A method for synthesizing ferrocenyl phosphine oxide compounds

Abstract

The application relates to a method for synthesizing ferrocene phosphine oxide compounds. Specifically, a ferrocene-substituted compound, diaryl phosphine oxide is used as raw material to realize C-H phosphine oxide reaction of ferrocene under the promotion of electricity. The application has the following advantages: the ferrocene-substituted compound is directly used as a C-H donor without guidance, no additional oxidant and metal catalyst are needed, the condition is mild, the substrate range is wide, and the yield is good.

Description

Technical Field

[0001] This invention relates to a method for synthesizing ferrocene phosphine oxides. Background Technology

[0002] Phosphine compounds with metallocene frameworks are highly active ligands or catalysts in asymmetric catalytic reactions. Previous methods for synthesizing ferrocene phosphine oxides generally require the introduction of phosphine groups onto ferrocene, necessitating air-sensitive lithium reagents or equivalent Lewis acids. These methods are typically cumbersome, generate significant waste, and usually require pre-installed directing groups and additional metal catalysts. This invention utilizes secondary phosphine oxides and non-directing ferrocene substitutes as starting materials to achieve the oxidation of metallocene CH4 phosphine under electro-promoted autocatalysis. This reaction offers advantages such as a broad substrate range, good yields, no need for additional expensive equivalent oxidants, and mild conditions.

[0003] In summary, this paper describes a method for directly synthesizing ferrocene-based phosphine oxides from readily available raw materials, using secondary phosphine oxides as phosphine sources and non-directed ferrocene substituted derivatives as CH donors. Summary of the Invention

[0004] The purpose of this invention is to provide a method for synthesizing ferrocene phosphine oxides, which is an electro-promoted, autocatalytic method for the CH phosphine oxidation of ferrocene.

[0005]

[0006] Reaction Equation 1: Synthesis of Ferrocene Phosphine Oxides

[0007] The specific operating steps are as follows (reaction equation 1):

[0008] Under a nitrogen atmosphere, benzo[a]ferrocene derivative 1, diarylphosphine oxide 2, electrolyte, and solvent were added to a three-necked flask, followed by the addition of a base. Positive and negative electrodes were then attached. The three-necked flask RVC (15mm long × 10mm wide × 5mm thick) served as the anode, and Pt (10mm long × 10mm wide × 0.3mm thick) served as the cathode. The distance between the electrodes was 25mm, and the planes containing the length and height of the two electrodes (anode and cathode) were arranged parallel to each other (the area of ​​the opposing surfaces of the anode and cathode placed in the reaction solution was 85mm²). 2 The reaction was carried out under constant current of 4.0 mA and stirred at 50 °C for 6 h, producing the target product 3. After the reaction was completed, the solvent was evaporated, and the mobile phase for column chromatography was petroleum ether / ethyl acetate (volume ratio).

[0009] The molar ratio of ferrocene substitute 1 to secondary phosphine compound 2 is 1:1.1-1:4, with a preferred ratio of 1:1.7-1:2.5.

[0010] The alkali is one or more of the following: NaOAc, Na2CO3, KH2PO4, K2HPO4, PhCO2Na, NaHCO3, NaOPiv, Et3N, TMEDA, Py, DMAP, DABCO, and DBU. The amount of alkali used is 1.4-4.5 molar equivalents of the amount of ferrocene-substituted compound 1, preferably 1.5-3 molar equivalents.

[0011] Electrolytes are n Bu4NPF6, n Bu4NBF4, n Bu4NCl, n Bu4NOAc, n Bu4NOTs, n One or more of Bu4NClO4 and NaClO4; the amount of electrolyte used is 0.30-2.4 molar equivalents of the amount of ferrocene substitute 1, preferably 0.6-1.5 molar equivalents.

[0012] The solvent is one or more of the following: acetone, dichloromethane, acetonitrile, dimethyl sulfoxide, water, ethanol, methanol, tert-amyl alcohol, N,N-dimethylformamide, trifluoroethanol, and hexafluoroisopropanol, preferably methanol; the amount of solvent used is 2.0-8.0 ml per millimole of ferrocene-substituted compound 1, preferably 5.0 ml.

[0013] The present invention has the following advantages:

[0014] First, using secondary phosphine oxides and non-directing ferrocene-substituted derivatives as starting materials, an electrocatalytic oxidation reaction of metallocene CH4 phosphine was achieved. Second, this reaction exhibits a broad substrate range, good yields, requires no additional expensive stoichiometric oxidants, and operates under mild conditions, making the reaction more environmentally friendly. Finally, the resulting ferrocene phosphine oxide can be converted to phosphine ligands in a single step.

[0015] The present invention has the following advantages: the undirected ferrocene substitutes can be used directly as CH donors without the need for additional oxidants and metal catalysts, under mild conditions, with a wide substrate range and good yields. Detailed Implementation

[0016] To better understand the present invention, the following examples are provided. The reaction materials and results of Examples 1-11 are shown in Table 1.

[0017] Table 1. Reaction results of ferrocene with different substitutions and diphenylphosphine oxide 2.

[0018]

[0019]

[0020]

[0021] Table 2. Reaction results of substituted ferrocene with different secondary phosphine oxides after 1 h.

[0022]

[0023]

[0024] Synthesis of raw materials

[0025] Synthesis of ferrocene 1a substitute: Ferrous chloride (1.27 g, 10 mmol) was placed in a Schlenk flask, and the atmosphere was changed to nitrogen three times. 50 mL of anhydrous THF was added, and the mixture was stirred overnight to obtain solution A. In another Schlenk flask, the atmosphere was changed to nitrogen three times, and 1,2,3,4,5-pentamethylcyclopentadiene (1.36 g, 10 mol) was added. The mixture was cooled to -78 °C, and then n-butyllithium (2.4 mol / L, 4.6 mL, 1...) was added. 1 mol), reacted for 1 hour to obtain solution B, transferred solution B to solution A, stirred for 1 hour, added cyclopentadienyl sodium solution (2 mol / L, 5 mL, 10 mol), reacted overnight, column chromatography, and used petroleum ether as eluent to obtain ferrocene substituted product 1a (Reference [1] Kang, D.; Ricci, F.; White, RJ; Plaxco, K. Wanal. Chem. 2016, 88, 10452-10458).

[0026] Ferrocene 1b was commercially available. Ferrocene substituted products 1c, 1d, 1e, 1f, and 1g were all prepared by the same method described above, with the same operating procedures and conditions. The difference was that 1,2,3,4-methyl-5-ethylcyclopentadiene, 1,2,3,4-methyl-5-isopropylcyclopentadiene, 1,2,3,4-methyl-5-phenylcyclopentadiene, 1,2,3,4-methyl-5-(4-fluoro)phenylcyclopentadiene, and 1,2,3,4-methyl-5-phenylethylcyclopentadiene were used to replace 1,2,3,4,5-pentamethylcyclopentadiene, respectively.

[0027] Synthesis of secondary phosphine oxide 2d: Magnesium shavings (972.4 mg, 40 mmol) were placed in a Schlenk flask, the atmosphere in the flask was changed to nitrogen three times, 10 mL of anhydrous THF was injected, and 4-chlorobromobenzene (5.74 g, 30 mmol) was added dropwise to prepare the corresponding Grignard reagent. The mixture was cooled to 0 °C, and diethyl phosphite (1.38 g, 10 mmol) was added dropwise. The mixture was stirred for one hour, and then reacted at room temperature overnight. Column chromatography was performed, and ethyl acetate: petroleum ether = 2:1 (volume ratio) was used as the eluent to obtain secondary phosphine oxide 2d (Reference [2] Molitor, S.; Becker, J.; Gessner, VHJAm. Chem. Soc. 2014, 136, 15517–15520).

[0028] Synthesis of other secondary phosphine oxides: Secondary phosphine oxide 2a was commercially available. Phosphine oxides 2b, 2c, and 2e were prepared by the same method as described above, with the difference being that 4-chlorobromobenzene was obtained by replacing 4-methylbromobenzene with equimolar amounts of bromobenzene, 4-methylbromobenzene, and 3,5-difluorobromobenzene, respectively.

[0029] Example 1

[0030] Under a nitrogen atmosphere, ferrocene-substituted compound 1 (0.2 mmol) and secondary phosphine compound 2 (0.4 mmol) were added sequentially to a three-necked flask. n Bu4NOAc (0.2 mmol), Et3N (0.4 mmol), and MeOH (5.0 mL) were used to prepare a reaction solution. A cathode and anode were placed in a three-necked flask, with an RVC electrode as the anode and a sheet Pt electrode as the cathode. The distance between the electrodes was 25 mm. The length and height planes of the two electrodes (anode and cathode) were parallel to each other (the lower parts of the cathode and anode were placed in the reaction solution, and the area of ​​the relative surfaces of the anode and cathode in the reaction solution was 85 mm²). 2 A constant current of 4.0 mA was passed between the cathode and anode, and the reaction was carried out at 50 °C for 6 hours. After the reaction, the mixture was separated by column chromatography (mobile phase: petroleum ether / ethyl acetate = 1:1, v / v) to obtain ferrocene phosphine oxide compound 3a in 71% yield. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H1N, C1N, and phosphine spectra), and high-resolution mass spectrometry. The detection data are as follows:

[0031] 3a: Yellow solid, mp 195.3-197.0℃, 67.8mg, 73% yield. 1H NMR (400MHz, CDCl3) δ7.61 (dd, J = 11.9, 7.5Hz, 4H), 7.46–7.33 (m, 6H), 3.99 (s, 4H), 1.82 (s, 15H); 13 C NMR (100MHz, CDCl3) δ135.6 (d, J = 104.6Hz), 131.5 (d, J = 9.6Hz), 131.1 (d, J = 2.7Hz), 12 8.1(d,J=11.8Hz),82.0,75.8(d,J=10.9Hz),74.2(d,J=12.9Hz),73.2(d,J=120.4Hz); 31 PNMR(162MHz,CDCl3)δ28.0; HRMS calculated for C 27 H 29 OPNaFe[M+Na] + 479.1198, found 479.1199. Example 2:

[0032] The operation process and conditions were the same as in Example 1. The difference from Example 1 is shown in Table 1. The yield of product 3b was 71% after column chromatography separation (mobile phase: petroleum ether / ethyl acetate = 1:2). The structure of the compound was identified by infrared and nuclear magnetic resonance (H1N, C1N and phosphine spectra).

[0033] The test data is as follows:

[0034] 3b; yellow solid, 54.8 mg, 71% yield. 1 H NMR (400MHz, CDCl3) δ7.71–7.63(m,4H),7.48(m,2H),7.41(m,4H),4.46(d,J=1.8Hz,2H),4.36(d,J=1.9Hz,2H),4.19(s,5H); 13 CNMR(100MHz, CDCl3)δ134.4(d,J=106.4Hz),131.6(d,J=2.8Hz),131.5(d,J=9.9Hz),1 28.2(d,J=12.1Hz),72.8(d,J=117.6Hz),72.3(d,J=12.9Hz),71.7(d,J=10.5Hz),69.7. 31 P NMR (162MHz, CDCl3) δ29.0;

[0035] The 3b (77.6 mg, 0.2 mmol) was dissolved in 2 mL of toluene, and triethylamine (81.5 mg, 0.8 mmol) and trimethylchlorosilane (65.2 mg, 0.6 mmol) were added. The mixture was then heated in an oil bath under reflux for 18 hours to obtain phosphine ligand 4 with a yield of 99%. This phosphine ligand has excellent activity in the selective construction of CC (Reference [3] Laulhé, S.; Blackburn, JM; Roizen, JL Org. Lett. 2016, 18, 4440-4443).

[0036]

[0037] Example 3:

[0038] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The yield of product 3C was 72%. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H NMR, C NMR and phosphine NMR), and high-resolution mass spectrometry.

[0039] The test data is as follows:

[0040] 3c: Yellow solid, mp 125.6-127.2℃, 67.6mg, 72% yield. 1 H NMR (400MHz, CDCl3) δ7.65–7.57(m,4H),7.45–7.39(m,2H),7.39–7.33(m,4H),4.00(s,2 H),3.99(s,2H),2.35(q,J=7.6Hz,2H),1.83(s,6H),1.83(s,6H),0.87(t,J=7.6Hz,3H); 13 C NMR (100MHz, CDCl3) δ135.5(d,J=104.7Hz), 131.5(d,J=9.9Hz), 131.1(d,J=2.8Hz), 128.0(d,J=11.9Hz) ,87.7,82.3,81.5,75.6(d,J=10.9Hz),74.0(d,J=13.0Hz),73.1(d,J=120.7Hz),19.9,15.3,11.3,11.1; 31 P NMR(162MHz, CDCl3)δ28.1; HRMS calculated forC 28 H 31 OPNaFe[M+Na] + 493.1354, found 493.1359

[0041] Example 4:

[0042] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The 3-day yield of the product was 64%. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H NMR, C NMR and phosphine NMR), and high-resolution mass spectrometry.

[0043] The test data is as follows:

[0044] 3d: Yellow solid, mp 85.5-87.0℃, 62.3mg, 64% yield. 1 H NMR (400MHz, CDCl3) δ7.64–7.55(m,4H),7.46–7.40(m,2H),7.40–7.33(m,4H),4.11(d,2H),4. 08(d,J=2.2Hz,2H),2.65(hept,J=7.1Hz,1H),1.85(s,6H),1.79(s,6H),1.16(d,J=7.1Hz,6H); 13 C NMR (100MHz, CDCl3) δ135.3(d,J=104.8Hz), 131.4(d,J=9.5Hz), 131.2(d,J=2.9Hz), 128.1(d,J=12.1Hz) ,92.0,82.5,81.0,75.4(d,J=10.9Hz),74.0(d,J=12.9Hz),72.7(d,J=121.3Hz),26.8,23.3,12.0,11.3; 31 P NMR(162MHz, CDCl3)δ28.9; HRMS calculated forC 29 H 33 OPNaFe[M+Na] + 507.1511, found 507.1507.

[0045] Example 5:

[0046] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The yield of product 3e was 77%. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H NMR, C NMR and phosphine NMR), and high-resolution mass spectrometry.

[0047] The test data is as follows:

[0048] 3e: Yellow solid, mp 42.9-44.2℃, 79.8mg, 77% yield. 1H NMR (400MHz, CDCl3) δ7.67–7.59(m,4H),7.47–7.34(m,8H),7.29–7.21(m,3 H), 4.12 (q, J = 2.0Hz, 2H), 4.08 (q, J = 1.9Hz, 2H), 1.94 (s, 6H), 1.91 (s, 6H). 13 C NMR (100MHz, CDCl3) δ136.9, 135.3 (d, J = 104.9Hz), 131.5 (d, J = 9.7Hz), 131.2 (d, J = 2.9Hz), 131.2, 128.1 (d, J = 11 .9Hz),127.7,126.2,88.0,83.0,82.0,76.7(d,J=10.7Hz),75.2(d,J=12.8Hz),73.4(d,J=119.8Hz),12.3,11.5; 31 P NMR(162MHz, CDCl3)δ28.0; HRMS calculated for C 32 H 32 OPFe[M+H] + 519.1535, found 519.1527.

[0049] Example 6:

[0050] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The yield of product 3f was 63%. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0051] The test data is as follows:

[0052] 3f: Yellow solid, mp 154.2-156.1℃, 67.8mg, 63% yield. 1 H NMR (400MHz, CDCl3) δ7.67–7.57(m,4H),7.49–7.41(m,2H),7.41–7.33(m,6H),6.97– 6.90(m,2H),4.10(q,J=2.0Hz,2H),4.07(q,J=1.8Hz,2H),1.91(s,6H),1.88(s,6H); 13C NMR (100MHz, CDCl3) δ161.4 (d, J = 245.1Hz), 135.2 (d, J = 105.0Hz), 132.6, 132.6 (d, J = 7.8Hz), 131.5 (d, J = 9.6Hz), 131.3 (d, J = 2.8Hz), 128.2 (d, J = 12.0Hz), 114.6 (d, J = 21.1Hz), 87.2, 82.8, 82.1, 76.7 (d, J = 10.7Hz), 75.2 (d, J = 12.7Hz), 73.4 (d, J = 119.8Hz), 12.2, 11.5. 31 P NMR (162MHz, CDCl3) δ 28.1; 19 F NMR(376MHz,CDCl3)δ-116.5.HRMS calculated for C 32 H 31 OPFFe[M+H] + 537.1440, found 537.1445.

[0053] Example 7:

[0054] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The yield of the product was 53% (3g). The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H NMR, C NMR, and phosphine NMR), and high-resolution mass spectrometry.

[0055] The test data is as follows:

[0056] 3g: Yellow solid, mp 50.8-51.9℃, 57.3mg, 52% yield, R f =0.40(petroleumether / ethyl acetate 20 / 1). 1 H NMR (700MHz, CDCl3) δ7.64–7.53(m,3H),7.42–7.36(m,2H),7.36–7.30(m,3H),7.28–7.22(m,2H),7.20–7.12(m,1H),7 .08(d,J=7.5Hz,2H),4.00(s,2H),3.99(s,2H),2.56(t,J=8.1Hz,2H),2.47(t,J=8.2Hz,2H),1.83(s,6H),1.77(s,6H). 13C NMR (175MHz, CDCl3) δ142.1, 135.3 (d, J = 104.7Hz), 131.4 (d, J = 9.6Hz), 131.2 (d, J = 2.6Hz), 128.6, 128.3, 128.1 (d, J = 1 2.0Hz),125.8,85.3,82.5,81.9,75.6(d,J=10.8Hz),74.0(d,J=12.8Hz),73.0(d,J=120.8Hz),37.4,29.4,11.4,11.2. 31 P NMR(162MHz, CDCl3)δ28.3; HRMS calculated for C 34 H 35 OPNaFe[M+Na] + 569.1667, found 569.1666.

[0057] Example 8:

[0058] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The product yield was 40% after 3 hours. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H NMR, C NMR, and phosphine NMR), and high-resolution mass spectrometry.

[0059] The test data is as follows:

[0060] 3h: Yellow solid, mp 64.8-66.6℃, 37.6mg, 40% yield. 1 H NMR (400MHz, CDCl3) δ7.76–7.66(m,2H),7.62–7.55(m,2H),7.49–7.43(m,1H),7.42–7.32(m,4H),7.28(d,J=7.3Hz,1H),4.21(s,1H) ,4.13(s,1H),4.06–4.02(m,1H),4.00(q,J=3.0Hz,1H),3.64(d,J=11.4Hz,3H),2.05(s,3H),2.04(s,3H),1.99(s,3H),1.97(s,3H); 13C NMR (100MHz, CDCl3) δ137.1, 132.5 (d, J = 132.2Hz), 131.6 (d, J = 2.8Hz), 131 .5(d,J=9.8Hz),131.2,128.4(d,J=12.9Hz),127.6,126.2,88.1,83.1,83.0 ,81.8,81.7,76.5(d,J=12.8Hz),76.4(d,J=11.8Hz),74.7(d,J=17.8Hz),74 .3(d,J=12.0Hz),71.8(d,J=165.3Hz),50.9(d,J=5.9Hz),12.0,11.9,11.3; 31 P NMR(162MHz, CDCl3)δ38.6; HRMS calculated forC 27 H 29 O2PNaFe[M+Na] + 495.1147, found 495.1145.

[0061] Example 9:

[0062] The operation process and conditions were the same as in Example 1. The difference from Example 1 is shown in Table 1. The yield of product 3i was 65%. The compound was subjected to infrared spectroscopy, nuclear magnetic resonance (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0063] The test data is as follows:

[0064] 3i: Yellow solid, mp 105.6-107.3℃, 71.3mg, 65% yield. 1 H NMR(400MHz, CDCl3)δ7.50(dd,J=11.7,7.8Hz,4H),7.41–7.36(m,2H),7.25–7.21(m,3H),7.17(dd,J= 8.1,2.6Hz,4H),4.10(q,J=2.0Hz,2H),4.06(q,J=1.8Hz,2H),2.35(s,6H),1.94(s,6H),1.93(s,6H); 13C NMR (100MHz, CDCl3) δ141.4 (d, J = 2.8Hz), 137.0, 132.3 (d, J = 107.3Hz), 131.5 (d, J = 10.1Hz), 131.2, 128.8 (d, J = 12.3 Hz),127.6,126.1,87.9,83.0,81.9,76.5(d,J=10.7Hz),75.2(d,J=12.8Hz),74.0(d,J=119.5Hz),21.6,12.3,11.6; 31 P NMR (162MHz, CDCl3) δ28.1; HRMS calculated for C 34 H 35 OPNaFe[M+Na] + 569.1667, found 569.1693.

[0065] Example 10:

[0066] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The yield of product 3j was 72%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0067] The test data is as follows:

[0068] 3j: Yellow solid, mp 128.7-129.3℃, 84.6mg, 72% yield. 1 H NMR (400MHz, CDCl3) δ7.50(dd,J=11.4,8.1Hz,4H),7.38–7.31(m,6H),7.28–7.24(m,3H),4.11(t,J=2.0Hz,2H),4.07(t,J=2.0Hz,2H),1.93(s,12H). 13 C NMR (100MHz, CDCl3) δ137.9 (d, J = 3.3Hz), 136.5, 133.4 (d, J = 106.2Hz), 132.7 (d, J = 10.6Hz), 131.0, 128.5 (d, J = 1 2.5Hz),127.6,126.3,88.1,83.1,82.2,76.9(d,J=11.0Hz),75.0(d,J=13.2Hz),72.4(d,J=122.3Hz),12.2,11.5. 31 P NMR(162MHz,CDCl3)δ27.1.HRMS calculated for C 32 H29 OPCl2NaFe[M+Na] + 609.0575, found 609.0578.

[0069] Example 11:

[0070] The operation process and conditions were the same as in Example 1. The difference from Example 1 was that, except for the differences described in Table 1, the yield of product 3k was 60%, and the structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0071] The test data is as follows:

[0072] 3k: Yellow solid, mp 121.8-122.2℃, 70.7mg, 60% yield. 1 H NMR (400MHz, CDCl3) δ7.44–7.38(m,2H),7.31–7.24(m,3H),7.17–7.06(m,J=5.0 Hz,4H),6.96–6.87(m,2H),4.18-4.17(m,2H),4.12-4.10(m,2H),1.92(s,12H); 13 C NMR (100MHz, CDCl3) δ162.8(ddd,J=253.8,19.6,11.0Hz),138.6(dt,J=103.9,6.5Hz),136.4,131.0,127.8,126.5,114.29(ddd,J=26.0,1 0.2, 1.6Hz) 107.4 (dt, J = 25.0, 1.7Hz), 88.5, 83.4, 82.4, 75.0 (d, J = 13.4Hz), 77.4 (d, J = 11.4Hz), 70.7 (d, J = 125.5Hz), 11.9 (d, J = 69.5Hz); 31 P NMR (162MHz, CDCl3) δ26.2 (t, J=6.4Hz); 19 F NMR(376MHz,CDCl3)δ-107.1(q,J=6.8Hz).HRMScalculated for C 32 H 28 OPF4Fe[M+H] + 591.1158, found 591.1154.

[0073] Comparative example: Replacing the electric current with an equivalent amount of oxidant:

[0074]

[0075] a Conditions: 1b (0.20 mmol), 2a (0.40 mmol), n Bu4NOAc (0.20 mmol), Et3N (0.40 mmol), oxidant (0.4 mmol), MeOH (4.0 mL), 50 °C, 6 h. Yield was determined by NMR spectroscopy using trimethoxybenzene as an internal standard.

Claims

1. A method for synthesizing ferrocenyl phosphine oxide, characterized in that: a ferrocene substituent 1 and a secondary phosphine compound 2 shown in the following formula are used as raw materials to generate a ferrocenyl phosphine oxide 3, and the reaction formula is as follows: The two R in the secondary phosphine compound 2 are independently one or two or more of phenyl, naphthyl, substituted phenyl, methoxy, and the substituent on the phenyl is one or two or more of chlorine, fluorine, methyl, and tert-butyl; ； The four R' in the ferrocene derivative 1 are one or two or more of hydrogen, methyl, ethyl, and C3-C6 alkyl; and R'' is one or two or more of hydrogen, methyl, ethyl, isopropyl, phenyl, phenethyl, substituted phenyl, C3-C6 alkyl, and the substituent on the phenyl is one or two or more of chlorine, fluorine, and trifluoromethyl; The specific operation steps are as follows:

2. The method according to claim 1, characterized in that: In a container, add the ferrocene derivative 1, the secondary phosphine compound 2, the electrolyte, the solvent and the base under nitrogen atmosphere to obtain a reaction solution; the container is provided with a cathode and an anode, the anode and the cathode are oppositely arranged with a distance of 15-40 mm, and part or all of the cathode and the anode are placed in the reaction solution of the reaction system, and the area of the opposite surfaces of the anode and the cathode placed in the reaction solution is 45-120 mm 2 Then, apply a current between the cathode and the anode. In the electrochemical reaction: the electrochemical constant reaction current is 2.0-6.0 mA, placed in 40-70 o C oil bath, the reaction time is 2-12 hours; the reaction is carried out in a solvent in the presence of an electrolyte; the reaction generates the target product 3; the solvent is one or more of acetone, dichloromethane, acetonitrile, dimethyl sulfoxide, water, ethanol, methanol, tert-pentanol, N,N-dimethylformamide, trifluoroethanol, hexafluoroisopropanol.

3. The method according to claim 1, characterized in that: The distance between the anode and the cathode is 18-30 mm, and the area of the opposite surface of the anode and the cathode in the reaction solution is 75-100 mm 2 ; in the electrochemical reaction: the electrochemical constant reaction current is 2.5-4.0 mA, placed in a 50-65 o C oil bath, and the reaction time is 4-8 hours. The molar ratio of the ferrocene substituent 1 to the secondary phosphine compound 2 is 1:1.1-1:

4.

4. The method according to claim 3, characterized in that: The molar ratio of the ferrocene substituent 1 to the secondary phosphine compound 2 is 1:1.7-1:2.

5.

5. The method according to claim 1, characterized in that: The base is one or two or more of NaOAc, Na2CO3, KH2PO4, K2HPO4, PhCO2Na (sodium benzoate), NaHCO3, NaOPiv (sodium pivalate), Et3N, TMEDA (tetramethyl ethylenediamine), Py (pyridine), DMAP (4-dimethylaminopyridine), DABCO (triethylenediamine), and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene); and the amount of the base is 1.4-4.5 molar equivalents of the amount of the ferrocene substituent 1.

6. The method according to claim 1, characterized in that:

7. The method according to claim 1, characterized in that: Electrolyte is n Bu4NPF6 (Tetrabutylammonium hexafluorophosphate), n Bu4NBF4 (Tetrabutylammonium tetrafluoroborate), n Bu4NCl (Tetrabutylammonium chloride), n Bu4NOAc (Tetrabutylammonium acetate), n Bu4NOTs (Tetrabutylammonium p-toluenesulfonate), n Bu4NClO4 (Tetrabutylammonium perchlorate), NaClO4 (Sodium perchlorate) one or more than two kinds; Electrolyte amount is 0.30 -2.4 mole equivalent of ferrocene substitute 1 amount. The amount of the solvent is 10.0-40.0 milliliters per millimole of the ferrocene substituent 1.

8. The method according to claim 1, characterized in that: After the reaction is completed, the solvent is rotary evaporated, and column chromatography is used for purification to obtain the product.

9. The method according to claim 1, characterized in that: The anode material is one or two or more of a carbon rod electrode, a carbon cloth electrode, a common glassy carbon electrode, an RVC electrode, and a Pt electrode; and the cathode material is one or two or more of a carbon rod electrode, a carbon cloth electrode, a common glassy carbon electrode, a Pt electrode, a Fe electrode, and a Ni electrode. ​ ​

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