Chiral benzoxazine diphosphine ligand and complex and application thereof

Abstract

The invention discloses a chiral benzoxazine diphosphine ligand and a complex and application thereof. The structure of the chiral benzoxadiphosphine ligand is shown as a formula (I), and in the formula (I), R1 is alkyl or aryl, R2 is alkyl or aryl, and R3 is at least one of fluorine, carbazolyl and 2, 6-dimethoxyphenyl. The chiral benzoxazine diphosphine ligand disclosed by the invention can be applied to two asymmetric reactions, namely cross dehydrogenation coupling of disilane hydrogen and benzyl alcohol under catalysis of rhodium and axial chiral Heck reaction of aryl trifluoromethanesulfonate and alkenyl ether under catalysis of palladium, and has excellent activity and relatively high enantioselectivity in the two asymmetric reactions; moreover, the chiral benzoxadiphosphine ligand can be directly synthesized from simple and easily available chiral aldehyde, and the preparation method is simple and easy to operate.

Description

Technical Field

[0001] This application relates to the field of catalyst ligand technology, and in particular to a chiral benzoxoxadiphosphine ligand, its complexes, and applications. Background Technology

[0002] Ferrocene-skeletal chiral phosphine ligands, particularly Josiphos and its analogues, have achieved great success in asymmetric catalysis since their introduction, and are widely used in various key chiral transformation processes such as hydrogenation and carbon-carbon bond formation. The high efficiency of these ligands stems from their unique rigid structure and precise control of the chiral environment. In the classic Josiphos synthetic route, chiral control follows a clear and widely accepted rule: the central chirality of the starting chiral Ugiamine ((R)- or (S)-N,N-dimethyl-1-ferroceneethylamine) directly and predictably induces the opposite ferrocene planar chirality in subsequent synthetic steps. The classic Josiphos synthetic route is as follows:

[0003] Specifically, starting from the (S)-configuration of Ugiamine, nucleophilic phosphineization ultimately yields a ferrocene framework with (Rp)-planar chirality (and vice versa), meaning the absolute configuration of the product is typically (Sc,Rp) or (Rc,Sp). This correspondence between "central chirality and planar chirality being opposite" has become common knowledge in the field and forms the design cornerstone of existing Josiphos analog synthesis.

[0004] However, this well-established synthetic route has an inherent limitation: it essentially locks in the correspondence between central chirality and planar chirality. This means that, starting from a given chiral Ugi amine, only a specific combination of chiralities ((Sc,Rp) or (Rc,Sp)) can be efficiently and specifically obtained as the final ligand. On the other hand, the fixed chiral Ugi amine also makes it difficult to change the chemical environment near the central chirality.

[0005] Therefore, there is an urgent need to develop a novel and flexible synthetic strategy that can break the inherent pattern of chiral control in traditional routes, achieve efficient synthesis of chiral bisphosphine ligands, and break the fixed relationship between the central chirality and planar chirality of ferrocene, making the chemical environment of central chirality more flexible and controllable. Summary of the Invention

[0006] The purpose of this application is to provide a novel chiral benzoxadiphosphine ligand, its complexes, and its applications.

[0007] To achieve the above objectives, this application adopts the following technical solution: One aspect of this application discloses a chiral benzoxadiphosphine ligand, the structure of which is shown in formula (I). Formula (I) ; Among them, R 1 It is alkyl or aryl, R 2 It is alkyl or aryl, R 3 It is at least one of fluorine, carbazole, and 2,6-dimethoxyphenyl.

[0008] It should be noted that this application develops a novel chiral benzoxane bisphosphine ligand with a ferrocene framework, which can be applied to the rhodium-catalyzed cross-dehydrogenation coupling of dialkylsilane and benzyl alcohol, and the palladium-catalyzed axial chiral Heck reaction of aryl trifluoromethanesulfonate and alkenyl ether, exhibiting good reactivity and high enantioselectivity in both reactions. More importantly, the preparation steps of this chiral benzoxane bisphosphine ligand are concise, allowing direct synthesis from readily available chiral aldehydes, avoiding lengthy linear synthesis steps and poor diastereoselectivity; and it can provide (… S c, S p)-configuration chiral bisphosphine ligands.

[0009] In one implementation of this application, R 1 Choose from any of the following structures, .

[0010] In one implementation of this application, R 2 Choose from any of the following structures, .

[0011] In one implementation of this application, in formula (I), Choose from any of the following structures, .

[0012] In one implementation of this application, the compound represented by formula (I) has any of the following structures. .

[0013] It should be noted that the 12 chiral benzoxoxane ligands with the specific structures described above are only 12 chiral benzoxoxane ligands specifically synthesized in one implementation of this application. It is understood that, under the inventive concept of this application, more chiral bisphosphine ligands containing a ferrocene skeleton can be synthesized, not limited to the above 12.

[0014] Another aspect of this application discloses a complex formed by the chiral benzoxide bisphosphine ligand of this application and metallic rhodium or metallic palladium, wherein the complex of the chiral benzoxide bisphosphine ligand and metallic rhodium is a bisphosphine tetrafluoroborate rhodium complex, and the complex of the chiral benzoxide bisphosphine ligand and metallic palladium is a bisphosphine palladium complex.

[0015] It should be noted that the chiral benzoxane bisphosphine ligand complex with rhodium, namely the bisphosphine tetrafluoroborate rhodium complex, can be applied to the cross-dehydrogenation coupling catalysis of dialkylsilane and benzyl alcohol, exhibiting good reactivity and high enantioselectivity. Similarly, the chiral benzoxane bisphosphine ligand complex with palladium, namely the bisphosphine palladium complex, can be applied to the axial chiral Heck reaction of aryl trifluoromethanesulfonate and alkenyl ether, also exhibiting good reactivity and high enantioselectivity.

[0016] Another aspect of this application discloses an enantioselective cross-dehydrogenation coupling method, which includes using the chiral benzoxadiphosphine ligand complex of this application with rhodium as a catalyst to achieve the deoxygenation C-Si bond coupling reaction of arylalkylsilanes and alkyl alcohols.

[0017] In one implementation of this application, the Rh(COD)2BF4 mixture of the chiral benzoxide bisphosphine ligands of this application is applied to a cross-dehydrogenation coupling reaction of disubstituted silanes and alcohols, and the reaction process is as follows: .

[0018] In one implementation of this application, the coupling reaction catalyzed by the bisphosphine tetrafluoroborate rhodium complex is carried out in an organic solvent, wherein the organic solvent is at least one selected from N,N-dimethylformamide, toluene, trifluorotoluene, carbon tetrachloride, dioxane, hexafluoroisopropanol, and ethyl acetate.

[0019] It should be noted that the key to the enantioselective cross-dehydrogenation coupling method of this application lies in using the rhodium tetrafluoroborate complex of this application as a catalyst, namely, the complex of the chiral benzoxadiphosphine ligand and metallic rhodium; therefore, it has advantages such as good reactivity and strong enantioselectivity. As for the other steps and conditions of the cross-dehydrogenation coupling reaction, refer to the existing enantioselective cross-dehydrogenation coupling methods, which will not be elaborated here.

[0020] Another aspect of this application discloses an enantioselective Heck coupling method, which includes using the complex of the chiral benzoxadiphosphine ligand of this application with palladium metal as a catalyst to achieve a Heck-type coupling reaction of aryl sulfonates and enol silyl ethers.

[0021] In one implementation of this application, the Pd2(dba)3 mixture of the chiral benzoxadiphosphine ligands of this application achieves an axially chiral Heck coupling reaction between substituted aryl trifluorosulfonate and enol ether compounds under organic solvent conditions, and the reaction process is as follows: .

[0022] In one implementation of this application, the Heck-type coupling reaction is carried out under organic solvent and alkaline conditions; wherein the organic solvent is at least one selected from N,N-dimethylformamide, toluene, trifluorotoluene, carbon tetrachloride, dioxane, hexafluoroisopropanol, and ethyl acetate; and the base is triethylamine, N,N -At least one of dimethyl diisopropyl ethylamine, potassium carbonate, and potassium tert-butoxide.

[0023] It should be noted that the key to the enantioselective Heck coupling method of this application lies in using the bisphosphine palladium complex of this application as a catalyst, namely, the complex of the chiral benzoxoxane bisphosphine ligand of this application with metallic palladium; therefore, it has advantages such as good reactivity and strong enantioselectivity. As for the other steps and conditions of the Heck coupling reaction, please refer to the existing enantioselective Heck coupling methods, which will not be elaborated here.

[0024] Due to the adoption of the above technical solutions, the beneficial effects of this application are as follows: The chiral benzoxadiphosphine ligand of this application can be applied to two asymmetric reactions: the rhodium-catalyzed cross-dehydrogenation coupling of dialkylsilane and benzyl alcohol, and the palladium-catalyzed axial chiral Heck reaction of aryl trifluoromethanesulfonate and alkenyl ether. It exhibits excellent activity and high enantioselectivity in both asymmetric reactions. Furthermore, the chiral benzoxadiphosphine ligand of this application can be directly synthesized from readily available chiral aldehydes, and the preparation method is simple and easy to operate. Attached Figure Description

[0025] Figure 1 This is the hydrogen nuclear magnetic resonance image of ligand 1 in the embodiments of this application; Figure 2 This is the carbon nuclear magnetic resonance image of ligand 1 in the embodiments of this application; Figure 3 This is the phosphorus nuclear magnetic resonance image of ligand 1 in the embodiments of this application; Figure 4 This is the hydrogen nuclear magnetic resonance image of ligand 3 in the embodiments of this application; Figure 5 This is the carbon nuclear magnetic resonance image of ligand 3 in the embodiments of this application; Figure 6 This is the phosphorus nuclear magnetic resonance image of ligand 3 in the embodiments of this application; Figure 7 This is the hydrogen nuclear magnetic resonance image of product 15 in the embodiments of this application; Figure 8 This is the carbon nuclear magnetic resonance image of product 15 in the embodiments of this application; Figures 9 to 12 This is a graph showing the liquid phase data of product 15 in the embodiments of this application; Figure 13 This is the hydrogen nuclear magnetic resonance image of product 18 in the embodiments of this application; Figure 14 This is the carbon nuclear magnetic resonance image of product 18 in the embodiments of this application; Figures 15 to 18 This is a graph showing the liquid phase data of product 18 in the embodiments of this application. Detailed Implementation

[0026] The present invention will now be described in further detail with reference to specific embodiments and accompanying drawings. In the following embodiments, many details are described to facilitate a better understanding of the present application. However, those skilled in the art will readily recognize that some features may be omitted in different situations, or may be replaced by other materials or methods. In some cases, certain operations related to the present application are not shown or described in the specification. This is to avoid obscuring the core parts of the present application with excessive description. For those skilled in the art, detailed description of these related operations is not necessary; the relevant operations can be fully understood based on the description in the specification and general technical knowledge in the art.

[0027] In this application, the serial numbers assigned to structural formulas or functional groups are themselves, such as "Formula (I)", "Ligand 1", "Ligand 2"... "Ligand 12", "R". 1 “R” 2 “R” 3 "etc." are used only to distinguish the objects being described and have no order or technical meaning.

[0028] Terminology Explanation: In this application, Pr represents propyl, Bu represents butyl, Ph represents phenyl, Cy represents cyclohexyl, Ad represents adamantyl, Me represents methyl, THP represents tetrahydropyranyl, and Ar represents aryl.

[0029] This application develops a modular synthetic strategy based on "phosphine click reagents". Through tandem nucleophilic addition and intramolecular aromatic nucleophilic substitution reactions, it achieves the efficient construction of chiral bisphosphine ligands (josiphos analogs) containing ferrocene skeletons. Furthermore, it realizes the Rh and Pd complex-mediated asymmetric coupling reaction of such chiral benzoxox bisphosphine ligands.

[0030] The chiral benzoxadiphosphine ligand of this application has the structure shown in formula (I). Formula (I) ; Among them, R 1 It is alkyl or aryl, R 2 It is alkyl or aryl, R 3 It is at least one of fluorine, carbazole, and 2,6-dimethoxyphenyl.

[0031] This application develops a series of chiral bisphosphine ligands containing a ferrocene framework, which are applied to enantioselective cross-dehydrogenation coupling and axial chiral Heck coupling reactions. Compared with the prior art, they have the following advantages: (1) The preparation steps of the chiral benzoxadiphosphine ligand in this application are short, and it can be directly synthesized from readily available chiral aldehydes; it avoids long linear synthesis steps and poor diastereoselectivity; and it can provide ( S c, S p)-configuration chiral bisphosphine ligands.

[0032] (2) The chiral benzoxadiphosphine ligand of this application can be used for two asymmetric reactions, namely, the rhodium-catalyzed cross-dehydrogenation coupling of dialkylsilane and benzyl alcohol, and the palladium-catalyzed axial chiral Heck reaction of aryl trifluoromethanesulfonate and alkenyl ether, and both have excellent activity and high enantioselectivity. Example

[0033] The synthesis process of the chiral benzoxazine bisphosphine ligand in this example is as follows:

[0034] Specifically, under an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen 19 (0.2 mmol, 66.3 mg) was dissolved in 2 mL of dry N,N-dimethylformamide. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) (Biode, BD148904) and the corresponding chiral aldehyde 20 (0.3 mmol, 119.5 mg) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0~20:1) as the eluent, yielding a diastereoselectivity greater than 20:1 to obtain an orange-yellow solid 1 (123.7 mg, 85% yield, >20:1 dr), labeled as ligand 1.

[0035] The hydrogen nuclear magnetic resonance image of product 1, i.e., ligand 1, is shown below. Figure 1 As shown, the carbon NMR spectrum is as follows: Figure 2 As shown, the phosphorus nuclear magnetic resonance image is as follows: Figure 3 As shown, the structural characterization data of product 1 are as follows: Orange solid, 123.7 mg, 85% yield, >20:1 dr. 1H NMR (400 MHz, CDCl3) δ (ppm)8.13 – 8.02 (m, 2H), 7.63 – 7.54 (m, 2H), 7.50 (t, J = 7.9 Hz, 1H), 7.44 –7.26 (m, 7H), 7.26-7.20 (m, 3H), 7.15 (d, J = 8.0 Hz, 1H), 7.09-6.97 (m, 6H), 6.08 (s, 1H), 4.33 (t, J = 2.2 Hz, 1H), 4.20-4.13 (m, 6H), 3.79 (s, 1H), 0.38(d, J = 12.3 Hz, 9H). 13 C NMR (150 MHz, CDCl3) δ (ppm) 165.8, 141.1, 141.0,141.0, 139.2, 138.5, 138.5, 138.5, 138.4, 137.3, 137.3, 137.3, 137.2, 135.4,135.3, 132.9, 132.7, 132.4, 129.3, 128.2, 128.1, 127.7, 127.7, 127.6, 125.7,125.2, 123.5, 123.3, 122.3, 122.2, 120.3, 120.1, 119.8, 112.5, 112.4, 110.2, 109.7, 95.4, 95.2, 95.0, 80.7, 80.7, 80.6, 80.5, 73.9, 73.8, 71.3, 71.3, 70.0, 69.7, 67.4, 34.7, 34.5, 31.8, 31.6, 26.9, 26.5, 26.4. 31 P NMR (162 MHz, CDCl3) δ (ppm) 7.27, -24.15. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 45 H 40 FeNOP2 + = 728.1929; Found 728.1927.

[0036] The preparation process of the substrate phosphine hydrogen 19 used in this example is as follows:

[0037] Specifically, it includes: Under argon protection, n-butyllithium (10 mmol, 1.0 eq.) (Bide, BD01880) was slowly added dropwise to an anhydrous THF (20 mL) solution of substrate 21 (3.4 g, 10 mmol, 1.0 eq.) at -78 °C. B.913796-100 mL), and stirred at this temperature for 2 hours. Then, at -78 °C, an anhydrous THF solution (2 mL) of tert-butyldichlorophosphine (1.6 g, 10 mmol, 1.0 eq.) (Bide, BD152469) was rapidly added to the above reaction mixture, and stirring continued at -78 °C for 2 hours. Next, LiAlH4 (20 mmol, 2.0 eq., 1.0 M THF solution) was slowly added dropwise to the mixture at -78 °C. After the addition was complete, the reaction mixture was gradually heated to room temperature and stirred for 4 hours. After the reaction was complete, the reaction was quenched with degassed H2O (0.2 mL) under ice-water bath conditions. Volatile solvents were removed using anhydrous and oxygen-free techniques, and the residue was diluted with degassed n-hexane (50 mL). Subsequently, the mixture was filtered through a diatomaceous earth mat under an argon atmosphere, and the filter cake was washed with degassed n-hexane (100 mL). All filtrates were collected and combined, and the solvent was removed under vacuum using anhydrous and oxygen-free technology to obtain the corresponding phosphine product, namely substrate phosphine hydrogen 19, which was a pale yellow solid weighing 2.2 g, with a yield of 63%.

[0038] Characterization data of substrate phosphine hydrogen 19: 1 H NMR (600 MHz, CDCl3) δ (ppm) 7.94 (d, J = 7.7 Hz, 2H), 7.24-7.17(m, 3H), 7.09 (q, J = 6.9 Hz, 2H), 7.03 (t, J = 8.8 Hz, 2H), 6.99 (d, J = 7.8Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 3.44 (dd, J = 223.6, 8.0 Hz, 1H), 0.72 (d, J = 12.7 Hz, 9H). 13 C NMR (150 MHz, CDCl3) δ (ppm) 165.0 (dd, J= 245.0, 9.0Hz), 141.9 (dd, J = 7.3, 4.7 Hz), 141.8 , 141.1 , 130.9 (d, J = 10.3 Hz), 125.9 (d, J = 39.7 Hz), 125.1 (d, J = 2.9 Hz), 124.04- 123.41 (m), 123.2 (d, J = 12.1 Hz), 120.2 (d, J = 15.7 Hz), 120.0 (d, J = 4.5 Hz), 115.2 (d, J =25.4 Hz), 110.6 (d, J = 1.8 Hz), 110.1, 77.2, 77.0, 76.8, 30.4 (d, J = 12.7Hz), 30.2 (d, J = 12.0 Hz). 19 F NMR (376 MHz, CDCl3) δ (ppm) -95.17. 31 P NMR (162 MHz, CDCl3) δ (ppm) -49.25 (d, J = 23.1 Hz). HRMS (ESI-TOF) m / z: [M+H]+Calcd for C 22 H 22 FNP + = 350.3966; Found 350.3968. The preparation process of substrate 20 used in this example is as follows (for specific synthesis steps, please refer to the following literature: 1. An Efficient Asymmetric Synthesis of 2-Substituted Ferrocenecarboxaldehydes, J. Org. Chem. 1997, 62 , 6733-6745. 2. Iron(II) Complexes Containing Chiral UnsymmetricalPNP′Pincer Ligands: Synthesis and Application in Asymmetric Hydrogenations, Organometallics2016, 35 , 3781−3787):

[0039] The specific steps are as follows: Under argon protection, ferrocene formaldehyde (25 g, 115 mmol, 1.0 eq.) (Biode, BD17778), trimethyl orthoformate (100 mL) (Yuanye Biotechnology, W11461), p-toluenesulfonic acid (1 g, 0.05 eq.) (Biode, BD01596849), and 2 mL of methanol were mixed. The mixture was heated to 90 °C overnight in a sealed tube. Subsequently, it was cooled to room temperature, and the reaction system was cooled to 0 °C. 10 g of potassium carbonate and 300 mL of anhydrous diethyl ether were added sequentially. The organic phase was filtered and concentrated to obtain crude 22.

[0040] In a dry 250 mL three-necked flask, dissolve 22 in 100 mL of dry chloroform, and then add ( S 1,2,4-triol (12.2 g, 115 mmol, 1.0 eq.) (Biode, BD48004), p-toluenesulfonic acid (1 g, 0.05 eq.) (Biode, BD01596849), and 4A molecular sieve (5 g) were used to heat the reaction system to 60 °C and react for 2 hours. After cooling, the crude product 23 was obtained by column chromatography (eluent polarity: petroleum ether to ethyl acetate volume ratio of 5:1).

[0041] Product 23 (16 g, 53 mmol, 1.0 eq.) was dissolved in anhydrous THF (200 mL). Sodium hydride (3.2 g, 80 mmol) was slowly added at 0 °C, and the mixture was stirred at 0 °C for 1 hour. Iodimethane (4.9 mL, 80 mmol) (Annegi, W610705) was then added, and the reaction was brought to room temperature and stirred overnight. The mixture was cooled to 0 °C, and 200 mL of ethyl acetate was added. Saturated ammonium chloride was slowly added dropwise until the sodium hydride was quenched. 100 mL of water was then added, and the organic phase was separated. The aqueous phase was extracted with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate. The solution was concentrated, and the target product 24 (10.4 g, 62% yield) was obtained by column chromatography.

[0042] 24 (6.0 g, 19 mmol, 1.0 eq.) was dissolved in 100 mL of anhydrous diethyl ether, cooled to -78 °C, and tert-butyllithium (21 mmol) was added dropwise while stirring at this temperature for 20 min. Subsequently, the mixture was stirred at 0 °C for 1 h. The reaction mixture was cooled back to -78 °C, and diphenylphosphine chloride (5.0 g, 22.8 mmol) (Bide, BD41155) was dissolved in 10 mL of anhydrous THF and slowly added to the reaction mixture. The mixture was then heated to room temperature and stirred overnight. Next, the reaction was quenched with saturated sodium bicarbonate solution, and the organic phase was extracted with 100 mL of diethyl ether. The organic phase was then washed with saturated brine, dried over anhydrous sodium sulfate, and the solution was concentrated to crude product 25. 25 was dissolved in 60 mL of dichloromethane under argon atmosphere, followed by the addition of p-toluenesulfonic acid (2.0 g) and 30 mL of degassed water, and stirred overnight at room temperature. The organic phase was separated, dried with sodium sulfate, and then concentrated by column chromatography. The target product 20 was obtained by column chromatography (1.85 g, 25% yield, two steps). Characterization data of substrate aldehyde 20: 1 H NMR (600 MHz, CDCl3) δ (ppm) 10.12 (s, 1H), 7.50-7.40 (m, 2H), 7.35-7.22 (m, 3H), 7.16-7.00 (m, 5H), 4.99 (s, 1H), 4.57 (s, 1H), 4.10 (s,5H), 3.95 (s, 1H). 31 P NMR (162 MHz, CDCl3) δ (ppm) -23.09.

[0043] Using the same method, the substrate phosphine hydrogen 19 (0.2 mmol, 66.3 mg) was dissolved in 2 mL of dry N,N-dimethylformamide, followed by the sequential addition of potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) (Biode, BD148904) and the corresponding chiral aldehyde 26 (0.3 mmol, 119.5 mg). The reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as the eluent, yielding a diastereoselectivity greater than 20:1 to obtain an orange-yellow solid 3 (116.9 mg, 79% yield, >20:1 dr), labeled as ligand 3. Ligand 3 was synthesized in this example, and its structural formula is as follows:

[0044] The hydrogen NMR spectrum of ligand 3 is shown below. Figure 4 As shown, the carbon NMR spectrum is as follows: Figure 5 As shown, the phosphorus nuclear magnetic resonance image is as follows: Figure 6 As shown, the structural characterization data of ligand 3 are as follows: Orange solid, 116.9 mg, 79% yield, >20:1 dr. 1 H NMR (400 MHz, CDCl3) δ (ppm)8.08 (d, J = 7.7 Hz, 1H), 8.05 (d, J = 7.2 Hz, 1H), 7.52 (t, J = 7.9 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.26 – 7.22 (m, 1H), 7.19– 7.12 (m, 4H), 7.08 (d, J = 7.5 Hz, 1H), 6.06 (s, 1H), 4.40-4024 (m, 6H), 4.15 (s, 1H), 4.06 (s, 1H), 2.41-2.32 (m, 1H), 2.20 – 2.05 (m, 2H), 1.93-1.86(m, 2H), 1.79-1.74 (m, 1H), 1.72 – 1.63 (m, 2H), 1.49 (s, 4H), 1.44 – 1.35(m, 3H), 1.34 – 1.26 (m, 1H), 1.14 – 0.81 (m, 6H), 0.68 (d, J = 12.1 Hz, 9H). 13 C NMR (150 MHz, CDCl3) δ (ppm) 166.0, 141.2 (d, J = 13.7 Hz), 141.0, 139.1,132.5, 125.6, 125.3, 123.6, 123.2, 122.3 (d, J = 25.0 Hz), 120.1, 119.8,119.7, 119.7, 112.4 (d, J = 8.9 Hz), 110.3, 109.6, 81.4 (dd, J = 27.2, 13.8Hz), 78.0 (d,J = 21.1 Hz), 70.4 (d, J = 4.0 Hz), 69.9, 68.9, 66.4, 36.6(d, J = 12.3 Hz), 35.6 (d, J = 12.3 Hz), 33.2 (d, J = 20.8 Hz), 32.3 (d, J =22.9 Hz), 31.6 (d, J = 13.6 Hz), 30.2 (d, J = 5.5 Hz), 30.1 (d, J = 11.0 Hz), 28.1 (d, J = 14.1 Hz), 27.6 (d, J = 6.9 Hz), 27.5 (d, J = 11.3 Hz), 27.1 (d, J = 14.6 Hz), 27.0 (d, J = 8.9 Hz), 26.4 (d, J = 13.2 Hz). 31 P NMR (162 MHz, CDCl3) δ (ppm) 6.18, -17.15. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 45 H 52 FeNOP2 + = 740.2868; Found 740.2866.

[0045] The preparation process of substrate 26 used in this example is the same as that of substrate 20. The same intermediates can be prepared by referring to the preparation method of substrate 20.

[0046]

[0047] The specific steps are as follows: 24 (6.0 g, 19 mmol, 1.0 eq.) was dissolved in 100 mL of anhydrous diethyl ether, cooled to -78 °C, and tert-butyllithium (21 mmol) was added dropwise while stirring at this temperature for 20 min. Subsequently, the mixture was stirred at 0 °C for 1 h. The reaction mixture was cooled back to -78 °C, and dicyclohexylphosphine chloride (5.3 g, 22.8 mmol) was dissolved in 10 mL of anhydrous THF and slowly added to the reaction mixture. The mixture was then heated to room temperature and stirred overnight. Next, the reaction was quenched with saturated sodium bicarbonate solution, and the organic phase was extracted with 100 mL of diethyl ether. The organic phase was then washed with saturated brine, dried over anhydrous sodium sulfate, and the solution was concentrated to crude product 27. 27 was dissolved in 60 mL of dichloromethane under argon atmosphere, followed by the addition of p-toluenesulfonic acid (2.0 g) and 30 mL of degassed water, and stirred overnight at room temperature. The organic phase was separated, dried over sodium sulfate, and then concentrated and column-secred. The target product 26 was obtained by column chromatography (2.18 g, 28% yield, two steps). Characterization data of substrate aldehyde 26: 1 H NMR (600 MHz, CDCl3) δ (ppm) 10.24 (d, J = 3.6 Hz, 1H), 5.05 (s,1H), 4.75 (s, 1H), 4.50 (s, 1H), 4.24 (s, 5H), 2.40 (d, J = 9.6 Hz, 1H), 2.15– 2.00 (m, 1H), 1.98-1.80 (m, 3H), 1.81 – 1.65 (m, 4H), 1.65 – 0.82 (m, 13H). 31 P NMR (162 MHz, CDCl3) δ (ppm) -16.72.

[0048] The chiral benzoxane bisphosphine ligand prepared in Example 1 was applied to the rhodium-catalyzed cross-dehydrogenation coupling of dialkylsilane and benzyl alcohol, as follows:

[0049] In an argon atmosphere at room temperature, the corresponding Rh(NBD)BF4 (1.5 mg, 0.004 mmol) (Biode, BD01167073) and ligand 1 (3.2 mg, 0.0044 mmol) were dissolved in 1 mL of dry anhydrous toluene. After stirring for 30 minutes, 13 (39.4 mg, 0.24 mmol) and 14 (21.6 mg, 0.2 mmol) (Biode, BD116108) were added sequentially, and the reaction was maintained with stirring for 12 hours until the starting material was completely consumed as detected by TLC. Subsequently, the mixture was purified by column chromatography using petroleum ether-dichloromethane (2:1) as the eluent, yielding a colorless oily liquid 15 (49.7 mg) in 92% yield. The enantiomeric ratio was determined to be 93.5:6.5 by chiral HPLC analysis.

[0050] The hydrogen NMR spectrum of product 15 is shown below. Figure 7 As shown, the carbon NMR spectrum is as follows: Figure 8 The characterization data for product 15 are shown below:

[0051] ( R )-(benzyloxy)(tert-butyl)(phenyl)silane (15) Colorless oil. 49.7 mg, 92% yield. 93.5:6.5 er Enantiomeric rario(er) was established by chiral HPLC with a Daicel Chiralpak OD-3 column (n-hexane, 0.6 mL / min), λ = 220 nm, temperature = 28 °C, t r (minor) = 8.923 min,t r (major) = 9.254 min. [α] D 20 = +40.2 (1.0, CHCl3). 1 H NMR (400 MHz, CDCl3) δ(ppm) 7.61-7.57 (m, 2H), 7.46 – 7.34 (m, 3H), 7.33-7.30 (m, 4H), 7.28-7.20(m, 1H), 4.84 – 4.72 (m, 3H), 1.00 (s, 9H). 13C NMR (100 MHz, CDCl3) δ (ppm)140.5, 134.5, 133.4, 130.0, 128.2, 127.8, 127.1, 126.3, 66.7, 25.7, 18.1. The liquid phase data of product 15 are as follows: Figures 9 to 12 As shown, where, Figure 9 The liquid phase spectrum of product 15, in which the R and S configurations are mixed in a 50% ratio, is shown. Figure 10 The percentage of the area of ​​the two peaks, R and S configurations, given in the liquid phase spectrum of racemic compound product 15. Figure 11 This is the liquid phase spectrum of product 15, a chiral compound synthesized using this strategy. Figure 12 The liquid phase spectrum of racemic compound product 15 shows the area percentages of the two peaks for the R and S configurations.

[0052] The substrate 13 used in this example is a known compound, and its preparation process is based on the following reference: Chemo- and Regioselective Palladium-Catalyzed Internal Hydrosilylation of gem-Difluoroallenes to Access β-Fluorinated Vinylsilanes, ACS Catal. 2025, 15, 13747-13756.

[0053] The chiral benzoxadiphosphine ligand prepared in Example 1 was applied to the palladium-catalyzed axially chiral Heck reaction of aryl trifluoromethanesulfonate with alkenyl ether, as follows:

[0054] In an argon-atmospheric glove box, the corresponding Pd2dba3 (2.3 mg, 0.0025 mmol) (BYD, BD21135) and ligand 1 (4.4 mg, 0.006 mmol) were dissolved in 0.5 mL of dry anhydrous toluene. After stirring for 30 minutes, 16 (40.3 mg, 0.1 mmol), 17 (39 μL, 0.3 mmol) (TCI, B0746), and DIPEA (52.6 μL, 0.3 mmol) (TCI, D1599) were added sequentially. The reaction was carried out at 80 °C with stirring for 36 hours until the starting material was completely consumed by TLC. Subsequently, the mixture was purified by column chromatography using toluene-ethyl acetate-triethylamine (100:5:3) as the eluent to give a pale yellow solid 18 (29.0 mg) in 82% yield. The enantiomeric ratio was determined to be 97.4:2.6 by chiral HPLC analysis.

[0055] The hydrogen NMR spectrum of product 18 is shown below. Figure 13 As shown, the carbon NMR spectrum is as follows: Figure 14 The characterization data for product 18 are shown below:

[0056] ( R )-1-(2-(1-butoxyvinyl)naphthalen-1-yl)isoquinoline (18) Pale yellow soil, 29.0 mg, 82% yield. Enantiomeric ratio was established as 97.4:2.6 by chiral HPLC analysis with a Daicel Chiralpak IAcolumn (n-hexane: i PrOH = 90:10, 1.0 mL / min), λ = 254 nm, temperature = 28 °C,t r (major) = 7.426 min, t r (minor) = 9.000 min. [α] D 20 = +42.3 (1.0, CHCl3). 1 HNMR (400 MHz, CDCl3) δ (ppm) 8.64 (d, J = 5.7 Hz, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.88 (t, J = 7.4 Hz, 2H), 7.74 (d, J = 8.6 Hz, 1H), 7.70 (d, J = 5.7 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.43 (t, J = 7.2 Hz,1H), 7.36 – 7.31 (m, 1H), 7.28 – 7.21 (m, 1H), 7.12 (d, J = 8.5 Hz, 1H), 4.25(d, J= 2.3 Hz, 1H), 4.02 (d, J = 2.3 Hz, 1H), 3.27-3.20 (m, 1H), 3.19-3.11(m, 1H), 0.97-0.73 (m, 4H), 0.64 (t, J = 7.0 Hz, 3H). 13 C NMR (100 MHz, CDCl3)δ (ppm) 161.0, 160.6, 142.0, 135.9, 135.1, 134.1, 133.4, 132.6, 129.9, 128.8,128.4, 127.8, 127.7, 126.8, 126.6, 126.4, 126.4, 126.3, 125.9, 119.6, 87.0,67.1, 30.2, 18.9, 13.6..

[0057] The liquid phase data of product 18 are as follows Figures 15 to 18 As shown, where, Figure 15 The liquid phase spectrum of product 18, in which the R and S configurations are mixed in a 50% ratio, is shown. Figure 16 The percentage of the area of ​​the two peaks, R and S configurations, given in the liquid phase spectrum of racemic compound product 18. Figure 17 This is the liquid phase spectrum of product 18, a chiral compound synthesized using this strategy. Figure 18 The liquid phase spectrum of racemic compound product 18 shows the area percentages of the two peaks for the R and S configurations.

[0058] The substrate 16 used in this example is a known compound, and its preparation process is based on the following literature: Synthesis of Axially Chiral QUINAP Derivatives by Ketone-Catalyzed Enantioselective Oxidation, Angew. Chem. Int. Ed. 2023, 62, e202309272.

[0059] The above description, in conjunction with specific embodiments, provides a further detailed explanation of this application and should not be construed as limiting the specific implementation of this application to these descriptions. Those skilled in the art to which this application pertains can make several simple deductions or substitutions without departing from the concept of this application.

Claims

1. A chiral benzo dioxaphospholane ligand characterized by: The structure is shown as formula (I), Formula (I) ; wherein R 1 is alkyl or aryl, R 2 is alkyl or aryl, R 3 is at least one of fluorine, carbazolyl and 2,6-dimethoxyphenyl.

2. The chiral benzoxazaphospholane ligand according to claim 1, characterized by: R 1 selected from any one of the following structures, 。 3. The chiral benzoxazaphospholane ligand according to claim 1, characterized by: R 2 selected from any one of the following structures, 。 4. The chiral benzoxazaphospholane ligand according to claim 1, characterized by: In formula (I), selected from any one of the following structures, 。 5. The chiral benzoxazaphospholane ligand according to claim 1, characterized by: The compound shown as formula (I) is any one of the following structures, 。 6. A complex of a chiral benzo dioxaphospholane ligand of any one of claims 1 to 5 complexed with a metal rhodium or a metal palladium, wherein, The complex of the chiral benzo-oxazaphospholane ligand and the metal rhodium is a rhodium complex of a diphosphine tetrafluoroborate, and the complex of the chiral benzo-oxazaphospholane ligand and the metal palladium is a palladium complex of a diphosphine.

7. A method of enantioselective cross-dehydrogenative coupling, characterized in that, The coupling reaction of the deoxygenated C-Si bond of arylalkylsilane and alkyl alcohol is realized by using the complex of the chiral benzo-oxazaphospholane ligand and the metal rhodium as a catalyst according to any one of 1-5.

8. The method of claim 7, wherein: The coupling reaction is carried out in an organic solvent, and the organic solvent is at least one of N,N-dimethylformamide, toluene, trifluorotoluene, carbon tetrachloride, dioxane, hexafluoroisopropanol, and ethyl acetate.

9. A method of enantioselective Heck coupling, characterized by: The Heck type coupling reaction of aryl sulfonate and enol silyl ether is realized by using the complex of the chiral benzo-oxazaphospholane ligand and the metal palladium as a catalyst according to any one of 1-5.

10. The method of claim 9, wherein: The Heck type coupling reaction is carried out under alkaline conditions and in an organic solvent; The organic solvent is at least one of N,N-dimethylformamide, toluene, trifluorotoluene, carbon tetrachloride, dioxane, hexafluoroisopropanol, and ethyl acetate; The base is at least one of triethylamine, N,N dimethyl diisopropyl ethylamine, potassium carbonate, and potassium tert-butoxide.

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