A reaction method for the decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime catalyzed by iron

Abstract

The present invention relates to a method for the iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid with a cyclic ketoxime. The method comprises the following steps: using a cinnamic acid compound and a cyclic ketoxime compound as raw materials, using an iron salt as a catalyst, and reacting them in a solvent at 90-150°C for 10-20 hours under a nitrogen atmosphere to prepare a remote cyanoalkyl olefin. The present invention provides a simple and effective iron-catalyzed decarboxylation / cyanoalkylation reaction of cinnamic acid for the production of remote cyanoalkyl olefins using cyclic ketoxime as a free radical precursor. Compared to the prior art, the present invention does not require an additional reducing agent and exhibits excellent radical tolerance. The reaction is applicable to a variety of cyclic ketoxime and cinnamic acid compounds, providing the corresponding products under mild, redox-neutral conditions.

Description

Technical Field

[0001] The invention relates to a reaction method for the decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime catalyzed by iron. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance some understanding of the overall background of the invention and should not be necessarily regarded as an admission or any form of suggestion that the information constitutes the prior art already known to those skilled in the art.

[0003] Alkyl-substituted alkenes are an important component in organic synthesis and are widely found in natural products, pharmaceuticals, pesticides, and organic materials (e.g., lubricating and protective materials). Among the various strategies for constructing alkyl-substituted alkenes, transition metal-catalyzed free radical decarboxylation alkylation of α,β-unsaturated carboxylic acids has attracted particular attention from chemists due to the availability and low toxicity of vinyl carboxylic acids. Alkenes can be alkylated by free radical addition / decarboxylation of alkyl radicals ( Figure 1 ).

[0004] In the past, reported alkyl radical addition reactions of vinyl carboxylic acids required external stoichiometric amounts of oxidants. In recent years, several redox-neutral radical decarboxylation reactions of α,β-unsaturated carboxylic acids have been developed. However, direct decarboxylative cyanation reactions of α,β-unsaturated carboxylic acids under redox-neutral catalytic systems are rare. For example, Duan Xinhua's group developed an iron-catalyzed radical decarboxylative cyanoalkylation to obtain cyano-substituted alkenes from cyclic ketoxime esters under redox-neutral conditions ( Figure 2 ).

[0005] Despite the existence of this ideal method, the decarboxylative alkylation reaction of unprotected cyclobutanone oxime with α, β-unsaturated carboxylic acids has not been reported so far. On the other hand, remote cyanoalkyl olefins have become attractive functional groups due to their versatility in converting to other functional groups. As far as the applicant is aware, cyanoalkyl radicals can be added to olefins to generate remote cyanoalkyl olefins, and there are now many methods for cyclic ketone oxime derivatives to generate cyanoalkyl radicals through transition metal catalysis, photocatalysis and electrocatalysis. In addition, in addition to these advances, recent studies have shown that unactivated cyclic ketone oximes can produce remote cyanoalkyl radicals through free radical-mediated C-C bond cleavage. Recently, Yuan Yu's group disclosed an iron-catalyzed free radical-mediated ring-opening olefination of cyclic ketone oximes to prepare various remote cyanoalkyl olefins ( Figure 3 ).

[0006] However, the stoichiometric usage of reducing agents limits their application in organic synthesis. Summary of the Invention

[0007] In view of the existing technology, the present invention studies the redox-neutral iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid to construct remote cyanoalkyl olefins ( Figure 4 ).

[0008] The technical solution adopted in the present invention is as follows:

[0009] The present invention provides a method for the decarboxylation / cyanoalkylation reaction of cinnamic acid and cyclic ketoxime catalyzed by iron, which comprises the following steps:

[0010] In a nitrogen atmosphere, cinnamic acid compounds and cyclic ketoxime compounds are used as raw materials, iron salts are used as catalysts, and the reaction is carried out at 90-150 °C in a solvent for 10-20 hours to prepare remote cyanoalkyl olefins.

[0011] Wherein, the cinnamic acid compound is 4-methylcinnamic acid, 3-methylcinnamic acid, 2-methylcinnamic acid, 4-tert-butylcinnamic acid, 4-isopropylcinnamic acid, 4-methoxycinnamic acid, 4-dimethylaminocinnamic acid, 4-fluorocinnamic acid, 3-fluorocinnamic acid, 2-fluorocinnamic acid, 4-chlorocinnamic acid, 3-chlorocinnamic acid, 2-chlorocinnamic acid, 4-bromocinnamic acid, 3-bromocinnamic acid, 2-bromocinnamic acid, 4-trifluoromethylcinnamic acid, 4-cyanocinnamic acid, 4-hydroxycinnamic acid, 4-phenylcinnamic acid, β-naphthyl acrylic acid, 5-phenylpentadienoic acid, 2-furan acrylic acid or 2-thiophene acrylic acid;

[0012] The cyclic ketone oxime compound is 3-tert-butoxycarbonylcyclobutanone oxime, 3-phenylcyclobutanone oxime, 3-ethoxycarbonylcyclobutanone oxime, 3-benzyloxycyclobutanone oxime, 3-oxetanone oxime, 3-thietanone oxime, 3-tert-butoxycarbonyl-3-azetidinone oxime, 2-methylcyclopentanone oxime, 2-methyl-3-oxetanone oxime or 2-phenylcyclohexanone oxime.

[0013] In one or some embodiments of the present invention, the solvent is dichloromethane (DCM), 1,2-dichloroethane (DCE), 1,4-dioxane (1.4-dioxane), trifluoromethylbenzene (PhCF3), chlorobenzene (PhCl), acetonitrile (MeCN), methyl tert-butyl ether (MTBE), N-methylpyrrolidone (NMP), benzene or toluene; preferably chlorobenzene, dichloromethane, 1,2-dichloroethane, trifluoromethylbenzene or N-methylpyrrolidone; further preferably chlorobenzene, dichloromethane, 1,2-dichloroethane, trifluoromethylbenzene; most preferably chlorobenzene.

[0014] In one or some embodiments of the present invention, the molar ratio of the cinnamic acid compound to the cyclic ketoxime compound is (0.2-5):1; preferably (2-5):1; more preferably (3-5):1; and most preferably 3:1.

[0015] In one or some embodiments of the present invention, the iron salt is FeCl2, FeCl3, FeBr2, FeBr3, Fe(OTf)2, Fe(OTf)3, Fe(acac)2, Fe(acac)3, FeI2 or FeSO4; preferably Fe(acac)2, Fe(acac)3, FeCl2, FeSO4, FeBr2 or FeI2; further preferably Fe(acac)2, Fe(acac)3 or FeCl2; most preferably Fe(acac)2.

[0016] In one or some embodiments of the present invention, the reaction temperature is 100-140°C; preferably 110-130°C, more preferably 120-130°C, and most preferably 120°C.

[0017] In one or some embodiments of the present invention, the ratio of the cinnamic acid compound, the cyclic ketoxime compound and the solvent is (0.02~0.55) mmol:0.1 mmol:(0.5~4) mL; preferably (0.2~0.5) mmol:0.1 mmol:(1~2) mL; further preferably (0.3~0.5) mmol:0.1 mmol:(1~2) mL; most preferably 0.3 mmol:0.1 mmol:2 mL.

[0018] In one or some embodiments of the present invention, the molar ratio of the cinnamic acid compound to the catalyst is 1:(0.05-0.30).

[0019] In one or some embodiments of the present invention, the reaction time is 12 to 18 hours; preferably 14 to 18 hours; more preferably 16 to 18 hours; most preferably 16 hours.

[0020] Compared with the related art known to the inventors, one of the technical solutions of the present invention has the following beneficial effects:

[0021] The present invention provides a simple and efficient iron-catalyzed decarboxylative cyanoalkylation reaction of cinnamic acid for the construction of remote cyanoalkyl olefins using cyclic ketoximes as free radical precursors. Compared to the prior art, the present invention does not require additional reducing agents and exhibits good radical tolerance. The reaction is applicable to a variety of cyclic ketoxime compounds and cinnamic acid compounds, providing the corresponding products under mild, redox-neutral conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings, which constitute a part of the specification of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0023] Figure 1 : Free radical addition / decarboxylation of alkenes.

[0024] Figure 2 : Iron-catalyzed free radical decarboxylative cyanoalkylation.

[0025] Figure 3 : Iron-catalyzed free radical-mediated ring-opening olefination of cyclic ketone oximes.

[0026] Figure 4 : Redox-neutral iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid.

[0027] Figure 5 : Substrate expansion of the cinnamic acid moiety.

[0028] Figure 6 : Substrate expansion of cyclic ketoxime moiety.

[0029] Figure 7 : Gram-scale reaction of the present invention. DETAILED DESCRIPTION

[0030] It should be noted that the following detailed descriptions are exemplary and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

[0031] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations and / or combinations thereof.

[0032] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0033] Example 1 Screening of solvents

[0034]

[0035] Table 1 Screening of solvents

[0036] Serial number solvent Yield (%) 1 dichloromethane 37 2 Ethylene dichloride 36 3 1,4-Dioxane 24 4 Trifluoromethylbenzene 35 5 chlorobenzene 39 6 Acetonitrile 21 7 Methyl tert-butyl ether 21 8 N-Methylpyrrolidone 29 9 benzene 24 10 Toluene 21

[0037] Reaction conditions: Cinnamic acid 1a (0.1 mmol, 1.0 equiv), cyclobutanone oxime 2a (0.5 mmol, 5.0 equiv), and FeBr2 were reacted in a solvent (2 mL) under nitrogen atmosphere for 16 h.

[0038] Solvent screening (Table 1): When the reaction conditions were initially screened, ferrous bromide was selected as the catalyst in this example, the substrate equivalent ratio 1a:2a = 1:5, the temperature was 120 о C is the initial condition, and the reaction solvent is screened. In this example, the reaction solvent was first screened and it was found that all the screened solvents allowed the reaction to proceed smoothly and produce the target product 3a. Among them, chlorobenzene as the reaction solvent achieved the most ideal reaction yield, reaching 39%. Therefore, chlorobenzene was selected as the reaction solvent in this example.

[0039] Example 2 Screening of substrate equivalent ratio

[0040]

[0041] Table 2 Screening of substrate equivalent ratio

[0042] Serial number Proportion Yield (%) 1 1a:2a = 2:1 44 2 1a:2a=3:1 51 3 1a:2a=4:1 51 4 1a:2a=5:1 51 5 1a:2a=1:2 41 6 1a:2a=1:3 41 7 1a:2a=1:4 40 8 1a:2a=1:5 39

[0043] Reaction conditions: Cinnamic acid 1a, cyclobutanone oxime 2a, and FeBr2 were reacted in chlorobenzene (2 mL) under nitrogen atmosphere for 16 h.

[0044] Screening of substrate equivalent ratios (Table 2): In the second step of this example, the substrate equivalent ratio was screened. This example found that increasing the equivalent of cinnamic acid helped improve the reaction yield. The reaction yield was optimal when the ratio of 1a:2a = 3:1. Further increasing the ratio of cinnamic acid did not increase the reaction yield. Therefore, this example determined the substrate equivalent ratio to be 3:1 (cinnamic acid:cyclobutanone oxime) (1a:2a = 3:1).

[0045] Example 3 Screening of iron catalysts

[0046]

[0047] Table 3 Screening of iron catalysts

[0048] Serial number Fe catalyst Yield (%) 1 <![CDATA[FeCl2]]> 58 2 <![CDATA[FeCl3]]> 41 3 <![CDATA[FeBr2]]> 51 4 <![CDATA[FeBr3]]> 30 5 <![CDATA[Fe(OTf)2]]> 25 6 <![CDATA[Fe(OTf)3]]> 12 7 <![CDATA[Fe(acac)2]]> 70 8 <![CDATA[Fe(acac)3]]> 65 9 <![CDATA[FeI2]]> 48 10 <![CDATA[Fe(NO3)•9H2O]]> ND 11 <![CDATA[FeSO4]]> 53

[0049] Reaction conditions: Cinnamic acid 1a (0.3 mmol, 1.0 equiv), cyclobutanone oxime 2a (0.1 mmol, 1.0 equiv), and iron catalyst were reacted in chlorobenzene (2 mL) under nitrogen atmosphere for 16 h.

[0050] Catalyst screening (Table 3): After determining the substrate equivalent ratio, this example screened the types of iron catalysts. This example found that except for Fe(NO3)•9H2O, other iron catalysts could enable the reaction to proceed smoothly. In addition, among the screened iron catalysts, the yield of divalent iron was higher than that of similar trivalent iron. Among them, Fe(acac)2 had the best yield, which could reach 70%. Therefore, this example determined Fe(acac)2 as the catalyst.

[0051] Example 4 Temperature screening

[0052]

[0053] Table 4 Temperature screening

[0054] Serial number <![CDATA[Temperature ( о °C)]]> Yield (%) 1 90 37 2 100 55 3 110 58 4 120 70 5 130 66 6 140 64

[0055] Reaction conditions: Cinnamic acid 1a (0.3 mmol, 3.0 equiv), cyclobutanone oxime 2a (0.1 mmol, 1.0 equiv), and Fe(acac)2 were reacted in chlorobenzene (2 mL) under nitrogen atmosphere for 16 h.

[0056] Temperature screening (Table 4): Afterwards, this example explored the reaction temperature. It was found that whether increasing or decreasing the temperature had a certain effect on the reaction yield, so 120 о C as the reaction temperature.

[0057] Example 5 Concentration screening

[0058]

[0059] Table 5 Concentration screening

[0060] Serial number PhCl (mL) Yield (%) 1 0.5 54 2 1.0 59 3 1.5 62 4 2.0 70

[0061] Reaction conditions: Cinnamic acid 1a (0.3 mmol, 3.0 equiv), cyclobutanone oxime 2a (0.1 mmol, 1.0 equiv), and FeBr2 were reacted in chlorobenzene under nitrogen atmosphere for 16 h.

[0062] Concentration screening (Table 5): Finally, it was envisioned to reduce the amount of solvent to increase the concentration of intermolecular reactions and thus improve the reaction yield, but it was ultimately found that reducing the amount of solvent would reduce the reaction yield.

[0063] Next, the optimal reaction conditions for this example were determined as follows: 1a (0.3 mmol), 2a (0.1 mmol), Fe(acac)2 (10 mol%) as catalyst, 2 mL PhCl as solvent, at 120 о C for 16 h.

[0064] Example 6 Substrate expansion

[0065] After determining the optimal reaction conditions, this example conducted a substrate universality study under the optimal conditions ( Figure 5 ). First, this example attempts to introduce some electron-donating groups, such as methyl, methoxy, tert-butyl, isopropyl, N,N-dimethylamino, hydroxyl, and phenyl (30%-78%), into the para position of the cinnamic acid benzene ring. After the introduction of these substituents, the target product can be obtained with medium to excellent yields. Then, this example introduces some electron-withdrawing groups, such as cyano and trifluoromethyl, into the para position of the cinnamic acid benzene ring, and the target product can also be obtained with medium to excellent yields (47%-63%). In addition, the benzene ring contains halogen groups, such as fluorine, chlorine, and bromine, and the target product can also be obtained with excellent yields (71%-75%). In addition, this example also attempts to use heterocyclic substrates, and it is found that after replacing the benzene ring with a furan ring or a thiophene ring, the target product can be obtained with excellent yields (82%-92%).

[0066] After expanding the substrates of the cinnamic acid part, this example further expanded the substrates of the cyclic ketoxime part ( Figure 6 Cyclic ketoximes substituted with phenyl, ester, or Bоc groups exhibit excellent reactivity, affording the corresponding cyanoalkylated products in good to excellent yields (73%-87%). This reaction is also applicable to thio-, oxo-, and nitrogen-substituted cyclic ketoximes, although yields are somewhat lower. Cyclopentanone and cyclohexanone oximes also react successfully, but with lower yields (26%-28%).

[0067] Example 7 Gram-scale reaction

[0068] In order to demonstrate the synthetic significance of this method, this example carried out a gram-scale reaction ( Figure 7 The template reaction was scaled up 100-fold, and 1.67 g of the target product (3a) was obtained with an isolated yield of 72%.

[0069] Thus, the present invention has developed a method for preparing remote nitriles by iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid using cinnamic acid as a free radical acceptor and activator, and converting them into the corresponding cyanoalkylated olefins in good to excellent yields.

[0070] The NMR data and mass spectrometry data of the compounds prepared in the above examples are as follows:

[0071]

[0072] 3a: 1 H NMR (800 MHz, CDCl3) δ 7.36–7.33 (m, 2H), 7.32–7.29 (m, 2H), 7.23–7.21 (m, 1H), 6.46 (d, J = 15.8 Hz, 1H), 6.13 (dt, J = 15.8, 7.1 Hz,1H), 2.40–2.37 (q, J = 6.6, 6.0 Hz, 4H), 1.85 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 137.1, 132.1, 128.6, 127.6, 127.4, 126.1, 119.6, 31.7,25.0, 16.5; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 12 H 14 N + : 172.1121; Actual value: 172.1122.

[0073]

[0074] 3b: 1 H NMR (800 MHz, CDCl3) δ 7.24 (d, J = 8.0 Hz, 2H), 7.11 (d, J =7.9 Hz, 2H), 6.43 (d, J = 15.8 Hz, 1H), 6.07 (dt, J = 15.7, 7.1 Hz, 1H), 2.40–2.34 (m, 4H), 2.33 (s, 3H), 1.84 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz,CDCl3) δ 136.9, 134.1, 131.7, 129.1, 126.3, 125.8, 119.4, 31.5, 24.8, 21.0,16.2; High-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 13 H 16 N + : 186.1277; Actual value: 186.1279.

[0075]

[0076] 3c: 1 H NMR (800 MHz, CDCl3) δ 7.20 (t, J = 7.5 Hz, 1H), 7.17–7.13 (m,2H), 7.05 (t, J = 7.1 Hz, 1H), 6.43 (d, J = 15.8 Hz, 1H), 6.11 (dt, J = 15.7,7.1 Hz, 1H), 2.41–2.34 (m, 4H), 2.34 (s, 3H), 1.84 (p, J = 7.2 Hz, 2H); 13 CNMR (200 MHz, CDCl3) δ 138.16, 137.05, 132.13, 128.51, 128.17, 127.40,126.83, 123.24, 119.60, 31.69, 25.04, 21.42, 16.44; HRMS-ESI (m / z) [M + H] + Theoretical value: C 13 H 16 N + : 186.1277; Actual value: 186.1278.

[0077]

[0078] 3d: 1 H NMR (800 MHz, CDCl3) δ 7.41–7.38 (m, 1H), 7.15 (td, J = 5.7,4.4, 2.5 Hz, 3H), 6.67 (d, J = 15.6 Hz, 1H), 5.99 (dt, J = 15.5, 7.0 Hz, 1H), 2.43–2.39 (m, 4H), 2.34 (s, 2H), 1.86 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz,CDCl3) δ 135.00, 133.83, 129.00, 128.69, 127.72, 126.02, 124.82, 124.21,118.29, 30.68, 23.76, 18.55, 15.15; High-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 13 H 16 N+ : 186.1277; Actual value: 186.1278.

[0079]

[0080] 3e: 1 H NMR (800 MHz, CDCl3) δ 7.33 (d, J = 8.3 Hz, 2H), 7.29 (d, J =8.3 Hz, 2H), 6.44 (d, J = 15.8 Hz, 1H), 6.08 (dt, J = 15.6, 7.1 Hz, 1H), 2.40–2.35 (m, 4H), 1.84 (p, J = 7.2 Hz, 2H), 1.31 (s, 9H); 13 C NMR (200 MHz,CDCl3) δ 150.48, 134.34, 131.81, 126.80, 125.81, 125.53, 119.62, 34.56,31.68, 31.31, 25.08, 16.40; High-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 16 H 22 N + : 228.1747; Actual value: 228.1748.

[0081]

[0082] 3f: 1 H NMR (400 MHz, CDCl3) δ 7.30–7.24 (m, 2H), 7.20–7.13 (m, 2H), 6.43 (d, J = 15.8 Hz, 1H), 6.07 (dt, J = 15.8, 7.1 Hz, 1H), 2.88 (hept, J =6.9 Hz, 1H), 2.41–2.28 (m, 4H), 1.82 (p, J = 7.2 Hz, 2H), 1.24 (d, J = 6.9Hz, 6H); 13 C NMR (200 MHz, CDCl3) δ 148.24, 134.76, 131.92, 126.70, 126.68,126.09, 119.64, 33.87, 31.69, 25.10, 23.99, 16.41; HRMS-ESI (m / z) [M + H]+ Theoretical value: C 15 H 20 N + : 214.1590; Actual value: 214.1591.

[0083]

[0084] 3g: 1 H NMR (800 MHz, CDCl3) δ 7.98 (d, J = 8.3 Hz, 2H), 7.40 (d, J =8.3 Hz, 2H), 6.50 (d, J = 15.8 Hz, 1H), 6.27 (dt, J = 15.7, 7.0 Hz, 1H), 3.91(d, J = 7.0 Hz, 3H), 2.45–2.38 (m, 4H), 1.87 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 157.84, 130.21, 128.75, 126.02, 124.21, 118.48, 112.82, 54.13,30.48, 23.95, 15.22; HRMS-ESI (m / z) [M + H] + Theoretical value: C 13 H 16 NO + :202.1226; Actual value:202.1228.

[0085]

[0086] 3h: 1 H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 7.7, 2.4 Hz, 2H), 6.69 (d, J= 7.8, 2H), 6.35 (d, J = 15.8 Hz, 1H), 5.94-5.86 (m, 1H), 2.93 (s, 6H), 2.38–2.28 (m, 4H), 1.79 (p, J = 7.2 Hz, 2H); 13C NMR (200 MHz, CDCl3) δ 149.12, 130.96, 126.12, 124.83, 122.36, 118.95, 111.66, 39.71, 30.88, 24.46, 15.48; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 14 H 19 N2 + : 215.1543; Actual value: 215.1541.

[0087]

[0088] 3i: 1 H NMR (800 MHz, CDCl3) δ 7.30 (ddd, J = 8.2, 5.2, 2.4 Hz, 2H), 7.02–6.97 (m, 2H), 6.48 (d, J = 11.5 Hz, 1H), 6.42 (d, J = 15.8 Hz, 1H),2.41–2.36 (m, 4H), 1.84 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 162.1(d, J = 246.5 Hz), 133.2 (d, J = 3.3 Hz), 130.9, 127.5 (d, J = 7.9 Hz), 127.3(d, J = 2.3 Hz), 119.6, 115.5 (d, J = 21.5 Hz), 31.6, 25.0, 16.5; HRMS-ESI (m / z) [M + H] + Theoretical value: C 12 H 13 FN + : 190.1027; Actual value: 190.1029.

[0089]

[0090] 3j: 1H NMR (800 MHz, CDCl3) δ 7.28–7.24 (m, 1H), 7.10 (d, J = 7.7 Hz,1H), 7.04 (dt, J = 10.2, 2.0 Hz, 1H), 6.93–6.89 (m, 1H), 6.43 (d, J = 15.8Hz, 1H), 6.15 (dt, J = 15.7, 7.1 Hz, 1H), 2.42–2.37 (m, 4H), 1.85 (p, J = 7.2Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 163.1 (d, J = 245.3 Hz), 139.4 (d, J = 7.7 Hz), 131.0 (d, J = 2.6 Hz), 130.0 (d, J = 8.4 Hz), 129.1, 122.0 (d, J = 2.8 Hz), 119.4, 114.3, 114.2 (d, J = 21.5 Hz), 114.0, 112.5 (d, J = 21.8 Hz),31.6, 24.9, 16.5; HRMS-ESI (m / z) [M + H] + Theoretical value: C 12 H 13 FN + :190.1027; Actual value:190.1027.

[0091]

[0092] 3k: 1 H NMR (400 MHz, CDCl3) δ 7.41 (td, J = 7.7, 1.7 Hz, 1H), 7.19 (tdd, J = 9.2, 5.2, 2.6 Hz, 1H), 7.10–6.98 (m, 2H), 6.60 (d, J = 16.0 Hz, 1H), 6.22 (dt, J = 16.0, 7.0 Hz, 1H), 2.43–2.39 (m, 4H), 1.87 (p, J = 7.2 Hz, 2H); 13C NMR (200 MHz,CDCl3) δ 160.0 (d, J = 248.7 Hz), 130.5 (d, J = 4.8 Hz),128.5 (d, J = 8.4 Hz), 127.2 (d, J = 3.9 Hz), 124.8 (d, J = 12.2 Hz), 124.5(d, J = 3.4 Hz), 124.1 (d, J = 3.5 Hz), 119.5, 115.7 (d, J = 22.2 Hz), 32.1,24.9, 16.5; HRMS-ESI (m / z) [M + H] + Theoretical value: C 12 H 13 FN + : 190.1027; Actual value: 190.1028.

[0093]

[0094] 3l: 1 H NMR (800 MHz, CDCl3) δ 7.27 (s, 4H), 6.41 (dt, J = 15.8, 1.3 Hz,1H), 6.11 (dt, J = 15.8, 7.0 Hz, 1H), 2.38 (s, 4H), 1.85 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 134.72, 132.05, 129.96, 127.84, 127.49, 126.42,118.60, 30.78, 24.03, 15.62; HRMS-ESI (m / z) [M + H] + Theoretical value: C 12 H 13 C1N + : 206.0731; Actual value: 206.0733.

[0095]

[0096] 3m: 1H NMR (800 MHz, CDCl3) δ 7.33 (t, J = 1.7 Hz, 1H), 7.25–7.18 (m,3H), 6.41 (d, J = 15.8 Hz, 1H), 6.15 (dt, J = 15.8, 7.1 Hz, 1H), 2.42-2.37(m, 4H), 1.85 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 138.97, 134.53, 130.76, 129.82, 129.28, 127.30, 125.99, 124.38, 119.45, 31.63, 24.86, 16.51; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 12 H 13 C1N + : 206.0731; Actual value: 206.0731.

[0097]

[0098] 3n: 1 H NMR (800 MHz, CDCl3) δ 7.49 (dd, J = 7.7, 1.3 Hz, 1H), 7.34 (dd,J = 7.9, 1.0 Hz, 1H), 7.24–7.14 (m, 2H), 6.83 (d, J = 15.8 Hz, 1H), 6.12 (dt,J = 15.7, 7.0 Hz, 1H), 2.46–2.40 (m, 4H), 1.88 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 135.26, 132.71, 130.63, 129.67, 128.39, 128.30, 126.84,126.72, 119.49, 31.85, 24.90, 16.50; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 12 H 13 C1N + : 206.0731; Actual value: 206.0732.

[0099]

[0100] 3o: 1 H NMR (800 MHz, CDCl3) δ 7.44–7.41 (m, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.40 (d, J = 15.8 Hz, 1H), 6.13 (dt, J = 15.8, 7.1 Hz, 1H), 2.41–2.36(m, 4H), 1.85 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 135.59, 131.21,130.43, 128.08, 127.19, 120.59, 119.03, 31.22, 24.42, 16.06; HRMS-ESI (m / z) [M + H] + Theoretical value: C 12 H 13 BrN + : 250.0226; Actual value: 250.0227.

[0101]

[0102] 3p: 1 H NMR (800 MHz, CDCl3) δ 7.44–7.41 (m, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.40 (d, J = 15.8 Hz, 1H), 6.13 (dt, J = 15.8, 7.1 Hz, 1H), 2.41–2.36(m, 4H), 1.85 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 138.19, 129.58, 129.14, 129.04, 128.26, 127.85, 123.75, 121.71, 118.37, 30.55, 23.79, 15.43; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 12 H 13 BrN + : 250.0226; Actual value: 250.0227.

[0103]

[0104] 3q: 1H NMR (800 MHz, CDCl3) δ 7.55–7.52 (m, 1H), 7.47 (dd, J = 7.8, 1.2Hz, 1H), 7.27–7.24 (m, 1H), 7.11–7.07 (m, 1H), 6.78 (d, J = 15.7 Hz, 1H), 6.08 (dt, J = 15.6, 7.0 Hz, 1H), 2.43 (qd, J = 7.8, 7.1, 2.3 Hz, 4H), 1.88(p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 136.73, 132.58, 130.59,130.50,128.37, 127.20, 126.66, 122.96, 119.21, 31.44, 24.56, 16.19; HRMS-ESI (m / z) [M + H] + Theoretical value: C 12 H 13 BrN + : 250.0226; Actual value: 250.0228.

[0105]

[0106] 3r: 1 H NMR (800 MHz, CDCl3) δ 7.56 (d, J = 8.1 Hz, 2H), 7.44 (d, J =8.1 Hz, 2H), 6.50 (d, J = 15.8 Hz, 1H), 6.25 (dt, J = 15.6, 7.0 Hz, 1H),2.44–2.39 (m, 4H), 1.87 (p, J = 7.2 Hz, 2H); 13 C NMR (200 MHz, CDCl3) δ 140.6,130.9, 130.6, 129.3 (q, J = 32.4 Hz), 126.3, 125.6 (q, J = 3.9 Hz), 124.3 (q,J = 271.7 Hz), 119.5, 31.8, 24.9, 16.6; HRMS-ESI (m / z) [M + H] + Theoretical value: C 13 H 13 F3N +: 240.0995; Actual value: 240.0997.

[0107]

[0108] 3s: 1 H NMR (800 MHz, CDCl3) δ 7.59 (d, J = 8.3 Hz, 2H), 7.42 (d, J =8.3 Hz, 2H), 6.49 (d, J = 15.8 Hz, 1H), 6.29 (dt, J = 15.8, 7.1 Hz, 1H),2.46–2.40 (m, 4H), 1.90–1.85 (m, 2H); 13 C NMR (200 MHz, CDCl3) δ 140.11, 131.03, 130.50, 129.17, 125.17, 117.89, 117.56, 109.18, 30.33, 23.27, 15.17; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 13 H 12 N2 + : 197.1073; Actual value: 197.1074.

[0109]

[0110] 3t: 1 H NMR (400 MHz, CDCl3) δ 7.25–7.20 (m, 2H), 6.83–6.73 (m, 2H),6.39 (d, J = 15.8 Hz, 1H), 5.97 (dt, J = 15.8, 7.1 Hz,1H), 2.41–2.32 (m, 4H),1.83 (p, J = 7.2 Hz, 4H); 13 C NMR (200 MHz, CDCl3) δ 155.04, 131.40, 130.07,127.41, 125.36, 119.65, 115.48, 31.64, 25.10, 16.43; HRMS-ESI (m / z) [M + H] + Theoretical value: C 12 H 14 No + : 188.1070; Actual value: 188.1071.

[0111]

[0112] 3u: 1 H NMR (800 MHz, CDCl3) δ 7.61–7.57 (m, 2H), 7.55 (d, J = 8.2 Hz,2H), 7.45–7.41 (m, 4H), 7.34 (t, J = 7.4 Hz, 1H), 6.50 (d, J = 15.8 Hz, 1H), 6.18 (dt, J = 15.7, 7.0 Hz, 1H), 2.44–2.36 (m, 4H), 1.89–1.82 (m, 2H); 13 C NMR (200 MHz, CDCl3) δ 140.42, 139.86, 135.87, 131.33, 128.55, 127.51, 127.05,127.02, 126.65, 126.25, 119.31, 31.48, 24.75, 16.20; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 18 H 18 N + : 248.1434; Actual value: 248.1433.

[0113]

[0114] 3v: 1 H NMR (800 MHz, CDCl3) δ 7.78 (dd, J = 12.4, 8.6 Hz, 3H), 7.69 (s,1H), 7.56 (dd, J = 8.5, 1.4 Hz, 1H), 7.47–7.41 (m, 2H), 6.62 (d, J = 15.8 Hz,1H), 6.25 (dt, J = 15.6, 7.0 Hz, 1H), 2.45–2.39 (m, 4H), 1.88 (p, J = 7.2 Hz,2H); 13C NMR (200 MHz, CDCl3) δ 134.20, 133.28, 132.52, 131.77, 127.87,127.72, 127.57, 127.32, 125.96, 125.48, 125.44, 123.05, 119.25, 31.44, 24.67,16.13; HRMS-ESI (m / z) [M + H] + Theoretical value: C 16 H 16 N + : 222.1277; Actual value: 222.1278.

[0115]

[0116] 3w: 1 H NMR (400 MHz, CDCl3) δ 7.45 – 7.38 (m, 2H), 7.35–7.29 (m, 2H), 7.26–7.20 (m, 1H), 7.09–6.71 (m, 1H), 6.54 (dd, J = 34.8, 15.6 Hz, 1H), 6.31–6.25 (m, 1H), 5.76–5.40 (m, 1H), 2.50–2.30 (m, 4H), 1.85–1.77 (m, 2H); 13 C NMR (200 MHz, CDCl3) δ 137.2, 132.6, 131.9, 131.4, 128.6, 127.4, 126.5, 126.2,119.5, 31.4, 24.9, 16.4; High-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 14 H 16 N + :198.1277; Actual value:198.1279.

[0117]

[0118] 3x: 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 1.5 Hz, 1H), 6.36 (dd, J =3.3, 1.8 Hz, 1H), 6.30–6.23 (m, 1H), 6.18 (d, J = 3.3 Hz, 1H), 6.10–6.02 (m,1H), 2.41–2.33 (m, 4H), 1.89 – 1.79 (m, 2H); 13 C NMR (200 MHz, CDCl3) δ 152.5, 141.6, 126.4, 120.5, 119.5, 111.2, 107.0, 31.4, 24.9, 16.4; high-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 10 H 12 NO + : 162.0913; Actual value: 162.0915.

[0119]

[0120] 3y: 1 H NMR (800 MHz, CDCl3) δ 7.12 (d, J = 5.1 Hz, 1H), 6.94 (dd, J =5.1, 3.5 Hz, 1H), 6.90 (d, J = 3.4 Hz, 1H), 6.58 (d, J = 15.6 Hz, 1H), 5.96(dt, J = 15.4, 7.1 Hz, 1H), 2.39–2.33 (m, 4H), 1.82 (p, J = 7.2 Hz, 2H); 13 CNMR (200 MHz, CDCl3) δ 142.2, 127.4, 127.3, 125.3, 125.0, 123.8, 119.5, 31.5,24.9, 16.4; HRMS-ESI (m / z) [M + H] + Theoretical value: C 10 H 12 NS + : 178.0685; Actual value: 178.0686.

[0121]

[0122] 3aa: 1H NMR (800 MHz, CDCl3) δ 7.36–7.29 (m, 4H), 7.26–7.21 (m, 1H), 6.51 (d, J = 15.7 Hz, 1H), 6.07 (d, J = 15.7 Hz, 1H), 2.79 (q, J = 6.7 Hz,1H), 2.69–2.53 (m, 4H),1.47 (s, 9H); 13 C NMR (200 MHz, CDCl3) δ 169.20,134.78, 132.02, 126.70, 125.73, 124.29, 122.48, 116.03, 80.31, 40.25, 32.72,26.09, 16.77; HRMS-ESI (m / z) [M + H] + Theoretical value: C 17 H 22 NO2 + : 271.1645;Actual value: 271.1645.

[0123]

[0124] 3ab: 1 H NMR (800 MHz, CDCl3) δ 7.39–7.34 (m, 2H), 7.31–7.20 (m, 8H), 6.47 (d, J = 15.8 Hz, 1H), 6.07–6.02 (m, 1H), 3.13 (p, J = 7.1 Hz, 1H), 2.72–2.63 (m, 4H); 13 C NMR (200 MHz, CDCl3) δ 141.43, 137.12, 133.19, 129.01,128.69, 127.63, 127.56, 127.30, 126.31, 126.28, 118.64, 42.14, 38.52, 23.94; HRMS-ESI (m / z) [M + H] + Theoretical value: C 18 H 18 N + : 248.1434; Actual value: 248.1434.

[0125]

[0126] 3ac: 1H NMR (800 MHz, CDCl3) δ 7.35–7.33 (m, 2H), 7.31 (t, J = 7.7 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 6.52 (d, J = 15.7 Hz, 1H), 6.06 (dt, J = 15.4,7.4 Hz, 1H), 4.25–4.19 (m, 2H), 2.89 (p, J = 6.8 Hz, 1H), 2.74–2.63 (m, 4H),1.29 (t, J = 7.1 Hz, 3H); 13 C NMR (200 MHz, CDCl3) δ 171.85, 136.55, 134.14,128.56, 127.66, 126.24, 124.02, 117.73, 61.48, 41.36, 34.39, 18.51, 14.15; HRMS-ESI (m / z) [M + H] + Theoretical value: C 15 H 18 NO2 + : 244.1332; Actual value: 244.1333.

[0127]

[0128] 3ad: 1 H NMR (800 MHz, CDCl3) δ 7.38–7.29 (m, 9H), 7.25–7.22 (m, 1H), 6.52 (d, J = 15.8 Hz, 1H), 6.17–6.11 (m, 1H), 4.66 (d, J = 2.6 Hz, 2H), 3.85–3.81 (m, 1H), 2.65–2.56 (m, 4H); 13 C NMR (101 MHz, CDCl3) δ 137.40, 136.89,134.05, 128.59 (d, J = 2.5 Hz), 128.06, 127.88, 127.58, 126.19, 123.82,74.23, 71.87, 37.37, 22.72; HRMS-ESI (m / z) [M + H] + Theoretical value: C 19 H 20 NO +: 278.1539; Actual value: 278.1541.

[0129]

[0130] 3ae: 1 H NMR (800 MHz, CDCl3) δ 7.38 (d, J = 7.4 Hz, 2H), 7.33 (t, J =7.6 Hz, 2H), 7.27 (d, J = 7.3 Hz, 1H), 6.57 (d, J = 12.9 Hz, 1H), 6.11 (dt, J= 14.7, 6.3 Hz, 1H), 4.17 (d, J = 74.9 Hz, 4H); 13 C NMR (200 MHz, CDCl3) δ135.91, 135.36, 128.71, 128.35, 126.71, 123.04, 116.01, 71.71, 54.68; HRMS-ESI (m / z) [M + H] + Theoretical value: C 11 H 12 NO + : 174.0913; Actual value: 174.1096.

[0131]

[0132] 3af: 1 H NMR (800 MHz, CDCl3) δ 7.41–7.39 (m, 2H), 7.34 (t, J = 7.7 Hz,2H), 7.29–7.27 (m, 1H), 6.58 (d, J = 15.7 Hz, 1H), 6.13 (dt, J = 15.4, 7.6Hz, 1H), 3.53 (dd, J = 7.6, 1.1 Hz, 2H), 3.25 (s, 2H); 13 C NMR (200 MHz,CDCl3) δ 134.06, 132.53, 126.83, 126.26, 124.64, 121.07, 114.55, 32.53,13.59; High-resolution mass spectrometry-electrospray ionization (m / z) [M + H] + Theoretical value: C 11 H 12 NS + : 190.0685; Actual value: 190.0684.

[0133]

[0134] 3ag: 1 H NMR (800 MHz, CDCl3) δ 7.38 (d, J = 7.4 Hz, 2H), 7.33 (t, J =7.6 Hz, 2H), 7.27 (d, J = 7.3 Hz, 1H), 6.57 (d, J = 12.9 Hz, 1H), 6.11 (dt, J= 14.7, 6.3 Hz, 1H), 4.17 (d, J = 74.7 Hz, 4H), 1.52 (s, 9H); 13 C NMR (200 MHz, CDCl3) δ 136.01, 128.71, 128.16, 126.56, 115.99, 82.12, 41.44, 34.46,28.26, 28.22; HRMS-ESI (m / z) [M + H] + Theoretical value: C 16 H 21 N2O2 + : 273.1598; Actual value: 273.1599.

[0135]

[0136] 3ah: 1 H NMR (400 MHz, CDCl3) δ 7.38–7.27 (m, 4H), 7.25–7.17 (m, 1H), 6.36 (d, J = 15.9 Hz, 1H), 6.04 (dd, J = 15.9, 8.2 Hz, 1H), 2.41–2.21 (m,3H), 1.77–1.44 (m, 4H), 1.11 (d, J = 6.7 Hz, 3H); 13 C NMR (200 MHz, CDCl3) δ137.39, 135.28, 129.13, 128.55, 127.13, 126.03, 119.72, 36.91, 35.85, 23.38,20.79, 17.25; HRMS-ESI (m / z) [M + H] + Theoretical value: C 14 H 18 N +: 200.1434; Actual value: 200.1435.

[0137]

[0138] 3ai: 1 H NMR (400 MHz, CDCl3) δ 7.39 (dd, J = 8.3, 1.2 Hz, 2H), 7.35–7.30 (m, 2H), 7.28–7.23 (m, 1H), 6.55 (d, J = 16.0 Hz, 0H), 6.09 (dd, J =16.0, 7.8 Hz, 1H), 4.12–4.01 (m, 1H), 3.73 (dt, J = 9.5, 6.4 Hz, 1H), 3.58 (dt, J = 9.5, 6.4 Hz, 1H), 2.59 (t, J = 6.4 Hz, 2H), 1.36 (d, J = 6.3 Hz,3H); 13 C NMR (200 MHz, CDCl3) δ 135.64, 131.39, 130.04, 128.07, 127.36,125.95, 117.43, 62.20, 21.01, 18.54; HRMS-ESI (m / z) [M + H] + Theoretical value: C 13 H 16 NO + : 202.1226; Actual value: 202.1229.

[0139] The above embodiments are preferred implementations of the present invention, but the implementations of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be considered equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. A method for the decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime catalyzed by iron, characterized in that: The method comprises the following steps: In a nitrogen atmosphere, cinnamic acid compounds and cyclic ketoxime compounds are used as raw materials, iron salts are used as catalysts, and the reaction is carried out at 90-150 °C in a solvent for 10-20 hours to prepare remote cyanoalkyl olefins. Wherein, the cinnamic acid compound is 4-methylcinnamic acid, 3-methylcinnamic acid, 2-methylcinnamic acid, 4-tert-butylcinnamic acid, 4-isopropylcinnamic acid, 4-methoxycinnamic acid, 4-dimethylaminocinnamic acid, 4-fluorocinnamic acid, 3-fluorocinnamic acid, 2-fluorocinnamic acid, 4-chlorocinnamic acid, 3-chlorocinnamic acid, 2-chlorocinnamic acid, 4-bromocinnamic acid, 3-bromocinnamic acid, 2-bromocinnamic acid, 4-trifluoromethylcinnamic acid, 4-cyanocinnamic acid, 4-hydroxycinnamic acid, 4-phenylcinnamic acid, β-naphthyl acrylic acid, 5-phenylpentadienoic acid, 2-furan acrylic acid or 2-thiophene acrylic acid; The cyclic ketone oxime compound is 3-tert-butoxycarbonylcyclobutanone oxime, 3-phenylcyclobutanone oxime, 3-ethoxycarbonylcyclobutanone oxime, 3-benzyloxycyclobutanone oxime, 3-oxetanone oxime, 3-thietanone oxime, 3-tert-butoxycarbonyl-3-azetidinone oxime, 2-methylcyclopentanone oxime, 2-methyl-3-oxetanone oxime or 2-phenylcyclohexanone oxime; The catalyst is FeCl2, FeCl3, FeBr2, FeBr3, Fe(OTf)2, Fe(OTf)3, Fe(acac)2, Fe(acac)3, FeI2 or FeSO4.

2. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 1, characterized in that: The solvent is dichloromethane, 1,2-dichloroethane, 1,4-dioxane, trifluoromethylbenzene, chlorobenzene, acetonitrile, methyl tert-butyl ether, N-methylpyrrolidone, benzene or toluene.

3. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 2, characterized in that: The solvent is chlorobenzene.

4. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 1, characterized in that: The molar ratio of the cinnamic acid compound to the cyclic ketoxime compound is (0.2-5):

1.

5. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 1, characterized in that: The catalyst is Fe(acac)2.

6. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 1, characterized in that: The reaction temperature is 100~140℃.

7. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 1, characterized in that: The ratio of the cinnamic acid compound, the cyclic ketoxime compound and the solvent is (0.02-0.55) mmol: 0.1 mmol: (0.5-4) mL.

8. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 1, characterized in that: The molar ratio of the cinnamic acid compound to the catalyst is 1:(0.05-0.30).

9. The reaction method of iron-catalyzed decarboxylation / cyanoalkylation of cinnamic acid and cyclic ketoxime as claimed in claim 1, characterized in that: The reaction time is 12~18h.

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