Synthesis of ferrocene phosphine ligand

Abstract

The invention discloses a novel method for synthesizing a ferrocenyl phosphine ligand compound, which comprises the following steps of: reacting a ferrocene compound serving as a starting material with a Grignard reagent and phosphorus trichloride under the action of tert-butyl lithium to generate a ferrocene phosphine ligand, and synthesizing a ferrocene diphosphine ligand in one step. The method is stable and high in practicability, and a novel method for synthesizing the ferrocene ligand compound is provided.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemical synthesis, and specifically relates to a method for synthesizing ferrocenylphosphine ligands. Background Art

[0002] Chiral ferrocene bisphosphine ligands are very important ligands in the field of asymmetric catalysis, and they have high catalytic activity and stereoselectivity. In recent years, the research on ferrocenylphosphine ligands has become a hot topic for organic synthesis experts. It has been found in the synthesis that introducing ferrocene derivatives as ligands into the reaction can increase the solubility of the catalyst in organic solvents, thereby realizing homogeneous catalytic reactions and significantly improving the catalytic effect. Compared with the commonly used palladium catalysts, it is cheaper and has better catalytic effects. Among them, chiral ferrocenylphosphine ligands are widely used in organic synthesis reactions such as carbon-carbon double bond addition reactions, allylic reactions, cross-coupling reactions, and asymmetric Aldol reactions. Therefore, finding a simple, safe, and low-cost production method has become the key to the research on ferrocenylphosphine ligands. Summary of the Invention

[0003] The purpose of the present invention is to provide a method for preparing ferrocene-based ligand compounds with simple method and stable process.

[0004] The method is as follows: The reaction formula is as follows:

[0005] The reaction steps of the present invention are as follows: Under the protection of an inert gas, ferrocene-based raw materials, MTBE, and tert-butyllithium are added to a dry reactor. At about -10°C, stir for 0.5 h to 1 h, then add phosphorus trichloride dropwise at -78°C, warm up to about -20°C to 10°C, add Grignard reagent, and after the reaction is complete, quench with saturated ammonium chloride. Then, after extraction, drying, concentration, and column chromatography, product 2 is obtained; Under the protection of an inert gas, the above-obtained product 2 is placed in a reaction flask, and acetic acid and di-tert-butylphosphine hydride are added together. React completely at 100°C, cool to room temperature, and after extraction, neutralize with sodium bicarbonate, wash with brine, and dry to obtain product 3. The molar ratio of the ferrocene-based compound, Grignard reagent, tert-butyllithium, and phosphorus trichloride is 1:2.1:1.1:1.1. The molar ratio of intermediate 2 and di-tert-butylphosphine hydride is 1:1. Brief Description of the Drawings

[0006] Figure 1 It is the 1H-NMR spectrum of the product obtained in the embodiment of the present invention. Detailed Description Example

[0008] Step 1: Preparation of Naphthyl Grignard Reagent Place magnesium strip (10.89 g) in a 500 mL dry three-necked flask, add 280 mL of dry tetrahydrofuran, protect with nitrogen. Slowly add 1-bromonaphthalene (85.42 g) dropwise from a constant pressure dropping funnel. After initiation, slowly add the remaining bromonaphthalene and react overnight at room temperature to obtain a grayish-white turbid liquid.

[0009] Weigh the raw material amine (38.57 g) into a 1 L four-necked flask, add 275 mL of methyl tert-butyl ether, protect with nitrogen. Slowly add tert-butyllithium (121 mL) at -10 °C. After addition, react for 0.5 h, raise the temperature to room temperature and react for 1 h, then cool to -78 °C. Slowly add phosphorus trichloride (21.63 g) dropwise. After addition, when the temperature naturally rises to -20 °C, slowly add the prepared Grignard reagent above, with the temperature not exceeding 10 °C. After addition, react at room temperature until the reaction is complete. Quench with saturated ammonium chloride, concentrate to remove the solvent, extract with ethyl acetate, wash successively with water, saturated sodium chloride solution, and dry over anhydrous sodium sulfate. After rotary evaporation, purify by column chromatography to obtain 35.3 g of a yellow solid, with a yield of 47.2%.

[0010] Step 2: Preparation of Naphthyl Ferrocene Ligand Compound Place the intermediate obtained from the previous step (35.3 g) in a 500 mL three-necked flask, add 87.5 mL of glacial acetic acid, protect with nitrogen. Add di-tert-butylphosphine hydride (10.01 g). After addition, raise the temperature to 100 °C and react, stir until the reaction is complete, stop heating, cool to room temperature, then wash successively with water, extract with dichloromethane, wash with sodium bicarbonate, saturated sodium chloride solution, and dry over anhydrous sodium sulfate. Remove the solvent by rotary evaporation to obtain a yellow foamy solid.

[0011] 1H NMR (400 MHz, Chloroform-d) δ 9.68 (t, J = 7.8 Hz, 1H), 8.16 (q, J= 3.6 Hz, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.87 – 7.67 (m, 4H), 7.59 (t, J =7.6 Hz, 1H), 7.47 (dt, J = 13.8, 5.4 Hz, 2H), 7.38 (t, J = 7.6 Hz, 1H), 7.34– 7.23 (m, 3H), 7.18 (t, J = 7.8 Hz, 1H), 4.47 (s, 1H), 4.33 (s, 1H), 4.22(s, 1H), 3.56 (d, J = 2.0 Hz, 6H), 1.90 (d, J = 7.2 Hz, 3H), 1.15 (d, J =10.4 Hz, 9H), 0.99 (d, J = 10.5 Hz, 9H).

Claims

1. The synthesis method of ferrocene phosphine complex, the key lies in the synthesis of Grignard reagent; The reaction is as follows:

2. According to claim 1, the solvents used in step 1 are analytically pure THF and redistilled THF.

3. According to claim 1, the molar ratio of compound 1 to Grignard reagent is 1:2.0 - 2.

5.

4. According to claim 1, the Grignard reagent is used for synthesizing ferrocene phosphine ligand.

5. According to claim 1, the lithium reagent used in step 1 is tert - butyllithium, and the phosphine reagent is phosphorus trichloride.

6. According to claim 1, it is characterized in that: The phosphine used in step 2 is di - tert - butylphosphine.

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