CN114920666B - Method for synthesizing o-alkenyl benzonitrile derivative by rhodium-catalyzed aryl boric acid and dinitrile derivative - Google Patents

Method for synthesizing o-alkenyl benzonitrile derivative by rhodium-catalyzed aryl boric acid and dinitrile derivative Download PDF

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CN114920666B
CN114920666B CN202210570200.5A CN202210570200A CN114920666B CN 114920666 B CN114920666 B CN 114920666B CN 202210570200 A CN202210570200 A CN 202210570200A CN 114920666 B CN114920666 B CN 114920666B
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黄良斌
郭晨霞
邢东辉
刘杰淳
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South China University of Technology SCUT
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Abstract

The invention belongs to the technical field of organic chemistry, and discloses a method for synthesizing an o-alkenyl benzonitrile derivative by rhodium-catalyzed aryl boric acid and a dinitrile derivative. The method comprises the steps of reacting a dinitrile derivative with aryl boric acid under the action of a rhodium catalyst, a phosphine ligand and alkali in a protective atmosphere by taking an organic solvent as a reaction medium, and carrying out subsequent treatment to obtain the o-alkenyl benzonitrile derivative. The invention successfully prepares the o-alkenyl benzonitrile derivative. The method of the invention uses rhodium as a catalyst and adopts phosphine ligand, and has higher yield and wide substrate applicability. In addition, the reaction of the invention takes the arylboronic acid as the raw material, and has the advantages of cheap and easy preparation of the raw material, simple and convenient operation and high atom economy.

Description

Method for synthesizing o-alkenyl benzonitrile derivative by rhodium-catalyzed aryl boric acid and dinitrile derivative
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing an o-alkenyl benzonitrile derivative by rhodium-catalyzed aryl boric acid and a dinitrile derivative.
Background
The arylboronic acid has the advantages of good functional group compatibility, high stability, low toxicity, easy operation, economy, easy obtainment, high reactivity and the like, is widely applied to carbon-carbon and carbon-heteroatom bond formation reactions under the condition of transition metal existence or no metal catalysis, and is an important synthetic building block of various medicines and active natural products.
Suzuki coupling reactions, (Development of Preformed Pd Catalysts for Cross-Coupling Reactions, beyond the 2010Nobel Prize.ACS.Catal.2012,2,1147-1164.) are a classical class of palladium-catalyzed carbon-carbon bond reactions. The oxidative coupling reaction of arylboronic acids as nucleophiles and another molecule of nucleophile in the presence of a copper catalyst and an oxidizing agent, i.e. the Chan-Lam coupling reaction, is also an important synthetic method for constructing functional molecules (Mechanistic Development and Recent Applications of the Chan-Lam amino. Chem. Rev.2019,119, 12491-12523.). In addition, rh, ni and Pd complexes have also received considerable attention in the study of the addition of phenylboronic acids to alkynes (Transition-Metal-Catalyzed Functionalization of Alkynes with Organoboron Reagents: new Trends, mechanistic Insights, and applications. ACS. Catalyst. 2021,11, 7513-7551.). The arylboronic acid can be converted into metal with a metal catalyst, and then carbon-carbon unsaturated bonds are inserted in the metal catalyst in a migration mode, and the obtained metal intermediate can undergo a series of serial processes to quench the reaction.
The above-mentioned reactions involving arylboronic acids share a common feature of achieving in situ functionalization of arylboronic acids. At present, the in-situ and ortho-position difunctional reaction modes of arylboronic acids are still relatively few: (1) The arylboronic acid oxidative difunctional reaction is a director-directed oxidative C-H arylation reaction. Cheng in 2012 reported that amide-directed oxidation C-H arylation and further cyclization with arylboronic acids gave cyclized phenanthrenone (Rhodium (III) -Catalyzed Oxidative C-HCoupling of N-Methoxybenzamides with Aryl Boronic Acids: one-position Synthesis of Phenanthridinones. Angew. Chem. Int. Ed.2012,51, 12343-12347.). (2) The reaction of arylboronic acids with the co-catalysis of palladium and norbornene (The Discovery of a Palladium (II) -Initiated Borono-Catellani reaction. Angew. Chem. Int. Ed.2018,57, 7161-7165.). However, this conversion is limited to aryl boronic acids with substituents in the ortho position and requires an equivalent amount of norbornene.
Aryl nitriles are widely found in agrochemicals, pharmaceuticals and natural products and are widely used and important structural motifs. For example, lenatinib is an anticancer drug and itravirin is an effective anti-HIV drug. (Pharmaceutical Substances: syntheses, patents, applications,4th ed.; thieme: stuttgart, 2001.). Cyano groups can be converted into a variety of useful functional groups such as carboxyl, carbamoyl, aminomethyl, carbonyl and heterocyclic groups and the like (Recent Developments and Perspectives in Palladium-Catalyzed Cyanation of Aryl Halides: synthesis of benzonitriles. Chem. Soc. Rev.2011,40,5049.). Therefore, efficient and selective synthesis of aryl nitriles is very important in both organic and pharmaceutical chemistry. There are many methods for preparing benzonitrile, as achieved by the Rosemund-von Braun reaction (ber.dtsch.chem. Ges.b 1919,52,1749.) or the Sandmeyer reaction (ber.dtsch.chem. Ges.1884,17,2650.), both of which require cumbersome post-treatments and stoichiometric CuCN.
The synthesized aryl nitriles can also form various other important chemical bonds through transition Metal Catalyzed C-CN bond cleavage (Recent Advances in Transition-Metal-Catalyzed C-CN bond activities.rsc adv.2014,4,47806.). In recent years, in order to avoid poisoning of transition metal catalysts and the environment by inorganic cyano sources, the activation of c—cn bonds and cyano transfer strategies have been widely studied to build nitrile compounds. Such as: electrophilic cyanation of aryl grignard or lithium reagents generated in situ from the corresponding aryl bromide or iodide with dimethyl malononitrile (DMMN) (Transnitrilation from Dimethylmalononitrile to Aryl Grignard and Lithium Reagents: A Practical Method for Aryl Nitrile Synthesis J.am. Chem. Soc.2015,137, 9481-9488). However, a disadvantage is that the alkyl nitriles are left as by-products, resulting in a comparatively low atom economy of the conversion. Under the precondition, the present invention constructs in-situ/ortho difunctional multi-substituted acyclic aromatic hydrocarbons of arylboronic acids by a tandem process of 1, 4-metal migration and cyano transfer.
Disclosure of Invention
Aiming at the problems and the shortcomings of the prior art, the invention aims to provide a method for synthesizing an o-alkenylbenzonitrile derivative from aryl boric acid and a dinitrile derivative under the catalysis of rhodium under mild conditions. The method of the invention uses the aryl boric acid which is rich in variety, low in cost and easy to obtain as a raw material, rhodium as a catalyst and a phosphine compound as a ligand, so as to obtain the o-alkenyl benzonitrile derivative with higher yield. The method has the advantages of safe and simple operation, wide substrate applicability, high atom economy, environmental protection and the like.
The aim of the invention is achieved by the following technical scheme:
a method for synthesizing an o-alkenyl benzene nitrile derivative by rhodium-catalyzed reaction of aryl boric acid and a dinitrile derivative, which comprises the following steps: in a protective atmosphere, taking an organic solvent as a reaction medium, reacting a dinitrile derivative with aryl boric acid under the action of a rhodium catalyst, a phosphine ligand and alkali, and carrying out subsequent treatment to obtain an o-alkenyl benzonitrile derivative;
the structure of the arylboronic acid is
Figure BDA0003659976930000021
The aromatic ring Ar 1 Is a substituted or unsubstituted phenyl, naphthyl, benzothienyl, quinolinyl, dibenzofuranyl, fused ring;
the substituted phenyl group is preferably a methyl-substituted phenyl group, a methoxy-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a trifluoromethoxy-substituted phenyl group, a cyano-substituted phenyl group, a phenyl-substituted phenyl group, a halogen-substituted phenyl group, an aldehyde-substituted phenyl group, an acetyl-substituted phenyl group, an ester-substituted phenyl group, an amide-substituted phenyl group, an olefin-substituted phenyl group.
The substitution includes ortho, para and/or meta substitution, which may be mono-, di-or tri-substitution, such as: p-methylphenyl, 3, 5-dimethylphenyl, and the like.
The structure of the dinitrile derivative is
Figure BDA0003659976930000031
The R is 1 Is a substituted or unsubstituted aryl group, benzyl (Ph-CH) 2 (-), heteroarylethyl, heteroarylmethyl;
the substituted aryl is preferably methoxy substituted phenyl, halogen substituted phenyl, phenyl substituted phenyl, ester substituted phenyl;
the unsubstituted aryl is preferably phenyl, naphthyl;
the substituted benzyl is preferably nitro-substituted benzyl, halogen-substituted benzyl, pyridine-substituted benzyl; the substitution herein refers to the substitution on the phenyl group in benzyl;
the substituted heteroarylmethyl is preferably a furanmethyl;
the aromatic ring Ar 2 Phenyl, pyridyl, quinolinyl, substituted or unsubstituted;
the substituted phenyl group is preferably trifluoromethyl substituted phenyl group, cyano substituted phenyl group, ester substituted phenyl group (ROOC substituted phenyl group), methyl substituted phenyl group, isopropyl substituted phenyl group;
the rhodium catalyst is more than one of (1, 5-cyclooctadiene) rhodium (I) chloride dimer (namely chlorine (1, 5-cyclooctadiene) rhodium dimer) and tri (triphenylphosphine) rhodium chloride.
The phosphine ligand is at least one of tri-2-furyl phosphine, triphenylphosphine, tricyclohexyl phosphine, dicyclohexyl phenylphosphine, tricyclopentyl phosphine tetrafluoroborate, tri (4-methoxyphenyl) phosphine, tri (4-trifluoromethylphenyl) phosphine, 2-diphenyl phosphine-2' - (N, N-dimethylamino) biphenyl, 2- (diphenyl phosphine) -2, 6-dimethoxy biphenyl and 2-diphenyl phosphine-biphenyl; preferably at least one of tri-2-furyl phosphine, triphenylphosphine and tricyclohexyl phosphine.
The temperature of the reaction is 25-150 ℃, preferably 60-100 ℃; the reaction time is 6-20 hours.
The reaction mole ratio of the dinitrile derivative to the arylboronic acid is 1: (1.2-2).
The molar ratio of the rhodium catalyst to the dinitrile derivative is (0.025-0.2): 1. The molar ratio of the phosphine ligand to the dinitrile derivative is (0.05-0.4): 1.
the organic solvent is at least one of methanol, ethanol, isopropanol, n-butanol, isobutanol, tertiary butanol, acetonitrile, acetone, 1, 2-dichloroethane, toluene, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, dimethylformamide (DMF) and dimethyl sulfoxide (DMSO); preferably at least one of 1, 2-dichloroethane, 1, 4-dioxane and toluene.
The alkali is at least one of sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide, lithium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, sodium phosphate, potassium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, cesium fluoride, pyridine and triethylamine; preferably, one or more of potassium phosphate, potassium carbonate, cesium carbonate and cesium fluoride.
The protective atmosphere is nitrogen.
The subsequent treatment refers to filtration, washing with ethyl acetate, removing organic solvent and separating by column chromatography.
The removal of the organic solvent refers to the removal of the organic solvent by reduced pressure distillation.
The eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 5:1-1:1.
The structure of the 2-substituted indole compound is that
Figure BDA0003659976930000041
The chemical reaction equation of the synthesis method of the invention:
Figure BDA0003659976930000042
the synthesis method of the invention has the following advantages and beneficial effects:
(1) The method of the invention uses rhodium metal as a catalyst and phosphine compounds as ligands, and has the characteristics of high yield, wide substrate applicability and the like; in addition, the invention takes the arylboronic acid and the dinitrile derivative as raw materials, and has the advantages of low-cost and easy preparation of raw materials, simple and convenient operation and high atom economy.
(2) The synthesis method has wide substrate adaptability and mild conditions, and is expected to be practically applied to mass production.
Drawings
FIG. 1 is a hydrogen spectrum of the target product obtained in example 1;
FIG. 2 is a hydrogen spectrum of the target product obtained in example 4;
FIG. 3 is a hydrogen spectrum of the target product obtained in example 7;
FIG. 4 is a hydrogen spectrum of the target product obtained in example 10;
FIG. 5 is a hydrogen spectrum of the target product obtained in example 13;
FIG. 6 is a hydrogen spectrum of the target product obtained in example 17;
FIG. 7 is a hydrogen spectrum of the target product obtained in example 20;
FIG. 8 is a hydrogen spectrum of the target product obtained in example 23;
FIG. 9 is a hydrogen spectrum of the target product obtained in example 26;
FIG. 10 is a hydrogen spectrum of the target product obtained in example 29.
Detailed Description
The present invention will be described in further detail with reference to examples, but embodiments of the present invention are not limited thereto.
Example 1
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 50 ml of toluene for 2 minutes under nitrogen. To the reaction vessel were successively added 7.5 mmol of phenylboronic acid, 0.25 mmol of tris (triphenylphosphine) rhodium chloride, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 60℃for 6 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 82%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.69 (t, j=7.8 hz, 2H), 7.60 (t, j=7.7 hz, 1H), 7.49 (t, j=7.5 hz, 1H), 7.40 (dq, j=14.1, 7.7hz, 4H), 7.25 (dt, j=6.9, 3.4hz, 3H), 7.16-7.07 (m, 2H), 6.83 (s, 1H), 3.65 (t, j=7.2 hz, 1H), 2.69 (pd, j=14.6, 6.1hz, 2H), 1.94-1.70 (m, 2H) hydrogen is shown in fig. 1.
13 C NMR (126 MHz, deuterated chloroform) δ 145.7,140.1,134.8,134.8 (d, j=2.1 Hz), 133.3,132.8,131.8,130.7,130.5,128.9,128.7,128.5,128.2,128.0 (d, j=3.3 Hz), 127.6,127.0,125.8 (q, j=5.3 Hz), 124.0 (q, j= 274.7 Hz), 119.9,118.0,111.5,36.5,33.6,29.0.
19 F NMR (471 MHz, deuterated chloroform) delta-60.58 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 26 H 20 F 3 N 2 417.1573; found (actual): 417.1569.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000051
example 2
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 50 ml of toluene for 2 minutes under nitrogen. To the reaction vessel were successively added 7.5 mmole of p-methylphenylboronic acid, 0.25 mmole of tris (triphenylphosphine) rhodium chloride, 0.5 mmole of tris-2-furyl phosphine, and 15 mmole of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 60℃for 6 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 72%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.68 (d, j=7.8 hz, 1H), 7.53-7.46 (m, 2H), 7.38 (dd, j=24.3, 7.7hz, 3H), 7.30-7.22 (m, 4H), 7.17-7.10 (m, 2H), 6.81 (s, 1H), 3.64 (dd, j=8.2, 6.3hz, 1H), 2.73-2.57 (m, 2H), 2.40 (s, 3H), 1.95-1.74 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 142.9,140.0,138.3,135.0 (d, j=2.1 Hz), 134.9,133.8,133.6,131.8,130.6,130.5,129.0,128.6,128.4 (d, j=29.7 Hz), 128.0,127.6,127.0,125.8 (q, j=5.4 Hz), 124.1 (q, j= 274.7 Hz), 120.0,118.2,111.3,36.6,33.7,29.0,20.7.
19 F NMR (471 MHz, deuterated chloroform) delta-60.60 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for (theory) C 27 H 22 F 3 N 2 431.1729; found (actual): 431.1721.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000061
example 3
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 50 ml of toluene for 2 minutes under nitrogen. To the reaction vessel were successively added 7.5 mmol of p-methoxyphenylboronic acid, 0.25 mmol of tris (triphenylphosphine) rhodium chloride, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 60℃for 6 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 72%.
The structural characterization data of the obtained product are as follows:
1 h NMR (400 MHz, deuterated chloroform) delta 7.68 (d, j=7.7 hz, 1H), 7.49 (t, j=7.6 hz, 1H), 7.43-7.33 (m, 2H), 7.32-7.24 (m, 4H), 7.18 (d, j=2.7 hz, 1H), 7.16-7.11 (m, 3H), 6.80 (s, 1H), 3.85 (s, 3H), 3.65 (dd, j=8.2, 6.2hz, 1H), 2.74-2.56 (m, 2H), 1.84 (dtd, j=30.1, 13.5,9.2,6.4hz, 2H).
13 C NMR (101 MHz, deuterated chloroform) δ 158.8,139.7,138.1,135.1,135.1,135.0,131.8,130.6,130.5,130.0,129.0,128.4 (q, j=30.3 Hz), 128.1,127.6,127.0,125.8 (q, j=5.2 Hz), 124.1 (d, j= 273.7 Hz), 120.0,119.5,118.0,117.6,112.2,36.6,33.8,29.1.
19 F NMR (471 MHz, deuterated chloroform) delta-60.62 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 22 F 3 N 2 O,447.1678; found (actual): 447.1668.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000062
example 4
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-trifluoromethoxyphenylboric acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 70%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.70 (d, j=7.8 hz, 1H), 7.56 (d, j=2.4 hz, 1H), 7.53-7.46 (m, 2H), 7.46-7.41 (m, 2H), 7.35 (d, j=7.5 hz, 1H), 7.29 (dd, j=5.0, 1.9hz, 3H), 7.17-7.09 (m, 2H), 6.84 (s, 1H), 3.66 (dd, j=8.0, 6.2hz, 1H), 2.73-2.57 (m, 2H), 1.94-1.73 (m, 2H) hydrogen spectra are shown in fig. 2.
13 C NMR (126 MHz, deuterated chloroform) δ 148.3,144.5,139.0,134.8,134.5,132.0,131.8,130.6,130.5,129.1,128.5 (d, j=29.9 Hz), 128.3,128.0,127.1,126.1 (q, j=5.2 Hz), 125.6,125.4,125.2,122.2 (d, j=215.5 Hz), 119.9,116.7,113.3,36.7,33.7,29.1.
19 F NMR (471 MHz, deuterated chloroform) delta-58.02 (s, 3F), -60.67 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 19 F 6 N 2 O,499.1250; found (actual): 499.1252.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000071
example 5
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-phenyl phenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 84%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.90 (s, 1H), 7.80 (d, j=8.1 hz, 1H), 7.69 (d, j=7.8 hz, 1H), 7.57 (d, j=7.6 hz, 2H), 7.52-7.44 (m, 4H), 7.43-7.35 (m, 3H), 7.26 (d, j=5.9 hz, 3H), 7.15 (d, j=7.3 hz, 2H), 6.90 (s, 1H), 3.68 (t, j=7.1 hz, 1H), 2.82-2.61 (m, 2H), 1.99-1.80 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 144.2,141.2,139.8,138.1,134.8 (d, j=1.8 Hz), 134.8,131.8,131.7,131.4,130.8,130.5,129.2,129.1,128.9,128.4 (q, j=30.2 Hz), 128.4,128.0,127.7,127.0,126.8,125.8 (q, j=5.4 Hz), 124.1 (q, j= 274.7 Hz), 119.9,118.0,112.0,36.5,33.7,28.9.
19 F NMR (471 MHz, deuterated chloroform) delta-60.49 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 32 H 24 F 3 N 2 493.1886; found (actual): 493.1880.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000081
example 6
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-cyanobenzeneboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 70%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.99 (s, 1H), 7.87 (dd, j=8.1, 1.8hz, 1H), 7.70 (d, j=7.7 hz, 1H), 7.52 (dd, j=10.7, 7.7hz, 2H), 7.45 (t, j=7.6 hz, 1H), 7.34 (d, j=7.6 hz, 1H), 7.28 (dd, j=4.9, 1.9hz, 3H), 7.13 (dd, j=6.8, 2.9hz, 2H), 6.88 (s, 1H), 3.68 (t, j=7.1 hz, 1H), 2.79-2.60 (m, 2H), 1.83 (dtd, j=25.7, 13.2,9.2,6.2hz, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 150.0,138.9,136.6,135.9,134.5,133.9 (d, j=2.3 Hz). 132.8,132.3,132.0,130.2,129.8,129.0,128.4,128.2,128.1,127.8,126.9,126.0 (q, j=5.3 Hz), 123.9 (q, j= 274.7 Hz), 119.7,116.1 (d, j=57.5 Hz), 112.9 (d, j=60.1 Hz), 36.5,33.6,28.7.
19 F NMR (471 MHz, deuterated chloroform) delta-60.58 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 19 F 3 N 3 441.1453; found (actual): 441.1463.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000082
example 7
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-trifluoromethylphenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 92%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.97 (s, 1H), 7.85 (d, j=8.1 hz, 1H), 7.70 (d, j=7.8 hz, 1H), 7.52 (dd, j=16.9, 8.0hz, 2H), 7.44 (t, j=7.7 hz, 1H), 7.36 (d, j=7.6 hz, 1H), 7.28 (d, j=3.9 hz, 3H), 7.14 (dd, j=6.7, 2.9hz, 2H), 6.87 (s, 1H), 3.67 (t, j=7.1 hz, 1H), 2.86-2.57 (m, 2H), 1.96-1.76 (m, 2H) the hydrogen spectra are shown in fig. 3.
13 C NMR (126 MHz, deuterated chloroform) δ 149.3,139.2,134.6,134.2 (d, j=2.3 Hz), 132.0 (d, j=4.2 Hz), 130.7 (q, j=34.0 Hz), 130.3,130.3,130.3,129.6,129.6,129.1,128.4 (q, j=29.8 Hz), 128.2,128.0,127.0,126.0 (q, j=5.3 Hz), 124.0 (q, j= 274.7 Hz), 122.8 (d, j=273.4 Hz), 119.8,116.7,112.6,36.6,33.6,28.9.
19 F NMR (471 MHz, deuterated chloroform) delta-60.63 (s, 3F), -63.01 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 19 F 6 N 2 484.1374; found (actual): 484.1380.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000091
example 8
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-fluorobenzeneboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 59%.
The structural characterization data of the obtained product are as follows:
1 h NMR (400 MHz, deuterated chloroform) delta 7.69 (dd, j=7.8, 1.3hz, 1H), 7.50 (t, j=7.3 hz, 1H), 7.45-7.39 (m, 2H), 7.39-7.31 (m, 3H), 7.31-7.26 (m, 3H), 7.18-7.07 (m, 2H), 6.82 (s, 1H), 3.65 (dd, j=8.1, 6.2hz, 1H), 2.77-2.51 (m, 2H), 1.97-1.71 (m, 2H).
13 C NMR (101 MHz, deuterated chloroform) δ 162.5,160.0,142.1 (d, j=3.8 Hz), 139.2,134.8,134.7 (d, j=2.1 Hz), 131.6 (d, j=60.9 Hz), 130.8 (d, j=8.3 Hz), 130.5,129.1,128.5 (d, j=29.7 Hz), 128.2,127.8,127.0,126.0 (q, j=5.3 Hz), 125.4 (t, j=340.2 Hz), 120.6 (d, j=21.3 Hz), 120.1,119.9,116.8 (d, j=2.9 Hz), 113.0 (d, j=9.3 Hz), 36.6,33.7,29.1.
19 F NMR (471 MHz, deuterated chloroform) delta-60.65 (s, 3F), -111.61 (s, F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 26 H 19 F 4 N 2 435.1479; found (actual): 435.1475.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000101
example 9
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-formylphenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 58%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ10.05 (s, 1H), 8.22 (d, j=1.7 hz, 1H), 8.11 (dd, j=7.9, 1.7hz, 1H), 7.71 (d, j=7.8 hz, 1H), 7.59 (d, j=8.0 hz, 1H), 7.52 (t, j=7.5 hz, 1H), 7.44 (t, j=7.7 hz, 1H), 7.37 (d, j=7.6 hz, 1H), 7.28 (dd, j=5.1, 1.9hz, 3H), 7.13 (dd, j=6.6, 3.0hz, 2H), 6.90 (s, 1H), 3.68 (t, j=7.1 hz, 1H), 2.71 (pd, j=14.6, 6.0hz, 2H), 1.93-1.69 (m, 2H).
13 C NMR(126MHz,CDCl 3 )δ189.4,151.2,139.4,135.7,134.6,134.6,134.2(q,J＝2.0Hz),133.2,132.0,130.3,130.3,129.7,129.1,128.8,128.4(q,J＝30.2Hz),128.2,128.0,126.0(q,J＝5.0Hz),125.1,122.9,119.8,116.9,112.8,77.3,77.0,76.8,36.6,33.7,28.8.
19 F NMR (471 MHz, deuterated chloroform) delta-60.57 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 20 F 3 N 2 O,445.1522; found (actual): 445.1516.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000102
example 10
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-acetylphenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 68%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ8.29 (d, j=1.9 hz, 1H), 8.17 (dd, j=8.1, 1.9hz, 1H), 7.70 (d, j=7.9 hz, 1H), 7.51 (dd, j=8.0, 5.1hz, 2H), 7.43 (t, j=7.7 hz, 1H), 7.37 (d, j=7.5 hz, 1H), 7.27 (dd, j=5.2, 1.9hz, 3H), 7.16-7.09 (m, 2H), 6.88 (s, 1H), 3.67 (dd, j=8.1, 6.2hz, 1H), 2.71 (td, j=9.4, 8.8,5.8hz, 2H), 2.65 (s, 3H), 1.84 (dtd, j=37.8, 13.9 hz, 3H) as shown in the spectrum of fig. 4.1H.
13 C NMR (126 MHz, deuterated chloroform) δ 195.3,149.8,139.5,136.5,134.7,134.3 (d, j=1.8 Hz), 133.4,132.3,132.0,131.7,130.4,129.3,129.0,128.4 (q, j=29.0 Hz), 128.2,128.0,127.0,126.0 (q, j=5.3 Hz), 124.0 (q, j=273.4 Hz), 119.8,117.2,112.2,36.5,33.7,28.8,26.5.
19 F NMR (471 MHz, deuterated chloroform) delta-60.58 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 28 H 22 F 3 N 2 O,459.1679; found (actual): 459.1670.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000111
example 11
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of p-methoxycarbonylphenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 70%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ8.38 (d, j=2.0 hz, 1H), 8.25 (dd, j=8.2, 1.8hz, 1H), 7.70 (d, j=7.8 hz, 1H), 7.55-7.47 (m, 2H), 7.43 (t, j=7.7 hz, 1H), 7.37 (d, j=7.6 hz, 1H), 7.27 (d, j=5.1 hz, 3H), 7.13 (dd, j=6.7, 2.8hz, 2H), 6.88 (d, j=2.8 hz, 1H), 3.97 (s, 3H), 3.67 (dd, j=8.1, 6.2hz, 1H), 2.70 (ddd, j=17.2, 11.8,7.0hz, 2H), 1.91-1.76 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 164.8,149.8,139.5,134.7,134.6,134.4,134.4,133.6,131.9,131.6,130.4,130.2,129.0,128.5,128.3,128.1,127.9,127.0,126.0 (q, j=5.4 Hz), 125.8,125.1,122.9,52.7,36.6,33.7,28.8.
19 F NMR (471 MHz, deuterated chloroform) delta-60.61 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 28 H 22 F 3 N 2 O 2 475.1628; found (actual): 475.1627.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000121
example 12
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. 7.5 mmol (4- (methylcarbamoyl) phenylboronic acid, 0.125 mmol (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol tri-2-furylphosphine and 15 mmol potassium phosphate are sequentially added into a reaction vessel, the obtained mixture is stirred at 100 ℃ for 20 hours, after the reaction is finished, ethyl acetate is used for filtering and washing, the mixed organic phase is distilled under reduced pressure to remove the solvent, and then the solvent is separated and purified by column chromatography, wherein the used column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 1:1, and the yield is 57%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ8.18 (d, j=1.8 hz, 1H), 8.05 (dd, j=8.1, 1.9hz, 1H), 7.69 (d, j=7.8 hz, 1H), 7.48 (dd, j=13.4, 7.8hz, 2H), 7.42 (t, j=7.7 hz, 1H), 7.34 (d, j=7.6 hz, 1H), 7.26 (dd, j=5.4, 1.8hz, 3H), 7.17-7.07 (m, 2H), 6.86 (s, 2H), 3.67 (dd, j=8.1, 6.2hz, 1H), 3.02 (d, j=4.7 hz, 3H), 2.76-2.61 (m, 2H), 1.93-1.72 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 165.6,148.3,139.5,134.7,134.6,134.5 (d, j=1.7 Hz), 132.0,131.9,131.5,131.4,130.4,129.2,129.1,128.4 (d, j=29.7 Hz), 128.2,127.9,127.0,126.0 (q, j=5.1 Hz), 124.0 (d, j=273.6 Hz), 119.9,117.4,111.9,77.3,77.0,76.7,36.6,33.7,28.9,26.9.
19 F NMR (471 MHz, deuterated chloroform) delta-60.55 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 28 H 23 F 3 N 3 O,474.1788; found (actual): 474.1785.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000122
example 13
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 4- (dimethylcarbamoyl) phenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 1:1, and the yield is 76%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.78 (d, j=1.7 hz, 1H), 7.72-7.64 (m, 2H), 7.51 (t, j=7.5 hz, 1H), 7.47-7.39 (m, 2H), 7.36 (d, j=7.5 hz, 1H), 7.32-7.23 (m, 3H), 7.14 (dd, j=7.3, 2.2hz, 2H), 6.85 (s, 1H), 3.79-3.55 (m, 1H), 3.08 (d, j=50.7 hz, 6H), 2.68 (pd, j=14.5, 5.9hz, 2H), 1.85 (ddtd, j=29.6, 13.6,7.6,7.0,4.0hz, 2H) hydrogen spectra are shown in fig. 5.
13 C NMR (126 MHz, deuterated chloroform) δ 168.7,146.8,139.6,136.4,134.7,134.5,134.4,131.9,131.9,131.4,131.3,130.3,129.0,128.9,128.4 (q, j=16.4 Hz), 128.1,127.9,127.0,125.9 (q, j=5.4 Hz), 124.0 (q, j= 274.7 Hz), 119.8,117.3,111.8,37.4 (d, j=504.0 Hz), 36.5,33.6,28.9.
19 F NMR (471 MHz, deuterated chloroform) delta-60.59 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 29 H 25 F 3 N 3 O,488.1944; found (actual): 488.1939.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000131
example 14
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 4-vinylphenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 46%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.78-7.66 (m, 2H), 7.62 (d, j=8.0 hz, 1H), 7.50 (t, j=7.4 hz, 1H), 7.41 (t, j=7.5 hz, 1H), 7.36 (d, j=7.8 hz, 2H), 7.31-7.19 (m, 2H), 7.18-7.07 (m, 2H), 6.85 (s, 1H), 6.71 (dd, j=17.5, 10.9hz, 1H), 5.84 (d, j=17.6 hz, 1H), 5.42 (d, j=10.9 hz, 1H), 3.65 (t, j=7.3 hz, 1H), 2.68 (tq, j=14.5, 8.6hz, 2H), 2.10-1.68 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 144.7,139.9,137.7,134.9,134.9 (d, j=1.7 Hz), 134.3,131.9,131.0,130.8,130.6,130.4,129.0,129.0,128.5 (d, j=29.5 Hz), 128.1,127.7,127.1,125.9 (q, j=5.2 Hz), 124.1 (d, j= 273.7 Hz), 120.0,118.0,116.8,111.9,36.6,33.8,29.0.
19 F NMR (471 MHz, deuterated chloroform) delta-60.63 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 28 H 22 F 3 N 2 443.1730; found (actual): 443.1725.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000141
example 15
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 3-methylphenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 94%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.68 (d, j=7.8 hz, 1H), 7.58 (d, j=7.9 hz, 1H), 7.48 (t, j=7.6 hz, 1H), 7.43-7.34 (m, 2H), 7.26 (d, j=5.8 hz, 3H), 7.21 (d, j=8.0 hz, 1H), 7.18 (s, 1H), 7.16-7.08 (m, 2H), 6.81 (s, 1H), 3.66 (t, j=7.1 hz, 1H), 2.67 (ddt, j=13.8, 9.0,5.4hz, 2H), 1.95-1.77 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 145.6,143.8,140.2,134.9,133.1,131.8,130.5,130.4,129.2,128.9,128.8,128.4,128.2,128.0,127.5,127.0,125.7 (q, j=5.2 Hz), 124.0 (q, j=273.4 Hz), 119.9,118.2,108.4,36.4,33.6,28.9,21.6.
19 F NMR (471 MHz, deuterated chloroform) delta-60.54 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 22 F 3 N 2 431.1730; found (actual): 431.1727.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000142
example 16
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in 3 ml of 1, 4-dioxane under nitrogen for 2 min. To the reaction vessel were successively added 7.5 mmol of 3-trifluoromethylphenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 64%.
The structural characterization data of the obtained product are as follows:
1 h NMR (400 MHz, deuterated chloroform) delta 7.87 (d, j=8.1 hz, 1H), 7.72 (d, j=7.8 hz, 2H), 7.62 (s, 1H), 7.53 (t, j=7.4 hz, 1H), 7.45 (t, j=7.7 hz, 1H), 7.37 (d, j=7.5 hz, 1H), 7.29 (dd, j=5.0, 1.9hz, 3H), 7.19-7.12 (m, 2H), 6.89 (s, 1H), 3.69 (dd, j=7.8, 6.3hz, 1H), 2.85-2.48 (m, 2H), 2.02-1.75 (m, 2H).
13 C NMR (101 MHz, deuterated chloroform) δ 146.8,139.0,134.8,134.6,134.5,134.2 (d, j=2.1 Hz), 134.0,132.1,132.0,130.3,129.1,128.5 (d, j=29.9 Hz), 128.2,128.0,127.0,126.0 (q, j=5.3 Hz), 125.5 (q, j=3.7 Hz), 125.0 (q, j=3.6 Hz), 123.4 (q, j=201.6 Hz), 119.8,116.8,115.2,36.6,33.6,28.9.
19 F NMR (471 MHz, deuterated chloroform) delta-60.63 (s, 3F), -63.33 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 19 F 6 N 2 485.1447; found (actual): 485.1441.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000151
example 17
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in 3 ml of 1, 4-dioxane under nitrogen for 2 min. To the reaction vessel were successively added 7.5 mmol of 2-fluorobenzeneboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 76%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.70 (d, j=7.8 hz, 1H), 7.56-7.48 (m, 2H), 7.43 (p, j=6.6, 5.7hz, 2H), 7.37 (dd, j=14.8, 7.6hz, 2H), 7.27 (d, j=6.0 hz, 3H), 7.20-7.09 (m, 2H), 6.85 (s, 1H), 3.71 (dd, j=8.4, 6.2hz, 1H), 2.65 (t, j=8.0 hz, 2H), 1.89 (ddt, j=39.6, 14.2,6.9hz, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 160.5,158.6,134.9,134.6,134.2,133.3 (d, j=19.8 Hz), 132.7,131.9,130.5,130.0 (d, j=8.7 Hz), 129.0,128.6 (d, j=30.0 Hz), 128.1,127.9,127.1,125.9 (q, j=5.3 Hz), 123.9 (d, j= 273.7 Hz), 120.7 (d, j=22.7 Hz), 120.0,116.8 (d, j=4.1 Hz), 114.3 (d, j=5.2 Hz), 36.5,33.6,28.9 (d, j=1.9 Hz).
19 F NMR (471 MHz, deuterated chloroform) δ -60.69 (s, 3F), -111.21 (t, j=7.0 hz, 1F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C26H19F4N2,435.1479; found (actual): 435.1475.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000161
example 18
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 3, 5-dimethylbenzeneboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 69%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.69 (d, j=7.8 hz, 1H), 7.50 (t, j=7.5 hz, 1H), 7.45-7.36 (m, 2H), 7.31-7.26 (m, 3H), 7.17-7.13 (m, 2H), 7.11 (s, 1H), 7.00 (s, 1H), 6.80 (s, 1H), 3.66 (t, j=7.2 hz, 1H), 2.76-2.60 (m, 2H), 2.56 (s, 3H), 2.40 (s, 3H), 1.98-1.77 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 146.1,143.2,142.7,140.6,135.1 (d, j=1.9 Hz), 135.0,131.8,130.6,130.1,130.1,128.9,128.4 (q, j=29.7 Hz), 128.0,127.5,127.1,126.6,125.8 (q, j=5.2 Hz), 124.1 (q, j=273.8 Hz), 120.0,117.4,109.1,36.6,33.7,29.1,21.6,20.7.
19 F NMR (471 MHz, deuterated chloroform) delta-60.58 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 28 H 24 F 3 N 2 445.1886; found (actual): 445.1882.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000162
example 19
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 2-naphthaleneboric acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 90%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ8.26 (s, 1H), 7.87 (d, j=8.3 hz, 2H), 7.81 (s, 1H), 7.70 (d, j=7.9 hz, 1H), 7.64 (t, j=7.5 hz, 1H), 7.58 (t, j=7.5 hz, 1H), 7.51 (t, j=7.5 hz, 1H), 7.41 (dd, j=14.3, 7.3hz, 2H), 7.25-7.19 (m, 3H), 7.10 (dd, j=6.5, 3.0hz, 2H), 6.91 (s, 1H), 3.66 (t, j=7.2 hz, 1H), 2.80 (ttd, j=20.4, 14.6,12.4,5.9hz, 2H), 1.98-1.75 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 140.3,139.6,135.5,134.9,134.8,134.4,131.8,131.3,130.7,130.6,129.4,128.9,128.3 (d, j=29.6 Hz), 128.0,127.9,127.9,127.6,127.6,126.9,126.1 (d, j=4.9 Hz), 125.8 (q, j=5.3 Hz), 124.1 (q, j= 274.7 Hz), 120.0,118.3,109.2,36.5,33.7,29.1.
19 F NMR (471 MHz, deuterated chloroform) delta-60.37 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 30 H 22 F 3 N 2 467.1730; found (actual): 467.1723.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000171
example 20
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in 3 ml of 1, 4-dioxane under nitrogen for 2 min. To the reaction vessel were successively added 7.5 mmol of 1-naphthalene boric acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 57%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ8.03 (dt, j=6.5, 3.6hz, 1H), 7.94-7.86 (m, 2H), 7.72 (dd, j=11.0, 7.8hz, 1H), 7.69-7.60 (m, 3H), 7.58-7.53 (m, 1H), 7.50 (d, j=4.3 hz, 1H), 7.43 (dp, j=13.1, 5.0,4.3hz, 1H), 7.26-7.17 (m, 3H), 7.12-7.05 (m, 2H), 6.89 (dd, j=8.6, 2.2hz, 1H), 3.62 (q, j=7.2 hz, 1H), 2.88-2.58 (m, 2H), 2.12-1.83 (m, 2H) hydrogen is shown in the spectrum of fig. 7.
13 CNMR (126 MHz, deuterated chloroform) delta 146.1 (d, j=17.9 Hz), 138.9 (d, j=9.5 Hz), 134.9 (d, j=1.4 Hz), 134.7 (d, j=11.3 Hz), 134.7 (d, j=12.3 Hz), 132.0 (d, j=3.4 Hz), 131.8 (d, j=9.8 Hz), 130.8 (d, j=1.7 Hz), 130.7 (d, j=5.1 Hz), 129.0,128.9,128.8 (d, j=3.6 Hz), 128.5,128.3 (dd, j=29.7, 11.3 Hz), 128.1,128.0,127.8 (d, j=5.9 Hz), 127.0 (d, j=5.0 Hz), 126.3 (d, j=2.3 Hz), 126.2 (d, j=3.1 Hz), 125.9 (dt, j=13.6, 5.3 Hz), 124.2 (d, j=6.273 (d), 21.7 Hz), 119.7 (d, j=5.3 Hz), 35.3 (d, j=3.6 Hz), 35 (d, j=9.7.3 Hz), 35 (d, j=5.3 Hz).
19 F NMR (471 MHz, deuterated chloroform) delta-60.45 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 30 H 22 F 3 N 2 467.1730; found (actual): 467.1724.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000181
Example 21
5 mmol of 2-phenyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 6-quinolineboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 80%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ9.04 (d, j=4.3 hz, 1H), 8.54 (s, 1H), 8.23 (d, j=8.2 hz, 1H), 7.81 (s, 1H), 7.72 (d, j=7.7 hz, 1H), 7.58 (dd, j=8.5, 4.2hz, 1H), 7.53 (t, j=7.5 hz, 1H), 7.43 (t, j=9.3 hz, 2H), 7.30-7.17 (m, 3H), 7.19-7.08 (m, 2H), 6.93 (s, 1H), 3.68 (t, j=7.2 hz, 1H), 2.87-2.72 (m, 2H), 1.99-1.79 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 152.3,146.2,140.7,139.7,136.7,135.9,134.7,131.9,131.4,130.5,130.1,129.0,128.5,128.2,128.0 (d, j=6.8 Hz), 127.8,127.0,125.9 (q, j=5.3 Hz), 125.2,123.9,123.0,119.9,117.6,112.9,36.6,33.7,29.1.
19 F NMR (471 MHz, deuterated chloroform) delta-60.47 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 29 H 21 F 3 N 3 468.1682; found (actual): 468.1673.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000182
example 22
5 mmol of 2- (4-methoxyphenyl) -2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 50 ml of toluene for 2 minutes under nitrogen. To the reaction vessel were successively added 7.5 mmol of phenylboronic acid, 0.25 mmol of tris (triphenylphosphine) rhodium chloride, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 60℃for 6 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 80%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.75-7.67 (m, 2H), 7.61 (t, j=7.7 hz, 1H), 7.51 (t, j=7.6 hz, 1H), 7.41 (dq, j=16.6, 7.8hz, 4H), 7.04 (d, j=8.3 hz, 2H), 6.83 (s, 1H), 6.79 (d, j=8.6 hz, 2H), 3.77 (s, 3H), 3.61 (t, j=7.3 hz, 1H), 2.67 (H, j=8.5 hz, 2H), 1.97-1.65 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 159.2,145.8,140.2,134.8 (d, j=2.1 Hz), 133.3,132.8,131.8,130.6,130.5,128.7,128.4 (d, j=29.8 Hz), 128.1,128.0,127.6,126.8,125.8 (q, j=5.3 Hz), 124.0 (q, j= 273.7 Hz), 120.2,118.0,114.3,111.5,55.2,35.7,33.7,28.9.
19 F NMR (471 MHz, deuterated chloroform) delta-60.59 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 22 F 3 N 2 O,447.1679; found (actual): 447.1676.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000191
example 23
5 mmol of 2- (4- [1,1' -biphenyl ] yl) -2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 50 ml of toluene for 2 minutes under nitrogen. To the reaction vessel were successively added 7.5 mmol of phenylboronic acid, 0.25 mmol of tris (triphenylphosphine) rhodium chloride, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 60℃for 6 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 64%.
The structural characterization data of the obtained product are as follows:
1 H NMR (500 MHz, deuterated chloroform) delta 7.74 (d, j=7.6 hz, 1H), 7.70 (d, j=7.8 hz, 1H), 7.64 (td, j=7.6, 1.4hz, 1H), 7.58-7.54 (m, 2H), 7.48 (dt, j=24.5, 8.0hz, 7H), 7.38 (t, j=7.4 hz, 3H), 7.22 (d, j=8.2 hz, 2H), 6.87 (s, 1H), 3.73 (t, j=7.1 hz, 1H), 2.82-2.65 (m, 2H), 2.00-1.80 (m, 2H) hydrogen spectra are shown in fig. 8.
13 C NMR (126 MHz, deuterated chloroform) δ 145.7,141.0,140.1,140.0,134.8,133.8,133.3,132.8,131.8,130.8,130.5,128.8,128.7,128.4 (d, j=29.8 Hz), 128.0,127.6,127.6,127.5,127.4,126.9,125.8 (q, j=5.2 Hz), 124.0 (d, j= 273.7 Hz), 119.9,118.0,111.5,36.1,33.6,28.9.
19 F NMR (471 MHz, deuterated chloroform) delta-60.53 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 32 H 24 F 3 N 2 493.1886; found (actual): 493.1880.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000201
example 24
5 mmol of 2- (4-fluorophenyl) -2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 6-quinolineboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 46%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.71 (dd, j=11.8, 7.9hz, 2H), 7.62 (td, j=7.7, 1.4hz, 1H), 7.51 (t, j=7.4 hz, 1H), 7.48-7.39 (m, 3H), 7.36 (d, j=7.6 hz, 1H), 7.10 (dd, j=8.6, 5.1hz, 2H), 6.95 (t, j=8.6 hz, 2H), 6.83 (s, 1H), 3.72-3.57 (m, 1H), 2.75-2.57 (m, 2H), 1.96-1.73 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 163.3,161.3,145.7,140.0,134.8 (d, j=1.8 Hz), 133.3,132.9,131.8,130.9,130.7 (d, j=3.3 Hz), 130.5,128.8 (d, j=1.9 Hz), 128.7,128.4 (d, j=29.6 Hz), 128.1,127.7,125.9 (q, j=5.3 Hz), 124.1 (d, j= 273.7 Hz), 118.9 (d, j= 220.6 Hz), 115.9 (d, j=21.8 Hz), 111.5,35.8,33.7,28.8.
19 F NMR (471 MHz, deuterated chloroform) δ -60.60 (s, 3F), -113.58 (tt, j=8.6, 4.8hz, 1F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 26 H 19 F 4 N 2 435.1479; found (actual): 435.1479.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000202
example 25
5 mmol of 2-benzyl-2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in 3 ml of 1, 4-dioxane under nitrogen for 2 min. To the reaction vessel were successively added 7.5 mmol of 6-quinolineboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 63%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.74-7.67 (m, 2H), 7.58 (td, j=7.7, 1.4hz, 2H), 7.50-7.38 (m, 3H), 7.36 (dd, j=7.9, 1.3hz, 1H), 7.28-7.19 (m, 3H), 7.09-7.02 (m, 2H), 6.82 (s, 1H), 2.83-2.73 (m, 2H), 2.73-2.60 (m, 3H), 1.60-1.47 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) δ 145.8,140.2,136.4,134.9,133.2,132.8,131.9,130.8,130.7,130.0 (d, j=14.5 Hz), 128.8,128.6,128.4 (d, j=11.1 Hz), 128.0,127.8,127.1,126.0 (q, j=5.3 Hz), 124.1 (d, j= 273.7 Hz), 120.8,118.0,111.6,37.8,33.0,29.6,29.2.
19 F NMR (471 MHz, deuterated chloroform) delta-60.60 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 22 F 3 N 2 431.1730; found (actual): 431.1726.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000211
example 26
5 mmol of 2- (furan-2-ylmethyl) -2- (4- (2- (trifluoromethyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 6-quinolineboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 21%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.72 (d, j=7.8 hz, 2H), 7.61 (dt, j=11.2, 7.7hz, 2H), 7.43 (dt, j=22.1, 8.0hz, 4H), 7.25 (d, j=6.2 hz, 1H), 6.84 (s, 1H), 6.24 (s, 1H), 6.03 (d, j=3.2 hz, 1H), 2.93-2.56 (m, 5H), 1.69-1.47 (m, 2H) hydrogen spectra are shown in fig. 9.
13 C NMR (126 MHz, deuterated chloroform) δ 150.0,145.8,142.0,140.2,135.0,133.3,132.9,132.0,130.9,130.7,128.9,128.7 (t, j=30.2 Hz), 128.0,127.8,126.0 (q, j=5.4 Hz), 125.2,120.6,118.1,111.6,110.4,107.8,30.5,30.2,29.5,29.1.
19 F NMR (471 MHz, deuterated chloroform) delta-60.70 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 25 H 20 F 3 N 2 O,421.1522; found (actual): 421.1516.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000221
example 27
5 mmol of 2-phenyl-2- (4- (2- (cyano) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 6-quinolineboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 55%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.73 (d, j=7.8 hz, 1H), 7.68 (dd, j=8.1, 1.4hz, 1H), 7.62 (td, j=7.7, 1.3hz, 1H), 7.54 (td, j=7.7, 1.4hz, 1H), 7.49-7.42 (m, 2H), 7.40 (dt, j=7.5, 3.7hz, 2H), 7.33-7.26 (m, 3H), 7.19 (dd, j=7.5, 2.0hz, 2H), 6.83 (s, 1H), 3.74 (dd, j=8.1, 6.2hz, 1H), 2.80 (dd, j=9.5, 6.4hz, 2H), 2.01-1.80 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform) delta 145.3,142.0,139.6,134.7,133.4,132.9,132.8,132.8,130.1,129.2,129.0,128.7,128.3,128.1,128.0,127.1,119.8,118.0,117.6,112.3,111.4,36.5,33.6,29.0.
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 26 H 20 N 3 374.1652; found (actual): 431.1649.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000222
example 28
5 mmol of methyl 2- (5, 5-dicyano-5-phenylpentanynyl) benzoate are stirred under nitrogen in 3 ml of 1, 4-dioxane for 2 min. To the reaction vessel were successively added 7.5 mmol of 6-quinolineboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 62%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ8.03 (dd, j=7.8, 1.4hz, 1H), 7.69 (dd, j=7.8, 1.3hz, 1H), 7.62 (td, j=7.6, 1.4hz, 1H), 7.57 (dd, j=7.9, 1.4hz, 1H), 7.49 (td, j=7.5, 1.5hz, 1H), 7.43-7.37 (m, 2H), 7.35(t,J＝7.9Hz,1H),7.28–7.21(m,3H),7.13–7.09(m,2H),7.07(s,1H),3.88(s,3H),3.72–3.65(m,1H),2.76(dd,J＝8.9,6.4Hz,2H),1.93–1.71(m,2H).
13 C NMR (126 MHz, deuterated chloroform) delta 167.1,146.6,138.0,136.3,135.2,134.9,133.3,132.9,132.3,130.7,130.4,129.2,129.0,128.9,128.0,127.7,127.6,127.0,120.1,118.3,111.4,52.0,36.2,34.0,28.4.
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 27 H 23 N 2 O 2 407.1754; found (actual): 407.1750.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000231
example 29
5 mmol of 2-phenyl-2- (4- (2- (methyl) phenyl) butynyl) malononitrile were stirred in advance in 3 ml of 1, 4-dioxane under nitrogen for 2 minutes. To the reaction vessel were successively added 7.5 mmol of 6-quinolineboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 63%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) delta 7.97 (s, 1H), 7.83 (dd, j=8.3, 1.9hz, 1H), 7.56 (d, j=8.2 hz, 1H), 7.28 (dd, j=5.1, 1.9hz, 3H), 7.23 (q, j=4.1 hz, 2H), 7.18-7.11 (m, 4H), 6.78 (s, 1H), 3.68 (dd, j=8.0, 6.4hz, 1H), 2.77 (dd, j=9.4, 6.7hz, 2H), 2.32 (s, 3H), 1.94-1.76 (m, 2H) hydrogen spectra are shown in fig. 10.
13 C NMR (126 MHz, deuterated chloroform) delta 150.1,136.8,136.7,134.9,134.8,134.7,130.4(q,J＝3.9Hz),130.3(q,J＝34.0Hz),130.2,129.4,129.3(q,J＝3.4Hz),129.0,128.3,128.2,128.1,127.0,125.8,122.8(d,J＝272.6Hz),120.0,117.1,112.5,36.6,33.9,28.7,20.0.
19 F NMR (471 MHz, deuterated chloroform) delta-62.92 (s, 3F).
HRMS(ESI-quadrupole)m/z:[M+H] + Calcd.for theory C 26 H 23 N 2 363.1856; found (actual): 363.1862.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000241
example 30
5 mmol of 2-phenyl-2- (4- (quinolinolato) butynyl) malononitrile were stirred in advance under nitrogen for 2 minutes in 3 ml of 1, 4-dioxane. To the reaction vessel were successively added 7.5 mmol of phenylboronic acid, 0.125 mmol of (1, 5-cyclooctadiene) rhodium (I) chloride dimer, 0.5 mmol of tris-2-furyl phosphine, and 15 mmol of potassium phosphate. The solvent was then added and the resulting mixture was stirred at 100℃for 20 hours. After the reaction was completed, the mixture was washed with ethyl acetate by filtration. The mixed organic phase was distilled under reduced pressure to remove the solvent. And separating and purifying by column chromatography to obtain the target product, wherein the column chromatography eluent is petroleum ether and ethyl acetate mixed solvent with the volume ratio of 5:1, and the yield is 40%.
The structural characterization data of the obtained product are as follows:
1 h NMR (500 MHz, deuterated chloroform) δ8.92 (dd, j=4.2, 1.7hz, 1H), 8.15 (d, j=8.1 hz, 1H), 8.02 (s, 1H), 7.78 (d, j=8.4 hz, 1H), 7.73 (d, j=7.7 hz, 1H), 7.61 (td, j=7.7, 1.4hz, 1H), 7.54-7.38 (m, 4H), 7.19 (d, j=6.6 hz, 3H), 7.15 (dd, j=7.5, 2.3hz, 2H), 6.91 (s, 1H), 3.73 (t, j=7.3 hz, 1H), 2.96 (t, j=8.0 hz, 2H), 2.07-1.84 (m, 2H).
13 C NMR (126 MHz, deuterated chloroform). Delta. 150.7,148.0,146.4,139.0,137.5,135.8,134.8,133.5,133.5,132.7,128.9,128.8,128.5,128.0,128.0,127.9,127.4,127.2,127.1,121.2,120.1,118.3,111.7,36.6,33.9,28.8.
HRMS(ESI-quadrupole)m/z:[M+H] + calcd.for theory C 28 H 22 N 3 400.1808; found (actual): 400.1804.
The structure of the resulting product was deduced from the above data:
Figure BDA0003659976930000242
the above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.

Claims (6)

1. A method for synthesizing an o-alkenyl benzene nitrile derivative by rhodium-catalyzed aryl boric acid and a dinitrile derivative, which is characterized by comprising the following steps of:
in a protective atmosphere, taking an organic solvent as a reaction medium, reacting a dinitrile derivative with aryl boric acid under the action of a rhodium catalyst, a phosphine ligand and alkali, and carrying out subsequent treatment to obtain an o-alkenyl benzonitrile derivative;
The structure of the arylboronic acid is
Figure FDA0004164313420000011
The Ar is as follows 1 Is a substituted or unsubstituted phenyl, naphthyl, benzothienyl, quinolinyl, dibenzofuranyl group;
the structure of the dinitrile derivative is
Figure FDA0004164313420000012
The R is 1 Is a substituted or unsubstituted aryl, a substituted or unsubstituted benzyl, a furanmethyl;
the Ar is as follows 2 Is a substituted or unsubstituted phenyl or pyridyl groupA quinolinyl group;
the structure of the o-alkenyl benzonitrile derivative is
Figure FDA0004164313420000013
Ar 1 Wherein the substituted phenyl is methyl substituted phenyl, methoxy substituted phenyl, halogen substituted phenyl, aldehyde substituted phenyl, acetyl substituted phenyl, ester substituted phenyl, amide substituted phenyl, olefin substituted phenyl;
Ar 1 wherein the substitution includes ortho, para and/or meta substitution, including mono-or di-substitution;
R 1 wherein the substituted aryl is methoxy substituted phenyl, halogen substituted phenyl, phenyl substituted phenyl;
the unsubstituted aryl is phenyl;
the substituted benzyl is nitro substituted benzyl, halogen substituted benzyl, pyridine substituted benzyl; the substitution herein refers to the substitution on the phenyl group in benzyl;
the substituted heteroarylmethyl is a furanmethyl;
Ar 2 Wherein the substituted phenyl is trifluoromethyl substituted phenyl, cyano substituted phenyl, ester substituted phenyl, methyl substituted phenyl;
the phosphine ligand is tri-2-furyl phosphine;
the rhodium catalyst is more than one of chlorine (1, 5-cyclooctadiene) rhodium dimer and tri (triphenylphosphine) rhodium chloride.
2. The rhodium-catalyzed synthesis of an orthoalkenylbenzonitrile derivative from an arylboronic acid and a dinitrile derivative according to claim 1, wherein: the organic solvent is at least one of methanol, ethanol, isopropanol, n-butanol, isobutanol, tertiary butanol, acetonitrile, acetone, 1, 2-dichloroethane, toluene, tetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, dimethylformamide and dimethyl sulfoxide;
the alkali is at least one of sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium hydroxide, lithium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, sodium phosphate, potassium hydrogen phosphate, sodium hydrogen phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, cesium fluoride, pyridine and triethylamine.
3. The rhodium-catalyzed synthesis of an orthoalkenylbenzonitrile derivative from an arylboronic acid and a dinitrile derivative according to claim 2, wherein: the organic solvent is more than one of 1, 2-dichloroethane, 1, 4-dioxane and toluene;
The alkali is more than one of potassium phosphate, potassium carbonate, cesium carbonate and cesium fluoride.
4. The rhodium-catalyzed synthesis of an orthoalkenylbenzonitrile derivative from an arylboronic acid and a dinitrile derivative according to claim 1, wherein:
the temperature of the reaction is 25-150 ℃; the reaction time is 6-20 hours;
the reaction mole ratio of the dinitrile derivative to the arylboronic acid is 1: (1.2-2);
the molar ratio of the rhodium catalyst to the dinitrile derivative is (0.025-0.2) 1; the molar ratio of the phosphine ligand to the dinitrile derivative is (0.05-0.4): 1.
5. the rhodium-catalyzed process for synthesizing an orthoalkenylbenzonitrile derivative from an arylboronic acid and a dinitrile derivative according to claim 4, wherein: the temperature of the reaction is 60-100 ℃.
6. The rhodium-catalyzed synthesis of an orthoalkenylbenzonitrile derivative from an arylboronic acid and a dinitrile derivative according to claim 1, wherein: the protective atmosphere is nitrogen;
the subsequent treatment refers to filtration, washing with ethyl acetate, removing organic solvent, and separating by column chromatography;
the step of removing the organic solvent refers to removing the organic solvent by reduced pressure distillation;
the eluent of the column chromatography is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 5:1-1:1.
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