2, 9-diaryl chiral phenanthroline ligand, copper complex as well as synthesis method and application of 2, 9-diaryl chiral phenanthroline ligand and copper complex

Abstract

The invention provides a 2, 9-diaryl chiral phenanthroline ligand, a copper complex as well as a synthesis method and application of the 2, 9-diaryl chiral phenanthroline ligand and the copper complex, and belongs to the technical field of asymmetric transition metal catalysts. The 2, 9-diaryl chiral phenanthroline ligand provided by the invention has a chemical structure represented by the following general formula: # imgabs0 #, in which R1 and R2 are respectively one of phenyl, substituted phenyl and C1-C8 alkyl. The 2, 9-diaryl chiral phenanthroline ligand provided by the invention has the advantages that the skeleton structure is rigid, and the coordination capability is strong; chiral amine is wide in source and easy to modify; amide is used as a linker, so that the synthesis of the ligand is greatly simplified; and a deeper chiral pocket is formed. A copper complex formed after a complexation reaction with a copper salt is used as a catalyst to realize an asymmetric insertion reaction of a C (sp3)-H bond in a (methylsulfonyl) carbamic acid aryl ethyl ester nitrogen bin molecule; the highest enantioselectivity (as high as 88: 12 enantioselectivity) known in the current literature in the asymmetric N-alkene insertion reaction in which a copper-catalyzed (methylsulfonyl) carbamic acid arylethyl ester substrate participates is obtained.

Description

Technical Field

[0001] The present invention relates to the technical field of asymmetric transition metal catalysts, and in particular to 2,9-diaryl chiral phenanthroline ligands, a synthesis method thereof, a copper complex obtained by complexing with a copper salt, and an application thereof in asymmetric transition metal catalysts. Background Art

[0002] The design and synthesis of chiral ligands have always been the focus of asymmetric transition metal catalysis research. Although many chiral ligands have been reported by researchers in the past few decades, a class of chiral ligands usually can only give excellent enantioselectivity in a few reactions. Developing new chiral ligands is the key to meeting the chiral control of different types of reactions. Phenanthroline is a typical diazine ligand, and its complexes with transition metals have been used as catalysts in many reactions, showing excellent catalytic performance [Zou Huina, Zhu Shoufei, Application of Phenanthroline Ligands in Iron-Catalyzed Reactions, Progress in Chemistry, 2020, 32, 1766-1803]. However, the types of chiral phenanthroline ligands are very limited, and successful applications are extremely rare. This may be because there are no sp 3 hybridized carbon atoms capable of introducing chiral centers on the phenanthroline ligand skeleton, and there are few methods for connecting the chiral structure to the phenanthroline skeleton. Summary of the Invention

[0003] In view of this, to solve the technical problem of the very limited types of chiral phenanthroline ligands in the prior art, in the first aspect, the present invention provides a 2,9-diaryl chiral phenanthroline ligand, which has a rigid skeleton structure, strong coordination ability; the chiral amine has a wide source and is easy to modify; the amide is used as a linker, which greatly simplifies the synthesis of the ligand; and a deeper chiral pocket is formed.

[0004] To achieve the above object, the present invention provides the following technical solutions:

[0005] A 2,9-diaryl chiral phenanthroline ligand has a chemical structure represented by the following general formula:

[0006]

[0007] Wherein, R 1 , R 2 are each independently one of a phenyl group, a substituted phenyl group, and a C 1 -C 8 alkyl group.

[0008] In the second aspect, the present invention also provides two synthesis methods for the above 2,9-diaryl chiral phenanthroline ligand, specifically as follows:

[0009] Synthesis method (1) is as follows:

[0010] The chiral 3,5-diaminobromobenzene is obtained by condensing 3,5-dicarboxybromobenzene with a chiral amine, and then coupling with bis(pinacolato)diboron under palladium-catalyzed conditions to obtain the corresponding aryl borate ester. Finally, the target ligand is obtained by Suzuki coupling reaction with 2,9-dichlorophenanthroline.

[0011] The synthesis method (2) is as follows:

[0012] Starting from 2,9-dichlorophenanthroline, it undergoes Suzuki coupling reaction with 3,5-dimethoxycarbonylphenylboronic acid to obtain 2,9-bis(3,5-dimethoxycarbonyl)phenylphenanthroline, which is then hydrolyzed to obtain 2,9-bis(3,5-dicarboxy)phenylphenanthroline, and finally condensed with a chiral amine to obtain the target ligand.

[0013] In the third aspect, the present invention also provides a copper complex, which is prepared by carrying out a complexation reaction between the above-mentioned 2,9-diaryl chiral phenanthroline ligand and a copper salt.

[0014] In the fourth aspect, the present invention also provides the application of the above-mentioned 2,9-diaryl chiral phenanthroline ligand or the above-mentioned copper complex in an asymmetric transition metal catalyst.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The 2,9-diaryl chiral phenanthroline ligand provided by the present invention has the following advantages:

[0017] (1) Rigid skeleton structure and strong coordination ability;

[0018] (2) The chiral amine has a wide source and is easy to modify;

[0019] (3) As an linker, the amide greatly simplifies the synthesis of the ligand;

[0020] (4) It forms a relatively deep chiral pocket.

[0021] The two synthesis methods provided by the present invention have a wide source of materials and simple operation steps.

[0022] The present invention uses the 2,9-diaryl chiral phenanthroline ligand to carry out a complexation reaction with a copper salt to prepare a copper complex. As a catalyst, it realizes the intramolecular C(sp 3 )-H bond asymmetric insertion reaction of (methanesulfonyl)carbamic acid aryl ethyl ester nitrene, and achieves the highest enantioselectivity (up to 88:12 enantioselectivity) known in the literature for the asymmetric nitrene insertion reaction involving (methanesulfonyl)carbamic acid aryl ethyl ester catalyzed by copper. Detailed embodiments

[0023] The present invention provides a 2,9-diaryl chiral phenanthroline ligand, which has a chemical structure represented by the following general formula:

[0024]

[0025] Wherein, R 1 and R 2 are each independently phenyl, substituted phenyl, or C 1 -C 8 alkyl, and R 1 and R 2 can be the same or different, and are selected according to actual needs.

[0026] In the present invention, the 2,9-diaryl chiral phenanthroline ligand can specifically be the following chemical structure:

[0027]

[0028] Wherein, Me is methyl, Et is ethyl, i Pr is isopropyl, t Bu is tert-butyl, Ph is phenyl, Ar is argon, and Bn is benzyl. Preferably, the 2,9-diaryl chiral phenanthroline ligand can also be one of a racemate, a levorotatory form, and a dextrorotatory form.

[0029] In the present invention, for the substituted phenyl, the substituent is one or more of C 1 -C 8 alkyl, C 1 -C 8 alkoxy, C 2 -C 8 acyloxy, hydroxyl, halogen, amino, (C 1 -C 8 acyl)amino, di(C 1 -C 8 alkyl)amino, C 1 -C 8 acyl, C 2 -C 8 ester group, and haloalkyl, and the number of substituents is 0-5.

[0030] In the present invention, the C 1 -C 8 acyl is one of formyl, acetyl, propionyl, n-butyryl, isobutyryl, n-valeryl, isovaleryl, sec-valeryl, pivaloyl, n-hexanoyl, isohexanoyl, neohexanoyl, sec-hexanoyl, n-heptanoyl, isoheptanoyl, neoheptanoyl, sec-heptanoyl, n-octanoyl, isooctanoyl, neooctanoyl, sec-octanoyl, 1-cyclopropylcarbonyl, 1-cyclobutylcarbonyl, 1-cyclopentylcarbonyl, 1-cyclohexylcarbonyl, and 1-cycloheptylcarbonyl.

[0031] In the present invention, the C 2 -C 8 acyloxy group is one of acetoxy, propionyloxy, n-butyryloxy, isobutyryloxy, n-valeryloxy, isovaleryloxy, sec-valeryloxy, pivaloyloxy, n-caproyloxy, isocaproyloxy, neocaproyloxy, sec-caproyloxy, n-heptanoyloxy, isoheptanoyloxy, neoheptanoyloxy, sec-heptanoyloxy, n-octanoyloxy, isooctanoyloxy, neooctanoyloxy, sec-octanoyloxy, 1-cyclopropylcarbonyloxy, 1-cyclobutylcarbonyloxy, 1-cyclopentylcarbonyloxy, 1-cyclohexylcarbonyloxy and 1-cycloheptylcarbonyloxy.

[0032] In the present invention, the C 2 -C 8 ester group is one of methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, n-pentyloxycarbonyl, isopentyloxycarbonyl, pentyloxycarbonyl, sec-pentyloxycarbonyl, tert-pentyloxycarbonyl, cyclopentyloxycarbonyl, n-hexyloxycarbonyl, isohexyloxycarbonyl, neohexyloxycarbonyl, sec-hexyloxycarbonyl, tert-hexyloxycarbonyl, cyclohexyloxycarbonyl, n-heptyloxycarbonyl, isoheptyloxycarbonyl, neoheptyloxycarbonyl, sec-heptyloxycarbonyl, tert-heptyloxycarbonyl and cycloheptyloxycarbonyl.

[0033] In the present invention, the haloalkyl group is a haloalkyl group containing fluorine, chlorine, bromine or iodine.

[0034] In the present invention, the C 1 -C 8 alkyl group is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-pentyl, n-hexyl, isohexyl, neohexyl, sec-hexyl, tert-hexyl, n-heptyl, isoheptyl, neoheptyl, sec-heptyl, tert-heptyl, n-octyl, isooctyl, neooctyl, sec-octyl or tert-octyl.

[0035] Second, the present invention also provides two synthesis methods of the above-mentioned 2,9-diaryl chiral phenanthroline ligand, which are specifically as follows:

[0036] Synthesis method (1) is as follows:

[0037] Chiral 3,5-diaminobromobenzene is obtained by condensing 3,5-dicarboxybromobenzene with chiral amine, and then coupled with bis(pinacolato)diboron under the condition of palladium catalysis to obtain the corresponding aryl borate ester, and finally the target ligand is obtained by Suzuki coupling reaction with 2,9-dichlorophenanthroline. Specifically, it can be:

[0038] (1) Using thionyl chloride as the solvent and DMF as the catalyst, 3,5-dicarboxy bromobenzene is converted into the corresponding acyl chloride. Subsequently, under the conditions of triethylamine as the acid-binding agent and DMAP as the catalyst, it is condensed with different types of chiral amines to obtain chiral amides:

[0039]

[0040] (2) Using Pd(dppf)Cl 2 as the catalyst, potassium acetate as the base, and 1,4-dioxane as the solvent, the corresponding aryl borate ester is obtained starting from chiral bromobenzene.

[0041]

[0042] (3) Using Pd(dppf)Cl 2 as the catalyst, Ba(OH) 2 ·8H 2 O as the base, toluene / water as the mixed solvent, the target ligand is obtained by coupling 2,9-dichlorophenanthroline with chiral aryl borate ester, or using Pd(dppf)Cl 2 as the catalyst, potassium carbonate as the base, 1,4-dioxane / water as the mixed solvent, the target ligand is obtained by coupling 2,9-dichlorophenanthroline with chiral aryl borate ester:

[0043]

[0044] Among them, R 1 , R 2 are respectively one of phenyl, substituted phenyl and C 1 -C 8 alkyl, and R 1 , R 2 can be the same or different, and are selected according to actual needs.

[0045] Preferably, the synthesis method (2) is as follows:

[0046] Starting from 2,9-dichlorophenanthroline, it undergoes a Suzuki coupling reaction with 3,5-dimethoxycarbonylphenylboronic acid to obtain 2,9-bis(3,5-dimethoxycarbonyl)phenylphenanthroline. Subsequently, it is hydrolyzed to obtain 2,9-bis(3,5-dicarboxy)phenylphenanthroline, and finally condensed with chiral amine to obtain the target ligand.

[0047] (1) Using Pd(PPh 3 ) 4 as the catalyst, sodium carbonate as the base, and toluene / ethanol / water as the mixed solvent. 2,9-Bis(3,5-dimethoxycarbonyl)phenylphenanthroline is obtained by coupling 2,9-dichlorophenanthroline with (3,5-dimethoxycarbonyl)phenylboronic acid.

[0048]

[0049] (2) Weigh 2,9-bis(3,5-dimethoxycarbonyl)phenylphenanthroline and potassium hydroxide into a three-necked flask equipped with a reflux condenser, add a mixed solvent of dioxane and water with a solvent ratio of 5:1, heat under reflux. After the reaction is completed, remove the organic solvent by rotary evaporation, slowly add 0.05 M hydrochloric acid aqueous solution, filter, and wash the filter cake with water to obtain 2,9-bis(3,5-dicarboxyl)phenylphenanthroline. The reaction formula is as follows:

[0050]

[0051] (3) Weigh 2,9-bis(3,5-dicarboxyl)phenylphenanthroline into a three-necked flask equipped with a reflux condenser. Add 10 mL of thionyl chloride and a few drops of DMF as a catalyst, and heat under reflux for two hours. After the reaction is completed, remove the solvent under vacuum. Under an ice-water bath, slowly drip a DMF solution of chiral amine, DMAP and triethylamine into the DMF solution of the acyl chloride prepared in the previous step. A chiral ligand is obtained. The reaction formula is as follows:

[0052]

[0053] Among them, R 1 , R 2 are respectively one of phenyl, substituted phenyl and C 1 -C 8 alkyl, R 1 , R 2 can be the same or different, and are selected according to actual needs.

[0054] Thirdly, the present invention also provides a copper complex, which is prepared by carrying out a complexation reaction between the above-mentioned 2,9-diaryl chiral phenanthroline ligand and a copper salt. Specifically, it can be:

[0055] The application of the 2,9-diaryl chiral phenanthroline ligand is characterized in that the 2,9-diaryl chiral phenanthroline ligand and copper trifluoromethanesulfonate are added into a reaction tube, and then a solvent is added. After complexation for two hours, potassium carbonate and phenethyl (methylsulfonyloxy)carbamate are added and the reaction is carried out to completion under stirring conditions.

[0056] The application of the 2,9-diaryl chiral phenanthroline ligand is characterized in that the conditions of the borohydride reaction are as follows: the dosage of the copper metal salt is 5 mol%, the dosage of the 2,9-diaryl chiral phenanthroline ligand is 6 mol%; the base is various organic bases and inorganic bases; the solvent used is an ether of C 1 -C 8 , toluene, dichloromethane; the reaction temperature is 0-50 °C; the reaction time is 1-24 hours.

[0057] In a fourth aspect, the present invention also provides the use of the above-mentioned 2,9-diaryl chiral phenanthroline ligand or the above-mentioned copper complex in an asymmetric transition metal catalyst. Specifically: the 2,9-diaryl chiral phenanthroline ligand is used as a chiral ligand for the asymmetric insertion reaction of copper-catalyzed intramolecular nitrene into the C(sp 3 )-H bond:

[0058]

[0059] Wherein: R 3 is phenyl, substituted phenyl, heteroaryl.

[0060] The technical solution of the present invention will be clearly and detailedly described below in conjunction with specific embodiments.

[0061] Term Explanation

[0062] The following abbreviations are used in the following examples, and their meanings are as follows:

[0063] Me is methyl, Et is ethyl, i Pr is isopropyl, t Bu is tert-butyl, Ph is phenyl, THF is tetrahydrofuran, DCM is dichloromethane, DCE is 1,2-dichloroethane, DMF is N,N-dimethylformamide, PE is petroleum ether, EA is ethyl acetate, Ms is methylsulfonyl, Ar is argon, CDCl 3 is deuterated chloroform.

[0064] eq. is equivalent, rt represents room temperature, TLC is thin layer chromatography, NMR is nuclear magnetic resonance, HRMS is high resolution mass spectrometry, HPLC is high performance liquid chromatography.

[0065] The solvents used were purified and dried by standard operations before use; all the reagents used were commercially available or synthesized according to the methods in the existing literature, and were purified before use.

[0066] Example 1

[0067] Synthesis of 3,5-diamidobromobenzene 3a-3i, 3a-3i, 1-3 are the compounds identified in the following chemical structures in this example:

[0068]

[0069] 3,5-Dicarboxy bromobenzene 1 (5.54 mmol, 1.36 g) was added to a 100 mL three-necked flask. The system was replaced with argon protection. Under the blowing state, 4 mL of thionyl chloride (55.5 mmol, 6.59 g) and three drops of N,N-dimethylformamide were added. It was heated to 90 °C. After reacting for two hours, it was desolvated under vacuum to obtain a bright yellow solid 2. Subsequently, 8 mL of dichloromethane was added to the flask. Under the condition of an ice-water bath, a dichloromethane solution of 10 (11.1 mmol) and triethylamine (11.1 mmol, 1.12 g) was added dropwise. After the dropwise addition was completed, it was restored to room temperature and stirred for 6 - 12 h. After the reaction was completed, water was added to quench the system under an ice-water bath. After liquid separation, it was extracted with dichloromethane (3 × 12 mL). The organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, the filtrate was rotary evaporated, and loaded onto a column by dry method. Column chromatography separation (PE / EA = 10:1 to 2:1, v / v) gave compounds 3a - 3i.

[0070] 5-Bromo-1,3-N,N-bis((R)-1-phenylethyl) isophthalamide (3a)

[0071]

[0072] White solid, isolated yield: 90%; melting point: 168.0 - 171.5 °C; R f = 0.5 (PE / EA = 3:1, v / v) [α] D 25 - 30.6 (c 0.50, CH 2 Cl 2 )

[0073] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.97 (t, J = 1.6 Hz, 1H), 7.87 (d, J = 1.4 Hz, 2H), 7.31 - 7.25 (m, 8H), 7.24 - 7.19 (m, 2H), 6.49 (d, J = 7.7 Hz, 2H), 5.21 (p, J = 7.1 Hz, 2H), 1.52 (d, J = 6.9 Hz, 6H).

[0074] 13 13C NMR (101 MHz, CDCl 3 ) δ 21.60, 49.73, 123.00, 123.97, 126.28, 127.67, 128.82, 132.85, 136.63, 142.54, 164.34.

[0075] HRMS (ESI) calcd for [C 24 H23 BrN 2 NaO 2 ,M+Na] + :473.0841; Found:473.0840.

[0076] The synthesis method of the following compounds (3b - 3s) is the same as that of Example 1.

[0077] 5 - Bromo - N,N - bis((R)-1-(2 - naphthyl)ethyl)isophthalamide (3b)

[0078]

[0079] White solid, isolated yield: 78%; melting point: >330.0 °C; R f = 0.6 (PE / EA = 2.5:1, v / v), [α] D 25 -24.4 (c 0.50, CH 2 Cl 2 ).

[0080] 1 H NMR (400 MHz, DMSO - d 6 ) δ 9.39 - 9.32 (m, 2H), 8.54 - 8.50 (m, 1H), 8.31 - 8.15 (m, 4H), 7.95 (d, J = 7.9 Hz, 2H), 7.84 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 7.1 Hz, 2H), 7.60 - 7.47 (m, 6H), 5.97 (p, J = 7.0 Hz, 2H), 1.64 (d, J = 6.9 Hz, 6H).

[0081] 13 C NMR (101 MHz, DMSO - d 6 ) δ 21.84, 45.54, 122.00, 123.17, 123.53, 125.98, 126.05, 126.50, 126.69, 127.78, 129.14, 130.85, 132.94, 133.81, 136.98, 140.50, 163.96.

[0082] HRMS (MALDI) calcd for [C 32 H 27 BrN 2 NaO 2 ,M+Na] + :573.1154; Found:573.1150.

[0083] 5-Bromo-N,N-bis((R)-1-(4-phenyl)phenethyl)isophthalamide (3c)

[0084]

[0085] White solid, isolated yield: 91%; melting point: 178.0 - 180.5 °C; R f = 0.4 (PE / EA = 3:1, v / v), [α] D 25 -16.2 (c 0.50, CH 2 Cl 2 ).

[0086] 1H NMR (400 MHz, DMSO-d6) δ 9.14 (d, J = 7.8 Hz, 2H), 8.39 (t, J = 1.6 Hz, 1H), 8.23 (d, J = 1.5 Hz, 2H), 7.73 - 7.59 (m, 8H), 7.51 - 7.42 (m, 8H), 7.35 (t, J = 7.3 Hz, 2H), 5.20 (t, J = 7.3 Hz, 2H), 1.53 (d, J = 7.0 Hz, 6H).

[0087] 13C NMR (101 MHz, DMSO-d6) δ 22.50, 49.13, 122.01, 126.49, 127.06, 127.12, 127.21, 127.75, 129.36, 132.91, 137.14, 139.18, 140.50, 144.28, 164.13.

[0088] HRMS (MALDI) calcd for [C36H31BrN2NaO2, M+Na]+: 625.1467; Found: 625.1466.

[0089] N,N-Dibenzyl-5-bromo-N,N-bis((R)-1-phenethyl)isophthalamide (3d)

[0090]

[0091] Yellow solid, isolated yield: 97%; melting point: 172.0 - 175.5 °C; R f = 0.6 (PE / EA = 3:1, v / v), [α] D 25 +19.5 (c 0.50, CH 2 Cl 2 ).

[0092] 11H NMR (400 MHz, acetone-d 6 ) δ 7.65 (br, 3H), 7.28 (m, 20H), 5.86 - 5.05 (m, 2H), 4.91 (br, 2H), 4.12 - 4.06 (m, 2H), 1.50 (d, J=7.1 Hz, 6H).

[0093] 13 13C NMR (101 MHz, acetone-d 6 ) δ 18.59, 46.25, 58.14, 123.05, 123.82, 127.52, 127.87, 128.35, 128.81, 129.04, 129.45, 130.89, 139.83, 140.77, 141.59, 170.29.

[0094] HRMS (MALDI) calcd for [C 38 H 35 BrN 2 NaO 2 , M + Na] + : 653.1780; Found: 653.1782.

[0095] (5-Bromo-1,3-phenylene)bis((S)-2-benzoylpyrrolidin-1-yl)methanone (3e)

[0096]

[0097] Yellow solid, isolated yield: 87%; melting point: 121.0 - 124.5 °C; R f = 0.5 (PE / EA = 2:1, v / v), [α] D 25 - 56.9 (c 0.70, CH 2 Cl 2 ).

[0098] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.50 - 7.00 (m, 22H), 6.78 (br, 1H), 5.43 - 5.25 (m, 2H), 4.51 (m, 2H), 4.05 - 3.64 (m, 1H), 3.12 (m, 3H), 2.18 - 1.63 (m, 8H).

[0099] 13 13C NMR (101 MHz, CDCl 3)δ24.29,27.85,49.47,53.37,59.54,122.18,124.72,126.49,126.94,128.10,128.52,128.76,129.46,131.87,138.93,141.49,141.92,167.68。

[0100] HRMS(ESI)calcd for[C 42 H 39 BrN 2 NaO 2 ,M+Na] + :705.2093;Found:705.2091。

[0101] (5-Bromo-1,3-phenylene)bis((S)-2-(di-p-tolylmethyl)pyrrolidin-1-yl)methanone(3f)

[0102]

[0103] Pale yellow foamy solid, isolated yield: 57%; melting point: 115.0 - 118.2 °C; R f =0.5(PE / EA=1:1, v / v), [α] D 25 -40.4(c 0.80,CH 2 Cl 2 )。

[0104] 1 H NMR(400MHz,CDCl 3 )δ7.82(s,2H),7.48 - 6.96(m,16H),6.75(s,1H),5.46 - 5.24(m,2H),4.56(m,2H),4.06 - 3.55(m,1H),3.31 - 2.91(m,3H),2.29 - 2.39(m,12H),2.18 - 1.59(m,8H)。

[0105] 13 C NMR(101MHz,CDCl 3 )δ21.18,24.37,27.87,49.41,52.70,59.61,122.25,124.71,128.63,128.80,129.24,129.30,131.96,135.80,136.37,138.70,138.98,139.17,167.66。

[0106] HRMS(MALDI)calcd for[C46 H 47 BrN 2 NaO 2 ,M+Na] + : 761.2719; Found: 761.2717.

[0107] (5-Bromo-1,3-phenylene)bis((S)-2-(bis(4-(tert-butyl)phenyl)methyl)pyrrolidin-1-yl)methanone) (3 g)

[0108]

[0109] White solid, isolated yield: 70%; melting point: 119.0 - 122.5 °C; R f = 0.5 (PE / EA = 5:1, v / v), [α] D 25 -48.3 (c 0.80, CH 2 Cl 2 ).

[0110] 1 H NMR (400 MHz, CDCl 3 ) δ 7.45 - 7.15 (m, 17H), 7.00 (m, 1H), 6.80 (m, 1H), 5.29 (m, 2H), 4.52 m, 2H), 4.14 - 3.47 (m, 1H), 3.29 - 2.83 (m, 3H), 2.13 - 1.56 (m, 8H), 1.28 (m, 36H).

[0111] 13 C NMR (101 MHz, CDCl 3 ) δ 24.32, 27.78, 31.51, 31.55, 34.39, 34.47, 49.38, 52.30, 59.72, 121.76, 124.98, 125.29, 128.44, 128.63, 129.18, 131.48, 138.41, 138.98, 139.46, 149.02, 149.60, 167.42.

[0112] HRMS (MALDI) calcd for [C 58 H 71 BrN 2 NaO 2 ,M+Na] + : 929.4597; Found: 929.4592.

[0113] (5-Bromo-1,3-phenylene)bis(((S)-2-(bis(3,5-dimethylphenyl)methyl)pyrrolidin-1-yl)methanone)(3h)

[0114]

[0115] White solid, isolated yield: 79%; melting point: 108.3 - 111.5 °C; R f = 0.7 (PE / EA = 3:1, v / v), [α] D 25 -68.9 (c 0.90, CH 2 Cl 2 ).

[0116] 1 H NMR (400 MHz, CDCl 3 ) δ 7.51 (m, 1H), 7.42 - 7.28 (m, 2H), 7.01 (br, 6H), 6.96 (br, 2H), 6.86 (br, 2H), 6.72 (br, 1H), 6.47 (s, 1H), 5.31 (br, 2H), 4.67 - 4.43 (m, 2H), 3.98 - 3.70 (m, 1H), 3.27 - 3.11 (m, 3H), 2.37 - 2.32 (m, 24H), 2.21 - 2.13 (m, 3H), 1.98 - 1.95 (m, 2H), 1.77 - 1.81 (m, 3H).

[0117] 13 C NMR (101 MHz, CDCl 3 ) δ 21.51, 24.36, 26.99, 27.84, 49.51, 52.77, 59.46, 121.42, 125.38, 126.62, 127.49, 128.11, 128.54, 131.37, 137.36, 137.76, 139.72, 141.34, 141.91, 167.42.

[0118] HRMS (MALDI) calcd for [C 50 H 55 BrN 2 NaO 2 , M + Na] + : 817.3345; Found: 817.3342.

[0119] (5-Bromo-1,3-phenylene)bis(((S)-2-(bis(3,5-di-tert-butylphenyl)methyl)pyrrolidin-1-yl)methanone)(3i)

[0120]

[0121] White solid, isolation yield: 81%; melting point: 132.0 - 136.5 °C; R f = 0.4 (PE / EA = 5:1, v / v), [α] D 25 - 25.7 (c 0.40, CH 2 Cl 2 ).

[0122] 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 - 7.41 (m, 1H), 7.35 - 7.21 (m, 12H), 6.90 - 6.72 (m, 2H), 5.21 (d, J = 6.5 Hz, 2H), 4.55 (d, J = 6.8 Hz, 2H), 3.97 - 3.54 (m, 1H), 3.16 - 2.98 (m, 3H), 2.02 - 1.97 (m, 4H), 1.80 - 1.66 (m, 4H), 1.34 - 1.26 (m, 72H).

[0123] 13 C NMR (101 MHz, CDCl 3 ) δ 24.27, 28.48, 31.56, 34.86, 49.59, 54.43, 61.02, 120.16, 120.57, 123.09, 123.95, 130.72, 139.86, 140.55, 141.13, 150.12, 150.36, 150.47, 150.76, 167.37.

[0124] HRMS (ESI) calcd for [C 74 H 103 BrN 2 O 2 , M + Na] + : 1153.7101; Found: 1153.7099.

[0125] Example 2: Preparation of 3,5 - diamidophenylboronic esters 4a - 4h, and 4a - 4h and 1 - 4 are the compounds identified in the following chemical structures in this example:

[0126] Synthesis of 3,5 - diamidophenylboronic ester (4)

[0127]

[0128] 3,5-diaminobromobenzene 3 (2 mmol), bis(pinacolato)diboron (2.4 mmol, 609.4 mg), Pd(dppf)Cl 2 (0.1 mmol, 72.6 mg) and potassium acetate (6 mmol, 588.6 mg) were weighed into a 25 mL reaction tube. The system was replaced with argon protection, and 6 mL of dry 1,4-dioxane was added. The mixture was heated to 100 °C and reacted for 4 - 12 hours. After the reaction was completed as detected by TLC, it was filtered through diatomaceous earth, the 1,4-dioxane was removed by rotary evaporation to obtain a brown foamy solid. Dichloromethane (8 mL) was added to dissolve it, and the organic phase was washed three times with water, then with saturated brine, dried over anhydrous sodium sulfate, filtered, the filtrate was rotary evaporated to dryness, and loaded onto a column by dry method. Column chromatography separation (PE / EA = 10:1 to 2:1, v / v) or reprecipitation with diethyl ether was carried out to obtain compounds 4a - 4h.

[0129] N,N-bis((R)-1-phenylethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalamide (4a)

[0130]

[0131] White solid, isolated yield: 98%; melting point: 178.0 - 180.8 °C; R f = 0.4 (PE / EA = 4:1, v / v), [α] D 25 -27.6 (c 0.50, CH 2 Cl 2 ).

[0132] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.35 (s, 1H), 8.28 (s, 2H), 7.40 - 7.29 (m, 8H), 7.26 - 7.23 (m, 2H), 6.59 (d, J = 7.8 Hz, 2H), 5.31 (t, J = 7.2 Hz, 2H), 1.57 (d, J = 6.9 Hz, 6H), 1.33 (s, 12H).

[0133] 13 13C NMR (101 MHz, CDCl 3 ) δ 21.72, 27.10, 49.53, 84.60, 126.45, 127.60, 128.84, 134.35, 135.76, 142.96, 165.77.

[0134] HRMS (MALDI) calcd for [C 30 H 35 N2 NaO 4 , M+Na] + : 521.2588; Found: 521.2585.

[0135] N,N-bis((R)-1-(2-naphthyl)ethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalamide (4b)

[0136]

[0137] White solid, isolated yield: 68%; melting point: 188.0 - 189.9 °C; R f = 0.5 (PE / EA = 2:1, v / v), [α] D 25 -20.4 (c 0.50, CH 2 Cl 2 ).

[0138] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.33 (s, 1H), 8.21 (s, 2H), 8.10 (d, J = 8.2 Hz, 2H), 7.81 (dd, J = 18.6, 7.9 Hz, 4H), 7.56 (d, J = 7.2 Hz, 2H), 7.53 - 7.39 (m, 6H), 6.55 - 6.58 (m, 2H), 6.10 (p, J = 7.1 Hz, 2H), 1.73 (d, J = 7.0 Hz, 6H), 1.30 - 1.29 (m, 12H).

[0139] 13 13C NMR (101 MHz, CDCl 3 ) δ 20.59, 24.85, 45.19, 84.46, 122.79, 123.34, 125.20, 125.87, 126.68, 128.55, 128.73, 128.77, 131.21, 133.93, 133.98, 135.65, 137.80, 165.29.

[0140] HRMS (MALDI) calcd for [C 38 H 39 BN 2 NaO 4 , M+Na] + : 621.2901; Found: 621.2898.

[0141] N,N-bis((R)-1-([1,1'-biphenyl]-4-yl)ethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalamide (4c)

[0142]

[0143] White solid, isolated yield: 72%; melting point: 158.4 - 161.5 °C; R f = 0.2 (PE / EA = 3:1, v / v), [α] D 25 -18.4 (c 0.50, CH 2 Cl 2 ).

[0144] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.41 (s, 1H), 8.32 (s, 2H), 7.53 (t, J = 7.2 Hz, 8H), 7.41 (t, J = 6.8 Hz, 8H), 7.32 (t, J = 7.3 Hz, 2H), 6.69 (d, J = 7.8 Hz, 2H), 5.35 (q, J = 7.1 Hz, 2H), 1.59 (d, J = 7.0 Hz, 6H), 1.32 (s, 12H).

[0145] 13 13C NMR (101 MHz, CDCl 3 ) δ 21.64, 24.91, 49.20, 84.49, 126.80, 127.11, 127.30, 127.46, 128.78, 134.23, 135.80, 140.41, 140.75, 141.98, 165.75.

[0146] HRMS (MALDI) calcd for [C 42 H 44 BN 2 O 4 , M+H] + : 651.3394; Found: 651.3392.

[0147] N,N-dibenzyl-N,N-bis((R)-1-phenylethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalamide (4d)

[0148]

[0149] White solid, isolated yield: 76%; melting point: 98.1 - 101.5 °C; R f = 0.5 (PE / EA = 3:1, v / v), [α] D 25 +107.8 (c 3.90, CH 2 Cl 2 ).

[0150] 1 H NMR (400 MHz, CDCl 3 ) δ 8.05 - 7.79 (m, 3H), 7.50 - 6.70 (m, 20H), 6.01 (br, 1H), 5.16 (s, 1H), 5.10 - 4.75 (m, 2H), 3.96 (d, J = 15.5 Hz, 2H), 1.45 (s, 6H), 1.31 (s, 12H).

[0151] 13 C NMR (101 MHz, CDCl 3 ) δ 18.96, 25.21, 45.93, 57.87, 84.58, 127.19, 127.68, 128.00, 128.42, 128.67, 128.99, 134.18, 137.04, 139.22, 140.48, 172.13.

[0152] HRMS (MALDI) calcd for [C 44 H 48 BN 2 O 4 , M + H] + : 679.3701; Found: 679.3685.

[0153] (5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-phenylene bis((S)-2-benzoylpyrrolidin-1-yl)methanone) (4e)

[0154]

[0155] White solid, isolated yield: 77%; melting point: 124.2 - 130.2 °C; R f = 0.5 (PE / EA = 1:1, v / v), [α] D 25 -51.5 (c 0.70, CH 2 Cl 2 ).

[0156] 1 H NMR (400 MHz, CDCl3 ) δ 7.82 (s, 2H), 7.48 - 6.96 (m, 21H), 5.46 - 5.24 (m, 2H), 4.55 - 4.57 (m, 2H), 4.06 - 3.55 (m, 1H), 3.31 - 2.91 (m, 3H), 2.18 - 1.59 (m, 8H), 1.34 - 1.33 (m, 12H).

[0157] 13 C NMR (101 MHz, CDCl 3 ) δ 24.30, 24.84, 25.00, 27.78, 49.46, 53.26, 59.26, 84.12, 126.32, 126.76, 128.04, 128.36, 128.43, 128.82, 129.56, 135.10, 136.46, 141.70, 142.08, 169.47.

[0158] HRMS (MALDI) calcd for [C 48 H 52 BN 2 O 4 , M + H] + : 731.4020; Found: 731.4018.

[0159] (5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-phenylene)bis(((S)-2-(di-p-tolylmethyl)pyrrolidin-1-yl)methanone) (4f)

[0160]

[0161] White solid, isolated yield: 81%; melting point: 135.2 - 139.2 °C; R f = 0.5 (PE / EA = 3:1, v / v), [α] D 25 -60.3 (c 4.7, CH 2 Cl 2 ).

[0162] 1 H NMR (400 MHz, CDCl 3)δ 7.83 (s, 2H), 7.25 (d, J = 7.3 Hz, 9H), 7.16 (d, J = 7.7 Hz, 4H), 7.04 (d, J = 7.8 Hz, 4H), 5.31 (s, 2H), 4.45 (d, J = 7.8 Hz, 2H), 3.19 - 2.97 (m, 4H), 2.34 - 2.26 (m, 12H), 2.05 (d, J = 7.4 Hz, 2H), 1.89 (d, J = 11.1 Hz, 3H), 1.73 (s, 3H), 1.33 (d, J = 5.9 Hz, 12H).

[0163] 13 C NMR (101 MHz, CDCl 3 )δ 21.07, 24.60, 24.85, 27.73, 49.36, 52.52, 59.24, 84.12, 128.43, 128.65, 128.71, 129.14, 129.38, 135.17, 135.62, 136.18, 136.44, 138.84, 139.28, 169.45.

[0164] HRMS (MALDI) calcd for [C 52 H 59 BN 2 NaO 4 , M + Na] + : 787.4646; Found: 787.4644.

[0165] (5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-phenylene)bis(((S)-2-(bis(4-(tert-butyl)phenyl)methyl)pyrrolidin-1-yl)methanone) (4 g)

[0166]

[0167] White solid, isolated yield: 72%; melting point: 103.1 - 108.8 °C; R f = 0.5 (PE / EA = 3:1, v / v), [α] D 25 - 47.8 (c 0.7 CH 2 Cl 2 ).

[0168] 1 H NMR (400 MHz, CDCl 3) δ 7.78 (br, 2H), 7.46 (br, 1H), 7.36 - 7.33 (m, 4H), 7.31 - 7.28 (m, 8H), 7.27 - 7.25 (m, 4H), 5.31 - 5.28 (m, 2H), 4.52 (d, J = 7.3 Hz, 2H), 3.24 - 2.97 (m, 4H), 2.08 - 2.03 (m, 2H), 1.93 - 1.89 (m, 2H), 1.68 - 1.60 (m, 4H), 1.34 - 1.33 (m, 12H), 1.32 - 1.26 (m, 36H).

[0169] 13 C NMR (101 MHz, CDCl 3 ) δ 24.25, 24.60, 27.53, 31.39, 31.46, 34.32, 34.43, 49.34, 52.04, 59.45, 84.08, 124.87, 125.15, 128.44, 128.61, 129.15, 134.73, 136.79, 138.68, 139.15, 148.82, 149.36, 169.33.

[0170] HRMS (ESI) m / z calcd for [C 64 H 83 BN 2 NaO 4 , M + Na] + : 977.6344; Found: 977.6344.

[0171] (5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-phenylene)bis(((S)-2-(bis(3,5-dimethylphenyl))methyl)pyrrolidin-1-yl)methanone) (4h)

[0172]

[0173] White solid, isolated yield: 78%; melting point: 121.8 - 125.5 °C; R f = 0.2 (PE / EA = 3:1, v / v), [α] D 25 - 38.4 (c 1.20, CH 2 Cl 2 ).

[0174] 1 H NMR (400 MHz, CDCl 3)δ 7.77 (br, 2H), 7.67 (br, 1H), 6.97 (br, 7H), 6.89 (br, 2H), 6.79 (br, 3H), 5.22 (q, J = 6.5 Hz, 2H), 4.49 (d, J = 7.0 Hz, 2H), 3.27 - 3.21 (m, 1H), 3.12 - 3.12 (m, 2H), 2.87 (br, 1H), 2.33 - 2.27 (m, 24H), 2.16 - 2.06 (m, 3H), 1.95 - 1.86 (m, 2H), 1.70 - 1.61 (m, 3H), 1.35 (br, 12H).

[0175] 13 C NMR (101 MHz, CDCl 3 ) δ 21.53, 24.85, 27.77, 49.73, 52.44, 59.51, 74.76, 84.16, 126.77, 127.67, 127.99, 128.39, 129.60, 134.44, 137.23, 137.35, 137.62, 141.53, 142.05, 169.23.

[0176] HRMS (MALDI) calcd for [C 56 H 68 BN 2 O 4 , M + H] + : 843.5272; Found: 843.5269.

[0177] Example 3: Synthesis of chiral ligands (6a - e, 6h), where 6a - e, 6h, 4 - 6 are the compounds identified in the following chemical structures in this example:

[0178]

[0179] Weigh successively 2,9 - dichloro - 1,10 - phenanthroline 5 (0.5 mmol, 124.0 mg), 3,5 - diamidobenzeneboronic acid pinacol ester 4 (1.2 mmol), Pd(dppf)Cl 2 (0.025 mmol, 18.0 mg) and Ba(OH) 2 ·8H 2O (4.0 mol, 1.26 g) was added to a 50 mL three-necked flask; a reflux condenser was set up, and the system was replaced with an argon atmosphere; subsequently, the well-degassed mixed solvent (toluene / water = 4:1, v / v) was transferred into the reaction flask using a syringe; finally, the reaction system was refluxed in an oil bath, and the reaction progress was monitored by TLC until the reaction was complete. Work-up: The reaction mixture was filtered under reduced pressure (using diatomaceous earth as a filter aid), and the filter cake was washed thoroughly with DCM or EA; after the filtrate was concentrated by evaporation, it was loaded onto a column by dry loading and separated by column chromatography (PE / EA = 3:1 to 1:1 or PE / Ac = 3:1 to 1:1 or DCM / EA = 3:1, v / v) to obtain compounds 6a-c.

[0180] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-phenylethyl)isophthalamide) (6a)

[0181]

[0182] White solid, isolated yield: 70%; melting point: 173.5 - 179.4 °C; R f = 0.6 (DCM / EA = 1:1, v / v), [α] D 25 -239.4 (c 0.7, CH 2 Cl 2 ).

[0183] 1 H NMR (400 MHz, CDCl 3 ) δ 8.73 (s, 4H), 8.37 (s, 2H), 8.26 (d, J = 8.3 Hz, 2H), 7.95 (d, J = 8.3 Hz, 2H), 7.75 (s, 2H), 7.47 (d, J = 7.6 Hz, 4H), 7.31 - 7.29 (m, 6H), 7.23 - 7.16 (m, 10H), 5.29 (t, J = 7.1 Hz, 4H), 2.21 (br, 4H), 1.52 (d, J = 6.9 Hz, 12H).

[0184] 13 C NMR (101 MHz, CDCl 3 ) δ 21.67, 49.73, 121.72, 126.25, 126.61, 127.32, 128.34, 128.59, 129.76, 135.10, 137.52, 140.18, 141.45, 143.07, 145.74, 165.50.

[0185] HRMS (MALDI) calcd for [C 60 H52 N 6 NaO 4 ,M+Na] + : 943.3948; Found: 943.3945.

[0186] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-(1-naphthyl)ethyl)isophthalamide) (6b)

[0187]

[0188] White solid, isolated yield: 63%; melting point: 270.2 - 275.0 °C; R f = 0.3 (PE / Ac = 2:1, v / v), [α] D 25 -196.2 (c 0.80, CH 2 Cl 2 ).

[0189] 1 H NMR (400 MHz, DMSO-d 6 ) δ 9.34 (d, J = 7.6 Hz, 4H), 9.01 (s, 4H), 8.70 (d, J = 8.4 Hz, 2H), 8.60 - 8.41 (m, 4H), 8.39 - 8.16 (m, 4H), 8.10 (s, 2H), 7.99 - 7.87 (m, 4H), 7.82 (d, J = 8.2 Hz, 4H), 7.64 (d, J = 7.2 Hz, 4H), 7.58 - 7.37 (m, 12H), 6.06 (t, J = 7.3 Hz, 4H), 1.61 (d, J = 6.8 Hz, 12H).

[0190] 13 C NMR (101 MHz, DMSO-d 6 ) δ 21.58, 45.17, 121.16, 122.60, 123.12, 125.51, 125.56, 126.17, 126.67, 127.21, 127.66, 128.23, 128.66, 128.98, 130.45, 133.37, 135.71, 137.72, 139.58, 140.39, 145.41, 155.28, 165.29.

[0191] HRMS (MALDI) calcd for [C 76 H 60 N 6 O 4 Na, M+Na] +: 1143.4568; Found: 1143.4555.

[0192] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-([1,1'-biphenyl]-4-yl)ethyl)isophthalamide) (6c)

[0193]

[0194] White solid, isolated yield: 62%; melting point: 145.7 - 149.5 °C; R f = 0.6 (DCM / Ac = 4:1, v / v), [α] D 25 +4.6 (c 4.7, CH 2 Cl 2 ).

[0195] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.59 (br, 4H), 8.42 (br, 2H), 7.96 (br, 2H), 7.73 (br, 2H), 7.65 - 7.60 (m, 2H), 7.47 - 7.43 (m, 11H), 7.41 - 7.30 (m, 20H), 7.28 - 7.22 (m, 5H), 5.26 (p, J = 7.0 Hz, 4H), 3.13 - 3.06 (m, 4H), 1.46 (d, J = 6.9 Hz, 12H).

[0196] 13 13C NMR (101 MHz, CDCl 3 ) δ 21.66, 49.53, 121.47, 126.41, 126.54, 126.55, 126.69, 126.96, 127.20, 128.07, 128.71, 129.79, 134.95, 137.25, 140.03, 140.58, 142.33, 145.50, 165.75.

[0197] HRMS (MALDI) calcd for [C 84 H 68 N 6 O 4 Na, M + Na] + : 1225.5380; Found: 1225.5389.

[0198]

[0199] Weigh 2,9-dichlorophenanthroline 5 (0.5 mmol, 124.0 mg), 3,5-diaminobenzeneboronic acid pinacol ester 4 (1.2 mmol), Pd(dppf)Cl 2 (0.025 mmol, 18.0 mg), and K 2 CO 3 (3.0 mol, 414.6 mg) into a 50 mL three-necked flask in sequence; set up a reflux condenser and replace the system with an argon atmosphere; then, use a syringe to transfer the thoroughly degassed mixed solvent (1,4-dioxane / water = 4:1, v / v) into the reaction flask; finally, place the reaction system in an oil bath for reflux reaction, and monitor the reaction progress by TLC until the reaction is complete. Post-treatment: The reaction solution is filtered under reduced pressure (using diatomaceous earth as a filter aid), and the filter residue is washed thoroughly with DCM or EA; after the resulting filtrate is concentrated by evaporation, it is loaded onto a column for dry-column chromatography separation (PE / EA = 3:1 to 1:1 or PE / Ac = 3:1 to 1:1 or DCM / EA = 3:1, v / v) to obtain compounds 6d, 6e, and 6h.

[0200] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-dibenzyl-N,N-bis((R)-1-phenylethyl) isophthalamide) (6d)

[0201]

[0202] White solid, isolated yield: 84%; melting point: 114.0 - 116.2 °C; R f = 0.4 (PE / EA = 2:1, v / v), [α] D 25 +6.2 (c 1.3, CH 2 Cl 2 ).

[0203] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.61 - 8.20 (m, 6H), 8.00 - 7.60 (m, 6H), 7.52 - 6.86 (m, 40H), 6.07 (br, 1H), 5.40 - 4.90 (m, 5H), 4.82 - 3.90 (m, 6H), 1.53 (br, 12H).

[0204] 13 13C NMR (101 MHz, CDCl 3)δ17.35,44.82,56.73,119.74,124.44,125.65,125.77,125.87,126.43,126.56,127.20,127.43,127.57,127.72,127.79,136.53,137.90,138.80,140.28,145.42,154.24,170.28。

[0205] HRMS(MALDI)calcd for[C 88 H 77 N 6 O 4 ,M+H] + :1281.6006;Found:1281.6005。

[0206] ((1,10-Phenanthroline-2,9-dicarbonyl)bis(benzene-5,1,3-tricarbonyl))tetrakis((S)-2-(bis(4-phenyl)methyl)pyrrolidin-1-yl)methanone)(6e)

[0207]

[0208] White solid, isolated yield: 72%; melting point: 193.0 - 195.2 °C; R f = 0.8 (DCM / MeOH = 10:1, v / v), [α] D 25 -50.4 (c 1.00, CH 2 Cl 2 ).

[0209] 1 H NMR(400MHz,CDCl 3 )δ8.41 - 8.27(m,4H),8.25(br,2H),7.95(d,J = 8.4Hz,2H),7.79(s,2H),7.45 - 7.35(m,14H),7.34 - 7.27(m,8H),7.26 - 7.16(m,12H),7.14 - 7.05(m,5H),6.98(br,1H),6.84(br,1H),6.76(br,1H),5.55 - 5.25(m,4H),4.84 - 4.50(m,4H),4.14 - 3.63(m,2H),3.34 - 3.08(m,6H),2.20 - 2.01(m,4H),1.88(s,5H),1.77 - 1.47(m,7H)。

[0210] 13 C NMR(101MHz,CDCl3 ) δ 24.31, 27.90, 49.52, 53.10, 59.47, 121.03, 126.34, 126.59, 126.76, 128.10, 128.20, 128.31, 128.47, 128.64, 128.93, 129.57, 137.13, 137.91, 141.80, 142.22, 146.49, 156.41, 169.14。

[0211] HRMS (MALDI) calcd for [C 96 H 85 N 6 O 4 , M + H] + : 1385.6632; Found: 1385.6632。

[0212] ((1,10 - Phenanthroline - 2,9 - diacyl)bis(benzene - 5,1,3 - triacyl))tetrakis((S)-2-(bis(3,5 - dimethylphenyl)methyl)pyrrolidin - 1 - yl)methanone)(6h)

[0213]

[0214] White solid, isolated yield: 34%; melting point: 172.5 - 177.7 °C; R f = 0.6 (PE / Ac = 1:1, v / v), [α] D 25 - 43.6 (c 0.90, CH 2 Cl 2 )。

[0215] 1 H NMR (400 MHz, CDCl 3 ) δ 8.35 (d, J = 8.4 Hz, 2H), 8.13 (br, 4H), 7.91 (d, J = 8.5 Hz, 2H), 7.88 (s, 2H), 7.39 (br, 2H), 7.08 - 6.80 (m, 20H), 6.73 (br, 4H), 5.29 (br, 4H), 4.45 (d, J = 7.5 Hz, 4H), 3.35 - 3.10 (m, 8H), 2.35 - 2.12 (m, 48H), 2.11 - 1.98 (m, 5H), 1.93 - 1.81 (m, 5H), 1.81 - 1.67 (br, 6H)。

[0216] 13 C NMR (101 MHz, CDCl 3)δ21.49,24.35,27.94,49.51,52.94,59.47,121.29,126.65,126.91,127.41,127.56,127.90,128.25,128.32,136.93,137.22,137.66,138.11,140.75,141.88,141.92,142.27,146.39,169.02。

[0217] HRMS(ESI)calcd for[C 112 H 116 N 6 O 4 Na 2 ,M+Na 2 2+ :827.4427;Found:827.4428。

[0218] Example 4:

[0219] Synthesis of 2,9-bis(3,5-dimethoxycarbonyl)phenylphenanthroline (8), and 5, 7 - 8 are the compounds identified by the following chemical structures in this example:

[0220]

[0221] Add 2,9-dichlorophenanthroline 5 (10 mmol, 2.48 g), (3,5-dimethoxycarbonyl)phenylboronic acid 7 (21 mmol, 5.0 g), Pd(PPh 3 ) 4 (0.5 mmol, 577.0 mg) and sodium carbonate (80 mmol, 8.48 g) into a 250 mL three-necked round-bottom flask equipped with a reflux condenser. After replacing the system with an argon atmosphere, add 40 mL of degassed toluene, 20 mL of ethanol, and 16 mL of water in sequence through a steel bridge. Heat under reflux and monitor the reaction progress by TLC. After the reaction is completed, filter, wash the filter cake with water, then rinse the filter cake with 40 mL of ethanol, and finally rinse the filter cake with dichloromethane. Compound 8 is obtained.

[0222] White solid, isolation yield: 98%; melting point: 260.5 - 266.5 °C; R f = 0.2 (DCM / EA = 2:1, v / v).

[0223] 1 H NMR(400MHz,CDCl 3 ​)δ9.24(d, J = 1.6 Hz, 4H), 8.82(t, J = 1.6 Hz, 2H), 8.41(d, J = 8.4 Hz, 2H), 8.24(d, J = 8.4 Hz, 2H), 7.88(s, 2H), 4.01(s, 12H).

[0224] 13 C NMR(101MHz, CDCl 3 )δ52.61, 100.13, 120.81, 126.76, 128.56, 131.49, 133.22, 137.56, 140.89, 146.35, 155.59, 166.40.

[0225] HRMS(MALDI) calcd for [C 32 H 25 N 2 O 8 , M + H] + : 565.1611; Found: 565.1608.

[0226] Example 5

[0227] Synthesis of 2,9 - bis(3,5 - dicarboxyphenyl)phenanthroline (9)

[0228]

[0229] Weighed 2,9 - bis(3,5 - dimethoxycarbonyl)phenylphenanthroline 8 (5 mmol, 2.8 g) and potassium hydroxide (50 mmol, 2.8 g) into a 100 mL three - necked flask equipped with a reflux condenser, added a mixed solvent of dioxane and water with a solvent ratio of 5:1, heated under reflux, and monitored the reaction progress by NMR. After the reaction was completed, the organic solvent was removed by rotary evaporation, and 0.05 M hydrochloric acid aqueous solution was slowly added, filtered, and the filter cake was washed with water to obtain 9.

[0230] Green solid, isolation yield: 89%; melting point: >330 °C; R f = 0.2 (DCM:MeOH = 2:1, v / v).

[0231] 1 H NMR(400MHz, DMSO - d 6 )δ9.05(s, 4H), 8.68(d, J = 8.3 Hz, 2H), 8.57(s, 2H), 8.47(d, J = 8.3 Hz, 2H), 8.08(s, 2H).

[0232] 13 C NMR(101MHz, DMSO - d 6)δ 120.84, 126.69, 128.26, 130.80, 131.69, 133.39, 137.92, 139.76, 145.49, 154.78, 167.14。

[0233] The solubility is too poor to be detected by HRMS.

[0234] Example 6

[0235] Synthesis of chiral ligands (6e - 6q), and 6e - 6q, 5 - 6, 11 are the compounds identified by the following chemical structures in this example:

[0236]

[0237] Step 1: Weigh 2,9 - bis(3,5 - dicarboxyphenyl)phenanthroline 9 (1 mmol, 508.4 mg) into a 100 mL three - necked flask equipped with a reflux condenser. Replace the system with an argon atmosphere, add 10 mL of thionyl chloride and a few drops of DMF as a catalyst, and heat under reflux for two hours. After the reaction is completed, remove the solvent under vacuum. It is directly used for the next step.

[0238] Step 2: Under an ice - water bath, slowly add a DMF solution of chiral amine 10 (6.0 mmol), DMAP (0.1 mmol, 12.2 mg), and triethylamine (8.0 mmol, 809.6 mg) dropwise to the DMF solution of 2,9 - bis(3,5 - dicarboxyphenyl)phenanthroline 11 prepared in the previous step. After the addition is complete, restore to room temperature and stir overnight. After the reaction is completed, add 15 mL of water to precipitate a large amount of yellow solid. Filter, wash the filter cake with water, then dissolve the filter cake in dichloromethane, dry it, and separate by column chromatography (PE / Ac = 5:1 to 1:1, v / v), and then recrystallize and purify in acetonitrile or tert - butyl methyl ether.

[0239] ((1,10 - phenanthroline - 2,9 - diacyl)bis(benzene - 5,1,3 - triacyl))tetrakis((S)-2 - (di - p - tolylmethyl)pyrrolidin - 1 - yl)methanone) (6f)

[0240]

[0241] White solid, isolation yield: 44%; melting point: 191.0 - 195.0 °C; R f = 0.4 (PE / Ac = 2:1, v / v), [α] D 25 -112.6 (c 3.7, CH 2 Cl 2 )。

[0242] 11H NMR (400 MHz, CDCl 3 ) δ 8.35 (d, J = 8.3 Hz, 2H), 8.20 (br, 3H), 7.97 (d, J = 8.3 Hz, 2H), 7.86 (s, 2H), 7.35 - 7.20 (m, 19H), 7.12 (d, J = 7.6 Hz, 8H), 7.02 (d, J = 7.6 Hz, 8H), 5.35 (br, 4H), 4.53 (br, 4H), 4.07 - 3.63 (m, 2H), 3.22 (br, 3H), 3.12 (br, 3H), 2.35 - 2.15 (m, 24H), 2.10 (s, 4H), 1.90 (s, 5H), 1.74 (s, 7H).

[0243] 13 13C NMR (101 MHz, CDCl 3 ) δ 21.05, 21.09, 24.40, 27.88, 49.53, 52.49, 59.47, 121.05, 126.36, 126.54, 128.27, 128.57, 128.74, 128.77, 129.17, 129.39, 135.56, 136.12, 137.06, 137.84, 138.98, 139.45, 140.72, 146.46, 156.56, 169.17.

[0244] HRMS (MALDI) calcd for [C 104 H 100 N 6 O 4 Na, M + Na] + : 1520.7731; Found: 1520.7726.

[0245] ((1,10 - Phenanthroline - 2,9 - dicarbonyl)bis(benzene - 5,1,3 - tricarbonyl))tetrakis(S) - 2 - (bis(4 - (tert - butyl)phenyl)methyl)pyrrolidin - 1 - yl)methanone)(S - 6g)

[0246]

[0247] White solid, isolated yield: 71%; melting point: 220.5 - 224.8 °C; R f = 0.5 (PE / Ac = 2:1, v / v), [α] D 25 - 42.4 (c 0.50, CH 2 Cl 2 ).

[0248] 11H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J = 8.3 Hz, 2H), 8.18 (s, 3H), 7.95 (d, J = 8.4 Hz, 2H), 7.86 (s, 2H), 7.43 (br, 2H), 7.37 - 7.27 (m, 21H), 7.27 - 7.24 (br, 3H), 7.23 - 7.17 (m, 8H), 6.85 - 7.02 (m, 1H), 5.40 - 5.25 (m, 4H), 4.59 (d, J = 7.5 Hz, 4H), 3.30 - 3.10 (m, 8H), 2.11 - 1.98 (m, 3H), 1.93 - 1.83 (m, 4H), 1.81 - 1.75 (m, 3H), 1.74 - 1.60 (m, 6H), 1.26 (br, 34H), 1.19 (br, 5H), 1.11 (br, 33H).

[0249] 13 13C NMR (101 MHz, CDCl 3 ) δ 24.33, 27.76, 31.31, 31.48, 34.27, 34.45, 49.42, 52.18, 59.59, 121.04, 124.90, 125.23, 126.06, 126.53, 128.28, 128.36, 128.56, 129.20, 137.09, 138.08, 138.93, 139.33, 140.71, 146.53, 148.79, 149.34, 156.58, 169.12.

[0250] HRMS (MALDI) calcd for [C 128 H 148 N 6 NaO 4 , M + Na] + : 1857.1487; Found: 1857.1441.

[0251] ((1,10 - Phenanthroline - 2,9 - dicarbonyl)bis(benzene - 5,1,3 - tricarbonyl))tetrakis((R)-2 - (bis(4 - (tert - butyl)phenyl)methyl)pyrrolidin - 1 - yl)methanone) (R - 6g)

[0252]

[0253] White solid, isolated yield: 71%; melting point: 219.6 - 225.7 °C; R f = 0.5 (PE / Ac = 2:1, v / v), [α] D 25+40.2(c0.50,CH 2 Cl 2 )。

[0254] 1 H NMR(400MHz,CDCl 3 )δ8.33(d,J = 8.3Hz,2H),8.18(s,3H),7.95(d,J = 8.4Hz,2H),7.86(s,2H),7.43(br,2H),7.37 - 7.27(m,21H),7.27 - 7.24(br,3H),7.23 - 7.17(m,8H),6.85 - 7.02(m,1H),5.40 - 5.25(m,4H),4.59(d,J = 7.5Hz,4H),3.30 - 3.10(m,8H),2.11 - 1.98(m,3H),1.93 - 1.83(m,4H),1.81 - 1.75(m,3H),1.74 - 1.60(m,6H),1.26(br,34H),1.19(br,5H),1.11(br,33H)。

[0255] 13 C NMR(101MHz,CDCl 3 )δ24.33,27.76,31.31,31.48,34.27,34.45,49.42,52.18,59.59,121.04,124.90,125.23,126.06,126.53,128.28,128.36,128.56,129.20,137.09,138.08,138.93,139.33,140.71,146.53,148.79,149.34,156.58,169.12。

[0256] HRMS(MALDI)calcd for[C 128 H 148 N 6 NaO 4 ,M+Na] + :1857.1487;Found:1857.1441。

[0257] (3R,3'R,3'R,3'R,5R,5'R,5'R,5”R)-(5,5'-(1,10 - phenanthroline - 2,9 - diyl)bis(isophthaloyl))tetrakis(5 - (bis(4 - (tert - butyl)phenyl)methyl)pyrrolidine - 1,3 - diyl)tetrakis(ethyl carbamate)(6j)

[0258]

[0259] Pale yellow solid, isolation yield: 57%; melting point: 214.0 - 219.6 °C; R f = 0.3 (PE / Ac = 3:1, v / v), [α] D 25 - 83.34 (c 1.30, CH 2 Cl 2 ).

[0260] 1 H NMR (400 MHz, CDCl 3 ) δ 8.48 - 8.30 (m, 1H), 8.20 - 8.02 (m, 1H), 8.01 - 7.82 (m, 4H), 7.45 - 6.75 (m, 38H), 5.41 (br, 2H), 5.31 - 5.10 (m, 2H), 4.98 (br, 1H), 4.86 (br, 1H), 4.77 (br, 2H), 4.65 - 4.45 (m, 3H), 3.80 - 3.65 (m, 1H), 3.60 - 3.40 (m, 2H), 3.31 - 2.97 (m, 10H), 2.52 - 2.32 (m, 3H), 2.20 (s, 2H), 2.01 - 1.85 (m, 2H), 1.80 - 1.66 (m, 1H), 1.37 - 1.22 (m, 46H), 1.20 - 1.02 (m, 30H), 1.01 - 0.83 (m, 16H).

[0261] 13 C NMR (101 MHz, CDCl 3 ) δ 15.22, 31.22, 31.38, 34.12, 34.29, 35.59, 52.71, 58.17, 72.44, 124.86, 124.99, 125.02, 125.22, 125.25, 125.71, 126.47, 126.65, 128.23, 128.98, 129.39, 137.00, 137.13, 137.44, 138.62, 146.20, 146.48, 148.88, 149.22, 149.59, 155.24, 155.58, 168.66.

[0262] HRMS (MALDI) calcd for [C 140 H 169 N 10 O 2 , M + H] + : 2183.2949; Found: 2183.2797.

[0263] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-(4'-methyl-[1,1'-biphenyl]-4-yl)ethyl)isophthalamide) (6k)

[0264]

[0265] White solid, isolated yield: 41%; melting point: 196.5 - 200.1 °C; R f = 0.5 (PE / Ac = 1:1, v / v), [α] D 25 -239.3 (c 0.60, CH 2 Cl 2 ).

[0266] 1 H NMR (400 MHz, CDCl 3 ) δ 8.72 (br, 4H), 8.43 (s, 2H), 8.17 (d, J = 8.3 Hz, 2H), 7.87 (br, 2H), 7.67 (s, 2H), 7.57 (br, 3H), 7.42 - 7.30 (m, 22H), 7.18 (br, 4H), 7.17 (br, 3H), 5.28 (t, J = 7.3 Hz, 4H), 2.35 (s, 12H), 1.50 (d, J = 6.9 Hz, 12H).

[0267] 13 C NMR (101 MHz, CDCl 3 ) δ 21.10, 21.81, 49.58, 120.86, 121.20, 126.29, 126.68, 126.80, 127.02, 127.93, 129.44, 129.81, 134.93, 136.91, 137.20, 137.72, 139.74, 139.94, 142.20, 145.30, 165.82.

[0268] HRMS (ESI) calcd for [C 88 H 77 KN 6 O 4 , M + K + H] 2+ : 660.2822; Found: 660.2819.

[0269] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-(4'-methyl-[1,1'-biphenyl]-4-yl)ethyl)isophthalamide) (6l)

[0270]

[0271] White solid, isolation yield: 44%; melting point: 211.2 - 214.5 °C; R f = 0.6 (PE / Ac = 2:1, v / v), [α] D 25 -220.3 (c 0.50, CH 2 Cl 2 ).

[0272] 1 H NMR (400 MHz, CDCl 3 ) δ 8.59 (br, 4H), 8.42 (br, 2H), 7.98 (br, 2H), 7.83 - 7.57 (m, 6H), 7.49 (br, 2H), 7.40 (br, 22H), 7.33 (br, 6H), 5.31 - 5.25 (m, 4H), 1.56 - 1.41 (m, 12H), 1.33 (s, 36H).

[0273] 13 C NMR (101 MHz, CDCl 3 ) δ 21.64, 31.37, 34.51, 49.51, 116.79, 125.66, 126.40, 126.63, 126.68, 127.08, 128.04, 129.77, 134.96, 137.23, 137.74, 139.91, 140.00, 140.04, 141.59, 142.04, 145.49, 150.15, 165.75.

[0274] HRMS (MALDI) calcd for [C 100 H 100 N 6 O 4 Na, M + Na] + : 1472.7731; Found: 1472.7715.

[0275] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-(3,5'-dimethyl-[1,1'-biphenyl]-4-yl)ethyl)isophthalamide) (6m)

[0276]

[0277] White solid, isolation yield: 70%; melting point: 178.3 - 184.0 °C; R f = 0.6 (PE / Ac = 1:1, v / v), [α]D 25 -239.5 (c1.1, CH 2 Cl 2 ).

[0278] 1 H NMR (400 MHz, CDCl 3 ) δ 8.68 (s, 4H), 8.41 (s, 2H), 8.04 (s, 2H), 7.73 (s, 5H), 7.55 (s, 2H), 7.41 (d, J = 7.9 Hz, 7H), 7.35 (d, J = 7.9 Hz, 7H), 7.07 (s, 7H), 6.93 (s, 4H), 5.37 - 5.22 (m, 4H), 2.30 (s, 24H), 1.51 (d, J = 6.9 Hz, 12H).

[0279] 13 C NMR (101 MHz, CDCl 3 ) δ 21.40, 21.68, 49.57, 121.31, 124.93, 126.29, 126.65, 127.24, 127.92, 128.86, 129.77, 134.94, 137.06, 138.14, 139.97, 140.29, 140.68, 142.29, 145.40, 165.88.

[0280] HRMS (MALDI) calcd for [C 92 H 84 N 6 O 4 Na, M + Na] + : 1359.6447; Found: 1359.6442.

[0281] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-(3,5'-di-tert-butyl-[1,1'-biphenyl]-4-yl)ethyl)isophthalamide) (6o)

[0282]

[0283] White solid, isolated yield: 34%; melting point: 207.0 - 209.0 °C; R f = 0.6 (PE / Ac = 2:1, v / v), [α] D 25 -231.0 (c 0.9, CH 2 Cl 2 ).

[0284] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.89 (br, 4H), 8.43 (br, 2H), 8.29 (br, 2H), 8.02 (br, 2H), 7.79 (br, 2H), 7.54 - 7.45 (m, 9H), 7.44 - 7.37 (m, 10H), 7.33 (br, 7H), 7.26 (br, 2H), 5.36 (t, J = 7.3 Hz, 4H), 2.19 - 2.15 (m, 9H), 1.56 (d, J = 6.9 Hz, 12H), 1.33 (br, 63H).

[0285] 13 13C NMR (101 MHz, CDCl 3 ) δ 21.82, 31.51, 34.93, 49.59, 121.33, 121.65, 126.40, 126.55, 127.71, 128.33, 129.83, 134.99, 137.64, 140.00, 140.28, 141.60, 142.04, 145.45, 145.61, 148.05, 151.00, 165.48.

[0286] HRMS (ESI) calcd for [C 116 H 132 N 6 NaO 4 , M + Na] + : 1696.0208; Found: 1696.0209.

[0287] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-(2',4',6'-triisopropyl-[1,1'-biphenyl]-4-yl)ethyl)isophthalamide) (6p)

[0288]

[0289] White solid, isolated yield: 52%; melting point: 208.0 - 211.5 °C; R f = 0.5 (PE / EA = 2:1, v / v), [α] D 25 - 199.2 (c 0.4, CH 2 Cl 2 ).

[0290] 1 1H NMR (400 MHz, CDCl 3) δ 8.82 (br, 3H), 8.43 (br, 2H), 8.10 (d, J = 8.1 Hz, 2H), 7.75 (br, 5H), 7.63 (s, 2H), 7.42 (d, J = 7.7 Hz, 7H), 7.11 (d, J = 7.7 Hz, 8H), 6.99 (s, 7H), 5.55 - 5.40 (m, 4H), 2.89 (p, J = 6.9 Hz, 4H), 2.53 (h, J = 6.6 Hz, 8H), 1.64 (d, J = 6.9 Hz, 12H), 1.27 (d, J = 6.8 Hz, 24H), 0.97 (d, J = 6.2 Hz, 48H).

[0291] 13 C NMR (101 MHz, CDCl 3 ) δ 21.54, 24.09, 24.29, 30.14, 34.26, 49.39, 120.52, 121.48, 126.01, 126.07, 126.60, 128.34, 129.92, 130.03, 134.79, 136.56, 137.60, 139.98, 141.12, 145.56, 146.55, 146.66, 147.84, 155.90, 165.35.

[0292] HRMS (MALDI) calcd for [C 120 H 140 N 6 O 4 Na, M + Na] + : 1752.0834; Found: 1752.0830.

[0293] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N-bis((R)-1-(4-bromophenyl)ethyl)isophthalamide) (6q)

[0294]

[0295] White solid, isolated yield: 39%; melting point: 187.9 - 193.0 °C; R f = 0.5 (DCM / Ac = 10:1, v / v), [α] D 25 -221.0 (c 0.60, CH 2 Cl 2 ).

[0296] 1 H NMR (400 MHz, CDCl 3) δ 8.67 (br, 4H), 8.43 (br, 2H), 8.34 (d, J = 8.3 Hz, 2H), 7.96 (d, J = 8.3 Hz, 2H), 7.84 (s, 2H), 7.49 (br, 3H), 7.29 (d, J = 8.1 Hz, 6H), 7.13 (d, J = 8.0 Hz, 7H), 5.25 - 5.11 (m, 4H), 1.44 (d, J = 7.0 Hz, 12H).

[0297] 13 C NMR (101 MHz, CDCl 3 ) δ 21.95, 48.39, 119.58, 121.07, 126.67, 127.53, 128.22, 128.44, 128.95, 131.06, 135.52, 137.72, 139.50, 144.27, 145.38, 155.15, 165.25.

[0298] HRMS (MALDI) calcd for [C 60 H 49 Br 4 N 6 O 4 , M + H] + : 1233.0549; Found: 1233.0518.

[0299] 5,5'-(1,10-Phenanthroline-2,9-dicarbonyl)bis(N,N,N,N-tetra(R)-1-phenylethyl)isophthalamide) (6r)

[0300]

[0301] White solid, isolated yield: 44%; melting point: 157.8 - 162.9 °C; R f = 0.3 (PE / EA = 1:1, v / v), [α] D 25 + 371.4 (c 1.3, CH 2 Cl 2 ).

[0302] 1 H NMR (400 MHz, CDCl 3)δ 8.37 (d, J = 8.3 Hz, 2H), 8.09 (d, J = 1.5 Hz, 4H), 7.93 (d, J = 8.3 Hz, 2H), 7.88 (s, 2H), 7.57 (s, 2H), 7.12 - 7.02 (m, 25H), 7.02 - 6.98 (m, 15H), 4.92 (br, 8H), 1.79 (br, 24H).

[0303] 13 C NMR (101 MHz, CDCl 3 ) δ 18.77, 27.01, 122.14, 124.78, 125.98, 126.66, 127.12, 127.89, 127.99, 128.34, 137.22, 139.38, 140.55, 141.28, 146.39, 157.42, 170.00.

[0304] HRMS (MALDI) calcd for [C 92 H 84 N 6 NaO 4 , M + Na] + : 1359.6452; Found: 1359.6458.

[0305] Example 7

[0306] Copper-catalyzed intramolecular azide-to-C(sp 3 )-H bond asymmetric insertion reaction, 22a and 23a are the compounds labeled in this example as follows:

[0307]

[0308] In a glove box filled with argon, copper(II) tetraacetonitrile hexafluorophosphate (0.005 mmol) and ligand 6e (0.006 mmol, 8.3 mg) were weighed into a dry 10 mL Schlenk tube equipped with a magnetic stir bar. It was taken out of the glove box. Under argon protection, dichloromethane (1.2 mL) was added. After complexation at room temperature for two hours, substrate 22a (0.1 mmol, 25.9 mg) and potassium carbonate (0.3 mmol, 41.4 mg) were added. The reaction was stirred at room temperature. The reaction progress was monitored by TLC. After complete conversion of the substrate, it was filtered through a short silica gel column. After evaporation of the solvent, 1,1,2,2-tetrachloroethane was added as an internal standard for NMR, and the yield was determined by 1 H NMR. Subsequently, the target product was isolated and purified by silica gel column chromatography (PE / EA = 3:1). The er value was determined by liquid chromatography.

[0309] Example 8

[0310] Effect of Metal Precursors on the Reaction

[0311] In a glove box filled with argon, a dry 10 mL Schlenk tube equipped with a magnetic stir bar was charged with a metal precursor (0.005 mmol) and ligand 6e (0.006 mmol, 8.3 mg). It was taken out of the glove box. Under argon protection, dichloromethane (1.2 mL) was added. After complexation at room temperature for two hours, substrate 22a (0.1 mmol, 25.9 mg) and potassium carbonate (0.3 mmol, 41.4 mg) were added. The reaction was stirred at room temperature. The reaction progress was monitored by TLC. After complete conversion of the substrate, it was filtered through a short silica gel column, and the solvent was removed by rotary evaporation. 1,1,2,2-Tetrachloroethane was added as an NMR internal standard, and the yield was determined by 1 1H NMR. Subsequently, the target product was isolated and purified by silica gel column chromatography (PE / EA = 3:1). The er value was determined by liquid chromatography.

[0312]

[0313] Table 1: Effect of Metal Precursors on the Reaction

[0314]

[0315]

[0316] a Reaction conditions: 0.1 mmol phenethyl (methylsulfonyloxy)carbamate (22a), 5 mol% metal precursor, 6 mol% 6e, 0.3 mmol K 2 2CO 3 , 1.0 mL dichloromethane. b The conversion and yield were determined by 1 1HNMR, with 1,1,2,2-tetrachloroethane as the internal standard. c Determined by HPLC chiral column. d 5 mol% NaBArF as an additive. e 10 mol% NaBArF as an additive.

[0317] Example 9

[0318] Effect of Bases on the Reaction

[0319] In a glove box filled with argon, a dry 10 mL Schlenk tube equipped with a magnetic stir bar was charged with Cu(OTf) 2(0.005 mmol, 1.8 mg) and ligand 6e (0.006 mmol, 8.3 mg). Take them out of the glove box. Under argon protection, add dichloromethane (1.2 mL). After complexing at room temperature for two hours, add substrate 22a (0.1 mmol, 25.9 mg) and base (0.3 mmol). Stir the reaction at room temperature. Monitor the reaction progress by TLC. After complete conversion of the substrate, filter through a short silica gel column, remove the solvent by rotary evaporation, add 1,1,2,2-tetrachloroethane as the NMR internal standard, and determine the yield by 1 1H NMR. Subsequently, separate and purify the target product by silica gel column chromatography (PE / EA = 3:1). Determine the er value by liquid chromatography.

[0320]

[0321] Table 2: Effect of base on the reaction

[0322]

[0323] a Reaction conditions: 0.1 mmol phenethyl (methylsulfonyloxy)carbamate (22a), 5 mol% metal precursor, 6 mol% 6e, 0.3 mmol base, 1.2 mL dichloromethane. b The conversion and yield were determined by 1 1H NMR with 1,1,2,2-tetrachloroethane as the internal standard. c Determined by HPLC chiral column. d 0.24 mmol K 2 CO 3 . e 0.12 mmol K 2 CO 3 .

[0324] Example 10

[0325] Effect of solvent on the reaction

[0326] In a dry 10 mL Schlenk tube equipped with a magnetic stir bar in a glove box filled with argon, weigh Cu(OTf) 2 (0.005 mmol, 1.8 mg) and ligand 6e (0.006 mmol, 8.3 mg). Take them out of the glove box. Under argon protection, add dichloromethane (1.2 mL). After complexing at room temperature for two hours, add substrate 22a (0.1 mmol, 25.9 mg) and K 2 CO 3 . Stir the reaction at room temperature. Monitor the reaction progress by TLC. After complete conversion of the substrate, filter through a short silica gel column, remove the solvent by rotary evaporation, add 1,1,2,2-tetrachloroethane as the NMR internal standard, and by 1The yield was determined by \(^1\)H NMR. Subsequently, the target product was separated and purified by silica gel column chromatography (PE / EA = 3:1). The er value was determined by liquid chromatography.

[0327]

[0328] Table 3: Effect of solvents on the reaction

[0329]

[0330] a Reaction conditions: 0.1 mmol phenethyl (methylsulfonyloxy)carbamate (22a), 5 mol% metal precursor, 6 mol% 6, 0.12 mmol K 2 CO 3 , 1.2 mL of solvent. b The conversion and yield were determined by 1 \(^1\)H NMR using 1,1,2,2-tetrachloroethane as the internal standard. c Determined by HPLC chiral column.

[0331] Example 11

[0332] Effect of ligands on the reaction

[0333] In a glove box filled with argon, Cu(OTf) 2 (0.005 mmol, 1.8 mg) and ligand 6 (0.006 mmol) were weighed into a dry 10 mL Schlenk tube equipped with a magnetic stir bar. It was taken out of the glove box. Under argon protection, dichloromethane (1.2 mL) was added. After complexing at room temperature for two hours, substrate 22a (0.1 mmol, 25.9 mg) and potassium carbonate (1.2 mmol, 16.6 mg) were added. The reaction was stirred at room temperature. The reaction progress was monitored by TLC. After the substrate was completely converted, it was filtered through a short silica gel column. After evaporation of the solvent, 1,1,2,2-tetrachloroethane was added as the NMR internal standard, and the yield was determined by 1 \(^1\)H NMR. Subsequently, the target product was separated and purified by silica gel column chromatography (PE / EA = 3:1). The er value was determined by liquid chromatography.

[0334]

[0335] Table 4: Effect of ligands on the reaction

[0336]

[0337] a Reaction conditions: 0.1 mmol phenethyl (methylsulfonyloxy)carbamate (22a), 5 mol% metal precursor, 6 mol% 6, 0.12 mmol K 2 CO3 , 1.2 mL of dichloromethane. b The conversion rate and yield were determined by 1 1H NMR with 1,1,2,2 - tetrachloroethane as the internal standard. c Determined using an HPLC chiral column.

[0338] Example 12

[0339] Effect of temperature on the reaction

[0340] In a glove box filled with argon, Cu(OTf) 2 (0.005 mmol, 1.8 mg) and ligand 6e (0.006 mmol, 8.3 mg) were weighed into a dry 10 mL Schlenk tube equipped with a magnetic stir bar. It was taken out of the glove box. Under argon protection, dichloromethane (1.2 mL) was added. After complexing at room temperature for two hours, substrate 22a (0.1 mmol, 25.9 mg) and potassium carbonate (1.2 mmol, 16.6 mg) were added. The reaction was stirred at different temperatures. The reaction progress was monitored by TLC. After the substrate was completely converted, it was filtered through a short silica gel column. After rotary evaporation to remove the solvent, 1,1,2,2 - tetrachloroethane was added as the NMR internal standard, and the yield was determined by 1 1H NMR. Subsequently, the target product was separated and purified by silica gel column chromatography (PE / EA = 3:1). The er value was determined by liquid chromatography.

[0341]

[0342] Table 5: Effect of metal precursors on the reaction

[0343]

[0344] a Reaction conditions: 0.1 mmol of phenethyl (methylsulfonyloxy) carbamate (22a), 5 mol% Cu(OTf) 2 , 6 mol% 6, 0.12 mmol K 2 2CO3 3 , 1.2 mL of dichloromethane. b The conversion rate and yield were determined by 1 1H NMR with 1,1,2,2 - tetrachloroethane as the internal standard. c Determined using an HPLC chiral column.

[0345] Example 13

[0346] Substrate evaluation

[0347]

[0348] In a glove box filled with argon, weigh metal Cu(OTf) 2 (0.015 mmol, 5.4 mg) and ligand 6g (0.018 mmol, 33.0 mg) into a dry 10 mL Schlenk tube equipped with a magnetic stir bar. Take it out of the glove box. Under argon protection, add dichloromethane (4.5 mL). After complexing at room temperature for two hours, add substrate 22 (0.3 mmol) and potassium carbonate (0.36 mmol, 49.6 mg). Stir the reaction at room temperature. Monitor the reaction progress by TLC. After the substrate is completely converted, filter through a short silica gel column, remove the solvent by rotary evaporation, add 1,1,2,2-tetrachloroethane as the NMR internal standard, and calculate the yield by 1H NMR. Subsequently, separate and purify the target product by silica gel column chromatography (PE / EA = 3:1). Determine the enantioselectivity er value (the molar ratio of the two enantiomers) by liquid chromatography.

[0349] Table 6: Copper-Catalyzed Intramolecular Asymmetric C-H Bond Insertion Reaction of Nitrenes a

[0350]

[0351]

[0352] a Reaction conditions: 0.3 mmol substrate 10, 5 mol% Cu(OTf) 2 , 6 mol% 6g, 0.36 mmol K 2 CO 3 , 1.2 mL dichloromethane. The yield was determined by 1 1H NMR, with 1,1,2,2-tetrachloroethane as the internal standard. The er was determined by HPLC chiral column.

[0353] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the inventive concept, several modifications and improvements can still be made, and these all belong to the protection scope of the present invention.

Claims

1. A 2,9-diaryl chiral phenanthroline ligand, characterized in that: The chemical structure has the following general formula: Among them, R 1 , R 2 Each of the above groups is one of phenyl, substituted phenyl and C1-C8 alkyl.

2. A 2,9-diaryl chiral phenanthroline ligand according to claim 1, characterized in that: Specifically: Among them, Me is methyl, Et is ethyl, i Pr is isopropyl, t Bu is tert-butyl, Ph is phenyl, Ar is argon, and Bn is benzyl.

3. A 2,9-diaryl chiral phenanthroline ligand according to claim 2, characterized in that, The 2,9-diaryl chiral o-phenanthroline ligand is one of a racemic isomer, a levorotatory isomer and a dextrorotatory isomer.

4. A 2,9-diaryl chiral phenanthroline ligand according to claim 1, characterized in that, The substituted phenyl group may be substituted by one or more of C1-C8 alkyl, C1-C8 alkoxy, C2-C8 acyloxy, hydroxy, halogen, amino, (C1-C8 acyl)amino, di(C1-C8 alkyl)amino, C1-C8 acyl, C2-C8 ester, and haloalkyl, and the number of substituents is 0-5.

5. A 2,9-diaryl chiral phenanthroline ligand according to claim 1, characterized in that, The C1-C8 acyl group is one of formyl, acetyl, propionyl, n-butyryl, isobutyryl, n-valeryl, isovaleryl, secondary valeryl, pivaloyl, n-hexanoyl, isohexanoyl, neohexanoyl, secondary hexanoyl, n-heptanoyl, isoheptanoyl, neoheptanoyl, secondary heptanoyl, n-octanoyl, isooctanoyl, neooctanoyl, secondary octanoyl, 1-cyclopropylformyl, 1-cyclobutylformyl, 1-cyclopentylformyl, 1-cyclohexylformyl and 1-cycloheptylformyl; The C2-C8 acyloxy group is one of acetoxy, propionyloxy, n-butyryloxy, isobutyryloxy, n-valeryloxy, isovaleryloxy, secondary valeryloxy, pivaloyloxy, n-hexanoyloxy, isohexanoyloxy, neohexanoyloxy, secondary hexanoyloxy, n-heptanoyloxy, isoheptanoyloxy, neoheptanoyloxy, secondary heptanoyloxy, n-octanoyloxy, isooctanoyloxy, neooctanoyloxy, secondary octanoyloxy, 1-cyclopropylformyloxy, 1-cyclobutylformyloxy, 1-cyclopentylformyloxy, 1-cyclohexylformyloxy and 1-cycloheptylformyloxy; The C2-C8 ester group is one of methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, n-pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxycarbonyl, secondary pentyloxycarbonyl, tert-pentyloxycarbonyl, cyclopentyloxycarbonyl, n-hexyloxycarbonyl, isohexyloxycarbonyl, neohexyloxycarbonyl, secondary hexyloxycarbonyl, tert-hexyloxycarbonyl, cyclohexyloxycarbonyl, n-heptyloxycarbonyl, isoheptyloxycarbonyl, neoheptyloxycarbonyl, secondary heptyloxycarbonyl, tert-heptyloxycarbonyl and cycloheptyloxycarbonyl; The haloalkyl group is a haloalkyl group containing fluorine, chlorine, bromine or iodine.

6. A 2,9-diaryl chiral phenanthroline ligand according to any one of claims 1-5, characterized in that, The C1-C8 alkyl group is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-pentyl, n-hexyl, isohexyl, neohexyl, sec-hexyl, tert-hexyl, n-heptyl, isoheptyl, neoheptyl, sec-heptyl, tert-heptyl, n-octyl, isooctyl, neooctyl, sec-octyl or tert-octyl.

7. A method for synthesizing a 2,9-diaryl chiral phenanthroline ligand according to any one of claims 1 to 6, characterized in that: Chiral 3,5-diamidobromobenzene is obtained by condensation of 3,5-dicarboxybromobenzene with chiral amine, which is then coupled with bipinacol borate under palladium catalysis to obtain the corresponding aryl borate, and finally the target ligand is obtained by Suzuki coupling reaction with 2,9-dichlorophenanthroline.

8. A method for synthesizing a 2,9-diaryl chiral phenanthroline ligand according to any one of claims 1-6, characterized in that, Starting from 2,9-dichlorophenanthroline, a Suzuki coupling reaction is carried out with 3,5-dimethoxycarbonylphenylboronic acid to obtain 2,9-di(3,5-dimethoxycarbonyl)phenylphenanthroline, which is then hydrolyzed to obtain 2,9-di(3,5-dicarboxy)phenylphenanthroline, and finally condensed with a chiral amine to obtain the target ligand.

9. A copper complex, characterized in that The 2,9-diaryl chiral o-phenanthroline ligand according to any one of claims 1 to 6 is prepared by complexing with a copper salt.

10. Use of a 2,9-diaryl chiral o-phenanthroline ligand according to any one of claims 1 to 6 or a copper complex according to claim 9 in an asymmetric transition metal catalyst.

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