Substituted 2,3-dihydrobenzo[d][1,3]oxaphosphole ligands, methods of making and using same

Abstract

This invention provides a 2,3-dihydrobenzo[d][1,3]oxaphosphazene derivative of formula (I) and its preparation method. Compound I is constructed by tandem nucleophilic addition (or nucleophilic substitution) and intramolecular S-NAr reaction. This method features simple preparation steps, high yield, and mild reaction conditions, solving the technical problems of complex synthesis steps and harsh conditions in the synthesis of oxaphosphine compounds in traditional prior art.

Description

[0001] This application claims priority to Chinese patent application CN202311544800.5 filed on November 17, 2023, and Chinese patent application CN202410608122.2 filed on May 15, 2024, the entire contents of which are incorporated herein by reference and form part of this application. Technical Field

[0002] This invention relates to the field of catalyst technology, specifically to a substituted 2,3-dihydrobenzo[d][1,3]oxaphosphanecyclopentene ligand, its preparation method, and its application. Background Technology

[0003] The substituted 2,3-dihydrobenzo[d][1,3]oxphosphine and 3,4-dihydrobenzo[d][1,4]oxphosphine compounds possess electron-rich aromatic skeletons, making them a preferred class of organophosphine ligand skeletons. The rigid and electron-rich intracyclic phosphine structure provides a robust coordination environment during catalysis, enabling more efficient and specific enantioselective conversion of substrates to products. In fact, these electron-rich organophosphine ligands have been widely developed and applied in transition metal-catalyzed cross-coupling reactions, transition metal-catalyzed asymmetric hydrogenation reactions, and asymmetric substitution reactions catalyzed by phosphine catalysts. For example, Tang's group developed a series of chiral oxaphosphacene ligands that can achieve the cross-coupling reaction of sterically hindered aryl bromides and boric acids. Furthermore, they utilized these electron-rich chiral ligands to achieve the enantioselective cyclization reaction of N-acetylenes. These electron-rich oxphosphine compounds have attracted widespread attention from scientists in recent years due to their excellent coordination activity. However, the synthesis of rigid cyclic phosphine structural fragments is rarely reported. The preparation routes for many electron-rich chiral oxophosphine ligands are relatively long, and some chiral ligand preparation processes require complex protection and deprotection procedures. Therefore, developing a short and efficient strategy for synthesizing rigid, electron-rich oxophosphine compounds is a research goal for many organic synthesis studies. In existing experimental techniques, the synthesis of 2,3-dihydrobenzo[d][1,3]oxophosphine compounds mainly involves nucleophilic substitution of the α-carbon of phosphine by an oxygen nucleophile on the aromatic ring. Currently, there is no direct synthesis of these important benzo[d][1,3]oxophosphine compounds via tandem nucleophilic addition / aromatic nucleophilic substitution. . Summary of the Invention

[0004] In view of the problems that need to be improved in the prior art, the problem to be solved by the present invention is to provide a 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand, whose complex with palladium exhibits excellent activity in the coupling reaction of sterically hindered aryl halides and arylboronic acids with C-C bonds or arylamines with CN bonds.

[0005] To achieve the above objectives, the present invention provides: On the one hand, the present invention provides a substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand, the structure of which is shown in formula (I). (I); Among them, R 4 The following are compounds: hydrogen, alkyl, alkenyl, cycloalkyl, heterocyclic, alkylOC(=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O), ferrocene, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, cycloalkylalkyl, heterocyclic alkyl, arylalkyl, or heteroarylalkyl; or, R 4 and R 5 Linked together, the carbon atoms linked to them form cycloalkyl or heterocyclic groups; or, R 4 and its adjacent R 6 They are linked together, forming cycloalkyl or heterocyclic groups with the carbon atoms they are linked to; X 1 For N or CR X1 ; X 2 For N or CR X2 ; R X1 and R X2 Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, -SO2NMe2, or halogen; =O or =S; or It does not exist; R 1 It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, -SO2NMe2, or halogen; R 2It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, -SO2NMe2, or halogen; Or R 1 and R 2 They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3 It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5 It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; R 6 It is hydrogen; n is 0 or 1; Or R 4 for ;in, X 1a For N or CR X1a ; X 2a For N or CR X2a ; R X1a and R X2a Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, fluorine, chlorine, bromine, or iodine; =O or =S; or It does not exist; Z represents a single bond, a cycloalkylene group, a heterocyclic group, an aryl group, a heteroaryl group, an alkylene group, or... ; R 1a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; R 2a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; Or R 1a and R 2a They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3a It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5a It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; m is 0 or 1; The alkyl, alkenyl, cycloalkyl, heterocyclic, aryl, heteroaryl, cycloalkylene, heterocyclic, arylene, heteroarylene, and alkylene groups mentioned in the single or complex groups mentioned above are each independently and optionally surrounded by 1, 2, 3, 4, or 5 groups selected from hydroxyl, amino, halogen, carboxyl, sulfonyl, alkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, alkylthio, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, alkylNH-, (alkyl)2N-, alkylOC Substituents of (=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O) and dicycloalkyloxyphospho(=O).

[0006] In some embodiments, the substituted 2,3-dihydrobenzo[d][1,3]oxaphosphacyclopentene ligand has the form shown in Formula IA or Formula II-A:

[0007] in, R 1 Selected from one of H, F, SO2NMe2; R X2 Selected from F, Cl, Br or I; R 3 Selected from aryl or alkyl groups; R 4 Selected from hydrogen, aryl, heteroaryl, or alkyl; The aryl or heteroaryl group is either unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents selected from halogen, PPh2, N(alkyl)2, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 alkylthio.

[0008] In some embodiments, R 1 Selected from H and F; R X2 Selected from F; R 3 Selected from C 6-10 One of aryl or C1-6 alkyl groups; R 4 Selected from C 6-10 One of aryl, heteroaryl (composed of 3-6 atoms), or C1-6 alkyl; The C 6-10Aryl, heteroaryl or C1-6 alkyl groups consisting of 3-6 atoms, are unsubstituted or replaced by 1, 2, 3, 4 or 5 atoms selected from halogens, PPh2, NMe 2、 SMe 2、 C1-6 haloalkyl, and / or C 1-6 The alkoxy group is replaced by a substituent.

[0009] In some embodiments, the substituted 2,3-dihydrobenzo[d][1,3]oxaphosphanecyclopentene ligand is selected from one of the following structures: .

[0010] In other embodiments, the present invention provides a substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand with the structure shown in formula (IB). (IB); where, R 4 The following are compounds: hydrogen, alkyl, alkenyl, cycloalkyl, heterocyclic, alkylOC(=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O), ferrocene, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, cycloalkylalkyl, heterocyclic alkyl, arylalkyl, or heteroarylalkyl; or, R 4 and R 5 Linked together, the carbon atoms linked to them form cycloalkyl or heterocyclic groups; or, R 4 and its adjacent R 6 They are linked together, forming cycloalkyl or heterocyclic groups with the carbon atoms they are linked to; X 1 For N or CR X1 ; X 2 For N or CR X2 ; R X1 and R X2 Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, or halogen; =O or =S; or It does not exist; R 1 It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; R 2 It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; Or R 1 and R 2 They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3 It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5 It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; R 6 It is hydrogen; n is 0 or 1; Or R 4 for ;in, X 1a For N or CR X1a ; X 2a For N or CR X2a ; R X1a and R X2a Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, fluorine, chlorine, bromine, or iodine; =O or =S; or It does not exist; Z represents a single bond, a cycloalkylene group, a heterocyclic group, an aryl group, a heteroaryl group, an alkylene group, or... ; R 1a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; R 2a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; Or R 1a and R 2a They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3a It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5a It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; m is 0 or 1 The alkyl, alkenyl, cycloalkyl, heterocyclic, aryl, heteroaryl, cycloalkylene, heterocyclic, arylene, heteroarylene, and alkylene groups mentioned in the single or complex groups mentioned above are each independently and optionally surrounded by 1, 2, 3, 4, or 5 groups selected from hydroxyl, amino, halogen, carboxyl, sulfonyl, alkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, alkylthio, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, alkylNH-, (alkyl)2N-, alkylOC Substituents of (=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O); The condition is that the structure shown in equation (IB) does not include the following structures: ; Or the condition is that, in the structure shown by the formula (IB), when R X1a When it is F, =O or =S; Or the condition is that, in the structure shown by the formula (IB), when R X1a When it is F, R 4 Hydrogen, alkenyl, cycloalkyl, heterocyclic, alkylOC(=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O), ferrocene, alkyloxy, cycloalkyloxy, heterocyclic oxy, aryloxy, heteroaryloxy, cycloalkylalkyl, heterocyclic alkyl, arylalkyl or heteroarylalkyl; or, R 4 and R 5 Linked together, the carbon atoms linked to them form cycloalkyl or heterocyclic groups; or, R 4 and its adjacent R 6 Linked together, the carbon atoms linked to them form cycloalkyl or heterocyclic groups; or R 4 for .

[0011] In some embodiments, and Each and every one of them is selected independently from: .

[0012] In some embodiments, R 4 Selected from: .

[0013] In some embodiments, R 3 Or R 3a Each is selected independently from: .

[0014] In some embodiments, Z is selected from: .

[0015] In some embodiments, the compound represented by Formula IB is selected from: .

[0016] On the other hand, the present invention provides a bisphosphine palladium acetate complex having the structure described in Formula II-B: (II-B); Among them, R 1 R 2 R 3 R 4 R 5 R 6 X 1 X 3 Y and n have the definitions described in this invention.

[0017] In some embodiments, the bisphosphine palladium acetate complex has The structure of R 4 It has the definition described in this invention.

[0018] In some embodiments, the bisphosphine palladium acetate complex has The structure of R 4 This invention has the definition described herein. On the other hand, this invention also provides a coupling reaction method using a bisphosphine palladium acetate complex prepared from the substituted benzoxophosphine ligands described herein, or the bisphosphine palladium acetate complex described herein, as a catalyst.

[0019] In some embodiments, the coupling reaction method is a CC coupling reaction, comprising: reacting an aryl halide and an arylboronic acid structure in the bisphosphine palladium acetate complex under organic solvent and alkaline conditions; or the coupling reaction method is a CN coupling reaction, comprising: reacting an aryl halide and an arylamine structure in the bisphosphine palladium acetate complex under organic solvent and alkaline conditions. The solvent is N,N - Dimethylformamide, toluene, trifluorotoluene, carbon tetrachloride, dioxane, hexafluoroisopropanol, ethyl acetate; the base is potassium tert-butoxide, sodium tert-butoxide, lithium methoxide, cesium carbonate, sodium acetate, sodium hydroxide, potassium hydroxide, sodium hydroxide.

[0020] In some embodiments, the arylboronic acid structure includes arylboronic acid or arylboronic ester; the aryl halide is an aryl chloride or an aryl bromide; and the aryl amine structure includes an aryl primary amine or an aryl secondary amine.

[0021] In some embodiments, the palladium bisphosphine acetate is used in the C / C bond formation reaction between aryl halides (e.g., aryl bromides) and arylboronic acids:

[0022] Wherein, X is chlorine or bromine. The ligand used is a compound. A more preferred structure is The amount of catalyst used is 0.1%.

[0023] In some embodiments, the palladium bisphosphine acetate is used in the CN bond formation reaction between aryl halides (e.g., aryl chlorides) and aromatic amine structures:

[0024] Wherein, X is chlorine or bromine. The ligand used is a compound. A more preferred structure is The amount of catalyst used is 0.05-2.5%.

[0025] On the other hand, the present invention provides a method for preparing a substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand, comprising: S11. Under inert gas protection, formula III is reacted with a base in an organic solvent and stirred to obtain a salt solution of formula III. S12. After adding the aldehyde or ethylene oxide derivative V shown in Formula IV to the obtained salt solution of Formula III, the reaction is carried out at 0-50 °C to obtain the 2,3-dihydrobenzo[d][1,3]oxaphosphanecyclopentene derivative shown in Formula I. , Among them, R 1 Selected from one of H, F, SO2NMe2; R X2 Selected from F, Cl, Br or I; R 3 Selected from aryl or alkyl; R 4 It is selected from one of aryl, heteroaryl, or alkyl; The aryl or heteroaryl group is either unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents selected from halogen, PPh2, N-alkyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 alkylthio.

[0026] The solvent described in this invention is not particularly limited, as long as it can dissolve the reactants represented by formulas (III), (IV), and (V) to a certain extent without inhibiting the reaction. In some embodiments, the organic solvent is selected from one or more of 1,4-dioxane, tetrahydrofuran, diethyl ether, dichloromethane, 1,2-dichloroethane, toluene, n-hexane, or dimethyl sulfoxide, and the base is selected from one or more of cesium carbonate, potassium carbonate, sodium carbonate, potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium ethoxide, sodium acetate, or sodium hydroxide.

[0027] In some embodiments, the organic solvent is selected from one or more of 1,4-dioxane, tetrahydrofuran, diethyl ether, dichloromethane, 1,2-dichloroethane, toluene, n-hexane, or dimethyl sulfoxide.

[0028] In some embodiments, the alkali is selected from one or more of cesium carbonate, potassium carbonate, sodium carbonate, potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium ethoxide, sodium acetate, or sodium hydroxide.

[0029] In some embodiments, in the mixed system of step S12, the molar ratio of arylphosphine hydrogen represented by Formula III, aldehyde represented by Formula IV or epoxy compound represented by Formula V, and base is 1:1.5:1.5.

[0030] In some embodiments, in the mixed system of step S22, the molar ratio of arylphosphine hydrogen represented by Formula III, the epoxy compound represented by Formula V, and the base is approximately 1:1.5:1.5.

[0031] The methods described herein may further include the use of suitable reaction conditions, and some non-limiting examples include the use of other inert solvents, reagents such as bases, and catalysts. The methods described herein may also include known purification methods such as crystallization, chromatography (liquid and gas chromatography, etc.), extraction, distillation, preparation, and reversed-phase HPLC. Reaction conditions such as temperature, reaction time, pressure, and gases (such as inert gases, air) can be appropriately adjusted according to the reaction.

[0032] Based on the technical solution of the present invention, the following beneficial effects are achieved: This invention provides a series of 2-halogenated 2,3-dihydrobenzo[d][1,3]oxaphosphacyclopentene compounds. These compounds possess electron-rich phosphine atoms, and the product molecules also contain active halogen groups such as fluorine atoms, which facilitates further functionalization to prepare complex phosphine ligands. More importantly, this strategy, based on a tandem nucleophilic addition (nucleophilic substitution) / aromatic nucleophilic substitution reaction, significantly shortens the synthetic route for constructing 2,3-dihydrobenzo[d][1,3]oxaphosphacyclopentene compounds. Starting from readily available phosphine hydrogens and aldehydes, the applicant developed a metal-free, highly efficient tandem nucleophilic addition / aromatic nucleophilic substitution reaction to efficiently synthesize 2,3-dihydrobenzo[d][1,3]oxaphosphacyclopentene derivatives, with simple preparation steps and mild conditions.

[0033]

[0034] Beneficial effects This invention provides a series of 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligands and their application in the C-C and CN bond coupling of aryl halides. The advantages over the prior art include: (1) The preparation steps of this type of ligand are short and can start from readily available aldehydes. Secondly, this type of ligand has electron-rich, rigid structure and is stable in air.

[0035] (2) The present invention can provide a phosphine ligand that can be applied to the coupling reaction of palladium-catalyzed aryl halides and has good reaction results.

[0036] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

[0037] Terminology Explanation Certain embodiments of the invention will now be described in detail, examples of which are illustrated by the accompanying structural and chemical formulas. The invention is intended to cover all alternatives, modifications, and equivalents, all of which are included within the scope of the invention as defined in the claims. Those skilled in the art will recognize that many similar or equivalent methods and materials can be used to practice the invention. The invention is by no means limited to the methods and materials described herein. In the event that one or more of the incorporated documents, patents, and similar materials differ from or contradict this application (including, but not limited to, defined terminology, application of terminology, described techniques, etc.), this application shall prevail.

[0038] It should be further appreciated that certain features of the invention, for clarity, have been described in multiple independent embodiments, but may also be provided in combination in a single embodiment. Conversely, various features of the invention, for brevity, have been described in a single embodiment, but may also be provided individually or in any suitable sub-combination.

[0039] Unless otherwise stated, all technical terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. All patents and publications related to this invention are incorporated herein by reference in their entirety.

[0040] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0041] In the following content, all numbers disclosed herein, whether or not they use words such as "approximately" or "about," are approximate values. The value of each number may vary by 1%, 2%, 5%, 7%, 8%, 10%, 15%, or 20%. Whenever a number with a value of N is disclosed, any numbers with values ​​of N+ / -1%, N+ / -2%, N+ / -3%, N+ / -5%, N+ / -7%, N+ / -8%, N+ / -10%, N+ / -15%, or N+ / -20% will be explicitly disclosed, where "+ / -" indicates addition or subtraction.

[0042] A single group refers to a group formed by only one type of group, such as alkyl, aryl, heteroaryl, etc.; a complex group refers to a group formed by the combination of two or more groups, such as arylalkyl, alkyloxy, alkylthio, cycloalkyloxy, heterocyclic alkyloxy, dicycloalkylphospho, etc. In this article, the complex groups are uniformly connected to the rest of the molecule by the group on the right. For example, in arylalkyl, the aryl group is attached to the alkyl group, and the complex group is connected to the rest of the molecule by the alkyl group as the linking point.

[0043] In this application, the alkyl group, whether as a single group or part of a complex group, refers to a carbon-atom-containing, saturated straight-chain or branched hydrocarbon group. In one embodiment, the alkyl group contains 1-6 carbon atoms, i.e., C1-6 alkyl; in another embodiment, the alkyl group contains 1-4 carbon atoms, i.e., C1-4 alkyl; and in yet another embodiment, the alkyl group contains 1-3 carbon atoms, i.e., C1-3 alkyl. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, and similar alkyl groups.

[0044] In this application, the alkenyl group, whether as a single group or part of a complex group, represents a straight-chain or branched monovalent hydrocarbon group containing carbon atoms, wherein there is at least one unsaturated site, i.e., one carbon-carbon sp2 double bond, including "cis" and "tans" orientation, or "E" and "Z" orientation. In one embodiment, the alkenyl group contains 2-6 carbon atoms, i.e., a C2-C6 alkenyl group; in another embodiment, the alkenyl group contains 2-4 carbon atoms, i.e., a C2-C4 alkenyl group. Examples of alkenyl groups include, but are not limited to, vinyl (-CH=CH2), allyl (-CH2CH=CH2), etc.

[0045] In this application, the cycloalkyl group, whether as a single group or part of a complex group, refers to a monocyclic, bicyclic, or tricyclic system containing a carbon atom, either monovalent or polyvalent (e.g., monocyclic, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl), or bicyclic, including spirocyclic, fused, or bridged systems (e.g., bicyclic [1.1.1]pentyl, bicyclic [2.2.1]heptyl, bicyclic [3.2.1]octyl, or bicyclic [5.2.0]nonyl, decahydronaphthyl, etc.), which may be fully saturated or contain one or more unsaturations, but may not contain any aromatic rings. In one embodiment In this scheme, the cycloalkyl group comprises 3-6 carbon atoms, such as C3-6 saturated or partially unsaturated cycloalkyl groups. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, etc. In one embodiment, the saturated or partially unsaturated cycloalkyl group is selected from: saturated monocyclic cycloalkyl, saturated bicyclic cycloalkyl, saturated tricyclic cycloalkyl, partially unsaturated monocyclic cycloalkyl, partially unsaturated bicyclic cycloalkyl, and partially unsaturated tricyclic cycloalkyl. C4-7 cycloalkyl refers to a cycloalkyl group with 4-7 ring atoms. C3-6 cycloalkyl refers to a cycloalkyl group with 3-6 ring atoms.

[0046] In this application, the heterocyclic group, whether as a single group or part of a complex group, refers to a saturated (i.e., "heterocyclic alkyl") or partially unsaturated monovalent monocyclic or bicyclic group having 2, 3, 4, 5, 6, 7, 8, or 9 carbon atoms in the ring and one or more (e.g., one, two, three, or four) heteroatom-containing groups selected from C(=O), O, S, S(=O), S(=O)2, and NR', where R' represents a hydrogen atom or a C1-6 alkyl or a halo-C1-6 alkyl. The heterocyclic group can be attached to the rest of the molecule by any one of the carbon atoms or a nitrogen atom (if present). Specifically, 3-10 membered heterocyclic groups are groups having 3-10 (e.g., 3-7, 4-6, or 5-6) carbon atoms and heteroatoms in the ring, such as, but not limited to, ethylene oxide, aziridinyl, azetidinyl, oxetanyl, tetrahydrofuranyl, dioxolinyl, pyrrolyl, pyrrolidone, imidazoalkyl, pyrazolyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, or trithianyl.

[0047] In this application, the aryl group, whether as a single group or part of a complex group, refers to an optional functional group or substituent derived from an aromatic carbon ring. The aryl group can be a monocyclic aryl (e.g., phenyl) or a polycyclic aryl. In other words, the aryl group can be a monocyclic aryl, a fused-ring aryl, two or more monocyclic aryl groups conjugated by carbon-carbon single bonds, a monocyclic aryl and a fused-ring aryl group conjugated by carbon-carbon single bonds, or two or more fused-ring aryl groups conjugated by carbon-carbon single bonds, wherein at least one ring is an aromatic ring. That is, unless otherwise stated, two or more aromatic groups conjugated by carbon-carbon single bonds can also be considered as the aryl group in this application. Fused-ring aryl groups may include, for example, bicyclic fused aryl (e.g., naphthyl), tricyclic fused aryl (e.g., phenanthrene, fluorene, anthracene), etc. The aryl group does not contain heteroatoms such as B, N, O, S, P, Se, and Si. Examples of aryl groups may include, but are not limited to, phenyl, naphthyl, fluorenyl, phenyl-naphthyl, spirodifluorenyl, anthracene, phenanthryl, biphenyl, terphenyl, triphenylene, perylene, benzo[9,10]phenanthryl, pyrene, benzofluoranthryl, alkyl, etc. An aryl group can represent a monocyclic, bicyclic, or tricyclic carbocyclic system containing 6-14 ring atoms, 6-12 ring atoms, or 6-10 ring atoms, wherein at least one ring is aromatic and has one or more attachment sites attached to the remainder of the molecule. Unless otherwise stated, the group "C" 6-14 "Aryl" indicates an aryl group containing 6-14 ring carbon atoms. In this application, the heteroaryl group, whether as a single group or part of a complex group, refers to a monovalent aromatic ring or its derivative containing 1, 2, 3, 4, 5, or 6 heteroatoms. The heteroatoms can be one or more of B, O, N, P, Si, Se, and S. The heteroaryl group can be a monocyclic or polycyclic heteroaryl group; in other words, it can be a single aromatic ring system or a system of multiple aromatic rings conjugated by carbon-carbon single bonds. Each aromatic ring system is either a monocyclic aromatic ring or a fused aromatic ring, wherein at least one ring is a heteroaryl ring. For example, heteroaryl groups may include thiopheneyl, furanyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, triazolyl, pyridyl, bipyridyl, pyrimidinyl, triazinyl, acridineyl, pyridazinyl, quinolinyl, quinazolinyl, quinoxazinyl, phenoxazinyl, phthalazinyl, pyridopyrimidinyl, pyridopyrazinyl, isoquinolinyl, indolyl, carbazoleyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzocarbazoleyl, benzothiaphenyl, dibenzothiaphenyl, thiaphenothiaphenyl, benzofuranyl, phenanthrololinyl, isoxazolyl, thiadiazolyl, phenthiaazinyl, silfluorenyl, dibenzofuranyl, and N- Phenylacetazole, N- Pyridylcarbazole, N-Methylcarbazolyl, etc., but not limited to these. A heteroaryl group can represent a monocyclic, bicyclic, or tricyclic ring system containing 5-14 ring atoms, or 5-12 ring atoms, or 5-10 ring atoms, wherein at least one ring is aromatic and has one or more attachment sites attached to the remainder of the molecule. Unless otherwise stated, a 5-14 membered heteroaryl group means a heteroaryl group containing 5-14 ring atoms.

[0048] Cycloalkylene, heterocyclic alkylene, aryl alkylene, heteroaryl alkylene, and alkylene are respectively used as linking groups in this invention. They are divalent groups, meaning they have two connection points that are connected to the rest of the molecule.

[0049] The term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0050] When describing the remainder of a molecule containing a group, it refers to the remainder excluding the substituents of that group itself.

[0051] In this application, "multiple" means two or more, such as two, three, four, five, six, etc.

[0052] The hydrogen atoms in the compound structure of this application include various isotopes of hydrogen, such as hydrogen (H), deuterium (D), or tritium (T).

[0053] Unless otherwise expressly indicated, the descriptive terms “each…independently”, “…each…independently”, and “…independently” used in this invention are interchangeable and should be interpreted broadly. They can mean that the specific options expressed by the same symbols in different groups do not affect each other, or that the specific options expressed by the same symbols in the same group do not affect each other.

[0054] The terms “optional,” “optionally,” or “arbitrarily” mean that the event or situation described below may, but is not necessarily, occur, and the description includes both the occurrence and non-occurrence of the event or situation. For example, “optionally replaced by…” means that the replacement may or may not occur.

[0055] When the terms “independent” and “arbitrarily” are used together, for example, “independently and arbitrarily replaced by…”, it means that specific options are replaced by or not replaced by each other without affecting each other.

[0056] The term "unsaturated" or "unsaturated" means that a portion contains one or more degrees of unsaturation.

[0057] Linking substituents are described in various parts of this invention. When the structure clearly requires a linking group, the Markush variable listed for that group should be understood as the linking group. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl" or "aryl," it should be understood that "alkyl" or "aryl" represents a linked alkylene group or an arylene group, respectively.

[0058] The term "two substituents linked together to form a ring" refers to the connection of two substituents through a bond or a long chain of one or more atoms, forming a ring together with the atoms between the two substituent positions in the parent molecule.

[0059] The term "substitution" refers to the replacement of one or more hydrogen atoms on a specific group by a specific substituent. The specific substituent is either the substituent described accordingly above or the substituent appearing in the various embodiments. Unless otherwise specified, a substituted group may have a substituent selected from a specific group at any substituted site of that group, and the substituents may be the same or different at each position, i.e., the various substitutions are independent of each other. Those skilled in the art will understand that the combinations of substituents contemplated in this invention are those that are stable or chemically feasible.

[0060] The term "room temperature" refers to the temperature of the reaction system being the same as the ambient temperature, without the need for cooling or heating. In some embodiments, room temperature refers to a temperature of approximately 10 to 40 degrees Celsius, and in other embodiments, room temperature refers to a temperature of approximately 25 to 35 degrees Celsius. Detailed Implementation

[0061] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. The specific embodiments described herein are for illustrative purposes only and are not intended to limit the invention in any way. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concepts of this disclosure. Such structures and techniques have also been described in many publications.

[0062] All reagents used in this invention can be purchased commercially or prepared by the methods described in this invention.

[0063] Example 1: Preparation of substrate phosphine III-1

[0064] Preparation of III-1: 1,3-Difluorobenzene (4.78 g, 42 mmol) and 50 mL of tetrahydrofuran solution were added to a 250 mL reaction flask, followed by the addition of butyllithium (42 mmol, 2.0 M, 21 mL). The reaction was carried out at low temperature for 2 hours, after which Et2NPCl (3.48 g, 20 mmol) was added. After 2 hours, the solvent was removed under reduced pressure, and a solution of hydrogen chloride in diethyl ether was added. Finally, the mixture was reduced with DIBAL-H, and the solvent was removed by filtration to obtain product III-1. Product III-1 did not require further purification.

[0065] Example 2: Preparation of substrate phosphine III-2

[0066] Preparation of III-2: 1,3-Difluorobenzene (4.78 g, 42 mmol) and 50 mL of tetrahydrofuran solution were added to a 250 mL reaction flask, followed by the addition of butyllithium (42 mmol, 2.0 M, 21 mL). The reaction was carried out at low temperature for 2 hours, after which tert-butylphosphine dichloride (3.18 g, 20 mmol) was added. After 2 hours, DIBAL-H was added for reduction (20 mmol). The solvent was removed by filtration to obtain product III-1. Product III-2 did not require further purification.

[0067] Example 3: Preparation of compound I-1

[0068] In an argon atmosphere at room temperature, the corresponding substrate phosphine III-1 (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding IV-1 benzaldehyde (0.3 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding the target product of formula I-1 in 93% yield with diastereoselectivity greater than 10:1.

[0069] Structural characterization data of product I-1: 1 H NMR (400 MHz, CDCl3) δ 7.45-7.30 (m, 7H), 6.95-6.83 (m, 3H), 6.69(td, J = 8.0, 3.9 Hz, 1H), 6.48 (s, 1H). 31P NMR (162 MHz, CDCl3) δ -32.30. 19 FNMR (377 MHz, CDCl3) δ -102.37, -102.61. 13 C NMR (151 MHz, CDCl3) δ 166.22,166.17, 165.65, 165.56, 164.94, 164.89, 164.83, 163.99, 163.90, 163.29,163.24, 163.18, 140.12, 139.96, 133.74, 133.68, 132.26, 132.22, 132.15,132.07, 128.67, 127.85, 127.83, 125.15, 125.10, 112.01, 111.98, 111.85,111.82, 111.78, 111.61, 108.30, 108.15, 107.16, 107.14, 88.17, 88.02, 77.21, 77.00, 76.79. High resolution: Calculated values: [M+H] + 345.0651, measured value: 345.0649. Example 4 Preparation of Compound I-2

[0070] The preparation steps were the same as in Example 1, except that p-methylbenzaldehyde was used as the substrate, and the target product of Formula I-2 was finally obtained with a yield of 73%, >20:1 dr, and colorless oil.

[0071] Structural characterization data of product I-2: 1 H NMR (600 MHz, CDCl3) δ 7.37-7.29 (m, 1H), 7.24 (dd, J = 8.0, 1.5Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.86 (td, J =8.1, 1.5 Hz, 1H), 6.68 (td, J = 8.0, 3.8 Hz, 1H), 6.45 (s, 1H), 2.32 (s, 1H). 31P NMR (162 MHz, CDCl3) δ -32.90. 19 F NMR (565 MHz, CDCl3) δ -102.39 – -102.65(m). 13 C NMR (151 MHz, CDCl3) δ 166.21, 165.57, 164.91, 164.01, 163.26,137.68, 137.08, 136.92, 133.66, 133.60, 132.15, 132.08, 132.01, 129.36,129.35, 125.17, 125.12, 111.99, 111.96, 111.83, 111.80, 108.20, 108.06,107.16, 107.14, 88.15, 88.01, 77.21, 77.00, 76.79, 21.11. High resolution: Calculated value: [M+H] + 359.0807, measured value: 359.0803. Example 5: Preparation of compound I-3

[0072] The preparation steps were the same as in Example 1, except that o-methylbenzaldehyde was used as the substrate, and the target product of Formula I-3 was finally obtained with a yield of 88%, >20:1 dr, and colorless oil.

[0073] Structural characterization data of product I-3: 1 H NMR (600 MHz, CDCl3) δ 7.41-7.32 (m, 1H), 7.23-7.18 (m, 1H), 7.14(t, J = 7.1 Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 6.90 (t, J = 8.1 Hz, 1H), 6.68(td, J = 8.0, 3.8 Hz, 1H), 6.58 (s, 1H), 2.38 (s, 1H). 31 P NMR (243 MHz, CDCl3) δ -37.48. 19 F NMR (565 MHz, CDCl3) δ -101.47, -103.10. 13C NMR (151 MHz, CDCl3) δ 166.91, 166.86, 165.54, 165.48, 165.42, 165.26, 165.17, 163.89,163.83, 163.77, 163.61, 163.52, 137.93, 137.79, 134.11, 134.08, 133.69,133.63, 132.86, 132.79, 132.71, 130.80, 130.79, 127.72, 127.70, 126.24,126.22, 124.23, 124.19, 112.05, 112.02, 111.89, 111.86, 108.16, 108.02, 106.96, 106.94, 85.61, 85.59, 85.57, 85.46, 85.44, 77.21, 77.00, 76.79, 19.88, 19.84. High resolution: Calculated values: [M+H] + 359.0807, measured value: 359.0805. Example 6: Preparation of compound I-4

[0074] The preparation steps were the same as in Example 1, except that m-methylbenzaldehyde was used as the substrate, and the target product of Formula I-4 was finally obtained with a yield of 69%, >20:1 dr, and colorless oil.

[0075] Structural characterization data of product I-4: 1 H NMR (600 MHz, CDCl3) δ 7.40 – 7.29 (m, 2H), 7.23 (t, J = 7.6 Hz,1H), 7.18 – 7.13 (m, 2H), 7.09 (d, J = 7.5 Hz, 1H), 6.92 (d, J = 8.2 Hz, 1H), 6.88 (td, J = 8.0, 1.7 Hz, 2H), 6.69 (td, J = 8.0, 3.9 Hz, 1H), 6.45 (s, 1H), 2.34 (s, 3H). 31 P NMR (243 MHz, CDCl3) δ -32.52 (m). 19F NMR (565 MHz, CDCl3) δ-102.48 (m), -102.55 (m). 13 C NMR (151 MHz, CDCl3) δ 166.30, 166.25, 165.65,165.56, 165.02, 164.96, 164.91, 163.99, 163.90, 163.37, 163.31, 163.26,140.11, 139.96, 138.49, 133.73, 133.66, 132.25, 132.18, 132.10, 128.72,128.70, 128.63, 125.83, 125.78, 122.28, 122.23, 112.03, 112.00, 111.88, 111.85, 108.26, 108.11, 107.19, 107.16, 88.26, 88.23, 88.21, 88.11, 88.09, 88.07, 77.25, 77.04, 76.83, 21.53. High resolution: Calculated values: [M+H] + 359.0807, measured value: 359.0805. Example 7: Preparation of compound I-5

[0076] The preparation steps were the same as in Example 1, except that 2,4,6-trimethoxybenzaldehyde was used as the substrate, and the target product of Formula I-5 was finally obtained with a yield of 46%, >20:1 dr, and a white solid.

[0077] Structural characterization data of product I-5: 1 H NMR (600 MHz, CDCl3) δ 7.35 – 7.27 (m, 1H), 7.21 (dd, J = 14.5, 8.1Hz, 1H), 6.88 – 6.80 (m, 3H), 6.65 (d, J = 8.1 Hz, 1H), 6.57 (td, J = 8.0,3.9 Hz, 1H), 6.11 (s, 2H), 3.80 (s, 3H), 3.66 (s, 6H). 31 P NMR (243 MHz, CDCl3) δ -32.48 – -47.61 (m). 19F NMR (565 MHz, CDCl3) δ -101.89 (m), -105.10– -107.50 (m). 13 C NMR (151 MHz, CDCl3) δ 166.94, 165.73, 164.07, 161.87, 159.47, 132.15, 132.09, 111.80, 111.65, 111.62, 109.41, 109.27, 106.49, 106.35, 106.00, 105.99, 90.91, 79.15, 79.02, 77.21, 77.00, 76.79, 55.70, 55.39. High resolution: Calculated values: [M+H] + : 435.0968, measured value: 435.0966. Example 8: Preparation of compound I-6

[0078] The preparation steps were the same as in Example 1, except that 3,5-di-tert-butyl-4-methoxybenzaldehyde was used as the substrate, and the target product of formula I-6 was finally obtained with a yield of 78%, >20:1 dr, and a white solid.

[0079] Structural characterization data of product I-6: 1 H NMR (400 MHz, CDCl3) δ 7.33 (qd, J = 8.2, 6.9 Hz, 1H), 7.22 (d, J =1.7 Hz, 1H), 6.94 – 6.82 (m, 1H), 6.68 (td, J = 8.0, 3.9 Hz, 1H), 6.42 (s,1H), 3.67 (s, 1H), 1.38 (s, 9H). 31 P NMR (162 MHz, CDCl3) δ -33.97 (m). 19 F NMR (377 MHz, CDCl3) δ -102.57 (m). 13C NMR (151 MHz, CDCl3) δ 166.23, 165.55,164.92, 163.99, 163.27, 159.18, 159.15, 143.90, 133.59, 133.54, 133.40,132.05, 131.98, 131.91, 123.62, 123.56, 111.98, 111.95, 111.83, 111.80,108.13, 107.99, 107.06, 107.04, 88.57, 88.43, 77.21, 77.00, 76.79, 64.22, 35.80, 31.93. High resolution: Calculated value: [M+H] + : 487.2008, Measured value: 487.2010. Example 9: Preparation of Product I-7

[0080] The preparation steps were the same as in Example 1, except that 4-trifluoromethylbenzaldehyde was used as the substrate, and the target product of formula I-7 was finally obtained with a yield of 33%, >5:1 dr, and colorless oil.

[0081] Structural characterization data of product I-7: 1 H NMR (600 MHz, CDCl3) δ 7.60 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 7.8Hz, 2H), 7.37 (dq, J = 23.3, 7.4, 6.7 Hz, 2H), 6.95 (d, J = 8.2 Hz, 1H), 6.89(t, J = 7.5 Hz, 2H), 6.72 (td, J = 8.0, 3.9 Hz, 1H), 6.51 (s, 1H). 31 P NMR (243 MHz, CDCl3) δ -30.37 (m). 19 F NMR (565 MHz, CDCl3) δ -62.60, -101.71 – -102.20 (m), -102.37 – -102.95 (m). 13C NMR (151 MHz, CDCl3) δ 165.95, 164.86, 163.20, 144.29, 134.07, 134.01, 132.52, 132.44, 132.37, 125.70, 125.50, 125.45, 112.13, 112.11, 111.98, 111.95, 108.72, 108.58, 107.26, 87.58, 87.42, 77.24, 77.02, 76.81, 14.21. High resolution: Calculated values: [M+H] + : 413.0524, measured value: 413.0522. Example 10: Preparation of Product I-8

[0082] The preparation steps were the same as in Example 1, except that 4-bromobenzaldehyde was used as the substrate, and the target product of formula I-8 was finally obtained with a yield of 79%, >10:1 dr, and colorless oil.

[0083] Structural characterization data of product I-8: 1 H NMR (600 MHz, CDCl3) δ 7.46 (d, J = 8.3 Hz, 1H), 7.41 – 7.29 (m,1H), 7.24 (d, J = 7.6 Hz, 1H), 6.91 (d, J = 8.2 Hz, 1H), 6.88 (t, J = 8.1 Hz, 1H), 6.70 (td, J = 8.0, 3.9 Hz, 1H), 6.42 (s, 1H). 31 P NMR (162 MHz, CDCl3) δ-31.54. 19 F NMR (565 MHz, CDCl3) δ -102.12, -102.6. 13C NMR (151 MHz, CDCl3) δ165.89, 165.55, 164.84, 163.98, 163.19, 139.20, 139.05, 133.91, 133.85,132.37, 132.29, 132.23, 131.77, 126.92, 126.86, 121.72, 121.70, 112.06,112.03, 111.91, 111.88, 108.53, 108.39, 107.21, 107.19, 87.59, 87.44, 77.21,77.00, 76.79. High resolution: Calculated value: [M+H] + : 422.9756, measured value: 422.9753. Example 11: Preparation of product I-9

[0084] The preparation steps were the same as in Example 1, except that 4-chlorobenzaldehyde was used as the substrate, and the target product of Formula I-9 was finally obtained with a yield of 83%, >20:1 dr, and colorless oil.

[0085] Structural characterization data of product I-9: 1 H NMR (600 MHz, CDCl3) δ 7.40 – 7.28 (m, 1H), 6.92 (d, J = 8.1 Hz, 1H), 6.88 (td, J = 8.2, 1.6 Hz, 1H), 6.71 (td, J = 8.0, 3.9 Hz, 1H), 6.45 (s,1H). 31 P NMR (243 MHz, CDCl3) δ -26.68 – -34.98 (m). 19 F NMR (565 MHz, CDCl3) δ-101.96 – -102.78 (m). 13C NMR (151 MHz, CDCl3) δ 165.96, 165.91, 165.64,165.55, 164.89, 164.84, 163.98, 163.89, 163.25, 163.19, 163.13, 138.66,138.50, 133.90, 133.84, 133.63, 133.60, 132.36, 132.29, 132.21, 128.84,128.83, 126.60, 126.54, 112.06, 112.03, 111.90, 111.87, 108.52, 108.37, 107.21, 107.19, 87.56, 87.41, 77.21, 77.00, 76.79. High resolution: Calculated values: [M+H] + 379.0261, measured value: 379.0259. Example 12: Preparation of compounds I-10 to I-22

[0086] In an argon atmosphere at room temperature, the corresponding substrate phosphine III-2 (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding 3-bromobenzaldehyde (0.3 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–50:1) as eluent, yielding the target product of formula I-10 as a colorless oily fluid with a diastereoselectivity greater than 20:1 and a yield of 84%.

[0087] Structural characterization data of product I-10: 1 H NMR (600 MHz, CDCl3) δ 7.38 (s, 1H), 7.37-7.28 (m, 2H), 7.20-7.12(m, 2H), 6.89 (d, J = 8.1 Hz, 1H), 6.70 (td, J = 8.0, 3.2 Hz, 1H), 5.95 (s,1H), 1.11 (d, J = 12.7 Hz, 9H). 31 P NMR (162 MHz, CDCl3) δ 13.53. 19F NMR (376MHz, CDCl3) δ -102.78. 13 C NMR (101 MHz, CDCl3) δ 165.47 (d, J = 8.6 Hz), 164.44 (dd, J = 247.8, 12.4 Hz), 143.56 (d, J = 17.2 Hz), 133.02 (d, J = 9.2Hz), 130.41 (d, J = 2.4 Hz), 130.11 (d, J = 1.3 Hz), 127.88 (d, J = 7.1 Hz), 123.53 (d, J = 7.6 Hz), 122.67 (d, J = 1.5 Hz), 108.92 (dd, J = 27.6, 20.6Hz), 108.29 (dd, J = 22.8, 1.8 Hz), 107.03 (d, J = 3.4 Hz), 84.08 (d, J =28.5 Hz), 32.10 (d, J = 20.5 Hz), 26.79 (d, J = 14.6 Hz, 3C). High resolution: Calculated value: [M+H] + 367.0257, measured value: 367.0261. Preparation of product I-11:

[0088] The preparation steps were the same as in Example 2, except that 4-iodobenzaldehyde was used as the substrate, and the target product of formula I-11 was finally obtained with a yield of 79%, >20:1 dr, and colorless oil.

[0089] 1 H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.4 Hz, 2H), 7.31 (td, J = 8.1,6.1 Hz, 1H), 7.03-6.97 (m, 2H), 6.87 (d, J= 8.1 Hz, 1H), 6.69 (td, J = 8.0,3.2 Hz, 1H), 5.93 (s, 1H), 1.10 (d, J = 12.8 Hz, 9H). 31 P NMR (162 MHz, CDCl3)δ 13.10. 19 F NMR (376 MHz, CDCl3) δ -102.76. 13 C NMR (101 MHz, CDCl3) δ 165.48(d, J = 8.7 Hz), 164.46 (dd, J = 247.7, 12.2 Hz), 140.94 (d, J = 17.1 Hz), 137.57 (d, J = 1.4 Hz, 2C), 132.97 (d, J = 9.2 Hz), 126.84 (d, J = 7.3 Hz, 2C), 108.96 (dd, J = 27.5, 20.6 Hz), 108.23 (dd, J = 22.7, 1.8 Hz), 106.96 (d, J = 3.4 Hz), 92.60 (d, J = 3.5 Hz), 84.32 (d, J = 28.1 Hz), 32.07 (d, J =20.8 Hz), 26.79 (d, J = 14.5 Hz, 3C). High resolution: Calculated value: [M+H] + :415.0118, measured value: 415.0122. Preparation of product I-12:

[0090] The preparation steps were the same as in Example 2, except that 3-chlorobenzaldehyde was used as the substrate, and the target product of formula I-12 was finally obtained with a yield of 50%, >20:1 dr, and colorless oil.

[0091] Structural characterization data of product I-12: 1H NMR (400 MHz, CDCl3) δ 7.34 (td, J = 8.3, 6.3 Hz, 1H), 7.23 – 7.10(m, 1H), 7.07 (dt, J = 7.5, 2.1 Hz, 0H), 6.92 (dd, J = 8.1, 0.8 Hz, 0H), 6.75– 6.65 (m, 0H), 6.29 (s, 0H), 1.14 (d, J = 12.4 Hz, 5H). 31 P NMR (162 MHz, CDCl3) δ 10.73. 19 F NMR (376 MHz, CDCl3) δ -102.65. 13 C NMR (101 MHz, CDCl3) δ166.19, 166.10, 166.03, 165.91, 163.57, 163.44, 138.06, 137.92, 133.00,132.91, 130.27, 130.21, 129.75, 129.73, 128.45, 128.42, 127.00, 126.98,125.92, 125.88, 109.68, 109.47, 109.40, 109.19, 108.47, 108.45, 108.24,108.22, 106.81, 106.77, 82.71, 82.42, 33.31, 33.09, 27.19, 27.05. High resolution: Calculated values: [M+H] + 323.0762, measured value: 323.0761. Preparation of product I-13:

[0092] The preparation steps were the same as in Example 2, except that 3-methylbenzaldehyde was used as the substrate, and the target product of formula I-13 was finally obtained with a yield of 86%, >20:1 dr, and colorless oil.

[0093] Structural characterization data of product I-13: 1 H NMR (400 MHz, CDCl3) δ 7.31 (td, J= 8.2, 6.1 Hz, 1H), 7.23-7.12(m, 1H), 7.08-7.01 (m, 3H), 6.88 (dd, J = 8.1, 0.8 Hz, 1H), 6.69 (tdd, J =8.0, 3.2, 0.8 Hz, 1H), 5.97 (s, 1H), 2.32 (s, 3H), 1.11 (d, J = 12.6 Hz, 9H). 31 P NMR (162 MHz, CDCl3) δ 12.04. 19 F NMR (376 MHz, CDCl3) δ -102.97. 13 C NMR (101 MHz, CDCl3) δ 165.82 (d, J = 8.4 Hz), 165.75-163.11 (m), 141.04 (d, J =16.7 Hz), 138.30 (d, J = 1.4 Hz), 132.76 (d, J = 9.1 Hz), 128.50 (d, J = 1.4Hz), 128.19 (d, J = 2.5 Hz), 125.50 (d, J = 7.4 Hz), 121.97 (d, J = 7.0 Hz), 109.32 (dd, J = 27.6, 20.7 Hz), 107.92 (dd, J = 22.8, 1.8 Hz), 106.92 (d, J =3.3 Hz), 84.92 (d, J = 27.6 Hz), 31.98 (d, J = 20.9 Hz), 26.82 (d, J = 14.5Hz, 3C), 21.48. High resolution: Calculated value: [M+H] + 303.1309, measured value: 303.1312. Preparation of product I-14:

[0094] The preparation steps were the same as in Example 2, except that 2,6-dimethoxybenzaldehyde was used as the substrate, and the target product of formula I-14 was finally obtained with a yield of 91%, >20:1 dr, and a white solid.

[0095] Structural characterization data of product I-14: 1 H NMR (400 MHz, CDCl3) δ 7.30-7.11 (m, 2H), 6.67-6.56 (m, 3H), 6.53(d, J = 8.3 Hz, 2H), 3.65 (s, 5H), 1.08 (d, J = 12.3 Hz, 9H). 31 P NMR (162MHz, CDCl3) δ 11.51. 19 F NMR (376 MHz, CDCl3) δ -104.35. 13 C NMR (101 MHz, CDCl3) δ 166.72 (d, J = 9.5 Hz), 163.29 (dd, J = 244.5, 12.1 Hz), 158.45,131.42 (d, J = 9.3 Hz), 129.61 (d, J = 1.8 Hz, 2C), 117.04 (d, J = 16.0 Hz), 111.89 (dd, J = 27.8, 18.1 Hz), 106.37 (dd, J = 23.2, 1.9 Hz), 106.01 (d, J =3.0 Hz), 104.18, 75.99 (d, J = 24.7 Hz, 2C), 55.66(s, 2C), 31.49 (d, J = 18.5Hz), 26.77 (dd, J = 14.7, 1.5 Hz, 3C). High resolution: Calculated value: [M+H] + 349.1363, measured value: 349.1366. Preparation of product I-15:

[0096] The preparation steps were the same as in Example 2, except that 2,4,6-trimethoxybenzaldehyde was used as the substrate, and the target product of formula I-15 was finally obtained with a yield of 93%, >20:1 dr, and a white solid.

[0097] Structural characterization data of product I-15: 1 H NMR (400 MHz, CDCl3) δ 7.18 (tdd, J = 7.9, 6.2, 1.3 Hz, 1H), 6.61(m, 2H), 6.49 (d, J = 3.8 Hz, 1H), 6.10 (s, 2H), 3.79 (s, 3H), 3.64 (s, 6H), 1.06 (d, J = 12.2 Hz, 9H). 31 P NMR (162 MHz, CDCl3) δ 10.67. 19 F NMR (376 MHz, CDCl3) δ -104.43. 13 C NMR (101 MHz, CDCl3) δ 166.58 (d, J = 9.5 Hz), 163.29(dd, J = 244.3, 12.0 Hz), 161.41 (d, J = 1.7 Hz), 159.23, 131.33 (d, J = 9.3Hz, 2C), 111.92 (dd, J = 27.9, 18.2 Hz), 109.92 (d, J = 16.1 Hz), 106.24 (dd, J = 23.3, 1.9 Hz), 105.98 (d, J = 3.0 Hz), 90.82(s, 2C), 75.89 (d, J = 24.0Hz), 55.58(s, 2C), 55.29, 31.37 (d, J = 18.5 Hz), 26.73 (dd, J = 14.8, 1.4Hz, 3C). High resolution: Calculated value: [M+H] + : 379.1469, Measured value: 379.1471. Preparation of compound I-16

[0098] In an argon atmosphere at room temperature, the corresponding substrate phosphine III-2 (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding 2-dimethylaminobenzaldehyde (0.3 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–50:1) as eluent, yielding the target product I-16 as a colorless oil in 79% yield with a diastereoselectivity greater than 5:1.

[0099] Structural characterization data of product I-16: 1 H NMR (400 MHz, CDCl3) δ7.31-7.18 (m, 3H), 7.10-7.05 (m, 1H), 7.00(td, J = 7.9, 7.0, 2.2 Hz, 1H), 6.87 (dd, J = 8.1, 0.8 Hz, 1H), 6.68-6.61 (m,1H), 6.31 (d, J = 1.8 Hz, 1H), 2.66 (s, 6H), 1.11 (d, J = 12.0 Hz, 9H). 31 PNMR (162 MHz, CDCl3) δ 13.78. 19 F NMR (377 MHz, CDCl3) δ -103.23. 13C NMR (100MHz, CDCl3) δ 166.48, 166.39, 165.90, 165.78, 163.45, 163.33, 150.95, 150.91,137.29, 137.15, 132.41, 132.32, 128.09, 128.06, 125.11, 125.06, 124.95,124.94, 121.75, 121.73, 110.95, 110.73, 110.67, 110.45, 107.82, 107.80,107.59, 107.57, 106.82, 106.78, 82.27, 82.00, 77.32, 77.00, 76.68, 45.31, 45.29, 32.60, 32.37. High resolution: Calculated values: [M+H] + 332.1574, measured value: 332.1576. Preparation of compound I-17:

[0100] In an argon atmosphere at room temperature, the corresponding substrate phosphine III-2 (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding 2-methylmercaptobenzaldehyde (0.3 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–50:1) as eluent, yielding the target product I-17 as a white solid with a yield greater than 93% and diastereoselectivity greater than 20:1.

[0101] Structural characterization data of product I-17: 1 H NMR (400 MHz, CDCl3) δ 7.36 – 7.27 (m, 2H), 7.20 (tt, J = 8.0, 1.8Hz, 1H), 7.07 – 6.99 (m, 2H), 6.91 (d, J = 8.6 Hz, 1H), 6.68 (td, J = 8.0,3.1 Hz, 1H), 6.36 (s, 1H), 2.54 (s, 3H), 1.14 (d, J = 12.3 Hz, 9H). 31P NMR (162 MHz, CDCl3) δ 9.67. 19 F NMR (377 MHz, CDCl3) δ -102.76. 13 C NMR (100 MHz, CDCl3) δ166.28, 166.19, 166.01, 165.88, 163.55, 163.42, 139.07, 138.92,133.89, 133.84, 132.82, 132.73, 127.84, 127.82, 127.61, 127.59, 125.67,125.65, 124.78, 124.73, 110.07, 109.86, 109.79, 109.58, 108.23, 108.22,108.01, 107.99, 106.72, 106.69, 82.88, 82.60, 77.32, 77.00, 76.68, 33.47, 33.45, 33.24, 33.23, 27.38, 27.24, 17.07, 17.04. High resolution: Calculated values: [M+H] + 335.1029, measured value: 335.1028. Preparation of compound I-18:

[0102] The preparation steps were the same as in Example 2, except that 2-diphenylphosphinobenzaldehyde was used as the substrate, and the target product of formula I-18 was finally obtained with a yield of 76%, >20:1 dr, and a white solid.

[0103] Structural characterization data of product I-18: 1 H NMR (400 MHz, CDCl3) δ 7.38-7.22 (m, 11H), 7.20 (dd, J = 7.2, 1.4Hz, 1H), 7.17-7.09 (m, 2H), 6.94 (dt, J = 8.9, 3.0 Hz, 1H), 6.83-6.75 (m,2H), 6.68 (td, J = 7.9, 3.1 Hz, 1H), 0.98 (d, J = 12.4 Hz, 9H). 31P NMR (162MHz, CDCl3) δ 10.45 (d, J = 20.8 Hz), -19.65 (d, J = 20.6 Hz). 19 F NMR (376MHz, CDCl3) δ -102.69. 13 C NMR (101 MHz, CDCl3) δ 166.46, 166.37, 165.91,165.79, 163.45, 163.33, 145.84, 145.69, 145.61, 145.46, 136.56, 136.45,135.89, 135.80, 134.70, 134.00, 133.84, 133.82, 133.64, 132.73, 132.64,132.60, 132.56, 132.46, 132.42, 129.59, 129.57, 128.80, 128.64, 128.58, 128.53, 128.46, 127.89, 127.86, 125.48, 125.42, 125.37, 110.41, 110.17, 109.90, 108.05, 108.03, 107.82, 107.80, 106.73, 106.69, 83.60, 83.32, 83.03, 77.32, 77.00, 76.68, 33.36, 33.13, 27.26, 27.23, 27.12, 27.09. High resolution: Calculated values: [M+H] + : 473.1594, Measured value: 473.1595. Preparation of product I-19:

[0104] The preparation steps were the same as in Example 2, except that ferrocene formaldehyde was used as the substrate, and the target product of formula I-19 was finally obtained with a yield of 66%, >10:1 dr, and yellow oil.

[0105] Structural characterization data of product I-19: 1 H NMR (400 MHz, CDCl3) δ 7.26 (td, J = 8.1, 6.2 Hz, 1H), 6.75 (d, J=7.3 Hz, 1H), 6.66 (td, J = 8.8, 3.3 Hz, 1H), 5.73 (s, 1H), 4.17 (m, 4H), 4.09(s, 5H), 1.09 (d, J = 12.5 Hz, 9H). 31 P NMR (162 MHz, CDCl3) δ 0.58. 19 F NMR (376 MHz, CDCl3) δ -103.56 (d, J = 1.9 Hz). 13 C NMR (101 MHz, CDCl3) δ 165.28(d, J = 8.7 Hz), 164.28 (dd, J = 246.8, 12.5 Hz), 132.59 (d, J = 9.2 Hz), 110.21 (dd, J = 27.4, 18.8 Hz), 107.44 (dd, J = 22.9, 1.9 Hz), 107.11 (d, J =3.3 Hz), 88.25 (d, J = 21.4 Hz), 82.21 (d, J = 26.6 Hz), 68.77 (d, J = 1.1Hz, 5C), 68.37 (dd, J = 14.2, 1.3 Hz, 2C), 67.09 (dd, J = 111.5, 8.6 Hz, 2C),31.75 (d, J = 18.8 Hz), 26.93 (d, J = 14.5 Hz, 3C). High resolution: Calculated value: [M+H] + 397.0814, measured value: 397.0811. Preparation of product I-20:

[0106] The preparation steps were the same as in Example 2, except that dithiophene formaldehyde was used as the substrate, and the target product of formula I-20 was finally obtained with a yield of 90%, >20:1 dr, and colorless oil.

[0107] Structural characterization data of product I-20: 1 H NMR (400 MHz, CDCl3) δ 7.27 (m, 1H), 7.21 (dd, J = 5.1, 1.2 Hz,1H), 7.13-7.05 (m, 1H), 6.93 (ddd, J = 4.9, 3.5, 1.1 Hz, 1H), 6.79 (dd, J =8.2, 0.8 Hz, 1H), 6.68 (tdd, J = 8.0, 3.3, 0.8 Hz, 1H), 6.15 (s, 1H), 1.08(d, J = 12.7 Hz, 9H). 31 P NMR (162 MHz, CDCl3) δ 9.51. 19 F NMR (376 MHz, CDCl3)δ -103.02. 13 C NMR (101 MHz, CDCl3) δ 164.63 (d, J = 8.6 Hz), 164.33 (dd, J =247.5, 12.5 Hz), 144.26 (d, J = 21.8 Hz), 132.85 (d, J = 9.1 Hz), 126.82, 125.42 (d, J = 3.2 Hz), 124.80 (d, J = 10.7 Hz), 109.56 (dd, J = 27.5, 19.9Hz), 108.05 (dd, J = 22.7, 1.9 Hz), 107.46 (d, J = 3.3 Hz), 80.97 (d, J =26.9 Hz), 32.02 (d, J = 20.1 Hz), 26.81 (d, J = 14.3 Hz, 3C). High resolution: Calculated value: [M+H] + : 295.0716, measured value: 295.0719. Preparation of product I-21:

[0108] The preparation steps were the same as in Example 2, except that 2-naphthaldehyde was used as the substrate, and the target product of Formula I-21 was finally obtained with a yield of 87%, >20:1 dr, and a white solid.

[0109] Structural characterization data of product I-21: 1 H NMR (400 MHz, CDCl3) δ 7.84-7.74 (m, 3H), 7.70 (s, 1H), 7.50-7.40(m, 2H), 7.40-7.27 (m, 2H), 6.96 (dd, J = 8.1, 0.7 Hz, 1H), 6.71 (td, J =7.7, 2.5 Hz, 1H), 6.18 (s, 1H), 1.16 (d, J = 12.6 Hz, 9H). 31 P NMR (162 MHz, CDCl3) δ 11.43. 19 F NMR (376 MHz, CDCl3) δ -102.87. 13 C NMR (101 MHz, CDCl3) δ165.83 (d, J = 8.7 Hz), 164.53 (dd, J = 247.5, 12.2 Hz), 138.31 (d, J = 16.7Hz), 133.17, 132.87 (d, J = 9.2 Hz), 132.71 (d, J = 1.8 Hz), 128.56, 127.92,127.66, 126.26, 125.89, 123.31 (d, J = 3.1 Hz), 123.24 (d, J = 3.2 Hz), 109.22 (dd, J = 27.5, 20.6 Hz), 108.08 (dd, J = 22.9, 1.8 Hz), 107.00 (d, J =3.3 Hz), 85.12 (d,J = 27.7 Hz), 32.11 (d, J = 21.4 Hz), 26.86 (d, J = 14.6Hz, 3C). High resolution: Calculated value: [M+H] + 339.1309, measured value: 339.1308. Preparation of product I-22:

[0110] The preparation steps were the same as in Example 2, except that pivalaldehyde was used as the substrate, and the target product of formula I-22 was finally obtained with a yield of 92%, >20:1 dr, and colorless oil.

[0111] Structural characterization data of product I-22: 1 H NMR (600 MHz, CDCl3) δ 7.20 (td, J = 8.1, 6.2 Hz, 1H), 6.69 (dd, J = 8.1, 0.8 Hz, 1H), 6.58 (tdd, J = 8.0, 3.3, 0.8 Hz, 1H), 4.57 (d, J = 1.6Hz, 1H), 1.00 (d, J = 12.6 Hz, 9H), 0.98 (s, 9H). 31 P NMR (243 MHz, CDCl3) δ -9.70. 19 F NMR (377 MHz, CDCl3) δ -103.33. 13 C NMR (151 MHz, CDCl3) δ 166.76,166.70, 164.83, 164.74, 163.19, 163.11, 132.28, 132.21, 110.14, 110.03,109.96, 109.85, 107.05, 107.04, 106.90, 106.89, 106.32, 106.30, 93.93, 93.73,77.23, 77.02, 76.81, 36.19, 36.08, 30.97, 30.85, 26.87, 26.77, 25.95, 25.89. High resolution: Calculated value: [M+H] +: 269.1465, Measured value: 269.1464. Example 13: Preparation of Compound II-1

[0112] In an argon atmosphere at room temperature, the corresponding substrate phosphine III-1 (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran, followed by the addition of potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding ( R )-Benzyloxymethyl ethylene oxide (0.3 mmol, 1.5 equiv.) was reacted with stirring until the reactants were completely consumed by TLC. The product was purified by column chromatography using degassed petroleum ether-ethyl acetate (100:0~10:1) as eluent, yielding the target product of formula II-1 as a colorless oily fluid with a diastereoselectivity greater than 20:1 and a yield of 86%.

[0113] Structural characterization data of product II-1: 1 H NMR (400 MHz, CDCl3) δ 7.39 – 7.28 (m, 7H), 7.14 (tdd, J = 8.3,6.9, 1.5 Hz, 1H), 6.84 (td, J = 8.2, 1.7 Hz, 2H), 6.72 (d, J = 8.2 Hz, 1H), 6.57 – 6.50 (m, 1H), 4.63 (s, 2H), 4.60 (d, J = 2.9 Hz, 1H), 4.49 – 4.34 (m,1H), 3.80 (ddd, J = 10.3, 5.6, 0.8 Hz, 1H), 3.71 – 3.62 (m, 1H), 2.62 (ddd, J = 13.3, 11.7, 6.6 Hz, 1H), 2.30 (ddd, J = 20.0, 13.3, 1.1 Hz, 1H). 31 P NMR (162 MHz, CDCl3) δ -74.51 (q, J = 42.1 Hz). 19 F NMR (377 MHz, CDCl3) δ -101.14(d, J = 43.1 Hz), -104.99 (d,J = 41.5 Hz). 13 C NMR (151 MHz, CDCl3) δ 171.15,166.22, 164.51, 162.87, 159.99, 137.86, 132.40, 130.03, 129.96, 128.43,127.77, 127.71, 113.60, 111.79, 111.61, 107.53, 107.38, 77.21, 77.00, 76.79,74.70, 74.67, 73.50, 73.18, 73.12, 60.38, 21.02, 20.56, 14.17. High resolution: Calculated values: [M+H] + : 403.1069, measured value: 403.1066. Example 14: Preparation of compound II-2

[0114] The preparation steps were the same as in Example 3, except that (R)-phenyl ethylene oxide was used as the substrate, and the target product of formula II-2 was finally obtained with a yield of 46%, 2:1 dr, and colorless oil.

[0115] Structural characterization data of product II-2: 1 H NMR (600 MHz, CDCl3) δ 7.48 (d, J = 7.7 Hz, 2H), 7.43 – 7.37 (m,2H), 7.37 – 7.29 (m, 2H), 7.17 (td, J = 8.3, 6.7 Hz, 1H), 6.89 – 6.82 (m,2H), 6.77 (d, J = 8.2 Hz, 1H), 6.59 (td, J = 8.5, 3.1 Hz, 1H), 5.25 (t, J =11.7 Hz, 1H), 3.37 – 2.85 (m, 1H), 2.43 (dd, J = 20.7, 13.4 Hz, 1H). 31 P NMR (243 MHz, CDCl3) δ -72.18 (m). 19F NMR (565 MHz, CDCl3) δ -101.06 (m), -104.80 (m). 13 C NMR (151 MHz, CDCl3) δ 166.22, 166.16, 166.10, 164.64, 164.56,164.51, 164.45, 163.03, 162.95, 160.74, 160.69, 141.42, 141.37, 132.53,132.46, 132.39, 130.16, 130.09, 128.89, 128.82, 128.67, 128.27, 128.18,128.11, 125.85, 113.80, 113.78, 111.81, 111.78, 111.65, 111.63, 107.64, 107.49, 77.55, 77.51, 26.00, 25.97. High resolution: Calculated values: [M+H] + 359.0807, measured value: 359.0809. Example 15: Synthesis process of ligands (using ligand 4 as an example)

[0116] In an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran, followed by the sequential addition of potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding 2,6-dimethoxybenzaldehyde (0.3 mmol, 1.5 equiv.), with stirring until the reactants were completely consumed by TLC. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a colorless oily liquid (4) in 88% yield with diastereoselectivity greater than 20:1.

[0117] Structural characterization data of product 4: 63.4 mg, 80% yield, 24 h, colorless oil. 1 H NMR (400 MHz, Chloroform-d) δ 7.23-7.14 (m, 2H), 6.57-6.40 (m, 5H), 3.85 (s, 3H), 3.64 (s,6H), 1.07(d, J = 11.9 Hz, 9H). 31 P NMR (162 MHz, Chloroform-d) δ 13.31. 13C NMR (101MHz, Chloroform-d) δ 166.2, 161.0 (d, J = 11.7 Hz), 158.7, 131.3, 129.4 (d, J = 1.8 Hz), 117.9 (d, J = 16.0 Hz), 112.2 (d, J = 14.5 Hz), 104.4, 103.7,101.8 (d, J = 2.4 Hz), 75.7 (d, J = 23.9 Hz), 55.8, 55.4, 31.8 (d, J = 19.4Hz), 27.3 (d, J = 14.2 Hz). Example 16: Synthesis process of ligands (using ligand 1 as an example)

[0118] In an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding 2-triphenylphosphine benzaldehyde (0.3 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a white solid (1) in 83% yield with diastereoselectivity greater than 20:1.

[0119] Structural characterization data of product 1: White solid, 80 mg, 83% yield, >20:1 dr. 1 H NMR (600 MHz, CDCl3) δ (ppm)7.35-7.31 (m, 6H), 7.31-7.23 (m, 6H), 7.20-7.13 (m, 2H), 7.10 (t, J = 7.3 Hz, 1H), 6.90 (dd, J = 7.5, 4.8 Hz, 1H), 6.74 (d, J = 4.5 Hz, 1H), 6.65 (d, J =8.1 Hz, 1H), 6.49 (dd, J= 8.1, 3.5 Hz, 1H), 3.81 (s, 3H), 0.96 (d, J = 12.0Hz, 9H). 13 C NMR (101 MHz, CDCl3) δ (ppm) 166.1, 162.4 (d, J = 11.7 Hz), 146.5 (dd, J = 22.9, 15.4 Hz), 136.6 (dd, J = 67.4, 10.5 Hz), 134.7, 134.1 (d, J =18.9 Hz), 133.9 (d, J = 19.4 Hz), 132.6, 129.7, 128.8 (d, J = 9.8 Hz), 128.7 (d, J = 4.8 Hz), 128.6 (d, J = 6.6 Hz), 127.7 (d, J = 2.1 Hz), 125.6 (t, J =5.7 Hz), 104.1, 103.1 (d, J = 2.0 Hz), 83.0 (t, J = 28.5 Hz), 55.5, 33.7 (d, J = 22.6 Hz), 27.6 (dd, J = 13.3, 2.8 Hz). 31 P NMR (243 MHz, CDCl3) δ (ppm)11.07 (d, J = 17.7 Hz), -19.44 (d, J = 17.6 Hz). Example 17: Synthesis process of ligands (using ligand 5 as an example)

[0120] In an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (4.0 mmol) was dissolved in 40 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (6.0 mmol, 1.5 equiv.) and the corresponding 2,4,6-trimethoxybenzaldehyde (6.0 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a white solid (5) in 89% yield with diastereoselectivity greater than 20:1.

[0121] Structural characterization data of product 5: White solid, 1.38 g, 89% yield, >20:1 dr. 1 H NMR (400 MHz, CDCl3) δ (ppm)7.17 (t, J = 8.1 Hz, 1H), 6.50-6.39 (m, 3H), 6.08 (s, 2H), 3.85 (s, 3H), 3.78 (s, 3H), 3.63 (s, 6H), 1.05 (d, J = 11.8 Hz, 9H). 13 C NMR (101 MHz, CDCl3) δ (ppm) 166.1, 161.3 (d, J = 1.5 Hz), 161.0 (d, J = 11.5 Hz), 159.5, 131.2,112.9 – 110.1 (m), 103.8, 101.7 (d, J = 2.2 Hz), 91.1, 75.6 (d, J = 23.2 Hz),55.8, 55.5, 31.8 (d, J = 19.2 Hz), 27.3 (d, J = 14.2 Hz). 31 P NMR (162 MHz, CDCl3) δ (ppm) 12.42. Example 18: Synthesis process of ligands (using ligand 51 as an example)

[0122] In an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran, followed by the sequential addition of potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding 2-methylbenzaldehyde (0.3 mmol, 1.5 equiv.), with stirring until the reactants were completely consumed by TLC. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a colorless oily liquid (51) in 88% yield with a diastereoselectivity greater than 20:1.

[0123] Structural characterization data of product 51: Colorless oil, 63 mg, 88% yield, >20:1 dr. 1 H NMR (600 MHz, CDCl3) δ (ppm)7.40-7.33 (m, 2H), 7.23-7.18 (dd, J = 7.2, 2.1 Hz, 3H), 7.17-7.12 (t, J = 7.0Hz, 1H), 6.95 (d, J = 8.2 Hz, 1H), 6.90 (t, J = 8.1 Hz, 2H), 6.68 (td, J =8.0, 3.8 Hz, 1H), 6.58 (s, 1H), 2.38 (s, 3H). 13 C NMR (151 MHz, CDCl3) δ (ppm)167.0 (d, J = 7.6 Hz), 164.8 (dt, J = 249.6, 8.7 Hz), 164.5 (dd, J = 249.4, 13.6 Hz), 138.0 (d, J = 21.0 Hz), 134.3 (d, J = 4.8 Hz), 133.8 (d, J = 9.2Hz), 132.9 (t, J = 10.7 Hz), 131.0 (d, J = 2.2 Hz), 127.9 (d, J = 3.3 Hz), 126.4 (d, J = 2.5 Hz), 124.4 (d, J= 6.2 Hz), 112.7 – 111.5 (m), 108.2 (d, J = 21.8 Hz), 107.1 (d, J = 3.4 Hz), 85.7 (d, J = 22.3 Hz), 20.0 (d, J = 6.3Hz). 19 F NMR (565 MHz, CDCl3) δ (ppm) -101.44 (m), -103.10 (m). 31 P NMR (243MHz, CDCl3) δ (ppm) -37.48 (td, J = 33.0, 32.4, 6.9 Hz). Example 19: Synthesis process of ligands (using ligand 52 as an example)

[0124] In an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran, followed by the sequential addition of potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding pyridine-2-carboxaldehyde (0.3 mmol, 1.5 equiv.), with stirring until the reactants were completely consumed by TLC. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a white solid, 52, in 88% yield with diastereoselectivity greater than 20:1.

[0125] Structural characterization data of product 52: Colorless oil, 51 mg, 88% yield, >20:1 dr. 1 H NMR (400 MHz, CDCl3) δ (ppm)8.59 (d, J = 4.9 Hz, 1H), 7.58 (td, J = 7.7, 1.8 Hz, 1H), 7.32 (td, J = 8.1,6.1 Hz, 1H), 7.20-7.09 (m, 2H), 6.91 (dd, J = 8.2, 0.8 Hz, 1H), 6.70 (tdd, J = 8.0, 3.2, 0.8 Hz, 1H), 6.09 (s, 1H), 1.14 (d, J= 12.7 Hz, 9H). 13 C NMR (101MHz, CDCl3) δ (ppm) 166.0-165.7 (m), 163.4 (d, J = 12.6 Hz), 160.6 (d, J =14.3 Hz), 149.7, 136.9, 132.9 (d, J = 9.2 Hz), 122.2 (d, J = 2.5 Hz), 119.3(d, J = 3.6 Hz), 109.7 (d, J = 27.7 Hz), 108.8-108.2 (m), 107.1 (d, J = 3.3Hz), 86.3 (d, J = 28.6 Hz), 32.3 (d, J = 21.4 Hz), 27.0 (d, J = 14.5 Hz). 19 FNMR (376 MHz, CDCl3) δ (ppm) -102.71. 31 P NMR (162 MHz, CDCl3) δ (ppm) 11.69. Example 20: Synthesis process of ligands (using ligand 53 as an example)

[0126] In an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.5 mmol) was dissolved in 2 mL of dry tetrahydrofuran, followed by the sequential addition of potassium tert-butoxide solid (0.6 mmol, 3.0 equiv.) and the corresponding 1,3-m-phenylenedialdehyde (0.2 mmol, 1.0 equiv.). The reaction was stirred until TLC analysis showed complete consumption of the starting material. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a white solid, 53, in 49% yield with a 6:1 diastereoselectivity.

[0127] Structural characterization data of product 53: White solid, 49 mg, 49% yield, 6:1 dr. 1 H NMR (400 MHz, CDCl3) δ (ppm)7.31-7.19 (m, 3H), 7.10 (d, J= 6.7 Hz, 3H), 6.79 (ddd, J = 13.7, 8.1, 0.8Hz, 2H), 6.67 (dt, J = 8.0, 4.1 Hz, 2H), 5.94 (d, J = 3.4 Hz, 2H), 1.08 (d, J = 12.6 Hz, 18H). 13 C NMR (101 MHz, CDCl3) δ (ppm) 165.8 (d, J = 8.5 Hz), 163.4(d, J = 12.4 Hz), 141.7 (d, J = 16.6 Hz), 132.9 (d, J = 9.2 Hz), 129.0, 124.0 (dt, J = 7.8, 2.1 Hz), 121.5 (t, J = 7.0 Hz), 109.4 (dd, J = 27.6, 20.8 Hz), 108.2 (d, J = 22.7 Hz), 107.1-106.6 (m), 84.9 (d, J = 28.1 Hz), 32.1 (d, J =20.8 Hz), 27.0 (d, J = 14.6 Hz). 19 F NMR (376 MHz, CDCl3) δ (ppm) -102.99. 31 PNMR (162 MHz, CDCl3) δ (ppm) 12.36, 12.30. HRMS (ESI-TOF) m / z: [M+H] + Calcdfor C 28 H 31 F2O2P2 + = 499.1762; Found 499.1761. Example 21: Synthesis process of ligands (using ligand 54 as an example)

[0128] In an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.5 mmol) was dissolved in 2 mL of dry tetrahydrofuran, followed by the sequential addition of potassium tert-butoxide solid (0.6 mmol, 3.0 equiv.) and the corresponding ferrocene dialdehyde (0.2 mmol, 1.0 equiv.), with stirring until the reactants were completely consumed by TLC. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a yellow liquid (54) in 49% yield with diastereoselectivity greater than 20:1.

[0129] Structural characterization data of product 54: Yellow oil, 53 mg, 44% yield, >20:1 dr. 1 H NMR (400 MHz, CDCl3) δ (ppm)7.24 (td, J = 8.1, 6.2 Hz, 2H), 6.74 (t, J = 7.8 Hz, 2H), 6.65 (tdd, J = 7.9,3.4, 1.5 Hz, 2H), 5.75 (d, J = 7.5 Hz, 2H), 4.24-3.97 (m, 8H), 1.07 (dd, J =12.6, 4.3 Hz, 18H). 13 C NMR (101 MHz, CDCl3) δ (ppm) 165.4 (dd, J = 8.8, 5.3Hz), 164.4 (ddd, J = 246.7, 12.4, 3.8 Hz), 132.8 (d, J = 9.1 Hz), 110.3 (ddd, J = 27.4, 19.0, 4.7 Hz), 107.7 (d, J = 22.9 Hz), 107.3 (dd, J = 5.2, 3.2 Hz), 89.1 (dd, J = 21.9, 15.5 Hz), 82.2 (dd, J = 26.6, 6.1 Hz), 69.4, 69.4 (d, J =30.5 Hz), 68.4 (dd, J= 46.1, 8.2 Hz), 67.5 (dd, J = 14.7, 8.0 Hz), 32.0 (d, J = 19.3 Hz), 27.1 (dd, J = 14.5, 2.6 Hz). 19 F NMR (376 MHz, CDCl3) δ (ppm) -103.46. 31 P NMR (162 MHz, CDCl3) δ (ppm) 1.63, 1.08. Example 22: Synthesis process of ligands (using ligand 55 as an example)

[0130] Under an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.2 mmol) was dissolved in 2 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding benzaldehyde (0.3 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until TLC analysis showed complete consumption of the starting material. Subsequently, sulfur powder (0.6 mmol, 3.0 equiv.) was added under an argon atmosphere, and the mixture was stirred at room temperature for 0.5 hours. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a white solid (55) in 91% yield with diastereoselectivity greater than 20:1.

[0131] Structural characterization data of product 55: White solid, 55 mg, yield 91%, >20:1 dr. 1 H NMR (400 MHz, CDCl3) δ (ppm)8.49 (dd, J = 3.9, 1.8 Hz, 1H), 7.41-7.32 (m, 5H), 7.25-7.22 (m, 2H), 5.93(d, J = 1.4 Hz, 1H), 1.36 (d, J = 17.6 Hz, 9H). 13 C NMR (101 MHz, CDCl3) δ (ppm) 158.0 (d, J = 28.7 Hz), 146.2 (d, J = 14.9 Hz), 140.4 (d, J = 101.5Hz), 133.8 (d,J = 2.2 Hz), 128.6 (d, J = 2.6 Hz), 128.1 (d, J = 1.8 Hz), 127.1 (d, J = 2.8 Hz), 126.9 (d, J = 4.3 Hz), 120.0 (d, J = 5.0 Hz), 79.2 (d, J = 40.4 Hz), 36.2 (d, J = 47.9 Hz), 24.4. 31 P NMR (162 MHz, CDCl3) δ (ppm)65.47. Example 23: Synthesis process of ligands (using ligand 21 as an example)

[0132] Under an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.2 mmol) was dissolved in 1 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.3 mmol, 1.5 equiv.) and the corresponding ethylene oxide solution (1.0 mL, 1.0 mmol, 5.0 equiv.) were added sequentially, and the reaction was stirred until the starting material was completely consumed by TLC. Then, sulfur powder (0.6 mmol, 3.0 equiv.) was added under an argon atmosphere, and the mixture was stirred at room temperature for 0.5 hours. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–20:1) as eluent, yielding a colorless oily liquid in 80% yield.

[0133] Structural characterization data of product 21: 82.0 mg, 80% yield, 24 h, colorless oil. 1 H NMR (400 MHz, CDCl3) δ(ppm) 7.33 (q, J = 7.9 Hz, 1H), 6.79-6.70 (m, 2H), 4.66-4.52 (m, 1H), 4.51-4.41 (m, 1H), 2.85-2.75 (m, 1H), 2.22-2.08 (m, 1H), 1.27 (d, J = 18.1 Hz, 9H). 13 C NMR (100 MHz, CDCl3) δ (ppm) 164.1 (d, J= 250.1 Hz), 160.5 (dd, J =7.3, 1.4 Hz), 133.5 (d, J = 10.7 Hz), 114.8 (dd, J = 4.4, 3.6 Hz), 109.1(dd, J = 23.2, 4.4 Hz), 105.4 (dd, J = 63.9, 22.8 Hz), 77.3, 77.0, 76.7, 63.4(d, J = 6.6 Hz), 35.8 (d, J = 52.1 Hz), 30.1 (d, J = 51.7 Hz), 25.3 (dd, J =4.3, 2.8 Hz). 19 F NMR (376 MHz, CDCl3) δ (ppm) -96.10. 31 P NMR (162 MHz, CDCl3)δ (ppm) 39.40. Example 24: Synthesis process of ligands (using ligand 23 as an example)

[0134] Under an argon atmosphere at room temperature, the corresponding substrate phosphine hydrogen (0.4 mmol) was dissolved in 1 mL of dry tetrahydrofuran. Potassium tert-butoxide solid (0.6 mmol, 1.5 equiv.) and the corresponding epoxide compound (0.6 mmol, 1.5 equiv.) were added sequentially, and the reaction was stirred until the starting material was completely consumed by TLC. Then, sulfur powder (4.0 mmol, 10.0 equiv.) was added under an argon atmosphere, and the mixture was stirred at room temperature for 2 hours. Purification was performed by column chromatography using degassed petroleum ether-ethyl acetate (100:0–5:1) as eluent, yielding a white solid, 23, in 89% yield.

[0135] Structural characterization data of product 23: White solid, 152 mg, 89% yield. 1 H NMR (400 MHz, CDCl3) δ (ppm) 7.38 (q, J = 8.1 Hz, 1H), 6.84-6.77 (m, 2H), 4.04-3.84 (m, 1H), 3.80-3.66 (m, 1H), 3.40 (t,J = 10.5 Hz, 1H), 2.95-2.82 (m, 1H), 2.70 (dd, J = 14.5, 6.0 Hz, 1H), 2.44 (d, J = 15.0 Hz, 1H), 2.22 (t, J = 14.9 Hz, 1H), 1.91-1.76 (m, 3H), 1.45 (s, 9H), 1.22 (d, J = 18.0 Hz, 9H). 13 C NMR (101 MHz, CDCl3) δ (ppm)164.2 (d, J = 253.0 Hz), 157.0 (d, J = 6.3 Hz), 154.7, 133.9 (d, J = 11.2Hz), 115.6 (dd, J = 4.5, 3.2 Hz), 110.0 (dd, J = 23.5, 4.6 Hz), 105.4 (dd, J = 64.3, 20.4 Hz), 79.8 , 75.7 (d, J = 5.8 Hz), 39.8, 39.3, 39.1, 39.0, 36.9,36.4, 31.8, 28.4, 24.7 (t, J = 2.9 Hz). 19 F NMR (376 MHz, CDCl3) δ (ppm) -95.21. 31 P NMR (162 MHz, CDCl3) δ (ppm) 32.17. Example 25: Palladium-catalyzed Suzuki coupling reaction

[0136] In an argon atmosphere at room temperature, the corresponding aryl chloride (0.5 mmol), phenylboronic acid (0.75 mmol), and potassium trimethylsilanoate (1.0 mmol) were added sequentially to 10 mL pressure-resistant sealed tubes, dissolved in 1 mL toluene. Finally, a pre-complexed palladium / ligand complex solution (0.1% mol) was added, and the reaction was carried out at 100 °C for 24 hours. The final product 49 or 50 was obtained by column chromatography.

[0137] Structural characterization data of product 49: 82.0 mg, 90% yield, 24 h, colorless oil. 1 H NMR (400 MHz, CDCl3): δ(ppm) 7.16-7.24 (m, 5H), 7.39 (dt, J = 7.0, 1.2 Hz, 1H,), 7.48 (dt, J = 7.0,1.1 Hz, 2H), 2.10 (s, 6H). 13 C NMR (100 MHz, CDCl3): δ (ppm) 141.8, 141.0,136.0, 129.0, 128.4, 127.2, 127.0, 126.6, 20.8. Structural characterization data of product 50: 86.5 mg, 95% yield, 24 h, colorless oil. 1 H NMR (400 MHz, DMSO- d 6 ) δ10.04 (s, 1H), 8.05-7.94 (m, 2H), 7.93-7.85 (m, 2H), 7.83-7.71 (m, 2H), 7.54-7.39 (m, 3H). 13 C NMR (101 MHz, DMSO- d 6 ) δ (ppm) 193.2, 146.3, 139.3, 135.6,130.6, 129.6, 129.1, 127.8, 127.6. Example 26: Palladium-catalyzed CN coupling reaction Ligand 56 was synthesized using the method described in Example 3.

[0138]

[0139] Structural characterization data of ligand 56: White solid. 1 H NMR (400 MHz, CDCl3): δ (ppm) 8.10 (dd, J = 7.7, 3.8 Hz, 2H), 7.56 (dd, J = 8.2, 2.9 Hz, 1H), 7.40 (ddd, J= 12.3, 8.7, 4.9 Hz, 4H),7.30 – 7.21 (m, 2H), 7.00 (dd, J = 7.7, 2.9 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.53 (d, J = 3.8 Hz, 1H), 6.17 (s, 2H), 3.82 (s, 3H), 3.74 (s, 6H), 0.59(d, J = 12.1 Hz, 9H). 13 C NMR (100 MHz, CDCl3): δ (ppm) 166.7, 161.3, 159.1,141.4, 139.1, 139.0, 138.9, 131.2, 125.8, 125.3, 124.2, 123.9, 123.6, 123.2,120.2, 119.9, 119.8, 119.7, 119.5, 119.4, 112.1, 112.0, 110.4, 110.3, 110.1,109.4, 91.0, 77.3, 77.0, 76.7, 75.5, 75.2, 55.7, 55.4, 31.4, 31.2, 26.5, 26.3. 31 P NMR (162 MHz, CDCl3) δ 15.52. Synthesized compound 57:

[0140] In an argon atmosphere at room temperature, the corresponding Pd2dba3 and ligand 56 were prepared into a toluene solution with a [Pd] molar concentration of 0.002 mmol / mL at a molar ratio of 0.5:2.2 (e.g., Pd2dba3 (0.05 mol%), 56 (0.22 mol%)). The complex solution was stirred for 30 minutes under an argon atmosphere. Subsequently, the corresponding carbazole (1.1 mmol) and sodium hydride (1.1 mmol) were added to a dry 10 mL pressure-resistant sealed tube, followed by 1 mL of toluene. The mixture was stirred at room temperature for 10 minutes, then chlorobenzene (1.0 mmol), the corresponding [Pd] catalyst, and toluene were added again, bringing the solvent volume to 3.0 mL. After the addition was complete, the reaction tube was placed at 110°C. o The reaction was carried out at C for 24 hours. The solvent was then removed by vacuum distillation, and the final target product 57 was obtained by column chromatography (using pure petroleum ether as eluent). The corresponding separation yields are as described in the above equations.

[0141] The reaction proceeds smoothly when Pd2dba3 is 0.025 mol% and 56 is 0.11 mol%.

[0142] Structural characterization data of product 57: White solid. 1 H NMR (400 MHz, CDCl3): δ (ppm) 8.09 (d, J = 7.8 Hz, 2H),7.53 – 7.46 (m, 4H), 7.41 – 7.31 (m, 5H), 7.23 (ddd, J = 8.0, 5.8, 2.3 Hz, 2H). 13 C NMR (400 MHz, CDCl3) δ 140.8, 137.6, 129.8, 127.3, 127.0, 125.9,123.3, 120.2, 119.9, 109.7, 77.3, 77.0, 76.7. Synthesize 58:

[0143] In an argon atmosphere at room temperature, the corresponding Pd2dba3 (4.6 mg, 0.005 mmol) and ligand 56 (11.55 mg, 0.022 mmol) were dissolved in 1 mL of toluene. The complex solution was stirred for 30 minutes under an argon atmosphere. Subsequently, the corresponding 2,6-dimethylchlorobenzene (0.2 mmol), 2,6-dimethylaniline (0.4 mmol), and sodium methoxide (0.4 mmol) were added to a dry 10 mL pressure-resistant sealed tube, followed by 1 mL of toluene. After the addition was complete, the reaction tube was placed at 110°C. o The reaction was carried out at C for 24 hours. The solvent was then removed by vacuum distillation, and the final target product 58 was obtained by column chromatography (using pure petroleum ether as eluent). The corresponding separation yields are as described in the above equations.

[0144] Structural characterization data of product 58: White solid, 45.1 mg, yield greater than 99%. 1 H NMR (400 MHz, CDCl3): δ (ppm) 6.97(d, J = 7.5 Hz, 4H), 6.83 (t, J = 7.5 Hz, 2H), 4.79 (s, 1H), 2.00 (s, 12H). 13C NMR (400 MHz, CDCl3) δ 13C NMR (101 MHz, CDCl3) δ 141.7, 129.5, 128.7,121.7, 77.3, 77.0, 76.7, 19.1. Example 27

[0145] Under an argon atmosphere, bromobenzene (3.14 g, 20 mmol), p-methoxyphenylboronic acid (3.65 g, 24 mmol), palladium acetate (44.8 mg, 0.2 mmol), and ligand I-15 (131.4 mg, 0.4 mmol) prepared in the present invention were added to a 100 mL flask. Then, sodium carbonate solution (3.0 M, 20 mL) and 20 mL of dimethoxyethane were added. The reaction system was heated under reflux for 24 hours. 4-Phenylacetyl ether (3.35 g, 91% yield) was obtained by column chromatography using petroleum ether and ethyl acetate as developing solvents (PE / EA = 20 / 1).

[0146] Example 28

[0147] Under an argon atmosphere, PhOTf (4.52 g, 20 mmol), m-methoxyphenylboronic acid (3.65 g, 24 mmol), palladium acetate (44.8 mg, 0.2 mmol), and ligand I-15 (131.4 mg, 0.4 mmol) were added to a 100 mL flask. Then, sodium carbonate solution (3.0 M, 20 mL) and 20 mL of dimethoxyethane were added. The reaction system was heated under reflux for 24 hours. 3-Phenylacetyl ether (3.50 g, 95% yield) was obtained by column chromatography using petroleum ether and ethyl acetate as the developing solvent (PE / EA = 20 / 1).

[0148] Example 29

[0149] Under an argon atmosphere, iodobenzene (4.08 g, 20 mmol), p-methoxyphenylboronic acid (3.65 g, 24 mmol), palladium acetate (44.8 mg, 0.2 mmol), and ligand I-15 (131.4 mg, 0.4 mmol) were added to a 100 mL flask. Then, sodium carbonate solution (3.0 M, 20 mL) and 20 mL of dimethoxyethane were added. The reaction system was heated under reflux for 24 hours. 4-Phenylacetyl ether (3.46 g, 94% yield) was obtained by column chromatography using petroleum ether and ethyl acetate as developing solvents (PE / EA = 20 / 1).

[0150] The method of this invention has been described through preferred embodiments. Those skilled in the art will readily be able to modify or appropriately alter and combine the methods and applications described herein within the scope, spirit, and context of this invention to implement and apply the technology of this invention. Those skilled in the art can refer to the content herein to appropriately improve process parameters. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of this invention.

Claims

1. A substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand, characterized in that, Its structure is shown in equation (I). （I）； Among them, R 4 The following are compounds: hydrogen, alkyl, alkenyl, cycloalkyl, heterocyclic, alkylOC(=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O), ferrocene, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, cycloalkylalkyl, heterocyclic alkyl, arylalkyl, or heteroarylalkyl; or, R 4 and R 5 Linked together, the carbon atoms linked to them form cycloalkyl or heterocyclic groups; or, R 4 and its adjacent R 6 They are linked together, forming cycloalkyl or heterocyclic groups with the carbon atoms they are linked to; X 1 For N or CR X1 ; X 2 For N or CR X2 ; R X1 and R X2 Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, -SO2NMe2, or halogen; =O or =S; or It does not exist; R 1 It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, -SO2NMe2, or halogen; R 2 It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, -SO2NMe2, or halogen; Or R 1 and R 2 They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3 It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5 It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; R 6 It is hydrogen; n is 0 or 1; Or R 4 for ; Among them, X 1a For N or CR X1a ;X 2a For N or CR X2a ; R X1a and R X2a Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, fluorine, chlorine, bromine, or iodine; =O or =S; or It does not exist; Z represents a single bond, a cycloalkylene group, a heterocyclic group, an aryl group, a heteroaryl group, an alkylene group, or... ; R 1a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; R 2a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; Or R 1a and R 2a They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3a It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5a It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; m is 0 or 1 The alkyl, alkenyl, cycloalkyl, heterocyclic, aryl, heteroaryl, cycloalkylene, heterocyclic, arylene, heteroarylene, and alkylene groups mentioned in the single or complex groups mentioned above are each independently and optionally surrounded by 1, 2, 3, 4, or 5 groups selected from hydroxyl, amino, halogen, carboxyl, sulfonyl, alkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, alkylthio, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, alkylNH-, (alkyl)2N-, alkylOC Substituents of (=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O) and dicycloalkyloxyphospho(=O).

2. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1, characterized in that, It has the characteristics shown in formula IA or formula II-A: ； in, R 1 Selected from one of H, F, SO2NMe2; R X2 Selected from F, Cl, Br or I; R 3 Selected from aryl or alkyl groups; R 4 Selected from hydrogen, aryl, heteroaryl, or alkyl; The aryl or heteroaryl group is either unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents selected from halogen, PPh2, N(alkyl)2, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 alkylthio.

3. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1 or 2, characterized in that, R 1 Selected from H and F; R X2 Selected from F; R 3 Selected from C 6-10 One of aryl or C1-6 alkyl groups; R 4 Selected from C 6-10 One of aryl, heteroaryl (composed of 3-6 atoms), or C1-6 alkyl; The C 6-10 Aryl, heteroaryl or C1-6 alkyl groups consisting of 3-6 atoms, are unsubstituted or replaced by 1, 2, 3, 4 or 5 atoms selected from halogens, PPh2, NMe 2、 SMe 2、 C1-6 haloalkyl, and / or C 1-6 The alkoxy group is replaced by a substituent.

4. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1 or 2, characterized in that, Choose from one of the following structures: 。 5. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1, characterized in that, Its structure is shown in equation IB. (I-B); in, R 4 The following are compounds: hydrogen, alkyl, alkenyl, cycloalkyl, heterocyclic, alkylOC(=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O), ferrocene, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, cycloalkylalkyl, heterocyclic alkyl, arylalkyl, or heteroarylalkyl; or, R 4 and R 5 Linked together, the carbon atoms linked to them form cycloalkyl or heterocyclic groups; or, R 4 and its adjacent R 6 They are linked together, forming cycloalkyl or heterocyclic groups with the carbon atoms they are linked to; X 1 For N or CR X1 ; X 2 For N or CR X2 ; R X1 and R X2 Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, or halogen; =O or =S; or It does not exist; R 1 It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; R 2 It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; Or R 1 and R 2 They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3 It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5 It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; R 6 It is hydrogen; n is 0 or 1; Or R 4 for ;in, X 1a For N or CR X1a ; X 2a For N or CR X2a ; R X1a and R X2a Each of these can be independently hydrogen, amino, hydroxyl, alkyl NH-, (alkyl)2N-, alkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, fluorine, chlorine, bromine, or iodine; =O or =S; or It does not exist; Z represents a single bond, a cycloalkylene group, a heterocyclic group, an aryl group, a heteroaryl group, an alkylene group, or... ; R 1a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; R 2a It can be hydrogen, alkyl, aryl, heteroaryl, alkyloxy, or halogen; Or R 1a and R 2a They are linked together, forming aryl or heteroaryl groups with the carbon atoms they are linked to. R 3a It can be hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, or alkyloxy; R 5a It can be hydrogen, alkyl, aryl, heteroaryl, or alkyloxy; m is 0 or 1 The alkyl, alkenyl, cycloalkyl, heterocyclic, aryl, heteroaryl, cycloalkylene, heterocyclic, arylene, heteroarylene, and alkylene groups mentioned in the single or complex groups mentioned above are each independently and optionally surrounded by 1, 2, 3, 4, or 5 groups selected from hydroxyl, amino, halogen, carboxyl, sulfonyl, alkyl, haloalkyl, cycloalkyl, heterocyclic, aryl, heteroaryl, alkyloxy, alkylthio, cycloalkyloxy, heterocyclicoxy, aryloxy, heteroaryloxy, alkylNH-, (alkyl)2N-, alkylOC Substituents of (=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O); The condition is that the structure shown in equation (IB) does not include the following structures: ； Or the condition is that, in the structure shown by the formula (IB), when R X1a When it is F, =O or =S; Or the condition is that, in the structure shown by the formula (IB), when R X1a When it is F, R 4 The following are compounds: hydrogen, alkenyl, alkyl, cycloalkyl, heterocyclic, alkylOC(=O)-, alkylC(=O)O-, dialkylphospho, diarylphospho, di(3,5-dimethyl-4-methoxyphenyl)phospho, di(3,5-di-tert-butyl-4-methoxyphenyl)phospho, dicycloalkylphospho, dialkoxyphospho, diaryloxyphospho, dicycloalkyloxyphospho, dialkylphospho(=O), diarylphospho(=O), dicycloalkylphospho(=O), dialkoxyphospho(=O), diaryloxyphospho(=O), dicycloalkyloxyphospho(=O), ferrocene, alkyloxy, cycloalkyloxy, heterocyclic oxy, aryloxy, heteroaryloxy, cycloalkylalkyl, heterocyclic alkyl, arylalkyl, or heteroarylalkyl; or, R 4 and R 5 Linked together, the carbon atoms linked to them form cycloalkyl or heterocyclic groups; or, R 4 and its adjacent R 6 Linked together, they form cycloalkyl or heterocyclic groups with the carbon atoms they are linked to; or R 4 for .

6. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1 or 5, characterized in that, and Each and every one of them is selected independently from: 。 7. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1 or 5, characterized in that, R 4 Selected from: 。 8. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1 or 5, characterized in that, R 3 Or R 3a Each is selected independently from: 。 9. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1 or 5, characterized in that, Z is selected from: 。 10. The substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand according to claim 1 or 5, characterized in that, The compounds represented by Formula I are selected from: 。 11. A bisphosphine palladium acetate complex, characterized in that, It has the structure described in Formula II-B: II-B; Among them, R 1 R 2 R 3 R 4 R 5 R 6 X 1 X 3 Y and n have the definitions described in any one of claims 1-10.

12. A coupling reaction method, characterized in that, The method uses a bisphosphine palladium acetate complex prepared by the substituted benzoxophosphine ligand according to any one of claims 1-10 or the bisphosphine palladium acetate complex according to claim 11 as a catalyst.

13. The method according to claim 12, characterized in that, The coupling reaction method is a CC coupling reaction, which includes: reacting the aryl halide and the arylboronic acid structure in the bisphosphine palladium acetate complex under organic solvent and alkaline conditions; Alternatively, the coupling reaction method may be a CN coupling reaction, comprising: reacting the aryl halide and the aromatic amine structure in the bisphosphine palladium acetate complex under organic solvent and alkaline conditions; The solvent is N,N - Dimethylformamide, toluene, trifluorotoluene, carbon tetrachloride, dioxane, hexafluoroisopropanol, ethyl acetate; the base is potassium tert-butoxide, sodium tert-butoxide, lithium methoxide, cesium carbonate, sodium acetate, sodium hydroxide, potassium hydroxide, sodium hydroxide.

14. The method according to claim 13, characterized in that, The arylboronic acid structures include arylboronic acid or arylboronic esters; the aryl halogenated products are aryl chlorides and aryl bromides; the aryl amine structures include primary amines or secondary amines.

15. A method for preparing a substituted 2,3-dihydrobenzo[d][1,3]oxaphosphazene ligand, comprising: S11. Under inert gas protection, Formula III is reacted with a base in an organic solvent and stirred to obtain a salt solution of Formula III. S12. After adding the aldehyde or ethylene oxide derivative V shown in Formula IV to the obtained salt solution of Formula III, the reaction is carried out at 0-50 °C to obtain the 2,3-dihydrobenzo[d][1,3]oxaphosphanecyclopentene derivative shown in Formula I. ， Among them, R 1 Selected from one of H, F, SO2NMe2; R X2 Selected from F, Cl, Br or I; R 3 Selected from aryl or alkyl; R 4 It is selected from one of aryl, heteroaryl, or alkyl; the aryl or heteroaryl group is unsubstituted or substituted by 1, 2, 3, 4, or 5 substituents selected from halogen, PPh2, N-alkyl, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 alkylthio.

16. The preparation method according to claim 15, wherein the organic solvent is selected from one or more of 1,4-dioxane, tetrahydrofuran, diethyl ether, dichloromethane, 1,2-dichloroethane, toluene, n-hexane, or dimethyl sulfoxide.

17. The preparation method according to claim 15, wherein the alkali is selected from one or more of cesium carbonate, potassium carbonate, sodium carbonate, potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium ethoxide, sodium acetate, or sodium hydroxide.

18. In the preparation method according to claim 15, the molar ratio of arylphosphine hydrogen represented by Formula III, aldehyde represented by Formula IV or epoxy compound represented by Formula V, and base in the mixed system in step S12 is 1:1.5:1.

5.

19. The use of the substituted 2,3-dihydrobenzo[d][1,3]oxaphosphacyclopentene ligand as described in any one of claims 1-10 or the substituted 2,3-dihydrobenzo[d][1,3]oxaphosphacyclopentene ligand prepared by any one of the preparation methods of claims 15-18 in the coupling reaction of arylboronic acids and haloaryl groups. ， in, Ar 1 and Ar 2 Each can be independently classified as aryl or heteroaryl.

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