Catalyst composition and application thereof in catalytic preparation of optically active secondary alcohol

Abstract

The invention relates to a catalyst composition and application thereof in catalytic preparation of optically active secondary alcohols, the catalyst composition comprises a chiral ionic bridged aryloxy alkoxy rare earth complex and an additive, and the additive is selected from one or more of pyrimidine, N, N-dicyclohexylmethylamine and 4, 4 '-dipyridyl. The catalyst composition can be used for synergistically catalyzing an asymmetric hydroboration reaction of chalcone and derivatives thereof and pinacolborane, and shows high catalytic activity and high enantioselectivity, the product yield is up to 99%, the ee value can reach 84%, and a reliable new way is provided for efficient and high-selectivity synthesis of optically active secondary alcohol.

Description

Technical Field

[0001] This invention relates to the fields of catalysis and organic synthesis, specifically to a catalyst composition and its application in the catalytic preparation of optically active secondary alcohols. Background Technology

[0002] Optically active secondary alcohols are a class of key chiral structural units, widely found in various natural products and pharmaceutical active molecules, and often used as important synthetic precursors for constructing complex bioactive molecules. As high-value intermediates in organic synthesis, these compounds provide well-defined chiral environments and are therefore often considered important chiral source reagents, playing an irreplaceable role in asymmetric synthesis. Among these, the asymmetric hydroboration reduction of ketones is the most direct and convenient method for obtaining optically active secondary alcohols.

[0003] Chalcones and their derivatives, as a class of structurally unique α,β-unsaturated ketones, exhibit significant bioactivity potential in their hydroboration reduction products—chiral diaryl methanols. Therefore, developing efficient and highly selective catalytic systems to achieve the asymmetric hydroboration of these substrates holds significant synthetic value and application prospects. However, achieving highly enantioselective hydroboration remains a challenge due to the competitive reduction potential of both the carbonyl group and the carbon-carbon double bond in chalcone substrates, and the higher demands placed on the stereocontrol ability of catalysts by their conjugated structures.

[0004] To address this challenge, researchers have focused on developing novel metal-catalyzed systems. For example, in 2018, Koert's group reported a catalytic system using bis-(1,5-cyclooctadiene)nickel and a chiral oxazoline ligand for the asymmetric hydroboration reduction of β-fluoroenones (Org. Lett. 2018, 20, 5071). However, this system exhibits low catalytic efficiency and poor generalizability across different substrates, with some products yielding only 12% and enantioselectivity (ee value) as low as 30%, limiting its practical application. In recent years, rare earth metal complexes have shown great potential in the field of asymmetric catalysis due to their unique Lewis acidity and coordination diversity. In 2020, Zhao Bei's research group successfully synthesized binuclear, diligandic rare-earth complexes by combining Trost ligands with a bridged proline structure with trisilane rare earth elements. They applied these complexes to the asymmetric hydroboration of simple ketones, achieving extremely high yields and excellent enantioselectivity (J. Org. Chem. 2020, 85, 10504). However, when this catalytic system was applied to chalcone substrates, although the reactivity was high, the enantioselectivity (ee value) of the product was only about 30%, indicating a significant deficiency in its ability to stereocontrol α,β-unsaturated ketones.

[0005] Chiral ionic bridged aryloxyalkane-oxyrare earth complexes, as a novel and tunable class of catalysts, have demonstrated excellent catalytic activity and high enantioselectivity in various asymmetric reactions such as hydrogenation and cycloaddition. However, the inventors discovered that when these high-performance complexes were directly applied to the asymmetric hydroboration reaction of chalcone and pinacol borane, a discrepancy arose between their performance in other systems: although the catalytic activity was maintained, the enantioselectivity (ee value) of the product was significantly lower. This contradiction of "high activity, low selectivity" highlights the inherent limitations of this type of catalyst in this specific reaction.

[0006] In summary, although significant progress has been made in the asymmetric hydroboration of ketones, existing catalytic systems for electron-deficient α,β-unsaturated ketones such as chalcones and their derivatives generally suffer from poor enantioselectivity or low catalytic efficiency, and highly efficient and selective catalytic schemes remain scarce. Therefore, there is an urgent need for a catalytic system that can be used to catalyze the asymmetric hydroboration of chalcones and their derivatives, possessing both high catalytic activity and high enantioselectivity, thus providing a reliable new route for the efficient and selective synthesis of optically active secondary alcohols. Summary of the Invention

[0007] To address the problems of poor enantioselectivity or low catalytic efficiency in existing catalytic systems for the asymmetric hydroboration of chalcones and their derivatives, and the insufficient enantioselectivity of high-performance chiral ionic bridged aryloxyalkane-oxyrare earth complexes in catalyzing the asymmetric hydroboration of chalcones, this invention provides a catalyst composition and its application in the catalytic preparation of optically active secondary alcohols. This catalyst composition comprises a chiral ionic bridged aryloxyalkane-oxyrare earth complex and specific additives, and can be used to synergistically catalyze the asymmetric hydroboration of chalcones and their derivatives with pinacol borane, exhibiting high catalytic activity and high enantioselectivity, thereby achieving the efficient preparation of various optically active secondary alcohols.

[0008] Specifically, the following technical solutions are provided: The first aspect of this invention provides a catalyst composition comprising a chiral ionic bridged aryloxyalkoxyrare earth complex and an additive; wherein... The structure of the chiral ionic bridged aryloxyalkane rare earth complex is shown below: , RE represents rare earth elements Lu, Yb, Gd, Sm, Nd, or Y; Ph represents phenyl. t Bu is tert-butyl; The additive is selected from one or more of pyrimidine, N,N-dicyclohexylmethylamine, and 4,4′-bipyridine.

[0009] This invention is an unexpected discovery made by the inventors during their research on the asymmetric hydroboration of chalcone catalyzed by chiral ionic bridged aryloxyalkane-rare earth complexes. Since chiral ionic bridged aryloxyalkane-rare earth complexes have exhibited excellent catalytic activity and high enantioselectivity in various asymmetric reactions such as hydrogenation and cycloaddition, the inventors attempted to apply these high-performance complexes to the asymmetric hydroboration of chalcone with pinacol borane. However, the results showed that although the catalytic activity was high, the enantioselectivity of the product was only about 25%, limiting the practical application of these chiral ionic bridged aryloxyalkane-rare earth complexes in the catalytic preparation of optically active secondary alcohols.

[0010] Based on this, the inventors attempted to introduce additives to modulate the catalytic performance of chiral ionic bridged aryloxyalkane-oxyrare earth complexes through coordination, electrostatic interactions, or influencing the reaction microenvironment. However, the impact of additive introduction on the reaction system is often unpredictable, and the following situations may occur: a significant decrease in catalytic activity, leading to a reduction in reaction efficiency; or the activity being suppressed while enantioselectivity is not improved or even decreased; or a slight increase in selectivity at the cost of a sharp slowdown in the reaction rate. Building on this, the inventors unexpectedly discovered through extensive experiments that introducing specific additives, such as pyrimidines and N,N... into the catalytic system of chiral ionic bridged aryloxyalkane-oxyrare earth complexes... - Dicyclohexylmethylamine or 4,4′-bipyridine can significantly improve the enantioselectivity (ee value up to 84%) of chiral ionic bridged aryloxyalkoxyrare earth complexes in the asymmetric hydroboration of chalcones and their derivatives, without significantly affecting or even improving the reactivity (yield up to 99%). Adding trimethylsilane, tetramethylethylenediamine, imidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), sodium carbonate, 2,4,6-trimethylpyridine, 4-aminopyridine, 2-aminomethylpyridine, benzidine, 2,2′-diaminobiphenyl, 3,3′-diaminobiphenyl, 4-phenylpyridine, 2,2′-bipyridine, [4,4′-bipyridine]-2,2′-diamine, 2,2′-dimethyl-4,4′-bipyridine, or [4,4′-bipyridine]-2,2′-dicarboxylic acid not only fails to effectively improve enantioselectivity, but also significantly reduces the catalytic activity of the catalyst (yield drops to 40%) and / or enantioselectivity (ee value drops to 0).

[0011] Further, the catalyst composition comprises a chiral ionic bridged aryloxyalkane lutetium oxide complex and 4,4′-bipyridine. Preferably, the molar ratio of the chiral ionic bridged aryloxyalkane lutetium oxide complex to 4,4′-bipyridine in the catalyst composition is 1:(1-5), such as 1:1, 1:2, 1:3, 1:4, 1:5, etc., including but not limited to the molar ratios listed above, and more preferably 1:3.

[0012] In this invention, the inventors discovered through extensive experiments that both excessive and insufficient 4,4′-bipyridine content in the above-mentioned catalyst composition affect catalytic activity and enantioselectivity. Based on the experimental results, they hypothesized that: 4,4′-bipyridine is a nitrogen-containing organic compound, while rare earth metals are nitrogen-loving elements. Upon addition of 4,4′-bipyridine, the chiral ionic bridged aryloxyalkaneoxetene complex in the system may react in situ with it, undergoing partial ligand exchange to generate a new, more efficient catalytic species. This species simultaneously contains a rare earth metal center, a bipyridine moiety, and a chiral prolyl fragment. When the amount of 4,4′-bipyridine is insufficient, the amount of this new catalytic species is relatively small, resulting in poor enantioselectivity control during catalysis. When 4,4′-bipyridine is in excess, all ligands may be exchanged, resulting in a new catalytic species that does not contain a chiral prolyl fragment, thus weakening the chiral control of the entire catalytic system. Alternatively, in the resulting new chiral catalyst species, the chiral pockets around the rare earth metals may not match the size of the substrate molecule, leading to weakened chiral control. Therefore, the molar ratio of the chiral ionic bridged aryloxyalkaneoxetene complex to 4,4′-bipyridine in the catalyst composition needs to be controlled within a suitable range, such as 1:(1-5), more preferably 1:3, to obtain a catalytic system with both high catalytic activity and high enantioselectivity.

[0013] The second aspect of the present invention provides the application of the catalyst composition described in the first aspect in the catalytic preparation of optically active secondary alcohols.

[0014] Furthermore, the optically active secondary alcohol is prepared by the asymmetric hydroboration reaction of chalcone and its derivatives catalyzed by the catalyst composition.

[0015] Further, under a protective atmosphere, the ketone shown in formula (1) is reacted with pinacolborane in the presence of the catalyst composition and organic solvent. After the reaction is complete, it is quenched to obtain the optically active secondary alcohol shown in formula (2).

[0016] The structures shown in equations (1) and (2) above are as follows: , Where X is N or CH, and R and R' are selected from one of H, CH3, OCH3, CF3, F, Br, Cl, and NO2, respectively.

[0017] Further, the molar ratio of the ketone, pinacol borane, and the chiral ionic bridged aryloxyalkane rare earth complex in the catalyst composition shown in formula (1) is 1:(1.2-1.5):(0.1-1), for example 1:1.2:0.1, 1:1.3:0.1, 1:1.4:0.1, 1:1.5:0.1, 1:1.2:0.2, 1:1.2:0.3, 1:1.2:0.4, 1:1.2:0.5, 1:1.2:0.6, 1:1.2:0.7, 1:1.2:0.8, 1:1.2:0.9, 1:1.2:1, etc.

[0018] Furthermore, the catalyst composition consists of a chiral ionic bridged aryloxyalkane lutetium complex and 4,4′-bipyridine in a molar ratio of 1:3.

[0019] Furthermore, the organic solvent is selected from one or more of toluene, diethyl ether, and anisole, more preferably diethyl ether.

[0020] Furthermore, the reaction temperature is preferably -40~30 ℃, such as -40 ℃, -30 ℃, -20 ℃, -10 ℃, 0 ℃, 10 ℃, 20 ℃, 25 ℃, etc., more preferably -10 ℃; the reaction time is preferably 18-24 h.

[0021] Furthermore, the protective atmosphere is an inert gas and / or nitrogen, such as argon, nitrogen, etc.

[0022] Furthermore, the reaction is quenched using silica gel.

[0023] Furthermore, after the quenching reaction, the product is purified by column chromatography.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides a catalytic composition of a chiral ionic bridged aryloxyalkoxyrare earth complex and a specific additive (e.g., 4,4′-bipyridine), and for the first time applies it to the asymmetric hydroboration reaction of chalcone and its derivatives. Under low rare earth metal complex catalyst dosage and mild reaction conditions, it can efficiently and selectively catalyze the asymmetric hydroboration of chalcone and its derivatives, and has a wide range of applicable substrates. It provides a reliable new route for the efficient and selective synthesis of various optically active secondary alcohols. Detailed Implementation

[0025] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments are not intended to limit the present invention. The raw materials used in the following embodiments are all commercially available, and the specific preparation operations and testing methods involved are all conventional methods in the art.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The terms “comprising” or “including” used in this invention may also be replaced with the closed form “is” or “consisting of”.

[0027] Example 1: This example involves the synthesis of different chiral ionic bridged aryloxyalkane rare earth complexes, as detailed below: Ligand precursor H2L 1 Synthesis: Add 50 mmol of [agent name] to a 250 mL round-bottom flask. S 7.6 mL of diphenylproline and formaldehyde solution were added, followed by 20 mL of methanol. The mixture was reacted at 65 °C for 30 min, then 2,4-di-tert-butylphenol was added and refluxed for 48 h. Heating was then stopped, and the mixture was cooled to room temperature. The mixture was filtered, and the filter cake was recrystallized from anhydrous ethanol. The white solid obtained by filtration was the ligand precursor H2L. 1 The yield is 80%, and the reaction formula is as follows:

[0028] compound H2L 1 The NMR characterization data are as follows: 1 H NMR (400 MHz, CDCl3, 25 °C): δ 7.60(m, 4H, ArH), 7.32 (m, 4H, ArH), 7.21 (m, 1H, ArH), 7.18-7.08 (m, 2H, ArH), 6.70 (s, 1H, ArH), 3.99 (m, 1H, NCH), 3.50 (d, J = 12.6 Hz, 1H, ArCH2), 3.33(d, J = 12.4 Hz, 1H, ArCH2N), 2.90 (s, 1H, NCH2), 2.43 (m, 1H, NCH2N), 2.15-2.01 (m, 1H, CH2CH2), 1.96-1.83 (m, 1H, CH2CH2), 1.70 (m, 2H, CH2CH2), 1.39 (s,9H, C(CH3)3), 1.24 (s, 9H, C(CH3)3).

[0029] Chiral ionic bridged aryloxyalkane-rare earth complexes were prepared according to the following reaction route:

[0030] Preparation of chiral ionic bridged aryloxyalkane lutetium oxide complexes: Under an argon atmosphere, the ligand precursor H2L was added to a strictly dehydrated and deoxygenated reaction flask. 1 (0.943 g, 2 mmol) was dissolved in tetrahydrofuran with thorough stirring and placed in an ice-salt bath. After 10 min, two equivalents of n-butyllithium (4 mmol) were slowly added dropwise using a syringe. After the addition was complete, the mixture was allowed to return to room temperature for one hour. The reaction solution was then added to LuCl3 (0.195 g, 1 mmol) that had been activated with tetrahydrofuran for 12 hours. The solution became clear initially, but gradually turned cloudy after 20 min. After reacting for 24 hours, the mixture was centrifuged, and the supernatant was slightly concentrated. A small amount of n-hexane was added, and the mixture was sealed and allowed to stand for several hours to precipitate colorless crystals. The crystals were recrystallized from tetrahydrofuran-n-hexane, and after being sealed and allowed to stand for several hours, colorless crystals precipitated, which is the ionic bridged aryloxyalkane lutetium oxide complex.

[0031] Preparation of chiral ionic bridged aryloxyalkane ytterbium oxide complexes: The preparation method is the same as that of chiral ionic bridged aryloxyalkane lutetium oxide complexes, except that equimolar amounts of YbCl3 are used instead of LuCl3.

[0032] Preparation of chiral ionic bridged aryloxyalkane-gadolinium complexes: The preparation method is the same as that of chiral ionic bridged aryloxyalkane-lutetium complexes, except that equimolar amounts of GdCl3 are used instead of LuCl3.

[0033] Preparation of chiral ionic bridged aryloxyalkane samarium oxide complexes: The preparation method is the same as that of chiral ionic bridged aryloxyalkane samarium oxide complexes, except that an equimolar amount of SmCl3 is used instead of LuCl3.

[0034] Preparation of chiral ionic bridged aryloxyalkane-neodymium oxide complexes: The preparation method is the same as that of chiral ionic bridged aryloxyalkane-lutetium oxide complexes, except that an equimolar amount of NdCl3 is used instead of LuCl3.

[0035] Preparation of chiral ionic bridged aryloxyalkane yttrium complexes: The preparation method is the same as that for chiral ionic bridged aryloxyalkane lutetium complexes, except that equimolar amounts of YCl3 are used instead of LuCl3.

[0036] Example 2: This example involves the asymmetric hydroboration reaction of chalcones catalyzed by different chiral ionic bridged aryloxyalkane-rare earth complexes to prepare optically active secondary alcohols with the following structures: * indicates that it is a chiral carbon.

[0037] The specific steps are as follows: Under anhydrous and oxygen-free conditions and under argon protection, 0.03 mmol of a chiral ionic bridged aryloxyalkane-oxyrare earth complex was added to a reaction flask, followed by 2 mL of toluene, then 0.36 mmol of pinacol borane. The mixture was stirred at -10 °C for 30 min, and finally 0.3 mmol of chalcone was added. The flask was sealed and the reaction was carried out at -10 °C for 24 hours. The reaction was quenched with silica gel powder after opening the flask. Column chromatography was performed using petroleum ether and ethyl acetate as developing solvents. The product 1,3-diphenylprop-2-en-1-ol was collected. The main product was in the R configuration. Its NMR characterization data are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.31 (m, 6H, Ph), 7.22 (m, 3H, Ph), 7.15 (m, 1H, Ph), 6.61 (d, 1H, J = 15.84 Hz, CH=CH), 6.31 (dd, J 1 = 15.84 Hz, J 2= ​​6.60 Hz,1H, CH=CH), 5.30 (d, J = 6.36 Hz, 1H, CH), 2.04 (s, 1H, OH).

[0038] The yields and ee values ​​of the products prepared by the asymmetric hydroboration of chalcones catalyzed by different chiral ionic bridged aryloxyalkoxide rare earth complexes are shown in the table below:

[0039] As shown in the table above, although the asymmetric hydroboration of chalcone catalyzed by chiral ionic bridged aryloxyalkoxyrare earth complexes has high reactivity, the enantioselectivity is poor and the product ee value does not exceed 25%.

[0040] Example 3: This example uses chiral ionic bridged aryloxyalkane lutetium oxide complexes with different additive combinations to catalyze the asymmetric hydroboration reaction of chalcones to prepare optically active secondary alcohols. The effects of additive types on catalytic activity and enantioselectivity are studied. The specific operation is as follows: Under anhydrous and oxygen-free conditions and under argon protection, 0.03 mmol of an ionic bridged aryloxyalkane lutetium oxide complex was added to a reaction flask, followed by 2 mL of toluene and 0.06 mmol of additive. After stirring at -10 °C for 15 min, 0.36 mmol of pinacol borane was added, and the mixture was stirred at -10 °C for 30 min. Finally, 0.3 mmol of chalcone was added, the tube was sealed, and the reaction was carried out at -10 °C for 24 hours. The reaction was quenched with silica gel powder after opening the flask, and column chromatography was performed using petroleum ether and ethyl acetate as developing solvents. The product 1,3-diphenylprop-2-en-1 alcohol was collected, with the main product being the R configuration.

[0041] The yields and ee values ​​of the products prepared by the asymmetric hydroboration of chalcones catalyzed by different additives and chiral ionic bridged aryloxyalkoxylutetium complexes are shown in the table below:

[0042] As shown in the table above, the effects of introducing additives into the catalytic system of chiral ionic bridged aryloxyalkane-oxyrare earth complexes on the reaction system are difficult to predict. For example, the introduction of tetramethylethylenediamine, imidazole, 4-aminopyridine, benzidine, 2,2′-diaminobiphenyl, 3,3′-diaminobiphenyl, [4,4′-bipyridine]-2,2′-diamine, or [4,4′-bipyridine]-2,2′-dicarboxylic acid not only failed to improve enantioselectivity but even significantly reduced it, and the activity was also greatly reduced. The introduction of trimethylsilane, sodium carbonate, or 2,2′-dimethyl-4,4′-bipyridine, while improving enantioselectivity, significantly reduced the reaction activity. The addition of pyrimidines, N,N -Dicyclohexylmethylamine or 4,4′-bipyridine can maintain high catalytic activity while significantly improving enantioselectivity. In particular, the combination of 4,4′-bipyridine as an additive with a chiral ionic bridged aryloxyalkoxylutetium complex to catalyze the asymmetric hydroboration of chalcones increases the ee value to 67%.

[0043] Example 4: This example uses a chiral ionic bridged aryloxyalkane lutetium oxide complex combined with 4,4′-bipyridine to catalyze the asymmetric hydroboration of chalcones to prepare optically active secondary alcohols. The effect of the amount of 4,4′-bipyridine added on catalytic activity and enantioselectivity is studied. The specific operation is as follows: Under anhydrous and oxygen-free conditions and under argon protection, 0.03 mmol of an ionic bridged aryloxyalkane lutetium oxide complex was added to a reaction flask, followed by 2 mL of toluene. Different amounts of additives were added (1.0 equivalent: 0.03 mol, 2.0 equivalent: 0.06 mol, 3.0 equivalent: 0.09 mol, 5.0 equivalent: 0.15 mol, 10.0 equivalent: 0.3 mol). After stirring at -10 °C for 15 min, 0.36 mmol of pinacol borane was added, and the mixture was stirred at -10 °C for 30 min. Finally, 0.3 mmol of chalcone was added, the tube was sealed, and the reaction was carried out at -10 °C for 24 hours. The reaction was quenched with silica gel powder after opening the flask, and column chromatography was performed using petroleum ether and ethyl acetate as developing solvents. The product 1,3-diphenylprop-2-en-1 alcohol was collected, with the main product being the R configuration.

[0044] The yields and ee values ​​of the products prepared by the asymmetric hydroboration of chalcones catalyzed by combinations of 4,4′-bipyridine and chiral ionic bridged aryloxyalkoxylutetium complexes are shown in the table below:

[0045] As shown in the table above, both insufficient and excessive addition of 4,4′-bipyridine will affect the catalytic activity and enantioselectivity of the chiral ionic bridged aryloxyalkane lutetium oxide complex. In particular, when the chiral ionic bridged aryloxyalkane lutetium oxide complex and 4,4′-bipyridine are combined in a molar ratio of 1:3 for catalysis, the ee value of the product can be further increased to 72%.

[0046] Example 5: In this example, a chiral ionic bridged aryloxyalkane lutetium oxide complex and 4,4′-bipyridine were combined in a molar ratio of 1:3 to catalyze the asymmetric hydroboration of chalcones to prepare optically active secondary alcohols. The effects of different solvents on catalytic activity and enantioselectivity were investigated. The specific operation is as follows: Under anhydrous and oxygen-free conditions and under argon protection, 0.03 mmol of an ionic bridged aryloxyalkane lutetium oxide complex was added to a reaction flask, followed by 2 mL of solvent and 0.09 mmol of 4,4′-bipyridine. After stirring at -10 °C for 15 min, 0.36 mmol of pinacol borane was added, and the mixture was stirred at -10 °C for 30 min. Finally, 0.3 mmol of chalcone was added, the tube was sealed, and the reaction was carried out at -10 °C for 24 hours. The reaction was quenched with silica gel powder after opening the flask, and column chromatography was performed using petroleum ether and ethyl acetate as developing solvents. The product 1,3-diphenylprop-2-en-1 alcohol was collected, with the main product being the R configuration.

[0047] The yields and ee values ​​of the products prepared by the asymmetric hydroboration of chalcones in different solvents using 4,4′-bipyridine and chiral ionic bridged aryloxyalkane lutetium oxide complexes in combination catalyzed by different solvents are shown in the table below:

[0048] As shown in the table above, in the asymmetric hydroboration of chalcone catalyzed by a combination of 4,4′-bipyridine and chiral ionic bridged aryloxyalkoxylutetium complexes, the type of solvent has a significant impact on the catalytic activity and enantioselectivity of the catalyst. When 2-methyltetrahydrofuran, phenethyl ether, 1,2-dichloroethane, 1,2-dibromoethane, acetonitrile, etc. are used as solvents, both the catalytic activity and enantioselectivity are significantly reduced, and the product ee value even drops to 0. However, when ether is used as a solvent, the enantioselectivity is further improved while maintaining high catalytic activity.

[0049] Example 6: In this example, a chiral ionic bridged aryloxyalkane lutetium oxide complex and 4,4′-bipyridine were combined in a molar ratio of 1:3 to catalyze the asymmetric hydroboration of chalcones to prepare optically active secondary alcohols. The effects of different reaction temperatures on catalytic activity and enantioselectivity were investigated. The specific operation is as follows: Under anhydrous and oxygen-free conditions and under argon protection, 0.03 mmol of an ionic bridged aryloxyalkane lutetium oxide complex was added to a reaction flask, followed by 2 mL of diethyl ether and 0.09 mmol of 4,4′-bipyridine. After stirring at a certain temperature for 15 min, 0.36 mmol of pinacol borane was added, and the mixture was stirred at a certain temperature for 30 min. Finally, 0.3 mmol of chalcone was added, the tube was sealed, and the reaction was carried out at a certain temperature (reaction temperature) for 24 hours. The reaction was quenched with silica gel powder after opening the flask, and column chromatography was performed using petroleum ether and ethyl acetate as developing solvents. The product 1,3-diphenylprop-2-en-1 alcohol was collected, and the main product was in the R configuration.

[0050] The yields and ee values ​​of the products prepared by the asymmetric hydroboration of chalcones using 4,4′-bipyridine and chiral ionic bridged aryloxyalkane lutetium oxide complexes at different temperatures are shown in the table below:

[0051] As shown in the table above, in the asymmetric hydroboration reaction of chalcone catalyzed by the combination of 4,4′-bipyridine and chiral ionic bridged aryloxyalkoxylutetium complex, the reaction temperature affects the catalytic activity and enantioselectivity of the catalyst. In the range of -40 to -10℃, the yield and ee value of the product both increase with the increase of the reaction temperature. When the temperature is further increased, the yield of the product does not change, but the ee value decreases.

[0052] Example 7: In this example, a chiral ionic bridged aryloxyalkane lutetium oxide complex and 4,4′-bipyridine were combined in a molar ratio of 1:3 to catalyze the asymmetric hydroboration of chalcone derivatives to prepare optically active secondary alcohols. The effects of different substrates on catalytic activity and enantioselectivity were investigated. The specific operation is as follows: Under anhydrous and oxygen-free conditions and under argon protection, 0.03 mmol of a chiral ionic bridged aryloxyalkane lutetium oxide complex was added to a reaction flask, followed by 2 mL of diethyl ether and 0.09 mmol of 4,4′-bipyridine. After stirring at -10 °C for 15 min, 0.36 mmol of pinacol borane was added, and the mixture was stirred at -10 °C for 30 min. Finally, 0.3 mmol of a chalcone derivative was added, the flask was sealed, and the reaction was carried out at -10 °C for 24 hours. The reaction was quenched with silica gel powder after opening the flask, and column chromatography was performed using petroleum ether and ethyl acetate as developing solvents to collect the product.

[0053] The yields and ee values ​​of the products prepared by the asymmetric hydroboration of different chalcone derivatives catalyzed by 4,4′-bipyridine and chiral ionic bridged aryloxyalkoxylutetium complexes are shown in the table below:

[0054]

[0055]

[0056] As shown in the table above, the catalyst composition of 4,4′-bipyridine and chiral ionic bridged aryloxyalkoxylutetium complex can be used to catalyze the asymmetric hydroboration reaction of different chalcone derivatives, and exhibits high reactivity and better enantioselectivity, making it suitable for the efficient preparation of different optically active secondary alcohols.

[0057] The above-described embodiments are merely preferred embodiments provided to fully illustrate the present invention, and the scope of protection of the present invention is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the claims.

Claims

1. A catalyst composition, characterized in that, It includes chiral ionic bridged aryloxyalkane-oxyrare earth complexes and additives; among which... The structure of the chiral ionic bridged aryloxyalkane rare earth complex is shown below: ， RE represents rare earth elements Lu, Yb, Gd, Sm, Nd, or Y; The additive is selected from one or more of pyrimidine, N,N-dicyclohexylmethylamine, and 4,4′-bipyridine.

2. The catalyst composition according to claim 1, characterized in that, The catalyst composition consists of a chiral ionic bridged aryloxyalkoxylutetium complex and 4,4′-bipyridine.

3. The catalyst composition according to claim 2, characterized in that, The molar ratio of the chiral ionic bridged aryloxyalkoxylutetium complex to 4,4′-bipyridine in the catalyst composition is 1:(1-5).

4. The use of a catalyst composition according to any one of claims 1-3 in the catalytic preparation of optically active secondary alcohols.

5. The application according to claim 4, characterized in that, Under a protective atmosphere, the ketone shown in formula (1) was reacted with pinacolborane in the presence of the catalyst composition and organic solvent. After the reaction was completed, the reaction was quenched to obtain the optically active secondary alcohol shown in formula (2). The structures shown in equations (1) and (2) above are as follows: ， Where X is N or CH, and R and R' are selected from one of H, CH3, OCH3, CF3, F, Br, Cl, and NO2, respectively.

6. The application according to claim 5, characterized in that, The molar ratio of the ketone, pinacol borane, and the chiral ionic bridged aryloxyalkane rare earth complex in the catalyst composition shown in formula (1) is 1:(1.2-1.5):(0.1-1).

7. The application according to claim 6, characterized in that, The catalyst composition consists of a chiral ionic bridged aryloxyalkane lutetium complex and 4,4′-bipyridine in a molar ratio of 1:

3.

8. The application according to claim 5, characterized in that, The organic solvent is selected from one or more of toluene, diethyl ether, and anisole.

9. The application according to claim 5, characterized in that, The reaction is carried out at a temperature of -40 to 30 °C for 18 to 24 hours.

10. The application according to claim 5, characterized in that, It must contain at least one of the following characteristics: (1) The protective atmosphere is an inert gas and / or nitrogen; (2) The reaction was quenched using silica gel; (3) After the quenching reaction, the product is purified by column chromatography.

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