WO2021253847A1

WO2021253847A1 - Use of deprotonated phenyl bridged β-ketimine lithium compound in hydroboration reaction

Info

Publication number: WO2021253847A1
Application number: PCT/CN2021/075895
Authority: WO
Inventors: 薛明强; 徐晓娟; 周帅; 康子晗; 洪玉标; 刘倩倩
Original assignee: 苏州大学
Priority date: 2020-06-16
Filing date: 2021-02-07
Publication date: 2021-12-23
Also published as: CN111760593A

Abstract

Disclosed is the use of a deprotonated phenyl bridged β-ketimine lithium compound in a hydroboration reaction. The hydroboration reaction involves using an ester and a borane as reaction substrates. In the present invention, the deprotonated phenyl bridged β-ketimine lithium compound which is disclosed for the first time is used to catalyze the hydroboration reaction of an ester and a pinacol borane, such that an efficient method for catalyzing hydroboration reactions is developed. The compound has a simple structure and is easy to synthesize, and is capable of catalyzing the hydroboration reaction of an ester and a borane with a high activity. Compared with existing catalytic systems, the amount of the catalyst is reduced, the temperature is milder, and the yield is higher.

Description

Application of Deprotonated Phenyl-Bridged β-Ketoimid Lithium Compound in Hydroboration Reaction

Technical field

The invention relates to a lithium compound and its application in the field of organic synthesis, in particular to a deprotonated β-ketoimide lithium compound, a preparation method thereof and its application in the hydroboration reaction of esters.

Background technique

In recent years, the borohydride reaction of esters has become one of the research hotspots of scientific researchers. There are more and more reports on the borohydride reaction of esters, mainly involving main group metal catalysts and rare earth metal catalysts. In 2014, Sadow’s research group reported that a Mg complex To ^M MgMe (To ^M = tris(4,4-dimethyl-2-oxazolinyl)phenyl borate) can efficiently catalyze the boron of esters. Hydrogenation reaction provides alkoxyborane product through ester cracking [Mukherjee, D.; Ellern, A.; Sadow, AD Chem. Sci . 2014 , 5 , 959.]. In 2017, the Nembenna research group reported that magnesium amide complexes such as Mg{N(SiMe ₃ ) ₂ } ₂ can efficiently catalyze the reaction of various esters and pinacol borane [Barman, MK; Baishya, A.; Nembenna , M. Dalton Trans . 2017 , 46 , 4152.]. In 2019, Sadow’s research group reported a rare earth complex containing Ln-C bond La{C(SiHMe ₂ ) ₃ } _{3 to} catalyze the borohydride reduction of ester and pinacol borane [Patnaik, S.; Sadow, AD Angew. Chem. 2019 , 131 , 2527.].

technical problem

The purpose of the present invention is to provide the application of a deprotonated phenyl bridged β-ketimide lithium compound in the borohydride reaction, which is a new ester borohydride reaction method and has a good substrate application range.

Technical solutions

In order to achieve the above-mentioned objective, the technical solution adopted in the present invention is the application of a deprotonated phenyl-bridged β-ketimide lithium compound in the hydroboration reaction, wherein the hydroboration reaction uses esters and borane as reaction substrates.

The invention also discloses a method for synthesizing boric acid esters, which includes the following steps. The deprotonated phenyl bridged β-ketimide lithium compound is used as a catalyst, esters and borane are used as raw materials, and boric acid is prepared through borohydride reaction. ester.

The chemical structural formula of the deprotonated phenyl bridged β-ketimide lithium compound of the present invention is as follows:

.

In the above technical solution, the reaction temperature was room temperature borohydride ~ 60 ^o C, the time is 1.5 to 2.5 hours, the reaction was terminated and then exposed to air, to give boronate different substituents.

In the above technical solution, the borane is pinacol borane; the ester is γ-valerolactone, methyl acetate, benzyl benzoate, methyl benzoate, and methyl 4-bromobenzoate.

In the above technical solution, the amount of the catalyst is 1% of the molar amount of the ester, and the molar ratio of the borane to the ester is 2.2:1.

In the present invention, the preparation method of the above-mentioned deprotonated phenyl bridged β-ketoimide lithium compound includes the following steps: a small molecule organic lithium solution and a ligand solution are mixed, and then reacted to obtain a catalyst deprotonated phenyl bridged β- Lithium ketimide compound; the chemical structural formula of the ligand is as follows:

.

In the present invention, in the small molecule organic lithium solution, the small molecule organic lithium includes n-butyl lithium, and the solvent is an alkyl solvent, such as hexane; in the ligand solution, the solvent is an ether solvent, such as tetrahydrofuran.

In the present invention, the molar ratio of small molecule organolithium to ligand is 4:1, and this ratio has not been reported in the synthesis and application of β-ketimine anionic ligand.

The reaction of synthesizing boric acid ester is as follows:

.

Beneficial effect

Due to the application of the above technical solutions, the present invention has the following advantages compared with the prior art: The present invention utilizes the first disclosed deprotonated phenyl bridged β-ketoimide lithium compound to catalyze the borohydride reaction of ester and pinacol borane, Therefore, an efficient method for catalyzing the hydroboration reaction has been developed. Its structure is simple and the synthesis is easy. It can ^{catalyze the hydroboration reaction of ester and borane with high activity at 60 oC} . The amount of catalyst is only 1% of the molar amount of ester. , The reaction can reach a yield of more than 90%. Compared with the existing catalytic system, the amount of catalyst is reduced, the temperature is milder, and the yield is higher.

Embodiments of the present invention

The catalyst of the present invention comes from another invention application filed by the applicant on the same day, and the name of the invention is a deprotonated β-ketimide lithium compound and a preparation method thereof. Existing organolithium reagents such as n-butyllithium require strict conditions for storage, such as ventilation, dryness, waterproofing, and heat resistance, and are harmful to experimenters during use. The deprotonated phenyl-bridging-ketoimide lithium disclosed in the present invention The compound is easy to store. It is usually placed in a glass bottle and placed in a conventional reagent cabinet. It can be prepared in large quantities at one time and used directly in the subsequent, which is harmless to experimenters during use.

The raw materials involved in the present invention are all commercially available products. Under the preparation method of the present invention, the specific operation steps and test and purification methods are all conventional methods in the field; the reactions of the synthesis examples are all carried out in the air.

Synthesis example: Synthesis of meta-phenyl-bridged β-ketimine ligand (L ^ph H ₂ ):

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Add 150 ml of absolute ethanol, 10.8 g of m-phenylenediamine (100 mmol), 20.5 mL of acetylacetone (200 mmol), and catalytic amount of p-toluenesulfonic acid into a three-necked flask. Heat to reflux for 24 hours to obtain a reddish brown liquid and light. The yellow solid mixture was filtered with suction, and the solid was recrystallized with absolute ethanol to obtain 24.5 g of light yellow needle-like crystals, with a yield of 90%, which was the ligand L ^ph H ₂ . ¹ H NMR (400 MHz, CDCl ₃ ): δ 12.47 (2H, s, NH), 7.32-7.27 (1H, m, ArH), 6.94-6.91 (2H, m, ArH), 6.86 (1H, s, ArH) ), 5.21 (2H, s, CH=C(CH ₃ )N), 2.10 (6H, s, CH ₃ ), 2.01 (6H, s, CH ₃ ). ¹³ C NMR (101 MHz, CDCl ₃ ): δ 196.54 (COCH ₃ ), 159.62 (C=CH), 139.63 (Ar-C), 129.71 (Ar-C), 121.45 (Ar-C), 120.43 (Ar- C), 98.20 (=CH), 29.25 (CH ₃ ), 19.94 (CH ₃ ). HRMS (ESI-MS) calcd. for C ₁₆ H ₂₀ N ₂ O ₂ [M+H] ⁺ : 273.1558, found: 273.1633.

Synthesis of deprotonated phenyl-bridged β-ketoimide lithium compound [L ^ph ^' Li ₄ (THF) ₄ ] _2:

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Under ice bath conditions, add the hexane solution of n-butyllithium (19.40 mmol, 2.5 M) to the L ^ph H ₂ (4.85 mmol) tetrahydrofuran solution, the solution gradually changed from pale yellow clear liquid to light orange-red turbidity After adding 1 minute, react for 12 h at room temperature; after the reaction, heat the reaction solution (100 ^o C) to turn it into orange-red clear liquid, concentrate the clear solution to turbidity and centrifuge, and continue the supernatant Concentrate to produce broken crystals, heat to dissolve, then cool to room temperature naturally, seal the bottle, and let stand for 1h at room temperature, and light yellow crystals precipitate out [L ^ph ^' Li ₄ (THF) ₄ ] ₂ {L ^ph ^' = C ₆ H ₄ [ N(CH ₃ )C=CHCO=CH ₂ ] ₂ }, conventionally separated and dried, and 2.13 g of product was obtained with a yield of 75%. The crystal structure is shown in Figure 1. Melting point: 194.6-196.7 ^o C. ¹ H NMR (400 MHz, C ₂ D ₆ SO): δ 7.60-7.13 (2H, m, ArH), 7.00-6.96 (2H, m, ArH), 6.09 (2H, s), 4.55 (4H, s) , 1.69-1.66 (6H, m). ¹³ C NMR (101 MHz, C ₂ D ₆ SO): δ 179.53, 163.77, 154.04, 129.35, 127.83, 117.68, 116.40, 95.55, 28.88, 21.95. IR (KBr): 2972.71, 2869.81, 1590.41, 1500.86, 1468.03, 1412.07, 1360.89, 1318.03, 1280.73, 1238.47, 1146.11, 1053.76, 1019.62, 970.28, 924.75, 887.93, 806.76, 748.66 643.56.

Compound [L ^ph ^' Li ₄ (THF) ₄ ] ₂ :

.

Example 1: [L ^ph ^' Li ₄ (THF) ₄ ] ₂ catalyzes the reduction reaction of benzyl benzoate and pinacol borane: Add catalyst 5.84 to the reaction flask after dehydration and deoxygenation under an inert gas atmosphere mg (0.005 mmol), add benzyl benzoate (94.9 μL, 0.5 mmol), pinacol borane (159.6 μL, 1.1 mmol), THF (200 μL), and ^{react at 60 o} C for 120 min. Then, use mesitylene (69.6 μL, 0.5 mmol) as the internal standard, stir evenly, use a dropper to pipette a drop into the NMR tube, and add CDCl _{3 to make a} solution. The calculated ¹ H spectrum yield is 96%. The nuclear magnetic data of the product: ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.34 – 7.22 (m, 10H, ArH), 4.91 (s, 4H, OCH ₂ ), 1.25 (s, 24H, CH ₃ ).

Example 2: [L ^ph ^' Li ₄ (THF) ₄ ] ₂ catalyzes the reduction reaction of methyl acetate and pinacol borane: Add catalyst 5.84 mg to the reaction flask after dehydration and deoxygenation under an inert gas atmosphere , Use a pipette to add methyl acetate (39.7 μL, 0.5 mmol), pinacol borane (159.6 μL, 1.1 mmol), THF (200 μL), and after ^{reacting at 60 o} C for 120 min, add mesitylene (69.6 μL, 0.5 mmol) is the internal standard. After stirring evenly, pipette a drop into the NMR tube, and add CDCl _{3 to make a} solution. The calculated ¹ H spectrum yield is 95%. NMR data of the product: ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.87 (q, J = 7.1 Hz, 2H, OCH ₂ ), 1.22 (s, 24H, OBpin), 1.19 (t, J = 6.0 Hz, 3H , CH ₃ ).

Example 3: [L ^ph ^' Li ₄ (THF) ₄ ] ₂ catalyzes the reduction reaction of γ-valerolactone and pinacol borane: Add catalyst to the reaction flask after dehydration and deoxygenation under inert gas atmosphere 5.84 mg, use a pipette to add γ-valerolactone (45.3 μL, 0.5 mmol), pinacol borane (159.6 μL, 1.1 mmol), THF (200 μL), and after ^{reacting at 25 o} C for 20 min, Use mesitylene (69.6 μL, 0.5 mmol) as the internal standard, stir evenly, use a dropper to pipette a drop into the NMR tube, and add CDCl _{3 to make a} solution. The calculated ¹ H spectrum yield is 30%.

Example 4: [L ^ph ^' Li ₄ (THF) ₄ ] ₂ catalyzes the reduction reaction of γ-valerolactone and pinacol borane: Add catalyst to the reaction flask after dehydration and deoxygenation under an inert gas atmosphere 5.84 mg, use a pipette to add γ-valerolactone (45.3 μL, 0.5 mmol), pinacol borane (159.6 μL, 1.1 mmol), THF (200 μL), and after ^{reacting at 25 o} C for 120 min, Use mesitylene (69.6 μL, 0.5 mmol) as the internal standard, stir evenly, use a dropper to pipette a drop into the NMR tube, and add CDCl _{3 to make a} solution. The calculated ¹ H spectrum yield is 98%. NMR data of the product: ¹ H NMR (400 MHz, CDCl ₃ ) δ 3.82 (t, J = 6.5 Hz, 4H, OCH ₂ ), 1.58 (dt, J = 14.6, 6.8 Hz, 4H, CH ₂ ), 1.43- 1.36 (m, 2H, CH ₂ ), 1.23 (s, 24H, OBpin).

Example 5: [L ^ph ^' Li ₄ (THF) ₄ ] ₂ catalyzes the reduction reaction of methyl p-bromobenzoate and pinacol borane: In an inert gas atmosphere, add to the reaction flask after dehydration and deoxygenation treatment Catalyst 5.84 mg, add methyl p-bromobenzoate (107.52 mg, 0.5 mmol), pinacol borane (159.6 μL, 1.1 mmol), THF (200 μL), and ^{react at 60 o} C for 120 min with a pipette Then, use mesitylene (69.6 μL, 0.5 mmol) as the internal standard, stir evenly, use a dropper to pipette a drop into the NMR tube, and add CDCl _{3 to make a} solution. The calculated ¹ H spectrum yield is 98%. NMR data of the product: ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.40 (d, J = 8.3 Hz, 2H, ArCH), 7.17 (d, J = 8.2 Hz, 2H, ArCH), 4.82 (s, 2H, OCH ₂ ), 1.20 (s, 12H, OBpin), 1.19 (s, 12H, OBpin).

Comparative example: The catalyst is replaced with the same molar amount:

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Under an inert gas atmosphere, 1.08 mg of catalyst was added to the reaction flask after dehydration and deoxygenation, and methyl p-bromobenzoate (107.52 mg, 0.5 mmol), pinacol borane (159.6 μL, 1.1 mmol), THF (200 μL), ^{react at 60 o} C for 120 min, use mesitylene (69.6 μL, 0.5 mmol) as the internal standard, stir evenly, pipette a drop into the NMR tube, add CDCl _{3 Make a} solution. The calculated ¹ H spectrum yield is 25%.

Internal standard calculation yield:

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The method for purifying boric acid esters of the present invention: after the reaction, the reaction mixture in the reaction flask is filtered, the filtrate is put into a vacuum drying oven, and excess pinacol borane and solvent THF are removed under reduced pressure to obtain pure boron Acid ester products.

β-Ketimines, as an important class of non-locene ligands, are easy to synthesize. Their charge and steric effects can be conveniently controlled by changing the substituents at the α and β positions, and they can interact with metals through a variety of coordination methods. Coordination to form a variety of metal complexes and other characteristics. However, compared with the study of β-diimine anionic ligands in organometallic chemistry, there are few reports on the application of β-ketimine anionic ligands. Existing reports focus on the complexes with single anion β-ketimine as the backbone. There has been no report on the compound (complex) of the double anion β-ketimine ligand so far.

In the present invention, when the β-ketimine ligand L ^ph H ₂ bridged by o-phenyl is reacted with four times equivalent of n-butyl lithium hexane solution in THF, the deprotonated o-phenyl bridge can be conveniently obtained. Connected β-ketimine lithium compound, in this compound, each β-ketimine unit is a di-anion, and the di-anion β-ketimine group is a kind of very active group, such as It can react with small molecules containing active hydrogen and small organic molecules with unsaturated bonds. At the same time, the compound can also be used as a precursor for the further synthesis of di-anion β-ketimine rare earth metal complexes. This compound is applied to the hydroboration reaction of esters, when 1 mol% deprotonated phenyl bridged β-ketimide lithium compound is used as a catalyst, the reaction temperature is 25-60 ^o C, and the reaction time is 120 min. Efficient reduction of esters and pinacol borane.

Claims

The application of the deprotonated phenyl bridged β-ketimide lithium compound in the hydroboration reaction is characterized in that the hydroboration reaction uses ester and borane as the reaction substrate; the deprotonated phenyl bridged β- The chemical structure of the lithium ketimide compound is as follows:

.
The application according to claim 1, wherein the temperature of the borohydride reaction is between room temperature and 60 °C , and the time is between 1.5 and 2.5 hours.
The application according to claim 1, wherein the borane is pinacol borane; the ester is γ-valerolactone, methyl acetate, benzyl benzoate, methyl benzoate, 4 -Methyl bromobenzoate.
The application according to claim 1, characterized in that the small molecule organolithium solution is mixed with the ligand solution, and then reacted to obtain the catalyst deprotonated phenyl bridged β-ketoimide lithium compound; the chemistry of the ligand The structural formula is as follows:

.
A method for synthesizing boric acid esters includes the following steps: using a deprotonated phenyl bridged β-ketimide lithium compound as a catalyst, esters and boranes as raw materials, and preparing boric acid esters through a borohydride reaction; The chemical structure of the proton phenyl bridged β-ketimide lithium compound is as follows:

.
The method for synthesizing boric acid esters according to claim 5, wherein the amount of the catalyst is 1% of the molar amount of the ester, and the molar ratio of the borane to the ester is 2.2:1.