P-chiral phosphine oxides containing alkynyl or triazole functional groups, and methods of making and using the same

Abstract

The application discloses a five-membered ring containing alkynyl or triazole functional group P The chiral phosphine oxide compound is obtained through Domino Heck-Sonogashira cascade reaction by taking a prochiral tertiary phosphine oxide compound containing a double ethylene group and phenylacetylene as raw materials, transition metal palladium catalyst and chiral TADDOL phosphoramidite ligand under the protection of inert gas P The chiral phosphine oxide compound has a product yield of 96% and an enantioselectivity ee value of 99%, and a diastereoselectivity dr value of greater than 20:1. The application adopts an asymmetric desymmetrization strategy, uses a Heck reaction to start and a Sonogashira reaction to end a cascade reaction, simultaneously constructs P The chiral and quaternary carbon chiral center has mild reaction conditions, simple operation and good substrate universality, provides a compound skeleton with diversity, and is successfully applied to a palladium-catalyzed asymmetric allyl substitution reaction as a chiral ligand.

Description

Technical Field

[0001] This invention belongs to the field of asymmetric catalysis technology, specifically relating to a five-membered ring containing an alkyne or triazole functional group. P - Chiral phosphine oxides, their preparation methods, and applications. Background Technology

[0002] By utilizing the two different stable oxidation states of the phosphorus center, phosphorus compounds can be widely applied in various fields, especially in asymmetric catalysis. Among these, compounds with chiral skeletons are of the greatest interest, such as BINAP ligands, TADDOL-type phosphoridamide ligands, and PHOX ligands. Compared to these chiral phosphorus molecules, compounds with chiral centers on the phosphorus atom (also known as...) are more suitable for synthesis. P- The development of stereochemical compounds is relatively limited. Currently, the reaction types being developed have limitations in terms of reaction substrates; metal-catalyzed asymmetric desymmetry reactions involving alkenyl tertiary phosphine oxides are rarely reported. Furthermore, the advantages of desymmetry reactions in constructing multiple chiral centers in one step, especially quaternary carbon chiral centers, have not been fully explored. Specifically, the simultaneous one-step construction of... P- Examples of chiral centers interacting with other chiral centers are even rarer. In recent years, desymmetrization tandem reactions initiated by the asymmetric Heck reaction have attracted widespread attention from chemists, but the termination of this reaction strategy mostly relies on… β -H elimination occurs without any subsequent cascade reactions. Although numerous studies have reported replacing the Heck reaction with atom or group transfer processes... β -H elimination steps have been studied extensively, primarily focusing on the construction of heterocyclic skeletons such as indole via Heck cyclization reactions. Reports on Domino-Heck asymmetric desymmetry reactions are scarce, and the substrates are mostly based on cyclic alkenes. Therefore, desymmetric tandem reactions initiated by the Heck reaction based on open-chain alkenes present considerable challenges. Furthermore, for P There is relatively little research on PN ligands with chiral centers. Most studies are based on chiral phosphonium ligands with oxazoline skeleton extensions, while there is less research on phosphonium ligands containing 1,2,3-triazole skeletons. Summary of the Invention

[0003] To address the shortcomings of existing technologies, this invention addresses the functionalization of alkynyl groups. P -Chiral compound ligands and their effects P A series of explorations were conducted on the synthesis of chiral-centered phosphine nitrogen ligands. The synthesized chiral phosphine oxides can be used to synthesize 1,2,3-triazoles via the Click reaction. P -Chiral phosphonooxides; benzo[5]-membered rings P -Chiral phosphonoxides and triazole-containing compounds P - Chiral phosphine oxides can be reduced to obtain configuration-retained compounds.P - chiral trivalent phosphine products and successful application as chiral ligands in palladium catalyzed asymmetric allylic substitution reactions.

[0004] To achieve the above object, the present application provides the following technical solutions.

[0005] A five-membered ring containing an alkynyl or triazole functional group P - chiral phosphine oxide compounds, the structural formula of the compounds is any one of the following general structures:

[0006] ;

[0007] wherein, * represents a chiral center atom, the configuration is R or S , Ar 1 is a benzene ring or a naphthalene ring;

[0008] R 1 is hydrogen, a C1-C6 saturated alkyl or halogen;

[0009] R 2 is an alkyl, halogen, alkoxy, phenyl or benzyl;

[0010] R 3 is an alkyl, halogen, alkoxy, phenyl, benzyl, thiophene, silane or naphthyl; wherein, the alkyl in R 3 is a C1-C6 saturated or unsaturated alkyl;

[0011] R 4 is an alkyl or benzyl.

[0012] Preferably, R 1 is hydrogen, a C1-C6 saturated alkyl or halogen;

[0013] R 2 is a C1-C6 alkyl, halogen, C1-C6 alkoxy, phenyl or benzyl;

[0014] R 3 is a C1-C6 alkyl, halogen, C1-C6 alkoxy, phenyl, benzyl, thiophene, silane or naphthyl; wherein, the alkyl in R 3 is a C1-C6 saturated or unsaturated alkyl;

[0015] R 4 is a C1-C6 alkyl or benzyl.

[0016] Preferably, R 1 is hydrogen, a C1-C6 saturated alkyl or halogen;

[0017] R 2saturated alkyl group having 1 to 6 carbon atoms, halogen, saturated alkoxy group having 1 to 3 carbon atoms, phenyl group or benzyl group; the hydrogen on the phenyl group can be substituted by halogen or saturated alkyl group having 1 to 6 carbon atoms;

[0018] R 3 alkyl group, halogen, alkoxy group, phenyl group, benzyl group, thienyl group, silane or naphthyl group; wherein R 3 alkyl group in the formula (1) is saturated or unsaturated alkyl group having 1 to 6 carbon atoms; R 3 the hydrogen on the alkyl group, silane or phenyl group can be substituted by any one of saturated alkyl group having 1 to 3 carbon atoms, saturated alkoxy group having 1 to 3 carbon atoms or phenyl group;

[0019] R 4 saturated alkyl group having 1 to 6 carbon atoms or benzyl group.

[0020] Preferably, halogen is fluorine or chlorine.

[0021] More preferably, R 3 the hydrogen on the phenyl group can also be substituted by any one of aldehyde group or cyano group.

[0022] The present application also provides a preparation method of prochiral tertiary phosphine oxide compound containing alkenyl group, comprising the following steps:

[0023] Step S1:

[0024]

[0025] Step S1: under inert gas protection, compound I is added with silanization reagent in acetonitrile to obtain compound I-1, then reacted at a specific temperature until the end, and then put into the next step after being concentrated to dryness under reduced pressure.

[0026] Step S2:

[0027]

[0028] Step S2: under inert gas protection, compound I-1 is added into dichloromethane as raw material, phosphorylchloridated with acylchlorination reagent under catalysis of N,N-dimethylformamide, and then put into the next step after being concentrated to dryness under reduced pressure after reaction at room temperature until the end.

[0029] Step S3:

[0030]

[0031] Step S3: After drying, the phosphine chloride compound I-2 is added to an ethyl ether dilution system under inert gas protection. The freshly prepared Grignard reagent is added to the phosphine chloride compound I-2 at 0°C, and then stirred at room temperature overnight. After extraction, column chromatography is used for separation and purification to obtain the prochiral tertiary phosphine oxide compound of formula II.

[0032] Step S4:

[0033]

[0034] In formula IV, * represents a chiral center atom, which is R or S.

[0035] The specific synthesis method of step S4 is as follows: under inert gas protection, the prochiral tertiary phosphine oxide compound of formula II and the alkyne nucleophile reagent with different substituents of formula III are used as reaction raw materials and added to an organic solvent. A palladium catalyst is used as a catalyst, and a ligand is used in the presence of a base. The reaction is stirred at 40-80°C for 12 hours. Then extraction, filtration, and reduced pressure concentration are performed. The obtained concentrated crude product is separated and purified by column chromatography to obtain the target compound, the benzopentacyclic ring of formula IV. P - Chiral phosphine oxide compound.

[0036] Step S5:

[0037]

[0038] In formula IV, R 3 Trimethylsilyl group.

[0039] In formula IV, formula V, and formula VI, * represents a chiral center atom, which is R or S.

[0040] Step S5: After adding formula IV to an organic solvent, a desilylation reagent is used for stirring until the reaction is completed. Then formula V and formula VI desilylation products are obtained after purification.

[0041] Step S6:

[0042]

[0043] In formula V and formula VII, * represents a chiral center atom, which is R or S.

[0044] Step S6: The desilylation compound of formula V, a catalyst, a reducing agent, a base, sodium azide, and bromide are weighed into a reactor and then added to an organic solvent. The reaction is stirred at 25-50°C overnight. The reaction progress is monitored by TLC. After the reaction is completed, extraction, filtration, and drying are performed. Formula VII, a triazolyl phosphine oxide compound, is obtained after column chromatography purification.

[0045] Step S7:

[0046]

[0047] In formulae VII, VIII, IV and IX: * represents a chiral center atom, R or S.

[0048] Step S7: first, the amine compound is added to the organic solvent in a round-bottom flask, and then the silane reagent is added to form a complex of silane and amine, and then the triazole of formula VII is added P - chiral phosphine oxide compound or IV P - chiral phosphine oxide compound, stirring at a specific temperature until the reaction is completed, and then placing the system into a low-temperature reactor after the system is cooled to room temperature to add a borane reagent, and reacting at room temperature until the reaction is completed. After extraction, concentration under reduced pressure, column chromatography separation and purification, the triazole phosphine boron compound of formula VIII or the phosphine boron compound of formula IX is obtained.

[0049] In the present application, the palladium catalyst in step S4 is selected from one of tris(dibenzylideneacetone)dipalladium, bis(dibenzylideneacetone)palladium, tris(dibenzylideneacetone)dipalladium chloroform adduct, allylpalladium chloride dimer, dichlorobis(triphenylphosphine)palladium, palladium chloride, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium, tetracarbonitrile palladium tetrafluoroborate, (1,5-cyclooctadiene)dichloropalladium, bis(tri-tert-butylphosphine)palladium, palladium acetate, bis(tri-tert-butylphosphine)palladium, diacetonitrile palladium chloride, and tetraphenylphosphine palladium.

[0050] In the present application, the ligand in step S4 is a chiral phosphine ligand, an achiral phosphine ligand, a hybrid ligand, a spiro ligand, etc.

[0051] In the present application, the base in step S4 can be an inorganic base (sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, potassium bicarbonate, etc.), a nitrogen-containing organic base (diethylamine, triethylamine, DIPEA, diisopropylamine, etc.).

[0052] In the present application, the organic solvent in step S4 can be dichloromethane, dichloroethane, acetonitrile, propionitrile, butyronitrile, valeronitrile, benzyl cyanide, 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, etc., or any mixture thereof.

[0053] In the present application, the feeding ratio of the method in step S4 is that the molar ratio between the prochiral tertiary phosphine oxide compound of formula II and the nucleophile of different substituents of formula III is 1: (1.0-2.0); the molar ratio between the prochiral tertiary phosphine oxide compound of formula II, the palladium metal precursor, the ligand, and the base is 1: (0.03-0.1): (0.06-0.2): (1.5-2); and the molar amount of the prochiral tertiary phosphine oxide compound of formula II to the volume of the organic solvent is 1 mmol: (1-10) mL.

[0054] In the present application, the reaction temperature in step S4 is 30-100°C.

[0055] In the present application, the desilication reagent in step S5 is one or more than two of cesium fluoride, potassium carbonate, tetrabutylammonium fluoride.

[0056] In the present application, the organic solvent in step S5 is one or two or any mixture of tetrahydrofuran, methanol.

[0057] In the present application, the reaction temperature in step S5 is 25- -20°C.

[0058] In the present application, the feeding ratio of the method in step S5 is: benzopentacyclic ring of formula IV P - chiral phosphine oxide compound: the molar ratio between desilication reagents is 1: (1.0-2.0); the molar amount of phosphine oxide compound of formula IV to the volume of organic solvent is 1 mmol: (2-5) mL.

[0059] In the present application, the catalyst in step S6 can be one of cuprous iodide, copper sulfate pentahydrate, copper acetate.

[0060] In the present application, the reducing agent in step S6 is sodium ascorbate.

[0061] In the present application, the base in step S6 can be one of cesium carbonate, sodium carbonate, potassium carbonate, triethylamine, diisopropyl ethylamine.

[0062] In the present application, the solvent in step S6 can be one or any mixture of dichloromethane, dichloroethane, tetrahydrofuran, methanol, N, N-dimethylformamide, acetonitrile, dimethyl sulfoxide, water, toluene.

[0063] In the present application, the temperature in step S6 is 25-60°C.

[0064] In the present application, the feeding ratio of the method in step S6 is: terminal alkyne of formula V P - chiral phosphine oxide compound: azide: bromide: catalyst: reducing agent: base: the molar ratio is 1: (1.05-1.5): (1.05-1.5): (0.1-0.5): (0.2-1): (1.1-2); the molar amount of phosphine oxide compound of terminal alkyne of formula V to the volume of organic solvent is 1 mmol: (25-35) mL.

[0065] In the present application, the organic solvent in step S7 is one or any mixture of methanol, ethanol, toluene, xylene, diethyl ether, chloroform, dichloromethane, dichloroethane, cyclopentyl methyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, 1,4-dioxane, acetonitrile, and N,N-dimethylformamide.

[0066] In the present application, the silane reagent in step S7 can be one or two or more of 1,1,3,3-tetramethyldisiloxane, triethoxysilane, triethylsilane, trimethoxysilane, trichlorosilane, and triphenylsilane.

[0067] In the present application, the amine compound in step S7 can be one of triethylamine and pyridine.

[0068] In the present application, the temperature in step S7 is -40-80℃.

[0069] As a preferred solution, the benzopentacyclic ring of the present application P - Method for preparing and using chiral phosphine oxide compounds:

[0070] In the present application, the molar ratio of the material of formula I to trimethylsilyl bromide in step S1 is 1:4, the reaction temperature is 50℃, and the reaction time is 2 hours.

[0071] In the present application, the molar ratio of the material of formula I-1 to N,N-dimethylformamide to acyl chlorination reagent in step S2 is 1:0.05:3, the reaction temperature is room temperature, and the reaction time is 4 hours.

[0072] In the present application, the molar ratio of the material I-2 to the format reagent in step S3 is 1:3.5, the reaction temperature is room temperature, the reaction time is 12 hours, and after acid-base extraction, vacuum concentration is followed by column chromatography for post-treatment.

[0073] In the present application, the molar ratio of the material II to III to palladium precursor to ligand to base in step S4 is 1:1.5:0.05:0.06:2, the reaction temperature is 40℃, the reaction time is 12 hours, and after vacuum concentration, column chromatography is performed for separation and purification.

[0074] In the present application, the palladium precursor in step S4 is selected from bis(dibenzylideneacetone)palladium.

[0075] In the present application, the base in step S4 is most preferably potassium carbonate.

[0076] In the present application, the solvent in step S4 is most preferably 1,4-dioxane.

[0077] In the present application, the molar ratio of the material IV in step S5 to the desiliconization reagent is 1:2, the reaction temperature is room temperature, the reaction time is 12 hours, and after the reaction is quenched by ammonium chloride, the liquid separation and vacuum concentration are carried out, and the separation and purification are carried out by column chromatography.

[0078] In the present application, the desiliconization reagent in step S5 is most preferably tetrabutylammonium fluoride.

[0079] In the present application, the solvent in step S5 is most preferably tetrahydrofuran.

[0080] In the present application, the molar ratio of the material V in step S6 to the azide: bromide: catalyst: reducing agent: base is 1:1.1:1.1:0.2:0.4:1.2, and the molar amount of the terminal alkyne phosphine oxide compound of formula V to the volume of the organic solvent is 1 mmol:(25-35) mL.

[0081] In the present application, the catalyst in step S6 is most preferably copper sulfate pentahydrate.

[0082] In the present application, the base in step S6 is most preferably potassium carbonate.

[0083] In the present application, the material of step S7 is formula VII 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.

[0084] In the present application, the amine in step S7 is most preferably pyridine.

[0085] The present application simultaneously protects the five-membered ring containing an alkyne group or a triazole functional group P- The application of chiral phosphine oxide compounds in asymmetric catalysis; further, the application in palladium-catalyzed asymmetric allylic substitution reactions.

[0086] The definition of the terms used in the present application: unless otherwise specified, the initial definition of a group or term provided herein applies throughout the specification; for terms not specifically defined herein, the meaning given to them by those skilled in the art in the light of the disclosure and the context should be given.

[0087] "Substitution" refers to the replacement of a hydrogen atom in a molecule by another different atom or molecule.

[0088] The minimum and maximum values of the carbon atom content in the hydrocarbon group are indicated by a prefix, for example, the prefix (Ca-Cb) alkyl indicates any alkyl group containing "a" to "b" carbon atoms. Therefore, for example, (C1-C4) alkyl refers to an alkyl group containing 1-4 carbon atoms.

[0089] The C1-C6 alkyl group refers to C1, C2, C3, C4, C5, C6 alkyl, i.e. straight-chain or branched alkyl having 1-6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl and the like. The C1-C6 alkoxy group also has the corresponding meaning to its radical.

[0090] Compared with the prior art, the present application has the following advantages:

[0091] The present application uses a palladium catalyst in combination with a chiral ligand as a catalyst to synthesize an alkynyl-containing benzopentacycle from a prochiral phosphine oxide compound P- The preparation of the chiral phosphine oxide compound and the triazole phosphine boron compound provides a route that is both efficient and has atomic economy, and the obtained series of phosphine compounds with high optical activity of the benzopentacycle skeleton have a chiral center of phosphine and a quaternary carbon chiral center, with a yield of up to 95%, an enantioselectivity ee value of up to 99%, and a diastereoselectivity dr value of greater than 20:1.

[0092] After the chiral phosphine oxide compound obtained by catalysis is subjected to TMS removal P- The click triazole product is synthesized after the chiral phosphine oxide compound is subjected to TMS removal, and then the phosphine oxide double bond is reduced and stabilized by borane, with a yield of 95% for the two-step continuous investment, to obtain two configurations of reduced trivalent phosphine products, which have the potential of P-N bidentate ligands and lay a foundation for subsequent applications. BRIEF DESCRIPTION OF DRAWINGS

[0093] Figure 1 It is a single crystal diffraction structure of compound VI in the embodiment 9 of the present application;

[0094] Figure 2 It is a racemic HPLC and chiral HPLC comparison of compound 3 obtained in the application test example 1.

[0095] Figure 3 It is a racemic HPLC and chiral HPLC comparison of compound 3 obtained in the application test example 2. DETAILED DESCRIPTION

[0096] The technical solutions of the present application will be described clearly and completely in combination with the embodiments and comparative examples of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0097] The test methods used in the following examples are conventional methods unless otherwise specified; the materials, reagents and the like used are reagents and materials that can be obtained commercially unless otherwise specified.

[0098] Example 1 Synthesis of prochiral phosphine oxide compounds II-1~II-4:

[0099] The diethyl phosphite compound of formula I was added with bromosilane reagent in acetonitrile, and reacted at 50°C for 2 hours to obtain compound I-1, which was then concentrated to dryness under reduced pressure and used in the next step. In the second step, the reaction system was diluted with dichloromethane, and the phosphine chlorination was carried out with oxalyl chloride at 0°C using N,N-dimethylformamide as the catalyst. After the reaction was completed at room temperature, compound I-2 was obtained, which was concentrated to dryness under reduced pressure. After compound I-2 was purged with argon for 3-5 times, the reaction system was diluted with ether, and the freshly prepared Grignard reagent was added at 0°C, followed by stirring overnight at room temperature. After the reaction was quenched, separated, filtered, dried, concentrated under reduced pressure, and separated and purified, the prochiral phosphine oxide compound of formula I-4 was obtained. The synthesis steps are as follows (the R groups can be determined by those skilled in the art according to the structural formula of compounds II-1~II-4, and will not be described again):

[0100] Step S1:

[0101]

[0102] Step S2:

[0103]

[0104] Step S3:

[0105]

[0106] Step S1: After purging with argon for three times, the starting material compound of formula I (10 mmol) was added with trimethylsilyl bromide (40 mmol) in acetonitrile (10 mL), and reacted at 50°C for two hours to obtain compound I-1, which was then concentrated to dryness under reduced pressure and used in the next step.

[0107] Step S2: After purging with argon for three times, compound I-1 was added with oxalyl chloride (30 mmol) in dichloromethane (10 mL) at 0°C using N,N-dimethylformamide (2-3 drops) as the catalyst for acyl chloride, and reacted at room temperature for 4 hours, and then concentrated to dryness under reduced pressure to obtain phosphine chloride compound I-2.

[0108] Step S3: After purging with argon three times, compound I-2 was added to diethyl ether (10 mL) and the freshly prepared Grignard reagent (40 mmol) was added to the phosphorochloridite compound I-2 and stirred at room temperature overnight. Subsequently, the reaction was quenched by the addition of saturated ammonium chloride solution (50 mL) and extracted with ethyl acetate three times. The organic phase was 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 the ratio of 3: 1 to obtain each prochiral phosphine oxide compound.

[0109] Each prochiral phosphine oxide compound was characterized as follows:

[0110] Compound II-1 was characterized as follows:

[0111]

[0112] Compound II-1 was a light yellow solid, 1.98 g, with a yield of 45% and a melting point of 127.0-134.0 °C.

[0113] 1 H NMR (400 MHz, CDCl3) 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).

[0114] 13 C NMR (100 MHz, CDCl3)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, JC-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).

[0115] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 34.98.

[0116] 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 .

[0117] HRMS (ESI) calcd for C 24 H 23 BrOP + [M+H] + 437.0664, found 437.0664.

[0118] The NMR data of compound II-2 are as follows:

[0119]

[0120] 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 ℃.

[0121] 1 H NMR (400 MHz, CDCl3) 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).

[0122] 13 C NMR (100 MHz, CDCl3) 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.

[0123] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 35.23.

[0124] 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 .

[0125] HRMS (ESI) calcd for C 25 H 25 BrOP + [M+H] + 451.0821, found 451.0822.

[0126] The NMR data of compound II-3 are as follows:

[0127]

[0128] 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 ℃.

[0129] 1 H NMR (400 MHz, CDCl3) 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).

[0130] 13 C NMR (100 MHz, CDCl3) 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).

[0131] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 34.74.

[0132] 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 .

[0133] HRMS (ESI) calcd for C 24 H 21 BrCl2OP + [M+H] + 504.9885, found 504.9885.

[0134] The NMR data of compound II-4 are as follows:

[0135]

[0136] Compound II-4 is a light yellow oil, 1.35 g, with a yield of 29%.

[0137] 1 H NMR (400 MHz, CDCl3) δ 8.34 – 8.25 (m, 1H), 7.63 (dd, J = 7.8, 4.0Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.42 (t, J= 7.6 Hz, 1H), 7.28 (t, J = 7.3 Hz, 4H), 7.24 – 7.14 (m, 6H), 4.95 (d, J = 4.5 Hz, 2H), 4.84 (d, J = 4.3 Hz,2H), 3.53 (d, J = 15.2 Hz, 2H), 3.44 (d, J = 15.2 Hz, 2H), 3.18 – 2.97 (m,4H).

[0138] 13 C NMR (100 MHz, CDCl3) δ 139.96 (d, J C-P = 10.0 Hz), 138.87 (d, J C-P = 1.2 Hz), 137.44 (d, J C-P = 5.5 Hz), 133.82 (d, J C-P = 7.9 Hz), 133.42 (d, J C-P = 2.5 Hz), 132.38 (d, J C-P = 90.0 Hz), 129.36, 128.34, 127.62 (d, J C-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).

[0139] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 36.94.

[0140] 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 .

[0141] HRMS (ESI) calcd for C 26 H 27 BrOP + [M+H] + 465.0977, found 465.0979.

[0142] Example 2 Synthesis of alkynyl-containing benzopentacycles P chiral phosphine oxide compound IV1

[0143]

[0144] Experimental procedure: In a 25 mL sealed tube, pre-chiral phosphine oxide compound formula II-1 (0.2 mmol), bis(dibenzylideneacetone)palladium (0.01 mmol), ligand (0.012 mmol), potassium carbonate (0.4 mmol) were added successively. Double-tube was connected, and the system was degassed three times under argon atmosphere, and the alkynyl reagent formula III-1 (0.3 mmol) and 1,4-dioxane (1 mL) were added under argon atmosphere. The reaction system was sealed and the reaction solution was carried out at 40 °C for 12 hours. After the reaction was completed, the reaction system was filtered through a small amount of silica gel and concentrated. The obtained concentrated product was separated and purified by column chromatography with petroleum ether: ethyl acetate = 5:1 to obtain benzopentacycle formula IV-1 as an orange-red oil, 85.3 mg, yield 93%, dr value 13:1, ee value 99%, (Daicel Chiralpak IA column), hexane / isopropanol = 80 / 20, flow rate 1.0 mL / min, 254 nm, P chiral phosphine oxide compound.

[0145] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound formula IV-1 as an orange-red oil, 85.3 mg, yield 93%, dr value 13:1, ee value 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).

[0146] The compound of formula IV-1 was characterized as follows:

[0147] 1 H NMR (400 MHz, CDCl3) δ 7.57 (t, J = 8.1 Hz, 1H), 7.46 (t, J = 7.6Hz, 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).

[0148] 13 C NMR (100 MHz, CDCl3) 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).

[0149] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.81, 52.69.

[0150] 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, 437cm -1 .

[0151] HRMS (ESI) calcd for C 32 H 28 OP + [M+H] + 459.1872, found 459.1872.

[0152] Example 3: Synthesis of Product IV-2

[0153]

[0154] The experimental method of Example 3 is the same as that of Example 2, using a prochiral phosphine oxide compound as shown in Formula II-2 and an alkynylating reagent as shown in Formula III-1. The remaining operation steps are the same as in Example 2, and the corresponding target compound IV-2 is finally obtained.

[0155] The obtained concentrated crude product was separated and purified by column chromatography to obtain the target compound Formula IV-2 as an orange red oil, 83.2 mg, yield 88%, dr value > 20: 1, ee value 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).

[0156] The compound of Formula IV-2 is characterized as follows:

[0157] 1 H NMR (400 MHz, CDCl3) 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).

[0158] 13 C NMR (100 MHz, CDCl3) 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).

[0159] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.81, 52.69.

[0160] 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, 437cm -1 .

[0161] HRMS (ESI) calcd for C 32 H 28 OP + [M+H] +459.1872, found 459.1872.

[0162] Example 4: Synthesis of product IV-3

[0163]

[0164] In formulae III-2 and IV-3, R 3 is .

[0165] The experimental method of Example 4 was referenced to Example 2, using the prochiral phosphine oxide compound as shown in formula II-1 and the alkynylating reagent as shown in formula III-2, and the remaining operation steps were the same as Example 2, and finally the corresponding target compound IV-3 was obtained.

[0166] 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, an ee value of 99%, (Daicel Chiralpak IA column), hexane / isopropanol = 90 / 10, flow rate 1.0 mL / min, 254 nm, t major = 21.2 min, t minor = 19.7 min. [α] 20 D = +17.1 (c = 0.1, chloroform).

[0167] The compound of formula IV-3 was characterized as follows:

[0168] 1 H NMR (400 MHz, CDCl3) 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).

[0169] 13 C NMR (100 MHz, CDCl3) 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.

[0170] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.89, 52.68.

[0171] 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 .

[0172] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0173] Example 5: Synthesis of product IV-4

[0174]

[0175] In formulae II-3 and IV-4, R 2 is .

[0176] The experimental method of Example 5 is referred to Example 2, using the prochiral phosphine oxide compound as shown in formula II-3 and the alkynylating reagent as shown in formula III-1, and the remaining operation steps are the same as Example 2, to finally obtain the corresponding target compound IV-4.

[0177] The obtained concentrated crude product is 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, 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).

[0178] The compound of formula IV-4 is characterized as follows:

[0179] 1 H NMR (400 MHz, CDCl3) 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).

[0180] 13 C NMR (100 MHz, CDCl3) 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, JC-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).

[0181] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.10, 53.29.

[0182] 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 .

[0183] HRMS (ESI) calcd for C 34 H 32 OP + [M+H] + 487.2185, found 487.2185.

[0184] Example 6: Synthesis of product IV-5

[0185]

[0186] In formulae III-3 and IV-5, R 3 is .

[0187] The experimental procedure of Example 6 was followed as in Example 2, using the prochiral phosphine oxide compound as shown in Formula II-1 and the alkynylating reagent as shown in Formula III-3, with the remaining procedure steps as in Example 2, to ultimately give the corresponding target compound IV-5.

[0188] The obtained concentrated crude product was purified by column chromatography to give the target compound Formula IV-5 as a brown oil, 88.2 mg, 85% yield, dr value of 16:1, 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 = 12.3 min. [a] 20 D = +39.2 (c = 0.1, chloroform).

[0189] The compound of Formula IV-5 was characterized as follows:

[0190] 1 H NMR (400 MHz, CDCl3) δ 7.56 (t, J = 8.1 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.34 (dd, J = 7.9, 2.3 Hz, 1H), 7.28 (td, 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 = 4.5 Hz, 1H), 4.97 (d, J = 4.5 Hz, 1H), 3.61 (s, 6H), 3.14 (s, 2H),2.91 (dd, J = 14.9, 6.4 Hz, 2H), 2.69 (dd, J = 17.9, 15.2 Hz, 1H), 2.56 (dd, J = 15.2, 6.8 Hz, 1H).

[0191] 13C NMR (100 MHz, CDCl3) δ 160.36, 150.52 (d, J C-P = 25.5 Hz), 145.36(d, J C-P = 2.9 Hz), 140.22 (d, J C-P = 2.9 Hz), 139.09 (d, J C-P = 9.2 Hz), 133.48(d, J C-P = 96.7 Hz), 132.53 (d, J C-P = 2.2 Hz), 129.12 (d, J C-P = 8.0 Hz),128.61, 128.38, 128.34, 128.24, 127.83, 127.17, 127.06 (d, J C-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).

[0192] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.78, 52.63.

[0193] 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 .

[0194] HRMS (ESI) calcd for C 34 H 32 O3P + [M+H] + 519.2084, found 519.2084.

[0195] Example 7: Synthesis of product IV-6

[0196]

[0197] The experimental procedure of Example 7 was followed according to Example 2, using the prochiral phosphine oxide compound as shown in Formula II-1 and the alkynylating reagent as shown in Formula III-4, and the remaining procedure steps were the same as Example 2, to finally obtain the corresponding target compound IV-6.

[0198] The obtained concentrated crude product was purified by column chromatography to obtain the target compound Formula IV-6 as a light 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).

[0199] The compound of Formula IV-6 was characterized as follows:

[0200] 1 H NMR (400 MHz, CDCl3) 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).

[0201] 13 C NMR (100 MHz, CDCl3) δ 150.14 (d, J C-P = 25.9 Hz), 145.40 (d, J C-P =2.6 Hz), 140.30 (d, J C-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.

[0202] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.23, 52.09.

[0203] 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 .

[0204] HRMS (ESI) calcd for C 29 H 32 OPSi + [M+H] + 455.1955, found 455.1950.

[0205] Example 8: Synthesis of product IV-7

[0206]

[0207] The experimental procedure of Example 8 was followed using the prochiral phosphine oxide compound as shown in Formula II-1 and the alkynylating reagent as shown in Formula III-5, and the remaining procedure steps were the same as Example 2 to give the corresponding target compound IV-7.

[0208] The obtained concentrated crude product was purified by column chromatography to give 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, 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 = 25.0min. [α] 20 D= +15.3 (c = 0.1, chloroform).

[0209] The compound of formula IV-7 was characterized as follows:

[0210] 1 H NMR (400 MHz, CDCl3) 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).

[0211] 13 C NMR (100 MHz, CDCl3) 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.

[0212] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.95, 52.62.

[0213] 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 .

[0214] HRMS (ESI) calcd for C 29 H 28 OP + [M+H] + 423.1872, found 423.1872.

[0215] Example 9: Synthesis of products V and VI

[0216]

[0217] Experimental procedure: Formula IV-6 benzopentacyclic ring P - Chiral phosphine oxide compound (0.2 mmol) was taken in tetrahydrofuran (1 mL) followed by addition of tetrabutyl ammonium fluoride reagent (0.3 mmol) and stirred at room temperature till completion of reaction. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate three times. The organic layer was concentrated under reduced pressure and the obtained concentrate was purified by column chromatography using petroleum ether: ethyl acetate in the ratio of 2:1 to get the terminal alkyne compound with TMS group removed P - Chiral phosphine oxide compound Formula V and VI compounds.

[0218] The obtained concentrated crude product was purified by column chromatography to get the target compound Formula V as light yellow oil, 32.1 mg, yield 42%, dr value > 20:1, ee value 98%, (Daicel Chiralpak IA column), hexane / isopropanol = 80 / 20, flow rate 1.0 mL / min, 254 nm, t major = 10.6 min, t minor = 9.7 min. [a] 20 D = +20.4 (c = 0.1, chloroform).

[0219] The obtained concentrated crude product was purified by column chromatography to get the target compound Formula VI as white solid, 44.4 mg, yield 58%, dr value > 20:1, ee value 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. [a] 20 D = +17.2 (c = 0.1, chloroform).

[0220] The compound of Formula V was characterized as follows:

[0221] 1 H NMR (400 MHz, CDCl3) 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 = 7.2Hz, 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).

[0222] 13 C NMR (100 MHz, CDCl3) 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).

[0223] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 52.60.

[0224] 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 .

[0225] HRMS (ESI) calcd for C 26 H 24 OP + [M+H] + 383.1559, found 383.1556.

[0226] The compound of formula VI was characterized as follows:

[0227] 1 H NMR (400 MHz, CDCl3) δ 7.88 (t, J = 8.9 Hz, 1H), 7.60 (t, J = 7.6Hz, 1H), 7.54 – 7.43 (m, 2H), 7.33 – 7.18 (m, 6H), 7.10 (dd, J = 7.1, 1.9 Hz,2H), 7.05 – 7.00 (m, 2H), 5.45 (d, J = 25.9 Hz, 1H), 3.14 (d, J= 2.6 Hz, 2H), 3.03 (dd, J = 18.1, 14.8 Hz, 1H), 2.82 (dd, J = 14.8, 7.3 Hz, 1H), 2.60 (d, J = 2.6 Hz, 3H), 1.96 (t, J = 2.6 Hz, 1H).

[0228] 13 C NMR (100 MHz, CDCl3) δ 156.58 (d, J C-P = 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).

[0229] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 42.07.

[0230] m.p.: 148.1-169.3 °C.

[0231] 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 .

[0232] HRMS (ESI) calcd for C 26 H 24 OP + [M+H] + 383.1559, found 383.1556.

[0233] Table 1 Single crystal data of compound VI

[0234]

[0235] Example 10: Synthesis of product VII

[0236]

[0237] Experimental procedure: Formula V (0.194 mmol), copper sulfate pentahydrate (0.04 mmol), sodium ascorbate (0.08 mmol), potassium carbonate (0.23 mmol), sodium azide (0.21 mmol) were added to a mixture of DMF: water (2: 1, 6 mL), followed by the addition of benzyl bromide (0.21 mmol) and stirred at 50 °C overnight. After the reaction was completed, the aqueous phase was extracted with ethyl acetate three times, concentrated under reduced pressure, and purified by column chromatography with petroleum ether: ethyl acetate in a ratio of 1: 1 to obtain a triazole compound P - chiral phosphine oxide compound Formula VII.

[0238] The obtained concentrated crude product was purified by column chromatography to obtain the target compound of Formula VII as a light yellow oil, 95.0 mg, yield 95%, dr value > 20: 1, ee value 98%, (Daicel Chiralpak IB column), hexane / isopropanol / CH2Cl2 = 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).

[0239] The compound of Formula VII was characterized as follows:

[0240] 1 H NMR (400 MHz, CDCl3) δ 7.54 (t, J = 8.2 Hz, 1H), 7.48 (t, J = 7.6 Hz, 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 = 4.6 Hz, 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).

[0241] 13 C NMR (100 MHz, CDCl3) 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 = 8.1 Hz), 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 = 8.3 Hz), 38.49 (d, J C-P = 61.8 Hz).

[0242] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 52.32.

[0243] 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 .

[0244] HRMS (ESI) calcd for C 33 H 31 N3OP + [M+H]+ 516.2199, found 516.2198.

[0245] Example 11: Synthesis of product VIII

[0246]

[0247] Experimental procedure: First, pyridine (6.2 mmol) was added to a 10 mL round bottom flask containing dry toluene (2 mL), trichlorosilane (3 mmol) was added, after stirring for five minutes at room temperature, the triazole of formula VII P - A solution of chiral phosphine oxide (0.2 mmol) in toluene (1 mL) was stirred at 80 °C for twelve hours, after cooling to room temperature, it was placed in a -40 °C cold bath, borane dimethyl sulfide complex (1 mmol) was added, after stirring for fifteen minutes at low temperature, it was removed to room temperature for two hours. After the reaction was completed, the reaction was quenched with saturated ammonium chloride, partitioned with ethyl acetate, the aqueous phase was extracted three times, filtered and concentrated, the obtained concentrate was separated and purified by column chromatography with petroleum ether: ethyl acetate = 1:1 to obtain the triazole chiral phosphine boron compound of formula ( S , R ) - VIII and formula ( R , R ) - VIII.

[0248] 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%, dr value > 20:1, ee value of 98%, (Daicel Chiralpak IB column), hexane / isopropanol / CH2Cl2 = 88 / 8 / 4, flow rate 1.0 mL / min, 230 nm, t major = 20.7 min, t minor = 25.2 min. [α] 20 D = +12.8 (c = 0.1, chloroform).

[0249] The compound of formula ( S , R ) - VIII was characterized as follows:

[0250] 1H NMR (400 MHz, CDC13) 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).

[0251] 13 C NMR (100 MHz, CDC13) 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).

[0252] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.75.

[0253] 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 .

[0254] HRMS (ESI) calcd for C 33 H 34 BN3P + [M+H] + 514.2578, found 514.2578.

[0255] The concentrated crude product obtained was purified by column chromatography to give the target compound (formula omitted). R , R VIII is a white powder with a yield of 38%, dr value > 20:1, ee value of 98% (Daicel Chiralpak IB column), hexane / isopropanol / CH2Cl2 = 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).

[0256] Mode( R , R The characterization of compounds Ⅷ-VIII is as follows:

[0257] 1H NMR (400 MHz, CDCl3) 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).

[0258] 13 C NMR (126 MHz, CDCl3) 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).

[0259] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 34.58.

[0260] 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 .

[0261] HRMS (ESI) calcd for C 33 H 34 BN3P + [M+H] + 514.2578, found 514.2578.

[0262] With reference to the above preparations and procedures, other compounds of the application claimed are as follows:

[0263]

[0264] Compound IV-8 was characterized as follows:

[0265] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 52.17.

[0266] 1 H NMR (400 MHz, CDCl3) δ 7.69 – 7.61 (m, 1H), 7.54 (tt, 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 = 7.4, 1.5 Hz,1H), 7.07 – 6.98 (m, 4H), 5.38 (dd, J = 4.7, 0.9 Hz, 1H), 5.03 (dd, 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).

[0267] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0268]

[0269] Compound IV-9 was characterized as follows:

[0270] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.46, 52.21.

[0271] 1 H NMR (400 MHz, CDCl3) 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).

[0272] HRMS (ESI) calcd for C32 H 27 ClOP + [M+H] + 493.1483, found 493.1486.

[0273]

[0274] Compound IV-10 was characterized as follows:

[0275] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.82, 52.24.

[0276] 1 H NMR (400 MHz, CDCl3) δ 7.55 (t, J = 8.1 Hz, 1H), 7.50 – 7.38 (m,2H), 7.27 (qd, J = 9.4, 8.4, 4.4 Hz, 1H), 7.18 (dt, J = 9.3, 6.6 Hz, 3H),7.13 – 6.95 (m, 9H), 6.73 – 6.63 (m, 2H), 5.30 (d, J = 4.6 Hz, 1H), 4.96 (d, J = 4.6 Hz, 1H), 3.66 (s, 3H), 3.22 (s, 2H), 2.82 (t, J = 15.8 Hz, 3H), 2.60(dd, J = 15.2, 6.7 Hz, 1H).

[0277] HRMS (ESI) calcd for C 33 H 30 O2P + [M+H] + 489.1978, found 489.1978.

[0278]

[0279] Compound IV-11 was characterized as follows:

[0280] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.82, 52.59.

[0281] 1 H NMR (400 MHz, CDCl3) δ 7.64 (t, J = 8.2 Hz, 1H), 7.54 (t, J = 7.6Hz, 1H), 7.43 (dd, J = 7.9, 2.5 Hz, 1H), 7.37 (td, 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 = 4.6Hz, 1H), 5.06 (d, J = 4.6 Hz, 1H), 3.24 (s, 2H), 2.99 (dd, J = 15.0, 4.8 Hz,2H), 2.80 (dd, J = 18.0, 15.3 Hz, 1H), 2.64 (dd, J = 15.2, 6.8 Hz, 1H), 2.24(s, 3H).

[0282] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2030.

[0283]

[0284] Compound IV-12 was characterized as follows:

[0285] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.78, 52.77.

[0286] 1 H NMR (400 MHz, CDCl3) δ 7.65 (t, J = 8.2 Hz, 1H), 7.55 (t, 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).

[0287] HRMS (ESI) calcd for C 32 H 27 ClOP + [M+H] + 493.1483, found 493.1483.

[0288]

[0289] Compound IV-13 was characterized as follows:

[0290] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.75, 52.61.

[0291] 1 H NMR (400 MHz, CDCl3) δ 7.64 (t, J = 8.1 Hz, 1H), 7.53 (t, J = 7.6 Hz, 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 = 4.4 Hz, 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).

[0292] HRMS (ESI) calcd for C 33 H 30 O2P + [M+H] + 489.1978, found 489.1981.

[0293]

[0294] Compound IV-14 was characterized as follows:

[0295] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.89, 52.68.

[0296] 1 H NMR (400 MHz, CDCl3) 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).

[0297] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0298]

[0299] Compound IV-15 was characterized as follows:

[0300] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.80, 52.83.

[0301] 1 H NMR (400 MHz, CDCl3) 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).

[0302] HRMS (ESI) calcd for C 32 H 27 ClOP + [M+H] + 493.1483, found 493.1483.

[0303]

[0304] Compound IV-16 was characterized as follows:

[0305] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.91, 52.72.

[0306] 1 H NMR (400 MHz, CDCl3) δ 7.64 (t, J = 8.1 Hz, 1H), 7.53 (t, J = 7.6Hz, 1H), 7.42 (dd, J = 7.7, 2.2 Hz, 1H), 7.36 (td, 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 = 4.4 Hz, 1H), 5.05 (d, J = 4.4 Hz, 1H), 3.73 (s, 3H), 3.23(s, 2H), 2.99 (dd, J = 14.9, 5.0 Hz, 2H), 2.81 (dd, J = 18.0, 15.2 Hz, 1H),2.63 (dd, J = 15.2, 6.7 Hz, 1H).

[0307] HRMS (ESI) calcd for C 33 H 30 O2P + [M+H] + 489.1978, found 489.1979.

[0308]

[0309] Compound IV-17 was characterized as follows:

[0310] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.78, 52.96.

[0311] 1 ​H NMR (400 MHz, CDCl3) 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).

[0312] HRMS (ESI) calcd for C 33 H 28 O2P + [M+H] + 487.1821, found 487.1820.

[0313]

[0314] Compound IV-18 was characterized as follows:

[0315] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 53.10.

[0316] 1 H NMR (400 MHz, CDCl3) 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).

[0317] HRMS (ESI) calcd for C 33 H 27 NOP + [M+H] + 484.1825, found 484.1823.

[0318]

[0319] Compound IV-19 was characterized as follows:

[0320] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.69, 52.85.

[0321] 1 H NMR (400 MHz, CDCl3) 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).

[0322] HRMS (ESI) calcd for C 33 H 37 F3OP + [M+H] + 527.1746, found 527.1747.

[0323]

[0324] Compound IV-20 was characterized as follows:

[0325] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.91, 52.82.

[0326] 1 H NMR (400 MHz, CDCl3) 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).

[0327] HRMS (ESI) calcd for C 38 H 32 OP + [M+H] + 535.2185, found 535.2185.

[0328]

[0329] Compound IV-21 was characterized as follows:

[0330] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.50, 52.26.

[0331] 1 H NMR (400 MHz, CDCl3) 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 =4.7 Hz, 1H), 4.97 (d, J = 4.7 Hz, 1H), 3.42 – 3.25 (m, 2H), 2.90 (dd, J =14.8, 8.4 Hz, 2H), 2.77 (dd, J = 18.2, 15.2 Hz, 1H), 2.61 (dd, J = 15.2, 7.0Hz, 1H).

[0332] HRMS (ESI) calcd for C 36 H 30 OP + [M+H] + 509.2029, found 509.2031.

[0333]

[0334] Compound IV-21 was characterized as follows:

[0335] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 52.86.

[0336] 1 H NMR (400 MHz, CDCl3) δ 7.78 – 7.60 (m, 5H), 7.56 (t, 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 = 6.6, 1.8 Hz, 2H), 5.39 (d, J = 4.7 Hz, 1H), 5.07 (d, J = 4.8 Hz, 1H), 3.30 (s, 2H), 3.02 (dd, J = 15.0, 5.6 Hz, 2H), 2.84 (dd, J = 17.9, 15.3 Hz, 1H), 2.67 (dd, J = 15.3, 6.9 Hz, 1H).

[0337] HRMS (ESI) calcd for C 36 H 30 OP + [M+H] + 509.2029, found 509.2028.

[0338]

[0339] Compound IV-23 was characterized as follows:

[0340] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.81, 52.44.

[0341] 1 H NMR (400 MHz, CDCl3) δ 7.63 (t, 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 = 4.2, 2.1 Hz, 1H), 5.37 (d, 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).

[0342] HRMS (ESI) calcd for C 32 H 32 OP + [M+H] + 463.2185, found 463.2187.

[0343]

[0344] Compound IV-24 was characterized as follows:

[0345] 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 56.42, 53.23.

[0346] 1 H NMR (500 MHz, CDCl3) δ 7.63 (t, J = 8.2 Hz, 1H), 7.55 (t, J = 7.6Hz, 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 = 5.2Hz, 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).

[0347] HRMS (ESI) calcd for C 30 H 26 OPS + [M+H] + 465.1437, found 465.1439.

[0348]

[0349] Compound IV-25 was characterized as follows:

[0350] 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 56.57, 53.40.

[0351] 1 H NMR (500 MHz, CDCl3) 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).

[0352] HRMS (ESI) calcd for C 30 H 26 OPS + [M+H] + 465.1437, found 465.1439.

[0353]

[0354] Compound IV-26 was characterized as follows:

[0355] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 51.72.

[0356] 1 H NMR (400 MHz, CDCl3) 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).

[0357] HRMS (ESI) calcd for C 31 H 34 O3P + [M+H] + 485.2240, found 485.2235.

[0358]

[0359] Compound IV-27 was characterized as follows:

[0360] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.97, 52.45.

[0361] 1 H NMR (400 MHz, CDCl3) 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).

[0362] HRMS (ESI) calcd for C 31 H 34 OP + [M+H] + 453.2342, found 453.2342.

[0363]

[0364] Compound IV-28 was characterized as follows:

[0365] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 52.79.

[0366] 1 H NMR (400 MHz, CDCl3) 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).

[0367] HRMS (ESI) calcd for C 33 H 30 OP + [M+H] + 473.2029, found 473.2029.

[0368]

[0369] Compound IV-29 was characterized as follows:

[0370] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 54.51, 51.66.

[0371] 1 H NMR (400 MHz, CDCl3) δ 7.51 (t,J = 8.3 Hz, 1H), 7.40 (d, 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 = 4.8 Hz, 1H), 5.07 (d, J = 4.8 Hz, 1H), 3.23 (s,2H), 3.06 (dd, J = 15.3, 4.3 Hz, 2H), 2.77 (dd, J = 17.5, 15.4 Hz, 1H), 2.62(dd, J = 15.3, 6.8 Hz, 1H).

[0372] HRMS (ESI) calcd for C 32 H 27 ClOP + [M+H] + 493.1483, found 493.1483.

[0373]

[0374] Compound IV-30 was characterized as follows:

[0375] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.02.

[0376] 1 H NMR (400 MHz, CDCl3) δ 7.91 – 7.82 (m, 2H), 7.71 (t, 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).

[0377] HRMS (ESI) calcd for C 36 H 30 OP + [M+H] + 509.2029, found 509.2029.

[0378]

[0379] Compound IV-31 was characterized as follows:

[0380] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 55.87, 52.61.

[0381] 1 H NMR (400 MHz, CDCl3) 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).

[0382] HRMS (ESI) calcd for C 32 H 26 Cl2OP + [M+H]+ 527.1093, found 527.1093.

[0383]

[0384] Compound IV-32 was characterized as follows:

[0385] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 53.91.

[0386] 1 H NMR (400 MHz, CDCl3) 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).

[0387] HRMS (ESI) calcd for C 22 H 24 OP + [M+H] + 335.1559, found 335.1559.

[0388] Example 12: Synthesis of product IX

[0389]

[0390] The experimental procedure of Example 12 was followed as in Example 11 using compound IV-1 as shown in formula IV-1P - chiral phosphine oxide, the remaining procedure steps are the same as Example 11, to give the corresponding target compound of formula ( S , R )-IX.

[0391] The obtained concentrated crude product was purified by column chromatography to give the target compound of formula ( S , R )-IX as a light yellow oil in 68% yield with a dr value > 20: 1 and 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).

[0392] The compound of formula ( S , R )-IX was characterized as follows:

[0393] 1 H NMR (400 MHz, CDCl3) 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).

[0394] 13 C NMR (100 MHz, CDCl3) 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).

[0395] 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 31.56.

[0396] FT-IR (neat) 2374, 1597, 1491, 1443, 1265, 1158, 1058, 1029, 909, 862, 757, 733, 700, 667 cm -1 .

[0397] HRMS (ESI) calcd for C 32 H 31 BP + [M-BH3] +443.5498, found 443.1926.

[0398] Application Example 1: Trivalent phosphine P - chiral phosphine compound S , R ) VIII was applied as ligand to the palladium catalyzed asymmetric allylic substitution reaction to synthesize compound 3. The reaction scheme is as follows:

[0399]

[0400] Experimental procedure: In a 10 mL Schlenk tube, compound 1 (0.2 mmol), compound 2 (0.6 mmol), toluene (1 mL), BSA (0.6 mmol) were added. The reaction mixture was stirred at room temperature for 16 h. TLC was used to monitor the reaction progress. After the reaction was completed, the reaction mixture was filtered through celite. The filtrate was concentrated and the obtained crude product was separated by silica gel column chromatography (PE:EA = 10:1) to give the target product compound 3 in 95% yield with 12% ee value. S , R ) VIII (0.03 mmol) was added. After being purged with argon for 5 times, 2 mL of methanol:toluene = 1:1 mixed solution was added. The reaction mixture was stirred at 80 °C for 12 h. After the reaction was completed, the reaction mixture was directly purged with argon. Potassium acetate (10 mol%) was added. After being purged with argon for 5 times, [Pd(C3H5)Cl]2(0.015 mmol), AgPF6(0.033 mmol) were added. The reaction mixture was stirred at room temperature for 6 h. After the reaction was completed, the reaction mixture was directly purged with argon. Compound 1 (0.2 mmol), compound 2 (0.6 mmol), toluene (1 mL), BSA (0.6 mmol) were added. The reaction mixture was stirred at room temperature for 16 h. TLC was used to monitor the reaction progress. After the reaction was completed, the reaction mixture was filtered through celite. The filtrate was concentrated and the obtained crude product was separated by silica gel column chromatography (PE:EA = 10:1) to give the target product compound 3 in 95% yield with 12% ee value. Figure 2 The figure shows the comparison of racemic (top) and chiral catalysis (bottom) effect of compound 3 (with HPLC chart corresponding retention time and peak area data).

[0401] The HPLC data of compound 3 is as follows, 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.

[0402] Application Example 2: Trivalent phosphine P - chiral phosphine compound S , R ) IX was applied as ligand to the palladium catalyzed asymmetric allylic substitution reaction to synthesize compound 3. The reaction scheme is as follows:

[0403]

[0404] The experimental method of application test example 2 was used with reference to application test example 1, and trivalent phosphine P -chiral phosphine compound was used S , R -IX, and the rest of the operation steps were the same as those of application test example 1, and the corresponding target compound 3 was finally obtained, with a yield of 78% and an ee value of 44%. Figure 3 The racemate (top) and chiral catalysis (bottom) effect comparison chart of compound 3 is shown in Figure 2.

[0405] The HPLC data of the obtained compound 3 is as follows: 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.

[0406] To demonstrate the beneficial effect of trivalent phosphine P -chiral phosphine compound in the asymmetric allyl substitution reaction, a control test example was set up, without adding trivalent phosphine P -chiral phosphine compound, and the rest of the conditions were unchanged, and the catalytic results of the three were as shown in Table 2.

[0407] Table 2 Catalytic effect comparison of trivalent phosphine P -chiral phosphine compound in asymmetric allyl substitution reaction

[0408] The catalytic reaction results shown in the table show that the trivalent phosphine P -chiral phosphine compound as a ligand applied to the palladium-catalyzed asymmetric allyl substitution reaction has a better catalytic effect, and shows good prospects for the ligand in the asymmetric allyl substitution reaction type.

[0409] Obviously, the above embodiments of the present application are only examples for clearly illustrating the technical solutions of the present application, and are not intended to limit the specific embodiments of the present application. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. Use of a P-chiral phosphine oxide compound containing an alkynyl or triazolyl functional group in a palladium-catalyzed asymmetric allylic substitution reaction, characterized in that, The structural formula of the compound is one of the following structural formulae: 、 ； The palladium-catalyzed asymmetric allylic substitution reaction is as follows: 。

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