CN118108666A

CN118108666A - Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof

Info

Publication number: CN118108666A
Application number: CN202410230056.XA
Authority: CN
Inventors: 陈智康; 王喆; 刘艳; 陈泳; 欧玮莹; 丸岡啓二
Original assignee: Guangdong University of Technology
Current assignee: Guangdong University of Technology
Priority date: 2024-02-29
Filing date: 2024-02-29
Publication date: 2024-05-31

Abstract

The invention belongs to the technical field of organic synthesis and chiral catalysis, and discloses an axillary nitrogen ligand (PYEs type ligand) with flexible electron supply characteristics. The chiral ligand provided by the invention is mainly structurally characterized by comprising binaphthyl, H8 binaphthyl shaft chiral frameworks, shaft chiral frameworks and a nitrogen ligand with flexible electron supply characteristics. The chiral binaphthyl PYEs ligand provided by the invention can be directly used for catalyzing simple asymmetric allyl substitution reaction, has excellent enantioselectivity and higher catalytic activity, and shows excellent activity in the asymmetric allyl substitution catalytic reaction, the yield can reach 95%, and the enantioselectivity can reach 95%. The method has mild reaction conditions, high efficiency and certain practical value, and is suitable for large-scale production. Meanwhile, the structure enriches PYEs ligand families and provides a certain thought for chiral catalysis and synthesis of chiral compounds.

Description

Axis chiral PYE-like nitrogen ligand compound and preparation method and application thereof

Technical Field

The invention belongs to the technical field of organic synthesis and chiral catalysis, and relates to a preparation method of an axial chiral ligand nitrogen-nitrogen double-tooth, single-tooth or heterozygous nitrogen ligand (PYE) and application of the ligand in simple asymmetric allyl substitution reaction.

Background

Ligands have played a vital role in transition metal catalysis. The ligand and the metal coordinate to change the electronic property of the metal center, the steric hindrance of the ligand can influence the space environment of the metal to participate in the reaction, the structure and the reactivity of the metal coordination center are strongly controlled, meanwhile, the most challenging in organic chemistry is to synthesize chiral compounds, which are generally intermediates for preparing various medicines, fine chemical products and natural products, and today, asymmetric catalysis of transition metal becomes one of the most effective and direct chiral generation processes, which is not separated from efficient metal catalysts. Therefore, the design and development of novel ligands has important scientific significance for advancing research in the fields of homogeneous catalysis, coordination chemistry and organometallic chemistry.

Pi-acid ligands predominate in transition metal homogeneous catalysis studies. Pi-acid ligand not only can provide lone pair electrons for central atoms to form sigma-coordination bonds, but also can receive feedback electrons of the central atoms by self-empty pi-orbitals. Such as phosphines, amines (pyridine, oxazolines), and the recently rapidly evolving N-heterocyclic carbene ligands (N-Heterocyclic Carbene abbreviated NHC. Such ligands have achieved significant achievements in transition metals DiPAMP-chiral bisphosphine ligands developed as taught by William S. Knowles [ knowles. W.S. Acc. Chem. Res.1983,16,106.]; ryoji Noyori teaches the developed chiral spiro-nitrogen-phosphine ligand family-SIPHOS and SIPHOS-PE [ Xie, J. ], Z.Q. -L.acta Chim. Sinica 2014,72,778.], and Robert Howard Grubbs teaches the developed carbenb ligand-containing Grubbs catalyst [ Grubbs, R.H.; wenzel, A.G.eds.Handbook of Metathesis nd Ed.; wiley-VCH: weinheim, germany,2015 et al, which can demonstrate the important value of pi-acid ligands for transition metal catalysis.

It has been demonstrated in known relevant reports that the electron donating ability of PYEs system ligands can be compared to pyridine, azacyclic carbenes, and even some electron rich phosphine ligands. Johnson group studies reported that the [ Ni (0) p-PYE ] complex can efficiently and selectively activate the C-F bond to undergo oxidative addition; meanwhile, the TEP (Tolman Electronic Parameter Torrman electronic parameter) parameter of cis- [ (CO) ₂ RhCl (PYE) ] complex is utilized to verify that the PYE ligand has the electron-donating ability comparable to NHC. The electron donating ability between the rhodium complex and the rhodium complex is compared by infrared comparison of the wave numbers of CO, the average value of NHC given in the literature in the lower graph is 2039cm ^-1, and the average value of PYEs ligand is 2038cm ^-1. It can be seen that PYEs ligand electron donating ability is similar to NHC [ Doster, m.e.; johnson, s.a. angelw.chem.int.ed.2009, 48,2185 ]. In recent years, development of ligands based on PYEs systems and research on their transition metal coordination have been advanced. For example, the Johnson group reports Ni-PYEs catalyzed C-H bond activated carbon tin coupling reaction studies [ Doster, M.E.; hatnean, j.a.; jeftic, t.; modi, S.; johnson, s.a.j.am.chem.soc.2010,132,11923 ]. The reported ligand design and development directions have focused on: firstly, from the coordination angle, the synthesis and coordination research of PYEs from single tooth to chelate double tooth, pincer type, multi-tooth and Hybrid with NHC (Hybrid); and secondly, on the electronic effect of the structure, synthesizing and coordination research of a mesoionic or mesoionic ligand based on the ortho, meta and para substituted pyridine aromatic ring. However, the related ligand PYEs with chiral structure as main skeleton has less research, and only one example of synthesis and coordination research based on carbon center chiral (R, R) -1, 2-cyclohexanediamine skeleton o-PYEs ligand is available, but no attempt is made to catalyze the reaction.

The Asymmetric Allyl Substitution (AAS) is a catalytic reaction method that can directly and effectively construct various chiral molecules, and is one of the powerful methods for forming carbon-carbon bonds and carbon heterobonds. While palladium-catalyzed AAS reactions have mild conditions and high functional group tolerance, palladium-catalyzed asymmetric allylic alkylation reactions have been reported for the first time from Trost, and have been of interest to researchers.

Disclosure of Invention

The invention provides a method for developing and synthesizing PYEs compounds with corresponding axial chirality by taking racemic, optical pure binaphthyl amine or hydrogenated binaphthyl amine which are cheap and easy to obtain as raw materials, wherein the method comprises enantiomer, diastereoisomer, racemate or catalytic acceptable salt thereof.

The primary object of the present invention is to provide a class of axial chiral ligand nitrogen-nitrogen bidentate or monodentate nitrogen ligands (PYEs).

It is another object of the present invention to provide a process for the preparation of the above PYE compounds.

The invention also provides application of the ligand in simple asymmetric allyl substitution reaction.

In order to achieve the above purpose, the invention adopts the following technical scheme:

the invention provides an axial chiral PYE nitrogen ligand compound, which has a structural formula as shown in the following formula I or formula II:

wherein R ¹ is selected from alkyl of C ₁～C₂₂, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl;

r ² is selected from the group consisting of hydrogen, C ₁～C₂₂ alkyl, phenyl, 3,4, 5-trifluorophenyl, 3, 5-bis (trifluoromethyl) phenyl, naphthyl, C ₅～C₆ aromatic heterocyclic substituents;

R ⁴ is selected from the group consisting of hydrogen, C ₁～C₂₂ alkyl, phenyl, 3,4, 5-trifluorophenyl, 3, 5-bis (trifluoromethyl) phenyl, naphthyl, C ₅～C₆ aromatic heterocyclic substituents;

R ³,R⁵,R⁶ is selected from hydrogen, hydrocarbon group of C ₁～C₂₂, phenyl;

X is selected from halogen ion, tetrafluoroborate ion, hexafluorophosphate ion, trifluoromethane sulfonate ion, sulfate ion, phosphate ion, acetate ion, hydroxide ion, tartrate ion.

Ring a is selected from the group consisting of an aliphatic ring of C _5～7, an aliphatic heterocyclic ring of C _5～7, a substituted aromatic ring of C _5～6, and an aromatic heterocyclic ring of C _5～6.

Preferably, the aromatic heterocycle of C ₅～C₆ is pyridine, pyrrole or thiophene.

Preferably, the heterocycle is an oxygen-, nitrogen-or sulfur-containing heterocycle.

More preferably, the structural formula is any one of the following:

Wherein R1 is selected from C ₁～C₂₂ alkyl, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl, R is selected from C ₁～C₅ alkyl, branched alkyl, substituted benzyl, substituted heterocycle, substituted aryl;

Further, halogen is chlorine, bromine or iodine.

In addition, the compounds include enantiomers, diastereomers, racemates or catalytically acceptable salts of the structural formulae.

The invention also protects the application of the axial chiral PYE nitrogen ligand compound in asymmetric catalytic reaction. Further, it is an asymmetric catalytic substitution reaction for catalyzing simple allyl substitution.

More specifically, the asymmetric catalytic reaction is to take the axial chiral PYE nitrogen ligand compound as a raw material in an organic solvent, add a palladium catalyst precursor with catalytic equivalent, then add a common allyl substituted substrate, dicarbonyl compound and alkali, and stir and react for 24-48 hours in an argon atmosphere to obtain a chiral substituted product. Further, the molar ratio of the allyl substituted substrate to the axichiral PYE-like nitrogen ligand compound is 100: 10-100: 1, a step of; the concentration of the allyl substituted substrate is 0.01M-0.1M; the alkali is potassium carbonate, cesium carbonate, BSA+potassium acetate, potassium tert-butoxide and sodium tert-butoxide; the concentration of alkali is 0.01M-0.2M, and the reaction temperature is 0-40 ℃; the selected organic solvent is one or more of toluene, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, 1, 4-dioxane and xylene; the catalyst precursor is allylpalladium (II) chloride dimer, tris (dibenzylideneacetone) dipalladium, bis (dibenzylideneacetone) palladium or palladium acetate.

The ligand compound provided by the invention can be used for preparing chiral compounds of various transition metals besides the catalytic reaction, for example, the axial chiral PYE nitrogen ligand compound is coordinated with the transition metal to obtain the corresponding metal catalyst. The transition metal may be iron, nickel, palladium, copper, rhodium, silver, platinum, etc.

The invention also provides a method for preparing the catalyst (axial chiral PYE nitrogen ligand compound) as follows:

Wherein R ¹～R⁶ in formulas 1,2,3, 4,5, 6, 7 are as defined in claim 1, and G is selected from the group consisting of nitrogen, phosphorus, oxygen, sulfur, and other heteroatom groups.

The preparation steps are briefly described as follows: in the presence of an organic solvent, alkali and a palladium catalyst, a compound shown in a formula 1 reacts with a compound shown in a formula 2 in a reactor for 4-24 hours to prepare a compound shown in a formula 3; in the presence of an organic solvent, carrying out substitution reaction on a compound shown in a formula 3 and an electrophile to obtain a compound shown in a formula 4; in the presence of a small amount of organic solvent, partially alkalizing the compound shown in the formula 4 to obtain a compound shown in the formula 5; wherein the above method is referred to in such a manner that the substrate represented by formula 6 synthesizes the corresponding nitrogen ligand compound.

In the above synthetic method, the organic solvent is one or more of methanol, ethanol, acetonitrile, tetrahydrofuran, toluene, xylene, diethyl ether, dioxane, dichloromethane and chloroform; the alkali is sodium tert-butoxide, potassium tert-butoxide and sodium hydroxide; the electrophile is iodo alkane, benzyl bromide, chloro alkane and methyl triflate; the palladium catalyst is tris (dibenzylideneacetone) dipalladium, bis (dibenzylideneacetone) palladium and palladium acetate.

Compared with the prior art, the invention has the beneficial effects that:

The chiral binaphthyl PYEs ligand provided by the invention can be directly used for catalyzing simple asymmetric allyl substitution reaction, has excellent enantioselectivity and higher catalytic activity, and shows excellent activity in the asymmetric allyl substitution catalytic reaction, the yield can reach 95%, and the enantioselectivity can reach 95%. The method has mild reaction conditions, high efficiency and certain practical value, and is suitable for large-scale production. Meanwhile, the structure enriches PYEs ligand families and provides a certain thought for chiral catalysis and synthesis of chiral compounds.

Drawings

FIG. 1 is a schematic structural diagram of a chiral compound obtained by coordination of an L1 ligand and a transition metal.

FIG. 2 is a schematic structural diagram of a chiral compound obtained by coordination of an L2 ligand and a transition metal.

Detailed Description

The technical solutions of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

The test methods used in the embodiment of the invention are all conventional methods unless specified otherwise; the materials, reagents and the like used, unless otherwise specified, are those commercially available.

EXAMPLE 1 Synthesis of Compound [ R-1]

In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and (R) - (+) -1,1' -bi-2-naphthylamine (284 mg,1 mmol) were added, and after air was replaced three times with argon, toluene (10 mL) was added, stirred for 10min, 4-bromopyridine hydrochloride (583.5 mg,4 mmol) was added, and the mixture was heated to 100℃in an oil bath, the progress of the reaction was monitored by TLC, and the reaction was stopped after the consumption of the starting material. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=10:1) gave the title compound as a yellow solid in yield 90％.¹HNMR(400MHz,Acetonitrile-d3)δ8.06(d,J＝8.9Hz,2H),7.98(d,J＝8.2Hz,2H),7.88(d,J＝6.0Hz,4H),7.68(d,J＝8.9Hz,2H),7.44(ddd,J＝8.2,6.8,1.2Hz,2H),7.25(ddd,J＝8.3,6.8,1.3Hz,2H),7.06(dd,J＝8.4,1.1Hz,2H),6.63(d,J＝6.6Hz,4H).¹³C NMR(101MHz,DMSO-d6)δ152.80,147.61,136.94,134.18,131.57,129.74,128.72,127.06,126.11,125.85,125.49,123.62,109.80.

EXAMPLE 2 Synthesis of Compound [ R-2]

Substrate [ R-1] (100 mg,0.23 mmol) was added to a schlenk tube containing magneton, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction cooled to room temperature, the system was directly pulled up and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target product as a yellow solid in the yield 89％.¹H NMR(400MHz,Acetonitrile-d3)δ9.28(s,2H),8.13(d,J＝8.8Hz,2H),7.99(dd,J＝7.9,3.3Hz,6H),7.53(d,J＝8.8Hz,2H),7.48(ddd,J＝8.2,6.7,1.2Hz,2H),7.29(ddd,J＝8.3,6.8,1.3Hz,2H),7.13(d,J＝8.5Hz,2H),7.06–6.95(m,4H),3.86(s,6H).¹³C NMR(101MHz,Acetonitrile-d3)δ156.17,144.13,133.64,133.59,132.99,131.01,130.04,128.65,127.68,127.06,126.15,124.38,109.57,45.42.

EXAMPLE 3 Synthesis of Compound L1

20ML of a 5M NaOH aqueous solution prepared in advance is added into a reaction flask filled with a magneton, 2mL of methanol is used for dissolving a compound [ R-2], the mixture is dropwise added into the reaction flask which is vigorously stirred, after all the mixture is added, an oil bath of the system is heated to 50 ℃, after the mixture is heated for 30-60min, the system is cooled to room temperature, and the solid is filtered to obtain a target compound as a yellow solid. Yield is good 70％.¹H NMR(400MHz,Methylene Chloride-d₂)δ7.70(dd,J＝8.4,4.6Hz,4H),7.15(ddd,J＝8.1,6.5,1.4Hz,2H),7.07(d,J＝8.7Hz,2H),7.00(ddd,J＝8.1,6.6,1.3Hz,2H),6.95(d,J＝8.3Hz,2H),6.55(d,J＝37.4Hz,4H),5.87(d,J＝40.9Hz,4H),3.22(s,6H).¹³C NMR(101MHz,Methylene Chloride-d₂)δ156.01,149.20,137.40,136.46,134.65,130.07,127.74,127.60,126.46,125.64,125.25,122.97,122.93,115.79,108.51,42.18.

EXAMPLE 4 Synthesis of Compound [ R-3]

In a reaction schlenk tube filled with magnetons, a substrate [ R-1] (438 mg,1 mmol) was added, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, phCH2Br (1.7 g,10 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw materials were consumed. After the reaction cooled to room temperature, the system was directly pulled up, and the residue was chromatographed on a silica gel column (CH ₂Cl₂: meoh=20:1) to give the target product as a yellow solid in the yield of 86％.¹HNMR(500MHz,Methanol-d₄)δ8.17(d,J＝7.4Hz,4H),8.14(d,J＝8.8Hz,2H),8.00(d,J＝8.2Hz,2H),7.62(d,J＝8.8Hz,2H),7.49(ddd,J＝8.2,6.9,1.2Hz,2H),7.43–7.34(m,10H),7.28(ddd,J＝8.3,6.8,1.3Hz,2H),7.12(dd,J＝8.4,1.0Hz,2H),6.87(d,J＝7.6Hz,4H),5.35(s,4H).¹³C NMR(126MHz,Methanol-d₄)δ156.37,143.02,134.69,133.49,133.47,132.95,130.71,129.16,129.07,128.62,128.43,128.15,127.31,126.62,125.94,123.36,60.75.

EXAMPLE 5 Synthesis of Compound L2

Adding 20mL of 5M NaOH aqueous solution prepared in advance into a reaction flask with a magneton, dissolving a compound [ R-3] by using 2mL of methanol, dropwise adding the mixture into the reaction flask with vigorous stirring, heating an oil bath of the system to 50 ℃ after all the mixture is added, heating the system for 30-60min, cooling the system to room temperature, filtering the solid to obtain a target compound, yellow solid and obtaining the yield 81％.¹H NMR(500MHz,Methanol-d₄)δ7.80(d,J＝8.8Hz,2H),7.77(d,J＝8.1Hz,2H),7.37(ddt,J＝8.1,6.5,1.2Hz,4H),7.35–7.30(m,2H),7.25(ddd,J＝8.0,6.6,1.3Hz,2H),7.21–7.10(m,8H),7.07(ddd,J＝8.0,6.6,1.3Hz,2H),7.02(ddt,J＝8.5,1.4,0.7Hz,2H),6.12(s,4H),4.85–4.75(m,4H).¹³C NMR(126MHz,Chloroform-d)δ155.71,147.98,137.26,136.22,136.10,134.67,130.33,129.14,128.48,127.99,127.61,127.39,126.47,126.39,125.40,123.39,123.20,115.68,108.80,58.80.

EXAMPLE 6 Synthesis of Compound R-4

In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and air were added three times after replacing air with argon, toluene (10 mL) was added, and after stirring for 10min, 3-bromopyridine (583.5 mg,3 mmol) was added, the mixture was heated to 100℃in an oil bath, the progress of the reaction was monitored by TLC, and the reaction was stopped after the consumption of the starting materials. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=50:1) afforded the title compound [ R-4] as a yellow solid in yield 87％.¹H NMR(400MHz,Chloroform-d)δ8.19(d,J＝2.7Hz,2H),8.12(dd,J＝4.7,1.4Hz,2H),7.93(d,J＝8.9Hz,2H),7.90–7.85(m,2H),7.60(d,J＝8.9Hz,2H),7.37(ddd,J＝8.0,6.7,1.2Hz,2H),7.30–7.26(m,5H),7.23(ddd,J＝8.3,2.8,1.5Hz,3H),7.18–7.12(m,2H),7.05(dd,J＝8.2,4.7Hz,2H),5.49(s,2H).¹³C NMR(101MHz,Chloroform-d)δ142.83,141.35,139.38,139.11,133.90,130.09,130.01,128.51,127.54,125.41,124.57,124.36,123.80,118.16,118.12.

EXAMPLE 7 Synthesis of Compound L3

In a schlenk tube containing magnetons, a substrate [ R-4] (100 mg,0.23 mmol) was added, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw materials were consumed. After the reaction cooled to room temperature, the system was directly pulled up, and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target L3 as a yellow solid in the yield of 90％.¹H NMR(400MHz,Acetonitrile-d3)δ8.27(t,J＝1.9Hz,2H),8.08(d,J＝8.8Hz,2H),7.99(d,J＝8.2Hz,2H),7.90–7.79(m,6H),7.65(d,J＝8.8Hz,2H),7.51–7.39(m,4H),7.31(ddd,J＝8.3,6.8,1.3Hz,2H),7.15(d,J＝8.5Hz,2H),4.00(s,6H).¹³C NMR(101MHz,Acetonitrile-d3)δ146.35,136.45,135.13,134.66,132.99,131.75,131.49,129.47,129.38,128.22,128.06,127.41,126.68,126.40,123.66,118.21,49.10.

EXAMPLE 8 Synthesis of Compound R-5

In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and (R) - (+) -1,1' -bi-2-naphthylamine (284 mg,1 mmol) were added, and after replacing air with argon three times, toluene (10 mL) was added, and after stirring for 10min, 2-bromopyridine (583.5 mg,2 mmol) was added, and the mixture was heated to 100℃in an oil bath, and the progress of the reaction was monitored by TLC and the reaction was stopped after the consumption of the starting material. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=100:1) afforded the title compound [ R-5] as a yellow solid in yield 80％.¹H NMR(400MHz,Chloroform-d)δ8.12(d,J＝8.9Hz,2H),8.03(dd,J＝5.2,1.9Hz,2H),7.98(d,J＝9.0Hz,2H),7.90(d,J＝8.1Hz,2H),7.37(ddd,J＝8.1,6.7,1.2Hz,2H),7.28-7.19(m,4H),7.12(d,J＝8.4Hz,2H),6.62-6.57(m,2H),6.54(d,J＝8.4Hz,2H),6.26(s,2H).¹³C NMR(101MHz,Chloroform-d)δ155.59,148.05,137.58,137.54,133.71,130.59,129.53,128.34,127.13,125.12,124.61,121.13,120.34,115.50,109.49.

EXAMPLE 9 Synthesis of Compound R-6

Substrate [ R-5] (100 mg,0.23 mmol) was added to a schlenk tube containing magneton, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction cooled to room temperature, the system was directly pulled up and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target compound [ R-6] as a yellow solid in the yield 94％.¹HNMR(400MHz,Acetonitrile-d3)δ9.26(s,2H),8.11(d,J＝8.8Hz,2H),7.98(dd,J＝7.9,3.3Hz,6H),7.52(d,J＝8.8Hz,2H),7.46(ddd,J＝8.2,6.7,1.2Hz,2H),7.28(ddd,J＝8.3,6.8,1.3Hz,2H),7.12(d,J＝8.5Hz,2H),6.98(d,J＝6.3Hz,4H),3.85(s,6H).¹³C NMR(101MHz,Acetonitrile-d3)δ156.59,144.56,134.07,134.01,133.41,131.43,130.46,129.07,128.10,127.49,126.58,124.81,109.99,45.84.

EXAMPLE 10 Synthesis of Compound L4

Adding 20mL of 5M NaOH aqueous solution prepared in advance into a reaction flask with a magneton, dissolving a compound [ R-6] by using 2mL of methanol, dropwise adding the mixture into the reaction flask with vigorous stirring, heating an oil bath of the system to 50 ℃ after all the mixture is added, heating the system for 30-60min, cooling the system to room temperature, filtering the solid to obtain a target compound, yellow solid L4, and obtaining the yield 81％.¹H NMR(400MHz,Chloroform-d)δ7.77–7.71(m,4H),7.33(dd,J＝8.5,1.2Hz,2H),7.23–7.06(m,6H),6.67(dd,J＝6.9,1.8Hz,2H),6.52(ddd,J＝9.4,6.3,1.8Hz,2H),6.34(dd,J＝9.5,1.3Hz,2H),5.46(td,J＝6.6,1.4Hz,2H),2.79(s,6H).¹³C NMR(101MHz,Chloroform-d)δ151.56,147.06,138.42,134.61,134.23,129.87,127.74,127.43,126.85,126.60,125.13,123.39,122.82,114.68,102.07,39.22.

EXAMPLE 11 Synthesis of Compound R-7

In a flask equipped with a magneton reactor, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), (R) -5,5', 6', 7', 8' -octahydro- [1,1 '-binaphthyl ] -2,2' -diamine (293 mg,1 mmol), sodium t-butoxide (768.8 mg,8 mmol) was added, after replacing air three times with argon, toluene (10 mL) was added, stirring was performed for 10min, 4-bromopyridine hydrochloride (583.5 mg,4 mmol) was added, the mixture was heated to 100℃in an oil bath, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=10:1) afforded the title compound [ R-7] as a yellow solid in yield 85％.¹H NMR(400MHz,Chloroform-d)δ8.08(d,J＝5.7Hz,4H),7.23(d,J＝8.2Hz,2H),7.12(d,J＝8.3Hz,2H),6.60(d,J＝6.3Hz,5H),5.75(s,2H),2.79(t,J＝6.2Hz,4H),2.15(t,J＝6.3Hz,4H),1.79-1.51(m,5H).¹³C NMR(101MHz,DMSO-d6)δ153.72,145.88,136.81,134.79,134.12,132.75,129.15,122.24,108.47,29.10,27.09,22.47,22.19.

EXAMPLE 12 Synthesis of Compound R-8

Substrate [ R-7] (100 mg,0.23 mmol) was added to a schlenk tube containing magneton, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, meI (653 mg,4.6 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw material was consumed. After the reaction cooled to room temperature, the system was directly pulled up and the residue was chromatographed on silica gel (DCM: meoh=10:1) to give the target compound [ R-8] as a yellow solid in the yield 92％.¹H NMR(400MHz,Methanol-d₄)δ8.02(d,J＝7.2Hz,4H),7.27(d,J＝8.2Hz,2H),7.20(d,J＝8.2Hz,2H),6.77(s,4H),3.96(s,6H),2.90(t,J＝6.1Hz,4H),2.34–2.15(m,4H),1.88–1.73(m,8H).¹³C NMR(101MHz,Methanol-d₄)δ157.60,144.97,139.41,139.34,133.89,133.17,131.34,123.75,45.58,30.78,28.64,23.91,23.56.

EXAMPLE 13 Synthesis of Compound L5

20ML of a 5M NaOH aqueous solution prepared in advance is added into a reaction flask filled with a magneton, 2mL of methanol is used for dissolving a compound [ R-8], the mixture is dropwise added into the reaction flask which is vigorously stirred, after all the mixture is added, an oil bath of the system is heated to 50 ℃, after the mixture is heated for 30-60min, the system is cooled to room temperature, and the solid is filtered to obtain a target compound L5 as a yellow solid. Yield is good 67％.¹HNMR(400MHz,Methylene Chloride-d₂)δ6.76(d,J＝8.0Hz,2H),6.55(dd,J＝7.8,2.3Hz,2H),6.45(d,J＝8.0Hz,2H),6.38(dd,J＝7.8,2.2Hz,2H),5.88(dd,J＝7.9,2.8Hz,2H),5.78(dd,J＝7.8,2.8Hz,2H),3.18(s,6H),2.63(t,J＝6.2Hz,4H),2.23–2.12(m,2H),1.96(dt,J＝17.0,6.4Hz,2H),1.66–1.46(m,8H).¹³C NMR(101MHz,Methylene Chloride-d₂)δ155.96,148.67,137.45,136.72,136.47,133.67,130.52,127.95,118.48,115.91,108.80,42.39,30.03,27.67,23.91,23.59.

EXAMPLE 14 Synthesis of Compound R-9

In a flask equipped with a magneton reaction vessel, tris (dibenzylideneacetone) dipalladium (22.9 mg,2.5 mol%), 1, 3-bis (diphenylphosphine) propane (23.5 mg,5.7 mol%), sodium t-butoxide (768.8 mg,8 mmol) and (R) - (+) -1,1' -bi-2-naphthylamine (284 mg,1 mmol) were added, and after air was replaced three times with argon, toluene (10 mL) was added and stirred for 10min, 4-bromoquinoline (832 mg,4 mmol) was added, and the mixture was heated to 100℃in an oil bath, and the reaction was stopped after the completion of the consumption of the raw materials by TLC. After the reaction was cooled to room temperature, the resulting mixture was diluted with ethyl acetate, extracted by pouring into water, washed with brine, the organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant, and the solvent was removed by rotary evaporator. Chromatography of the residue on a silica gel column (DCM: meoh=10:1) afforded the title compound [ R-9] as a yellow solid in yield 90％.¹H NMR(500MHz,Chloroform-d)δ8.36(d,J＝5.2Hz,2H),8.03(d,J＝8.9Hz,2H),7.96(t,J＝8.9Hz,4H),7.80(d,J＝8.9Hz,2H),7.58(ddd,J＝8.3,6.8,1.3Hz,2H),7.50(td,J＝7.2,6.7,1.1Hz,2H),7.39(td,J＝7.5,6.8,1.2Hz,2H),7.30(d,J＝8.4Hz,2H),7.27–7.22(m,2H),7.16(d,J＝8.4Hz,2H),6.93(d,J＝5.2Hz,2H),6.34(s,2H).¹³C NMR(126MHz,Chloroform-d)δ150.60,149.00,146.32,137.12,133.60,131.01,130.24,130.17,129.57,128.83,127.93,125.70,125.55,124.90,121.69,121.10,120.33,119.54,103.45.

EXAMPLE 15 Synthesis of Compound R-10

In a reaction schlenk tube filled with magnetons, a substrate [ R-9] (100 mg,0.19 mmol) was added, vacuum was applied to the tube for 3 to 4 times, an ultra-dry acetonitrile solvent was added under argon, stirring was performed at room temperature for 10 minutes, phCH ₂ Br (178 mg,10 mmol) was added under argon, the mixture was heated to 82℃in an oil bath, the reaction was allowed to proceed overnight, the progress of the reaction was monitored by TLC, and the reaction was stopped after the raw materials were consumed. After the reaction cooled to room temperature, the system was directly pulled up, and the residue was chromatographed on a silica gel column (CH ₂Cl₂: meoh=20:1) to give the target compound [ R-10] as a yellow solid in the yield 81％.¹H NMR(400MHz,Methanol-d₄)δ8.32(d,J＝8.4Hz,2H),7.97(d,J＝8.6Hz,2H),7.91–7.79(m,4H),7.56(dd,J＝11.3,6.4Hz,6H),7.41–7.29(m,4H),7.26–7.13(m,12H),6.98–6.90(m,4H),6.51(d,J＝7.5Hz,2H),5.51–5.31(m,4H).

EXAMPLE 16 Synthesis of Compound L6

Adding 20mL of 5M NaOH aqueous solution prepared in advance into a reaction flask with a magneton, dissolving a compound [ R-10] by using 2mL of methanol, dropwise adding the mixture into the reaction flask with vigorous stirring, heating an oil bath of the system to 50 ℃ after all the mixture is added, heating the system for 30-60min, cooling the system to room temperature, filtering the solid to obtain a target compound L2 and a yellow solid [ L6], and obtaining the yield 68％.¹H NMR(400MHz,Methylene Chloride-d₂)δ7.94(d,J＝8.0Hz,2H),7.68(t,J＝9.1Hz,4H),7.26–7.03(m,16H),6.96(d,J＝7.3Hz,4H),6.87–6.77(m,4H),6.54(d,J＝8.0Hz,2H),5.86(d,J＝7.9Hz,2H),4.80(d,J＝16.9Hz,2H),4.68(d,J＝16.8Hz,2H).¹³C NMR(101MHz,Methylene Chloride-d₂)δ153.73,139.29,138.98,136.29,134.49,130.32,128.92,127.89,127.83,127.68,126.22,126.14,126.08,125.88,125.58,125.30,123.18,122.94,122.54,114.93,102.40,55.36.

Application example 1

The ligands prepared in example 3 and example 5 were used in asymmetric allylic substitution reactions of the following formulas. The following is the product P1 produced by catalysis: allyl palladium (II) chloride dimer (2 mol%) chiral nitrogen ligand (4.4 mol%), potassium carbonate (3 eq.) were added sequentially to a10 mL schlenk tube, after 3 argon changes, 3mL toluene was added, stirring was performed at room temperature for 10min, substrate S1 (0.2 mmol) was added, stirring was performed at room temperature for 10min, dimethyl malonate (3 eq.) was added, reaction was performed at room temperature for 24h, and tlc detected the progress of the reaction. After the reaction, the crude product obtained by concentration is filtered by using diatomite and is subjected to silica gel column chromatography (PE: EA=100:1-50:1) to separate the target product P1. The catalytic results are shown in Table 1 below.

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TABLE 1 catalytic results

Sequence number	Ligand	Yield (%)	ee(％)
				1	L1	93	91
2	L2	99	95

Application example 2

The ligand prepared in example 5 was used in an asymmetric allylic substitution reaction, and the reaction formula is as follows. The following is the product P2 produced by catalysis: allyl palladium (II) chloride dimer (2 mol%), chiral nitrogen ligand (4.4 mol%), potassium carbonate (3 eq.) were added sequentially to a 10mL schlenk tube, 3mL toluene was added after 3 argon changes, stirring was performed at room temperature for 10min, substrate S1 (0.2 mmol) was added, stirring was performed at room temperature for 10min, tetrahydropyrrole (3 eq.) was added, reaction was performed at room temperature for 24h, and tlc detected the progress of the reaction. After the reaction, the crude product obtained by concentration is filtered by using diatomite and is subjected to silica gel column chromatography (PE: EA=100:1-50:1) to separate to obtain a target product P2. The catalytic results are shown in Table 2 below.

TABLE 2 catalytic results graphs

Sequence number	Ligand	Yield (%)	ee(％)
				1	L2	99	92

Application example 3

The ligand prepared in example 5 was used in an asymmetric allylic substitution reaction and the reaction formula was as follows. The following is the product P3 produced by catalysis: allyl palladium (II) chloride dimer (5 mol%), chiral nitrogen ligand (10 mol%), cesium carbonate (3 eq.) were added sequentially to a 10mL schlenk tube, after 3 argon changes, 3mL of 1, 4-dioxane was added, stirring was performed at room temperature for 10min, substrate S1 (0.2 mmol) was added, stirring was performed at room temperature for 10min, benzyl alcohol (3 eq.) was added, oil bath at 50 ℃ was performed for 24h, and tlc detected the progress of the reaction. After the reaction, the crude product obtained by concentration is filtered by using diatomite and is subjected to silica gel column chromatography (PE: EA=100:1-50:1) to separate to obtain a target product P3.

The catalytic results are shown in Table 3 below:

Sequence number	Ligand	Yield (%)	ee(％)
				1	L2	87	85

The ligand prepared in the example 3 is applied to a transition metal coordination reaction to obtain the target transition metal catalyst.

In addition, the L3 to L6 ligands have better effects with reference to the catalytic reaction, and show good prospects in asymmetric allyl substitution reaction.

Application example 4

The ligand prepared in example 3 was coordinated to copper and a single crystal structure was successfully obtained.

An amount of L1 ligand (30 mg,1 eq.) and Cu (ii) catalyst (1 eq.) were weighed into a reaction flask, 2mL DCM was added, stirred at room temperature for 2-6h, and tlc monitored the progress of the reaction. After the reaction, the reaction system was concentrated, and then the DCM diethyl ether was recrystallized to obtain the target product. The single crystal results verify that the absolute configuration of the ligand is the R configuration. The following data are single crystal characterization data:

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Application example 5

The ligand prepared in example 3 was coordinated with Pd and successfully obtained as a single crystal structure.

An amount of L1 ligand (30 mg,1 eq.) and Pd (ii) catalyst (1 eq.) were weighed into a reaction flask, 2mL DCM was added, stirred at room temperature for 2-6h, and tlc monitored the progress of the reaction. After the reaction, the reaction system was concentrated, and then the DCM diethyl ether was recrystallized to obtain the target product. The single crystal results verify that the absolute configuration of the ligand is the R configuration. The following data are single crystal characterization data:

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it should be understood that the foregoing description of the specific embodiments is merely illustrative of the invention, and is not intended to limit the invention, and that any modifications, equivalents, improvements, etc. that fall within the spirit and principles of the invention are intended to be included within the scope of the invention.

Claims

1. An axial chiral PYE nitrogen ligand compound is characterized by being shown in the following formula I or formula II:

2. The axichiral PYE nitrogen ligand compound of claim 1, wherein the aromatic heterocycle of C ₅～C₆ is pyridine, pyrrole or thiophene.

3. The axichiral PYE nitrogen ligand compound according to claim 1, wherein the heterocycle is an oxygen-, nitrogen-or sulfur-containing heterocycle.

4. The axial chiral PYE nitrogen ligand compound according to claim 1, wherein the structural formula is any one of the following:

5. The axichiral PYE nitrogen ligand compound of claim 4, wherein halogen is chlorine, bromine or iodine.

6. The axichiral PYE nitrogen ligand compound of claim 1, further comprising an enantiomer, diastereomer, racemate or a catalytically acceptable salt of said structural formula.

7. Use of an axichiral PYE nitrogen ligand compound according to claim 1 in an asymmetric catalytic reaction.

8. The use according to claim 7, characterized in that it is for catalyzing asymmetric catalytic substitution reactions of simple allyl substitution.

9. The use according to claim 7, wherein the asymmetric catalytic reaction is carried out in an organic solvent using the axichiral PYE nitrogen ligand compound as a raw material, adding a catalytic equivalent of palladium catalyst precursor, adding a commonly used allyl substituted substrate, dicarbonyl compound and alkali, and stirring under argon atmosphere for reacting for 24-48 hours to obtain chiral substituted product.

10. The use according to claim 7, wherein the axial chiral PYE nitrogen ligand compound is coordinated to a transition metal to give the corresponding metal catalyst.