Chiral tertiary amine phosphine-palladium complex stable to air as well as preparation method and application of chiral tertiary amine phosphine-palladium complex

Abstract

The invention provides a chiral tertiary amine phosphine-palladium complex stable to air as well as a preparation method and application of the chiral tertiary amine phosphine-palladium complex, and belongs to the technical field of palladium complexes. The chiral tertiary amine phosphine-palladium complex which is stable to air is prepared by utilizing the reaction of the chiral tertiary amine phosphine ligand which is not easily oxidized by oxygen and the metal palladium salt, has the special performance of preventing zero-valent palladium from being oxidized and inactivated in the oxidation-reduction process, and specifically and efficiently catalyzes the novel asymmetric self-coupling reaction of arylboronic acid and boric acid ester. The complex has the advantages of simple synthesis, high yield, easy separation and purification of products, wide raw material sources, mild reaction conditions, short route, low cost, convenient storage, transportation and use, high catalytic efficiency, wide application range of substrates, good enantioselectivity and the like; the chiral tertiary amine phosphine ligand has important theoretical and application values for designing, discovering and synthesizing a new type of chiral tertiary amine phosphine ligand with stable air and moisture and expanding asymmetric reaction in which metal palladium participates, especially oxygen-sensitive reaction.

Description

Technical Field

[0001] The present invention relates to the technical field of palladium complexes, and particularly to an air-stable chiral tertiary amine phosphine-palladium complex, a preparation method thereof and an application thereof. Background Art

[0002] Chiral synthesis and asymmetric catalysis are the main methods for synthesizing chiral substances. Asymmetric catalysis can achieve chiral amplification and chiral value addition, and is the most efficient method for obtaining chiral compounds. Asymmetric catalysis includes biocatalysis, asymmetric metal catalysis and organocatalytic small molecule catalysis, each having its own advantages and disadvantages. Although enzymatic catalysis is highly efficient and specific, it has strict requirements for the reaction environment; metal catalysis has a wide range of activation of chemical bonds and can activate inert chemical bonds, but its tolerance to functional groups is relatively poor and it is very sensitive to the structure of ligands and reaction substrates; while organocatalytic small molecule catalysis has good tolerance to functional groups, but its activation and catalytic modes are relatively limited.

[0003] In the process of asymmetric catalysis, one is the regulation of reaction activity, and the other is the control of stereoselectivity. On the one hand, chiral ligands can affect the activation ability of the metal center towards the substrate by activation or deactivation. On the other hand, through their own chiral environment, they can control or influence the stereoselectivity of the reaction. Due to the wide variety of metal types and their diverse activities, they are easily regulated by ligands and can catalyze various chemical transformations with different requirements. In the past half century since the 1960s, asymmetric metal catalysis has developed rapidly. Transition metal catalysis has long occupied a dominant position and has become a frontier research direction in organic synthesis methodology and an important branch of homogeneous catalysis. Among them, chiral phosphine ligands play a crucial role. Different types of novel chiral phosphine ligands have been developed and used in asymmetric organic transformations, and are widely applied in the fields of organic catalysis and pharmaceutical and chemical industries. For example, reactions such as asymmetric allylic substitution, asymmetric dearomatization, asymmetric Heck reaction, asymmetric cross-coupling, asymmetric C-H bond functionalization, asymmetric coupling of π systems, asymmetric addition, asymmetric hydrogenation, and asymmetric organocatalytic reactions (W. Fu and W. Tang. ACS Catalysis 2016, 8, 4814 - 4858). Chiral phosphine ligands have become one of the most common and reliable tools for organic chemists. Although phosphine ligands have a wide range of practical applications, high efficiency, and selectivity, their synthesis is usually relatively complex. Most phosphine ligands are sensitive to air (T. Imamoto. Chemical Reviews 2024, 14, 8657 - 8739). Especially after forming complexes with metals, the zero-valent metal easily oxidizes the trivalent phosphorus in the phosphine ligand to pentavalent phosphorus, thereby easily losing its catalytic activity. For example, the tetrakis(triphenylphosphine)palladium complex obtained by the reaction of metal palladium salts with triphenylphosphine is a common palladium catalyst with wide applications. However, due to its high sensitivity to air, its synthesis, transportation, storage, and application conditions are relatively harsh. In order to make the application of metal palladium more convenient and extensive, it is very important to discover, design, and synthesize air-stable phosphine-palladium complex catalysts, especially for redox reactions that require the participation of oxygen, etc.

[0004] Currently, the research on air-stable phosphine-palladium complex catalysts is relatively scarce. The processes of preparing metal complex catalysts by reacting metal palladium salts with phosphine ligands are all rather cumbersome, with high condition requirements, high production costs, long reaction times, low efficiency, and low purity of the target products. Usually, they need to be carried out under relatively harsh conditions such as anhydrous and anaerobic. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide an air-stable chiral tertiary amine phosphine-palladium complex, its preparation method and application. The chiral tertiary amine phosphine-palladium complex provided by the present invention is simple to synthesize, the raw materials are cheap and easily available, stable in air and moisture, and easy to store, transport and use.

[0006] In order to achieve the above-mentioned invention purpose, the present invention provides the following technical solutions:

[0007] The present invention provides an air-stable chiral tertiary amine phosphine-palladium complex, which comprises a metal palladium salt PdX2 and a chiral tertiary amine phosphine ligand, and the molar ratio of the chiral tertiary amine phosphine ligand to the metal palladium salt is 2:1;

[0008] The air-stable chiral tertiary amine phosphine-palladium complex has a C2-symmetric structure shown in Formulas 1a to 1h:

[0009]

[0010]

[0011] Among them, the Ar is

[0012] The R, R 2 , R 3 , R 4 , R 5 each independently includes a hydrogen atom, an alkyl group with 1 to C 30 , a silyl group with 1 to C 30 , a haloalkyl group with 1 to C 30 , an alkenyl group with 2 to C 30 , an alkynyl group with 2 to C 30 , a halogen, a hydroxyl group, an alkoxy group, an acyloxy group, a mercapto group, a thioether group, a nitro group, a carbonyl group, a carboxyl group, an ester group, an amino group, a substituted amino group, an imino group, a cyano group, a phosphonate group, a phosphine, an amide group, a sulfonyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an alkylaminocarbonyl group, an arylaminocarbonyl group, a substituted or unsubstituted aryl group with 6 to C 50 , a fused aryl group, a polycyclic aryl group, a substituted or unsubstituted aralkyl group with 7 to C 50 , a substituted or unsubstituted aralkoxy group with 7 to C 50 , a substituted or unsubstituted aralkylthiol group with 7 to C 50 , a substituted or unsubstituted heteroaryl group with 7 to C 50 , a substituted or unsubstituted aromatic amino group with 7 to C 30 , a heteroaryl group, a fused heteroaryl group, a polycyclic heteroaryl group, one or several of them;

[0013] The R 1 includes a hydrogen atom, an alkyl group with 1 to C 30Substituted or unsubstituted alkyl and cycloalkyl, substituted or unsubstituted aryl having 5 to C 50 substituted or unsubstituted aryl having 5 to C 50 substituted or unsubstituted fused aryl having 5 to C 50 substituted or unsubstituted condensed aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted fused heterocyclic group, one or more of substituted or unsubstituted fused heterocyclic groups;

[0014] Said R 1 independently has one or more chiral centers;

[0015] Said Y includes at least one of a hydrogen atom, an oxygen atom, a sulfur atom, a phosphorus atom, and a silicon atom;

[0016] Said R 6 includes substituted or unsubstituted aryl having 5 to C 50 substituted or unsubstituted fused aryl having 5 to C 50 substituted or unsubstituted condensed aryl having 5 to C 50 substituted or unsubstituted condensed aryl having 5 to C 50 substituted or unsubstituted aryloxy having 5 to C; at least one of C1 to C 30 substituted or unsubstituted alkyl and cycloalkyl;

[0017] Said R* is a chiral amine and has one or more chiral centers. Said R* includes at least one of S-phenethylamine, S-naphthylethylamine, phenylglycinol, and (1R,2S) 1-amino-2-indanol;

[0018] Said halogen includes one or more of F, Cl, Br, and I; said condensed aryl includes one or more of naphthalene, anthracene, phenanthrene, and carbazole; said heteroaryl includes one or more of thiophene, benzothiophene, fluorene, furan, benzofuran, benzopyrrole, pyridine, quinoline, and benzoquinoline; said condensed heterocyclic group includes one or more of tetrahydroquinoline, dihydroindole, and dihydropyran;

[0019] The palladium metal salt PdX2 includes one or more of palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium nitrate, palladium trifluoroacetate, bis(acetonitrile)palladium dichloride, tetrakis(triphenylphosphine)palladium, bis(benzonitrile)palladium chloride, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, palladium neopentanoate, palladium benzoate, bis(acetylacetonato)palladium, palladium hexafluoroacetylacetonate, tetrakis(acetonitrile)palladium(II) tetrafluoroborate, allylpalladium chloride dimer, norbornadiene palladium dichloride, tris(dibenzylideneacetone)dipalladium / chloroform adduct, (1,5-cyclooctadiene)palladium dichloride, (2-butenyl)palladium chloride dimer, (1,5-cyclooctadiene)palladium bromide, chloro(1,5-cyclooctadiene)methylpalladium, bis(pyridine)palladium dichloride, dichlorodiamminepalladium, sodium chloropalladate, potassium tetrabromopalladate, ammonium hexachloropalladate, dichlorotetraamminepalladium, potassium hexachloropalladate, palladium hydroxide, potassium tetrachloropalladate, bis(isoquinoline)palladium dichloride, tetraammine dichloropalladium, dichloro(ethylenediamine)palladium dichlorotetraamminepalladium hydrate, (2,2′-bipyridine)palladium dichloride, lithium tetrachloropalladate(II) hydrate, tetrakis(acetonitrile)palladium(II) bis(trifluoromethanesulfonate), dichloro(N,N,N′,N′-tetramethylethylenediamine)palladium, 1,2-bis(phenylsulfinyl)ethane palladium(II) diacetate, dimethyl(N,N,N′,N′-tetramethylethylenediamine)palladium(II), bis(2,2,6,6-tetramethyl-3,5-heptanedionato)palladium, bis(3,5,3′,5′-dimethoxydibenzylideneacetone)palladium, (1,5-cyclooctadiene)bis(trimethylsilylmethyl)palladium(II), di-μ-chlorobis[(1,2,3-η)-1-phenyl-2-propen-1-yl]dipalladium, allylchloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl]palladium, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridine)dichloropalladium, allylchloro[1,3-bis(2,6-di-isopropylphenyl)-4,5-dihydroimidazol-2-yl]palladium, dichloro(di-μ-chloro)bis[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]dipalladium(II), allyl(1,3-di(mesityl)-1H-imidazol-2(3H)-ylidene)palladium(IV) chloride, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II).

[0020] Preferably, the R, R 2 , R 3 , R 4 , R 5 each independently includes one or more of a hydrogen atom, a methyl group, an ethyl group, a 1-naphthyl group, a phenyl group, a p-chlorophenyl group, a p-cyanophenyl group, a 3,5-bistrifluorophenyl group, and a tert-butyl group;

[0021] The R 1including one or more of a hydrogen atom, a phenyl group, a p-chlorophenyl group, a p-cyanophenyl group, a 3,5-bis(trifluorophenyl) group, and a tert-butyl group;

[0022] the Y includes at least one of a hydrogen atom, an oxygen atom, a sulfur atom, and a silicon atom;

[0023] the R 6 includes at least one of a phenyl group and a triphenyl group;

[0024] the R* is a chiral amine having one or more chiral centers, and the R* includes at least one of S-phenethylamine, S-naphthylethylamine, phenylglycinol, and (1R,2S)-1-amino-2-indanol;

[0025] the metal palladium salt PdX2 includes at least one of palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium nitrate, and palladium trifluoroacetate.

[0026] Preferably, the air-stable chiral tertiary amine phosphine-palladium complex has a chemical structure shown in any one of Formula 1a-1 to Formula 1a-20, Formula 1b-1 to Formula 1b-5, Formula 1c-1 to Formula 1c-5, Formula 1d-1 to Formula 1d-5, Formula 1e-1 to Formula 1e-5, Formula 1f-1 to Formula 1f-5, Formula 1g-1 to Formula 1g-5, and Formula 1h-1 to Formula 1h-14:

[0027]

[0028]

[0029]

[0030] The present invention also provides a preparation method of the air-stable chiral tertiary amine phosphine-palladium complex according to the above technical solution, which is characterized by including the following

[0031] After mixing a chiral tertiary amine phosphine ligand, a metal palladium salt, and a solvent S1, a complexation reaction is carried out to obtain an air-stable chiral tertiary amine phosphine-palladium complex;

[0032] The chiral tertiary amine phosphine ligand has a structure shown in Formula 2a-1 to Formula 2a-20, Formula 2b-1 to Formula 2b-5, Formula 2c-1 to Formula 2c-5, Formula 2d-1 to Formula 2d-5, Formula 2e-1 to Formula 2e-5, Formula 2f-1 to Formula 2f-5, Formula 2g-1 to Formula 2g-5, and Formula 2h-1 to Formula 2h-14:

[0033]

[0034]

[0035]

[0036] Preferably, the molar ratio of the chiral tertiary amine phosphine ligand to the palladium salt is 2:1.

[0037] Preferably, the solvent S1 is one or more of an alcohol solvent, an alkane solvent, an aromatic solvent, an ether solvent, and a nitrile solvent;

[0038] The alcohol solvent is one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, cyclohexanol, ethylene glycol, butanediol, hexanediol, and glycerol; the alkane solvent is one or more of n-hexane, cyclohexane, heptane, and petroleum ether; the aromatic solvent is one or more of benzene, toluene, xylene, mesitylene, chlorobenzene, and bromobenzene; the ether solvent is one or more of methyl tert-butyl ether, tetrahydrofuran, and dioxane; the nitrile solvent is one or more of acetonitrile, propionitrile, and valeronitrile;

[0039] The volume ratio of the solvent S1 to the amount of substance of the palladium salt is (1-20) mL: 1 mmol.

[0040] Through the solvent S1 of the above types and dosages, the present invention can fully dissolve the chiral tertiary amine phosphine ligand at room temperature, promoting the smooth progress of the complexation reaction.

[0041] Preferably, when the solvent S1 used is azeotropic with water, an azeotropic water separator is used for azeotropic water separation.

[0042] The present invention performs azeotropic water separation through an azeotropic water separator, improving the reaction rate, promoting the reaction to proceed more thoroughly, and increasing the reaction yield.

[0043] Preferably, the temperature of the complexation reaction is 0 °C to 30 °C; the time of the complexation reaction is 1 to 4 h. By controlling the temperature and time of the complexation reaction, the present invention promotes the reaction to proceed more thoroughly and increases the reaction yield.

[0044] The present invention also provides an application of the air-stable chiral tertiary amine phosphine-palladium complex described in the above technical solution in a catalytic asymmetric self-coupling reaction.

[0045] In the present invention, the asymmetric self-coupling reaction is preferably an asymmetric self-coupling reaction of boric acid and boric acid esters.

[0046] The present invention also provides an application of the air-stable chiral tertiary amine phosphine-palladium complex described in the above technical solution in a palladium-catalyzed reaction, an oxygen-involved reaction, an organic reaction involving tertiary amines and phosphines;

[0047] The palladium-catalyzed reactions include at least one of hydrogenation reaction, Suzuki–Miyaura reaction, Miyaura borylation reaction, Buchwald-Hartwig reaction, Heck reaction, Sonogashira reaction, Stille coupling reaction, Tsuji-Trost reaction, carbonylation coupling reaction, Saegusa oxidation reaction, Fukuyama coupling reaction, dearomatization reaction, Fukuyama reduction reaction, Fujiwara-Moritani reaction, Hiyama coupling, Yu Jinquan C-H activation reaction, Sanford reaction, Alper carbonylation reaction, Trost cyclopentanation reaction, C-O bond formation reaction, Stoltz α-allyl ketone asymmetric synthesis reaction, Hegedus indole synthesis reaction, Kumada coupling reaction, Narasaka-Heck cyclization reaction, Murahashi coupling reaction, diazotization reaction, cycloaddition reaction; The reactions involving oxygen include at least one of Cham-Lam reaction, boric acid coupling reaction, olefin oxidative coupling.

[0048] The present invention also provides an application of the air-stable chiral tertiary amine phosphine-palladium complex described in the above technical solution in the derivative synthesis of chiral catalysts and materials, medicines, pesticides and intermediates.

[0049] In the present invention, the chiral catalyst preferably includes a chiral quaternary ammonium salt and a chiral quaternary phosphonium salt phase transfer catalyst.

[0050] The present invention discloses an air-stable chiral tertiary amine phosphine-palladium complex, which is prepared by reacting a type of chiral tertiary amine phosphine ligand that is not easily oxidized by oxygen with a metal palladium salt (PdX2). The chiral tertiary amine phosphine-palladium complex has special properties of being stable to oxygen and moisture, and it has a special performance of being able to prevent zero-valent palladium from being oxidized and deactivated during the redox process, and specifically and efficiently catalyzes the asymmetric self-coupling reaction of arylboronic acids and boronic esters. Since most of the known chiral tertiary amine phosphine ligands (or chiral phosphine ligands) are sensitive to oxygen and moisture, with long synthesis routes, harsh reaction conditions, and cumbersome storage and use, while the chiral tertiary amine phosphine-palladium complex provided by the present invention has the advantages of simple synthesis, high yield, easy separation and purification of the product, wide source of raw materials, mild reaction conditions, short route, low cost, convenient storage, transportation and use, high catalytic efficiency, wide substrate scope, good enantioselectivity, etc., overcoming the main defects of the synthesis and properties of the existing chiral tertiary amine phosphine ligands. Therefore, the chiral tertiary amine phosphine-palladium complex provided by the present invention has important theoretical and application values for the design, discovery and synthesis of new types of air- and moisture-stable chiral tertiary amine phosphine ligands and for expanding asymmetric reactions involving metal palladium, especially oxygen-sensitive reactions. Description of the Drawings

[0051] Figure 1 This is the single crystal structure diagram of complex 1b-1 in the present invention;

[0052] Figure 2 This is the single crystal structure diagram of complex 1f-1 in the present invention;

[0053] Figure 3 This is the single crystal structure diagram of complex 1g-1 in the present invention. Detailed implementation manners

[0054] In the present invention, unless otherwise specified, the raw materials used are all conventional commercially available products in the art.

[0055] Next, the technical solutions in the present invention will be clearly and completely described in conjunction with the embodiments in the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without creative efforts shall fall within the protection scope of the present invention.

[0056] The representative synthesis route and process of the chiral tertiary amine phosphine ligand described in the present invention can refer to the relevant literature: K. Shibatomi and Y. Uozumi. Tetrahedron: Asymmetry 2002, 13, 1769–1772; Wang Lixin, Lu Sen, Wan Wenjuan, Tian Fang, Zhang Qianmao; CN 115025814 B, 2022.

[0057] Example 1

[0058] The preparation method of an air-stable chiral tertiary amine phosphine ligand (abbreviated as ligand 2b-1) having the structure shown in Formula 2b-1 is as follows:

[0059] The preparation route is shown in the following formula,

[0060]

[0061] In the first step, 244.2 mg of the amino amide having the structure shown in Formula 3b-1 was added to 3 mL of methanol at 25 °C to obtain an amino amide solution; in the second step, 290.1 mg of diphenylphosphine benzaldehyde was added to the amino amide solution under stirring, and the mixture was stirred and reacted at 80 °C under reflux for 3 h. After the reaction was completed, methanol was removed by rotary evaporation, and the target product ligand 2b-1 was obtained by column chromatography, totaling 500.5 mg, with a yield of 97% and a product purity of 99%.

[0062] The characterization data of ligand 2b-1 are: m.p. 186-187 °C, 1HNMR(400 MHz, Chloroform-d) δ 7.44 (d, J = 8.0 Hz, 2H), 7.39 - 7.31 (m, 10H), 7.25 - 7.14 (m, 5H), 7.05 (t, J = 7.6 Hz, 1H), 7.02 - 6.98 (m, 1H), 6.73 (d, J = 6.0 Hz, 1H), 4.04 (dd, J = 9.2, 6.4 Hz, 1H), 2.99 (dt, J = 10.8, 4.8 Hz, 1H), 2.06 - 1.93 (m, 3H), 1.79 - 1.73 (m, 1H), 1.61 (s, 2H), 1.43 (s, 2H), 1.26 - 1.22 (m, 1H), 1.11 - 1.03 (m, 2H). 13 C NMR(101 MHz, Chloroform-d) δ 177.05, 144.36 (d, J = 22.22 Hz), 137.41, 136.63 (d, J = 9.09 Hz), 135.92 (d, J = 8.08 Hz), 135.45 (d, J = 6.06 Hz), 134.92, 134.42 (d, J = 20.20 Hz), 134.02 (d, J = 19.19 Hz), 129.72, 129.21, 129.02, 128.92, 128.85, 128.83, 128.46 (t, J = 8.08 Hz), 124.88, 124.83, 124.65, 120.37, 74.89, 74.63, 63.07, 61.59, 38.17, 28.47, 27.06, 25.90, 24.28, 23.54, 20.68. 31 P NMR(162 MHz, Chloroform-d) δ -16.19.

[0063] Examples 2 to 10

[0064] The ligand 2b-1 was prepared according to the method of Example 1, except that the solvent methanol was replaced with n-propanol, isopropanol, n-butanol, tert-butanol, cyclohexanol, ethylene glycol, butanediol, hexanediol, and glycerol, respectively.

[0065] Example 11

[0066] A chiral tertiary amine phosphine-palladium metal complex that is stable in air, having the structure shown in Formula 1b-1 below, abbreviated as Complex 1b-1;

[0067] The preparation method of the chiral tertiary amine phosphine-palladium metal complex is as follows:

[0068] The preparation route is as shown in the following formula,

[0069]

[0070] Step 1: Add 18 mg of palladium dichloride to 2 mL of acetonitrile at 25 °C and stir to obtain an acetonitrile solution of palladium dichloride; Step 2: Dissolve 102 mg of ligand 2b-1 prepared in Example 1 in 2 mL of acetonitrile under stirring until dissolved to obtain an acetonitrile solution of the ligand; Step 3: Under the condition of rapid stirring, drop the acetonitrile solution of the ligand prepared in the second step into the acetonitrile solution of palladium dichloride prepared in the first step, and stir and react at a temperature of 25 °C to the reflux condition of the acetonitrile solvent for 1.5 h. After the reaction, filter, wash, drain, and dry in vacuum at 60 °C for 4 h to obtain 119 mg of the target product complex 1b-1, with a yield of 99% and a product purity of 99%.

[0071] The characterization data of the complex 1b-1 are as follows: 31 PNMR (162 MHz, CDCl3) δ 8.22. The single crystal structure of the complex 1b-1 is as Figure 1 shown.

[0072] Examples 12 to 21

[0073] Prepare the complex 1b-1 according to the method of Example 11. The difference from Example 11 is that the solvent S1 acetonitrile is replaced with methanol, n-propanol, isopropanol, n-butanol, tert-butanol, cyclohexanol, ethylene glycol, butanediol, hexanediol, and glycerol respectively.

[0074] Examples 22 to 25

[0075] Prepare other complexes 1b of the same series according to the method of Example 11. The difference from Example 11 is that the raw material ligand 2b-1 is replaced with ligands of formula 2b-2, 2b-3, 2b-4, and 2b-5, and finally purified by column chromatography.

[0076] Examples 26 to 78

[0077] Prepare an air-stable chiral tertiary amine phosphine-palladium complex according to the method of Example 11, except that: palladium dichloride is replaced with palladium bromide, palladium iodide, palladium acetate, palladium nitrate, palladium trifluoroacetate, bis(acetonitrile)palladium dichloride, tetrakis(triphenylphosphine)palladium, bis(benzonitrile)palladium chloride, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, palladium neopentanoate, palladium benzoate, bis(acetylacetonato)palladium, palladium hexafluoroacetylacetonate, tetrakis(acetonitrile)palladium(II) tetrafluoroborate, allyl palladium chloride dimer, norbornadiene palladium dichloride, tris(dibenzylideneacetone)dipalladium / chloroform adduct, (1,5-cyclooctadiene)palladium dichloride, (2-butenyl)palladium chloride dimer, (1,5-cyclooctadiene)palladium bromide, chloro(1,5-cyclooctadiene)methylpalladium, bis(pyridine)palladium dichloride, dichloroamminepalladium, sodium chloropalladate, potassium tetrabromopalladate, ammonium hexachloropalladate, dichloro(tetraammine)palladium, potassium hexachloropalladate, palladium hydroxide, potassium tetrachloropalladate, bis(isoquinoline)palladium dichloride, tetraamminepalladium dichloride, dichloro(ethylenediamine)palladium dichloro(tetraammine)palladium hydrate, (2,2′-bipyridine)palladium dichloride, lithium tetrachloropalladate(II) hydrate, tetrakis(acetonitrile)palladium(II) bis(trifluoromethanesulfonate), dichloro(N,N,N′,N′-tetramethylethylenediamine)palladium, 1,2-bis(phenylsulfinyl)ethane palladium(II) diacetate, dimethyl(N,N,N′,N′-tetramethylethylenediamine)palladium(II), bis(2,2,6,6-methyl-3,5-heptanedionato)palladium, bis(3,5,3′,5′-dimethoxydibenzylideneacetone)palladium, (1,5-cyclooctadiene)bis(trimethylsilylmethyl)palladium(II), di-μ-chloro bis[(1,2,3-η)-1-phenyl-2-propen-1-yl]dipalladium, allylchloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl]palladium, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridine)palladium dichloride, allylchloro[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-yl]palladium, dichloro(di-μ-chloro)bis[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]dipalladium(II), allyl(1,3-bis(mesityl)-1H-imidazol-2(3H)-ylidene)palladium(IV) chloride, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II), to obtain the complex 1b in various anionic states.

[0078] Example 79

[0079] A method for preparing an air-stable chiral tertiary amine phosphine palladium metal complex, abbreviated as complex 1f-1:

[0080] The preparation route is shown in the following formula,

[0081]

[0082] Step 1: Add 18 mg of palladium dichloride to 2 mL of acetonitrile at 25 °C and stir to obtain an acetonitrile solution of palladium dichloride; Step 2: Dissolve 100 mg of ligand 2f-1 in 2 mL of acetonitrile under stirring until dissolved to obtain an acetonitrile solution of imidazolyltriphenylphosphine; Step 3: Under rapid stirring conditions, drop the acetonitrile solution of imidazolyltriphenylphosphine prepared in Step 2 into the acetonitrile solution of palladium dichloride prepared in Step 1, and stir and react at a temperature of 25 °C to the solvent reflux condition for 1.5 h. After the reaction, filter, wash, drain, and dry in vacuum at 70 °C for 5 h to obtain 117 mg of the target product complex 1f-1, with a yield of 92% and a product purity of 99%.

[0083] The characterization data of catalyst 1f-1 are as follows: 31 PNMR (162 MHz, CDCl3) δ 8.69.

[0084] The single crystal structure of the complex 1f-1 is as Figure 2 shown:

[0085] Examples 80 to 89

[0086] Prepare the complex 1f-1 according to the method of Example 79. The difference from Example 79 is that the solvent S1 acetonitrile is replaced with methanol, n-propanol, isopropanol, n-butanol, tert-butanol, cyclohexanol, ethylene glycol, butanediol, hexanediol, and glycerol respectively.

[0087] Examples 90 to 93

[0088] Prepare other complexes 1f of the same series according to the method of Example 79. The difference from Example 79 is that the raw material ligand 2f-1 is replaced with ligands of formula 2f-2, 2f-3, 2f-4, and 2f-5, and finally column chromatography purification is carried out.

[0089] Examples 94 to 146

[0090] Prepare an air-stable chiral tertiary amine phosphine-palladium complex according to the method of Example 79. The difference from Example 79 is that palladium dichloride is replaced with palladium bromide, palladium iodide, palladium acetate, palladium nitrate, palladium trifluoroacetate, bis(acetonitrile)palladium dichloride, tetrakis(triphenylphosphine)palladium, bis(benzonitrile)palladium chloride, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, palladium neopentanoate, palladium benzoate, bis(acetylacetonato)palladium, palladium hexafluoroacetylacetonate, tetrakis(acetonitrile)palladium(II) tetrafluoroborate, allyl palladium chloride dimer, norbornadiene palladium dichloride, tris(dibenzylideneacetone)dipalladium / chloroform adduct, (1,5-cyclooctadiene)palladium dichloride, (2-butenyl)palladium chloride dimer, (1,5-cyclooctadiene)palladium bromide, chloro(1,5-cyclooctadiene)methylpalladium, bis(pyridine)palladium dichloride, dichloroamminepalladium, sodium chloropalladate, potassium tetrabromopalladate, ammonium hexachloropalladate, dichloro(tetraammine)palladium, potassium hexachloropalladate, palladium hydroxide, potassium tetrachloropalladate, bis(isoquinoline)palladium dichloride, tetraamminepalladium dichloride, dichloro(ethylenediamine)palladium dichloro(tetraammine)palladium hydrate, (2,2'-bipyridine)palladium dichloride, lithium tetrachloropalladate(II) hydrate, tetrakis(acetonitrile)palladium(II) bis(trifluoromethanesulfonate), dichloro(N,N,N',N'-tetramethylethylenediamine)palladium, 1,2-bis(phenylsulfinyl)ethane palladium(II) diacetate, dimethyl(N,N,N',N'-tetramethylethylenediamine)palladium(II), bis(2,2,6,6-methyl-3,5-heptanedionato)palladium, bis(3,5,3',5'-dimethoxydibenzylideneacetone)palladium, (1,5-cyclooctadiene)bis(trimethylsilylmethyl)palladium(II), di-μ-chlorobis[(1,2,3-η)-1-phenyl-2-propen-1-yl]dipalladium, allylchloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl]palladium, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridine)palladium dichloride, allylchloro[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-yl]palladium, dichloro(di-μ-chloro)bis[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]dipalladium(II), allyl(1,3-bis(mesityl)-1H-imidazol-2(3H)-ylidene)palladium(IV) chloride, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II). Under other identical conditions, complexes 1f in various anionic states are obtained.

[0091] Example 147

[0092] An air-stable chiral tertiary amine phosphine palladium metal complex catalyst has the structure shown in Formula 1g-1 below, abbreviated as Complex 1g-1;

[0093] The preparation method of the chiral tertiary amine phosphine-palladium metal complex is as follows:

[0094] The preparation route is as shown in the following formula,

[0095]

[0096] The first step: Add 18 mg of palladium dichloride to 2 mL of acetonitrile at 25 °C and stir to obtain an acetonitrile solution of palladium dichloride; The second step: Dissolve 102 mg of ligand 2g-1 in 2 mL of acetonitrile under stirring until dissolved to obtain an acetonitrile solution of imidazolyltriphenylphosphine; The third step: Under the condition of rapid stirring, add the acetonitrile solution of imidazolyltriphenylphosphine prepared in the second step dropwise to the acetonitrile solution prepared in the first step, stir and react at a temperature of 25 °C to the solvent reflux condition for 1.5 h. After the reaction is completed, filter, wash, drain, and dry in vacuum at 50 °C for 3 h to obtain 119 mg of the target product complex 1g-1, with a yield of 85% and a product purity of 99%.

[0097] The characterization data of complex 1g-1 are as follows: 31 PNMR(162 MHz, CDCl3) δ 7.75. The single crystal structure of the complex 1g-1 is as Figure 3 shown.

[0098] Examples 148 to 157

[0099] Prepare complex 1g-1 according to the method of Example 147. The difference from Example 147 is that the solvent S1 acetonitrile is replaced with methanol, n-propanol, isopropanol, n-butanol, tert-butanol, cyclohexanol, ethylene glycol, butanediol, hexanediol, and glycerol.

[0100] Examples 158 to 161

[0101] Prepare other complexes 1g of the same series according to the method of Example 148. The difference from Example 148 is that the raw material ligand 2g-1 is replaced with formulas 2g-2, 2g-3, 2g-4, 2g-5, and other conditions are the same. Finally, purify by column chromatography.

[0102] Examples 162 to 214

[0103] Prepare an air-stable chiral tertiary amine phosphine-palladium complex according to the method of Example 148, differing from Example 148 in that: palladium bromide, palladium iodide, palladium acetate, palladium nitrate, palladium trifluoroacetate, bis(acetonitrile)dichloropalladium, tetrakis(triphenylphosphine)palladium, bis(benzonitrile)chloropalladium, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, palladium pivalate, palladium benzoate, bis(acetylacetonate)palladium, palladium hexafluoroacetylacetonate, tetrakis(acetonitrile)palladium(II) tetrafluoroborate, allyl chloride palladium dimer, norbornadiene dichloropalladium, tris(dibenzylideneacetone)dipalladium / chloroform adduct, (1,5-cyclooctadiene)dichloropalladium, (2-butenyl)chloropalladium dimer, (1,5-cyclooctadiene)palladium bromide, chloro(1,5-cyclooctadiene)methylpalladium, bis(pyridine)dichloropalladium, dichlorodiamminepalladium, sodium chloropalladate, potassium tetrabromopalladate, ammonium hexachloropalladate, dichlorotetraamminepalladium, potassium hexachloropalladate, palladium hydroxide, potassium tetrachloropalladate, bis(isoquinoline)dichloropalladium, tetrachlorodiamminepalladium, dichloro(ethylenediamine)palladium dichlorotetraamminepalladium hydrate, (2,2′-bipyridine)dichloropalladium, lithium tetrachloropalladate(II) hydrate, tetrakis(acetonitrile)palladium(II) bis(trifluoromethanesulfonate), dichloro(N,N,N′,N′-tetramethylethylenediamine)palladium, 1,2-bis(phenylsulfinyl)ethane palladium(II) diacetate, dimethyl(N,N,N′,N′-tetramethylethylenediamine)palladium(II), bis(2,2,6,6-tetramethyl-3,5-heptanedionato)palladium, bis(3,5,3′,5′-dimethoxydibenzylideneacetone)palladium, (1,5-cyclooctadiene)bis(trimethylsilylmethyl)palladium(II), di-μ-chlorobis[(1,2,3-η)-1-phenyl-2-propen-1-yl]dipalladium, allyl chloride[1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl]palladium, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridine)dichloropalladium, allyl chloride[1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-yl]palladium, dichloro(di-μ-chloro)bis[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]dipalladium(II), allyl(1,3-di(mesityl)-1H-imidazol-2(3H)-ylidene)chloropalladium(IV), [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II), with other conditions being the same, to obtain 1 g of the complex in each anionic state.

[0104] Application Example 1

[0105] Apply the chiral tertiary amine phosphine-palladium complex complex 1b-1 prepared in Example 11 as a catalyst to the asymmetric self-coupling reaction of asymmetric boric acid and borate ester to synthesize a compound 4a having the structure shown by the following formula. The steps are as follows:

[0106] The reaction formula is as follows:

[0107]

[0108] To a test tube equipped with a magnetic stir bar, 2-methoxy-1-naphthaleneboronic acid compound 5a (0.5 mmol, 1.0 equiv), chiral tertiary amine phosphine-palladium complex 1b-1 (10 mol%), potassium phosphate (1.0 equiv) were added. Subsequently, acetonitrile (2.0 mL) was added. Then, the asymmetric self-coupling reaction was carried out at 40 °C under an air atmosphere. After the reaction was completed (monitored by TLC), the precipitate was filtered out and washed with a solvent. After concentration under reduced pressure, the target product compound 4a (R in the structure 1 = H) was purified by silica gel column chromatography.

[0109] Characterization data of compound 4a: It is a white powder. HPLC resolution conditions: Chiralcel IC-H (n-hexane / isopropanol = 99 / 1, flow rate 1.0 mL / min, λ = 280 nm), t R (minor) = 3.93 min, t R (major) = 4.43 min, 1 1H NMR (CDCl3, 400 MHz): δ = 7.79 - 7.73 (m, 4H), 7.45 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.6 Hz, 2H), 7.17 - 7.14 (m, 4H), 3.03 (s, 6H); 13 13C NMR (CDCl3, 100 MHz): δ = 157.75, 134.74, 129.54, 129.12, 127.82, 126.90, 126.52, 123.74, 118.87, 105.90, 55.41.

[0110] The chiral tertiary amine phosphine-palladium complex provided by the present invention is applied to the asymmetric self-coupling reaction of asymmetric boric acid and borate esters. Only in the presence of oxygen (in the presence of air), this complex can highly selectively catalyze the asymmetric self-coupling reaction of boric acid and borate esters. Currently, no similar chiral self-coupling reaction has been found.

[0111] Comparative Examples 1 - 20

[0112] Compound 4a was prepared according to the method of Application Example 1. The difference from Application Example 1 is that the chiral tertiary amine phosphine-palladium complex 1b-1 was replaced with the ligands shown in the following Formula L1 - Formula L20, respectively.

[0113]

[0114] The research results show that under the same conditions, the known ligands L1-L20 in Comparative Examples 1-20 cannot catalyze the asymmetric self-coupling reaction of boric acid and boronic esters to occur.

[0115] The above results indicate that the chiral tertiary amine phosphine-palladium complex provided by the present invention can catalyze the asymmetric coupling synthesis of chiral binaphthyl compounds from boric acid and boronic esters in an air atmosphere, with good yields and excellent enantioselectivity, which cannot be achieved by other catalysts. The chiral tertiary phosphine-palladium complex disclosed in the present invention has the advantages of inexpensive and easily available synthesis raw materials, simple synthesis routes and processes, high yields, easy separation and purification of products, low costs, convenient storage, transportation and use, high catalytic efficiency, wide substrate scope, and good enantioselectivity, overcoming the difficulties in the synthesis of existing chiral tertiary amine phosphine ligands and their performance defects. It has important theoretical and application values for the design, discovery, and synthesis of new types of air- and moisture-stable chiral tertiary amine phosphine ligands, as well as the expansion of asymmetric reactions involving palladium metal, especially oxygen-sensitive redox reactions.

[0116] In order to explore the coupling reaction mechanism of boric acid and boronic esters, ligand stability, and complex stability, the following verification experiments were carried out:

[0117] The respective verification formulas are as follows:

[0118]

[0119] A) Compound 4a was prepared according to the method of Application Example 1, except that the amount of the chiral tertiary amine phosphine-palladium complex 1b-1 was 5 mol%, and the reaction was carried out in a nitrogen atmosphere.

[0120] The result of verification experiment A) was that the reaction could not proceed, and compound 4a was not prepared.

[0121] B) Compound 4a was prepared according to the method of Application Example 1, except that the amount of the chiral tertiary amine phosphine-palladium complex 1b-1 was 5 mol%, and the reaction was carried out in an oxygen atmosphere.

[0122] The result of verification experiment B) was that the reaction proceeded successfully, and compound 4a was prepared with a 91% yield and 96% ee.

[0123] C) Compound 4a was prepared respectively according to the methods of Comparative Examples 1-20, except that the amount of ligands L1-L20 was 10 mol% and the amount of PdCl2 was 5 mol%.

[0124] The result of verification experiment C) was that the reaction could not proceed, and compound 4a was not prepared.

[0125] D) Dissolve the ligand 2b-1 in acetonitrile and heat-treat it at 40 °C in an air atmosphere for 2 months. After NMR detection, the ligand 2b-1 still exists stably.

[0126] E) Dissolve the complex 1b-1 in acetonitrile and heat-treat it at 40 °C in an air atmosphere for 2 months. After NMR detection, the ligand 1b-1 still exists stably.

[0127] F) Mix the ligands L1, L5-L19 with palladium dichloride and acetonitrile respectively, and heat-treat them at 40 °C in an air atmosphere for 2 months. After NMR detection, the ligands L1, L5-L19 are all deteriorated and cannot exist stably.

[0128] Application Example 2

[0129] Use the complex 1g-1 prepared in Example 148 as a catalyst to catalyze the asymmetric Suzuki cross-coupling reaction to synthesize the chiral binaphthyl compound 7a. The steps are as follows:

[0130] Synthesis route:

[0131]

[0132] Add the complex 1g-1 (5% mol), 1-bromo-2-methyl compound 6a (44 mg, 0.2 mmol, 1.0 equivalent), potassium phosphate (5.0 equivalents) to a test tube equipped with a magnetic stir bar. Subsequently, add 2-methoxy-1-naphthylboronic acid compound 5a (1.0 mmol, 5.0 equivalents) and toluene (2.0 mL), and then react at 80 °C in an air atmosphere. After the reaction is completed (monitored by TLC), filter out the precipitate and wash it with a solvent. After concentration under reduced pressure, purify it by silica gel column chromatography to obtain the target product compound 7a with a yield of 91% and 95% ee.

[0133] Characterization data of compound 7a: It is a white powder. HPLC resolution conditions: Chiralcel IC-H (n-hexane / isopropanol = 99 / 1, flow rate 1.0 mL / min, λ = 254 nm), t R (minor) = 3.93 min, t R (major) = 4.43 min, 11H NMR (500 MHz, CDCl3): δ 7.97 (d, J = 8.4 Hz, 1H), 7.87 - 7.87 (m, 3H), 7.51 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 9.2 Hz, 1H), 7.37 - 7.35 (m, 1H), 7.33 - 7.31 (m, 1H), 7.21 - 7.19 (m, 2H), 7.12 (d, J = 7.9 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 3.75 (s, 3H), 2.10 (s, 3H); 13 13C NMR (125 MHz, CDCl3): δ 154.4, 135.0, 133.6, 133.2, 132.3, 132.1, 129.3, 129.2, 128.6, 128.0, 127.9, 127.8, 127.5, 126.5, 125.8, 125.7, 125.1, 124.7, 123.6, 113.8, 56.6, 20.3.

[0134] Application Examples 3 - 5

[0135] Compound 7a was prepared according to the method of Application Example 2, except that the catalyst was replaced with complex 1b - 1, complex 1f - 1, and complex 1a - 1, respectively.

[0136] The results of using complexes 1a - 1, 1b - 1, 1f - 1, and 1g - 1 of the present invention in the above - mentioned reaction are shown in the following formula.

[0137]

[0138] It can be seen that when the chiral tertiary amine phosphine - palladium complex of the present invention is applied to the asymmetric Suzuki cross - coupling reaction for the synthesis of chiral binaphthyl compounds, enantioselective cross - coupling reaction is achieved, providing a new strategy for the synthesis of chiral binaphthyl compounds. Moreover, as a catalyst for the Suzuki - Miyaura cross - coupling reaction, the chiral tertiary amine phosphine - palladium complex of the present invention can synthesize chiral binaphthyl compounds under an air atmosphere, with good yields and excellent enantioselectivity. Among them, as shown in the above formula, the effect of using complex 1g - 1 in the reaction is the best (91% yield, 95% ee). This indicates that the phosphine atom in the chiral tertiary amine phosphine - palladium complex of the present invention is not easily oxidized by oxygen, is a complex stable to air, and has good catalytic performance for the Suzuki - Miyaura cross - coupling reaction.

[0139] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims

1. A chiral tertiary amine phosphine-palladium complex that is stable to air, characterized in that, It includes palladium metal salt PdX2 and a chiral tertiary amine phosphine ligand, and the molar ratio of the chiral tertiary amine phosphine ligand to the palladium metal salt is 2:1; The air-stable chiral tertiary amine phosphine-palladium complex has a C2-symmetric structure shown in Formulas 1a to 1h: Among them, the Ar is The R, R 2 , R 3 , R 4 , R 5 Each independently includes hydrogen atoms, C1~C 30 Alkyl, C1~C 30 Silane groups, C1~C 30 haloalkyl, C2~C 30 Alkenyl, C2~C 30 alkynyl, halogen, hydroxyl, alkoxy, acyloxy, mercapto, thioether, nitro, carbonyl, carboxyl, ester, amino, substituted amino, imino, cyano, phosphonate, phosphine, amide, sulfonyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, substituted or unsubstituted C6~C 50 aryl, aryl, fused aryl, substituted or unsubstituted C7~C 50 Arylalkyl, substituted or unsubstituted C7~C 50 Aralkyloxy, substituted or unsubstituted C7~C 50 Aryl alkylthiol, substituted or unsubstituted C7~C 50 Aromatic heterocyclic group, substituted or unsubstituted C7~C 30 One or more of an aromatic amine group, an aromatic heterocyclic group, a fused heterocyclic group, and a condensed heterocyclic group; The R 1 includes a hydrogen atom, a C1-C 30 substituted or unsubstituted alkyl and cycloalkyl, a C5-C 50 substituted or unsubstituted aryl, a C5-C 50 substituted or unsubstituted fused aryl, a C5-C 50 substituted or unsubstituted condensed aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted fused heterocycle, or one or more of substituted or unsubstituted fused heterocyclic groups; The R 1 independently has one or more chiral centers; The Y includes at least one of a hydrogen atom, an oxygen atom, a sulfur atom, a phosphorus atom, and a silicon atom; The R 6 includes a substituted or unsubstituted aryl group having 5 to 50 carbon atoms, a substituted or unsubstituted fused aryl group having 5 to 50 carbon atoms, a substituted or unsubstituted polycyclic aryl group having 5 to 50 carbon atoms, and a substituted or unsubstituted aryloxy group having 5 to 50 carbon atoms; at least one of a substituted or unsubstituted alkyl group and a cyclic alkyl group having 1 to 30 carbon atoms; The R* is a chiral amine having one or more chiral centers, and the R* includes at least one of S-phenylethylamine, S-naphthylethylamine, phenylglycinol, and (1R,2S)1-amino-2-indanol; The halogen includes one or more of F, Cl, Br, and I; the condensed aryl group includes one or more of naphthalene, anthracene, phenanthrene, and carbazole; the heteroaryl group includes one or more of thiophene, benzothiophene, fluorene, furan, benzofuran, benzopyrrole, pyridine, quinoline, and benzoquinoline; the condensed heterocyclic group includes one or more of tetrahydroquinoline, dihydroindole, and dihydropyran; The metal palladium salt PdX2 includes one or more of palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium nitrate, palladium trifluoroacetate, bis(acetonitrile)palladium dichloride, tetrakis(triphenylphosphine)palladium, bis(benzonitrile)palladium chloride, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, palladium neopentanoate, palladium benzoate, bis(acetylacetonato)palladium, palladium hexafluoroacetylacetonate, tetrakis(acetonitrile)palladium(II) tetrafluoroborate, allylpalladium chloride dimer, norbornadiene palladium dichloride, tris(dibenzylideneacetone)dipalladium / chloroform adduct, (1,5-cyclooctadiene)palladium dichloride, (2-butenyl)palladium chloride dimer, (1,5-cyclooctadiene)palladium bromide, chloro(1,5-cyclooctadiene)methylpalladium, bis(pyridine)palladium dichloride, dichlorodiamminepalladium, sodium chloropalladate, potassium tetrabromopalladate, ammonium hexachloropalladate, dichlorotetraamminepalladium, potassium hexachloropalladate, palladium hydroxide, potassium tetrachloropalladate, bis(isoquinoline)palladium dichloride, tetraammine dichloropalladium, dichloro(ethylenediamine)palladium dichlorotetraamminepalladium hydrate, (2,2′-bipyridine)palladium dichloride, lithium tetrachloropalladate(II) hydrate, tetrakis(acetonitrile)palladium(II) bis(trifluoromethanesulfonate), dichloro(N,N,N',N'-tetramethylethylenediamine)palladium, 1,2-bis(phenylsulfinyl)ethane palladium(II) diacetate, dimethyl(N,N,N',N'-tetramethylethylenediamine)palladium(II), bis(2,2,6,6-tetramethyl-3,5-heptanedionato)palladium, bis(3,5,3',5'-dimethoxydibenzylideneacetone)palladium, (1,5-cyclooctadiene)bis(trimethylsilylmethyl)palladium(II), di-μ-chlorobis[(1,2,3-η)-1-phenyl-2-propen-1-yl]dipalladium, allylchloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl]palladium, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridine)palladium dichloride, allylchloro[1,3-bis(2,6-di-isopropylphenyl)-4,5-dihydroimidazol-2-yl]palladium, dichloro(di-μ-chloro)bis[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]dipalladium(II), allyl(1,3-di(mesityl)-1H-imidazol-2(3H)-ylidene)palladium(IV) chloride, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II).

2. The air-stable chiral tertiary amine phosphine-palladium complex according to claim 1, wherein Said R, R 2 , R 3 , R 4 , R 5 each independently includes one or more of a hydrogen atom, a methyl group, an ethyl group, a 1-naphthyl group, a phenyl group, a p-chlorophenyl group, a p-cyanophenyl group, a 3,5-bis(trifluorophenyl) group, and a tert-butyl group; The R 1 comprises one or more of a hydrogen atom, a phenyl group, a p-chlorophenyl group, a p-cyanophenyl group, a 3,5-bis(trifluorophenyl) group, and a tert-butyl group; The Y includes at least one of a hydrogen atom, an oxygen atom, a sulfur atom, and a silicon atom; The R 6 comprises at least one of a hydrogen atom, a phenyl group, and a triphenyl group; The R* is derived from a chiral amine and has one or more chiral centers. The R* includes at least one of S-phenylethylamine, S-naphthylethylamine, phenylglycinol, and (1R,2S)1-amino-2-indanol; The metal palladium salt PdX2 includes at least one of palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium nitrate, and palladium trifluoroacetate.

3. The air-stable chiral tertiary amine phosphine-palladium complex according to claim 2, wherein The air-stable chiral tertiary amine phosphine-palladium complex has any of the chemical structures shown in Formula 1a-1 to Formula 1a-20, Formula 1b-1 to Formula 1b-5, Formula 1c-1 to Formula 1c-5, Formula 1d-1 to Formula 1d-5, Formula 1e-1 to Formula 1e-5, Formula 1f-1 to Formula 1f-5, Formula 1g-1 to Formula 1g-5, Formula 1h-1 to Formula 1h-14:

4. A method for preparing an air-stable chiral tertiary amine phosphine-palladium complex according to any one of claims 1 to 3, characterized in that, including the following Mix the chiral tertiary amine phosphine ligand, metal palladium salt and solvent S1, and then carry out a complexation reaction to obtain an air-stable chiral tertiary amine phosphine-palladium complex; The chiral tertiary amine phosphine ligand has the structures shown in the following Formula 2a-1 to Formula 2a-20, Formula 2b-1 to Formula 2b-5, Formula 2c-1 to Formula 2c-5, Formula 2d-1 to Formula 2d-5, Formula 2e-1 to Formula 2e-5, Formula 2f-1 to Formula 2f-5, Formula 2g-1 to Formula 2g-5, Formula 2h-1 to Formula 2h-14:

5. The preparation method according to claim 4, characterized in that, The solvent S1 is one or more of an alcohol solvent, an alkane solvent, an aromatic hydrocarbon solvent, an ether solvent, and a nitrile solvent; The alcohol solvent is one or more of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, cyclohexanol, ethylene glycol, butanediol, hexanediol, and glycerol; the alkane solvent is one or more of n-hexane, cyclohexane, heptane, and petroleum ether; the aromatic hydrocarbon solvent is one or more of benzene, toluene, xylene, mesitylene, chlorobenzene, and bromobenzene; the ether solvent is one or more of methyl tert-butyl ether, tetrahydrofuran, and dioxane; the nitrile solvent is one or more of acetonitrile, propionitrile, and valeronitrile; The volume ratio of the solvent S1 to the amount of substance of the metal palladium salt is (1 to 20) mL: 1 mmol.

6. The preparation method according to claim 4, characterized in that When the used solvent S1 is azeotropic with water, an azeotropic water separator is used for azeotropic water separation.

7. The preparation method according to claim 4, characterized in that, The temperature of the complexation reaction is 0 °C to 30 °C; the time of the complexation reaction is 1 to 4 h.

8. The application of the air-stable chiral tertiary amine phosphine-palladium complex according to any one of claims 1 to 3 in a catalytic asymmetric self-coupling reaction.

9. The application of the air-stable chiral tertiary amine phosphine-palladium complex according to any one of claims 1 to 3 in a palladium-catalyzed reaction, a reaction involving oxygen, an organic reaction involving a tertiary amine and a phosphine; The palladium-catalyzed reactions include at least one of hydrogenation reaction, Suzuki–Miyaura reaction, Miyaura borylation reaction, Buchwald-Hartwig reaction, Heck reaction, Sonogashira reaction, Stille coupling reaction, Tsuji-Trost reaction, carbonylation coupling reaction, Saegusa oxidation reaction, Fukuyama coupling reaction, dearomatization reaction, Fukuyama reduction reaction, Fujiwara-Moritani reaction, Hiyama coupling, Yu Jinquan C-H activation reaction, Sanford reaction, Alper carbonylation reaction, Trost cyclopentanation reaction, C-O bond formation reaction, Stoltz α-allyl ketone asymmetric synthesis reaction, Hegedus indole synthesis reaction, Kumada coupling reaction, Narasaka-Heck cyclization reaction, Murahashi coupling reaction, diazotization reaction, cycloaddition reaction; The reactions involving oxygen include at least one of Cham-Lam reaction, boric acid coupling reaction, olefin oxidative coupling.

10. Use of the air-stable chiral tertiary amine phosphine-palladium complex according to any one of claims 1 to 3 in the derivative synthesis of chiral catalysts and materials, medicines, pesticides and intermediates.

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