Chiral ferrocene skeleton diphosphine ligand and application thereof in catalyst

Abstract

The application of a kind of chiral ferrocene skeleton diphosphine ligand and catalyst, the disclosed ligand is a new type of ferrocene skeleton diphosphine ligand, the ligand has the advantages of low cost, simple synthesis and good stability. The metal complex of the ligand shows very excellent catalytic activity in C-N coupling reaction, can efficiently catalyze the coupling of halogenated hydrocarbon, sulfonate and other building blocks with ammonia, amine or hydrazine compounds, and has important industrial application value.

Description

Technical Field

[0001] This invention belongs to the field of fine chemicals and relates to chiral ligands and their applications, specifically to a chiral ferrocene skeleton bisphosphine ligand and its application in catalysts. Background Technology

[0002] Transition metal complex-catalyzed C-N coupling reactions offer advantages such as inexpensive and readily available substrates, high catalytic efficiency, and simple post-processing, leading to their widespread application in pharmaceuticals, pesticides, and fragrances. A key to a practical C-N coupling reaction lies in a highly active metal complex catalyst with good substrate compatibility, while ligands are essential for achieving superior performance. Therefore, developing novel ligands with excellent properties has always been a core focus of C-N coupling reaction research.

[0003] The ferrocene framework is a superior framework for ligand design, and numerous excellent ligands have been developed based on it. Josiphos is a prime example, exhibiting excellent catalytic performance in asymmetric hydrogenation, C-N coupling, and Suzuki coupling reactions. Although a large number of ligands have been reported, few have been truly applied in industrial production due to drawbacks such as low catalytic activity, cumbersome preparation, difficult modification, and high cost. Therefore, developing novel ligands that are highly active, easily synthesized, and readily modifiable is of great significance. Summary of the Invention

[0004] To overcome the shortcomings of the prior art, the present invention aims to provide a chiral ferrocene skeleton bisphosphine ligand and its application in catalysts. The bisphosphine ligand connects three dominant ferrocene skeletons and introduces easily modifiable side-chain phosphine groups. Compared with the reported Josiphos, it not only adds two sterically hindered and electrochemically rich ferrocene skeletons, but also has a very simple and efficient synthetic route.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0006] A class of chiral ferrocene-based bisphosphine ligands, characterized by a general structural formula as shown in Formula 1:

[0007] ;

[0008] In the formula:

[0009] R 1 It is an aliphatic group consisting of C1 to C6 alkyl and cycloalkyl groups; C6 to C 20 Aromatic groups;

[0010] R 2 It is an aliphatic group of C1-C6 alkyl and cycloalkyl groups; benzyl groups of C7-C6... 20The aromatic group and aliphatic group are combined groups; the C6-C of the aryl group. 20 Aromatic groups within.

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

[0012] .

[0013] Furthermore, a method for preparing a class of chiral ferrocene framework bisphosphine ligands, including the following synthetic route;

[0014] .

[0015] Furthermore, this ligand is used in the preparation of metal complex catalysts.

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

[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 friendship effect of this invention is:

[0019] The ligands disclosed in this invention are a novel class of ferrocene-based bisphosphine ligands, which possess advantages such as low cost, simple synthesis, and good stability. The metal complexes of these ligands exhibit excellent catalytic activity in C-N coupling reactions, efficiently catalyzing the coupling of building blocks such as halogenated hydrocarbons and sulfonates with ammonia, amines, or hydrazine compounds, thus possessing significant industrial application value. Detailed Implementation

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

[0021] A. Ligand synthesis

[0022] Implementation Example 1

[0023]

[0024] At 0 °C, a 1.3 M tert-butyllithium (8.1 mL, 10.5 mmol) pentane solution was slowly added dropwise to a (R)-1 (2.57 g, 10 mmol) methyl tert-butyl ether solution. After the addition was complete, the temperature was raised to room temperature and the reaction was allowed to proceed for 1.5 h. The reaction solution was then placed below -78 °C again, and PCl3 (1.5 g, 10.9 mmol) was slowly added using a syringe. The temperature was then slowly raised to room temperature and the reaction was allowed to proceed for 6 h.

[0025] 5.81 g (22 mmol) of ferrocene bromo was weighed and added to a Schlenk reaction tube. The tube was evacuated / charged with Ar, and 30 mL of tetrahydrofuran was added with stirring. The temperature was lowered to -35 °C. After the addition was complete, the reaction was allowed to proceed for 30 min. The reaction mixture was then stirred for 6 h under an ice bath. Saturated ammonium chloride solution was added to the reaction mixture to quench the reaction. After the solution separated into layers, the organic phase was washed successively with distilled water and saturated brine, then dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and purified by column chromatography (petroleum ether:triethylamine = 50:1) to obtain product (R,S)-3, a yellow bubbly solid, 4.65 g, 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] Di-tert-butylphosphine (146 mg, 1 mmol) was added to a 5 mL solution of monophosphine intermediate (R,S)-3 (657 mg, 1 mmol) in glacial acetic acid, and the reaction temperature was raised to 102 °C. 31 P NMR was monitored until the reaction was complete. After cooling to room temperature, the reaction solution was diluted with dichloromethane, washed successively with water, saturated NaHCO3 solution and saturated NaCl, dried, evaporated to dryness, and subjected to column chromatography (ethyl acetate: petroleum ether = 1:30) to give 538 mg of bisphosphine ligand L1, an orange-yellow solid, 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 glacial acetic acid (5 mL) solution of the monophosphine intermediate (R,S)-3 (657 mg, 1 mmol), and the reaction temperature was raised to 102 °C. 31 P NMR was monitored until the reaction was complete. After cooling to room temperature, the reaction solution was diluted with dichloromethane, washed successively with water, saturated NaHCO3 solution and saturated NaCl, dried, evaporated to dryness, and subjected to column chromatography (ethyl acetate: petroleum ether = 1:30) to give 567 mg of bisphosphine ligand L2, an orange-yellow solid, 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 glacial acetic acid (5 mL) solution of the monophosphine intermediate (R,S)-3 (657 mg, 1 mmol), and the reaction temperature was raised to 102 °C. 31 P NMR was monitored until the reaction was complete. After cooling to room temperature, the reaction solution was diluted with dichloromethane, washed successively with water, saturated NaHCO3 solution and saturated NaCl, dried, evaporated to dryness, and subjected to column chromatography (ethyl acetate: petroleum ether = 1:30) to give 600 mg of bisphosphine ligand L3, an orange-yellow 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. The mixture was stirred in tetrahydrofuran (2 mL) at room temperature for 25 min. After adding 8 mL of tetrahydrofuran, p-dichlorobenzene (735 mg, 5.0 mmol), NaOMe (1.22 g, 22.5 mmol), and 80% hydrazine hydrate (1.25 g, 25.0 mmol) were added sequentially. After removing the reaction flask from the glove box, the reaction was stirred at 110 °C for 36 h. The reaction was monitored until completion by thin-layer chromatography (ethyl acetate: petroleum ether = 1:1). After the reaction temperature was lowered to room temperature, the mixture was filtered through diatomaceous earth and the filter cake was washed with ethyl acetate. The resulting eluent was extracted with saturated NaCl solution (20 mL * 3 times). After concentrating the organic phase, it was acidified with 37% concentrated hydrochloric acid to pH = 3-4, producing a white solid. The solid was filtered and washed with ethyl acetate to obtain the corresponding white product. After drying, it was weighed to obtain 742 mg, 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 class of chiral ferrocene-based bisphosphine ligands, characterized in that, The general structural formula is shown in Formula 1: ； In the formula: R 1 It consists of C1 to C6 alkyl and cycloalkyl groups; R 2 It is a C1 to C6 alkyl and cycloalkyl group; an aryl group with C6 to C6 alkyl groups. 20 Aromatic groups within.

2. The chiral ferrocene framework bisphosphine ligand according to claim 1, characterized in that, Formula 1 is selected from: 。 3. A method for preparing a class of chiral ferrocene-based bisphosphine ligands, characterized in that, The synthetic route includes; In the formula: R is a C1–C6 alkyl or cycloalkyl group; aryl group is a C6–C6 alkyl group. 20 Aromatic groups within.

4. The application of the chiral ferrocene framework bisphosphine ligand according to claim 1, characterized in that, This material is used to prepare metal complex catalysts, which are used to catalyze C-N coupling reactions, and the metal in the metal complex catalyst is palladium.

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