CN104513274B - A kind of chiral pincerlike compounds of P and its palladium complex - Google Patents

Abstract

The invention relates to a P chiral pincer compound (II) and its palladium complex (I) and their synthesis method. Palladium complex (I) (where X represents ‑Cl, R represents a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and the chirality of the two Ps is both R configuration or S configuration) through the compound ( II) Synthesized by coordination reaction with divalent palladium salt. Palladium complex (I) (wherein, X is a group selected from ‑Br, ‑I, ‑OAc, ‑OTf, ‑BF ₄ , ‑SbF ₆ ) represented by X The palladium complex (I) of ‑Cl passes through an anion Synthesized by exchange reaction. The palladium complex (I) of the present invention can be used as a chiral catalyst in various asymmetric reactions, such as asymmetric Micheal addition, asymmetric Heck coupling reaction, asymmetric Suzuki-Miyaura coupling reaction, asymmetric allyl basement reaction, etc.

Description

A P chiral pincer compound and its palladium complex

technical field

The invention relates to a P chiral pincer compound and its palladium complex, as well as their synthesis method.

Background technique

Organophosphorus compounds show a wide variety of biological activities due to their chemical properties and have been widely used in the pharmaceutical industry, such as α-amino and α-hydroxyphosphonic acids and their derivatives have been used as antibiotics, antineoplastic agents, enzyme inhibitors agent. Some organophosphorus compounds such as phosphoric acid esters, phosphine oxides, and organic phosphonic acids have been applied in the fields of materials and organic synthesis. In addition, organophosphorus compounds are also used as ligands to coordinate with metals and carry out catalytic reactions and catalytic reactions without metal participation. For example, phosphine oxides are used as chiral Lewis base catalysts. However, before the discovery of asymmetric catalytic hydrophosphine reactions, these chiral organophosphorus compounds required chemically equivalent chiral auxiliary agents or tedious resolution methods to prepare. Therefore, it is of great significance to develop efficient chiral phosphorus ligands and metal complexes to synthesize these chiral organophosphorus compounds in a catalytic manner.

Since C.J.Moulton and B.L.Shaw first reported the tridentate ligand clamp and its metal complexes in 1976 (reference 1), it has attracted many chemists to devote themselves to it because of its high stability and catalytic activity. research in this area. However, the report on the synthesis of chiral pincer-metal complexes and their application in asymmetric catalysis is relatively late, and the reported chiral pincer-metal complexes use nitrogen as the electron donor for pincer-metal complexes. Complexes are mostly. Chiral pincer-metal complexes with phosphorus as electron donors are difficult to synthesize and have poor catalytic effects, so they have received little attention.

In contrast, a large number of chiral bidentate phosphine ligands have been developed and widely used. Among these chiral bisphosphine ligands, the phosphorus chiral metal complexes based on methyl tert-butylphosphine exhibit excellent catalytic performance (references 2-6).

references:

Reference 1: Moulton, C.J.; Shaw, B.L.J. Chem. Soc., Dalton Trans. 1976, 1020

Reference 2: Imamoto, T.; Watanabe, J.; Wada, Y.; Masuda, H.; Yamada, H.; 120, 1635.

Reference 3: Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999, 64, 2988.

Reference 4: Imamoto, T.; Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005, 127, 11934.

Reference 5: Tamura, K.; Sugiya, M.; Yoshida, K.; Yanagisawa, A.; Imamoto, T. Org. Lett. 2010, 12, 4400.

Reference 6: Imamoto, T. Tamura, K.; Zhang, Z.; Horiuchi, Y.; Sugiya, M.; Yoshida, K.; Yanagisawa, A.; ,1754.

However, there is no research on pincer compounds containing chiral methyl tert-butylphosphine groups and their palladium complexes.

Contents of the invention

The invention relates to a pincer compound containing a chiral methyl tert-butylphosphine group and a palladium complex thereof. In the technical field, pincer compounds are also called pincer compounds, and correspondingly, pincer palladium complexes are also called pincer-Pd complexes.

The present invention combines the characteristics of high stability and high catalytic activity of pincer metal complexes with the very good asymmetric induction effect of chiral methyl tert-butylphosphine group in asymmetric catalytic reactions, designs and A P chiral pincer compound and its palladium complex were synthesized through a simple route. In addition, the pincer-shaped palladium complexes of the present invention are also called P-chiral PCP-type pincer-shaped palladium complexes.

The present invention relates to the following.

First, the present invention relates to a P chiral pincer compound, the chemical formula of which is shown in the following formula (II):

Wherein, R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and the chiralities of the two Ps are both R configuration or S configuration.

In addition, the present invention also relates to a synthesis method of a P chiral pincer compound, the P chiral pincer compound is a compound represented by the following chemical formula (II), the P chiral pincer compound represented by the chemical formula (II) Form compound is obtained by deborane reaction of P chiral pincer compound protected by borane represented by chemical formula (III),

In formula (II) and formula (III), R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and the chiralities of the two Ps are both R configuration or S configuration.

In the synthesis method of the P chiral pincer compound of the present invention, the deborane reaction is preferably carried out in the following manner: at 0°C to 35°C, the P chiral pincer compound represented by chemical formula (III) and The sulfonic acid was stirred in the first organic solvent for 0.5 to 1.5 hours, then, the organic volatiles were removed under reduced pressure, and then degassed alkali metal hydroxide-ethanol-water solution was added, and stirred at 40°C to 60°C for 1 to 4 hours, thereby obtaining the P chiral pincer compound represented by the chemical formula (II).

In the synthesis method of the P chiral pincer compound of the present invention, preferably: the first organic solvent is selected from toluene, tetrahydrofuran, dichloromethane, acetonitrile, methanol, ether, n-hexane, acetone, chloroform, ethyl acetate , benzene, ethanol, isopropanol, 1,4-dioxane, dimethylsulfoxide, dimethylformamide; the sulfonic acid is selected from methanesulfonic acid, trifluoromethanesulfonic acid , any one of benzenesulfonic acid and p-toluenesulfonic acid; the alkali metal hydroxide is any one selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide and cesium hydroxide.

The present invention also relates to a P chiral PCP-type pincer palladium complex, the chemical formula of which is shown in the following formula (I):

Wherein, X is a group selected from -Cl, -Br, -I, -OAc, -OTf, -BF ₄ , -SbF ₆ , and R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms. Group, the chirality of the two Ps is both R configuration or S configuration.

The present invention also relates to a synthetic method of a P chiral PCP-type pincer palladium complex, characterized in that,

The P chiral PCP-type pincer palladium complex is represented by the following chemical formula (I-A) or (I-B),

The P chiral PCP-type pincer palladium complex represented by the chemical formula (I-A) is obtained by a coordination reaction between the P chiral pincer compound represented by the chemical formula (II) and a divalent palladium salt,

The P chiral PCP-type pincer palladium complex represented by chemical formula (I-B) is selected from potassium bromide, potassium iodide, silver acetate, and trifluoromethyl through the P chiral PCP pincer palladium complex represented by chemical formula (I-A). Any one compound of silver sulfonate, silver fluoroborate, and silver hexafluoroantimonate is obtained by anion exchange reaction,

In formulas (I-A), (I-B) and (II), R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and the chirality of the two Ps is both R configuration or S structure,

In formula (IB), X ¹ is a group selected from -Br, -I, -OAc, -OTf, -BF ₄ , -SbF ₆ ,

The divalent palladium salt is selected from palladium chloride, two (acetonitrile) palladium chloride, dichloro tetraammine palladium, two (triphenylphosphine) palladium dichloride, allyl palladium chloride dimer, ( Any one of 1,5-cyclooctadiene) palladium dichloride.

In the synthesis method of the P-chiral PCP-type pincer palladium complex of the present invention, preferably: the coordination reaction is carried out in the second organic solvent at 0°C to 111°C and under stirring conditions for 8 to 72 hours; the anion exchange reaction is carried out in the third organic solvent at 0°C to 35°C and under stirring in the dark for 18 to 48 hours; the second organic solvent and the third organic solvent Each is selected from toluene, tetrahydrofuran, dichloromethane, acetonitrile, methanol, ether, n-hexane, acetone, chloroform, ethyl acetate, benzene, ethanol, isopropanol, 1,4-dioxane, dimethyl ethylene Any one of sulfone and dimethylformamide.

The present invention also relates to a borane-protected P chiral pincer compound, the chemical formula of which is shown in the following formula (III):

Wherein, R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and the chiralities of the two Ps are both R configuration or S configuration.

The present invention also relates to a synthetic method of a borane-protected P chiral pincer compound, characterized in that,

The borane-protected P chiral pincer compound is represented by the following chemical formula (III),

The borane-protected P chiral pincer compound represented by chemical formula (III) combines the borane-protected P chiral phosphine represented by chemical formula (IV) with 4,6-bis( Chloromethyl) m-dialkylbenzene is obtained by nucleophilic substitution reaction,

In formulas (V) and (III), R represents a group selected from a hydrogen atom or an alkyl group having 1 to 4 carbon atoms,

In the formulas (IV) and (III), the chiralities of the two Ps are R configuration or S configuration at the same time.

In the synthesis method of the borane-protected P chiral pincer compound of the present invention, preferably, the nucleophilic substitution reaction is carried out in the following manner: the first compound containing the borane-protected P chiral phosphine represented by chemical formula (IV) The solution of the four organic solvents is treated with a strong base at -80°C to 0°C, and then the fourth organic solvent containing 4,6-bis(chloromethyl)m-dialkylbenzene represented by chemical formula (V) is added. The solvent solution is mixed and stirred for 1 to 24 hours, thereby obtaining a borane-protected P chiral pincer compound represented by chemical formula (III).

In the synthesis method of the borane-protected P chiral pincer compound of the present invention, preferably: the fourth organic solvent is selected from toluene, tetrahydrofuran, dichloromethane, acetonitrile, methanol, ether, acetone, chloroform, ethyl acetate , benzene, ethanol, isopropanol, tert-butanol, n-hexane, 1,4-dioxane, dimethyl sulfoxide, dimethylformamide; the strong base is selected from n-butyl Any one of base lithium, sec-butyl lithium, tert-butyl lithium, potassium tert-butoxide, sodium methoxide, sodium ethoxide, sodium hydride, and lithium diisopropylamide.

The phosphorous chiral PCP pincer palladium complex (I) synthesized according to the present invention can be used as a chiral catalyst in various asymmetric reactions, such as asymmetric Micheal addition and asymmetric Heck coupling reaction , asymmetric Suzuki-Miyaura coupling reaction, asymmetric allylation reaction, etc., have high catalytic activity and stereoselectivity, and have good application prospects.

Detailed ways

First of all, for the sake of simplicity, in the following description, for the "P chiral PCP-type pincer palladium complex represented by chemical formula (I)" of the present invention, sometimes only "(I)" or "palladium complex ( I)" to represent; similarly, for the "P chiral pincer compound represented by chemical formula (II)" of the present invention, sometimes only "(II)" or "compound (II)" is used to represent; similarly, For the "borane-protected P chiral pincer compound represented by chemical formula (III)" of the present invention, it is sometimes only represented by "(III)" or "compound (III)"; similarly, for the " The borane-protected P chiral phosphine represented by chemical formula (IV) is sometimes only represented by "(IV)" or "compound (IV)"; in the same way, for the present invention "by chemical formula (V) 4,6-bis(chloromethyl)m-dialkylbenzene" is sometimes only represented by "(V)" or "compound (V)".

(1) The synthetic method of the P chiral pincer compound of borane protection represented by chemical formula (III)

The synthetic method of the borane-protected P chiral pincer compound represented by chemical formula (III) can be represented by the following reaction formula:

In formulas (V) and (III), R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and R is preferably selected from a hydrogen atom, methyl, ethyl, propyl, iso Any one of propyl, n-butyl, isobutyl, and tert-butyl. In the formulas (IV) and (III), the symbol * is marked to indicate that P has chirality, and the chiralities of the two Ps are R configuration or S configuration at the same time. In the synthesis method of the borane-protected P chiral pincer compound represented by chemical formula (III) of the present invention, for the reaction conditions of nucleophilic substitution, as long as the compound can be synthesized from compound (IV) and compound (V) (III) will do. In the present invention, considering the mildness of the reaction conditions and ease of operation, the nucleophilic substitution reaction is preferably carried out as follows: the fourth organic compound containing P chiral phosphine protected by borane represented by chemical formula (IV) The solution of the solvent is treated with a strong base at -80°C to 0°C, and thereafter, the fourth organic solvent containing 4,6-bis(chloromethyl)m-dialkylbenzene represented by chemical formula (V) is added The solutions are mixed and stirred for 1-24 hours, so as to obtain the borane-protected P chiral pincer compound represented by the chemical formula (III). Wherein, the fourth organic solvent can be appropriately selected according to known techniques, as long as the above-mentioned nucleophilic substitution reaction can be carried out, preferably the fourth organic solvent is selected from toluene, tetrahydrofuran, methylene chloride, acetonitrile, methanol, ether, acetone, chloroform , Ethyl acetate, benzene, ethanol, isopropanol, tert-butanol, n-hexane, 1,4-dioxane, dimethyl sulfoxide, dimethylformamide. Wherein, the strong base can be appropriately selected according to known techniques, as long as the above-mentioned nucleophilic substitution reaction can be carried out, the preferred strong base is selected from n-butyllithium, sec-butyllithium, tert-butyllithium, potassium tert-butoxide, methanol Any one of sodium, sodium ethoxide, sodium hydride, and lithium diisopropylamide. For the temperature conditions in the nucleophilic substitution reaction, it can be properly selected according to the known technology and the selected strong base type, as long as the above-mentioned nucleophilic substitution reaction can be carried out, the preferred temperature range is -80°C to 0°C as mentioned above. ℃. For the stirring conditions such as the stirring speed and the stirring mode in the stirring operation, as long as the appropriate stirring conditions are selected according to known techniques to ensure that the reaction can proceed smoothly. For the reaction time, it can be appropriately set according to the actual situation, such as the amount of reaction raw materials and the desired yield, etc., preferably 1 to 72 hours, more preferably 5 to 48 hours, and even more preferably 12 to 24 hours . The obtained borane-protected P chiral pincer compound represented by chemical formula (III) can be refined according to needs, and the specific refining method can be performed according to known techniques by using appropriate washing, extraction, filtration, concentration, drying, etc. .

(2) P chiral pincer compound represented by chemical formula (II) and its synthesis method

The synthetic method of the P chiral pincer compound (II) of the present invention can be represented by the following reaction formula:

In formula (II) and formula (III), R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and R is preferably selected from a hydrogen atom, methyl, ethyl, propyl, Any one of isopropyl, n-butyl, isobutyl, and tert-butyl. In formula (II)), the symbol * is marked to indicate that P has chirality, and the chirality of two Ps is R configuration or S configuration at the same time.

In the synthesis method of the P-chiral pincer compound (II) of the present invention, as far as the reaction conditions of the deborane reaction are concerned, only deborane can be removed in (III). In the present invention, considering the mildness of the reaction conditions and ease of operation, the deborane reaction is preferably carried out in the following manner: at 0°C to 35°C, the borane-protected P chiral clamp represented by chemical formula (III) Form compound and sulfonic acid are stirred in the first organic solvent for 0.5 to 1.5 hours, then, the organic volatiles are removed under reduced pressure, and then degassed alkali metal hydroxide-ethanol-water solution is added, at 40°C to 60°C Stir for 1-4 hours to obtain the P chiral pincer compound represented by chemical formula (II). Wherein, the first organic solvent can be appropriately selected according to known techniques, as long as the above-mentioned deborane reaction can be carried out, preferably the first organic solvent is selected from toluene, tetrahydrofuran, methylene chloride, acetonitrile, methanol, ether, n-hexane, Any of acetone, chloroform, ethyl acetate, benzene, ethanol, isopropanol, 1,4-dioxane, dimethylsulfoxide, and dimethylformamide. Among them, the sulfonic acid is preferably any one selected from methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. Wherein, the alkali metal hydroxide is any one selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, and cesium hydroxide. For the decompression condition, as long as most of the organic solvent can be removed, it can be set according to the actual situation, such as the amount of the reaction raw material and the type of the organic solvent used in the reaction. For the stirring conditions such as the stirring speed and the stirring mode in the stirring operation, as long as the appropriate stirring conditions are selected according to known techniques to ensure that the reaction can proceed smoothly. For the alkali metal hydroxide-ethanol-aqueous solution, as long as the strong alkaline solution prepared with alkali metal hydroxide, ethanol and water according to the known technology gets final product, for example, lithium hydroxide-ethanol-aqueous solution, hydrogen Sodium oxide-ethanol-water solution, or potassium hydroxide-ethanol-water solution. The obtained P-chiral pincer compound represented by chemical formula (II) can be refined as required, and the specific purification method can be performed by appropriate washing, extraction, filtration, concentration, drying and other operations according to known techniques.

(3) P chiral PCP-type pincer palladium complex represented by chemical formula (I) and its synthesis method

For the "P chiral PCP pincer palladium complex represented by chemical formula (I)" of the present invention, it can be represented by chemical formula (IA) or (IB) respectively according to the difference of X in chemical formula (I). Specifically, in chemical formula (I), when X represents -Cl, it is actually chemical formula (IA); in chemical formula (I), when X represents a group selected from -Br, -I, -OAc (acetate) , -OTf (trifluoromethanesulfonate), -BF ₄ , -SbF ₆ groups, it is actually the chemical formula (IB); this representation is for easier description of the palladium complex (I) of the present invention resolve resolution. For the "P chiral PCP-type pincer palladium complex represented by chemical formula (IA)" of the present invention, for the sake of simplicity, in the following description, sometimes only "(IA)" or "palladium complex (IA) "; for the "P chiral PCP-type pincer palladium complex represented by chemical formula (IB)" of the present invention, for the sake of simplicity, in the following description, sometimes only "(IB)" or "palladium complex Things (IB)" to represent.

The synthetic method of palladium complex (I) of the present invention can be expressed with following reaction formula:

In formulas (IA), (IB) and (II), R represents a group selected from a hydrogen atom or an alkyl group with 1 to 4 carbon atoms, and the chirality of the two Ps is both R configuration or S Configuration; in formula (IB), X ¹ is a group selected from -Br, -I, -OAc, -OTf, -BF ₄ , -SbF ₆ .

In the synthesis method of the palladium complex (I) of the present invention, specifically, for the coordination reaction from (II) to (I-A), as long as it can Next, (II) performs a coordination reaction with a divalent palladium salt to obtain a palladium complex (I-A). Wherein, the divalent palladium salt is selected from palladium chloride, bis(acetonitrile) palladium chloride, tetraammine palladium dichloride, bis(triphenylphosphine) palladium dichloride, allyl palladium chloride dimer, ( Any one of 1,5-cyclooctadiene) palladium dichloride. In the above-mentioned coordination reaction, in view of the mildness of the reaction conditions and ease of operation, it is preferably carried out in the second organic solvent at 0° C. to 111° C. under stirring for 8 to 72 hours. Wherein, the second organic solvent can be appropriately selected according to known techniques, as long as the above-mentioned coordination reaction can be carried out, the preferred second organic solvent is selected from toluene, tetrahydrofuran, methylene chloride, acetonitrile, methanol, ether, n-hexane, acetone , chloroform, ethyl acetate, benzene, ethanol, isopropanol, 1,4-dioxane, dimethyl sulfoxide, and dimethylformamide. The reaction temperature can be appropriately set in consideration of the type of organic solvent to be used according to actual conditions, and is preferably 0°C to 111°C, more preferably 0 to 60°C, and even more preferably 0 to 50°C. The reaction time can be appropriately set according to other reaction conditions, but is preferably 8 to 72 hours, more preferably 24 to 72 hours, and still more preferably 24 to 36 hours. For stirring conditions, as long as the stirring conditions such as suitable stirring speed and stirring mode are selected according to known techniques to ensure that the reaction can proceed smoothly. The obtained (I-A) can be refined as required, and the specific purification method can be performed by using appropriate washing, extraction, filtration, concentration, drying and other operations according to known techniques.

In addition, in the synthesis method of the palladium complex (I) of the present invention, specifically, for the anion exchange reaction from (I-A) to (I-B), as long as it can In the case of , it is enough to obtain (I-B) from (I-A) through anion exchange reaction. The compound used for the anion exchange reaction with (I-A) is any one selected from potassium bromide, potassium iodide, silver acetate, silver trifluoromethanesulfonate, silver fluoroborate, and silver hexafluoroantimonate. In the above-mentioned anion exchange reaction, in view of the mildness of the reaction conditions and ease of operation, it is preferably carried out in the third organic solvent at 0° C. to 35° C. under stirring in a dark place for 18 to 48 hours. Wherein, the third organic solvent can be appropriately selected according to known techniques, as long as the above-mentioned anion exchange reaction can be carried out, preferably the third organic solvent is selected from toluene, tetrahydrofuran, methylene chloride, acetonitrile, methanol, ether, n-hexane, acetone , chloroform, ethyl acetate, benzene, ethanol, isopropanol, 1,4-dioxane, dimethyl sulfoxide, and dimethylformamide. The reaction temperature is preferably 0°C to 35°C, more preferably 0°C to 20°C, even more preferably 20°C to 35°C. The reaction time can be appropriately set according to other reaction conditions, but is preferably 18 to 48 hours, more preferably 24 to 48 hours, and still more preferably 18 to 24 hours. For stirring conditions, as long as the stirring conditions such as suitable stirring speed and stirring mode are selected according to known techniques to ensure that the reaction can proceed smoothly. The obtained (I-B) can be refined as required, and the specific purification method can be performed by using appropriate washing, extraction, filtration, concentration, drying and other operations according to known techniques.

In addition, in the present invention, the above-mentioned first organic solvent, second organic solvent, third organic solvent and fourth organic solvent can be the same or different respectively, and the selection of specific types can be appropriately selected according to various conditions in specific reactions, It is sufficient as long as the desired reaction can be carried out.

Example:

Specific examples are given below for compounds (III), (II) and palladium complexes (I) involved in the present invention and their synthesis methods. Apparently, the protection scope of the present invention is not limited to the following examples.

In the following examples: according to the different substituents R in the chemical formula (I), the palladium complexes (I) are respectively represented as (I-a), (I-b), (I-c), (I-d), (I-e); according to the chemical formula The different substituents R in (II) represent the compounds (II) as (II-a), (II-b), (II-c), (II-d), (II-e) respectively; according to the chemical formula According to the difference of the substituent R in (III), the compound (III) is respectively represented as (III-a), (III-b), (III-c), (III-d), (III-e); according to the chemical formula According to the different substituents R in (V), compounds (V) are represented as (V-a), (V-b), (V-c), (V-d), (V-e), respectively, and the specific corresponding relationships are shown in Table 1 below.

Table 1:

In the present invention, as mentioned above, it is obvious that the substituent R is not affected in the synthesis reaction, so what is obtained by nucleophilic substitution from compound (V-a) is (III-a), and further, by (III-a ) is (II-a) obtained by deborane reaction, further, (I-a) is obtained by coordination reaction from (II-a). Similarly, (III-b) is obtained from compound (V-b) through nucleophilic substitution, further, (II-b) is obtained from (III-b) through deborane reaction, further, (II- b) After the coordination reaction, (I-b) is obtained. (III-c) is obtained from compound (V-c) through nucleophilic substitution, further, (II-c) is obtained from (III-c) through deborane reaction, and further, (II-c) is obtained through The coordination reaction gives (I-c). (III-d) is obtained from compound (V-d) through nucleophilic substitution, further, (II-d) is obtained from (III-d) through deborane reaction, and further, (II-d) is obtained through The coordination reaction gives (I-d). (III-e) is obtained from compound (V-e) through nucleophilic substitution, further, (II-e) is obtained from (III-e) through deborane reaction, and further, (II-e) is obtained through The coordination reaction gives (I-e).

In addition, in the following examples, the palladium complex (I-b) is respectively represented as (I-b-A), (I-b-B1), (I-b-B2), (I-b-B3) according to the difference of X in its chemical formula (I) , (I-b-B4), (I-b-B5), (I-b-B6), the specific corresponding relationship is shown in Table 2 below.

Table 2:

In addition, in the following examples, the yield is a numerical value calculated according to the following calculation formula.

In the following examples, the percent enantiomeric excess (ie, ee values) was determined by HPLC (chiral column). The instrument used for HPLC analysis is LC-2010 of Shimadzu Corporation, and the specific operating conditions are: Daicel Chiralcel OD-H, OJ-H column, IC-3column, IE-H column or AD- H column Chiral chromatography column.

In the embodiment of the present invention, the instrument used for NMR analysis is Varian's MERCURY plus-400 (400MHz, ¹ H; 100MHz, ¹³ C; 162MHz, ³¹ P; 376MHz, ¹⁹ F) spectrometer. The instrument used for mass spectrometry was a Waters Micromass Q-TOF Premier Mass Spectrometer. The instrument used for melting point determination is SGW X-4micro melting point apparatus. The instrument used for the determination of optical rotation value [α] ²⁵ _D is Rudolph Research Analytical Autopol VI automatic polarimeter (50mm, 589nm).

Embodiment 1: Preparation of compound (III-a)

Compound (III-a) is (S,S)-1,5-bis((borane tert-butylmethylphosphine)methylene)benzene.

(IV) (3.10g, 33mmol) in n-hexane (33mL) was cooled to -80°C, and then sec-butyllithium in n-hexane solution (34.7mL of1.0M hexane solution, 34.7mmol) was added dropwise, until sec-butyl After the addition of baselithium was completed, the stirring was continued at -80°C for half an hour, and a solution of (V-a) (2.69g, 15mmol) in n-hexane (15mL) was added in one go. Then the reaction solution was slowly warmed to room temperature and stirred overnight, and the reaction solution was transferred to a suspension of ethyl acetate (40 mL) and water (70 mL). The organic layer was separated, and the aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were washed twice with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a viscous oil. Add n-hexane to the oily product, stir to see white solid particles, and filter to obtain compound (III-a) (3.65 g, yield 72%).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₁₈ H ₃₈ B ₂ P ₂ Na ⁺ ,361.2533; Measured value: 361.2539.

Embodiment 2: Preparation of compound (III-b)

Compound (III-b) is (S,S)-1,5-bis((borane tert-butylmethylphosphine)methylene)-2,4-dimethylbenzene.

Cool the solution of (IV) (3.89g, 33mmol) in tetrahydrofuran (33mL) to -80°C, then add n-butyllithium in n-hexane solution (21.4mL of1.62M hexane solution, 34.7mmol) dropwise, until n-butyl After the dropwise addition of lithium was completed, the stirring was continued at -80°C for half an hour, and then a solution of (V-b) (3.05 g, 15 mmol) in tetrahydrofuran (15 mL) was added in one go. Then the reaction solution was slowly raised to room temperature and stirred overnight, and most of the THF was evaporated, and the reaction solution was transferred to a suspension of ethyl acetate (40 mL) and water (70 mL). The organic layer was separated, and the aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were washed twice with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a viscous oil. Add n-hexane to the oily product, stir to see white solid particles, and filter to obtain compound (III-b) (4.24 g, yield 77%).

Melting point: 151-152℃; [a] ²⁵ _D =-60.9(c1.0, EtOAc).

¹ H NMR (400MHz, CDCl ₃ ): δ=7.08(s,1H),6.98(s,1H),3.04-2.92(m,4H),2.29(s,6H),1.25(d, ³ J _PH = 13.6Hz,18H),1.08(d, ² J _PH =9.2Hz,6H),0.75-0.05(br q,6H); ³¹ P NMR(162MHz,CDCl ₃ ):δ=30.3(m).

¹³ C NMR (100MHz, CDCl ₃ ): δ=135.6(vt, J=3.3Hz), 133.3(vt, J=2.4Hz), 132.7(vt, J=3.4Hz), 129.5, (q, J=5.3 Hz)28.2(d,J=32.5Hz),25.39(d,J=2.0Hz),24.7(d,J=27.4Hz),20.3,5.0(d,J=34.1Hz).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₂₀ H ₄₂ B ₂ P ₂ Na ⁺ ,389.2840; found value: 389.2892.

Embodiment 3: Preparation of compound (III-c)

Compound (III-c) is (S,S)-1,5-bis((borane tert-butylmethylphosphine)methylene)-2,4-diethylbenzene.

Cool the solution of (IV) (3.89g, 33mmol) in tetrahydrofuran (33mL) to -80°C, then add n-butyllithium in n-hexane solution (21.4mL of1.62M hexane solution, 34.7mmol) dropwise, until butyllithium After the dropwise addition, continue to stir at -80°C for half an hour, and then add (V-c) (15mmol) in tetrahydrofuran (15mL) all at once. Then the reaction solution was slowly raised to room temperature and stirred overnight, and most of the THF was evaporated, and the reaction solution was transferred to a suspension of ethyl acetate (40 mL) and water (70 mL). The organic layer was separated, and the aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were washed twice with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a viscous oil. Add n-hexane to the oily product, stir to see the formation of white solid particles, and filter to obtain compound (III-c) (4.49 g, yield 76%).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₂₂ H ₄₆ B ₂ P ₂ Na ⁺ ,417.3159; Measured value: 417.3158.

Embodiment 4: Preparation of compound (III-d)

Compound (III-d) is (S,S)-1,5-bis((borane tert-butylmethylphosphine)methylene)-2,4-diisopropylbenzene.

Cool the solution of (IV) (3.89g, 33mmol) in 1,4-dioxane (40mL) to -0°C, then add NaH (34.7mmol) in a nitrogen atmosphere, and continue to stir at -0°C for half an hour, A solution of (V-d) (15 mmol) in 1,4-dioxane (15 mL) was added in one portion. Then the reaction solution was slowly raised to room temperature and stirred overnight, and most of the 1,4-dioxane was evaporated, and the reaction solution was transferred to a suspension of ethyl acetate (40 mL) and water (70 mL). The organic layer was separated, and the aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were washed twice with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a viscous oil. Add n-hexane to the oily substance, stir to see white solid particles, and filter to obtain compound (III-d) (4.94g, yield 78%).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₂₄ H ₅₀ B ₂ P ₂ Na ⁺ ,445.3472; Measured value: 445.3470.

Embodiment 5: Preparation of compound (III-e)

Compound (III-e) is (S,S)-1,5-bis((borane tert-butylmethylphosphine)methylene)-2,4-di-tert-butylbenzene.

Cool the solution of (IV) (3.89g, 33mmol) in tetrahydrofuran (33mL) to -80°C, then add n-butyllithium in n-hexane solution (21.4mL of1.62M hexane solution, 34.7mmol) dropwise, until butyllithium After the dropwise addition, continue to stir at -80°C for half an hour, and then add (V-e) (15mmol) in tetrahydrofuran (15mL) all at once. Then the reaction solution was slowly warmed to room temperature and stirred overnight, and the reaction solution was transferred to a suspension of ethyl acetate (40 mL) and water (70 mL). The organic layer was separated, and the aqueous phase was extracted with ethyl acetate (30 mL). The combined organic phases were washed twice with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a viscous oil. Add n-hexane to the oil, stir to see white solid particles, and filter to obtain compound (III-e) (5.12 g, yield 75%).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₂₆ H ₅₄ B ₂ P ₂ Na ⁺ ,473.3785; Measured value: 473.3783.

Embodiment 6: Preparation of compound (II-a)

Compound (II-a) is (S,S)-1,5-bis((tert-butylmethylphosphine)methylene)benzene.

(III-a) (224mg, 0.66mmol) was added to a 25mL two-neck round-bottom flask, vacuum-filled with nitrogen was cycled 4 times, then dry degassed toluene (5mL) was added and the mixture was cooled to 0°C. Trifluoromethanesulfonic acid (980 mg, 6.6 mmol, 10.0 equiv.) was dropped into the cooled reaction flask. After the trifluoromethanesulfonic acid was dropped, the mixture was stirred at 0° C. for 30 minutes, and then stirred at room temperature for 1 hour. Remove volatiles such as toluene under reduced pressure (also can not remove volatiles such as toluene, but will add excessive alkali, to neutralize acid, so more convenient, have reduced this step of underpressure distillation under nitrogen protection). A viscous orange-red oil remained in the flask. Degassed potassium hydroxide-ethanol-water solution (KOH, 360 mg, 6.56 mmol, ethanol/water=9 mL/6 mL) was added to the flask. The reaction solution was stirred at 50° C. for 2 hours, cooled to room temperature, and extracted with degassed toluene (30 mL×3). The extracts were combined and dried over anhydrous sodium sulfate. The dried toluene solution was passed through a column of basic alumina and the alumina was washed with degassed toluene. The toluene was spin-dried to obtain a yellowish viscous oil (II-a).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₁₈ H ₃₂ P ₂ Na ⁺ ,333.1877; Measured value: 333.1874.

Embodiment 7: Preparation of compound (II-b)

Compound (II-b) is (S,S)-1,5-bis((tert-butylmethylphosphine)methylene)-2,4-dimethylbenzene.

(III-b) (240mg, 0.66mmol) was added to a 25mL two-neck round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, then dry degassed toluene (5mL) was added and the mixture was cooled to 0°C. Trifluoromethanesulfonic acid (983mg, 6.6mmol, 10.0equiv.) was dropped into the cooled reaction flask. After the trifluoromethanesulfonic acid was dropped, the mixture was stirred at 0°C for 30 minutes, and then stirred at room temperature for 1 hour. Remove volatiles such as toluene under reduced pressure (also can not remove volatiles such as toluene, but will add excessive alkali, to neutralize acid, so more convenient, have reduced this step of underpressure distillation under nitrogen protection). A viscous orange-red oil remained in the flask. Degassed potassium hydroxide-ethanol-water solution (KOH, 735 mg, 13.1 mmol, ethanol/water=13.5 mL/1.5 mL) was added to the flask. The reaction solution was stirred at 50° C. for 2 hours, cooled to room temperature, and extracted with degassed toluene (30 mL×3). The extracts were combined and dried over anhydrous sodium sulfate. The dried toluene solution was passed through a column of basic alumina and the alumina was washed with degassed toluene. The toluene was spin-dried to obtain a yellowish viscous oil (II-b).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculation value: C ₂₀ H ₃₆ P ₂ Na ⁺ ,361.2190; Measured value: 360.2188.

Embodiment 8: Preparation of compound (II-b)

At 20°C, add (III-b) (240mg, 0.66mmol) into a 25mL two-necked round-bottomed flask, vacuum-fill with nitrogen cycle 4 times, and then add dry and degassed tetrahydrofuran (5mL). Add methanesulfonic acid (6.6 mmol, 10.0 equiv.) dropwise into the reaction flask, and continue stirring at 20° C. for 1 hour after the methanesulfonic acid drops completely. Remove volatiles such as tetrahydrofuran under reduced pressure (you can also not remove volatiles such as tetrahydrofuran, but add excess alkali to neutralize the acid, which is more convenient and reduces the step of vacuum distillation under nitrogen protection). A viscous orange-red oil remained in the flask. Degassed sodium hydroxide-ethanol-water solution (NaOH, 524 mg, 13.1 mmol, ethanol/water=13.5 mL/1.5 mL) was added to the flask. The reaction solution was stirred at 60° C. for 1 hour, cooled to room temperature, and extracted with degassed toluene (30 mL×3). The extracts were combined and dried over anhydrous sodium sulfate. The dried toluene solution was passed through a column of basic alumina and the alumina was washed with degassed toluene. The toluene was spin-dried to obtain a yellowish viscous oil (II-b).

Embodiment 9: Preparation of compound (II-b)

At 35°C, add (III-b) (240mg, 0.66mmol) into a 25mL two-neck round-bottomed flask, vacuumize and nitrogen cycle 4 times, then add dry and degassed methanol (5mL). Pour p-toluenesulfonic acid (6.6mmol, 10.0equiv.) into the reaction flask dropwise, and continue stirring at 0°C for 0.5 hours after the p-toluenesulfonic acid drops completely. Remove volatiles such as methanol under reduced pressure (you can also not remove volatiles such as methanol, but add excess alkali to neutralize the acid, which is more convenient and reduces the step of vacuum distillation under nitrogen protection). A viscous orange-red oil remained in the flask. Degassed lithium hydroxide-ethanol-water solution (LiOH, 314 mg, 13.1 mmol, ethanol/water=13.5 mL/1.5 mL) was added to the flask. The reaction solution was stirred at 50° C. for 3 hours, cooled to room temperature, and extracted with degassed toluene (30 mL×3). The extracts were combined and dried over anhydrous sodium sulfate. The dried toluene solution was passed through a column of basic alumina and the alumina was washed with degassed toluene. The toluene was spin-dried to obtain a yellowish viscous oil (II-b).

Example 10: Preparation of compound (II-c)

Compound (II-c) is (S,S)-1,5-bis((tert-butylmethylphosphine)methylene)-2,4-diethylbenzene.

(III-c) (256mg, 0.66mmol) was added to a 25mL two-neck round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, then dry degassed toluene (5mL) was added and the mixture was cooled to 0°C. Trifluoromethanesulfonic acid (980 mg, 6.6 mmol, 10.0 equiv.) was dropped into the cooled reaction flask. After the trifluoromethanesulfonic acid was dropped, the mixture was stirred at 0° C. for 30 minutes, and then stirred at room temperature for 1 hour. Remove volatiles such as toluene under reduced pressure (also can not remove volatiles such as toluene, but will add excessive alkali, to neutralize acid, so more convenient, have reduced this step of underpressure distillation under nitrogen protection). A viscous orange-red oil remained in the flask. Degassed potassium hydroxide-ethanol-water solution (KOH, 360 mg, 6.56 mmol, ethanol/water=9 mL/6 mL) was added to the flask. The reaction solution was stirred at 50° C. for 2 hours, cooled to room temperature, and extracted with degassed toluene (30 mL×3). The extracts were combined and dried over anhydrous sodium sulfate. The dried toluene solution was passed through a column of basic alumina and the alumina was washed with degassed toluene. The toluene was spin-dried to obtain a yellowish viscous oil (II-c).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₂₂ H ₄₀ P ₂ Na ⁺ ,389.2503; Measured value: 389.2500.

Example 11: Preparation of compound (II-d)

Compound (II-d) is (S,S)-1,5-bis((tert-butylmethylphosphine)methylene)-2,4-diisopropylbenzene.

(III-d) (272mg, 0.66mmol) was added to a 25mL two-neck round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, then dry degassed toluene (5mL) was added and the mixture was cooled to 0°C. Trifluoromethanesulfonic acid (980 mg, 6.6 mmol, 10.0 equiv.) was dropped into the cooled reaction flask. After the trifluoromethanesulfonic acid was dropped, the mixture was stirred at 0° C. for 30 minutes, and then stirred at room temperature for 1 hour. Remove volatiles such as toluene under reduced pressure (also can not remove volatiles such as toluene, but will add excessive alkali, to neutralize acid, so more convenient, have reduced this step of underpressure distillation under nitrogen protection). A viscous orange-red oil remained in the flask. Degassed potassium hydroxide-ethanol-water solution (KOH, 360 mg, 6.56 mmol, ethanol/water=9 mL/6 mL) was added to the flask. The reaction solution was stirred at 50° C. for 2 hours, cooled to room temperature, and extracted with degassed toluene (30 mL×3). The extracts were combined and dried over anhydrous sodium sulfate. The dried toluene solution was passed through a column of basic alumina and the alumina was washed with degassed toluene. The toluene was spin-dried to obtain a yellowish viscous oil (II-d).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₂₄ H ₄₄ P ₂ Na ⁺ ,417.2816; Measured value: 417.2813.

Example 12: Preparation of compound (II-e)

Compound (II-e) is (S,S)-1,5-bis((tert-butylmethylphosphine)methylene)-2,4-di-tert-butylbenzene.

(III-e) (288mg, 0.66mmol) was added to a 25mL two-neck round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, then dry degassed toluene (5mL) was added and the mixture was cooled to 0°C. Trifluoromethanesulfonic acid (980 mg, 6.6 mmol, 10.0 equiv.) was dropped into the cooled reaction flask. After the trifluoromethanesulfonic acid was dropped, the mixture was stirred at 0° C. for 30 minutes, and then stirred at room temperature for 1 hour. Remove volatiles such as toluene under reduced pressure (also can not remove volatiles such as toluene, but will add excess alkali, to neutralize acid, like this is more convenient, has reduced this step of underpressure distillation under nitrogen protection). A viscous orange-red oil remained in the flask. Degassed potassium hydroxide-ethanol-water solution (KOH, 360 mg, 6.56 mmol, ethanol/water=9 mL/6 mL) was added to the flask. The reaction solution was stirred at 50° C. for 2 hours, cooled to room temperature, and extracted with degassed toluene (30 mL×3). The extracts were combined and dried over anhydrous sodium sulfate. The dried toluene solution was passed through a column of basic alumina and the alumina was washed with degassed toluene. The toluene was spin-dried to obtain a yellowish viscous oil (II-e).

HRMS-TOF(m/z): [M+Na] ⁺ Theoretical calculated value: C ₂₆ H ₄₈ P ₂ Na ⁺ ,445.3129; Measured value: 445.3125.

Example 13: Preparation of palladium complex (I-b-A)

Palladium complex (I-b-A) is (S,S)-2,6-bis((tert-butylmethylphosphine)methylene)-3,5-dimethylphenylpalladium chloride complex.

Bis(acetonitrile)palladium chloride (170mg, 0.66mmol) was added into a 25mL round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, and then dry and degassed toluene (1.5mL) was added. Add the toluene solution (6 mL) of (II-b) into the toluene suspension of bis(acetonitrile)palladium chloride at room temperature, stir for 8 hours under reflux, cool down to room temperature, spin dry the solvent, and use 200-300 mesh The product was purified on a silica gel column (ethyl acetate/petroleum ether=1/10-1/3) to obtain a yellow solid (I-b-A) (201 mg, yield 63%).

Melting point: 280-282℃.

¹ H NMR (400MHz, CDCl ₃ ): δ=6.66(s,1H),3.36(vt, ² J _PH =4.0Hz,1H),3.22(vt,J _PH =4.4Hz,1H),2.97(vt, J _PH =4.0Hz,1H),2.93(vt,J _PH =4.4Hz,1H),2.22(s,6H),1.54(vt,J _PH =2.4Hz,6H),1.24(vt,J _PH =7.2 Hz,18H).

³¹ P NMR (162MHz, CDCl ₃ ): δ=47.3(s).

¹³ C NMR (100MHz, CDCl ₃ ): δ=160.0, 145.5(t, J=10.6Hz), 132.2(t, J=9.7Hz, 5H), 128.7, 66.0, 36.0(t, J=12.4Hz), 31.1(t, J=12.4Hz), 26.8(t, J=9.7Hz, 2.2H), 22.5(s), 15.5(s), 7.9(t, J=9.7Hz).

HRMS(ESI): Theoretical calculated value: C ₂₀ H ₃₅ P ₂ Pd[M-Cl] ⁺ 443.1249, found value: 443.1266.

Example 14: Preparation of palladium complex (I-b-A)

Bis(acetonitrile)palladium chloride (170mg, 0.66mmol) was added into a 25mL round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, and then dry and degassed toluene (1.5mL) was added. Add the toluene solution (6 mL) of (II-b) into the toluene suspension of bis(acetonitrile)palladium chloride at 0°C, stir at 0°C for 72 hours, spin the solvent to dry, and use a 200-300 mesh silica gel column The product was purified (ethyl acetate/petroleum ether=1/10-1/3) to obtain a yellow solid (I-b-A) (182 mg, yield 57%).

Example 15: Preparation of palladium complex (I-b-A)

Palladium chloride (0.66mmol) was added into a 25mL round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, and then dry and degassed tetrahydrofuran (1.5mL) was added. Add (II-b) tetrahydrofuran solution (6 mL) into palladium chloride tetrahydrofuran suspension at room temperature, and stir at 60°C for 8 hours, spin to dry the solvent, and purify the product with a 200-300 mesh silica gel column (ethyl acetate Ester/petroleum ether=1/10-1/3), a yellow solid (I-b-A) (185 mg, yield 58%) was obtained.

Example 16: Preparation of palladium complex (I-b-A)

Bis(triphenylphosphine)palladium dichloride (0.66mmol) was added into a 25mL round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, and then dry and degassed methanol (1.5mL) was added. Add the methanol solution (6 mL) of (II-b) into the methanol suspension of bis(triphenylphosphine)palladium dichloride at room temperature, stir at 50°C for 24 hours, spin the solvent dry, and use 200-300 The product was purified on a silica gel column (ethyl acetate/petroleum ether=1/10-1/3) to obtain a yellow solid (I-b-A) (169 mg, yield 53%).

Example 17: Preparation of palladium complex (I-b-A)

(1,5-Cyclooctadiene)palladium dichloride (0.66mmol) was added into a 25mL round-bottomed flask, vacuum-filled with nitrogen was cycled 4 times, and then dry and degassed toluene (1.5mL) was added. The temperature of the reaction solution was raised to 50°C, and the toluene solution (6 mL) of (II-b) was added to the toluene suspension of (1,5-cyclooctadiene)palladium dichloride, and the brownish yellow suspension immediately became clear and turned dark brown. Raise the temperature of the reaction solution to 50°C, and stir at 50°C for 24 hours, cool down to room temperature, spin the solvent, and purify the product with a 200-300 mesh silica gel column (ethyl acetate/petroleum ether=1/10-1/3) , to obtain a yellow solid (I-b-A) (156 mg, yield 49%).

Embodiment 18: Preparation of palladium complex (I-b-B1)

Palladium complex (I-b-B1) is (S,S)-2,6-bis((tert-butylmethylphosphine)methylene)-3,5-dimethylbenzenepalladium bromide complex.

A mixture of (I-b-A) (719.0 mg, 1.5 mmol), potassium bromide (1.58 mmol, 1.05 equiv.) and toluene (30 mL) was stirred in the dark for 24 hours at 20°C. After filtration, the solid was washed with ethyl acetate, and the mother liquor was spin-dried to give a light gray solid (I-b-B1) (747 mg, yield 95%).

HRMS(ESI): Theoretical calculated value: C ₂₀ H ₃₅ P ₂ Pd[M-Br] ⁺ 443.1249, found value: 443.1240.

Embodiment 19: Preparation of palladium complex (I-b-B2)

Palladium complex (I-b-B2) is (S,S)-2,6-bis((tert-butylmethylphosphine)methylene)-3,5-dimethylbenzenetrifluoromethanesulfonate palladium complex.

A mixture of (I-b-A) (719.0 mg, 1.5 mmol), silver trifluoromethanesulfonate (1.58 mmol, 1.05 equiv.) and methanol (30 mL) was stirred in the dark for 18 hours at 35°C. After filtration, the solid was washed with ethyl acetate, and the mother liquor was spin-dried to give a light gray solid (I-b-B2) (872 mg, yield 98%).

Melting point: 173-175℃.

¹ H NMR (400MHz, CDCl ₃ ): δ=6.64(s, 1H), 3.16(vt, J _PH =4.8Hz, 1H), 3.12(vt, J _PH =4.8Hz, 1H), 2.94(br s, 1H),2.90(br s,1H),2.20(s,6H),1.65(vt,J _PH =2.8Hz,6H),1.14(vt,J _PH =8.0Hz,18H).

¹³ C NMR (100MHz, CDCl ₃ ): δ=150.7, 145.8(t, J=10.8Hz), 132.2(t, J=10.3Hz), 129.4, 120.1(q, J=316.8Hz), 33.8(t, J=13.2Hz), 31.2(t, J=12.0Hz), 27.0(vt, J=3.2Hz), 22.3, 7.7(t, J=10.8Hz).

³¹ P NMR (162MHz, CDCl ₃ ): δ=50.7(s).

¹⁹ F NMR (376MHz, CDCl ₃ ): δ=-78.6.

HRMS(ESI): Theoretical calculated value: C ₂₀ H ₃₅ P ₂ Pd[M-OTf] ⁺ 443.1249, measured value: 443.1240.

Embodiment 20: Preparation of palladium complex (I-b-B3)

The palladium complex (I-b-B3) is (S,S)-2,6-bis((tert-butylmethylphosphine)methylene)-3,5-dimethylphenylpalladium iodide complex.

A mixture of (I-b-A) (719.0 mg, 1.5 mmol), potassium iodide (1.58 mmol, 1.05 equiv.) and methanol (30 mL) was stirred in the dark for 18 hours at 35°C. After filtration, the solid was washed with ethyl acetate, and the mother liquor was spin-dried to obtain a light gray solid (I-b-B3) (814 mg, yield 95%).

Melting point: 232-234°C.

¹ H NMR (400MHz, CDCl ₃ ): δ=6.65(s,1H),3.35(vt,J _PH =4.4Hz,1H),3.31(vt,J _PH =4.4Hz,1H),3.08(vt,J _PH =3.6Hz,1H),3.04(vt,J _PH =3.6Hz,1H),2.24(s,6H),1.76(vt,J _PH =2.4Hz,6H),1.16(vt,J _PH =7.6Hz ,18H).

¹³ C NMR (100MHz, CDCl ₃ ): δ=167.4, 145.7(t, J=10.4Hz), 131.6(t, J=10.0Hz), 128.6, 37.0(t, J=12.6Hz), 31.4(t, J=12.4Hz), 27.7(vt, J=2.8Hz), 22.7, 10.0(t, J=11.6Hz).

³¹ P NMR (162MHz, CDCl ₃ ): δ=49.6(s).

[α] ²⁵ _D =-122.5(c0.3,CHCl ₃ ).

HRMS(ESI): Theoretical calculated value: C ₂₀ H ₃₅ P ₂ Pd[MI] ⁺ 443.1249, measured value: 443.1241.

Embodiment 21: Preparation of palladium complex (I-b-B4)

Palladium complex (I-b-B4) is (S,S)-2,6-bis((tert-butylmethylphosphine)methylene)-3,5-dimethylphenylacetic acid palladium complex.

A mixture of (I-b-A) (719.0mg, 1.5mmol), silver acetate (262.9mg, 1.58mmol, 1.05equiv.), tetrahydrofuran (30mL) was stirred in the dark for 48 hours at 0°C. After filtration, the solid was washed with ethyl acetate, and the mother liquor was spin-dried to obtain a light gray solid (I-b-B4) (739 mg, yield 98%).

Melting point: 149-151℃.

¹ H NMR (400MHz, C ₆ D ₆ ): δ=6.71(s,1H),2.97(br,1H),2.93(br,1H),2.58(vt,J _PH =4.4Hz,1H),2.54( vt,J _PH =4.4Hz,1H),2.31(s,3H),2.09(s,6H),1.22(t,J _PH =2.4Hz,6H),1.04(t,J _PH =7.6Hz,18H) .

¹³ C NMR(100MHz,C ₆ D ₆ ):δ=175.6,156.9,145.1(t,J _PC =10.5Hz),132.1(t,J _PC =9.2Hz),128.6,35.0(t,J _PC =12.4 Hz), 29.8(t, J _PC =12.9Hz), 25.9(vt, J _PC =3.3Hz), 22.1, 8.5(t, J _PC =9.8Hz).

³¹ P NMR (162MHz, C ₆ D ₆ ):δ=46.4(s).

HRMS(ESI): Theoretical calculated value: C ₂₀ H ₃₅ P ₂ Pd[M-OAc] ⁺ 443.1249, found value: 443.1266.

Embodiment 22: Preparation of palladium complex (I-b-B5)

Palladium complex (I-b-B5) is (S,S)-2,6-bis((tert-butylmethylphosphine)methylene)-3,5-dimethylbenzenetetrafluoroborate palladium complex.

A mixture of (IbA) (719.0 mg, 1.5 mmol), silver fluoroborate (1.58 mmol, 1.05 equiv.) and toluene (30 mL) was stirred in the dark for 24 hours at 20°C. After filtration, the solid was washed with ethyl acetate, and the mother liquor was spin-dried to obtain a light gray solid (Ib-B5) (741 mg, yield 93%). HRMS(ESI): Theoretical calculated value: C ₂₀ H ₃₅ P ₂ Pd[M-BF ₄ ] ⁺ 443.1249, found value: 443.1239.

Embodiment 23: Preparation of palladium complex (I-b-B6)

Palladium complex (I-b-B6) is (S,S)-2,6-bis((tert-butylmethylphosphine)methylene)-3,5-dimethylbenzenehexafluoroantimonate palladium complex.

A mixture of (I-b-A) (719.0 mg, 1.5 mmol), silver hexafluoroantimonate (1.58 mmol, 1.05 equiv.) and toluene (30 mL) was stirred in the dark for 24 hours at 20°C. After filtration, the solid was washed with ethyl acetate, and the mother liquor was spin-dried to give a light gray solid (I-b-B6) (949 mg, yield 93%).

HRMS(ESI): Theoretical calculated value: C ₂₀ H ₃₅ P ₂ Pd[M-SbF ₆ ] ⁺ 443.1249, measured value: 443.1238.

Example 24 below is an example of the use of the palladium complex (I) of the present invention in the asymmetric Micheal addition of diarylphosphines to nitroalkenes.

Example 24:

The reaction shown in the following reaction formula proceeds.

That is, diarylphosphine (0.315mmol, 1.05equiv.) represented by chemical formula (VII) was added dropwise to dichloromethane of palladium complex (Ib-B4) (3.0mg, 2mol%) at -40°C solution (3.0mL), after stirring for 5 minutes, add nitroalkene (0.30mmol, 1.0equiv.) represented by chemical formula (VI), then add H ₂ O ₂ aqueous solution ( 30%, 80μL). After continuing to stir at room temperature for 2 hours, a saturated Na ₂ S ₂ O ₃ aqueous solution (0.15 mL) was added, the volatile solvent was evaporated, and the product (VIII) was obtained after separation and purification by column chromatography. The specific results are shown in Table 3 below.

table 3:

As shown in Table 3, the palladium complex (I) obtained by the present invention can be well applied in the asymmetric Micheal addition reaction of diarylphosphine to nitroalkene, showing a very high asymmetric induction catalytic effect, and It shows good stereoselectivity and has good application prospects.

Claims (10)

1. a kind of chiral pincerlike compounds of the P of borine protection, shown in chemical formula such as following formula (III)：

Wherein, R represents that it is R configurations simultaneously that the chirality of two P, which is, selected from the group of hydrogen atom or carbon atom number for 1~4 alkyl Or S configurations.

2. a kind of synthetic method of the chiral pincerlike compounds of the P of borine protection, which is characterized in that

The chiral pincerlike compounds of P of borine protection represent by following chemical formula (III)s,

The chiral pincerlike compounds of P of the borine represented by chemical formula (III) protection pass through the borine that is represented by chemical formula (IV) Dialkyl benzene carries out nucleophilic substitution between the P chiral phosphines hydrogen of protection and the 4,6- bis- (chloromethyl) represented by chemical formula (V) And obtain,

In formula (V) and (III), R is represented selected from the group of hydrogen atom or carbon atom number for 1~4 alkyl,

In formula (IV) and (III), it is R configurations or S configurations simultaneously that the chirality of two P, which is,.

3. the synthetic method of the chiral pincerlike compounds of the P of borine protection as claimed in claim 2, which is characterized in that

The nucleophilic substitution carries out as follows：The P protected containing the borine represented by chemical formula (IV) is chiral The solution of 4th organic solvent of hydrogen phosphide is handled at -80 DEG C~0 DEG C with highly basic, later, is added in and is contained by chemical formula (V) solution of the 4th organic solvent of dialkyl benzene be mixed and stirred for 1~24 hour between 4, the 6- bis- (chloromethyl) represented, So as to obtain the chiral pincerlike compounds of P protected by the borine that chemical formula (III) represents.

4. the synthetic method of the chiral pincerlike compounds of the P of borine protection as claimed in claim 3, which is characterized in that

4th organic solvent is selected from toluene, tetrahydrofuran, dichloromethane, acetonitrile, methanol, ether, acetone, chloroform, second Appointing in acetoacetic ester, benzene, ethyl alcohol, isopropanol, the tert-butyl alcohol, n-hexane, 1,4- dioxane, dimethyl sulfoxide, dimethylformamide Meaning is a kind of,

The highly basic is selected from n-BuLi, s-butyl lithium, tert-butyl lithium, potassium tert-butoxide, sodium methoxide, sodium ethoxide, sodium hydride, two Any one in isopropylamino lithium.

5. a kind of synthetic method of the chiral pincerlike compounds of P, which is characterized in that

The chiral pincerlike compounds of the P are the compounds represented by following chemical formula (II)s,

The chiral pincerlike compounds of the P represented by chemical formula (II) by chemical formula (III) described in claim 1 by being represented The chiral pincerlike compounds of P of borine protection carry out the reaction of boron removal alkane and obtain,

In formula (II) and formula (III), R represents the group selected from the alkyl that hydrogen atom or carbon atom number are 1~4, two P's It is R configurations or S configurations simultaneously that chirality, which is,.

6. the synthetic method of the chiral pincerlike compounds of P as claimed in claim 5, which is characterized in that

The boron removal alkane reaction carries out as follows：At 0 DEG C~35 DEG C, the borine represented by chemical formula (III) is protected The chiral pincerlike compounds of the P of shield and sulfonic acid stir 0.5~1.5 hour in the first organic solvent, and then, remove has under reduced pressure Machine volatile matter adds alkali metal hydroxide-ethanol-water solution of degassing, is stirred 1~4 hour at 40 DEG C~60 DEG C, So as to obtain the chiral pincerlike compounds of P represented by chemical formula (II).

7. the synthetic method of the chiral pincerlike compounds of P as claimed in claim 6, which is characterized in that

First organic solvent be selected from toluene, tetrahydrofuran, dichloromethane, acetonitrile, methanol, ether, n-hexane, acetone, Any one in chloroform, ethyl acetate, benzene, ethyl alcohol, isopropanol, Isosorbide-5-Nitrae-dioxane, dimethyl sulfoxide, dimethylformamide,

The sulfonic acid is any one in methanesulfonic acid, trifluoromethanesulfonic acid, benzene sulfonic acid, p-methyl benzenesulfonic acid,

The alkali metal hydroxide is selected from lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide Any one.

8. a kind of P chiralitys PCP type pincer palladium complexes, shown in chemical formula such as following formula (I)：

Wherein, X is selected from-Cl ,-Br ,-I ,-OAc ,-OTf ,-BF₄、-SbF₆Group, R represented selected from hydrogen atom or carbon atom Group of the number for 1~4 alkyl, it is R configurations or S configurations simultaneously that the chirality of two P, which is,.

9. a kind of synthetic method of P chiralitys PCP type pincer palladium complexes, which is characterized in that

The P chiralitys PCP type pincer palladium complexes represent by following chemical formulas (I-A) or (I-B),

The P chirality PCP type pincer palladium complexes represented by chemical formula (I-A) pass through by any one of claim 5-7 the methods The chiral pincerlike compounds of P that the chemical formula (II) of preparation represents carry out complexation reaction with divalent palladium salt and obtain,

The P chiralitys PCP that is represented by chemical formula (I-A) is passed through by the P chirality PCP type pincer palladium complexes that chemical formula (I-B) represents Type pincer palladium complex and times for being selected from potassium bromide, potassium iodide, silver acetate, silver trifluoromethanesulfonate, silver fluoborate, silver hexafluoroantimonate A kind of compound of anticipating carries out anion exchange reaction and obtains,

In formula (I-A), (I-B) and (II), the group for the alkyl that R expressions are selected from hydrogen atom or carbon atom number is 1~4, two The chirality of a P be simultaneously for R configurations or S configurations,

In formula (I-B), X¹It is selected from-Br ,-I ,-OAc ,-OTf ,-BF₄、-SbF₆Group,

The divalent palladium salt be selected from palladium bichloride, two (acetonitrile) palladium bichlorides, four ammonia palladium of dichloro, bis- (triphenylphosphine) palladium chlorides, Any one in chlorination Allylpalladium dimer, (1,5- cyclo-octadiene) palladium chloride.

10. the synthetic method of P chiralitys PCP type pincer palladium complexes as claimed in claim 9, which is characterized in that

The complexation reaction is in a second organic solvent and at 0 DEG C~111 DEG C and to carry out 8~72 under agitation small When,

The anion exchange reaction in third organic solvent and at 0 DEG C~35 DEG C and under agitation in the dark into Row 18~48 hours,

Second organic solvent and the third organic solvent be respectively selected from toluene, tetrahydrofuran, dichloromethane, Acetonitrile, methanol, ether, n-hexane, acetone, chloroform, ethyl acetate, benzene, ethyl alcohol, isopropanol, 1,4- dioxane, diformazan are sub- Any one in sulfone, dimethylformamide.