A method for synthesizing a benzoferrocenyl phosphine oxide compound

Abstract

The application relates to a synthesis method of a benzoferrocenyl phosphine oxide compound. Specifically, a non-oriented benzoferrocene substituent, a diaryl phosphine oxide, is used as raw material, and a C-H phosphine oxide reaction of benzoferrocene is realized under the promotion of electricity. The application has the following advantages: the non-oriented benzoferrocene substituent is directly used as a C-H donor, no additional oxidant and metal catalyst are needed, the condition is mild, a wide substrate range is provided, and a good yield is obtained.

Description

Technical Field

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

[0002] Phosphine ligands in the ferrocene framework are very rare. Due to the obvious chiral control advantage of ferrocene framework ligands or catalysts in asymmetric catalysis, more and more reports focus on the design of ferrocene. Previously, nitrogen-atomized ferrocene was a good small molecule catalyst. Therefore, the synthesis of phosphine compounds in the ferrocene framework is very promising.

[0003] Phosphine compounds with a benzo[a]ferrocene framework are ligands or catalysts with good activity in asymmetric catalytic reactions. Previous methods for synthesizing benzo[a]ferrocene phosphine oxides generally require air-sensitive lithium reagents to introduce phosphine groups onto the benzo[a]ferrocene, resulting in cumbersome operations or significant waste generation. Furthermore, they typically require pre-installed directing groups and additional metal catalysts. This invention uses diarylphosphine oxides and undirected substituted benzo[a]ferrocene derivatives as starting materials to achieve the CH phosphine oxidation reaction on benzo[a]ferrocene under electro-promoted autocatalysis. This reaction offers advantages such as a broad substrate range, good yields, no need for additional expensive equivalence oxidants, and mild conditions. Most importantly, it produces a single product with high regioselectivity.

[0004] In summary, this paper describes a method for the direct electrochemical synthesis of phosphine oxides with a benzo[a]ferrocene framework, starting from readily available raw materials, using diarylphosphine oxides as phosphine sources and non-directed benzo[a]ferrocene substituted derivatives as CH donors. Summary of the Invention

[0005] The purpose of this invention is to provide a method for synthesizing benzo[a]ferrocene phosphine oxides, which is an electro-promoted, autocatalytic method for the CH phosphine oxidation reaction of benzo[a]ferrocene.

[0006]

[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 used a mesh-like glassy carbon as the anode (15 mm long × 10 mm wide × 5 mm thick) and a platinum sheet as the cathode (10 mm long × 10 mm wide × 0.3 mm thick). The distance between the electrodes was 20 mm, and the planes containing the length and height of the two electrodes (anode and cathode) were parallel to each other (the area of ​​the opposing surfaces of the anode and cathode placed in the reaction solution was 80 mm²). 2The reaction was carried out under constant current of 2.0 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 benzo[a]ferrocene substituted compound 1 to diarylphosphine oxide compound 2 is 1:1.1-1:3, with a preferred ratio of 1:1.5-1:2.

[0010] The base is one or more of sodium acetate, sodium carbonate, potassium phosphate, sodium benzoate, sodium bicarbonate, sodium pentovalinate, triethylamine, diisopropylethylamine, tetramethylethylenediamine, pyridine, 4-dimethylaminopyridine, and triethylenediamine. The amount of base used is 1.0-4.0 molar equivalents of the amount of benzo[a]ferrocene-substituted product 1, preferably 1.2-2.5 molar equivalents.

[0011] The electrolyte is one or more of tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium chloride, tetrabutylammonium acetate, tetrabutylammonium perchlorate, and lithium perchlorate; the amount of electrolyte used is 0.20-2.0 molar equivalents of the amount of benzo[a]ferrocene substituted product 1, preferably 0.5-1 molar equivalents.

[0012] The solvent is one or more of the following: nitromethane, 1,2-dichloroethane, acetonitrile, dimethyl sulfoxide, water, ethanol, methanol, N,N-dimethylacetamide, N,N-dimethylformamide, trifluoroethanol, and hexafluoroisopropanol, preferably methanol; the amount of solvent used is 1.0-10.0 mL per millimole of benzo[a]ferrocene-substituted compound 1, preferably 4.0 mL.

[0013] The present invention has the following advantages:

[0014] First, using diarylphosphine oxides and non-directing benzo[a]ferrocene substituted products as starting materials, a highly regioselective CH phosphine oxidation reaction on benzo[a]ferrocene was achieved under electro-promoted autocatalysis. Second, this reaction exhibits a broad substrate range, good yield, requires no additional expensive equivalence oxidant, and operates under mild conditions, making the reaction more environmentally friendly. Finally, the obtained benzo[a]ferrocene phosphine oxide can be converted to phosphine ligands in one step. Furthermore, this phosphine oxide has a deep blue-violet color, showing potential value in the preparation of fluorescent probes.

[0015] The present invention has the following advantages: the undirected benzo[a]ferrocene substituted derivatives 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 1-18 are shown in Table 1.

[0017] Table 1. Reaction results of different benzo[a]ferrocene derivatives with different diarylphosphine oxides

[0018]

[0019]

[0020]

[0021]

[0022]

[0023] Synthesis of raw materials

[0024] Synthesis of benzo[a]ferrocene and its substituted derivative 1f: Ferrous chloride (2.53 g, 20 mmol) was placed in a Schlenk flask, and the atmosphere was changed to nitrogen three times. 60 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 pentamethylcyclopentadiene (2.72 g, 20 mmol) was added. The mixture was cooled to -78 °C, and n-butyllithium (2.4 mol / L, 9.2 mL, 22 mmol) was added. The reaction was allowed to proceed for 1 hour to obtain solution B. Then, in yet another Schlenk flask, the atmosphere was changed to nitrogen three times, and... 4-Bromo-1H-indene (3.9 g, 20 mmol) was cooled to -78 °C and injected with n-butyllithium (2.4 mol / L, 9.2 mL, 22 mmol). After reacting for 3 hours, solution C was obtained. Solution B was transferred to solution A and stirred for 1 hour. Then, solution C was added to the above stirred solution and reacted overnight. Column chromatography was performed, and petroleum ether was used as the eluent to obtain 1f benzoferrocene (Reference [1] Thimmaih, M. Luck, LRFang, SJ Organometallic. Chem. 2007, 692, 1956-1962.).

[0025] Synthesis of other substituted benzo[a]ferrocene derivatives: 1a, 1b, 1c, 1d and 1e were all prepared by the above method, with the same operation process and conditions as above. The difference is that 4-bromo-1H-indene was obtained by replacing 4-bromo-1-indene with equimolar amounts of 4-bromo-1-methylindene, 1,4-dimethylindene, 4-phenyl-1-methylindene, 1-methylindene and indene, respectively.

[0026] Synthesis of secondary phosphine oxide 2f: 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 2f (Reference [2] Molitor, S.; Becker, J.; Gessner, VHJAm. Chem. Soc. 2014, 136, 15517–15520).

[0027] Synthesis of other phosphine oxides: Secondary phosphine oxide 2a was commercially available. Phosphine oxides 2b, 2c, 2d, 2e, 2g, 2h, 2i, 2j, 2k, and 2l were all prepared by the above method, with the same operation process and conditions as above. The difference is that 4-methylbromobenzene, 4-tert-butylbromobenzene, 4-phenylbromobenzene, 4-trifluoromethoxybromobenzene, 4-fluorobromobenzene, 3,5-dimethylbromobenzene, 3-chlorobromobenzene, 3-methoxybromobenzene, 3,5-difluorobromobenzene, and 2-bromothiophene were used to replace 4-chlorobromobenzene, respectively.

[0028] Example 1

[0029] Under a nitrogen atmosphere, 0.2 mmol of benzo[a]ferrocene derivative 1, 0.4 mmol of diarylphosphine oxide 2, 0.2 mmol of tetrabutylammonium acetate, 0.4 mmol of triethylamine, and 4.0 mL of methanol were added sequentially to a three-necked flask. Anode and cathode electrodes were then placed in the flask, with a mesh glassy carbon electrode as the anode and a sheet platinum electrode as the cathode. The anode and cathode were positioned opposite each other, with their lower parts submerged in the reaction solution. The distance between the electrodes was 20 mm, and the length and height planes of the two electrodes (anode and cathode) were parallel to each other (the area of ​​the opposing surfaces of the anode and cathode in the reaction solution was 80 mm²). 2 A 2.0 mA current was passed between the anode and cathode, and the reaction was carried out at 50 °C for 6 hours. After the reaction, the compound was separated by column chromatography (mobile phase: petroleum ether / ethyl acetate = 4:1, volume ratio) to obtain benzo[2]ferrocene phosphine oxide compound 3a in 75% yield. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H1N, C1N and phosphine spectra) and high-resolution mass spectrometry.

[0030] The test data is as follows:

[0031] 3a: Purple solid, mp 227.2-229.1℃, 89.6mg, 75%.1 H NMR (400MHz, CDCl3) δ7.73–7.65(m,2H),7.60–7.53(m,1H),7.52–7.41(m,5H),7.38–7.30(m,2H),7.09(d d,J=7.1,1.9Hz,1H),6.56(dd,J=15.5,7.0Hz,2H),4.83(s,1H),4.28(s,1H),1.86(s,3H),1.68(s,15H); 13 C NMR (100MHz, CDCl3) δ133.0 (d, J = 104.6Hz), 132.48 (d, J = 9.5Hz), 132.46 (d, J = 103.7Hz), 13 1.84(d,J=2.7Hz), 131.82(d,J=9.9Hz), 131.7(d,J=2.9Hz), 131.3(d,J=3.5Hz), 130.4(d,J= 12.3Hz),130.0(d,J=105.9Hz),128.52(d,J=12.4Hz),128.50(d,J=12.1Hz),121.7(d,J=14 .9Hz),91.9(d,J=9.9Hz),90.6,89.3(d,J=8.8Hz),78.5,69.2(d,J=2.0Hz),66.9,13.6,9.6. 31 P NMR(162MHz,CDCl3)δ29.4.HRMS calculated forC 32 H 32 OPBrNaFe[M+Na] + 621.0616, found 621.0627.

[0032] Example 2:

[0033] 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 3b was 56%. 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.

[0034] The test data is as follows:

[0035] 3b: Purple gum, 70.0mg, 56% yield. 1H NMR (400MHz, CDCl3) δ7.57(dd,J=11.6,7.8Hz,2H),7.37–7.27(m,4H),7.13(dd,J=8.0,2.6Hz,2H),7.08(dd,J=7.1,1. 8Hz,1H),6.55(dd,J=15.4,7.1Hz,1H),4.86(s,1H),4.27(s,1H),2.42(s,3H),2.32(s,3H),1.86(s,3H),1.68(s,15H). 13 C NMR (100MHz, CDCl3) δ142.1 (d, J = 2.8Hz), 141.9 (d, J = 2.8Hz), 132.5 (d, J = 10.0Hz), 131.8 (d,J=10.5Hz),130.6(d,J=105.4Hz),130.9(d,J=3.5Hz),130.2(d,J=12.2Hz),130.0(d,J =106.9Hz), 129.5(d,J=106.1Hz), 129.3(d,J=2.5Hz), 129.1(d,J=2.4Hz), 121.7(d,J=14. 9Hz),91.9(d,J=9.8Hz),90.5,89.3(d,J=9.1Hz),78.4,69.2,66.8,21.7,21.7,13.6,9.6. 31 P NMR(162MHz,CDCl3)δ29.4.HRMS calculated for C 34 H 37 OPBrFe[M+H] + 627.1109, found 627.1090.

[0036] Example 3:

[0037] 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 62%. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0038] The test data is as follows:

[0039] 3c: Purple solid, mp 168.0-168.8℃, 88.9mg, 62% yield. 1H NMR (700MHz, CDCl3) δ7.61(t,J=9.4Hz,2H),7.49(d,J=7.9Hz,2H),7.39(t,J=9.8Hz,2H),7.34(d,J=7.8Hz,2H),7.10(d,J =7.1Hz,1H),6.62(dd,J=15.5,7.1Hz,1H),4.87(s,1H),4.28(s,1H),1.87(s,3H),1.68(s,15H),1.35(s,9H),1.26(s,9H); 13 C NMR (175MHz, CDCl3) δ155.1, 154.83, 154.82, 132.4 (d, J = 9.9Hz), 131.6 (d, J = 10 .1Hz),130.79,130.77,130.6(d,J=105.4Hz),130.29,130.28,130.2,129.7,12 9.4(d,J=106.2Hz),125.5(d,J=12.1Hz),121.8(d,J=14.6Hz),92.1(d,J=10.0H z),90.4,89.4(d,J=8.8Hz).78.4,69.2,66.7,35.1,35.0,31.3,31.2,13.7,9.6. 31 P NMR(162MHz,CDCl3)δ29.1.HRMS calculated forC 40 H 49 OPBrFe[M+H] + 711.2048, found 711.2048.

[0040] Example 4:

[0041] 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 60%. 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.

[0042] The test data is as follows:

[0043] 3d: Purple solid, mp 222.9-224.5℃, 84.8mg, 60% yield. 1H NMR (400MHz, CDCl3) δ7.89–7.69(m,4H),7.69–7.52(m,6H),7.51–7.32(m,3H),7.15(d,J=7. 0Hz,1H),6.71(dd,J=15.8,7.2Hz,1H),4.93(s,1H),4.33(s,1H),1.90(s,3H),1.72(s,15H); 13 C NMR (100MHz, CDCl3) δ144.6 (d, J = 2.1Hz), 144.4, 140.1, 133.0 (d, J = 9.8Hz), 132.3 (d ,J=9.9Hz),131.33,131.30,131.2,131.1(d,J=104.89Hz),130.4,130.3,130.1(d,J =106.3Hz),129.0(d,J=9.8Hz),128.2(d,J=13.7Hz),127.4,127.3,127.1,121.7(d, J=15.0Hz),91.9(d,J=9.8Hz),90.7,89.4(d,J=8.9Hz),78.5,69.2,66.9,13.7,9.6. 31 P NMR(162MHz,CDCl3)δ29.1.HRMS calculated for C 44 H 41 OPBrFe[M+H] + 751.1422, found 711.1421.

[0044] Example 5:

[0045] The operation process and conditions are the same as in Example 1. The difference from Example 1 is shown in Table 1. The yield of product 3e is 84%. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0046] The test data is as follows:

[0047] 3e: Purple solid, mp 172.5-173.3℃, ​​128.7mg, 84% yield. 1H NMR (700MHz, CDCl3) δ7.62 (dt, J=163.1, 9.7Hz, 4H), 7.26 (dd, J=120.5, 8.2Hz, 4H), 7.11 (d, J= 7.1Hz,1H),6.56(dd,J=15.8,7.1Hz,1H),4.76(s,1H),4.30(s,1H),1.88(s,3H),1.67(s,15H). 13 CNMR (175MHz, CDCl3) δ152.1, 152.0, 134.4 (d, J = 10.6Hz), 133.8 (d, J = 11.1Hz), 132.2 (d, J = 3 .3Hz),131.3(d,J=106.0Hz),130.5(d,J=105.2Hz),130.3(d,J=12.4Hz),128.9(d,J=108.4H z),121.6(d,J=15.1Hz),120.63(d,J=7.8Hz),120.56(d,J=7.6Hz),120.4(q,J=258.9Hz),12 0.3(q,J=258.7Hz),91.5(d,J=10.2Hz),91.0,89.4(d,J=9.0Hz),78.5,69.0,67.1,13.6,9.5. 31 P NMR (162MHz, CDCl3) δ 27.2. 19 F NMR(376MHz, CDCl3)δ-57.5,-57.6.HRMS calculated for C 34 H 30 OPBrF6NaFe[M+Na] + 789.0262, found 789.0260.

[0048] Example 6:

[0049] 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 80%. The structure of the compound was identified by infrared spectroscopy, nuclear magnetic resonance (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0050] The test data is as follows:

[0051] 3f: Purple solid, mp 235.4-235.9℃, 106.9mg, 80% yield. 1H NMR(400MHz, CDCl3) δ7.61(dd,J=11.2,8.1Hz,2H),7.48(dd,J=8.4,2.2Hz,2H),7.42–7.30(m,4H),7.08( dd,J=7.1,1.9Hz,1H),6.52(dd,J=15.7,7.0Hz,1H),4.77(s,1H),4.31(s,1H),1.87(s,3H),1.64(s,15H); 13 C NMR (100MHz, CDCl3) δ 138.6 (d, J = 2.7Hz), 138.4 (d, J = 2.5Hz), 133.7 (d, J = 10.5Hz), 133. 1(d,J=10.7Hz),131.9(d,J=2.8Hz),131.2(d,J=105.9Hz),130.4(d,J=105.3Hz).130.2( d,J=12.4Hz),129.0(d,J=107.6Hz),128.94(d,J=12.7Hz),128.91(d,J=12.4Hz),121.5 (d,J=15.2Hz),91.4(d,J=10.4Hz),90.8,89.2(d,J=9.2Hz),78.4,68.9,67.0,13.5,9.5. 31 P NMR(162MHz,CDCl3)δ27.9.HRMS calculated for C 32 H 30 OPBrCl2NaFe[M+Na] + 688.9836, found 688.9840.

[0052] Example 7:

[0053] 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 68% (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.

[0054] The test data is as follows:

[0055] 3g: Purple solid, mp 224.0-226.0℃, 85.9mg, 68% yield. 1H NMR (700MHz, CDCl3) δ7.71–7.63(m,2H),7.48–7.41(m,2H),7.22–7.15(m,2H),7.09(dd,J=7.0,1.9Hz) ,7.06–7.00(m,2H),6.52(dd,J=15.7,7.0Hz,1H),4.77(s,1H),4.29(s,1H),1.87(s,3H),1.66(s,15H); 13 C NMR (175MHz, CDCl3) δ165.0 (dd, J=253.6, 3.1Hz), 164.9 (dd, J=253.0, 3.0Hz), 134.7 (dd, J=10.9, 8.6H z),134.1(dd,J=11.5,8.7Hz),131.7(d,J=3.3Hz),130.2(d,J=12.2Hz),129.5(d,J=107.9Hz),128.7( dd,J=107.3,3.1Hz),128.1(dd,J=106.6,3.2Hz),121.5(d,J=14.8Hz),115.90(dd,J=21.3,13.4Hz),1 15.87(dd,J=21.2,13.2Hz),91.5(d,J=10.1Hz),90.7,89.2(d,J=8.9Hz),78.4,68.9,66.9,13.5,9.4. 31 PNMR (162MHz, CDCl3) δ27.9; 19 F NMR(376MHz, CDCl3)δ-106.8,-107.1.HRMS calculated forC 32 H 31 OPBrF2Fe[M+H] + 635.0608, found 635.0611.

[0056] Example 8:

[0057] 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 60% 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.

[0058] The test data is as follows:

[0059] Purple solid, mp 242.5-242.8℃, 78.8mg, 60% yield. 1H NMR (700MHz, CDCl3) δ7.30(d,J=12.0Hz,2H),7.17(s,1H),7.10(dd,J=7.1,1.7Hz,1H),7.07(d,J=12.3Hz,2H),7.04( s,1H),6.59(dd,J=15.3,7.1Hz,1H),4.88(s,1H),4.27(s,1H),2.34(s,6H),2.22(s,6H),1.87(s,3H),1.68(s,15H); 13 C NMR(175MHz, CDCl3)δ138.03(d,J=12.6Hz).137.99(d,J=12.7Hz),133.50(d,J=2.8Hz),13 3.47(d,J=2.9Hz),132.9(d,J=103.7Hz),132.5(d,J=102.7Hz),130.8(d,J=3.2Hz),130.4( d,J=104.4Hz),130.3(d,J=12.2Hz),130.1(d,J=9.3Hz).129.3(d,J=9.6Hz),121.8(d,J=14 .7Hz),92.1(d,J=9.9Hz),90.4,89.4(d,J=8.8Hz),78.4,69.2,66.7,21.5,21.4,13.7,9.6; 31 P NMR(162MHz, CDCl3)δ29.4; HRMS calculated for C 36 H 41 OPBrFe[M+H] + 655.1422, found 655.1431.

[0060] Example 9:

[0061] 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 70%. The compound was subjected to infrared spectroscopy, nuclear magnetic resonance (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0062] The test data is as follows:

[0063] 3i: Purple solid, mp 192.2-193.9℃, 68.8mg, 70% yield. 1H NMR(700MHz, CDCl3)δ7.68(d,J=12.0Hz,1H),7.60–7.51(m,3H),7.47–7.38(m,2H),7.24–7.20(m,2H),7 .11(d,J=7.1Hz,1H),6.58(dd,J=16.1,7.1Hz,1H),4.77(s,1H),4.30(s,1H),1.87(s,3H),1.67(s,15H); 13 C NMR (175MHz, CDCl3) δ135.3, 135.2, 135.1, 134.9 (d, J = 103.1Hz), 134.2 (d, J = 101.8Hz ),132.30,132.28,132.26,132.25,132.1(d,J=10.4Hz),131.6(d,J=10.5Hz),130.5, 130.45,130.40,130.0(d,J=12.9Hz),129.7(d,J=10.0Hz),128.5(d,J=108.1Hz),121 .6(d,J=15.1Hz),91.4(d,J=10.2Hz),91.0,89.3(d,J=9.1Hz),78.5,69.0,67.1,13.6; 31 P NMR(162MHz,CDCl3)δ27.1.HRMS calculated for C 32 H 30 OPBrCl2NaFe[M+Na] + 688.9836, found 688.9843.

[0064] Example 10:

[0065] 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 54%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0066] The test data is as follows:

[0067] 3j: Purple solid, mp 215.6-216.9℃, 68.8mg, 54% yield. 1H NMR(700MHz, CDCl3)δ7.68(d,J=12.0Hz,1H),7.60–7.51(m,3H),7.47–7.38(m,2H),7.24–7.20(m,2H),7 .11(d,J=7.1Hz,1H),6.58(dd,J=16.1,7.1Hz,1H),4.77(s,1H),4.30(s,1H),1.87(s,3H),1.67(s,15H); 13 C NMR (175MHz, CDCl3) δ135.3, 135.2, 135.1, 134.9 (d, J = 103.1Hz), 134.2 (d, J = 101.8Hz ),132.30,132.28,132.26,132.25,132.1(d,J=10.4Hz),131.6(d,J=10.5Hz),130.5, 130.45,130.40,130.0(d,J=12.9Hz),129.7(d,J=10.0Hz),128.5(d,J=108.1Hz),121 .6(d,J=15.1Hz),91.4(d,J=10.2Hz),91.0,89.3(d,J=9.1Hz),78.5,69.0,67.1,13.6; 31 P NMR(162MHz,CDCl3)δ27.1.HRMS calculated for C 34 H 36 OPBrNaFe[M+Na] + 681.0827, found 681.0826.

[0068] Example 11:

[0069] 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 3k was 85%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0070] The test data is as follows:

[0071] 3k: Purple solid, mp 183.0-184.2℃, 128.5mg, 85% yield. 1H NMR(400MHz, CDCl3)δ7.22(dd,J=12.6,5.3Hz,3H),7.14(dd,J=7.2,2.0Hz,1H),7.09–6.96(m,3H),6 .96–6.89(m,1H),6.60(dd,J=16.1,7.1Hz,1H),4.73(s,1H),4.33(s,1H),1.90(s,3H),1.66(s,15H). 13 C NMR(175MHz, CDCl3)δ163.13(ddd,J=254.3,19.8,10.8Hz).163.06(ddd,J=254.3,19.6,10.8Hz).136.5(d t,J=104.0,6.6Hz),135.6(dt,J=102.5,6.6Hz),133.2(d,J=3.7Hz),130.5(d,J=12.6Hz),127.1(d,J=110 .8Hz), 121.5 (d, J=15.3Hz), 115.3 (ddd, J=20.8, 10.0, 5.1Hz), 114.7 (ddd, J=20.6, 10.6, 5.0Hz), 108.1 (t d,J=25.1,1.8Hz),91.3,91.2(d,J=10.3Hz),89.4(d,J=9.4Hz),78.6,68.8(d,J=2.2Hz),67.4,13.6,9.6; 31 P NMR (162MHz, CDCl3) δ26.2 (p, J=6.3Hz); 19 F NMR(376MHz, CDCl3)δ-106.5(d,J=6.6Hz),-106.6(d,J=6.5Hz).HRMS calculated for C 32 H 28 OPBrF4NaFe[M+Na] + 693.0239, found 693.0235.

[0072] Example 12:

[0073] 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 3l was 65%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0074] The test data is as follows:

[0075] 3l: Purple solid, mp 216.8-218.8℃, 79.5mg, 65% yield,1 H NMR (400MHz, CDCl3) δ7.79(t,J=4.5Hz,1H),7.62(t,J=4.5Hz,1H),7.49(dd,J=7.5,3.5Hz,1H),7.32(dd,J=7.8,3.6Hz,1H),7.24–7. 22(m,1H),7.14–7.10(m,1H),7.09–7.05(m,1H),6.77(dd,J=17.1,7.1Hz,1H),5.03(s,1H),4.33(s,1H),1.90(s,3H),1.66(s,15H). 13 C NMR (100MHz, CDCl3) δ137.1(d,J=10.2Hz), 136.2(d,J=11.1Hz), 135.2(d,J=107 .4Hz),134.04(d,J=110.8Hz),134.03(d,J=4.6Hz),133.7(d,J=4.4Hz),131.9, 131.0(d,J=118.8Hz), 129.6(d,J=13.3Hz), 128.2(d,J=14.5Hz), 121.7(d,J=16 .1Hz),91.5(d,J=11.4Hz),90.9,89.4(d,J=9.1Hz),78.4,69.1,66.9,13.6,9.6; 31 P NMR (162MHz, CDCl3) δ15.2; HRMScalculated for C 28 H 29 OS2PFe[M+H] + 610.9925, found 610.9931.

[0076] Example 13:

[0077] The operation process and conditions were the same as in Example 1. The difference from Example 1 is shown in Table 1. The product 3m yield was 56%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0078] The test data is as follows:

[0079] 3m: Purple solid, mp 221.5-222.3℃, 59.8mg, 56% yield, 1H NMR(400MHz, CD2Cl2)δ7.61–7.55(m,2H),7.45(dd,J=7.4,1.7Hz,1H),7.42–7.37(m,4H),7.37–7.32(m,2H),7.2 9–7.24(m,2H),6.61(dd,J=15.7,6.7Hz,1H),4.58(s,1H),4.04(s,1H),2.26(s,3H),1.73(s,3H),1.50(s,15H). 13 C NMR (100MHz, CD2Cl2) δ145.6(d,J=3.0Hz), 134.3(d,J=103.1Hz), 133.6(d,J=102.5Hz), 132.6(d,J=9.3Hz),132.1(d,J=9.9Hz),131.8(d,J=2.8Hz),131.7,131.6(d,J=10.0Hz) ,128.7(d,J=3.4Hz),128.6(d,J=3.5Hz),127.4(d,J=107.8Hz),119.0(d,J=14.5Hz),91 .4(d,J=9.6Hz),89.8(d,J=8.5Hz),89.6,78.1,68.0(d,J=2.6Hz),64.6,20.2,13.7,9.6. 31 P NMR(162MHz,CD2Cl2)δ28.3; HRMScalculated for C 33 H 35 OPNaFe[M+Na] + 557.1667, found 557.1668.

[0080] Example 14:

[0081] 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 3n was 57%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0082] The test data is as follows:

[0083] 3n: Black green solid, mp 210.2-211.7℃, 70.4mg, 57% yield (accompanied by a small amount of ethyl acetate, the yield of the product has been adjusted accordingly). 1H NMR (400MHz, CDCl3) δ7.78–7.69(m,4H),7.57–7.45(m,7H),7.41–7.33(m,2H),6.92(s, 1H),6.83(dd,J=15.6,6.7Hz,1H),5.00(s,1H),4.49(s,1H),1.83(s,3H),1.50(s,15H). 13 C NMR (100MHz, CDCl3) δ147.1 (d, J = 3.3Hz), 140.3, 133.6 (d, J = 104.3Hz), 132.9 (d, J =103.2Hz),132.5(d,J=9.4Hz),131.9(d,J=9.8Hz),131.6(d,J=2.9Hz),131.5(d,J =2.5Hz),130.9(d,J=11.3Hz),129.3(d,J=106.8Hz),128.5,128.4,128.37,128.3 ,128.27,128.0,92.1(d,J=8.4Hz),88.5(d,J=8.7Hz),78.3,67.9,65.4,13.7,9.6. 31 P NMR(162MHz,CDCl3)δ29.4.HRMS calculated for C 38 H 38 OPFe[M+H] + 597.2004, found 597.2009.

[0084] Example 15:

[0085] 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 3O was 46%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0086] The test data is as follows:

[0087] 3o: Purple solid, mp 190.4-191.6℃, 51.0mg, 46% yield (accompanied by a small amount of ethyl acetate, the yield of the product has been adjusted accordingly). 1H NMR (400MHz, CDCl3) δ7.75–7.65(m,2H),7.58–7.43(m,7H),7.43–7.38(m,1H),7.38– 7.28(m,2H),6.87–6.71(m,2H),4.84(s,1H),4.18(s,1H),1.82(s,3H),1.61(s,15H). 13 C NMR (100MHz, CDCl3) δ135.1(d,J=2.5Hz), 133.5(d,J=103.8Hz), 133.0(d,J=103.2Hz), 132.5(d,J=9.2Hz),131.9(d,J=9.9Hz),131.6(d,J=2.6Hz),131.5(d,J=2.8Hz),130.9( d,J=11.3Hz),130.1(d,J=107.3Hz),128.4(d,J=12.0Hz),128.3(d,J=11.9Hz).119.9( d,J=14.3Hz),90.8(d,J=10.3Hz),90.0,88.0(d,J=7.3Hz),77.9,67.6,66.0,13.5,9.8. 31 P NMR(162MHz,CDCl3)δ29.5.HRMS calculated for C 32 H 33 OPNaFe[M+Na] + 543.1511, found 543.1485.

[0088] Example 16:

[0089] The operation process and conditions were the same as in Example 1. The difference from Example 1 is shown in Table 1. The 3p yield of the product was 37%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0090] The test data is as follows:

[0091] 3p: Purple solid, mp 157.9-158.7℃, 39.5mg, 37% yield (accompanied by a small amount of ethyl acetate, the yield of the product has been adjusted accordingly). 1H NMR (400MHz, CDCl3) δ7.80–7.67(m,2H),7.59(d,J=8.6Hz,1H),7.56–7.44(m,5H),7.43–7.38(m,1H),7.36–7.28( m,2H),6.89(t,J=7.7Hz,1H),6.81(dd,J=15.8,6.2Hz,1H),4.92(s,1H),4.33(s,1H),3.79(s,1H),1.70(s,15H). 13 C NMR (100MHz, CDCl3) δ134.9 (d, J = 3.1Hz), 133.3 (d, J = 103.9Hz), 132.7 (d, J = 103.4Hz), 132.4 (d, J=9.5Hz), 131.8 (d, J=9.8Hz), 131.6 (d, J=2.7Hz), 131.4 (d, J=2.8Hz), 131.0 (d, J=11.3Hz), 130. 1(d,J=105.8Hz),128.40(d,J=3.4Hz),128.36(d,J=12.2Hz),128.32(d,J=12.0Hz),128.28(d,J= 3.0Hz), 119.9 (d, J = 14.3Hz), 90.1 (d, J = 9.2Hz), 87.4 (d, J = 8.2Hz), 78.4, 78.0, 67.4, 65.9, 10.1. 31 P NMR(162MHz,CDCl3)δ26.3.HRMS calculated forC 31 H 32 OPFe[M+H] + 507.1535, found 507.1526.

[0092] 3p (152.1 mg, 0.3 mmol) was dissolved in 4 mL of toluene, and triethylamine (183.4 mg, 1.8 mmol) and trimethylchlorosilane (203.2 mg, 1.5 mmol) were added. The mixture was reacted at 110 °C for 24 hours and then separated by chiral preparative chromatography to generate chiral phosphine ligand 4. This ligand showed good chiral control activity in asymmetric allyl substitution reactions (Reference [2] Molitor, S.; Becker, J.; Gessner, VHJAm. Chem. Soc. 2014, 136, 15517–15520).

[0093]

[0094] Example 17:

[0095] The operation process and conditions were the same as in Example 1. The differences from Example 1 are shown in Table 1. The product 3q yield was 66%. The structure of the compound was identified by NMR (H1N, C1N, and phosphine spectra) and high-resolution mass spectrometry.

[0096] The test data is as follows:

[0097] 3q: Purple solid, mp 181.4-182.7℃, 77.3mg, 66% yield. 1 H NMR (400MHz, CDCl3) δ7.76–7.66(m,2H),7.60–7.54(m,1H),7.53–7.41(m,5H),7.38–7.31(m,2H),7.11(dd,J=7.1,1 .8Hz,1H),6.58(dd,J=15.4,7.0Hz,1H),5.00–4.95(m,1H),4.50–4.45(m,1H),3.86(t,J=2.6Hz,1H),1.73(s,15H); 13 C NMR (175MHz, CDCl3) δ132.9 (d, J = 104.8Hz), 132.4 (d, J = 9.5Hz), 132.6, 132.4, 132.3, 132.2 (d, J = 105.84Hz), 131.8, 131.75, 131.7, 131.6, 131 .0,130.4(d,J=12.1Hz),130.2,129.6,128.5,128.4,121.7(d,J=14.8H z),91.1(d,J=9.9Hz),88.8(d,J=8.7Hz),79.00,78.8,69.0,66.7,9.8. 31 P NMR(162MHz,CDCl3)δ28.9.HRMS calculated for C 31 H 31 OBrPFe[M+H] + 585.0640, found 585.0642.

[0098] Comparative example: Replacing the electric current with an equivalent amount of oxidant:

[0099]

[0100]

[0101] a Conditions: 1a (0.20 mmol), 2a (0.40 mmol), nBu4NOAc (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 benzo[a]ferrocene phosphine oxides, characterized in that: Using benzo[a]ferrocene derivative 1 and secondary phosphine compound 2 as raw materials, ferrocene phosphine oxide compound 3 is generated, as shown in the following reaction formula: , Wherein R is one or more of hydrogen, bromine, methyl, phenyl, naphthyl, phenyl containing a substituent, and C2-C5 alkyl, and the substituent on the phenyl is one or more of bromine, chlorine, fluorine, and nitro. R' is one or more of hydrogen, methyl, phenyl, bromine, naphthyl, phenyl containing a substituent, and C2-C5 alkyl, and the substituent on the phenyl group is one or more of bromine, chlorine, fluorine, and nitro. In secondary phosphine compound 2, the two Ar atoms are each individually one or more of the following: phenyl, 4-methylphenyl, 4-chlorophenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-phenylphenyl, 4-tert-butylphenyl, 3,5-dimethylphenyl, 3,5-difluorophenyl, 3-chlorophenyl, 3-methoxyphenyl, 2-thienyl, substituted phenyl, and thienyl containing a substituent at the 2-position. The substituent on the thienyl group is one of methyl, bromine, or chlorine, and the substituent on the phenyl group is one or more of C2-C5 alkyl or C2-C5 alkoxy. The specific steps are as follows: Under a nitrogen atmosphere, benzo[a]ferrocene derivative 1, diarylphosphine oxide 2, electrolyte, solvent, and base are added to a container to obtain a reaction solution. The container is equipped with anode and cathode, with the anode and cathode positioned opposite each other at a distance of 10-35 mm. Part or all of the cathode and anode are immersed in the reaction solution, and the surface area of ​​the anode and cathode in the reaction solution is 35-100 mm². 2 Then, a current is applied between the cathode and the anode; In the electrochemical reaction: the constant electrochemical reaction current is 1.0-3.0 mA, placed in an oil bath at 25-70 °C, and the reaction time is 4-12 hours; the reaction is carried out in a solvent in the presence of an electrolyte; the reaction produces the target product 3.

2. The method according to claim 1, characterized in that: The specific steps are as follows: Under a nitrogen atmosphere, benzo[a]ferrocene derivative 1, diarylphosphine oxide 2, electrolyte, solvent, and base are added to a container to obtain a reaction solution. The container is equipped with anode and cathode, with the anode and cathode positioned opposite each other at a distance of 15-25 mm. Part or all of the cathode and anode are immersed in the reaction solution, and the surface area of ​​the anode and cathode in the reaction solution is 70-100 mm². 2 Then, a current is applied between the cathode and the anode; In the electrochemical reaction: the constant electrochemical reaction current is 1.3-2.5 mA, placed in an oil bath at 40-60 °C, and the reaction time is 6-10 h; the reaction is carried out in a solvent in the presence of an electrolyte; the reaction produces the target product 3.

3. The method according to claim 1 or 2, characterized in that: The molar ratio of benzo[2]ferrocene substituted compound 1 to diarylphosphine oxide compound 2 is 1:1.1-1:

3.

4. The method according to claim 3, characterized in that: The molar ratio of benzo[2]ferrocene derivative 1 to diarylphosphine oxide 2 is 1:1.5-1:

2.

5. The method according to claim 2, characterized in that: The base is one or more of sodium acetate, sodium carbonate, potassium phosphate, sodium benzoate, sodium bicarbonate, sodium pentovane, triethylamine, diisopropylethylamine, tetramethylethylenediamine, pyridine, 4-dimethylaminopyridine, and triethylenediamine; the amount of base used is 1.0-4.0 molar equivalents of the amount of benzo[a]ferrocene substituted product 1.

6. The method according to claim 5, characterized in that: The amount of alkali used is 1.2-2.5 molar equivalents of the amount of benzo[a]ferrocene substituted product 1.

7. The method according to claim 1, characterized in that: The electrolyte is one or more of tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium chloride, tetrabutylammonium acetate, tetrabutylammonium perchlorate, and lithium perchlorate; the amount of electrolyte used is 0.20-2.0 molar equivalents of the amount of benzo[a]ferrocene substituted product 1.

8. The method according to claim 7, characterized in that: The amount of electrolyte used is 0.5-1 molar equivalent of the amount of benzo[a]ferrocene substituted product 1.

9. The method according to claim 1, characterized in that: The solvent is one or more of the following: nitromethane, 1,2-dichloroethane, acetonitrile, dimethyl sulfoxide, water, ethanol, methanol, N,N-dimethylacetamide, N,N-dimethylformamide, trifluoroethanol, and hexafluoroisopropanol. The amount of solvent used is 1.0-10.0 mL per 0.2 mmol of benzo[a]ferrocene-substituted compound 1.

10. The method according to claim 9, characterized in that: The solvent is methanol; the amount of solvent used is 4.0 mL per 0.2 mmol of benzoferrocene-substituted compound 1.

11. The method according to claim 1, characterized in that: The reaction anode material is one or more of the following: carbon rod electrode, carbon cloth electrode, ordinary glassy carbon electrode, mesh glassy carbon electrode, and platinum electrode; The cathode material is one or more of the following: carbon rod electrode, carbon cloth electrode, ordinary glassy carbon electrode, platinum electrode, and nickel electrode.

12. The method according to claim 1, characterized in that: After the reaction was complete, the solvent was evaporated, and the product was purified by column chromatography to obtain the product.

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