Five-membered ring P-chiral phosphine oxide compound containing alkynyl or triazole functional group as well as preparation method and application of five-membered ring P-chiral phosphine oxide compound

Abstract

The invention discloses a five-membered ring P-chiral phosphine oxide compound containing alkynyl or triazole functional groups, which is characterized in that under the protection of inert gas, a prochiral tertiary phosphine oxide compound containing dialkenyl and phenylacetylene are used as raw materials, in the presence of a transition metal palladium catalyst and a chiral TADDOL phosphoramidite ligand, Domino Heck-Sonogashira cascade reaction is carried out to obtain the P-chiral phosphine oxide compound, and the P-chiral phosphine oxide compound is used as a raw material for preparing the five-membered ring P-chiral phosphine oxide compound containing alkynyl or triazole functional groups. The yield of the obtained product is up to 96%, the enantioselectivity ee value is up to 99%, and the diastereoselectivity dr value is greater than 20: 1. According to the present invention, the asymmetric desymmetry strategy is adopted, the Heck reaction is adopted to start the cascade reaction, the Sonogashira reaction is adopted to terminate the cascade reaction, the P-chiral center and the quaternary carbon chiral center are simultaneously constructed, the reaction conditions are mild, the operation is simple, the substrate universality is good, the diversified compound skeleton is provided, and the chiral ligand is successfully used as the chiral ligand to be used in the palladium-catalyzed asymmetric allyl substitution reaction.

Description

Technical Field

[0001] The present invention belongs to the technical field of asymmetric catalysis, and particularly relates to a five-membered ring containing alkynyl or triazole functional groups P -chiral phosphine oxides and their preparation methods and applications. Background Art

[0002] By utilizing two different stable oxidation states of the phosphorus center, phosphorus compounds can be widely applied in different application fields, especially in the field of asymmetric catalysis. Among them, compounds with chiral skeletons have received the most attention. For example, BINAP ligands, TADDOL-type skeleton phosphoramidite ligands, PHOX ligands, etc. Compared with these chiral phosphorus molecules, due to synthetic reasons, the development of compounds with chiral centers on phosphorus atoms (also known as P- stereocompounds) is less. In the currently developed reaction types, the reaction substrates are limited, and there are few reports on the metal-catalyzed asymmetric desymmetrization reaction involving alkenyl tertiary phosphine oxides. At the same time, the advantage of constructing multiple chiral centers, especially quaternary carbon chiral centers, in one step of the desymmetrization reaction has not been fully explored. Among them, the example of constructing P- chiral centers and other chiral centers in one step is even rarer. In recent years, the desymmetrization tandem reaction triggered by the asymmetric Heck reaction has attracted the attention of a wide range of chemists, but the end of this reaction strategy mostly relies on β -H elimination and does not involve other tandem reactions. Although there are many literature reports on replacing the β -H elimination step of the Heck reaction with an atom or group transfer process, the focus is mainly on constructing heterocyclic skeletons such as indole by the Heck cyclization reaction, and there are few research reports on the Domino-Heck asymmetric desymmetrization reaction, and most of the substrates are based on cyclic olefins. Therefore, the desymmetrization tandem reaction triggered by the Heck reaction based on acyclic olefins is somewhat challenging. In addition, the research on P P-N ligands with chiral centers is relatively less. Most of them are chiral phosphine-nitrogen ligands based on the extension of the oxazoline skeleton, and there is less research on phosphine-nitrogen ligands containing a 1,2,3-triazole skeleton. Summary of the Invention

[0003] Aiming at the deficiencies in the prior art, a series of explorations are carried out in the present invention on the synthesis of alkynyl-functionalized P -chiral compound ligands and phosphine-nitrogen ligands centered on P chirality. The prepared chiral phosphine oxides can be used to synthesize 1,2,3-triazole P -chiral phosphine oxides through the Click reaction; the P -chiral phosphine oxides of the benzofive-membered ring and the triazole-containing P -chiral phosphine oxides can obtain configurationally stableP - Chiral trivalent phosphine products and have been successfully applied as chiral ligands in palladium-catalyzed asymmetric allylic substitution reactions.

[0004] To achieve the above-mentioned invention objectives, the present invention provides the following technical solutions: A five-membered ring containing an alkynyl or triazole functional group P - Chiral phosphine oxide compound, the structural formula of the compound is any one of the following general structural formulas: ; Wherein, * represents a chiral center atom, and the configuration is R or S , Ar 1 is a benzene ring or a naphthalene ring; R 1 is hydrogen, a saturated alkyl group of C1-C6 or a halogen; R 2 is an alkyl group, a halogen, an alkoxy group, a phenyl group or a benzyl group; R 3 is an alkyl group, a halogen, an alkoxy group, a phenyl group, a benzyl group, a thiophene, a silane or a naphthalene group; wherein, the alkyl group in R 3 is a saturated or unsaturated alkyl group of C1-C6; R 4 is an alkyl group or a benzyl group.

[0005] Preferably, R 1 is hydrogen, a saturated alkyl group of C1-C6 or a halogen; R 2 is an alkyl group of C1-C6, a halogen, an alkoxy group of C1-C6, a phenyl group or a benzyl group; R 3 is an alkyl group of C1-C6, a halogen, an alkoxy group of C1-C6, a phenyl group, a benzyl group, a thiophene, a silane or a naphthalene group; wherein, the alkyl group in R 3 is a saturated or unsaturated alkyl group of C1-C6; R 4 is an alkyl group of C1-C6 or a benzyl group.

[0006] Preferably, R 1 is hydrogen, a saturated alkyl group of C1-C6 or a halogen; R 2 is a saturated alkyl group of C1-C6, a halogen, a saturated alkoxy group of C1-C3, a phenyl group or a benzyl group; the hydrogen on the phenyl group can be substituted by a halogen or a saturated alkyl group of C1-C6; R 3 is an alkyl group, a halogen, an alkoxy group, a phenyl group, a benzyl group, a thiophene, a silane or a naphthalene group; wherein, the alkyl group in R 3 is a saturated or unsaturated alkyl group of C1-C6; R 3The hydrogen on the alkyl, silane or phenyl group can be substituted by any one of the following substituents: a saturated alkyl group with 1 to 3 carbon atoms, a saturated alkoxy group with 1 to 3 carbon atoms, or a phenyl group; R 4 is a saturated alkyl group with 1 to 6 carbon atoms or a benzyl group.

[0007] Preferably, the halogen is fluorine or chlorine.

[0008] More preferably, the hydrogen on the phenyl group in R 3 can also be substituted by any one of the following substituents: an aldehyde group or a cyano group.

[0009] The present invention also provides a preparation method of a prochiral tertiary phosphine oxide compound containing an alkenyl group, comprising the following steps: Step S1:

[0010] Step S1: Under the protection of an inert gas, a silanization reagent is added to Compound I in acetonitrile to obtain Compound I-1, and then the reaction is carried out at a specific temperature until the end. After concentration under reduced pressure to a dry state, it is put into the next reaction.

[0011] Step S2:

[0012] Step S2: Under the protection of an inert gas, Compound I-1 is used as a raw material and added to dichloromethane. Under the catalysis of N,N-dimethylformamide, after cooling to 0 °C, it is phosphonylated with an acyl chloride reagent, and after the reaction is carried out at room temperature until the end, it is concentrated under reduced pressure to a dry state and then put into the next reaction.

[0013] Step S3:

[0014] Step S3: Under the protection of an inert gas, the dried phosphonyl chloride Compound I-2 is added to an ether dilution system, and the freshly prepared Grignard reagent is added to Compound I-2 at 0 °C, and then stirred overnight at room temperature. After extraction, it is separated and purified by column chromatography to obtain the prochiral tertiary phosphine oxide Compound II.

[0015] Step S4:

[0016] In Formula IV: * represents a chiral center atom, which is R or S; The specific synthesis method of step S4 is as follows: Under the protection of inert gas, the prochiral tertiary phosphine oxide compound of formula II and the alkyne nucleophile with different substituents of formula III are added as reaction raw materials into an organic solvent. Using a palladium catalyst with a ligand as the catalyst, under the condition of the presence of a base, the reaction is stirred at 40 - 80 °C for 12 hours; Subsequently, extraction, filtration, and concentration under reduced pressure are carried out, and the obtained concentrated crude product is separated and purified by column chromatography to obtain the target compound, the benzofive-membered ring of formula IV P -chiral phosphine oxide compound.

[0017] Step S5:

[0018] In formula IV, R 3 Trimethylsilyl group.

[0019] In formula IV, formula V and formula VI: * represents a chiral center atom, which is R or S.

[0020] Step S5: After adding formula IV to an organic solvent, it is placed in a low-temperature reactor, and a desilylation reagent is used to stir until the reaction ends, and then it is purified to obtain the desilylated products of formula V and formula VI.

[0021] Step S6:

[0022] In formula V and formula VII: * represents a chiral center atom, which is R or S.

[0023] Step S6: Weigh the desilylated compound of formula V, catalyst, reducing agent, base, sodium azide, and bromide into the reactor, then add an organic solvent, stir overnight at 25 - 50 °C, monitor the reaction progress by TLC, after the reaction ends, carry out extraction, filtration, drying, and purify by column chromatography to obtain the triazole-based phosphine oxide compound of formula VII.

[0024] Step S7:

[0025] In formula VII, VIII, IV, IX: * represents a chiral center atom, which is R or S.

[0026] Step S7: First, add the amine compound to the organic solvent in a round-bottom flask, add a silane reagent to form a complex of silane and the amine, then add the triazole-based P -chiral phosphine oxide compound of formula VII or IV P -chiral phosphine oxide compound, stir at a specific temperature until the reaction ends, then after the system cools to room temperature, place it in a low-temperature reactor and add a borane reagent, and react at room temperature until the end. After extraction, concentration under reduced pressure, and separation and purification by column chromatography, the triazole-based phosphine borane compound of formula VIII or the phosphine borane compound of formula IX is obtained.

[0027] In the present invention, in step S4, the palladium catalyst is selected from one of tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, tris(dibenzylideneacetone)dipalladium chloroform adduct, allylpalladium chloride dimer, dichlorobis(triphenylphosphine)palladium, palladium chloride, dichlorobis[1,1'-bis(diphenylphosphino)ferrocene]palladium, palladium tetrafluoroborate tetraacetonitrile, dichlorobis(1,5-cyclooctadiene)palladium, bis(tritert-butylphosphine)palladium, palladium acetate, bis(tritert-butylphosphine)palladium, dichlorobis(acetonitrile)palladium, tetrakis(triphenylphosphine)palladium.

[0028] In the present invention, the ligand in step S4 is a chiral phosphine ligand, an achiral phosphine ligand, a hybrid ligand, a spiro ligand, etc.

[0029] In the present invention, the base in step S4 can be an inorganic base (such as sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, potassium bicarbonate, etc.), a nitrogen-containing organic base (such as diethylamine, triethylamine, DIPEA, diisopropylamine, etc.).

[0030] In the present invention, the organic solvent in step S4 can be one or any mixture of dichloromethane, dichloroethane, acetonitrile, propionitrile, butyronitrile, valeronitrile, benzonitrile, phenylacetonitrile, diethyl ether, dibutyl ether, methyl tert-butyl ether, anisole, ethylene glycol dimethyl ether, ethyl acetate, 1,4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, trifluorotoluene, chloroform, acetone.

[0031] In the present invention, the feeding ratio of the method in step S4 is as follows: the molar ratio between the prochiral tertiary phosphine oxide compound of formula II and the nucleophile with different substituents of formula III is 1:(1.0 - 2.0); the molar ratio between the prochiral tertiary phosphine oxide compound of formula II:palladium metal precursor:ligand:base is 1:(0.03 - 0.1):(0.06 - 0.2):(1.5 - 2); the molar amount of the prochiral tertiary phosphine oxide compound of formula II and the volume ratio of the organic solvent is 1 mmol:(1 - 10) mL.

[0032] In the present invention, the reaction temperature in step S4 is 30 - 100 °C.

[0033] In the present invention, the desilylation reagent in step S5 is one or more than two of cesium fluoride, potassium carbonate, tetrabutylammonium fluoride.

[0034] In the present invention, the organic solvent in step S5 is one or two or any mixture of tetrahydrofuran and methanol.

[0035] In the present invention, the reaction temperature in step S5 is 25 - -20 °C.

[0036] In the present invention, the feeding ratio of the method in step S5 is: formula IV benzo five-membered ring P-Chiral phosphine oxide: The molar ratio between the desilylation reagents is 1:(1.0 - 2.0); The molar amount of the phosphine oxide of Formula IV and the volume of the organic solvent have a ratio of 1 mmol:(2 - 5) mL.

[0037] In the present invention, the catalyst described in step S6 can be one of cuprous iodide, copper sulfate pentahydrate, and copper acetate.

[0038] In the present invention, the reducing agent described in step S6 is sodium ascorbate.

[0039] In the present invention, the base described in step S6 can be one of cesium carbonate, sodium carbonate, potassium carbonate, triethylamine, and diisopropylethylamine.

[0040] In the present invention, the solvent described in step S6 can be one of dichloromethane, dichloroethane, tetrahydrofuran, methanol, N,N-dimethylformamide, acetonitrile, dimethyl sulfoxide, water, and toluene or any mixture thereof.

[0041] In the present invention, the temperature described in step S6 is 25 - 60 °C.

[0042] In the present invention, the feeding ratio of the method described in step S6 is: Terminal alkyne of Formula V P -Chiral phosphine oxide: Azide: Bromide: Catalyst: Reducing agent: Base have a molar ratio of 1:(1.05 - 1.5):(1.05 - 1.5):(0.1 - 0.5):(0.2 - 1):(1.1 - 2); The molar amount of the terminal alkyne phosphine oxide of Formula V and the volume of the organic solvent have a ratio of 1 mmol:(25 - 35) mL.

[0043] In the present invention, the organic solvents described in step S7 are one of methanol, ethanol, toluene, xylene, ether, chloroform, dichloromethane, dichloroethane, cyclopentyl methyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, acetonitrile, and N,N-dimethylformamide or any mixture thereof.

[0044] In the present invention, the silane reagent described in step S7 can be one or more of 1,1,3,3-tetramethyldisiloxane, triethoxysilane, triethylsilane, trimethoxysilane, trichlorosilane, and triphenylsilane.

[0045] In the present invention, the amine compound described in step S7 can be one of triethylamine and pyridine.

[0046] In the present invention, the temperature described in step S7 is -40 - 80 °C.

[0047] As a preferred embodiment, in the method for the preparation and application of a benzo five-membered ring P -chiral phosphine oxide of the present invention: In the present invention, the molar ratio of the material of Formula I in step S1 to trimethylsilyl bromide is 1:4, the reaction temperature is 50 °C, and the reaction time is 2 hours.

[0048] In the present invention, the molar ratio of the material of Formula I-1, N,N-dimethylformamide, and acyl chloride reagent in step S2 is 1:0.05:3, the reaction temperature is room temperature, and the reaction time is 4 hours.

[0049] In the present invention, the molar ratio of Material I-2 to Grignard reagent in step S3 is 1:3.5, the reaction temperature is room temperature, the reaction time is 12 hours. After acid-base extraction, it is concentrated under reduced pressure and then post-treated by column chromatography.

[0050] In the present invention, the molar ratio of Material II, III, palladium precursor, ligand, and base in step S4 is 1:1.5:0.05:0.06:2, the reaction temperature is 40 °C, the reaction time is 12 hours. After concentration under reduced pressure, it is separated and purified by column chromatography.

[0051] In the present invention, the palladium precursor in step S4 is selected from bis(dibenzylideneacetone)palladium.

[0052] In the present invention, the base in step S4 is most preferably selected from potassium carbonate.

[0053] In the present invention, the solvent in step S4 is most preferably selected from 1,4-dioxane.

[0054] In the present invention, the molar ratio of Material IV to desilylation reagent in step S5 is 1:2, the reaction temperature is room temperature, the reaction time is 12 hours. After quenching the reaction with ammonium chloride, liquid separation and concentration under reduced pressure are carried out, and separation and purification are carried out by column chromatography.

[0055] In the present invention, the desilylation reagent in step S5 is most preferably selected from tetrabutylammonium fluoride.

[0056] In the present invention, the solvent in step S5 is most preferably selected from tetrahydrofuran.

[0057] In the present invention, the molar ratio between Material V, azide:bromide: catalyst:reductant:base in step S6 is 1:1.1:1.1:0.2:0.4:1.2; the molar amount of the terminal alkyne phosphine oxide of Formula V to the volume of the organic solvent is 1 mmol:(25 - 35) mL.

[0058] In the present invention, the catalyst in step S6 is most preferably selected from copper sulfate pentahydrate.

[0059] In the present invention, the base in step S6 is most preferably selected from potassium carbonate.

[0060] In the present invention, the material of Formula VII in step S7 P-Chiral phosphine oxide compound: trichlorosilane: amine = 1:15:31. Chiral trivalent phosphine compound: borane dimethyl sulfide complex = 1:5, the reaction temperature is room temperature, and the reaction time is two hours.

[0061] In the present invention, the amine in step S7 is most preferably selected from pyridine.

[0062] The present invention simultaneously protects the five-membered ring containing an alkynyl or triazole functional group P- Application of chiral phosphine oxide compounds in asymmetric catalysis; further, it is to protect the application in palladium-catalyzed asymmetric allylic substitution reactions.

[0063] Definition of terms used in the present invention: Unless otherwise specified, the initial definitions provided for groups or terms herein apply to such groups or terms throughout the specification; for terms not specifically defined herein, their meanings should be given based on the disclosure content and context, which can be understood by those skilled in the art.

[0064] "Substituted" means that a hydrogen atom in a molecule is replaced by other different atoms or molecules.

[0065] The minimum and maximum carbon atom contents in a hydrocarbon group are indicated by a prefix. For example, the prefix (Ca~Cb) alkyl indicates any alkyl containing "a" to "b" carbon atoms. Thus, for example, (C1~C4) alkyl refers to an alkyl containing 1 to 4 carbon atoms.

[0066] The C1~C6 alkyl refers to alkyls of C1, C2, C3, C4, C5, and C6, that is, straight-chain or branched-chain alkyls having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, and so on. The C1-C6 alkoxy group also has a corresponding meaning to its group.

[0067] Compared with the prior art, the beneficial effects of the present invention are: The present invention uses a palladium catalyst combined with a chiral ligand as a catalyst to synthesize an alkynyl-containing benzo five-membered ring from a prochiral phosphine oxide P- The preparation of chiral phosphine oxide compounds and triazole-based phosphine boron compounds provides an efficient and atom-economical route. A series of phosphine oxide compounds with highly optically active phosphine chiral centers and quaternary carbon chiral centers in the benzo five-membered ring skeleton are obtained, with a maximum yield of 95% and a maximum enantioselectivity ee value of 99%, and a diastereomeric dr value selectivity greater than 20:1.

[0068] For the catalytically obtained P-After the chiral phosphine oxide compound undergoes de-TMS, the click triazole product is synthesized. Subsequently, the phosphine-oxygen double bond is reduced and stabilized with borane. The yield of the two-step consecutive addition is 95%, and the reduced trivalent phosphine products with two configurations are obtained. This compound has the potential of a P-N bidentate ligand, laying a foundation for subsequent applications. Description of the Drawings

[0069] Figure 1 It is the single crystal diffraction structure of Compound VI in Example 9 of the present invention; Figure 2 It is the comparison between the racemic HPLC and chiral HPLC of Compound 3 obtained in Application Test Example 1.

[0070] Figure 3 It is the comparison between the racemic HPLC and chiral HPLC of Compound 3 obtained in Application Test Example 2. Detailed Description of the Invention

[0071] Next, the technical solutions of the present invention will be clearly and completely described in conjunction with the embodiments and comparative examples of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts fall within the scope of protection of the present invention.

[0072] Unless otherwise specified, the test methods used in the following examples are all conventional methods; the materials, reagents, etc. used, unless otherwise specified, are reagents and materials that can be obtained from commercial channels.

[0073] Example 1 Synthesis of prochiral phosphine oxide compounds II-1 to II-4: Diethyl phosphite compounds of formula I are used as starting materials. Bromosilane reagent is added in acetonitrile, and the reaction is carried out at 50 °C for 2 hours to obtain Compound I-1, and then it is concentrated under reduced pressure to a dry state and put into the next step of reaction. In the second step, N,N-dimethylformamide is used as a catalyst, and the reaction system is diluted with dichloromethane. Phosphoryl chloride is carried out with oxalyl chloride at 0 °C, and then the reaction is carried out at room temperature until the end to obtain the phosphoryl chloride compound of Compound I-2, which is concentrated under reduced pressure to a dry state. After Compound I-2 is purged with argon 3-5 times, the reaction system is diluted with diethyl ether, and the freshly prepared Grignard reagent is added at 0 °C, and then stirred overnight at room temperature. After quenching the reaction, liquid separation, filtration, drying, concentration under reduced pressure, and separation and purification, the prochiral phosphine oxide compound of formula I-4 is obtained. The synthesis steps are as follows (those skilled in the art can determine each R group according to the structural formulas of Compounds II-1 to II-4, and will not be elaborated): Step S1:

[0074] Step S2:

[0075] Step S3:

[0076] Step S1: After purging with argon three times, trimethylsilyl bromide (40 mmol) was added to the starting raw material compound of formula Ⅰ (10 mmol) in acetonitrile (10 mL), and the reaction was carried out at 50 °C for two hours to obtain compound Ⅰ-1, which was then concentrated under reduced pressure to a dry state and fed into the next reaction.

[0077] Step S2: After purging with argon three times, at 0 °C, with N,N-dimethylformamide (2 - 3 drops) as a catalyst, oxalyl chloride (30 mmol) was added to compound Ⅰ-1 in dichloromethane (10 mL) for acyl chlorination. After reacting at room temperature for 4 hours, it was concentrated under reduced pressure to a dry state to obtain the phosphonyl chloride compound Ⅰ-2.

[0078] Step S3: After purging with argon three times, compound Ⅰ-2 was added to diethyl ether (10 mL) at 0 °C, and the freshly prepared Grignard reagent (40 mmol) was added to the phosphonyl chloride compound Ⅰ-2, and the mixture was stirred overnight at room temperature. Subsequently, saturated ammonium chloride solution (50 mL) was added to quench the reaction, and the organic phase was extracted three times with ethyl acetate and then washed with saturated sodium bicarbonate solution (50 mL) and concentrated under reduced pressure. The crude product was purified by column chromatography using petroleum ether:ethyl acetate in a ratio of 3:1 to obtain each prochiral phosphine oxide compound.

[0079] The characterization of each prochiral phosphine oxide compound is as follows: The characterization of compound Ⅱ-1 is as follows:

[0080] Compound Ⅱ-1 is a light yellow solid, 1.98 g, with a yield of 45%, and a melting point of 127.0 - 134.0 °C.

[0081] 1 H NMR (400 MHz, CDCl 3 ) δ 7.98 (ddd, J = 11.5, 7.6, 1.8 Hz, 1H), 7.40(ddd, J = 7.9, 4.1, 0.9 Hz, 1H), 7.35 – 7.29 (m, 5H), 7.25 – 7.16 (m, 7H),5.36 (dd, J = 4.8, 0.8 Hz, 2H), 5.24 (dd, J= 4.8, 0.7 Hz, 2H), 3.59 – 3.45(m, 4H).

[0082] 13 C NMR (100 MHz, CDCl 3 )δ 140.95 (d, J C-P = 3.2 Hz), 138.98 (d, J C-P =9.9 Hz), 137.43 (d, J C-P = 5.4 Hz), 133.50 (d, J C-P = 7.9 Hz), 133.16 (d, J C-P =2.5 Hz), 132.08 (d, J C-P = 91.7 Hz), 128.16, 127.60, 127.30 (d, J C-P = 9.3 Hz),126.60 (d, J C-P = 0.6 Hz), 123.32 (d, J C-P = 7.1 Hz), 117.95 (d, J C-P = 9.4 Hz),35.63 (d, J C-P = 64.6 Hz).

[0083] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 34.98.

[0084] FT-IR (KBr) 3080, 3064, 3048, 2923, 2902, 1621, 1577, 1556, 1492,1444, 1404, 1301, 1211, 1199, 1153, 1129, 1099, 1071, 1018, 939, 907, 897,854, 774, 756, 730, 720, 705, 637, 615, 585, 505, 461, 432, 415 cm -1 .

[0085] HRMS (ESI) calcd for C 24 H 23 BrOP + [M+H] + 437.0664, found 437.0664.

[0086] The NMR data of compound Ⅱ-2 are as follows:

[0087] Compound Ⅱ-2 is a light yellow solid, 1.08 g, with a yield of 24% and a melting point of 85.7 - 88.1 °C.

[0088] 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 (dd, J = 11.9, 2.0 Hz, 1H), 7.36 – 7.27(m, 5H), 7.24 – 7.14 (m, 6H), 7.05 – 6.99 (m, 1H), 5.36 (dd, J = 4.7, 0.7 Hz,2H), 5.23 (dd, J = 4.7, 0.4 Hz, 2H), 3.57 – 3.44 (m, 4H), 2.24 (s, 3H).

[0089] 13 C NMR (100 MHz, CDCl 3 ) δ 140.99 (d, J C-P = 3.2 Hz), 139.06 (d, J C-P =9.9 Hz), 137.84 (d, J C-P = 5.5 Hz), 137.53 (d, J C-P = 9.4 Hz), 134.00 (d, J C-P =2.6 Hz), 133.37 (d, J C-P = 8.4 Hz), 131.47 (d, J C-P= 91.5 Hz), 128.13, 127.58, 126.64, 119.81 (d, J C-P = 7.1 Hz), 117.87 (d, J C-P = 9.4 Hz), 35.65 (d, J C-P = 64.6 Hz), 20.70.

[0090] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 35.23.

[0091] FT-IR (KBr) 1593, 1496, 1443, 1420, 1384, 1351, 1301, 1281, 1266, 1254, 1215, 1199, 1160, 1151, 1142, 1099, 1016, 893, 878, 818, 779, 754, 699, 670, 640, 462 cm -1 .

[0092] HRMS (ESI) calcd for C 25 H 25 BrOP + [M+H] + 451.0821, found 451.0822.

[0093] The NMR data of compound Ⅱ-3 are as follows:

[0094] Compound Ⅱ-3 is a light yellow solid, 1.16 g, with a yield of 23% and a melting point of 86.3 - 88.7 °C.

[0095] 1 H NMR (400 MHz, CDCl 3 ) δ 7.90 (ddd, J = 11.3, 7.4, 1.7 Hz, 1H), 7.46– 7.40 (m, 1H), 7.37 – 7.25 (m, 3H), 7.25 – 7.14 (m, 7H), 5.33 (d, J = 4.7Hz, 2H), 5.22 (d, J= 4.8 Hz, 2H), 3.60 – 3.40 (m, 4H).

[0096] 13 C NMR (100 MHz, CDCl 3 ) δ 138.21 (d, J C-P = 3.1 Hz), 136.98 (d, J C-P =10.0 Hz), 136.40 (d, J C-P = 5.4 Hz), 132.51 (d, J C-P = 7.7 Hz), 132.49, 132.27(d, J C-P = 2.5 Hz), 130.61 (d, J C-P = 91.7 Hz), 127.22, 126.94, 126.40 (d, J C-P = 9.4 Hz), 122.15 (d, J C-P = 7.1 Hz), 117.39 (d, J C-P = 9.5 Hz), 34.71 (d, J C-P = 64.5 Hz).

[0097] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 34.74.

[0098] FT-IR (KBr) 3448, 3061, 3029, 2927, 1619, 1591, 1578, 1558, 1491,1417, 1392, 1193, 1143, 1127, 1094, 835, 751, 733, 671, 448 cm -1 .

[0099] HRMS (ESI) calcd for C 24 H 21 BrCl 2 OP + [M+H]+ 504.9885, found 504.9885.

[0100] The NMR data of Compound II-4 are as follows:

[0101] Compound II-4 is a light yellow oil, 1.35 g, with a yield of 29%.

[0102] 1 H NMR (400 MHz, CDCl 3 ) δ 8.34 – 8.25 (m, 1H), 7.63 (dd, J J = 7.8, 4.0Hz, 1H), 7.55 (t, J J = 7.5 Hz, 1H), 7.42 (t, J J = 7.6 Hz, 1H), 7.28 (t, J J = 7.3Hz, 4H), 7.24 – 7.14 (m, 6H), 4.95 (d, J J = 4.5 Hz, 2H), 4.84 (d, J J = 4.3 Hz,2H), 3.53 (d, J J = 15.2 Hz, 2H), 3.44 (d, J J = 15.2 Hz, 2H), 3.18 – 2.97 (m,4H).

[0103] 13 C NMR (100 MHz, CDCl 3 ) δ 139.96 (d, J C-P J = 10.0 Hz), 138.87 (d, J C-P J =1.2 Hz), 137.44 (d, J C-P J = 5.5 Hz), 133.82 (d, J C-P J = 7.9 Hz), 133.42 (d, J C-P J =2.5 Hz), 132.38 (d, J C-P J = 90.0 Hz), 129.36, 128.34, 127.62 (d, JC-P = 9.3 Hz), 126.27, 123.33 (d, J C-P = 6.9 Hz), 116.50 (d, J C-P = 9.7 Hz), 43.95 (d, J C-P = 2.1 Hz), 35.30 (d, J C-P = 64.7 Hz).

[0104] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 36.94.

[0105] FT-IR (neat) 3060, 3026, 2905, 1640, 1601, 1578, 1558, 1494, 1452, 1418, 1274, 1193, 1127, 1074, 1019, 896, 845, 737, 699, 619, 602, 543, 479, 446 cm -1 .

[0106] HRMS (ESI) calcd for C 26 H 27 BrOP + [M+H] + 465.0977, found 465.0979.

[0107] Example 2 Synthesis of alkynyl-containing benzo-fused five-membered ring P -chiral phosphine oxide Ⅳ1

[0108] Experimental procedure: In a sealed tube with a volume of 25 mL, add prochiral phosphine oxide compound of formula II-1 (0.2 mmol), bis(dibenzylideneacetone)palladium (0.01 mmol), ligand (0.012 mmol), and potassium carbonate (0.4 mmol) in sequence. Connect the double manifold, evacuate and replace the gas three times under argon atmosphere, and add alkyne reagent of formula III-1 (0.3 mmol) and 1,4-dioxane (1 mL) while maintaining the gas flow. Seal the reaction system, and carry out the reaction at 40 °C for 12 hours. After the reaction is completed, filter the reaction system through a small amount of silica gel and concentrate it. The obtained concentrate is purified by column chromatography with petroleum ether:ethyl acetate at a ratio of 5:1 to obtain benzo-fused five-membered ring of formula IV-1 P -chiral phosphine oxide.

[0109] The obtained concentrated crude product was purified by column chromatography to obtain the target compound of formula IV-1 as an orange-red oil, 85.3 mg, with a yield of 93%, a dr value of 13:1, and an ee value of 99% (Daicel Chiralpak IA column), hexane / isopropanol = 80 / 20, flow rate 1.0 mL / min, 254 nm, t major = 10.3 min, t minor = 9.4 min. [α] 20 D =+16.9 (c=0.1, chloroform).

[0110] The characterization of compound of formula IV-1 is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.57 (t, J = 8.1 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.35 (dd, J = 7.7, 2.1 Hz, 1H), 7.29 (td, J = 7.3, 2.9 Hz, 1H), 7.25– 7.16 (m, 3H), 7.15 – 7.05 (m, 10H), 7.03 – 6.94 (m, 2H), 5.30 (d, J = 4.5 Hz, 1H), 4.98 (d, J = 4.5 Hz, 1H), 3.17 (s, 2H), 2.92 (dd, J= 15.0, 5.1 Hz, 2H), 2.72 (dd, J = 17.7, 15.5 Hz, 1H), 2.56 (dd, J = 15.3, 6.9 Hz, 1H).

[0111] 13 C NMR (100 MHz, CDCl 3 ) δ 150.59 (d, J C-P = 25.6 Hz), 145.52 (d, J C-P = 3.2 Hz), 140.31 (d, J C-P = 3.1 Hz), 139.17 (d, J C-P = 9.2 Hz), 133.54 (d, J C-P = 96.7 Hz), 132.59 (d, J C-P = 2.4 Hz), 131.63, 129.21 (d, J C-P = 8.3 Hz), 128.67, 128.44, 128.41, 128.31, 128.20, 127.97, 127.89, 127.22, 127.09 (d, J C-P = 12.3 Hz), 126.46, 123.19, 117.69 (d, J C-P = 9.3 Hz), 86.52, 83.95, 52.65 (d, J C-P = 5.9 Hz), 41.00 (d, J C-P = 65.8 Hz), 38.52 (d, J C-P = 62.1 Hz), 34.26 (d, J C-P = 7.4 Hz).

[0112] 31 P{ 1 H} NMR (162 MHz, CDCl 3) δ 55.81, 52.69.

[0113] FT-IR (neat) 3057, 2920, 2850, 1672, 1595, 1490, 1443, 1401, 1274, 1185, 1158, 1127, 1070, 1028, 1000, 910, 843, 755, 691, 593, 573, 476, 437 cm -1 .

[0114] HRMS (ESI) calcd for C 32 H 28 OP + [M+H] + 459.1872, found 459.1872.

[0115] Example 3: Synthesis of Product Ⅳ-2

[0116] The experimental method of Example 3 refers to Example 2, using the prochiral phosphine oxide compound shown in Formula Ⅱ-2 and the alkynylation reagent shown in Formula Ⅲ-1. The remaining operation steps are the same as those in Example 2, and the corresponding target compound Ⅳ-2 is finally obtained.

[0117] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound of Formula Ⅳ-2 as an orange-red oil, 83.2 mg, with a yield of 88%, a dr value > 20:1, and an ee value of 99% (Daicel Chiralpak IC column), hexane / isopropanol = 85 / 15, flow rate 1.0 mL / min, 254 nm, t major = 52.9 min, t minor = 49.3 min. [α] 20 D =+12.4 (c=0.1, chloroform).

[0118] The characterization of the compound of Formula Ⅳ-2 is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.57 (t, J = 8.1 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.35 (dd, J= 7.7, 2.1 Hz, 1H), 7.29 (td, J = 7.3, 2.9 Hz, 1H), 7.25– 7.16 (m, 3H), 7.15 – 7.05 (m, 10H), 7.03 – 6.94 (m, 2H), 5.30 (d, J = 4.5Hz, 1H), 4.98 (d, J = 4.5 Hz, 1H), 3.17 (s, 2H), 2.92 (dd, J = 15.0, 5.1 Hz,2H), 2.72 (dd, J = 17.7, 15.5 Hz, 1H), 2.56 (dd, J = 15.3, 6.9 Hz, 1H).

[0119] 13 C NMR (100 MHz, CDCl 3 ) δ 150.59 (d, J C-P = 25.6 Hz), 145.52 (d, J C-P =3.2 Hz), 140.31 (d, J C-P = 3.1 Hz), 139.17 (d, J C-P = 9.2 Hz), 133.54 (d, J C-P =96.7 Hz), 132.59 (d, J C-P = 2.4 Hz), 131.63, 129.21 (d, J C-P = 8.3 Hz), 128.67,128.44, 128.41, 128.31, 128.20, 127.97, 127.89, 127.22, 127.09 (d, J C-P = 12.3Hz), 126.46, 123.19, 117.69 (d, J C-P = 9.3 Hz), 86.52, 83.95, 52.65 (d, J C-P= 5.9 Hz), 41.00 (d, J C-P = 65.8 Hz), 38.52 (d, J C-P = 62.1 Hz), 34.26 (d, J C-P = 7.4 Hz).

[0120] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.81, 52.69.

[0121] FT-IR (neat) 3057, 2920, 2850, 1672, 1595, 1490, 1443, 1401, 1274, 1185, 1158, 1127, 1070, 1028, 1000, 910, 843, 755, 691, 593, 573, 476, 437 cm -1 .

[0122] HRMS (ESI) calcd for C 32 H 28 OP + [M+H] + 459.1872, found 459.1872.

[0123] Example 4: Synthesis of Product Ⅳ-3

[0124] In formulas Ⅲ-2 and Ⅳ-3, R 3 is .

[0125] The experimental method of Example 4 refers to Example 2, using the prochiral phosphine oxide compound shown in Formula Ⅱ-1 and the alkynylation reagent shown in Formula Ⅲ-2. The remaining operation steps are the same as those in Example 2, and the corresponding target compound Ⅳ-3 is finally obtained.

[0126] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound Formula Ⅳ-3 as a light brown oil, 87.9 mg, with a yield of 93%, a dr value of 12:1, and an ee value of 99%, (Daicel Chiralpak IA column), hexane / isopropanol = 90 / 10, flow rate 1.0 mL / min, 254 nm, tmajor = 21.2 min, t minor = 19.7 min. [α] 20 D = +17.1 (c=0.1, chloroform).

[0127] The characterization of the compound of Formula IV - 3 is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.55 (t, J = 8.1 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.34 (dd, J = 7.9, 2.3 Hz, 1H), 7.27 (td, J = 7.4, 2.7 Hz, 1H), 7.22–7.14 (m, 3H), 7.12 – 7.04 (m, 5H), 6.99 (t, J = 9.1 Hz, 4H), 6.90 (d, J = 7.8 Hz, 2H), 5.29 (d, J = 4.5 Hz, 1H), 4.97 (d, J = 4.5 Hz, 1H), 3.14 (s, 2H), 2.90 (dd, J = 14.9, 4.8 Hz, 2H), 2.71 (dd, J = 17.9, 15.1 Hz, 1H), 2.55 (dd, J = 15.2, 6.8 Hz, 1H), 2.18 (s, 3H).

[0128] 13 C NMR (100 MHz, CDCl 3 ) δ 150.55 (d, J C-P = 25.7 Hz), 145.49 (d, J C-P = 2.9 Hz), 140.25 (d, J C-P = 2.9 Hz), 139.12 (d, J C-P = 9.1 Hz), 137.92, 133.48 (d,J C-P = 96.6 Hz), 132.50 (d, J C-P = 2.2 Hz), 131.44, 129.12 (d, J C-P = 7.6Hz), 128.89, 128.58, 128.36, 128.26 (d, J C-P = 10.2 Hz), 127.81, 127.16,127.13, 127.03 (d, J C-P = 12.6 Hz), 126.39, 120.06, 117.59 (d, J C-P = 9.2 Hz),85.70, 83.95, 52.56 (d, J C-P = 5.8 Hz), 40.93 (d, J C-P = 65.7 Hz), 38.43 (d, J C-P = 62.0 Hz), 34.21 (d, J C-P = 7.3 Hz), 21.42.

[0129] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.89, 52.68.

[0130] FT-IR (neat) 3057, 2922, 2852, 1674, 1595, 1509, 1495, 1445, 1403,1266, 1181, 1159, 1126, 1073, 1031, 1001, 911, 816, 761, 698, 574, 528, 504,440 cm -1 .

[0131] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0132] Example 5: Synthesis of Product Ⅳ-4

[0133] In Formulas Ⅱ-3 and Ⅳ-4, R 2 is .

[0134] The experimental method of Example 5 refers to Example 2, using the prochiral phosphine oxide compound shown in Formula Ⅱ-3 and the alkynylation reagent shown in Formula Ⅲ-1. The remaining operation steps are the same as those in Example 2, and the corresponding target compound Ⅳ-4 is finally obtained.

[0135] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound Formula Ⅳ-4 as a light yellow oil, 79.8 mg, with a yield of 82%, a dr value of 11:1, and an ee value of 93% (Daicel Chiralpak IC column), hexane / isopropanol = 80 / 20, flow rate 1.0 mL / min, 254 nm, t major = 35.6 min, t minor = 22.0min. [α] 20 D =+11.9 (c=0.1, chloroform).

[0136] The characterization of Compound Formula Ⅳ-4 is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.66 (t, J = 8.0 Hz, 1H), 7.65 – 7.56 (m,1H), 7.53 (dd, J = 7.8, 2.3 Hz, 1H), 7.43 (dq, J = 5.5, 3.3, 2.5 Hz, 2H),7.32 – 7.23 (m, 6H), 7.22 – 7.10 (m, 6H), 6.86 – 6.72 (m, 2H), 4.84 (dd, J =4.7, 1.8 Hz, 1H), 4.67 (d, J = 4.5 Hz, 1H), 3.45 (s, 2H), 3.30 – 3.14 (m,2H), 2.93 (q, J = 16.8 Hz, 2H), 2.40 (dd, J= 16.1, 7.7 Hz, 1H), 2.29 (t, J =16.7 Hz, 1H), 2.07 – 1.89 (m, 2H).

[0137] 13 C NMR (100 MHz, CDCl 3 ) δ 151.32 (d, J C-P = 27.4 Hz), 140.44 (d, J C-P =9.7 Hz), 138.90 (d, J C-P = 1.4 Hz), 137.08, 134.23 (d, J C-P = 96.0 Hz), 132.83(d, J C-P = 2.3 Hz), 131.78, 130.61, 129.36, 128.98 (d, J C-P = 8.4 Hz), 128.43,128.38, 128.36, 128.26, 128.07, 127.09, 126.35, 125.51 (d, J C-P = 12.8 Hz),123.37, 116.38 (d, J C-P = 9.3 Hz), 86.38, 83.81, 49.97 (d, J C-P = 4.6 Hz),45.95 (d, J C-P = 4.8 Hz), 43.86 (d, J C-P = 2.3 Hz), 38.19 (d, J C-P = 63.6 Hz),35.23 (d, J C-P = 3.4 Hz), 34.43 (d, J C-P = 66.9 Hz).

[0138] 31 P{ 11H NMR (162 MHz, CDCl 3 ) δ 55.10, 53.29.

[0139] FT-IR (neat) 3059, 3026, 2921, 2852, 1639, 1596, 1491, 1454, 1443, 1403, 1261, 1216, 1181, 1163, 1139, 1072, 1030, 897, 844, 808, 756, 740, 692, 612, 588, 528, 490, 441, 406 cm -1 .

[0140] HRMS (ESI) calcd for C 34 H 32 OP + [M+H] + 487.2185, found 487.2185.

[0141] Example 6: Synthesis of Product Ⅳ-5

[0142] In formulas Ⅲ-3 and Ⅳ-5, R 3 is .

[0143] The experimental method of Example 6 refers to Example 2, using the prochiral phosphine oxide compound shown in Formula Ⅱ-1 and the alkynylation reagent shown in Formula Ⅲ-3. The remaining operation steps are the same as those in Example 2, and the corresponding target compound Ⅳ-5 is finally obtained.

[0144] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound Formula Ⅳ-5 as a brown oil, 88.2 mg, with a yield of 85%, a dr value of 16:1, and an ee value of 98% (Daicel Chiralpak IA column), hexane / isopropanol = 80 / 20, flow rate 1.0 mL / min, 254 nm, t major = 23.0 min, t minor = 12.3min. [α] 20 D =+39.2 (c=0.1, chloroform).

[0145] The characterization of the compound of Formula Ⅳ-5 is as follows: 11H NMR (400 MHz, CDCl 3 ) δ 7.56 (t, J J = 8.1 Hz, 1H), 7.46 (t, J J = 7.6Hz, 1H), 7.34 (dd, J J = 7.9, 2.3 Hz, 1H), 7.28 (td, J J = 7.4, 2.9 Hz, 1H), 7.24– 7.14 (m, 3H), 7.14 – 7.02 (m, 5H), 7.01 – 6.94 (m, 2H), 6.25 (s, 3H), 5.29(d, J J = 4.5 Hz, 1H), 4.97 (d, J J = 4.5 Hz, 1H), 3.61 (s, 6H), 3.14 (s, 2H),2.91 (dd, J J = 14.9, 6.4 Hz, 2H), 2.69 (dd, J J = 17.9, 15.2 Hz, 1H), 2.56 (dd, J J = 15.2, 6.8 Hz, 1H).

[0146] 13 13C NMR (100 MHz, CDCl 3 ) δ 160.36, 150.52 (d, J C-P J = 25.5 Hz), 145.36(d, J C-P J = 2.9 Hz), 140.22 (d, J C-P J = 2.9 Hz), 139.09 (d, J C-P J = 9.2 Hz), 133.48(d, J C-P J = 96.7 Hz), 132.53 (d, J C-P J = 2.2 Hz), 129.12 (d, J C-P J = 8.0 Hz),128.61, 128.38, 128.34, 128.24, 127.83, 127.17, 127.06 (d, JC-P = 12.1 Hz), 126.38, 124.43, 117.64 (d, J C-P = 9.2 Hz), 109.36, 101.42, 86.24, 83.92, 55.37, 52.53 (d, J C-P = 5.9 Hz), 40.98 (d, J C-P = 65.8 Hz), 38.40 (d, J C-P = 62.2 Hz), 34.17 (d, J C-P = 7.3 Hz).

[0147] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.78, 52.63.

[0148] FT-IR (neat) 2924, 2850, 1673, 1586, 1495, 1445, 1420, 1354, 1300, 1275, 1194, 1153, 1062, 1026, 1001, 928, 836, 761, 699, 683, 574, 477, 437 cm -1 .

[0149] HRMS (ESI) calcd for C 34 H 32 O 3 P + [M+H] + 519.2084, found 519.2084.

[0150] Example 7: Synthesis of Product Ⅳ-6

[0151] The experimental method of Example 7 refers to Example 2, using the prochiral phosphine oxide shown in Formula Ⅱ-1 and the alkynylation reagent shown in Formula Ⅲ-4. The remaining operation steps are the same as those in Example 2, and the corresponding target compound Ⅳ-6 is finally obtained.

[0152] The obtained concentrated crude product was separated and purified by column chromatography to give the target compound Formula IV-6 as a pale yellow oil, 76.4 mg, with a yield of 84%, a dr value > 20:1, an ee value of 98% (Daicel Chiralpak IA column), hexane / isopropanol = 90 / 10, flow rate 1.0 mL / min, 254 nm, t major = 9.6 min, t minor = 8.7 min. [α] 20 D =+11.6 (c=0.1, chloroform).

[0153] The characterization of the compound of Formula IV-6 is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.65 (t, J = 8.4 Hz, 1H), 7.56 (tt, J = 7.4, 1.5 Hz, 1H), 7.46 – 7.35 (m, 2H), 7.34 – 7.24 (m, 3H), 7.23 – 7.12 (m, 5H), 7.04 (dd, J = 7.9, 1.8 Hz, 2H), 5.39 (dd, J = 4.8, 0.9 Hz, 1H), 5.03 (dd, J = 4.7, 1.2 Hz, 1H), 3.06 (s, 2H), 2.94 (dd, J = 14.7, 4.2 Hz, 2H), 2.76 (dd, J = 18.4, 15.2 Hz, 1H), 2.62 (dd, J = 15.2, 7.0 Hz, 1H), 0.00 (s, 9H).

[0154] 13 C NMR (100 MHz, CDCl 3 ) δ 150.14 (d, J C-P = 25.9 Hz), 145.40 (d, J C-P = 2.6 Hz), 140.30 (d, JC-P = 3.1 Hz), 139.11 (d, J C-P = 9.4 Hz), 133.68 (d, J C-P =96.9 Hz), 132.39 (d, J C-P = 2.4 Hz), 129.14 (d, J C-P = 8.1 Hz), 128.57, 128.38,128.27, 128.17, 127.80, 127.17, 127.03, 126.43, 117.54 (d, J C-P = 9.2 Hz),103.58, 88.83, 52.26 (d, J C-P = 6.2 Hz), 40.88 (d, J C-P = 65.7 Hz), 38.56 (d, J C-P = 61.9 Hz), 34.70 (d, J C-P = 8.0 Hz), -0.21.

[0155] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.23, 52.09.

[0156] FT-IR (neat) 3059, 2958, 2176, 1593, 1495, 1444, 1403, 1301, 1250,1231, 1214, 1193, 1165, 1139, 1074, 1034, 1000, 909, 840, 760, 727, 698, 653,643, 631, 603, 576, 467, 438 cm -1 .

[0157] HRMS (ESI) calcd for C 29 H 32 OPSi + [M+H] + 455.1955, found 455.1950.

[0158] Example 8: Synthesis of Product Ⅳ-7

[0159] The experimental method of Example 8 refers to Example 2, using the prochiral phosphine oxide compound shown in Formula Ⅱ-1 and the alkynylation reagent shown in Formula Ⅲ-5. The remaining operation steps are the same as those in Example 2, and the corresponding target compound Ⅳ-7 is finally obtained.

[0160] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound Formula Ⅳ-7 as a light yellow oil, 71.8 mg, with a yield of 85%, a dr value of 8:1, and an ee value of 98% (Daicel Chiralpak IA column), hexane / isopropanol = 93 / 7, flow rate 1.0 mL / min, 254 nm, t major = 28.1 min, t minor = 25.0 min. [α] 20 D =+15.3 (c=0.1, chloroform).

[0161] The characterization of Compound Ⅳ-7 is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.62 (dd, J = 9.0, 7.4 Hz, 1H), 7.54 (tt, J = 7.6, 1.5 Hz, 1H), 7.36 (ddd, J = 11.9, 7.7, 2.9 Hz, 2H), 7.29 – 7.21 (m,3H), 7.21 – 7.10 (m, 5H), 7.02 – 6.96 (m, 2H), 5.37 (d, J = 4.7 Hz, 1H), 5.03(d, J = 4.7 Hz, 1H), 3.00 – 2.88 (m, 4H), 2.75 (dd, J = 18.5, 15.2 Hz, 1H),2.54 (dd, J = 15.2, 6.8 Hz, 1H), 1.06 – 0.97 (m, 1H), 0.56 (ddt, J= 6.4, 5.0, 2.8 Hz, 2H), 0.45 – 0.28 (m, 2H).

[0162] 13 C NMR (100 MHz, CDCl 3 ) δ 150.45 (d, J C-P = 26.1 Hz), 145.80 (d, J C-P = 2.6 Hz), 140.35 (d, J C-P = 3.2 Hz), 139.17 (d, J C-P = 9.5 Hz), 133.68 (d, J C-P = 97.0 Hz), 132.41 (d, J C-P = 2.5 Hz), 129.10 (d, J C-P = 8.1 Hz), 128.57, 128.38, 128.15 (d, J C-P = 10.2 Hz), 127.80, 127.13, 127.09, 127.00 (d, J C-P = 12.4 Hz), 126.44, 117.56 (d, J C-P = 9.2 Hz), 87.19, 71.70, 52.62 (d, J C-P = 5.9 Hz), 40.59 (d, J C-P = 65.9 Hz), 38.56 (d, J C-P = 61.8 Hz), 33.67 (d, J C-P = 7.8 Hz), 8.05 (d, J C-P = 2.7 Hz), -0.53.

[0163] 31 P{ 1 H} NMR (162 MHz, CDCl 3) δ 55.95, 52.62.

[0164] FT-IR (neat) 3058, 2223, 1621, 1593, 1495, 1444, 1402, 1301, 1230, 1215, 1192, 1164, 1138, 1073, 1029, 1001, 907, 881, 844, 811, 762, 726, 698, 643, 601, 573, 476, 436 cm -1 .

[0165] HRMS (ESI) calcd for C 29 H 28 OP + [M+H] + 423.1872, found 423.1872.

[0166] Example 9: Synthesis of Products V and VI

[0167] Experimental procedure: The benzo-fused five-membered ring of Formula IV-6 P -Chiral phosphine oxide (0.2 mmol) was added to tetrahydrofuran (1 mL), and then tetrabutylammonium fluoride reagent (0.3 mmol) was added. The mixture was stirred at room temperature until the reaction was complete. The reaction was quenched with water, and the aqueous phase was extracted three times with ethyl acetate. The organic phase was concentrated under reduced pressure, and the resulting concentrate was purified by column chromatography using a 2:1 ratio of petroleum ether to ethyl acetate to obtain the terminal alkyne with the TMS group removed P -Chiral phosphine oxide compounds of Formulas V and VI.

[0168] The resulting concentrated crude product was purified by column chromatography to obtain the target compound of Formula V as a pale yellow oil, 32.1 mg, with a yield of 42%, a dr value > 20:1, and an ee value of 98% (Daicel Chiralpak IA column), hexane / isopropanol = 80 / 20, flow rate 1.0 mL / min, 254 nm, t major = 10.6 min, t minor = 9.7min. [α] 20 D =+20.4 (c=0.1, chloroform).

[0169] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound. Compound VI was a white solid, 44.4 mg, with a yield of 58%, a dr value > 20:1, and an ee value of 98% (Daicel Chiralpak IA column), hexane / isopropanol = 80 / 20, flow rate 1.0 mL / min, 254 nm, t major = 9.6 min, t minor = 11.4 min. [α] 20 D =+17.2 (c=0.1, chloroform).

[0170] The characterization of compound V is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 (t, J = 8.4 Hz, 1H), 7.55 (t, J = 7.7 Hz, 1H), 7.38 (dd, J = 7.5, 2.8 Hz, 2H), 7.26 (dd, J = 7.9, 2.1 Hz, 3H), 7.18 (dd, J = 5.2, 2.3 Hz, 3H), 7.12 (dd, J = 6.7, 2.9 Hz, 2H), 6.99 (d, J = 7.2 Hz, 2H), 5.37 (d, J = 4.1 Hz, 1H), 5.05 (d, J = 4.7 Hz, 1H), 3.04 (s, 2H), 2.96 (dd, J = 15.0, 7.2 Hz, 2H), 2.77 (ddd, J = 18.1, 15.1, 2.1 Hz, 1H), 2.59 (ddd, J = 15.3, 7.0, 2.2 Hz, 1H), 1.91 (d, J = 2.6 Hz, 1H).

[0171] 13 C NMR (100 MHz, CDCl 3 ) δ 149.99 (d,J C-P = 25.7 Hz), 145.21 (d, J C-P =2.8 Hz), 140.19 (d, J C-P = 3.3 Hz), 138.99 (d, J C-P = 9.2 Hz), 133.41 (d, J C-P =96.8 Hz), 132.56 (d, J C-P = 2.4 Hz), 129.25 (d, J C-P = 8.3 Hz), 128.62, 128.34,128.33 (d, J C-P = 10.1 Hz), 127.79, 127.23, 127.01, 126.79 (d, J C-P = 12.3 Hz),126.35, 117.66 (d, J C-P = 9.3 Hz), 80.59, 71.88, 52.03 (d, J C-P = 6.1 Hz),40.56 (d, J C-P = 65.7 Hz), 38.32 (d, J C-P = 62.1 Hz), 33.01 (d, J C-P = 7.7 Hz).

[0172] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 52.60.

[0173] FT-IR (neat) 3293, 3057, 2923, 1733, 1621, 1593, 1574, 1495, 1443, 1402, 1301, 1230, 1194, 1164, 1137, 1074, 1030, 1001, 903, 845, 762, 699, 644, 603, 574, 472, 437 cm -1 .

[0174] HRMS (ESI) calcd for C 26 H 24 OP + [M+H] + 383.1559, found 383.1556.

[0175] The characterization of the compound of Formula VI is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (t, J J = 8.9 Hz, 1H), 7.60 (t, J J = 7.6Hz, 1H), 7.54 – 7.43 (m, 2H), 7.33 – 7.18 (m, 6H), 7.10 (dd, J J = 7.1, 1.9 Hz,2H), 7.05 – 7.00 (m, 2H), 5.45 (d, J J = 25.9 Hz, 1H), 3.14 (d, J J = 2.6 Hz,2H), 3.03 (dd, J J = 18.1, 14.8 Hz, 1H), 2.82 (dd, J J = 14.8, 7.3 Hz, 1H), 2.60(d, J J = 2.6 Hz, 3H), 1.96 (t, J J = 2.6 Hz, 1H).

[0176] 13 C NMR (100 MHz, CDCl 3 ) δ 156.58 (d, J C-P J = 2.0 Hz), 149.95 (d, J C-P= 25.4 Hz), 145.70 (d, J C-P = 2.8 Hz), 141.72 (d, J C-P = 17.5 Hz), 135.58 (d, J C-P = 101.9 Hz), 132.37 (d, J C-P = 2.5 Hz), 128.94, 128.80 (d, J C-P = 8.3 Hz), 128.73 (d, J C-P = 10.4 Hz), 128.69, 128.29, 127.13, 127.06, 126.90 (d, J C-P = 12.3 Hz), 125.84, 119.03 (d, J C-P = 98.4 Hz), 80.81, 71.90, 52.34 (d, J C-P = 6.0 Hz), 44.31 (d, J C-P = 70.9 Hz), 32.66 (d, J C-P = 8.7 Hz), 19.35 (d, J C-P = 7.3 Hz).

[0177] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 42.07.

[0178] m.p.: 148.1 - 169.3 °C.

[0179] FT-IR (neat) 3310, 2918, 1603, 1573, 1492, 1444, 1422, 1406, 1378, 1263, 1229, 1219, 1182, 1164, 1137, 1078, 1056, 1032, 998, 981, 902, 880, 826, 810, 798, 763, 751, 740, 702, 652, 634, 601, 575, 555, 494, 466, 449 cm -1 .

[0180] HRMS (ESI) calcd for C 26 H 24 OP + [M+H] + 383.1559, found 383.1556.

[0181] Table 1 Single crystal data of Compound VI

[0182] Example 10: Synthesis of Product VII

[0183] Experimental procedure: Add compound V (0.194 mmol), copper sulfate pentahydrate (0.04 mmol), sodium ascorbate (0.08 mmol), potassium carbonate (0.23 mmol), and sodium azide (0.21 mmol) into a mixed solution of DMF:water (2:1, 6 mL), then add benzyl bromide (0.21 mmol), and stir overnight at 50 °C. After the reaction is completed, extract the aqueous phase three times with ethyl acetate, concentrate under reduced pressure, and purify by column chromatography using petroleum ether:ethyl acetate at a ratio of 1:1 to obtain the triazole-based P -chiral phosphine oxide Compound VII.

[0184] The obtained concentrated crude product was purified by column chromatography to obtain the target compound Compound VII as a pale yellow oil, 95.0 mg, with a yield of 95%, a dr value > 20:1, and an ee value of 98% (Daicel Chiralpak IB column), hexane / isopropanol / CH 2 Cl 2 = 80 / 10 / 10, flow rate 1.0 mL / min, 230 nm, t major = 26.7 min, t minor= 35.2 min. [α] 20 D = +20.0 (c = 0.1, chloroform).

[0185] The characterization of the compound of formula VII is as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.54 (t, J = 8.2 Hz, 1H), 7.48 (t, J = 7.6Hz, 1H), 7.35 (dd, J = 7.9, 2.5 Hz, 1H), 7.32 – 7.21 (m, 7H), 7.18 – 7.11 (m,3H), 7.03 (ddd, J = 12.8, 7.0, 2.0 Hz, 6H), 6.44 (s, 1H), 5.31 (d, J = 4.6Hz, 1H), 5.34 – 5.19 (m, 2H), 4.98 (d, J = 4.7 Hz, 1H), 3.68 (d, J = 15.0 Hz,1H), 3.51 (dd, J = 15.0, 2.9 Hz, 1H), 2.80 (dd, J = 14.5, 6.6 Hz, 2H), 2.65 –2.54 (m, 2H).

[0186] 13 C NMR (100 MHz, CDCl 3 ) δ 149.10 (d, J C-P = 26.6 Hz), 146.10 (d, J C-P =1.6 Hz), 143.45, 140.07 (d, J C-P = 3.2 Hz), 138.74 (d, J C-P = 9.5 Hz), 134.50,134.28 (d, J C-P = 96.5 Hz), 132.10 (d, J C-P= 2.5 Hz), 129.30 (d, J C-P = 8.1Hz), 128.78, 128.50, 128.24, 128.11, 128.03 (d, J C-P = 10.1 Hz), 127.59,127.54, 127.12, 126.99, 126.96, 126.18, 122.34, 117.34 (d, J C-P = 9.1 Hz),53.62, 52.78 (d, J C-P = 5.8 Hz), 39.46 (d, J C-P = 65.1 Hz), 38.98 (d, J C-P = 8.3Hz), 38.49 (d, J C-P = 61.8 Hz).

[0187] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 52.32.

[0188] FT-IR (neat) 3058, 2923, 2853, 1593, 1495, 1443, 1403, 1361, 1302,1259, 1184, 1126, 1053, 1029, 906, 767, 728, 699, 599, 560, 437 cm -1 .

[0189] HRMS (ESI) calcd for C 33 H 31 N 3 OP + [M+H] + 516.2199, found 516.2198.

[0190] Example 11: Synthesis of Product VIII

[0191] Experimental procedure: First, pyridine (6.2 mmol) was added to a 10 mL round-bottom flask containing anhydrous toluene (2 mL), and trichlorosilane (3 mmol) was added. After stirring at room temperature for five minutes, a toluene solution (1 mL) of the triazole-based P -chiral phosphine oxide compound (0.2 mmol) was added. The mixture was stirred at 80 °C for twelve hours, then cooled to room temperature, placed in a -40 °C low-temperature reaction bath, and borane dimethyl sulfide complex (1 mmol) was added. After stirring at low temperature for fifteen minutes, it was transferred to room temperature and reacted for two hours. After the reaction was completed, the reaction was quenched with saturated ammonium chloride, and liquid separation was carried out with ethyl acetate. The aqueous phase was extracted three times, filtered and concentrated. The obtained concentrate was separated and purified by column chromatography using petroleum ether:ethyl acetate at a ratio of 1:1 to obtain the triazole-based chiral phosphine boron compound of formula ( S , R , R )-Ⅷ and formula ( R , )-Ⅷ.

[0192] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound of formula ( S , R )-Ⅷ as a white powder, with a yield of 59%, a dr value > 20:1, an ee value of 98%, (Daicel Chiralpak IB column), hexane / isopropanol / CH 2 Cl 2 = 88 / 8 / 4, flow rate 1.0 mL / min, 230 nm, t major minor = 20.7 min, t 20 = 25.2 min. [α] D 1 = +12.8 (c = 0.1, chloroform).

[0193] The characterization of the compound of formula ( S , R )-Ⅷ is as follows: 1 1H NMR (400 MHz, CDCl 3 ) δ 7.45 – 7.34 (m, 2H), 7.33 – 7.21 (m, 8H), 7.21 – 7.08 (m, 5H), 7.06 – 6.99 (m, 2H), 6.98 – 6.91 (m, 2H), 6.13 (s, 1H), 5.35 – 5.22 (m, 2H), 5.21 (dd, J= 4.2, 0.8 Hz, 1H), 4.83 (d, J = 4.4 Hz,1H), 3.73 (d, J = 15.0 Hz, 1H), 3.45 (dd, J = 15.1, 1.6 Hz, 1H), 2.86 – 2.68(m, 2H), 2.56 (dd, J = 15.4, 4.2 Hz, 1H), 2.40 (dd, J = 15.4, 8.2 Hz, 1H),0.50 (br, 3H).

[0194] 13 C NMR (100 MHz, CDCl 3 ) δ 150.87 (d, J C-P = 12.3 Hz), 147.34, 143.64,139.98 (d, J C-P = 2.3 Hz), 139.89 (d, J C-P = 6.5 Hz), 134.46, 133.61 (d, J C-P =54.1 Hz), 131.28 (d, J C-P = 2.2 Hz), 130.56 (d, J C-P = 11.7 Hz), 128.97,128.68, 128.43, 128.36, 128.27, 127.94, 127.82, 127.20, 127.14, 127.12,126.50, 122.20, 117.54 (d, J C-P = 8.7 Hz), 57.37 (d, J C-P = 4.0 Hz), 53.85,39.25 (d, J C-P = 6.0 Hz), 35.15 (d, J C-P = 33.7 Hz), 34.11 (d, J C-P = 24.4 Hz).

[0195] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 32.75.

[0196] FT-IR (neat) 3057, 2925, 2373, 1599, 1495, 1444, 1359, 1301, 1260, 1221, 1156, 1056, 1029, 904, 863, 765, 699, 606, 558, 456 cm -1 .

[0197] HRMS (ESI) calcd for C 33 H 34 BN 3 P + [M+H] + 514.2578, found 514.2578.

[0198] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound of formula ( R , R )-Ⅷ as a white powder, with a yield of 38%, a dr value > 20:1, an ee value of 98%, (Daicel Chiralpak IB column), hexane / isopropanol / CH 2 Cl 2 = 88 / 8 / 4, flow rate 1.0 mL / min, 230 nm, t major = 27.4 min, t minor = 31.7 min. [α] 20 D =+9.8 (c=0.1, chloroform).

[0199] The compound of formula ( R , R )-Ⅷ was characterized as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.46 – 7.15 (m, 12H), 7.18 – 7.09 (m, 3H), 7.12 – 7.05 (m, 2H), 6.97 – 6.89 (m, 2H), 5.74 (s, 1H), 5.32 – 5.17 (m, 3H), 4.79 (d,J = 4.5 Hz, 1H), 4.25 (d, J = 16.2 Hz, 1H), 3.34 (dd, J = 16.2, 1.8Hz, 1H), 2.91 – 2.74 (m, 2H), 2.42 (d, J = 6.2 Hz, 2H), 0.41 (br, 3H).

[0200] 13 C NMR (126 MHz, CDCl 3 ) δ 150.17 (d, J C-P = 12.1 Hz), 147.17, 141.70,139.73, 139.48 (d, J C-P = 6.9 Hz), 134.20 (d, J C-P = 53.6 Hz), 131.93, 131.64,130.72 (d, J C-P = 11.6 Hz), 129.48, 129.41, 129.10, 128.98, 128.75, 128.42,128.02, 127.57, 126.98, 126.89, 126.41, 123.56, 117.75 (d, J C-P = 8.6 Hz),57.05 (d, J C-P = 4.0 Hz), 55.69, 37.70 (d, J C-P = 5.9 Hz), 34.44 (d, J C-P = 62.1Hz), 34.40 (d, J C-P = 4.7 Hz).

[0201] 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 34.58.

[0202] FT-IR (neat) 2921, 2851, 2382, 1712, 1559, 1494, 1444, 1361, 1261, 1211, 1144, 1081, 1057, 1029, 906, 855, 767, 734, 698, 645, 607, 558, 495, 456 cm -1 .

[0203] HRMS (ESI) calcd for C 33 H 34 BN 3 P + [M+H] + 514.2578, found 514.2578.

[0204] Referring to the above preparation and treatment, the compounds claimed in other parts of the present invention are as follows:

[0205] The characterization of Compound IV-8 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 52.17.

[0206] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.69 – 7.61 (m, 1H), 7.54 (tt, J J = 7.3, 1.5Hz, 1H), 7.48 (dd, J = 7.8, 2.6 Hz, 1H), 7.37 (tdd, J = 7.3, 3.2, 1.1 Hz, 1H), 7.33 – 7.22 (m, 3H), 7.22 – 7.12 (m, 6H), 7.09 (dd, J J = 7.4, 1.5 Hz, 1H), 7.07 – 6.98 (m, 4H), 5.38 (dd, J J = 4.7, 0.9 Hz, 1H), 5.03 (dd, J J = 4.8, 1.0 Hz, 1H), 3.37 – 3.25 (m, 2H), 3.01 – 2.78 (m, 3H), 2.66 (dd, J= 15.2, 6.9 Hz, 1H), 2.01 (s, 3H).

[0207] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0208]

[0209] The characterization of compound Ⅳ-9 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.46, 52.21.

[0210] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.64 (t, J = 8.3 Hz, 1H), 7.55 (t, J = 7.6Hz, 1H), 7.47 (dd, J = 7.7, 2.5 Hz, 1H), 7.37 (td, J = 7.4, 3.1 Hz, 1H), 7.30– 7.23 (m, 4H), 7.23 – 7.12 (m, 7H), 7.10 (dd, J = 8.2, 6.6 Hz, 3H), 5.38 (d, J = 4.7 Hz, 1H), 5.05 (d, J = 4.7 Hz, 1H), 3.32 (s, 2H), 2.97 (dd, J = 14.9, 2.7 Hz, 2H), 2.84 (dd, J = 18.2, 15.2 Hz, 1H), 2.67 (dd, J = 15.2, 6.9 Hz, 1H).

[0211] HRMS (ESI) calcd for C 32 H 27 ClOP + [M+H] +493.1483, found 493.1486.

[0212]

[0213] The characterization of Compound Ⅳ-10 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.82, 52.24.

[0214] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.55 (t, J J = 8.1 Hz, 1H), 7.50 – 7.38 (m,2H), 7.27 (qd, J J = 9.4, 8.4, 4.4 Hz, 1H), 7.18 (dt, J J = 9.3, 6.6 Hz, 3H),7.13 – 6.95 (m, 9H), 6.73 – 6.63 (m, 2H), 5.30 (d, J J = 4.6 Hz, 1H), 4.96 (d, J J = 4.6 Hz, 1H), 3.66 (s, 3H), 3.22 (s, 2H), 2.82 (t, J J = 15.8 Hz, 3H), 2.60(dd, J J = 15.2, 6.7 Hz, 1H).

[0215] HRMS (ESI) calcd for C 33 H 30 O 2 P + [M+H] + 489.1978, found 489.1978.

[0216]

[0217] The characterization of Compound Ⅳ-11 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.82, 52.59.

[0218] 11H NMR (400 MHz, CDCl 3 ) δ 7.64 (t, J J = 8.2 Hz, 1H), 7.54 (t, J J = 7.6Hz, 1H), 7.43 (dd, J J = 7.9, 2.5 Hz, 1H), 7.37 (td, J J = 7.5, 3.1 Hz, 1H), 7.34– 7.21 (m, 3H), 7.24 – 7.09 (m, 5H), 7.12 – 6.91 (m, 6H), 5.38 (d, J J = 4.6Hz, 1H), 5.06 (d, J J = 4.6 Hz, 1H), 3.24 (s, 2H), 2.99 (dd, J J = 15.0, 4.8 Hz,2H), 2.80 (dd, J J = 18.0, 15.3 Hz, 1H), 2.64 (dd, J J = 15.2, 6.8 Hz, 1H), 2.24(s, 3H).

[0219] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2030.

[0220]

[0221] The characterization of compound Ⅳ-12 is as follows: 31 P{ 1 1H} NMR (162 MHz, CDCl 3 ) δ 55.78, 52.77.

[0222] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.65 (t, J J = 8.2 Hz, 1H), 7.55 (t, J J = 7.6Hz, 1H), 7.40 (dd, J= 7.7, 2.8 Hz, 2H), 7.32 – 7.25 (m, 3H), 7.23 – 7.14 (m,4H), 7.17 – 7.09 (m, 4H), 7.08 – 7.04 (m, 3H), 5.38 (d, J = 4.6 Hz, 1H), 5.06(d, J = 4.7 Hz, 1H), 3.25 (s, 2H), 3.03 (dd, J = 15.0, 7.4 Hz, 2H), 2.76 (dd, J = 17.8, 15.3 Hz, 1H), 2.62 (dd, J = 15.3, 7.0 Hz, 1H).

[0223] HRMS (ESI) calcd for C 32 H 27 ClOP + [M+H] + 493.1483, found 493.1483.

[0224]

[0225] The characterization of compound Ⅳ-13 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.75, 52.61.

[0226] 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 (t, J = 8.1 Hz, 1H), 7.53 (t, J = 7.6Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.36 (td, J = 7.5, 2.5 Hz, 1H), 7.31 –7.12 (m, 9H), 7.07 (t, J = 7.6 Hz, 2H), 6.83 – 6.67 (m, 3H), 5.38 (d, J = 4.4Hz, 1H), 5.06 (d, J( = 4.5 Hz, 1H), 3.70 (s, 3H), 3.24 (s, 2H), 3.00 (dd, J =15.0, 5.6 Hz, 2H), 2.79 (t, J = 16.5 Hz, 1H), 2.64 (dd, J = 15.3, 6.7 Hz,1H).

[0227] HRMS (ESI) calcd for C 33 H 30 O 2 P + [M+H] + 489.1978, found 489.1981.

[0228]

[0229] The characterization of compound Ⅳ-14 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.89, 52.68.

[0230] 1 H NMR (400 MHz, CDCl 3 ) δ 7.55 (t, J = 8.1 Hz, 1H), 7.44 (t, J = 7.6Hz, 1H), 7.34 (dd, J = 7.9, 2.3 Hz, 1H), 7.27 (td, J = 7.4, 2.7 Hz, 1H), 7.22– 7.14 (m, 3H), 7.12 – 7.04 (m, 5H), 6.99 (t, J = 9.1 Hz, 4H), 6.90 (d, J =7.8 Hz, 2H), 5.29 (d, J = 4.5 Hz, 1H), 4.97 (d, J = 4.5 Hz, 1H), 3.14 (s,2H), 2.90 (dd, J = 14.9, 4.8 Hz, 2H), 2.71 (dd, J= 17.9, 15.1 Hz, 1H), 2.55(dd, J = 15.2, 6.8 Hz, 1H), 2.18 (s, 3H).

[0231] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0232]

[0233] The characterization of compound Ⅳ-15 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.80, 52.83.

[0234] 1 H NMR (400 MHz, CDCl 3 ) δ 7.57 (t, J = 8.1 Hz, 1H), 7.47 (t, J = 7.6Hz, 1H), 7.31 (d, J = 6.9 Hz, 2H), 7.26 – 7.15 (m, 3H), 7.15 – 6.99 (m, 9H),7.00 – 6.93 (m, 2H), 5.31 (d, J = 4.4 Hz, 1H), 4.98 (d, J = 4.4 Hz, 1H), 3.16(s, 2H), 2.94 (dd, J = 14.9, 7.4 Hz, 2H), 2.70 (dd, J = 17.9, 15.3 Hz, 1H),2.54 (dd, J = 15.3, 6.7 Hz, 1H).

[0235] HRMS (ESI) calcd for C 32 H 27 ClOP + [M+H] + 493.1483, found 493.1483.

[0236]

[0237] Compound Ⅳ-16 was characterized as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.91, 52.72.

[0238] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.64 (t, J J = 8.1 Hz, 1H), 7.53 (t, J J = 7.6Hz, 1H), 7.42 (dd, J J = 7.7, 2.2 Hz, 1H), 7.36 (td, J J = 7.6, 2.2 Hz, 1H), 7.31– 7.23 (m, 3H), 7.21 – 7.10 (m, 7H), 7.08 – 7.03 (m, 2H), 6.79 – 6.67 (m,2H), 5.38 (d, J J = 4.4 Hz, 1H), 5.05 (d, J J = 4.4 Hz, 1H), 3.73 (s, 3H), 3.23(s, 2H), 2.99 (dd, J J = 14.9, 5.0 Hz, 2H), 2.81 (dd, J J = 18.0, 15.2 Hz, 1H),2.63 (dd, J J = 15.2, 6.7 Hz, 1H).

[0239] HRMS (ESI) calcd for C 33 H 30 O 2 P + [M+H] + 489.1978, found 489.1979.

[0240]

[0241] Compound Ⅳ-17 was characterized as follows: 31 P{ 1 H} NMR (162 MHz, CDCl3 ) δ 55.78, 52.96.

[0242] 1 H NMR (400 MHz, CDCl 3 ) δ 9.93 (s, 1H), 7.71 (d, J = 8.2 Hz, 2H), 7.67(t, J = 8.1 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.39 (dq, J = 6.2, 3.7, 3.3Hz, 2H), 7.36 – 7.25 (m, 5H), 7.23 – 7.12 (m, 5H), 7.09 – 7.03 (m, 2H), 5.39(d, J = 4.4 Hz, 1H), 5.07 (d, J = 4.4 Hz, 1H), 3.30 (s, 2H), 3.05 (dd, J =15.0, 7.9 Hz, 2H), 2.78 (dd, J = 17.8, 15.3 Hz, 1H), 2.63 (dd, J = 15.3, 6.8Hz, 1H).

[0243] HRMS (ESI) calcd for C 33 H 28 O 2 P + [M+H] + 487.1821, found 487.1820.

[0244]

[0245] Compound Ⅳ-18 was characterized as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 53.10.

[0246] 1 H NMR (400 MHz, CDCl 3 ) δ 7.66 (t, J = 8.0 Hz, 1H), 7.56 (t, J= 7.6Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.43 – 7.34 (m, 2H), 7.32 – 7.24 (m, 5H),7.22 – 7.12 (m, 5H), 7.07 – 7.01 (m, 2H), 5.39 (d, J = 4.1 Hz, 1H), 5.06 (d, J = 4.1 Hz, 1H), 3.29 (d, J = 2.5 Hz, 2H), 3.14 – 2.97 (m, 2H), 2.76 (t, J =16.5 Hz, 1H), 2.61 (dd, J = 15.3, 6.4 Hz, 1H).

[0247] HRMS (ESI) calcd for C 33 H 27 NOP + [M+H] + 484.1825, found 484.1823.

[0248]

[0249] The characterization of compound Ⅳ-19 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.69, 52.85.

[0250] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.69 – 7.63 (m, 1H), 7.59 – 7.52 (m, 1H),7.44 (d, J = 8.2 Hz, 2H), 7.39 (dd, J = 6.4, 2.6 Hz, 2H), 7.29 (dd, J = 7.9,5.7 Hz, 5H), 7.22 – 7.13 (m, 5H), 7.09 – 7.03 (m, 2H), 5.39 (d, J = 4.7 Hz,1H), 5.07 (d, J= 4.8 Hz, 1H), 3.28 (s, 2H), 3.05 (dd, J = 15.1, 8.3 Hz, 2H),2.78 (dd, J = 17.9, 15.3 Hz, 1H), 2.62 (dd, J = 15.3, 7.0 Hz, 1H).

[0251] HRMS (ESI) calcd for C 33 H 37 F 3 OP + [M+H] + 527.1746, found 527.1747.

[0252]

[0253] The characterization of compound Ⅳ-20 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.91, 52.82.

[0254] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.57 (t, J = 8.1 Hz, 1H), 7.51 – 7.40 (m,3H), 7.39 – 7.27 (m, 6H), 7.27 – 7.15 (m, 6H), 7.14 – 7.05 (m, 5H), 7.03 –6.96 (m, 2H), 5.30 (d, J = 4.5 Hz, 1H), 4.98 (d, J = 4.5 Hz, 1H), 3.19 (s,2H), 2.93 (dd, J = 14.9, 5.6 Hz, 2H), 2.73 (dd, J = 17.9, 15.3 Hz, 1H), 2.56(dd, J = 15.2, 6.8 Hz, 1H).

[0255] HRMS (ESI) calcd for C 38 H 32 OP+ [M+H] + 535.2185, found 535.2185.

[0256]

[0257] The characterization of Compound Ⅳ-21 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.50, 52.26.

[0258] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.68 – 7.58 (m, 3H), 7.54 – 7.42 (m, 3H),7.39 – 7.29 (m, 3H), 7.29 – 7.18 (m, 5H), 7.14 – 7.00 (m, 7H), 5.30 (d, J J =4.7 Hz, 1H), 4.97 (d, J J = 4.7 Hz, 1H), 3.42 – 3.25 (m, 2H), 2.90 (dd, J J =14.8, 8.4 Hz, 2H), 2.77 (dd, J J = 18.2, 15.2 Hz, 1H), 2.61 (dd, J J = 15.2, 7.0Hz, 1H).

[0259] HRMS (ESI) calcd for C 36 H 30 OP + [M+H] + 509.2029, found 509.2031.

[0260]

[0261] The characterization of Compound Ⅳ-22 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 52.86.

[0262] 1 1H NMR (400 MHz, CDCl 3) δ 7.78 – 7.60 (m, 5H), 7.56 (t, J J = 7.5 Hz,1H), 7.49 – 7.35 (m, 4H), 7.33 – 7.23 (m, 4H), 7.23 – 7.13 (m, 5H), 7.10 (dd, J J = 6.6, 1.8 Hz, 2H), 5.39 (d, J J = 4.7 Hz, 1H), 5.07 (d, J J = 4.8 Hz, 1H),3.30 (s, 2H), 3.02 (dd, J J = 15.0, 5.6 Hz, 2H), 2.84 (dd, J J = 17.9, 15.3 Hz,1H), 2.67 (dd, J J = 15.3, 6.9 Hz, 1H). HRMS (ESI) calcd for C 36 H 30 OP + [M+H] + 509.2029, found 509.2028.

[0263]

[0264] The characterization of compound Ⅳ-23 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.81, 52.44.

[0265] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.63 (t, J J = 8.2 Hz, 1H), 7.59 – 7.50 (m,1H), 7.42 – 7.34 (m, 2H), 7.30 – 7.22 (m, 3H), 7.21 – 7.11 (m, 5H), 7.04 –7.00 (m, 2H), 5.83 (dt, J J = 4.2, 2.1 Hz, 1H), 5.37 (d, J J = 4.5 Hz, 1H), 5.04(d, J= 4.7 Hz, 1H), 3.12 (s, 2H), 2.93 (dd, J = 14.8, 5.2 Hz, 2H), 2.77 (dd, J = 18.4, 15.2 Hz, 1H), 2.59 (dd, J = 15.2, 6.8 Hz, 1H), 1.97 (dt, J = 7.9, 3.9 Hz, 2H), 1.86 (dq, J = 5.2, 3.2, 2.7 Hz, 2H), 1.49 (tdt, J = 10.0, 5.5, 2.6 Hz, 4H).

[0266] HRMS (ESI) calcd for C 32 H 32 OP + [M+H] + 463.2185, found 463.2187.

[0267]

[0268] The characterization of Compound Ⅳ-24 is as follows: 31 P{ 1 H} NMR (202 MHz, CDCl 3 ) δ 56.42, 53.23.

[0269] 1 H NMR (500 MHz, CDCl 3 ) δ 7.63 (t, J = 8.2 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.38 (ddd, J = 14.7, 7.4, 2.7 Hz, 2H), 7.32 – 7.24 (m, 4H), 7.20 (dd, J = 5.2, 2.0 Hz, 2H), 7.15 (dd, J = 6.6, 3.1 Hz, 2H), 7.11 (d, J = 5.2 Hz, 1H), 7.06 (dd, J = 7.1, 1.9 Hz, 2H), 6.98 (d,J = 3.6 Hz, 1H), 6.86 (dd, J = 5.2, 3.6 Hz, 1H), 5.39 (d, J = 4.7 Hz, 1H), 5.07 (d, J = 4.8 Hz, 1H),3.27 (s, 2H), 3.02 (dd, J = 15.1, 3.9 Hz, 2H), 2.74 (dd, J = 17.6, 15.2 Hz,1H), 2.63 (dd, J = 15.3, 7.0 Hz, 1H).

[0270] HRMS (ESI) calcd for C 30 H 26 OPS + [M+H] + 465.1437, found 465.1439.

[0271]

[0272] The characterization of Compound Ⅳ-25 is as follows: 31 P{ 1 H} NMR (202 MHz, CDCl 3 ) δ 56.57, 53.40.

[0273] 1 H NMR (500 MHz, CDCl 3 ) δ 7.67 – 7.62 (m, 1H), 7.55 (tt, J = 7.5, 1.4Hz, 1H), 7.43 – 7.36 (m, 2H), 7.30 – 7.25 (m, 4H), 7.22 – 7.18 (m, 3H), 7.17– 7.12 (m, 3H), 7.07 – 7.04 (m, 2H), 6.88 (dd, J = 4.9, 1.2 Hz, 1H), 5.39(dd, J = 4.8, 0.9 Hz, 1H), 5.06 (dd, J= 4.8, 1.1 Hz, 1H), 3.23 (s, 2H), 3.06–2.96 (m, 2H), 2.79 (dd, J = 18.0, 15.3 Hz, 1H), 2.62 (dd, J = 15.3, 6.9 Hz,1H).

[0274] HRMS (ESI) calcd for C 30 H 26 OPS + [M+H] + 465.1437, found 465.1439.

[0275]

[0276] The characterization of Compound Ⅳ-26 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 51.72.

[0277] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.63 (t, J = 8.2 Hz, 1H), 7.56 (t, J = 7.6Hz, 1H), 7.40 (ddd, J = 16.7, 7.7, 3.5 Hz, 2H), 7.31 – 7.23 (m, 3H), 7.23 –7.15 (m, 3H), 7.12 (dd, J = 6.6, 3.2 Hz, 2H), 6.98 (dd, J = 7.9, 1.8 Hz, 2H),5.37 (d, J = 4.7 Hz, 1H), 5.07 (d, J = 1.6 Hz, 1H), 5.02 (d, J = 4.8 Hz, 1H),3.50 – 3.24 (m, 4H), 3.17 – 3.05 (m, 2H), 2.91 (dd, J = 14.7, 8.6 Hz, 2H),2.72 (dd, J= 18.2, 15.2 Hz, 1H), 2.60 (dd, J = 15.2, 7.1 Hz, 1H), 1.08 (dt, J = 8.6, 7.1 Hz, 6H).

[0278] HRMS (ESI) calcd for C 31 H 34 O 3 P + [M+H] + 485.2240, found 485.2235.

[0279]

[0280] The characterization of Compound Ⅳ-27 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.97, 52.45.

[0281] 1 H NMR (400 MHz, CDCl 3 ) δ 7.63 (t, J = 8.2 Hz, 1H), 7.57 – 7.51 (m,1H), 7.38 (dt, J = 7.6, 3.2 Hz, 1H), 7.30 – 7.23 (m, 5H), 7.19 (dd, J = 5.1,2.1 Hz, 2H), 7.16 – 7.11 (m, 2H), 7.02 – 6.97 (m, 2H), 5.37 (d, J = 4.4 Hz,1H), 5.03 (d, J = 4.7 Hz, 1H), 2.99 (s, 2H), 2.92 (dd, J = 14.8, 10.2 Hz,2H), 2.83 – 2.73 (m, 1H), 2.56 (dd, J = 15.2, 6.8 Hz, 1H), 2.02 – 1.94 (m,2H), 1.27 (dt, J = 14.5, 7.3 Hz, 2H), 1.21 – 1.05 (m, 4H), 0.81 (t,J = 7.1Hz, 3H).

[0282] HRMS (ESI) calcd for C 31 H 34 OP + [M+H] + 453.2342, found 453.2342.

[0283]

[0284] The characterization of compound Ⅳ-28 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 52.79.

[0285] 1 H NMR (400 MHz, CDCl 3 )δ 7.36 (d, J = 9.3 Hz, 1H), 7.33 – 7.24 (m,5H), 7.23 – 7.16 (m, 8H), 7.14 (qd, J = 4.7, 3.9, 1.9 Hz, 2H), 7.10 – 7.06(m, 2H), 5.37 (dd, J = 4.7, 0.9 Hz, 1H), 5.06 (dd, J = 4.8, 1.1 Hz, 1H), 3.22(s, 2H), 2.98 (dd, J = 14.9, 3.8 Hz, 2H), 2.79 (dd, J = 17.9, 15.2 Hz, 1H),2.64 (dd, J = 15.3, 6.9 Hz, 1H), 2.32 (s, 3H).

[0286] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0287]

[0288] The characterization of compound Ⅳ-29 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 54.51, 51.66.

[0289] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.51 (t, J J = 8.3 Hz, 1H), 7.40 (d, J J = 1.9Hz, 1H), 7.36 – 7.26 (m, 4H), 7.26 – 7.17 (m, 8H), 7.20 – 7.11 (m, 2H), 7.11– 7.03 (m, 2H), 5.39 (d, J J = 4.8 Hz, 1H), 5.07 (d, J J = 4.8 Hz, 1H), 3.23 (s,2H), 3.06 (dd, J J = 15.3, 4.3 Hz, 2H), 2.77 (dd, J J = 17.5, 15.4 Hz, 1H), 2.62(dd, J J = 15.3, 6.8 Hz, 1H).

[0290] HRMS (ESI) calcd for C 32 29 27 H + 35 + ClOP [M+H]

[0291]

[0292] The characterization of compound Ⅳ-30 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.02.

[0293] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.91 – 7.82 (m, 2H), 7.71 (t, J J = 8.1 Hz,1H), 7.47 (dd, J= 11.2, 8.5 Hz, 2H), 7.32 – 7.19 (m, 8H), 7.22 – 7.13 (m,8H), 5.41 (d, J = 4.9 Hz, 1H), 5.13 (d, J = 4.9 Hz, 1H), 3.68 (d, J = 17.0Hz, 1H), 3.53 (dd, J = 17.0, 1.4 Hz, 1H), 3.47 – 3.27 (m, 2H), 2.98 (t, J =16.5 Hz, 1H), 2.45 (dd, J = 15.9, 7.2 Hz, 1H).

[0294] HRMS (ESI) calcd for C 36 H 30 OP + [M+H] + 509.2029, found 509.2029.

[0295]

[0296] The characterization of compound Ⅳ-31 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 55.87, 52.61.

[0297] 1 H NMR (400 MHz, CDCl 3 ) δ 7.69 (td, J = 8.2, 7.6, 1.3 Hz, 1H), 7.59(tt, J = 7.4, 1.5 Hz, 1H), 7.44 (dd, J = 7.5, 3.0 Hz, 2H), 7.30 – 7.17 (m,9H), 7.13 – 7.05 (m, 2H), 7.03 – 6.95 (m, 2H), 5.38 (d, J = 4.7 Hz, 1H), 5.10(d, J= 4.7 Hz, 1H), 3.22 (s, 2H), 3.10 – 2.85 (m, 2H), 2.80 (dd, J = 18.1,15.3 Hz, 1H), 2.57 (dd, J = 15.3, 6.8 Hz, 1H).

[0298] HRMS (ESI) calcd for C 32 H 26 Cl 2 OP + [M+H] + 527.1093, found 527.1093.

[0299]

[0300] The characterization of compound Ⅳ-32 is as follows: 31 P{ 1 H} NMR (162 MHz, CDCl 3 ) δ 53.91.

[0301] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.75 (t, J = 8.1 Hz, 1H), 7.57 (t, J = 7.6Hz, 1H), 7.48 (dd, J = 7.8, 2.4 Hz, 1H), 7.45 – 7.36 (m, 3H), 7.30 – 7.23 (m,3H), 4.97 (dt, J = 4.5, 1.6 Hz, 1H), 4.80 (d, J = 4.7 Hz, 1H), 2.96 (dd, J =17.0, 14.3 Hz, 1H), 2.83 (s, 2H), 2.78 (t, J = 14.1 Hz, 1H), 2.51 (t, J =16.2 Hz, 1H), 2.23 (dd, J = 15.6, 6.8 Hz, 1H), 1.85 (dt, J = 2.7, 1.1 Hz,3H), 1.55 (s, 3H).

[0302] HRMS (ESI) calcd for C 22 H 24 OP + [M+H] + 335.1559, found 335.1559.

[0303] Example 12: Synthesis of Product IX

[0304] The experimental method of Example 12 refers to Example 11, using the P -chiral phosphine oxide shown in Formula IV-1, and the remaining operation steps are the same as those in Example 11, and the corresponding target compound ( S , R )-IX was finally obtained.

[0305] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound of formula ( S , R )-IX as a light yellow oil, with a yield of 68%, a dr value > 20:1, an ee value of 99%, (Daicel Chiralpak IA column), hexane / isopropanol = 95 / 5, flow rate 1.0 mL / min, 254 nm, t major = 7.8 min, t minor = 8.3 min. [α] 20 D =+90.9 (c=0.1, chloroform).

[0306] The compound of formula ( S , R )-IX was characterized as follows: 1 H NMR (400 MHz, CDCl 3 ) δ 7.46 (ddt, J = 9.3, 7.2, 1.8 Hz, 2H), 7.35 –7.27 (m, 5H), 7.22 – 7.14 (m, 8H), 7.14 – 7.09 (m, 2H), 7.04 (dd, J = 7.8,1.8 Hz, 2H), 5.29 (d, J = 4.0 Hz, 1H), 4.93 (d, J= 4.3 Hz, 1H), 3.19 (s, 2H), 3.00 – 2.80 (m, 2H), 2.79 (dd, J = 15.0, 3.3 Hz, 1H), 2.56 (dd, J = 15.0, 8.8 Hz, 1H).

[0307] 13 C NMR (100 MHz, CDCl 3 ) δ 151.57 (d, J C-P = 12.0 Hz), 146.30 (d, J C-P = 1.5 Hz), 140.19 (d, J C-P = 5.5 Hz), 140.14, 132.28 (d, J C-P = 54.2 Hz), 131.61, 131.45 (d, J C-P = 2.2 Hz), 130.42 (d, J C-P = 11.6 Hz), 128.65, 128.45 (d, J C-P = 9.3 Hz), 128.42, 128.21, 127.98, 127.94, 127.38, 127.26, 126.95 (d, J C-P = 8.3 Hz), 126.64, 123.19, 117.70 (d, J C-P = 8.5 Hz), 86.45, 83.95, 56.67 (d, J C-P = 2.7 Hz), 36.85 (d, J C-P = 33.9 Hz), 33.84 (d, J C-P = 16.6 Hz), 33.69 (d, J C-P = 2.4 Hz).

[0308] 31 P{ 11H NMR (162 MHz, CDCl 3 ) δ 31.56.

[0309] FT-IR (neat) 2374, 1597, 1491, 1443, 1265, 1158, 1058, 1029, 909, 862, 757, 733, 700, 667 cm -1 .

[0310] HRMS (ESI) calcd for C 32 H 31 BP + [M - BH 3 + 443.5498, found 443.1926.

[0311] Application Test Example 1: Trivalent Phosphine P -Chiral Phosphine Compound ( S , R )-Ⅷ was used as a ligand in the palladium-catalyzed asymmetric allylic substitution reaction to synthesize Compound 3. The reaction formula is as follows:

[0312] Experimental Procedure: Add Compound ( S , R )-Ⅷ (0.03 mmol) into a 10 mL Schlenk reaction tube. After purging with argon 5 times, add 2 mL of a mixed solution of methanol:toluene = 1:1, and stir at 80 °C for 12 h. Cool the reaction to room temperature, and then successively add [Pd(C 3 H 5 )Cl] 2 (0.015 mmol), AgPF 6 (0.033 mmol), and react at room temperature for 6 h in the dark. After the reaction is cooled, directly dry the system, then add potassium acetate (10 mol%), purge with argon 5 times, successively add Compound 1 (0.2 mmol), Compound 2 (0.6 mmol), toluene (1 mL), and BSA (0.6 mmol), and stir at room temperature for 16 h while monitoring the reaction progress by TLC. After the reaction is completed, filter through diatomaceous earth, concentrate the obtained crude product, and perform silica gel column chromatography (PE:EA = 10:1) to separate the target product Compound 3 with a yield of 95% and an ee value of 12%. Figure 2 Figure shows a comparison diagram of the racemate (upper) and chiral catalysis (lower) effects of Compound 3 (including retention time and peak area data corresponding to the HPLC diagram). ​

[0313] The HPLC data of the obtained compound 3 are as follows. The ee value is 12%, (Daicel Chiralpak AD-H column), hexane / isopropanol = 90 / 10, flow rate 1.0 mL / min, 254 nm, t major = 9.2 min, t minor = 11.8 min.

[0314] Application Test Example 2: Trivalent Phosphine P -Chiral Phosphine Compound ( S , R )-IX was used as a ligand in the palladium-catalyzed asymmetric allylic substitution reaction to synthesize compound 3. The reaction formula is as follows:

[0315] The experimental method of Application Test Example 2 refers to Application Test Example 1, using the trivalent phosphine P -Chiral Phosphine Compound ( S , R )-IX. The remaining operation steps are the same as those in Application Test Example 1. Finally, the corresponding target compound 3 was obtained with a yield of 78% and an ee value of 44%. Figure 3 The comparison chart of the racemate (upper) and chiral catalysis (lower) effects of compound 3 (including the retention time and peak area data corresponding to the HPLC chart) is shown.

[0316] The HPLC data of the obtained compound 3 are as follows. The ee value is 44%, (Daicel Chiralpak AD-H column), hexane / isopropanol = 90 / 10, flow rate 1.0 mL / min, 254 nm, t major = 9.2 min, t minor = 11.8 min.

[0317] To demonstrate the beneficial effects of the trivalent phosphine P -Chiral Phosphine Compound in the asymmetric allylic substitution reaction, a control test example was set up without adding the trivalent phosphine P -Chiral Phosphine Compound, with the other conditions unchanged. The catalytic results of the three are shown in Table 2 below:

[0318] Table 2 Comparison of the catalytic effects of the trivalent phosphine P -Chiral Phosphine Compound in the asymmetric allylic substitution reaction

[0319] The catalytic reaction results described in the table show that trivalent phosphine P -chiral phosphine compounds have good catalytic effects when used as ligands in palladium-catalyzed asymmetric allylic substitution reactions, showing good prospects for this type of ligand in asymmetric allylic substitution reactions.

[0320] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the technical solutions of the present invention, rather than limitations on the specific implementation manners of the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principle of the claims of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

1. A five-membered ring containing an alkynyl or triazole functional group P - a chiral phosphine oxide compound, characterized in that The structural formula of the compound is any one of the following general structural formulas: ； Among them, * represents the chiral center atom, and the configuration is R or S ,Ar 1 A benzene ring or a naphthalene ring; R 1 is hydrogen, C1~C6 saturated alkyl or halogen; R 2 is alkyl, halogen, alkoxy, phenyl or benzyl; R 3 is alkyl, halogen, alkoxy, phenyl, benzyl, thiophene, silane or naphthyl; wherein R 3 The alkyl group is a saturated or unsaturated alkyl group of C1 to C6; R 4 is an alkyl group or a benzyl group.

2. The five-membered ring containing an alkynyl or triazole functional group according to claim 1 P - a chiral phosphine oxide compound, characterized in that R 1 is hydrogen, C1~C6 saturated alkyl or halogen; R 2 is C1~C6 alkyl, halogen, C1~C6 alkoxy, phenyl or benzyl; R 3 is C1~C6 alkyl, halogen, C1~C6 alkoxy, phenyl, benzyl, thiophene, silane or naphthyl; wherein R 3 The alkyl group is a saturated or unsaturated alkyl group of C1 to C6; R 4 It is a C1~C6 alkyl or benzyl group.

3. The five-membered ring containing an alkynyl or triazole functional group according to claim 1 P - a chiral phosphine oxide compound, characterized in that R 1 is hydrogen, C1~C6 saturated alkyl or halogen; R 2 It is a C1~C6 saturated alkyl, halogen, C1~C3 saturated alkoxy, phenyl or benzyl; the hydrogen on the phenyl group may be substituted by halogen or C1~C6 saturated alkyl; R 3 is alkyl, halogen, alkoxy, phenyl, benzyl, thiophene, silane or naphthyl; wherein R 3 The alkyl group is a saturated or unsaturated alkyl group of C1~C6; R 3 The hydrogen on the alkyl, silane or phenyl group may be substituted by any of the following substituents: a C1-C3 saturated alkyl group, a C1-C3 saturated alkoxy group or a phenyl group; R 4 It is a C1~C6 saturated alkyl or benzyl group.

4. The five-membered ring containing an alkynyl or triazole functional group according to claim 1 P - a chiral phosphine oxide compound, characterized in that Halogen is fluorine or chlorine.

5. The five-membered ring containing an alkynyl or triazole functional group according to claim 3 P - a chiral phosphine oxide compound, characterized in that R 3 The hydrogen on the phenyl group may be replaced by any of the following substituents: aldehyde group or cyano group.

6. The five-membered ring containing an alkynyl or triazole functional group according to claim 1 P -Application of chiral phosphine oxides in asymmetric catalysis.

7. The use according to claim 6, characterized in that: The compound is used for palladium-catalyzed asymmetric allylic substitution reaction.

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