Method for preparing chiral alkyl boron compound by catalyzing asymmetric hydroboration reaction of trisubstituted olefin with cobalt complex catalyst

Abstract

The invention discloses a method for preparing a chiral alkyl boron compound by catalyzing asymmetric hydroboration reaction of trisubstituted olefin with a cobalt complex catalyst, the trisubstituted olefin is in an E / Z mixed or single configuration, and the method comprises the following steps: by taking trisubstituted olefin as a raw material, pinacolborane as a boron source and a CoX2-TIP complex or CoX2-OIP complex as a catalyst, carrying out asymmetric hydroboration reaction on the trisubstituted olefin and the CoX2-TIP complex or the CoX2-OIP complex to prepare the chiral alkyl boron compound. And under the action of a reducing agent, carrying out asymmetric hydroboration reaction to prepare the chiral alkyl boron compound as shown in a formula II. The method is suitable for various different types of E / Z mixed trisubstituted olefins, the substrate synthesis method of the olefins is simple and convenient, the reaction condition is mild, the operation is simple and convenient, and the atom economy is high. The conversion rate of the reaction is relatively good and can reach gt generally; and the selectivity of the enantiomer is also relatively high and is generally 86%-98%.

Description

TECHNICAL FIELD

[0001] The present method relates to a method for preparing chiral alkylboron compounds by asymmetric borohydration of E / Z-mixed trisubstituted olefins catalyzed by an imine pyridine thiazoline (TIP) cobalt complex catalyst. BACKGROUND

[0002] Olefins are an important part of the petrochemical industry, and the downstream demand is growing at a high speed. At present, a large number of products still rely on imports. The high value-added reaction of olefins has always been the focus of chemists.

[0003] The asymmetric hydrofunctionalization of olefins can construct a variety of chiral compounds with high added value, [a) Marder, T. B. Chem. Soc. Rev. 2021, 50, 13129-13188; b) Westcott, S. A. Chem. Soc. Rev. 2022, 51, 8877-8922] but often requires a single configuration of olefins as starting materials, because starting from different configurations of olefins often gives a pair of enantiomers [a) Takacs, J. M. ACS Catal. 2018, 8, 10530-10536]. Since the energy difference between the two configurations of olefins is small, the olefins prepared in industry are usually mixed olefins, and it is extremely challenging to convert mixed olefins into chiral compounds with a single configuration, especially mixed trisubstituted olefins [a) Lin, G. Q. Sci. China. Chem. 2023, 66, 1261-1287], the reasons are as follows: 1. Trisubstituted olefins have low reactivity due to their large steric hindrance. 2. Lack of catalysts suitable for asymmetric conversion of mixed trisubstituted olefins. Mixed trisubstituted olefins in industry are generally treated as waste.

[0004] Organoboron compounds have attracted extensive attention from researchers in the field of organic synthetic chemistry due to their ability to be efficiently and selectively converted into a variety of functional groups, and are a very practical synthetic building block. H C. Brown and Akira Suzuki won the Nobel Prize in Chemistry in 1979 and 2010, respectively, for "developing new methods of organic synthesis using organoboron compounds" and "developing palladium-catalyzed coupling reactions of organoboron compounds and organic halides". Therefore, developing a method for constructing chiral organoboron compounds with high added value from industrial waste-mixed trisubstituted olefins to realize "waste into treasure" has great scientific significance.

[0005] The Lu Zhan research group of Zhejiang University has been committed to the hydrogenation and hydrogen functionalization of unsaturated hydrocarbon compounds for a long time [a) Lu, Z.J. Am. Chem. Soc. 2022, 144, 17359-17364; b) Lu, Z. Acc. Chem. Res. 2021, 54, 2701-2716]. In view of the extremely challenging status quo of asymmetric conversion of mixed tri-substituted alkenes, we plan to take advantage of the characteristics of abundant metal catalysts to "turn waste into treasure" and realize the normal borohydration of mixed tri-substituted alkenes, and realize the high value-added conversion of mixed tri-substituted alkenes. SUMMARY

[0006] The application can obtain good conversion rate and enantiomeric selectivity by using the catalyst formed by the complex of the imine pyridine thiazoline nitrogen-containing tridentate ligand (TIP) or the imine pyridine oxazoline nitrogen-containing tridentate ligand (OIP) and the cheap metal cobalt to catalyze the asymmetric borohydration of E / Z-mixed tri-substituted alkenes. The application substrate range is wide, and the method has good functional group tolerance. The chiral organic boron compounds constructed can be converted into chiral alkyl alcohols, potassium fluoroborate, alkyl halides, alkyl amines and the like, and industrial waste can be converted into high value-added chiral compounds. The method can also be used for kilogram scale amplification under low load conditions (such as 1 mol %).

[0007] The application is realized by the following technical schemes:

[0008] A method for preparing chiral alkyl boron compounds by using a cobalt complex catalyst to catalyze the asymmetric borohydration of tri-substituted alkenes, wherein the tri-substituted alkenes are E / Z mixed or single configuration, and the method comprises the following steps: taking tri-substituted alkenes shown in formula I as raw materials, pinacol borane as a boron source, and CoX2-TIP complex or CoX2-OIP complex as a catalyst, and then performing asymmetric borohydration under the action of a reducing agent to prepare chiral alkyl boron compounds shown in formula II.

[0009]

[0010] In formula II, * represents a chiral carbon atom.

[0011] The reaction formula of the application can be represented by the following formula:

[0012]

[0013] In formula I or formula II, R 1 is optionally a C6-C20 aromatic group or a C4-C 10 N-, O-containing heterocyclic aromatic group;

[0014] In the formula, the C4-C 1 C4-C 10the N-, O-containing heterocyclic aromatic group is pyridyl, pyrrolyl, thienyl, indolyl, dibenzothiophenyl or benzofuranyl, preferably pyridyl, dibenzothiophenyl or benzofuranyl;

[0015] the R 1 C4-C 10 H on the N-, O-containing heterocyclic aromatic group is unsubstituted or substituted with one or more substituents C, which is C1-C3 alkyl or C1-C3 alkoxy;

[0016] H on the C6-C20 aromatic group is unsubstituted or substituted with one or more substituents F, which is C1-C 10 alkyl, C1-C 10 alkoxy, C1-C 10 alkylamino, C6-C 10 aromatic group, pinacol boron group, adamantyl methanol group or triphenyl ethenyl, preferably substituent F is C1-C3 alkyl or C1-C3 alkoxy.

[0017] Further, the C6-C20 aromatic group is preferably naphthyl or a group shown in formula III

[0018]

[0019] the R 1 , in the group shown in formula III, R 4 , R 5 , R 6 , R 7 , R 8 is optionally any one of H, halogen, C1-C 10 alkyl, C1-C 10 alkoxy, C6-C 10 aromatic group, C3-C 10 cycloalkyl, benzyloxy, C2-C 10 ester, C1-C 10 alkylthio, t-butyl dimethyl silyloxy, trifluoromethyl, dimethylamino, morpholino, piperonyl, menthyl oxy, sugar group or cholesteric ester group, R 4 , R 5 , R 6 , R 7 , R 8 are all H, formula III is phenyl; the halogen is F, Cl or Br; the sugar group can be glucose group.

[0020] in formula I or formula II, R 2R is optionally selected from the group consisting of C1-C6 alkyl, C6-C10 aryl, which are unsubstituted or substituted by one or more substituents D, said substituents D being C1-C5 alkoxy, phenyl, C1-C3 ester or 1,3-dioxolanyl.

[0021] Further, R 1 is preferably 6-methoxynaphthyl, pyridyl, 2-methoxypyridyl, dibenzothiophenyl, benzofuranyl or a group of formula III.

[0022] Further, R 1 is preferably 6-methoxynaphthyl, pyridyl, 2-methoxypyridyl, dibenzothiophenyl, benzofuranyl or a group of formula III.

[0023] The menthoxyl, glucosyl or cholesteryl ester group is preferably represented by the following formula a, b or c:

[0024]

[0025] R 2 is preferably C1-C6 alkyl or phenyl; the H of the C1-C6 alkyl is unsubstituted or substituted by a substituent D, R 2 is C1-C6 alkyl and the H of the alkyl group is substituted by a substituent D, R 2 may be represented by R D — (CH2) m —, m is an integer from 1 to 6, and said substituent D is preferably phenyl or 1,3-dioxolanyl.

[0026] More preferably R 2 is methyl, propyl, phenyl or (1,3-dioxolan-2-yl)methyl;

[0027] The tri-substituted olefin of formula I used in the present application can be a mixture of (E / Z) tri-substituted olefins or a single E or Z configuration olefin, without limitation of the E / Z configuration ratio, any E / Z ratio mixture of olefins or a single E configuration olefin or Z configuration olefin can be used in the present process, and the chiral characteristics of the chiral alkyl boron compound product prepared from the starting material of different configuration ratio are the same.

[0028] The chiral alkyl boron compound prepared by the present application can be further used as a synthon to convert the Bpin group into other functional groups, such as hydroxyl, halogen, alkenyl, aryl, heteroaryl, amino, etc. Specifically, the chiral alkyl boron compound is reacted with inorganic base (sodium hydroxide), 3,5-di(trifluoromethyl)-1-bromobenzene, vinylmagnesium bromide, thiophene, H2N-DABCO, etc. to substitute the Bpin group to obtain hydroxyl, bromine, vinyl, thiophenyl, phenyl amido, etc., which are all common reactions known to those skilled in the art.

[0029] As a further improvement, the synthesis method of the present application adds 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, N,N-dimethylformamide, preferably diethyl ether.

[0030] The amount of the organic solvent is generally 0.4-2 mL / mmol based on the amount of substance of the tri-substituted alkene of formula I.

[0031] The reducing agent of the present application is any one of triethyl sodium borohydride, tri-sec-butyl sodium borohydride, triethyl lithium borohydride, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium tert-amyl alcohol, sodium ethoxide, sodium methoxide, potassium methoxide, preferably triethyl sodium borohydride, lithium tert-butoxide, sodium ethoxide or sodium methoxide, more preferably lithium tert-butoxide.

[0032] As a further improvement, the ratio of the amount of substance of the tri-substituted alkene of formula I, pinacol borane, catalyst, reducing agent of the present application is 1:1-2:0.00001-0.1:0.06-0.3, preferably 1:1.5-2:0.001-0.1:0.03-0.3.

[0033] The ratio of the amount of catalyst and reducing agent is preferably 1:2-4, more preferably 1:3.

[0034] As a further improvement, the reaction temperature of the present application is 0°C- room temperature.

[0035] The reaction time is 10-40 hours, preferably 12-24 hours.

[0036] The reaction of the present application is carried out under inert gas protection, preferably nitrogen.

[0037] As a further improvement, after the reaction of the present application is completed, the obtained crude product is subjected to post-treatment to obtain the chiral alkyl boron compound of formula II, and the post-treatment means includes thin layer chromatography, column chromatography or vacuum distillation, preferably column chromatography.

[0038] The catalyst used in the present invention is a CoX2-TIP complex (TIP: pyridine imine thiazoline ligand) or a CoX2-OIP complex (OIP: pyridine imine oxazoline ligand). The CoX2-TIP complex or the CoX2-OIP complex is an optically pure compound represented by formula IV or its enantiomer or racemate. In formula IV, Y is S or O. When Y is S, formula IV is a CoX2-TIP complex. When Y is O, formula IV is a CoX2-OIP complex.

[0039] In Formula IV, R 9 is unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or aryl a which is unsubstituted or substituted by 1-4 substituents b; the aryl a is benzyl, phenyl 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;

[0040] R 10 is H, unsubstituted or substituted by 1-2 C1-C4 alkoxy groups 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or an aryl group b which is unsubstituted or substituted by 1-3 substituents b; the aryl group b is phenyl 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;

[0041] R 11 、R 12 、R 13 Each is independently H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro, or C5-C12 cycloalkyl which is unsubstituted or substituted with 1-3 substituents a;

[0042] R 14 、R 15 Each is independently H, unsubstituted or C1-C4 substituted by 1-2 C1-C4 alkoxy groups 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or aryl a which is unsubstituted or substituted with 1 to 3 substituents b;

[0043] R 16is H, unsubstituted or substituted by 1-2 C1-C4 alkoxy groups 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or aryl a which is unsubstituted or substituted with 1 to 3 substituents b;

[0044] In formula IV, * represents a chiral carbon atom.

[0045]

[0046] X is any one of F, Cl, Br, I, OAc, and CF3SO3, preferably Cl or I.

[0047] Furthermore, the catalyst CoX2-TIP complex or CoX2-OIP complex is preferably a compound represented by Formula IV, wherein R 11 、R 12 、R 13 All are H; preferably R 10 is a C1-C4 alkyl, phenyl or naphthyl group; preferably R 9 is C1-C4 alkyl, benzyl, 2,6-dimethylphenyl, 2,6-diethylphenyl or 2-tert-butylphenyl; preferably R 14 、R 15 is H, preferably R 16 is C1-C4 alkyl, benzyl or phenyl; X is Cl or I.

[0048] Furthermore, the catalyst used is preferably as shown in Formula IV-1, IV-2 or IV-3:

[0049]

[0050] In the present invention, the compound represented by formula IV can be prepared by the following method:

[0051] Under nitrogen protection, the chiral imine-containing pyridine compound represented by formula (1) and the cobalt salt CoX2 are reacted in an organic solvent for 1 to 10 hours to prepare a metal complex represented by formula IV; the organic solvent is tetrahydrofuran or 2-methyltetrahydrofuran;

[0052]

[0053] R in formula (1) 9 ~R 16 , Y and * are as described above.

[0054] When Y in formula (1) is O, it is a chiral imine-containing quinoline oxazoline compound shown in formula (1-1); when Y is S, it is a chiral imine-containing pyridine thiazoline compound shown in formula (1-2)

[0055]

[0056] X in the cobalt salt CoX2 is defined as before.

[0057] The molar ratio of the chiral imine-containing pyridine compound of formula (1) to the cobalt salt CoX2 is 2.2-0.9:1, preferably 1.1-0.9:1, more preferably 1.1-1:1.

[0058] The synthesis of the metal complex of formula IV can be carried out at low or high temperatures, for example at temperatures of -20 to 150°C, preferably at room temperature.

[0059] The chiral imine-containing pyridine compound of formula (1) can be prepared according to the method disclosed in the literature Angew. Chem. Int. Ed. 2022, 61, e202205619. The specific method is as follows:

[0060] (a) The 2-acyl-6-bromopyridine compound of formula (2) is subjected to condensation reaction with the amine compound of formula (3) under the action of a catalyst to prepare the compound of formula (4);

[0061] (b) The compound of formula (4) is subjected to coupling reaction with the oxazoline compound of formula (5) under the catalysis of a transition metal inorganic salt and an organic phosphine ligand, an inorganic base under nitrogen protection to prepare the chiral imine-containing quinoline oxazoline compound of formula (1-1).

[0062] (c) The compound of formula (1-1) is subjected to reaction with a sulfur source under nitrogen protection to prepare the chiral imine-containing pyridine thiazoline compound of formula (1-2).

[0063]

[0064]

[0065] R 9 ~R 16 , as described before.

[0066] In the step (a), the molar ratio of the 2-acyl-6-bromopyridine compound of formula (2) to the amine compound of formula (3) is 1:1-10, preferably 1:1-5, more preferably 1:1-2.

[0067] The step (a) is carried out under the action of a catalyst, which is a protonic acid or a molecular sieve, preferably p-toluenesulfonic acid, and the amount of the catalyst is 1-5% of the amount of the 2-acyl-6-bromopyridine compound of formula (2).

[0068] The reaction solvent of step (a) is an organic solvent, preferably toluene, benzene or xylene, more preferably toluene.

[0069] The reaction of step (a) requires heating to reflux, water is removed by a water trap, and the reaction is carried out for 15-30 hours.

[0070] Step (b) is a coupling reaction catalyzed by transition metal Ru, Rh, Pd, Ir inorganic salt and organic phosphine ligand, inorganic base.

[0071] The step (b) is carried out under the catalysis of transition metal inorganic salt, organic phosphine ligand and inorganic base, the transition metal inorganic salt refers to the inorganic salt of Ru, Rh, Pd, Ir, preferably palladium acetate. The inorganic base is preferably lithium tert-butoxide; the organic phosphine ligand is preferably 1,2-bis(diphenylphosphino)ethane.

[0072] In step (b), the molar ratio of the compound represented by formula (4), the oxazoline compound represented by formula (5), the transition metal inorganic salt, the organic phosphine ligand, and the inorganic base is 1:1-5:0.01-1:0.02-2:2-10, preferably 1:1-3:0.01-0.1:0.02-0.1:2-4.

[0073] The step (b) is carried out in an organic solvent, and the organic solvent is any one of benzene, carbon tetrachloride, petroleum ether, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, trichloromethane, toluene, xylene, cyclohexane, n-hexane, n-heptane, dioxane, acetonitrile, preferably dioxane. The reaction temperature is -0°C to 150°C, preferably heating to reflux for reaction, and the reaction time is 1 hour to 48 hours.

[0074] The step (c) is carried out in the presence of a sulfur source, and the sulfur source is phosphorus pentasulfide or Lawesson's reagent, preferably phosphorus pentasulfide. The molar ratio of the compound represented by formula (1-1) to phosphorus pentasulfide is 1:1-5, preferably 1:1.5.

[0075] The reaction solvent of step (c) is an organic solvent, preferably toluene, benzene or xylene, more preferably toluene.

[0076] The reaction of step (c) requires heating to reflux for reaction, and the reaction time is 4-8 hours.

[0077] The method of the present application provides an effective method for synthesizing optically active alkyl boron compounds with high enantioselectivity from CoX2-TIP complex or CoX2-OIP complex, especially chiral CoX2-TIP complex or CoX2-OIP complex, using E / Z mixed or single configuration trisubstituted olefins and pinacolborane as catalyst. The method is suitable for various types of E / Z mixed trisubstituted olefins, and is not limited to single configuration trisubstituted olefins.

[0078] The prior art generally uses E or Z single configuration trisubstituted olefins as substrates for catalytic reaction to obtain good yield and enantioselectivity. For E / Z mixed trisubstituted olefin substrates, catalysis is difficult, and due to the influence of olefin configuration on the enantioselectivity of the product, the yield and enantioselectivity of chiral products are low. The present application is particularly directed to the study of E / Z mixed trisubstituted olefin substrates, and the catalyst used has high activity, which significantly improves the yield of E / Z mixed trisubstituted olefin substrates to generate chiral products with optical activity.

[0079] In addition, the substrates of trisubstituted olefins in the present application are rich in types and have wider applicability. If a chelating group (a group with nitrogen, oxygen, sulfur atoms and other coordination atoms, such as hydroxyl, amine, ester, etc.) is connected to the olefin group, the chelation induction between the chelating group and the catalyst center can reduce the activation energy of the reaction, and chiral products can be more easily obtained. However, for mixed configuration olefin substrates without chelating groups, the reaction activation energy is high, and there is a lack of suitable reaction system to catalyze the generation of high optical activity organic boron compounds. The present application solves the above problems, and there is no restriction on the groups on the olefin substrate. Mixed configuration olefins without chelating groups can be catalyzed to obtain organic boron compounds with high yield and high enantioselectivity, and therefore have greater application value.

[0080] The synthesis method of the olefin substrate of the present application is simple, the reaction conditions of the method of the present application are mild, the operation is simple, and the atom economy is high. In addition, the reaction does not require the addition of any other toxic transition metal (such as ruthenium, rhodium, palladium, etc.) salt, and has great practical application value in drug and material synthesis. The conversion rate of the reaction of the present application is also good, and generally can reach > 90%, and the enantioselectivity is also high, generally being 86% to 98%. BRIEF DESCRIPTION OF DRAWINGS

[0081] Figure 1 Figure 1 shows the single crystal structure of the compound of asymmetric borohydration product II-7. DETAILED DESCRIPTION

[0082] The technical solutions of the present application are further specifically described below through specific examples, but the protection scope of the present application is not limited thereto.

[0083] The catalyst used in the examples is shown below, a compound of formula IV-1 or IV-2, referred to as CoCl2-TIP.

[0084] The metal complex is preferably used in an amount of 0.001 to 10 mol%, more preferably 0.1 to 5 mol%.

[0085] The catalyst synthesis route is as follows:

[0086]

[0087] The catalyst synthesis steps are as follows, the 2-acyl-6-bromopyridine compound of formula (2) and the amine compound of formula (3) are commercially available, the oxazoline compound of formula (5) is prepared according to the literature (J. Chen, T. Xi, Z. Lu Org. Chem. Front., 2018, 5, 247.).

[0088] Preparation of 6-bromo-2-imine pyridine (4)

[0089] 2-tert-butylaniline (formula (2), 3.2831 g, 22 mmol, 1.1 equiv) and 6-bromo-2-acetylpyridine (3.72 g, 20 mmol, 1.0 equiv) were dissolved in 30 mL of toluene, p-toluenesulfonic acid monohydrate (0.1902 g, 1.0 mmol, 5 mol%) was catalyzed, and the reaction was carried out under reflux for 12 h. Methanol recrystallization gave 4.67 g (14.2 mmol, 71% yield) of 6-bromo-2-imine pyridine (4).

[0090] Synthesis of imine pyridine oxazoline (6):

[0091] Under nitrogen protection, 6-bromo-2-imine pyridine (4) (3.4528 g, 10 mmol, 1 equiv) and (S)-isopropyl oxazoline ring (1.36 g, 12 mmol, 1.2 equiv) were dissolved in 30 mL of 1,4-dioxane, palladium acetate (0.0600 g, 0.025 mmol, 2.5 mol%), 1,2-bis(diphenylphosphino)ethane (0.1200 g, 0.028 mmol, 2.8 mol%), lithium tert-butoxide (1.60 g, 20 mmol, 2 equiv), followed by freeze, pump, melt cycle operation 3 times, after nitrogen is added, and then heated to boiling, and the reaction is carried out for 24 h to obtain 2.1616 g (5.95 mmol, 59% yield) of imine pyridine oxazoline-containing compound (6).

[0092] Synthesis of imine pyridine thiazoline ligand (TIP):

[0093] Imine pyridine oxazoline (6) (2.1616 g, 5.95 mmol, 1 equiv) and phosphorus pentasulfide (1.9827 g, 8.92 mmol, 1.5 equiv) in 50 mL of toluene under nitrogen, then heated to boiling for 4 h to give 1.4228 g (3.912 mmol, 66% yield) of imine pyridine thiazoline ligand.

[0094] Synthesis of catalyst:

[0095] In a dry 100 mL round bottom flask, under N2, add (0.95 eq.) anhydrous cobalt chloride, add dry THF to make the concentration of cobalt chloride 0.1 M, stir, then add prepared TIP ligand (1.0 eq.) dissolved in a small amount of THF to the flask, stir at room temperature for 12 h. After reaction, dry the solvent, wash with dry Et2O three times, dry with vacuum pump to give green solid powder product IV-1. For synthesis of formula IV-2, replace 2-tert-butylaniline (formula (2)) with 2,6-diethylaniline, (S)-isopropyl oxazoline ring with ethyl thiazoline ring ligand, and anhydrous cobalt chloride with anhydrous cobalt iodide.

[0096]

[0097] Example 1: Asymmetric borohydration of E / Z-mixed trisubstituted olefins catalyzed by chiral CoX2-TIP complex

[0098] Standard condition A:

[0099] In a dry 10 mL reaction tube, add (chiral) CoCl2-TIP (IV-1) complex (0.025 mmol), lithium tert-butoxide (0.075 mmol), E / Z-mixed trisubstituted olefin (0.5 mmol), pinacolborane (0.75 mmol), diethyl ether (0.2 mL) at room temperature, then stir at room temperature or 0 °C for 12-24 h, then column chromatography to isolate the product.

[0100] Standard condition B:

[0101] In a dry 10 mL reaction tube, add (chiral) CoI2-TIP (IV-2) complex (0.050 mmol), lithium tert-butoxide (0.150 mmol), E / Z-mixed trisubstituted olefin (0.5 mmol), pinacolborane (0.75 mmol), diethyl ether (0.4 mL) at room temperature, then stir at room temperature or 0 °C for 12-24 h, then column chromatography to isolate the product.

[0102] The chemical formulas and E / Z ratios of E / Z-mixed trisubstituted olefin substrates I-1 to I-20 are shown below.

[0103]

[0104] II-1: (R)-2-(2-(4-methoxyphenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0105] (R)-2-(2-(4-methoxyphenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0106] HPLC, HPLC conditions: Chiral OJ-H, n-hexane / i-PrOH=98 / 2, 0.8mL / min, n=220nm, t r 5.8(major),6.6(minor). 1 H NMR: (400MHz, CDCl3) δ7.10 (d, J=8.8Hz, 2H), 6.80 (d, J=8.4Hz, 2H), 3.78 (s, 3H), 2.72-2.65(m,1H),1.65-1.53(m,2H),1.22-1.06(m,14H),0.76(t,J=7.2Hz,3H); 13 C NMR: (100MHz, CDCl3) δ157.6,139.4,128.3,113.3,82.8,55.2,42.4,32.4,24.64,24.59,12.2; IR(cm -1 ):2975,2928,1612,1512,1370,1248cm -1 ;HRMS(ESI)calculated for[C 17 H 27 BNaO3] + (M+Na + )requires m / z 313.1945,foundm / z 313.1946.

[0107] II-2: (R)-2-(2-(4-cyclohexylphenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0108] (R)-2-(2-(4-cyclohexylphenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0109] CDCl3) δ 7.11-7.06 (m, 4H), 2.73-2.65 (m, 1H), 2.46-2.41 (m, 1H), 1.82-1.71 (m, 5H), 1.64-1.55 (m, 2H), 1.40-1.35 (m, 4H), 1.22-1.06 (m, 15H), 0.78 (dd, J = 7.6, 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 145.4, 144.6, 127.3, 126.3, 82.8, 44.2, 42.9, 34.56, 34.55, 32.2, 27.0, 26.2, 24.65, 24.57, 12.3; IR (cm -1 ): 2975, 2854, 1512, 1368, 1322, 1146; HRMS (ESI) calculated for [C 22 H 35 BNaO2] + (M+Na + ) requires m / z 365.2622, found m / z 365.2624.

[0110] II-3: (R)-2-(2-([1,1'-biphenyl]-4-yl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0111] (R)-2-(2-([1,1'-biphenyl]-4-yl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0112] CDCl3) δ 7.11-7.06 (m, 4H), 2.73-2.65 (m, 1H), 2.46-2.41 (m, 1H), 1.82-1.71 (m, 5H), 1.64-1.55 (m, 2H), 1.40-1.35 (m, 4H), 1.22-1.06 (m, 15H), 0.78 (dd, J = 7.6, 7.2 Hz, 3H); 13C NMR: (100 MHz, CDC13) δ 146.5, 141.3, 138.5, 128.6, 127.9, 126.9, 126.8, 126.7, 82.9, 42.9, 32.2, 24.7, 24.6, 12.3; IR (cm -1 ): 2976, 2926, 1485, 1369, 1323, 1145; HRMS (ESI) calculated for [C 22 H 29 BNaO2] + (M+Na + ) requires m / z 359.2153, found m / z 359.2155.

[0113] II-4: (R)-tert-butyldimethyl(4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)butan-2-yl)phenoxy)silane

[0114] (R)-tert-butyldimethyl(4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)butan-2-yl)phenoxy)silane

[0115] Hz, 2H), 2.70-2.63 (m, 1H), 1.63-1.48 (m, 2H), 1.16-1.05 (m, 14H), 0.97 (s, 9H), 0.75 (dd, J = 7.6, 7.2 Hz, 3H), 0.16 (s, 6H); 13 C NMR: (100 MHz, CDC13) δ 153.5, 139.9, 128.3, 119.5, 82.8, 42.5, 32.6, 25.7, 24.7, 24.6, 18.2, 12.2, -4.5; IR (cm -1 ): 2959, 2930, 1608, 1510, 1467, 1367; HRMS (ESI) calculated for [C 22 H 39 BNaO3Si] + (M+Na + ) requires m / z 413.2654, found m / z 413.2653.

[0116] II-5: (R)-4,4,5,5-tetramethyl-2-(2-(4-(methylthio)phenyl)butyl)-1,3,2- dioxaborolane

[0117] (R)-4,4,5,5-tetramethyl-2-(2-(4-(methylthio)phenyl)butyl)-1,3,2-dioxaborolan

[0118] MHz, CDCl3) δ 7.18 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 2.74-2.66 (m, 1H), 2.45 (s, 3H), 1.66-1.51 (m, 2H), 1.20-1.04 (m, 14H), 0.76 (t, J = 7.6 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 144.5, 134.8, 128.0, 126.9, 82.9, 42.7, 32.1, 24.64, 24.60, 16.4, 12.1; IR (cm -1 ): 2977, 2925, 1492, 1370, 1322, 1146; HRMS (ESI) calculated for [C 17 H 27 BNaO2S] + (M + Na + ) requires m / z 329.1717, found m / z 329.1717.

[0119] II-6: (R)-N,N-dimethyl-4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2- yl)aniline

[0120] (R)-N,N-dimethyl-4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2- yl)aniline

[0121] MHz, CDCl3) δ 7.06 (d, J = 7.6 Hz, 2H), 6.68 (d, J = 7.6 Hz, 2H), 2.89 (s, 6H), 2.69-2.61 (m, 1H), 1.64-1.50 (m, 2H), 1.21-1.07 (m, 14H), 0.77 (t, J = 7.2 Hz, 3H); 13C NMR: (100 MHz, CDC13) δ 149.0, 135.8, 127.9, 112.9, 82.8, 42.2, 41.0, 32.2, 24.6, 12.2; IR (cm-1): 2977, 2925, 1615, 1521, 1369, 1322; HRMS (ESI) calculated for [C -1 ]: 2971, 2925, 1613, 1515, 1370, 1323; HRMS (ESI) calculated for [C 18 H 31 BNO2] + (M+H + ) requires m / z 304.2442, found m / z 304.2445.

[0122] II-7: (R)-4-(4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)phenyl)morpholine

[0123] (R)-4-(4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)phenyl)morpholine

[0124] 8.4 Hz, 2H), 3.85 (dd, J = 4.8, 4.4 Hz, 4H), 3.10 (dd, J = 4.8, 4.4 Hz, 4H), 2.71-2.63 (m, 1H), 1.64-1.53 (m, 2H), 1.20-1.03 (m, 14H), 0.76 (t, J = 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 149.0, 135.8, 127.9, 112.9, 82.8, 42.2, 41.0, 32.2, 24.6, 12.2; IR (cm-1): 2977, 2925, 1615, 1521, 1369, 1322; HRMS (ESI) calculated for [C -1 ]: 2971, 2925, 1613, 1515, 1370, 1323; HRMS (ESI) calculated for [C 20 H 33 BNO3] + (M+H + ) requires m / z 304.2442, found m / z 304.2445.

[0125] II-8: (R)-4,4,5,5-tetramethyl-2-(2-(4-(trifluoromethyl)phenyl)butyl)-1,3,2-dioxaborolane

[0126] (R)-2-(2-(4-fluorophenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0127] MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 2.84-2.77 (m, 1H), 1.69-1.58 (m, 2H), 1.26-1.02 (m, 14H), 0.77 (dd, J = 7.6, 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 151.5, 128.0 (q, J = 29.2 Hz, CF3CCH), 127.8, 125.0 (q, J = 3.6 Hz, CF3CCH), 124.4 (q, J = 270.5 Hz, CF3CCH), 83.0, 43.1, 32.0, 24.60, 24.56, 12.1; 19 F NMR: (376 MHz, CDC13) δ -62.2. IR (cm -1 ): 2976, 2929, 1618, 1371, 1326, 1125; HRMS (ESI) calculated for [C 17 H 24 BF3NaO2] + (M + Na + ) requires m / z 351.1714, found m / z 351.1711.

[0128] II-9: (R)-2-(2-(4-fluorophenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0129] (R)-2-(2-(4-fluorophenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0130] δ 7.14 (dd, J = 8.4, 5.6 Hz, 2H), 6.94 (dd, J = 8.4, 4.8 Hz, 2H), 2.76-2.68 (m, 1H), 1.66-1.49 (m, 2H), 1.22-1.03 (m, 14H), 0.76 (t, J = 7.2 Hz, 3H); 13C NMR: (100 MHz, CDC13) δ 161.1 (d, J = 252.3 Hz), 142.8 (d, J = 2.9 Hz), 128.7 (d, J = 8.0 Hz), 114.6 (d, J = 21.1 Hz), 82.9, 42.5, 32.4, 24.64, 24.57, 12.1; 19 F NMR: (376 MHz, CDC13) δ -118.1; IR (cm -1 ): 2977, 2929, 1604, 1510, 1370, 1322; HRMS (ESI) calculated for [C 16 H 24 BFNaO2] + (M + Na + ) requires m / z 301.1746, found m / z 301.1742.

[0131] II-10: (R)-2-(2-(4-bromophenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0132] (R)-2-(2-(4-bromophenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0133] CDC13) δ 7.37 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H), 2.74-2.66 (m, 1H), 1.63-1.53 (m, 2H), 1.17-1.05 (m, 14H), 0.75 (dd, J = 7.6, 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 146.2, 131.0, 129.3, 119.2, 83.0, 42.7, 32.1, 24.65, 24.58, 12.1; IR (cm -1 ): 2976, 2927, 1486, 1369, 1322, 1145; HRMS (ESI) calculated for [C 16 H 24 BBrNaO2] + (M + Na + ) requires m / z 361.0945, found m / z 361.0942.

[0134] II-11: (R)-3-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)benzoate

[0135] methyl

[0136] (R)-3-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)benzoate

[0137] 1H), 3.91 (s, 3H), 2.85-2.77 (m, 1H), 1.70-1.59 (m, 2H), 1.22-1.04 (m, 14H), 0.77 (dd, J = 7.6, 7.2 Hz, 3H), 13 C NMR: (100 MHz, CDC13) δ 167.4, 147.6, 132.2, 129.8, 128.7, 128.1, 127.1, 82.9, 52.0, 43.1, 31.9, 24.63, 24.56, 12.2; IR (cm -1 ): 2976, 2929, 1724, 1368, 1279, 1209; HRMS (ESI) calculated for [C 18 H 27 BNaO4] + (M + Na + ) requires m / z 341.1895, found m / z 341.1894.

[0138] II-12: (R)-2-(2-fluorophenyl)-1-butanol

[0139] (R)-2-(2-fluorophenyl)butan-1-ol

[0140] 0.65, CHCl3). 67% ee. 1 H NMR: (400 MHz, CDC13) δ 7.23-7.19 (m, 2H), 7.14-7.10 (m, 1H), 7.06-7.02 (m, 1H), 3.80 (d, J = 6.4 Hz, 2H), 3.13-3.06 (m, 1H), 1.86-1.76 (m, 1H), 1.66-1.58 (m, 1H), 1.39 (s, 1H), 0.86 (t, J = 7.6 Hz, 3H); 13C NMR: (100 MHz, CDC13) δ 161.5 (d, J = 243.5 Hz), 129.1, 128.9 (d, J = 5.1 Hz), 127.9 (d, J = 8.7 Hz), 124.2 (d, J = 3.0 Hz), 115.5 (d, J = 23.3 Hz), 66.07, 66.06, 43.2, 24.0, 11.9; 19 F NMR: (376 MHz, CDC13) δ -118.2; IR (cm -1 ): 2963, 2934, 1724, 1491, 1283, 1225; HRMS (ESI) calculated for [C 10 H 13 FNaO] + (M+Na + ) requires m / z 191.0843, found m / z 191.0840.

[0141] II-13: (R)-2-(2-(4-methoxyphenyl)-3-phenylpropyl)-4,4,5,5-tetramethyl-1,3,2-dio xaborolane

[0142] (R)-2-(2-(4-methoxyphenyl)-3-phenylpropyl)-4,4,5,5-tetramethyl-1,3,2-dio xaborolane

[0143] MHz, CDC13) δ 7.21-7.12 (m, 3H), 7.07-7.01 (m, 4H), 6.76 (d, J = 8.8 Hz, 2H), 3.76 (s, 3H), 3.12-3.04 (m, 1H), 2.82 (d, J = 7.6 Hz, 2H), 1.18-1.05 (m, 14H); 13 C NMR: (100 MHz, CDC13) δ 157.7, 140.8, 138.6, 129.3, 128.4, 127.9, 125.6, 113.3, 82.9, 55.2, 46.4, 42.7, 24.7, 24.5; IR (cm -1 ): 2978, 2929, 1611, 1512, 1369, 1247; HRMS (ESI) calculated for [C 22 H 29 BNaO3] + (M+Na +) requires m / z 375.2102, found m / z 375.2101.

[0144] II-14: (R)-2-(2-(4-methoxyphenyl)-4-methylpentyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane

[0145] (R)-2-(2-(4-methoxyphenyl)-4-methylpentyl)-4,4,5,5-tetramethyl-1,3,2-dio xaborolane

[0146] MHz, CDCI3) δ 7.12 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.77 (s, 3H), 2.91-2.83 (m, 1H), 1.55-1.48 (m, 1H), 1.38-1.26 (m, 2H), 1.15-1.01 (m, 14H), 0.85 (d, J = 6.0 Hz, 3H), 0.80 (d, J = 6.0 Hz, 3H); 13 C NMR: (100 MHz, CDCI3) δ 157.5, 139.6, 128.2, 113.4, 82.8, 55.2, 49.2, 38.3, 25.5, 24.7, 24.6, 23.5, 21.9; IR (cm -1 ): 2954, 2837, 1612, 1511, 1465, 1368; HRMS (ESI) calculated for [C 19 H 31 BNaO3] + (M+Na + ) requires m / z 375.2102, found m / z 375.2101.

[0147] II-14: (R)-2-(2-(4-methoxyphenyl)-4-methylpentyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane

[0148] (R)-2-(2-(4-methoxyphenyl)-4-methylpentyl)-4,4,5,5-tetramethyl-1,3,2-dio xaborolane

[0149] MHz, CDCI3) δ 7.11 (d, J = 8.4 Hz, 2H), 6.79 (d, J = 8.4 Hz, 2H), 4.78 (dd, J = 4.8, 4.4 Hz, 1H), 3.91-3.80 (m, 4H), 3.77 (s, 3H), 2.83-2.76 (m, 1H), 1.73-1.45 (m, 4H), 1.21-1.09 (m, 14H); 13 C NMR: (100 MHz, CDCI3) δ 157.7, 138.8, 128.3, 113.4, 104.5, 82.9, 64.73, 64.69, 55.2, 40.6, 33.7, 32.0, 24.63, 24.57; IR (cm -1 ): 2978, 2929, 1611, 1583, 1512, 1370; HRMS (ESI) calculated for [C 20 H 31 BNaO5] + (M+Na + ) requires m / z 385.2157, found m / z 385.2156.

[0150] II-16: (R)-2-methoxy-5-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)pyridine

[0151] (R)-2-methoxy-5-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)pyridine

[0152] HPLC, HPLC conditions: Chiral AD-H, n-hexane / i-PrOH = 99 / 1, 0.5 mL / min, n = 254 nm, t r 13.8 (major), 14.2 (minor). 1 H NMR: (400 MHz, CDCI3) δ 7.98-7.97 (m, 1H), 7.44-7.41 (m, 1H), 6.69-6.67 (m, 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 = 7.4 Hz, 3H); 13C NMR: (100 MHz, CDC13) δ 162.6, 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 ): 2977, 2927, 1606, 1573, 1493, 1367; HRMS (ESI) calculated for [C 16 H 27 BNaO3] + (M+Na + ) requires m / z 292.2079, found m / z 292.2078.

[0153] II-17: (R)-2-(2-(6-methoxynaphthalen-2-yl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0154] (R)-2-(2-(6-methoxynaphthalen-2-yl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0155] (400 MHz, CDC13) δ 7.68-7.64 (m, 2H), 7.55 (s, 1H), 7.34-7.31 (m, 1H), 7.11-7.09 (m, 2H), 3.90 (s, 3H), 2.92-2.84 (m, 1H), 1.73-1.64 (m, 2H), 1.30-1.05 (m, 14H), 0.79 (dd, J = 7.6, 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 156.9, 142.4, 133.0, 129.00, 128.92, 126.58, 126.51, 125.7, 118.3, 105.5, 82.9, 55.2, 43.1, 32.1, 24.66, 24.57, 12.3; IR (cm -1 ): 2975, 2930, 1635, 1606, 1369, 1319; HRMS (ESI) calculated for [C 21 H 29 BNaO3] + (M+Na + ) requires m / z 363.2102, found m / z 363.2105.

[0156] II-18: 2-((R)-2-(4-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)phenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0157] 2-((R)-2-(4-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)phenyl)butyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

[0158] 6.79 (d, J = 8.4 Hz, 2H), 3.96 (td, J = 10.4, 4.0 Hz, 1H), 2.70-2.63 (m, 1H), 2.26-2.11 (m, 2H), 1.71-1.40 (m, 6H), 1.22-0.96 (m, 17H), 0.91 (dd, J = 6.8, 6.4 Hz, 6H), 0.80-0.75 (m, 6H); 13 C NMR: (100 MHz, CDC13) δ 156.4, 139.2, 128.3, 115.5, 82.8, 77.6, 48.0, 42.5, 40.4, 34.5, 32.4, 31.4, 25.9, 24.6, 23.6, 22.1, 20.7, 16.5, 12.3; IR (cm -1 ): 2957, 2925, 1610, 1508, 1368, 1322; HRMS (ESI) calculated for [C 26 H 43 BNaO3] + (M+Na + ) requires m / z 437.3197, found m / z 437.3201.

[0159] II-19: (2R,3R,4S,5R,6S)-2-(acetyloxymethyl)-6-(4-((R)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triacetate

[0160] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(4-((R)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)phenoxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0161] Hz,2H),6.89(d,J=8.4Hz,2H),5.32-5.23(m,2H),5.16(dd,J=9.6,9.2Hz ,1H),5.03(d,J=7.6Hz,1H),4.33-4.28(m,1H),4.18-4.14(m,1H),3.87- 3.83(m,1H),2.74-2.67(m,1H),2.09(s,3H),2.06(s,3H),2.05(s,3H),2 .04(s,3H),1.66-1.49(m,2H),1.19-1.05(m,14H),0.76(t,J=7.2Hz,3H); 13 C NMR: (100MHz, CDCl3) δ170.5,170.2,169.3,169.2,154.9,142.4,128.3,116.6,99.4,82.8 ,72.6,71.8,71.1,68.2,61.9,42.4,32.1,24.59,24.54,20.60,20.53,20.49,12.1; IR(cm -1 ):2974,2928,1754,1509,1370,1210; HRMS(ESI)calculated for[C 30 H 43 BNaO 12 ] + (M+Na + )requires m / z 629.2740, found m / z 629.2745.II-20: 2,3,4,7,8,9,10,11,12,13,14,15,16,17-Tetrahydro-1H-cyclopentaphenanthren-3-yl 4-(R)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaboronan-2-yl)butan-2-yl)benzoate

[0162] 2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 4-((R)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-2-yl)benzoate

[0163] (d, J = 8.4 Hz, 2H), 5.41 (d, J = 4.0 Hz, 1H),, 4.88-4.80 (m, 1H), 2.84-2.77 (m, 1H), 2.45 (d, J = 7.6 Hz, 2H), 2.04-1.20 (m, 24H), 1.15-1.10 (m, 14H), 1.07-1.00 (m, 7H), 0.92 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 6.8 Hz, 6H), 0.76 (dd, J = 7.6, 7.2 Hz, 3H), 0.69 (s, 3H); 13 C NMR: (100 MHz, CDC13) δ 166.2, 152.8, 139.7, 129.4, 128.4, 127.4, 122.7, 83.0, 74.3, 56.7, 56.1, 50.0, 43.3, 42.3, 39.7, 39.5, 38.2, 37.0, 36.6, 36.2, 35.8, 31.96, 31.91, 31.85, 28.2, 28.0, 27.9, 24.7, 24.6, 24.3, 23.8, 22.8, 22.5, 21.0, 19.4, 18.7, 12.1, 11.8; IR (cm -1 ): 2930, 1715, 1462, 1370, 1273, 1112; HRMS (ESI) calculated for [C 44 H 69 BNaO4] + (M + Na + ) requires m / z 695.5181, found m / z 695.5183.

[0164] Example 2 One-pot preparation of gram scale single configuration chiral alkyl boron compounds from E / Z mixture of trisubstituted and disubstituted alkenes using CoCl2-TIP (IV-1) (1.0 mol%)

[0165]

[0166] A dry reaction tube was charged with (chiral) CoCl2-TIP (0.050 mmol), lithium tert-butoxide (0.015 mmol), three different configurations of mixed alkenes (5.0 mmol), pinacolborane (7.5 mmol), diethyl ether (0.4 mL) at 0 °C, and the mixture was stirred at 0 °C for 12 h. The product was isolated by column chromatography. Oily liquid, 94% yield, Optical Rotation: [a] 20 D = -32.5 (c 1.75, CHCl3). 91% ee. 1 H NMR: (400 MHz, CDC13) δ 7.10 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.4 Hz, 2H), 3.78 (s, 3H), 2.72-2.65 (m, 1H), 1.65-1.53 (m, 2H), 1.22-1.06 (m, 14H), 0.76 (t, J = 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 157.6, 139.4, 128.3, 113.3, 82.8, 55.2, 42.4, 32.4, 24.64, 24.59, 12.2

[0167] Example 3

[0168] A dry reaction tube was charged with (chiral) CoCl2-TIP (0.050 mmol), lithium tert-butoxide (0.015 mmol), three different configurations of mixed alkenes (5.0 mmol), pinacolborane (7.5 mmol), diethyl ether (0.4 mL) at 0 °C, and the mixture was stirred at 0 °C for 12 h. The product was isolated by column chromatography. Oily liquid, 94% yield, Optical Rotation: [a]

[0169]

[0170] Example 4 Application of chiral alkylboron compounds

[0171]

[0172] A dry reaction tube was charged with the chiral alkyl boron compound (0.50 mmol), ethyl ether (4.0 mL), aqueous sodium hydroxide (3 M, 4.0 mL), and 30% hydrogen peroxide (3.0 mL) at room temperature, stirred for 3 h at room temperature, extracted with ethyl ether (3x), dried over anhydrous sodium sulfate, and purified by column chromatography to give the product. Oily liquid, 97% yield, Optical Rotation: [a] 20 D = -17.0 (c 1.33, CHCI3) 91% ee. 1 H NMR: (400 MHz, CDCI3) δ 7.12 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 3.76-3.63 (m, 2H), 2.66-2.59 (m, 1 H), 1.78-1.69 (m, 1 H), 1.56-1.50 (m, 1 H), 1.47 (br, 1 H), 0.82 (t, J = 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDCI3) δ 158.3, 134.0, 128.9, 113.9, 67.3, 55.2, 49.5, 25.0, 11.9; HRMS (ESI) calcd for [C 11 H 16 NaO2] + (M + Na + ) requires m / z 203.1043, found m / z 203.1042.

[0173]

[0174] A dry reaction tube was charged with the chiral alkyl boron compound (0.50 mmol), ethyl ether (4.0 mL), aqueous sodium hydroxide (3 M, 4.0 mL), and 30% hydrogen peroxide (3.0 mL) at room temperature, stirred for 3 h at room temperature, extracted with ethyl ether (3x), dried over anhydrous sodium sulfate, and purified by column chromatography to give the product. Oily liquid, 97% yield, Optical Rotation: [a] 20D =+9.4(c 1.12,CHCl3).90%ee. 1 H NMR: (400MHz, CDCl3) δ7.09 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.4 Hz, 2H), 3.80 (s, 3H), 3.53 (d, J = 7. 2Hz,2H),2.82-2.78(m,1H),1.99-1.92(m,1H),1.63-1.55(m,1H),0.81(dd,J=7.6,7.2Hz,3H); 13 C NMR: (100MHz, CDCl3) δ158.5,134.2,128.6,113.9,55.2,49.0,39.1,27.1,11.9.

[0175]

[0176] Under a nitrogen atmosphere, a chiral alkyl boron compound (0.2 mmol) and 2 mL of tetrahydrofuran were added to a dry reaction tube. The tube was then placed in a zero-degree atmosphere and vinyl magnesium bromide (0.8 mL, 1.0 M in THF, 0.8 mmol) was slowly added dropwise. The reaction was stirred at zero degrees for 3 hours. Iodine (0.8 mmol) dissolved in 2 mL of methanol was then slowly added dropwise to the above system. The reaction was stirred at zero degrees for 1 hour, and the tube was transferred to room temperature. The reaction was quenched with saturated sodium thiosulfate aqueous solution, extracted three times with diethyl ether, then dried over anhydrous sodium sulfate, and finally separated by column chromatography to obtain the product. The oily liquid, 83% yield, Optical Rotation: [α] 20 D =-1.7(c 1.61,CHCl3).91%ee.1H NMR: (400MHz, CDCl3) δ7.06 (d, J = 8.4Hz, 2H), 6.83 (d, J = 8.8Hz, 2H), 5.72-5.61 (m, 1H), 4.97-4.89 (m, 2H), 3.79 (s, 3H), 2.50-2.26 (m, 3H), 1.7 5-1.47 (m, 2H), 0.77 (dd, J = 7.6, 7.2Hz, 3H); 13CNMR: (100MHz, CDCl3) δ 157.8, 137.4, 137.3, 128.6, 115.6, 113.6, 55.2, 46.8, 41.1, 29.0, 12.1.

[0177]

[0178] In a dry reaction tube under nitrogen atmosphere, thiophene (0.4 mmol) and 2 mL of tetrahydrofuran were added, then the tube was placed in an atmosphere of -78 °C, n-butyllithium (160 μL, 2.5 M in hexanes, 0.4 mmol) was added slowly dropwise, and after stirring the reaction for 10 min at -78 °C, the tube was transferred to room temperature, and stirred for 3 h. Then the tube was transferred again to an atmosphere of -78 °C, the chiral alkyl boron compound (0.2 mmol) dissolved in 2 mL of tetrahydrofuran was added slowly dropwise to the above system, stirred for 1 h at -78 °C, NBS (0.4 mmol) dissolved in 2 mL of tetrahydrofuran was added slowly dropwise to the above system, stirred for 1 h at -78 °C, and finally the tube was transferred to room temperature, stirred for 1 h, the reaction was quenched with saturated aqueous sodium thiosulfate solution, extracted with ether three times, then dried with anhydrous sodium sulfate, and finally column chromatography was used to isolate the product. Oily liquid, 73% yield, Optical Rotation: [a] 20 D = +44.8 (c 1.65, CHCl3). 90% ee. 1 H NMR: (400 MHz, CDC13) δ 7.08-7.06 (m, 3H), 6.86-6.83 (m, 3H), 6.63 (d, J = 2.8 Hz, 1H), 3.80 (s, 3H), 3.15-3.03 (m, 2H), 2.75-2.68 (m, 1H), 1.79-1.58 (m, 2H), 0.79 (dd, J = 7.6, 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 157.9, 143.5, 136.5, 128.6, 126.4, 125.1, 123.1, 113.6, 55.1, 49.1, 37.3, 28.8, 12.0; HRMS (ESI) calculated for [C 15 H 18 NaOS] + (M + Na + ) requires m / z 269.0971, found m / z 269.0972.

[0179]

[0180] A dry reaction tube was charged with chiral alkyl boron compound (0.1 mmol), H2N-DABCO (0.11 mmol), 2 mL THF and KOtBu (0.24 mmol) under nitrogen atmosphere at room temperature. The tube was warmed to 80 °C and stirred for 3 h, then BzCl (0.15 mmol) and TEA (0.2 mmol) were added and stirred at room temperature for 3 h. The reaction was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate three times, then dried over anhydrous sodium sulfate and finally column chromatography to isolate the product. Oily liquid, 54% yield, Optical Rotation: [a] 20 D = +9.2 (c 0.59, CHCl3). 90% ee. 1 HNMR: (400 MHz, CDC13) δ 7.59 (d, J = 7.2 Hz, 2H), 7.47-7.35 (m, 3H), 7.14 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 5.92 (br, 1H), 3.97-3.91 (m, 1H), 3.81 (s, 3H), 3.35-3.28 (m, 1H), 2.78-2.71 (m, 1H), 1.81-1.58 (m, 2H), 0.85 (dd, J = 7.6, 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDC13) δ 167.3, 158.4, 134.7, 134.3, 131.3, 128.7, 128.5, 126.7, 114.1, 55.2, 46.7, 45.3, 26.9, 11.9; IR (cm -1 ): 2962, 2926, 1643, 1514, 1250, 1180; HRMS (ESI) calculated for [C 18 H 22 NO2] + (M+H + ) requires m / z 284.1645, found m / z 284.1646.

Claims

1. A method for preparing chiral alkyl boron compounds by asymmetric hydroboration of trisubstituted olefins catalyzed by a cobalt complex catalyst, wherein the trisubstituted olefins are of E / Z mixed or single configuration, characterized in that The method comprises: using a trisubstituted olefin represented by formula I as a raw material, pinacol borane as a boron source, and a CoX2-TIP complex or a CoX2-OIP complex as a catalyst, and performing an asymmetric hydroboration reaction under the action of a reducing agent to prepare a chiral alkyl boron compound represented by formula II; In formula II, * represents a chiral carbon atom; In Formula I or Formula II, R 1 Any one of C6-C20 aromatic group or C4-C 10 N, O-containing heterocyclic aromatic group; The H on the C6-C20 aromatic group is not substituted or is substituted by one or more substituents F, wherein the substituent F is C1-C 10 Alkyl, C1-C 10 Alkoxy, C1-C 10 Alkylamino, C6-C 10 aromatic groups, pinacol boron groups, adamantane methanol groups or triphenylvinyl groups; The C6-C20 aromatic group is a naphthyl group or a group represented by formula III In the group represented by formula III, R 4 、R 5 、R 6 、R 7 、R 8 Selected from H, halogen, C1-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 aromatic groups, C3-C 10 Cycloalkyl, benzyloxy, C2-C 10 Ester group, C1-C 10 any one of alkylthio, tert-butyldimethylsilyloxy, trifluoromethyl, dimethylamino, morpholinyl, piperonyl, mentholoxy, saccharyl or cholesterol ester groups, R 4 、R 5 、R 6 、R 7 、R 8 When all are H, the halogen represented by formula III is phenyl; the halogen is F, Cl or Br; In Formula I or Formula II, R 2 The group may be selected from the following groups which are unsubstituted or substituted with one or more substituents D: a C1-C6 alkyl group, a C6-C10 aromatic group; the substituent D is a C1-C5 alkoxy group, a phenyl group, a C1-C3 ester group or a 1,3-dioxolane group.

2. The method according to claim 1, wherein The catalyst is a CoX2-TIP complex or a CoX2-OIP complex, and the CoX2-TIP complex or the CoX2-OIP complex is an optically pure compound represented by formula IV or its enantiomer or racemate, wherein Y is S or O. When Y is S, formula IV is a CoX2-TIP complex, and when Y is O, formula IV is a CoX2-OIP complex; In Formula IV, R 9 is unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or aryl a which is unsubstituted or substituted by 1-4 substituents b; the aryl a is benzyl, phenyl 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 10 is H, unsubstituted or substituted by 1-2 C1-C4 alkoxy groups 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or an aryl group b which is unsubstituted or substituted by 1-3 substituents b; the aryl group b is phenyl 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 independently H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro, or C5-C12 cycloalkyl which is unsubstituted or substituted with 1-3 substituents a; R 14 、R 15 Each is independently H, unsubstituted or C1-C4 substituted by 1-2 C1-C4 alkoxy groups 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or aryl a which is unsubstituted or substituted with 1 to 3 substituents b; R 16 is H, unsubstituted or substituted by 1-2 C1-C4 alkoxy groups 12 Alkyl, unsubstituted or substituted with 1-3 substituents a C5~C 12 cycloalkyl, or aryl a which is unsubstituted or substituted with 1 to 3 substituents b; In formula IV, * represents a chiral carbon atom; X is any one of F, Cl, Br, I, OAc, and CF3SO3.

3. The method according to claim 2, wherein The catalyst is a compound represented by Formula IV, wherein R 11 、R 12 、R 13 Both H; R 10 is a C1-C4 alkyl, phenyl or naphthyl group; R 9 is a C1-C4 alkyl group, benzyl, 2,6-dimethylphenyl, 2,6-diethylphenyl or 2-tert-butylphenyl group; R 14 、R 15 H, R 16 is C1-C4 alkyl, benzyl or phenyl; X is Cl or I.

4. The method according to claim 2, wherein The catalyst is shown in formula IV-1, IV-2 or IV-3:

5. The method according to claim 1, wherein The R 1 In the above, the C4~C 10 The heterocyclic aromatic group containing N and O is pyridyl, pyrrolyl, thienyl, indolyl, dibenzothienyl or benzofuranyl; the R 1 In the above, the C4~C 10 The H on the heterocyclic aromatic group containing N and O is not substituted or is substituted by one or more substituents C, and the substituent C is a C1-C3 alkyl group or a C1-C3 alkoxy group.

6. The method according to claim 1, wherein The R 1 is 6-methoxynaphthyl, pyridyl, 2-methoxypyridyl, dibenzothienyl, benzofuranyl or a group represented by formula III; The group represented by formula III is a phenyl group or a substituted phenyl group having 1-2 substituents, wherein the substituents on the substituted phenyl group are halogen, C1-C5 alkyl, C1-C5 alkoxy, phenyl, cyclohexyl, benzyloxy, methoxyacyl, C1-C3 alkylthio, tert-butyldimethylsilyloxy, trifluoromethyl, dimethylamino, morpholinyl, piperonyl, mentholoxy, saccharyl or cholesterol ester; R 2 is a C1-C6 alkyl group or a phenyl group; the H on the C1-C6 alkyl group is unsubstituted or substituted by a substituent D, and the substituent D is a phenyl group or a 1,3-dioxolane group.

7. The method according to claim 1, wherein An organic solvent is added in the method, and the organic solvent is any one of benzene, carbon tetrachloride, toluene, tetrahydrofuran, ether, dichloromethane, acetonitrile, dioxane, petroleum ether, cyclohexane, n-hexane, ethyl acetate, chloroform, and N,N-diformamide.

8. The method according to claim 1, wherein The reducing agent is any one of sodium triethylborohydride, sodium tri-sec-butylborohydride, lithium triethylborohydride, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium tert-amylate, sodium ethoxide, sodium methoxide, and potassium methoxide.

9. The method according to claim 1, wherein The molar ratio of the trisubstituted olefin represented by formula I, pinacol borane, catalyst and reducing agent is 1:1-2:0.00001-0.1:0.06-0.

3.

10. The method according to claim 1, wherein The reaction temperature is 0°C to room temperature.

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