Alkoxy-substituted biphenyl chiral monophosphine ligand and preparation method thereof

Abstract

The invention discloses an alkoxy-substituted biphenyl chiral monophosphine ligand and a preparation method thereof, and belongs to the technical field of organic synthesis. The structural general formula of the alkoxy-substituted biphenyl chiral monophosphine ligand is as follows: # imgabs0 #, R1 is selected from substituted or unsubstituted aryl, and the substituted group is selected from at least one of hydrogen atom, methyl, halogen and naphthyl; r2 is selected from at least one of a hydrogen atom, a methyl group, a phenyl group, an isopropyl group, a tertiary butyl group, an amino group, an epoxy pentacyclic ring, a halogen, a trifluoromethyl group and a trifluoromethoxy group; r3 is selected from at least one of benzyl, ethyl, n-hexyl, methoxy methyl ether, isopropyl and naphthyl methyl; and R4 is selected from at least one of a hydrogen atom, a methoxy group, an n-butyl group and a p-methoxyphenyl group. The ligand disclosed by the invention has relatively high efficiency and excellent performance in transition metal catalysis, the synthesis method is simple, and the biphenyl type chiral monophosphine ligand can be constructed in one step.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to an alkoxy-substituted biphenyl-based chiral monophosphine ligand and a preparation method thereof. Background Art

[0002] In the field of asymmetric synthesis, the chiral regulation mechanism of transition metal catalytic systems is closely related to ligand structure design. It is worth noting that chiral phosphine ligands, with their unique electronic effects and steric hindrance regulation capabilities, occupy an important position in the rapidly developing frontier field of cross-coupling reactions and have become the focus of research in the synthetic chemistry community. Taking axially chiral monophosphine ligands with biaryl skeletons as an example, such ligands with excellent stereocontrol capabilities have been successfully applied in various transition metal-catalyzed asymmetric transformations. However, the synthesis steps of such ligands are too lengthy. Starting from axially chiral binaphthols, it is necessary to go through three-step reactions to generate axially chiral phosphine oxide compounds, and then reduce them to obtain this type of ligand. This leads to problems such as large limitations on substituent groups, cumbersome steps, and low overall yields, which greatly affect the development of this type of ligand. Summary of the Invention

[0003] Aiming at the deficiencies of the prior art, the present invention provides an alkoxy-substituted biphenyl-based chiral monophosphine ligand and a preparation method thereof.

[0004] In the first aspect of the present invention, an alkoxy-substituted biphenyl-based chiral monophosphine ligand is provided, and the structural general formula of the alkoxy-substituted biphenyl-based chiral monophosphine ligand is as shown in Formula 3:

[0005]

[0006] Wherein, R 1 is selected from substituted or unsubstituted aryl, and the substituted groups are selected from at least one of a hydrogen atom, a methyl group, and a halogen; R 2 is selected from at least one of a hydrogen atom, a methyl group, a phenyl group, an isopropyl group, a tert-butyl group, an amino group, an epoxy pentacyclic ring, a halogen, a trifluoromethyl group, and a trifluoromethoxy group; R 3 is selected from at least one of a benzyl group, an ethyl group, a n-hexyl group, a methoxymethylether group, an isopropyl group, and a naphthylmethyl group; R 4 is selected from at least one of a hydrogen atom, a methoxy group, a n-butyl group, and a p-methoxyphenyl group; preferably, the halogen is selected from at least one of Br, F, and Cl.

[0007] The second aspect of the present invention provides a method for preparing the alkoxy-substituted biphenyl-based chiral monophosphine ligand described in the first aspect above, which comprises the following steps: mixing compound 1, compound 2, a catalyst, a base, a chiral ligand, and a solvent, reacting under a nitrogen atmosphere, and then obtaining the alkoxy-substituted biphenyl-based chiral monophosphine ligand through post-treatment; wherein, the structural formula of compound 1 is as shown in formula 1, and the structure of compound 2 is as shown in formula 2:

[0008]

[0009] In formula 1: R 1 and R 2 are respectively and independently defined in the same way as R 1 and R 2 in formula 3 in the first aspect above; in formula 2: R 3 and R 4 are respectively and independently defined in the same way as R 3 and R 4 in formula 3 in the first aspect above.

[0010] Preferably, the catalyst is zero-valent palladium.

[0011] Preferably, the catalyst includes at least one of tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, and bis(tritert-butylphosphine)palladium; preferably, the catalyst is tetrakis(triphenylphosphine)palladium.

[0012] Preferably, the chiral ligand is selected from at least one of R-(+)-1,1'-binaphthalene-2,2'-bis(diphenylphosphine), (S)-(-)-2-[2-(diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline, (S)-(+)-2-[2-(diphenylphosphino)phenyl]-4-phenyl-2-oxazoline, (4S,5S)-2-(2-(diphenylphosphino)phenyl)-4,5-diphenyl-4,5-dihydrooxazole, and (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene; preferably, the chiral ligand is (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene.

[0013] Preferably, the base includes at least one of potassium carbonate, potassium phosphate, cesium carbonate, lithium tert-butoxide, and cesium pivalate; preferably, the base is potassium carbonate.

[0014] Preferably, the solvent includes at least one of toluene, tetrahydrofuran, 2-methyltetrahydrofuran, and water;

[0015] Preferably, the solvent is a mixed solvent of 2-methyltetrahydrofuran and water, and the volume ratio of 2-methyltetrahydrofuran to water is 1 to 10:1; preferably, the volume ratio of 2-methyltetrahydrofuran to water is 10:1.

[0016] Preferably, the molar ratio of the catalyst, chiral ligand, compound 1 to compound 2 is 0.05:0.05 to 0.15:1:1.2; preferably, the molar ratio of the catalyst, chiral ligand, compound 1 to compound 2 is 0.05:0.15:1:1.2.

[0017] Preferably, the molar ratio of the base to compound 1 is 1 to 4:1; preferably, the molar ratio of the base to compound 1 is 3:1.

[0018] Preferably, the temperature of the reaction is 120 to 140 °C and the time is 24 to 48 h; preferably, the temperature of the reaction is 120 °C and the time is 36 to 48 h.

[0019] The beneficial technical effects of the present invention are as follows:

[0020] The present invention provides a new synthetic method for alkoxy-substituted biphenyl-based chiral monophosphine ligands. The raw materials of the synthetic route are cheap and easily available, the unit operations are simple, the equipment requirements are low, and it is suitable for rapidly constructing a new library of biphenyl-based chiral monophosphine ligands. The synthesized ligands have high efficiency and excellent performance in transition metal catalysis. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 It is the hydrogen spectrum of the compound prepared in Example 1 of the present invention.

[0022] Figure 2 It is the carbon spectrum of the compound prepared in Example 1 of the present invention.

[0023] Figure 3 It is the phosphorus spectrum of the compound prepared in Example 1 of the present invention.

[0024] Figure 4 It is the hydrogen spectrum of the compound prepared in Example 24 of the present invention.

[0025] Figure 5 It is the carbon spectrum of the compound prepared in Example 24 of the present invention.

[0026] Figure 6 It is the phosphorus spectrum of the compound prepared in Example 24 of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0027] The present invention provides an alkoxy-substituted biphenyl-based chiral monophosphine ligand and a preparation method thereof. The alkoxy-substituted biphenyl-based chiral monophosphine ligand of the present invention uses compound 1 and compound 2 as raw materials, zero-valent palladium as a catalyst, under the protection of an inert gas, in a solvent, in the presence of a base and a chiral ligand, controlling the reaction temperature, and the raw materials are subjected to an asymmetric Suzuki-Miyaura cross-coupling reaction through a catalytic method by the catalyst to obtain the product.

[0028] It can be understood that the present invention does not limit the preparation of compound 1 and compound 2, and any preparation method that can achieve the purpose of the present invention is within the protection scope of the present invention. Exemplarily, compound 1 of the present invention can be prepared through the following synthetic route:

[0029]

[0030] Compound 2 can be synthesized through the following synthetic route:

[0031]

[0032] In some embodiments, the synthetic route of the alkoxy-substituted biphenyl-based chiral monophosphine ligand is as follows:

[0033]

[0034] It can be understood that the definitions of R 1 , R 2 , R 3 and R 4 are the same as those described above. L is tris(4-methoxy-3,5-dimethylphenyl)phosphine, and L* is a chiral ligand.

[0035] It can be understood that the catalyst used in the present invention has the effect of improving the reaction efficiency; the chiral ligand has the effect of improving the enantioselectivity. The present invention selects a halogenated aromatic hydrocarbon containing trivalent phosphorus and a naphthyl borate containing an alkoxy group, and through the cooperation of the catalyst and the chiral ligand, an asymmetric Suzuki-Miyaura cross-coupling reaction occurs to obtain an alkoxy-substituted biphenyl-based chiral monophosphine ligand. The preparation method is simple and the catalytic efficiency is high.

[0036] It can be understood that both the catalyst and the chiral ligand used in the present invention can be obtained by commercial purchase.

[0037] The following describes the present invention in detail with reference to examples.

[0038] Example 1

[0039] (S)-[2-(2-Benzyloxynaphthalen-1-yl)phenyl]diphenylphosphine, and its synthetic route is as follows:

[0040]

[0041] The synthesis steps include:

[0042] Synthesis of (2-bromophenyl)diphenylphosphine: In a dry reaction tube, o-bromoiodobenzene (5.0 mmol), diphenylphosphine (5.0 mmol), triethylamine (6.25 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.025 mmol) were added, and then dissolved in 8 mL of toluene. The system was stirred at 85 °C for 16 h under a nitrogen atmosphere. After the reaction was completed, the solvent was removed, and 1.46 g of the product was obtained by column chromatography with a yield of 86%.

[0043] Synthesis of 2-benzyloxy-1-naphthaleneboronic acid pinacol ester: In a dry Schlenk tube, 2-benzyloxy-1-bromonaphthalene (5.0 mmol), palladium acetate (0.05 mmol), tris(4-methoxy-3,5-dimethylphenyl)phosphine (0.055 mmol), cesium carbonate (7.5 mmol), bis(pinacolato)diboron (7.5 mmol) and ethyl acetate (2.5 mL) were added. The mixture was stirred at 90 °C for 36 h under a nitrogen atmosphere. After the reaction was completed, it was filtered through diatomaceous earth. The filtrate was concentrated and the product was obtained by column chromatography. 1.12 g of the product was obtained with a yield of 62%.

[0044] Synthesis of (S)-[2-(2-benzyloxynaphthalen-1-yl)phenyl]diphenylphosphine:

[0045] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium(0) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. The mixture was stirred at 120 °C for 36 h under a nitrogen atmosphere. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, it was separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 89.5 mg of the product was obtained with a yield of 91% and an enantiomeric excess value of 93%. 1 H NMR(500MHz,CDCl3)δ7.77(d,J=9.0Hz,2H),7.72(d,J=8.1Hz,1H),7.46–7.43(m,3H),7.39–7.26(m,5H),7.25–7.01(m,14H),4.95(d,J=12.6Hz,1H),4.76(d,J=12.6Hz,1H);13 13C NMR (126 MHz, CDCl3) δ 153.2, 143.1 (d, J = 33.4 Hz), 138.8 (d, J = 11.1 Hz), 137.7, 137.64, 137.55 (d, J = 4.0 Hz), 134.1 (d, J = 1.9 Hz), 133.72 (d, J = 1.7 Hz), 133.70 (d, J = 20.4 Hz), 133.4 (d, J = 19.1 Hz), 131.2 (d, J = 5.9 Hz), 129.3, 128.9, 128.8, 128.2, 128.1 (d, J = 11.6 Hz), 127.94 (d, J = 7.2 Hz), 127.86, 127.7, 127.64, 127.56, 127.2, 126.3, 126.0, 125.4, 125.3, 123.4, 114.5, 70.2; 31 31P NMR (202 MHz, CDCl3) δ -13.54.

[0046] The synthesis methods of Compounds 1 and 2 in the following examples are the same as those in Example 1, and the raw materials can be selected according to the specific structures of Compounds 1 and 2 in each example, which will not be elaborated here.

[0047] Example 2

[0048] (S)-2-(2-Benzyloxynaphthalen-1-yl)-5-methylphenyldiphenylphosphine, and its synthetic route is as follows:

[0049]

[0050] The synthesis steps include:

[0051] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-5-methylphenyl)diphenylphosphine (0.2 mmol, 70.8 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Under a nitrogen atmosphere, stir at 120 °C for 36 hours. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography, eluted with petroleum ether:ethyl acetate = 40:1, and dried in vacuo to obtain 89.3 mg of the product, with a yield of 88% and an enantiomeric excess value of 92%. 11H NMR (500 MHz, CDCl3) δ 7.75 (d, J = 9.0 Hz, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 7.25–7.00 (m, 21H), 4.95 (d, J = 12.8 Hz, 1H), 4.77 (d, J = 12.9 Hz, 1H), 2.32 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 153.3, 140.2 (d, J = 33.6 Hz), 138.3 (d, J = 11.4 Hz), 137.8 (d, J = 3.2 Hz), 137.8, 137.7 (d, J = 3.5 Hz), 137.0, 134.6 (d, J = 2.2 Hz), 134.0 (d, J = 1.9 Hz), 133.7 (d, J = 20.7 Hz), 133.4 (d, J = 18.9 Hz), 131.1 (d, J = 6.4 Hz), 129.9, 129.2, 128.8, 128.2, 128.1, 128.0 (d, J = 6.7 Hz), 127.91, 127.86, 127.7 (d, J = 6.4 Hz), 127.2, 126.3, 125.9, 125.5, 125.3 (d, J = 7.4 Hz), 123.3, 114.7, 70.3, 21.4; 31 31P NMR (202 MHz, CDCl3) δ -13.44.

[0052] Example 3

[0053] (S)-2-(2-Benzyloxynaphthalen-1-yl)-4-methylphenyldiphenylphosphine, and its synthetic route is as follows:

[0054]

[0055] The synthesis steps include:

[0056] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-4-methylphenyl)diphenylphosphine (0.2 mmol, 70.8 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 36 h. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, the residue was separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 65.0 mg of the product was obtained with a yield of 64% and an enantiomeric excess of 93%. 1 H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 9.0 Hz, 1H), 7.73 (d, J = 8.1 Hz, 1H), 7.27–7.03 (m, 22H), 4.98 (d, J = 12.8 Hz, 1H), 4.80 (d, J = 12.8 Hz, 1H), 2.38 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 153.2 (d, J = 1.4 Hz), 143.1 (d, J = 34.2 Hz), 138.9, 138.1 (d, J = 3.4 Hz), 138.0, (d, J = 3.2 Hz), 137.8, 135.1 (d, J = 9.6 Hz), 134.3 (d, J = 2.1 Hz), 133.8 (d, J = 2.0 Hz), 133.6 (d, J = 20.4 Hz), 133.3 (d, J = 18.8 Hz), 131.9 (d, J = 6.4 Hz), 129.2, 128.8, 128.6, 128.2, 128.0, 127.94, 127.91, 127.85, 127.6, 127.2, 126.4, 125.9, 125.6 (d, J = 7.2 Hz), 125.5, 123.4, 114.7, 70.4, 21.3; 31 P NMR (162 MHz, CDCl3) δ -14.71.

[0057] Example 4

[0058] (S)-2-(2-Benzyloxynaphthalen-1-yl)-4,5-dimethylphenyldiphenylphosphine, and its synthetic route is as follows:

[0059]

[0060] The synthesis steps include:

[0061] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-4,5-dimethylphenyl)diphenylphosphine (0.2 mmol, 73.6 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 48 hours. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, the residue was separated by column chromatography, eluting with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 79.4 mg of the product was obtained, with a yield of 76% and an enantiomeric excess value of 91%. 1 HNMR(500MHz,CDCl3)δ7.75(d,J=9.0Hz,1H),7.73(d,J=8.1Hz,1H),7.28–7.01(m,21H),4.97(d,J=13.0Hz,1H),4.80(d,J=13.0Hz,1H),2.29(s,3H),2.24(s,3H); 13 C NMR(126MHz,CDCl3)δ153.3,140.8(d,J=34.4Hz),138.3(d,J=9.4Hz),138.2(d,J=8.9Hz),137.8(d,J=20.2Hz),135.9,135.3(d,J=2.4Hz),135.1(d,J=9.8Hz),134.0,133.6(d,J=20.3Hz),133.3(d,J=19.0Hz),132.4(d,J=6.9Hz),129.0,128.8,128.2,127.95,127.97,127.92,127.90,127.85,127.6(d,J=5.2Hz),127.2,126.4,125.8,125.62,125.57,123.3,114.8,70.4,19.7;; 31 P NMR(202MHz,CDCl3)δ-14.68.

[0062] Example 5

[0063] (S)-2-(2-Benzyloxynaphthalen-1-yl)-4-isopropylphenyldiphenylphosphine, and its synthetic route is as follows:

[0064]

[0065] The synthesis steps include:

[0066] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-4-isopropylphenyl)diphenylphosphine (0.2 mmol, 76.4 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate, the solvent is removed, and then separated by column chromatography. Elute with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 69.6 mg of the product is obtained, with a yield of 65% and an enantiomeric excess value of 93%. 1 HNMR(500MHz,CDCl3)δ7.79(d,J=9.0Hz,1H),7.75(d,J=8.0Hz,1H),7.26–7.18(m,10H),7.16–7.03(m,10H),7.02–6.95(m,2H),4.97(d,J=12.4Hz,1H),4.69(d,J=12.4Hz,1H),2.97–2.92(m,1H),1.28(d,J=3.8Hz,3H),1.26(d,J=3.8Hz,3H); 13 C NMR(126MHz,CDCl3)δ153.2,149.8,143.1(d,J=34.0Hz),138.1(d,J=13.1Hz),138.0(d,J=12.7Hz),137.7,135.4(d,J=9.8Hz),134.3(d,J=2.1Hz),133.8,133.7(d,J=20.3Hz),133.3(d,J=18.7Hz),129.4(d,J=6.3Hz),129.2,128.8,128.1,128.02,127.96,127.8,127.73,127.68,127.6,127.1,126.3,126.0,125.9,125.6,123.4,114.6,70.1,33.9,23.9; 31 P NMR(202MHz,CDCl3)δ-14.53.

[0067] Example 6

[0068] (S)-2-(2-Benzyloxynaphthalen-1-yl)-5-tert-butylphenyldiphenylphosphine, and its synthetic route is as follows:

[0069]

[0070] The synthesis steps include:

[0071] In a dry Schlenk tube, add tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-5-tert-butylphenyl)diphenylphosphine (0.2 mmol, 79.2 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Under a nitrogen atmosphere, stir at 120 °C for 36 hours. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 83.5 mg of the product is obtained, with a yield of 76% and an enantiomeric excess value of 87%. 1 HNMR(500MHz,CDCl3)δ7.77(d,J=9.0Hz,1H),7.73(d,J=8.1Hz,1H),7.48(dd,J=7.9,2.1Hz,1H),7.32(dd,J=4.1,2.1Hz,1H),7.27–6.99(m,20H),4.95(d,J=12.5Hz,1H),4.78(d,J=12.6Hz,1H),1.25(s,9H); 13 C NMR(126MHz,CDCl3)δ153.3(d,J=1.5Hz),150.0,140.0(d,J=33.0Hz),138.0,137.9(d,J=3.5Hz),137.8(d,J=4.1Hz),133.9(d,J=1.7Hz),133.7(d,J=20.3Hz),133.4(d,J=19.0Hz),131.6(d,J=1.8Hz),130.8(d,J=6.4Hz),129.2,128.9,128.08,128.05,127.94,127.88,127.8,127.7,127.64,127.62,127.1,126.3,125.9,125..8,125.7(d,J=9.1Hz),123.4,114.9,70.4,34.7,31.3; 31P NMR (202 MHz, CDCl3) δ -12.45.

[0072] Example 7

[0073] (S)-2-(2-Benzyloxynaphthalen-1-yl)-4-tert-butylphenyldiphenylphosphine, and its synthetic route is as follows:

[0074]

[0075] The synthesis steps include:

[0076] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-4-tert-butylphenyl)diphenylphosphine (0.2 mmol, 79.2 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate, the solvent is removed, and then separated by column chromatography. Elute with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 94.8 mg of the product is obtained, with a yield of 86% and an enantiomeric excess value of 90%. 1 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J = 9.0 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.35–7.27 (m, 2H), 7.23–6.83 (m, 20H), 4.91 (d, J = 12.3 Hz, 1H), 4.60 (d, J = 12.3 Hz, 1H), 1.26 (s, 9H); 1313C NMR (126 MHz, CDCl3) δ 153.2, 152.0, 142.7 (d, J = 33.5 Hz), 138.1 (d, J = 13.2 Hz), 137.9 (d, J = 12.2 Hz), 137.8, 135.0 (d, J = 9.7 Hz), 134.0 (d, J = 1.8 Hz), 133.8 (d, J = 2.2 Hz), 133.7 (d, J = 20.3 Hz), 133.4 (d, J = 19.0 Hz), 129.2, 128.8, 128.4 (d, J = 6.1 Hz), 128.1, 128.03, 127.97, 127.8, 127.7, 127.6, 127.1, 126.3, 126.1 (d, J = 7.3 Hz), 126.0, 125.7, 124.6, 123.4, 114.6, 70.0, 34.7, 31.3; 31 31P NMR (202 MHz, CDCl3) δ -14.81.

[0077] Example 8

[0078] (S)-3-(2-Benzyloxynaphthalen-1-yl)-[1,1'-biphenyl]-4-yl diphenylphosphine, and its synthesis route is as follows:

[0079]

[0080] The synthesis steps include:

[0081] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), [3-bromo-(1,1'-biphenyl)-4-yl] diphenylphosphine (0.2 mmol, 83.2 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether: ethyl acetate = 40:1. After vacuum drying, 99.2 mg of the product is obtained, with a yield of 87% and an enantiomeric excess value of 93%. 1HNMR(500MHz, CDCl3) δ 7.79 (d, J = 9.0Hz, 1H), 7.73 (d, J = 8.1Hz, 1H), 7.63–7.57 (m, 4H), 7.41–7.33 (m, 3H), 7.30–7.03 (m, 20H), 4.99 (d, J = 12.7Hz, 1H), 4.78 (d, J = 12.6Hz, 1H); 13 C NMR(126MHz, CDCl3) δ 153.2, 143.5 (d, J = 33.6Hz), 141.5, 140.4, 137.8 (d, J = 11.3Hz), 137.7 (d, J = 2.9Hz), 137.6, 134.7, 133.724, 133.722 (d, J = 20.4Hz), 133.4 (d, J = 19.1Hz), 129.8 (d, J = 6.1Hz), 129.4, 128.8, 128.7, 128.2, 128.1, 128.03, 127.96, 127.9, 127.8, 127.7, 127.5, 127.2, 127.1, 126.4, 126.14, 126.08, 125.4, 125.2 (d, J = 7.0Hz), 123.4, 114.6, 70.24; 31 P NMR(202MHz, CDCl3) δ -14.20.

[0082] Example 9

[0083] (S)-3-(2-Benzyloxynaphthalen-1-yl)-4-diphenylphosphino-N,N-dimethylaniline, and its synthetic route is as follows:

[0084]

[0085] The synthesis steps include:

[0086] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), 3-bromo-4-diphenylphosphino-N,N-dimethylaniline (0.2 mmol, 76.6 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 36 h. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, the residue was separated by column chromatography, eluting with petroleum ether:ethyl acetate = 30:1. After vacuum drying, 94.1 mg of the product was obtained, with a yield of 88% and an enantiomeric excess value of 93%. 1 H NMR (400 MHz, CDCl3) δ 7.79–7.69 (m, 2H), 7.31 (d, J = 8.9 Hz, 1H), 7.23 (d, J = 1.3 Hz, 1H), 7.21–7.04 (m, 18H), 6.74 (dd, J = 8.7, 2.8 Hz, 1H), 6.66 (dd, J = 3.8, 2.7 Hz, 1H), 4.98 (d, J = 12.8 Hz, 1H), 4.81 (d, J = 13.0 Hz, 1H), 2.91 (s, 6H); 13 C NMR (101 MHz, CDCl3) δ 153.1 (d, J = 1.7 Hz), 150.7, 144.4 (d, J = 36.8 Hz), 139.4 (d, J = 12.8 Hz), 139.2 (d, J = 12.7 Hz), 137.9, 135.7 (d, J = 2.4 Hz), 134.0 (d, J = 1.8 Hz), 133.3 (d, J = 20.0 Hz), 133.1 (d, J = 18.4 Hz), 128.9, 128.8, 128.1, 127.9, 127.81, 127.77, 127.7, 127.63, 127.57, 127.3, 127.1, 126.4, 125.8 (d, J = 2.7 Hz), 123.3, 123.2 (d, J = 4.9 Hz), 114.9, 114.5 (d, J = 7.0 Hz), 111.9,, 70.4, 40.1; 31 P NMR (162 MHz, CDCl3) δ -16.09.

[0087] Example 10

[0088] (S)-6-(2-Benzyloxynaphthalen-1-yl)benzod[d][1,3]dioxol-5-yldiphenylphosphine, and its synthesis route is as follows:

[0089]

[0090] The synthesis steps include:

[0091] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (6-bromobenzod[d][1,3]dioxol-5-yl)diphenylphosphine (0.2 mmol, 76.8 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 48 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 30:1. After vacuum drying, 54.9 mg of the product is obtained, with a yield of 51% and an enantiomeric excess value of 95%. 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 9.0 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.29–7.01 (m, 19H), 6.79 (d, J = 3.5 Hz, 1H), 6.77 (d, J = 2.5 Hz, 1H), 6.02–6.00 (m, 2H), 4.99 (d, J = 12.9 Hz, 1H), 4.81 (d, J = 12.9 Hz, 1H); 13 C NMR (101 MHz, CDCl3) δ 153.5 (d, J = 1.9 Hz), 148.7, 147.3, 138.3 (d, J = 13.6 Hz), 138.1 (d, J = 13.2 Hz), 137.8 (d, J = 37.0 Hz), 137.7, 134.1 (d, J = 2.2 Hz), 133.4 (d, J = 20.4 Hz), 133.2 (d, J = 18.8 Hz), 131.1 (d, J = 10.8 Hz), 129.4, 128.9, 128.3, 128.12, 128.05, 128.01, 127.95, 127.7, 127.3, 126.4, 126.1, 125.4, 125.0 (d,, J = 8.4 Hz), 123.4, 114.6, 113.6 (d, J = 1.8 Hz), 111.4 (d, J = 7.2 Hz), 101.2, 70.3;31 P NMR (162 MHz, CDCl3) δ -13.70.

[0092] Example 11

[0093] (S)-2-Benzyloxy-[1,2'-binaphthalen]-3'-yldiphenylphosphine, and its synthetic route is as follows:

[0094]

[0095] The synthesis steps include:

[0096] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (3-bromonaphthalen-2-yl)diphenylphosphine (0.2 mmol, 78.0 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography, eluted with petroleum ether:ethyl acetate = 40:1, and dried in vacuo to obtain 76.7 mg of the product, with a yield of 70% and an enantiomeric excess value of 89%. 1 H NMR (400 MHz, CDCl3) δ 7.83–7.75 (m, 3H), 7.71 (t, J = 5.4 Hz, 3H), 7.52–7.39 (m, 2H), 7.24–6.97 (m, 19H), 4.99 (d, J = 12.8 Hz, 1H), 4.82 (d, J = 12.8 Hz, 1H); 13 C NMR (101 MHz, CDCl3) δ 153.5, 139.1 (d, J = 31.9 Hz), 138.0 (d, J = 12.3 Hz), 137.7, 137.3 (d, J = 13.0 Hz), 136.9, 136.8, 134.2, 134.0, 133.9, 133.8, 133.61, 133.57, 132.7, 130.0 (d, J = 5.7 Hz), 129.5, 128.7, 128.3, 128.2, 128.1, 128.00, 127.95, 127.6, 127.5, 127.2, 126.6, 126.4, 125.9 (d, J = 3.9 Hz), 125.4, 124.7 (d, J = 6.5 Hz), 123.3, 114.5, 70.3; 31P NMR (162 MHz, CDCl3) δ -12.22.

[0097] Example 12

[0098] (S)-2-(2-Benzyloxynaphthalen-1-yl)-5-fluorophenyl diphenylphosphine, and its synthesis route is as follows:

[0099]

[0100] The synthesis steps include:

[0101] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-5-fluorophenyl)diphenylphosphine (0.2 mmol, 71.6 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Under a nitrogen atmosphere, stir at 120 °C for 36 hours. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography, eluted with petroleum ether:ethyl acetate = 40:1, and dried in vacuo to obtain 79.4 mg of the product, with a yield of 77% and an enantiomeric excess value of 93%. 1 H NMR (500 MHz, CDCl3) δ 7.77 (d, J = 9.0 Hz, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.31–7.01 (m, 21H), 6.97 (dt, J = 9.3, 2.9 Hz, 1H), 4.96 (d, J = 12.5 Hz, 1H), 4.76 (d, J = 12.5 Hz, 1H); 1313C NMR (126 MHz, CDCl3) δ 162.2 (d, J = 248.5 Hz), 153.3, 142.0 (dd, J = 15.0, 4.6 Hz), 138.5 (dd, J = 32.1, 3.2 Hz), 137.6, 136.7 (d, J = 13.0 Hz), 136.6 (d, J = 12.7 Hz), 133.78 (d, J = 20.9 Hz), 133.75, 133.4 (d, J = 19.4 Hz), 132.8 (t, J = 6.6 Hz), 129.6, 128.7, 128.5, 128.3, 128.2 (d, J = 7.1 Hz), 128.1, 128.0, 127.7, 127.3, 126.3, 126.1, 125.1, 123.9 (d, J = 6.9 Hz), 123.4, 120.2 (d, J = 20.8 Hz), 116.1 (d, J = 21.4 Hz), 114.3, 70.1; 31 31P NMR (202 MHz, CDCl3) δ -12.80; 19 19F NMR (471 MHz, CDCl3) δ -114.48.

[0102] Example 13

[0103] (S)-2-(2-Benzyloxynaphthalen-1-yl)-4-fluorophenyldiphenylphosphine, and its synthetic route is as follows:

[0104]

[0105] The synthesis steps include:

[0106] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-4-fluorophenyl)diphenylphosphine (0.2 mmol, 71.6 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate, the solvent is removed, and then separated by column chromatography. Elute with petroleum ether:ethyl acetate = 40:1, and vacuum dry to obtain 79.5 mg of the product, with a yield of 78% and an enantiomeric excess value of 96%. 11H NMR (500 MHz, CDCl3) δ 7.74 (d, J = 9.0 Hz, 1H), 7.68 (d, J = 8.2, 1H), 7.20–6.94 (m, 22H), 4.92 (d, J = 12.6 Hz, 1H), 4.72 (d, J = 12.7 Hz, 1H); 13 13C NMR (126 MHz, CDCl3) δ 163.3 (d, J = 249.6 Hz), 153.1 (d, J = 1.6 Hz), 145.6 (dd, J = 35.8, 8.2 Hz), 137.6 (d, J = 4.3 Hz), 137.50, 137.46, 136.2 (dd, J = 8.3, 1.8 Hz), 134..5 (dd, J = 11.0, 3.4 Hz), 133.6 (d, J = 20.7 Hz), 133..4 (d, J = 1.8 Hz), 133.3 (d, J = 19.1 Hz), 129.8, 128.7, 128.3, 128.1 (d, J = 6.9 Hz), 128.03, 127.98, 127.9, 127.8, 127.3, 126.4, 126.3, 125.0, 124.1 (d, J = 7.1 Hz), 123.5, 118.2 (dd, J = 20.3, 6.4 Hz), 114.9 (d, J = 20.3 Hz), 114.4, 70.2; 31 31P NMR (202 MHz, CDCl3) δ -15.41; 19 19F NMR (471 MHz, CDCl3) δ -112.85.

[0107] Example 14

[0108] (S)-2-(2-Benzyloxynaphthalen-1-yl)-5-chlorophenyl diphenylphosphine, and its synthesis route is as follows:

[0109]

[0110] The synthesis steps include:

[0111] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-5-chlorophenyl)diphenylphosphine (0.2 mmol, 74.8 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 36 h. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate, the solvent was removed, and the residue was separated by column chromatography, eluting with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 87.2 mg of the product was obtained, with a yield of 83% and an enantiomeric excess value of 92%. 1 H NMR (500 MHz, CDCl3) δ 7.78 (d, J = 9.0 Hz, 1H), 7.72 (d, J = 8.2 Hz, 1H), 7.42 (dd, J = 8.2, 2.2 Hz, 1H), 7.33–7.00 (m, 21H), 4.96 (d, J = 12.5 Hz, 1H), 4.77 (d, J = 12.6 Hz, 1H); 13 C NMR (126 MHz, CDCl3) δ 153.2, 141.7 (d, J = 15.7 Hz), 141.4 (d, J = 32.4 Hz), 137.5, 136.6 (d, J = 12.7 Hz), 136.5 (d, J = 12.8 Hz), 133.8 (d, J = 20.9 Hz), 133.6, 133.5, 133.40 (d, J = 19.3 Hz), 133.37, 132.6 (d, J = 5.6 Hz), 129.7, 129.1, 128.7, 128.5, 128.3, 128.2 (d, J = 7.1 Hz), 128.13, 128.08, 127.7, 127.3, 126.3, 126.2, 125.1, 123.7 (d, J = 7.0 Hz), 123.4, 114.3, 70.2; 31 P NMR (202 MHz, CDCl3) δ -12.78.

[0112] Example 15

[0113] (S)-2-(2-Benzyloxynaphthalen-1-yl)-4-(trifluoromethyl)phenyl diphenylphosphine, and its synthetic route is as follows:

[0114]

[0115] The synthesis steps include:

[0116] In a dry Schlenk tube, palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-4-trifluoromethylphenyl)diphenylphosphine (0.2 mmol, 81.6 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 36 hours. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, the residue was separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 57.3 mg of the product was obtained, with a yield of 51% and an enantiomeric excess value of 92%. 1 HNMR(500MHz,CDCl3)δ7.82(d,J=9.0Hz,1H),7.75(d,J=8.2,1H),7.65–7.55(m,2H),7.35(dd,J=8.1,3.1Hz,1H),7.28–6.97(m,19H),5..00(d,J=12.5Hz,1H),4.76(d,J=12.4Hz); 13 C NMR(126MHz,CDCl3)δ153.2,144.5(d,J=15.1Hz),143.5(d,J=32.8Hz),137.4,136.32(d,J=26.5Hz),136.31,134.2,133.9(d,J=21.3Hz),133.5(d,J=19.6Hz),133.2(d,J=2.1Hz),130.9(q,J=32.2Hz),130.0,128.7,128.6,128.3,128.2(d,J=3.3Hz),128.12,128.07,128.0(q,J=3.8Hz),127.8,127.4,126.39,126.38,124.9,124.2(q,J=273.4Hz),124.1(q,J=3.4Hz),123.54,123.48(d,J=2.1Hz),114.1,70.1; 31 P NMR(202MHz,CDCl3)δ-13.23; 19 F NMR(471MHz,CDCl3)δ-62.44.

[0117] Example 16

[0118] (S)-2-(2-Benzyloxynaphthalen-1-yl)-5-(trifluoromethyl)phenyl diphenylphosphine, and its synthesis route is as follows:

[0119]

[0120] The synthesis steps include:

[0121] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromo-5-(trifluoromethyl)phenyl)diphenylphosphine (0.2 mmol, 84.8 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate, the solvent is removed, and then separated by column chromatography. Elute with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 94.8 mg of the product is obtained, with a yield of 82% and an enantiomeric excess value of 94%. 1 H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 9.0 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H), 7.35–7.04 (m, 22H), 5.04 (d, J = 12.4 Hz, 1H), 4.77 (d, J = 12.4 Hz, 1H); 13 C NMR (126 MHz, CDCl3) δ 153.1, 149.8, 145.1 (d, J = 34.6 Hz), 138.0 (d, J = 12.8 Hz), 137.4, 137.0 (d, J = 13.1 Hz), 136.9, 135.6, 133.7 (d, J = 20.8 Hz), 133.4 (d, J = 19.5 Hz), 129.9, 128.7, 128.4, 128.3, 128.24, 128.18, 128.04, 128.01, 127.99, 127.8, 127.3, 126.4, 126.3, 124.9, 123.6, 123.3 (d, J = 6.0 Hz), 119.8, 119.5 (q, J = 258.3 Hz), 114.1, 70.0; 31 P NMR (202 MHz, CDCl3) δ -14.89; 19 F NMR (471 MHz, CDCl3) δ -57.51.

[0122] Example 17

[0123] (S)-2-(2-Benzyloxynaphthalen-1-yl)phenylbis(p-tolyl)phosphine, and its synthesis route is as follows:

[0124]

[0125] The synthesis steps include:

[0126] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)bis(p-tolyl)phosphine (0.2 mmol, 73.6 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, dry the reaction system with anhydrous sodium sulfate, remove the solvent, and then separate by column chromatography. Elute with petroleum ether:ethyl acetate = 40:1, and obtain 70.8 mg of the product after vacuum drying. The yield is 68%, and the enantiomeric excess value is 94%. 1 H NMR(400MHz,CDCl3)δ7.79(d,J=9.0Hz,1H),7.77–7.69(m,1H),7.47–7.42(m,1H),7.38–7.33(m,1H),7.32–7.05(m,11H),7.04–6.78(m,8H),4.98(d,J=13.1Hz,1H),4.76(d,J=12.6Hz,1H),2.24(s,6H); 13 C NMR(101MHz,CDCl3)δ153.2,142.8(d,J=32.7Hz),139.5(d,J=11.8Hz),137.9,137.8,137.5,134.2(d,J=5.9Hz),134.1(d,J=5.5Hz),133.9,133.8,133.6(d,J=9.5Hz),133.4,131.2(d,J=5.8Hz),129.3,128.9,128.80,128..78,128.76,128.7,128.2,127.6(d,J=12.7Hz),127.1,126.3,125.9,125.5,125.4,123.3,114.6,70.3,21.2; 31 P NMR(162MHz,CDCl3)δ-15.23.

[0127] Example 18

[0128] (S)-2-(2-Benzyloxynaphthalen-1-yl)phenylbis(3,5-dimethylphenyl)phosphine, and its synthetic route is as follows:

[0129]

[0130] The synthesis steps include:

[0131] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)bis(3,5-dimethylphenyl)phosphine (0.2 mmol, 79.2 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 60.4 mg of the product is obtained, with a yield of 55% and an enantiomeric excess value of 92%. 1 HNMR(400MHz,CDCl3)δ7.78(d,J = 8.9Hz,1H),7.72(s,1H),7.49–7.40(m,1H),7.37–7.35(m,2H),7.31–7.18(m,6H),7.13–7.02(m,4H),6.83–6.69(m,4H),6.63(d,J = 8.0Hz,2H),5.04(d,J = 12.6Hz,1H),4.92(d,J = 12.6Hz,1H),2.08(s,6H),2.06(s,6H); 1313C NMR (101 MHz, CDCl3) δ 153.1, 142.7 (d, J = 32.7 Hz), 139.7 (d, J = 12.3 Hz), 137.8, 137.5, 137.2 (d, J = 6.6 Hz), 137.1 (d, J = 7.7 Hz), 136.9 (d, J = 12.1 Hz), 133.9, 131.9, 131.7, 131.2, 131.1, 131.0, 130.0, 129.6, 129.2, 128.9, 128.5, 128.2, 127.5 (d, J = 3.5 Hz), 127.1, 126.3, 125.7 (d, J = 7.1 Hz), 125.5, 125.4, 123.3, 114.9, 70.5, 21.1; 31 31P NMR (162 MHz, CDCl3) δ -12.52..

[0132] Example 19

[0133] (S)-2-(2-Benzyloxynaphthalen-1-yl)phenylbis(4-fluorophenyl)phosphine, and its synthetic route is as follows:

[0134]

[0135] The synthesis steps include:

[0136] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)bis(4-fluorophenyl)phosphine (0.2 mmol, 75.2 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography, eluted with petroleum ether:ethyl acetate = 40:1, and dried in vacuo to obtain 83.7 mg of the product, with a yield of 79% and an enantiomeric excess value of 88%. 11H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 9.0 Hz, 1H), 7.78–7.69 (m, 1H), 7.47 (dd, J = 7.4, 1.4 Hz, 1H), 7.40–7.36 (m, 1H), 7.34–7.29 (m, 1H), 7.28–7.13 (m, 7H), 7.09–7.04 (m, 3H), 7.01–6.95 (m, 4H), 6.85–6.64 (m, 4H), 5.01 (d, J = 12.4 Hz, 1H), 4.82 (d, J = 12.4 Hz, 1H); 13 13C NMR (101 MHz, CDCl3) δ 163.1 (d, J = 249.5 Hz), 162.8 (d, J = 248.5 Hz), 153.1 (d, J = 1.4 Hz), 142.8 (d, J = 33.0 Hz), 138.7 (d, J = 11.1 Hz), 137.5, 135.6 (dd, J = 22.4, 8.1 Hz), 135.2 (dd, J = 20.8, 7.8 Hz), 133.6 (d, J = 1.8 Hz), 133.43, 133.42, 132.8 (dd, J = 7.2, 3.4 Hz), 132.6 (dd, J = 7.5, 3.4 Hz), 131.4 (d, J = 5.8 Hz), 129.5, 129.1, 128.8, 128.2, 127.7, 127.3, 126.3, 126.1, 125.2, 125.0 (d, J = 7.3 Hz), 123.5, 115.3 (dd, J = 14.2, 7.0 Hz), 115.1 (dd, J = 14.2, 7.1 Hz), 114.5, 70.3; 31 31P NMR (162 MHz, CDCl3) δ -15.55 (t, J = 4.6 Hz); 19 19F NMR (376 MHz, CDCl3) δ -112.88 (d, J = 7.7 Hz), -113.41 (d, J = 8.2 Hz).

[0137] Example 20

[0138] (S)-2-(2-Benzyloxynaphthalen-1-yl)phenylbis(4-chlorophenyl)phosphine, and its synthesis route is as follows:

[0139]

[0140] The synthesis steps include:

[0141] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)bis(4-chlorophenyl)phosphine (0.2 mmol, 81.6 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 36 h. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, the residue was separated by column chromatography, eluted with petroleum ether:ethyl acetate = 40:1, and dried in vacuo to obtain 76.8 mg of the product, with a yield of 68% and an enantiomeric excess value of 88%. 1 H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.47 (dd, J = 7.5, 1.4 Hz, 1H), 7.39–7.35 (m, 1H), 7.35–7.15 (m, 8H),, 7.09–7.04 (m, 5H), 7.02–6.95 (m, 2H), 6.95–6.90 (m, 4H), 5.00 (d, J = 12.4 Hz, 1H), 4.78 (d, J = 12.4 Hz, 1H); 13 C NMR (101 MHz, CDCl3) δ 153.1 (d, J = 1.6 Hz), 143.0 (d, J = 33.5 Hz), 138.0 (d, J = 10.5 Hz), 137.4, 135.7 (d, J = 2.6 Hz), 135.5 (d, J = 2.2 Hz), 135.0 (d, J = 21.6 Hz), 134.6 (d, J = 20.1 Hz), 134.2, 133.57, 133.55, 131.4 (d, J = 5.9 Hz), 129.6, 129.3, 128.8, 128.4, 128.3, 128.24, 128.23, 128.18, 127.8 (d, J = 4.0 Hz), 127.3, 126.4, 126.2, 125.1, 124.8 (d, J = 7.4 Hz), 123.5, 114.4, 70.3; 31 P NMR (162 MHz, CDCl3) δ -15.13.

[0142] Example 21

[0143] (S)-2-(2-Benzyloxynaphthalen-1-yl)phenylbis(naphthalen-2-yl)phosphine, and its synthetic route is as follows:

[0144]

[0145] The synthesis steps include:

[0146] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)bis(naphthalen-2-yl)phosphine (0.2 mmol, 88.0 mg), 2-benzyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 86.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 h under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 99.1 mg of the product is obtained, with a yield of 83% and an enantiomeric excess value of 90%. 1 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 9.0 Hz, 1H), 7.71 (dd, J = 7.8, 2.2 Hz, 3H), 7.63 (d, J = 8.4 Hz, 1H), 7.60–7.46 (m, 4H), 7.46–7.08 (m, 17H), 7.03–6.99 (m, 3H), 4.93 (d, J = 12.5 Hz, 1H), 4.71 (d, J = 12.6 Hz, 1H); 13 13C NMR (101 MHz, CDCl3) δ 153.2, 143.2 (d, J = 33.1 Hz), 138.7 (d, J = 11.1 Hz), 137.6, 135.1 (d, J = 12.9 Hz), 134.8 (d, J = 13.1 Hz), 134.6, 134.4, 134.1, 133.8, 133.5 (d, J = 20.4 Hz), 133.2, 133.1, 133.0, 132.9, 131.3 (d, J = 6.1 Hz), 130.3 (d, J = 10.9 Hz), 130.1 (d, J = 11.7 Hz), 129.4, 129.1, 128.8, 128.2, 128.0, 127.9, 127.7, 127.6, 127.52, 127.49, 127.47, 127.3, 127.24, 127.21, 126.3, 126.2, 125.92, 125.86, 125.8, 125.2, 123.4, 114.6, 70.3; 31 31P NMR (162 MHz, CDCl3) δ -12.19.

[0147] Example 22

[0148] (S)-2-(2-Ethoxynaphthalen-1-yl)phenyl diphenylphosphine, and its synthetic route is as follows:

[0149]

[0150] The synthesis steps include:

[0151] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-ethoxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 71.6 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Under a nitrogen atmosphere, stir at 120 °C for 36 hours. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 73.1 mg of the product is obtained, with a yield of 85% and an enantiomeric excess value of 93%. 1 H NMR(500MHz,CDCl3)δ7.75(d,J = 9.0Hz,1H),7.68(d,J = 8.1Hz,1H),7.37(d,J = 1.5Hz,1H),7.28(d,J = 1.4Hz,1H),7.25–6.91(m,16H),3.88(dq,J = 9..5,6.9Hz,1H),3.67(dq,J = 9.5,7.0Hz,1H),0.98(t,J = 7.0Hz,3H); 13 C NMR(126MHz,CDCl3)δ153.5,143.4(d,J = 33.7Hz),138.7(d,J = 10.6Hz),138.0(d,J = 13.4Hz),137.8,134.2(d,J = 2.0Hz),133.9,133.7,133.5,133.4,131.2(d,J = 6.2Hz),129.2,128.9,128.5,128.03(d,J = 3.2Hz),127.97,127.9(d,J = 11.8Hz),127.6,127.4,125.9,125.3,124.8(d,J = 7.5Hz),123.1,114.0,64.1,14.9; 31P NMR (202 MHz, CDCl3) δ -13.80.

[0152] Example 23

[0153] (S)-2-(2-Hexylnaphthalen-1-yl)phenyl diphenylphosphine, and its synthetic route is as follows:

[0154]

[0155] The synthesis steps include:

[0156] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-hexyloxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 85.0 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate, the solvent is removed, and then separated by column chromatography. Elute with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 70.0 mg of the product is obtained, with a yield of 72% and an enantiomeric excess value of 93%. 1 H NMR (500 MHz, CDCl3) δ 7.82 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 1.6 Hz, 1H), 7.37–7.27 (m, 2H), 7.26–7.00 (m, 15H), 3.84 (dt, J = 9.1, 6.9 Hz, 1H), 3.71 (ddd, J = 9.0, 6.9, 5.9 Hz, 1H), 1.50–1.36 (m, 2H), 1..27–1.08 (m, 6H), 0.83 (t, J = 7.1 Hz, 3H); 1313C NMR (126 MHz, CDCl3) δ 153.6 (d, J = 2.0 Hz), 143.3 (d, J = 33.6 Hz), 138.7 (d, J = 10.9 Hz), 138.0 (d, J = 6.1 Hz), 137.9 (d, J = 6.3 Hz), 134.1 (d, J = 1.8 Hz), 133.8 (d, J = 1.8 Hz), 133.7 (d, J = 20.7 Hz), 133.4 (d, J = 19.1 Hz), 131.2 (d, J = 6.2 Hz), 129.2, 128.8, 128.5, 128.0 (d, J = 5.6 Hz), 127.93 (d, J = 3.6 Hz), 127.87, 127.8, 127.6, 127.4, 125.9, 125.3, 124.9 (d, J = 7.5 Hz), 123.1, 114.2, 68.8, 31.5, 29.2, 25.4, 22.5, 14.0; 31 31P NMR (202 MHz, CDCl3) δ -13.69.

[0157] Example 24

[0158] (S)-2-(2-Methoxymethoxynaphthalen-1-yl)phenyl diphenylphosphine, and its synthesis route is as follows:

[0159]

[0160] The synthesis steps include:

[0161] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-methoxymethoxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 75.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate, the solvent is removed, and then separated by column chromatography. Elute with petroleum ether:ethyl acetate = 40:1, and vacuum dry to obtain 52.8 mg of the product, with a yield of 59% and an enantiomeric excess value of 94%. 11H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 9.0 Hz, 1H), 7.76 (d, J = 8.1 Hz, 1H), 7.48–7.42 (m, 2H), 7.38–7.35 (m, 1H), 7.33–7.09 (m, 13H), 7.05–7.02 (m, 2H), 4.86 (d, J = 7.0 Hz, 1H), 4.66 (d, J = 7.0 Hz, 1H), 3.19 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 152.2, 143.2 (d, J = 33.9 Hz), 138.6 (d, J = 11.0 Hz), 137.8 (d, J = 12.8 Hz), 137.7 (d, J = 12.8 Hz), 134.4 (d, J = 2.0 Hz), 133.7, 133.6 (d, J = 3.1 Hz), 133.4 (d, J = 2.1 Hz), 131.2 (d, J = 6.2 Hz), 129.4, 129.2, 128.9, 128.10, 128.06, 128.02, 128.01, 127.96, 127.6 (d, J = 9.3 Hz), 126.0, 125.5 (d, J = 7.2 Hz), 125.4, 123.6, 116.0, 94.7, 55.6; 31 31P NMR (202 MHz, CDCl3) δ -14.15.

[0162] Example 25

[0163] (S)-2-(2-Isopropoxynaphthalen-1-yl)phenyl diphenylphosphine, and its synthesis route is as follows:

[0164]

[0165] The synthesis steps include:

[0166] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-isopropoxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 74.9 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 36 h. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, the residue was separated by column chromatography, eluting with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 53.8 mg of the product was obtained with a yield of 60% and an enantiomeric excess value of 85%. 1 H NMR (500 MHz, CDCl3) δ 7.81 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 8.2 Hz, 1H), 7.46–7.38 (m, 1H), 7.36–7.30 (m, 2H), 7.28–7.18 (m, 8H), 7.16–7.00 (m, 7H), 4.47–4.42 (m, 1H), 1.05 (d, J = 6.0 Hz, 3H), 0.99 (d, J = 6.1 Hz, 3H); 13 C NMR (126 MHz, CDCl3) δ 152.6, 143.8 (d, J = 34.6 Hz), 138.6 (d, J = 10.5 Hz), 138.2 (d, J = 13.4 Hz), 138.1, 134.5 (d, J = 2.3 Hz), 134.1 (d, J = 1.9 Hz), 133.6 (d, J = 20.7 Hz), 133.2 (d, J = 18.5 Hz), 131.2 (d, J = 6.5 Hz), 129.0, 128.8, 128.6, 128.1, 128.01,, 127.95, 127.9, 127.6 (d, J = 6.0 Hz), 127.4, 126.4 (d, J = 7.4 Hz), 125.8, 125.4, 123.2, 116.2, 71.0, 22.2, 22.1; 31 P NMR (202 MHz, CDCl3) δ -14.17.

[0167] Example 26

[0168] (S)-2-(2-(Naphthalen-1-ylmethoxy)naphthalen-1-yl)phenyl diphenylphosphine, and its synthetic route is as follows:

[0169]

[0170] The synthesis steps include:

[0171] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-(naphthalen-1-ylmethoxy)-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 98.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 h under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 72.1 mg of the product is obtained, with a yield of 66% and an enantiomeric excess value of 89%. 1 H NMR (500 MHz, CDCl3) δ 7.86–7.80 (m, 2H), 7.79–7.73 (m, 2H), 7.70 (d, J = 8.5, 1H), 7.49–7.41 (m, 2H), 7.40–7.34 (m, 2H), 7.33–7.21 (m, 6H), 7.20–7.03 (m, 10H), 7.02–6.95 (m, 2H), 5.38 (d, J = 12.9 Hz, 1H), 5.18 (d, J = 13.0 Hz, 1H); 13 C NMR (126 MHz, CDCl3) δ 153.3, 143.0 (d, J = 33.5 Hz), 138.8 (d, J = 11.0 Hz), 137.6 (d, J = 12.8 Hz), 137.5 (d, J = 12.7 Hz), 134.2 (d, J = 2.0 Hz), 133.7 (d, J = 20.6 Hz), 133.5 (d, J = 19.2 Hz), 133.4, 132.9, 131.3 (d, J = 6.2 Hz), 130.6, 129.4, 129.0, 128.9, 128.5, 128.11, 128.05, 128.0, 127.6, 127.9, 127.8, 127.74, 127.67, 127.6, 126..0, 125.8 (d, J = 7.4 Hz), 125.6, 125.5, 125.3, 124.8, 123.5, 123.2, 115.1, 69.2; 31 P NMR (202 MHz, CDCl3) δ -13.82.

[0172] Example 27

[0173] (S)-2-(2-(Naphthalen-2-ylmethoxy)naphthalen-1-yl)phenyl diphenylphosphine, and its synthetic route is as follows:

[0174]

[0175] The synthesis steps include:

[0176] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-(naphthalen-2-ylmethoxy)-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 98.4 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 68.6 mg of the product is obtained, with a yield of 63% and an enantiomeric excess value of 89%. 1 H NMR(500MHz,CDCl3)δ7.82–7.67(m,4H),7.64–7.60(m,1H),7.53–7.46(m,2H),7.43–7.40(m,3H),7.37–7.35(m,1H),7.32–7.29(m,1H),7.27–7.21(m,2H),7.20–7.01(m,11H),6.98–6.90(m,2H),5.13(d,J=12.8Hz,1H),4.92(d,J=12.8Hz,1H); 1313C NMR (126 MHz, CDCl3) δ 153.2, 143.1 (d, J = 33.3 Hz), 139.0 (d, J = 11.4 Hz), 137.5 (d, J = 8.1 Hz), 137.4 (d, J = 8.3 Hz), 135.2, 134.1, 133.8 (d, J = 20.7 Hz), 133.4 (d, J = 19.1 Hz), 133.2, 132.7, 131.3 (d, J = 6.0 Hz), 129.4, 129.0, 128.8, 128.2, 128.04, 127.98, 127.90, 127.88, 127.85, 127.8, 127.73, 127.66, 127.61, 127.58, 126.0 (d, J = 6.5 Hz), 125.7, 125.4, 125.4, 125.1, 124.4, 123.4, 114.6, 70.3; 31 31P NMR (202 MHz, CDCl3) δ -13.48.

[0177] Example 28

[0178] (S)-2-(2-Benzyloxy-6-methoxynaphthalen-1-yl)phenyl diphenylphosphine, and its synthesis route is as follows:

[0179]

[0180] The synthesis steps include:

[0181] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-benzyloxy-6-methoxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 93.6 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 20:1. After vacuum drying, 75.5 mg of the product is obtained, with a yield of 72% and an enantiomeric excess value of 95%. 1HNMR(500MHz, CDCl3) δ 7.68 (d, J = 9.0 Hz, 1H), 7.51–7.42 (m, 1H), 7.37–7.34 (m, 1H), 7.32–7.26 (m, 2H), 7.24–6.99 (m, 18H), 6.85 (dd, J = 9.2, 2.6 Hz, 1H), 4.93 (d, J = 12.6 Hz, 1H), 4.75 (d, J = 12.6 Hz, 1H), 3.84 (s, 3H); 13 C NMR(126MHz, CDCl3) δ 155.9, 151.8, 143.2 (d, J = 33.5 Hz), 138.7 (d, J = 11.4 Hz), 137.5, 137.7 (d, J = 7.1 Hz), 137.6 (d, J = 7.5 Hz), 134.1 (d, J = 1.9 Hz), 133.7 (d, J = 20.7 Hz), 133.4 (d, J = 19.1 Hz), 131.2 (d, J = 5.9 Hz), 129.7, 129.2 (d, J = 2.1 Hz), 128.9, 128.2, 128.1, 128.0, 127.91, 127.87, 127.7, 127.6, 127.1, 127.0, 126.4, 125.8 (d, J = 7.5 Hz), 118.8, 115.4, 105.6, 70.5, 55.2; 31 P NMR(202MHz, CDCl3) δ -13.69.

[0182] Example 29

[0183] (S)-2-(2-Benzyloxy-6-butylnaphthalen-1-yl)phenyl diphenylphosphine, and its synthesis route is as follows:

[0184]

[0185] The synthesis steps include:

[0186] In a dry Schlenk tube, tetrakis(triphenylphosphine)palladium (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-benzyloxy-6-n-butyl-1-naphthylboronic acid pinacol ester (0.24 mmol, 99.9 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL) were added. Under a nitrogen atmosphere, the mixture was stirred at 120 °C for 36 h. After the reaction was completed, the reaction system was dried over anhydrous sodium sulfate. After removing the solvent, the residue was separated by column chromatography, eluting with petroleum ether:ethyl acetate = 40:1. After vacuum drying, 92.9 mg of the product was obtained, with a yield of 84% and an enantiomeric excess value of 93%. 1 HNMR(400MHz,CDCl3)δ7.70(d,J=9.0Hz,1H),7.50(d,J=1.7Hz,1H),7.46–7.42(m,1H),7.38–7.25(m,3H),7.23–6.93(m,18H),4.95(d,J=12.6Hz,1H),4.76(d,J=12.6Hz,1H),2.67(t,J=7.7Hz,2H),1.65–1.60(m,2H),1.43–1.32(m,2H),0.93(t,J=7.3Hz,3H); 13 C NMR(101MHz,CDCl3)δ152.6(d,J=1.6Hz),143.3(d,J=33.3Hz),138.8(d,J=11.3Hz),137.8(d,J=5.2Hz),137.7,137.6(d,J=9.1Hz),134.1(d,J=1.8Hz),133.8(d,J=20.5Hz),133.4(d,J=19.1Hz),132.2(d,J=1.8Hz),131.2(d,J=6.1Hz),129.0,128.8(d,J=11.3Hz),128.14,128.07,128.0,127.93,127.92,127.86,127.7,127.6,127.5,127.1,126.4,126.0,125.3,125.3,114.7,70.4,35.4,33.4,22.3,14.0; 31 P NMR(162MHz,CDCl3)δ-13.52.

[0187] Example 30

[0188] (S)-2-(2-Benzyloxy-6-(4-methoxyphenyl)naphthalen-1-yl)phenyl diphenylphosphine, and its synthesis route is as follows:

[0189]

[0190] The synthesis steps include:

[0191] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-benzyloxy-6-p-methoxyphenyl-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 111.9 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 h under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 20:1. After vacuum drying, 86.8 mg of the product is obtained, with a yield of 72% and an enantiomeric excess value of 92%. 1 H NMR (500 MHz, CDCl3) δ 7.82 (d, J = 2.0 Hz, 1H), 7.77 (d, J = 9.0 Hz, 1H), 7.54–7.48 (m, 2H), 7.42 (d, J = 1.4 Hz, 1H), 7.32–7.27 (m, 3H), 7.23 (d, J = 3.6 Hz, 1H), 7.17–7.14 (m, 4H), 7.12–6.97 (m, 13H), 6.95–6.89 (m, 2H), 4.92 (d, J = 12.6 Hz, 1H), 4.73 (d, J = 12.7 Hz, 1H), 3.78 (s, 3H); 1313C NMR (126 MHz, CDCl3) δ 156.0, 153.1, 143.1 (d, J = 33.4 Hz), 138.8 (d, J = 11.2 Hz), 137.7, 137.6 (d, J = 4.3 Hz), 137.5 (d, J = 4.6 Hz), 135.6, 134.1, 133.84 (d, J = 20.4 Hz), 133.81, 133.4 (d, J = 19.1 Hz), 132.7, 131.2 (d, J = 5.9 Hz), 129.5, 129.1, 129..0, 128.2 (d, J = 4.5 Hz), 128.2, 128.1, 128.0, 127.9 (d, J = 6.2 Hz), 127.8, 127.6, 127.2, 126.4, 125.9, 125.6, 125.3 (d, J = 7.2 Hz), 124.9, 115.0, 114.2, 70.3, 55.4; 31 31P NMR (202 MHz, CDCl3) δ -13.61.

[0192] Example 31

[0193] (S)-2-(2-Benzyloxy-7-methoxynaphthalen-1-yl)phenyl diphenylphosphine, and its synthesis route is as follows:

[0194]

[0195] The synthesis steps include:

[0196] In a dry Schlenk tube, add palladium tetrakis(triphenylphosphine) (0.01 mmol, 11.6 mg), (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene (0.03 mmol, 15.5 mg), potassium carbonate (0.6 mmol, 82.9 mg), (2-bromophenyl)diphenylphosphine (0.2 mmol, 68.0 mg), 2-benzyloxy-7-methoxy-1-naphthaleneboronic acid pinacol ester (0.24 mmol, 93.6 mg), water (0.1 mL) and 2-methyltetrahydrofuran (1 mL). Stir at 120 °C for 36 hours under a nitrogen atmosphere. After the reaction is completed, the reaction system is dried with anhydrous sodium sulfate. After removing the solvent, it is separated by column chromatography and eluted with petroleum ether:ethyl acetate = 20:1. After vacuum drying, 76.9 mg of the product is obtained, with a yield of 73% and an enantiomeric excess value of 86%. 1HNMR(400MHz,CDCl3)δ7.72(d,J=8.9Hz,1H),7.63(d,J=8.9Hz,1H),7.47–7.45(m,1H),7.40–7.29(m,3H),7.25–7.02(m,16H),6.91(dd,J=8.9,2.5Hz,1H),6.32(d,J=2.4Hz,1H),5.00(d,J=12.6Hz,1H),4.83(d,J=12.6Hz,1H),3.48(s,3H); 13 C NMR(101MHz,CDCl3)δ157.7,153.8,143.3(d,J=33.6Hz),139.0(d,J=10.8Hz),137.9(d,J=12.9Hz),137.8,137.6(d,J=13.2Hz),135.1,134.0,133.8,133.2(d,J=18.7Hz),131.1(d,J=6.1Hz),129.2,129.0(d,J=5.9Hz),128.3,128.2,128.02,127.95,127.91,127.85,127.62,127.57,127.2,126.3,124.4,116.1,111.9,103.6,70.1,54.8; 31 P NMR(162MHz,CDCl3)δ - 13.54.

[0197] Example 32

[0198] Basically the same as Example 1, except that the solvent was changed. The solvent in this example was 1 mL of 2 - methyltetrahydrofuran. The yield of the obtained product was 73%, and the enantiomeric excess value was 92%.

[0199] Example 33

[0200] Basically the same as Example 1, except that the solvent was changed. The solvent in this example was 1 mL of tetrahydrofuran and 0.1 mL of water. The yield of the obtained product was 59%, and the enantiomeric excess value was 93%.

[0201] Comparative Example 1

[0202] Basically the same as Example 1, except that Compound 1 was modified to (2 - iodophenyl)diphenylphosphine. The yield of the obtained product was 45%, and the enantiomeric excess value was 65%.

[0203] Comparative Example 2

[0204] Basically the same as Example 1, except that Compound 1 was modified to (2 - chlorophenyl))diphenylphosphine. The yield of the obtained product was <5%.

[0205] Comparative Examples 3-5 compare the effects of ligands, and the structures of the ligands used are as follows:

[0206]

[0207] Comparative Example 3

[0208] The same as Example 1, except that the ligand was changed. The ligand used in this comparative example was L1. The yield of the obtained product was 42%, and the enantiomeric excess was 20%.

[0209] Comparative Example 4

[0210] The same as Example 1, except that the ligand was changed. The ligand used in this comparative example was L2. The yield of the obtained product was 49%, and the enantiomeric excess was 36%.

[0211] Comparative Example 5

[0212] The same as Example 1, except that the ligand was changed. The ligand used in this comparative example was L3. The yield of the obtained product was 43%, and the enantiomeric excess was 54%.

[0213] Comparative Example 6

[0214] The same as Example 1, except that the type of catalyst was changed. The catalyst used in this comparative example was Pd(OAc)2. The yield of the obtained product was 69% and the enantiomeric excess was 86%.

[0215] Comparative Example 7

[0216] The same as Example 1, except that the type of base was changed. The base used in this comparative example was potassium hydroxide. The yield of the obtained product was 47%, and the enantiomeric excess was 94%.

[0217] The above description is merely a preferred embodiment of the present invention, and the present invention is not limited to the above embodiment. It is understood that other improvements and variations directly derived or imagined by those skilled in the art without departing from the spirit and concept of the present invention should be considered to be included in the scope of protection of the present invention.

Claims

1. An alkoxy-substituted biphenyl-based chiral monophosphine ligand, characterized in that, The general structural formula of the alkoxy-substituted biphenyl chiral monophosphine ligand is shown in Formula 3: Among them, R 1 is selected from substituted or unsubstituted aryl, and the substituted group is selected from at least one of a hydrogen atom, a methyl group, and a halogen; R 2 selected from at least one of a hydrogen atom, a methyl group, a phenyl group, an isopropyl group, a tert-butyl group, an amino group, an epoxy pentacyclic ring, a halogen, a trifluoromethyl group, and a trifluoromethoxy group; R 3 selected from at least one of benzyl, ethyl, n-hexyl, methoxymethylether group, isopropyl, naphthylmethyl; R 4 Selected from at least one of a hydrogen atom, a methoxy group, a n-butyl group, and a p-methoxyphenyl group.

2. The alkoxy-substituted biphenyl-based chiral monophosphine ligand according to claim 1, wherein, The halogen is selected from at least one of Br, F, and Cl.

3. A method for preparing an alkoxy-substituted biphenyl-based chiral monophosphine ligand according to any one of claims 1-2, characterized in that, It includes the following steps: Mix compound 1, compound 2, a catalyst, a base, a chiral ligand, and a solvent, react under a nitrogen atmosphere, and obtain the alkoxy-substituted biphenyl chiral monophosphine ligand after post-treatment; Among them, the structural formula of compound 1 is shown in Formula 1, and the structure of compound 2 is shown in Formula 2: In Formula 1: R 1 , R 2 are respectively and independently defined in the same way as R 1 , R 2 in Formula 3 in any one of Claims 1-2; In Formula 2: R 3 , R 4 are defined independently and are the same as the definitions of R 3 , R 4 in Formula 3 in any one of Claims 1-2.

4. The preparation method according to claim 3, wherein The catalyst is zero-valent palladium; The catalyst includes at least one of tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, and bis(tritert-butylphosphine)palladium; Preferably, the catalyst is tetrakis(triphenylphosphine)palladium.

5. The preparation method according to claim 3, characterized in that, The chiral ligand is selected from at least one of R-(+)-1,1'-binaphthalene-2,2'-bis(diphenylphosphine), (S)-(-)-2-[2-(diphenylphosphino)phenyl]-4-isopropyl-2-oxazoline, (S)-(+)-2-[2-(diphenylphosphino)phenyl]-4-phenyl-2-oxazoline, (4S,5S)-2-(2-(diphenylphosphino)phenyl)-4,5-diphenyl-4,5-dihydrooxazole, and (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene; Preferably, the chiral ligand is (2S)-1-[(4S)-4,5-dihydro-4-phenyl-2-oxazolyl]-2-(diphenylphosphino)ferrocene.

6. The preparation method according to claim 3, characterized in that, The base includes at least one of potassium carbonate, potassium phosphate, cesium carbonate, lithium tert-butoxide, and cesium pivalate; Preferably, the base is potassium carbonate.

7. The preparation method according to claim 6, characterized in that, The solvent includes at least one of toluene, tetrahydrofuran, 2-methyltetrahydrofuran, and water; Preferably, the solvent is a mixed solvent of 2-methyltetrahydrofuran and water, and the volume ratio of 2-methyltetrahydrofuran to water is 1-10:1; Preferably, the volume ratio of 2-methyltetrahydrofuran to water is 10:

1.

8. The preparation method according to claim 2, wherein, The molar ratio of the catalyst, chiral ligand, compound 1 to compound 2 is 0.05:0.05-0.15:1:1.2; Preferably, the molar ratio of the catalyst, chiral ligand, compound 1 to compound 2 is 0.05:0.15:1:1.

2.

9. The preparation method according to claim 2, wherein The molar ratio of the base to compound 1 is 1-4:1, Preferably, the molar ratio of the base to compound 1 is 3:

1.

10. The preparation method according to claim 2, characterized in that, The temperature of the reaction is 120-140 °C, and the time is 24-48 h; Preferably, the temperature of the reaction is 120 °C, and the time of the reaction is 36-48 h.

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