Trifluoromethyl-containing polysubstituted phosphorus-doped six-membered ring phosphine oxide compound as well as preparation method and application of trifluoromethyl-containing polysubstituted phosphorus-doped six-membered ring phosphine oxide compound

Abstract

The invention discloses a trifluoromethyl-containing polysubstituted phosphorus-doped six-membered ring phosphine oxide compound as well as a preparation method and application of the trifluoromethyl-containing polysubstituted phosphorus-doped six-membered ring phosphine oxide compound. A diene-containing three-stage phosphine oxide compound is used as a raw material, a trifluoromethyl reagent and a nucleophilic reagent are used, in the presence of a transition metal copper catalyst and a pyridine-oxazoline ligand, a free radical domino cyclization reaction is initiated to obtain the compound, C-O, C-N and C-C coupling is realized, and the variety of the nucleophilic reagent can be changed, so that the structure of the product is diversified. The diastereoisomers can be separated, the yield of a single diastereomer can reach 85%, and the diastereoisomers have excellent diastereoselectivity. The invention provides a novel reaction mode of constructing a polysubstituted phosphorus-doped six-membered ring by mediation of free radicals, the reaction condition is mild, the operation is simple, the substrate universality is good, a novel skeleton structure of an organic phosphine reagent is provided, and the variety diversity of the organic phosphine reagent is expanded. The synthesized compound can be used as a catalyst to be applied to Appel reaction, and has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of catalysis technology and relates to a trifluoromethyl-containing polysubstituted phosphorus-hexagonal phosphine oxide compound and a preparation method and application thereof, and more particularly to a polysubstituted phosphorus-hexagonal novel organic phosphine reagent as a catalyst for Appel reaction. Background Art

[0002] Organophosphine reagents play a crucial role in organic synthesis. Wittig, Staudinger, Appel, and Mitsunobu reactions mediated by organophosphorus compounds are of great significance in scientific research and industrial production. Nucleophilic substitution of alcohols by halides plays an important role in the synthesis of natural products and the formation of reactive intermediates. Traditional halogenation of alcohols typically uses highly reactive reagents such as thionyl chloride or phosphorus trichloride [Appel, R. Angew. Chem., Int. Ed. 1975, 14 , 801.] This may result in low functional group compatibility and stereospecificity, or require prior activation of the alcohol, resulting in low atom economy. The Appel reaction can use a trivalent phosphine reagent and chloride to form a chlorophosphonium salt that reacts with the alcohol, which can greatly improve stereospecificity to produce the corresponding haloalkyl. However, there is a major drawback: a stoichiometric amount of trivalent phosphine reagent is required, and a stoichiometric amount of phosphine oxide R3P=O is produced as a byproduct, resulting in low atom economy [Longwitz L., Werner T., Pure Appl. Chem. 2019, 91 , 95–102.], which affects the post-treatment process and the efficient separation of products. Therefore, a reducing agent is introduced into the reaction system to reduce P(V) to P(III), thereby realizing the catalytic cycle, avoiding the generation of by-products, improving economic benefits, and complying with the concept of green chemistry [Pei MY; Li D.; Green Synthesis and Catalysis .2023, 4 , 135–149.], the research on this catalytic mode has developed rapidly in recent years. In the P(Ⅲ) / P(V) catalytic cycle, the reduction of P(V) to P(Ⅲ) is a reverse thermodynamic process, and the cyclic P(V)=O has a lower reduction energy barrier than the non-cyclic P(V)=O [Hérault, D., Chem. Soc. Rev. 2015, 44, 2508.], the design of special skeleton organophosphine reagents is favored by organic synthetic chemists [Kwon O.; Guo HC, Chem. Rev . 2018, 118 , 10049−10293.], however, the research on phosphorus heterocycles as catalysts for Appel reaction mainly focuses on phosphorus heterocycles with five-membered rings and bridged phosphorus heterocycles with phosphine oxides [O'Brien CJ, Angew. Chem. Int. Ed.2014, 53 , 12907–12911.], while phosphorus-hexagonal phosphine oxide compounds are only used as cases in screening conditions, and there are few reports on their research.

[0003] Phosphorus heterocycles are an important branch of organophosphorus compounds. Due to their unique structure and properties, phosphorus heterocycles not only show a wide range of application potential in the fields of coordination chemistry and catalysis, but also have important development value in the fields of medicinal chemistry and materials [Bruch A., Angew. Chem. Int. Ed., 2011, 50 , 12094-12098.]. Currently, the methods for constructing functional phosphorus-containing six-membered ring compounds mainly use pre-prepared phosphorus-containing substrates and active metal reagents. These methods have the disadvantages of harsh reaction conditions, poor atom economy, poor functional group tolerance, easy oxidation and instability of substrates, many side reactions, low yields or difficulty in large-scale preparation [Keller, PA, J. Org. Chem. 2015, 80 , 9774–9780.]. Therefore, the exploration of simple and efficient new methods for the construction of phosphorus heterocycles has attracted the attention of organic synthetic chemists. In recent years, the strategy for the construction of phosphorus heterocycles from diene phosphine oxides is commonly seen in transition metal-catalyzed olefin metathesis reactions [Gouverneur, V., Angew. Chem. Int. Ed. 2009, 48 , 762–766.] or electrophilic substitution occurs by forming carbocations under superacidic conditions [Thibaudeau, S., Angew. Chem. Int. Ed. 2019, 58 , 1355–1360.], but the product skeleton structure is simple and limited by the substrate itself. There are few reports on the construction of multi-substituted phosphorus hexacyclic rings by cheap transition metal-catalyzed radical domino cyclization reactions involving alkenyl tertiary phosphine oxide compounds. Due to the high activity of free radical intermediates and the complexity of the reaction process, diene phosphine oxide compounds are used as substrates to efficiently control the regioselectivity and stereoselectivity of the phosphorus hexacyclic rings, and inhibit free radical coupling, β The competition of side reactions such as -H elimination, quenching, and hydrogen abstraction is quite challenging. The synthesis of nitrogen heterocycles and oxygen heterocycles containing quaternary carbon centers through free radical domino cyclization has attracted much attention from scholars at home and abroad [Kiss L., Chem. Eur. J. 2023, 29 , e202203499.], but most of them terminate the reaction with free radicals without adding nucleophiles to construct diverse skeletons, and this type of catalytic reaction has not been reported in the synthesis of phosphorus heterocyclic phosphine oxide compounds. Summary of the Invention

[0004] In response to the current state of synthesis of phosphanic hexacyclic rings, this invention introduces a trifluoromethyl functional group into phosphine oxide compounds through a three-component, inexpensive transition metal copper-catalyzed free radical domino cyclization reaction. This simultaneously constructs a multi-substituted phosphanic hexacyclic phosphine oxide compound containing a phosphine chiral center and two quaternary carbon chiral centers, achieving multiple coupling modes such as C–O, C–N, and C–C. This allows for varying the type of nucleophilic reagent and diversifying the product structure. The resulting phosphanic hexacyclic phosphine oxide compound is used as a catalyst in the Appel reaction, providing a novel skeleton structure for organophosphine reagents and expanding their diversity. The trifluoromethyl group, as a strong electron-withdrawing group, possesses high chemical and metabolic stability and significant lipophilicity. Its introduction into the phosphanic heterocyclic molecule can modulate the lipophilic-hydrophilic balance of the entire molecule, making it more easily penetrate cell membranes and biological barriers, thus facilitating the development of new drugs.

[0005] To achieve the above objectives, the present invention provides the following technical solutions:

[0006] A trifluoromethyl-containing multi-substituted phosphorus-hexagonal phosphine oxide compound, comprising any one of the following structural formulas (1), (2), and (3):

[0007] Among them, in the general structural formula (1):

[0008] Ar 1 is a benzene ring, a benzo-1,3-dioxolane ring or a naphthalene ring; n is an integer, and n is 0, 1 or 2;

[0009] R 1 is hydrogen, a halogen atom, a trifluoromethyl group, a C1~C6 saturated alkoxy group, or a C1~C6 saturated alkyl group;

[0010] R 2 is a C1~C6 saturated alkyl group, a phenyl group or a benzyl group; wherein the hydrogen atom on the phenyl group or the benzyl group may be substituted by a C1~C3 saturated alkyl group or a halogen atom;

[0011] R 3 is hydrogen, C1~C6 saturated alkyl, C1~C6 cycloalkyl, benzyl, phenyl, 、 、 、 or ;

[0012] In the general structural formula (2):

[0013] Ar 1’ is phenyl; R 1’ is hydrogen or C1~C3 saturated alkyl; R 2’ is phenyl;

[0014] R 4 Phenyl, substituted phenyl, 、 、 or ;Substituted phenyl means that the hydrogen on the phenyl group may be replaced by a C1~C3 saturated alkyl group or a halogen atom;

[0015] In the general structural formula (3):

[0016] Ar 1” is phenyl; R 1” is hydrogen or C1~C3 saturated alkyl; R 2” is phenyl;

[0017] R 5 for 、 、 、 、 、 、 、 or .

[0018] Preferably, in the general structural formula (1):

[0019] Ar 1 is a benzene ring, a benzo-1,3-dioxolane ring or a naphthalene ring; n is an integer, and n is 0, 1 or 2;

[0020] R 1 is hydrogen, a halogen atom, a trifluoromethyl group, a C1~C3 saturated alkoxy group, or a C1~C3 saturated alkyl group;

[0021] R 2 is a C1-C6 saturated alkyl, phenyl or benzyl group; wherein the hydrogen on the phenyl or benzyl group may be substituted by a halogen atom; the halogen atom is bromine or chlorine;

[0022] R 3 is hydrogen, C1~C3 saturated alkyl, cyclohexyl, benzyl, phenyl, 、 、 、 or ;

[0023] In the general structural formula (2):

[0024] Ar 1’ is a benzene ring; R 1’ is hydrogen or C1~C3 saturated alkyl; R 2’ is phenyl;

[0025] R 4 Phenyl, substituted phenyl, 、 、 or ; The substituted phenyl group means that the hydrogen on the phenyl group may be replaced by a C1~C3 saturated alkyl group or a halogen atom; the halogen atom is bromine or chlorine;

[0026] In the general structural formula (3):

[0027] Ar 1” is phenyl; R 1” is hydrogen or C1~C3 saturated alkyl; R 2” is phenyl;

[0028] R 5 for 、 、 、 、 、 、 、 ,or .

[0029] The present invention also provides a method for preparing the above compound, comprising the following steps:

[0030] Step S1:

[0031] Under the protection of inert gas, compound I is added with a silanization reagent in acetonitrile to obtain compound I-1, which is then reacted to completion. The mixture is then concentrated under reduced pressure to a dry state and then used in the next reaction.

[0032] Step S2:

[0033] Under the protection of inert gas, compound Ⅰ-1 was used as raw material, dichloromethane was added as solvent, and the mixture was cooled to 0°C. Under the catalysis of N,N-dimethylformamide, the phosphonic acid was chlorinated with an acyl chloride reagent. The mixture was transferred to room temperature for reaction until completion, and then the mixture was concentrated under reduced pressure to dryness and put into the next reaction.

[0034] Step S3:

[0035] Under inert gas, dry phosphonyl chloride compound I-2 is added to an ether dilution system. Freshly prepared Grignard reagent I-3 is added to phosphonyl chloride compound I-2 at 0°C, and the mixture is stirred overnight at room temperature. After extraction, the product is separated and purified by column chromatography to obtain diene phosphine oxide compound II.

[0036] Step S4:

[0037] Under inert gas protection, an organic solvent was added to a reaction system containing diene phosphine oxide compound II, oxygen nucleophile reagent III containing different substituents, and trifluoromethyl reagent IV as raw materials. A copper metal precursor and a ligand were used as catalysts. The system was stirred at 40-80 °C, followed by extraction, filtration, and concentration under reduced pressure. The resulting concentrated crude product was separated and purified by column chromatography to obtain the target compound V, a phosphorus-containing six-membered ring phosphine oxide compound with oxygen as the nucleophile.

[0038] When the diene phosphine oxide compounds II in the general structural formulas (1), (2) and (3) are the same, Ar 1 、R 1 、R 2 and R 3 same.

[0039] Step S5:

[0040] Under inert gas protection, an organic solvent was added to a reaction system containing a diene phosphine oxide compound II, a nitrogen nucleophile VI containing different substituents, and a trifluoromethyl reagent IV as raw materials. A copper metal precursor and a ligand were used as catalysts. The reaction was stirred at 40-80°C, followed by extraction, filtration, and concentration under reduced pressure. The resulting concentrated crude product was separated and purified by column chromatography to obtain the target compound VII, a phosphorus-containing six-membered ring phosphine oxide compound with nitrogen as a nucleophile.

[0041] Step S6:

[0042] Under inert gas protection, an organic solvent was added to a reaction system containing diene phosphine oxide compound II, carbon nucleophile containing different substituents VIII, and trifluoromethyl reagent IV as raw materials. A copper metal precursor and a ligand were used as catalysts. The system was stirred at 40-80 °C, followed by extraction, filtration, and concentration under reduced pressure. The resulting concentrated crude product was separated and purified by column chromatography to obtain the target compound IX, a phosphorus-containing six-membered ring phosphine oxide compound with carbon as a nucleophile.

[0043] In the present invention, the copper metal precursor (copper catalyst) in step S4, step S5 and step S6 is selected from one of tetraacetonitrile copper tetrafluoroborate, tetraacetonitrile copper hexafluorophosphate, cuprous acetate, cuprous chloride, cuprous bromide, cuprous oxide, cuprous iodide, cuprous fluoride, cuprous sulfide, cuprous cyanide, cuprous acetylene and cuprous nitrate.

[0044] In the present invention, the ligands in step S4, step S5 and step S6 are chiral nitrogen ligands, achiral nitrogen ligands, hybrid ligands (heterocyclic ligands), spirocyclic ligands, etc.

[0045] In the present invention, the CF3 (trifluoromethyl) reagent in step S4, step S5 and step S6 is selected from one of 3.3-dimethyl-1-(trifluoromethyl)-1,2-benzoiodoxolane, 1-trifluoromethyl-1,2-benzidoyl-3(1H)-one, trifluoromethyltrimethylsilane, diphenyl(trifluoromethyl)sulfonium trifluoromethanesulfonate, S-(trifluoromethyl)dibenzothiophene tetrafluoroborate, S-(trifluoromethyl)dibenzothiophene trifluoromethanesulfonate, 5-(trifluoromethyl)-5H-dithiaanthraquinone-5-phosphinothioate, sodium trifluoromethanesulfinate and trifluoroiodomethane.

[0046] In the present invention, the organic solvent in step S4, step S5 and step S6 is one of dichloromethane, dichloroethane, acetonitrile, propionitrile, butyronitrile, valeronitrile, benzonitrile, benzyl cyanide, ethyl 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, or any mixture thereof.

[0047] In the present invention, the feed ratios in step S4, step S5, and step S6 are as follows: the molar ratio of the diene phosphine oxide compound II to the nucleophilic reagents with different substituents is 1:(1.0-2.0); the molar ratio of the diene phosphine oxide compound II: the copper metal precursor: the ligand is 1:(0.03-0.2):(0.06-0.4); and the volume ratio of the molar amount of the diene phosphine oxide compound II to the organic solvent is 1 mmol:(1-10) mL.

[0048] As a preferred embodiment, the molar ratio of the material of formula I and the silanization agent in step S1 is 1:4, the reaction temperature is 50° C., and the reaction time is 2 hours.

[0049] 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.

[0050] In the present invention, the molar ratio of the material formula I-2 and the Grignard reagent I-3 in step S3 is 1:1.4, the reaction temperature is room temperature, the reaction time is 12 hours, and the acid-base extraction is followed by reduced pressure concentration and post-treatment by column chromatography.

[0051] In the present invention, the molar ratio of diene phosphine oxide compound II, various types of nucleophilic reagents, CF3 reagent, copper metal precursor, and ligand in steps S4, S5, and S6 is 1:5:1.5:0.1:0.11, the reaction temperature is 70°C, the reaction time is 12 hours, and the reaction is concentrated under reduced pressure and then purified by column chromatography.

[0052] In the present invention, the copper metal precursor in step S4, step S5 and step S6 is selected from copper tetrafluoroborate tetraacetonitrile.

[0053] In the present invention, the CF3 (trifluoromethyl) reagent in step S4, step S5 and step S6 is selected from 3,3-dimethyl-1-(trifluoromethyl)-1,2-benzoiodooxolane.

[0054] In the present invention, the optimal ligand in step S4, step S5 and step S6 is selected from (S)-4-tert-butyl-2-(2-pyridyl)oxazoline.

[0055] In the present invention, the organic solvent in step S4, step S5 and step S6 is selected from 1,2-dichloroethane.

[0056] The present invention simultaneously protects the application of the trifluoromethyl-containing multi-substituted phosphorus hexacyclic phosphine oxide compound in catalysis; further, the invention protects the application of the trivalent phosphine-containing compound in in-situ catalysis of the Appel reaction.

[0057] Definitions of terms used in the present invention: Unless otherwise stated, the initial definitions provided for groups or terms in this document apply to the groups or terms throughout the specification; for terms that are not specifically defined herein, they should be given the meaning that a person skilled in the art would give them based on the disclosure and context.

[0058] "Substitution" refers to the replacement of a hydrogen atom in a molecule by another different atom or molecule.

[0059] The minimum and maximum carbon atom content of a hydrocarbon group is indicated by a prefix. For example, the prefix C1-C4 alkyl indicates any alkyl group containing from "a" to "b" carbon atoms. Thus, for example, C1-C4 alkyl refers to an alkyl group containing from 1 to 4 carbon atoms.

[0060] The C1-C6 alkyl group refers to a C1, C2, C3, C4, C5, or C6 alkyl group, i.e., a linear or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, etc. C1-C6 alkoxy also has the same meaning as the group to which it refers.

[0061] C1-C6 saturated alkyl refers to a straight or branched saturated alkyl group (i.e., a hydrocarbon group containing only single bonds) consisting of 1 to 6 carbon atoms, without double or triple bonds. C1-C6 saturated alkoxy also has the same meaning as the group to which it refers.

[0062] Compared with the prior art, the present invention has the following beneficial effects:

[0063] The present invention provides a new model for the copper-catalyzed free radical domino cyclization reaction for the synthesis of trifluoromethyl-containing polysubstituted phosphino six-membered ring phosphino oxide compounds from diene phosphino oxide compounds. The yield of a single diastereoisomer can reach 85%, which opens up a new idea for the synthesis of phosphino six-membered ring phosphino oxide compounds. Through a three-component reaction, a trifluoromethyl functional group is introduced into the phosphino oxide compound, and three chiral centers are constructed at the same time. By adding an external nucleophilic reagent, a variety of C–O, C–N, and C–C coupling reactions can be achieved. The type of nucleophilic reagent can be changed to diversify the product structure, greatly enriching the reaction strategy and the skeleton structure of the phosphino oxide product. The phosphino six-membered ring phosphino oxide compound provided by the present invention is used as a catalyst in the Appel reaction, providing a new skeleton structure for organic phosphine reagents and expanding the diversity of their types. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] Figure 1 This is a route for synthesizing diene phosphine oxide compound II according to Example 1 of the present invention;

[0065] Figure 2 This is the single crystal diffraction structure of compound IX-2 of the present invention. DETAILED DESCRIPTION

[0066] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. Unless otherwise specified, the test methods used in the embodiments of the present invention are conventional methods; the materials, reagents, etc. used, unless otherwise specified, are reagents and materials that can be obtained from commercial channels.

[0067] Example 1 Synthesis of Diene Phosphine Oxide Compound II:

[0068] Using diethyl phosphite compound I as the starting material, a bromosilane reagent is added to acetonitrile, and the reaction is carried out at 50°C for 2 hours to obtain compound I-1, which is then concentrated under reduced pressure to a dry state and put into the next reaction. In the second step, N,N-dimethylformamide is used as a catalyst, the reaction system is diluted with dichloromethane, and phosphonochlorination is carried out with oxalyl chloride at 0°C, and then the reaction is completed at room temperature to obtain compound I-2 phosphonochloride compound, which is concentrated under reduced pressure to a dry state. After compound I-2 is filled with argon 3-5 times, the reaction system is diluted with ether, and the freshly prepared Grignard reagent I-3 is added at 0°C, followed by stirring at room temperature overnight. After quenching the reaction, separating the liquids, filtering, drying, concentrating under reduced pressure, and separating and purifying, the diene phosphine oxide compound II is obtained. The synthesis steps are as follows Figure 1 As shown (those skilled in the art can determine each R group based on the structural formula of compounds I-1 to I-3, which will not be described in detail). The synthesis steps are described as follows:

[0069] Step S1: After purging with argon three times, trimethylsilyl bromide (40 mmol) was added to the starting material compound I (10 mmol) in acetonitrile (10 mL), and the mixture was 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 reaction.

[0070] Step S2: After purging with argon three times, at 0°C, N, N-dimethylformamide (2-3 drops) was used as a catalyst to carry out phosphonyl chlorination with oxalyl chloride (30 mmol). Compound I-1 was chlorinated by adding oxalyl chloride (30 mmol) to dichloromethane (10 mL). After reacting at room temperature for 4 hours, the mixture was concentrated under reduced pressure to dryness to obtain phosphonyl chloride compound I-2.

[0071] Step S3: After three purgings with argon, compound I-2 was added to diethyl ether (10 mL) at 0°C. The freshly prepared Grignard reagent (15 mmol) was added to the phosphonyl chloride compound I-2, and the mixture was stirred overnight at room temperature. The reaction was then quenched by the addition of saturated ammonium chloride solution (50 mL). The organic phase was extracted three times with ethyl acetate, washed with saturated sodium bicarbonate solution (50 mL), and concentrated under reduced pressure. The crude product was purified by column chromatography using a 3:1 ratio of petroleum ether to ethyl acetate to obtain the diene phosphine oxide compound.

[0072] The characterization of each diene phosphine oxide compound is as follows:

[0073] The characterization data of compound II-1 are as follows:

[0074]

[0075] White solid (2.0 g, 56% yield). Melting point: 88.1–92.9 °C. 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 35.60. 1 H NMR (400 MHz, CDCl3) δ 7.52 (dd, 2H), 7.37 (td, J = 7.3,1.5 Hz, 1H), 7.29 – 7.20 (m, 12H), 5.37 (d, J = 4.5 Hz, 2H), 5.17 (d, J = 4.6Hz, 2H), 3.30 – 3.10 (m, 4H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 141.23 (d,J C-P =3.3 Hz), 139.00 (d, J C-P = 8.7 Hz), 131.57 (d, J C-P = 2.8 Hz), 131.44 (d, J C-P =95.2 Hz), 131.13 (d, J C-P = 8.9 Hz), 128.45, 128.11 (d, J C-P = 11.5 Hz),127.80, 126.45, 117.94 (d, J C-P = 8.8 Hz), 37.28 (d, J C-P = 63.4 Hz). FT-IR(KBr): 3085, 3053, 2945, 2905, 1621, 1573, 1493, 1437, 1303, 1231, 1192, 1115,1092, 1070, 1029, 945, 894, 869, 776, 761, 744, 727, 698, 627, 613, 589, 523,491, 481, 470 cm -1 . HRMS (ESI) calcd for C 24 H 24 OP + [M+H] + 359.1559, found359.1561.

[0076] The characterization data of compound II-2 are as follows:

[0077]

[0078] White solid (1.3 g, 34% yield). Melting point: 128.2–133.0 °C. 31 P{ 1 H} NMR (202MHz, CDCl3) δ 41.97. 1 H NMR (500 MHz, CDCl3) δ 7.36 – 7.32 (m, 5H), 7.32 –7.27 (m, 5H), 7.26 – 7.20 (m, 3H), 7.13 (dt, J = 7.8, 1.8 Hz, 2H), 5.48 (d, J = 4.3 Hz, 2H), 5.30 (d, J = 4.4 Hz, 2H), 2.98 – 2.83 (m, 6H). 13 C NMR (126MHz, CDCl3) δ 141.00 (d, J C-P = 3.5 Hz), 139.22 (d, J C-P = 8.1 Hz), 131.77 (d, J C-P = 7.4 Hz), 129.96 (d, J C-P = 5.3 Hz), 128.69, 128.67, 128.09, 126.91 (d, J C-P = 2.9 Hz), 126.37, 118.00 (d, J C-P = 8.8 Hz), 35.89 (d, J C-P = 60.9 Hz),34.92 (d, J C-P = 60.6 Hz). FT-IR (KBr): 3083, 3057, 3028, 2951, 2911, 1673,1599, 1495, 1445, 1412, 1301, 1275, 1238, 1190, 1147, 1129, 1067, 1029, 913,903, 862, 780, 733, 700, 487 cm -1 . HRMS (ESI) calcd for C 25 H 26 OP + [M+H] + 373.1716, found 373.1721.

[0079] The characterization data of compound II-3 are as follows:

[0080]

[0081] White solid (2.0 g, 52% yield). Melting point: 135.0–156.5 °C. 31 P{ 1 H} NMR (162MHz, CDCl3) δ 33.76. 1 H NMR (400 MHz, CDCl3) δ 7.78 (ddd, J = 12.4, 7.5, 1.8Hz, 1H), 7.30 (td, J = 8.2, 1.8 Hz, 1H), 7.24 – 7.12 (m, 10H), 6.95 (tt, J =7.5, 1.2 Hz, 1H), 6.47 (dd, J = 8.3, 5.5 Hz, 1H), 5.31 (dd, J = 5.0, 1.2 Hz,2H), 5.22 (dd, J = 5.0, 1.1 Hz, 2H), 3.51 (s, 3H), 3.38 – 3.20 (m, 4H). 13 CNMR (100 MHz, CDCl3) δ 158.43 (d, J C-P = 5.1 Hz), 141.39 (d, J C-P = 3.2 Hz),139.34 (d, J C-P = 9.9 Hz), 135.23 (d, J C-P = 4.3 Hz), 133.48 (d, J C-P = 2.2 Hz),127.84, 127.16, 126.25 (d, J C-P = 1.2 Hz), 120.57 (d, J C-P = 10.5 Hz), 118.57(d, J C-P = 93.4 Hz), 117.01 (d, J C-P = 9.2 Hz), 109.39 (d, JC-P = 6.9 Hz),54.52, 36.34 (d, J C-P = 64.1 Hz). FT-IR (KBr): 3085, 3050, 2901, 2834, 1621,1590, 1575, 1493, 1478, 1463, 1444, 1431, 1406, 1302, 1274, 1242, 1223, 1199,1155, 1078, 1023, 940, 907, 897, 855, 775, 756, 732, 707, 639, 587, 501, 479,417 cm -1 . HRMS (ESI) calcd for C 25 H 26 O2P + [M+H] + 389.1665, found 389.1669.

[0082] The characterization data of compound II-4 are as follows:

[0083]

[0084] White solid (2.1 g, 50% yield). Melting point: 93.3–97.9 °C. 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 34.93. 1 H NMR (500 MHz, CDCl3) δ 7.49 (ddd, J = 11.2, 8.1, 1.3 Hz,2H), 7.40 (td, J = 7.4, 1.4 Hz, 1H), 7.28 (td, J = 7.5, 2.8 Hz, 2H), 7.22 –7.15 (m, 8H), 5.34 (d, J = 4.5 Hz, 2H), 5.13 (d, J = 4.5 Hz, 2H), 3.26 – 3.08(m, 4H). 13 C NMR (126 MHz, CDCl3) δ 139.42 (d, J C-P = 3.2 Hz), 137.95 (d, JC-P =9.1 Hz), 133.61, 131.69 (d, J C-P = 2.8 Hz), 131.04 (d, J C-P = 95.6 Hz), 130.98(d, J C-P = 9.0 Hz), 128.46, 128.22 (d, J C-P = 11.8 Hz), 127.77, 118.31 (d, J C-P = 8.9 Hz), 37.27 (d, J C-P = 63.4 Hz). FT-IR (KBr): 3081, 3052, 2904, 1616,1590, 1493, 1436, 1411, 1396, 1299, 1188, 1156, 1113, 1095, 1011, 943, 904,863, 832, 765, 733, 695, 676, 651, 628, 490, 473, 455, 440, 422 cm -1 . HRMS(ESI) calcd for C 27 H 29 F3O2P + [M+H] + 473.1852, found 473.1854.

[0085] The characterization data of compound II-5 are as follows:

[0086]

[0087] Brown oil (1.3 g, 32% yield). 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 38.14. 1 HNMR (500 MHz, CDCl3) δ 8.63 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H),7.79 (d, J = 7.9 Hz, 1H), 7.67 (dd, J= 14.2, 7.1 Hz, 1H), 7.52 (ddd, J =8.4, 6.7, 1.6 Hz, 1H), 7.48 (t, J = 6.7 Hz, 1H), 7.29 (td, J = 7.7, 2.3 Hz,1H), 7.21 – 7.17 (m, 4H), 7.16 – 7.12 (m, 6H), 5.31 (d, J = 4.4 Hz, 2H), 5.16(d, J = 4.6 Hz, 2H), 3.51 – 3.36 (m, 4H). 13 C NMR (126 MHz, CDCl3) δ 141.07(d, J C-P = 3.5 Hz), 139.33 (d, J C-P = 8.5 Hz), 133.64 (d, J C-P = 9.3 Hz), 133.45(d, J C-P = 8.9 Hz), 132.90 (d, J C-P = 3.1 Hz), 132.71 (d, J C-P = 8.5 Hz),129.17, 128.82 (d, J C-P = 67.2 Hz), 128.24, 127.67, 127.17, 126.40, 126.14,126.10 (d, J C-P = 3.8 Hz), 124.27 (d, J C-P = 12.8 Hz), 118.04 (d, J C-P = 9.0Hz), 37.56 (d, J C-P= 63.9 Hz). FT-IR (KBr): 3080, 3055, 2959, 2918, 1673,1506, 1495, 1445, 1271, 1208, 1182, 1156, 1143, 1027, 985, 801, 774, 758,730, 698, 670, 441, 432 cm -1 . HRMS (ESI) calcd for C 28 H 26 OP + [M+H] + 409.1716, found 409.1722.

[0088] The characterization data of compound II-6 are as follows:

[0089]

[0090] Brown oil (925 mg, 23% yield). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 35.75. 1 HNMR (400 MHz, CDCl3) δ 7.29 – 7.26 (m, 5H), 7.25 – 7.20 (m, 5H), 7.05 (ddd, J = 11.7, 7.9, 1.5 Hz, 1H), 6.86 (dd, J = 10.5, 1.4 Hz, 1H), 6.68 (dd, J = 7.9,2.4 Hz, 1H), 5.92 (s, 2H), 5.39 (d, J = 4.6 Hz, 2H), 5.18 (d, J = 4.6 Hz, 2H), 3.25 – 3.07 (m, 4H). 13 C NMR (126 MHz, CDCl3) δ 150.41 (d, J C-P = 3.0 Hz),147.49 (d, J C-P = 17.6 Hz), 141.11 (d, J C-P = 3.4 Hz), 138.94 (d, JC-P = 8.7Hz), 132.10 (d, J C-P = 9.7 Hz), 128.33, 127.67, 126.36, 124.16 (d, J C-P = 99.0Hz), 117.83 (d, J C-P = 9.0 Hz), 110.52 (d, J C-P = 11.9 Hz), 108.22, 101.41,37.33 (d, J C-P = 63.9 Hz). FT-IR (KBr): 3056, 3025, 2901, 1674, 1501, 1484,1446, 1426, 1338, 1301, 1244, 1184, 1143, 1114, 1064, 1036, 932, 900, 809,777, 755, 729, 699, 641, 599, 420 cm -1 . HRMS (ESI) calcd for C 25 H 24 O3P + [M+H] + 403.1458, found 403.1464.

[0091] The characterization data of compound II-7 are as follows:

[0092]

[0093] Colorless oil (1.3 g, 34% yield). 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 38.13. 1 HNMR (500 MHz, CDCl3) δ 7.41 (ddd, J = 12.5, 7.7, 1.4 Hz, 1H), 7.25 – 7.20 (m,11H), 7.07 (tt, J = 7.6, 1.8 Hz, 1H), 7.02 (dd, J = 7.8, 4.3 Hz, 1H), 5.34(d, J= 4.3 Hz, 2H), 5.19 (d, J = 4.4 Hz, 2H), 3.34 – 3.17 (m, 4H), 2.47 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 141.62 (d, J C-P = 8.3 Hz), 141.14 (d, J C-P = 3.6Hz), 139.19 (d, J C-P = 8.5 Hz), 132.10 (d, J C-P = 10.1 Hz), 131.46 (d, J C-P =10.9 Hz), 131.38 (d, J C-P = 2.7 Hz), 129.29 (d, J C-P = 91.9 Hz), 128.15,127.51, 126.24, 125.08 (d, J C-P = 11.8 Hz), 117.63 (d, J C-P = 8.8 Hz), 36.98(d, J C-P = 63.1 Hz), 21.56 (d, J C-P = 3.0 Hz). FT-IR (KBr): 3055, 3025, 2922,1674, 1596, 1496, 1445, 1409, 1271, 1179, 1131, 1081, 1029, 1000, 834, 804,752, 697, 562, 552, 518, 447, 418 cm -1 . HRMS (ESI) calcd for C 25 H 26 OP + [M+H] + 373.1716, found373.1721.

[0094] The characterization data of compound II-8 are as follows:

[0095]

[0096] White solid (1.6 g, 37% yield). Melting point: 101.6–105.6 °C. 31 P{ 1 H} NMR (202MHz, CDCl3) δ 34.94. 19 F NMR (471 MHz, CDCl3) δ –63.19. 1 H NMR (500 MHz, CDCl3)δ 7.55 (dd, J = 10.6, 8.0 Hz, 2H), 7.39 (dd, J = 8.3, 2.3 Hz, 2H), 7.22 –7.13 (m, 10H), 5.35 (d, J = 4.6 Hz, 2H), 5.17 (d, J = 4.7 Hz, 2H), 3.31 –3.13 (m, 4H). 13 C NMR (126 MHz, CDCl3) δ 140.67 (d, J C-P = 3.1 Hz), 138.50 (d, J C-P = 9.0 Hz), 135.62 (d, J C-P = 91.6 Hz), 132.96 (qd, J C-F = 32.3, J C-P = 2.5Hz), 131.46 (d, J C-P = 9.1 Hz), 128.29, 127.75, 126.23, 124.56(q, J C-F = 273.7Hz), 124.49 (dq, J C-P = 11.4 Hz, J C-F = 3.5 Hz), 118.04 (d, J C-P = 9.1 Hz),37.09 (d, J C-P= 63.6 Hz). FT-IR (KBr): 3091, 3053, 2958, 2910, 1615, 1601,1574, 1497, 1445, 1415, 1399, 1329, 1242, 1220, 1193, 1162, 1127, 1101, 1061,1029, 1018, 1000, 944, 901, 844, 829, 778, 751, 731, 703, 630, 616, 598, 591,528, 496, 443, 416 cm -1 . HRMS (ESI) calcd for C 25 H 23 F3OP + [M+H] + 427.1433, found427.1439.

[0097] Example 2 Synthesis of Multi-substituted Phosphatic Six-membered Ring Phosphine Oxide Compound V Using Oxygen as Nucleophile

[0098] The reaction steps are as follows:

[0099] Specific experimental procedures: To a 10 mL sealed tube, diene phosphine oxide II (0.2 mmol), copper tetrafluoroborate tetraacetonitrile (0.02 mmol), ligand (0.022 mmol), and 3,3-dimethyl-1-(trifluoromethyl)-1,2-benzoiodooxolane (0.3 mmol) were added in sequence. The system was purged and purged five times under argon. 1,2-Dichloroethane (1 mL) and an oxygen nucleophile (1 mmol) were added, maintaining the purging. The reaction system was sealed and allowed to react at 70°C for 12 hours. After completion of the reaction, the copper salt was removed by washing with sodium bicarbonate solution, the mixture was dried, filtered, and concentrated under reduced pressure. Compound V was then purified by column chromatography using a 4:1 ratio of petroleum ether:ethyl acetate.

[0100] The characterization data of compound V-1 are as follows:

[0101]

[0102] Off-white solid (73.4 mg, 80% yield, dr 11.4 / 1). Melting point: 149.6–156.1 °C. 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 32.86. 19 F{ 1H} NMR (471 MHz, CDCl3) δ -58.62. 1 HNMR (500 MHz, CDCl3) δ 7.90 (ddd, J = 11.6, 7.7, 1.8 Hz, 2H), 7.71 – 7.67 (m,2H), 7.57 – 7.50 (m, 3H), 7.43 – 7.37 (m, 4H), 7.33 – 7.29 (m, 3H), 7.20 (t, J = 7.3 Hz, 1H), 3.10 (dq, J = 15.4, 10.6 Hz, 1H), 2.99 (d, J = 14.9 Hz, 1H),2.91 (ddd, J = 17.6, 15.2, 2.0 Hz, 1H), 2.81 – 2.69 (m, 2H), 2.63 (s, 3H),2.62 – 2.48 (m, 2H), 2.40 (dd, J = 15.4, 7.7 Hz, 1H). 13 C{ 1 H} NMR (126 MHz,CDCl3) δ 145.83 (d, J C-P = 12.7 Hz), 142.49 (d, J C-P = 4.9 Hz), 133.07 (d, J C-P =99.7 Hz), 132.05 (d, J C-P = 2.7 Hz), 130.65 (d, J C-P = 9.2 Hz), 128.80 (d, J C-P = 11.8 Hz), 128.59, 128.29, 128.08, 127.05, 126.78, 125.77 (q, J C-F = 279.4Hz), 125.57, 78.87, 49.97, 48.94 (d, J C-P = 8.4 Hz), 43.95 (q,J C-F = 25.9 Hz),39.41, 38.08 (d, J C-P = 60.5 Hz), 35.01 (d, J C-P = 65.7 Hz). FT-IR (KBr): 3061,3035, 2992, 2944, 2915, 2820, 1497, 1448, 1437, 1426, 1405, 1383, 1323, 1255,1200, 1117, 1000, 969, 941, 913, 898, 872, 846, 832, 790, 769, 745, 702, 681,632, 593, 573, 542, 532, 517, 472, 439 cm -1 . HRMS (ESI) calcd for C 26 H 27 F3O2P + [M+H] + 459.1695, found 459.1692.

[0103] The characterization data of compound V-2 are as follows:

[0104]

[0105] White solid (81.2 mg, 80% yield, dr 17.3 / 1). Melting point: 188.8–190.4 °C. 31 P{ 1 H}NMR (202 MHz, CDCl3) δ 34.62. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ -58.25. 1 H NMR (500 MHz, CDCl3) δ 8.96 (d, J = 8.6 Hz, 1H), 8.12 – 8.05 (m, 2H), 7.96 (d, J = 8.2 Hz, 1H), 7.69 – 7.65 (m, 3H), 7.62 – 7.57 (m, 2H), 7.48 – 7.43 (m, 4H), 7.37 – 7.32 (m, 3H), 7.24 (dd, J= 7.1 Hz, 1H), 3.34 (dq, 1H), 3.08 – 2.99(m, 4H), 2.94 (d, J = 15.2 Hz, 1H), 2.84 (dd, J = 15.6, 7.0 Hz, 1H), 2.76(dq, J = 15.4, 10.7 Hz, 1H), 2.55 (s, 3H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ146.30 (d, J C-P = 12.6 Hz), 143.29 (d, J C-P = 6.6 Hz), 134.04 (d, J C-P = 9.1Hz), 133.44 (d, J C-P = 3.0 Hz), 133.23 (d, J C-P = 8.9 Hz), 131.34 (d, J C-P = 8.9Hz), 129.84, 129.49, 129.08, 128.61 (d, J C-P = 44.8 Hz), 127.97 (d, J C-P = 43.4Hz), 126.83, 126.78, 126.64, 126.03 (q, J C-F = 279.5 Hz), 125.98, 125.95,125.91, 124.76 (d, J C-P = 13.2 Hz), 79.36, 50.63, 47.83 (d, J C-P = 9.3 Hz),45.14 (q, J C-F = 25.5 Hz), 39.63, 38.65 (d, J C-P = 61.3 Hz), 33.52 (d, J C-P=65.8 Hz). FT-IR (KBr): 3058, 2972, 2924, 2828, 1595, 1497, 1447, 1386, 1324,1256, 1113, 988, 967, 941, 915, 895, 860, 823, 801, 774, 750, 701, 681, 633,592, 575, 550, 520, 490, 469, 436, 422 cm -1 . HRMS (ESI) calcd for C 30 H 29 F3O2P + [M+H] + 509.1852, found 509.1852.

[0106] The characterization data of compound V-3 are as follows:

[0107]

[0108] Colorless oil (75.7 mg, 75% yield, dr 11.6 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.49. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.61. 1 H NMR (400 MHz, CDCl3)δ 7.68 – 7.64 (m, 2H), 7.47 – 7.39 (m, 5H), 7.36 – 7.31 (m, 3H), 7.29 (dd, J = 10.9, 1.5 Hz, 1H), 7.27 – 7.19 (m, 1H), 6.97 (dd, J = 7.9, 2.4 Hz, 1H), 6.05 (s, 2H), 3.07 (dq, J = 15.5, 10.6 Hz, 1H), 2.96 (d, J = 14.9 Hz, 1H),2.87 (ddd, J = 17.6, 15.3, 2.0 Hz, 1H), 2.78 – 2.68 (m, 2H), 2.64 (s, 3H), 2.61 – 2.44 (m, 2H), 2.37 (ddd,J = 15.4, 7.8, 1.2 Hz, 1H). 13 C{ 1 H} NMR (100MHz, CDCl3) δ 151.08 (d, J C-P = 3.0 Hz), 148.39 (d, J C-P = 17.9 Hz), 146.03 (d, J C-P = 12.8 Hz), 142.71 (d, J C-P = 5.4 Hz), 128.76, 128.44, 128.22, 127.12, 126.93, 126.29 (d, J C-P = 10.1 Hz), 126.23 (d, J C-P = 103.4 Hz), 125.87 (q, J C-F = 279.4 Hz), 125.76, 110.19 (d, J C-P = 12.3 Hz), 109.04 (d, J C-P = 14.7 Hz),101.86, 79.07 (d, J C-P = 1.4 Hz), 50.24, 48.69 (d, J C-P = 8.4 Hz), 44.29 (q, J C-F = 25.9 Hz), 39.53 (dd, J C-F = 3.1, J C-P = 1.8 Hz), 38.82 (d, J C-P = 60.9Hz), 35.42 (d, J C-P= 66.1 Hz). FT-IR (KBr): 3067, 2986, 2934, 2918, 1508,1447, 1428, 1385, 1322, 1249, 1192, 1123, 1067, 1036, 970, 933, 900, 847,834, 814, 788, 768, 731, 714, 698, 681, 644, 636, 601, 574, 539, 506, 418 cm -1 . HRMS (ESI) calcd for C 27 H 27 F3O4P + [M+H] + 503.1594, found 503.1593.

[0109] The characterization data of compound V-4 are as follows:

[0110]

[0111] Colorless oil (76.2 mg, 81% yield, dr 9.3 / 1). 31 P{ 1 H} NMR (202 MHz, CDCl3)δ 39.71. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.48. 1 H NMR (500 MHz, CDCl3) δ 7.57– 7.52 (m, 2H), 7.42 – 7.38 (m, 3H), 7.36 (td, J = 5.5, 4.8, 2.1 Hz, 7H),7.33 – 7.29 (m, 2H), 7.26 – 7.23 (m, 1H), 3.37 – 3.25 (m, 2H), 2.82 (dq, J =15.5, 10.7 Hz, 1H), 2.71 – 2.62 (m, 2H), 2.61 (s, 3H), 2.59 – 2.40 (m, 4H), 2.23 (dd, J = 15.1, 8.5 Hz, 1H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 145.26 (d, JC-P = 10.3 Hz), 142.73 (d, J C-P = 6.0 Hz), 131.57 (d, J C-P = 8.1 Hz), 129.90 (d, J C-P = 5.4 Hz), 129.03 (d, J C-P = 2.5 Hz), 128.76, 128.37, 128.18, 127.31 (d, J C-P = 3.1 Hz), 126.90, 126.85, 125.86, 125.75 (d, J C-F = 279.4 Hz), 79.23,50.13, 48.73 (d, J C-P = 7.3 Hz), 45.53 (q, J C-F = 26.5 Hz), 39.90 (d, J C-P =63.8 Hz), 39.69, 34.38 (d, J C-P = 59.1 Hz), 33.63 (d, J C-P = 62.4 Hz). FT-IR(KBr): 3061, 3031, 2943, 2826, 1497, 1447, 1407, 1381, 1327, 1262, 1200,1157, 1120, 1067, 1002, 968, 942, 911, 855, 825, 768, 731, 699, 643, 590,573, 492 cm -1 . HRMS (ESI) calcd for C 27 H 29 F3O2P + [M+H] + 473.1852, found473.1852.

[0112] The characterization data of compound V-5 are as follows:

[0113]

[0114] Colorless oil (66.2 mg, 68% yield, dr 10.4 / 1). 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 32,88. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.38. 1 H NMR (500 MHz, CDCl3)δ 7.90 (dd, J = 10.5, 7.2 Hz, 2H), 7.61 – 7.53 (m, 5H), 7.29 (d, J = 8.1 Hz,2H), 7.24 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 7.9 Hz, 2H), 3.06 (dq, J = 15.3,10.7 Hz, 1H), 2.97 (d, J = 14.4 Hz, 1H), 2.91 (d, J = 17.4 Hz, 1H), 2.76 (t, J = 15.7 Hz, 1H), 2.70 – 2.64 (m, 4H), 2.57 – 2.48 (m, 2H), 2.42 – 2.34 (m,4H), 2.31 (s, 3H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 143.10 (d, J C-P = 12.8 Hz),139.51 (d, J C-P = 4.8 Hz), 137.90, 136.40, 133.37 (d, J C-P = 99.3 Hz), 132.07(d, J C-P = 2.8 Hz), 130.79 (d, J C-P = 9.5 Hz), 129.36, 129.05, 128.86 (d, J C-P=11.7 Hz), 127.15, 125.94 (q, J C-F = 279.5 Hz), 125.55, 78.89, 49.96, 49.19 (d, J C-P = 8.0 Hz), 44.04 (q, J C-F = 25.8 Hz), 39.26, 38.09 (d, J C-P = 60.5 Hz),35.48 (d, J C-P = 65.5 Hz), 21.10, 20.91. FT-IR (KBr): 3057, 3026, 2942, 2826,1515, 1438, 1381, 1319, 1262, 1194, 1116, 1069, 1020, 969, 930, 909, 849,817, 735, 695, 674, 644, 581, 547, 538, 501, 474 cm -1 . HRMS (ESI) calcd forC 28 H 31 F3O2P + [M+H] + 487.2008, found 487.2007.

[0115] The characterization data of compound V-6 are as follows:

[0116]

[0117] Colorless oil (77.7 mg, 74% yield, dr 11.2 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 31.56. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.45. 1 H NMR (400 MHz, CDCl3)δ 7.86 (ddd, J= 11.7, 7.9, 1.6 Hz, 2H), 7.65 – 7.61 (m, 2H), 7.61 – 7.50 (m,3H), 7.42 – 7.38 (m, 2H), 7.34 – 7.28 (m, 4H), 3.04 (dq, J = 15.5, 10.6 Hz,1H), 2.89 (ddd, J = 17.7, 15.2, 2.0 Hz, 2H), 2.77 – 2.70 (m, 1H), 2.68 (s,3H), 2.63 (d, J = 14.9 Hz, 1H), 2.59 – 2.44 (m, 2H), 2.37 (dd, J = 15.4, 7.8Hz, 1H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 144.35 (d, J C-P = 12.6 Hz), 141.05 (d, J C-P = 4.6 Hz), 134.28, 132.87, 132.63 (d, J C-P = 100.2 Hz), 132.38 (d, J C-P =2.8 Hz), 130.70 (d, J C-P = 9.4 Hz), 129.01 (d, J C-P = 11.9 Hz), 128.94, 128.80,128.57, 127.16, 125.66 (q, J C-F = 279.5 Hz), 78.72 (d, J C-P = 1.5 Hz), 50.08,49.10 (d, J C-P = 8.4 Hz), 43.98 (q, J C-F = 25.8 Hz), 39.42 (dd, J C-F = 3.0, J C-P= 1.6 Hz), 37.56 (d, J C-P = 60.5 Hz), 35.42 (d, J C-P = 65.3 Hz). FT-IR (KBr):3058, 2941, 2827, 1593, 1574, 1494, 1438, 1381, 1311, 1260, 1114, 1012, 969,948, 934, 906, 824, 779, 741, 695, 663, 644, 634, 592, 578, 566, 527, 492,473, 459 cm -1 . HRMS (ESI) calcd for C 26 H 25 Cl2F3O2P + [M+H] + 527.0916, found527.0915.

[0118] The characterization data of compound V-7 are as follows:

[0119]

[0120] Yellow oil (85.3 mg, 81% yield, dr 11.7 / 1). 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 32.58. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.54, –63.02. 1 H NMR (500 MHz, CDCl3) δ 8.06 (dd, J = 11.1, 8.0 Hz, 2H), 7.82 (dd, J = 8.3, 2.3 Hz, 2H),7.66 – 7.61 (m, 2H), 7.47 – 7.39 (m, 4H), 7.37 – 7.32 (m, 3H), 7.24 (t, J =7.4 Hz, 1H), 3.12 (dq, J = 15.4, 10.5 Hz, 1H), 2.98 (d, J= 15.0 Hz, 1H),2.93 – 2.76 (m, 3H), 2.68 (dd, J = 15.3, 7.4 Hz, 1H), 2.63 (s, 3H), 2.62 –2.54 (m, 1H), 2.46 (ddd, J = 15.5, 7.6, 1.4 Hz, 1H). 13 C{ 1 H} NMR (126 MHz,CDCl3) δ 145.79 (d, J C-P = 12.8 Hz), 142.59 (d, J C-P = 6.0 Hz), 137.80 (d, J C-P = 96.1 Hz), 134.04 (qd, J C-F = 32.5, J C-P = 2.5 Hz), 131.52 (d, J C-P = 9.6 Hz),128.98, 128.55, 128.37, 127.08, 126.88, 126.08 (q, J C-P = 279.5 Hz), 125.82(d, J C-P = 3.7 Hz), 125.71, 123.88 (q, J C-F = 273.12 Hz) 78.90, 50.47, 48.29(d, J C-P = 8.5 Hz), 44.72 (q, J C-F = 25.8 Hz), 39.50, 39.05 (d, J C-P = 60.9 Hz),34.67 (d, J C-P= 66.1 Hz). FT-IR (KBr): 3062, 3037, 2937, 1736, 1498, 1448,1399, 1325, 1263, 1124, 1018, 969, 944, 912, 897, 829, 789, 769, 746, 701,680, 595, 575, 552, 525, 504, 420 cm -1 . HRMS (ESI) calcd for C 27 H 26 F6O2P + [M+H] + 527.1569, found 527.1568.

[0121] The characterization data of compound V-8 are as follows:

[0122]

[0123] White solid (65.2 mg, 67% yield, dr 8.8 / 1). Melting point: 187.8–189.2 °C. 31 P{ 1 H}NMR (202 MHz, CDCl3) δ 31.56. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.61. 1 H NMR (500 MHz, CDCl3) δ 8.15 (ddd, J = 13.3, 7.5, 1.8 Hz, 1H), 7.87 (d, 2H), 7.59(ddt, J = 8.7, 6.8, 1.6 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 7.39 – 7.31 (m,5H), 7.25 – 7.19 (m, 2H), 6.98 (dd, J = 8.3, 5.4 Hz, 1H), 3.89 (s, 3H), 3.11(dt, J = 14.4, 1.9 Hz, 1H), 3.01 (ddt, J = 17.2, 15.0, 2.1 Hz, 1H), 2.89 (dq,1H), 2.82 (dd, J= 14.7, 8.6 Hz, 1H), 2.78 (s, 3H), 2.71 (dd, J = 14.9, 10.7Hz, 1H), 2.64 (ddt, J = 16.9, 14.4, 2.7 Hz, 1H), 2.41 (d, J = 14.4 Hz, 1H),2.22 (dq, J = 15.6, 10.8 Hz, 1H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 159.42 (d, J C-P = 4.2 Hz), 146.13 (d, J C-P = 13.9 Hz), 142.19, 135.35 (d, J C-P = 5.9 Hz),134.54 (d, J C-P = 2.2 Hz), 128.51, 128.33, 128.22, 128.21, 126.79, 125.96 (q, J C-F = 279.5 Hz), 125.56, 121.52 (d, J C-P = 10.9 Hz), 119.54 (d, J C-P = 97.8Hz), 110.91 (d, J C-P = 6.8 Hz), 79.23, 55.66, 51.58 (d, J C-P = 7.2 Hz), 49.07,42.27 (q, J C-F = 25.9 Hz), 39.69, 34.13 (d, J C-P= 123.5 Hz), 34.12. FT-IR(KBr): 3066, 3026, 2989, 2947, 2826, 1591, 1578, 1497, 1479, 1410, 1381,1321, 1259, 1196, 1069, 1016, 968, 944, 910, 871, 847, 801, 789, 762, 693,632, 591, 571, 540, 519, 484, 432 cm -1 . HRMS (ESI) calcd for C 27 H 29 F3O3P + [M+H] + 489.1801, found 489.1800.

[0124] The characterization data of compound V-9 are as follows:

[0125]

[0126] Colorless oil (86.9 mg, 74% yield, dr 11.1 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 34.85. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ -58.42. 1 H NMR (400 MHz, CDCl3)δ 8.50 – 8.43 (m, 1H), 8.30 (dd, J = 10.8, 8.5 Hz, 1H), 8.02 (d, 1H), 7.90(dd, J = 6.9, 2.7 Hz, 1H), 7.81 (d, 2H), 7.71 – 7.62 (m, 2H), 7.47 (t, J =7.7 Hz, 2H), 7.43 (d, J = 7.7 Hz, 2H), 7.38 – 7.32 (m, 3H), 7.24 (dd, 1H), 3.46 (dd, J = 14.6, 7.8 Hz, 1H), 3.23 (dd, J= 15.3, 9.4 Hz, 1H), 3.18 – 3.04(m, 3H), 2.86 (dd, 1H), 2.76 – 2.67 (m, 4H), 2.40 (dq, J = 15.3, 10.8 Hz,1H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 145.95 (d, J C-P = 13.5 Hz), 142.58 (d, J C-P = 3.4 Hz), 136.24 (d, J C-P = 2.2 Hz), 132.56 (d, J C-P = 9.1 Hz), 130.70 (d, J C-P = 96.6 Hz), 129.34 (d, J C-P = 7.7 Hz), 128.99, 128.67, 128.51, 128.44, 128.41,128.29, 127.89, 127.64, 127.00 (d, J C-P = 4.9 Hz), 126.93, 126.14 (d, J C-P =20.8 Hz), 125.94 (q, J C-F = 279.68 Hz), 125.64, 79.37, 50.24 (d, J C-P = 8.7Hz), 49.64, 43.20 (q, J C-F = 26.1 Hz), 39.85 (t, J C-P = 2.2 Hz), 34.72 (d, J C-P = 62.0 Hz), 32.93 (d, J C-P= 67.5 Hz). FT-IR (KBr): 3059, 2933, 2825, 1548,1497, 1447, 1381, 1313, 1261, 1216, 1191, 1153, 1138, 1120, 1083, 1068, 968,944, 910, 895, 866, 822, 789, 770, 744, 732, 713, 699, 680, 670, 641, 610,588, 572, 534, 513, 444, 419 cm -1 . HRMS (ESI) calcd for C 30 H 28 BrF3O2P + [M+H] + 587.0957, found 587.0955.

[0127] The characterization data of compound V-10 are as follows:

[0128]

[0129] White solid (67.8 mg, 72% yield, dr 10.8 / 1). Melting point: 167.3–170.2 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 34.27. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.43. 1 H NMR (400 MHz, CDCl3) δ 7.70 (dd, J = 12.6, 7.8 Hz, 1H), 7.62 (d, J = 7.3 Hz, 2H),7.50 – 7.38 (m, 5H), 7.40 – 7.29 (m, 5H), 7.26 – 7.21 (m, 1H), 3.24 (dq, J =15.5, 10.7 Hz, 1H), 3.01 – 2.81 (m, 4H), 2.81 (s, 4H), 2.75 – 2.61 (m, 1H), 2.60 (dd, J = 15.0, 6.8 Hz, 1H), 2.54 (s, 3H). 13 C{1 H} NMR (100 MHz, CDCl3) δ146.36 (d, J C-P = 12.5 Hz), 143.28 (d, J C-P = 6.2 Hz), 142.31 (d, J C-P = 8.2Hz), 132.44 (d, J C-P = 10.7 Hz), 132.12, 132.10, 131.13, 130.58 (d, J C-P = 10.7Hz), 128.78, 128.44, 128.11, 126.84, 126.05, 126.03 (q, J C-F = 279.5 Hz),125.91 (d, J C-P = 3.6 Hz), 79.23 (d, J C-P = 1.7 Hz), 50.46, 48.16 (d, J C-P = 9.0Hz), 44.82 (q, J C-F = 25.9 Hz), 39.56 (dd, J C-F = 3.0, J C-F = 1.8 Hz), 38.15 (d, J C-P = 61.0 Hz), 33.09 (d, J C-P = 65.9 Hz), 21.74 (d, J C-P = 3.6 Hz). FT-IR(KBr): 3061, 2949, 2923, 2825, 1498, 1402, 1379, 1310, 1256, 1188, 1087,1033, 968, 939, 917, 897, 869, 804, 786, 753, 734, 719, 700, 686, 575, 558,485, 469, 443, 434, 413 cm -1. HRMS (ESI) calcd for C 27 H 29 F3O2P + [M+H] + 473.1852, found 473.1851.

[0130] The characterization data of compound V-11 are as follows:

[0131]

[0132] White solid (66 mg, 74% yield, dr 13.2 / 1). Melting point: 132.1–134.9 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 33.70. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.78. 1 H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 11.7, 7.5 Hz, 2H), 7.58 (d, J = 7.7 Hz, 2H),7.53 (d, J = 7.1 Hz, 1H), 7.47 (td, J = 7.6, 2.6 Hz, 2H), 7.42 – 7.35 (m,4H), 7.34 – 7.28 (m, 3H), 7.23 (t, J = 7.2 Hz, 1H), 3.09 – 2.80 (m, 5H), 2.75(s, 1H), 2.62 (d, J = 16.3 Hz, 1H), 2.58 – 2.40 (m, 2H). 13 C NMR (100 MHz, CDCl3) δ 148.78 (d, J C-P = 9.7 Hz), 146.53 (d, J C-P = 11.4 Hz), 133.21 (d, J C-P = 98.2 Hz), 132.06 (d, J C-P = 2.9 Hz), 130.81 (d,J C-P = 9.7 Hz), 128.81,128.79 (d, J C-P = 12.0 Hz), 128.77, 127.70, 126.95, 125.89 (q, J C-F = 279.1Hz), 125.80, 124.55, 74.04 (d, J C-P = 2.1 Hz), 47.92 (q, J C-F = 25.9 Hz), 45.10(d, J C-P = 11.6 Hz), 43.91 (d, J C-P = 61.3 Hz), 39.34 (d, J C-P = 1.9 Hz), 36.73(d, J C-P = 63.5 Hz). FT-IR (KBr): 3166, 3061, 3027, 2970, 2948, 2927, 1495,1446, 1438, 1376, 1346, 1311, 1261, 1185, 1141, 1121, 1062, 1035, 1000, 968,881, 827, 797, 773, 750, 736, 699, 682, 592, 572, 532, 511, 485, 467 cm -1 .HRMS (ESI) calcd for C 25 H 25 F3O2P + [M+H] + 445.1539, found 445.1539.

[0133] The characterization data of compound V-12 are as follows:

[0134]

[0135] Colorless oil (68.9 mg, 73% yield, dr 10.7 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.27.19 F{ 1 H} NMR (376 MHz, CDCl3) δ -58.60. 1 H NMR (400 MHz, CDCl3)δ 7.91 (ddd, J = 11.6, 7.7, 1.8 Hz, 2H), 7.75 – 7.68 (m, 2H), 7.64 – 7.50 (m,3H), 7.47 – 7.38 (m, 4H), 7.33 (t, J = 7.7 Hz, 3H), 7.23 (t, J = 7.2 Hz, 1H),3.14 – 2.88 (m, 4H), 2.84 – 2.69 (m, 2H), 2.69 – 2.46 (m, 3H), 2.44 (dd, J =15.5, 7.8 Hz, 1H), 0.88 (t, J = 6.9 Hz, 3H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ145.96 (d, J C-P = 12.7 Hz), 143.26 (d, J C-P = 4.8 Hz), 133.34 (d, J C-P = 99.5Hz), 132.17 (d, J C-P = 2.9 Hz), 130.82 (d, J C-P = 9.4 Hz), 128.93 (d, J C-P =11.8 Hz), 128.69, 128.37, 128.15, 127.10, 126.92, 125.89 (q, J C-F = 279.3 Hz),125.72, 78.56 (d, J C-P = 1.7 Hz), 57.52, 49.57 (d, J C-P = 8.2 Hz), 44.11 (q, J C-F= 25.8 Hz), 39.63 (dd, J C-P = 3.3, 1.8 Hz), 38.59 (d, J C-P = 60.2 Hz),35.43 (d, J C-P = 65.7 Hz), 15.20. FT-IR (KBr): 3059, 3033, 2974, 2927, 1498,1447, 1439, 1383, 1310, 1261, 1189, 1169, 1140, 1120, 1085, 1066, 962, 911,843, 747, 716, 698, 680, 644, 590, 518, 487, 434 cm -1 . HRMS (ESI) calcd forC 27 H 29 F3O2P + [M+H] + 473.1852, found 473.1851.

[0136] The characterization data of compound V-13 are as follows:

[0137]

[0138] Yellow oil (57.8 mg, 56% yield, dr 10.5 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.40. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.68. 1 H NMR (400 MHz, CDCl3)δ 7.66 (d, J = 7.7 Hz, 2H), 7.50 – 7.43 (m, 6H), 7.42 – 7.32 (m, 6H), 7.26(t, 1H), 7.00 (t, J = 7.8 Hz, 2H), 6.82 (t, J = 7.3 Hz, 1H), 6.24 (d, J = 8.1Hz, 2H), 3.19 (d, J= 15.4 Hz, 1H), 3.07 (t, J = 17.4 Hz, 1H), 3.00 – 2.86(m, 4H), 2.73 (t, J = 15.8 Hz, 1H), 2.61 (dd, J = 14.9, 6.7 Hz, 1H). 13 C{ 1 H}NMR (100 MHz, CDCl3) δ 153.93, 145.96 (d, J C-P = 11.4 Hz), 144.37 (d, J C-P = 6.7Hz), 132.64 (d, J C-P = 101.9 Hz), 132.16, 130.49 (d, J C-P = 9.6 Hz), 129.27,129.11, 128.84 (d, J C-P = 11.8 Hz), 128.21, 128.10, 126.68, 126.06, 125.96,125.89 (q, J C-F = 279.4 Hz), 121.57, 118.71, 81.52, 49.22 (d, J C-P = 12.2 Hz),46.92 (q, J C-F = 25.7 Hz), 39.74 (dd, J C-P = 3.4, 1.8 Hz), 36.59 (d, J C-P = 64.7Hz), 35.44 (d, J C-P= 62.9 Hz). FT-IR (KBr): 3060, 3035, 1597, 1489, 1447,1438, 1377, 1262, 1186, 1117, 1084, 1032, 1000, 974, 909, 877, 863, 836, 787,733, 696, 644, 617, 605, 590, 548, 526, 493 cm -1 . HRMS (ESI) calcd forC 31 H 29 F3O2P + [M+H] + 521.1852, found 521.1854.

[0139] The characterization data of compound V-14 are as follows:

[0140]

[0141] Colorless oil (76.7 mg, 72% yield, dr 10.2 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.22. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.61. 1 H NMR (400 MHz, CDCl3)δ 7.88 – 7.74 (m, 4H), 7.59 – 7.52 (m, 1H), 7.52 – 7.40 (m, 6H), 7.39 – 7.31(m, 3H), 7.28 – 7.18 (m, 4H), 6.95 (dd, J = 6.7, 2.9 Hz, 2H), 4.03 (d, J =11.2 Hz, 1H), 3.77 (d, J = 11.2 Hz, 1H), 3.13 – 2.98 (m, 3H), 2.90 (d, J =15.1 Hz, 1H), 2.77 (dd, 1H), 2.67 – 2.50 (m, 3H). 13 C{ 1 H} NMR (100 MHz, CDCl3)δ 145.99 (d, JC-P = 12.5 Hz), 142.88 (d, J C-P = 5.2 Hz), 138.09, 133.12 (d, J C-P = 99.6 Hz), 132.15 (d, J C-P = 2.9 Hz), 130.75 (d, J C-P = 9.3 Hz), 128.91 (d, J C-P = 11.8 Hz), 128.88, 128.45, 128.40, 128.33, 127.44, 127.21, 127.16,126.91, 125.88 (q, J C-F = 279.4 Hz), 125.81, 79.45 (d, J C-P = 1.6 Hz), 64.41,49.51 (d, J C-P = 9.0 Hz), 44.67 (q, J C-F = 25.7 Hz), 39.63 (dd, J C-P = 3.3, 1.8Hz), 37.89 (d, J C-P = 60.7 Hz), 35.49 (d, J C-P = 65.6 Hz). FT-IR (KBr): 3060,3031, 2917, 2866, 1497, 1447, 1438, 1381, 1310, 1261, 1198, 1120, 1085, 1060,1036, 1000, 969, 911, 833, 779, 735, 716, 697, 645, 591, 513, 482 cm -1 . HRMS(ESI) calcd for C 32 H 31 F3O2P + [M+H] + 535.2008, found 535.2009.

[0142] The characterization data of compound V-15 are as follows:

[0143]

[0144] Colorless oil (67.2 mg, 70% yield, dr 11.5 / 1). 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 30.85. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.66. 1 H NMR (500 MHz, CDCl3)δ 7.95 – 7.87 (m, 4H), 7.62 – 7.56 (m, 3H), 7.47 (t, J = 7.6 Hz, 2H), 7.40 –7.30 (m, 5H), 7.23 (t, J = 7.0 Hz, 1H), 3.44 (hept, J = 6.2 Hz, 1H), 3.29 (t, J = 15.7 Hz, 1H), 3.20 (dt, J = 14.6, 2.2 Hz, 1H), 2.86 – 2.72 (m, 2H), 2.27(ddd, J = 28.4, 14.5, 6.2 Hz, 3H), 2.11 (dq, J = 15.7, 10.7 Hz, 1H), 1.00 (d, J = 6.1 Hz, 3H), 0.76 (d, J = 6.1 Hz, 3H). 13 C{ 1 H} NMR (126 MHz, CDCl3) 145.53(d, J C-P = 12.7 Hz), 141.71, 133.00 (d, J C-P = 99.9 Hz), 132.27 (d, J C-P = 3.0Hz), 130.82 (d, J C-P = 8.9 Hz), 129.04 (d,J C-P = 11.5 Hz), 128.64, 128.55,128.39, 128.23, 127.04, 125.92 (q, J C-F =279.34 Hz), 125.49, 79.12, 64.89,53.28 (d, J C-P = 5.7 Hz), 41.57 (q, J C-F = 26.4 Hz), 40.25, 37.29 (d, J C-P =58.1 Hz), 36.29 (d, J C-P = 66.0 Hz), 25.38, 24.21. FT-IR (KBr): 3060, 3035,2973, 2929, 1498, 1447, 1438, 1382, 1321, 1261, 1197, 1161, 1139, 1118, 1018,965, 931, 911, 897, 856, 839, 787, 774, 749, 716, 697, 680, 644, 584, 545,523, 506 cm -1 . HRMS (ESI) calcd for C 28 H 31 F3O2P + [M+H] + 487.2008, found487.2008.

[0145] The characterization data of compound V-16 are as follows:

[0146]

[0147] Yellow oil (81.0 mg, 77% yield, dr 11.2 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 30.92. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.64. 1 H NMR (400 MHz, CDCl3)δ 7.91 (dd, J= 8.9 Hz, 4H), 7.63 – 7.53 (m, 3H), 7.45 (t, J = 7.6 Hz, 2H),7.40 – 7.29 (m, 5H), 7.24 (dd, J = 12.8, 5.8 Hz, 1H), 3.26 (t, J = 16.0 Hz,1H), 3.18 (d, J = 14.8 Hz, 1H), 3.12 – 3.03 (m, 1H), 2.89 – 2.73 (m, 2H),2.37 (d, J = 14.6 Hz, 1H), 2.34 – 2.24 (m, 2H), 2.14 (dq, J = 15.5, 10.8 Hz,1H), 2.07 – 1.91 (m, 1H), 1.63 – 1.50 (m, 2H), 1.49 – 1.41 (m, 1H), 1.40 –1.29 (m, 1H), 1.29 – 1.13 (m, 2H), 1.10 – 0.94 (m, 3H), 0.94 – 0.78 (m, 1H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 145.68 (d, J C-P = 12.7 Hz), 142.10, 133.15 (d, J C-P = 99.8 Hz), 132.23 (d, J C-P = 2.9 Hz), 130.83 (d, J C-P = 8.9 Hz), 129.03(d, J C-P = 11.7 Hz), 128.49, 128.39, 128.17, 127.01, 125.95 (q, J C-F = 279.5Hz), 125.54, 78.96, 70.98, 53.03 (d, J C-P = 6.1 Hz), 41.92 (q, J C-F= 26.5 Hz),40.04, 37.57 (d, J C-P = 58.3 Hz), 36.16 (d, J C-P = 66.2 Hz), 34.90 (d, J C-P =157.5 Hz), 25.44, 24.51 (d, J C-P = 7.9 Hz). FT-IR (KBr): 2932, 2855, 1498,1447, 1438, 1382, 1309, 1261, 1198, 1167, 1139, 1120, 1037, 966, 942, 911,895, 843, 780, 751, 715, 698, 602, 588, 518, 493 cm -1 . HRMS (ESI) calcd forC 31 H 35 F3O2P + [M+H] + 527.2321, found 527.2322.

[0148] The characterization data of compound V-17 are as follows:

[0149]

[0150] Yellow oil (73.7 mg, 66% yield, dr 12 / 1). 31 P{ 1 H} NMR (202 MHz, CDCl3)δ 31.58. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.60. 1 H NMR (500 MHz, CDCl3) δ 7.91(dd, 2H), 7.81 (d, J = 7.8 Hz, 2H), 7.59 – 7.54 (m, 1H), 7.51 (td, J = 7.5,2.3 Hz, 2H), 7.46 (t, J = 7.7 Hz, 2H), 7.38 (t, J= 8.2 Hz, 3H), 7.35 – 7.27(m, 4H), 7.27 – 7.20 (m, 4H), 3.81 (d, J = 15.2 Hz, 1H), 3.62 (d, J = 15.2Hz, 1H), 3.16 – 3.06 (m, 2H), 2.99 (dq, J = 15.5, 10.6 Hz, 1H), 2.80 (t, J =15.8 Hz, 1H), 2.68 (d, J = 14.9 Hz, 1H), 2.56 (dd, J = 13.3, 6.2 Hz, 1H),2.54 – 2.49 (m, 1H), 2.41 (dq, J = 15.4, 10.6 Hz, 1H). 13 C{ 1 H} NMR (100 MHz,CDCl3) δ 145.56 (d, J C-P = 12.7 Hz), 141.67 (d, J C-P = 3.5 Hz), 132.90 (d, J C-P = 100.3 Hz), 132.27 (d, J C-P = 2.9 Hz), 131.70, 130.88 (d, J C-P = 9.2 Hz),128.97 (d, J C-P = 11.8 Hz), 128.94, 128.73, 128.54, 128.49, 128.34, 127.62,127.06, 125.84 (q, J C-F = 279.4 Hz), 125.63, 122.62, 85.78, 85.61, 80.17 (d, J C-P = 1.4 Hz), 51.70, 50.32 (d, J C-P = 7.7 Hz), 43.30 (q, J C-F= 26.0 Hz),39.78 (dd, J C-P = 3.2, 1.7 Hz), 37.98 (d, J C-P = 59.6 Hz), 35.67 (d, J C-P = 65.4Hz). FT-IR (KBr): 3059, 2932, 2855, 2230, 1498, 1447, 1438, 1382, 1309, 1261,1198, 1167, 1139, 1120, 1037, 966, 942, 911, 843, 780, 751, 715, 698, 643,602, 588, 518 cm -1 . HRMS (ESI) calcd for C 34 H 31 F3O2P + [M+H] + 559.2008, found559.2007.

[0151] The characterization data of compound V-18 are as follows:

[0152]

[0153] Yellow oil (67.4 mg, 64% yield, dr 12.6 / 1). 31 P{ 1 H} NMR (202 MHz, CDCl3) δ 32.52. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.50. 1 H NMR (500 MHz, CDCl3)δ 7.90 (dd, J = 11.3, 7.1 Hz, 2H), 7.84 (d, J = 7.8 Hz, 2H), 7.61 – 7.52 (m,3H), 7.49 (t, J = 7.6 Hz, 2H), 7.42 – 7.36 (m, 3H), 7.35 – 7.29 (m, 3H), 7.23(t, J = 7.2 Hz, 1H), 6.26 – 6.23 (m, 1H), 5.96 (d,J = 3.2 Hz, 1H), 3.98 (d, J = 11.8 Hz, 1H), 3.67 (d, J = 11.8 Hz, 1H), 3.13 – 2.99 (m, 3H), 2.80 (t, J = 15.7 Hz, 1H), 2.73 (d, J = 14.9 Hz, 1H), 2.56 (dd, J = 14.8, 7.2 Hz, 1H),2.53 – 2.42 (m, 2H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 151.52, 145.74 (d, J C-P =12.7 Hz), 142.65, 142.20 (d, J C-P = 4.1 Hz), 133.02 (d, J = 99.8 Hz), 132.23(d, J C-P = 2.8 Hz), 130.89 (d, J C-P = 9.2 Hz), 129.00, 128.90, 128.56, 128.44,127.53, 127.01, 126.31 (q, J C-F = 279.15 Hz) 125.68, 110.33, 108.62, 79.47,57.03, 50.14 (d, J C-P = 7.5 Hz), 43.57 (q, J C-F = 25.7 Hz), 39.71, 38.23 (d, J C-P = 59.7 Hz), 35.52 (d, J C-P= 65.7 Hz). FT-IR (KBr): 3059, 2924, 1602,1498, 1447, 1438, 1382, 1311, 1261, 1198, 1120, 1084, 1035, 1015, 969, 951,920, 885, 833, 788, 742, 698, 644, 630, 590, 515, 480 cm -1 . HRMS (ESI) calcdfor C 30 H 29 F3O3P + [M+H] + 525.1801, found 525.1802.

[0154] The characterization data of compound V-19 are as follows:

[0155]

[0156] Yellow oil (73.6 mg, 68% yield, dr 11.1 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.05. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.61. 1 H NMR (400 MHz, CDCl3)δ 7.83 – 7.78 (m, 2H), 7.76 (d, J = 7.8 Hz, 2H), 7.60 – 7.52 (m, 1H), 7.51(dd, J = 7.7, 2.6 Hz, 2H), 7.48 – 7.42 (m, 4H), 7.38 – 7.32 (m, 3H), 7.25 (t, J = 7.2 Hz, 1H), 7.18 (dd, J = 5.0, 3.0 Hz, 1H), 6.77 (d, J = 2.9 Hz, 1H),6.71 (d, J = 5.0 Hz, 1H), 4.05 (d, J = 11.3 Hz, 1H), 3.76 (d, J= 11.3 Hz,1H), 3.12 – 2.96 (m, 3H), 2.89 (d, J = 15.1 Hz, 1H), 2.77 (t, J = 15.8 Hz,1H), 2.67 – 2.58 (m, 2H), 2.54 (dd, J = 15.5, 8.0 Hz, 1H). 13 C{ 1 H} NMR (100MHz, CDCl3) δ 146.02 (d, J C-P = 12.5 Hz), 142.84 (d, J C-P = 5.4 Hz), 139.03,133.15 (d, J C-P = 99.5 Hz), 132.16 (d, J C-P = 2.9 Hz), 130.73 (d, J C-P = 9.3Hz), 128.92 (d, J C-P = 11.8 Hz), 128.89, 128.44, 128.41, 127.10, 126.93,126.76, 125.86 (q, J C-F = 279.5 Hz), 125.84, 125.80, 121.82, 79.43 (d, J C-P =1.5 Hz), 60.36, 49.30 (d, J C-P = 8.8 Hz), 44.72 (q, J C-F = 25.9 Hz), 39.61 (d, J C-P = 3.2 Hz), 37.88 (d, J C-P = 60.7 Hz), 35.55 (d, J C-P= 65.2 Hz). FT-IR(KBr): 3059, 2948, 2868, 1497, 1447, 1438, 1382, 1310, 1261, 1197, 1167,1140, 1120, 1083, 1035, 1000, 969, 910, 833, 732, 697, 643, 593, 544, 513,479 cm -1 . HRMS (ESI) calcd for C 30 H 29 F3O2PS + [M+H] + 541.1573, found 541.1575.

[0157] The characterization data of compound V-20 are as follows:

[0158]

[0159] Colorless oil (40.6 mg, 41% yield, dr 11.1 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.27. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.60. 1 H NMR (400 MHz, CDCl3)δ 7.91 (dd, J = 10.7, 7.4 Hz, 2H), 7.67 (d, J = 7.8 Hz, 2H), 7.60 – 7.53 (m,3H), 7.45 – 7.41 (m, 4H), 7.36 – 7.30 (m, 3H), 7.23 (t, J = 7.3 Hz, 1H), 5.49(ddt, J = 17.2, 10.3, 6.8 Hz, 1H), 4.95 – 4.84 (m, 2H), 3.08 (dq, J = 15.3,10.7 Hz, 1H), 3.01 – 2.91 (m, 2H), 2.89 – 2.80 (m, 2H), 2.75 (d, J = 15.9 Hz,1H), 2.70 – 2.56 (m, 3H), 2.48 (dd,J = 15.4, 7.5 Hz, 1H), 1.98 (hept, J =7.3 Hz, 2H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 146.04 (d, J C-P = 12.6 Hz), 143.23(d, J C-P = 5.6 Hz), 135.26, 133.44 (d, J C-P = 99.5 Hz), 132.11 (d, J C-P = 2.6Hz), 130.80 (d, J C-P = 9.3 Hz), 128.92, 128.81, 128.72, 128.37, 128.14,126.90, 125.88 (q, J C-F = 279.5 Hz), 125.81, 116.49, 78.53, 61.68, 48.56 (d, J C-P = 8.7 Hz), 44.84 (q, J C-F = 25.7 Hz), 39.51, 38.97 (d, J C-P = 60.6 Hz),35.25 (d, J C-P = 65.7 Hz), 34.25. FT-IR (KBr): 3062, 2953, 2920, 2873, 1643,1498, 1446, 1386, 1314, 1264, 1188, 1117, 1066, 998, 969, 912, 863, 835, 747,732, 701, 679, 649, 589, 524, 486, 435 cm -1 . HRMS (ESI) calcd for C 29 H 31 F3O2P + [M+H] + 499.2008, found 499.2009.

[0160] The characterization data of compound V-21 are as follows:

[0161]

[0162] Yellow oil (60.4 mg, 54% yield, dr 10.2 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 32.23. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.58. 1 H NMR (400 MHz, CDCl3)δ 7.90 (ddd, J = 11.6, 8.0, 1.6 Hz, 2H), 7.73 (dd, J = 7.4, 1.7 Hz, 2H), 7.58– 7.50 (m, 3H), 7.45 (dt, J = 7.8, 3.8 Hz, 4H), 7.36 (td, J = 7.3, 4.9 Hz,3H), 7.30 – 7.26 (m, 2H), 7.26 – 7.20 (m, 4H), 6.20 (d, J = 16.0 Hz, 1H),5.92 (dt, J = 15.9, 5.5 Hz, 1H), 3.66 (ddd, J = 12.5, 5.6, 1.6 Hz, 1H), 3.33(ddd, J = 12.6, 5.3, 1.7 Hz, 1H), 3.15 – 2.99 (m, 2H), 2.92 (t, J = 17.5 Hz,2H), 2.79 (t, J = 15.6 Hz, 1H), 2.72 – 2.58 (m, 2H), 2.54 (dd, J = 15.5, 7.7 Hz, 1H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 145.99 (d, J C-P = 12.5 Hz), 142.98 (d, J C-P= 5.4 Hz), 136.76, 133.19 (d, J C-P = 99.5 Hz), 132.19 (d, J C-P = 2.9 Hz),131.21, 130.77 (d, J C-P = 9.2 Hz), 129.01, 128.89, 128.86, 128.58, 128.47,128.34, 127.66, 126.98, 126.39, 126.07 (q, J C-F = 279.5 Hz),125.84, 125.61,79.16 (d, J C-P = 1.6 Hz), 63.20, 48.94 (d, J C-P = 9.1 Hz), 44.71 (q, J C-F = 25.3Hz), 39.60, 38.45 (d, J C-P = 60.6 Hz), 35.31 (d, J C-P = 65.2 Hz). FT-IR (KBr):3059, 3027, 2918, 2862, 2228, 1497, 1447, 1438, 1381, 1310, 1261, 1186, 1118,1070, 1034, 967, 910, 837, 734, 696, 644, 590, 528, 510, 441 cm -1 . HRMS (ESI)calcd for C 34 H 33 F3O2P + [M+H] + 561.2165, found 561.2165.

[0163] Example 3 Synthesis of Multi-substituted Phosphatic Six-membered Ring Phosphine Oxide Compound VII Using Nitrogen as Nucleophile

[0164]

[0165] Specific experimental procedures: To a 10 mL sealed tube, diene phosphine oxide II (0.2 mmol), copper tetrafluoroborate tetraacetonitrile (0.02 mmol), ligand (0.022 mmol), and 3,3-dimethyl-1-(trifluoromethyl)-1,2-benzimidoxolane (0.3 mmol) were added in sequence. The reaction system was sealed with argon gas, and 1,2-dichloroethane (1 mL) and a nitrogen nucleophile (1 mmol) were added while maintaining the gas flow. The reaction system was sealed and reacted at 70°C for 12 hours. After completion of the reaction, the copper salt was removed by washing with sodium bicarbonate solution, the mixture was dried, filtered, and concentrated under reduced pressure. Compound VII was then purified by column chromatography using petroleum ether:ethyl acetate in a ratio of 4:1.

[0166] The characterization data of compound VII-1 are as follows:

[0167]

[0168] White solid (47.9 mg, 42% yield, dr 12.1 / 1). Melting point: 249.5–253.1 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 32.83. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.55. 1 H NMR (400 MHz, CDCl3) δ 7.78 (dd, J = 13.2, 7.7 Hz, 4H), 7.60 (d, J = 8.9 Hz, 1H),7.46 (t, J = 8.2 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.37 – 7.27 (m, 8H), 7.25– 7.15 (m, 2H), 7.12 (t, J = 7.4 Hz, 1H), 6.08 (d, J = 8.9 Hz, 1H), 4.90 (s,1H), 4.43 (dd, J = 16.4, 7.1 Hz, 1H), 3.47 (d, J = 14.9 Hz, 1H), 3.03 – 2.87(m, 3H), 2.77 (dd, 1H), 2.50 (dd, J= 14.8, 7.1 Hz, 1H), 2.37 (dq, J = 15.4,10.7 Hz, 1H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 154.69, 147.15, 146.06 (d, J C-P =3.8 Hz), 145.77 (d, J C-P = 12.1 Hz), 137.31, 133.33 (d, J C-P = 99.9 Hz), 132.01(d, J C-P = 3.0 Hz), 130.92 (d, J C-P = 9.2 Hz), 129.65, 128.95, 128.91, 128.81,127.96, 127.56, 127.36, 126.75, 125.95 (q, J C-F = 279.3 Hz), 125.76, 123.22,122.81, 113.42, 60.84, 48.74 (d, J C-P = 9.0 Hz), 43.91 (q, J C-F = 29.6, 27.2Hz), 40.18, 35.83 (d, J C-P = 64.3 Hz), 33.33 (d, J C-P = 62.7 Hz). FT-IR (KBr):3254, 3155, 3107, 3056, 2959, 1619, 1584, 1540, 1482, 1447, 1420, 1396, 1343,1253, 1228, 1185, 1140, 1115, 1035, 961, 893, 850, 825, 786, 713, 693, 650,616, 591, 525, 497, 481, 444 cm -1 . HRMS (ESI) calcd for C 34 H 31 F3N2OP+ [M+H] + 571.2121, found 571.2121.

[0169] The characterization data of compound VII-2 are as follows:

[0170]

[0171] Brown solid (36 mg, 32% yield, dr 13.9 / 1). Melting point: 191.1-192.5 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 33.01. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ -58.66. 1 H NMR (400 MHz, CDCl3) δ 7.62 -7.53 (m, 9H), 7.48 (dd, J = 12.7, 7.1 Hz, 3H), 7.41- 7.33 (m, 4H), 7.32 – 7.27 (m, 2H), 7.23 (d, J = 8.0 Hz, 1H), 7.16 (t, J =7.4 Hz, 1H), 6.17 – 6.12 (m, 1H), 6.11 (s, 1H), 4.43 (s, 1H), 3.20 – 2.97 (m,4H), 2.89 (d, J = 15.6 Hz, 1H), 2.81 (dd, J = 14.8, 11.1 Hz, 3H). 13 C NMR (100MHz, CDCl3) δ 146.13 (d, J C-P = 6.7 Hz), 145.08 (d, J C-P = 10.6 Hz), 140.51,134.36, 132.58 (d, J C-P = 99.4 Hz), 132.15 (d, J C-P = 2.7 Hz), 130.59 (d, J C-P=9.2 Hz), 129.46, 129.17, 129.01, 128.93 (d, J C-P = 11.7 Hz), 128.00, 127.56,127.43, 127.30, 126.40, 126.33, 126.30, 126.23, 125.79 (q, J C-F = 279.3 Hz),122.61, 118.89, 108.74, 60.03 (d, J C-P = 2.3 Hz), 50.40 (d, J C-P = 16.2 Hz),47.48 (q, J C-F = 25.5 Hz), 39.42, 34.95 (d, J C-P = 64.2 Hz), 33.17 (d, J C-P =66.4 Hz). FT-IR (KBr): 3419, 3273, 3058, 2957, 1631, 1602, 1548, 1524, 1497,1472, 1447, 1438, 1382, 1329, 1253, 1221, 1185, 1141, 1118, 1088, 1070, 1033,965, 892, 839, 816, 787, 743, 713, 703, 673, 644, 619, 592, 583, 509, 494,474 cm -1 . HRMS (ESI) calcd for C 35 H 32 F3NOP + [M+H] + 570.2168, found 570.2169.

[0172] The characterization data of compound VII-3 are as follows:

[0173]

[0174] Colorless oil (64 mg, 61% yield, dr 12.1 / 1). 31 P{ 1H} NMR (162 MHz, CDCl3)δ 33.40. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.55. 1 H NMR (400 MHz, CDCl3) δ 8.02(d, J = 5.0 Hz, 1H), 7.81 (dd, J = 11.5, 7.4 Hz, 2H), 7.62 – 7.51 (m, 3H),7.47 (d, J = 7.9 Hz, 2H), 7.42 – 7.34 (m, 5H), 7.31 – 7.25 (m, 3H), 7.19 (t, J = 7.3 Hz, 1H), 6.76 (s, 1H), 6.54 (dd, J = 7.1, 5.1 Hz, 1H), 6.49 (d, J =8.4 Hz, 1H), 4.29 – 4.08 (m, 2H), 3.14 (t, J = 16.1 Hz, 1H), 2.55 (d, J =14.6 Hz, 1H), 2.35 (d, J = 14.3 Hz, 1H), 2.27 (dd, J = 14.1, 7.6 Hz, 1H),2.06 (dd, J = 13.9, 4.9 Hz, 2H). 13 C NMR (100 MHz, CDCl3) δ 156.90, 148.00,147.90 (d, J C-P = 11.6 Hz), 146.51 (d, J C-P = 12.7 Hz), 137.24, 132.66 (d, J C-P = 2.9 Hz), 131.99 (d, J C-P = 99.4 Hz), 130.41 (d, J C-P = 9.2 Hz), 129.14 (d, J C-P= 11.8 Hz), 128.76, 128.62, 127.20, 126.85, 126.53 (q, J C-F = 279.1 Hz),125.36, 124.82, 113.17, 109.79, 59.05 (d, J C-P = 4.6 Hz), 43.48 (d, J C-P = 6.0Hz), 42.75 (d, J C-P = 59.2 Hz), 40.79 (d, J C-P = 3.2 Hz), 40.39 (q, J C-F = 25.5Hz), 34.36 (d, J C-P = 66.6 Hz). FT-IR (KBr): 3302, 3056, 2925, 2855, 1602,1526, 1484, 1445, 1437, 1420, 1374, 1339, 1290, 1256, 1187, 1150, 1116, 1086,1052, 1035, 985, 964, 829, 773, 737, 697, 681, 580, 517, 482, 419 cm -1 . HRMS(ESI) calcd for C 30 H 29 F3N2OP + [M+H] + 521.1964, found 521.1964.

[0175] The characterization data of compound VII-4 are as follows:

[0176]

[0177] Colorless oil (59 mg, 60% yield, dr 13.9 / 1). 31 P{ 1 H} NMR (202 MHz, CDCl3)δ 31.65. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.23. 1H NMR (500 MHz, CDCl3) δ 8.12(dd, J = 11.0, 7.2 Hz, 2H), 7.61 – 7.55 (m, 3H), 7.44 (d, J = 1.7 Hz, 1H),7.41 – 7.37 (m, 2H), 7.35 – 7.31 (m, 3H), 7.26 – 7.15 (m, 5H), 6.58 (d, J =2.5 Hz, 1H), 5.84 (t, J = 2.1 Hz, 1H), 3.62 (dd, J = 16.0, 6.3 Hz, 1H), 3.58– 3.49 (m, 2H), 3.31 (dq, J = 15.3, 10.5 Hz, 1H), 2.82 (t, J = 16.6 Hz, 1H),2.73 (ddd, J = 16.9, 14.6, 2.4 Hz, 1H), 2.58 (dq, J = 15.7, 10.9 Hz, 1H),2.50 (dd, J = 14.8, 7.9 Hz, 1H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 144.96 (d, J C-P = 5.2 Hz), 144.81 (d, J C-P = 12.5 Hz), 138.08, 132.71 (d, J C-P = 100.7 Hz),132.35 (d, J C-P = 2.9 Hz), 131.22 (d, J C-P = 9.4 Hz), 129.73, 128.96, 128.88(d, J C-P = 12.1 Hz), 128.53, 128.36, 126.91, 126.21, 125.87 (q, J C-F= 279.5Hz), 125.52, 106.09, 66.04, 48.00 (d, J C-P = 10.1 Hz), 44.70 (q, J C-F = 25.6Hz), 40.42, 39.83 (d, J C-P = 24.3 Hz), 32.67 (d, J C-P = 65.7 Hz). FT-IR (KBr):3059, 3030, 2944, 1498, 1448, 1438, 1425, 1387, 1313, 1256, 1189, 1160, 1121,1086, 1048, 1035, 1000, 970, 911, 831, 750, 696, 645, 620, 582, 532, 512, 482cm -1 . HRMS (ESI) calcd for C 28 H 27 F3N2OP + [M+H] + 495.1808, found 495.1807.

[0178] The characterization data of compound VII-5 are as follows:

[0179]

[0180] Brown oil (72.9 mg, 65% yield, dr 2.3 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3)δ 33.81. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.66. 1 H NMR (400 MHz, CDCl3) δ 7.65(d, J = 7.9 Hz, 2H), 7.60 (dd, J = 11.6, 7.6 Hz, 2H), 7.48 (d, J = 8.1 Hz,2H), 7.45 – 7.35 (m, 6H), 7.32 (dd, J= 12.9, 5.7 Hz, 2H), 7.29 – 7.24 (m,1H), 6.50 (d, J = 7.4 Hz, 1H), 6.38 (t, J = 7.7 Hz, 1H), 5.76 (d, J = 7.9 Hz,1H), 4.37 (s, 1H), 4.32 (t, J = 8.7 Hz, 2H), 3.12 (d, J = 9.0 Hz, 2H), 3.09 –3.03 (m, 2H), 2.98 (d, J = 15.1 Hz, 1H), 2.84 – 2.78 (m, 2H), 2.79 – 2.62 (m,3H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 148.08, 146.20 (d, J C-P = 6.4 Hz), 144.64(d, J C-P = 11.2 Hz), 132.96 (d, J C-P = 99.1 Hz), 132.06 (d, J C-P = 3.0 Hz),130.71, 130.63, 128.92, 128.89, 128.80, 128.48, 127.35 (d, J C-P = 11.8 Hz),126.65, 126.22, 125.83 (q, J C-F = 279.2 Hz), 125.59, 120.61, 114.18, 113.43,70.90, 59.72, 50.74 (d, J C-P = 13.8 Hz), 46.66 (q, J C-F = 25.5 Hz), 39.48,35.82 (d, J C-P = 62.8 Hz), 34.00 (d, J C-P= 65.8 Hz), 30.66. FT-IR (KBr): 3407,3057, 2965, 1623, 1591, 1493, 1446, 1437, 1379, 1340, 1308, 1256, 1189, 1142,1118, 1085, 1068, 1039, 999, 964, 936, 910, 863, 834, 729, 698, 644, 590,547, 511, 491, 443 cm -1 . HRMS (ESI) calcd for C 33 H 32 F3NO2P + [M+H] + 562.2117, found 562.2118.

[0181] The characterization data of compound VII-6 are as follows:

[0182]

[0183] Brown solid (58.8 mg, 57% yield, dr 12.2 / 1). Melting point: 173.4–176.3 °C. 31 P{ 1 H}NMR (202 MHz, CDCl3) δ 33.79. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.71. 1 H NMR(500 MHz, CDCl3) δ 7.56 – 7.48 (m, 9H), 7.45 – 7.35 (m, 5H), 7.31 – 7.27 (m,1H), 6.97 (dd, J = 8.5, 7.3 Hz, 2H), 6.64 (t, J = 7.4 Hz, 1H), 5.92 (d, 2H), 4.23 (s, 1H), 3.09 (dq, J = 15.3, 10.6 Hz, 1H), 3.00 – 2.90 (m, 3H), 2.90 –2.74 (m, 3H), 2.72 (dd, 1H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 146.63 (d, JC-P =7.2 Hz), 145.07 (d, J C-P = 10.6 Hz), 143.15, 132.70 (d, J C-P = 99.4 Hz), 132.16(d, J C-P = 3.0 Hz), 130.60 (d, J C-P = 9.4 Hz), 129.38, 129.09, 128.96, 128.88,127.94, 127.23, 126.30, 126.21, 125.78 (q, J C-F = 279.3 Hz), 118.04, 115.51,59.82 (d, J C-P = 2.3 Hz), 50.22 (d, J C-P = 16.0 Hz), 47.47 (q, J C-F = 25.6 Hz),39.36, 34.99 (d, J C-P = 64.0 Hz), 33.35 (d, J C-P = 65.8 Hz). FT-IR (KBr): 3292,3057, 2955, 2853, 1600, 1538, 1498, 1439, 1382, 1316, 1252, 1201, 1185, 1140,1085, 1035, 1001, 993, 964, 893, 878, 867, 833, 787, 747, 715, 693, 607, 550,504, 484, 441 cm -1 . HRMS (ESI) calcd for C 31 H 30 F3NOP + [M+H] + 520.2012, found520.2016.

[0184] The characterization data of compound VII-7 are as follows:

[0185]

[0186] Brown solid (79.4 mg, 66% yield, dr 8.3 / 1). Melting point: 192.2–194.7 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 32.41. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.67. 1 H NMR (400 MHz, CDCl3) δ 7.62 (dd, J = 11.6, 7.6 Hz, 2H), 7.57 – 7.49 (m, 7H), 7.44(d, J = 6.4 Hz, 3H), 7.38 (t, J = 7.6 Hz, 2H), 7.29 (t, J = 7.8 Hz, 1H), 6.76(dt, J = 15.4, 7.9 Hz, 2H), 6.04 (s, 1H), 5.81 (d, J = 7.9 Hz, 1H), 4.33 (s,1H), 3.14 – 3.04 (m, 1H), 2.99 (d, J = 15.7 Hz, 2H), 2.81 (d, J = 15.4 Hz, 2H), 2.80 – 2.63 (m, 3H). 13 C NMR (100 MHz, CDCl3) δ 145.83 (d, J C-P = 6.4 Hz),144.82 (d, J C-P = 10.3 Hz), 144.61, 132.49 (d, J C-P = 99.6 Hz), 132.30, 130.60(d, J C-P = 9.4 Hz), 130.27, 129.46, 129.08, 128.96, 128.06, 127.45, 126.21,126.10, 125.73 (q, J C-F= 278.8 Hz), 122.88, 120.91, 118.10, 113.76, 59.93,50.47 (d, J C-P = 16.0 Hz), 47.25 (q, J C-F = 24.9 Hz), 39.39, 35.34 (d, J C-P =63.8 Hz), 33.25 (d, J C-P = 66.4 Hz). FT-IR (KBr): 3417, 3278, 3068, 2957,1593, 1526, 1496, 1478, 1447, 1438, 1383, 1332, 1252, 1185, 1120, 1032, 1001,986, 964, 901, 873, 840, 786, 771, 752, 702, 607, 553, 517, 496, 484, 434 cm -1 . HRMS (ESI) calcd for C 31 H 29 BrF3NOP + [M+H] + 598.1117, found 598.1119.

[0187] The characterization data of compound VII-8 are as follows:

[0188]

[0189] Brown oil (75.2 mg, 63% yield, dr 8.8 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3)δ 33.28. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –59.03. 1 H NMR (400 MHz, CDCl3) δ 7.59– 7.49 (m, 7H), 7.49 – 7.45 (m, 2H), 7.43 – 7.38 (m, 4H), 7.35 – 7.29 (m,3H), 6.79 (t, J = 7.8 Hz, 1H), 6.47 (t,J = 7.6 Hz, 1H), 5.93 (d, J = 8.2 Hz,1H), 5.16 (s, 1H), 3.07 (t, J = 17.0 Hz, 2H), 3.01 – 2.86 (m, 4H), 2.83 (d, J = 11.0 Hz, 2H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 145.81 (d, J C-P = 7.4 Hz),144.54 (d, J C-P = 11.3 Hz), 140.92, 132.91, 132.78 (d, J C-P = 99.2 Hz), 132.16(d, J C-P = 2.8 Hz), 130.55 (d, J C-P = 9.5 Hz), 129.48, 129.23, 128.94 (d, J C-P =11.9 Hz), 127.82, 127.56, 127.43, 126.65, 126.05, 125.75 (q, J C-F = 279.3 Hz),118.71, 115.68, 110.23, 60.05 (d, J C-P = 2.3 Hz), 48.79 (q, J C-F = 25.6 Hz),48.46 (d, J C-P = 15.4 Hz), 39.17, 35.88 (d, J C-P = 63.9 Hz), 34.68 (d, J C-P=64.6 Hz). FT-IR (KBr): 3389, 3059, 3026, 2940, 1595, 1500, 1459, 1446, 1437,1405, 1377, 1318, 1261, 1186, 1142, 1114, 1086, 1067, 1034, 1021, 1000, 978,908, 866, 822, 773, 744, 697, 645, 609, 590, 551, 526, 495, 482, 442, 419 cm -1 . HRMS (ESI) calcd for C 31 H 29 BrF3NOP + [M+H] + 598.1117, found 598.1119.

[0190] The characterization data of compound VII-9 are as follows:

[0191]

[0192] Brown solid (61 mg, 51% yield, dr 10.8 / 1). Melting point: 169.2–172.3 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 32.66. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –64.61. 1 H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 11.5, 7.6 Hz, 2H), 7.55 – 7.48 (m, 7H), 7.45(td, J = 7.9, 2.8 Hz, 3H), 7.37 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 7.7 Hz,1H), 7.03 (d, J = 8.6 Hz, 2H), 5.77 (d, J = 8.5 Hz, 2H), 4.28 (s, 1H), 3.15 –2.97 (m, 2H), 2.95 (d, J= 13.7 Hz, 1H), 2.87 – 2.72 (m, 4H), 2.68 (dd, J =14.6, 7.4 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 145.95 (d, J C-P = 6.5 Hz), 144.87(d, J C-P = 10.5 Hz), 142.18, 132.50 (d, J C-P = 100.2 Hz), 132.28 (d, J C-P = 2.8Hz), 131.82, 130.53 (d, J C-P = 9.4 Hz), 129.42, 129.05, 129.00 (d, J C-P = 11.9Hz), 127.99, 127.40, 126.22, 126.12, 125.71 (q, J C-F = 279.4 Hz), 116.89,109.93, 59.85 (d, J C-P = 2.2 Hz), 50.35 (d, J C-P = 16.1 Hz), 47.31 (q, J C-F =25.9 Hz), 39.37, 35.14 (d, J C-P = 63.7 Hz), 33.25 (d, J C-P = 65.3 Hz). FT-IR(KBr): 3419, 3283, 3176, 3036, 2959, 1595, 1529, 1490, 1447, 1439, 1383,1312, 1252, 1185, 1140, 1118, 1033, 1001, 965, 913, 894, 869, 827, 786, 750,703, 654, 633, 616, 573, 548, 503, 486, 445, 419 cm -1. HRMS (ESI) calcd forC 31 H 29 BrF3NOP + [M+H] + 598.1117, found 598.1125.

[0193] The characterization data of compound VII-10 are as follows:

[0194]

[0195] Yellow oil (50 mg, 47% yield, dr 9.9 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ33.04. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.62. 1 H NMR (400 MHz, CDCl3) δ 7.62 –7.55 (m, 5H), 7.54 – 7.48 (m, 4H), 7.44 – 7.39 (m, 3H), 7.38 (d, J = 7.9 Hz,2H), 7.29 (t, J = 7.3 Hz, 1H), 6.79 (d, J = 8.1 Hz, 2H), 5.88 (d, J = 8.4 Hz, 2H), 4.12 (s, 1H), 3.10 (dq, J = 15.3, 10.7 Hz, 1H), 2.97 (t, J = 15.7 Hz,2H), 2.95 – 2.86 (m, 1H), 2.87 – 2.76 (m, 3H), 2.72 (dd, J = 15.1, 8.3 Hz,1H), 2.16 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 146.80 (d, J C-P = 6.8 Hz), 145.10(d, J C-P = 10.8 Hz), 140.75, 132.80 (d, J C-P= 99.2 Hz), 132.06 (d, J C-P = 2.8Hz), 130.58 (d, J C-P = 9.3 Hz), 129.53, 129.26, 128.85, 128.84 (d, J C-P = 11.8Hz), 127.80, 127.19, 127.13, 126.27, 126.21, 125.77 (q, J C-F = 279.4 Hz),115.62, 59.82 (d, J C-P = 2.3 Hz), 50.41 (d, J C-P = 15.5 Hz), 47.25 (q, J C-F =25.8 Hz), 39.37 (d, J C-P = 1.6 Hz), 35.06 (d, J C-P = 63.8 Hz), 33.38 (d, J C-P =65.7 Hz), 20.37. FT-IR (KBr): 3421, 3289, 3057, 3025, 2918, 1616, 1514, 1496,1446, 1438, 1381, 1303, 1253, 1185, 1140, 1117, 1087, 1034, 1000, 964, 910,895, 870, 815, 788, 772, 738, 702, 593, 506, 482, 442 cm -1 . HRMS (ESI) calcdfor C 32 H 32 F3NOP + [M+H] + 534.2168, found 534.2175.

[0196] The characterization data of compound VII-11 are as follows:

[0197]

[0198] Brown oil (54.1 mg, 51% yield, dr 9.4 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3)δ 33.54. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –59.01. 1 H NMR (400 MHz, CDCl3) δ 7.63– 7.53 (m, 4H), 7.53 – 7.46 (m, 5H), 7.44 – 7.36 (m, 5H), 7.31 – 7.27 (m,1H), 6.94 (d, J = 7.2 Hz, 1H), 6.74 (t, J = 7.7 Hz, 1H), 6.55 (t, J = 7.3 Hz,1H), 5.87 (d, J = 8.0 Hz, 1H), 4.25 (s, 1H), 3.12 – 3.00 (m, 3H), 2.99 – 2.89(m, 3H), 2.85 (d, J = 15.8 Hz, 1H), 2.78 (dd, J = 14.7, 7.7 Hz, 1H), 1.29 (s,3H). 13 C NMR (100 MHz, CDCl3) δ 146.64 (d, J C-P = 7.1 Hz), 145.12 (d, J C-P =11.0 Hz), 141.23, 132.71 (d, J C-P = 99.3 Hz), 132.13 (d, J C-P = 2.9 Hz), 130.60(d, J C-P = 9.4 Hz), 130.51, 129.52, 128.99, 128.92 (d, J C-P = 12.1 Hz), 127.92,127.10, 126.38, 126.18, 126.02, 125.74 (q, JC-F = 279.3 Hz), 122.85, 117.46,114.25, 59.79 (d, J C-P = 2.4 Hz), 48.75 (q, J C-F = 25.7 Hz), 39.21, 35.77 (d, J C-P = 64.7 Hz), 34.24 (d, J C-P = 65.6 Hz), 16.50. FT-IR (KBr): 3430, 3058,3024, 2937, 1604, 1588, 1509, 1479, 1446, 1377, 1315, 1260, 1183, 1116, 1066,1034, 999, 954, 909, 876, 823, 773, 747, 700, 644, 590, 559, 526, 492, 450,419 cm -1 . HRMS (ESI) calcd for C 32 H 32 F3NOP + [M+H] + 534.2168, found 534.2169.

[0199] Example 4 Synthesis of Multi-substituted Phosphatic Six-membered Ring Phosphine Oxide Compound IX Using Carbon as Nucleophile

[0200]

[0201] Specific experimental procedures: To a 10 mL sealed tube, diene phosphine oxide II (0.2 mmol), copper tetrafluoroborate tetraacetonitrile (0.02 mmol), ligand (0.022 mmol), and 3,3-dimethyl-1-(trifluoromethyl)-1,2-benzoiodooxolane (0.3 mmol) were added in sequence. The reaction system was sealed under argon flow and purged five times. 1,2-Dichloroethane (1 mL) and a carbon nucleophile (1 mmol) were added while maintaining the flow. The reaction system was sealed and allowed to react at 70°C for 12 hours. After completion of the reaction, the copper salt was removed by washing with sodium bicarbonate, the reaction mixture was dried, filtered, and concentrated under reduced pressure. Compound IX was then purified by column chromatography using a 4:1 ratio of petroleum ether:ethyl acetate to afford compound IX.

[0202] The characterization data of compound IX-1 are as follows:

[0203]

[0204] Brown solid (56 mg, 57% yield, dr 11.2 / 1). Melting point: 151.3–157.5 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 29.88. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.44. 1 H NMR (400 MHz, CD3CN) δ 8.74 (s, 1H), 7.91 (dd, J = 10.7, 7.3 Hz, 2H), 7.79 (d, J = 7.8 Hz, 2H), 7.60 (dd, J = 7.1, 1.6 Hz, 1H), 7.56 (dd, J = 7.7, 2.6 Hz,2H), 7.52 (d, J = 8.0 Hz, 2H), 7.41 – 7.33 (m, 4H), 7.26 (td, J = 7.3, 4.8Hz, 2H), 6.44 (q, J = 2.4 Hz, 1H), 5.87 (q, J = 2.9 Hz, 1H), 5.81 – 5.75 (m,1H), 3.44 (dd, J = 14.7, 2.4 Hz, 1H), 3.33 (tt, J = 15.3, 2.5 Hz, 1H), 3.09(dq, J = 15.6, 11.2 Hz, 1H), 2.77 (ddt, J = 17.2, 14.4, 2.6 Hz, 1H), 2.56 (d, J = 14.7 Hz, 1H), 2.45 (dd, J = 14.7, 7.4 Hz, 1H), 2.31 (dd, J = 15.6, 6.9Hz, 1H), 2.27 – 2.24 (m, 1H). 13 C NMR (100 MHz, CDCl3) δ 145.96 (d,J C-P = 12.4Hz), 144.43 (d, J C-P = 1.9 Hz), 140.31 (d, J C-P = 11.2 Hz), 132.96 (d, J C-P =99.0 Hz), 132.22 (d, J C-P = 2.9 Hz), 130.71 (d, J C-P = 9.0 Hz), 128.94 (d, J C-P = 11.5 Hz), 128.66, 128.62, 127.96, 127.30, 127.08, 125.96 (q, J C-F = 279.4Hz), 125.39, 118.08, 107.61, 103.71, 50.07 (d, J C-P = 7.9 Hz), 44.30 (d, J C-P =3.0 Hz), 42.35 (q, J C-F = 26.6 Hz), 40.32, 38.81 (d, J C-P = 58.9 Hz), 34.52 (d, J C-P = 65.7 Hz). FT-IR (KBr): 3330, 3217, 3060, 2959, 1758, 1716, 1647, 1600,1574, 1498, 1446, 1438, 1381, 1339, 1310, 1259, 1184, 1142, 1118, 1035, 1001,966, 915, 897, 834, 754, 699, 580, 537, 502, 472, 444, 419 cm -1 . HRMS (ESI)calcd for C 29 H 28 F3NOP + [M+H] +494.1855, found 494.1856.

[0205] The characterization data of compound IX-2 are as follows:

[0206]

[0207] Single crystal structure such as Figure 2 As shown, brown solid (66.3 mg, 61% yield, dr 13.7 / 1). Melting point: 214.3–215.5 °C. 31 P{ 1 H} NMR (162 MHz, (CD3)2SO) δ 29.72. 19 F{ 1 H} NMR (376 MHz, (CD3)2SO) δ –57.16. 1 H NMR (400 MHz, (CD3)2SO) δ 10.89 (d, J = 2.6 Hz, 1H),8.01 (ddd, J = 16.3, 11.6, 7.2 Hz, 4H), 7.62 (d, J = 8.0 Hz, 2H), 7.58 – 7.48(m, 3H), 7.38 (t, J = 7.6 Hz, 2H), 7.32 (t, J = 7.7 Hz, 2H), 7.27 (dd, J =7.8, 5.1 Hz, 2H), 7.20 (t, J = 7.1 Hz, 2H), 7.11 (d, J = 2.6 Hz, 1H), 6.92(t, J = 7.6 Hz, 1H), 6.70 (t, J = 7.6 Hz, 1H), 3.62 (t, J = 15.1 Hz, 1H),3.48 (d, J = 14.4 Hz, 1H), 3.15 (dq, J = 15.3, 11.3 Hz, 1H), 2.88 (d, J =14.3 Hz, 1H), 2.75 (t, J = 15.7 Hz, 1H), 2.64 (dd, J= 14.5, 7.2 Hz, 1H),2.38 (dd, J = 15.5, 7.0 Hz, 1H), 2.17 (dq, J = 15.4, 11.6 Hz, 1H). 13 C NMR (100 MHz, (CD3)2SO) δ 146.40 (d, J C-P = 12.7 Hz), 145.03, 136.88, 133.97 (d, J C-P = 97.4 Hz), 131.65 (d, J C-P = 2.5 Hz), 130.91 (d, J C-P = 9.1 Hz), 128.76,128.48 (d, J C-P = 11.3 Hz), 128.08, 127.35, 126.93 (d, J C-P = 14.3 Hz), 126.51,126.42 (q, J C-F = 279.8 Hz), 125.88, 124.13, 120.65, 120.04, 119.88, 118.15,118.03, 111.53, 49.77, 44.07 (d, J C-P = 3.4 Hz), 40.35 (q, J C-F = 24.5 Hz),36.18 (d, J C-P = 58.5 Hz), 34.51 (d, J C-P= 64.8 Hz). FT-IR (neat): 3164, 3058,2919, 1724, 1600, 1496, 1438, 1400, 1381, 1341, 1308, 1255, 1186, 1161, 1113,1070, 1000, 964, 896, 859, 836, 826, 787, 740, 697, 638, 624, 603, 558, 547,541, 530, 489, 475, 437, 427 cm -1 . HRMS (ESI) calcd for C 33 H 30 F3NOP + [M+H] + 544.2012, found 544.2013.

[0208] Table 1 Single crystal data of compound IX-2

[0209] The characterization data of compound IX-3 are as follows:

[0210]

[0211] Brown solid (68 mg, 60% yield, dr 12.6 / 1). Melting point: 157.6–165.1 °C. 31 P{ 1 H}NMR (162 MHz, CDCl3) δ 29.16. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.49. 1 H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.8 Hz, 2H), 7.84 (dd, J = 10.3, 7.5 Hz, 2H),7.55 – 7.45 (m, 3H), 7.44 – 7.35 (m, 6H), 7.29 (d, J = 6.7 Hz, 1H), 7.23 (d, J = 6.9 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.14 (d, J= 8.1 Hz, 1H), 7.10 (t, J = 7.6 Hz, 1H), 6.85 (t, J = 7.6 Hz, 1H), 6.80 (s, 1H), 3.72 (d, J = 15.3Hz, 1H), 3.68 (s, 3H), 3.43 (d, J = 14.4 Hz, 1H), 3.22 (dq, J = 15.6, 10.8Hz, 1H), 2.99 (t, J = 16.1 Hz, 1H), 2.75 (d, J = 14.4 Hz, 1H), 2.42 (dd, J =16.0, 6.3 Hz, 1H), 2.29 (dd, J = 14.7, 6.4 Hz, 1H), 2.12 (dq, J = 15.6, 10.8Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 146.30 (d, J C-P = 12.2 Hz), 144.82, 137.78,133.40 (d, J C-P = 98.8 Hz), 132.01 (d, J C-P = 2.9 Hz), 130.85 (d, J C-P = 8.7Hz), 128.82 (d, J C-P = 11.5 Hz), 128.68, 128.57, 128.31, 127.10, 126.98 (d, J C-P = 13.7 Hz), 126.77, 126.15 (q, J C-F = 279.5 Hz), 125.50, 125.02, 124.05,121.83, 120.53, 119.08, 109.55, 52.04 (d, J C-P = 6.9 Hz), 44.64 (d, JC-P = 3.5Hz), 41.09 (q, J C-F = 25.3 Hz), 40.80, 37.52 (d, J C-P = 58.9 Hz), 36.12 (d, J C-P = 65.8 Hz), 32.75. FT-IR (KBr): 3057, 3031, 2957, 2228, 1600, 1537, 1496,1400, 1328, 1307, 1258, 1192, 1138, 1001, 964, 927, 894, 857, 833, 810, 784,737, 643, 606, 599, 563, 547, 520, 500, 485, 461, 428 cm -1 . HRMS (ESI) calcdfor C 34 H 32 F3NOP + [M+H] + 558.2168, found 558.2175.

[0212] The characterization data of compound IX-4 are as follows:

[0213]

[0214] Yellow oil (27 mg, 24% yield, dr 8.5 / 1). 31 P{ 1 H} NMR (162 MHz, CDCl3) δ30.82. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.43. 1 H NMR (400 MHz, CDCl3) δ 7.81(dd, J = 10.3, 7.6 Hz, 2H), 7.58 – 7.47 (m, 5H), 7.34 – 7.27 (m, 5H), 7.27 –7.21 (m, 2H), 7.15 (dd, J = 10.2, 8.0 Hz, 2H), 6.37 (dd, J = 8.7, 2.6 Hz,1H), 6.12 (d, J= 2.6 Hz, 1H), 3.72 (s, 3H), 3.66 (t, J = 16.5 Hz, 1H), 3.30– 3.15 (m, 5H), 2.87 (dd, J = 19.3, 14.7 Hz, 2H), 2.51 (dd, J = 16.1, 6.6 Hz,1H), 2.36 (dd, J = 14.8, 6.9 Hz, 1H), 2.16 (dq, J = 15.6, 11.0 Hz, 1H). 13 CNMR (100 MHz, CDCl3) δ 159.99, 158.35, 146.77, 146.08 (d, J C-P = 12.4 Hz),133.91 (d, J C-P = 98.3 Hz), 131.93 (d, J C-P = 2.7 Hz), 130.70 (d, J C-P = 8.7Hz), 130.51, 128.83 (d, J C-P = 11.4 Hz), 128.33, 127.81, 127.68, 126.84,126.10 (q, J C-F = 279.9 Hz), 125.99, 125.86, 125.59, 103.57, 100.68, 55.36,55.00, 50.96 (d, J C-P = 7.8 Hz), 46.25 (d, J C-P = 3.1 Hz), 42.42 (q, J C-F = 24.7Hz), 40.29, 36.25 (d, J C-P = 61.0 Hz), 33.82 (d, J C-P= 65.5 Hz). FT-IR (KBr):3058, 3025, 2938, 2837, 1608, 1581, 1498, 1438, 1416, 1382, 1308, 1259, 1209,1138, 1118, 1087, 1032, 964, 910, 838, 786, 733, 697, 643, 602, 574, 549,534, 504, 443, 419 cm -1 . HRMS (ESI) calcd for C 33 H 33 F3O3P + [M+H] + 565.2114, found 565.2124.

[0215] The characterization data of compound IX-5 are as follows:

[0216]

[0217] Gray solid (74 mg, 62% yield, dr 14.7 / 1). Melting point: 254.4–258.4 °C. 31 P{ 1 H}NMR (202 MHz, CDCl3) δ 29.77. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.34. 1 H NMR (500 MHz, CDCl3) δ 7.85 (dd, J = 10.3, 7.6 Hz, 2H), 7.71 (d, J = 7.8 Hz, 2H),7.59 – 7.50 (m, 3H), 7.42 – 7.35 (m, 6H), 7.29 (tt, J = 5.4, 2.9 Hz, 1H),7.27 – 7.20 (m, 3H), 7.00 (d, J = 7.9 Hz, 2H), 6.98 (d, J = 8.7 Hz, 2H), 6.90(t, J = 7.2 Hz, 1H), 6.88 (d, J= 8.8 Hz, 2H), 5.76 (s, 1H), 3.44 (d, J =14.5 Hz, 1H), 3.29 (t, J = 15.8 Hz, 1H), 3.13 (dq, J = 15.6, 10.7 Hz, 1H),2.94 (t, J = 16.1 Hz, 1H), 2.67 (d, J = 14.5 Hz, 1H), 2.30 – 2.19 (m, 2H),2.14 (dq, J = 15.5, 10.8 Hz, 1H). 13 C{ 1 H} NMR (126 MHz, CDCl3) δ 146.25 (d, J C-P = 12.1 Hz), 145.69, 143.94 (d, J C-P = 11.8 Hz), 142.82, 141.40, 133.37 (d, J C-P = 98.8 Hz), 132.13 (d, J C-P = 2.6 Hz), 130.83 (d, J C-P = 9.1 Hz), 129.41,128.92 (d, J C-P = 11.4 Hz), 128.61, 128.50, 128.42, 127.13, 126.76, 126.74,126.10 (q, J C-F = 279.4 Hz), 125.49, 121.22, 117.97, 117.27, 50.87 (d, J C-P =7.3 Hz), 47.08 (d, J C-P = 3.3 Hz), 41.37 (q, J C-F = 26.1 Hz), 40.59, 38.97 (d, J C-P = 59.1 Hz), 35.27 (d,J C-P = 65.5 Hz). FT-IR (KBr): 3267, 3183, 3056,3035, 1597, 1526, 1495, 1446, 1437, 1427, 1380, 1315, 1258, 1188, 1163, 1138,1116, 1081, 1035, 963, 842, 829, 813, 785, 748, 732, 706, 693, 592, 581, 536,510, 500 cm -1 . HRMS (ESI) calcd for C 37 H 34 F3NOP + [M+H] + 596.2325, found596.2326.

[0218] The characterization data of compound IX-6 are as follows:

[0219]

[0220] Brown solid (64 mg, 60% yield, dr 14.2 / 1). Melting point: 92.5–96.7 °C. 31 P{ 1 H} NMR (162 MHz, CDCl3) δ 29.31. 19 F{ 1 H} NMR (376 MHz, CDCl3) δ –58.46. 1 H NMR (400MHz, CDCl3) δ 7.83 (dd, J = 10.3, 7.6 Hz, 2H), 7.70 (d, J = 7.8 Hz, 2H), 7.58– 7.48 (m, 3H), 7.42 – 7.35 (m, 6H), 7.32 – 7.27 (m, 1H), 7.23 (t, J = 7.3Hz, 1H), 6.91 (d, J = 8.6 Hz, 2H), 6.42 (d, J = 8.5 Hz, 2H), 3.70 (s, 1H), 3.41 (d, J = 14.5 Hz, 1H), 3.28 (t, 1H), 3.12 (dq,J = 15.6, 10.7 Hz, 1H),2.92 (t, J = 14.7, 2.4 Hz, 1H), 2.75 (s, 3H), 2.65 (d, J = 14.5 Hz, 1H), 2.21(dd, J = 15.6, 6.7 Hz, 2H), 2.11 (dq, J = 15.6, 10.8 Hz, 1H). 13 C{ 1 H} NMR (100MHz, CDCl3) δ 147.49, 146.37 (d, J C-P = 12.5 Hz), 145.99, 140.51 (d, J C-P =12.1 Hz), 132.04 (d, J C-P = 2.8 Hz), 130.82 (d, J C-P = 8.9 Hz), 128.90, 128.79,128.56, 128.50, 128.30, 127.07, 126.62, 126.56, 126.12 (q, J C-F = 279.7 Hz),125.49, 112.16, 51.01 (d, J C-P = 7.3 Hz), 46.91 (d, J C-P = 3.6 Hz), 41.33 (q, J C-F = 25.8 Hz), 40.60 (dd, J C-F = 3.2 Hz, J C-P = 1.9 Hz), 39.05 (d, J C-P = 58.7Hz), 35.32 (d, J C-P= 65.3 Hz), 30.70. FT-IR (KBr): 3330, 3057, 3026, 2924,2813, 1614, 1521, 1497, 1446, 1437, 1382, 1325, 1307, 1255, 1194, 1118, 1088,1034, 1000, 965, 910, 837, 785, 733, 699, 679, 644, 581, 539, 502 cm -1 . HRMS(ESI) calcd for C 32 H 32 F3NOP + [M+H] + 534.2168, found 534.2169.

[0221] The characterization data of compound IX-7 are as follows:

[0222]

[0223] Brown solid (75 mg, 67% yield, dr 19.0 / 1). Melting point: 148.6–153.2 °C. 31 P{ 1 H}NMR (202 MHz, CDCl3) δ 29.72. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.36. 1 H NMR (500 MHz, CDCl3) δ 7.83 (dd, J = 10.7, 7.3 Hz, 2H), 7.70 (d, J = 7.8 Hz, 2H),7.58 – 7.48 (m, 3H), 7.39 – 7.34 (m, 6H), 7.31 – 7.26 (m, 1H), 7.23 (t, J =7.3 Hz, 1H), 6.59 (d, J = 2.2 Hz, 1H), 6.44 (dd, J = 8.4, 2.2 Hz, 1H), 6.39(d, J = 8.4 Hz, 1H), 4.15 (td, J = 4.2, 1.7 Hz, 2H), 3.38 (d, J= 14.5 Hz,1H), 3.32 (s, 2H), 3.26 (t, J = 15.8 Hz, 1H), 3.07 (dq, J = 15.6, 10.7 Hz,1H), 2.91 (t, J = 16.2 Hz, 1H), 2.57 (d, J = 14.5 Hz, 1H), 2.19 (ddd, J =21.6, 15.2, 6.2 Hz, 2H), 2.08 (dq, J = 15.8, 11.0 Hz, 1H). 13 C{ 1 H} NMR (126MHz, CDCl3) δ 146.25 (d, J C-P = 12.5 Hz), 145.51, 143.59, 142.88 (d, J C-P =12.2 Hz), 133.37 (d, J C-P = 98.8 Hz), 132.07 (d, J C-P = 2.7 Hz), 131.80, 130.83(d, J C-P = 8.7 Hz), 128.86 (d, J C-P = 11.4 Hz), 128.56, 128.47, 128.33, 127.08,126.64, 126.12 (q, J C-F = 279.7 Hz), 125.45, 118.95, 115.42, 114.05, 65.34,51.03 (d, J C-P = 7.1 Hz), 46.89 (d, J C-P = 3.3 Hz), 41.12 (q, J C-F = 25.5 Hz),40.89, 40.59, 38.85 (d, J C-P = 58.9 Hz), 35.43 (d, JC-P = 65.4 Hz). FT-IR(KBr): 3298, 3057, 3027, 2949, 2874, 1618, 1600, 1585, 1518, 1446, 1381,1353, 1306, 1256, 1190, 1117, 1040, 1000, 967, 910, 854, 830, 785, 729, 698,636, 608, 592, 546, 504 cm -1 . HRMS (ESI) calcd for C 33 H 32 F3NO2P + [M+H] + 562.2117, found 562.2119.

[0224] The characterization data of compound IX-8 are as follows:

[0225]

[0226] Brown solid (50 mg, 43% yield, dr 16.7 / 1). Melting point: 129.5–132.8 °C. 31 P{ 1 H}NMR (202 MHz, CDCl3) δ 29.78. 19 F{ 1 H} NMR (471 MHz, CDCl3) δ –58.33. 1 H NMR (500 MHz, CDCl3) δ 7.82 (dd, J = 10.3, 7.7 Hz, 2H), 7.68 (d, J = 7.8 Hz, 2H),7.57 – 7.48 (m, 3H), 7.41 – 7.33 (m, 6H), 7.29 (tt, J = 5.3, 2.3 Hz, 1H),7.22 (t, J = 7.3 Hz, 1H), 6.98 – 6.85 (m, 1H), 6.80 (d, J = 2.3 Hz, 1H), 6.48(dd, J = 8.6, 2.4 Hz, 1H), 6.25 (d, J = 8.5 Hz, 1H), 3.52 (dd,J = 6.3, 3.6Hz, 2H), 3.34 (d, J = 14.5 Hz, 1H), 3.22 (t, J = 15.7 Hz, 1H), 3.10 (dq, J =15.6, 10.7 Hz, 1H), 2.96 (dd, J = 6.7, 3.5 Hz, 2H), 2.95 – 2.87 (m, 1H), 2.57(d, J = 14.5 Hz, 1H), 2.21 (dd, J = 14.7, 6.4 Hz, 1H), 2.15 (dd, J = 15.9,6.0 Hz, 1H), 2.10 – 2.01 (m, 1H). 13 C{ 1 H} NMR (100 MHz, CDCl3) δ 146.17 (d, J C-P = 12.4 Hz), 145.58, 141.49 (d, J C-P = 12.0 Hz), 139.85, 133.34 (d, J C-P =98.6 Hz), 132.04, 130.77 (d, J C-P = 8.8 Hz), 128.84 (d, J C-P = 11.4 Hz),128.55, 128.43, 128.29, 127.07, 126.59, 126.08 (q, J C-F = 279.4 Hz), 125.45,124.02, 123.98, 115.45, 115.27, 50.86 (d, J C-P = 7.1 Hz), 46.86 (d, J C-P = 3.4Hz), 42.19, 41.22 (q, J C-F = 24.1 Hz), 40.54, 38.94 (d, J C-P= 58.6 Hz), 35.15(d, J C-P = 65.5 Hz), 25.99. FT-IR (KBr): 3309, 3057, 3025, 2928, 2851, 1601,1506, 1446, 1381, 1354, 1311, 1255, 1190, 1116, 1033, 1000, 965, 909, 829,785, 697, 644, 600, 586, 545, 502, 442 cm -1 . HRMS (ESI) calcd for C 33 H 32 F3NOPS + [M+H] + 578.1889, found 578.1890.

[0227] Application test example: A trifluoromethyl-containing multi-substituted phosphorus-hexagonal phosphine oxide compound is used as a catalyst to catalyze the Appel reaction to synthesize compound 2, wherein the Appel reaction is as follows:

[0228] The catalyst used is 2 mol% of the compounds V-1, V-4, V-5 and V-6 provided in the examples of the present invention;

[0229] The catalyst used is 5 mol% of the compounds V-2, V-11, VII-6, IX-3 and IX-6 provided in the examples of the present invention.

[0230] Experimental Procedure: In a 10 mL sealed tube, weigh the catalyst (0.01 mmol or 0.02 mmol). Purge the tube five times under argon. Add ultra-dry toluene (1 mL), phenylethylene oxide (0.2 mmol), phenylsilane (0.3 mmol), and hexachloroacetone (0.28 mmol) in that order. Seal the reaction system and incubate at 100°C for 24 hours. After completion of the reaction, wash with water, extract with ethyl acetate, dry, filter, and concentrate under reduced pressure. Purify the concentrate by column chromatography using petroleum ether.

[0231] According to the above steps, the present invention selects various types of prepared hexaphosphine-phosphine oxide compounds as catalysts to demonstrate the structure-activity relationship between the substituent type in the hexaphosphine ring structure and the catalytic effect in the Appel catalytic reaction. The catalytic results are shown in Table 2 below:

[0232] Table 2 Structure-activity relationship between substituent type in phosphorus hexacyclic ring structure and catalytic effect in Appel catalysis

[0233] The catalytic reaction results described in the table show that polysubstituted phosphorus heterocyclic six-membered ring phosphine oxide compounds can achieve good catalytic effects when used as catalysts in Appel reaction, and phosphorus heterocyclic rings with various skeleton structures are applicable. Compared with the reported phosphine oxide compounds as catalysts [ J. Org. Chem . 2019, 84 , 7863-7870], under the condition of the same reaction substrate, 10 mol% is required to realize the Appel reaction of phenyl oxirane, while the catalyst amount of the multi-substituted phosphorus-hexacyclic phosphine oxide compound can be reduced to 2-5 mol% and still obtain a good catalytic effect, indicating that the catalytic efficiency of the catalyst based on the framework structure of the multi-substituted phosphorus-hexacyclic phosphine oxide compound has been significantly improved; this result is close to the Appel catalytic ability of the currently known best phosphorus-four-membered phosphine oxide catalyst [ Org. Lett. 2023, 25 , 9114-9118]. The phosphorus-hexacyclic phosphine oxide compounds reported in this patent have better preparation universality and scalability, which makes the further development of this type of phosphorus-hexacyclic phosphine oxide catalysts have good prospects and catalyst synthesis scalability, and lays a good foundation for further exploration of the development and application of various types of phosphorus-hexacyclic phosphine oxide catalysts.

[0234] Obviously, the specific implementation scheme described above is only a further detailed description of the purpose, technical solutions and beneficial effects of the present invention. It should be understood that the above is only a specific example of the present invention and is not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A trifluoromethyl-containing multi-substituted phosphorus hexahedral phosphine oxide compound, characterized in that: Including any one of the following structural formulas (1), (2), and (3): ； Among them, in the general structural formula (1): Ar 1 is a benzene ring, a benzo-1,3-dioxolane ring or a naphthalene ring; n is an integer, n is 0, 1 or 2; R 1 is hydrogen, a halogen atom, a trifluoromethyl group, a C1~C6 saturated alkoxy group, or a C1~C6 saturated alkyl group; R 2 is a C1~C6 saturated alkyl group, a phenyl group or a benzyl group; wherein the hydrogen atom on the phenyl group or the benzyl group may be substituted by a C1~C3 saturated alkyl group or a halogen atom; R 3 is hydrogen, C1~C6 saturated alkyl, C1~C6 cycloalkyl, benzyl, phenyl, 、 、 、 or ; In the general structural formula (2): Ar 1’ is phenyl; R 1’ is hydrogen or C1~C3 saturated alkyl; R 2’ is phenyl; R 4 Phenyl, substituted phenyl, 、 、 or ;Substituted phenyl means that the hydrogen on the phenyl group may be replaced by a C1~C3 saturated alkyl group or a halogen atom; In the general structural formula (3): Ar 1” is phenyl; R 1” is hydrogen or C1~C3 saturated alkyl; R 2” is phenyl; R 5 for 、 、 、 、 、 、 、 or .

2. The trifluoromethyl-containing multi-substituted phosphorus hexahedral phosphine oxide compound according to claim 1, characterized in that: In the general structural formula (1): Ar 1 is a benzene ring, a benzo-1,3-dioxolane ring or a naphthalene ring; n is an integer, n is 0, 1 or 2; R 1 is hydrogen, a halogen atom, a trifluoromethyl group, a C1~C3 saturated alkoxy group, or a C1~C3 saturated alkyl group; R 2 is a C1-C6 saturated alkyl, phenyl or benzyl group; wherein the hydrogen on the phenyl or benzyl group may be substituted by a halogen atom; the halogen atom is bromine or chlorine; R 3 is hydrogen, C1~C3 saturated alkyl, cyclohexyl, benzyl, phenyl, 、 、 、 or ; In the general structural formula (2): Ar 1’ is a benzene ring; R 1’ is hydrogen or C1~C3 saturated alkyl; R 2’ is phenyl; R 4 Phenyl, substituted phenyl, 、 、 or ; The substituted phenyl group means that the hydrogen on the phenyl group may be replaced by a C1~C3 saturated alkyl group or a halogen atom; the halogen atom is bromine or chlorine; In the general structural formula (3): Ar 1” is phenyl; R 1” is hydrogen or C1~C3 saturated alkyl; R 2” is phenyl; R 5 for 、 、 、 、 、 、 、 or .

3. Use of the trifluoromethyl-containing multi-substituted phosphorus hexacyclic phosphine oxide compound according to claim 1 in the Appel reaction.

4. The use according to claim 3, characterized in that A multi-substituted phosphorus-hexacyclic phosphine oxide compound containing trifluoromethyl is used as a catalyst to catalyze the Appel reaction; the Appel reaction is a compound As a reaction substrate, the catalyst is then added, and then ultra-dry toluene, phenylsilane and hexachloroacetone are added in sequence, the reaction system is closed, and the reaction is carried out at 100°C for 24 hours to obtain .

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