Oxazoline phosphine ligand and preparation method thereof

Abstract

The present invention belongs to the field of organic chemical ligands and discloses a nitrogen-nitrogen-phosphorus ligand having a structure of the general formula I or its tautomers, enantiomers, and diastereomers: #imgabs0#R 1 、R 5 R is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, hydroxyl, aldehyde, carboxyl, ester, halogen, trifluoromethyl, cyano, acyl, amide, amino, nitro, phenyl, benzyl, sulfonyl, sulfonic acid, and mercapto; 2 is selected from one of the following structures: alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, ester, -CH2OBn, or substituted phenyl or benzyl, or R 2 With R 4 connected to form a five-membered ring and an acene ring; the R 3 is selected from hydrogen or alkyl; said R 4 is selected from hydrogen, alkyl, alkoxy, alkenyl, alkynyl, phenyl, benzyl; W is PR2 or P(O)R2, and R is selected from phenyl, naphthyl, cyclohexyl, and substituted phenyl. The present invention also discloses a preparation method and use of nitrogen-nitrogen-phosphorus ligands.

Description

[0001] This application is a divisional application with application number 2021109447966, application date August 17, 2021, and invention name "A nitrogen-nitrogen-phosphorus ligand, its preparation method and use". Technical Field

[0002] The invention belongs to the field of organic chemical ligands, in particular to a nitrogen-nitrogen-phosphorus ligand and a preparation method and application thereof. Background Art

[0003] Chiral oxazoline scaffolds are widely present in chiral ligand structures and have important applications in transition-metal-catalyzed asymmetric reactions. In addition to common chiral scaffold types such as bisoxazoline and trisoxazoline, chiral oxazoline scaffolds can also form bi- and multidentate ligands with various heteroatoms. Among these, chiral P,N-bidentate ligands formed with aryl or alkyl phosphines have been widely used in recent years in a variety of asymmetric chemical reactions catalyzed by metals such as palladium, iridium, cobalt, and copper.

[0004] With the recent development of free radical asymmetric chemistry, there is a pressing need to develop chiral ligands with diverse backbone types to effectively control the stereoselective properties of free radical intermediates. Chiral bisoxazoline ligands and cinchona alkaloid-derived nitrogen-nitrogen-phosphorus ligands have been successfully applied in asymmetric cross-coupling reactions involving free radical intermediates, asymmetric 1,2-difunctionalization of alkenes, and oxidative asymmetric coupling reactions of alkyl carbon-hydrogen bonds. Given the diverse nature of free radical reactions, the development of a wider range of chiral ligands is crucial to address diverse reaction requirements. Summary of the Invention

[0005] The purpose of the present invention is to provide a novel nitrogen-nitrogen-phosphorus ligand based on a chiral oxazoline skeleton.

[0006] Another object of the present invention is to provide a method for preparing the nitrogen-nitrogen-phosphorus ligand.

[0007] Another object of the present invention is to provide uses of the nitrogen-nitrogen-phosphorus ligand.

[0008] In order to achieve one of the above purposes, the present invention adopts the following technical solutions:

[0009] A nitrogen-nitrogen-phosphorus ligand having the structure of general formula I or its tautomers, enantiomers, and diastereomers:

[0010]

[0011] R 1 Selected from hydrogen, alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, hydroxyl, aldehyde, carboxyl, ester, halogen, trifluoromethyl, cyano, acyl, amide, amino, nitro, phenyl, benzyl, sulfonyl, sulfonic acid, and mercapto;

[0012] R 2 Select one of the following structures:

[0013] Alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, ester, -CH2OBn, or

[0014] phenyl or benzyl substituted by alkyl, alkoxy, alkenyl, alkynyl, phenyl, halogen, trifluoromethyl, ester, trifluoromethylphenyl, or

[0015] R 2 With R 4 Connected to form a five-membered ring and a phenyl ring, forming structure;

[0016] The R 3 is selected from hydrogen or alkyl, and R 3 With R 2 different;

[0017] The R 4 is selected from hydrogen, alkyl, alkoxy, alkenyl, alkynyl, phenyl, benzyl, or

[0018] R 4 With R 2 Connected to form a five-membered ring and a phenyl ring, forming structure;

[0019] R 5 is selected from hydrogen, alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, hydroxyl, aldehyde, carboxyl, ester, halogen, trifluoromethyl, cyano, acyl, amide, amino, nitro, phenyl, benzyl, sulfonyl, sulfonic acid, mercapto, or

[0020] The benzene ring and the substituted benzene ring are combined to form a naphthalene ring, that is, structure;

[0021] W is PR2 or P(O)R2,

[0022] R is selected from phenyl, naphthyl, cyclohexyl, Among them, R 6 is selected from alkyl, alkoxy, trifluoromethyl, halogen, phenyl, phenoxy, dimethylphenyl, m represents an integer of 1 to 5, when m ≥ 2, the presence of two or more R 6 Same or different.

[0023] Furthermore, the R 1 Selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, halogen, trifluoromethyl, cyclohexyl, cyclopentyl, vinyl, ethynyl, -OH, -CHO, -COOH, -CN, -NH2, -NO2, phenyl, benzyl.

[0024] Furthermore, the R 1 Selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, halogen, trifluoromethyl, vinyl, ethynyl, -OH, -CHO, -COOH, -CN, phenyl.

[0025] Furthermore, the R 1 Selected from hydrogen, halogen, trifluoromethyl, alkoxy.

[0026] Furthermore, the R 1 Selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl, (C1-C4)alkoxy.

[0027] Furthermore, the R 1 Selected from hydrogen, fluorine, trifluoromethyl, methoxy.

[0028] Furthermore, the R 2 Select one of the following structures:

[0029] Alkyl, cycloalkyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, ester group, -CH2OBn, or

[0030] phenyl or benzyl substituted by alkyl, phenyl, halogen, trifluoromethyl, ester, trifluoromethylphenyl, or

[0031] R 2 With R 4 Connected to form a five-membered ring and a phenyl ring.

[0032] Furthermore, the R 2 Select one of the following structures:

[0033] (C1-C6) alkyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, -CO2 t Bu, -CH2OBn, or

[0034] Phenyl or benzyl substituted by (C1-C6) alkyl, phenyl, halogen, trifluoromethyl, -CO2Et, trifluoromethylphenyl, or

[0035] R 2 With R 4 Connected to form a five-membered ring and a phenyl ring.

[0036] Furthermore, the R 2 Select one of the following structures:

[0037] (C1-C6) alkyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, -CO2 t Bu, -CH2OBn, or

[0038] benzyl substituted by (C1-C6)alkyl, phenyl, halogen, trifluoromethyl, -CO2Et, trifluoromethylphenyl, or

[0039] R 2 With R 4 Connected to form a five-membered ring and a phenyl ring.

[0040] Furthermore, the R 2 Select one of the following structures:

[0041] Ethyl, propyl, butyl, pentyl, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, -CO2 t Bu, -CH2OBn, or

[0042] benzyl substituted by methyl, butyl, phenyl, fluorine, trifluoromethyl, -CO2Et, p-trifluoromethylphenyl, or

[0043] R 2 With R 4 Connected to form a five-membered ring and a phenyl ring.

[0044] Furthermore, the R 2 Select one of the following structures:

[0045] Ethyl, isopropyl, sec-butyl, isobutyl, tert-butyl, -CH2 t Bu, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, -CO2 t Bu, -CH2OBn, or

[0046] R 7 is methyl, tert-butyl, phenyl, fluorine, trifluoromethyl, -CO2Et, p-trifluoromethylphenyl, or

[0047] R 2 With R 4 Connected to form a five-membered ring and a phenyl ring.

[0048] Furthermore, the R 3 Selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl.

[0049] Furthermore, the R 3 is selected from hydrogen or methyl.

[0050] Furthermore, the R 4 is selected from hydrogen, (C1-C4) alkyl, methoxy, ethoxy, vinyl, ethynyl, phenyl, benzyl, or

[0051] R 4 With R 2Connected to form a five-membered ring and a phenyl ring.

[0052] Furthermore, the R 4 Selected from hydrogen, (C1-C4) alkyl, phenyl, or

[0053] R 4 With R 2 Connected to form a five-membered ring and a phenyl ring.

[0054] Furthermore, the R 4 Selected from hydrogen, methyl, ethyl, phenyl, or

[0055] R 4 With R 2 Connected to form a five-membered ring and a phenyl ring.

[0056] Furthermore, the R 5 is selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, cyclopentyl, cyclohexyl, vinyl, ethynyl, -OH, -CHO, -COOH, halogen, trifluoromethyl, -CN, -NH2, -NO2, phenyl, benzyl, or

[0057] The benzene ring is combined with the substituted benzene ring to form a naphthalene ring.

[0058] Furthermore, the R 5 is selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, cyclopentyl, cyclohexyl, vinyl, ethynyl, -OH, -CHO, -COOH, halogen, trifluoromethyl, -CN, -NH2, -NO2, phenyl, benzyl, or

[0059] The benzene ring is combined with the substituted benzene ring to form a naphthalene ring.

[0060] Furthermore, the R 5 Selected from hydrogen, (C1-C4) alkyl, or

[0061] The benzene ring is combined with the substituted benzene ring to form a naphthalene ring.

[0062] Furthermore, the R 5 Selected from hydrogen, methyl, or

[0063] The benzene ring is combined with the substituted benzene ring to form a naphthalene ring.

[0064] Furthermore, the R is selected from phenyl, naphthyl, Among them, R 6 Selected from (C1-C4) alkyl, (C1-C4) alkoxy, trifluoromethyl, phenyl, dimethylphenyl.

[0065] Furthermore, the R 6Selected from methyl, ethyl, propyl, butyl, methoxy, trifluoromethyl, phenyl, dimethylphenyl.

[0066] Further, the R is selected from Ph, 2-Me-Ph, 3-Me-Ph, 4-Me-Ph, 2-Et-Ph, 3-Et-Ph, 4-Et-Ph, 2- i Pr-Ph, 3- i Pr-Ph, 4- i Pr-Ph, 2- t Bu-Ph, 3- t Bu-Ph, 4- t Bu-Ph, 2-Ph-Ph, 3-Ph-Ph, 4-Ph-Ph, 2-CF3-C6H4, 3-CF3-C6H4, 4-CF3-C6H4, 2,6-Me2-C6H3, 3,5-Me2C6H3, 2,6-Et2-C6H3, 3,5-Et2C6H3, 2,6- i Pr2-C6H3、3,5- i Pr2-C6H3、2,6- t Bu2-C6H3、3,5- t Bu2-C6H3, 2,6-Ph2-C6H3, 3,5-Ph2-C6H3, 2,6-(CF3)2-C6H3, 3,5-(CF3)2-C6H3, 2,6-(OMe)2C6H3, 3,5-(OMe)2C6H3, 2,6-(3,5-Me2C6H3) 2-C6H3, 2,6-(2,6-Me2C6H3)2-C6H3, 3,5-(3,5-Me2C6H3)2-C6H3, 3,5-(2,6-Me2C6H3)2-C6H3, 2,4,6-Me3-C6H2, 2,4,6-Et3-C6H2, 2,4,6- i Pr3-C6H2、2,4,6- t Bu3-C6H2, 2,4,6-Ph3-C6H2, 2,4,6-(CF3)3-C6H2, 2,4,6-(OMe)3-C6H2, 3,5-di t Bu2-4-OMe-Ph, 1-naphthyl, 2-naphthyl.

[0067] Further, the R is selected from Ph, 2-Me-Ph, 2- i Pr-Ph, 4-CF3-C6H4, 2,6-Me2-C6H3, 3,5-Me2C6H3, 3,5-Ph2-C6H3, 3,5-(OMe)2C6H3, 3,5- t Bu2-C6H3、3,5- iPr2C6H3, 3,5-(CF3)2-C6H3, 2,4,6-Et3-C6H2, 3,5-di t Bu2-4-OMe-Ph, 3,5-(3,5-Me2C6H3)2-C6H3, 1-naphthyl.

[0068] Furthermore, the nitrogen-nitrogen-phosphorus ligand is selected from one of the following structures:

[0069]

[0070]

[0071] A method for preparing a nitrogen-nitrogen phosphine ligand comprises the following steps:

[0072]

[0073] Compound S1 reacts with compound S2 to obtain intermediate S3;

[0074] Intermediate S3 reacts with compound S4 to obtain the product;

[0075] R 1 、R 2 、R 3 、R 4 、R 5 , W are as defined above.

[0076] Furthermore, when W is PR2, the method further comprises the step of reacting it with an oxidant to oxidize it to P(O)R2:

[0077]

[0078] Furthermore, the preparation method comprises the following steps:

[0079] Compound S1 reacts with Lewis acid and compound S2 to obtain intermediate S3;

[0080] The intermediate S3 reacts with a carbodiimide condensing agent, a catalyst, and a compound S4 to obtain a product.

[0081] Carbodiimide condensing agents refer to the following compounds: dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI); catalysts refer to the following compounds: pyridine, triethylamine, diethylamine; Lewis acids refer to the following compounds: ferric chloride, aluminum chloride, zinc chloride, trifluoromethanesulfonate.

[0082] Furthermore, the Lewis acid is zinc chloride, the carbodiimide condensing agent is EDCI, and the catalyst is DMAP. EDCI refers to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, and DMAP refers to 4-dimethylaminopyridine.

[0083] Furthermore, the preparation method comprises the following steps:

[0084] Compound S1, Lewis acid, and compound S2 are reacted in a molar ratio of 1:(1-3):(1-3) in chlorobenzene at 100-150° C., and after post-treatment, intermediate S3 is obtained;

[0085] The intermediate S3, a carbodiimide condensing agent, a catalyst and a compound S4 are reacted in a molar ratio of 1:(2-6):(1.5-3):(1.1-3) in dichloromethane at room temperature, and the product is obtained after post-treatment.

[0086] Furthermore, the oxidant is an aqueous solution of hydrogen peroxide.

[0087] Furthermore, compound I is reacted with 30 wt % aqueous hydrogen peroxide solution in a molar ratio of 1:(1-4) in dichloromethane at room temperature, and the product is obtained after post-treatment.

[0088] The ligand of the present invention is used in asymmetric reactions, especially in asymmetric cross-coupling reactions to synthesize alkynes.

[0089] As used herein, "alkyl" refers to a saturated aliphatic hydrocarbon group, which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 12 carbon atoms, and more preferably an alkyl group containing 1 to 6 carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl.

[0090] As used herein, "cycloalkyl" refers to a non-aromatic carbocyclic ring typically having 3 to 8 ring carbon atoms. The ring may be saturated or have one or more carbon-carbon double bonds. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, and cyclohexenyl.

[0091] As used herein, "alkoxy" refers to -O-(alkyl) and -O-(cycloalkyl), wherein alkyl and cycloalkyl are as defined herein, the alkyl group contains 1 to 20 carbon atoms, and the cycloalkyl group contains 3 to 8 carbon atoms. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentoxy, 2-pentoxy, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, 3-hexoxy, 3-methylpentoxy, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, and cyclohexyloxy. Alkoxy groups typically have 1 to 7 carbon atoms attached through an oxygen bridge.

[0092] As used herein, "alkenyl" refers to an unsaturated branched or straight-chain alkyl group having at least one carbon-carbon double bond, the double bond being obtained by removing one molecule of hydrogen from the adjacent carbon atom of the parent alkyl group. Preferably, the alkenyl group contains 2 to 20 carbon atoms, and more preferably, the alkenyl group contains 2 to 6 carbon atoms. The group can be in a cis or trans configuration about one or more double bonds. Typical alkenyl groups include, but are not limited to, vinyl; propenyl, such as prop-1-ene-1-yl, prop-1-ene-2-yl, prop-2-ene-1-yl (allyl), prop-2-ene-2-yl; butenyl, such as but-1-ene-1-yl, but-1-ene-2-yl, 2-methyl-prop-1-ene-1-yl, but-2-ene-1-yl, but-2-ene-1-yl, but-2-ene-2-yl, but-1,3-diene-1-yl, but-1,3-diene-2-yl.

[0093] As used herein, "alkynyl" refers to an unsaturated, branched or straight-chain alkyl group having at least one carbon-carbon triple bond, wherein the triple bond is formed by removing two hydrogen atoms from adjacent carbon atoms of a parent alkyl group. Alkynyl groups containing 2 to 20 carbon atoms are preferred, and alkynyl groups containing 3 to 6 carbon atoms are more preferred. Typical alkynyl groups include, but are not limited to, ethynyl; propynyl, such as prop-1-yn-1-yl and prop-2-yn-1-yl; and butynyl, such as but-1-yn-1-yl, but-1-yn-3-yl and but-3-yn-1-yl.

[0094] As used herein, "hydroxy" refers to the group -OH; and "aldehyde" as used herein refers to the group -CHO.

[0095] As used herein, "carboxy" refers to the group -COOH.

[0096] As used herein, "ester group" refers to -C(O)O(alkyl) or -C(O)O(phenyl), wherein alkyl and phenyl are as defined herein, and the alkyl group contains 1 to 20 carbon atoms. Ester-substituted phenyl groups can be formed by the phenolic hydroxyl group of a benzene ring and a carboxylic acid, such as PhOCOCH3 and PhOPiv, or by the carboxyl group of a benzene ring and an alcohol, such as PhCOOCH3.

[0097] As used herein, the term "halogen" refers to fluorine, chlorine, bromine and iodine.

[0098] As used herein, "trifluoromethyl" refers to -CF3; and "cyano" as used herein refers to -CN.

[0099] As used herein, "aryl" refers to a 6-membered carbocyclic aromatic ring, such as benzene; a bicyclic ring system in which at least one ring is carbocyclic and aromatic, such as naphthalene, indane, and 1,2,3,4-tetrahydronaphthalene; and a tricyclic ring system in which at least one ring is carbocyclic and aromatic, such as fluorene.

[0100] As used herein, "acyl" refers to the groups (alkyl)-C(O)-, (cycloalkyl)-C(O)-, and (aryl)-C(O)-, wherein the groups are attached to the parent structure through a carbonyl functional group, and wherein the alkyl, cycloalkyl, and aryl groups are as described herein, the alkyl groups contain 1 to 20 carbon atoms, and the cycloalkyl groups contain 3 to 8 carbon atoms.

[0101] As used herein, "amido" refers to the group -CONR b R c , where R b is selected from hydrogen, alkyl, cycloalkyl, aryl, R c is selected from alkyl, cycloalkyl, aryl; or R b and R c Together with the nitrogen to which they are attached, they form a 5- to 8-membered nitrogen-containing heterocycloalkyl group, which optionally contains 1 or 2 additional heteroatoms selected from O, N and S in the heterocycloalkyl ring. The definitions of alkyl, cycloalkyl and aryl are as described herein, the alkyl group contains 1 to 20 carbon atoms, and the cycloalkyl group is 3 to 8 carbon atoms.

[0102] As used herein, "amino" refers to -NH2; and "nitro" as used herein refers to -NO2.

[0103] As used herein, "phenyl" refers to As used herein, "phenoxy" refers to PhO-.

[0104] As used herein, "sulfonyl" refers to the following groups: -S(O2)-(alkyl), -S(O2)-(aryl), -S(O2)-(amino). Alkyl, aryl, and amino are as defined herein, and the alkyl group contains 1 to 20 carbon atoms.

[0105] As used herein, "sulfonic acid" refers to -SO3H; "mercapto" as used herein refers to -SH;

[0106] As used herein, "dimethylphenyl" refers to a phenyl group having two methyl substituents, wherein the two methyl groups may be 2,3, 2,4, 2,5, 2,6, 3,4, 3,5, 3,6, 4,5, 4,6, or 5,6 substituted.

[0107] As used herein, "naphthylmethyl" refers to

[0108] As used herein, "benzyl" refers to PhCH2-; and "phenethyl" as used herein refers to PhCH2CH2-.

[0109] As used herein, "phenyl or benzyl substituted with trifluoromethylphenyl" refers to phenyl or benzyl substituted with p-trifluoromethylphenyl, o-trifluoromethylphenyl, or m-trifluoromethylphenyl.

[0110] The term "substituted phenyl" or "substituted benzyl" as used herein refers to either single or multiple substitutions. For example, "substituted phenyl" includes: (1) a single substituent on the benzene ring; (2) two or more identical or different substituents on the benzene ring. The substitution may occur at any of the 2, 3, 4, 5, or 6 positions on the benzene ring.

[0111] The present invention has the following beneficial effects:

[0112] The present invention uses chiral oxazoline and phosphine amide as core skeletons, and synthesizes a novel class of nitrogen-nitrogen-phosphorus compounds through derivatization. These compounds can serve as ligands for asymmetric reactions. In particular, because the electronic and steric effects of the phosphorus on the ligands can be controlled, the electronic and steric effects of the chiral oxazoline substituents can also be controlled. These compounds offer unique advantages in free radical asymmetric reactions, including high catalytic efficiency, a wide range of substrate applications, high yields, and good enantioselectivity. The ligands of the present invention are not only widely applicable to oxidative asymmetric cross-coupling reactions of various types of alkyl carbon-hydrogen bonds with terminal alkynes, but are also of great significance for the development of novel catalytic systems to resolve other types of free radical asymmetric reactions. DETAILED DESCRIPTION

[0113] All reactions were carried out under an argon atmosphere. Unless otherwise stated, chemicals were purchased from commercial products and were not further purified. Chlorobenzene and dichloromethane used in the experiments were anhydrous solvents. Thin layer chromatography (TLC) used 60F254 silica gel plates. Silica gel column chromatography used Qingdao Marine Silica Gel (particle size 0.040-0.063 mm). TLC color development used UV light (254 nm) or iodine. NMR spectra were characterized using a Bruker DPX 400 nuclear magnetic resonance instrument. 1 H NMR at 400 MHz, 31 P NMR is at 162 MHz, the solvent is deuterated chloroform, and tetramethylsilane (TMS) is used as the internal standard. The unit of chemical shift is ppm, and the unit of coupling constant is Hz. 1 In H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, p represents quintet, m represents multiplet, and br represents broad.

[0114] General synthesis method of ligands:

[0115]

[0116] Step 1: Compound S1 (20 mmol), compound S2 (20-60 mmol, preferably 20 mmol), and anhydrous zinc chloride (20-60 mmol, preferably 40 mmol) were placed in a 100 mL sealed tube, purged with argon three times, and 40 mL of chlorobenzene was added. The mixture was then stirred at 100-150° C. (preferably 130° C.) for 24-72 hours, and detected by TLC until compound S1 completely disappeared. Post-treatment: Cool to room temperature, add water and ethyl acetate, add 2 mL of ethylenediamine, and stir until the system is clear. The mixture was then extracted with ethyl acetate, the organic layer was separated, dried, filtered, and concentrated in vacuo. The residue thus obtained was purified by silica gel column to obtain intermediate S3 (40-80% yield).

[0117] Step 2: To a solution of intermediate S3 (10 mmol) and compound S4 (11-20 mmol, preferably 12 mmol) in 50 mL of dichloromethane was added EDCI (20-60 mmol, preferably 30 mmol) and DMAP (15-30 mmol, preferably 20 mmol). The reaction was stirred at room temperature for 24 hours and quenched by adding water. The organic layer was separated, dried, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel column to give the product (60-80% yield).

[0118] When W is PR2, the process further comprises the step of reacting it with an aqueous hydrogen peroxide solution to oxidize it to P(O)R2:

[0119]

[0120] To a solution of the ligand (1 mmol) in 10 mL of dichloromethane was added a 30 wt% aqueous hydrogen peroxide solution (containing 1-4 mmol of hydrogen peroxide, preferably 2 mmol). The reaction was stirred at room temperature for 12 hours and concentrated in vacuo. The residue thus obtained was purified by silica gel column to give the oxidized ligand (90-98% yield).

[0121] Example 1

[0122]

[0123] Characterization data of ligand 1: 1 H NMR (400 MHz, CDCl3) 1H NMR (400MHz, CDCl3) δ12.91(s,1H),8.82(d,J=8.4Hz,1H),7.94–7.80(m,2H),7.50–7.26(m,13H),7.21–7.05(m ,2H),4.42(dd,J=8.6,7.7Hz,1H),4.20–4.03(m,2H),1.76(dq,J=13.3,6.7Hz,1H),0.93(dd,J=6.7,3.7Hz,6H). 13 C NMR (100MHz, CDCl3) δ167.4,163.63,141.63,141.40,140.12,138.65,138 .47,138.42,138.40,138.35,138.29,134.78,134.07,133.99,133.87,133 .79,132.52,130.34,129.01,128.50,128.43,128.41,128.37,128.30,12 7.51,127.47,122.38,120.05,113.40,72.84,69.52,33.21,19.04,18.74. 31 P NMR (162 MHz, CDCl3) δ-8.21.

[0124] Example 2

[0125]

[0126] Characterization data of ligand 2: 1 H NMR (400MHz, CDCl3) δ12.84(s,1H),8.80(d,J=8.4Hz,1H),7.94(dd,J=7.9,1.3Hz,1H),7.68(dd,J=7.3,3.8Hz,1H),7.48(t,J=7.4Hz,1H ),7.42–7.23(m,15H),7.13(t,J=7.6Hz,1H),7.05–6.95(m,2H),5.55–5.37(m,1H),4.81(dd,J=10.0,8.6Hz,1H),4.31(t,J=8.5Hz,1H). 13C NMR (100MHz, CDCl3) δ167.22,164.74,141.68,141.02,140.21,138.91,138.67,138.58,138.26,134.78,134.12,133.91,133.86,133. 66,132.88,130.32,129.17,128.87,128.39,128.32,128.27,127.85,127.59,127.55,126.63,122.47,120.26,113.19,73.21,69.91. 31 P NMR (162 MHz, CDCl3) δ -7.84.

[0127] Example 3

[0128]

[0129] Characterization data of ligand 3: 1 H NMR (400MHz, CDCl3) δ12.79(s,1H),8.84(d,J=8.3Hz,1H),7.89(d,J=7.8Hz,1H) ,7.83(d,J=3.4Hz,1H),7.47(t,J=7.8Hz,1H),7.43–7.30(m,12H),7.29–7.18(m ,5H),7.12(dd,J=14.0,6.6Hz,2H),4.79–4.57(m,1H),4.39(t,J=8.9Hz,1H),4. 12(t,J=8.0Hz,1H), 3.11(dd,J=13.8,6.6Hz,1H), 2.84(dd,J=13.8,7.4Hz,1H). 13 C NMR (100MHz, CDCl3) δ167.37,164.11,141.39,141.17,140.14,138.90,138.67,138.58,138.46,137.63,134.94,134.07,133.98,133 .87,133.77,132.69,130.43,129.07,128.62,128.42,128.33,127.44,127.40,126.66,122.44,120.16,113.34,70.81,67.74,42.14. 31 PNMR (162MHz,CDCl3)δ-8.02.

[0130] Example 4

[0131]

[0132] Characterization data of ligand 4: 1 H NMR(400MHz, CDCl3)δ0.83(d,J=1.2Hz,9H),3.98–4.19(m,2H),4.30(dd,J=9.6,8.1Hz,1H),7 .01–7.11(m,2H),7.26–7.46(m,13H),7.75–7.89(m,2H),8.75(d,J=8.4Hz,1H),12.83(s,1H). 31 P NMR (162 MHz, CDCl3) δ-8.42.

[0133] Example 5

[0134]

[0135] Characterization data of ligand 5: 1 H NMR (400MHz, CDCl3) δ12.75(s,1H),8.70(dd,J=8.5,1.1Hz,1H),7.87(ddd,J=7.8,3.9,1.3Hz,1 H),7.82(dd,J=7.9,1.7Hz,1H),7.54(td,J=7.5,1.3Hz,1H),7.43(td,J=7.6,1.3Hz,1H),7.40-7 .18(m,15H),7.10(ddd,J=7.8,3.9,1.2Hz,1H),7.02(td,J=7.7,1.2Hz,1H),5.75(d,J=7.9Hz,1H ), 5.42 (ddd, J = 8.2, 6.9, 1.7Hz, 1H), 3.52 (dd, J = 18.1, 6.9Hz, 1H), 3.37 (dd, J = 17.9, 1.6Hz, 1H). 13 C NMR (101MHz, CDCl3) δ167.1,163.9,141.7,141.5,141.3,139.9,139.7,13 9.1,138.8,138.6,138.5,138.1,138.0,134.8,134.1,133.9,133.8,133.6 ,132.5,129.0,128.7,128.4,128.31,128.27,128.25,128.22,128.15,127 .49,127.45,127.41,125.5,125.0,122.3,120.0,113.3,81.7,76.6,39.8. 31 P NMR (162 MHz, CDCl3) δ -7.84.

[0136] Example 6

[0137]

[0138] Characterization data of ligand 6: 1 H NMR (400MHz, CDCl3) δ12.87(s,1H),8.77(d,J=8.4Hz,1H),7.92–7.89(m,1H),7.84–7.82(m,1H),7.43–7.35(m,3H),7.34–7.27(m,10 H),7.13–6.99(m,2H),4.43(t,J=8.8Hz,1H),4.28–4.21(m,1H),3.95(t,J=8.1Hz,1H),1.63(p,J=7.4Hz,2H),0.93(t,J=7.4Hz,3H). 13 C NMR (101MHz, CDCl3) δ167.2,163.6,141.4,141.2,140.0,138.8,138.6,138.5,138.42,138.36,138.3,134.8,134.0,133.9,133. 8,133.7,132.4,130.3,128.9,128.4,128.3,128.30,128.28,128.2,127.4,127.4,122.3,120.0,113.3,71.0,68.0,28.9,10.4. 31 PNMR (162MHz,CDCl3)δ-8.06.

[0139] Example 7

[0140]

[0141] Characterization data of ligand 7: 1 H NMR (400MHz, CDCl3) δ12.51(s,1H),8.59(d,J=8.5Hz,1H),7.79(d,J=7.8Hz,1H),7.74–7.71(m,1H),7.38–7.16(m,16H),7.04–7.00(m,2H),4.6 1(p,J=7.5Hz,1H),4.32(t,J=8.9Hz,1H),4.06(t,J=8.1Hz,1H),3.10(dd,J=13.8,6.3Hz,1H),2.77(dd,J=13.8,7.7Hz,1H),1.22–1.17(m,36H). 13C NMR (101MHz, CDCl3) δ167.4,163.9,150.1,150.0,150.0,140.6,140.4,1 40.3,140.0,137.6,137.3,137.2,137.0,134.2,132.5,129.8,129.0,128 .8,128.6,128.5,128.4,128.3,128.2,127.83,127.0,127.0,126.6,122 .3,122.3,122.1,120.1,113.2,70.6,67.7,42.1,34.8,34.8,31.4,31.3. 31 PNMR (162MHz,CDCl3)δ-4.26.

[0142] Example 8

[0143]

[0144] Characterization data of ligand 8: 1 H NMR (400MHz, CDCl3) δ12.46(s,1H),8.68(d,J=8.4Hz,1H),7.80(d,J=7.8Hz,1H),7.72(dd,J=7.6, 4.7Hz,1H),7.38(t,J=7.9Hz,1H),7.31(dd,J=7.7,3.0Hz,1H),7.25–7.13(m,8H),7.02(t,J=7.6Hz ,1H),6.84–6.82(m,4H),4.61(dt,J=14.2,7.2Hz,1H),4.34(t,J=8.9Hz,1H),4.06(t,J=8.0Hz,1H ), 3.05(dd,J=13.8,6.2Hz,1H),2.79–2.48(m,15H),1.19(q,J=7.5Hz,6H),0.83(q,J=7.3Hz,12H). 13 C NMR (101MHz, CDCl3) δ167.2,163.9,149.0,148.8,144.2,141.7,141.4,140.43,140.36,140.2,137.6,133.7,132.5,132.2,129.7,129 .0,128.9,128.6,127.4,127.1,126.6,126.3,126.2,121.9,120.2,113.1,70.6,67.8,42.1,28.5,28.4,28.4,28.3,28.2,15.1,15.1. 31P NMR (162MHz, CDCl3) δ-27.87.

[0145] Example 9

[0146]

[0147] Characterization data of ligand 9: 1 H NMR (400MHz, CDCl3) δ13.10 (s, 1H), 8.69 (d, J = 8.5Hz, 1H), 7.87 (t, J = 8.7Hz, 4H), 7.71 (t,J=6.8Hz,4H),7.44(q,J=7.8Hz,2H),7.32(t,J=7.6Hz,1H),7.26–7.17(m,5H),7.1 1(t,J=7.6Hz,1H),6.91(dd,J=7.8,4.1Hz,1H),4.77–4.69(m,1H),4.41(t,J=8.9Hz,1 H), 4.15 (t, J = 8.0Hz, 1H), 3.09 (dd, J = 13.8, 7.0Hz, 1H), 2.87 (dd, J = 13.8, 7.3Hz, 1H). 31 P NMR (162 MHz, CDCl3) δ-5.6.

[0148] Example 10

[0149]

[0150] Characterization data of ligand 10: 1 H NMR(400MHz, CDCl3)δ12.83(d,J=4.5Hz,1H),8.75(dd,J=8.6,3.9Hz,1H),7.86–7.81(m,2H),7.43–7.28(m,13H),7.0 9–7.04(m,2H),4.38(t,J=8.8Hz,1H),4.14(q,J=8.6Hz,1H),4.02(t,J=8.3Hz,1H),1.55–1.44(m,2H),1.14–1.03(m,

[0151] 1H), 0.86–0.78 (m, 6H). 13C NMR (101MHz, CDCl3) δ167.4,163.4,141.7,138.1,134.7,134.0,133.9,133.8,133.7,132.4,130.2, 128.9,128.4,128.3,128.3,128.2,127.4,122.3,120.0,113.4,71.5,69.4,39.6,25.7,15.1,11.1. 31 P NMR (162 MHz, CDCl3) δ-8.35.

[0152] Example 11

[0153]

[0154] Characterization data of ligand 11: 1 H NMR (400MHz, CDCl3) δ12.80(s,1H),8.80(d,J=8.5Hz,1H),7.98–7.95(m,1H),7.83(d,J=7 .8Hz,1H),7.80–7.78(m,1H),7.69–7.63(m,2H),7.44(td,J=8.1,7.2,4.2Hz,2H),7.37(t, J=7.9Hz,1H),7.33–7.19(m,14H),7.09–6.99(m,3H),4.73(p,J=7.3Hz,1H),4.24(t,J=8.9 Hz, 1H), 4.12 (t, J = 7.8Hz, 1H), 3.50 (dd, J = 14.2, 6.4Hz, 1H), 3.10 (dd, J = 14.2, 7.8Hz, 1H). 13 C NMR (101MHz, CDCl3) δ167.0,163.9,140.9,140.7,140.0,138.8,138.6,138.5,138.4,134.7,133.8,133.8,133.7,133.6,133.6,133.5,132.5,1 31.7,130.2,128.9,128.8,128.2,128.2,128.1,128.1,127.3,127.1,12 6.7,126.0,125.6,125.3,123.2,122.2,119.9,113.0,71.0,66.6,39.3. 31 P NMR (162 MHz, CDCl3) δ-7.89.

[0155] Example 12

[0156]

[0157] Characterization data of ligand 12: 1 H NMR (400MHz, CDCl3) δ12.72(s,1H),8.78(dt,J=8.6,2.3Hz,1H),7.84(dq,J=7.9,1.7Hz,1H),7 .76–7.64(m,4H),7.61(s,1H),7.44–7.40(m,3H),7.31–7.28(m,11H),7.12–7.04(m,2H),6.97( ddd,J=7.8,4.3,1.7Hz,1H),6.91(td,J=7.5,1.4Hz,1H),4.74(dq,J=9.4,7.2Hz,1H),4.38(t,J =8.9Hz, 1H), 4.14 (t, J = 8.0Hz, 1H), 3.19 (dd, J = 13.8, 7.0Hz, 1H), 2.97 (dd, J = 13.8, 7.2Hz, 1H). 13 C NMR (101MHz, CDCl3) δ167.1,163.9,140.8,140.6,139.9,138.4,138.4,138.3,135.0,134.6,133.8,133.7,133.6,133.5,133.3,132. 4,132.0,130.0,128.9,128.2,128.1,128.0,128.0,127.4,127.3,127.2,127.0,125.9,125.3,122.2,119.8,113.1,70.6,67.5,42.1. 31 P NMR (162 MHz, CDCl3) δ-8.04.

[0158] Example 13

[0159]

[0160] Characterization data of ligand 13: 1 H NMR(400MHz, CDCl3)δ12.87(s,1H),8.74(dd,J=8.5,3.9Hz,1H),7.88–7.81(m,2H),7.43–7.29(m,1 3H),7.09–7.03(m,2H),4.42–4.33(m,1H),4.09–4.00(m,2H),1.73–1.59(m,5H),1.27–0.83(m,6H). 13C NMR (101MHz, CDCl3) δ167.4,163.3,141.7,141.5,140.0,138.3,138.2,138.2,134.6,134.0,133.9,133.8,133.7,132.4 ,130.1,128.8,128.3,128.3,128.2,127.4,127.4,122.3,120.0,113.4,71.8,69.5,42.9,29.6,29.2,26.3,25.9,25.8. 31 P NMR (162 MHz, CDCl3) δ-8.39.

[0161] Example 14

[0162]

[0163] Characterization data of ligand 14: 1 H NMR (400MHz, CDCl3) δ12.74(s,1H),8.79(d,J=8.4Hz,1H),7.83(d,J=7.9Hz,1H),7.72(dd,J=7.8,3.9Hz,1H),7.46(d,J=7.5Hz,2H),7.42–7.27(m,

[0164] 16H),7.20–7.00(m,6H),4.61(p,J=7.4Hz,1H),4.36(t,J=8.9Hz,1H),4.06(t,J=8.0Hz,

[0165] 1H), 3.00 (dd, J=13.8, 7.4Hz, 1H), 2.81 (dd, J=13.9, 6.7Hz, 1H). 13 C NMR (101MHz, CDCl3) δ167.2,164.0,141.1,140.9,140.5,140.0,139.1,138.6,138.5,138.4,138.4,138.3,136 .7,134.8,133.9,133.6,132.6,130.3,129.3,129.0,128.6,128.4,128.3,128.2,128.2,128.2,127.3,127.2,

[0166] 127.1,127.0,126.8,122.3,120.0,113.2,70.8,67.6,41.8. 31 P NMR (162 MHz, CDCl3) δ-8.10.

[0167] Example 15

[0168]

[0169] Characterization data of ligand 15: 1 H NMR (400MHz, CDCl3) δ12.53(s,1H),8.38(d,J=8.4Hz,1H),7.74(ddd,J=7.7,3.7,1.3Hz,1H),7 .52(td,J=7.5,1.3Hz,1H),7.43(td,J=7.6,1.3Hz,1H),7.37-7.12(m,13H),7.08(ddd,J=7.8, 4.0,1.2Hz,1H),7.07-6.94(m,2H),6.75(ddd,J=11.5,8.3,1.1Hz,1H),5.65(d,J=8.0Hz,1H), 5.47(ddd,J=8.2,6.7,1.8Hz,1H), 3.49(dd,J=18.1,6.7Hz,1H), 3.39(dd,J=18.2,1.7Hz,1H). 13 C NMR (101MHz, CDCl3) δ167.1,162.8,162.3,162.2,160.2,141.3,141.2,140.9,140.7,140.6,139.6,138.8,138.6,137.9,137.8,137.7,137.6,

[0170] 134.6,134.1,133.88,133.85,133.7,133.0,132.9,130.3,128.6,128.5,128.33,128.31,128.28,

[0171] 128.2,128.12,128.05,127.4,127.3,127.20,127.16,125.5,125.3,125.2,124.9,115.99,115.96,

[0172] 110.6,110.3,103.3,103.2,82.4,75.0,39.7. 19 F NMR (376MHz, CDCl3) δ-106.56; 31 P NMR (162 MHz, CDCl3) δ-7.61.

[0173] Example 16

[0174]

[0175] Characterization data of ligand 16: 1 H NMR (400MHz, CDCl3) δ10.81 (s, 1H), 8.44-8.40 (m, 1H), 7.58 (ddd, J = 7.5, 3.6, 1.6Hz,1H),7.50-7.32(m,4H),7.34-7.28(m,5H),7.25-7.16(m,4H),7.13-7.0 9(m,2H),7.06-7.01(m,1H),6.94(d,J=7.6Hz,1H),6.77(td,J=7.6,1.2Hz,1H ), 5.72 (d, J=7.8Hz, 1H), 5.48 (ddd, J=7.7, 5.6, 2.2Hz, 1H), 3.49-3.39 (m, 2H). 13 C NMR (101MHz, CDCl3) δ167.0,162.3,141.0,140.5,140.3,139.5,138.7,138.6,138.4,13 7.6,137.5,137.4,134.53,134.51,134.2,134.1,134.0,133.9,131.1,130.6,130.0(q,J C-F =31.8Hz),128.8,128.7,128.6,128.5,

[0176] 128.5,128.3,128.2,127.5,127.3,127.2,125.5,124.7,124.6,123.6(q,J C-F =272.1Hz),121.7(q,J C-F =5.5Hz),114.3-114.2(m,1C),83.8,76.4,39.0. 19 F NMR (376MHz, CDCl3) δ-58.86. 31 PNMR (162MHz,CDCl3)δ-7.52.

[0177] Example 17

[0178]

[0179] Characterization data of ligand 17: 1H NMR(400MHz, CDCl3)δ10.62(s,1H),7.99-7.86(m,2H),7.78-7.60(m,4H),7. 52(ddd,J=7.3,4.0,1.5Hz,1H),7.44-7.25(m,5H),7.24-7.12(m,5H),7.08( td,J=7.4,3.1Hz,2H),6.87(dt,J=8.2,4.1Hz,1H),6.80(d,J=7.6Hz,1H),5. 68(d,J=7.6Hz,1H), 5.48(ddd,J=7.5,5.0,2.3Hz,1H), 3.46(t,J=3.3Hz,2H). 13 C NMR (101MHz, CDCl3) δ166.3,166.2,161.6,141.0,140.5,140.4,139.3,137.9,134.5,134. 4,132.5,132.4,132.14,132.11,132.0,131.9,131.8,131.6,131.5,131.39,131.37,131. 2,131,1,130.9,130.5,130.0,129.90,129.85,129.5,128.8,128.2,128.1,127.90,127.8 6,127.8,127.6,125.3,124.6,124.4,122.0,121.9-121.6(m,1C),115.0,83.9,76.2,38.8. 19 FNMR (376MHz,CDCl3)δ-58.92. 31 P NMR (162 MHz, CDCl3) δ 29.95.

[0180] Example 18

[0181]

[0182] Characterization data of ligand 18: 1H NMR (400MHz, CDCl3) δ12.21(s,1H),8.50(dd,J=8.6,1.1Hz,1H),7.77(dd,J=8.0 ,1.6Hz,1H),7.39(ddd,J=7.8,3.7,1.3Hz,1H),7.33(tq,J=4.3,1.8Hz,3H),7.28 -7.11(m,12H),7.05-6.91(m,6H),5.14(td,J=9.3,7.5Hz,1H),4.30(t,J=9.1Hz ,1H),4.05(dd,J=8.7,7.5Hz,1H),3.98(d,J=9.2Hz,1H),1.20(d,J=8.4Hz,36H). 13 C NMR (101MHz, CDCl3) δ167.5,164.2,150.08,150.05,150.02,149.98,141.8,141.5,139. 9,134.2,132.4,129.6,128.8,128.7,128.4,128.31,128.29,128.2,128.1,127.0,126.7 126.4,122.3,122.2,122.1,120.3,113.3,70.1,70.1,56.7,34.8,34.7,31.33,31.31. 31 P NMR (162 MHz, CDCl3) δ -4.35.

[0183] Example 19

[0184]

[0185] Characterization data of ligand 19: 1 H NMR (400MHz, CDCl3) δ11.95 (s, 1H), 8.04-7.93 (m, 1H), 7.77-7.69 (m, 2H), 7.61 (dd, J = 1 9.6,13.1Hz,4H),7.46(dd,J=11.7,8.5Hz,3H),7.37-7.31(m,1H),7.30-7.26(m,1H),7. 25-7.13(m,9.6H),7.07-6.99(m,3H),6.96(t,J=7.6Hz,1H),5.18(q,J=8.0Hz,1H),4.3 1(t,J=9.1Hz,1H), 4.03(t,J=8.4Hz,1H), 3.96(d,J=9.7Hz,1H), 1.20(d,J=2.1Hz,36H). 13C NMR (101MHz, CDCl3) δ166.3,166.28,164.1,150.3,150.1,142.0,141.7,140.5,140. 4,139.3,135.1,135.0,133.3,132.7,132.5,132.4,132.1,131.8,131.8,131.7,131 .5,129.7,129.6,128.8,128.8,128.4,128.3,128.2,127.1,127.0,126.8,126.6,126.3,126.3,126.2,126.2,125.5,122.4,120.4,113.7,70.3,70.2,56.8,34.9,31.3. 31 P NMR (162 MHz, CDCl3) δ 32.34.

[0186] Example 20

[0187]

[0188] Characterization data of ligand 20: 1 H NMR (400MHz, CDCl3) δ12.47(s,1H),8.61(dd,J=8.5,1.1Hz,1H),7.82-7.69(m,2H),7.48(td,J=7.5,1.3Hz,1H),7.40(td,J=7.6,1.4Hz,1H),7.38 -7.17(m,9H),7.07-7.00(m,1H),6.96(td,J=7.7,1.2Hz,1H),5.72(d,J= 8.0Hz,1H),5.44-5.32(m,1H),3.74-3.21(m,8H),1.28(d,J=9.9Hz,36H). 31 P NMR (162 MHz, CDCl3) δ-5.64.

[0189] Example 21

[0190]

[0191] Characterization data of ligand 21: 1H NMR (400MHz, CDCl3) δ12.86(s,1H),8.71(dd,J=8.5,1.1Hz,1H),7.86(ddd,J=7.8,3.9,1.3Hz,1H),7.81(dd,J =7.9,1.7Hz,1H),7.77(t,J=1.8Hz,1H),7.71-7.64(m,5H),7.58-7.49(m,9H),7.46(td,J=7.6,1.3Hz,1H),7.3 7(ddt,J=7.3,5.8,1.1Hz,8H),7.34-7.27(m,7H),7.25-7.19(m,3H),7.01(ddd,J=8.1,7.4,1.2Hz,1H),5.56( d, J=8.0Hz, 1H), 5.33 (ddd, J=8.3, 7.0, 1.7Hz, 1H), 3.48 (dd, J=18.1, 7.0Hz, 1H), 3.32 (dd, J=18.2, 1.7Hz, 1H). 31 P NMR (162 MHz, CDCl3) δ-5.35.

[0192] Example 22

[0193]

[0194] Characterization data of ligand 22: 1 H NMR (400MHz, chloroform-d) δ12.80 (s, 1H), 8.63–8.57 (m, 2H), 8.49 (dd, J = 8.5, 4.8Hz, 1H),7.97-7.90(m,1H),7.88-7.74(m,5H),7.55(td,J=7.6,1.3Hz,1H),7.50-7 .27(m,11H),7.21-7.16(m,1H),7.09-6.92(m,4H),5.78(d,J=8.0Hz,1H),5.45 (ddd,J=8.3,6.9,1.7Hz,1H),3.55(dd,J=18.0,6.9Hz,1H),3.44-3.34(m,1H). 31 P NMR (162 MHz, chloroform-d) δ-26.03.

[0195] Example 23

[0196]

[0197] Characterization data of ligand 23: 1H NMR (400 MHz, chloroform-d) δ 12.59 (s, 1H), 8.64 (dd, J = 8.5, 1.1 Hz, 1H), 7.90-7.75 (m, 2H), 7.50 (td, J = 7.5, 1.3 Hz, 1H), 7.39 (td, J = 7.6, 1.3 Hz, 1H), 7.36-7.29 (m, 2H), 7.29-7.23 (m, 4H), 7.23-7.17 (m, 3H), 7.0 7-6.96(m,3H),6.92-6.73(m,3H),5.70(d,J=7.9Hz,1H),5.39(ddd,J=8.2,6.8,1.7Hz,1H),3.88-3. 70(m,2H),3.50(dd,J=18.0,6.8Hz,1H),3.35(dd,J=18.0,1.6Hz,1H),1.13(dt,J=12.7,6.5Hz,9H). 31 P NMR (162 MHz, chloroform-d) δ-28.64.

[0198] Example 24

[0199]

[0200] Characterization data of ligand 24: 1 H NMR (400 MHz, chloroform-d) δ 12.54 (s, 1H), 8.59 (dd, J = 8.5, 1.1 Hz, 1H), 7.80 (dd, J = 7.9, 3.4 Hz, 2H), 7.49 (t, J = 7.5 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.37-7.28 (m, 4H), 7.26 (d, J = 3.1 Hz, 3H), 7.19 (d, J = 8.2 Hz, 4H),7.07(dd,J=7.8,4.0Hz,1H),6.99(dd,J=8.2,7.4Hz,1H),5.71(d,J=8.0Hz,1H),5.39(dd,J=8 .2,7.0Hz,1H),3.50(dd,J=18.0,7.0Hz,1H),3.34(dd,J=17.9,1.7Hz,1H),1.20(d,J=3.9Hz,36H). 31 P NMR (162 MHz, chloroform-d) δ -4.36.

[0201] Example 25

[0202]

[0203] Characterization data of ligand 25: 1H NMR (400 MHz, chloroform-d) δ 12.28 (s, 1H), 8.30–8.20 (m, 1H), 8.06 (dd, J = 8.5, 1.2 Hz, 1H), 7.83–7.63 (m, 6H), 7.56–7.41 (m, 2H), 7.36–7.20 (m, 8H), 7.19–

[0204] 7.08(m,1H),7.08–6.94(m,4H),5.69(d,J=7.8Hz,1H),5.42(ddd,J=8.0,6 .8, 1.5Hz, 1H), 3.53 (dd, J=18.1, 6.8Hz, 1H), 3.39 (dd, J=18.1, 1.5Hz, 1H). 31 P NMR (162 MHz, chloroform-d) δ 30.98.

[0205] Example 26

[0206]

[0207] Characterization data of ligand 26: 1 H NMR (400MHz, chloroform-d) δ12.58 (s, 1H), 8.69 (dd, J = 9.3, 5.2 Hz, 1H), 7.84 (ddd, J =7.6,3.8,1.4Hz,1H),7.62–7.49(m,2H),7.44(td,J=7.6,1.4Hz,1H),7.36 –7.14(m,15H),7.12–7.04(m,2H),5.77(d,J=7.9Hz,1H),5.45(ddd,J=8.3, 6.9, 1.7Hz, 1H), 3.54 (dd, J=18.0, 6.9Hz, 1H), 3.38 (dd, J=18.0, 1.7Hz, 1H). 19 F NMR (376 MHz, chloroform-d) δ -119.46. 31 P NMR (162 MHz, chloroform-d) δ -7.75.

[0208] Example 27

[0209]

[0210] Characterization data of ligand 27: 1H NMR (400 MHz, chloroform-d) δ10.68 (s, 1H), 8.61–8.11 (m, 1H), 7.60–7.53 (m, 1H), 7.51–7.45 (m, 1H), 7.44–7.36 (m, 3H), 7.21 (dd, J = 9.1, 3.5 Hz, 3H), 7.18–7.08 (m, 4H), 7.08–7.03 (m, 2H), 7.02–6.97 (m, 1H), 6.94 (t, J = 7.4 Hz, 1H), 6.8 5(t,J=7.4Hz,1H),6.77(dd,J=7.7,4.2Hz,1H),6.69–6.60(m,1H),5.70(d,J=7.8Hz,1H),5.45(ddd,J=7.8,6.1 ,1.7Hz,1H),3.45(dd,J=18.2,6.3Hz,1H),3.37(d,J=18.0Hz,1H),2.41(d,J=1.6Hz,3H),2.23(d,J=1.7Hz,3H). 19 F NMR (376 MHz, chloroform-d) δ -58.87. 31 P NMR (162 MHz, chloroform-d) δ-24.20.

[0211] Example 28

[0212]

[0213] Characterization data of ligand 28: 1 H NMR (400 MHz, chloroform-d) δ 10.55 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.49–7.27 (m, 6H), 7.24–7.17 (m, 3H), 7.15 (t, J = 7.4 Hz, 1H), 7.10–7.03 (m, 2H), 6.96 (ddd, J = 7.5, 3.9, 1.7 Hz, 1H), 6.91–6.80 (m, 3H), 6.68 (dd, J = 7.7, 4.0 Hz ,1H),5.69(d,J=7.8Hz,1H),5.45(ddd,J=7.8,6.0,1.8Hz,1H),3.88(q,J=7.2Hz,1H),3.79–3.60(m,1H),3. 53–3.28(m,2H),1.18(d,J=6.8Hz,3H),1.14(d,J=6.7Hz,3H),1.01(d,J=6.8Hz,3H),0.96(d,J=6.8Hz,3H). 19 F NMR (376 MHz, chloroform-d) δ -58.90. 31P NMR (162 MHz, chloroform-d) δ-29.37.

[0214] Example 29

[0215]

[0216] Characterization data of ligand 29: 1 H NMR (400 MHz, CHLOROFORM-d) δ 12.90 (s, 1H), 8.85 (dd, J = 8.5, 1.2 Hz, 1H), 8.06 (dd, J = 7.9, 1.6 Hz, 1H), 7.72 (ddd, J = 7.8, 3.9, 1.3 Hz, 1H), 7.51 (ddd, J = 8.8, 7.3, 1.7 Hz, 1H), 7.34–7.23 (m, 11H), 7.16 (dtd, J = 10.9, 7.6, 1.3 Hz, 2H), 7.12–7.01 (m, 6H), 7.00–6.88 (m, 6H), 5.99 (d, J = 10.1 Hz, 1H), 5.80 (d, J = 10.0 Hz, 1H). 31 P NMR (162 MHz, chloroform-d) δ -7.89.

[0217] Example 30

[0218]

[0219] Characterization data of ligand 30: 1 H NMR (400MHz, chloroform-d) δ12.90 (s, 1H), 8.85 (dd, J = 8.6, 1.2Hz, 1H), 8.07 (dd, J = 7. 9,1.6Hz,1H),7.72(dd,J=7.3,3.9Hz,1H),7.51(ddd,J=8.8,7.4,1.7Hz,1H),7 .34–7.21(m,11H),7.17(dtd,J=10.8,7.5,1.3Hz,2H),7.11–7.01(m,5H),6.9 4(dtd,J=8.8,7.8,3.3Hz,6H), 6.00(d,J=10.1Hz,1H), 5.80(d,J=10.1Hz,1H). 31 P NMR (162 MHz, chloroform-d) δ -7.90.

[0220] Example 31

[0221]

[0222] Characterization data of ligand 31: 1H NMR (400MHz, chloroform-d) δ12.33 (s, 1H), 8.68 (dd, J = 8.5, 1.2Hz, 1H), 7.80 (dd, J = 7. 9,1.6Hz,1H),7.47–7.41(m,1H),7.40–7.36(m,1H),7.31(d,J=3.6Hz,7H),7. 28–7.18(m,15H),7.18–7.10(m,3H),7.08–6.88(m,5H),5.14(td,J=9.2,6.9H z, 1H), 4.33 (t, J = 9.1Hz, 1H), 4.10 (dd, J = 8.8, 7.2Hz, 1H), 4.04–3.94 (m, 1H). 31 P NMR (162 MHz, chloroform-d) δ -8.12.

[0223] Example 32

[0224]

[0225] Characterization data of ligand 32: 1 H NMR (400MHz, CDCl3) δ12.21(s,1H),8.55(dd,J=8.4,1.2Hz,1H),7.78(dd,J=8.0,1 .6Hz,1H),7.40–7.33(m,2H),7.29–7.15(m,9H),7.09–6.89(m,12H),5.13(td,J=9. 2,7.6Hz,1H),4.33(t,J=9.1Hz,1H),4.07(dd,J=8.8,7.4Hz,1H),3.98(d,J=9.3Hz, 1H), 2.82–2.70 (m, 4H), 1.15 (dd, J=7.2, 2.0Hz, 12H), 1.11 (dd, J=7.2, 6.0Hz, 12H). 31 P NMR (162 MHz, CDCl3) δ-5.92.

[0226] Example 33

[0227]

[0228] Characterization data of ligand 33: 1H NMR(400MHz, CDCl3) δ12.25(s,1H),8.71(dd,J=8.6,1.1Hz,1H),7.82(dd,J=7.9,1.7Hz,1H), 7.73–7.67(m,4H),7.65(dd,J=7.7,1.7Hz,2H),7.39(ddd,J=8.7,7.2,1.7Hz,1H),7.32–7.28( m,5H),7.27–7.14(m,11H),7.11–7.05(m,3H),7.03–6.89(m,10H),4.81(td,J=9.5,7.8Hz,1H) ,4.16(t,J=9.0Hz,1H),3.99–3.91(m,1H),3.80(d,J=9.8Hz,1H),2.35(s,12H),2.34(s,12H). 31 P NMR (162 MHz, CDCl3) δ-5.96.

[0229] Example 34

[0230]

[0231] Characterization data of ligand 34: 1 H NMR (400MHz, CDCl3) δ12.34(s,1H),8.69(d,J=8.5Hz,1H),7.80(dd,J=7.9,1.6Hz,1H),7.77–7.69(m ,2H),7.65(ddd,J=9.5,7.6,1.7Hz,4H),7.53(dd,J=7.0,1.8Hz,8H),7.39(td,J=7.9,7.4,2.1Hz,8H ),7.35–7.26(m,6H),7.24–7.08(m,6H),7.06–6.99(m,4H),6.93(t,J=7.4Hz,2H),6.87(t,J=7.2Hz, 1H), 4.92(td,J=9.4,7.5Hz,1H), 4.22(t,J=9.0Hz,1H), 3.99(t,J=8.1Hz,1H), 3.84(d,J=9.6Hz,1H). 31 PNMR (162MHz,CDCl3)δ-5.74.

[0232] Example 35

[0233]

[0234] Characterization data of ligand 35: 1H NMR (400MHz, CDCl3) δ12.33(s,1H),8.78(d,J=8.5Hz,1H),7.83(dd,J=7.9,1.6Hz,1H),7.49–7 .38(m,2H),7.33(t,J=7.5Hz,1H),7.30–7.12(m,8H),7.11–7.01(m,4H),6.99(t,J=7.2Hz,1H) ,6.49(ddd,J=14.4,8.1,2.3Hz,4H),6.42(t,J=2.3Hz,2H),5.13(td,J=9.4,7.3Hz,1H),4.35( t, J=9.1Hz, 1H), 4.09 (dd, J=8.7, 7.3Hz, 1H), 3.97 (d, J=9.4Hz, 1H), 3.70 (s, 6H), 3.69 (s, 6H). 31 P NMR (162 MHz, CDCl3) δ -4.70.

[0235] Example 36

[0236]

[0237] Characterization data of ligand 36: 1 H NMR (400MHz, CDCl3) δ12.25 (s, 1H), 8.66 (d, J = 8.4Hz, 1H), 7.79 (dd, J = 8.0, 1.6Hz, 1H), 7.3 8(td,J=6.6,6.1,1.8Hz,2H),7.30(td,J=7.6,1.3Hz,1H),7.26–7.15(m,5H),7.15–7.06(m ,4H),7.06–6.92(m,6H),6.89(dd,J=7.6,3.8Hz,4H),5.07(td,J=9.3,7.3Hz,1H),4.31(t, J=9.1Hz, 1H), 4.06 (dd, J=8.7, 7.4Hz, 1H), 3.95 (d, J=9.2Hz, 1H), 2.22 (s, 6H), 2.19 (s, 6H). 31 P NMR (162 MHz, CDCl3) δ-8.27.

[0238] Example 37

[0239]

[0240] Characterization data of ligand 37: 1H NMR (400MHz, CDCl3) δ10.48–10.37(m,1H),8.17(dd,J=7.8,1.9Hz,1H),7.42–7.31(m,7H),7.21(dd,J=8.5,1.8Hz,3H),7.19–7.07(m,5H),7.04–6 .93(m,2H),5.72(d,J=7.9Hz,1H),5.47(ddd,J=8.0,6.3,1.9Hz,1H),3.4 4(dd,J=18.1,6.3Hz,1H),3.40–3.33(m,1H),1.22(s,18H),1.18(s,18H). 19 F NMR (376MHz, CDCl3) δ-58.91. 31 PNMR (162MHz,CDCl3)δ-4.92.

[0241] Example 38

[0242]

[0243] Characterization data of ligand 38: 1 H NMR (400MHz, CDCl3) δ12.68(s,1H),8.75(d,J=8.4Hz,1H),7.84(dd,J=7.9,1.7Hz,1H),7.70(ddd,J=7.7,3.9,1.3Hz,1H),7.46–7.38(m,1H),7.38–

[0244] 7.31(m,2H),7.29–7.20(m,10H),7.14–7.00(m,4H),6.81(t,J=8.6Hz,2H),4.41–4.35(m,1H),4.04 (q, J=7.0Hz, 1H), 2.93 (dd, J=13.9, 7.5Hz, 1H), 2.75 (dd, J=13.9, 6.7Hz, 1H), 1.29 (d, J=6.3Hz, 3H). 19 F NMR (376MHz, CDCl3) δ-116.29. 31 P NMR (162 MHz, CDCl3) δ-8.30.

[0245] Example 39

[0246]

[0247] Characterization data of ligand 39: 1H NMR (400MHz, CDCl3) δ12.69(s,1H),8.76(d,J=8.5Hz,1H),7.85(d,J=7.9Hz,1H),7.69( dd,J=7.8,3.9Hz,1H),7.41(t,J=7.9Hz,1H),7.38–7.19(m,12H),7.08(dd,J=8.1,5.1Hz ,4H),6.80(t,J=8.5Hz,2H),4.21(q,J=6.3Hz,1H),4.09(q,J=6.8Hz,1H),2.91(dd,J=1 3.8,7.5Hz,1H),2.74(dd,J=13.8,6.4Hz,1H),1.67–1.49(m,2H),0.92(t,J=7.4Hz,3H). 19 F NMR (376MHz, CDCl3) δ-116.30. 31 P NMR (162 MHz, CDCl3) δ-8.32.

[0248] Example 40

[0249]

[0250] Characterization data of ligand 40: 1 H NMR (400MHz, CDCl3) δ12.58(s,1H),8.77(d,J=8.5Hz,1H),8.00(d,J=7.2Hz,1H),7.85(d,J=7.9Hz,1H),7. 45–7.29(m,13H),7.07(d,J=6.9Hz,2H),4.85(t,J=9.4Hz,1H),4.54(dt,J=25.6,9.1Hz,2H),1.39(s,9H). 31 P NMR (162 MHz, CDCl3) δ-7.94.

[0251] Example 41

[0252]

[0253] Characterization data of ligand 41: 1H NMR (400MHz, CDCl3) δ12.67(s,1H),8.72(d,J=8.4Hz,1H),7.82(t,J=8.0Hz,2H),7.48–7.27(m,13H),7.06(t,J=7.6Hz,2H),4.49(t,J =8.8Hz, 1H), 4.33 (dq, J = 9.4, 4.6, 2.8Hz, 1H), 3.86 (t, J = 8.4Hz, 1H), 1.68 (dd, J = 14.0, 6.6Hz, 1H), 1.45 (d, J = 6.0Hz, 1H), 0.84 (s, 9H). 31 P NMR (162 MHz, CDCl3) δ-8.66.

[0254] Example 42

[0255]

[0256] Characterization data of ligand 42: 1 H NMR (400MHz, CDCl3) δ12.87(s,1H),8.77(d,J=8.5Hz,1H),7.86–7.79(m,1H),7.75(dd,J=7.8,1.6Hz,1H),7.41(ddd,J=8.7,7.3,1.7Hz,1H),7.36–

[0257] 7.28(m,11H),7.22(td,J=7.5,1.3Hz,1H),7.15–7.08(m,5H),7.08–7.01(m, 2H), 4.28 (d, J = 8.3Hz, 1H), 3.99 (d, J = 8.3Hz, 1H), 2.89 (s, 2H), 1.40 (s, 3H). 31 P NMR (162 MHz, CDCl3) δ-7.58.

[0258] Example 43

[0259]

[0260] Characterization data of ligand 43: 1H NMR (400MHz, CDCl3) δ12.60 (s, 1H), 8.77 (d, J = 8.5Hz, 1H), 7.85 (t, J = 9.2Hz, 3H), 7.69 (dd, J = 7. 8,3.9Hz,1H),7.46(t,J=7.9Hz,1H),7.38–7.29(m,11H),7.23(d,J=7.7Hz,3H),7.09(q,J=5.8, 3.8Hz,2H),4.66(p,J=7.4Hz,1H),4.43(t,J=9.0Hz,1H),4.35(dt,J=13.8,6.3Hz,2H),4.10(t, J=8.0Hz, 1H), 3.04 (dd, J=13.9, 7.6Hz, 1H), 2.91 (dd, J=13.9, 6.4Hz, 1H), 1.37 (t, J=7.1Hz, 3H). 31 P NMR (162 MHz, CDCl3) δ-8.30.

[0261] Example 44

[0262]

[0263] Characterization data of ligand 44: 1 H NMR(400MHz, CDCl3)δ12.91(s,1H),8.76(dd,J=8.5,1.1Hz,1H),7.90–7.81(m,2H),7.56(dd,J=8.0,5.8Hz, 4H),7.44(ddd,J=8.7,7.4,1.7Hz,1H),7.38(ddd,J=7.7,5.8,4.0Hz,5H),7.31(td,J=7.5,1.2Hz,1H),7.24– 7.14(m,5H),7.09(td,J=7.6,1.2Hz,1H),7.00(ddd,J=7.7,3.9,1.3Hz,1H),4.66(dt,J=9.5,7.2Hz,1H),4. 39(t,J=8.9Hz,1H), 4.12(dd,J=8.5,7.4Hz,1H), 3.08(dd,J=13.8,6.8Hz,1H), 2.83(dd,J=13.8,7.3Hz,1H). 19 F NMR (376MHz, CDCl3) δ-62.72. 31 P NMR (162 MHz, CDCl3) δ-8.06.

[0264] Example 45

[0265]

[0266] Characterization data of ligand 45: 1 H NMR (400MHz, CDCl3) δ12.77(s,1H),8.77–8.65(m,1H),7.84(td,J=8.9,7.9,4.0Hz,2H),7.45– 7.34(m,3H),7.34–7.27(m,10H),7.12–7.02(m,2H),4.46(ddd,J=9.4,7.8,1.5Hz,1H),4.36(q d,J=8.7,5.5Hz,1H),3.90(td,J=7.9,1.5Hz,1H),1.66(ddd,J=15.2,12.6,6.7Hz,1H),1.55(d dd,J=13.9,9.0,5.5Hz,3H), 1.35(ddd,J=13.8,8.7,5.6Hz,1H), 0.85(dd,J=10.1,6.6Hz,6H). 31 P NMR (162 MHz, CDCl3) δ-8.27.

[0267] Example 46

[0268]

[0269] Characterization data of ligand 46: 1 H NMR (400MHz, CDCl3) δ12.61 (s, 1H), 8.70 (d, J = 8.4Hz, 1H), 7.81 (dd, J = 7.9, 1.6Hz, 1H), 7.72 (d,J=1.8Hz,2H),7.67(dt,J=7.8,2.1Hz,5H),7.55–7.44(m,8H),7.42–7.27(m,16H),7.09– 7.02(m,1H),6.99(dt,J=8.6,4.2Hz,2H),6.85–6.73(m,2H),4.48–4.33(m,1H),4.29(t,J=8 .9Hz, 1H), 3.98 (t, J = 7.9Hz, 1H), 2.83 (dd, J = 13.9, 7.0Hz, 1H), 2.66 (dd, J = 14.0, 6.8Hz, 1H). 19 F NMR (376MHz, CDCl3) δ-115.40. 31 PNMR (162MHz,CDCl3)δ-5.35.

[0270] Example 47

[0271]

[0272] Characterization data of ligand 47: 1 H NMR (400MHz, CDCl3) δ12.65(s,1H),8.78(dd,J=8.5,1.1Hz,1H),7.83(dd,J=7.9,1.6Hz,1H),7.63(dd, J=4.5,1.8Hz,1H),7.40(ddd,J=8.7,7.3,1.7Hz,1H),7.21(dd,J=7.8,3.2Hz,1H),7.13–7.01(m,6H),6. 94(td,J=7.3,3.0Hz,4H),6.77–6.70(m,2H),4.59(dd,J=9.4,7.1Hz,1H),4.38(t,J=8.9Hz,1H),4.06(t ,J=8.0Hz,1H),2.97(dd,J=13.8,6.9Hz,1H),2.83–2.73(m,1H),2.27(s,3H),2.10(s,6H),2.07(s,6H). 19 F NMR (376MHz, CDCl3) δ-116.15. 31 P NMR (162MHz, CDCl3) δ-23.54.

[0273] Example 48

[0274]

[0275] Characterization data of ligand 48: 1 H NMR (400MHz, CDCl3) δ12.58(s,1H),8.73(d,J=8.5Hz,1H),7.82(dd,J=7.9,1.6Hz,1H),7.65(dt,J=7.8,3 .4Hz,1H),7.39(ddd,J=8.6,7.2,1.7Hz,1H),7.21(td,J=5.4,2.3Hz,1H),7.08(ddd,J=8.5,4.9,2.2Hz,4H ),7.06–7.00(m,1H),7.00–6.89(m,5H),6.83–6.74(m,2H),4.67–4.52(m,1H),4.39(t,J=8.9Hz,1H),4.05 (t,J=8.0Hz,1H),2.94(dd,J=13.9,7.5Hz,1H),2.84–2.76(m,1H),2.23(s,3H),2.09(s,6H),2.07(s,6H). 19 FNMR (376MHz, CDCl3) δ-116.08. 31P NMR (162MHz, CDCl3) δ-22.32.

[0276] Example 49

[0277]

[0278] Characterization data of ligand 49: 1 H NMR (400MHz, CDCl3) δ12.84(s,1H),8.78(d,J=8.4Hz,1H),8.33(d,J=4.6Hz,1H),7.85(dd,J=7.9,1.6H z,1H),7.77–7.73(m,1H),7.72(d,J=3.2Hz,1H),7.66–7.61(m,1H),7.54–7.39(m,3H),7.16–7.04(m,3H ),6.97(qd,J=5.5,2.6Hz,6H),6.58–6.48(m,2H),4.60(dd,J=9.4,7.2Hz,1H),4.39(t,J=8.9Hz,1H),4 .11–4.03(m,1H),2.96(dd,J=13.9,6.8Hz,1H),2.77(dd,J=13.9,6.8Hz,1H),2.13(s,6H),2.11(s,6H). 19 FNMR (376MHz, CDCl3) δ-115.88. 31 P NMR (162MHz, CDCl3) δ-21.97.

[0279] Example 50

[0280]

[0281] Characterization data of ligand 50: 1 H NMR (400MHz, CDCl3) δ12.17 (s, 1H), 8.65 (d, J = 8.4Hz, 1H), 7.81 (dd, J = 8.0, 1.7Hz, 1H), 7.47–7.35(m,2H),7.28–7.16(m,9H),7.08–6.94(m,5H),6.91–6.80(m,4H),5.21(td,J= 9.3,7.3Hz,1H),4.38(t,J=9.1Hz,1H),4.11(dd,J=8.8,7.3Hz,1H),4.02(d,J=9.1Hz,1 H), 2.61 (tt, J = 14.6, 9.1 Hz, 12H), 1.23 ( q, J = 7.6 Hz, 6H), 0.84 ( dt, J = 14.3, 7.2 Hz, 12H). 31P NMR (162MHz, CDCl3) δ-27.78.

[0282] Example 51

[0283]

[0284] Characterization data of ligand 51: 1 H NMR (400MHz, CDCl3) δ10.88(s,1H),8.58(dd,J=7.2,2.4Hz,1H),7.66–7.59(m,1H),7.53–7.41(m,2H),7.38–7.26(m,12H),7.16–7.08(m,2H),7.08–

[0285] 7.01(m,1H),6.94(t,J=8.6Hz,2H),4.61–4.49(m,1H),4.44(t,J=9.0Hz,1H),4. 11(t,J=8.2Hz,1H), 2.97(dd,J=14.0,6.8Hz,1H), 2.72(dd,J=14.0,7.3Hz,1H). 19 FNMR (376MHz, CDCl3) δ-59.07,-116.18. 31 P NMR (162 MHz, CDCl3) δ-8.04.

[0286] Example 52

[0287]

[0288] Characterization data of ligand 52: 1 H NMR (400MHz, CDCl3) δ12.79 (s, 1H), 8.80 (d, J = 8.5Hz, 1H), 7.88 (ddd, J = 7.8 ,4.6,1.8Hz,2H),7.46(ddd,J=8.7,7.4,1.7Hz,1H),7.40–7.28(m,14H),7.2 0–7.04(m,4H),4.74–4.57(m,1H),4.39(t,J=8.9Hz,1H),4.12(t,J=8.0Hz,1 H), 3.13 (dd, J=14.0, 6.2Hz, 1H), 2.78 (dd, J=14.0, 7.7Hz, 1H), 1.32 (s, 9H). 31 P NMR (162 MHz, CDCl3) δ-8.12.

[0289] Example 53

[0290]

[0291] Characterization data of ligand 53: 1 H NMR (400MHz, CDCl3) δ12.36(s,1H),8.68(d,J=9.2Hz,1H),7.67(ddd,J=7.8,3.8,1.3H z,1H),7.37–7.26(m,11H),7.26–7.21(m,2H),7.11–7.03(m,3H),6.99(dd,J=9.2,3.1H z,1H),6.84–6.76(m,2H),4.56(dq,J=9.5,7.2Hz,1H),4.37(t,J=8.9Hz,1H),4.04(t, J=8.0Hz, 1H), 3.79 (s, 3H), 2.93 (dd, J=14.0, 7.4Hz, 1H), 2.79 (dd, J=14.0, 6.4Hz, 1H). 19 F NMR (376MHz, CDCl3) δ-116.25. 31 P NMR (162 MHz, CDCl3) δ-8.41.

[0292] Example 54

[0293]

[0294] Characterization data of ligand 54: 1 H NMR (400MHz, CDCl3) δ12.75(s,1H),8.77(d,J=8.4Hz,1H),7.85(ddd,J=9.6,7.8,2.7Hz,2H),7.47–7.37(m,1H),7.29(q,J=4.5,3.8Hz,17H),7.12–

[0295] 6.99(m,2H),4.60–4.49(m,3H),4.42(t,J=9.0Hz,1H),4.25(t,J=7.9Hz,1H),3.67(dd,J=9.5,4.5Hz,1H),3.50(dd,J=9.5,6.4Hz,1H). 31 P NMR (162 MHz, CDCl3) δ-7.81.

[0296] Example 55

[0297]

[0298] Characterization data of ligand 55: 1H NMR (400MHz, CDCl3) δ12.58(s,1H),8.76(d,J=8.5Hz,1H),7.84(d,J=7.9Hz,1H),7.74–7.58(m,1H),7.37(d,J=55.8Hz,15H),7.18(t,J=7.8Hz,2H) ,7.07(t,J=7.9Hz,2H),4.74–4.52(m,1H),4.40(t,J=9.0Hz,1H),4.08(t, J=8.1Hz, 1H), 3.04 (dd, J=14.0, 7.3Hz, 1H), 2.88 (dd, J=14.1, 6.7Hz, 1H). 19 F NMR (376MHz, CDCl3) δ-62.56. 31 P NMR (162 MHz, CDCl3) δ-7.98.

[0299] Example 56

[0300]

[0301] Characterization data of ligand 56: 1 H NMR (400MHz, CDCl3) δ12.55(s,1H),8.75(d,J=8.5Hz,1H),7.84(d,J=7.9Hz,1H), 7.67(dd,J=7.7,3.1Hz,1H),7.43(t,J=7.9Hz,1H),7.39–7.22(m,15H),7.18(t,J =7.5Hz,1H),7.07(d,J=7.3Hz,2H),4.60(p,J=7.6Hz,1H),4.41(t,J=8.9Hz,1H), 4.05(t,J=8.0Hz,1H), 3.00(dd,J=14.0,7.9Hz,1H), 2.87(dd,J=14.0,6.0Hz,1H). 19 F NMR (376MHz, CDCl3) δ-62.29. 31 P NMR (162 MHz, CDCl3) δ-8.12.

[0302] Example 57

[0303]

[0304] Characterization data of ligand 57: 1H NMR (400MHz, CDCl3) δ12.77(s,1H),8.78(d,J=8.5Hz,1H),7.90–7.70(m,2H),7.30(d,J=9.7Hz,13H),7.06(dq,J=15.2,7.8Hz,3H),6.96(d,J=12.5H z,3H),4.60(t,J=7.9Hz,1H),4.31(t,J=9.0Hz,1H),4.06(t,J=8.0Hz,1H) ,3.03(dd,J=13.8,6.3Hz,1H),2.72(dd,J=13.8,7.9Hz,1H),2.25(s,3H). 31 P NMR (162 MHz, CDCl3) δ -7.82.

[0305] Example 58

[0306]

[0307] Characterization data of ligand 58: 1 H NMR (400MHz, CDCl3) δ12.72(s,1H),8.77(dd,J=8.5,1.1Hz,1H),7.85(dd,J=7.9,1.7Hz,1H),7.74(ddd,J=6 .8,3.8,1.9Hz,1H),7.46–7.41(m,1H),7.38(ddd,J=6.2,5.3,3.2Hz,4H),7.29(dd,J=5.7,2.5Hz,10H),7.2 3–7.12(m,6H),7.07(td,J=7.6,1.2Hz,1H),7.02(ddd,J=7.5,3.8,1.8Hz,1H),4.71–4.58(m,1H),4.41(dd, J=9.4,8.5Hz,1H), 4.12(dt,J=8.5,6.3Hz,2H), 3.05(dd,J=13.9,7.2Hz,1H), 2.84(dd,J=13.8,6.8Hz,1H). 19 F NMR (376MHz,CDCl3)δ-62.36. 31 P NMR (162 MHz, CDCl3) δ-8.22.

[0308] Example 59

[0309]

[0310] Characterization data of ligand 59: 1H NMR (400MHz, CDCl3) δ12.81 (s, 1H), 8.74 (d, J = 8.4Hz, 1H), 7.90 (dd, J = 7.7, 3.8Hz, 1H), 7.84(d,J=7.9Hz,1H),7.47–7.25(m,13H),7.20(dd,J=13.9,7.0Hz,3H),7.12–7.03(m,2 H),6.99(d,J=7.2Hz,2H),4.41(t,J=8.8Hz,1H),4.27(p,J=7.6Hz,1H),3.91(t,J=8.1Hz ,1H),2.70(dt,J=14.4,7.3Hz,1H),2.59(dt,J=13.8,8.1Hz,1H),1.88(q,J=7.5Hz,2H). 31 P NMR (162 MHz, CDCl3) δ-8.44.

[0311] Example 60

[0312] The ligand of the present invention is applied to the free radical asymmetric oxidative Sonogashira cross coupling reaction to synthesize alkynes.

[0313] To an oven-dried Schlenk tube equipped with a magnetic stir bar, CuTc (cuprous thiophene-2-carboxylate, 10 mol% equivalents), ligand L5 (15 mol%), 4-cyanophenylacetylene (1.0 equivalents), an oxidant (3.0 equivalents), and cesium carbonate (4.0 equivalents) were added. The argon atmosphere was replaced three times, followed by the addition of chlorobenzene (1.0 mL) and tetralin (0.13 mL, 10.0 equivalents). The reaction was then allowed to proceed at 0°C for 120 h. After completion of the reaction (monitored by TLC), the precipitate was filtered off and washed with the solvent, the solution was evaporated, and the product was purified by silica gel column chromatography (petroleum ether = 100) to give the product in 60% yield and 82% ee.

[0314]

[0315] Characterization data of the product: colorless oil, HPLC conditions: Chiralcel OJ-H (n-hexane / isopropanol = 98 / 2, flow rate 1.0 mL / min, λ = 254 nm), t R (minor)=19.0min,t R (major)=24.4min. 1H NMR (400MHz, CDCl3) δ7.58-7.54(m,2H),7.50-7.45(m,3H),7.21-7.15(m,2H),7.14-7.08(m,1H), 4.04(t,J=6.4Hz,1H),2.87-2.78(m,2H),2.26-2.13(m,1H),2.13-1.94(m,2H),1.87-1.78(m,1H). 13 C NMR (101 MHz, CDCl3) δ 136.3, 135.5, 132.2, 131.9, 129.4, 129.0, 128.9, 126.8, 126.1, 118.6, 111.0, 98.1, 80.2, 32.1, 30.0, 29.1, 21.2. HRMS (ESI) m / z accurate mass calculation C 19 H 16 N[M+H] + 258.1277, measured value 258.1275.

[0316] The results of the above reaction using the ligands of the present invention are shown in the following table (L1 represents the ligand of Example 1, and so on):

[0317] ligand Yield (%) ee(%) ligand Yield (%) ee(%) L1 47 49 L12 49 54 L2 51 66 L13 53 51 L3 62 48 L14 52 61 L4 41 38 L15 61 87 L5 60 82 L16 65 92 L6 47 32 L17 60 92 L7 46 58 L18 45 43 L8 22 15 L19 44 40 L9 33 52 L20 52 91 L10 50 72 L21 55 90 L11 57 52

[0318] It can be seen that the ligands of the present invention can be used with copper salts as catalysts for the oxidation of terminal alkynes and benzylic / allylic carbon-hydrogen bond substrates by Sonogashira C(sp)C(sp 3 ) asymmetric cross-coupling reaction to construct a chiral carbon-carbon triple bond with good yield and excellent enantioselectivity.

[0319] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. An oxazoline phosphine ligand having the structure of general formula I or its tautomers, enantiomers, or diastereomers: ； R 1 Selected from hydrogen, fluorine, trifluoromethyl, methoxy; R 2 Select one of the following structures: Ethyl, isopropyl, sec-butyl, isobutyl, tert-butyl, -CH2 t Bu, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh2, -CO2 t Bu, -CH2OBn, or , R 7 is methyl, tert-butyl, phenyl, fluorine, trifluoromethyl, -CO2Et, p-trifluoromethylphenyl, or R 2 With R 4 connected and together with the oxazoline ring to form ; R 3 is selected from hydrogen or methyl; R 4 Selected from hydrogen, methyl, ethyl, phenyl; R 5 Selected from hydrogen, methyl, or The benzene ring is combined with the substituted benzene ring to form a naphthalene ring; W is PR2 or P(O)R2, R is selected from Ph, 2-Me-Ph, 2- i Pr-Ph, 4-CF3-C6H4, 2,6-Me2-C6H3, 3,5-Me2C6H3, 3,5-Ph2-C6H3, 3,5-(OMe)2C6H3, 3,5- t Bu2-C6H3、3,5- i Pr2C6H3, 3,5-(CF3)2-C6H3, 2,4,6-Et3-C6H2, 3,5-di t Bu2-4-OMe-Ph, 3,5-(3,5-Me2C6H3)2-C6H3, 1-naphthyl.

2. An oxazoline phosphine ligand, characterized in that Select one of the following structures: 。 3. A method for preparing the oxazoline phosphine ligand according to claim 1, comprising the following steps: ； Compound S1 reacts with compound S2 to obtain intermediate S3; Intermediate S3 reacts with compound S4 to obtain the product; R 1 、R 2 、R 3 、R 4 、R 5 , W as defined in claim 1.

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