A novel chiral platinum complex, its preparation method and application

Abstract

The present invention discloses a novel chiral platinum complex and its preparation method and application, wherein the chiral platinum complex is a metal complex formed by a two-component nitrogen ligand L N and a phosphine ligand L P with platinum, and the structural general formula is as follows: wherein: * is a carbon chiral center; n is an integer from 0 to 8. Due to the differences in the chiral nitrogen ligand and chiral phosphine ligand therein, such metal complexes have different activities and asymmetric induction abilities. Such catalysts have a wide range of uses. For example, in the asymmetric nucleophilic addition reaction of a nucleophile to a novel α,β-unsaturated chiral platinum carbene formed by this catalyst, the activity and asymmetric induction ability of the platinum catalyst can be changed by changing the types of the chiral nitrogen ligand and phosphine ligand.

Description

Technical Field

[0001] The present invention relates to the technical field of complexes, particularly to the technical field of chiral platinum complexes, and specifically to a novel platinum complex formed by platinum with nitrogen ligand L N and phosphine ligand L P , a preparation method thereof, and the application of such metal complexes in catalytic asymmetric addition reactions. Background Art

[0002] Asymmetric catalytic synthesis is a hot topic in the current research field of organic synthetic chemistry (Ohkuna, T.; Kitamura, M.; Noyori, R. Catalytic Asymmetric Synthesis, Wiley, New York, 2000). The key to asymmetric catalytic synthesis is how to design and synthesize catalysts with high enantioselectivity and high catalytic activity. The currently developed catalyst systems that have achieved great success have greatly promoted the industrial application of asymmetric catalytic reactions and created huge economic benefits. The design and synthesis of chiral ligands provide a way for transition metal catalysis to achieve stereochemical selectivity, and new catalytic modes for improving efficiency and selectivity have been discovered (Jacobsen, E. N., Pfaltz, A. & Yamamoto, H. Comprehensive asymmetric catalysis, Springer, Berlin, New York, 1999).

[0003] The chiral environment of transition metal catalysts has traditionally been optimized by modifying the structure of a single chiral ligand. However, the synthesis of chiral catalysts by combining two independent chiral ligands with a transition metal is of great significance rather than designing more complex ligands (Ding, K. Synergistic effect of binary component ligands in chiral catalyst library engineering for enantioselective reactions. Chem. Commun. 909 - 921 (2008); Reetz, M. T. Combinatorial transition - metal catalysis: mixing monodentate ligands to control enantio -, diastereo -, and regioselectivity. Angew. Chem. Int. Ed. 47, 2556 - 2588 (2008)). In particular, the interaction of two independent ligands with the metal center can finely tune the chemical system and provide rapid multi - dimensional optimization in terms of controlling the reactivity and stereocontrol ability of the corresponding metal complexes.

[0004] Given the importance of ligand and catalyst screening in accelerating the development of catalytic reactions in academic and industrial applications, we infer that multi - ligand catalysts would actually accelerate the optimization of useful reactions and process development to provide new reactivity and performance. Thus, assembling a binary - component ligand metal catalyst M(L * 1)(L * 2) is of great significance for constructing a modular, tunable, and structurally diverse M(L * 1)(L * 2) catalyst library. In addition, by changing individual components respectively, a meaningful catalyst library can be quickly constructed, making it easier to identify the most effective ligands, which not only helps to identify new catalysts with broad prospects but also helps to identify the best system for specific asymmetric reactions. Summary of the Invention

[0005] The object of the present invention is to fill the gaps in the prior art and provide a class of novel chiral platinum complexes, specifically metal complexes Pt(L N )(L P formed by a two - component nitrogen ligand L N and a phosphine ligand L P) Another object of the present invention is to provide a method for preparing the above chiral platinum complex. In addition, such catalysts play an important catalytic role in the asymmetric nucleophilic addition reaction of nucleophiles to a novel α,β-unsaturated chiral platinum carbene formed by the catalyst. By changing the types of chiral nitrogen ligands and phosphine ligands, the activity and asymmetric induction ability of the platinum catalyst can be changed. Therefore, such platinum catalysts have high research value and application value.

[0006] In the first aspect of the present invention, a novel chiral platinum complex is provided. The novel chiral platinum complex of the present invention is a metal complex formed by a two-component nitrogen ligand L N and a phosphine ligand L P with platinum, and includes a divalent platinum salt, a nitrogen ligand L N and a phosphine ligand L P , and the structural general formula is as follows:

[0007]

[0008] Wherein:

[0009] * is a carbon chiral center (the carbon chiral center can be a racemic carbon chiral center, a left-handed carbon chiral center or a right-handed carbon chiral center); n is an integer from 0 to 8.

[0010] R is selected from hydrogen, alkyl, ester group, aryl and various substituted aryls, heterocyclic and various substituted heterocyclics, metallocenes (iron, ruthenium, titanium, zirconium, etc.) and various substituted metallocenes (iron, ruthenium, titanium, zirconium, etc.); R 1 , R 2 , R 3 , R 4 are each independently selected from hydrogen, alkyl, aryl and various substituted aryls, heterocyclic and various substituted heterocyclics; R 5 , R 6 , R 7 are each independently selected from alkyl, aryl and various substituted aryls, heterocyclic and various substituted heterocyclics, metallocenes (iron, ruthenium, titanium, zirconium, etc.) and various substituted metallocenes (iron, ruthenium, titanium, zirconium, etc.); Z is selected from O, S, CH2, NR; X is selected from halide ions, carboxylate groups of C1-C8, sulfate groups, perchlorate groups, tetrakis(3,5-bis(trifluoromethyl)phenyl)borate groups, tetrakis(pentafluorophenyl)borate groups, tetrakis(perfluorotert-butoxy)aluminate ions, tetrakis(hexafluoroisopropoxy)aluminate ions, hexafluorophosphate groups, hexafluoroantimonate groups, tetrafluoroborate groups, trifluoromethanesulfonate groups.

[0011] The nitrogen ligand is a chiral nitrogen ligand or a racemic nitrogen ligand, and is selected from one of the following structural general formulas I, II, and III:

[0012] Nitrogen ligand L N Structural general formula

[0013]

[0014] The phosphine ligand is a chiral phosphine ligand or a racemic phosphine ligand, and is selected from one of the following general structural formulas IV:

[0015] Phosphine ligand L P General structural formula

[0016]

[0017] The novel chiral platinum complex of the present invention includes racemates, dextrorotatory isomers, and levorotatory isomers having the same chemical structural formula but different steric structures and optical rotation properties.

[0018] In the second aspect of the present invention, a preparation method of the above novel chiral platinum complex is provided.

[0019] The preparation method of the novel chiral platinum complex of the present invention includes the following steps:

[0020] Under the protection of nitrogen or argon, a platinum metal precursor, a nitrogen ligand, and a phosphine ligand are placed in a solvent and stirred for reaction to prepare an intermediate product, and then an anion exchange is carried out with a metal salt to obtain a two-component nitrogen ligand L N and phosphine ligand L P The metal complex formed with platinum, that is, the novel chiral platinum complex.

[0021] The molar ratio of the platinum metal precursor, the nitrogen ligand, and the phosphine ligand is 1:1.0 - 1.3:1.0 - 1.3.

[0022] The reaction temperature is 0 - 50 °C, and the reaction time is 1 - 24 hours.

[0023] The platinum metal precursor is selected from PtCl2, [(C2H4)PtCl2]2, or PtCl2(COD).

[0024] The metal salt used for anion exchange during the reaction is selected from sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, ammonium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, thallium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate, sodium tetrakis(pentafluorophenyl)borate, sodium tetrakis(perfluorotert-butoxy)aluminate, sodium tetrakis(hexafluoroisopropoxy)aluminate, silver trifluoromethanesulfonate, silver tetrafluoroborate, silver hexafluorophosphate, or silver hexafluoroantimonate.

[0025] The solvent is selected from one or more of acetone, toluene, tetrahydrofuran, or dichloromethane.

[0026] In the third aspect of the present invention, an application of the above novel chiral platinum complex in the asymmetric nucleophilic addition reaction of a novel α,β-unsaturated platinum carbene formed by a nucleophile to the complex is provided.

[0027] The reaction formula of the said asymmetric nucleophilic addition reaction is as follows:

[0028]

[0029] Wherein: [Pt] represents a platinum catalyst, which is the said novel chiral platinum complex.

[0030] R 8 is selected from hydrogen, halogen, methyl, methoxy, and the benzene ring can be mono-substituted, di-substituted or multi-substituted; R 9 is selected from alkyl, aryl and various substituted aryls, heterocyclic and various substituted heterocyclics; R 10 is selected from alkyl, aryl and various substituted aryls, heterocyclic and various substituted heterocyclics.

[0031] [Cu] represents a copper catalyst, which is a complex formed by copper trifluoromethanesulfonate and chiral nitrogen ligand L N The structural general formula is as follows:

[0032]

[0033] The said reaction is carried out under the protection of argon or nitrogen. Add the platinum catalyst, copper catalyst, reactants and solvent into a reaction flask, and stir until the reaction ends.

[0034] The said solvent is one or more of dichloromethane, acetone, 1,4-dioxane, tetrahydrofuran or toluene.

[0035] Based on substrate 1, the dosage of the platinum catalyst is 1-15 mol%, and the dosage of the copper catalyst is 5-10 mol%.

[0036] Based on substrate 1, the reactant concentration in the system is 0.001-10.0 M; the reaction temperature is 0-50 °C; the reaction time is 12-48 hours.

[0037] The products obtained from the reaction include optically active indole phosphonate compounds and indole ester compounds, and these products and their derivatives have important application values.

[0038] The beneficial effects of the present invention are as follows:

[0039] 1. The present invention provides a novel chiral platinum complex, which is a complex formed by chiral nitrogen ligand (L N ) and phosphine ligand (L P ) with platinum. In the asymmetric nucleophilic addition reaction of nucleophiles to the novel ɑ,β-unsaturated chiral platinum carbene formed by this complex, by changing the types of chiral nitrogen ligand and phosphine ligand, the activity and asymmetric induction ability of the platinum complex are changed. Therefore, this type of platinum complex has high research value and application value.

[0040] 2. The present invention also provides a preparation method of the above-mentioned novel chiral platinum complex. The novel chiral platinum complex is synthesized by reacting a platinum metal precursor, a nitrogen ligand, and a phosphine ligand in a solvent and then performing an anion exchange. The preparation method is simple and easy to operate. Detailed implementation mode

[0041] The following implementation examples will help to further understand the present invention, but do not limit the content of the present invention. The preparation method of the present invention can be further embodied by the preparation process of representative compounds as follows:

[0042] Example 1: Preparation of (R,R)-Pt-M1 and (R,R)-Pt-M2 complexes

[0043]

[0044] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.469 g, 0.80 mmol) was added to a solution of (R,R)-L N 2 (0.471 g, 1.60 mmol) and P(C6F5)3 (0.851 g, 1.60 mmol) in acetone (4.0 mL). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure to remove the solvent, and the residue was purified by column chromatography to obtain (R,R)-Pt-M1 (yellow solid, 0.332 g, 19% yield) and (R,R)-Pt-2 (yellow solid, 0.610 g, 20% yield).

[0045] (R,R)-Pt-M1: 1 1H NMR (600 MHz, CDCl3) δ 4.46–4.28 (m, 3H), 4.22–4.12 (m, 1H), 4.05 (brs, 1H), 3.76 (brs, 1H), 1.98 (brs, 6H), 1.15 (brs, 9H), 0.85 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 176.13, 167.31, 146.99 (d, J = 255.5 Hz), 144.33 (d, J = 253.6 Hz), 137.68 (d, J = 247.2 Hz), 100.48, 75.53, 70.33, 69.36, 40.39, 34.28, 33.97, 26.32, 25.96, 25.78, 25.5. 31 31P NMR (243 MHz, CDCl3) δ -44.10, J P-Pt = 4150 Hz. 1919F NMR (565 MHz, CDCl3) δ -119.64, -124.62, -125.45, -125.63, -129.71, -130.41, -144.09, -145.53, -146.03, -157.95, -158.99. ESI-MS: calculated [C 35 H 30 Cl2F 15 N2O2PPt + H] + : 1092.0903, found: 1092.0900.

[0046] (R,R)-Pt-M2: 1 1H NMR (600 MHz, CDCl3) δ 4.64 (brs, 1H), 4.45–4.35 (m, 3H), 4.28–4.19 (m, 1H), 3.89–3.78 (m, 1H), 3.45 (brs, 1H), 3.37 (brs, 1H), 1.99 (brs, 3H), 1.76 (brs, 3H), 1.23 (brs, 9H), 1.06 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 174.65, 171.05, 147.13 (d, J = 254.8 Hz), 144.53 (d, J = 263.2 Hz), 137.78 (d, J = 254.8 Hz), 100.93 (d, J = 63.0 Hz), 70.21, 65.01, 61.53, 45.93, 34.15, 33.58, 27.41, 26.43, 25.07, 25.03. 31 31P NMR (243 MHz, CDCl3) δ -41.64, J P-Pt = 3980 Hz, -43.96, J P-Pt = 4165 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.70, -124.71, -125.93, -126.98, -128.66, -131.32, -143.84, -144.28, -145.81, -158.02, -158.48, -158.84. ESI-MS: calculated [C 53 H 32 C l4 F 30 N2O3P2Pt2 + Na] + : 1928.9351, found: 1928.9346.

[0047] Example 2: Preparation of (R,R)-Pt-M1 Complex

[0048]

[0049] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 1 (0.177 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to obtain (R,R)-Pt-M1 (yellow solid, 0.439 g, 67% yield). 1 1H NMR (600 MHz, CDCl3) δ 4.46–4.28 (m, 3H), 4.22–4.12 (m, 1H), 4.05 (brs, 1H), 3.76 (brs, 1H), 1.98 (brs, 6H), 1.15 (brs, 9H), 0.85 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 176.13, 167.31, 146.99 (d, J = 255.5 Hz), 144.33 (d, J = 253.6 Hz), 137.68 (d, J = 247.2 Hz), 100.48, 75.53, 70.33, 69.36, 40.39, 34.28, 33.97, 26.32, 25.96, 25.78, 25.5. 31 31P NMR (243 MHz, CDCl3) δ -44.10, J P-Pt = 4150 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.64, -124.62, -125.45, -125.63, -129.71, -130.41, -144.09, -145.53, -146.03, -157.95, -158.99. ESI-MS: calculated [C 35 H 30 Cl2F 15 N2O2PPt+H] + : 1092.0903, found: 1092.0900.

[0050] Example 3: Preparation of (R,R)-Pt-M3 Complex

[0051]

[0052] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 3 (0.201 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R,R)-Pt-M3 (yellow solid, 0.522 g, 77% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.54–7.17 (m, 10H), 5.33 (brs, 2H), 4.78 (brs, 2H), 4.27 (brs, 2H), 2.10 (s, 6H). 13 13C NMR (151 MHz, CDCl3) δ 173.36, 169.84, 147.00 (d, J = 255.1 Hz), 144.27 (d, J = 264.7 Hz), 137.56 (d, J = 258.4 Hz), 128.87, 128.70, 128.32, 100.96, 75.85, 70.71, 40.06, 25.43. 31 31P NMR (243 MHz, CDCl3) δ -43.61, J P-Pt = 4133 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.94, -126.30, -130.19, -130.24, -130.53, -144.93, -147.74, -147.78, -158.73, -158.87, -159.44. ESI-MS: calculated [C 39 H 22 Cl2F 15 N2O2PPt+H] + : 1132.0277, found: 1132.0267.

[0053] Example 4: Preparation of (R,R)-Pt-M4 complex

[0054]

[0055] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L NA toluene (1.5 mL) solution of 4 (0.126 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography to give (R,R)-Pt-M4 (yellow solid, 0.449 g, 74% yield). 1 1H NMR (600 MHz, CDCl3) δ 4.46 (brs, 2H), 4.27 (brs, 2H), 3.88 (brs, 2H), 1.84 (s, 6H), 1.42 (brs, 6H). 13 13C NMR (151 MHz, CDCl3) δ 170.59, 147.21 (d, J = 254.0 Hz), 144.44 (d, J = 262.0 Hz), 137.75 (d, J = 256.5 Hz), 101.14 (d, J = 58.5 Hz), 74.75, 62.54, 39.49, 25.04, 20.96. 31 31P NMR (243 MHz, CDCl3) δ -43.07, J P-Pt = 4080 Hz. 19 19F NMR (565 MHz, CDCl3) δ -120.85, -124.99, -130.16, -130.21, -130.26, -144.94, -159.30. ESI-MS: calculated [[C 29 H 18 Cl2F 15 N2O2PPt+H] + : 1007.9964, found: 1007.9965.

[0056] Example 5: Preparation of (R,R)-Pt-M5 complex

[0057]

[0058] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 5 (0.160 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography to give (R,R)-Pt-M5 (yellow solid, 0.493 g, 77% yield). 11H NMR (600 MHz, CDCl3) δ 4.59–3.84 (m, 6H), 1.85 (s, 6H), 1.09–0.71 (m, 14H). 13 13C NMR (151 MHz, CDCl3) δ 172.68, 168.00, 147.18 (d, J = 254.5 Hz), 144.38 (d, J = 262.7 Hz), 137.70 (d, J = 252.9 Hz), 101.08, 72.13, 69.48, 39.58, 31.03, 25.18, 18.94, 16.05. 31 31P NMR (243 MHz, CDCl3) δ -43.09, J P-Pt = 4073 Hz. 19 19F NMR (565 MHz, CDCl3) δ -120.25, -124.67, -127.48, -129.39, -129.72, -129.77, -129.82, -131.02, -144.26, -159.02. ESI-MS: calculated [[C 33 H 26 Cl2F 15 N2O2PPt + H] + : 1064.0590, found: 1064.0584.

[0059] Example 6: Preparation of (R,R)-Pt-M6 complex

[0060]

[0061] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 6 (0.218 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R,R)-Pt-M6 (yellow solid, 0.437 g, 63% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.33–7.27 (m, 4H), 7.25–7.18 (m, 6H), 4.52 (brs, 2H), 4.26–4.20 (m, 2H), 4.12–4.03 (m, 2H), 3.60 (brs, 2H), 2.77–2.70 (m, 2H), 1.83 (s, 6H). 13CNMR(151MHz,CDCl3)δ170.92,147.24(d,J=254.3Hz),144.49(d,J=262.4Hz),137.84(d,J=238.1Hz),137.05,129.44,128.78,126.89,101.17(d,J=58.1Hz),72.64,67.90,40.99,39.61,24.94. 31 P NMR(243MHz,CDCl3)δ-43.27,J P-Pt =4092Hz. 19 F NMR(565MHz,CDCl3)δ-120.82,-126.84,-130.16,-130.21,-130.26,-144.68,-158.94,-159.16.ESI-MS:calculated[C 41 H 26 Cl2F 15 N2O2PPt+H] + :1160.0590,found:1160.0586.

[0062] Example 7: Preparation of (R,R)-Pt-M7 complex

[0063]

[0064] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 7 (0.216 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R,R)-Pt-M7 (yellow solid, 0.560 g, 81% yield). 1 H NMR(600MHz,CDCl3)δ7.44–7.27(m,10H),5.52(brs,1H),4.80(brs,3H),4.41(brs,1H),4.12(brs,1H),2.98(brs,3H),1.90(s,5H). 1313C NMR (151 MHz, CDCl3) δ 174.23, 167.52, 146.97 (d, J = 250.5 Hz), 144.22 (d, J = 262.9 Hz), 142.40, 137.48 (d, J = 244.6 Hz), 129.87, 128.67, 127.65, 126.79, 100.55, 75.85, 70.70, 50.13, 36.47, 24.64. 31 31P NMR (243 MHz, CDCl3) δ -42.83, J P-Pt = 4097 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.16, -122.65, -125.88, -128.00, -130.15, -132.82, -144.36, -145.85, -146.90, -158.10, -158.97. ESI-MS: calculated 41 C 24 H 15 Cl2F + N2O2PPt + H]

[0065] Example 8: Preparation of (R,R,S,S)-Pt-M8 Complex

[0066]

[0067] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R,S,S)-L N 8 (0.292 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R,R,S,S)-Pt-M8 (yellow solid, 0.511 g, 66% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.09–6.94 (m, 20H), 6.10 (d, J = 10.4 Hz, 2H), 5.77 (brs, 2H), 2.36 (brs, 6H). 1313C NMR (151 MHz, CDCl3) δ 171.67, 147.00 (d, J = 255.0 Hz), 144.30 (d, J = 263.5 Hz), 137.52 (d, J = 250.0 Hz), 135.44, 129.00, 127.92, 127.85, 127.55, 126.51, 100.82, 86.14, 74.90, 40.64, 25.80. 31 31P NMR (243 MHz, CDCl3) δ -44.08, J P-Pt = 4129 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.83, -126.46, -130.40, -144.81, -158.61, -159.45. ESI-MS: calculated [[C 51 H 30 Cl2F 15 N2O2PPt+H] + : 1284.0903, found: 1284.0901.

[0068] Example 9: Preparation of (R,R,S,S)-Pt-M9 Complex

[0069]

[0070] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R,S,S)-L N 9 (0.291 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R,R,S,S)-Pt-M9 (yellow solid, 0.586 g, 76% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.16–6.90 (m, 20H), 6.10 (d, J = 9.8 Hz, 2H), 5.86 (brs, 2H), 2.44 (brs, 2H), 2.04 (brs, 2H). 1313C NMR (151 MHz, CDCl3) δ 168.88, 146.89 (d, J = 252.7 Hz), 144.26 (d, J = 264.2 Hz), 137.33 (d, J = 262.8 Hz), 135.30, 129.04, 127.95, 127.80, 127.48, 127.37, 127.01, 126.75, 126.51, 100.21 (d, J = 43.4 Hz), 86.47, 74.01, 19.59, 17.40. 31 31P NMR (243 MHz, CDCl3) δ -42.36, J P-Pt = 4082 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.74, -126.34, -130.21, -144.09, -146.71, -157.93, -158.86. ESI-MS: calculated [[C 51 H 28 Cl2F 15 N2O2PPt + H] + : 1282.0746, found: 1282.0748.

[0071] Example 10: Preparation of (R,R,S,S)-Pt-M10 Complex

[0072]

[0073] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R,S,S)-L N 10 (0.214 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R,R,S,S)-Pt-M10 (yellow solid, 0.391 g, 56% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.72 (brs, 2H), 7.32–7.16 (m, 2H), 5.54 (brs, 2H), 5.35 (brs, 2H), 3.44–3.31 (m, 2H), 3.29–3.17 (m, 2H), 1.83 (brs, 2H), 1.70 (s, 2H). 1313C NMR(151MHz, CDCl3) δ 167.92, 147.13 (d, J = 254.0 Hz), 144.37 (d, J = 263.0 Hz), 139.71, 137.71 (d, J = 256.3 Hz), 129.14, 127.27, 126.65, 125.11, 100.82 (d, J = 61.1 Hz), 84.57, 75.60, 39.42, 18.72, 17.21. 31 31P NMR(243MHz, CDCl3) δ -43.81, J P-Pt = 4048 Hz. 19 19F NMR(565MHz, CDCl3) δ -119.71, -125.04, -126.18, -130.03, -144.06, -157.91, -158.30, -158.80. ESI-MS: calculated 41 C 20 H 15 Cl2F + N2O2PPt + H]

[0074] Example 11: Preparation of (R,R,S,S)-Pt-M11 Complex

[0075]

[0076] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R,S,S)-L N 11 (0.281 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to obtain (R,R,S,S)-Pt-M11 (yellow solid, 0.243 g, 48% yield). 1 1H NMR(600MHz, CDCl3) δ 7.46–7.30 (m, 3H), 7.23–7.05 (m, 3H), 5.36 (brs, 4H), 3.36–3.16 (m, 4H), 1.39 (brs, 4H), 1.36 (s, 18H). 1313C NMR (151 MHz, CDCl3) δ 169.69, 165.81, 150.76, 147.17 (d, J = 253.8 Hz), 144.39 (d, J = 262.3 Hz), 137.46 (d, 258.2 Hz), 136.86, 136.71, 126.41, 124.55, 100.97, 85.21, 76.05, 38.74, 34.85, 31.46, 18.76, 16.83. 31 31P NMR (243 MHz, CDCl3) δ -42.08, J P-Pt = 4029 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.16, -125.83, -130.13, -144.24, -158.65. ESI-MS: calculated [[C 49 H 36 Cl2F 15 N2O2PPt+H] + : 1266.1372, found: 1266.1376.

[0077] Example 12: Preparation of (R,R)-Pt-M12 Complex

[0078]

[0079] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 12 (0.151 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R,R)-Pt-M12 (yellow solid, 0.441 g, 70% yield). 1 1H NMR (600 MHz, CDCl3) δ 4.37 (brs, 6H), 1.02 (brs, 18H). 13 13C NMR (151 MHz, CDCl3) Unknown NMR (151 MHz, ) δ 160.17, 152.69, 147.05 (d, J = 253.5 Hz), 144.33 (d, J = 263.0 Hz), 137.65 (d, J = 251.6 Hz), 100.57, 76.18, 70.98, 34.15, 26.15. 31 31P NMR (243 MHz, CDCl3) δ -44.11, J P-Pt= 4274 Hz. 19 19F NMR (565 MHz, CDCl3) Unknown NMR (565 MHz, ) δ -119.70, -124.29, -126.79, -128.79, -131.52, -144.08, -145.79, -158.29, -159.06. ESI-MS: calculated [C 32 H 24 Cl2F 15 N2O2PPt+Na] + : 1072.0253, found: 1072.0260.

[0080] Example 13: Preparation of (R)-Pt-M13 Complex

[0081]

[0082] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a solution of (R)-L N 13 (0.187 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol) in acetone (1.5 mL). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R)-Pt-M13 (red solid, 0.559 g, 84% yield). 1 1H NMR (600 MHz, CDCl3) δ 5.79 (brs, 1H), 5.45 (s, 1H), 4.56–4.41 (m, 4H), 4.39–4.16 (m, 6H), 1.24 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 173.39, 147.15 (d, J = 251.7 Hz), 144.36 (d, J = 256.0 Hz), 137.77 (d, J = 260.9 Hz) 100.95, 76.05, 72.16, 72.06, 70.43, 70.02, 65.42, 33.97, 26.52. 31 31P NMR (243 MHz, CDCl3) δ -42.84, J P-Pt = 4002 Hz. 1919F NMR (565 MHz, CDCl3) δ -120.21, -124.34, -126.88, -129.01, -131.87, -144.30, -145.14, -146.45, -158.29, -159.50, -159.66, -159.70. ESI-MS: calculated [C 35 H 21 Cl2F 15 FeNOPPt + H] + : 1108.9568, found: 1108.9567.

[0083] Example 14: Preparation of (R)-Pt-M14 Complex

[0084]

[0085] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a solution of (R)-L N 14 (0.110 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol) in acetone (1.5 mL). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (R)-Pt-M14 (yellow solid, 0.382 g, 65% yield). 1 1H NMR (600 MHz, CDCl3) δ 4.43–4.24 (m, 3H), 1.59 (s, 9H), 1.15 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 180.91, 147.03 (d, J = 252.2 Hz), 144.29 (d, J = 260.4 Hz), 137.63 (d, J = 252.8 Hz), 100.47, 76.95, 69.88, 35.29, 34.11, 29.31, 26.34. 31 31P NMR (243 MHz, CDCl3) δ -44.21, J P-Pt = 4112 Hz. 19 19F NMR (565 MHz, CDCl3) δ -120.21, -124.61, -125.72, -126.45, -129.48, -130.53, -131.30, -144.03, -144.43, -146.12, -157.95, -159.06. ESI-MS: calculated [C 29 H 21 Cl2F 15NOPPt+Na] + :1003.0038,found:1003.0037.

[0086] Example 15: Preparation of (R,R)-Pt-M15 Complex

[0087]

[0088] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 1 (0.177 g, 0.60 mmol) and P(o-Tol)3 (0.183 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 hours. The reaction solution was concentrated under reduced pressure and purified by column chromatography to obtain (R,R)-Pt-M15 (yellow solid, 0.358 g, 69% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.60–7.32 (m, 6H), 7.26–6.93 (m, 6H), 4.45–4.23 (m, 3H), 4.20–4.11 (m, 1H), 4.09–3.96 (m, 1H), 3.95–3.74 (m, 1H), 3.10 (brs, 3H), 2.10 (brs, 3H), 1.53 (d, 6H), 1.34 (s, 3H), 1.07 (s, 9H), 0.89 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 174.79, 168.74, 143.96, 142.52, 133.76, 131.53, 130.81, 125.06, 75.37, 70.48, 69.06, 40.09, 34.59, 34.01, 26.50, 26.04, 25.74, 23.07. 31 31P NMR (243 MHz, CDCl3) δ -1.26, J P-Pt = 3720 Hz. ESI-MS: calculated [C 38 H 51 Cl2N2O2PPt+H] + : 864.2786, found: 864.2785.

[0089] Example 16: Preparation of (R,R)-Pt-M16 Complex

[0090]

[0091] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene (1.5 mL) solution of (R,R)-L N 1 (0.177 g, 0.60 mmol) and P(o-Anisyl)3 (0.211 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure to remove the solvent and purified by column chromatography to give (R,R)-Pt-M16 (yellow solid, 0.157 g, 29% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.41–7.34 (m, 4H), 7.03–6.87 (m, 4H), 6.83–6.70 (m, 4H), 4.53–4.40 (m, 1H), 4.32–4.26 (m, 2H), 4.20–4.12 (m, 1H), 4.12–3.99 (m, 1H), 3.88–3.83 (m, 1H), 3.53 (brs, 9H), 1.28 (brs, 6H), 1.22 (brs, 9H), 0.88 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 173.83, 168.66, 160.35, 131.88, 119.51, 116.33, 115.86, 110.57, 75.29 (d, J = 9.0 Hz), 69.01, 55.03, 40.23, 33.95, 25.86, 24.48. 31 31P NMR (243 MHz, CDCl3) δ -11.16, J P-Pt = 3937 Hz. ESI-MS: calculated [C 38 H 51 Cl2N2O5PPt + H] + : 912.2633, found: 912.2634.

[0092] Example 17: Preparation of (S,S)-Pt-M1 complex

[0093]

[0094] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a toluene solution of (S,S)-L NA toluene (1.5 mL) solution of 1 (0.177 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure and purified by column chromatography to give (S,S)-Pt-M1 (yellow solid, 0.419 g, 65% yield). 1 1H NMR (600 MHz, CDCl3) δ 4.46–4.28 (m, 3H), 4.22–4.12 (m, 1H), 4.05 (brs, 1H), 3.76 (brs, 1H), 1.98 (brs, 6H), 1.15 (brs, 9H), 0.85 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 176.13, 167.31, 146.99 (d, J = 255.5 Hz), 144.33 (d, J = 253.6 Hz), 137.68 (d, J = 247.2 Hz), 100.48, 75.53, 70.33, 69.36, 40.39, 34.28, 33.97, 26.32, 25.96, 25.78, 25.5. 31 31P NMR (243 MHz, CDCl3) δ -44.10, J P-Pt = 4150 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.64, -124.62, -125.45, -125.63, -129.71, -130.41, -144.09, -145.53, -146.03, -157.95, -158.99. ESI-MS: calculated [C 35 H 30 Cl2F 15 N2O2PPt+H] + : 1092.0903, found: 1092.0900.

[0095] Example 18: Preparation of (S,S)-Pt-M15 Complex

[0096]

[0097] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to (R,R)-L NA toluene (1.5 mL) solution of 1 (0.177 g, 0.60 mmol) and P(o-Tol)3 (0.183 g, 0.60 mmol). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography to give (R,R)-Pt-M15 (yellow solid, 0.332 g, 64% yield). 1 1H NMR (600 MHz, CDCl3) δ 7.60–7.32 (m, 6H), 7.26–6.93 (m, 6H), 4.45–4.23 (m, 3H), 4.20–4.11 (m, 1H), 4.09–3.96 (m, 1H), 3.95–3.74 (m, 1H), 3.10 (brs, 3H), 2.10 (brs, 3H), 1.53 (d, 6H), 1.34 (s, 3H), 1.07 (s, 9H), 0.89 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 174.79, 168.74, 143.96, 142.52, 133.76, 131.53, 130.81, 125.06, 75.37, 70.48, 69.06, 40.09, 34.59, 34.01, 26.50, 26.04, 25.74, 23.07. 31 31P NMR (243 MHz, CDCl3) δ -1.26, J P-Pt = 3720 Hz. ESI-MS: calculated [C 38 19 51 l2N2O2PPt+H] + : 864.2786, found: 864.2785.

[0098] Example 19: Preparation of (R)-Pt-M17 complex

[0099]

[0100] Under a nitrogen atmosphere, [(C2H4)PtCl2]2 (0.176 g, 0.30 mmol) was added to a solution of (R)-L N 15 (0.145 g, 0.60 mmol) and P(C6F5)3 (0.319 g, 0.60 mmol) in acetone (1.5 mL). The mixture was stirred at 25 °C for 24 h. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography to give (R)-Pt-M17 (yellow solid, 0.474 g, 76% yield). 11H NMR (600 MHz, CDCl3) δ 4.44–4.34 (m, 3H), 4.16–4.08 (m, 2H), 2.01 (s, 3H), 1.73 (s, 3H), 1.25–1.20 (m, 3H), 1.19 (s, 9H). 13 13C NMR (151 MHz, CDCl3) δ 175.40, 171.85, 147.05 (d, J = 252.3 Hz), 144.33 (d, J = 260.5 Hz), 137.72 (d, J = 251.2 Hz), 100.53, 76.84, 70.35, 61.88, 45.70, 34.40, 26.36, 25.16, 13.91. 31 31P NMR (243 MHz, CDCl3) δ -43.81, J P-Pt = 4146 Hz. 19 19F NMR (565 MHz, CDCl3) δ -119.82, -124.50, -125.76, -129.35, -130.78, -143.97, -144.35, -146.01, -157.94, -159.01. ESI-MS: calculated [[C 31 H 23 Cl2F 15 NO3PPt + Na] + : 1061.0093, found: 1061.0081.

[0101] Example 20: Catalytic Activity and Asymmetric Induction Ability of Different Platinum Catalysts in Reaction Examples

[0102]

[0103]

[0104] Under an argon atmosphere, Cu(OTf)2 (3.6 mg, 0.010 mmol, 10 mol%) and (R,R,S,S)-L N 11 (5.7 mg, 0.012 mmol, 12 mol%) were added to 1.0 mL of acetone, and the mixture was stirred at room temperature for 1 hour. Subsequently, substrate 2a (0.20 mmol, 2.0 equiv), 1a (0.10 mmol, 1.0 equiv), novel chiral platinum catalyst Pt-M (5.5 mg, 0.005 mmol, 5 mol%) and 1.0 mL of acetone were added, and the reaction was carried out at 35 °C for 48 hours; the reaction was quenched with water, extracted with dichloromethane, dried over anhydrous magnesium sulfate, and the target product was obtained by column chromatography. The structure of the product was determined by NMR analysis, and the ee value was obtained by high performance liquid chromatography (HPLC) analysis.

[0105] Example 21: Synthesis of Chiral Indole Compounds by Platinum / Copper Dual-Catalyzed Asymmetric Olefin Addition Reaction of β-Ketophospholipids

[0106]

[0107] Under an argon atmosphere, Cu(OTf)2 (3.6 mg, 0.010 mmol, 10 mol%) and (R,R,S,S)-L N 11 (5.7 mg, 0.012 mmol, 12 mol%) were added to 1.0 mL of acetone, and the mixture was stirred at room temperature for 1 hour. Subsequently, substrate 2 (0.20 mmol, 2.0 equiv), 1 (0.10 mmol, 1.0 equiv), the novel chiral platinum catalyst Pt-M1 (5.5 mg, 0.005 mmol, 5 mol%), and 1.0 mL of acetone were added, and the reaction was carried out at 35 °C for 48 hours; the reaction was quenched with water, extracted with dichloromethane, dried over anhydrous magnesium sulfate, and the target product was obtained by column chromatography. The structure of the product was determined by NMR analysis, and the optical purity of the product was analyzed by high-performance liquid chromatography (HPLC). The substrate scope is shown in the following formula:

[0108]

[0109] Example 22: Synthesis of Chiral Indole Compounds by Platinum / Copper Dual-Catalyzed Asymmetric Olefin Addition Reaction of β-Ketolipids

[0110]

[0111] Under an argon atmosphere, Cu(OTf)2 (3.6 mg, 0.010 mmol, 10 mol%) and (R,R,S,S)-L N 2 (6.3 mg, 0.012 mmol, 12 mol%) were added to 0.5 mL of 1,4-dioxane, and the mixture was stirred at room temperature for 1 hour. Subsequently, substrate 4 (0.10 mmol, 1.0 equiv), 1 (0.20 mmol, 2.0 equiv), and the novel chiral platinum catalyst Pt-M (4.3 mg, 0.005 mmol, 5 mol%) were added, and the reaction was carried out at 20 °C for 48 hours. The reaction was quenched with water, extracted with dichloromethane, dried over anhydrous magnesium sulfate, and the target product was obtained by column chromatography. The structure of the product was determined by NMR analysis, and the optical purity of the product was analyzed by high-performance liquid chromatography (HPLC). The substrate scope is shown in the following formula:

[0112]

[0113] In summary, the present invention provides a novel chiral platinum complex, using a nitrogen ligand (L N ), a phosphine ligand (LP ) The novel chiral platinum complex was synthesized by reacting a platinum precursor with an anion exchange in a solvent. Such complexes play an important catalytic role in the asymmetric nucleophilic addition reaction of nucleophiles to the novel α,β-unsaturated chiral platinum carbene formed by the complex. By changing the types of chiral nitrogen ligands and phosphine ligands, the activity and asymmetric induction ability of the platinum complex can be changed. Therefore, such platinum complexes have high research value and application value.

[0114] In this specification, the invention has been described with reference to specific embodiments thereof. However, it is obvious that various modifications and variations can still be made without departing from the spirit and scope of the invention. Therefore, the specification and drawings should be regarded as illustrative rather than restrictive.

Claims

1. A chiral platinum complex, characterized in that Selected from the following structures: 。 2. A method for preparing the chiral platinum complex according to claim 1, characterized in that Comprising the following steps: Under the protection of nitrogen or argon, a platinum metal precursor, a nitrogen ligand, and a phosphine ligand are placed in a solvent and stirred for reaction to obtain the chiral platinum complex; The platinum metal precursor is selected from PtCl2, [(C2H4)PtCl2]2, or PtCl2(COD); The nitrogen ligand is selected from one of the following structures: ； The phosphine ligand is selected from one of the following structures: 。 3. The preparation method according to claim 2, wherein: The molar ratio of the platinum metal precursor, the nitrogen ligand, and the phosphine ligand is 1:1.0 - 1.3:1.0 - 1.

3.

4. The preparation method according to claim 2, wherein: The reaction temperature is 0 - 50 °C, and the reaction time is 1 - 24 hours.

5. The application of the chiral platinum complex according to claim 1 in an asymmetric nucleophilic addition reaction, wherein: The reaction formula of the asymmetric nucleophilic addition reaction is: ； Wherein: R 8 is selected from hydrogen, halogen, methyl, methoxy, and the benzene ring is mono-substituted, di-substituted or multi-substituted; R 9 is selected from alkyl or aryl; R 10 is selected from alkyl or aryl; [Pt] represents a platinum catalyst, which is the chiral platinum complex; [Cu] represents a copper catalyst, and the structural formula is as follows: 。 6. The application according to claim 5, wherein: Under the protection of argon or nitrogen, the chiral platinum complex, the copper catalyst, the reactants, and the solvent are added to a reaction flask and stirred until the reaction ends; the solvent is one or more of dichloromethane, acetone, 1,4 - dioxane, tetrahydrofuran, or toluene.

7. The application of the chiral platinum complex according to claim 1 in an asymmetric nucleophilic addition reaction, wherein: The reaction formula of the asymmetric nucleophilic addition reaction is: ； The target compound 3 is selected from compounds having the following structures: ； [Pt] represents a platinum catalyst, which is the chiral platinum complex (R,R)-Pt-M1; [Cu] represents a copper catalyst, and the structural formula is as follows: 。 8. The application according to claim 7, wherein: Under the protection of argon or nitrogen, the chiral platinum complex, the copper catalyst, the reactants, and the solvent are added to a reaction flask and stirred until the reaction ends; the solvent is one or more of dichloromethane, acetone, 1,4 - dioxane, tetrahydrofuran, or toluene.

9. The application of the chiral platinum complex according to claim 1 in an asymmetric nucleophilic addition reaction, wherein: The reaction formula of the asymmetric nucleophilic addition reaction is: ； The target compound 5 is selected from compounds having the following structures: ； [Pt] represents a platinum catalyst, which is the chiral platinum complex (R,R)-Pt-M15; [Cu] represents a copper catalyst, and the structural formula is as follows: 。 10. The application according to claim 9, wherein: Under the protection of argon or nitrogen, the chiral platinum complex, the copper catalyst, the reactants, and the solvent are added to a reaction flask and stirred until the reaction ends; the solvent is one or more of dichloromethane, acetone, 1,4 - dioxane, tetrahydrofuran, or toluene.

Images