CN114560892A - Chiral tridentate nitrogen phosphine ligand synthesized based on ferrocene skeleton and application thereof - Google Patents

Chiral tridentate nitrogen phosphine ligand synthesized based on ferrocene skeleton and application thereof Download PDF

Info

Publication number
CN114560892A
CN114560892A CN202210175430.1A CN202210175430A CN114560892A CN 114560892 A CN114560892 A CN 114560892A CN 202210175430 A CN202210175430 A CN 202210175430A CN 114560892 A CN114560892 A CN 114560892A
Authority
CN
China
Prior art keywords
ligand
chiral
isopropanol
cdcl
nmr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202210175430.1A
Other languages
Chinese (zh)
Inventor
叶金星
刘成玉
张磊
程瑞华
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangdong University of Technology
Original Assignee
Guangdong University of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangdong University of Technology filed Critical Guangdong University of Technology
Publication of CN114560892A publication Critical patent/CN114560892A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F17/00—Metallocenes
    • C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
    • C07C29/145—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones with hydrogen or hydrogen-containing gases
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/092—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings with aromatic radicals attached to the chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/827—Iridium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Abstract

The invention belongs to the technical field of asymmetric catalysis, and discloses a chiral tridentate nitrogen phosphine ligand synthesized based on a ferrocene skeleton, and a preparation method and application thereof. The chiral tridentate nitrogen phosphine ligand has a structure shown as a general formula (I), and R1The regulation of the groups can be achieved by using different amino acids as starting materials. The ligand of the invention reacts with the metallic iridium complex to form a catalyst complex, which can be used in the high-efficiency asymmetric hydrogenation of ketone. The phosphine nitrogen-nitrogen ligand has the advantages of simple synthesis, low cost, stable property, high catalytic activity, mild reaction condition and practical value.

Description

Chiral tridentate nitrogen phosphine ligand synthesized based on ferrocene skeleton and application thereof
Technical Field
The invention belongs to the technical field of asymmetric catalysis, and particularly relates to a chiral tridentate nitrogen phosphine ligand synthesized based on a ferrocene skeleton and application thereof.
Background
The chirality is like the left and right hands of human being, but they can not coincide with each other, and is the basic attribute existing in nature. Biomacromolecules, many active substances acting on receptors, amino acids, peptides, proteins, DNA, RNA, etc., which constitute an important basis in life activities, mostly have chiral characteristics (Analytical Chemistry,2006,78, 2093.). The chiral recognition of enantiomers and receptors differs significantly, resulting in different or even widely different physiological activities. Early on, many catastrophic consequences resulted from the lack of knowledge of chirality, the most classical of which was the thalidomide (reaction stop) event (Tetrahedron Asymmetry,1993,4, 2401). Thalidomide, developed by the pharmaceutical factory of southern German and West, was used as a prescription in 1957, which prevents nausea in pregnant women, controls mental stress and has a hypnotic effect during pregnancy. Therefore, this drug is called "stop-reaction". However, subsequent studies have demonstrated that only (R) -configured thalidomide has sedative effects and can alleviate pregnancy in pregnant women, while (S) -configured thalidomide has teratogenic side effects.
The nobel prize of chemistry in 2001 awarded three organic chemists, professor Knowles and Sharpless in the united states, professor Noyori in japan, which made a prominent contribution in the field of synthesis of chiral compounds (chem. rev.2007,107, 4863.). This demonstrates the very important presence of chiral compounds in our daily lives. Asymmetric catalysis is the most direct method for synthesizing chiral compounds at present, and most asymmetric catalysis is more prone to catalytic reaction by using chiral transition metal complexes. Ketones are common prochiral substances which contain carbon-oxygen double bonds which can be reduced to give carbon chiral centres. Chiral alcohols play an important role in chiral compounds, are a class of important and general organic synthesis building blocks, contain chiral secondary alcohol fragments in a plurality of medicaments and natural products, and play an important role in the pharmaceutical and chemical industries. Asymmetric hydrogenation catalysis of ketones is considered to be the most economical and environmentally friendly method for the synthesis of chiral alcohols and is also one of the most suitable routes for industrial production.
The development of the Noyori catalyst has driven the explosion of ruthenium chemistry. Ru (II) X, first developed by Noyori2BINAP systems (J.Am.chem.Soc.1993,115, 144; J.Am.chem.Soc.1995,117,2675.) exhibit very high specific selectivity for the asymmetric hydrogenation of beta-ketonates (aliphatic, aromatic) and gamma-ketonates, and the ee value of the products is between 85% and 99%. On the basis, a plurality of ruthenium-axis chiral diphosphine systems are developed, so that the asymmetric hydrogenation of various functional group ketones is successfully realized, and the satisfaction is achievedAs a result, iridium-catalyzed asymmetric hydrogenation of ketones is less reported than ruthenium-catalyzed asymmetric hydrogenation of ketones, and is mostly used for asymmetric hydrogenation of olefins. In 2007, the Peruzzin group achieved asymmetric hydrogenation of simple ketones using an iridium catalytic system, but only moderate ee values were obtained, with relatively poor selectivity. In 2010, an iridium/spiro chiral ligand reported by Zhou Qilin project group enables an iridium catalyst to be developed unprecedentedly in asymmetric hydrogenation of ketone, a pyridine group is introduced on the basis of a nitrogen phosphine ligand to enhance coordination, and the catalyst Ir-SpiroPAP is synthesized, so that the catalyst Ir-SpiroPAP shows high activity and selectivity in an asymmetric hydrogenation experiment of simple aromatic ketone (J.Am.chem.Soc.2010, 132.4538.; org.chem.Front.2014,1, 190.). Subsequently, the Zhongching project group introduces thioether groups on the basis of chiral nitrogen phosphine ligands, increases steric hindrance of metal centers, and has better effect on catalysis of beta-ketoester (Angew. chem. int. Ed.2015,54,8791.). A series of tridentate nitrogen phosphine ligands (Tetrahedron: asymmetry.2013,24,1567.) containing ferrocene face chirality are designed in Zhang Shengyong topic group in 2013, and introduction of ferrocene provides ideas for researchers. Based on the structure of ferrocene, a series of ligands are designed in a Zymou topic group and a Househou topic group, and show high activity and high selectivity in asymmetric hydrogenation of ketone (org.Lett.2016,18,2938.; chem.Eur.J.2017,23,970.; CN 105732725B; CN 105153229B; CN 107722068B).
Disclosure of Invention
In order to overcome the defects of the prior art, the invention mainly aims to provide a chiral tridentate nitrogen phosphine ligand synthesized based on a ferrocene skeleton.
The invention also aims to provide an application of the chiral tridentate nitrogen phosphine ligand synthesized based on the ferrocene skeleton in the asymmetric hydrogenation reaction of ketone; the ligand of the invention has the characteristics of high reaction efficiency, good selectivity, mild condition, economy, environmental protection, easy industrialization and the like.
The purpose of the invention is realized by the following technical scheme:
a chiral tridentate nitrogen phosphine ligand synthesized based on a ferrocene skeleton, wherein the ligand has a structure shown as a general formula (I):
Figure BDA0003518899690000031
wherein R is1Is alkyl, aryl or R1-1A substituted aryl group; the R is1-1The substituent is halogen, alkyl, phenyl or alkoxy;
R2is R2-1Substituted benzenesulfonyl radicals
Figure BDA0003518899690000032
The R is2-1The substituent is a hydrogen atom or an alkyl group; r2-1May be one or more, and when plural, may be the same or different;
R3is alkyl, aryl or R3-1Substituted aryl, said R3-1The substituent is alkyl, alkoxy, aryloxy, aryl or halogen; r3-1May be one or more, and when plural, may be the same or different;
in the formula (I), the structure is a stereogenic center and is in an R configuration or an S configuration.
Said ligands, each ligand comprising two corresponding isomers, preferably a compound comprising the structure:
Figure BDA0003518899690000041
the chiral tridentate nitrogen phosphine ligand synthesized based on the ferrocene skeleton is applied to the asymmetric hydrogenation reaction of ketone.
The application comprises the following steps:
(1) reacting a metal iridium complex with a chiral tridentate nitrogen phosphine ligand synthesized based on a ferrocene skeleton in a solvent A to obtain a complex of the chiral tridentate nitrogen phosphine ligand;
(2) carrying out asymmetric hydrogenation reaction on ketone, the complex of the chiral tridentate nitrogen phosphine ligand obtained in the step (1), a solvent B and alkali at the temperature of 25-100 ℃ and under the hydrogen pressure of 0.1-10.0MPa for 1-96h to obtain a chiral amino alcohol compound; the ketone is a compound with a structure shown in a formula (II), and the structural formula of the chiral amino alcohol compound is shown in a formula (III);
Figure BDA0003518899690000042
wherein R in the formula (II) and the formula (III)4Is alkyl, alkenyl, aryl or heteroaryl; r5Is alkyl, R5-1Substituted alkyl or ester group, said R5-1Is halogen (fluorine, chlorine, bromine), hydroxyl, primary amine, secondary amine or ester group.
The iridium complex of the metal in the step (1) is [ Ir (COD) Cl]2、[Ir(COE)2Cl]2、[Ir(NBD)2Cl]2、[Ir(COD)OMe]2、[Ir(COD)2]X and [ Ir (NBD)2]Any one of X, wherein X is BF4 -、BArF-、PF6 -、CF3SO3 -Or ClO4 -。
The molar ratio of the metal iridium complex in the step (1) to the chiral tridentate nitrogen phosphine ligand synthesized based on the ferrocene skeleton is 1: 1-4.
The solvent A in the step (1) is one of n-hexane, dichloromethane, toluene, tetrahydrofuran, methanol, ethanol, isopropanol and n-butanol.
And (3) the alkali in the step (2) is more than one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium carbonate, potassium carbonate, sodium methoxide and sodium ethoxide.
And (3) the solvent B in the step (2) is more than one of n-hexane, dichloromethane, dichloroethane, 1, 4-dioxane, toluene, tetrahydrofuran, methanol, ethanol, isopropanol and n-butanol.
The molar ratio of the complex of the chiral tridentate nitrogen phosphine ligand in the step (1) to the aminoketone compound in the step (2) is 1: 500-100000.
The asymmetric hydrogenation of ketones can be used, in particular in the asymmetric hydrogenation of simple ketones, to selectively obtain S-or R-chiral alcohols.
Compared with the prior art, the invention has the following advantages and effects:
(1) the ligand of the invention has simple synthesis and high stability, is easy to regulate and control in steric hindrance and electrical property, and can realize asymmetric hydrogenation of various substrates.
(2) The method has the advantages of mild reaction conditions, simple operation and simple and convenient post-treatment.
(3) The asymmetric hydrogenation reaction of the ketone has high activity, high selectivity and high conversion number, the dosage of the catalyst can be reduced to one ten thousandth, and the asymmetric hydrogenation catalyst has wide industrial application value.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
Example 1: synthesis of ligand L1a
Figure BDA0003518899690000061
Adding compound 1(30mmol, 7.71g) and anhydrous ether (60mL) into a 500mL three-neck flask under the nitrogen atmosphere, placing the reaction system at-40 ℃ for stirring, slowly dropwise adding n-butyl lithium (15mL, 2.5M) into the reaction system, stirring for 1 hour, transferring the reaction to room temperature for stirring for 2 hours, dissolving diphenyl phosphine chloride (13.23g, 60mmol) into 20mL ether, slowly dropwise adding into the reaction system, transferring the reaction to an oil bath after dropwise adding is finished, and heating and refluxing overnight; the reaction was quenched with saturated aqueous sodium bicarbonate solution, extracted with methyl tert-butyl ether, and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and purified by column chromatography to give 7.4g of a yellow solid with a yield of 56%.
Figure BDA0003518899690000062
3g of Compound 2 was dissolved in 6mL of acetic anhydride and reacted at 60 ℃ overnight under a nitrogen atmosphere. After the reaction is finished, acetic anhydride is removed by reduced pressure distillation to obtain a crude product 3, and the crude product is directly used for the next step without purification and low-temperature storage.
Figure BDA0003518899690000063
Compound 3(228mg, 0.5mmol) and compound 4(229mg, 1.0mmol) were refluxed in anhydrous MeOH (2mL) under nitrogen overnight and the solvent was evaporated in vacuo to give the crude product. After chromatography on a silica gel column with petroleum ether/ethyl acetate (v/v) ═ 20:1 to 3:1 as eluent, 195.5mg of a yellow solid were obtained in 57% yield.1H NMR(600MHz,CDCl3)δ7.67(d,J＝8.2Hz,2H),7.44(ddt,J＝7.7,5.8,2.3Hz,2H),7.36(dt,J＝4.7,1.6Hz,3H),7.29(d,J＝8.0Hz,2H),7.25-7.16(m,6H),6.85-6.78(m,2H),5.30(s,2H),4.37(dd,J＝2.6,1.4Hz,1H),4.27(t,J＝2.5Hz,1H),3.95(s,5H),3.66-3.60(m,2H),3.57(dd,J＝9.6,4.6Hz,1H),2.92(ddd,J＝12.5,7.8,4.5Hz,1H),2.45(s,4H),1.10(d,J＝6.4Hz,3H).13C NMR(151MHz,CDCl3)δ143.13,140.31,140.24,139.72,137.25,137.22,137.18,135.13,134.99,132.87,132.75,129.58,129.05,128.64,128.35,128.32(d,J＝3.2Hz),128.08,128.03,127.71,127.22,126.90(d,J＝2.6Hz),98.42(d,J＝22.2Hz),74.28(d,J＝8.9Hz),71.49(d,J＝4.8Hz),69.68(d,J＝4.3Hz),69.49,69.29,58.29,49.07,47.57(d,J＝5.9Hz),21.55,19.52.
Example 2: synthesis of ligand L1b
Figure BDA0003518899690000071
Starting material 1(20mmol, 5.14g) was placed in a 250mL three-necked flask at-20 ℃ and replaced with nitrogen three times, 40mL of diethyl ether was added, sec-butyllithium (17mL, 1.6M) was added dropwise, reaction was carried out at room temperature for 2h after completion of the addition, cooling to-78 ℃ and PCl was added3(2mL) was dissolved in 10mL of diethyl ether, and after dropwise addition, the reaction was allowed to slowly warm to room temperature overnight. The reaction was cooled further to-78 deg.C and the prepared Grignard reagent (60mmol Mg, 66mmol halohydrocarbon in 40mL anhydrousTHF) was added, the mixture was slowly warmed to room temperature overnight after the dropwise addition, quenched with saturated ammonium chloride, extracted with methyl tert-butyl ether, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated by rotary evaporation, and subjected to column chromatography to give 4.77g of an orange solid with a yield of 48%.
Figure BDA0003518899690000072
2g of Compound 6 was dissolved in 4mL of acetic anhydride and reacted at 60 ℃ overnight under a nitrogen atmosphere. After the reaction was completed, acetic anhydride was distilled off under reduced pressure to obtain a crude product 7 which was used in the next step without purification.
Figure BDA0003518899690000081
Compound 7(228mg, 0.5mmol) and compound 4(290mg, 1mmol) were refluxed in anhydrous MeOH (2mL) under nitrogen overnight and the solvent was evaporated in vacuo to give the crude product. After chromatography on a silica gel column with petroleum ether/ethyl acetate (v/v) ═ 20:1 to 3:1 as eluent, 178mg of a yellow solid were obtained in 48% yield.1H NMR(600MHz,CDCl3)δ7.67(d,J＝8.2Hz,2H),7.32(s,J＝4.7,1.6Hz,1H),7.29(d,J＝8.0Hz,2H),7.25-7.16(m,6H),6.85-6.78(m,2H),5.30(s,2H),4.37(dd,J＝2.6,1.4Hz,1H),4.27(t,J＝2.5Hz,1H),3.95(s,5H),3.66-3.60(m,2H),3.57(dd,J＝9.6,4.6Hz,1H),2.92(ddd,J＝12.5,7.8,4.5Hz,1H),2.45(s,4H),1.10(d,J＝6.4Hz,3H).13C NMR(151MHz,CDCl3)δ144.13,141.31,141.24,140.72,137.25,137.22,137.18,137.12,137.10,136.87,136.85,132.63,132.61,131.05,131.03,130.27,129.58,129.05,128.08,127.71,127.22,126.90(d,J＝2.6Hz),98.42(d,J＝22.2Hz),74.28(d,J＝8.9Hz),71.49(d,J＝4.8Hz),69.68(d,J＝4.3Hz),69.49,69.29,58.29,49.07,47.57(d,J＝5.9Hz),22.48,22.43,21.55,19.52.
Example 3: the synthesis of ligands L1c, L1d was performed as in example 2
Example 4: synthesis of ligand L5
Figure BDA0003518899690000082
Compound 2(228mg, 0.5mmol) and compound 9(318mg, 1mmol) were refluxed in anhydrous MeOH (2mL) under nitrogen overnight and the solvent was evaporated in vacuo to give the crude product. After chromatography on a silica gel column with petroleum ether/ethyl acetate (v/v) ═ 20:1 to 3:1 as eluent, 175mg of a yellow solid were obtained in 49% yield.1H NMR(600MHz,CDCl3)δ7.49-7.41(m,2H),7.38-7.32(m,3H),7.22(tq,J＝8.0,2.5Hz,8H),6.94(s,2H),6.75-6.67(m,2H),5.21-5.08(m,1H),4.40(dt,J＝2.9,1.6Hz,1H),4.29(t,J＝2.5Hz,1H),3.95(s,5H),3.73-3.64(m,2H),3.57(dd,J＝9.3,5.0Hz,1H),2.72(ddd,J＝12.5,7.7,4.9Hz,2H),2.53(s,6H),2.37-2.33(m,1H),2.32(s,3H),1.21(d,J＝6.4Hz,3H).13C NMR(151MHz,CDCl3)δ143.13,142.31,141.12,141.13,140.24,139.72,137.25,137.22,137.18,135.13,134.99,132.87,132.75,129.58,128.35,128.32(d,J＝3.2Hz),128.08,128.03,127.71,127.22,126.90(d,J＝2.6Hz),98.42(d,J＝22.2Hz),74.28(d,J＝8.9Hz),71.49(d,J＝4.8Hz),69.68(d,J＝4.3Hz),69.49,69.29,58.29,49.07,47.57(d,J＝5.9Hz),23.06,21.55,20.93,19.52.
Examples 5 to 16: the ligands were prepared according to the same methods as in example 1, example 2, example 3 and example 4. The reaction results are shown in table 1 below:
table 1 characterization of the prepared ligand structures and data
Figure BDA0003518899690000091
Figure BDA0003518899690000101
Figure BDA0003518899690000111
Figure BDA0003518899690000121
Figure BDA0003518899690000131
Example 17: asymmetric hydrogenation of 1a to produce 2a
Figure BDA0003518899690000132
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 99%, 99% ee(s).1H NMR(400MHz,CDCl3)δ7.41-7.02(m,5H),4.82(q,J＝6.5Hz,1H),2.42(s,1H),1.44(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ145.89,128.49,127.43,125.44,70.33,25.17.
Example 19: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1b (6.3mg, 0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 99%, 98% ee (S).
Example 20: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1c (7.6mg, 0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, quickly separating by column chromatography, removing the catalyst and alkali, and carrying out rotary evaporation and concentration to obtain a pure product 2 a. Colorless liquid, yield 98%, 98% ee (S).
Example 21: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L2a (5.9mg, 0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 98%, 96% ee (S).
Example 22: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L3a (5.9mg, 0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 98%, 95% ee (S).
Example 23: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L4(5.8mg, 0.0084mmol) were dissolved in isopropanol (2mL)Stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 99%, 45% ee (S).
Example 24: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L5(6.0mg, 0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 99%, 95% ee (S).
Example 25: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), sodium tert-butoxide (4.0mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 99%, 93% ee (S).
Example 26: asymmetric hydrogenation of 1a to produce 2a
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Acetophenone (240mg, 2mmol), sodium hydroxide (1.6mg, 0.04mmol) and catalyst solution were added(100. mu.L) was dissolved in isopropanol (4mL) and placed in an autoclave, into which 30atm hydrogen was flushed and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 a. Colorless liquid, yield 99%, 94% ee (S).
Example 27: preparation of 2b by asymmetric hydrogenation of 1b
Figure BDA0003518899690000171
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1b (268.4mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol), catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 b. Colorless liquid, yield 98%, 97% ee(s).1HNMR(400MHz,CDCl3)δ7.45-7.12(m,5H),4.54(td,J＝6.7,2.5Hz,1H),2.23(d,J＝2.8Hz,1H),1.85-1.62(m,2H),0.89(t,J＝7.4Hz,3H).13C NMR(101MHz,CDCl3)δ144.63,128.39,127.48,126.02,75.99,31.88,10.19.
Example 28: preparation of 2c by asymmetric hydrogenation of 1c
Figure BDA0003518899690000172
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1c (398.0mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. After the reaction is finished, the solvent is removed by rotary evaporation, and the column chromatography is quickAnd (4) quickly separating, removing the catalyst and alkali, and performing rotary evaporation and concentration to obtain a pure product 2 c. Colorless liquid, yield 98%, 98% ee (S).1HNMR(400MHz,CDCl3)δ7.44(d,J＝8.4Hz,2H),7.19(d,J＝8.5Hz,2H),4.79(q,J＝6.5Hz,1H),2.65(s,1H),1.42(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ144.79,131.51,127.19,121.09,69.67,25.23.
Example 29: preparation of 2d by asymmetric hydrogenation of 1d
Figure BDA0003518899690000181
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1d (309.2mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 d. Colorless liquid, yield 99%, 98% ee(s).1HNMR(400MHz,CDCl3)δ7.51-6.96(m,4H),4.82(q,J＝6.5Hz,1H),2.44(s,1H),1.43(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ144.26,133.00,128.57,126.81,69.67,25.24.
Example 30: asymmetric hydrogenation of 1e to 2e
Figure BDA0003518899690000182
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1e (268.3mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. After the reaction is finished, the solvent is removed by rotary evaporation, and column chromatography is carried outAnd (3) quickly separating, removing the catalyst and alkali, and performing rotary evaporation and concentration to obtain a pure product 2 e. Colorless liquid, yield 99%, 99% ee (S).1H NMR(400MHz,CDCl3)δ7.21(d,J＝8.1Hz,2H),7.12(d,J＝7.9Hz,2H),4.77(td,J＝6.5,2.6Hz,1H),2.45(d,J＝2.9Hz,1H),2.32(s,3H),1.42(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ142.97,137.05,129.15,125.43,70.15,25.11,21.14.
Example 31: asymmetric hydrogenation of 1f to produce 2f
Figure BDA0003518899690000191
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1f (300.4mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol), catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 f. Colorless liquid, yield 99%, 99% ee (S).1H NMR(400MHz,CDCl3)δ7.24(d,J＝8.6Hz,2H),6.83(d,J＝8.7Hz,2H),4.77(q,J＝6.4Hz,1H),3.75(s,3H),2.69(s,1H),1.42(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ158.83,138.17,126.70,113.78,69.77,55.27,25.07.
Example 32: asymmetric hydrogenation of 1g to produce 2g
Figure BDA0003518899690000192
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1g (309.2mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol), catalyst solution (100. mu.L) was dissolved in isopropanol (4mL) and placed in an autoclave, which was pressurizedThe reaction kettle is flushed with 30atm of hydrogen and stirred for 12 hours at room temperature. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 g. Colorless liquid, yield 98%, 98% ee(s).1H NMR(400MHz,CDCl3)δ7.33(q,J＝1.3,0.7Hz,1H),7.31-7.08(m,3H),4.81(q,J＝6.5Hz,1H),2.50(s,1H),1.44(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ147.87,134.31,129.78,127.49,125.63,123.56,69.73,25.21.
Example 33: 1h asymmetric hydrogenation to 2h
Figure BDA0003518899690000201
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1h (300.1mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol), catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product for 2 hours. Colorless liquid, yield 98%, 99% ee (S).1H NMR(400MHz,CDCl3)δ7.22(t,J＝8.1Hz,1H),6.93-6.84(m,2H),6.77(ddd,J＝8.2,2.6,1.1Hz,1H),4.86-4.71(m,1H),3.76(s,3H),2.64(d,J＝2.2Hz,1H),1.43(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ158.60,146.64,128.40,116.67,111.72,109.84,69.10,54.11,24.08.
Example 34: asymmetric hydrogenation of 1i to produce 2i
Figure BDA0003518899690000202
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. The reaction mixture of 1i (340.4mg,2mmol), lithium tert-butoxide (3.4mg, 0.04mmol), catalyst solution (100. mu.L) was dissolved in isopropanol (4mL) and placed in an autoclave, into which 30atm hydrogen was flushed and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 i. White solid, yield 99%, 99% ee(s).1H NMR(400MHz,CDCl3)δ7.90-7.67(m,4H),7.57-7.41(m,3H),5.04(q,J＝6.5Hz,1H),2.26(s,1H),1.58(d,J＝6.4Hz,3H).13C NMR(101MHz,CDCl3)δ143.31,133.37,132.94,128.31,128.03,127.75,126.18,125.83,123.96,123.88,70.42,25.19.
Example 35: asymmetric hydrogenation of 1j to produce 2j
Figure BDA0003518899690000211
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1j (378.1mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and a catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was purged with 30atm hydrogen and stirred at room temperature for 12 hours. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 j. Colorless liquid, yield 98%, 96% ee (S).1H NMR(400MHz,CDCl3)δ7.46-7.25(m,2H),7.10(dd,J＝8.2,2.1Hz,1H),4.81-4.51(m,1H),3.19-2.99(m,1H),1.39(d,J＝6.5Hz,3H).13C NMR(101MHz,CDCl3)δ145.97,132.40,131.06,130.38,127.41,124.79,69.09,25.21.
Example 36: asymmetric hydrogenation of 1k to produce 2k
Figure BDA0003518899690000212
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg, 0.0084)mmol) was dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1k (118.6mg, 0.8mmol), lithium tert-butoxide (1.68mg, 0.02mmol), catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 k. Colorless liquid, yield 98%, 99% ee (S).1H NMR(400MHz,CDCl3)δ8.13-7.99(m,1H),7.93-7.86(m,1H),7.79(dt,J＝8.2,1.0Hz,1H),7.70-7.65(m,1H),7.60-7.44(m,3H),5.61(q,J＝6.5Hz,1H),2.72-2.42(m,1H),1.65(dd,J＝6.5,0.8Hz,3H).13C NMR(101MHz,CDCl3)δ141.44,133.81,130.29,128.92,127.90,126.04,125.58,125.56,123.22,122.05,67.03,24.40.
Example 37: 1l asymmetric hydrogenation to 2l
Figure BDA0003518899690000221
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1L (242.2mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol) and a catalyst solution (100. mu.L) were dissolved in isopropanol (4mL) and placed in an autoclave, which was purged with 30atm hydrogen and stirred at room temperature for 12 hours. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain 2l of a pure product. Colorless liquid, yield 98%, 97% ee (S).1H NMR(400MHz,CDCl3)δ8.53-8.52(m,1H),7.70-7.66(m,1H),7.28–7.27(m,1H),7.20-7.18(m,1H),4.89(q,J＝6.6Hz,1H),4.31(s,1H),1.50(d,J＝6.6Hz,3H).13C NMR(101MHz,CDCl3)δ163.20,148.12,136.82,122.22,119.28,68.82,24.23.
Example 38: asymmetric hydrogenation of 1m to 2m
Figure BDA0003518899690000222
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1m (242.2mg, 2mmol), lithium tert-butoxide (3.4mg, 0.04mmol),catalyst and process for preparing sameThe solution (100. mu.L) was dissolved in isopropanol (4mL) and placed in an autoclave, into which 30atm hydrogen was flushed and stirred at room temperature for 12 h. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product of 2 m. Yield 98%, 96% ee (S).1H NMR(400MHz,CDCl3)δ7.23(dd,J＝4.8Hz,1.2Hz,1H),6.96-6.95(m,2H),5.10(q,J＝6.6Hz,1H),2.48(s,1H),1.58(d,J＝6.6Hz,3H)；13C NMR(101MHz,CDCl3)δ150.0,126.7,124.4,123.2,66.2,25.3.
Example 39: asymmetric hydrogenation of 1n to 2n
Figure BDA0003518899690000231
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. 1n (59.2mg, 0.4mmol), lithium tert-butoxide (1.68mg, 0.02mmol) and a catalyst solution (100. mu.L) were dissolved in isopropanol (2mL) and placed in an autoclave, which was purged with 30atm hydrogen and stirred at room temperature for 12 hours. And after the reaction is finished, removing the solvent by rotary evaporation, performing column chromatography rapid separation, removing the catalyst and alkali, and performing rotary evaporation concentration to obtain a pure product 2 n. Colorless liquid, yield 98%, 30% ee (S).1HNMR (400MHz, CDCl)3)δ7.29-7.24(m,2H),7.23-7.19(m,3H)，3.87-3.79(m,1H),2.80-2.60(m,2H),1.88-1.72(m,2H),1.23(d,J＝6.0Hz,3H).13C NMR(101MHz,CDCl3)δ142.0,128.42,128.25,125.78,67.65,40.28,32.21,23.26。
Examples 40-44 asymmetric hydrogenation of different halo ketones to chiral alcohols
Under the nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Ketone (0.4mmol), lithium hydroxide (0.4mg, 0.02mmol) and catalyst solution (100. mu.L) were dissolved in isopropanol (2-4mL) and placed in an autoclave, into which 30atm hydrogen was flushed and stirred at room temperature for 12 h. After the reaction is finished, the solvent is removed by rotary evaporation, the target product is obtained by column chromatography rapid separation, the separation yield is measured, the ee value is measured by HPLC, and the reaction results are shown in Table 2.
Table 2: results of asymmetric hydrogenation of different haloketones to chiral alcohols
Figure BDA0003518899690000241
Examples 45-51 asymmetric hydrogenation of different hydroxy ketones and amino ketones to chiral alcohols
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. Ketone (0.4mmol), lithium tert-butoxide (1.7mg, 0.04mmol) and the catalyst solution (100. mu.L) were dissolved in isopropanol (2-4mL) and placed in an autoclave, which was flushed with 30atm hydrogen and stirred at room temperature for 12 h. After the reaction is finished, the solvent is removed by rotary evaporation, the target product is obtained by column chromatography rapid separation, the separation yield is measured, the ee value is measured by HPLC, and the reaction results are shown in Table 3.
Table 3: asymmetric hydrogenation of different hydroxy and amino ketones to chiral alcohols
Figure BDA0003518899690000251
Examples 52-56 asymmetric hydrogenation of different ketoesters to chiral alcohols
Under nitrogen atmosphere, [ Ir (COD) Cl]2(2.8mg,0.004mmol) and ligand L1a (5.8mg,0.0084mmol) were dissolved in isopropanol (2mL) and stirred at room temperature for 2.5h to prepare an orange catalyst solution. The ketone (0.4mmol), lithium tert-butoxide (b) (iii)1.7mg, 0.04mmol), the catalyst solution (100. mu.L) was dissolved in isopropanol (2-4mL) and placed in a high pressure autoclave, into which 30atm hydrogen was flushed and stirred at room temperature for 12 h. After the reaction is finished, the solvent is removed by rotary evaporation, the target product is obtained by column chromatography rapid separation, the separation yield is measured, the ee value is measured by HPLC, and the reaction results are shown in Table 4.
Table 4: asymmetric hydrogenation of different ketoesters to chiral alcohols
Figure BDA0003518899690000261
The NMR data and the carbon spectrum data of the hydrogenated products of the above examples 40 to 56 are as follows:
(R) -2-chloro-1-phenylethanol 2p:1H NMR(400MHz,CDCl3)δ3.12-3.67(m,1H),3.72-3.74(m,1H),4.89(m,1H),7.33-7.35(m,5H)；13C NMR(101MHz,CDCl3)δ50.9,74.2,126.2,128.5,128.8,140.1.
(R) -2-bromo-1-phenylethanol 2q:1H NMR(400MHz,CDCl3)δ7.39-7.31(m,5H),4.93(dt,J＝9.0,3.2Hz,1H),3.64(dd,J＝10.5,3.3Hz,1H),3.55(dd,J＝10.5,9.0Hz,1H),2.70(d,J＝3.2Hz,1H).13C NMR(101MHz,CDCl3)δ140.21,128.65,128.44,125.92,73.75,40.19.
(R) -2-chloro-1- (4-methylphenyl) ethanol 2R:1H NMR(400MHz,CDCl3)δ7.29-7.24(m,2H),7.23-7.16(m,2H),4.86(dd,J＝8.74,3.50Hz,1H),3.75-3.71(m,1H),3.63(dd,J＝11.16,8.72,1H),2.52(bs,1H),2.34(s,3H).13C NMR(100MHz,CDCl3)δ:21.2,50.9,73.9,125.9,129.4,136.9,138.3.
(R) -2-chloro-1- (p-bromophenyl) ethanol 2s:1H NMR(400MHz,CDCl3)δ7.52-7.48(m,2H),7.27-7.25(m,2H),4.87-4.84(m,1H),3.70(dd,J＝11.3,3.5Hz,1H),3.59(dd,J＝11.3,8.6Hz,1H),2.85(d,J＝2.8Hz,1H).13C NMR(101MHz,CDCl3)δ138.79,131.73,127.72,122.30,73.32,50.54.
(R) -1-phenylethane-1, 2-diol 2t:1H NMR(400MHz,CDCl3)δ7.41-7.22(m,5H),4.78(dd,J＝8.2,2.9Hz,1H),3.77-3.66(m,1H),3.65-3.57(m,1H),3.21(s,1H).13C NMR(101MHz,CDCl3)δ68.0,74.8,126.1,127.9,128.5,140.5.
r-1- (4-bromophenyl) ethane-1, 2-diol 2u:1H NMR(400MHz,DMSO)δ7.86-7.77(m,2H),7.70-7.60(m,2H),4.85(d,J＝4.4Hz,2H),3.45(t,J＝4.6Hz,1H).13CNMR(101MHz,DMSO)141.41,130.90,128.02,120.70,73.79,67.06.
(R) -1-naphthylethane-1, 2-diol 2v:1H NMR(400MHz,DMSO)δ8.33(s,1H),7.96-7.67(m,4H),7.63-7.44(m,2H),4.93(d,J＝4.6Hz,2H),3.53(t,J＝4.7Hz,1H).13C NMR(101MHz,DMSO)δ139.43,133.39,133.12,127.53,127.51,127.24,125.66,125.38,124.84,124.17,74.65,67.24.
(S) -2- (benzyl (methyl) amino) -1- (2-thienyl) ethanol 2w:1H NMR(400MHz,CDCl3)δ7.36-7.15(m,5H),7.11(dd,J＝5.0,1.2Hz,1H),6.86(dd,J＝5.0,3.5Hz,1H),6.81(dd,J＝2.9,1.8Hz,1H),5.17-5.01(m,1H),3.55(d,J＝12.8Hz,1H),3.39(d,J＝12.8Hz,1H),2.73(ddd,J＝12.9,8.8,4.3Hz,1H),2.57(ddd,J＝12.7,5.6,3.7Hz,1H),2.16(s,3H),2.03-1.83(m,2H).13C NMR(101MHz,CDCl3)δ149.55,137.57,129.26,128.54,127.48,126.60,123.71,122.31,62.85,56.23,41.67.
(S) -3- (1- (4-phenylpiperazine)) -1- (2-thienyl) propan-1-ol 2x:1H NMR(400MHz,CDCl3)δ7.30-7.16(m,3H),6.96(dd,J＝5.0,3.5Hz,1H),6.94-6.83(m,14H),5.18(t,J＝5.6Hz,1H),3.20(t,J＝5.0Hz,4H),2.91-2.50(m,6H),2.16-1.92(m,2H).13CNMR(101MHz,CDCl3)δ151.09,149.40,129.20,126.71,123.86,122.41,120.07,116.30,71.96,56.79,53.25,49.28,33.83.
(S) -1-phenyl-3- (1-piperidinyl) propan-1-ol 2y:1H NMR(400MHz,CDCl3)δ7.43-7.29(m,4H),7.27-7.13(m,1H),4.93(t,J＝5.8Hz,1H),3.74(t,J＝4.7Hz,2H),2.85-2.26(m,6H),1.99-1.76(m,2H).13C NMR(101MHz,CDCl3)δ144.74,128.26,127.00,125.51,75.45,66.94,57.52,53.68,33.46.
(S) -3- (methylamino) -1- (2-thienyl) propan-1-ol 2z:1H NMR(400MHz,CDCl3)δ7.18(dd,J＝1.2Hz,4.8Hz,1H),6.95-6.93(m,1H),6.91-6.90(m,1H),5.15(dd,J＝3.2Hz,8.4Hz,1H),3.93(br s,2H),2.94-2.88(m,1H),2.85-2.79(m,1H),2.40(s,3H),1.99-1.84(m,2H)；13C NMR(101MHz,CDCl3)δ149.39,126.28,123.32,122.54,71.68,50.32,37.22,36.21.
(R) -2-hydroxy-2-phenylacetic acid methyl ester 4a:1H NMR(400MHz,CDCl3)δ7.43-7.30(m,5H),5.18(s,1H),3.76(s,3H),3.52(brs,1H).13C NMR(101MHz,CDCl3)δ174.21,138.32,128.26,128.15,126.46,72.28,53.10.
(R) -2-hydroxy-2- (4-methoxyphenyl) acetic acid methyl ester 4b:1H NMR(CDCl3,400MHz)δ7.29(d,J＝8.8Hz,2H),6.90(d,J＝8.8Hz,2H),4.76-4.79(dd,J＝3.6,8.0Hz,1H),3.81(s,3H),3.71-3.74(m,1H),3.63-3.68(m,1H)；13C NMR(CDCl3,100MHz)δ159.26,132.81,127.25,114.13,74.24,68.21,55.24.
(S) -3-hydroxy-3-phenylpropionic acid methyl ester 4c:1H NMR(400MHz,CDCl3)δ2.73(dd,J＝3.8Hz,J＝16.4Hz,1H),2.79(dd,J＝9.1Hz,16.4Hz,1H),3.19(d,J＝2.3Hz,1H),3.74(s,3H),5.14-5.17(m,1H),7.29-7.40(m,5H).13C NMR(101MHz,CDCl3)δ172.79,142.55,128.58,127.85,125.68,70.32,51.94,43.22；
(S) -3- (4-chlorophenyl) -3-hydroxypropionic acid methyl ester 4d:1H NMR(400MHz,CDCl3)δ:7.34-7.30(m,4H),5.11(dd,J＝8.2,4.6Hz,1H),3.73(s,3H),3.35(s,1H),2.77-2.66(m,2H)；13C NMR(101MHz,CDCl3)δ:142.85,133.13,128.61,127.03,73.62,61.33,40.42.
(S) -3-hydroxy-3-naphthylpropionic acid methyl ester 4e:1H NMR(400MHz,CDCl3)δ7.90-7.77(m,1H),7.58-7.42(m,1H),5.35-5.32(m,1H),4.20(q,J＝7.1Hz,1H),3.39(d,J＝3.5Hz,1H),2.97-2.71(m,1H),1.27(t,J＝7.1Hz,1H)；13C NMR(101MHz,CDCl3)δ171.24,139.19,133.33,133.20,128.14,128.07,127.57,126.12,126.01,124.52,123.47,70.46,60.93,43.33,14.21.
the above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (10)

1. A chiral tridentate nitrogen phosphine ligand based on ferrocene skeleton synthesis is characterized in that: the ligand has a structure shown as a general formula (I):
Figure FDA0003518899680000011
wherein R is1Is alkyl, aryl or R1-1A substituted aryl group; the R is1-1The substituent is halogen, alkyl, phenyl or alkoxy;
R2is R2-1A substituted benzenesulfonyl group; the R is2-1The substituent is a hydrogen atom or an alkyl group;
R3is alkyl, aryl or R3-1Substituted aryl, said R3-1The substituent is alkyl, alkoxy, aryloxy, aryl or halogen;
in the formula (I), the structure is a stereogenic center and is in an R configuration or an S configuration.
2. The chiral tridentate azophoshine ligand synthesized based on a ferrocene skeleton as claimed in claim 1, wherein: the ligand includes a compound of the structure:
Figure FDA0003518899680000012
3. the use of a chiral tridentate azaphosphino ligand based on ferrocene skeleton synthesis according to claim 1 or 2 in asymmetric hydrogenation of ketones.
4. Use according to claim 3, characterized in that it comprises the following steps:
(1) reacting a metal iridium complex with a chiral tridentate nitrogen-phosphine ligand synthesized based on a ferrocene skeleton in a solvent A to obtain a complex of the chiral tridentate nitrogen-phosphine ligand;
(2) carrying out asymmetric hydrogenation reaction on ketone, the complex of the chiral tridentate nitrogen phosphine ligand obtained in the step (1), a solvent B and alkali at the temperature of 25-100 ℃ and under the hydrogen pressure of 0.1-10.0MPa for 1-96h to obtain a chiral amino alcohol compound; the ketone is a compound with a structure shown in a formula (II), and the structural formula of the chiral amino alcohol compound is shown in a formula (III);
Figure FDA0003518899680000021
wherein R in the formula (II) and the formula (III)4Is alkyl, alkenyl, aryl or heteroaryl; r5Is alkyl, R5-1Substituted alkyl or ester group, said R5-1Is halogen, hydroxyl, primary amine, secondary amine or ester group.
5. Use according to claim 4, characterized in that: the iridium complex of the metal in the step (1) is [ Ir (COD) Cl]2、[Ir(COE)2Cl]2、[Ir(NBD)2Cl]2、[Ir(COD)OMe]2、[Ir(COD)2]X and [ Ir (NBD)2]Any one of X, wherein X is BF4 -、BArF-、PF6 -、CF3SO3 -Or ClO4 -。
6. Use according to claim 4, characterized in that: the molar ratio of the metal iridium complex in the step (1) to the chiral tridentate nitrogen phosphine ligand synthesized based on the ferrocene skeleton is 1: 1-4.
7. Use according to claim 4, characterized in that: the solvent A in the step (1) is one of n-hexane, dichloromethane, toluene, tetrahydrofuran, methanol, ethanol, isopropanol and n-butanol.
8. Use according to claim 4, characterized in that: and (3) the alkali in the step (2) is more than one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium hydroxide, potassium hydroxide, lithium hydroxide, cesium carbonate, potassium carbonate, sodium methoxide and sodium ethoxide.
9. Use according to claim 4, characterized in that: and (3) the solvent B in the step (2) is more than one of n-hexane, dichloromethane, dichloroethane, 1, 4-dioxane, toluene, tetrahydrofuran, methanol, ethanol, isopropanol and n-butanol.
10. Use according to claim 4, characterized in that: the molar ratio of the complex of the chiral tridentate nitrogen phosphine ligand in the step (1) to the aminoketone compound in the step (2) is 1: 500-100000.
CN202210175430.1A 2021-08-18 2022-02-24 Chiral tridentate nitrogen phosphine ligand synthesized based on ferrocene skeleton and application thereof Pending CN114560892A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2021109501015 2021-08-18
CN202110950101 2021-08-18

Publications (1)

Publication Number Publication Date
CN114560892A true CN114560892A (en) 2022-05-31

Family

ID=81715506

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210175430.1A Pending CN114560892A (en) 2021-08-18 2022-02-24 Chiral tridentate nitrogen phosphine ligand synthesized based on ferrocene skeleton and application thereof

Country Status (1)

Country Link
CN (1) CN114560892A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116102524A (en) * 2023-02-28 2023-05-12 华东理工大学 Asymmetric synthesis method of beta-amino alcohol compound

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107722068A (en) * 2017-11-09 2018-02-23 凯特立斯（深圳）科技有限公司 Three tooth aminophosphine ligands and its complex and its application in the asymmetric catalytic hydrogenation of ketone
CN108774271A (en) * 2018-02-08 2018-11-09 浙江工业大学 A kind of chiral nitrogen nitrogen phosphine tridentate ligand and its application based on ferrocene frame having ferrocene frame

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107722068A (en) * 2017-11-09 2018-02-23 凯特立斯（深圳）科技有限公司 Three tooth aminophosphine ligands and its complex and its application in the asymmetric catalytic hydrogenation of ketone
CN108774271A (en) * 2018-02-08 2018-11-09 浙江工业大学 A kind of chiral nitrogen nitrogen phosphine tridentate ligand and its application based on ferrocene frame having ferrocene frame

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LIANG ZHIQIN 等: "Scope and Mechanism on Iridium-f-Amphamide Catalyzed Asymmetric Hydrogenation of Ketones", 《CHINESE JOURNAL OF CHEMISTRY》, vol. 36, no. 9, pages 851 - 856 *
ZHANG LEI 等: "Iridium-Catalyzed Asymmetric Hydrogenation of Simple Ketones with Tridentate PNN Ligands Bearing Unsymmetrical Vicinal Diamines", 《J. ORG. CHEM.》, vol. 88, pages 2942 - 2951 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116102524A (en) * 2023-02-28 2023-05-12 华东理工大学 Asymmetric synthesis method of beta-amino alcohol compound

Similar Documents

Publication Publication Date Title
CN105732387B (en) The method of novel C -2` phase transfer catalyst photooxidation beta-dicarbonyl compound asymmetry 'alpha '-hydroxylation
CN112916042A (en) Chiral quaternary ammonium salt phase transfer catalyst based on tetramethyl spiroindane skeleton and preparation method thereof
CN100482644C (en) Chiral diene ligand, synthesis method and its application in asymmetric reaction
CN114560892A (en) Chiral tridentate nitrogen phosphine ligand synthesized based on ferrocene skeleton and application thereof
CN113549062B (en) Chiral quaternary ammonium salt phase transfer catalyst with high steric hindrance derived from cinchona alkaloid and synthesis method thereof
CN108558635B (en) Preparation method of 3-aryl propiolic acid and 3-aryl propiolic acid ester compound
CN111718372B (en) Axial chiral phosphine-alkene ligand and preparation method and application thereof
CN112724168A (en) Chiral pyridine derived N, B ligand, preparation method and application in iridium-catalyzed asymmetric boronation reaction
CN109824579B (en) Preparation method of (S) -phenyl (pyridine-2-yl) methanol derivative
CN111217809B (en) Chiral nitrogen-containing diene ligand and preparation method and application thereof
CN109535120B (en) Preparation method of 7-substituted-3, 4,4, 7-tetrahydrocyclobutane coumarin-5-ketone
CN111320651B (en) Chiral amino-pyridine-phosphine tridentate ligand, manganese complex, preparation method and application thereof
CN102344431A (en) Method for preparing nebivolol hydrochloride
CN114644663A (en) Chiral tridentate nitrogen phosphine ligand and application thereof in asymmetric hydrogenation reaction of ketone
CN103073590A (en) Chiral aromatic spiroketal skeleton double phosphine ligand, preparation method and uses thereof
CN112675920B (en) Mono-chiral center catalyst, preparation thereof and method for catalytically synthesizing chiral alcohol compound and chiral alpha-allyl alcohol
CN111217847B (en) Thiosilane ligand, preparation method thereof and application thereof in aryl boronization catalytic reaction
CN111039767B (en) Method for preparing deuterated aldehyde by using triazole carbene as catalyst
CN114308121A (en) Phosphine oxide catalyst and preparation method and application thereof
CN109776400B (en) Preparation method of (R) -phenyl (pyridine-2-yl) methanol derivative
CN111718363B (en) Preparation method of borate compound
CN114768866B (en) Chiral deuterated Maruoka phase transfer catalyst, preparation method thereof and application thereof in asymmetric catalytic reaction
CN110194760B (en) Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones
CN116410126A (en) Ligand, ruthenium complex, preparation method thereof and application of ligand and ruthenium complex in catalyzing alkyne semi-hydrogenation reaction
CN113999207B (en) Pyridyl-containing chiral NNN tridentate ligand, asymmetric catalytic hydrogenation synthesis thereof and application of pyridyl-containing chiral NNN tridentate ligand in asymmetric catalytic reaction

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination