-isomer was provided. 1 H NMR(400MHz,Chloroform-d)δ7.97-7.88(m,2H),7.58-7.50(m,1H),7.4-7.41 (m,2H),7.30-7.18(m,4H),7.03-6.92(m,2H),6.85-6.78(m,2H),6.59(dd,J=1 5.6,10.3Hz,1H),6.39(d,J=15.6Hz,1H),6.15(dd,J=15.1,10.3Hz,1H),5.92( dd,J=15.2,7.0Hz,1H),4.21(q,J=7.1Hz,1H),3.77(s,3H),3.46-3.35(m,2H). 13 C NMR(100MHz,Chloroform-d)δ198.1,161.6(d,J=244.6Hz),159.2,139.2(d,J=3.3Hz),137.1,135.7,133.3,131 .5,131.0,130.2,129.3(d,J=7.8Hz),128.7,128.2,127.5,126.7,115.5(d,J=21.2Hz),114.2,55.4,44.7,43.1. 19F NMR(375MHz,Chloroform-d)δ-116.5.HRMScalculated for C 26 H 24 FO 2 [M+H] + 387.1755, found 387.1760.

[0047] Example 5

[0048] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3eb is 41%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0049]

[0050] (4E,6E)-7-(4-Methoxyphenyl)-3-methyl-1-phenylhepta-4,6-dien-1-one(3eb):Prepared according to the general procedure A,yellow oil,R f =0.4(PE / EA=30 / 1), 25.1mg, 41% yield(EE / ZE=12 / 1), NMR date for main product EE-isomer was provided. 1 H NMR(400MHz,Chloroform-d)δ7.97-7.94(m,2H),7.58-7.54(m,1H),7.49-7.45(m,2H),7.31-7.29(m,2H),6.85-6.83(m,2H),6.60(dd,J=15.6,10.2 Hz,1H),6.42(d,J=15.6Hz,1H),6.22(dd,J=15.2,10.3Hz,1H),5.79(dd,J =15.2,6.5Hz,1H),3.80(s,3H),3.09-2.92(m,3H),1.15(d,J=6.2Hz,3H). 13C NMR(100MHz,Chloroform-d)δ199.4,159.1,138.4,137.4,133.1,130.6,130.5,129.5,128.7,128.2,127.5,127.3,114.2,55.4,45.7,33.0,20.4.HRMS calculated for C 21 H 23 O 2 [M+H] + 307.1693, found 307.1705.

[0051] Example 6

[0052] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3fb is 27%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0053]

[0054] (5E,7E)-8-(4-Methoxyphenyl)-4-methylocta-5,7-dien-2-one(3fb):Preparedaccording to the general procedure A,yellow oil,R f =0.5(PE / EA=30 / 1), 13.2mg, 27% yield(EE / ZE=9 / 1), NMR date for main product EE-isomer was provided. 1 H NMR (400MHz, Chloroform-d) δ7.31-7.29(m,2H),6.85-6.83(m,2H),6.59(dd,J=15.6,10.2Hz,1H),6.42(d,J=15.7Hz,1H),6.18(dd,J= 15.2,10.2Hz,1H),5.68(dd,J=15.2,7.4Hz,1H),3.80(s,3H),2.86-2.76(m,1H),2.54-2.39(m,2H),2.13(s,3H),1.07(d,J=6.8Hz,3H). 13HRMS calculated for C 16 H 21 O 2 [M+H] + 245.1536,found 245.1549.found 345.1210.

[0055] Example 7

[0056] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3bc is 85%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0057]

[0058] (4E,6E)-7-(4-Ethylphenyl)-3-(4-methoxyphenyl)-1-phenylhepta-4,6-dien-1-one(3bc):Prepared according to the general procedure A,colorless oil,R f =0.2(PE / EA=20 / 1), 67.2mg, 85% yield. 1 H NMR(400MHz,Chloroform-d)δ7.97-7.95(m,2H),7.59-7.54(m,1H),7.48-7.44(m,2H),7.28(d,J =8.0Hz,2H),7.24-7.20(m,2H),7.14(d,J=8.0Hz,2H),6.90-6.86(m,2H),6.71(dd,J=15.6,10.2 Hz,1H),6.44(d,J=15.6Hz,1H),6.19(dd,J=15.3,10.2Hz,1H),6.00(dd,J=15.2,7.0Hz,1H),4.2 1(q,J=6.9Hz,1H),3.80(s,3H),3.49-3.39(m,2H),2.63(q,J=7.6Hz,2H),1.24(t,J=7.6Hz,3H). 13C NMR(100MHz,Chloroform-d)δ198.4,158.3,143.6,137.2,136.9,135.4,135.0,133.1,131.6, 130.6,128.8,128.7,128.19,128.17,128.1,126.3,114.1,55.3,44.8,43.1,28.7,15.6.HRMS calculated for C 28 H 29 O 2 [M+H] + 397.2162, found 397.2169.

[0059] Example 8

[0060] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3bd is 85%. The compound is subjected to nuclear magnetic resonance (hydrogen spectrum, carbon spectrum and fluorine spectrum) and high-resolution mass spectrometry.

[0061]

[0062] (4E,6E)-7-(4-Fluorophenyl)-3-(4-methoxyphenyl)-1-phenylhepta-4,6-dien-1-one(3bd):Prepared according to the general procedure A,yellow oil,R f =0.5(PE / EA=30 / 1), 65.8mg, 85% yield. 1 H NMR(400MHz,Chloroform-d)δ7.97-7.94(m,2H),7.58-7.54(m,1H),7.48-7.44(m,2 H),7.31-7.28(m,2H),7.23-7.20(m,2H),7.00-6.95(m,2H),6.89-6.86(m,2H),6.6 4(dd,J=15.6,10.2Hz,1H),6.40(d,J=15.7Hz,1H),6.17(dd,J=15.3,10.2Hz,1H),6 .01(dd,J=15.2,7.0Hz,1H),4.21(q,J=7.1Hz,1H),3.79(s,3H),3.49-3.38(m,2H). 13C NMR(100MHz,Chloroform-d)δ198.3,162.2(d,J=246.9Hz),158.4,137.5,137.2,135.3,133.7(d,J=3.3Hz),133.2 ,130.3,128.78,128.75,128.73,128.71,128.2,127.7(d,J=7.9Hz),115.6(d,J=21.6Hz),114.2,55.4,44.7,43.1. 19 F NMR(375MHz,Chloroform-d)δ-114.6.HRMS calculated forC 26 H 24 FO 2 [M+H] + 387.1755, found 387.1752.

[0063] Example 9

[0064] The operation process and conditions are the same as those in Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3be is 67%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0065]

[0066] (4E,6E)-3-(4-Methoxyphenyl)-1-phenyl-7-(m-tolyl)hepta-4,6-dien-1-one(3be):Prepared according to the general procedure A,yellow oil,R f =0.5(PE / EA=30 / 1), 51.2 mg, 67% yield(EE / ZE=16 / 1), NMR date for main product EE-isomer was provided. 1 H NMR (400 MHz, Chloroform-d) 1H NMR(400MHz,Chloroform-d)δ7.97-7.95(m,2H),7.59-7.55(m,1H),7.48-7.44(m ,2H),7.24-7.14(m,5H),7.04-7.01(m,1H),6.90-6.86(m,2H),6.74(dd,J=15.6,1 0.3Hz, 1H), 6.43 (d, J = 15.6Hz, 1H), 6.19 (dd, J = 15.3, 10.2Hz, 1H), 6.02 (dd, J = 15. 2,7.0Hz,1H),4.21(q,J=7.0Hz,1H),3.80(s,3H),3.49-3.39(m,2H),2.34(s,3H). 13 C NMR(100MHz,Chloroform-d)δ198.4,158.3,138.1,137.4,137.3,137.2,135.4,133.2,131.7, 130.6,128.8,128.7,128.5,128.24,128.19,127.1,123.5,114.2,55.4,44.8,43.1,21.5.HRMS calculated forC 27 H 27 O 2 [M+H] + 383.2006, found 383.2011.

[0067] Example 10

[0068] The operation process and conditions are the same as those of Example 1. The difference from Example 1 is that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different. The yield of the product 3bf is 70%. The structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0069]

[0070] (4E,6E)-7-(Furan-2-yl)-3-(4-methoxyphenyl)-1-phenylhepta-4,6-dien-1-one(3bf):Prepared according to the general procedure A,colorless oil,R f =0.4(PE / EA=30 / 1), 50.0mg, 70% yield. 1H NMR(400MHz,Chloroform-d)δ7.95-7.92(m,2H),7.58-7.53(m,1H),7.48-7.43(m,2H),7.32 (d,J=1.8Hz,1H),7.22-7.17(m,2H),6.87-6.85(m,2H),6.65(dd,J=15.6,10.4Hz,1H),6.35( dd,J=3.4,1.8Hz,1H),6.24(d,J=15.6Hz,1H),6.20(d,J=3.3Hz,1H),6.12(dd,J=15.3,10.4 Hz, 1H), 6.00 (dd, J=15.2, 6.9Hz, 1H), 4.19 (q, J=7.0Hz, 1H), 3.78 (s, 3H), 3.47-3.36 (m, 2H). 13 C NMR(100MHz,Chloroform-d)δ198.4,158.3,153.3,142.0,137.6,137.2,135.3,133.2, 130.1,128.8,128.7,128.2,127.6,119.3,114.1,111.6,108.0,55.4,44.7,43.1.HRMS calculated for C 24 H 23 O 3 [M+H] + 359.1642, found 359.1641.

[0071] Embodiment 11

[0072] The operation process and conditions are the same as those of Example 1, except that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different, the solvent is isopropanol, the yield of the product 3bg is 74%, and the structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0073]

[0074] (E)-3-(4-Methoxyphenyl)-5,6-dimethyl-1-phenylhepta-4,6-dien-1-one(3bg):Prepared according to the general procedure A, i PrOH(1.0mL),70℃,colorless oil,R f =0.4 (PE / EA=30 / 1), 47.1 mg, 74% yield.1 H NMR(400MHz,Chloroform-d)δ7.92(d,J=7.6Hz,2H),7.55(t,J=7.3Hz,1H),7.44(t,J=7.5Hz,2H),7.22-7.20(m,2H),6.85-6.83(m,2H),5.73(d,J=9.4H z,1H),5.00(s,1H),4.89(s,1H),4.44-4.36(m,1H),3.77(s,3H),3.43(dd, J=16.2,6.6Hz,1H),3.32(dd,J=16.2,7.4Hz,1H),1.87(s,3H).1.85(s,3H). 13 C NMR(100MHz,Chloroform-d)δ198.7,158.1,144.5,137.3,136.6,135.4,133.1,130. 4,128.7,128.4,128.2,114.1,112.2,55.4,46.2,39.7,21.1,14.3.HRMScalculated for C 22 H 25 O 2 [M+H] + 321.1849, found 321.1848.

[0075] Example 12

[0076] The operation process and conditions are the same as those in Example 1, except that the 1,3-butadiene described in Table 1 is different, the solvent is methanol, the yield of the product 3ah is 80%, and the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry. Compound 3ah is a known compound

[0077]

[0078] (E)-1,3-Diphenylhepta-4,6-dien-1-one(3ah):Prepared according to the general procedure A,colorless oil,R f =0.5(PE / EA=30 / 1), 41.1 mg, 80% yield(EE / ZE=10 / 1), NMR date for main product EE-isomer was provided. 1H NMR(400MHz,Chloroform-d)δ7.95-7.89(m,2H),7.56-7.52(m,1H),7.46-7.42 (m,2H),7.33-7.24(m,4H),7.22-7.18(m,1H),6.29(dt,J=17.0,10.1Hz,1H),6. 05(dd,J=15.3,10.2Hz,1H),5.91(dd,J=15.3,7.0Hz,1H),5.10(dd,J=16.9,1.6 Hz, 1H), 4.99 (dd, J=10.1, 1.6Hz, 1H), 4.18 (q, J=7.0Hz, 1H), 3.48-3.36 (m, 2H). 13 HRMS calculated for C 19 H 19 O 2 [M+H] + 263.1430, found 263.1440.

[0079] Example 13

[0080] The operation process and conditions are the same as those of Example 1, except that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different, the solvent is methanol, the yield of the product 4a is 36%, and the structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum and fluorine spectrum) and high-resolution mass spectrometry.

[0081]

[0082] (E)-4-Allylidene-3-(4-fluorophenyl)-1-phenylnonan-1-one(4a):Preparedaccording to the general procedure B,colorless oil,R f =0.4(PE / EA=30 / 1),E and Z-products could be separated in this case(E / Z=4 / 1,the ratio wasdetermined by crude 1 H NMR), 25.0 mg, 36% yield.1 H NMR(400MHz,Chloroform-d)δ7.91-7.89(m,2H),7.58-7.53(m,1H),7.46-7.42(m,2H),7.23-7.17(m ,2H),6.97-6.91(m,2H),6.59(dt,J=16.8,10.4Hz,1H),5.98(d,J=10.8Hz,1H),5.16(dd,J=16.8,2. 0Hz,1H),5.07(dd,J=10.1,2.0Hz,1H),4.15(t,J=7.3Hz,1H),3.48(dd,J=16.7,6.5Hz,1H),3.38(dd ,J=16.7,8.1Hz,1H),2.26-2.19(m,1H),1.91-1.84(m,1H),1.43-1.16(m,6H),0.85(t,J=6.9Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ198.3,161.7(d,J=244.5Hz),145.4,138.8(d,J=3.2Hz),137.3,133.2,133.1,1 29.7(d,J=7.9Hz),128.7,128.1,125.3,116.6,115.3(d,J=21.2Hz),46.1,43.5,32.1,31.3,29.0,22.6,14.1. 19 F NMR(375MHz,Chloroform-d)δ-116.6.HRMS calculated forC 24 H 28 FO[M+H] + 351.2119, found 351.2123.

[0083] Embodiment 14

[0084] The operation process and conditions are the same as those of Example 1, except that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different, the solvent is methanol, the yield of the product 4b is 45%, and the structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum and fluorine spectrum) and high-resolution mass spectrometry.

[0085]

[0086] (E)-4-(2-(Benzyloxy)ethyl)-3-(4-fluorophenyl)-1-phenylhepta-4,6-dien-1-one(4b):Preparedaccording to the general procedure B,colorless oil,R f =0.4(PE / EA=30 / 1),E and Z-products could be separated in this case(E / Z=5 / 1,theratio was determined by crude 1 H NMR),18.6mg,45%yield(0.10mmol scale). 1 HNMR(400MHz,Chloroform-d)δ7.90-7.87(m,2H),7.54(t,J=7.4Hz,1H),7.43(t,J=7.6Hz,2H),7.34-7.25(m,5H),7.19-7.16(m,2H),6.95-6.90(m,2H),6.59(dt,J=16.8,10.4Hz,1H),6.06(d,J=10.8Hz,1H),5.18(dd,J=16.8,1.9Hz,1H),5.10(dd,J=10.2,1.9Hz,1H),4.42(s,2H),4.16(t,J=7.3Hz,1H),3.49(dd,J=16.9,6.5Hz,1H),3.41-3.33(m,3H),2.60-2.53(m,1H),2.31-2.24(m,1H). 13 C NMR(100MHz,Chloroform-d)δ198.1,161.7(d,J=244.9Hz),141.1,138.4,138.3(d,J=3.2Hz),137.1,133.2,132.9,129.7(d,J=7.7Hz),128.7,128.5,128.1,127.7,127.7,127.1,117.5,115.4(d,J=21.3Hz),73.0,69.3,46.7,43.1,31.7. 19 F NMR(375MHz,Chloroform-d)δ-116.3.HRMS calculated for C 28 H 28 FO 2 [M+H] +415.2068, found 415.2073.

[0087] Embodiment 15

[0088] The operation process and conditions are the same as those of Example 1, except that the α,β-unsaturated ketone compound and / or 1,3-butadiene described in Table 1 are different, the solvent is methanol, the yield of the product 4c is 50%, and the structure of the compound is identified by nuclear magnetic resonance (hydrogen spectrum, carbon spectrum) and high-resolution mass spectrometry.

[0089]

[0090] (E)-4-(2-(Benzyloxy)ethyl)-1,3-diphenylhepta-4,6-dien-1-one(4n):Preparedaccording to the general procedure B,colorless oil,R f =0.4(PE / EA=30 / 1),E and Z-products could be separated in this case(E / Z=4 / 1,the ratio wasdetermined by crude 1 H NMR), 19.7mg, 50% yield (0.10mmolscale). 1 H NMR(400MHz,Chloroform-d)δ7.89(d,J=7.7Hz,2H),7.54(t,J=7.4Hz,1H),7.42(t,J=7.6Hz, 2H),7.34-7.22(m,9H),7.19-7.15(m,1H),6.59(dt,J=16.7,10.4Hz,1H),6.07(d,J=10.8Hz, 1H),5.17(dd,J=16.7,1.9Hz,1H),5.08(dd,J=10.1,1.9Hz,1H),4.40(s,2H),4.18(t,J=7.3H z,1H),3.54(dd,J=16.9,7.1Hz,1H),3.43-3.34(m,3H),2.62-2.55(m,1H),2.33-2.26(m,1H). 13C NMR(100MHz,Chloroform-d)δ198.3,142.7,141.2,138.6,137.3,133.1,133.0,128.7,128.6 ,128.5,128.3,128.1,127.7,127.6,127.1,126.8,117.2,73.0,69.4,47.5,43.1,31.8.HRMS calculated for C 28 H 29 O 2 [M+H] + 397.2162, found 397.2156.

[0091] Comparative Example 1

[0092] The raw materials, operation process and conditions were the same as those in Example 1, except that no nickel catalyst was added and the product 3aa was not obtained.

[0093] Comparative Example 2

[0094] The raw materials, operation process and conditions were the same as those in Example 1, except that no ligand L1 was added and no product 3aa was obtained.

[0095] Comparative Example 3

[0096] The raw materials, operation process and conditions are the same as those in Example 1, except that no additives are added, and the product 3aa can be obtained with a yield of 63%.

Claims

1. A method for the nickel-catalyzed hydrodienylation of an α,β-unsaturated ketone and a 1,3-diene, characterized in that: Using α,β-unsaturated ketone and 1,3-diene as raw materials, the reaction occurs selectively at the 1-position or 4-position of the olefin to generate two regioselective conjugated diene derivatives; The reaction formula is as follows: The α,β-unsaturated ketone 1 includes one or two of aromatic α,β-unsaturated ketone and alkyl α,β-unsaturated ketone derivatives; the substituent R 2 is one or more of phenyl, 4-methoxyphenyl, 4-isopropylphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 3-methoxyphenyl, 3-methylphenyl, 3-fluorophenyl, 2-methoxyphenyl, 2-methylphenyl, 2-fluorophenyl, 2-naphthyl, and methyl, R 1 It is one or more of 4-methoxyphenyl, 4-fluorophenyl, 2-methylphenyl, 2,4-dimethoxyphenyl, methyl, etc.; The 1,3-diene compound 2 includes one or more of an aryl olefin and an alkyl olefin derivative; in the case of an aryl olefin, the substituent R 3 is one or more of phenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-ethylphenyl, 4-tert-butylphenyl, 3-methylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2-furyl, N-ethylcarbazolyl; when the alkyl olefin derivative is used, the 1,3-diene compound 2 includes one or more of 2,3-dimethyl 1,3-butadiene, 1,3-butadiene, 1-phenyl-3,5-hexadiene, 1-benzyloxy-3,5-hexadiene, 1,3-nonadiene, etc. (in this case, the corresponding R 1 are phenyl, 4-methoxyphenyl, 4-fluorophenyl, R 2 is one or more of phenyl and 4-fluorophenyl).

2. The method according to claim 1, characterized in that: The α,β-unsaturated ketone compound includes one or two of aromatic substituted α,β-unsaturated ketone and alkyl substituted α,β-unsaturated ketone derivatives; the specific structure of the α,β-unsaturated ketone compound is one or more of the following structural formulas: The 1,3-diene compound includes one or more of aromatic 1,3-diene and alkyl 1,3-diene; wherein the specific structure of the compound is one or more of the following structural formulas:

3. The method according to claim 1 or 2, characterized in that: The specific steps are as follows: The reaction is carried out in a reactor, and a nickel catalyst, a monophosphine ligand, an additive, an α,β-unsaturated ketone, a solvent, and a 1,3-diene are added in sequence under the protection of an inert atmosphere (such as one or more of nitrogen and argon), and the reaction is carried out at 40-100° C. (preferably 60-80° C., more preferably 70-80° C.) for 12-24 hours (preferably 16-20 hours); after the reaction is completed, a conjugated diene derivative is separated and obtained.

4. The method according to claim 1, 2 or 3, characterized in that: The molar ratio of the α,β-unsaturated ketone compound to the 1,3-diene is 1:3-1:1, preferably 1:2-1:1, and more preferably 1:1.5-1:

1.

5. The method according to claim 1, 2 or 3, characterized in that: The nickel catalyst used is bis(1,5-cyclooctadiene)nickel, and the amount of the nickel catalyst used is 1-10% molar equivalent (relative to the α,β-unsaturated ketone compound), preferably 5-10% molar equivalent, and more preferably 8-10%.

6. The method according to claim 1, 2 or 3, characterized in that: The additive is one or more of benzoquinone, tetrachlorobenzoquinone, 2,6-dimethylbenzoquinone, 1,4-naphthoquinone, 1,2-naphthoquinone, 2,3-dichloro-1,4-naphthoquinone, 2,3-dichloro-5,6-dicyanobenzoquinone, menadione, anthraquinone, phenol, potassium peroxymonosulfonate, iodobenzene acetate, and methyl fumarate; preferably one or more of benzoquinone, 1,4-naphthoquinone, and 1,2-naphthoquinone; the amount of the additive is 5-50% molar equivalent (relative to the α, β-unsaturated ketone compound), preferably 5-20% molar equivalent, and more preferably 5-10%.

7. The method according to claim 2 or 3, characterized in that: The solvent is changed to one or more of toluene, n-hexane, dichloromethane, dichloroethane, nitrogen methyl pyrrolidone, acetonitrile, tetrahydrofuran, 1,4-dioxane, ethyl acetate, ethanol, tert-butanol, N,N-dimethylformamide; preferably one or more of N,N-dimethylformamide and tert-butanol. The amount of the solvent is 5-10 ml, preferably 5-6 ml, per mmol of the α,β-unsaturated ketone compound.

8. The method according to claim 2 or 3, characterized in that: The ligand is a monophosphine ligand or a diphosphine ligand, one or more of the compounds shown in the following structures L1, L2, L3, L4, L5, L6, L7, L8, and L9; preferably one or more of L1 and L2; the amount of tricyclohexylphosphine ligand is 10-30% molar equivalent (relative to the α, β-unsaturated ketone compound), preferably 10-20% molar equivalent, more preferably 15-20%;

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