A synthetic method for the disilylation of iron-catalyzed non-activated gem-difluoroalkenes

Abstract

This invention belongs to the field of organic synthesis, specifically relating to an iron-catalyzed method for the disilylation of unactivated gem-difluoroallene compounds. This invention uses gem-difluoroallene compounds as reaction substrates, triethylsilyloborate as a silicon source, and an iron salt as a catalyst. In the presence of a base, ligands, and an organic solvent, the disilylation of activated gem-difluoroallene compounds is catalyzed. This invention achieves selective disilylation of activated gem-difluoroallene compounds via iron catalysis, and is simple, safe, reliable, and broad-spectrum.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for the synthesis of iron-catalyzed, non-activated gem-difluoroalkenes by disilylation. Background Technology

[0002] Introducing gem-difluoroalkenyl groups into drug molecules can alter and regulate recognition sites. However, due to challenges such as the extremely similar high energies of the two CF bonds in the gem-difluoroalkenyl structure, crowded steric environments, uncontrollable self-coupling and cross-selectivity, and poor stability with olefin substrates, the selective activation and functionalization of the gem-difluoroalkenyl CF bonds has remained a focus of continuous attention for chemists. Alkenylsilane compounds, as important building blocks in organic synthesis, can be used in palladium-catalyzed Hiyama cross-coupling reactions, Fleming-Tamao oxidation reactions, and Sakurai allylation reactions to construct C-C bonds.

[0003] In recent years, silanization reactions of allenes have been reported one after another, including the use of noble metals such as Pd, Au, and Ru as catalysts and photocatalysis to achieve silanization reactions of allenes. These reactions mostly involve attacking the internal carbon atoms of allenes, followed by hydrosilylation to obtain silanized olefins or allyl silicon structures.

[0004] In 2017, Xu Yunhe reported a copper-catalyzed silanization reaction of propyne epoxides, and the reaction equation is as follows:

[0005]

[0006] This method allows for precise prediction and control of several different product types under mild reaction conditions by adjusting the types and amounts of base and solvent. When CuCN is used as a catalyst, diisopropylethylamine as a base, and methanol as a solvent, silyl-substituted allenyl alkyl alcohols are generated. It exhibits good compatibility with different functional groups and achieves high yields even when using aliphatic alkyl-substituted alkyl chains. When the base and solvent are K₂CO₃ and DMF, respectively, a disilyl-substituted butadiene structure with a trans configuration is produced. Using various aryl-substituted propyne epoxides as substrates yields good yields and good stereoselectivity for synthesizing the target product; however, the yield decreases significantly when directly attached to an alkyl group. Using 1-pentanol as a solvent yields alkenyl-silyl alkyl alcohol structures. Under these conditions, only aryl-substituted propyne epoxides yield the target structure with excellent yield and selectivity, while other aliphatic substituted compounds fail to produce the target product. This reaction achieves highly selective silylation using only a base and solvent.

[0007] In 2019, Manolis Stratakis used titanium dioxide as a support and gold nanoparticles as a catalyst to achieve a highly stereoselective disilylation reaction of the terminal double bonds of unactivated allenes. The reaction equation is as follows:

[0008]

[0009] This method offers mild reaction conditions and a short reaction time, requiring only 1% mmol of Au / TiO2 catalyst at 25 °C to achieve disilylation of monosubstituted and 1,1-disubstituted allenes. The authors also found that if the solvent contains a small amount of water, excess Et2SiH2 needs to be added to compensate for the influence of hydrosilylation products generated from the reaction of silylation products and water on the disilylation reaction. For the relatively fast-reacting monosubstituted allenes, the product selectivity of dehydrogenation disilylation compared to hydrosilylation is between 65-79%, while for 1,1-disubstituted allenes, the relative selectivity is also higher (>80%). In the case of monosubstituted alkenes, disilylation exhibits high E-stereoselectivity, with diastereoselectivity ranging from 87% to >97%.

[0010] Currently, there is a lack of systematic research on the iron-catalyzed silanization of gem-difluoroallenes. Most current work involves the coordination of highly reactive noble metals with the internal or terminal sites of allenes, followed by transmetalation to obtain the corresponding silanized products, or the formation of metallic silicon species followed by addition to unsaturated olefins and reductive elimination to obtain the corresponding products. In existing studies on the silanization of allenes, most require the allene to be linked to an aromatic ring; reactions involving the silanization of allenes directly linked to alkyl chains are relatively rare, and those capable of achieving selective monosilanization and disilanization are even fewer. However, gem-difluoroallenes have important applications in medicine and synthesis; therefore, developing selective disilanization reactions of unactivated gem-difluoroallenes under mild conditions is of great significance.

[0011] Although iron catalysts are relatively inert compared to other active transition metal catalysts, they possess important advantages such as low cost and lower biotoxicity. Therefore, achieving a more environmentally friendly and efficient selective disilylation reaction of gem-difluoroalkenes under iron catalysis would be of great significance. Based on this, this invention develops a synthetic method for the selective disilylation of unactivated gem-difluoroalkenes catalyzed by iron. Summary of the Invention

[0012] This invention addresses the problems of uncontrollable self-coupling and cross-selectivity, poor olefin substrate stability, and the current research that relies on noble metals as catalysts. It creatively develops a method for the selective disilylation of unactivated gemdifluoroalkenes catalyzed by iron.

[0013] To achieve the above objectives, the present invention provides the following technical solution:

[0014] A method for synthesizing iron-catalyzed, non-activated gem-difluoroalkenes by disilylation includes the following steps:

[0015] Using gem-difluoroalkenes as reaction substrates, triethyl silyboronic acid ester as silicon source, and iron salt as catalyst, the disilylation reaction of gem-difluoroalkenes was catalyzed in the presence of base, ligand, and organic solvent.

[0016] Furthermore, the gem-difluoroalkene compound has the following general structural formula:

[0017]

[0018] In the formula, R' = hydrogen, R = phenethyl or R' = benzyl, R = benzyl or R' = methyl, R = p-methoxyphenethyl or R' = hydrogen, R = 5-n-propyl-1,3-benzodioxolane or R' = methyl, R = 5-ethyl-1,3-benzodioxolane or R' = hydrogen, R = p-tert-butylphenylpropyl.

[0019] Furthermore, the iron salt is selected from one of Fe(OAc)2, Fe(OTf)2, Fe(OTf)3, Fe(SO4)3, FeF2, FeF3, FeCl2, FeCl3, FeBr3, tris(dibenzoylmethyl)ferric, and ferric tristearate.

[0020] Furthermore, the alkali is selected from sodium methoxide and sodium tert-butoxide.

[0021] Further, the ligand is selected from one of 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene, 1,3-bis(diphenylphosphine)propane, 2,2'-diphenylphosphine-1,1'-binaphthyl, 2-di-tert-butylphosphine-2',4',6'-triisopropylbiphenyl, 2-(di-tert-butylphosphine)biphenyl, bis(adamantane-1-yl)(butyl)phosphine hydroiodate, 1,5-bis(diphenylphosphine)pentane, and 1,1'-bis(diphenylphosphine)ferrocene.

[0022] Furthermore, the organic solvent is selected from one of tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, n-hexane, dimethyl ether, and cyclopentyl methyl ether.

[0023] Furthermore, the temperature of the dual silanization reaction is 60–90°C.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0025] 1. This invention realizes the selective disilylation reaction of iron-catalyzed non-activated gem-difluoroalkenes, with mild reaction conditions, simple operation, and safety and reliability.

[0026] 2. This invention uses inexpensive iron salts as catalysts, thus avoiding the use of precious metal catalysts.

[0027] 3. The synthesis method of the present invention can be applied to unactivated gem-difluoroalkenes and has a broad spectrum. Attached Figure Description

[0028] Figure 1 The 1H NMR spectrum of product 3a of this invention.

[0029] Figure 2 The carbon NMR spectrum of product 3a of this invention. Detailed Implementation

[0030] To facilitate understanding of the present invention, a more comprehensive description will be given below. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a thorough and complete understanding of the disclosure of the present invention.

[0031] Nuclear magnetic resonance spectrum of the compound synthesized in this invention 1 H NMR, 13 C NMR was performed using a Bruker AVANCE III 400MHz NMR spectrometer. In the NMR spectrum, chemical shifts are represented by the letter δ, with units of ppm; peak types are labeled as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, s = septet; coupling constants are represented by the letter J, with units of Hz.

[0032] Example 1

[0033]

[0034] The synthesis was performed in a glove box: Ferrous acetate (0.02 mmol), 1,1'-bis(diphenylphosphine)ferrocene (0.04 mmol), and sodium tert-butoxide (0.80 mmol) were added sequentially to a 25 mL Schlenk tube at room temperature. The tube was then evacuated and purged with nitrogen three times. The corresponding gemdifluoroalkenes (1a, 0.2 mmol), Et3Si-Bpin (2a, 0.6 mmol), and dried and degassed tetrahydrofuran (THF, 1.0 mL) were added sequentially. The reaction tube was placed in a 70 °C magnetic stirrer for 12 h. After the reaction was completed and cooled to room temperature, 1.5 mL of saturated ammonium chloride aqueous solution was added to quench the reaction. The mixture was then extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by rapid column chromatography (PE) to obtain the corresponding product in 34% yield.

[0035] Example 2

[0036] The effects of ligand, catalyst, oxidant, reaction temperature and reaction time on the reaction were investigated (taking the synthesis of 2-methyl-1-(pyridin-2-yl)indole as an example).

[0037] (1) The influence of alkali type

[0038] Unactivated gem-difluoroalkene (1a) was selected as the reactant, triethyl silyboronic acid ester (2a, Et3Si-Bpin) as the silicon source, 2-(di-tert-butylphosphine)biphenyl (Johnphos) as the reaction ligand, tetrahydrofuran (THF) as the reaction solvent, and ferrous acetate (Fe(OAc)2) as the catalyst. The bases were screened. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.0 equivalent, relative to the molar number of 1a, the same below), Fe(OAc)2 (0.1 equivalent), Johnphos (0.2 equivalent), THF (1.0 mL), reacted at 70 °C for 12 h. The amount of base used was 4.0 equivalent in all cases. The experimental results are shown in Table 1.

[0039] Table 1. Effect of base type on reaction yield

[0040]

[0041] Based on the experimental results, MeONa and t-BuONa were selected as bases for subsequent experiments.

[0042] (2) Reaction system with MeONa as base

[0043] ① The influence of ligand type

[0044] Based on the above research, different types of ligands were further investigated. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.0 equivalent), Fe(OAc)2 (0.1 equivalent), MeONa (4.0 equivalent), and THF (1.0 mL), reacted at 70 °C for 12 h. The amount of ligand used was 0.2 equivalent for all cases. The experimental results are shown in Table 2.

[0045] Table 2 Effect of ligand type on reaction yield

[0046]

[0047]

[0048] The experimental results show that phosphine and amine ligands were used in this part of the experiment, and nitrogen ligands and carbene ligands with strong coordination ability were also tried. The results indicate that phosphine ligands showed better reaction performance, with Xantphos achieving the highest yield of 23%. Among nitrogen ligands, except for a few, the yields were generally poor. Amine and carbene ligands showed poor reaction performance, with only 1,3-bis(2,4,6-trimethylphenyl)imidazolium hydrochloride achieving a yield of 16%. Phosphine ligands exhibit better coordination ability than nitrogen and amine ligands. Furthermore, Xantphos has a strong rigid structure, which stabilizes the structure of the catalyst and ligand after coordination, while its large steric hindrance further regulates the insertion site of Fe-Si species with allenes. Therefore, Xantphos is tentatively selected as the optimal ligand for subsequent condition screening.

[0049] ② The influence of catalyst type

[0050] The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.0 equivalent), MeONa (4.0 equivalent), Xantphos (0.2 equivalent), and THF (1.0 mL), reacted at 70 °C for 12 h. The catalyst dosage was 0.1 equivalent for all reactions. The effect of catalyst type on the yield was investigated, and the experimental results are shown in Table 3.

[0051] Table 3 Effect of catalyst type on yield

[0052]

[0053] The experimental results show that when using iron catalysts with strong electron-withdrawing capabilities, such as FeF3, the yield is 14%, while the yield of catalysts with strong electron-donating capabilities, such as Fe(EtO)3, is lower. Furthermore, the catalytic effect of divalent iron catalysts is significantly higher than that of trivalent catalysts in the entire system. The highest yield of 23% can be achieved when using FeF2, possibly because the electron-withdrawing Fe catalysts may more easily form stable Ligand-Fe-Si species during coordination. Based on the experimental results, Fe(OAc)2 was selected as the optimal catalyst.

[0054] ③ Effect of reaction temperature

[0055] Based on the above research, the reaction temperature was further investigated. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.0 equivalent), MeONa (4.0 equivalent), Xantphos (0.2 equivalent), Fe(OAc)2 (0.1 equivalent), THF (1.0 mL), and the reaction temperature was 12 h. The effect of reaction temperature on the yield was investigated, and the experimental results are shown in Table 4.

[0056] Table 4 Effect of reaction temperature on yield

[0057]

[0058] The experimental results show that at lower reaction temperatures, both reactants 1a and 2a have a certain amount remaining. As the temperature increases, the conversion rate of the reactants gradually increases. When the reaction temperature rises to 70℃, reactant 1a completely reacts with further increases in temperature, but the yield decreases gradually. Further investigation revealed that the more reactive nature of substrate 1a led to its decomposition at high temperatures, thus affecting its reaction with substrate 2a. Too low a temperature inhibits the activity of the Fe catalyst; therefore, 70℃ was chosen as the optimal reaction temperature.

[0059] (3) Reaction system with t-BuONa as base

[0060] ① The influence of ligand type

[0061] Based on the above research, the ligand type was further investigated using t-BuONa as the base. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.0 equivalent), t-BuONa (4.0 equivalent), Fe(OAc)2 (0.1 equivalent), THF (1.0 mL), reacted at 70 °C for 12 h. The amount of ligand used was fixed at 0.2 equivalents, and the effect of ligand type on yield was investigated. The experimental results are shown in Table 5.

[0062] Table 5. Effect of ligand type on yield

[0063]

[0064] Experimental data show that the yield of phosphine ligands is generally higher than that of nitrogen ligands, with higher yields among phosphine ligands exhibiting greater steric hindrance. This is likely because phosphine has a stronger coordinating ability than nitrogen, and the relatively large steric hindrance provides some stability to the formed Ligand-Fe-Si species within the system. Furthermore, the larger steric effect restricts the reaction sites of the reactants in the allene, further favoring the formation of disilicon species in the reaction. Based on the experimental results, Johnphos was determined to be the optimal ligand.

[0065] ② Effect of Et3Si-Bpin dosage on raw material

[0066] Considering that the starting material Et3Si-Bpin(2a) may affect the valence state of the catalyst, and thus the migration and insertion of the metal-coordinated complex, the amount of starting material Et3Si-Bpin(2a) was investigated. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), t-BuONa (4.0 equivalent), Johnphos (0.2 equivalent), Fe(OAc)2 (0.1 equivalent), and THF (1.0 mL), reacted at 70 °C for 12 h. The effect of the amount of starting material Et3Si-Bpin(2a) on the yield was investigated, and the experimental results are shown in Table 6.

[0067] Table 6 Effect of Et3Si-Bpin dosage on yield

[0068]

[0069] The experimental results show that the optimal amount of Et3Si-Bpin is 3.5 equivalents. A higher amount of Et3Si-Bpin not only facilitates the formation of Fe-Si species participating in the reaction, but the free Bpin species also regulate the valence state of the catalyst in the system. This may reduce the high-valence iron complex formed in the system to complete the entire catalytic cycle. However, with further increases in the amount of Et3Si-Bpin, its reducing effect becomes too strong, inhibiting the transfer of single electrons from Fe. Therefore, when the amount is too high, the yield decreases.

[0070] ③ The influence of catalyst type

[0071] Based on the above research, the effect of catalyst type on the reaction was further investigated. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.5 equivalent), t-BuONa (4.0 equivalent), Johnphos (0.2 equivalent), and THF (1.0 mL), reacted at 70 °C for 12 h. The catalyst dosage was fixed at 0.1 equivalent for all reactions, and the effect of catalyst type on the yield was investigated. The experimental results are shown in Table 7.

[0072] Table 7 Effect of catalyst type on yield

[0073]

[0074]

[0075] The experimental results show that the reaction effect is better when using an electron-withdrawing iron catalyst. Among them, the highest yield reached 58% when Fe(OTf)2 was used as the catalyst. This may be because the electron-withdrawing property of trifluoromethanesulfonate is conducive to the combination of Fe and free Si in the solvent. Therefore, Fe(OTf)2 was selected as the optimal reaction catalyst.

[0076] ④ Effect of solvent type and dosage

[0077] Based on the above reactions, the effect of the type of solvent on the yield was investigated. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.5 equivalent), t-BuONa (4.0 equivalent), Fe(OTf)2 (0.1 equivalent), and Johnphos (0.2 equivalent), reacted at 70 °C for 12 h. The solvent volume was fixed at 1.0 mL for all reactions. The experimental results are shown in Table 8.

[0078] Table 8 Effect of different solvents on yield

[0079]

[0080] The experimental results show that the yield is higher when using ether solvents, while the overall yield is lower when using alkyl or benzene solvents. This is presumably because ether solvents have better solubility for both the reactants and products, which enhances the coordination ability of the reactants. The reaction yield is best when using THF as the reaction solvent, reaching 50%.

[0081] Based on the above reactions, the effect of the amount of solvent THF was further optimized. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.5 equivalent), t-BuONa (4.0 equivalent), Fe(OTf)2 (0.1 equivalent), Johnphos (0.2 equivalent), reacted at 70℃ for 12 h. The experimental results are shown in Table 9.

[0082] Table 9 Effect of THF solvent dosage on yield

[0083]

[0084] The experimental results show that the amount of solvent THF has a significant impact on the reaction yield. As the amount of solvent THF increases, the reaction yield gradually increases and reaches the highest yield at 1.5 mL. Therefore, the optimal amount of solvent THF is 1.5 mL.

[0085] ⑤ Effect of reaction temperature

[0086] Based on the above research, the reaction temperature was further investigated. The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.5 equivalent), t-BuONa (4.0 equivalent), Fe(OTf)2 (0.1 equivalent), Johnphos (0.2 equivalent), THF (1.5 mL), and the reaction time was 12 h. The effect of reaction temperature on the yield was investigated, and the experimental results are shown in Table 10.

[0087] Table 10 Effect of reaction temperature on yield

[0088]

[0089] The experimental results show that when the reaction temperature is too low, the overall reaction rate decreases, leading to a decrease in yield. When the reaction temperature is increased above 70℃, the decomposition of substrate 1a further reduces the yield. Therefore, 70℃ was chosen as the optimal reaction temperature.

[0090] ⑥ Effect of t-BuONa dosage

[0091] The reaction conditions were: 1a (0.2 mmol, 1.0 equivalent), 2a (3.5 equivalent), Fe(OTf)2 (0.1 equivalent), Johnphos (0.2 equivalent), and THF (1.5 mL), reacted at 70 °C for 12 h. The effect of t-BuONa dosage on the yield was investigated, and the experimental results are shown in Table 11.

[0092] Table 11 Effect of t-BuONa dosage on yield

[0093]

[0094] The experimental results show that the amount of alkali has a significant impact on the reaction yield. When the amount of t-BuONa is 3.0 equivalents, the yield is only 11%, while when the amount is increased to 4.0 equivalents, the yield can reach 60%. Through analysis of the above experimental data, tert-butanol may participate in the coordination reaction in the system, forming a sterically hindered Fe species together with the catalyst ligand. Therefore, 4.0 equivalents was selected as the optimal amount.

[0095] The above experiments determined the optimal reaction conditions for the reaction of gem-difluoroalkene (1a) with Et3Si-Bpin (2a) to produce 3a as follows: 0.20 mmol (1.0 equivalent) of 1a, 0.70 mmol (3.5 equivalent) of 2a, 0.02 mmol (0.1 equivalent) of Fe(OTf)2 catalyst, 0.80 mmol (4.0 equivalent) of t-BuONa base, 0.02 mmol (0.1 equivalent) of Johnphos ligand, 1.5 mL of THF solvent, a reaction temperature of 70 °C, and a reaction time of 12 h. Under these conditions, the yield of the target product 3a can reach 60%.

[0096] Example 3

[0097] By modifying the structure of gem-difluoroalkene (1a), its broad-spectrum activity was investigated using the optimized conditions obtained in Example 2, and the results are as follows:

[0098]

[0099] The following are the NMR characteristics of each product:

[0100]

[0101] (5-Phenylan-1-yne-1,3-diyl)bis(triethylsilane)

[0102] 1 H NMR (400MHz, CDCl3): δ7.27-7.31(dd,J=4.0,8.0Hz,2H),7.24-7.14(m,3H),3.04(ddd,J=13.4,9.0,4.4Hz,1H),2.67 (dt,J=13.3,8.1Hz,1H),1.84-1.74(m,1H),1.74-1.64(m,1H),0.98(dt,J=24.4,7.9Hz,18H),0.68-0.55(m,12H)ppm.

[0103] 13 C NMR (100MHz, CDCl3) δ142.3,128.6,128.3,125.7,110.5,82.2,35.7,31.6,17.6,7.6 7.4,4.8,2.4.

[0104]

[0105] (3-Benzyl-4-phenyl-1-butyn-1,3-diyl)bis(triethylsilane)

[0106] 1 H NMR (400MHz, CDCl3): δ7.25-7.05(m,10H),3.21(s,2H),0.97-0.85(m,18H),0.84-0.75(m,2H),0.61-0.49(m,12H)ppm.

[0107]

[0108] (5-(4-methoxyphenyl)-3-methylpentan-1-yne-1,3-diyl)bis(triethylsilane)

[0109] 1H NMR (400MHz, CDCl3): δ7.01-7.11 (dd, J=8.4, 14.08Hz, 2H), 6.87-6.76 (t, J=8.56Hz, 2H), 3.77 (d, J=4.5Hz, 3H), 2.6 8-2.59(m,1H),2.37-2.28(m,1H),2.21-2.10(m,1H),1.71-1.62(m,1H),1.06-0.80(m,18H),0.72-0.49(m,12H)ppm.

[0110]

[0111] (5-(benzo[d][1,3]dioxono-5-yl)-4-methylpent-1-yne-1,3-diyl)bis(triethylsilane)

[0112] 1 H NMR (400MHz, CDCl3): δ6.70(t,J=6.5Hz,1H),6.64(d,J=1.6Hz,1H),6.62-6.54(m,1H),5.90(s,2H),4.28(d,J=6.7Hz,1H),2.57(dd,J=13 .1,6.5Hz,1H),2.42(dd,J=13.2,7.7Hz,1H),2.33(dt,J=13.8,6.9Hz,1H),0.93(ddt,J=15.7,11.0,7.3Hz,20H),0.75-0.48(m,12H)ppm.

[0113]

[0114] (5-(benzo[d][1,3]dioxono-5-yl)-3-methylpent-1-yne-1,3-diyl)bis(triethylsilane)

[0115] 1 H NMR (400MHz, CDCl3): δ6.71(d,J=7.9Hz,1H),6.66(d,J=1.6Hz,1H),6.62(dd,J=8.0,1.7Hz,1H),5.90(s,2 H),2.65-2.56(m,2H),2.17-2.10(m,2H),1.64(s,3H),0.91(t,J=7.9Hz,18H),0.56(q,J=7.6Hz,11H)ppm.

[0116]

[0117] (5-(4-(tert-butyl)phenyl)-4-methylpentan-1-yne-1,3-diyl)bis(triethylsilane)

[0118] 1 H NMR (400MHz, CDCl3): δ7.31-7.26(m,2H),7.08(dd,J=7.9,6.1Hz,3H),4.32(d,J=6.6Hz,1H),2.64(dd,J=13 .0,6.2Hz,1H),2.46(dd,J=13.0,7.8Hz,1H),2.74-7.34(m,1H),1.04-0.82(m,21H),0.67-0.43(m,12H)ppm.

[0119] The above description is only for better explaining the embodiments of the present invention and is not intended to limit them. Any modifications or equivalent substitutions that do not depart from the spirit and scope of the present invention shall fall within the scope of the present invention.

Claims

1. A method for the synthesis of iron-catalyzed non-activated gem-difluoro allene compounds bis-silylated, characterized by, The method comprises the following steps: The double silylation reaction of gem-difluoro allene compound is catalyzed by using gem-difluoro allene compound as a reaction substrate, triethyl silyl borate as a silicon source, and iron salt as a catalyst in the presence of a base, a ligand and an organic solvent; The gem-difluoro allene compound has the following general structure: ； In the formula, R'=hydrogen, R=phenethyl or R'=benzyl, R=benzyl or R'=methyl, R=para-methoxyphenethyl or R'=hydrogen, R=5-n-propyl-1,3-benzodioxolane or R'=methyl, R=5-ethyl-1,3-benzodioxolane or R'=hydrogen, and R=para-tert-butylphenylpropyl; The iron salt is selected from one of Fe(OAc)2, Fe(OTf)2, Fe(OTf)3, Fe(SO4)3, FeF2, FeF3, FeCl2, FeCl3, FeBr3, tris(dibenzoylmethyl) iron, and iron tristearate; The base is selected from one of sodium methoxide and sodium tert-butoxide; The ligand is selected from one of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,3-bis(diphenylphosphino)propane, 2,2'-diphenylphosphino-1,1'-binaphthyl, 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl, 2-(di-tert-butylphosphino)biphenyl, bis(adamantane-1-yl)(butyl)phosphine hydroiodide, 1,5-bis(diphenylphosphino)pentane, and 1,1'-bis(diphenylphosphino)ferrocene; The organic solvent is selected from one of tetrahydrofuran, methyl tert-butyl ether, 1,4-dioxane, n-hexane, dimethyl ether, and cyclopentyl methyl ether; The temperature of the double silylation reaction is 60-90 DEG C.

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