A catalyst composition and its use in the catalytic preparation of optically active secondary alcohols

Abstract

The present application relates to a kind of catalyst composition and its application in catalytic preparation optically active secondary alcohol, the catalyst composition includes chiral ionic bridged aryloxyalkane rare earth complex and additive, the additive is selected from one or more of pyrimidine, N,N-dicyclohexylmethylamine, 4,4'-dipyridyl.The above-mentioned catalyst composition can be used for synergistically catalyzing asymmetric borohydration of chalcone and its derivatives with pinacol borane, and show high catalytic activity and high enantioselectivity, product yield is as high as 99%, ee value can reach 84%, provide a reliable new way for the efficient, high selective synthesis of optically active secondary alcohol.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of catalysis and organic synthesis, in particular to a catalyst composition and its application in catalytic preparation of optically active secondary alcohol. BACKGROUND

[0002] Optically active secondary alcohol is a kind of key chiral structural unit, which not only exists widely in various natural products and drug active molecules, but also is often used as an important synthetic precursor to construct complex bioactive molecules. As high-value intermediates in organic synthesis, such compounds can provide a clear chiral environment, and thus are often regarded as important chiral source reagents, playing an irreplaceable role in asymmetric synthesis. Among them, the asymmetric borohydride reduction of ketone is the most direct and convenient method to obtain optically active secondary alcohol.

[0003] Chalcone and its derivatives, as a class of special α,β-unsaturated ketones, have significant biological activity potential. Therefore, developing an efficient and highly selective catalytic system to realize the asymmetric borohydride reduction of such substrates has important synthetic value and application prospect. However, due to the competitive reduction possibility of both carbonyl and carbon-carbon double bond in chalcone substrate, and the higher requirement of its conjugated structure on the stereocontrol ability of the catalyst, it has been a challenge to realize the borohydride reduction with high enantioselectivity.

[0004] In order to overcome this challenge, researchers have been committed to developing new metal catalytic systems. For example, in 2018, Koert group reported the use of a catalytic system composed of bis-(1,5-cyclooctadiene) nickel and chiral oxazoline ligand for the asymmetric borohydride reduction of β-fluoro enone compounds (Org. Lett. 2018, 20, 5071). However, the catalytic efficiency of this system is low, and the universality for different substrates is poor, with the yield of some products only 12% and the enantioselectivity (ee value) as low as 30%, which limits its practical application. In recent years, rare earth metal complexes have shown great potential in asymmetric catalysis due to their unique Lewis acidity and coordination diversity. In 2020, Zhao Bei group combined Trost ligand with trisilane rare earth metal to successfully synthesize binuclear double ligand rare earth complex, and applied it to the asymmetric borohydride reduction of simple ketones, achieving very high yield and excellent enantioselectivity (J. Org. Chem. 2020, 85, 10504). However, when this catalytic system is applied to chalcone substrates, although the reaction activity is very high, the enantioselectivity (ee value) of the product is only about 30%, indicating that its stereocontrol ability for α,β-unsaturated ketones is obviously insufficient.

[0005] Chiral ionic bridged aryloxoalkoxo rare earth complexes, as a class of catalysts with novel structure and tunable performance, have been proved to be of excellent catalytic activity and high enantioselectivity in a variety of asymmetric reactions such as hydrogenation and cycloaddition. However, the inventors found that when such excellent performance complexes were directly applied to the asymmetric borohydration of chalcone with pinacolborane, a situation inconsistent with their performance in other systems occurred: although the catalytic activity was maintained, the enantioselectivity (ee value) of the product was significantly low. This contradiction of "high activity and low selectivity" highlights the inherent limitations of this class of catalysts when faced with this particular reaction.

[0006] In summary, although significant progress has been made in the asymmetric borohydration of ketones, for electron-deficient α,β-unsaturated ketones such as chalcones and their derivatives, existing catalytic systems generally have the problem of poor enantioselectivity or low catalytic efficiency, and efficient and selective catalytic schemes are still lacking. Therefore, there is an urgent need for a catalytic system that can be used to catalyze the asymmetric borohydration of chalcones and their derivatives, and has high catalytic activity and high enantioselectivity, thereby providing a reliable new approach for the efficient and selective synthesis of optically active secondary alcohols. SUMMARY

[0007] To solve the problem of poor enantioselectivity or low catalytic efficiency of existing catalytic systems for the asymmetric borohydration of chalcones and their derivatives, and the defect of poor enantioselectivity of excellent chiral ionic bridged aryloxoalkoxo rare earth complexes in catalyzing the asymmetric borohydration of chalcones, the present application provides a catalyst composition and its application in the catalytic preparation of optically active secondary alcohols. The catalyst composition comprises a chiral ionic bridged aryloxoalkoxo rare earth complex and a specific additive, which can be used to synergistically catalyze the asymmetric borohydration of chalcones and their derivatives with pinacolborane, and exhibits high catalytic activity and high enantioselectivity, thereby achieving efficient preparation of different optically active secondary alcohols.

[0008] Specifically, the following technical solutions are provided:

[0009] The first aspect of the present application provides a catalyst composition comprising a chiral ionic bridged aryloxoalkoxo rare earth complex and an additive; wherein,

[0010] The structure of the chiral ionic bridged aryloxoalkoxo rare earth complex is as follows:

[0011] ,

[0012] RE is a rare earth element Lu, Yb, Gd, Sm, Nd or Y; Ph is a phenyl group, t Bu is a tert-butyl group;

[0013] The additive is selected from one or more of pyrimidine, N,N-dicyclohexylmethylamine, 4,4'-bipyridine.

[0014] The present application is an unexpected discovery of the inventors in the process of studying the asymmetric borohydride reaction of chalcone catalyzed by chiral ionic bridged aryloxyalkoxyl rare earth complexes. Since chiral ionic bridged aryloxyalkoxyl rare earth complexes have shown excellent catalytic activity and high enantioselectivity in hydrogenation, cycloaddition and other asymmetric reactions, the inventors tried to apply such excellent complexes to the asymmetric borohydride reaction of chalcone and pinacolborane. However, the results showed that although the catalytic activity was high, the enantioselectivity of the product was only about 25%, which limited the practical application of such chiral ionic bridged aryloxyalkoxyl rare earth complexes in the catalytic preparation of optically active secondary alcohols.

[0015] Therefore, the inventors tried to introduce additives to regulate the catalytic performance of the chiral ionic bridged aryloxyalkoxyl rare earth complexes by coordination, electrostatic interaction or influencing the reaction microenvironment. However, the introduction of additives often has unpredictable effects on the reaction system, which may result in the following situations: significant decrease in catalytic activity, leading to reduced reaction efficiency; or inhibition of activity while no improvement or even decrease in enantioselectivity; or slight improvement in selectivity at the cost of a sharp decrease in reaction rate. Based on this, the inventors unexpectedly found that the introduction of specific additives, such as pyrimidine, N,N - Dicyclohexylmethylamine or 4,4'-bipyridine can significantly improve the enantioselectivity (ee value up to 84%) of chiral ionic bridged aryloxyalkoxyl rare earth complexes in the asymmetric borohydride reaction of chalcone and its derivatives, and the reaction activity is not significantly affected or even improved (yield up to 99%). However, the introduction of 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, etc. not only cannot effectively improve the enantioselectivity, but also greatly reduces the catalytic activity (yield reduced to 40%) and / or enantioselectivity (ee value reduced to 0) of the catalyst.

[0016] Further, the catalyst composition consists of the chiral ionic bridged aryloxy luteum complex and 4,4'-bipyridine, preferably, the molar ratio of the chiral ionic bridged aryloxy luteum complex to 4,4'-bipyridine in the catalyst composition is 1:(1-5), for example 1:1, 1:2, 1:3, 1:4, 1:5, etc., including but not limited to the above-mentioned molar ratio, more preferably 1:3.

[0017] In the present application, the inventors have found through a large number of experiments that too much or too little 4,4'-bipyridine in the above-mentioned catalyst composition will affect the catalytic activity and enantioselectivity, and based on the experimental results, the following is speculated: 4,4'-bipyridine is a nitrogen-containing organic compound, and rare earth metals are elements that are attracted to nitrogen. After adding 4,4'-bipyridine, the chiral ionic bridged aryloxy luteum complex in the system may react in situ, undergo partial ligand exchange, and generate a new more efficient catalytic species that contains a rare earth metal center, a bipyridine part, and a chiral prolinol fragment. When the amount of 4,4'-bipyridine is insufficient, the amount of this new catalytic species is small, so the enantioselectivity control during catalysis is poor. When 4,4'-bipyridine is excessive, complete ligand exchange may occur, resulting in a new catalytic species that does not contain a chiral prolinol fragment, thereby weakening the chiral control ability of the entire catalytic system; or the chiral pocket around the rare earth metal in the new chiral catalyst species may not match the size of the substrate molecule, resulting in weakened chiral control. Therefore, the molar ratio of the chiral ionic bridged aryloxy luteum complex to 4,4'-bipyridine in the catalyst composition needs to be controlled within a suitable range, for example 1:(1-5), more preferably 1:3, so as to obtain a catalytic system with high catalytic activity and high enantioselectivity.

[0018] The second aspect of the present application provides a use of the catalyst composition of the first aspect in the catalytic preparation of optically active secondary alcohols.

[0019] Further, the optically active secondary alcohol is prepared by the asymmetric borohydride reaction of chalcone and its derivatives catalyzed by the catalyst composition.

[0020] Further, under a protective atmosphere, the ketone shown in formula (1) is reacted with pinacol borane in the presence of the catalyst composition and an organic solvent, and after the reaction is complete, the optically active secondary alcohol shown in formula (2) is obtained.

[0021]

[0022] The structures of the above-mentioned formula (1) and formula (2) are as follows:

[0023] ,

[0024] wherein X is N or CH, and R and R' are independently selected from H, CH3, OCH3, CF3, F, Br, Cl, NO2.

[0025] Further, the molar ratio of the ketone represented by formula (1), pinacolborane and the chiral ionic bridged aryloxyalkane rare earth complex in the catalyst composition 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.

[0026] Further, the catalyst composition is composed of the chiral ionic bridged aryloxyalkane lutetium complex and 4,4'-bipyridine in a molar ratio of 1:3.

[0027] Further, the organic solvent is selected from one or more of toluene, diethyl ether, anisole, and more preferably diethyl ether.

[0028] Further, the temperature of the reaction is preferably -40-30 ℃, for example, -40 ℃, -30 ℃, -20 ℃, -10 ℃, 0 ℃, 10 ℃, 20 ℃, 25 ℃, etc., and more preferably -10 ℃; and the time of the reaction is preferably 18-24 h.

[0029] Further, the protective atmosphere is inert gas and / or nitrogen, for example, argon, nitrogen, etc.

[0030] Further, silica gel is used to quench the reaction.

[0031] Further, after quenching the reaction, the step of purifying the product by column chromatography is further included.

[0032] Compared with the prior art, the present application has the following beneficial effects:

[0033] The present application provides a catalyst composition of a chiral ionic bridged aryloxyalkane rare earth complex and a specific additive (for example, 4,4'-bipyridine), and applies it to the asymmetric borohydration reaction of chalcone and its derivatives for the first time. The catalyst can efficiently and selectively catalyze the asymmetric borohydration of chalcone and its derivatives under low rare earth metal complex catalyst dosage and mild reaction conditions, and is suitable for a wide range of substrates, and provides a reliable new way for the efficient and selective synthesis of different optically active secondary alcohols. DETAILED DESCRIPTION

[0034] The application will be further described in conjunction with specific examples to make those skilled in the art better understand and implement the application, but the examples are not intended to limit the application. The raw materials used in the following examples are commercially available, and the specific preparation operations and test methods involved are conventional methods in the art.

[0035] 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 application belongs. The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the content clearly dictates otherwise. The term "comprising" or "containing" as used herein is to be interpreted in a non-limiting way.

[0036] Example 1: This example relates to the synthesis of different chiral ionic bridged aryloxyalkane rare earth complexes, as follows:

[0037] Synthesis of ligand precursor H2L 1 : In a 250 mL round bottom flask, 50 mmol of S diphenylprolinol and formaldehyde solution 7.6 mL were added, 20 mL of methanol was added, and the reaction was carried out at 65 °C for 30 min, then 2,4-di-tert-butylphenol was added, and the reaction was carried out at reflux for 48 h, then heating was stopped, and the reaction was cooled to room temperature, filtered, and the filter cake was recrystallized with anhydrous ethanol, and filtered to obtain white solid, which was the ligand precursor H2L 1 , yield 80%, and the reaction formula is as follows:

[0038]

[0039] Compound H2L 1 The nuclear magnetic resonance data of compound H2L 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).

[0040] Chiral ionic bridged aryloxyalkane-rare earth complexes were prepared according to the following reaction route:

[0041]

[0042] 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.

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] Preparation of chiral ionic bridged aryloxyalkoxy yttrium complex: the preparation method is consistent with that of chiral ionic bridged aryloxyalkoxy lutetium complex, except that equimolar amount of YCl3 is used instead of LuCl3.

[0048] Example 2: This example relates to the asymmetric borohydration reaction of chalcone catalyzed by different chiral ionic bridged aryloxyalkoxy rare earth complexes alone, to prepare optically active secondary alcohol with the following structure:

[0049] , * represents a chiral carbon.

[0050] The specific operation is as follows:

[0051] Under anhydrous and anaerobic conditions, under argon protection, 0.03 mmol of chiral ionic bridged aryloxyalkoxy rare earth complex is added to a reaction bottle, 2 mL of toluene is then added, followed by 0.36 mmol of pinacol borane, stirring at -10 ℃ for 30 min, and finally 0.3 mmol of chalcone is added, and the tube is sealed for reaction at -10 ℃ for 24 hours. The reaction is quenched with silica gel powder, and column chromatography is performed with petroleum ether and ethyl acetate as developing agents. The product 1,3-diphenylprop-2-en-1-ol is collected, and the main product is in R configuration, with the following NMR characterization data: 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).

[0052] The yield and ee value of the product prepared by the asymmetric borohydration reaction of chalcone catalyzed by different chiral ionic bridged aryloxyalkoxy rare earth complexes as catalysts are shown in the following table:

[0053]

[0054] As can be seen from the above table, the asymmetric borohydration reaction of chalcone catalyzed by chiral ionic bridged aryloxyalkoxy rare earth complexes alone has high reaction activity, but poor enantioselectivity, with the ee value of the product not exceeding 25%.

[0055] Example 3: In this example, the asymmetric borohydration reaction of chalcone catalyzed by the combination of chiral ionic bridged aryloxyalkoxide lutetium complex and different additives was used to prepare optically active secondary alcohol, and the effects of additive types on catalytic activity and enantioselectivity were studied. The specific operation is as follows:

[0056] Under anhydrous and anaerobic conditions, argon protection, 0.03 mmol of ionic bridged aryloxyalkoxide lutetium complex was added to the reaction bottle, 2 mL of toluene was added, 0.06 mmol of additive was added, and after stirring at-10 ℃ for 15 min, 0.36 mmol of pinacol borane was added, and stirred at-10 ℃ for 30 min. Finally, 0.3 mmol of chalcone was added, and the tube was sealed and reacted at-10 ℃ for 24 hours. The reaction was quenched with silica gel powder, and column chromatography was performed with petroleum ether and ethyl acetate as developing agent. The product 1,3-diphenylprop-2-en-1-ol was collected, and the main product was R configuration.

[0057] The yield and ee value of the product prepared by the asymmetric borohydration reaction of chalcone catalyzed by the combination of different additives and chiral ionic bridged aryloxyalkoxide lutetium complex are shown in the following table:

[0058]

[0059] As can be seen from the above table, the introduction of additives into the catalytic system of chiral ionic bridged aryloxyalkoxide rare earth complex has unpredictable effects on the reaction system. For example, the introduction of tetramethyl ethylenediamine, imidazole, 4-aminopyridine, diphenylamine, 2,2'-diaminobiphenyl, 3,3'-diaminobiphenyl, [4,4'-bipyridine]-2,2'-diamine or [4,4'-bipyridine]-2,2'-dicarboxylic acid not only does not improve the enantioselectivity, but also significantly reduces it, and the activity is also greatly reduced. The introduction of trimethylsilane, sodium carbonate or 2,2'-dimethyl-4,4'-bipyridine improves the enantioselectivity, but significantly reduces the reaction activity. However, the addition of pyrimidine, N,N dicyclohexylmethylamine or 4,4'-bipyridine can maintain high catalytic activity while significantly improving enantioselectivity. Especially, the combination of 4,4'-bipyridine as additive and chiral ionic bridged aryloxyalkoxide lutetium complex catalyzing the asymmetric borohydration reaction of chalcone, the ee value is increased to 67%.

[0060] Example 4: In this example, the asymmetric borohydration reaction of chalcone catalyzed by the combination of chiral ionic bridged aryloxyalkoxide lutetium complex and 4,4'-bipyridine was used to prepare optically active secondary alcohol, and the effects of 4,4'-bipyridine addition amount on catalytic activity and enantioselectivity were studied. The specific operation is as follows:

[0061] Under anhydrous and anaerobic condition, 0.03 mmol of ionic bridged aryloxyalkane oxy-lutetium complex was added into a reaction bottle, 2 mL of toluene was added, different contents of additives (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) were added, and the mixture was stirred at -10 ℃ for 15 min, then 0.36 mmol of pinacol borane was added, the mixture was stirred at -10 ℃ for 30 min, finally 0.3 mmol of chalcone was added, the mixture was reacted at -10 ℃ for 24 h, the reaction was quenched by silica gel powder, and column chromatography was performed with petroleum ether and ethyl acetate as developing agents, and the product 1,3-diphenylprop-2-en-1-ol was collected, and the main product was in R configuration.

[0062] The yield and ee value of the product prepared by the asymmetric borohydration reaction of chalcone catalyzed by the combination of different contents of 4,4'-bipyridine and chiral ionic bridged aryloxyalkane oxy-lutetium complex are shown in the following table:

[0063]

[0064] As shown in the above table, too little or too much 4,4'-bipyridine will affect the catalytic activity and enantioselectivity of the chiral ionic bridged aryloxyalkane oxy-lutetium complex, and when the chiral ionic bridged aryloxyalkane oxy-lutetium complex is combined with 4,4'-bipyridine at a molar ratio of 1:3 for catalysis, the ee value of the product can be further improved to 72%.

[0065] In this embodiment, the optical active secondary alcohol is prepared by the asymmetric borohydration reaction of chalcone catalyzed by the combination of chiral ionic bridged aryloxyalkane oxy-lutetium complex and 4,4'-bipyridine at a molar ratio of 1:3, and the effects of different solvents on the catalytic activity and enantioselectivity are studied, and the specific operation is as follows:

[0066] Under anhydrous and anaerobic condition, 0.03 mmol of ionic bridged aryloxyalkane oxy-lutetium complex was added into a reaction bottle, 2 mL of toluene was added, different contents of additives (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) were added, and the mixture was stirred at -10 ℃ for 15 min, then 0.36 mmol of pinacol borane was added, the mixture was stirred at -10 ℃ for 30 min, finally 0.3 mmol of chalcone was added, the mixture was reacted at -10 ℃ for 24 h, the reaction was quenched by silica gel powder, and column chromatography was performed with petroleum ether and ethyl acetate as developing agents, and the product 1,3-diphenylprop-2-en-1-ol was collected, and the main product was in R configuration.

[0067] The yield and ee value of the product prepared by the asymmetric borohydration reaction of chalcone catalyzed by the combination of different contents of 4,4'-bipyridine and chiral ionic bridged aryloxyalkane oxy-lutetium complex are shown in the following table:

[0068]

[0069] From the above table, in the asymmetric borohydration reaction of chalcone catalyzed by 4,4'-bipyridine combined with chiral ionic bridged aryloxyalkane lutetium complex, the type of solvent has a significant influence on the catalytic activity and enantioselectivity of the catalyst. When 2-methyltetrahydrofuran, anisole, 1,2-dichloroethane, 1,2-dibromoethane, acetonitrile, etc. are used as solvents, the catalytic activity and enantioselectivity are significantly reduced, and the ee value of the product is even reduced to 0; while using diethyl ether as the solvent, the enantioselectivity is further improved while maintaining high catalytic activity.

[0070] Example 6: In this example, chiral ionic bridged aryloxyalkane lutetium complex combined with 4,4'-bipyridine at a molar ratio of 1:3 is used to catalyze the asymmetric borohydration reaction of chalcone to prepare optically active secondary alcohol, and the influence of different reaction temperatures on the catalytic activity and enantioselectivity is studied. The specific operation is as follows:

[0071] Under anhydrous and anaerobic conditions, argon protection, 0.03 mmol of ionic bridged aryloxyalkane lutetium complex is added to the reaction bottle, then 2 mL of diethyl ether is added, 0.09 mmol of 4,4'-bipyridine is added, and after stirring at a certain temperature for 15 min, 0.36 mmol of pinacol borane is added, and stirred at a certain temperature for 30 min. Finally, 0.3 mmol of chalcone is added, and the tube is sealed and reacted at a certain temperature (reaction temperature) for 24 hours. The reaction is quenched with silica gel powder, and petroleum ether and ethyl acetate are used as developing agents for column chromatography. The product 1,3-diphenylprop-2-en-1-ol is collected, and the main product is R configuration.

[0072] The yield and ee value of the product prepared by 4,4'-bipyridine combined with chiral ionic bridged aryloxyalkane lutetium complex catalyzing the asymmetric borohydration reaction of chalcone at different temperatures are shown in the following table:

[0073]

[0074] From the above table, in the asymmetric borohydration reaction of chalcone catalyzed by 4,4'-bipyridine combined with chiral ionic bridged aryloxyalkane lutetium complex, the reaction temperature will affect the catalytic activity and enantioselectivity of the catalyst. Within the temperature range of -40~ -10℃, the yield and ee value of the product increase with the increase of the reaction temperature. When the temperature is further increased, the yield of the product remains unchanged, but the ee value decreases.

[0075] Example 7: This example uses chiral ionic bridged aryloxyalkane oxo-lutetium complex combined with 4,4'-bipyridine in a molar ratio of 1:3 to catalyze the asymmetric borohydride reaction of chalcone derivatives to prepare optically active secondary alcohol, and the effects of different substrates on catalytic activity and enantioselectivity are studied. The specific operation is as follows:

[0076] Under anhydrous and anaerobic conditions, argon protection, 0.03 mmol of chiral ionic bridged aryloxyalkane oxo-lutetium complex was added to the reaction bottle, 2 mL of ether was added, 0.09 mmol of 4,4'-bipyridine was added, and after stirring at-10 ℃ for 15 min, 0.36 mmol of pinacol borane was added, and stirred at-10 ℃ for 30 min. Finally, 0.3 mmol of chalcone derivative was added, and the tube was sealed and reacted at-10 ℃ for 24 hours. The reaction was quenched with silica gel powder, and column chromatography was performed with petroleum ether and ethyl acetate as developing agents. The product was collected.

[0077] The yield and ee value of the product prepared by the asymmetric borohydride reaction of different chalcone derivatives catalyzed by 4,4'-bipyridine and chiral ionic bridged aryloxyalkane oxo-lutetium complex are shown in the following table:

[0078]

[0079]

[0080]

[0081] As can be seen from the above table, the catalyst composition of 4,4'-bipyridine and chiral ionic bridged aryloxyalkane oxo-lutetium complex can be used to catalyze the asymmetric borohydride reaction of different chalcone derivatives, and shows high reaction activity and good enantioselectivity, and is suitable for efficient preparation of different optically active secondary alcohols.

[0082] The above examples are only preferred examples for fully illustrating the present application, and the protection scope of the present application is not limited thereto. Equivalent substitutions or transformations made by those skilled in the art on the basis of the present application are within the protection scope of the present application. The protection scope of the present application is subject to 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, it 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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