Chiral phosphine ligand TANKPhos as well as preparation method and application thereof

Abstract

The invention discloses a chiral phosphine ligand TANKPhos as well as a preparation method and application thereof, and belongs to the technical field of asymmetric reaction reagents. The chiral phosphine ligand TANKPhos and the preparation method thereof have the advantages that the chiral phosphine ligand TANKPhos prepared by the aid of the method can greatly increase ee (enantiomeric excess) values of desymmetric reduction Heck reaction in enantioselective desymmetric reduction Heck reaction by taking basic framework raw materials as raw materials to prepare ligand reagents for asymmetric reaction on the basis of basic frameworks, the chiral phosphine ligand TANKPhos can be used for preparing chiral phosphine ligand TANKPhos, and the chiral phosphine ligand TANKPhos can be used for preparing the chiral phosphine ligand TANKPhos. And more possibilities are provided for expanded application of the desymmetric reduction Heck reaction.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of asymmetric reagent, and particularly relates to a chiral phosphine ligand TANKPhos and a preparation method and application thereof. BACKGROUND

[0002] Enantioselective desymmetrization reaction has a unique role in enantioselective construction of complex ring system and multiple consecutive chiral centers. If potential symmetry in natural products is found, and enantioselective desymmetrization reaction is used to synthesize corresponding polycyclic skeleton and multiple chiral centers, the synthesis route of natural products can be greatly shortened, and synthesis efficiency is improved. The desymmetrization Heck reaction of spiro ring system catalyzed by palladium is very efficient in constructing the mother nucleus skeleton of octalobate sesquiterpene natural product, but the known chiral ligands all get racemic results. Therefore, it is very important and necessary to develop a new type of chiral phosphine ligand to realize the asymmetric reaction.

[0003] We designed the desymmetrization Heck reaction of spiro ring system catalyzed by palladium, and considered using the reaction in the synthesis of octalobate sesquiterpene natural product, but up to now, there is no successful asymmetric reaction report of the reaction. Because the reaction needs to use a large steric hindrance phosphine ligand, and the known chiral phosphine ligands used in common palladium catalysis reaction either have too small steric hindrance to catalyze the reaction to occur, or get racemic products. Although we found that individual known chiral phosphine ligands can induce the occurrence of the asymmetric reaction in a large number of experimental verifications, the highest ee value can only be 7%. Therefore, it is of great significance to develop a new chiral phosphine ligand to improve the ee value of the reaction for the desymmetrization Heck reaction of octalobate sesquiterpene natural product. SUMMARY

[0004] The application aims to provide a chiral phosphine ligand TANKPhos to solve the technical problems that the existing desymmetrization Heck reaction is difficult to successfully react and has a low ee value.

[0005] To achieve the above object, the technical scheme adopted by the application is as follows:

[0006] A chiral phosphine ligand TANKPhos, which has a structure as shown in formula I:

[0007]

[0008] In formula I, R 1 is one of C1-C 10 alkyl;

[0009] R 2 , R 2‘ , R 3 , R 3’ , R4 , R 4‘ , R 5 , R 5’ , R 6 , R 6‘ each independently is H, C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, C6-C10 aryl, or one or two of them together form a C5-C10 cycloalkane, a 5- to 10- membered heterocyclic ring or a 5- to 10-membered heteroaromatic ring; the heteroatoms in the 5- to 10-membered heterocyclic ring or the 5- to 10-membered heteroaromatic ring are one or more of N, O or S, the number of heteroatoms being 1 to 3; 20 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen,

[0010] R 7 is one of C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 10 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen,

[0011] R 8 is one of C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen, 9 is one of C1-C4 alkyl, C1-C4 alkoxy, C3-C6 cycloalkyl, halogen,

[0012] in formula I, denotes the relative configuration of the P atom and the adjacent C atom, when is , is when is , is

[0013] In one embodiment of the present application, the compound according to formula I is more preferably the structure of R

[0014]

[0015] In one embodiment of the present application, the compound according to formula I is more preferably, R 7 the structure of R

[0016]

[0017]

[0018] The preparation method of the chiral phosphine ligand TANKPhos comprises the following steps:

[0019] (1) As shown in the following reaction formula, compound 1 is dissolved in dichloromethane under room temperature reaction conditions, and NBS is added, and the stirring state is continuously reacted for 8-24 h; after the reaction, quenching, extraction and rotary evaporation are performed to obtain a crude product of yellowish oil compound 2, the crude product 2 is dissolved in tetrahydrofuran, then the prepared solution is cooled to 0°C and a tetrahydrofuran solution of tetrabutylammonium fluoride is added dropwise, and the stirring reaction is performed for 30-60 min; after the reaction is completed, quenching, extraction and column chromatography are performed to obtain white solid compound 3;

[0020]

[0021] (2) As shown in the following reaction formula, compound 3, Sphos, potassium fluoride and compound 4 are added in 1,4-dioxane as a solvent, then Pd2(dba)3 is added to the solution, and the system is heated to 100°C for reaction for 6-24 h; after the reaction is completed, quenching, extraction and column chromatography are performed to obtain white solid compound 5;

[0022]

[0023] (3) As shown in the following reaction formula, compound 5 and triethylamine are added in dichloromethane as a solvent under room temperature reaction conditions, then the solution is cooled to 0°C and PhNTf2 is added thereto, after the addition is completed, the system is restored to room temperature and maintained for reaction for 2-5 h; after the reaction is completed, quenching, extraction and column chromatography are performed to obtain white solid compound 6;

[0024]

[0025] (4) As shown in the following reaction formula, compound 7 is dissolved in tetrahydrofuran as a solvent to form solution A, and compound 6, BIDME and Pd2(dba)3 are added in tetrahydrofuran as a solvent to form solution B, the solution B is added dropwise into the solution A, and the system is heated to 70°C for reflux reaction for 6-24 h; after the reaction is completed, quenching, extraction and column chromatography are performed to obtain white solid compound 8;

[0026]

[0027] (5) As shown in the following reaction formula, tetrahydrofuran is added to completely dissolve compound 8 under room temperature conditions, then the solution is cooled to -78°C and an LDA tetrahydrofuran solution is added dropwise thereto, after the addition is completed, the cooling stirring is maintained for 1 h, then R 7small molecule reagent, continue to stir at -78°C for 1 h, then slowly raise to room temperature and stir for 6-24 h; after complete reaction, quench, extract, column chromatography to obtain white solid compound 9;

[0028]

[0029] (6) as shown in the following reaction formula, add compound 9, triethylamine, and add toluene to completely dissolve the above compound; then cool the solution to 0°C, and then drop tri-chlorosilane into it, after completion, keep cooling and stirring for 15 min, then raise the system to 70°C and stir for 6-24 h, after complete reaction, quench, extract, and spin dry to dissolve the obtained crude product in THF, cool the obtained solution to 0°C, and then drop tetrabutylammonium fluoride in tetrahydrofuran solution into it, and stir for 2 h, after complete reaction, quench, extract, column chromatography to obtain white solid compound ligand I;

[0030]

[0031] As preferred, in step (1), the quenching reagent for preparing compound 3 is saturated sodium thiosulfate solution, and the extracted organic phase is ethyl acetate; the quenching reagent for preparing compound 4 is water, and the extracted organic phase is a mixed solvent of dichloromethane / isopropyl alcohol, and the column chromatography eluent is a mixed solvent of methanol / dichloromethane.

[0032] As preferred, in step (2), the quenching reagent is saturated ammonium chloride solution, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of ethyl acetate / petroleum ether.

[0033] As preferred, in step (3), the quenching reagent is water, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of ethyl acetate / petroleum ether.

[0034] As preferred, in step (4), the quenching reagent is saturated ammonium chloride solution, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of ethyl acetate / petroleum ether.

[0035] As preferred, in step (5), the quenching reagent is saturated ammonium chloride solution, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of acetone / petroleum ether.

[0036] As preferred, in step (6), the quenching reagent is 30% sodium hydroxide aqueous solution, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of acetone / petroleum ether.

[0037] The present application provides a chiral phosphine ligand TANKPhos, and a preparation route thereof as shown in the following formula:

[0038]

[0039] Application of chiral phosphine ligand TANKPhos as desymmetrization reagent in enantioselective desymmetrization reduction Heck reaction.

[0040] Compared with the prior art, the present application has the following beneficial effects:

[0041] The chiral phosphine ligand TANKPhos prepared by the method of the present application can greatly improve the ee value of the desymmetrization reduction Heck reaction in the enantioselective desymmetrization reduction Heck reaction, and provides more possibilities for the expanded application of the desymmetrization reduction Heck reaction. BRIEF DESCRIPTION OF DRAWINGS

[0042] Figure 1 H NMR chart of compound 1-10 obtained in Example 1 1 H NMR chart of compound 1-10 obtained in Example 1

[0043] Figure 2 C NMR chart of compound 1-10 obtained in Example 1 13 C NMR chart of compound 1-10 obtained in Example 1

[0044] Figure 3 PNMR chart of compound 1-10 obtained in Example 1 31 PNMR chart of compound 1-10 obtained in Example 1

[0045] Figure 4 H NMR chart of compound 1-12 obtained in Example 2 1 H NMR chart of compound 1-12 obtained in Example 2

[0046] Figure 5 C NMR chart of compound 1-12 obtained in Example 2 13 C NMR chart of compound 1-12 obtained in Example 2

[0047] Figure 6 PNMR chart of compound 1-12 obtained in Example 2 31 PNMR chart of compound 1-12 obtained in Example 2

[0048] Figure 7 H NMR chart of compound 1-14 obtained in Example 3 1 H NMR chart of compound 1-14 obtained in Example 3

[0049] Figure 8 C NMR chart of compound 1-14 obtained in Example 3 13 C NMR chart of compound 1-14 obtained in Example 3

[0050] Figure 9 PNMR chart of compound 1-14 obtained in Example 3 31 PNMR chart of compound 1-14 obtained in Example 3

[0051] Figure 10 H NMR chart of compound 1-16 obtained in Example 4 1 H NMR chart of compound 1-16 obtained in Example 4

[0052] Figure 11 Compound 1-16 obtained in Example 4 13 C NMR spectrum;

[0053] Figure 12 Compound 1-16 obtained in Example 4 31 PNMR images;

[0054] Figure 13 Compound 1-18 obtained in Example 5 1 H NMR spectrum;

[0055] Figure 14 Compound 1-18 obtained in Example 5 13 C NMR spectrum;

[0056] Figure 15 Compound 1-18 obtained in Example 5 31 PNMR images;

[0057] Figure 16 Compound 1-20 obtained in Example 5 1 H NMR spectra;

[0058] Figure 17 Compound 1-20 obtained in Example 5 13 C NMR spectrum;

[0059] Figure 18 Compound 1-20 obtained in Example 5 31 PNMR diagram. DETAILED DESCRIPTION

[0060] The present invention will be further described below with reference to the accompanying drawings and various embodiments. The embodiments of the present invention include but are not limited to the following embodiments.

[0061] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials are commercially available unless otherwise specified.

[0062] Example 1

[0063] This embodiment provides a specific structure of a chiral phosphine ligand TANKPhos, and the synthesis route is as follows:

[0064]

[0065] The specific steps include:

[0066] (1) Synthesis of Compounds 1-3

[0067] A 100 ml round bottom flask was charged with compound 1-1 (1.50 g, 3.23 mmol) and dissolved in 25 ml of dichloromethane at room temperature. To the solution was then added NBS (862 mg, 4.84 mmol) and the reaction was stirred for 10 h, TLC was used to check if the reaction was complete.

[0068] After the reaction was complete, the system was quenched with 20 ml of saturated sodium thiosulfate solution, the aqueous phase was extracted with ethyl acetate (3 x 25 mL), the organic phase was combined, dried over anhydrous magnesium sulfate, and concentrated and rotary evaporated to give the crude product of compound 1-3 as a light yellow oil. The crude product was used directly in the subsequent reaction without further purification.

[0069] The crude product 1-2 was dissolved in 30 ml of tetrahydrofuran, the prepared solution was then cooled to 0 °C and 1 M tetrabutylammonium fluoride in tetrahydrofuran (4.80 ml, 1.5 mmol) was added dropwise. The reaction was stirred for 30 min, TLC was used to check if the reaction was complete.

[0070] After the reaction was complete, the system was quenched with 20 ml of water, the aqueous phase was extracted with a mixture of dichloromethane / isopropyl alcohol = 5:1 (3 x 25 mL), the organic phase was combined, dried over anhydrous magnesium sulfate, and concentrated and rotary evaporated to give the crude product of compound 1-3 as a light yellow solid. The crude product was purified by silica gel column chromatography using methanol / dichloromethane = 1:40 as the eluent, and finally white solid compound 1-3 (788 mg, 80%, 2 steps) was obtained.

[0071] Compound 1-3: 1 H NMR (600 MHz, CD3OD) δ = 77.51 (d, J = 8.5 Hz, 1H), 6.44 (dd, J = 8.5, 4.7 Hz, 1H), 4.85 (dd, J = 14.4, 3.7 Hz, 1H), 4.42 (dd, J = 14.4, 10.7 Hz, 1H), 1.29 (d, J = 16.9 Hz, 9H) ppm; 13 C NMR (151 MHz, CD3OD) δ = 163.6 (d, J = 17.5 Hz), 160.7 (d, J = 2.6 Hz), 140.6, 110.8 (d, J = 6.8 Hz), 103.6 (d, J = 91.4 Hz), 96.3 (d, J = 6.9 Hz), 67.5 (d, J = 60.0 Hz), 34.5 (d, J = 74 Hz), 24.7 ppm; 31 P NMR (243 MHz, CD3OD) δ = 69.8 ppm. IR (film) v max = 3448, 2966, 1599, 1438, 1158, 1036 cm -1HRMS (ESI) calcd for C 11 H 15 O3PBr + [M+H] + 304.9937, found304.9941. (C = 1.0, CHCl3).

[0072] (2) Synthesis of compound 1-5

[0073] Take a 25 ml round bottom flask, add compound 1-3 (1.10 g, 3.60 mmol), Sphos (325 mg, 0.79 mmol), potassium fluoride (1.05 g, 18.0 mmol), compound 1-5 (1.60 g, 7.20 mmol) at room temperature and add 18 ml 1,4-dioxane to dissolve the above compounds. Then add Pd2(dba)3 (330 mg, 0.36 mmol) to the solution and heat the system to 100 °C for 12 h, check the reaction completion of compound 1-3 by TLC.

[0074] After the reaction is complete, add 30 ml saturated ammonium chloride solution to quench the system, extract the aqueous phase with ethyl acetate (3 x 40 mL), combine the organic phase, dry over anhydrous magnesium sulfate, and concentrate and dry to obtain a light yellow oil of crude compound 1-5. Purify the crude product by silica gel column chromatography using methanol / methylene chloride = 1:50 as the eluent to obtain white solid compound 1-5 (1.30 g, 91%).

[0075] Compound 1-5: 1 H NMR (600 MHz, CD3OD) δ = 8.53 (s, 1H), 8.06 (dd, J = 8.6, 2.8 Hz, 2H), 7.64 (dq, J = 8.8, 1.0 Hz, 1H), 7.50 (dq, J = 8.8, 1.0 Hz, 1H), 7.45 (dddd, J = 12.6, 8.5, 6.5, 1.2 Hz, 2H), 7.38 (ddd, J = 8.8, 6.5, 1.3 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.33 (dd, J = 6.5, 1.3 Hz, 1H), 6.75 (dd, J = 8.1, 4.5 Hz, 1H), 4.57 (dd, J = 14.5, 3.1 Hz, 1H), 4.14 (dd, J = 14.5, 10.7 Hz, 1H), 1.36 (d, J = 16.6 Hz, 9H) ppm; 13C NMR (151 MHz, CD3OD) δ = 165.9 (d, J = 16.9 Hz), 161.6 (d, J = 2.3 Hz), 141.0, 133.0 (d, J = 9.2 Hz), 132.1, 132.0, 129.6 (d, J = 12.5 Hz), 128.0, 127.2, 127.0, 126.6 (d, J = 18.9 Hz), 126.1 (d, J = 17.7 Hz), 116.0 (d, J = 5.6 Hz), 109.4 (d, J = 6.6 Hz), 101.8 (d, J = 93.6 Hz), 66.8 (d, J = 60.6 Hz), 34.6 (d, J = 74.1 Hz), 24.8 ppm; 31 P NMR (243 MHz, CD3OD) δ = 69.1 ppm. IR (film) v max = 3455, 3052, 2963, 2925, 1599, 1162, 1044, 736 cm -1 HRMS (ESI) calcd for C 25 H 24 O3P + [M+H] + 403.1458, found 403.1461. (C = 1.0, CHCl3).

[0076] (3) Synthesis of compound 1-6

[0077] Take a 25 ml round bottom flask, add compound 1-5 (300 mg, 0.75 mmol), triethylamine (0.42 ml, 3.00 mmol) at room temperature and add 10 ml dichloromethane to dissolve the above compound. Then the solution is cooled to 0 °C and PhNTf2 (357 mg, 1.00 mmol) is added to it. After the addition, the system is allowed to return to room temperature and the reaction is maintained for 3 h. Thin layer chromatography is used to check if the compound 1-5 has reacted completely.

[0078] After complete reaction, 10 ml of water is added to the system to quench the reaction. The aqueous phase is extracted with ethyl acetate (3 x 10 mL) and the combined organic phases are dried over anhydrous magnesium sulfate and concentrated and rotary evaporated to obtain the crude compound 1-6 as a light yellow oil. The crude product is purified by column chromatography on silica gel using ethyl acetate / petroleum ether = 1:4 as eluent to obtain compound 1-6 as a white solid (348 mg, 87%).

[0079] Compound 1-6: 1H NMR (600 MHz, CDC13) δ = 8.07 (dd, J = 8.9, 2.1 Hz, 2H), 7.60 (d, J = 8.2 Hz, 1H), 7.51 (dd, J = 8.5, 5.6 Hz, 2H), 7.46 (dddd, J = 16.3, 10.2, 5.7, 2.2 Hz, 2H), 7.36 (d, J = 3.6 Hz, 2H), 7.32 (dd, J = 8.3, 3.4 Hz, 1H), 4.44 (d, J = 14.2 Hz, 1H), 4.37 (dd, J = 14.2, 10.5 Hz, 1H), 1.34 (d, J = 16.6 Hz, 9H) ppm; 13 C NMR (600 MHz, CDC13) δ = 164.5 (d, J = 16.0 Hz), 149.6, 139.5, 131.4 (d, J = 18.9 Hz), 130.2 (d, J = 27.8 Hz), 129.1, 128.8, 128.4, 128.3, 126.7, 126.3, 125.7 (d, J = 7.1 Hz), 125.3, 125.2 (d, J = 22.3 Hz), 118.7 (q, J = 320 Hz), 113.9 (d, J = 4.4 Hz), 66.5 (d, J = 60.1 Hz), 31.1, 24.2 ppm; 31 P NMR (243 MHz, CDC13) δ = 62.7 ppm. IR (film) v max = 2967, 1593, 1428, 1216, 1138, 841, 750 cm -1 HRMS (ESI) calcd for C 26 H 23 O5PSF3 + [M+H] + 535.0950, found 535.0952. (C = 0.5, CHCl3).

[0080] (4) Synthesis of compound 1-8

[0081] A 50 ml round bottom flask was charged with 9-bromoanthracene (1.44 g, 5.60 mmol) and 7 ml of tetrahydrofuran at room temperature to dissolve it. The solution was cooled to -78 °C and 1.6 M n-butyllithium in hexanes (3.50 ml, 5.60 mmol) was added dropwise to it carefully and the reaction was stirred for 30 min. Then a solution of zinc bromide (1.33 g, 5.88 mmol) in 5 ml of tetrahydrofuran was prepared and added dropwise to the previous solution of 9-bromoanthracene. After mixing the solution was slowly warmed to 0 °C and stirred for 20 min to obtain the zinc reagent 1-7 solution. Another 25 ml round bottom flask was charged with compound 1-6 (750 mg, 1.40 mmol), BIDME (102 mg, 0.31 mmol) and Pd2(dba)3(128 mg, 0.14 mmol) at room temperature to completely dissolve them in 5 ml of tetrahydrofuran and stirred for 15 min. The mixture was added dropwise to the freshly prepared zinc reagent 1-7 solution and the reaction was refluxed at 70 °C for 8 h. The reaction was monitored by thin layer chromatography to check if compound 1-6 was completely reacted.

[0082] After complete reaction, 20 ml of saturated ammonium chloride solution was added to quench the reaction and the aqueous phase was extracted with ethyl acetate (3 x 20 mL). The combined organic phases were dried over anhydrous magnesium sulfate and concentrated to dryness to obtain the crude compound 1-8 as a light yellow oil. The crude product was purified by column chromatography on silica gel using ethyl acetate / petroleum ether = 1 :2 as eluent to obtain compound 1-8 as a white solid (630 mg, 80%).

[0083] Compound 1-8: 1 H NMR (600 MHz, CD3OD) δ = 8.67 (d, J = 19.9 Hz, 2H), 8.21 - 8.09 (m, 4H), 7.92 - 7.88 (m, 2H), 7.86 - 7.83 (m, 1H), 7.82 (dd, J = 7.4, 0.7 Hz, 1H), 7.73 (dq, J = 8.5, 1.0 Hz, 1H) 7.61 - 7.48 (m, 8H), 7.39 (dd, J = 7.3, 3.7 Hz, 1H), 4.59 (dd, J = 14.7, 4.0 Hz, 1H), 4.21 (dd, J = 14.7, 10.8 Hz, 1H), 0.53 (d, J = 16.6 Hz, 9H) ppm; 13C NMR (151 MHz, CDC13) δ = 164.3 (d, J = 18.7 Hz), 142.0, 137.8 (d, J = 10.1 Hz), 134.0, 131.7, 131.5, 131.5, 131.3, 130.7, 130.5, 130.3, 129.1 (d, J = 4.4 Hz), 128.8 (d, J = 2.4 Hz), 128.3 (d, J = 12.7 Hz), 127.9, 127.8, 127.1, 126.7, 126.4, 126.3, 126.2, 126.1, 126.0, 125.9, 125.8, 125.6, 125.0, 116.3 (d, J = 114.3 Hz), 66.0 (d, J = 55.1 Hz), 33.6 (d, J = 72.0 Hz), 23.8 ppm; 31 P NMR (243 MHz, CD3OD) δ = 66.8 ppm. IR (film) v max = 3054, 2926, 1547, 1374, 1182, 1036, 734 cm - 1 HRMS (ESI) calcd for C 39 H 31 O2PNa + [M+Na] + 585.1954, found 585.1960. (C = 0.5, CHCl3).

[0084] (5) Synthesis of compound 1-9

[0085] Take a 25 ml round bottom flask, add compound 1-8 (56.3 mg, 0.10 mmol) at room temperature, and add 1.0 ml of tetrahydrofuran to completely dissolve the above compound. Then the solution is cooled to -78°C, and 2M LDA tetrahydrofuran solution (0.10 ml, 0.20 mmol) is added dropwise. After the addition is completed, the solution is stirred for 1 h while keeping the temperature at -78°C. Then (2-bromoethoxy) tert-butyldimethylsilane (71.8 mg, 0.30 mmol) is added dropwise, and the solution is stirred for 1 h while keeping the temperature at -78°C. Then the temperature is slowly raised to room temperature, and the solution is stirred for 8 h. TLC is used to determine whether the reaction of compound 1-8 is complete.

[0086] After the reaction was completed, 2 ml of saturated aqueous ammonium chloride solution was added to quench the reaction, and the aqueous phase was extracted with ethyl acetate (3 x 3 mL). The combined organic phase was dried over anhydrous magnesium sulfate and concentrated to dryness to obtain the crude product of compound 1-9 as a light yellow solid. The crude product was purified by silica gel column chromatography using acetone / petroleum ether = 1 :6 as the eluent to finally obtain white solid compound 1-9 (36.0 mg, 50%).

[0087] Compound 1-9: 1 H NMR (600 MHz, acetone-d6) δ = 8.72 (d, J = 11.0 Hz, 2H), 8.24 - 8.16 (m, 3H), 8.11 (ddt, J = 8.4, 1.4, 0.7 Hz, 1H), 8.02 - 7.93 (m, 2H), 7.88 (dq, J = 8.1, 0.9 Hz, 1H), 7.84 (dq, J = 8.6, 1.0 Hz, 1H), 7.80 (dd, J = 7.4, 0.7 Hz, 1H), 7.62 - 7.44 (m, 8H), 7.35 (dd, J = 7.4, 3.4 Hz, 1H), 4.66 - 4.55 (m, 1H), 3.49 - 3.43 (m, 1H), 3.24 - 3.14 (m, 1H), 1.96 - 1.83 (m, 2H), 0.64 (s, 9H), 0.54 (d, J = 15.6 Hz, 9H), -0.31 (s, 3H), -0.42 (s, 3H) ppm; 13 C NMR (151 MHz, acetone-d6) δ = 163.2 (d, J = 18.6 Hz), 143.0 (d, J = 6.04 Hz), 138.1 (d, J = 2.1 Hz), 135.0 (d, J = 2.0 Hz), 132.6 (d, J = 14.6 Hz), 132.3 (d, J = 8.6 Hz), 131.9, 131.7, 131.5, 131.3, 131.1, 129.7, 129.6, 129.5, 129.3, 128.5 (d, J = 17.5 Hz), 128.2, 127.4, 127.0 (d, J = 8.8 Hz), 126.9, 126.8 (d, J = 3.5 Hz), 126.8, 126.4, 126.2, 126.1 (d, J = 8.3 Hz) 125.9, 124.8 (d, J = 6.0 Hz), 117.8, 117.3, 71.5, 71.1, 59.1 (d, J = 8.0 Hz), 34.1, 33.8, 33.7, 26.1, 23.8, 18.5, -5.5, -5.8 ppm; 31 P NMR (243 MHz, acetone-d6) δ 59.0 ppm. IR (film) vmax = 3054, 2954, 2928, 2856, 1221, 1087, 734 cm -1 .HRMS (ESI) calcd for C 47 H 50 O3PSi + [M+H] + 721.3261, found 721.3263. (C = 0.3, CHCl3).

[0088] (7) Synthesis of Ligand 1-10

[0089] Take a 10 ml Schlenk tube, add compound 1-9 (36.0 mg, 0.05 mmol), triethylamine (0.12 ml, 0.90 mmol) and 1.0 ml of toluene to completely dissolve the above compound. Then cool the solution to 0 °C, and then add trichlorosilane (36 μL, 0.40 mmol) dropwise. After the addition, keep stirring for 15 min, then warm the system to 70 °C and stir for 8 h. TLC test to determine whether the compound 1-9 is completely reacted.

[0090] After complete reaction, slowly add 2 ml of 30% aqueous sodium hydroxide solution to the system and continuously stir until the solution is clear. The aqueous phase is extracted with ethyl acetate (3 x 3 mL), and the combined organic phase is dried over anhydrous magnesium sulfate and concentrated and rotary evaporated to obtain the crude product of the reduction of compound 1-9. The crude product is directly used in the subsequent reaction without further purification.

[0091] Take a 25 ml round-bottom flask, add the above compound 1-9 reduction product at room temperature, and add 1.0 ml of tetrahydrofuran to completely dissolve the above compound. Then cool the solution to 0 °C, and then add 1M tetrabutylammonium fluoride in tetrahydrofuran solution (0.10 ml, 0.10 mmol) dropwise. After the addition, keep stirring for 30 min. TLC test to determine whether the starting material is completely reacted.

[0092] After complete reaction, slowly add 2 ml of water to quench the reaction, and the aqueous phase is extracted with ethyl acetate (3 x 3 mL), and the combined organic phase is dried over anhydrous magnesium sulfate and concentrated and rotary evaporated to obtain the crude product of compound 1-10 as a light yellow oil. The crude product is purified by silica gel column chromatography using acetone / petroleum ether = 1:3 as the eluent, and finally white solid ligand 1-10 (18.0 mg, 60%) is obtained.

[0093] Ligand 1-10: 1H NMR (600 MHz, acetone-d6) d = 8.70 (s, 2H), 8.23 - 8.17 (m, 5H), 8.04 (dt, J = 8.5, 1.1 Hz, 1H), 7.93 (dd, J = 8.7, 1.0 Hz, 1H), 7.83 (dd, J = 8.7, 1.0 Hz, 1H), 7.60 - 7.48 (m, 10H), 7.32 (dd, J = 7.4, 3.3 Hz, 1H), 5.00 (dd, J = 9.1, 5.5 Hz, 1H), 3.40 - 3.34 (m, 1H), 3.32 - 3.24 (m, 1H), 2.02 - 1.93 (m, 1H), 1.79 - 1.69 (m, 1H), 0.53 (d, J = 12.1 Hz, 9H) ppm; 13 C NMR (151 MHz, CDC13) d = 161.6, 142.5 (d, J = 16.5 Hz), 136.3, 134.4, 132.6, 131.7 (d, J = 3.8 Hz), 131.7, 131.5, 131.0, 130.6, 130.3, 129.1, 128.9 (d, J = 1.4 Hz), 128.8, 128.7, 127.5, 127.3, 127.2, 127.1, 126.5 (d, J = 10.2 Hz), 125.9, 125.9, 125.7 (d, J = 2.7 Hz), 125.6, 125.5, 125.5, 125.4 (d, J = 5.9 Hz), 125.2, 121.8, 81.4 (d, J = 24.6 Hz), 60.1 (d, J = 13.9 Hz), 38.3 (d, J = 25.4 Hz), 31.3 (d, J = 19 Hz), 27.2 (d, J = 13.4 Hz) ppm; 31 P NMR (243 MHz, acetone-d6) d 3.1 ppm. IR (film) v max = 3442, 2963, 2926, 1262, 1076, 1024, 804 cm -1 HRMS (ESI) calcd for C 41 H 35 O2PNa + [M+Na] + 613.2267, found 613.2270. (C = 0.5, CHCl3).

[0094] Example 2

[0095] On the basis of Example 1, in step (6), R 7The ligand is changed to iodomethane to give the structure shown in 1-12.

[0096]

[0097] A 25 ml round bottom flask was charged with compound 1-8 (56.3 mg, 0.10 mmol) at room temperature and 1.0 ml of tetrahydrofuran was added to completely dissolve the compound. The solution was then cooled to -78 °C and 2M LDA tetrahydrofuran solution (0.10 ml, 0.20 mmol) was added dropwise. After the addition was completed, the solution was stirred for 1 h while maintaining the temperature at -78 °C. Then iodomethane (28.4 mg, 0.20 mmol) was added dropwise and the solution was stirred for 1 h while maintaining the temperature at -78 °C. The solution was then slowly warmed to room temperature and stirred for 8 h. The reaction was checked by thin layer chromatography.

[0098] After the reaction was completed, 2 ml of saturated aqueous ammonium chloride solution was added to quench the reaction. The aqueous phase was extracted with ethyl acetate (3 x 3 mL) and the combined organic phases were dried over anhydrous magnesium sulfate and concentrated and dried in vacuo to give the crude product of compound 1-11 as a light yellow solid. The crude product was purified by column chromatography on silica gel using acetone / petroleum ether = 1 :4 as the eluent to give compound 1-11 (37.4 mg, 65%) as a white solid.

[0099] Compound 1-11: 1 H NMR (600 MHz, acetone-d6) δ = 8.73 (d, J = 10.3 Hz, 2H), 8.25 - 8.18 (m, 3H), 8.12 (ddd, J = 8.4, 1.3, 0.7 Hz, 1H), 8.01 - 7.95 (m, 2H), 7.94 - 7.88 (m, 1H), 7.83 (dq, J = 8.7, 1.0 Hz, 1H), 7.78 (dd, J = 7.4, 0.7 Hz, 1H), 7.63 - 7.46 (m, 8H), 7.35 (dd, J = 7.4, 3.4 Hz, 1H), 4.62 - 4.56 (m, 1H), 1.28 - 1.25 (m, 3H), 0.52 (d, J = 15.6 Hz, 9H) ppm; 13C NMR (151 MHz, acetone-d6) δ = 163.2, 142.9, 138.1 (d, J = 2.0 Hz), 135.2 (d, J = 2.4 Hz), 132.6 (d, J = 4.5 Hz), 132.4, 132.3, 132.2 (d, J = 1.1 Hz), 131.6, 131.4, 131.2, 129.6 (d, J = 10.3 Hz), 129.5, 129.4, 128.6, 128.4, 128.2, 127.4, 127.1, 126.9 (d, J = 2.0 Hz), 126.8, 126.7, 126.7, 126.4 (d, J = 26.9 Hz), 126.1 (d, J = 13.9 Hz), 125.9, 124.7, 124.6, 71.4 (d, J = 60.6 Hz), 33.6 (d, J = 70.0 Hz), 23.9, 15.5 ppm; 31 P NMR (243 MHz, acetone-d6) δ = 58.2 ppm. IR (film) v max = 3054, 2963, 2926, 2855, 1262, 1015, 735 cm -1 HRMS (ESI) calcd for C 40 H 33 O2PNa + [M+Na] + 599.2110, found 599.2112. (C = 0.23, CHCI3).

[0100]

[0101] Take a 10 ml Schlenk tube, add compound 1-11 (37.4 mg, 0.06 mmol), triethylamine (0.13 ml, 0.96 mmol) at room temperature and add 1.0 ml of toluene to completely dissolve the above compound. Then cool the solution to 0 °C and add trichlorosilane (43 μL, 0.48 mmol) dropwise. After the addition, keep the solution cold and stir for 15 min, then warm the system to 70 °C and stir for 8 h. Check the reaction completion of compound 1-11 by thin layer chromatography.

[0102] After complete reaction, 2 ml of 30% sodium hydroxide aqueous solution was slowly added to the system and stirred constantly until the solution was clear. The aqueous phase was extracted with ethyl acetate (3 x 3 mL) and the combined organic phase was dried over anhydrous magnesium sulfate and concentrated and rotary evaporated to give the crude product of compound 1-12 as a light yellow solid. The crude product was purified by silica gel column chromatography using acetone / petroleum ether = 1 :20 as the eluent to give finally the white solid of compound ligand 1-12 (20.2 mg, 60%).

[0103] Ligand 1-12: 1 H NMR (600 MHz, acetone-d6) δ = 8.70 (s, 2H), 8.27 - 8.14 (m, 5H), 8.05 (d, J = 7.6 Hz, 1H), 7.94 (dd, J = 8.7, 1.2 Hz, 1H), 7.86 (dd, J = 8.8, 1.2 Hz, 1H), 7.62 - 7.47 (m, 9H), 7.33 (dd, J = 7.4, 3.3 Hz, 1H), 4.90 (qd, J = 7.1, 1.4 Hz, 1H), 1.34 - 1.30 (m, 3H), 0.53 (d, J = 12.1 Hz, 9H); 13 C NMR (151 MHz, acetone-d6) δ = 162.7, 143.4 (d, J = 24.2 Hz), 137.2, 135.0, 133.9, 132.6, 132.6 (d, J = 1.0 Hz), 132.5, 131.7, 131.4, 131.1, 130.0 129.6, 129.5, 129.4, 128.2 (d, J = 3.7 Hz), 128.2, 127.8, 127.7, 127.5, 127.3, 126.7 (d, J = 22.5 Hz), 126.4 (d, J = 2.2 Hz), 126.2 (d, J = 6.0 Hz), 126.1 (d, J = 11.8 Hz), 125.8 (d, J = 4.1 Hz), 122.5, 79.8 (d, J = 23.4 Hz), 31.4 (d, J = 20.1 Hz), 27.5 (d, J = 14.6 Hz), 21.8 (d, J = 30.1 Hz) ppm; 31 P NMR (243 MHz, acetone-d6) δ = 6.6 ppm. IR (film) v max = 3054, 2964, 2927, 2858, 1261, 1041, 735 cm -1 HRMS (ESI) calcd for C 40 H 34 OP + [M+H] +561.2342, found 561.2344. (C = 0.26, CHCI3).

[0104] Example 3

[0105] In Example 1, in step (6), R 7 The ligand is changed to iodoethane, and the structure shown in 1-14 can be obtained.

[0106]

[0107] In the above formula, a 25 ml round-bottom flask was taken, and compound 1-8 (56.3 mg, 0.10 mmol) was added at room temperature, and 1.0 ml of tetrahydrofuran was added to completely dissolve the above compound. Subsequently, the solution was cooled to -78°C, and 2M LDA tetrahydrofuran solution (0.10 ml, 0.20 mmol) was added dropwise, and after the addition was completed, the stirring was continued for 1 h while cooling, and then iodoethane (31.2 mg, 0.20 mmol) was added dropwise to the system, and the stirring was continued for 1 h while maintaining -78°C, and then it was slowly warmed to room temperature and stirred for 8 h. Thin layer chromatography was performed to check whether the reaction of compound 1-8 was complete.

[0108] After the reaction was completed, 2 ml of saturated aqueous ammonium chloride solution was added to the system to quench the reaction, and the aqueous phase was extracted with ethyl acetate (3 x 3 mL), and the combined organic phases were dried over anhydrous magnesium sulfate and concentrated and dried in vacuo to obtain a yellowish solid crude product of compound 1-13. The crude product was purified by silica gel column chromatography using a solvent of acetone / petroleum ether = 1:4 as an eluent, and finally white solid compound 1-13 (38.4 mg, 65%) was obtained.

[0109] Compound 1-13: 1 H NMR (600 MHz, acetone-d6) δ = 8.72 (d, J = 18.6 Hz, 2H), 8.25 - 8.18 (m, 3H), 8.11 (dq, J = 8.6, 1.0 Hz, 1H), 8.02 - 7.96 (m, 2H), 7.94 - 7.89 (m, 1H), 7.84 (dd, J = 8.4, 1.0 Hz 1H), 7.79 (dd, J = 7.4, 0.8 Hz, 1H), 7.63 - 7.45 (m, 8H), 7.34 (dd, J = 7.4, 3.4 Hz, 1H), 4.37 (dt, J = 7.7, 5.4 Hz, 1H), 1.80 - 1.68 (m, 2H), 0.74 (d, J = 7.4 Hz, 3H), 0.57 (d, J = 15.5 Hz, 9H) ppm; 13C NMR (151 MHz, acetone-d6) δ = 163.3, 143.1 (d, J = 5.4 Hz), 138.0 (d, J = 2.0 Hz), 132.5 (d, J = 4.4 Hz), 132.3 (d, J = 6.6 Hz), 132.1, 131.8, 131.5, 131.3, 131.2, 129.6 (d, J = 11.6 Hz), 129.4 (d, J = 20.1 Hz), 128.5 (d, J = 6.3 Hz), 128.2, 127.4, 127.1, 126.9 (d, J = 1.5 Hz), 126.8 (d, J = 4.1 Hz), 126.7 (d, J = 8.5 Hz), 126.4 (d, J = 21.1 Hz), 126.2, 125.9 (d, J = 18.4 Hz), 124.6 (d, J = 5.4 Hz), 76.0 (d, J = 61.6 Hz), 33.9 (d, J = 62.5 Hz), 24.3, 23.7, 10.1 (d, J = 6.5 Hz) ppm; 31 P NMR (243 MHz, acetone-d6) δ = 58.7 ppm. IR (film) v max = 2964, 2926, 2855, 1724, 1262, 1096, 1025 cm -1 HRMS (ESI) calcd for C 41 H 35 O2PNa + [M+Na] + 613.2267, found 613.2270. (C = 0.22, CHCl3).

[0110]

[0111] As above, take a 10 ml Schlenk tube, add compound 1-13 (38.4 mg, 0.06 mmol), triethylamine (0.13 ml, 0.96 mmol) and 1.0 ml of toluene to completely dissolve the above compound at room temperature. Then the solution is cooled to 0 °C, and trichlorosilane (43 μL, 0.48 mmol) is added dropwise. After the addition is complete, the solution is stirred for 15 min at 0 °C, and then the system is warmed to 70 °C and stirred for 8 h. TLC is used to determine whether the reaction of compound 1-13 is complete.

[0112] After complete reaction, 2 ml of 30% sodium hydroxide aqueous solution was slowly added to the system and stirred constantly until the solution was clear, the aqueous phase was extracted with ethyl acetate (3 x 3 mL), the combined organic phase was dried over anhydrous magnesium sulfate and concentrated to dryness to obtain the crude product of compound 1-14 as a light yellow solid. The crude product was purified by silica gel column chromatography using acetone / petroleum ether = 1 :20 as the eluent to finally obtain white solid compound ligand 1-14 (20.7 mg, 60%)

[0113] Ligand 1-14: 1 H NMR (600 MHz, acetone-d6) δ = 8.70 (s, 2H), 8.22 - 8.16 (m, 5H), 8.01 (ddq, J = 8.4, 2.0, 1.0 Hz, 1H), 7.93 (dq, J = 8.7, 1.0 Hz, 1H), 7.87 (dq, J = 8.7, 1.0 Hz, 1H), 7.61 - 7.47 (m, 9H), 7.31 (dd, J = 7.4, 3.3 Hz, 1H), 4.69 (t, J = 6.9 Hz, 1H), 1.73 - 1.58 (m, 2H), 0.76 (t, J = 7.3 Hz, 3H), 0.52 (d, J = 12.1 Hz, 9H) ppm; 13 C NMR (151 MHz, acetone-d6) δ = 163.3, 143.2 (d, J = 16.8 Hz), 137.2, 134.8, 134.0, 132.6, 132.6, 132.5, 131.7, 131.4, 131.1, 130.0, 129.6, 129.5, 129.4 (d, J = 2.2 Hz), 128.2 (d, J = 3.3 Hz), 127.7 (d, J = 10.4 Hz), 127.4 (d, J = 10.4 Hz), 126.8, 126.6, 126.4, 126.2, 126.2, 126.1, 126.0, 125.6 (d, J = 3.82 Hz), 85.7 (d, J = 25.6 Hz), 31.3 (d, J = 20.2 Hz), 29.2, 27.4 (d, J = 14.7 Hz), 10.4 (d, J = 12.5 Hz) ppm; 31 P NMR (243 MHz, acetone-d6) δ = 1.4 ppm. IR (film) v max = 3054, 2964, 2930, 2859, 1262, 1096, 1025 cm -1 .HRMS (ESI) calcd for C 41 H 36 OP + [M+H] +575.2498, found 575.2502. (C = 0.25, CHCl3).

[0114] Example 4

[0115] On the basis of Example 1, in step (6), R 7 The ligand is changed to acetone, and the structure shown as 1-16 can be obtained.

[0116]

[0117] In the above formula, a 25 ml round-bottom flask was taken, and compound 1-8 (56.3 mg, 0.10 mmol) was added at room temperature, and 1.0 ml of tetrahydrofuran was added to completely dissolve the above compound. Subsequently, the solution was cooled to -78°C, and 2M LDA tetrahydrofuran solution (0.10 ml, 0.20 mmol) was added dropwise thereto, and after the addition was completed, the stirring was continued for 1 h while cooling, and then acetone (59 μL, 0.80 mmol) was added dropwise to the system, and the stirring was continued for 1 h while maintaining -78°C, and then it was slowly warmed to room temperature and stirred for 8 h. Thin layer chromatography was performed to check whether compound 1-8 was completely reacted.

[0118] After the complete reaction, 2 ml of saturated aqueous ammonium chloride solution was added to the system to quench the reaction, and the aqueous phase was extracted with ethyl acetate (3 x 3 mL), and the combined organic phase was dried over anhydrous magnesium sulfate and concentrated and dried in vacuo to obtain a yellowish oil of crude compound 1-15. The crude product was purified by silica gel column chromatography using acetone / petroleum ether = 1:3 as the eluent, and finally white solid compound 1-15 (40.3 mg, 65%) was obtained.

[0119] Compound 1-15: 1 H NMR (600 MHz, acetone-d6) δ = 8.73 (d, J = 13.9 Hz, 2H), 8.23 - 8.19 (m, 3H), 8.13 (ddt, J = 8.5, 1.3, 0.7 Hz, 1H), 8.03 (dt, J = 8.7, 1.1 Hz, 1H), 8.02 - 7.97 (m, 1H), 7.93 (dq, J = 8.7, 1.0 Hz, 1H), 7.81 (dd, J = 7.4, 0.8 Hz, 1H), 7.76 (dd, J = 8.7, 1.0 Hz, 1H), 7.63 - 7.53 (m, 8H), 7.53 - 7.45 (m, 2H), 7.39 (dd, J = 7.4, 3.6 Hz, 1H), 4.23 (d, J = 3.0 Hz, 1H), 1.15 (s, 3H), 0.97 (s, 3H), 0.63 (d, J = 16.0 Hz, 9H) ppm; 13C NMR (151 MHz, acetone-d6) δ = 164.2 (d, J = 18.9 Hz), 142.9 (d, J = 5.9 Hz), 138.4 (d, J = 2.3 Hz), 134.4 (d, J = 1.8 Hz), 132.5 (d, J = 2.3 Hz), 132.3 (d, J = 4.5 Hz), 131.9, 131.8, 131.4 (d, J = 9.2 Hz), 131.2, 129.7 (d, J = 17.5 Hz), 129.5, 129.1, 128.7 (d, J = 2.3 Hz), 128.3, 127.4 (d, J = 16.9 Hz), 127.1, 126.9, 126.8 (d, J = 4.4 Hz), 126.8, 126.4 (d, J = 16.9 Hz), 126.1, 125.9 (d, J = 17.3 Hz), 124.5 (d, J = 5.43 Hz), 116.5 (d, J = 85.9 Hz), 78.9 (d, J = 59.6 Hz), 73.9 (d, J = 15.1 Hz), 34.4 (d, J = 70.1 Hz), 27.5, 23.4 ppm; 31 PNMR (243 MHz, acetone-d6) δ = 64.3 ppm. IR (film) v max = 3435, 2965, 2929, 1548, 1380, 1032, 735 cm -1 .HRMS (ESI) calcd for C 42 H 38 O3P + [M+H] + 621.2553, found 621.2558. (C = 0.3, CHCl3).

[0120]

[0121] As above, take a 10 ml Schlenk tube, add compound 1-15 (40.3 mg, 0.06 mmol), triethylamine (0.13 ml, 0.96 mmol) and add 1.0 ml of toluene to completely dissolve the above compound at room temperature. Subsequently, cool the solution to 0 °C and then add trichlorosilane (43 μL, 0.48 mmol) dropwise. After the addition, keep the solution cold and stir for 15 min, then warm the system to 70 °C and stir for 8 h. Check the reaction completion of compound 1-15 by thin layer chromatography.

[0122] After complete reaction, 2 ml of 30% sodium hydroxide aqueous solution was slowly added to the system and stirred constantly until the solution was clear, the aqueous phase was extracted with ethyl acetate (3 x 3 mL), the combined organic phase was dried over anhydrous magnesium sulfate and concentrated to dryness to obtain the crude product of compound 1-16 as a light yellow solid. The crude product was purified by silica gel column chromatography using acetone / petroleum ether = 1 :20 as the eluent to finally obtain white solid compound ligand 1-16 (21.7 mg, 60%)

[0123] Ligand 1-16: 1 HNMR (600 MHz, CDC13) δ = 8.57 (d, J = 9.0 Hz, 2H), 8.16 (d, J = 8.6 Hz, 1H), 8.14 - 8.07 (m, 4H), 7.94 (d, J = 8.7 Hz, 1H), 7.89 (dd, J = 7.2, 2.4 Hz, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.62 - 7.47 (m, 9H), 7.30 (dd, J = 7.4, 3.3 Hz, 1H), 4.47 (d, J = 1.3 Hz, 1H), 1.18 (s, 3H), 1.08 (s, 3H), 0.52 (d, J = 12.1 Hz, 9H) ppm; 13 C NMR (151 MHz, CDC13) δ = 163.2, 142.0 (d, J = 16.8 Hz), 136.3, 134.2 (d, J = 10.7 Hz), 132.6, 131.6 (d, J = 7.7 Hz), 131.5 (d, J = 9.9 Hz), 131.0, 130.6, 130.2, 129.3, 128.9, 128.7 (d, J = 16.0 Hz), 127.5, 127.4, 127.2, 127.1, 126.6, 126.1, 125.8, 125.7, 125.6, 125.4, 125.4, 125.3, 125.2, 125.2, 121.0, 91.3 (dd, J = 29.3 Hz, 2.0 Hz), 73.3 (d, J = 19.6 Hz), 31.1 (d, J = 19.0 Hz), 27.0, 25.2 ppm; 31 P NMR (243 MHz, CDC13) δ = -2.69 ppm. IR (film) v max = 3574, 2967, 2932, 1383, 1028, 887, 735 cm - 1 .HRMS (ESI) calcd for C 42 H 38 O2P + [M+H] +605.2604, found 605.2607. (C = 1.0, CHCI3).

[0124] Example 5

[0125] In Example 1, in step (6), R 7 The ligand is changed to MOMBr, and the structure shown in 1-18 can be obtained.

[0126]

[0127] A 25 ml round bottom flask was charged with compound 1-8 (56.3 mg, 0.10 mmol) at room temperature and 1.0 ml of tetrahydrofuran was added to completely dissolve the compound. The solution was then cooled to -78 °C and 2M LDA tetrahydrofuran solution (0.15 ml, 0.30 mmol) was added dropwise. After the addition was completed, the solution was stirred for 1 h while maintaining the cooling. Then, bromomethyl methyl ether (50 mg, 0.40 mmol) was added dropwise to the system, and the stirring was continued for 1 h while maintaining the temperature at -78 °C. The temperature was then slowly increased to room temperature and the stirring was continued for 8 h. Thin layer chromatography was used to determine whether the reaction of compound 1-8 was complete.

[0128] After the reaction was complete, 2 ml of saturated aqueous ammonium chloride solution was added to quench the reaction. The aqueous phase was extracted with ethyl acetate (3 x 3 mL), and the combined organic phases were dried over anhydrous magnesium sulfate and concentrated and dried in vacuo to obtain a yellowish oil of crude compound 1-17. The crude product was purified by column chromatography on silica gel using acetone / petroleum ether = 1:6 as the eluent, and white solid compound 1-17 (33.8 mg, 60%, dr = 3.3:1) was finally obtained.

[0129] Compound 1-17: 1 H NMR (600 MHz, acetone-d6) δ = 8.73 (d, J = 17.1 Hz, 2H), 8.22 - 8.18 (m, 3H), 8.13 (ddt, J = 9.1, 1.3, 0.7 Hz, 1H), 7.98 (dd, J = 8.7, 1.0 Hz, 1H), 7.95 - 7.89 (m, 2H), 7.85 (dd, J = 7.4, 0.8 Hz, 1H), 7.82 (dq, J = 8.7, 1.0 Hz, 1H), 7.60 - 7.49 (m, 8H), 7.42 (dd, J = 7.4, 3.5 Hz, 1H), 5.51 (d, J = 15.3 Hz, 1H), 4.48 (d, J = 6.5 Hz, 1H), 4.43 (d, J = 6.4 Hz, 1H), 2.99 (s, 3H), 0.65 (d, J = 15.6 Hz, 9H) ppm; 13C NMR (151 MHz, acetone-d6) δ = 163.6 (d, J = 18.6 Hz), 161.8 (d, J = 17.4 Hz), 143.5 (d, J = 5.9 Hz), 142.6 (d, J = 5.6 Hz), 138.4 (d, J = 2.4 Hz), 138.1 (d, J = 2.3 Hz), 135.0, 134.5, 132.5 (d, J = 9.8 Hz), 132.3, 132.3, 132.2 (d, J = 6.5 Hz), 132.1, 131.8, 131.8, 131.6, 131.6, 131.4, 131.4, 131.1, 129.7, 129.6 (d, 13.8 Hz), 129.6, 129.5, 129.4, 129.2, 128.6 (d, J = 10.9 Hz), 128.6, 128.4, 128.3, 128.2, 127.8 (d, J = 8.6 Hz), 127.4 (d, J = 13.0 Hz) 127.3, 127.0 (d, J = 13.1 Hz), 126.9 (d, J = 3.2 Hz), 126.9, 126.8, 126.8, 126.8, 126.7, 126.4 (d, J = 22.5 Hz), 126.2 (d, J = 6.6 Hz), 126.1, 125.9, 125.9, 124.9 (d, J = 5.3 Hz), 124.6 (d, J = 9.4 Hz), 117.8 (d, J = 86.1 Hz) 116.7 (d, J = 86.2 Hz), 95.5 (d, J = 7.6 Hz), 94.1 (d, J = 82.9 Hz), 75.1 (d, J = 117.0 Hz), 72.7, 59.1, 55.7, 49.4, 34.1 (d, J = 71.3 Hz), 33.5 (d, J = 70.2 Hz), 27.5, 23.7 ppm; 31 PNMR (243 MHz, acetone-d6) δ = 51.4 ppm. IR (film) v max = 3055, 2963, 2927, 2855, 1263, 1017, 736 cm -1 .HRMS (ESI) calcd for C 41 H 36 O3P + [M+H] + 607.2397, found 607.2401. (C = 0.21, CHCI3).

[0130]

[0131] Into a 25 ml round bottom flask, add compound 1-17 (33.8 mg, 0.06 mmol) at room temperature and dissolve the compound completely by adding 1.0 ml dichloromethane. Then cool the solution to 0 °C and add 1 M boron tribromide solution in dichloromethane (0.12 ml, 0.12 mmol) dropwise. Keep stirring for 10 min after the addition is completed. Check the reaction completion by TLC.

[0132] After the reaction is completed, add 2 ml methanol slowly to the system and keep stirring until the solution is completely decolorized. Dry the system directly to get the crude product of compound 17 demethylated. The crude product is directly used for the next reaction without further purification.

[0133] Into a 10 ml Schlenk tube, add the above demethylated crude product, triethylamine (0.13 ml, 0.96 mmol) at room temperature and dissolve the compound completely by adding 1.0 ml toluene. Then cool the solution to 0 °C and add trichlorosilane (43 μL, 0.48 mmol) dropwise. Keep stirring for 15 min after the addition is completed. Then warm the system to 70 °C and keep stirring for 8 h. Check the reaction completion by TLC.

[0134] After the reaction is completed, add 2 ml 30% aqueous sodium hydroxide solution slowly to the system and keep stirring until the solution is clear. Extract the aqueous phase with ethyl acetate (3 x 3 mL) and combine the organic phases. Dry over anhydrous magnesium sulfate and concentrate to dryness to get the crude product of compound 1-18 as a light yellow solid. Purify the crude product by silica gel column chromatography using acetone / petroleum ether = 1:20 as the eluent. Finally get compound ligand 1-18 (20.8 mg, 60%) as a white solid.

[0135] Ligand 1-18: 1 H NMR (600 MHz, CDC13) δ = 8.50 (d, J = 13.9 Hz, 2H), 8.04 (ddd, J = 21.7, 10.2, 7.4 Hz, 5H), 7.85 (d, J = 8.4 Hz, 2H), 7.78 - 7.74 (m, 1H), 7.51 - 7.42 (m, 10H), 7.25 (dd, J = 7.4, 3.4 Hz, 1H), 4.75 (dd, J = 9.1, 3.8 Hz, 1H), 3.78 - 3.71 (m, 1H), 3.56 - 3.45 (m, 1H), 0.44 (d, J = 12.6 Hz, 9H) ppm; 13C NMR (151 MHz, acetone-d6) δ = 162.4, 143.1 (d, J = 16.7 Hz), 137.2, 134.8, 133.9, 132.6 (d, J = 6.0 Hz), 132.5 (d, J = 8.7 Hz), 131.8, 131.2 (d, J = 9.8 Hz), 129.8, 129.6, 129.4, 129.3 (d, J = 3.3 Hz), 128.4 (d, J = 4.1 Hz), 128.2, 127.7, 127.6 (d, J = 4.8 Hz), 127.5, 126.7, 126.6, 126.5 (d, J = 14.3 Hz), 126.2, 126.1, 126.1, 126.0, 122.3, 78.7 (d, J = 0.3 Hz), 65.3, 31.3 (d, J = 18.9 Hz), 27.7 (d, J = 14.2 Hz) ppm; 31 PNMR (243 MHz, acetone-d6) δ = 8.4 ppm. IR (film) v max = 3573, 2967, 2932, 1383, 1028, 756, 735 cm -1 HRMS (ESI) calcd for C 40 H 34 O2P + [M+H] + 577.2291, found 577.2289. (C = 0.27, CHCl3).

[0136] Example 6

[0137] On the basis of Example 1, in step (6), the ligand R 7 is changed to Br-(CH2)3-OTBS, the structure shown as 1-20 can be obtained.

[0138]

[0139] Take a 25 ml round bottom flask, at room temperature, add compound 1-8 (56.3 mg, 0.10 mmol), and add 1.0 ml of tetrahydrofuran to completely dissolve the above compound. Then the solution is cooled to -78°C, and then 2M LDA tetrahydrofuran solution (0.10 ml, 0.20 mmol) is added dropwise, after the addition is completed, keep cooling and stirring for 1 h, then (3-bromopropoxy)-tert-butyldimethylsilane (76.0 mg, 0.30 mmol) is added dropwise to the system, continue to keep -78°C stirring for 1 h, then slowly raise to room temperature and stir for 8 h. TLC test whether compound 1-8 is completely reacted.

[0140] After the reaction was completed, 2 ml of saturated aqueous ammonium chloride solution was added to quench the reaction, and the aqueous phase was extracted with ethyl acetate (3 x 3 mL). The combined organic phase was dried over anhydrous magnesium sulfate and concentrated to dryness to obtain the crude product of compound 1-19 as a light yellow solid. The crude product was purified by silica gel column chromatography using acetone / petroleum ether = 1 :6 as the eluent to finally obtain white solid compound 1-19 (37.0 mg, 50%).

[0141] Compound 1-19: 1 H NMR (400 MHz, acetone-d6) d = 8.71 (d, J = 8.4 Hz, 2H), 8.24 - 8.17 (m, 3H), 8.11 (d, J = 8.5 Hz, 1H), 8.01 - 7.95 (m, 2H), 7.93 - 7.87 (m, 1H), 7.84 (dq, J = 8.6, 1.0 Hz, 1H), 7.79 (dd, J = 7.4, 0.7 Hz, 1H), 7.61 - 7.43 (m, 8H), 7.34 (dd, J = 7.5, 3.4 Hz, 1H), 4.52 - 4.44 (m, 1H), 3.47 - 3.35 (m, 2H), 1.86 - 1.72 (m, 2H), 1.39 - 1.25 (m, 2H), 0.79 (s, 9H), 0.56 (d, J = 15.5 Hz, 9H), -0.08 (s, 3H), -0.10 (s, 3H) ppm; 13 C NMR (151 MHz, acetone-d6) d = 163.2, 143.1 (d, J = 5.6 Hz), 138.0 (d, J = 2.1 Hz), 135.0 (d, J = 2.1 Hz), 132.5 (d, J = 6.2 Hz), 132.3 (d, J = 7.7 Hz), 132.1, 131.7, 131.5, 131.3, 131.2, 129.7, 129.6 (d, J = 11.0 Hz), 129.5, 129.4, 129.0, 128.5 (d, J = 10.9 Hz), 128.2, 127.4, 127.0, 126.9, 126.9, 126.8, 126.8, 126.7, 126.4, 126.3, 126.1, 126.0, 125.9, 124.7 (d, J = 5.4 Hz), 117.6 (d, J = 83.9 Hz), 74.9 (d, J = 61.9 Hz), 64.6, 33.8 (d, J = 70.4 Hz) ppm; 31 P NMR (243 MHz, acetone-d6) d = 58.7 ppm. IR (film) v max = 3055, 2959, 2928, 2857, 1261, 1096, 837 cm-1 HRMS (ESI) calcd for C 48 H 52 O3PSi + [M+H] + 735.3418, found 735.3421. (C = 0.5, CHCl3).

[0142]

[0143] Take a 10 ml Schlenk tube, add compound 1-19 (37.0 mg, 0.05 mmol), triethylamine (0.12 ml, 0.90 mmol) and 1.0 ml of toluene to completely dissolve the above compound at room temperature. Then cool the solution to 0 °C, and add trichlorosilane (36 μL, 0.40 mmol) dropwise. After the addition, keep the solution stirring for 15 min, then warm the system to 70 °C and stir for 8 h. TLC test to check if the compound 1-19 is completely reacted.

[0144] After the complete reaction, slowly add 2 ml of 30% aqueous sodium hydroxide solution to the system and continuously stir until the solution is clear. Extract the aqueous phase with ethyl acetate (3 x 3 mL), combine the organic phases, dry over anhydrous magnesium sulfate, and concentrate to dryness to obtain the reduced crude product of compound 1-19. The crude product is used directly for the subsequent reaction without further purification.

[0145] Take a 25 ml round-bottom flask, add the above reduced product at room temperature, and add 1.0 ml of tetrahydrofuran to completely dissolve the above compound. Then cool the solution to 0 °C, and add 1 M tetrabutylammonium fluoride in tetrahydrofuran solution (0.10 ml, 0.10 mmol) dropwise. After the addition, keep the solution stirring for 30 min. TLC test to check if the starting material is completely reacted.

[0146] After the complete reaction, slowly add 2 ml of water to quench the reaction, extract the aqueous phase with ethyl acetate (3 x 3 mL), combine the organic phases, dry over anhydrous magnesium sulfate, and concentrate to dryness to obtain the crude product of compound 1-20 as a light yellow oil. Purify the crude product by silica gel column chromatography using acetone / petroleum ether = 1:3 as the eluent to obtain the ligand 1-20 as a white solid (18.2 mg, 60%).

[0147] Ligand 1-20: 1H NMR (600 MHz, acetone-d6) δ = 8.69 (d, J = 3.4 Hz, 2H), 8.23 - 8.15 (m, 5H), 8.04 (d, J = 8.0 Hz, 1H), 7.93 (dd, J = 8.7, 1.0 Hz, 1H), 7.87 (dd, J = 8.6, 1.0 Hz, 1H), 7.61 - 7.48 (m, 9H), 7.31 (dd, J = 7.4, 3.3 Hz, 1H), 4.80 (t, J = 7.1 Hz, 1H), 3.42 (t, J = 6.4 Hz, 2H), 1.77 - 1.67 (m, 2H), 1.48 - 1.38 (m, 2H), 0.53 (d, J = 12.0 Hz, 9H) ppm; 13 C NMR (151 MHz, acetone-d6) δ = 163.2, 143.2 (d, J = 16.9 Hz), 137.2, 134.8, 133.9, 133.4, 132.6, 132.5, 131.7, 131.4, 131.1, 130.0, 129.6, 129.5, 129.3 (d, J = 3.8 Hz), 128.3 (d, J = 3.5 Hz), 128.1, 127.7 (d, J = 16.3 Hz), 127.4 (d, J = 15.7 Hz), 126.7, 126.5 (d, J = 9.2 Hz), 126.4, 126.2 (d, J = 8.9 Hz), 126.1 (d, J = 12.2 Hz), 125.6 (d, J = 4.1 Hz), 122.3, 84.4 (d, J = 25 Hz), 62.0 (d, J = 18.6 Hz), 32.9 (d, J = 25.7 Hz), 31.4 (d, J = 21 Hz), 27.4 (d, J = 14.8 Hz) ppm; 31 PNMR (243 MHz, acetone-d6) δ = 2.0 ppm. IR (film) v max = 3447, 2966, 2928, 1261, 1083, 1025, 735 cm -1 .HRMS (ESI) calcd for C 42 H 37 O2PNa + [M+Na] + 627.2423, found 627.2426. (C = 0.5, CHCl3).

[0148] Experimental Example

[0149] Experimental Example, as follows:

[0150]

[0151] To a flask under Ar protection was added compound 1a (50 mg, 90 pmol, 1.0 equiv), phosphine ligand (11 pmol, 12 mol%), sodium formate (12.2 mg, 0.18 mmol, 2.0 equiv), triethylamine (38 pL, 0.27 mmol, 3.0 equiv) and tetrabutylammonium bromide (58 mg, 0.18 mmol, 2.0 equiv) and palladium catalyst (4.5 pmol / 9 pmol, 5 mol% / 10 mol%) at room temperature and the mixture was dissolved in 1.0 ml 1,4-dioxane. The system was warmed to 90 °C and kept stirring for 12 h. The reaction was quenched with saturated aqueous ammonium chloride solution, extracted with ethyl acetate, washed with saturated NaCl, dried over anhydrous magnesium sulfate, filtered and dried in vacuum. The product was purified on a silica gel chromatography column (eluent: ethyl acetate / petroleum ether 1 / 6) to give 2a.

[0152] Compound 2a: ee value was determined by ultra performance chromatography (UPCC) with the following conditions: OD-3, CO2 / MeOH = 90 / 10, v = 1.0 mL / min, l = 220.0 nm; t b (major) = 5.429 min, t b (minor) = 5.117 min; R f = 0.65 (silica gel, EtOAc / petroleum ether 1:2); 1 H NMR (400 MHz, CDC13) d = 6.77 (d, J = 9.1 Hz, 2H), 6.69 (d, J = 9.1 Hz, 2H), 5.62 (t, J = 2.4 Hz, 1H), 4.04 - 3.95 (m, 2H), 3.96 - 3.86 (m, 3H), 3.73 (s, 3H), 3.67 (d, J = 9.0 Hz, 1H), 2.93 (dd, J = 18.7, 3.8 Hz, 1H), 2.82 (dd, J = 17.5, 2.3 Hz, 1H), 2.76 (dd, J = 17.5, 2.3 Hz, 1H), 2.72 (dd, J = 19.3, 3.8 Hz, 1H), 2.46 (d, J = 18.7 Hz, 1H), 2.38 (d, J = 19.3 Hz, 1H), 1.09 (s, 3H), 1.04 (s, 3H) ppm; 13C NMR (101 MHz, CDC13) δ = 207.3, 206.0, 154.3, 152.3, 147.6, 118.7, 115.3, 115.3, 114.7, 73.4, 70.1, 65.2, 65.0, 55.8, 51.6, 45.0, 44.9, 44.6, 44.3, 22.1, 6.5 ppm; IR (film) v max = 2913, 1740, 1708, 1509, 1415, 1231, 1090, 1029, 826, 751, 689 cm –1 ; HRMS (ESI) calcd for C 23 H 26 NaO6 + [M+Na] + 421.1622, found 421.1616.

[0153] The reaction results of different phosphine ligands, the amount of phosphine ligand and palladium catalyst, and the amount of palladium catalyst are shown in Table 1 using the above operation:

[0154] Table 1 Reaction results of different phosphine ligands and palladium catalysts (X represents the amount of palladium catalyst)

[0155]

[0156]

[0157] The ligands L1-L13 in Table 1 are respectively the ligands prepared in Examples 1-6 of the present application and existing ligands, and their structures are as follows:

[0158]

[0159] The above examples are only one of the preferred embodiments of the present application, and should not be used to limit the protection scope of the present application, but any modification or polishing without substantial meaning made within the main design idea and spirit of the present application, and the technical problems solved are still consistent with the present application, should be included in the protection scope of the present application.

Claims

1. A chiral phosphine ligand TANKPhos, characterized in that Its structure is as shown in Formula I: In Formula I, R 1 C1~C 10 One of the alkyl groups; R 2 、R 2‘ 、R 3 、R 3’ 、R 4 、R 4‘ 、R 5 、R 5’ 、R 6 、R 6‘ Each is independently H, C1~C 10 Alkyl, C1~C 10 Alkoxy, C3~C 10 Cycloalkyl, halogen, C6~C 20 One of the aromatic groups or together form a C5~C 10 One of cycloalkane, 5-10 membered heterocycle or 5-10 membered heteroaromatic ring; the heteroatoms in the 5-10 membered heterocycle or 5-10 membered heteroaromatic ring are one or more of N, O or S, and the number of heteroatoms is 1 to 3; R 7 C1~C 10 Alkyl, C1~C 10 Alkoxy, C1~C 10 Alcohol, C1~C 10 Amine, C1~C 10 Carboxylic acid, C1~C 10 One of the amides; R 8 is one of C1 to C4 alkyl groups; R 9 is one of C1 to C4 alkyl groups; In Formula I, and Represents the relative configuration of the P atom and the adjacent C atom. for hour, for when for hour, for 2. The chiral phosphine ligand TANKPhos according to claim 1, characterized in that The structures are selected from one of the following structures:

3. The chiral phosphine ligand TANKPhos according to claim 1, characterized in that The structure of R7 is selected from one of the following structures:

4. The method for preparing the chiral phosphine ligand TANKPhos according to any one of claims 1 to 3, characterized in that: The steps include: (1) The following reaction formula is used: under room temperature, compound 1 is dissolved in dichloromethane, and NBS is added, and the reaction is continued under stirring for 8 to 24 hours; after the reaction, the mixture is quenched, extracted, and dried to obtain a crude product of compound 2 as a pale yellow oil. The crude product 2 is dissolved in tetrahydrofuran, and the resulting solution is then cooled to 0°C and a tetrahydrofuran solution of tetrabutylammonium fluoride is added dropwise. The mixture is stirred for 30 to 60 minutes. After the reaction is completed, the mixture is quenched, extracted, and subjected to column chromatography to obtain compound 3 as a white solid. (2) The following reaction formula: 1,4-dioxane is used as a solvent, compound 3, Sphos, potassium fluoride, and compound 4 are added, and then Pd2(dba)3 is added to the solution, and the system is heated to 100°C for 6 to 24 hours. After the reaction is complete, the mixture is quenched, extracted, and column chromatographed to obtain a white solid compound 5; (3) The following reaction formula: Under room temperature reaction conditions, compound 5 and triethylamine were added to dichloromethane as solvent, and then the solution was cooled to 0°C and PhNTf2 was added thereto. After the addition was complete, the system was returned to room temperature and the reaction was maintained for 2 to 5 hours. After the reaction was complete, the mixture was quenched, extracted, and column chromatography was performed to obtain a white solid compound 6; (4) As shown in the following reaction formula, at room temperature, compound 7 is dissolved in tetrahydrofuran as a solvent to form solution A, and compound 6, BIDME and Pd2(dba)3 are then added to tetrahydrofuran as a solvent to form solution B. Solution B is added dropwise to solution A, and the temperature is raised to 70°C and refluxed for 6 to 24 hours. After the reaction is complete, the mixture is quenched, extracted, and subjected to column chromatography to obtain compound 8 as a white solid; (5) As shown in the following reaction formula, under room temperature, tetrahydrofuran was added to completely dissolve compound 8, and then the solution was cooled to -78 °C and LDA tetrahydrofuran solution was added dropwise thereto. After the addition, the system was kept cooled and stirred for 1 hour, and then a solution that can form R was added dropwise. 7 The mixture was stirred at -78°C for 1 hour, then slowly warmed to room temperature and stirred for 6 to 24 hours. After the reaction was complete, the mixture was quenched, extracted, and subjected to column chromatography to obtain a white solid compound 9. (6) The following reaction formula is used: Compound 9 and triethylamine are added at room temperature, and toluene is added to completely dissolve the above compounds; the solution is then cooled to 0°C and trichlorosilane is added dropwise thereto. After the addition is complete, the system is kept cooled and stirred for 15 minutes. The system is then heated to 70°C and stirred for 6 to 24 hours. After the reaction is complete, the system is quenched, extracted, and dried to obtain a crude product which is dissolved in THF. The resulting solution is cooled to 0°C and a tetrahydrofuran solution of tetrabutylammonium fluoride is added dropwise thereto and stirred for 2 hours. After the reaction is complete, the system is quenched, extracted, and subjected to column chromatography to obtain a white solid compound, ligand I.

5. The method for preparing the chiral phosphine ligand TANKPhos according to claim 4, characterized in that: In step (1), the quenching reagent for preparing compound 3 is a saturated sodium thiosulfate solution, and the extracted organic phase is ethyl acetate; the quenching reagent for preparing compound 4 is water, the extracted organic phase is a mixed solvent of dichloromethane / isopropanol, and the column chromatography eluent is a mixed solvent of methanol / dichloromethane.

6. The method for preparing the chiral phosphine ligand TANKPhos according to claim 4, characterized in that: In step (2), the quenching reagent is a saturated ammonium chloride solution, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of ethyl acetate / petroleum ether.

7. The method for preparing the chiral phosphine ligand TANKPhos according to claim 4, characterized in that: In step (3), the quenching reagent is water, the extraction organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of ethyl acetate / petroleum ether.

8. The method for preparing the chiral phosphine ligand TANKPhos according to claim 4, characterized in that: In step (4), the quenching reagent is a saturated ammonium chloride solution, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of ethyl acetate / petroleum ether.

9. The method for preparing the chiral phosphine ligand TANKPhos according to claim 4, characterized in that: In step (5), the quenching reagent is a saturated ammonium chloride solution, the extracted organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of acetone / petroleum ether.

10. The method for preparing the chiral phosphine ligand TANKPhos according to claim 4, characterized in that: In step (6), the quenching reagent is a 30% sodium hydroxide aqueous solution, the extraction organic phase is ethyl acetate, and the column chromatography eluent is a mixed solvent of acetone / petroleum ether.

11. Use of the chiral phosphine ligand TANKPhos according to any one of claims 1 to 3 as a desymmetrization agent in an enantioselective desymmetrization reduction Heck reaction.

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