Chiral ferrocene skeleton diphosphine ligand and application of chiral ferrocene skeleton diphosphine ligand in catalyst

Abstract

The invention relates to a chiral ferrocene skeleton diphosphine ligand and an application thereof in a catalyst, and the disclosed ligand is a novel ferrocene skeleton diphosphine ligand, and the ligand has the advantages of low cost, simple synthesis, good stability and the like. The metal complex of the ligand shows very excellent catalytic activity in CN coupling reaction, can efficiently catalyze coupling of building blocks such as halogenated hydrocarbon and sulfonate with ammonia, amine or hydrazine compounds, and has important industrial application value.

Description

Technical Field

[0001] The invention belongs to the field of fine chemicals, relates to a chiral ligand and an application thereof, and specifically relates to a chiral ferrocene skeleton diphosphine ligand and an application thereof in a catalyst. Background Art

[0002] The C-N coupling reaction catalyzed by transition metal complexes has the advantages of cheap and readily available substrates, high catalytic efficiency, and simple post-processing. It is widely used in the fields of medicine, pesticides, and fragrances. The key to a practical C-N coupling reaction lies in a metal complex catalyst with high activity and good substrate compatibility, while the ligand is the key to obtaining excellent performance. Therefore, the development of new ligands with excellent performance has always been the core content of C-N coupling reaction research.

[0003] The ferrocene skeleton is a dominant skeleton in ligand design. There are countless excellent ligands developed based on this skeleton. Josiphos is an excellent representative among them, showing excellent catalytic performance in asymmetric catalytic hydrogenation, C-N coupling and Suzuki coupling reactions. Although a large number of ligands have been reported, there are not many examples of their real application in industrial production due to their low catalytic activity, cumbersome preparation, difficult modification and high price. Therefore, it is of great significance to develop new ligands with high activity, simple synthesis and easy modification. Summary of the invention

[0004] In order to overcome the deficiencies of the above-mentioned prior art, the purpose of the present invention is to provide a chiral ferrocene skeleton bisphosphine ligand and its application in a catalyst. The bisphosphine ligand connects three advantageous ferrocene skeletons and introduces a side chain phosphine group that is easy to modify. Compared with the reported Josiphos, it not only adds two sterically hindered and electron-rich ferrocene skeletons, but also the synthesis route is very simple and efficient.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] A chiral ferrocene framework diphosphine ligand, characterized in that the general structural formula is as shown in Formula 1:

[0007] ;

[0008] Where:

[0009] R 1 C1~C6 alkyl and cycloalkyl fatty groups; C6~C 20 Aromatic groups;

[0010] R 2 The fatty groups are C1-C6 alkyl and cycloalkyl groups; the C7-C 20The combination of aromatic groups and aliphatic groups; the C6~C 20 Aromatic groups within.

[0011] Furthermore, the general structural formula 1 includes its stereoisomers as follows:

[0012] .

[0013] Furthermore, a method for preparing a chiral ferrocene skeleton diphosphine ligand, the synthesis route includes:

[0014] .

[0015] Furthermore, the ligand is used to prepare a metal complex catalyst.

[0016] Furthermore, the metal complex catalyst is used to catalyze C−N coupling reaction, Suzuki coupling reaction, hydrogenation reaction, olefin metathesis reaction, isomerization reaction, Diels-Alder reaction, Heck reaction, Aldol reaction, Michael addition reaction or asymmetric epoxidation reaction.

[0017] Furthermore, the metal in the metal complex catalyst is ruthenium (Ru), rhodium (Rh), iridium (Ir), palladium (Pd), platinum (Pt), iron (Fe), cobalt (Co), nickel (Ni) or manganese (Mn).

[0018] The friendly effects of the present invention are:

[0019] The ligand disclosed in the present invention is a new type of ferrocene skeleton diphosphine ligand, which has the advantages of low cost, simple synthesis and good stability. The metal complex of this type of ligand exhibits very excellent catalytic activity in C-N coupling reaction, and can efficiently catalyze the coupling of building blocks such as halogenated hydrocarbons and sulfonates with ammonia, amines or hydrazine compounds, and has important industrial application value. DETAILED DESCRIPTION

[0020] The present invention is further described below in conjunction with embodiments, but the present invention is not limited to the following embodiments.

[0021] A. Synthesis of Ligands

[0022] Implementation Example 1

[0023]

[0024] At 0 °C, slowly add 1.3 M tert-butyl lithium (8.1 mL, 10.5 mmol) in pentane to a solution of (R)-1 (2.57 g, 10 mmol) in methyl tert-butyl ether. After the addition is complete, warm the temperature to room temperature and react for 1.5 h. Place the reaction solution below -78 °C again, slowly add PCl3 (1.5 g, 10.9 mmol) with a syringe, and slowly warm the temperature to room temperature and react for 6 h.

[0025] Bromoferrocene 2 (5.81 g, 22 mmol) was weighed and added to a Schlenk reaction tube. The mixture was evacuated / filled with Ar and 30 mL of tetrahydrofuran was added and stirred. The temperature was lowered to -35 °C. After the addition was completed, the reaction was allowed to proceed for 30 min. The reaction solution was mixed under ice bath and continued to be stirred for 6 h. Saturated ammonium chloride solution was added to the reaction solution to quench the reaction. After the solution was separated, the organic phase was washed with distilled water and saturated brine in sequence, then dried over anhydrous sodium sulfate, filtered, and spin-dried. The product (R,S)-3 was separated and purified by column chromatography (petroleum ether: triethylamine = 50:1) to obtain 4.65 g of yellow foamy solid with a yield of 70.8%. 1 H NMR (400 Hz, CDCl3) δ 4.65 –3.90 (m, 25H), 3.65 – 3.55 (m, 1H), 2.19 (s, 6H), 1.35 – 1.24 (m, 3H); 31 P NMR (162 Hz, CDCl3) δ -41.26; HRMS (ESI) calcd for C 34 H 37 Fe3NP [M+H] + : 658.0712,Found: 658.0696.

[0026] Implementation Example 2

[0027]

[0028] To a solution of the monophosphine intermediate (R,S)-3 (657 mg, 1 mmol) in glacial acetic acid (5 mL) was added di-tert-butylphosphine (146 mg, 1 mmol), and the reaction temperature was raised to 102 °C. 31 P NMR monitoring until the reaction is complete. After cooling to room temperature, the reaction solution was diluted with dichloromethane, washed with water, saturated NaHCO3 solution and saturated NaCl in sequence, dried, spin-dried, and column chromatography (ethyl acetate: petroleum ether = 1:30) was performed to obtain bisphosphine ligand L1 as an orange solid (538 mg) with a yield of 71%. 1H NMR (400 Hz, CDCl3) δ 4.48 –4.11 (m, 11H), 3.92 (s, 5H), 3.90 (s, 5H), 3.71 (s, 5H), 3.19 (d, J = 8.2 Hz,1H), 1.87 – 1.73 (m, 3H), 1.33 (d, J = 10.5 Hz, 9H), 1.22 (d, J = 11.0 Hz, 9H); 31 P NMR (162 Hz, CDCl3) δ 47.91 (d, J = 23.9 Hz), -50.89 (d, J = 21.6 Hz); HRMS (ESI)calcd for C 40 H 49 Fe3P2 [M+H] + : 759.1358, Found: 759.1364.

[0029] Implementation Example 3

[0030]

[0031] Dicyclohexylphosphine (198 mg, 1 mmol) was added to a solution of monophosphine intermediate (R,S)-3 (657 mg, 1 mmol) in glacial acetic acid (5 mL), and the reaction temperature was raised to 102 °C. 31 P NMR monitoring until the reaction is complete. After cooling to room temperature, the reaction solution was diluted with dichloromethane, washed with water, saturated NaHCO3 solution and saturated NaCl in sequence, dried, spin-dried, and column chromatography (ethyl acetate: petroleum ether = 1:30) was performed to obtain bisphosphine ligand L2 as an orange solid (567 mg) with a yield of 70%. 1 H NMR (400 Hz, CDCl3) δ4.53 –4.22 (m, 11H), 4.04 (s, 5H), 4.03 (s, 5H), 3.92 (s, 5H), 2.87 (d, J = 7.3 Hz,1H), 2.06 – 1.58 (m, 13H), 1.35 – 1.17 (m, 12H); 31 P NMR (162 Hz, CDCl3) δ13.35 (d, J = 12.8 Hz), -45.27 (d, J = 13.4 Hz); HRMS (ESI)calcd forC 44 H 53 Fe3P2 [M+H] +: 811.1671, Found: 811.1659.

[0032] Implementation Example 4

[0033]

[0034] Diphenylphosphine (186 mg, 1 mmol) was added to a solution of the monophosphine intermediate (R,S)-3 (657 mg, 1 mmol) in glacial acetic acid (5 mL), and the reaction temperature was raised to 102 °C. 31 P NMR monitoring until the reaction is completed. After cooling to room temperature, the reaction solution was diluted with dichloromethane, washed with water, saturated NaHCO3 solution and saturated NaCl in sequence, dried, spin-dried, and column chromatography (ethyl acetate: petroleum ether = 1:30) was performed to obtain bisphosphine ligand L3, 600 mg of orange solid, with a yield of 75%. 1 H NMR (400 Hz, CDCl3) δ 7.49 –7.07 (m, 10H), 4.62 (s, 1H), 4.54 – 4.23 (m, 10H), 4.15 (s, 5H), 4.13 (s,5H), 4.08 (s, 5H), 3.12 (d, J = 7.1 Hz, 1H), 1.19 (t, J = 7.0 Hz, 3H); 31 P NMR (162 Hz, CDCl3) δ 5.07, -37.58 (d, J = 15.2 Hz); HRMS (ESI)calcd for C 44 H 41 Fe3P2[M+H] + : 799.0732, Found: 799.0710.

[0035] B. Catalytic C-N coupling reaction

[0036]

[0037] Implementation Example 5

[0038] In an inert atmosphere glove box, [Pd(allyl)Cl]2 (0.9 mg, 0.05 mol%) and L1 (3.8 mg, 0.12 mol%) were added to a 100 mL sealed tube with a sealing ring, stirred in tetrahydrofuran (2 mL) at room temperature for 25 min, and then 8 mL of tetrahydrofuran was added, followed by p-dichlorobenzene (735 mg, 5.0 mmol), NaOMe (1.22 g, 22.5 mmol) and 80% hydrazine hydrate (1.25 g, 25.0 mmol). After taking out the reaction bottle from the glove box, the reaction was stirred at 110 °C for 36 hours. The reaction was monitored by thin layer chromatography until completion (ethyl acetate: petroleum ether = 1:1). After the reaction temperature dropped to room temperature, the mixture was filtered on diatomaceous earth, and the filter cake was washed with ethyl acetate. The resulting eluate was extracted with a saturated NaCl solution (20 mL*3 times). After the organic phase was concentrated, 37% concentrated hydrochloric acid was added dropwise to acidify to pH = 3-4 to produce a white solid. The solid was filtered and washed with ethyl acetate to obtain the corresponding product as a white solid. After drying, 742 mg was weighed, with a yield of 83%. 1 H NMR (400 Hz, DMSO-d6) δ 10.35 (d, J =9.4 Hz, 3H), 8.47 (s, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.15 – 6.90 (m, 2H).

Claims

1. A chiral ferrocene framework diphosphine ligand, characterized in that: The general structural formula is shown in Formula 1: ； Where: R 1 C1~C6 alkyl and cycloalkyl fatty groups; C6~C 20 Aromatic groups; R 2 The fatty groups are C1-C6 alkyl and cycloalkyl groups; the C7-C 20 The combination of aromatic groups and aliphatic groups; the C6~C 20 Aromatic groups within.

2. A chiral ferrocene skeleton diphosphine ligand according to claim 1, characterized in that: The general structural formula 1 includes its stereoisomers as follows: 。 3. A method for preparing a chiral ferrocene skeleton diphosphine ligand, characterized in that: The synthetic routes include; 。 4. The chiral ferrocene framework diphosphine ligand according to claim 1, characterized in that: The ligand is used for preparing metal complex catalyst.

5. The chiral ferrocene framework diphosphine ligand according to claim 1, characterized in that: The metal complex catalyst is used to catalyze C−N coupling reaction, Suzuki coupling reaction, hydrogenation reaction, olefin metathesis reaction, isomerization reaction, Diels-Alder reaction, Heck reaction, Aldol reaction, Michael addition reaction or asymmetric epoxidation reaction.

6. The chiral ferrocene framework diphosphine ligand according to claim 4, characterized in that: The metal in the metal complex catalyst is ruthenium (Ru), rhodium (Rh), iridium (Ir), palladium (Pd), platinum (Pt), iron (Fe), cobalt (Co), nickel (Ni) or manganese (Mn).

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