Cinchonine-derived tetrazole tridentate chiral N, N, P-ligand (Zhenspace peak type chiral anion ligand) as well as preparation method and application of cinchona-alkali-derived tetrazole tridentate chiral N, N, P-ligand

Abstract

The invention belongs to the field of organic chemical ligands, and discloses a cinchona alkali-derived tetrazole tridentate N, N, P-ligand (Zhang Pan peak type chiral anion ligand) with a structure as shown in a general formula I and a synthesis method of the ligand. According to the invention, a cinchona alkali tetrazole derivative and large steric hindrance trivalent phosphorus are used as a core skeleton; the tridentate N, N, P-ligands with novel structures (such skeleton ligands are named Zhang-Ph type chiral anion ligands) are developed, the novel chiral ligands have rich structural characteristics, the electronic effect and steric effect of aryl substituents on trivalent phosphorus can be regulated and controlled, and additional weak acting force can be provided through alkyl chains, so that the chiral ligand can be used for preparing chiral ligand compounds with high selectivity. Therefore, excellent enantioselectivity is induced. The ligand disclosed by the invention can be widely applied to the three-dimensional convergent free radical asymmetric cross-coupling reaction of secondary dialkyl substituted halogenated alkane and sulfoximide, and has important guiding significance for developing a novel catalytic system to solve other types of three-dimensional convergent free radical asymmetric reactions.

Description

Technical Field

[0001] The present invention belongs to the field of organic chemical chiral ligands, and specifically is a cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand (Zhang Yufeng type chiral anionic ligand) and a preparation method and use thereof. Background Art

[0002] Quinine and its analogs are an important class of chiral natural products that are widely present in nature. Based on their complex spatial structure and multiple coordination sites, they have been used in asymmetric catalytic reactions of small organic molecules. In recent years, with the rapid development of the field of cheap 3d transition metal asymmetric catalysis, the demand for various new chiral ligand skeletons has increased. The nitrogen-nitrogen-phosphorus (N,N,P) chiral anionic ligands derived from quinine and its analogs contain a tertiary amine, a trivalent phosphorus, and an amide structure (which can be deprotonated to form an amide anion under the action of a base). The tertiary amine and trivalent phosphorus can form a coordination bond with the metal, and the amide nitrogen can form an ionic bond with the metal after deprotonation of the base to form a metal-centered electron-rich chiral complex for catalytic reactions. This type of anionic ligand can enhance the reducing ability of transition metals, allowing them to undergo a single electron transfer reaction with halogenated alkanes to produce alkyl radical species; it can also solve the problem of transition metal poisoning, thereby solving some problems that cannot be solved by neutral ligands. Therefore, the design and synthesis of new anionic ligands has become a research hotspot in the field of metal asymmetric catalysis.

[0003] As transition metal-catalyzed radical asymmetric chemistry has received increasing attention, new metals and chiral ligand skeletons have become research hotspots. Previously, it has been reported that nitrogen-nitrogen-phosphorus ligands derived from quinine molecules were used in copper-catalyzed radical asymmetric coupling chemistry at activated sites such as the ben position, propargyl position, allylic position, amide α-position, ketone α-position, and cyano α-position. However, since the substituents on the phosphorus of the previously synthesized ligands were all commercially available aromatic or alkyl groups, they had structural limitations, especially for the asymmetric catalytic effect on secondary alkyl radical intermediates at non-activated sites. The discrimination of dialkyl prochiral substrates is small, and it is difficult for ordinary catalytic systems to effectively distinguish them, resulting in low stereoselectivity and low optical purity of the products. The asymmetric catalytic construction of chiral compounds involving such compounds is a very important difficulty and challenge to be solved in organic chemistry. It is necessary to further develop more types of chiral anionic ligands to provide specific stereo environments for such reactions, so as to achieve a broader spectrum of asymmetric catalytic systems.

[0004] Therefore, further modification of the cinchona alkaloid-type ligand skeleton structure to obtain new cinchona alkaloid compounds has important application value for enriching the types of this type of catalyst and expanding its application range. Summary of the invention

[0005] The purpose of the present invention is to provide a tridentate N,N,P-chiral anionic ligand (named in Chinese as Zhang Yufeng type chiral anionic ligand, the full English name is Zhang Yu-Feng type chiral anionic ligands, abbreviated as ZhangCAL) with wide application and novel structure.

[0006] In a first aspect, the present invention provides a cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound represented by general formula I, or its tautomers, enantiomers, and diastereomers:

[0007] Among them, the R 1 is selected from substituted or unsubstituted alkyl; The R 2 Each independently selected from a substituted or unsubstituted alkyl group, a substituted or unsubstituted monocyclic aromatic group, a C6-C14 substituted or unsubstituted condensed ring group; The R 3 Selected from alkoxy; The carbon atom marked with * is an R configuration, an S configuration, or an achiral carbon atom.

[0008] In some of the cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compounds of the general formula I of the first aspect, or their tautomers, enantiomers, and diastereomers, multiple R 2 Each independently selected from a C6~C14 fused ring group, the fused ring group is formed by condensing at least one first ring and at least one second ring, the first ring is selected from a C3~C6 cycloalkyl group, and the second ring is selected from a monocyclic aromatic group.

[0009] In some of the cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compounds of the general formula I of the first aspect, or their tautomers, enantiomers, and diastereomers, multiple R 2 Each independently selected from a monocyclic aromatic group, any hydrogen on the monocyclic aromatic group is replaced by R a Replacement, structure such as: , wherein n is selected from any positive integer from 1 to 3, and the plurality of R a each independently selected from hydrogen, substituted or unsubstituted methyl, substituted or unsubstituted adamantyl, substituted or unsubstituted n-propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylsilyl, substituted or unsubstituted alkylgermanyl, In some of the cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compounds of the general formula I of the first aspect, or their tautomers, enantiomers, and diastereomers, the Ra Any one of alkoxy and isopropyl, wherein R a Structure like -OR aa , the R aa Each independently selected from substituted or unsubstituted methyl, substituted or unsubstituted monocyclic aryl, substituted or unsubstituted isopropyl; The R selected from isopropyl a Structure , the R ab is selected from substituted or unsubstituted methyl, unsubstituted ethyl, substituted or unsubstituted octyl, substituted or unsubstituted propyl, substituted or unsubstituted butyl, substituted or unsubstituted hexyl, substituted or unsubstituted nonyl, substituted or unsubstituted decyl, substituted or unsubstituted undecyl to hexadecyl, substituted or unsubstituted cyclohexane, Or, the R a2 is selected from substituted ethyl, said R ab Any hydrogen atom is replaced by tert-butyl or ethyl.

[0010] In some of the cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compounds of the general formula I of the first aspect, or their tautomers, enantiomers, and diastereomers, the R a Selected from alkylsilyl, the alkylsilyl structure is as follows , the R ac is selected from methyl, ethyl, tert-butyl, n-butyl, n-octyl, n-hexyl, n-dodecyl, n-octadecyl, cyclohexyl, and the plurality of R ad Each is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl and n-hexyl.

[0011] In some of the cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compounds of the general formula I of the first aspect, or their tautomers, enantiomers, and diastereomers, the R ac is selected from ethyl, any hydrogen on the ethyl is replaced by a monocyclic aromatic group, and the R ac Selected from tert-butyl, wherein any hydrogen on the tert-butyl is replaced by isopropyl.

[0012] In some of the cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compounds of the general formula I of the first aspect, or their tautomers, enantiomers, and diastereomers, the R a Selected from alkylgermanium groups, the alkylgermanium group structure is as follows: , Multiple R ae Each is independently selected from methyl and ethyl.

[0013] In some of the cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compounds of the general formula I of the first aspect, or their tautomers, enantiomers, and diastereomers, the R a is selected from methyl, wherein any hydrogen on the methyl is replaced by halogen.

[0014] The second aspect of the present invention proposes a specific form of the cinchona alkaloid-derived tetrazole tridentate N,N,P-ligand described in the first aspect, the structure of which is shown below:

[0015]

[0016]

[0017]

[0018]

[0019]

[0020]

[0021]

[0022]

[0023]

[0024]

[0025]

[0026] .

[0027] The third aspect of the present invention provides a method for preparing the cinchona alkaloid-derived tetrazole tridentate N,N,P-ligand described in the first aspect, comprising the following steps:

[0028] Compound S2 reacts with diethyl phosphite to obtain intermediate S3;

[0029] Intermediate S3 reacts with methyl o-iodobenzoate to obtain intermediate S4;

[0030] Intermediate S4 reacts with arylboronic acid to obtain intermediate S5;

[0031] Deoxygenation of intermediate S5 gave intermediate S6;

[0032] Intermediate S6 is hydrolyzed to give intermediate S7;

[0033] The intermediate S7 and the quinine derivative S8 undergo a condensation reaction to obtain a product; The R 1 Selected from ethyl; The R 2 As defined in any embodiment of the first aspect; The R 3 Selected from methoxy.

[0034] The fourth aspect of the present invention provides an α-methylbenzylamine asymmetric catalytic method, comprising:

[0035] Adding compound 1, compound 2 and an organic solvent into a reaction system consisting of a copper salt, a ligand and a base, and reacting under light with a wavelength of 350 to 400 nanometers to obtain a product a1;

[0036] Mix metallic magnesium and compound a1, then add alcohol and react under controlled temperature to obtain product a2.

[0037] The terms "alkylsilyl" and "alkylsilyl" mean that the hydrogen atoms in the methylsilyl (-SiH3) group are independently replaced by 1, 2 or 3 alkyl groups. Among them, in some embodiments, the alkylsilyl group is a lower alkylsilyl group formed by 1, 2 or 3 C1~12 alkyl groups connected to the silicon atom. In other embodiments, the alkylsilyl group is a lower alkylsilyl group formed by 1, 2 or 3 C1~9 alkyl groups connected to the silicon atom. In other embodiments, the alkylsilyl group is a lower alkylsilyl group formed by 1, 2 or 3 C1~6 alkyl groups connected to the silicon atom. In other embodiments, the alkylsilyl group is a lower alkylsilyl group formed by 1, 2 or 3 C1~4 alkyl groups connected to the silicon atom. In still other embodiments, the alkylsilyl group is a lower alkylsilyl group formed by 1, 2 or 3 C1~3 alkyl groups connected to the silicon atom. Suitable alkylsilyl groups may be monoalkylsilyl, dialkylsilyl or trialkylsilyl. Examples of alkylsilyl groups include, but are not limited to, trimethylsilyl (-Si(CH3)3), triethylsilyl (-Si(CH2CH3)3), tri-n-propylsilyl (-Si(CH2CH2CH3)3), and the like.

[0038] The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon radical, the carbon ring may contain 3 to 20 carbon atoms, preferably 3 to 12 (e.g. 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) carbon atoms, more preferably 3 to 6 carbon atoms. Wherein the partially unsaturated monocyclic or polycyclic hydrocarbon radical is a saturated cycloalkyl radical or may optionally contain one, two or more double bonds and / or triple bonds on its ring, thereby forming a so-called cycloalkenyl or cycloalkynyl radical.

[0039] The cinchona alkaloid-derived tetrazole tridentate N,N,P-ligand (Zhang Yufeng type chiral anionic ligand) of the present invention has good application in asymmetric reactions, especially in the reaction of synthesizing α-chiral amines by asymmetric cross-coupling of free radicals.

[0040] Unless otherwise stated, chemicals were purchased from commercial products and were not further purified. Solvents such as dichloromethane and tetrahydrofuran used in the experiments were all anhydrous solvents. Thin layer chromatography (TLC) used 60F254 silica gel plates. Silica gel column chromatography used Qingdao Ocean Silica Gel (particle size 0.040-0.063 mm). TLC color development used UV light (254 nm) or iodine. NMR spectra were characterized using a Bruker DPX 400 nuclear magnetic resonance instrument. 1 HNMR is 400MHz, the solvent is deuterated chloroform, and tetramethylsilane (TMS) is used as the internal standard. The unit of chemical shift is ppm, and the unit of coupling constant is Hz. 1 In HNMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, p represents quintet, and m represents multiplet.

[0041] As used herein, the term "halogen" refers to fluorine, chlorine, bromine and iodine.

[0042] The present invention has the following beneficial effects: The present invention uses cinchona tetrazolium derivatives and large sterically hindered trivalent phosphorus as core skeletons, develops a type of novel tridentate N,N,P-ligands (such skeleton ligands are named Zhang Yufeng type chiral anionic ligands), and successfully applies them to asymmetric catalytic reactions. This type of novel chiral ligand has rich structural characteristics, the electronic effect and steric effect of the aromatic substituent on the trivalent phosphorus can be regulated, and can provide additional weak forces through the alkyl chain, thereby inducing excellent enantioselectivity. The ligand of the present invention can not only be widely used in stereo-convergent free radical asymmetric cross-coupling reactions of secondary dialkyl-substituted halogenated alkanes and sulfonyl imides, but also has important guiding significance for the development of novel catalytic systems to solve other types of stereo-convergent free radical asymmetric reactions. DETAILED DESCRIPTION

[0043] The following will be combined with the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field based on the present application belong to the scope of protection of the present application.

[0044]

[0045] Step 1: Weigh magnesium chips in a 500 ml double-necked bottle containing a magnetic rod, place a reflux condenser on the bottle and a constant pressure dropping funnel, and replace the argon protection. Dissolve compound S1 (200 mmol) in 200 mL tetrahydrofuran (THF) and add a constant pressure dropping funnel, slowly add it to the bottle, and then keep it at 60 ° C for 2 hours to prepare the Grignard reagent S2. No post-treatment is required, cool to 0 ° C, add diethyl phosphite (60 mmol) dropwise, slowly warm to room temperature, and react for 2 hours. Post-treatment: Add 200 mL of 3.0 M hydrochloric acid, stir until the solid is completely dissolved, then extract with ethyl acetate, separate the organic layer, dry over anhydrous sodium sulfate, filter and concentrate in vacuo, and the residue obtained is chromatographed on a silica gel column to obtain intermediate S3 (50% yield).

[0046] Step 2: Intermediate S3 (100 mmol), methyl o-iodobenzoate (150 mmol), alpha-methylbenzylamine (20 mmol), cuprous iodide (20 mmol) and potassium carbonate (300 mmol) were placed in a 500 mL round-bottom flask, argon was replaced three times, and toluene (250 mL) was added. After reflux for 24 hours, water was added to quench, the organic layer was separated, and ethyl acetate was extracted three times. The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue thus obtained was purified by silica gel column to obtain the product (40-80% yield).

[0047] Step 3: Intermediate S4 (100 mmol), arylboronic acid (450 mmol), tetrakistriphenylphosphine palladium (5 mmol) and sodium carbonate (600 mmol) were placed in a 2000 mL round-bottom flask, argon was replaced three times, and toluene (600 mL) and water (600 mL) were added. After reflux for 24 hours, ethyl acetate was extracted three times, and the combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue thus obtained was purified by silica gel column to obtain product S5 (40-80% yield).

[0048] Step 4: Intermediate S5 (100 mmol), triphenylphosphine (150 mmol) and trichlorosilane (1 mol) were placed in a 500 mL round-bottom flask, and toluene (100 mL) and tetrahydrofuran (100 mL) were added. After reflux for 24 hours, ice water was added to quench, and ethyl acetate was extracted three times. The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue thus obtained was purified by silica gel column to obtain product S6 (60-80% yield).

[0049] Step 5: Intermediate S6 (100 mmol) and lithium hydroxide (2 mol) were placed in a 500 mL round-bottom flask, and water (150 mL) and tetrahydrofuran (150 mL) were added. After reflux for 24 hours, 3.0 M hydrochloric acid was added to dissolve the solid, extracted three times with ethyl acetate, and the combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue thus obtained was purified by silica gel column to obtain product S7 (60-80% yield).

[0050] Step 6: Intermediate S7 (100 mmol), intermediate S8 (100 mmol), EDCI (150 mmol) and DMAP (10 mmol) were placed in a 500 mL round-bottom flask and dichloromethane (250 mL) was added. After reacting at room temperature for 16 hours, saturated ammonium chloride solution was added to quench the reaction, and dichloromethane was extracted three times. The combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue thus obtained was purified by silica gel column to obtain the final product ligands 1 to 53 (50-80% yield) depending on the input of arylboronic acid.

[0051]

[0052] Characterization data of ligand 1: 11H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.71 (s, 1H), 7.70 – 7.65 (m, 5H), 7.62 – 7.52 (m, 10H), 7.48 (t, J = 2.1 Hz, 2H), 7.47 – 7.41 (m, 9H), 7.40 – 7.35 (m, 5H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 2.98 (ddd, J = 12.1, 7.1, 4.6 Hz, 1H), 2.89 – 2.81 (m, 1H), 2.81 – 2.64 (m, 2H), 2.05 (dtt, J = 6.6, 5.3, 3.8 Hz, 1H), 1.92 (dt, J = 12.5, 5.5 Hz, 1H), 1.85 – 1.51 (m, 4H), 1.42 (qdd, J = 7.6, 6.1, 5.0 Hz, 2H), 0.87 (td, J = 7.5, 1.5 Hz, 3H). Characterization data of ligand 2: 1 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.07 – 7.89 (m, 8H), 7.85 – 7.66 (m, 12H), 7.66 – 7.35 (m, 20H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.62 (m, 5H), 2.05 (dtt, J = 6.6, 5.3, 3.8 Hz, 1H), 1.92 (dt, J = 12.5, 5.5 Hz, 1H), 1.82 – 1.49 (m, 4H), 1.42 (qdd, J = 7.6, 6.1, 5.0 Hz, 2H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0053] Characterization data of ligand 3: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.06 (t, J = 1.9 Hz, 2H), 8.02 – 7.88 (m, 16H), 7.74 – 7.65 (m, 6H), 7.65 –7.46 (m, 14H), 7.44 – 7.37 (m, 2H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd,J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.36 –2.64 (m, 4H), 2.05 (dtt, J = 6.6, 5.3, 3.8 Hz, 1H), 1.92 (dt, J = 12.5, 5.5Hz, 1H), 1.84 – 1.51 (m, 4H), 1.42 (qdd, J = 7.6, 6.1, 5.0 Hz, 2H), 0.87 (td,J = 7.5, 1.5 Hz, 3H). Characterization data of ligand 4: 1H NMR (400 MHz, CDCl3) δ 8.56 – 8.48 (m, 2H), 8.38 (d, J = 2.4 Hz, 2H), 8.21 – 8.14 (m, 10H), 8.14 – 8.09 (m, 2H), 8.03 (t, J =2.1 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.79 (td, J = 13.3, 2.2 Hz, 2H), 7.75– 7.68 (m, 6H), 7.66 – 7.53 (m, 20H), 7.49 (dddd, J = 11.2, 7.1, 4.1, 1.8 Hz,1H), 7.42 (s, 1H), 7.39 (td, J = 7.5, 1.4 Hz, 1H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz,1H), 3.37 – 2.67 (m, 5H), 2.05 (dtt, J = 6.6, 5.3, 3.8 Hz, 1H), 1.92 (dt, J =12.5, 5.5 Hz, 1H), 1.84 – 1.73 (m, 2H), 1.69 (dddd, J = 11.9, 7.1, 4.7, 3.9Hz, 1H), 1.59 (dddd, J = 12.4, 7.3, 4.8, 4.0 Hz, 1H), 1.42 (qdd, J = 7.6,6.1, 5.0 Hz, 2H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0054] Characterization data of ligand 5: 1H NMR (400 MHz, CDCl3) δ 8.66 (dd, J = 8.4, 1.3 Hz,2H), 8.21 – 8.05 (m, 6H), 8.02 – 7.94 (m, 10H), 7.92 – 7.85 (m, 4H), 7.85 –7.68 (m, 12H), 7.66 – 7.45 (m, 12H), 7.45 – 7.35 (m, 3H), 7.23 (dd, J = 8.6,2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6,5.5 Hz, 1H), 3.02 – 2.64 (m, 5H), 2.05 (dtt, J = 6.6, 5.3, 3.8 Hz, 1H), 1.92 (dt, J = 12.5, 5.5 Hz, 1H), 1.84 – 1.64 (m, 3H), 1.59 (dddd, J = 12.4, 7.3,4.8, 4.0 Hz, 1H), 1.42 (qdd, J = 7.6, 6.1, 5.0 Hz, 2H), 0.87 (td, J = 7.5,1.5 Hz, 3H). Characterization data of ligand 6: 1 H NMR (400 MHz, CDCl3) δ 8.25 – 8.05 (m, 2H), 8.00(d, J = 8.7 Hz, 1H), 7.75 – 7.53 (m, 5H), 7.53 – 7.44 (m, 9H), 7.44 – 7.33(m, 12H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.34 – 2.64 (m, 5H), 2.14 –1.45 (m, 8H), 1.34 (s, 36H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0055] Characterization data of ligand 7: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H),8.00 (d, J = 8.7 Hz, 2H), 7.89 (t, J = 2.2 Hz, 1H), 7.77 – 7.31 (m, 16H),7.31 – 7.13 (m, 9H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.55 –2.64 (m, 6H), 2.40 (s, 12H), 2.15 – 1.32 (m, 8H), 0.87 (td, J = 7.5, 1.5 Hz,3H). Characterization data of ligand 8: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.75 – 7.63 (m, 1H), 7.60 (ddd, J = 13.3, 7.1, 1.4Hz, 1H), 7.53 – 7.33 (m, 10H), 7.33 – 7.09 (m, 12H), 5.23 (dd, J = 8.5, 6.5Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.34 – 2.64 (m, 5H),2.24 (s, 24H), 2.10 – 1.29 (m, 8H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0056] Characterization data of ligand 9: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.80 (t, J = 2.1 Hz, 1H), 7.77 – 7.52 (m, 11H), 7.49 (dddd, J = 8.9, 7.1, 4.1, 2.0 Hz, 1H), 7.44 – 7.33 (m, 8H), 7.33 – 7.14(m, 5H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.61 – 3.41 (m, 3H),3.37 – 2.84 (m, 3H), 2.81 – 2.62 (m, 2H), 2.05 (dtt, J = 6.6, 5.3, 3.8 Hz,1H), 1.92 (dt, J = 12.5, 5.4 Hz, 1H), 1.84 – 1.49 (m, 4H), 1.42 (qdd, J =7.6, 6.1, 4.9 Hz, 4H), 1.29 (dd, J = 25.0, 6.7 Hz, 24H), 0.87 (td, J = 7.5,1.5 Hz, 3H). Characterization data of ligand 10: 1 H NMR (400 MHz, CDCl3) δ 8.45 (t, J = 2.0 Hz, 2H), 8.25 – 8.05 (m, 18H), 8.05 – 7.92 (m, 2H), 7.83 – 7.66 (m, 8H), 7.61 (tdd, J= 13.3, 7.0, 1.4 Hz, 1H), 7.55 – 7.36 (m, 18H), 7.23 (dd, J = 8.6, 2.7 Hz,1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz,1H), 3.36 – 2.88 (m, 2H), 2.88 – 2.64 (m, 3H), 2.12 – 1.82 (m, 2H), 1.82 –1.49 (m, 4H), 1.42 (qdd, J = 7.6, 6.1, 5.0 Hz, 2H), 0.87 (td, J = 7.5, 1.5Hz, 3H).

[0057] Characterization data of ligand 11: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 2H), 7.80 – 7.35 (m, 11H), 7.32 (s, 8H), 7.23 (dd, J =8.6, 2.7 Hz, 2H), 6.86 (ddd, J = 2.7, 1.6, 0.7 Hz, 2H), 5.22 (dd, J = 8.6,6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.37 – 2.59 (m,5H), 2.17 (s, 24H), 2.05 (dtt, J = 6.6, 5.3, 3.8 Hz, 1H), 1.92 (dt, J = 12.5,5.5 Hz, 1H), 1.84 – 1.49 (m, 4H), 1.42 (qdd, J = 7.6, 6.1, 5.0 Hz, 2H), 0.87(td, J = 7.5, 1.5 Hz, 3H). Characterization data of ligand 12: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.91 (t, J = 2.1 Hz, 1H), 7.77 – 7.66 (m, 8H), 7.61(tdd, J = 13.2, 7.0, 1.3 Hz, 2H), 7.53 – 7.46 (m, 6H), 7.46 – 7.31 (m, 6H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H),3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.37 – 2.59 (m, 5H), 2.10 – 1.51 (m, 6H), 1.35 (s, 74H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0058] Characterization data of ligand 13: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H),8.00 (d, J = 8.7 Hz, 1H), 7.83 (t, J = 2.2 Hz, 1H), 7.77 – 7.30 (m, 10H),7.23 (dd, J = 8.6, 2.7 Hz, 1H), 6.97 (d, J = 2.0 Hz, 8H), 6.50 (t, J = 2.1Hz, 4H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 24H), 3.82 (s, 3H), 3.47(dt, J = 6.6, 5.5 Hz, 1H), 3.37 – 2.59 (m, 5H), 2.12 – 1.32 (m, 8H), 0.87(td, J = 7.5, 1.5 Hz, 3H). Characterization data of ligand 14: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.82 (d, J = 2.2 Hz, 1H), 7.77 – 7.53 (m, 8H), 7.53– 7.33 (m, 3H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 7.05 (d, J = 2.0 Hz, 8H), 6.48 (t, J = 2.2 Hz, 4H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 4.68 (hept, J = 5.7Hz, 8H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.34 – 2.62 (m, 5H), 2.07 – 1.48 (m, 5H), 1.42 (qdd, J = 7.6, 6.1, 4.9 Hz, 2H), 1.32 (dd, J =25.1, 5.7 Hz, 48H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0059] Characterization data of ligand 15: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H),8.00 (d, J = 8.7 Hz, 1H), 7.82 (t, J = 2.2 Hz, 1H), 7.77 – 7.53 (m, 10H),7.53 – 7.27 (m, 16H), 7.27 – 7.05 (m, 18H), 7.05 – 6.91 (m, 16H), 6.43 (t, J= 2.2 Hz, 4H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J =6.6, 5.5 Hz, 1H), 3.36 – 2.65 (m, 4H), 2.10 – 1.20 (m, 8H), 0.87 (td, J =7.5, 1.6 Hz, 3H). Characterization data of ligand 16: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H),8.09 (t, J = 2.2 Hz, 2H), 8.05 – 7.92 (m, 10H), 7.91 (t, J = 2.2 Hz, 1H),7.77 – 7.53 (m, 9H), 7.53 – 7.31 (m, 3H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.55 – 2.62 (m, 5H), 2.12 –1.27 (m, 8H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0060] Characterization data of ligand 17: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.80 – 7.53 (m, 8H), 7.53 – 7.35 (m, 10H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.80(s, 12H), 3.53 – 2.56 (m, 6H), 2.17 (s, 24H), 2.09 – 1.29 (m, 8H), 0.87 (td,J = 7.5, 1.5 Hz, 3H). Characterization data of ligand 18: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H),8.00 (d, J = 8.7 Hz, 1H), 7.83 (t, J = 2.2 Hz, 1H), 7.77 – 7.33 (m, 15H),7.23 (dd, J = 8.6, 2.8 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.77 (s, 12H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.34 – 2.59 (m, 5H), 2.23 –1.96 (m, 74H), 1.96 – 1.26 (m, 57H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0061] Characterization data of ligand 19: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.83 (t, J = 2.2 Hz, 2H), 7.77 – 7.53 (m, 7H), 7.53– 7.33 (m, 10H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.77 (s, 12H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.37 – 2.61(m, 4H), 2.10 – 1.48 (m, 5H), 1.42 (s, 74H), 0.87 (td, J = 7.5, 1.5 Hz, 3H). Characterization data of ligand 20: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 2H), 7.80 – 7.66 (m, 7H), 7.66– 7.30 (m, 12H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.58 (m, 5H), 2.10– 1.49 (m, 22H), 1.49 – 1.23 (m, 50H), 0.87 (td, J = 7.5, 1.5 Hz, 3H), 0.79 –0.60 (m, 24H).

[0062] Characterization data of ligand 21: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 2H), 7.80 – 7.66 (m, 7H), 7.66– 7.36 (m, 9H), 7.33 (d, J = 2.1 Hz, 4H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H),3.39 – 2.61 (m, 4H), 2.07 – 1.45 (m, 20H), 1.45 – 1.16 (m, 68H), 0.94 – 0.66 (m, 27H). Characterization data of ligand 22: 1 H NMR (400 MHz, CDCl3)δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 2H), 7.80 – 7.66 (m, 8H), 7.66– 7.30 (m, 12H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.52 (dt, J = 10.3, 5.8 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.23 (tq, J = 5.8, 1.0 Hz,2H), 2.98 (ddd, J = 12.1, 7.1, 4.6 Hz, 1H), 2.91 – 2.61 (m, 3H), 2.12 – 1.49 (m, 15H), 1.49 – 1.16 (m, 62H), 1.07 – 0.71 (m, 52H).

[0063] Characterization data of ligand 23: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 2H), 7.80 – 7.66 (m, 6H), 7.66– 7.30 (m, 12H), 7.23 (dd, J = 8.6, 2.7 Hz, 1H), 5.52 (dt, J = 10.3, 5.8 Hz,1H), 5.36 (ddt, J = 10.4, 2.0, 1.1 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H),3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.23 (ddt, J = 6.9, 5.8, 1.1Hz, 2H), 3.06 – 2.62 (m, 4H), 2.12 – 1.49 (m, 18H), 1.49 – 1.15 (m, 81H),1.10 – 0.75 (m, 50H). Characterization data of ligand 24: 1 H NMR (400 MHz, CDCl3)δ 8.16 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.77 – 7.63 (m, 7H), 7.63 – 7.17 (m, 12H), 7.11 (d,J = 2.2 Hz, 4H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J =6.6, 5.5 Hz, 1H), 3.23 (tq, J = 5.8, 1.0 Hz, 2H), 3.03 – 2.59 (m, 4H), 2.15 –1.51 (m, 28H), 1.51 – 1.15 (m, 114H), 1.04 – 0.79 (m, 51H).

[0064] Characterization data of ligand 25: 1H NMR (400 MHz, CDCl3)δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 1H), 7.78 – 7.64 (m, 6H), 7.64– 7.52 (m, 1H), 7.52 – 7.36 (m, 6H), 7.33 (d, J = 2.1 Hz, 8H), 7.23 (dd, J =8.6, 2.7 Hz, 1H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J =6.6, 5.5 Hz, 1H), 3.37 – 2.53 (m, 5H), 2.04 – 1.49 (m, 18H), 1.46 – 1.18 (m,134H), 0.98 – 0.63 (m, 48H). Characterization data of ligand 26: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.85 (m, 3H), 7.80 – 7.64 (m, 5H), 7.64 – 7.16 (m, 16H), 5.22 (dd, J =8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.69(m, 5H), 2.14 – 1.48 (m, 40H), 1.48 – 1.15 (m, 157H), 0.98 – 0.63 (m, 30H).

[0065] Characterization data of ligand 27: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 2H), 7.75 – 7.66 (m, 7H), 7.66– 7.14 (m, 14H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.59 – 2.54(m, 6H), 2.15 – 1.49 (m, 45H), 1.49 – 1.10 (m, 168H), 0.98 – 0.68 (m, 29H). Characterization data of ligand 28: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.85 (m, 3H), 7.80 – 7.64 (m, 6H), 7.64 – 7.16 (m, 16H), 5.22 (dd, J =8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.69(m, 5H), 2.14 – 1.48 (m, 26H), 1.48 – 1.15 (m, 202H), 0.98 – 0.63 (m, 30H).

[0066] Characterization data of ligand 29: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.85 (m, 4H), 7.80 – 7.64 (m, 5H), 7.64 – 7.16 (m, 16H), 5.22 (dd, J =8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.69(m, 4H), 2.14 – 1.48 (m, 27H), 1.48 – 1.15 (m, 218H), 0.98 – 0.63 (m, 30H). Characterization data of ligand 30: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.85 (m, 4H), 7.80 – 7.64 (m, 5H), 7.64 – 7.16 (m, 16H), 5.22 (dd, J =8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.69(m, 4H), 2.14 – 1.48 (m, 27H), 1.48 – 1.15 (m, 234H), 0.98 – 0.63 (m, 30H).

[0067] Characterization data of ligand 31: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.85 (m, 4H), 7.80 – 7.64 (m, 5H), 7.64 – 7.16 (m, 16H), 5.22 (dd, J =8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.69(m, 4H), 2.14 – 1.48 (m, 27H), 1.48 – 1.15 (m, 250H), 0.98 – 0.63 (m, 30H). Characterization data of ligand 32: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.85 (m, 4H), 7.80 – 7.64 (m, 5H), 7.64 – 7.16 (m, 16H), 5.22 (dd, J =8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.69(m, 4H), 2.14 – 1.48 (m, 27H), 1.48 – 1.15 (m, 266H), 0.98 – 0.63 (m, 30H).

[0068] Characterization data of ligand 33: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 2H), 7.78 – 7.52 (m, 8H), 7.52– 7.30 (m, 5H), 7.30 – 7.09 (m, 8H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s,3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.37 – 2.54 (m, 4H), 2.12 – 1.35 (m,96H), 1.33 (d, J = 1.5 Hz, 48H), 0.87 (td, J = 7.5, 1.6 Hz, 3H). Characterization data of ligand 34: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H),8.07 – 7.83 (m, 5H), 7.80 – 7.53 (m, 5H), 7.53 – 7.35 (m, 5H), 7.32 (s, 8H),7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.51 (m, 4H), 2.10 – 1.49 (m, 22H),1.49 – 1.18 (m, 50H), 0.87 (td, J = 7.5, 1.5 Hz, 3H), 0.74 (s, 72H).

[0069] Characterization data of ligand 35: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 (t, J = 2.1 Hz, 2H), 7.77 – 7.66 (m, 5H), 7.66– 7.53 (m, 1H), 7.49 (ddt, J = 9.4, 5.3, 2.1 Hz, 1H), 7.46 – 7.36 (m, 2H), 7.31 (dd, J = 9.6, 2.2 Hz, 10H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J= 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.37 – 2.59 (m, 4H), 2.10 – 1.49 (m, 26H), 1.49 – 1.15 (m, 82H), 0.88 (t, J = 6.4 Hz,51H). Characterization data of ligand 36: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H),8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.86 – 7.31 (m, 18H),7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.39 – 2.62 (m, 5H), 2.14 – 1.32 (m, 8H),0.87 (td, J = 7.5, 1.5 Hz, 3H), 0.32 (s, 72H).

[0070] Characterization data of ligand 37: 1H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H),8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.88 – 7.31 (m, 18H),7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz, 1H), 3.37 – 2.59 (m, 5H), 2.14 – 1.31 (m, 8H),0.92 (s, 72H), 0.87 (td, J = 7.5, 1.5 Hz, 3H), 0.40 (s, 48H). Characterization data of ligand 38: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H),8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 – 7.66 (m, 15H),7.61 (tdd, J = 13.2, 7.0, 1.4 Hz, 1H), 7.55 – 7.33 (m, 3H), 7.23 (dd, J =8.6, 2.7 Hz, 1H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J =6.6, 5.5 Hz, 1H), 3.37 – 2.61 (m, 5H), 2.12 – 1.51 (m, 6H), 1.51 – 1.35 (m,10H), 1.27 (h, J = 7.1 Hz, 8H), 1.15 – 1.02 (m, 32H), 0.94 (t, J = 7.2 Hz, 24H), 0.87 (td, J = 7.5, 1.5 Hz, 3H), 0.28 (s, 48H).

[0071] Characterization data of ligand 39: 1H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.91 – 7.66 (m, 10H), 7.61 (tdd, J = 13.2, 7.0, 1.3 Hz, 2H), 7.53 – 7.35 (m, 6H), 7.23 (dd, J =8.6, 2.7 Hz, 2H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J =6.6, 5.5 Hz, 1H), 3.37 – 2.64 (m, 5H), 2.07 – 1.53 (m, 6H), 1.53 – 1.34 (m,10H), 1.34 – 1.16 (m, 65H), 1.16 – 1.04 (m, 26H), 0.94 – 0.80 (m, 40H), 0.28(s, 48H). Characterization data of ligand 40: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.31 (m, 20H), 7.23 (dd, J = 8.6, 2.7 Hz,2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz,1H), 3.39 – 2.53 (m, 5H), 2.12 – 0.75 (m, 211H), 0.28 (s, 48H).

[0072] Characterization data of ligand 41: 1H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.31 (m, 21H), 7.23 (dd, J = 8.6, 2.7 Hz,2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.47 (dt, J = 6.6, 5.5 Hz,1H), 3.39 – 2.53 (m, 5H), 2.12 – 0.75 (m, 306H), 0.28 (s, 48H). Characterization data of ligand 42: 1 H NMR (400 MHz, CDCl3)δ 8.31 (t, J = 2.2 Hz, 2H),8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.85 – 7.31 (m, 18H),7.23 (dd, J = 8.6, 2.8 Hz, 2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.55 – 2.62 (m, 6H), 2.12 – 1.26 (m, 12H), 1.02 – 0.71 (m, 103H), 0.38 (s,48H).

[0073] Characterization data of ligand 43: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H),8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.86 – 7.33 (m, 19H),7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.56 – 2.62 (m, 6H), 2.14 – 1.21 (m, 95H), 0.87 (td, J = 7.5, 1.6 Hz, 3H),0.41 (d, J = 1.5 Hz, 48H). Characterization data of ligand 44: 1 H NMR (400 MHz, CDCl3) δ 8.32 (dt, J = 10.8, 2.2 Hz,4H), 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.89 (d, J = 2.2 Hz,8H), 7.85 – 7.30 (m, 8H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J = 8.6,6.6 Hz, 1H), 3.83 (s, 3H), 3.56 – 2.61 (m, 6H), 2.10 – 1.31 (m, 8H), 1.15 –0.75 (m, 123H).

[0074] Characterization data of ligand 45: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H),8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.86 – 7.31 (m, 15H),7.28 – 7.13 (m, 5H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.58 –2.59 (m, 6H), 2.20 – 1.31 (m, 24H), 1.06 (dd, J = 25.0, 7.0 Hz, 160H), 0.87(td, J = 7.5, 1.5 Hz, 3H). Characterization data of ligand 46: 1H NMR (400 MHz, CDCl3) δ 8.33 (dt, J = 20.7, 2.2 Hz,4H), 8.18 (d, J = 8.6 Hz, 2H), 8.08 – 7.91 (m, 7H), 7.86 – 7.31 (m, 12H),7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.63 – 2.47 (m, 6H), 2.10 – 1.27 (m, 31H), 1.27 – 1.05 (m, 48H), 0.83 (dd, J= 25.0, 8.2 Hz, 147H).

[0075] Characterization data of ligand 47: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 8.05 – 7.92 (m, 8H), 7.81 – 7.31 (m, 13H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.55– 2.61 (m, 6H), 2.12 – 1.53 (m, 6H), 1.53 – 1.15 (m, 97H), 1.09 – 0.60 (m,123H).

[0076] Characterization data of ligand 48: 1H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 8.07 – 7.91 (m, 8H), 7.86 – 7.33 (m, 13H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.55– 2.59 (m, 6H), 2.09 – 1.49 (m, 6H), 1.49 – 0.66 (m, 316H). Characterization data of ligand 49: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 8.03 – 7.88 (m, 7H), 7.88 – 7.33 (m, 14H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.66– 2.58 (m, 6H), 2.15 – 1.49 (m, 6H), 1.49 – 0.77 (m, 140H).

[0077] Characterization data of ligand 50: 1 H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H),8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.83 – 7.31 (m, 19H),7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.50 – 2.67 (m, 6H), 2.06 – 0.79 (m, 258H). Characterization data of ligand 51: 1H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 2.2 Hz, 2H), 8.18 (d, J = 8.6 Hz, 2H), 8.00 (d, J = 8.7 Hz, 2H), 7.85 – 7.30 (m, 19H), 7.30 – 7.08 (m, 34H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.56 –2.61 (m, 6H), 2.56 – 2.36 (m, 16H), 2.10 – 1.34 (m, 47H), 1.05 (dd, J = 25.0,7.4 Hz, 96H), 0.87 (td, J = 7.5, 1.5 Hz, 3H).

[0078] Characterization data of ligand 52: 1 H NMR (400 MHz, CDCl3) δ 8.25 – 8.07 (m, 5H), 8.00 (d, J = 8.7 Hz, 2H), 7.80 – 7.33 (m, 18H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 5.23 (dd, J = 8.5, 6.5 Hz, 1H), 3.83 (s, 3H), 3.56 – 2.65 (m, 6H), 2.15 –1.32 (m, 7H), 0.87 (td, J = 7.5, 1.5 Hz, 3H), 0.61 (s, 72H). Characterization data of ligand 53: 1H NMR (400 MHz, CDCl3) δ 8.27 – 8.07 (m, 5H), 8.00 (d, J = 8.7 Hz, 2H), 7.78 – 7.30 (m, 14H), 7.23 (dd, J = 8.6, 2.7 Hz, 2H), 7.04 (t, J = 2.2 Hz, 4H), 5.22 (dd, J = 8.6, 6.6 Hz, 1H), 3.83 (s, 3H), 3.56– 2.62 (m, 6H), 2.14 – 1.31 (m, 55H), 1.07 (t, J = 7.3 Hz, 72H), 0.87 (td, J= 7.5, 1.6 Hz, 3H). The ligand of the invention is applied to the stereo-convergent free radical asymmetric cross-coupling reaction of secondary non-activated dialkyl halide alkane and sulfenyl imine.

[0079]

[0080] CuI (copper iodide, 10 mol% equivalent), ligand 37 (15 mol% equivalent), Cs2CO3 (cesium carbonate, 4.0 equivalent) were added to an oven-dried Schlenk tube equipped with a magnetic stirring bar, and the argon atmosphere was replaced three times. Compound 1 (secondary iodoalkane, 0.2 mmol), compound 2 (di-4-methylphenylsulfenyl imide, 0.2 mmol), isopropyl ether ( i Pr2O, 4.0 mL). Then, under irradiation with a 390 nm LED lamp (10 W), the reaction was allowed to proceed for 72 h at room temperature. After the reaction was completed (monitored by TLC), the precipitate was filtered out and washed with ethyl acetate, and then the solution was evaporated and purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1) to obtain product a1 with a yield of 62% and 79% ee.

[0081] Characterization data of product a1: oily liquid. HPLC conditions: Chiralcel IA (n-hexane / isopropanol = 90 / 10, flow rate 1.0 mL / min, λ = 254 nm), t R (minor) = 6.56 min, t R (major) = 12.83min. 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 8.1 Hz, 4H), 2.98 – 2.89 (m, 1H), 2.36 (s, 6H), 2.03 – 1.96 (m, 1H), 1.80 – 1.73 (m, 3H), 1.69 – 1.61 (m, 1H), 1.41 – 1.32 (m, 1H), 1.30 – 0.92 (m, 8H). 13 C NMR (100 MHz, CDCl3) δ 142.6, 142.5, 139.4, 138.4, 129.6,129.5, 128.8, 128.5, 55.4, 46.1, 29.8, 29.6, 26.8, 26.6, 21.8, 21.4. . HRMS(ESI) m / z accurate mass calculation C 20 H 30 NOS [M + H] + 356.2043, measured value 356.2031.

[0082] The product a1 is desulfinyl protected to obtain compound a2: Magnesium chips (10 equivalents) and compound a1 (1 equivalent) were added to an oven-dried Schlenk tube equipped with a magnetic stirring bar, and the argon gas was replaced three times, followed by the addition of methanol (MeOH, 0.1 M). Then, the mixture was stirred at 0 °C until the magnesium chips were completely dissolved, and the mixture was heated to room temperature for 1 h. After the reaction was completed (monitored by TLC), the system was cooled to 0 °C, and a 1,4-dioxane solution of hydrochloric acid was added to the system. After the reaction was completed (monitored by TLC), water was added to dissolve the mixture, and the mixture was washed with ethyl acetate. The aqueous phase was alkalized with ammonia water, extracted with ethyl acetate three times, and concentrated to obtain product a2 with a yield of 90%.

[0083]

[0084]

[0085] The reaction results of the existing ligands La~Li and the ligands of the present invention are shown in the following table (L1 represents ligand 1, and so on): The reaction results are shown in the following table (L1 represents ligand 1, and so on): It can be seen that in the stereo-convergent free radical asymmetric cross-coupling reaction of secondary non-activated halogenated alkanes and sulfenyl imines, the ligands of the present invention have advantages over existing ligands in terms of stereoselectivity and reaction efficiency. Therefore, designing new multidentate anionic ligands can achieve more types of asymmetric reactions.

[0086] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound represented by general formula I, or its tautomers, enantiomers, and diastereomers: ； in, The R 1 is selected from substituted or unsubstituted alkyl; The R 2 Each independently selected from a substituted or unsubstituted alkyl group, a substituted or unsubstituted monocyclic aromatic group, a C6-C14 substituted or unsubstituted condensed ring group; The R 3 Selected from alkoxy; The carbon atom marked with * is an R configuration, an S configuration, or an achiral carbon atom.

2. The cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound of general formula I according to claim 1, or its tautomers, enantiomers, and diastereomers, characterized in that: Multiple R 2 Each independently selected from a C6~C14 fused ring group, the fused ring group is formed by condensing at least one first ring and at least one second ring, the first ring is selected from a C3~C6 cycloalkyl group, and the second ring is selected from a monocyclic aromatic group.

3. The cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound of general formula I according to claim 1, or its tautomers, enantiomers, and diastereomers, characterized in that: Multiple R 2 Each independently selected from a monocyclic aromatic group, any hydrogen on the monocyclic aromatic group is replaced by R a Replacement, structure such as: , wherein n is selected from any positive integer from 1 to 3, and the plurality of R a each independently selected from hydrogen, unsubstituted methyl, substituted or unsubstituted adamantyl, substituted or unsubstituted n-propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylsilyl, substituted or unsubstituted alkylgermanyl, Or, the R a is selected from methyl, wherein any hydrogen on the methyl is replaced by halogen.

4. The cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound of general formula I according to claim 3, or its tautomers, enantiomers, and diastereomers, characterized in that: The R a Any one of alkoxy and isopropyl, wherein R a Structure like -OR aa , the R aa Each independently selected from substituted or unsubstituted methyl, substituted or unsubstituted monocyclic aryl, substituted or unsubstituted isopropyl; The R selected from isopropyl a Structure , the R ab is selected from substituted or unsubstituted methyl, unsubstituted ethyl, substituted or unsubstituted octyl, substituted or unsubstituted propyl, substituted or unsubstituted butyl, substituted or unsubstituted hexyl, substituted or unsubstituted nonyl, substituted or unsubstituted decyl, substituted or unsubstituted undecyl to hexadecyl, substituted or unsubstituted cyclohexane, Or, the R ab is selected from substituted ethyl, said R ab Any hydrogen atom is replaced by tert-butyl or ethyl.

5. The cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound of general formula I according to claim 3, or its tautomers, enantiomers, and diastereomers, characterized in that: The R a Selected from alkylsilyl, the alkylsilyl structure is as follows , the R ac is selected from methyl, ethyl, tert-butyl, n-butyl, n-octyl, n-hexyl, n-dodecyl, n-octadecyl, cyclohexyl, and a plurality of said R ad Each is independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl and n-hexyl.

6. The cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound of general formula I according to claim 5, or its tautomers, enantiomers, and diastereomers, characterized in that: The R ac is selected from ethyl, any hydrogen on the ethyl is replaced by a monocyclic aromatic group, and the R ac Selected from tert-butyl, wherein any hydrogen on the tert-butyl is replaced by isopropyl.

7. The cinchona alkaloid-derived tetrazole tridentate chiral N,N,P-ligand compound of general formula I according to claim 3, or its tautomers, enantiomers, and diastereomers, characterized in that: The R a Selected from alkylgermanium groups, the alkylgermanium group structure is as follows: , Multiple R ae Each is independently selected from methyl and ethyl.

8. A cinchona alkaloid-derived tetrazole tridentate N,N,P-ligand, the structure of which is shown below: ； ； ； ； ； ； ； ； ； ； ； ； 。 9. A method for preparing a tetrazole tridentate N,N,P-ligand derived from cinchona alkaloids, comprising the following steps: ； Compound S2 reacts with diethyl phosphite to obtain intermediate S3; ； Intermediate S3 reacts with methyl o-iodobenzoate to obtain intermediate S4; ； Intermediate S4 reacts with arylboronic acid to obtain intermediate S5; ； Deoxygenation of intermediate S5 gave intermediate S6; ； Intermediate S6 is hydrolyzed to give intermediate S7; ； The intermediate S7 and the quinine derivative S8 undergo a condensation reaction to obtain a product; The R 1 Selected from ethyl; The R 2 As defined in any one of claims 1 to 8; The R 3 Selected from methoxy.

10. An α-methylbenzylamine asymmetric catalytic method comprising: ； Adding compound 1, compound 2 and an organic solvent into a reaction system consisting of a copper salt, a ligand and a base, and reacting under light with a wavelength of 350 to 400 nanometers to obtain a product a1; ； Mix metallic magnesium and compound a1, then add alcohol and react under controlled temperature to obtain product a2.

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