Chiral bisoxazoline phosphine tridentate ligand compound as well as preparation method and application thereof

Abstract

The invention discloses a chiral bisoxazoline phosphine tridentate ligand compound as well as a preparation method and application thereof. The invention provides a compound as shown in a formula I. The chiral bisoxazoline phosphine tridentate ligand of the compound shown in the formula I can be used as a catalyst for asymmetric reaction catalyzed by transition metal, the catalytic effect is remarkable, the product yield is high, and the product er value is high. # imgabs0 #

Description

Technical Field

[0001] The invention specifically relates to a chiral bis-oxazoline phosphine tridentate ligand compound and a preparation method and application thereof. Background Art

[0002] In recent years, with the development of synthesis methods and the emergence of advanced analytical techniques, more and more chiral compounds can be obtained through chiral synthesis. The key to chiral synthesis lies in efficient chiral catalysts. In metal organic catalysis, the catalytic efficiency of chiral catalysts and their chiral induction ability mainly depend on chiral ligands. There are several classification methods for chiral ligands: according to the number of coordinated atoms, they can be divided into monodentate, bidentate, and polydentate ligands; according to the type of coordinated atoms, they are mainly nitrogen, oxygen, phosphorus, sulfur, etc.; according to the type of chiral center of the ligand, they are mainly divided into central chirality, axial chirality, and face chirality. Central chirality, due to the asymmetric factors of chiral carbon or other atoms in the molecule, the molecule has chirality. Axial chirality, the left and right chirality are distinguished by an axis in the molecule, and this axis is the chiral axis. For example, allene-type or biphenyl-type optically active compound molecules. Face chirality, the molecule distinguishes chirality on a plane, and this plane is the chiral plane, such as optically active basket-type compounds. The spiro carbon atom in the middle of the spirocyclic molecule has a tetrahedral structure, and the planes of the two connected rings are almost vertical, and the two rings are difficult to rotate freely. Therefore, when there are substituents on the rings, the molecule has axial chirality (specific reference S.-F. Zhu, Q.-L. Zhou, in Privileged Chiral Ligands and Catalysts, Ed.: Q.-L. Zhou, Wiley-VCH, Weinheim, 2011, pp. 137-170.).

[0003] Chiral bis-oxazoline phosphine tridentate ligands are an important chiral heterocyclic tridentate compound. This type of structure is not only widely present in natural products with physiological activity and small drug molecules, but also a chiral auxiliary group and chiral ligand frequently used in chiral synthesis. At present, the synthesis of chiral bis-oxazoline phosphine tridentate ligands usually relies on the condensation reaction of chiral amino alcohols as starting materials with carboxylic acid derivatives. However, due to the limited source of chiral amino alcohols and the lengthy synthesis steps, it is of great synthetic significance to develop a more efficient and direct asymmetric catalytic synthesis method for chiral bis-oxazoline phosphine tridentate ligands. Summary of the invention

[0004] The present invention provides a class of chiral bis-oxazoline phosphine tridentate ligand compounds and a preparation method and application thereof. The chiral bis-oxazoline phosphine tridentate ligand of the present invention can be used as a catalyst for asymmetric reactions catalyzed by transition metals, has a significant catalytic effect, a good product yield, and a high product er value.

[0005] The present invention provides a compound of formula I,

[0006]

[0007] in,

[0008] R 1 is a C1-C6 alkyl group, a 6-10 membered aryl group or is replaced by one or more R 1-1 Substituted 6-10 membered aryl;

[0009] R 1-1 are independently halogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy or -NR 2 R 2 ;

[0010] R 2 are independently H or C1-C6 alkyl;

[0011] Ring A is a 3-8 membered cycloalkyl group, and the ring A is optionally substituted with one or more R a replace;

[0012] R a are independently H, halogen, C1-C6 alkyl or C1-C6 alkoxy;

[0013] Or, any two adjacent R a Together with the atoms to which it is attached, it forms a 6-10 membered aromatic group.

[0014] In some embodiments, each C 1-6 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl or sec-butyl, for example methyl.

[0015] In some embodiments, each halogen is fluorine, chlorine, bromine, or iodine, preferably fluorine.

[0016] In some embodiments, each 6-10 membered aryl group is independently phenyl or naphthyl, for example phenyl.

[0017] In some embodiments, each C1-C6 alkoxy group is independently -O-methyl, -O-ethyl, -O-n-propyl, -O-isopropyl, -O-n-butyl, -O-tert-butyl, -O-isobutyl, or -O-sec-butyl; for example, -O-methyl.

[0018] In some embodiments, each 3-8 membered cycloalkyl is independently a 4-7 membered cycloalkyl, such as cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl.

[0019] In some embodiments, the cycloalkyl group is a saturated cycloalkyl group.

[0020] In some embodiments, R1 isopropyl, phenyl or is replaced by one or more R 1-1 Substituted phenyl; preferably, R 1 It is phenyl.

[0021] In some embodiments, R 1-1 are independently C1-C6 alkyl or C1-C6 alkoxy; preferably, R 1-1 is independently tert-butyl or methoxy.

[0022] In some embodiments, Ring A is cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl.

[0023] In some embodiments, the two Ring A's are the same.

[0024] In some embodiments, any two adjacent R a Together with the atoms it is attached to, it forms a phenyl group.

[0025] In some embodiments, R a are independently H, halogen or C1-C6 alkyl.

[0026] In some embodiments, Ring A is selected from:

[0027] In some embodiments, the compound of formula I is a compound of formula II-1, II-2, II-3 or II-4:

[0028]

[0029] Among them, the R 1 and Ring A are as described in any one of Formula I of the present invention.

[0030] In some embodiments, the compound of formula I is a compound of formula II-1 or I-2:

[0031]

[0032] Wherein, the R1 and ring A are as described in any one of formula I of the present invention.

[0033] In some embodiments, the compound of formula I is selected from any of the following compounds:

[0034]

[0035] The present invention provides a compound of formula III,

[0036]

[0037] wherein Ring A is defined as above;

[0038] X 2 is F, Cl, Br or I.

[0039] The present invention provides a composition comprising an effective amount of the compound of formula I as described above, and a transition metal catalyst.

[0040] In one embodiment, the molar ratio of the compound of formula I to the transition metal catalyst is 1:1.

[0041] In one embodiment, the transition metal catalyst is CoI2.

[0042] The present invention also provides a method for preparing the compound of formula I, which comprises the following steps:

[0043] In a solvent, the compound of formula III and the compound of formula IV react in the presence of a lithium reagent to obtain a compound of formula I.

[0044]

[0045] Among them, R 1 , R a , n and ring A are as defined above;

[0046] X 1 and X 2 are each independently F, Cl, Br or I.

[0047] In one embodiment, the lithium reagent is n-butyllithium, sec-butyllithium, tert-butyllithium, methyllithium, phenyllithium or lithium diisopropylamide, preferably n-butyllithium.

[0048] In one embodiment, the solvent is one or more of an aromatic hydrocarbon solvent, a halogenated hydrocarbon solvent, an ether solvent, an alcohol solvent, an amide solvent and a sulfoxide solvent; preferably, the solvent is an ether solvent, such as tetrahydrofuran.

[0049] In one embodiment, the molar ratio of the compound of formula III to the compound of formula IV is 1:(2-3), for example 1:2.2.

[0050] In one embodiment, the molar ratio of the compound of formula III to the lithium reagent is 1:(1-1.5), for example 1:1.

[0051] In one embodiment, the amount of the solvent used is 0.1-10 mmol of the compound of formula III per 1 mL of solvent, for example, 0.3 mmol of the compound of formula III per mL of solvent.

[0052] In one embodiment, the reaction temperature is -80 to 0°C, preferably -80 to 40°C, for example -78°C.

[0053] In one embodiment, the reaction time is 1 to 10 hours, for example 2 hours.

[0054] In one embodiment, the reaction is carried out in the presence of nitrogen.

[0055] In one embodiment, the order of adding materials in the reaction is to react the compound of formula III with the lithium reagent, and then add the compound of formula IV.

[0056] In one embodiment, the reaction further comprises the following post-treatment steps: extraction with water and EA, drying, concentration, and separation by column chromatography (preferably PE:EA=9:1) to obtain the compound of formula I. In one embodiment, the preparation method of the compound of formula I comprises the following steps:

[0057] (1) reacting the compound of formula III with the lithium reagent in the solvent;

[0058] (2) Add the compound of formula IV to the solution obtained in step (1) to react to obtain the compound of formula I.

[0059] The present invention also provides a use of a compound of formula I, wherein the compound of formula I is used as a catalyst for the asymmetric addition reaction of an aldehyde compound and a halogenated olefin.

[0060] In one embodiment, the aldehyde compound is a compound of formula V:

[0061]

[0062] Among them, R 4 is halogen, C1-C6 alkyl, C1-C6 alkoxy, -NR 2 R 2 , a C1-C6 alkyl group substituted by one or more halogens or a silicon group substituted by three C1-C6 alkyl groups;

[0063] R 2 are independently C1-C6 alkyl.

[0064] In one embodiment, the halogenated olefin is a compound of formula VI:

[0065]

[0066] Among them, R 5 is a 6-10 membered aromatic group;

[0067] X 3 It is a halogen.

[0068] In a certain embodiment, the aldehyde compound is any of the following compounds:

[0069]

[0070] In one embodiment, the halogenated olefin is the following compound:

[0071]

[0072] In one embodiment, the asymmetric addition reaction of the aldehyde compound and the halogenated olefin comprises the following steps:

[0073] In a solvent, in the presence of the compound of formula I, a transition metal catalyst and zinc, the compound of formula V and the compound of formula VI undergo the following reaction to obtain a compound of formula VII;

[0074]

[0075] Among them, R 4 , R 5 and X 3 The definition of is as above.

[0076] In one embodiment, the solvent is a nitrile solvent, preferably acetonitrile.

[0077] In one embodiment, the amount of the solvent used is 0.01-1 mmol of the compound of formula V per 1 mL of solvent, for example 0.1 mmol of the compound of formula V per mL of solvent.

[0078] In one embodiment, the transition metal catalyst is cobalt iodide.

[0079] In one embodiment, the zinc is zinc powder.

[0080] In one embodiment, the molar ratio of the compound of formula I to the transition metal catalyst is (0.5-2):1, for example 1:1.

[0081] In one embodiment, the molar ratio of the compound of formula I to the compound of formula V is (0.001-0.2):1, for example 0.05:1.

[0082] In one embodiment, the molar ratio of the compound of formula V to the compound of formula VI is 1:(1-3), for example 1:1.5.

[0083] In one embodiment, the molar ratio of the compound of formula V to zinc is 1:(1-3), for example 1:2.

[0084] In one embodiment, the reaction time is 1 to 48 hours, for example 12 hours.

[0085] In one embodiment, the reaction is carried out under light-protected conditions.

[0086] In a certain embodiment, the reaction further comprises the following post-treatment steps: silica gel column filtration, DCM elution, concentration and column chromatography (preferably PE:EA=9:1) to separate and obtain the compound of formula VII.

[0087] Terminology explanation:

[0088] The term "one or more" may mean, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more.

[0089] In the present application, the term "cycloalkyl" refers to a saturated or partially saturated, monocyclic or polycyclic (such as bicyclic) non-aromatic hydrocarbon group. For example, "3-8 membered cycloalkyl" refers to a cycloalkyl group having 3-8 ring carbon atoms (such as 3, 4, 5, 6, 7 or 8). Common cycloalkyl groups include (but are not limited to) monocyclic cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclobutene, cyclopentene, cyclohexene, etc.

[0090] The term "C1-C6 alkyl substituted by one or more halogens" refers to a C1-C6 alkyl group optionally substituted by one or more (eg, 1-3) halogens. 1-6 Alkyl. When there are more than one halogen substituent, the halogens may be the same or different and may be located on the same or different C atoms. Examples of haloalkyl include, for example, -CH2F, -CHF2, -CF3, -CCl3, -C2F5, -C2Cl5, -CH2CF3, -CH2Cl or -CH2CH2CF3.

[0091] The term "three C1-C6 alkyl-substituted silicon groups" refers to silicon groups independently substituted by three C1-C6 alkyl groups, wherein the C1-C6 alkyl groups may be the same or different, for example, TMS, TES, IPDMS, DEIPS, TBS, TIPS.

[0092] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0093] The reagents and raw materials used in the present invention are commercially available.

[0094] The positive improvement effect of the present invention is that the chiral bis-oxazoline phosphine tridentate ligand of the present invention can be used as a catalyst for asymmetric reactions catalyzed by transition metals, with significant catalytic effect, good product yield and high product er value. DETAILED DESCRIPTION

[0095] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0096] HOBt 1-Hydroxybenzotriazole

[0097] EDCI 1-Ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride

[0098] DCM Dichloromethane

[0099] EA Ethyl acetate

[0100] PE Petroleum Ether

[0101] DBU 1,8-diazobispiro[5.4.0]undec-7-ene

[0102] rt room temperature

[0103] THF Tetrahydrofuran

[0104] Example 1

[0105] As shown in the reaction scheme below, taking the preparation of compound II-a as an example, the general preparation method of the chiral bis-oxazoline phosphine tridentate ligand (Formula I) of the present invention is described in detail in this embodiment:

[0106] Add o-bromobenzoic acid (20 mmol, 1.0 eq), amino alcohol (22 mmol, 1.1 eq), HOBt (24 mmol, 1.2 eq), EDCI (24 mmol, 1.2 eq), diisopropylethylamine (40 mmol, 2.0 eq), and 20 mL DCM to a 100 mL round-bottom flask and stir at room temperature for 3 h. Add water and extract with DCM three times. Dry the organic phase with anhydrous sodium sulfate, concentrate with rotary evaporation, and perform column chromatography (DCM:EA=3:1). Collect the product, concentrate with rotary evaporation, and dry under vacuum to obtain 5.81 g of a white solid with a yield of 95%.

[0107]

[0108] According to the preparation method of Example 1, only the substituent of the reaction substrate was changed to prepare the following amide intermediates II-a to II-f:

[0109]

[0110]

[0111] Example 2

[0112] Add amide intermediate II-a (19.4mmol, 1eq) and 10mL DCM to a 100mL round-bottom flask, stir at 0℃ for 10min, add DBU (116.4mmol, 6eq), add perfluorosulfonyl fluoride (58.2mmol, 3eq), move to room temperature, and stir for 1h. Add water, extract with DCM 3 times, dry the organic phase with anhydrous sodium sulfate, concentrate by rotary evaporation, column chromatography (PE:EA=6:1), collect the product, concentrate by rotary evaporation, and dry in vacuo to obtain 3.84g of light yellow oil, with a yield of 70%.

[0113]

[0114] According to the preparation method of Example 2, II-a was replaced by II-b to II-f to prepare the chiral oxazoline intermediates III-b to III-f as shown below:

[0115]

[0116] Example 3

[0117] Replace the nitrogen atmosphere in a 100mL round-bottom flask, add oxazoline intermediate III-a (4.4mmol, 2.2eq), 10mL THF, stir at -78℃ for 10min, add n-butyl lithium (4.4mmol, 2.2eq), stir at -78℃ for 1h. Add dichlorophenylphosphine (dissolved in 5mL THF, 0.36g, 1eq), stir at -78℃ for 1h, move to room temperature, and stir overnight. Add water, extract with EA 3 times, dry the organic phase with anhydrous sodium sulfate, concentrate by rotary evaporation, column chromatography (PE:EA=9:1), collect the product, concentrate by rotary evaporation, and dry in vacuo to obtain 0.35g of light yellow oil, with a yield of 34%.

[0118]

[0119] According to the preparation method of Example 3, III-a was replaced by III-b to III-f to prepare the following chiral bis-oxazoline phosphine tridentate ligands IV-b to IV-f respectively:

[0120]

[0121] The yield and structural identification data of the compound of formula Ia are as follows:

[0122] Pale yellow oil, yield 34%. 1H NMR (400MHz, CDCl3) δ7.88–7.79(m,2H),7.36–7.19(m,9H),6.98–6.89(m,2H),4.23(dt,J=10.8,7.4Hz,2H),4.1 9–4.07(m,2H),3.76–3.65(m,2H),1.59–1.41(m,2H),1.41–1.30(m,2H),1.10–0.98(m,2H),0.87–0.72(m,12H).

[0123] The yield and structural analysis characterization data related to Ib are as follows:

[0124] Red solid, yield 17%. 1 H NMR(400MHz,CDCl3)δ7.82(s,2H),7.34–

[0125] 7.03(m,17H),6.83(d,J=12.8Hz,2H),5.55(t,J=5.5Hz,1H),5.42(t,J=5.6Hz ,1H),5.16(tt,J=11.4,5.8Hz,2H),3.36–3.15(m,3H),3.02(d,J=17.4Hz,1H).

[0126] The yield and structural analysis characterization data related to Ic are as follows:

[0127] Pale yellow oil, yield 18%.

[0128] 1H NMR(400MHz, CDCl3)δ8.10(dd,J=7.4,3.8Hz,2H),7.71–7.44(m,9H),7.19(ddd,J=9.8 ,7.4,3.2Hz,2H),5.33–4.97(m,2H),4.81(dt,J=31.0,7.2Hz,2H),2.31–1.32(m,12H).

[0129] Example 4 Asymmetric addition reaction of benzaldehyde catalyzed by CoI2 / chiral bis(oxazoline)phosphine tridentate ligand

[0130] In this example, the complex formed in situ by the chiral bis-oxazoline phosphine tridentate ligand and CoI2 is used as a chiral catalyst to catalyze the asymmetric addition reaction of benzaldehyde, which is used to illustrate the application of the chiral bis-oxazoline phosphine tridentate ligand compound in the present invention in asymmetric catalysis.

[0131]

[0132] How to do it:

[0133] In a glove box, add cobalt iodide (0.01mmol, 0.05eq), ligand Ic (0.01mmol, 0.05eq), 2mL acetonitrile to an 8mL reaction bottle, stir for 10min, add zinc powder (0.4mmol, 2eq), p-trifluorobenzaldehyde (0.2mmol, 1eq), trans-phenylvinyl iodide (0.3mmol, 1.5eq). React in the dark for 12h. Filter through a short silica gel column, elute with DCM, concentrate by rotary evaporation, column chromatography (PE:EA=9:1), collect the product, concentrate by rotary evaporation, and dry in vacuo to obtain 54.2mg of a white solid, with a yield of 97%, er=96:4, optical rotation 0.3275 (tested in chloroform, concentration is 1g / 100mL), mass spectrum: 261.0886 (molecular weight after dehydroxylation); 1 H NMR (400MHz, CDCl3) δ7.55(ddd,m,4H),7.41–7.16(m,5H),6.69(dd,J=15.8,5.0Hz ,1H),6.32(dt,J=16.4,5.6Hz,1H),5.42(t,J=6.8Hz,1H),2.34(d,J=30.2Hz,1H).

[0134] Example 5 Asymmetric addition reaction of benzaldehyde catalyzed by CoI2 / chiral bis(oxazoline)phosphine tridentate ligand

[0135]

[0136] The operation method is the same as that of Example 4, with a yield of 85%, er=94:6, optical rotation 12.6224 (tested in chloroform, concentration 1 g / 100 mL), mass spectrum: 265.1407 (molecular weight after dehydroxylation); 1 H NMR (400MHz, CDCl3) δ7.56(d,J=8.0Hz,2H),7.42(dd,J=16.2,7.6Hz,4H),7.32(t,J=7.4Hz,2H),7.25(t,J=7.2 Hz, 1H), 6.71 (d, J = 15.8Hz, 1H), 6.40 (dd, J = 15.8, 6.6Hz, 1H), 5.38 (d, J = 6.4Hz, 1H), 2.26 (s, 1H), 0.30 (s, 9H).

[0137] Example 6 Asymmetric addition reaction of benzaldehyde catalyzed by CoI2 / chiral bis(oxazoline)phosphine tridentate ligand

[0138]

[0139] The operation method is the same as that of Example 4, with a yield of 80%, er=96:4, optical rotation of 0.5429 (tested in chloroform, concentration of 1 g / 100 mL), mass spectrum: 227.0621 (molecular weight after dehydroxylation); 1 H NMR (400MHz,CDCl3) 1 H NMR (400MHz, CDCl3) δ7.49–7.20(m,9H),6.68(d,J=15.8Hz,1H),6.32(dd,J=15.9,6.8Hz,1H),5.34(d,J=6.6Hz,1H),2.31(s,1H).

Claims

1. A compound of formula I, in, R 1 is a C1-C6 alkyl group, a 6-10 membered aryl group or is replaced by one or more R 1-1 Substituted 6-10 membered aryl; R 1-1 are independently halogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy or -NR 2 R 2 ; R 2 are independently H or C1-C6 alkyl; Ring A is a 3-8 membered cycloalkyl group, and the ring A is optionally substituted with one or more R a replace; R a are independently H, halogen, C1-C6 alkyl or C1-C6 alkoxy; Or, any two adjacent R in the same ring A a Together with the atoms to which it is attached, it forms a 6-10 membered aromatic group.

2. The compound of formula (I) according to claim 1, characterized in that It meets one or more of the following conditions: (1) Each C 1-6 Alkyl is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl or sec-butyl, for example methyl; (2) each halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (3) each 6-10 membered aryl group is independently phenyl or naphthyl, for example phenyl; (4) each C1-C6 alkoxy group is independently -O-methyl, -O-ethyl, -O-n-propyl, -O-isopropyl, -O-n-butyl, -O-tert-butyl, -O-isobutyl or -O-sec-butyl; for example -O-methyl; (5) each 3-8 membered cycloalkyl group is independently a 4-7 membered cycloalkyl group, such as cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; and (6) The cycloalkyl group is a saturated cycloalkyl group.

3. The compound of formula I according to claim 1, characterized in that It meets one or more of the following conditions: (1)R 1 isopropyl, phenyl or is replaced by one or more R 1-1 Substituted phenyl; preferably, R 1 is phenyl; (2)R 1-1 are independently C1-C6 alkyl or C1-C6 alkoxy; preferably, R 1-1 are independently tert-butyl or methoxy; (3) Ring A is cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; (4) The two rings A are identical; (5) Any two adjacent R a together with the atoms to which it is attached, form a phenyl group; and (6)R a are independently H, halogen or C1-C6 alkyl.

4. The compound of formula I according to claim 1, characterized in that Ring A is selected from:

5. The compound of formula I according to any one of claims 1 to 4, characterized in that The compound of formula I is a compound of formula II-1, II-2, II-3 or II-4: Among them, the R 1 and Ring A is as described in any one of claims 1 to 4.

6. The compound of formula I according to claim 1, characterized in that The compound of formula I is selected from any one of the following compounds:

7. A compound of formula III, in, The definition of Ring A is as described in any one of claims 1 to 6; X 2 is F, Cl, Br or I.

8. A composition comprising an effective amount of a compound of formula I as described in any one of claims 1 to 6, and a transition metal catalyst; Preferably, the molar ratio of the compound of formula I to the transition metal catalyst is 1:1; Preferably, the transition metal catalyst is CoI2.

9. A method for preparing a compound of formula I, comprising the following steps: In a solvent, the compound of formula III and the compound of formula IV react in the presence of a lithium reagent to obtain a compound of formula I. in, R 1 , R a , n and ring A are defined as any one of claims 1 to 6; X 1 and X 2 are each independently F, Cl, Br or I.

10. The preparation method according to claim 9, characterized in that: The preparation method meets one or more of the following conditions: (1) The lithium reagent is n-butyl lithium, sec-butyl lithium, tert-butyl lithium, methyl lithium, phenyl lithium or lithium diisopropylamide, preferably n-butyl lithium; (2) The solvent is one or more of an aromatic hydrocarbon solvent, a halogenated hydrocarbon solvent, an ether solvent, an alcohol solvent, an amide solvent and a sulfoxide solvent; preferably, the solvent is an ether solvent, such as tetrahydrofuran; (3) The molar ratio of the compound of formula III to the compound of formula IV is 1:(2-3), for example 1:2.2; (4) The molar ratio of the compound of formula III to the lithium reagent is 1:(1-1.5), for example 1:1; (5) The reaction temperature is -80 to 0°C, preferably -80 to 40°C, for example -78°C; (6) The reaction time is 1 to 10 hours, for example 2 hours; (7) the reaction is carried out in the presence of nitrogen; and (8) A method for preparing a compound of formula I, comprising the following steps: ① In the solvent, the compound of formula III reacts with the lithium reagent; ② Add the compound of formula IV to the solution obtained in step ① to react to obtain the compound of formula I.

11. Use of a compound of formula I as a catalyst for the asymmetric addition reaction of an aldehyde compound and a halogenated olefin.

12. The use according to claim 11, characterized in that It meets one or both of the following conditions: (1) The aldehyde compound is a compound of the following formula V: Among them, R 4 is halogen, C1-C6 alkyl, C1-C6 alkoxy, -NR 2 R 2 , a C1-C6 alkyl group substituted by one or more halogens or a silicon group substituted by three C1-C6 alkyl groups; R 2 are independently C1-C6 alkyl; (2) The halogenated olefin is a compound of formula VI: Among them, R 5 is a 6-10 membered aromatic group; X 3 It is a halogen.

13. The use according to claim 11, characterized in that It meets one or both of the following conditions: (1) The aldehyde compound is any of the following compounds: (2) The halogenated olefin is the following compound:

14. The use according to any one of claims 11 to 13, characterized in that: The asymmetric addition reaction of the aldehyde compound and the halogenated olefin comprises the following steps: In a solvent, in the presence of the compound of formula I, a transition metal catalyst and zinc, the compound of formula V and the compound of formula VI undergo the following reaction to obtain a compound of formula VII; Among them, R 4 , R 5 and X 3 as defined in claim 12 or 13; Preferably, the solvent is a nitrile solvent, preferably acetonitrile; Preferably, the transition metal catalyst is cobalt iodide; Preferably, the zinc is zinc powder; Preferably, the molar ratio of the compound of formula I to the transition metal catalyst is (0.5-2):1, for example, 1:1; preferably, the molar ratio of the compound of formula I to the compound of formula V is (0.001-0.2):1, for example, 0.05:1; preferably, the molar ratio of the compound of formula V to the compound of formula VI is 1:(1-3), for example, 1:1.5; preferably, the molar ratio of the compound of formula V to zinc is 1:(1-3), for example, 1:2; Preferably, the reaction time is 1 to 48 hours, for example 12 hours; Preferably, the reaction is carried out under light-proof conditions.

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