Method for catalytically synthesizing alkyl boron compound containing remote chiral center by using novel cobalt catalyst

Abstract

The method comprises the following steps: taking trisubstituted olefin as shown in a formula I-1 or I-2 as a raw material, taking pinacolborane as a boron source, taking a CoX2-OIP complex as a catalyst, and reacting under the action of a reducing agent to obtain the alkyl boron compound containing the remote chiral center, wherein the trisubstituted olefin is in an E / Z mixed or single configuration; and carrying out asymmetric hydroboration reaction to prepare the chiral alkyl boron compound as shown in the formula II-1 or II-2. The alkyl boron compound containing the remote chiral center is synthesized by a simple method for the first time, substituent groups of trisubstituted olefin are not limited by chelating groups, the reaction conversion rate is relatively good, and the enantiomer selectivity is relatively high and is generally 85%-98%.

Description

Technical Field

[0001] This method relates to a process for synthesizing alkylboron compounds containing a long-range chiral center by catalyzing the asymmetric hydroboration of trisubstituted olefins using an imine pyridine oxazoline (OIP) cobalt complex catalyst. Background Technology

[0002] Alkenes play a crucial role in organic synthesis due to their wide application in high-value-added compound transformations. In the asymmetric transformation of alkenes, the configuration of the carbon-carbon double bond significantly influences the stereoconfiguration of chiral compounds. While trisubstituted E / Z mixed alkenes can be readily generated via elimination, Wittig, and HWE reactions, the enantiomeric transformation of E / Z mixed alkenes into chiral products remains highly challenging. To overcome this challenge, some research groups have employed a strategy of adding chelating groups to the substrate to coordinate with transition metals, thereby forming stable metal rings that determine the dominant conformation. Despite some progress using this strategy, highly enantioselective functionalization of weakly functionalized trisubstituted E / Z mixed alkenes has not yet been reported. The hydroboration of alkenes, first developed by HC Brown for the rapid acquisition of high-value and readily derivatized organoboron compounds, is now widely used in academia and industry. The strategy of replacing chelating groups through isomerization has proven to be a feasible approach for obtaining enantiomeric transformations of trisubstituted alkenes.

[0003] However, this also presents several challenges: 1) It is difficult to distinguish the stereoconfigurations of E- and Z-isomers when inserting olefins into metal hydride bonds using stereoselectivity; 2) Chiral metal catalysts must recognize thermodynamically unfavorable isomerization reactions and direct functionalization reactions of metal carbon species, which is also a considerable challenge; 3) Side reactions must be carefully considered, such as uncontrolled hydrogen functionalization producing a mixture of primary, secondary, and tertiary carbon products, and alkane byproducts from hydrogenation. This necessitates a highly rational design approach for the catalyst.

[0004] In existing technologies, trisubstituted olefins with a single E or Z configuration containing a guiding group are generally used as substrates for catalytic reactions, which can achieve good yields and enantioselectivity. However, for E / Z mixed trisubstituted olefin substrates without guiding groups, catalysis is difficult, and the yield and enantioselectivity of chiral products are low due to the influence of olefin configuration on the enantioselectivity of the product. Moreover, if the alkenyl group of the trisubstituted olefin is attached to a chelating group (a group with coordinating atoms such as nitrogen, oxygen, and sulfur atoms, such as hydroxyl, amino, and ester groups), the chelation-induced effect between the chelating group and the catalyst center lowers the activation energy of the reaction, making it easier to obtain chiral products. However, for mixed-configuration olefin substrates without chelating groups, the activation energy of the reaction is high, and existing technologies lack suitable reaction systems to catalyze the acquisition of highly optically active organoboron compounds.

[0005] In addition, existing technologies make it difficult to synthesize alkylboron compounds with remote chiral centers. They cannot be constructed using other simple methods and are difficult to obtain from inexpensive and readily available alkenes. Generally, boron functional groups need to be added beforehand, followed by asymmetric hydrogenation, but such methods have not been reported.

[0006] The research group of Professor Lu Zhan at Zhejiang University has long been committed to the research of hydrogenation and hydrogen functionalization reactions of unsaturated hydrocarbons [a) Lu, Z. J. A.M. Chem. Soc. 2022, 144, 17359-17364; b) Lu, Z. Acc. Chem. Res. 2021, 54, 2701–2716]. Addressing the highly challenging situation of asymmetric conversion of mixed trisubstituted olefins, this invention aims to utilize the abundant metal catalysts to "turn waste into treasure"—achieving the normalized hydroboration reaction of mixed trisubstituted olefins, thus realizing the high-value-added conversion of mixed trisubstituted olefins. Summary of the Invention

[0007] This invention utilizes a catalyst formed by complexing an imine-pyridine-oxazoline nitrogen-containing tripentate ligand (OIP) with inexpensive cobalt to catalyze the asymmetric hydroboration of E / Z-mixed trisubstituted alkenes. This catalyst can catalyze the synthesis of alkylboron compounds with long-range chiral centers, achieving excellent conversion and enantioselectivity. This method has a broad substrate range and good functional group tolerance; however, the alkylboron compounds with long-range chiral centers synthesized using this method are difficult to synthesize rapidly using other methods.

[0008] This invention is achieved through the following technical solution:

[0009] A novel cobalt catalyst is used to catalyze the synthesis of alkylboron compounds containing a long-range chiral center, wherein the trisubstituted olefin is an E / Z mixed or single configuration. The method is as follows: using the trisubstituted olefin shown in formula I-1 or I-2 as a raw material, using pinacolborane as a boron source, and using CoX2-OIP complex as a catalyst, an asymmetric hydroboration reaction is carried out under the action of a reducing agent to obtain the chiral alkylboron compound shown in formula II-1 or II-2.

[0010]

[0011]

[0012] In formula II-1 or II-2, * represents a chiral carbon atom.

[0013] The chiral alkylboron compounds shown in Formula II-2 are remotely chiral alkylboron compounds.

[0014] The reaction formula of the present invention can be represented by the following formulas (A) and (B):

[0015]

[0016]

[0017] In formulas I-1, I-2, II-1, or II-2, R 1 Aromatic groups can be selected from C6 to C20 or C4 to C20. 10 Heterocyclic aryl groups containing N and O;

[0018] The R 1 In the middle, C4~C 10 The N- or O-containing heterocyclic aryl group is pyridyl, pyrrole, thiophene, indolyl, dibenzothiophene, or benzofuranyl, preferably pyridyl, indolyl, dibenzothiophene, or benzofuranyl;

[0019] The R 1 In the context, C4~C 10 The H on the N- or O-containing heterocyclic aryl group is not substituted or is substituted by one or more substituent Cs, wherein the substituent Cs are C1-C3 alkyl or C1-C3 alkoxy groups;

[0020] The H on the aromatic group of the C6-C20 group is not substituted or is substituted by one or more substituents F, wherein the substituents F are C1-C20. 10 Alkyl, C1-C 10 alkoxy groups, C1-C 10 alkylamine group, C6-C 10 The aromatic group, pinacolboryl group, adamantane methanol group or triphenylvinyl group.

[0021] Furthermore, the aromatic group of C6 to C20 is preferably naphthyl or a group represented by Formula III.

[0022]

[0023] In the group represented by Formula III, R 4 R 5 R 6 R 7 R 8 Choose from H, C1-C 10 Alkyl, C1-C 10 alkoxy groups, C1-C 10 alkylamine group, C6-C 10 R is any one of aromatic group, pinacolboryl group, adamantane methanol group or triphenylvinyl group. 4 R 5 R 6 R 7 R 8 When all atoms are H, Formula III represents a phenyl group.

[0024] In formula I-1 or II-1, R 2 Choose from the following groups that are either unsubstituted or substituted by one or more substituents D: C1-C6 alkyl groups, C6 ... 10 The aromatic group; the substituent D is a C1 to C5 alkoxy group.

[0025] In Equation I-2, R 4 The following groups, optionally derived from H or unsubstituted or substituted by one or more substituents D, are C1-C6 alkyl groups; wherein the substituent D is a C1-C5 alkoxy group. In preferred formula I-2, R... 4 For H.

[0026] In formulas I-2 and II-2, R3 is an unsubstituted or substituted group E of the following: C2-C6 alkyl group, C6 ... 10 Aromatic groups, C4-C 10 The substituent E is a heterocyclic aryl group containing N or O, wherein the substituent E is a C1-C5 alkoxy group, a C3-C10 cycloalkyl group, or a C6-C12 aromatic group. Preferably, the substituent E is a C1-C5 alkoxy group, a cyclohexyl group, or a phenyl group. Preferably, R3 is an unsubstituted or substituted group E of the following: a C2-C6 alkyl group.

[0027] Furthermore, the R 1 Preferably, it is 2-methoxypyridyl, dibenzothiophene, benzofuranyl, N-indolyl or a group represented by Formula III.

[0028] The R 1 In the formula III, the group is preferably a substituted phenyl group with 1-2 substituents, and the substituents on the substituted phenyl group are preferably C1-C5 alkoxy, C1-C5 alkylamine, pinacolboryl, adamantanemethylol or triphenylvinyl.

[0029] In formula I-1 or II-1, R 2 Preferably, it is a C1-C6 alkyl group.

[0030] In Equation I-2, R 4 H is preferred.

[0031] In formulas I-2 and II-2, R is preferred. 3 For a C2-C6 alkyl group that is unsubstituted or substituted by one or more substituents E, when the H on the alkyl group is substituted by a substituent E, R 3 It can be represented as R E —(CH2) m —, m is an integer from 2 to 6, and the substituent E is preferably an alkoxy, cyclohexyl or phenyl group of C1 to C5.

[0032] The trisubstituted olefins represented by formula I-1 or I-2 used in this invention can be (E / Z) mixed trisubstituted olefins or single E or Z olefins. The E and Z configuration ratios are not limited. Mixed olefins with any E / Z ratio configuration or single E or Z olefins can be used in this method. Moreover, the chiral characteristics of the chiral alkylboron compound products prepared from raw materials with different configuration ratios are the same.

[0033] The chiral alkylboron compounds prepared by this invention can be further used as synthons to convert the Bpin group into other functional groups, such as hydroxyl, halogen, alkenyl, aryl, heteroaryl, amino, etc. Specifically, the chiral alkylboron compounds react with inorganic bases (sodium hydroxide), 3,5-bis(trifluoromethyl)-1-bromobenzene, vinyl magnesium bromide, thiophene, H2N-DABCO, etc., to replace the Bpin group with hydroxyl, bromine, vinyl, thiophene, phenylamide, etc., which are all commonly used reactions known to those skilled in the art.

[0034] As a further improvement, an organic solvent is added to the synthesis method described in this invention. The organic solvent is any one of benzene, carbon tetrachloride, toluene, tetrahydrofuran, diethyl ether, dichloromethane, acetonitrile, dioxane, petroleum ether, cyclohexane, n-hexane, ethyl acetate, chloroform, and N,N-dicarboxamide, preferably diethyl ether.

[0035] The amount of the organic solvent used is generally 0.1 to 5 mL / mmol, preferably 0.4 to 2 mL / mmol, based on the amount of the trisubstituted olefin shown in Formula I-1 or I-2.

[0036] The reducing agent of the present invention is any one of sodium triethylborohydride, sodium trisec-butylborohydride, potassium triethylborohydride, lithium triethylborohydride, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium tert-pentoxide, sodium ethoxide, sodium methoxide, and potassium methoxide, preferably sodium triethylborohydride, potassium triethylborohydride, lithium tert-butoxide, sodium ethoxide, or sodium methoxide, and more preferably potassium triethylborohydride.

[0037] As a further improvement, the molar ratio of the trisubstituted olefin, pinacolborane, CoX2-OIP complex, and reducing agent shown in Formula I-1 or I-2 of the present invention is 1:1 to 3:0.00001-0.1:0.06-0.3, preferably 1:1.5 to 2:0.001 to 0.1:0.03 to 0.3.

[0038] The preferred ratio of CoX2-OIP complex to reducing agent is 1:2 to 4, more preferably 1:3.

[0039] As a further improvement, the reaction temperature of this invention is room temperature. The reaction time is 10 to 40 hours, preferably 12 to 24 hours.

[0040] As a further improvement, after the reaction of the present invention, the crude product is post-processed to obtain a chiral alkylboron compound of formula II-1 or II-2. The post-processing means include thin-layer chromatography, column chromatography or vacuum distillation, preferably column chromatography.

[0041] As a further improvement, it is preferable to add the CoX2-OIP complex and the reducing agent to the reaction system in batches. In a preferred embodiment, the method is carried out according to the following steps:

[0042] The trisubstituted olefin, pinacolborane, the first part of the CoX2-OIP complex, and the first part of the reducing agent are added to an organic solvent and subjected to an asymmetric hydroboration reaction at room temperature for 10 to 15 hours. Then, the remaining CoX2-OIP complex and reducing agent are added and reacted at room temperature for 10 to 15 hours to obtain the chiral alkylboron compound shown in formula II-1 or II-2.

[0043] The amount of the first part of the CoX2-OIP complex is preferably 40-60% of the total amount of the CoX2-OIP complex, more preferably 50%.

[0044] The amount of the first reducing agent is preferably 40-60% of the total amount of reducing agent, more preferably 50%.

[0045] The catalyst used in this invention is a CoX2-OIP complex (OIP: pyridineimine oxazoline ligand), which is an optically pure compound of formula IV or its enantiomer or racemate.

[0046]

[0047] In equation IV, R 9 It is an unsubstituted or C1-C4 alkoxy group substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12 The aryl group a is a cycloalkyl group, or an unsubstituted or aryl group a substituted with 1-4 substituents b; the aryl group a is benzyl, phenyl, or naphthyl; the substituent a is a C1-C4 alkyl or C1-C4 alkoxy; the substituent b is a C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F, or Cl;

[0048] R 10 It is H, unsubstituted or C1-C4 substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12The cycloalkyl group, or the aryl group b, is either unsubstituted or substituted with 1-3 substituents b; the aryl group b is phenyl, anthracene, or naphthyl; the substituent a is C1-C4 alkyl or C1-C4 alkoxy; the substituent b is C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F, or Cl;

[0049] R 11 R 12 R 13 Each is independent of H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro or unsubstituted or substituted with 1-3 substituents a, C5-C12 cycloalkyl;

[0050] R 14 R 15 Each of the following is an independent H, unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12 Cycloalkyl groups, or unsubstituted or aryl a groups substituted with 1-3 substituents b;

[0051] R 16 Each of the following is an independent H, unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12 Cycloalkyl groups, or unsubstituted or aryl a groups substituted with 1-3 substituents b;

[0052] In Formula IV, * represents a chiral carbon atom.

[0053] X is any one of F, Cl, Br, I, OAc, CF3SO3, and acetylacetone (acac), preferably Cl or Br.

[0054] Furthermore, the catalyst CoX2-OIP complex is preferably a compound represented by Formula IV, wherein R is preferred in Formula IV. 11 R 12 R 13 R 14 All are H; R is preferred. 10 It is a C1-C4 alkyl, phenyl, 4-trifluoromethylphenyl, 4-tert-butylphenyl, 3-trifluoromethylphenyl, 3-methylphenyl, 3,5-dichlorophenyl, 2-anthrayl or 2-naphthyl; preferably R 9 It is a C1-C4 alkyl, benzyl, 2,6-diisopropylphenyl, or 2-tert-butylphenyl; preferably R 14 R 15 For H, R is preferred.16 X is a C1-C4 alkyl, benzyl, or phenyl group; X is Cl.

[0055] Furthermore, the chiral CoX2-OIP complex used is preferably as shown in Formula IV-1.

[0056]

[0057] In this invention, the compound represented by Formula IV can be prepared by the following method:

[0058] Under nitrogen protection, the chiral imine-containing pyridine oxazoline compound shown in formula (1) and cobalt salt CoX2 are reacted in an organic solvent for 1 to 10 hours to prepare the metal complex shown in formula IV; the organic solvent is tetrahydrofuran or 2-methyltetrahydrofuran.

[0059]

[0060] R in equation (1) 9 ~R 16 *As previously stated.

[0061] The definition of X in cobalt salt CoX2 is as described above.

[0062] The molar ratio of the chiral imine-containing pyridine thiazoline compound and the cobalt salt CoX2 shown in formula (1) is 2.2 to 0.9:1, preferably 1.1 to 0.9:1, and more preferably 1.1 to 1:1.

[0063] The synthesis of the metal complex shown in Formula IV can be carried out at low or high temperatures, such as -20 to 150°C, but preferably at room temperature.

[0064] The chiral imine-containing pyridine oxazoline compound represented by formula (1) can be prepared according to the following method, referring to the literature Angew. Chem. Int. Ed. 2022, 61, e202205619:

[0065] (a) The 2-acyl-6-bromopyridine compound shown in formula (3) and the amine compound shown in formula (4) undergo a condensation reaction under the action of a catalyst to obtain the compound shown in formula (5);

[0066] (b) Under nitrogen protection, the compound shown in formula (5) and the oxazoline compound shown in formula (6) undergo a coupling reaction in the presence of transition metal inorganic salts, organophosphine ligands and inorganic bases to prepare the chiral imine-containing quinoline oxazoline compound shown in formula (1).

[0067] R 9 -NH2 (4)

[0068]

[0069] R 9 ~R 16 As mentioned above.

[0070] In step (a), the molar ratio of the 2-acyl-6-bromopyridine compound represented by formula (3) to the amine compound represented by formula (4) is 1:1-10, preferably 1:1-5, and more preferably 1:1-2.

[0071] Step (a) is carried out in the presence of a catalyst, which is a protic acid or molecular sieve, preferably p-toluenesulfonic acid, and the amount of the catalyst is 1 to 5% of the amount of the 2-acyl-6-bromopyridine compound shown in formula (3).

[0072] The reaction solvent in step (a) is an organic solvent, preferably toluene, benzene, or xylene, and more preferably toluene.

[0073] The reaction in step (a) requires heating to reflux, water separation by a water separator, and reaction time of 15 to 30 hours.

[0074] Step (b) is a coupling reaction catalyzed by transition metal Ru, Rh, Pd, Ir inorganic salts and organophosphine ligands, and inorganic bases.

[0075] Step (b) is carried out under the catalysis of a transition metal inorganic salt, an organophosphine ligand, and an inorganic base. The transition metal inorganic salt refers to the inorganic salts of Ru, Rh, Pd, and Ir, preferably palladium acetate. The inorganic base is preferably lithium tert-butoxide; the organophosphine ligand is preferably 1,2-bis(diphenylphosphine)ethane.

[0076] In step (b), the molar ratio of the compound shown in formula (5), the oxazoline compound shown in formula (6), the transition metal inorganic salt, the organophosphorus ligand, and the inorganic base is 1:1-5:0.01-1:0.02-2:2-10, preferably 1:1 to 3:0.01-0.1:0.02-0.1:2-4.

[0077] Step (b) is carried out in an organic solvent, which is any one of benzene, carbon tetrachloride, petroleum ether, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, n-hexane, n-heptane, dioxane, and acetonitrile, preferably dioxane. The reaction temperature is -0°C to 150°C, preferably heated to reflux, and the reaction time is 1 hour to 48 hours.

[0078] This invention also provides a cobalt complex catalyst for catalyzing the asymmetric hydroboration of trisubstituted olefins to prepare chiral alkylboron compounds, wherein the cobalt complex catalyst is a chiral CoX2-OIP complex as shown in Formula IV-1.

[0079]

[0080] The chiral CoX2-OIP complex shown in Formula IV-1 can be used to catalyze the asymmetric hydroboration of trisubstituted alkenes to prepare remotely chiral alkylboron compounds.

[0081] This invention provides an efficient method for the highly enantioselective synthesis of optically active alkylborane compounds, particularly those containing long-range chiral alkylborane centers, using CoX2-OIP complexes, especially chiral CoX2-OIP complexes, as catalysts, from E / Z mixed or mono-configured trisubstituted olefins. The method is applicable to various types of E / Z mixed trisubstituted olefins and is not limited to mono-configured trisubstituted olefins.

[0082] This invention solves the technical problem in the prior art where the yield and enantioselectivity of chiral products in the catalytic reaction of trisubstituted olefin substrates lacking guiding groups are low. The trisubstituted olefins of this invention have a wider variety of substrates and greater applicability. If a chelating group (a group with coordinating atoms such as nitrogen, oxygen, and sulfur atoms, such as hydroxyl, amino, or ester groups) is attached to the alkenyl group, the chelation-induced effect between the chelating group and the catalyst center lowers the activation energy, making it easier to obtain chiral products. However, for mixed-configuration olefin substrates without chelating groups, the activation energy is high, and there is a lack of suitable reaction systems to catalyze the production of highly optically active organoboron compounds. This invention solves the above problems, as it does not restrict the groups on the alkenyl substrate, can catalyze mixed-configuration olefins without chelating groups, and the substrate is not limited by chelating groups, allowing for the production of organoboron compounds with high yields and high enantioselectivity, thus possessing greater application value.

[0083] Furthermore, the novel cobalt catalyst of this invention can catalyze the synthesis of alkylboron compounds containing long-range chiral centers, a first discovery of this invention. In product II-2, the alkylboron group Bpin is attached to a position far from the chiral carbon atom, yielding a long-range chiral alkylboron compound. The synthesis of such long-range chiral centers is difficult, cannot be constructed using other simple methods, and is hard to obtain using inexpensive and readily available alkenes. Generally, it requires pre-addition of boron functional groups followed by asymmetric hydrogenation, but such methods have not been reported. This invention, for the first time, utilizes inexpensive olefin substrates and a novel catalyst to synthesize long-range chiral alkylboron compounds using a simple method, representing a pioneering achievement in this field.

[0084] The olefin substrate synthesis method of this invention is simple, the catalyst is readily synthesized, the reaction conditions are mild, the operation is simple, and it has high atom economy. Furthermore, the reaction does not require the addition of any other toxic transition metal salts (such as ruthenium, rhodium, palladium, etc.), making it of great practical application value in pharmaceutical and material synthesis. The conversion rate of the reaction in this invention is also good, and the enantioselectivity is also high, generally 85%–98%. Attached Figure Description

[0085] Figure 1 Single-crystal structure diagram of the compound shown in the example chiral catalyst chiral CoCl2-OIP.

[0086] Figure 2 Single crystal structure diagram of the II-6 remote chiral alkyl boron compound prepared in Example 1, CCDC:2344335. Detailed Implementation

[0087] The technical solution of the present invention will be further described in detail below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0088] The catalyst used in the examples is shown below, the compound represented by Formula IV-1, abbreviated as CoCl2-OIP.

[0089] The preferred amount of the metal complex used is 0.001-10 mol%, more preferably 0.1-5 mol%.

[0090] The catalyst synthesis route is as follows:

[0091]

[0092] The specific synthesis steps of the catalyst are as follows: the 2,6-dibromopyridine compound shown in formula (2) and the amine compound shown in formula (4) are commercially available; the veberamide compound shown in formula (1) is prepared according to the literature (J.Am.Chem.Soc.2022,144,12924.); and the oxazoline compound shown in formula (6) is prepared according to the literature (Org.Chem.Front.,2018,5,247.).

[0093] Preparation of (6-bromopyridin-2-yl)(naphth-2-yl)methyl ketone (3)

[0094] Under a nitrogen atmosphere, using a 250 mL three-necked round-bottom flask, 2,6-dibromopyridine (3.6873 g, 15.7 mmol, 1.0 equiv) was dissolved in 100 mL of anhydrous diethyl ether. The solution was cooled to -78 °C, and n-butyllithium (6.3 mL, 2.5 M) was slowly added dropwise. After stirring for 0.5 hours, N-methoxy-N-methyl-2-naphthylcarboxamide (3.7248 g, 17.3 mmol, 1.1 equiv) was dissolved in 20 mL of anhydrous diethyl ether and slowly added to the above system. After the addition was complete, the three-necked round-bottom flask was brought back to room temperature and stirred for another 3.5 hours. The reaction was quenched by adding 50 mL of saturated ammonium chloride aqueous solution dropwise. The mixture was extracted with diethyl ether as the extractant, dried with anhydrous sodium sulfate, and slurried with n-hexane to obtain 3.1834 g (65% yield) of (6-bromopyridin-2-yl)(naphth-2-yl)methyl ketone (3).

[0095] Preparation of 1-(6-bromopyridin-2-yl)-N-(2,6-diisopropylphenyl)-1-(naphth-2-yl)methylimine (5)

[0096] 2,6-Diisopropylaniline (2.4801 g, 14 mmol, 1.4 equiv) and (6-bromopyridin-2-yl)(naphth-2-yl)methyl ketone (3.1099 g, 10 mmol, 1.0 equiv) were dissolved in 20 mL of toluene. The reaction was catalyzed by p-toluenesulfonic acid monohydrate (0.1902 g, 1.0 mmol, 10 mol%) and the mixture was heated under reflux for 12 h to remove water. The product was then recrystallized from ethanol to give 3.1092 g (67% yield) of 1-(6-bromopyridin-2-yl)-N-(2,6-diisopropylphenyl)-1-(naphth-2-yl)methylimine (5).

[0097] (S)-N-(2,6-Diisopropylphenyl)-1-(6-(4-isopropyl-4,5-dihydrooxazol-2-yl)pyridine-2-

[0098] Synthesis of 1-(naphthyl-2-yl)methylimine (7):

[0099] Under a nitrogen atmosphere, in a dry 100 mL reaction flask, palladium acetate (0.0736 g, 0.325 mmol, 5 mol%), 1,2-bis(diphenylphosphine)ethane (0.1554 g, 0.390 mmol, 6 mol%), lithium tert-butoxide (1.0407 g, 13.0 mmol, 2 equiv), and (S)-isopropyloxazoline ring (1.4700 g, 7.8 mmol, 1.2 equiv) were added sequentially. The reaction was then cyclically frozen, evacuated, and melted three times. Nitrogen was then added, followed by the addition of 1-(6-bromopyridin-2-yl)-N-(2,6-diisopropylphenyl)-1-(naphth-2-yl)methylimine (5) (3.0559 g, 6.5 mmol, 1 equiv) and 20 mL of [amount missing]. After heating to boiling in 1,4-dioxane, the reaction was carried out for 24 h. Column chromatography yielded 1.9656 g (61% yield) of (S)-N-(2,6-diisopropylphenyl)-1-(6-(4-isopropyl-4,5-dihydrooxazol-2-yl)pyridin-2-yl)-1-(naphth-2-yl)methylimine (7), thus obtaining the OIP ligand.

[0100] Synthesis of catalyst (IV-1):

[0101] Under a nitrogen atmosphere, anhydrous cobalt chloride (0.95 eq.) was added to a dry 100 mL reaction flask, followed by 0.1 M dry tetrahydrofuran solution. The mixture was stirred, and then the prepared OIP ligand (1.0 eq.) was dissolved in a small amount of tetrahydrofuran and added to the reaction flask. The mixture was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was evaporated, the product was washed three times with dry Et₂O, and then dried using a vacuum oil pump to obtain a yellow solid powder product IV-1.

[0102]

[0103] Example 1: Asymmetric hydroboration of E / Z-mixed trisubstituted alkenes catalyzed by chiral CoX2-OIP complex

[0104] Standard Condition A:

[0105] Under a nitrogen atmosphere, (chiral) CoCl2-OIP(IV-1) complex (0.0125 mmol), E / Z-mixed trisubstituted olefin (0.25 mmol), pinacol borane (0.375 mmol), diethyl ether (0.5 mL), and triethylborohydride (0.0375 mmol) were added to a dry 10 mL reaction tube. After stirring at room temperature for 12 hours, chiral CoCl2-OIP(IV-1) complex (0.0125 mmol) and triethylborohydride (0.0375 mmol) were added again. After stirring at room temperature for 12 hours, the product was separated by column chromatography.

[0106] The chemical formulas and E / Z ratios of the E / Z-mixed trisubstituted olefin substrates I-1 to I-11 are shown below.

[0107]

[0108] II-1:(S)-2-(1H-indol-1-yl)but-1-ol

[0109] CDCl3)δ7.62(d,J=7.6Hz,1H),7.38(d,J=8.0Hz,1H),7.23-7.08(m,3H),6.54(s,1H),4.3 8-4.23(m,1H),3.87-3.82(m,2H),1.94-1.81(m,2H),1.60(br,1H),0.82(t,J=7.2Hz,3H); 13 C NMR: (100MHz, CDCl3) δ136.8,128.5,124.4,121.5,121.0,119.5,109.5,102.1,65.2,59.8,24.3,10.7; IR(cm -1 ):3425,2965,2930,2860,1462,1311; HRMS(ESI)calculatedfor[C 12 H 16 NO] + (M+H + )requires m / z 190.1226,found m / z 190.1227.

[0110] II-2:(R)-2-methoxy-5-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)but-2-yl)pyridine

[0111] [α] 20 D =+10.2(c 1.25,CHCl3).98%ee. 1 H NMR: (400MHz, CDCl3) δ7.98 (d, J=2.0Hz, 1H), 7.42 (dd, J=8.8, 2.4Hz, 1H), 6.68 (d, J=8.4Hz, 1H) ,3.91(s,3H),2.74-2.66(m,1H),1.68-1.48(m,2H),1.19-1.02(m,14H),0.77(t,J=7.2Hz,3H); 13C NMR: (100MHz, CDCl3) δ162.6,145.7,137.4,134.9,110.3,83.0,53.2,39.7,31.9,24.67,24.56,12.1; IR(cm -1 ):2975,2927,1606,1492,1369,1322; HRMS(ESI)calculated for[C 16 H 27 BNO3] + (M+H + )requires m / z292.2079, found m / z 292.2078.

[0112] II-3:(R)-2-(2-(dibenzo[b,d]thiophene-2-yl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane

[0113] [α] 20 D =+5.9(c 1.86,CHCl3).98%ee. 1 H NMR: (400MHz, CDCl3) δ8.15-8.12(m,1H),7.98(s,1H),7.83-7.81(m,1H),7.74(d,J=8.4Hz,1H),7.45-7.40(m,2H),7. 32(d,J=8.4Hz,1H),2.96-2.90(m,1H),1.78-1.66(m,2H),1.36-1.18(m,2H),1.06(s,12H),0.82(t,J=7.6,7.2Hz,3H); 13 C NMR: (100MHz, CDCl3) δ143.8,139.8,136.7,135.7,135.4,126.6,126.3,12 4.1,122.8,122.3,121.4,120.5,82.9,43.3,32.4,24.7,24.6,12.3; IR(cm -1 ):2974,2927,1466,1369,1321,1145; HRMS(ESI)calculated for[C 22 H 27 [BNaO2S] + (M+Na + )requiresm / z 389.1717, found m / z 389.1720.

[0114] II-4:(R)-2-(2-(benzofuran-2-yl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborane D =+30.6(c 1.43,CHCl3).97%ee. 1 H NMR: (400MHz, CDCl3) δ7.46(d,J=8.4Hz,1H),7.39(d,J=7.2Hz,1H),7.20-7.13(m,2H),6.38( s,1H),3.07-3.00(m,1H),1.84-1.68(m,2H),1.28-1.17(m,14H),0.89(dd,J=7.6,7.2Hz,3H); 13 C NMR: (100MHz, CDCl3) δ163.7,154.5,128.9,122.8,122.1,120.1,110.7,101.1,83.1,36.6,28.9,24.75,24.68,11.5; IR(cm -1 ):2973,2931,1457,1372,1325,1257; HRMS(ESI)calculated for[C 18 H 25 [BNaO3] + (M+Na + )requires m / z 323.1789, found m / z 323.1792.

[0115] II-5:(R)-2-(3-(4-methoxyphenyl)pentyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane

[0116] (R)-2-(3-(4-methoxyphenyl)pentyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0117] Standard Condition A: Oily liquid, 90% yield, Optical Rotation: [α] 20 D =+2.5(c 1.26,CHCl3).90%ee. 1H NMR: (400MHz, CDCl3) δ7.03 (d, J = 8.4Hz, 2H), 6.81 (d, J = 8.4Hz, 2H), 3.78 (s, 3H), 2.31-2.24 (m, 1H), 1.78 -1.64(m,2H),1.57-1.48(m,2H),1.21(s,12H),0.75(dd,J=7.6,7.2Hz,3H),0.62(dd,J=8.8,7.6Hz,2H); 13 C NMR: (100MHz, CDCl3) δ157.6,137.7,128.7,113.5,82.8,55.2,49.4,30.9,29.2,24.81,24.77,12.3; IR(cm -1 ):2975,2929,1512,1374,1313,1246; HRMS(ESI)calculated for[C 18 H 29 [BNaO3] + (M+Na + )requires m / z 327.2102, found m / z 327.2104.

[0118] II-6:(R)-4,4,5,5-Tetramethyl-2-(4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxoborane-2-yl)pent-3-yl)phenyl)-1,3,2-dioxoborane

[0119]

[0120] Standard condition A: White solid, 80% yield, Optical Rotation: [α] 20 D =+4.1(c 1.43,CHCl3).92%ee.Determined by HPLC after conversion to the corresponding alcoholwhich was prepared according to apreviously reported procedure, 2 HPLCconditions: Chiral AS-H, n-hexane / i-PrOH=90 / 10, 1.0mL / min, n=220nm, t r 16.4 (major), 22.7 (minor). 1H NMR: (400MHz, CDCl3) δ7.72(d,J=7.2Hz,2H),7.14(d,J=7.2Hz,2H),2.38-2.33(m,1H),1.81-1.67 (m,2H),1.61-1.49(m,2H),1.34(s,12H),1.21(s,12H),0.75(t,J=7.2Hz,3H),0.63-0.59(m,2H); 13 C NMR: (100MHz, CDCl3) δ149.2,134.7,127.4,83.5,82.8,50.4,30.7,28.9,24.84,24.80,24.75,12.2; IR(cm -1 ):2978,2927,1612,1364,1320,1146; HRMS(ESI)calculated for[C 23 H 38 B2NaO4] + (M+Na + )requires m / z 423.2848, found m / z 423.2852.

[0121] II-7:(S)-2-(3-(4-methoxyphenyl)octyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane

[0122] (S)-2-(3-(4-methoxyphenyl)octyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0123] Standard Condition A: Oily liquid, 72% yield, Optical Rotation: [α] 20 D =+0.5(c 1.19,CHCl3).91%ee. 1 H NMR: (400MHz, CDCl3) δ7.03(d,J=8.8Hz,2H),6.81(d,J=8.4Hz,2H),3.78(s,3H),2.39-2.32(m,1H ),1.73-1.47(m,4H),1.29-1.10(m,18H),0.82(dd,J=6.8,6.4Hz,3H),0.61(dd,J=8.4,8.0Hz,2H); 13C NMR: (100MHz, CDCl3) δ157.6,138.0,128.6,113.5,82.8,55.2,47.4,36.4,31.9,31.3,27.3,24.82,24.77,22.5,14.1; IR(cm -1 ):2927,2860,1612,1511,1374,1147; HRMS(ESI)calculated for[C 21 H 35 [BNaO3] + (M+Na + )requires m / z 369.2571,foundm / z 369.2572.

[0124] II-8:(S)-2-(3-(4-methoxyphenyl)nonyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane Rotation:[α] 20 D =-0.4(c 1.52,CHCl3).91%ee. 1 H NMR: (400MHz, CDCl3) δ7.03 (d, J = 8.4Hz, 2H), 6.81 (d, J = 8.4Hz, 2H), 3.78 (s, 3H), 2.39-2.32 (m, 1H ),1.76-1.46(m,4H),1.27-1.15(m,20H),0.84(dd,J=7.2,6.4Hz,3H),0.61(dd,J=8.4,8.0Hz,2H); 13 C NMR: (100MHz, CDCl3) δ157.6,138.1,128.6,113.5,82.8,55.2,47.4,36.4,31.8,31.3,29.4,27.6,24.82,24.78,22.6,14.1; IR (cm -1 ):2929,2856,1610,1512,1373,1320; HRMS(ESI)calculated for[C 22 H 37 [BNaO3] + (M+Na + )requires m / z 383.2728,foundm / z 383.2728.

[0125] II-9:(S)-4-(1-cyclohexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)pentan-3-yl)-N,N-dimethylaniline

[0126] [α] 20 D =+2.6(c 1.16,CHCl3).92%ee. 1 H NMR: (400MHz, CDCl3) δ6.98 (d, J = 8.4Hz, 2H), 6.68 (d, J = 8.4Hz, 2H), 2.90 (s, 6H), 2.30-2.23 ( m,1H),1.72-1.48(m,8H),1.26-0.97(m,19H),0.84-0.73(m,2H),0.62(dd,J=8.4,8.0Hz,2H); 13 C NMR: (100MHz, CDCl3) δ148.9,134.4,128.3,112.8,82.7,47.5,40.9,37.8,35.5,33.53,33.50,33.2,31.4,26.7,26.5,26.4,24.82,24.78; IR (cm -1 ):2925,2851,1615,1521,1371,1323; HRMS(ESI)calculatedfor[C 25 H 43 BNO2] + (M+H + )requires m / z 400.3381,found m / z 400.3383.

[0127] II-10:(S)-2-(3-(4-methoxyphenyl)-6-phenylhexyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane [α] 20 D =-5.2(c 1.29,CHCl3).90%ee. 1 H NMR: (400MHz, CDCl3) δ7.25-7.21(m,2H),7.16-7.09(m,2H),7.03(d,J=8.4Hz,2H),6.80(d,J=8.4Hz ,2H),3.78(s,3H),2.58-2.38(m,3H),1.74-1.43(m,6H),1.21(s,12H),0.60(dd,J=8.4,8.0Hz,2H); 13C NMR: (100MHz, CDCl3) δ157.6,142.7,137.6,128.6,128.4,128.1,125.5,113.5,82.8,55.2,47.3,36.0,35.9,31.3,29.5,24.81,24.76; IR(cm -1 ):2982,2929,1610,1511,1373,1247; HRMS(ESI)calculated for[C 25 H 35 [BNaO3] + (M+Na + )requires m / z 417.2571, found m / z 417.2574.

[0128] II-11: (S)-2-(5-methoxy-3-(4-methoxyphenyl)pentyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0129] Standard Condition A: Oily liquid, 53% yield, Optical Rotation: [α] 20 D =-6.3(c 1.05,CHCl3).85%ee. 1 H NMR: (400MHz, CDCl3) δ7.03 (d, J = 8.4Hz, 2H), 6.81 (d, J = 8.4Hz, 2H), 3.78 (s, 3H), 3.30-3.2 4(m,5H),2.40-2.35(m,1H),1.78-1.38(m,6H),1.21(s,12H),0.61(dd,J=8.4,8.0Hz,2H); 13 C NMR: (100MHz, CDCl3) δ157.7,137.5,128.6,113.6,82.8,72.9,58.4,55.2,47.3,32.8,31.2,27.8,24.82,24.77; IR(cm -1 ):2928,2860,1610,1512,1375,1248; HRMS(ESI)calculated for[C 20 H 33 [BNaO4] + (M+Na+ )requiresm / z 371.2364, found m / z 371.2367.

[0130] II-12:2-((R)-3-(4-(((3R,5R,7R)-adamantane-1-yl)methoxy)phenyl)pentyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane

[0131] orolane

[0132] Standard Condition A: Oily liquid, 64% yield, Optical Rotation: [α] 20 D =+1.7(c 2.00,CHCl3).89%ee.Determined by HPLC, 1 H NMR: (400MHz, CDCl3) δ7.01(d,J=6.8Hz,2H),6.80(d,J=6.8Hz,2H),3.46(s,2H),2.29-2.23(m,1H),2.01(s,3H) ,1.76-1.65(m,15H),1.58-1.46(m,2H),1.21(s,12H),0.75(dd,J=6.0,5.6Hz,3H),0.61(dd,J=6.8,6.4Hz,2H); 13 C NMR: (100MHz, CDCl3) δ157.7,137.2,128.6,114.1,82.8,78.2,49.4,39.5,37.2,33.7,31.0,29.2,28.2,24.81,24.76,12.3; IR(cm -1 ):2905,2850,1612,1511,1373,1242; HRMS(EI)calculated for[C 28 H 43 BO3] + (M+H + )requires m / z 437.3336,found m / z437.3337.

[0133] II-13:(R)-4,4,5,5-Tetramethyl-2-(3-(4-(1,2,2-triphenylvinyl)phenyl)pentyl)-1,3,2-dioxaborane

[0134] AD-H,n-hexane / i-PrOH=99 / 1,1.0mL / min,n=220nm,t r 4.0 (major), 4.5 (minor). 1 H NMR: (400MHz, CDCl3) δ7.10-6.97(m,15H),6.90(d,J=8.0Hz,2H),6.83(d,J=8.0Hz,2H),2.26-2.19(m,1H),1 .75-1.60(m,2H),1.52-1.37(m,2H),1.23(s,12H),0.70(dd,J=7.6,7.2Hz,3H),0.58(dd,J=8.4,8.0Hz,2H); 13 C NMR: (100MHz, CDCl3) δ143.9,143.8,143.8,141.2,141.0,140.4,131.4,131.3,131.0,127.6,1 27.5,127.4,127.2,126.25,126.22,126.16,82.8,49.8,30.6,29.0,24.82,24.79,12.1; IR(cm -1 ):2916,2867,1540,1509,1374,1146; HRMS(ESI)calculated for[C 21 H 35 [BNaO3] + (M+Na + )requires m / z 551.3092,found m / z551.3090.

[0135] Example 2

[0136] At room temperature, a (chiral) CoCl2-TIP complex or CoCl2-OIP complex (0.025 mmol, chemical formula of the complex shown in the reaction formula below), sodium triethylborohydride (0.075 mmol), E / Z-mixed trisubstituted olefin (0.5 mmol), pinacolborane (0.75 mmol), and diethyl ether (1 mL) were added to a dry 10 mL reaction tube. After stirring at room temperature for 12 hours, the product was separated by column chromatography, as shown in the reaction formula below. The product yield, ee value, and product ratio data obtained by different complexes as catalysts are as follows. It can be seen that only the complex obtained by L17 ligand (i.e., IV-1 in this invention) has a better catalytic effect.

[0137]

[0138] Example 3: Application and Transformation of Chiral Alkyl Boron Compounds

[0139]

[0140] At room temperature, a chiral alkylboron compound (0.50 mmol), diethyl ether (4.0 mL), sodium hydroxide aqueous solution (3 M, 4.0 mL), and 30% hydrogen peroxide (3.0 mL) were added sequentially to a dry reaction tube. The mixture was stirred at room temperature for 3 h, extracted three times with diethyl ether, dried over anhydrous sodium sulfate, and finally separated by column chromatography to obtain the product. The product was an oily liquid with a 97% yield. Determined by HPLC, HPLC conditions: Chiral AS-H, n-hexane / i-PrOH = 99 / 1, 1.0 mL / min, n = 220 nm, t r 20.3(major),26.3(minor).91%ee. 1 H NMR: (400MHz, CDCl3) δ7.07 (d, J = 8.4Hz, 2H), 6.83 (d, J = 8.4Hz, 2H), 3.79 (s, 3H), 3.56-3. 43(m,2H),2.66-2.59(m,1H),1.96-1.75(m,2H),1.28-1.11(m,8H),0.83(t,J=6.8Hz,3H); 13 C NMR: (100MHz, CDCl3) δ157.9,137.2,128.4,113.8,76.7,61.3,55.2,41.6,39.8,37.1,31.9,27.1,22.5,14.0.

Claims

1. A method for synthesizing alkylboron compounds containing long-range chiral centers using a novel cobalt catalyst, characterized in that... The method is as follows: using a trisubstituted olefin of formula I-1 or I-2 as a raw material, wherein the trisubstituted olefin is an E / Z mixed or single configuration, using pinacolborane as a boron source, and CoX2-OIP complex as a catalyst, an asymmetric hydroboration reaction is carried out under the action of a reducing agent to obtain a chiral alkylboron compound of formula II-1 or II-2. In formula II-1 or II-2, * represents a chiral carbon atom; In formulas I-1, I-2, II-1, or II-2, R 1 Aromatic groups can be selected from C6 to C20 or C4 to C20. 10 Heterocyclic aryl groups containing N and O; The R 1 In the context, C4~C 10 The H on the N- or O-containing heterocyclic aryl group is not substituted or is substituted by one or more substituent Cs, wherein the substituent Cs are C1-C3 alkyl or C1-C3 alkoxy groups; The H on the aromatic group of the C6-C20 group is not substituted or is substituted by one or more substituents F, wherein the substituents F are C1-C20. 10 Alkyl, C1-C 10 alkoxy groups, C1-C 10 alkylamine group, C6-C 10 The aromatic group, pinacolboryl group, adamantane methanol group or triphenylvinyl group; In formula I-1 or II-1, R 2 Choose from the following groups that are either unsubstituted or substituted by one or more substituents D: C1-C6 alkyl groups, C6 ... 10 The aromatic group; the substituent D is a C1-C5 alkoxy group; In Equation I-2, R 4 The following groups may be selected from H or be unsubstituted or substituted by one or more substituents D: C1-C6 alkyl groups; wherein the substituent D is a C1-C5 alkoxy group; In formulas I-2 and II-2, R3 is an unsubstituted or substituted group E of the following: C2-C6 alkyl group, C6 ... 10 Aromatic groups, C4-C 10 The heterocyclic aryl group containing N and O, wherein the substituent E is a C1-C5 alkoxy group, a C3-C10 cycloalkyl group, or a C6-C12 aromatic group.

2. The method as described in claim 1, characterized in that... The catalyst is a CoX2-OIP complex, which is an optically pure compound of formula IV or its enantiomer or racemate. In equation IV, R 9 It is an unsubstituted or C1-C4 alkoxy group substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12 The aryl group a is a cycloalkyl group, or an unsubstituted or aryl group a substituted with 1-4 substituents b; the aryl group a is benzyl, phenyl, or naphthyl; the substituent a is a C1-C4 alkyl or C1-C4 alkoxy; the substituent b is a C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F, or Cl; R 10 It is H, unsubstituted or C1-C4 substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12 The cycloalkyl group, or the aryl group b, is either unsubstituted or substituted with 1-3 substituents b; the aryl group b is phenyl, anthracene, or naphthyl; the substituent a is C1-C4 alkyl or C1-C4 alkoxy; the substituent b is C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F, or Cl; R 11 R 12 R 13 Each is independent of H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro or unsubstituted or substituted with 1-3 substituents a, C5-C12 cycloalkyl; R 14 R 15 Each of the following is an independent H, unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12 Cycloalkyl groups, or unsubstituted or aryl a groups substituted with 1-3 substituents b; R 16 Each of the following is an independent H, unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C6 12 Cycloalkyl groups, or unsubstituted or aryl a groups substituted with 1-3 substituents b; In Formula IV, * represents a chiral carbon atom; X is any one of F, Cl, Br, I, OAc, CF3SO3, or acetylacetone.

3. The method as described in claim 2, characterized in that... The catalyst CoX2-OIP complex is a compound represented by formula IV, where R... 11 R 12 R 13 Both are H; R 10 It is a C1-C4 alkyl, phenyl, 4-trifluoromethylphenyl, 4-tert-butylphenyl, 3-trifluoromethylphenyl, 3-methylphenyl, 3,5-dichlorophenyl, 2-anthrayl or 2-naphthyl; R 9 It is a C1-C4 alkyl, benzyl, 2,6-diisopropylphenyl, or 2-tert-butylphenyl; R 14 R 15 For H, R 16 X is a C1-C4 alkyl, benzyl, or phenyl group; X is Cl.

4. The method as described in claim 2, characterized in that... The chiral CoX2-OIP complex is shown in Formula IV-1.

5. The method as described in claim 1, characterized in that... The R 1 In the middle, C4~C 10 The N- or O-containing heterocyclic aryl groups are pyridinyl, pyrroleyl, thiopheneyl, indolyl, dibenzothiopheneyl, or benzofuranyl; The aromatic group of C6 to C20 is preferably naphthyl or a group represented by Formula III. In the group represented by Formula III, R 4 R 5 R 6 R 7 R 8 Choose from H, C1-C 10 Alkyl, C1-C 10 alkoxy groups, C1-C 10 alkylamine group, C6-C 10 R is any one of aromatic group, pinacolboryl group, adamantane methanol group or triphenylvinyl group. 4 R 5 R 6 R 7 R 8 When all atoms are H, Formula III represents a phenyl group.

6. The method as described in claim 5, characterized in that... The R 1 It is 2-methoxypyridyl, dibenzothiophene, benzofuranyl, N-indolyl or the group shown in Formula III, wherein the group shown in Formula III is phenyl or a substituted phenyl containing 1-2 substituents, and the substituents on the substituted phenyl are C1-C5 alkoxy, C1-C5 alkylamine, pinacolboryl, adamantanemethylol or triphenylvinyl. In equations I-1 and II-1, R 2 It is an alkyl group of C1-C6; In Equation I-2, R 4 For H; In formulas I-2 and II-2, R3 is a C2-C6 alkyl group that is not substituted or is substituted by one or more substituents E, wherein the substituent E is a C1-C5 alkoxy, cyclohexyl or phenyl.

7. The method as described in claim 1, characterized in that... The method involves adding an organic solvent, which is any one of benzene, carbon tetrachloride, toluene, tetrahydrofuran, diethyl ether, dichloromethane, acetonitrile, dioxane, petroleum ether, cyclohexane, n-hexane, ethyl acetate, chloroform, and N,N-dicarboxamide.

8. The method as described in claim 1, characterized in that... The reducing agent is any one of sodium triethylborohydride, sodium trisec-butylborohydride, potassium triethylborohydride, lithium triethylborohydride, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium tert-pentoxide, sodium ethoxide, sodium methoxide, and potassium methoxide.

9. The method as described in claim 1, characterized in that... The molar ratio of the trisubstituted olefin, pinacolborane, CoX2-OIP complex, and reducing agent shown in Formula I-1 or I-2 is 1:1 to 3:0.00001-0.1:0.06-0.

3.

10. A cobalt complex catalyst for catalyzing the asymmetric hydroboration of trisubstituted olefins to prepare chiral alkylboron compounds, said cobalt complex catalyst being a chiral CoX2-OIP complex as shown in Formula IV-1.

Images