CN115611878A - 3-arylamine (acylamino) pyridine oxazoline chiral ligand and preparation and application thereof - Google Patents

3-arylamine (acylamino) pyridine oxazoline chiral ligand and preparation and application thereof Download PDF

Info

Publication number
CN115611878A
CN115611878A CN202211263878.5A CN202211263878A CN115611878A CN 115611878 A CN115611878 A CN 115611878A CN 202211263878 A CN202211263878 A CN 202211263878A CN 115611878 A CN115611878 A CN 115611878A
Authority
CN
China
Prior art keywords
substituted
aryl
formula
acyl
oxazoline
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
CN202211263878.5A
Other languages
Chinese (zh)
Inventor
李圣坤
来继星
杨娟
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.)
Guizhou University
Original Assignee
Guizhou University
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 Guizhou University filed Critical Guizhou University
Priority to CN202211263878.5A priority Critical patent/CN115611878A/en
Publication of CN115611878A publication Critical patent/CN115611878A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • 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
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
    • B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • 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
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
    • B01J2231/4211—Suzuki-type, i.e. RY + R'B(OR)2, in which R, R' are optionally substituted alkyl, alkenyl, aryl, acyl and Y is the leaving group
    • 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
    • B01J2531/824—Palladium
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Pest Control & Pesticides (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Plant Pathology (AREA)
  • Environmental Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Dentistry (AREA)
  • Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Inorganic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a 3-aryl (acyl) amine pyridine oxazoline chiral ligand, and a preparation method and an application thereof. The invention provides a 3-aryl (acyl) amine pyridine oxazoline chiral ligand which has a structural general formula shown in a formula 1; r in the formula 1 is
Figure DDA0003892260150000011
Figure DDA0003892260150000012
N in formula 1 is 0 or 1. The 3-aryl (acyl) amine pyridine oxazoline chiral ligand is a multifunctional ligand molecule with both chemical catalytic activity and biological pharmacological activity, can be used for catalyzing asymmetric addition reaction of aryl boric acid to quinolinone, and has good bacteriostatic activity to various agricultural pathogenic bacteria. Has important significance for the research fields of biology and chemistry.
Figure DDA0003892260150000013

Description

3-aryl (acyl) amine pyridine oxazoline chiral ligand and preparation and application thereof
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a 3-aryl (acyl) amine pyridine oxazoline chiral ligand, and a preparation method and an application thereof.
Background
"ligands" (Ligand) play an important role in both the biological and chemical research fields: (1) In biology, a ligand can interact with biomolecules such as proteins, and further cause specific biological effects, such as disease treatment or target research; (2) In chemistry, particularly in metal organic chemistry, a ligand can be complexed with a specific metal to form a certain complex, so that the steric effect and the electronic effect of the metal are changed, and the preparation of functional molecules is realized, and the method is particularly used for various organic synthesis transformations.
Heterocyclic compounds containing oxazoline are widely distributed in active natural products and drug molecules, and play an important role in drug molecule design and compound discovery. The complex formed by complexing pyridine-oxazoline ligand and metal shows excellent catalytic performance in many types of reactions, and has been successfully applied to various asymmetric catalytic reactions.
However, no "multifunctional" ligand molecule with both chemical catalytic activity and biopharmacological activity has been reported.
Disclosure of Invention
The 3-aryl (acyl) amine pyridine oxazoline chiral ligand has chemical catalytic activity and biological pharmacological activity, can be used for catalyzing asymmetric addition reaction of aryl boric acid to quinolinone, and has good bacteriostatic activity on various agricultural pathogenic bacteria. Has important significance for the research field of biology and chemistry.
In order to achieve the above purpose, the invention provides the following technical scheme:
the invention provides a 3-aryl (acyl) amine pyridine oxazoline chiral ligand which has a structural general formula shown in a formula 1:
Figure BDA0003892260130000011
n in the formula 1 is 1 or 0;
r in the formula 1 is
Figure BDA0003892260130000012
Figure BDA0003892260130000013
The above-mentioned
Figure BDA0003892260130000021
R in (1) 1 Comprising C 1 ～C 8 Chain hydrocarbon group, phenyl, substituted phenyl, benzyl, substituted benzyl, naphthyl, methoxy formyl, amido, phenyl substituted amido, benzyl substituted amido, hydroxymethyl, carboxyl and C 1 ～C 6 Carboxylic acid hydrocarbyl ester group of (C) 1 ～C 6 A hydrocarbyl carbonyl, a phenylcarbonyl, a substituted phenylcarbonyl, or a substituted hydroxymethyl;
the above-mentioned
Figure BDA0003892260130000022
R in (1) 2 Including hydrogen, methyl, ethyl, isopropyl, n-butyl, sec-butyl, isobutyl, cyclohexyl, methoxycarbonyl, hydroxymethyl, C 1 ～C 6 A carboxylic acid alkyl ester group, an aryl group or an aryl methylene group;
r in the formula 1 3 Including hydrogen, halogen, C 1 ～C 6 Alkyl, phenyl, arylmethylene, methoxy, phenoxy, alkylcarbonyl, halomethyl, alkoxymethyl, halogen-substituted phenyl, C 1 ～C 6 Hydrocarbyl-substituted phenyl, C 1 ～C 6 Alkoxy-substituted phenyl, C 1 ～C 6 A hydrocarbylamino-substituted phenyl group;
ar in the formula 1 comprises phenyl, halogenated phenyl and C 1 ～C 6 Hydrocarbyl-substituted phenyl, C 1 ～C 6 Alkoxy-substituted phenyl, C 1 ～C 6 Hydrocarbylamino-substituted phenyl, C 1 ～C 6 Halogen-substituted hydrocarbyl phenyl, alkylcarbonyl-substituted phenyl, naphthyl, substituted naphthyl, pyridine, substituted pyridine, pyrimidine, substituted pyrimidine, pyrazine, substituted pyrazine, quinoline, substituted quinoline, isoquinoline, substituted isoquinoline, indole, substituted indole, thiazole, substituted thiazole, pyrazole, substituted pyrazole, thiophene, substituted thiophene, furan or substituted furan.
Preferably, said R is 1 Wherein the substituent on the substituted phenyl group includes C 1 ～C 6 One or more of the alkyl, alkoxy and halogenated alkyl, wherein the number of the substituent groups on the substituted phenyl is 1-5;
the R is 1 Wherein the substituent of the substituted benzyl group is located on the benzene ring, and the substituent of the substituted benzyl group comprises C 1 ～C 6 One or more of alkyl, alkoxy and halogenated alkyl, and the number of the substituent groups is 1 to 5;
the R is 1 Wherein the substituent of the substituted phenylcarbonyl group is on the benzene ring and includes C 1 ～C 6 One or more of alkyl, alkoxy and halogenated alkyl, and the number of the substituent groups is 1 to 5;
the R is 1 Wherein the substituent of the substituted hydroxymethyl group is located on a carbon atom of the hydroxymethyl group, and the substituent includes C 1 ～C 6 One or two of hydrocarbyl, phenyl and substituted phenyl.
Preferably, said R is 3 Including hydrogen, methyl, methoxy, fluoro, chloro or trifluoromethyl.
Preferably, the Ar comprises:
Figure BDA0003892260130000031
any one of them.
Preferably, theR is as described above 1 The method comprises the following steps:
Figure BDA0003892260130000032
any one of them.
Preferably, said R is 2 The method comprises the following steps:
Figure BDA0003892260130000033
any one of them.
Preferably, the compound has any one of the structures shown in formula 1-1 to formula 1-15:
Figure BDA0003892260130000034
Figure BDA0003892260130000041
the invention provides a preparation method of a 3-aryl (acyl) amine pyridine oxazoline chiral ligand, which comprises the following steps:
mixing an amino alcohol compound with a structure shown in a formula 2, a formula 3, a formula 4 or a formula 5, a 3-bromo-2-cyanopyridine compound with a structure shown in a formula 6, an organic zinc catalyst and an organic solvent for cyclization reaction to obtain a 3-bromopyridine oxazoline compound with a structure shown in a formula 7;
Figure BDA0003892260130000042
3-bromopyridine oxazoline compounds with the structure shown in the formula 7, arylamine, palladium catalyst, organic phosphine ligand, alkali carbonate and organic solvent are mixed for C-N cross coupling reaction to obtain the 3-aryl (acyl) amine pyridine oxazoline chiral ligand with the structural general formula shown in the formula 1.
The invention provides the 3-aryl (acyl) amine pyridine oxazoline chiral ligand and the chemically acceptable salt of the pesticide thereof in the technical scheme or the 3-aryl (acyl) amine pyridine oxazoline compound and the chemically acceptable salt of the pesticide thereof prepared by the preparation method in the technical scheme as the application of the bacteriostatic agent for agricultural pathogenic bacteria.
The invention provides an application of the 3-aryl (acyl) amine pyridine oxazoline chiral ligand in the technical scheme or the 3-aryl (acyl) amine pyridine-oxazoline compound prepared by the preparation method in the technical scheme in catalyzing asymmetric addition reaction of aryl boric acid to quinolinone.
The invention provides a 3-aryl (acyl) amine pyridine oxazoline chiral ligand which has a structural general formula shown in a formula 1. The chiral ligand provided by the invention takes pyridine-oxazoline as a skeleton structure, and simultaneously modifies arylamine on the 3-position of a pyridine ring, and uses R 1 And R 2 、
Figure BDA0003892260130000051
The obtained 3-aryl (acyl) amine pyridine oxazoline chiral ligand is a multifunctional ligand molecule with both chemical catalytic activity and biological pharmacological activity, can be used for catalyzing asymmetric addition reaction of aryl boric acid to quinolinone, and has good bacteriostatic activity to various agricultural pathogenic bacteria. The example result shows that when the 3-aryl (acyl) amine pyridine oxazoline chiral ligand provided by the invention is used for catalyzing the asymmetric addition reaction of arylboronic acid to quinolinone, the enantiomeric excess value (ee value) of the addition product is 73-95%; the results of bacteriostasis tests on agricultural pathogenic bacteria show that the 3-aryl (acyl) amine pyridine oxazoline chiral ligand provided by the invention has good bacteriostatic activity on rhizoctonia solani and sclerotinia sclerotiorum.
The invention provides a preparation method of a 3-aryl (acyl) amine pyridine oxazoline chiral ligand, which comprises the following steps: mixing an amino alcohol compound with a structure shown in a formula 2, a formula 3, a formula 4 or a formula 5, a 3-bromo-2-cyanopyridine compound with a structure shown in a formula 6, an organic zinc catalyst and an organic solvent for cyclization reaction to obtain a 3-bromopyridine oxazoline compound with a structure shown in a formula 7; 3-bromopyridine oxazoline compounds with the structure shown in the formula 7, arylamine, palladium catalyst, organic phosphine ligand, alkali carbonate and organic solvent are mixed for C-N cross coupling reaction to obtain the 3-aryl (acyl) amine pyridine oxazoline chiral ligand with the structural general formula shown in the formula 1. The preparation method provided by the invention prepares the 3-aryl (acyl) amine pyridine oxazoline chiral ligand which can be used for catalyzing asymmetric addition reaction of aryl boric acid to quinolinone and an agricultural pathogenic bacteria bacteriostatic agent simultaneously by sequentially carrying out epoxidation reaction and C-N cross coupling reaction, has simple preparation method and is suitable for industrial production.
Drawings
FIG. 1 is a scheme for the synthesis of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with a structure shown in formula 1-1 provided in example 1 of the present invention;
FIG. 2 is a scheme for the synthesis of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with a structure shown in formula 1-2 provided in example 2 of the present invention;
FIG. 3 is a synthesis scheme of a 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1-3 provided in example 3 of the present invention;
FIG. 4 is a synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-4 provided in example 4 of the present invention;
FIG. 5 is a synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-5 provided in example 5 of the present invention;
FIG. 6 is a scheme showing the synthesis of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1 to 6 provided in example 6 of the present invention;
FIG. 7 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-7 provided in example 7 of the present invention;
FIG. 8 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-8 provided in example 8 of the present invention;
FIG. 9 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-9 provided in example 9 of the present invention;
FIG. 10 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-10 provided in example 10 of the present invention;
FIG. 11 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-11 provided in example 11 of the present invention;
FIG. 12 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1 to 12 provided in example 12 of the present invention;
FIG. 13 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-13 provided in example 13 of the present invention;
FIG. 14 is a scheme showing the synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-14 provided in example 14 of the present invention;
fig. 15 is a synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-15 provided in example 15 of the present invention;
fig. 16 is a synthesis scheme of 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-16 provided in example 16 of the present invention;
FIG. 17 is a schematic diagram of the asymmetric addition reaction of arylboronic acids to quinolinones catalyzed by 3-ar (acyl) aminopyridine oxazoline chiral ligands prepared in example 11 of application example 1 of this invention;
FIG. 18 is a scheme showing the asymmetric addition reaction of arylboronic acids to quinolinones catalyzed by 3-ar (amido) pyridinoxazine type chiral ligands prepared in example 12 of application example 2;
FIG. 19 is a scheme showing the asymmetric addition of arylboronic acids to quinolinones catalyzed by chiral ligands of the 3-ar (acyl) aminopyridine oxazoline class prepared in example 13 of application example 3 of this invention;
FIG. 20 is a scheme showing the asymmetric addition reaction of arylboronic acids to quinolinones catalyzed by 3-ar (amido) pyridinozoline type chiral ligands prepared in example 14 of application example 4 of the present invention;
FIG. 21 is a schematic diagram of the asymmetric addition reaction of arylboronic acids to quinolinones catalyzed by chiral ligands of the 3-ar (acyl) aminopyridine oxazoline class prepared in example 15 of application example 5 of the present invention;
FIG. 22 is a schematic diagram of asymmetric addition reaction of arylboronic acids to quinolinones catalyzed by 3-ar (acyl) amine pyridine oxazoline chiral ligands prepared in example 16 of application example 6 of the present invention.
Detailed Description
The invention provides a 3-aryl (acyl) amine pyridine oxazoline chiral ligand which has a structural general formula shown in a formula 1:
Figure BDA0003892260130000061
n in the formula 1 is 1 or 0;
r in the formula 1 is
Figure BDA0003892260130000071
Figure BDA0003892260130000072
The above-mentioned
Figure BDA0003892260130000073
R in (1) 1 Comprising C 1 ～C 8 Chain hydrocarbon group, phenyl, substituted phenyl, benzyl, substituted benzyl, naphthyl, methoxy formyl, amido, phenyl substituted amido, benzyl substituted amido, hydroxymethyl, carboxyl and C 1 ～C 6 Carboxylic acid hydrocarbyl ester group of (1), C 1 ～C 6 A hydrocarbyl carbonyl, a phenylcarbonyl, a substituted phenylcarbonyl, or a substituted hydroxymethyl;
the described
Figure BDA0003892260130000074
R in (1) 2 Including hydrogen, methyl, ethyl, isopropyl, n-butyl, sec-butyl, isobutyl, cyclohexyl, methoxycarbonyl, hydroxymethyl, C 1 ～C 6 A carboxylic acid alkyl ester group, an aryl group or an aryl methylene group;
r in the formula 1 3 Including hydrogen, halogen, C 1 ～C 6 Alkyl, phenyl, aryl methylene, methoxy, phenoxyAlkyl carbonyl, halogenated methyl, alkoxy methyl, halogen substituted phenyl, C 1 ～C 6 Hydrocarbyl-substituted phenyl, C 1 ～C 6 Alkoxy-substituted phenyl, C 1 ～C 6 A hydrocarbylamino-substituted phenyl group;
ar in the formula 1 comprises phenyl, halogenated phenyl and C 1 ～C 6 Hydrocarbyl-substituted phenyl, C 1 ～C 6 Alkoxy-substituted phenyl, C 1 ～C 6 Hydrocarbylamino-substituted phenyl, C 1 ～C 6 Halogen-substituted hydrocarbyl phenyl, alkylcarbonyl-substituted phenyl, naphthyl, substituted naphthyl, pyridine, substituted pyridine, pyrimidine, substituted pyrimidine, pyrazine, substituted pyrazine, quinoline, substituted quinoline, isoquinoline, substituted isoquinoline, indole, substituted indole, thiazole, substituted thiazole, pyrazole, substituted pyrazole, thiophene, substituted thiophene, furan or substituted furan.
In the present invention, said R 1 C in (1) 1 ～C 6 Carboxylic acid hydrocarbyl ester group of (C) 1 ～C 6 Specifically the number of carbon atoms in the ester group.
In the present invention, said R 1 The substituent on the substituted phenyl group in (1) preferably includes C 1 ～C 6 And (3) one or more of a hydrocarbon group, a hydrocarbon oxy group and a halogenated hydrocarbon group, wherein the number of the substituents on the substituted phenyl group is 1 to 5.
In the present invention, said R 1 Wherein the substituent of the substituted benzyl group is located on the benzene ring, the substituent on the substituted benzyl group preferably includes C 1 ～C 6 And one or more of alkyl, alkoxy and halogenated alkyl, and the number of the substituent is 1 to 5.
In the present invention, said R 1 The substituent of the substituted phenylcarbonyl group in (1) is located on the benzene ring, and the substituent preferably includes C 1 ～C 6 And one or more of alkyl, alkoxy and halogenated alkyl, and the number of the substituent is 1 to 5.
In the present invention, said R 1 Wherein the substituent of the substituted hydroxymethyl group is located on a carbon atom of the hydroxymethyl group, the substituent preferably comprises C 1 ～C 6 One or two of hydrocarbyl, phenyl and substituted phenyl.
In the present invention, said R 3 Preferably hydrogen, methyl, methoxy, fluoro, chloro or trifluoromethyl are included.
In the present invention, the Ar preferably includes:
Figure BDA0003892260130000081
any one of them.
In the present invention, said R 1 Preferably comprising:
Figure BDA0003892260130000082
any one of them.
In the present invention, said R 2 Preferably comprising:
Figure BDA0003892260130000083
any one of them.
In the present invention, the 3-aryl (acyl) amine pyridine oxazoline chiral ligand preferably has any one of the structures shown in formula 1-1 to formula 1-15:
Figure BDA0003892260130000084
Figure BDA0003892260130000091
the invention provides a preparation method of a 3-aryl (acyl) amine pyridine oxazoline chiral ligand, which comprises the following steps:
mixing an amino alcohol compound with a structure shown in a formula 2, a formula 3, a formula 4 or a formula 5, a 3-bromo-2-cyanopyridine compound with a structure shown in a formula 6, an organic zinc catalyst and an organic solvent for cyclization reaction to obtain a 3-bromopyridine oxazoline compound with a structure shown in a formula 7;
Figure BDA0003892260130000092
mixing a 3-bromopyridine oxazoline compound with a structure shown in a formula 7, arylamine, a palladium catalyst, an organic phosphine ligand, alkali metal carbonate and an organic solvent to perform C-N cross coupling reaction to obtain a 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structural general formula shown in a formula 1.
In the present invention, all the preparation starting materials/components are commercially available products well known to those skilled in the art unless otherwise specified.
According to the invention, an aminoalcohol compound with a structure shown in formula 2, formula 3, formula 4 or formula 5, a 3-bromo-2-cyanopyridine compound with a structure shown in formula 6, an organic zinc catalyst and an organic solvent (hereinafter referred to as a first organic solvent) are mixed (hereinafter referred to as a first mixture) for cyclization reaction, so as to obtain a 3-bromopyridine oxazoline compound with a structure shown in formula 7.
In the present invention, the amino alcohol compound having a structure represented by formula 2 is preferably S-2-aminopropanol, S-2-aminobutanol, S-valinol, S-leucinol, S-isoleucinol, S-tert-leucinol, S-phenylglycinol, S-phenylalaninol, 1S, 2R-2-amino-diphenylethanol or R-2-aminobutanol.
In the present invention, the 3-bromo-2-cyanopyridine compound having the structure represented by formula 6 is particularly preferably 3-bromo-2-cyanopyridine.
In the present invention, the molar ratio of the aminoalcohol compound having the structure represented by formula 2, formula 3, formula 4 or formula 5 to the 3-bromo-2-cyanopyridine compound having the structure represented by formula 6 is preferably 3.6.
In the present invention, the organic zinc catalyst is particularly preferably zinc acetate.
In the present invention, the molar ratio of the 3-bromo-2-cyanopyridine compound having the structure represented by formula 6 to the organozinc catalyst is preferably 3.6.
In the present invention, the first organic solvent is particularly preferably chlorobenzene. In the present invention, the amount of the first chiral solvent is not particularly limited, and the cyclization reaction can be smoothly carried out.
In the present invention, said mixing preferably comprises the steps of: dissolving an aminoalcohol compound with a structure shown in a formula 2, a formula 3, a formula 4 or a formula 5 and a 3-bromo-2-cyanopyridine compound with a structure shown in a formula 6 in a first organic solvent to obtain a mixed solution; mixing the mixed solution and the organozinc catalyst at room temperature.
In the present invention, the cyclization reaction is preferably carried out under heating under reflux. The incubation time for the cycloreaction is preferably overnight. The cyclization reaction is preferably carried out under stirring.
In the present invention, a cyclization reaction solution is obtained after the cyclization reaction, and in the present invention, the cyclization reaction solution is preferably subjected to post-treatment to obtain a 3-bromopyridine oxazoline compound having a structure represented by formula 7. In the present invention, the post-treatment preferably comprises the steps of: adding water into the cyclization reaction liquid for quenching, and then extracting by using an organic solvent to obtain an organic extraction phase; and (3) sequentially washing, drying, removing a solvent and purifying by column chromatography to obtain the 3-bromopyridine oxazoline compound with the structure shown in the formula 7. In the present invention, the organic solvent for organic solvent extraction is preferably ethyl acetate; the number of times of the organic solvent extraction is preferably 3; the volume ratio of the organic solvent for organic solvent extraction to the first organic solvent is preferably 10. In the present invention, the washing solvent is preferably a saturated sodium chloride solution; the number of washes is preferably 2; the volume ratio of the washing solvent to the first organic solvent at each washing is preferably 10. In the present invention, the drying agent is preferably anhydrous sodium sulfate. The invention preferably adopts a vacuum distillation mode to remove the solvent. In the present invention, the column chromatography purification is preferably performed by using a silica gel column, and the eluent used in the column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 1.
After obtaining the 3-bromopyridine oxazoline compound with the structure shown in the formula 7, the invention mixes the 3-bromopyridine oxazoline compound with the structure shown in the formula 7, arylamine, palladium catalyst, organic phosphine ligand, alkali carbonate and organic solvent (hereinafter referred to as second organic solvent) for C-N cross coupling reaction (hereinafter referred to as second mixture) to obtain the 3-aryl (acyl) amine pyridine oxazoline chiral ligand with the structural general formula shown in the formula 1.
In the present invention, the arylamine is particularly preferably aniline, 4-fluoroaniline, 3-fluoroaniline, 2-fluoroaniline, 4-methylaniline or 4-methoxyaniline.
In the present invention, the molar ratio of the 3-bromopyridine oxazoline compound having a structure represented by formula 7 to the arylamine is preferably 0.2.
In the present invention, the palladium catalyst is particularly preferably palladium acetate.
In the present invention, the molar ratio of the 3-bromopyridine oxazoline compound having a structure represented by formula 7 to the palladium catalyst is preferably 0.2.
In the present invention, the organophosphine ligand is particularly preferably 5-biphenylphosphine-9, 9-dimethylxanthene (Xantphos).
In the present invention, the molar ratio of the palladium catalyst to the organophosphine ligand is preferably 0.02.
In the present invention, the alkali metal carbonate is specifically cesium carbonate.
In the present invention, the molar ratio of the palladium catalyst to the alkali metal carbonate is preferably 0.02.
In the present invention, the second organic solvent is particularly preferably 1, 4-dioxane. The invention has no special requirement on the dosage of the second organic solvent, and the C-N cross coupling reaction is ensured to be smoothly carried out.
In the present invention, the second mixing preferably comprises the steps of: mixing a 3-bromopyridine oxazoline compound with a structure shown in a formula 9, a formula 10, a formula 11 or a formula 12, an organic phosphine ligand, alkali metal carbonate and arylamine to obtain a mixed raw material; and mixing the mixed raw material and a second organic solvent in a protective gas atmosphere. In the present invention, the protective gas atmosphere is preferably a nitrogen atmosphere.
In the present invention, the temperature of the C-N cross-coupling reaction is preferably 100 ℃. In the present invention, the incubation time for the C-N cross-coupling reaction is preferably 24 hours. In the present invention, the C — N cross-coupling reaction is preferably performed in a protective gas atmosphere, which is preferably a nitrogen atmosphere.
In the invention, a coupling reaction liquid is obtained after the C-N cross coupling reaction is finished, and the invention preferably carries out post-treatment on the coupling reaction liquid to obtain the 3-aryl (acyl) amine pyridine oxazoline chiral ligand. In the present invention, the post-treatment preferably comprises the steps of: cooling the coupling reaction solution to room temperature, and then sequentially carrying out: removing the solvent and purifying by column chromatography to obtain the 3-aryl (acyl) amine pyridine oxazoline chiral ligand. In the present invention, a specific embodiment of the solvent removal is preferably distillation under reduced pressure. The column chromatography purification preferably adopts a silica gel column; the eluent used for the column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 3.
The invention provides the 3-aryl (acyl) amine pyridine oxazoline chiral ligand and the chemically acceptable salt of the pesticide thereof in the technical scheme or the 3-aryl (acyl) amine pyridine oxazoline compound and the chemically acceptable salt of the pesticide thereof prepared by the preparation method in the technical scheme as the application of the bacteriostatic agent for agricultural pathogenic bacteria.
In the present invention, the agricultural pathogenic bacteria preferably include one or more of Rhizoctonia solani (Rhizoctonia solani), rhizoctonia cerealis (Rhizoctonia cerealis), sclerotiella sclerotiorum (Sclerotinia sclerotiorum), fusarium graminearum (Fusarium graminearum), rhizoctonia cerealis (Gaeumannomyces graminis), botrytis cinerea (Botrytis cinerea), phytophthora infestans (Phytophthora infestans), phytophthora capsici (Phytophthora capsici), phytophthora solani (Alternaria solani), rhizoctonia oryzae (Fusarium fujikuroi), phytophthora solani (Fusarium solanum), colletotrichum cucumeri (Coletotrichum lagenarium) and Pyricularia oryzae (Pyricularia oryzae).
The invention provides application of the 3-aryl (acyl) amine pyridine oxazoline chiral ligand or the 3-aryl (acyl) amine pyridine-oxazoline compound prepared by the preparation method in the technical scheme in catalyzing asymmetric addition reaction of aryl boric acid to quinolinone.
In the present invention, the 3-ar (amido) amidopyridine-oxazoline compound is used as a catalyst for the asymmetric addition reaction.
In the present invention, the catalyst for the asymmetric addition reaction preferably further includes a palladium catalyst, more preferably palladium trifluoroacetate.
In the present invention, the molar ratio of the 3-ar (amido) amine pyridine-oxazoline compound to the palladium catalyst is preferably 0.012.
In the present invention, the arylboronic acid is particularly preferably phenylboronic acid.
In the present invention, the molar ratio of the arylboronic acid to the quinolinone is preferably 0.2.
In the present invention, the raw material for the asymmetric addition reaction preferably further includes water; the molar ratio of said water to said quinolinone is preferably 0.15.
In the present invention, the non-para-addition reaction is preferably carried out in an organic solvent, and the organic solvent is particularly preferably anhydrous trifluorotoluene. The invention has no special requirement on the dosage of the anhydrous benzotrifluoride, and the asymmetric addition reaction is ensured to be smoothly carried out.
In the invention, the temperature of the asymmetric addition reaction is preferably 70 ℃, and the holding time of the asymmetric addition reaction is preferably 2h; the non-addition reaction is preferably carried out under stirring. The invention preferably uses TLC tracking to monitor the completion of the unpaired reaction.
In the present invention, the addition reaction liquid is obtained after the completion of the addition reaction, and in the present invention, it is preferable to obtain an addition product by post-treating the addition reaction liquid. In the present invention, the post-treatment preferably comprises the steps of: and (3) carrying out reduced pressure concentration on the addition reaction liquid, and carrying out column chromatography purification on the obtained concentrated solution to obtain the addition product. In the present invention, the eluent used for the column chromatography purification is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is preferably 10.
In order to further illustrate the present invention, the following detailed description of the technical solutions provided by the present invention is made with reference to the accompanying drawings and examples, but they should not be construed as limiting the scope of the present invention.
Example 1
Preparing a 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in a formula 1-1 according to a synthesis scheme shown in a figure 1:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-2-aminopropanol (270mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL of chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring overnight under reflux, quenching the reaction system with water, extracting with ethyl acetate (10 mL multiplied by 3), washing with saturated sodium chloride solution (10 mL multiplied by 2), drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V: eluent) Petroleum ether /V Acetic acid ethyl ester =1: 1) To obtain 3-bromopyridine oxazoline intermediate L1 which is yellow oily and has the yield of 47 percent.
Intermediate L1 (49mg, 0.2mmol), 4, 5-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow oil, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown as a formula 1-1, which is marked as 3L1, and the yield is 54 percent.
3L1 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.39(s,1H),8.09(s,1H),7.60(dd,J＝9.3,3.8Hz,1H),7.44–7.31(m,2H),7.24(dd,J＝8.1,3.7Hz,2H),7.19–7.04(m,2H),4.55–4.48(m,2H),3.99(t,J＝4.8Hz,1H),1.39(t,J＝3.8Hz,3H).
example 2
The 3-aryl (acyl) amine pyridine oxazoline chiral ligands with the structures shown in the formulas 1-2 are prepared according to the synthesis scheme shown in figure 2:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-2-aminobutanol (320mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring overnight under reflux, quenching the reaction system with water, extracting with ethyl acetate (10 mL x 3), washing with saturated sodium chloride solution (10 mL x 2), drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =1: 1) To obtain 3-bromopyridine oxazoline intermediate L2 which is yellow oily and has the yield of 52 percent.
Intermediate L2 (51mg, 0.2mmol), 4, 5-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) The chiral 3-aryl (acyl) amine pyridine oxazoline ligand with the structure shown in the formula 1-2 is recorded as 3L2, and the yield is 46 percent.
3L2 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.53(s,1H),8.11(d,J＝4.1Hz,1H),7.65(dd,J＝8.9,3.2Hz,1H),7.39–7.37(m,2H),7.29–7.23(m,2H),7.21–7.08(m,2H),4.54(t,J＝8.3Hz,1H),4.42–4.35(m,1H),4.09(t,J＝6.9Hz,1H),1.84–1.63(m,2H),1.06(t,J＝8.1Hz,3H).
example 3
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-3 according to a synthesis scheme shown in figure 3:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-valinol (371mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL of chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring overnight under reflux, quenching the reaction system with water, extracting with ethyl acetate (10 mL. Times.3), and adding saturated sodium chloride solution (10 mL. Times.3)mL × 2), dried over anhydrous sodium sulfate, evaporated under reduced pressure to remove the solvent, and subjected to silica gel column chromatography (eluent: v Petroleum ether /V Acetic acid ethyl ester =1: 1) To obtain 3-bromopyridine oxazoline intermediate L3 which is yellow oily and has the yield of 55 percent.
Intermediate L3 (54mg, 0.2mmol), 4, 5-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL of 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating solvent under reduced pressure, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow oil, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in a formula 1-3, which is marked as 3L3, and the yield is 63 percent.
3L3 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.58(s,1H),8.06(s,1H),7.62(d,J＝5.6Hz,1H),7.38–7.27(m,2H),7.23–6.99(m,4H),4.45(t,J＝6.8Hz,1H),4.19–4.09(m,2H),1.79(m,1H),1.03(t,J＝3.6Hz,3H),0.94(t,J＝3.6Hz,3H).
example 4
3-aryl (acyl) amine pyridine oxazoline chiral ligands of the structures shown in formulas 1-4 were prepared according to the synthetic scheme shown in FIG. 4:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-leucinol (421mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL of chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring overnight under reflux, quenching the reaction system with water, extracting with ethyl acetate (10 mL x 3), washing with saturated sodium chloride solution (10 mL x 2), drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =1: 1) To obtain 3-bromopyridine oxazoline intermediate L4 which is yellow oily and has the yield of 62 percent.
Intermediate L4 (57mg, 0.2mmol), 4, 5-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, and N was 2 Replacement ofAdding 1mL of 1, 4-dioxane for reaction at 100 deg.C for 24h, cooling to room temperature, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow oil, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1 to 4, which is marked as 3L4, and the yield is 65 percent.
3L4 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.49(s,1H),8.06(s,1H),7.72–7.54(m,1H),7.35–7.31(m,2H),7.20(dd,J＝7.4,4.3Hz,2H),7.16–7.04(m,2H),4.60–4.38(m,2H),4.00–3.96(m,1H),1.86–1.80(m,1H),1.73–1.59(m,1H),1.46–1.40(m,1H),0.97(d,J＝4.4Hz,6H).
example 5
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-5 according to a synthesis scheme shown in figure 5:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-isoleucinol (421mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL of chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring under reflux overnight, quenching the reaction system with water, extracting with ethyl acetate (10 mL x 3), washing with saturated sodium chloride solution (10 mL x 2), drying with anhydrous sodium sulfate, evaporating under reduced pressure to remove solvent, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Acetic acid ethyl ester =1: 1) To obtain 3-bromopyridine oxazoline intermediate L5 which is yellow oily and has the yield of 62 percent.
Intermediate L5 (57mg, 0.2mmol), 4, 5-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, and N was 2 Replacing for three times, adding 1mL of 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating solvent under reduced pressure, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow oil, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1 to 5, which is marked as 3L5, and the yield is 75 percent.
3L5 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.60(s,1H),8.12(d,J＝4.5Hz,1H),7.67(d,J＝7.4Hz,1H),7.41–7.37(m,2H),7.25(d,J＝7.9Hz,2H),7.21–7.11(m,2H),4.49(t,J＝8.3Hz,1H),4.35–4.30(m,1H),4.17(t,J＝8.1Hz,1H),1.72–1.69(m,2H),1.35–1.26(m,1H),0.99(t,J＝7.3Hz,3H),0.94(t,J＝5.5Hz,3H).
13 C NMR(126MHz,Chloroform-d)δ163.5,142.9,140.3,138.6,129.6,128.8,125.9,123.7,122.0,120.3,71.7,69.3,39.5,26.1,15.0,11.4.
example 6
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-6 according to a synthesis scheme shown in figure 6:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-tert-leucinol (421mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL of chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring under reflux overnight, quenching the reaction system with water, extracting with ethyl acetate (10 mL x 3), washing with saturated sodium chloride solution (10 mL x 2), drying with anhydrous sodium sulfate, evaporating under reduced pressure to remove solvent, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =1: 1) To obtain 3-bromopyridine oxazoline intermediate L6, yellow solid with yield of 58%.
Intermediate L6 (57mg, 0.2mmol), 4, 5-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, and N was 2 Replacing for three times, adding 1mL of 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating solvent under reduced pressure, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) The obtained yellow solid, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in a formula 1-6 is recorded as 3L6, and the yield is 72 percent.
3L6 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d):δ10.67(s,1H),8.10(dd,J＝4.3,1.4Hz,1H),7.68(dd,J＝8.6,1.4Hz,1H),7.38-7.35(m,2H),7.22(d,J＝7.3Hz,1H),7.18(dd,J＝8.7,4.4Hz,1H),7.12-7.08(m,1H),4.41(dd,J＝9.8,8.4Hz,1H),4.28-4.19(m,2H),0.98(s,9H).
13 C NMR(126MHz,Chloroform-d):δ163.6,142.9,140.4,138.6,129.6,128.8,126.0,123.6,121.8,120.4,76.5,67.7,34.0,26.0.
example 7
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-7 according to a synthesis scheme shown in figure 7:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-phenylglycinol (493mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL of chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring overnight under reflux, quenching the reaction system with water, extracting with ethyl acetate (10 mL x 3), washing with saturated sodium chloride solution (10 mL x 2), drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =1: 1) To obtain 3-bromopyridine oxazoline intermediate L7 which is yellow oily and has the yield of 64 percent.
Intermediate L7 (60mg, 0.2mmol), 4, 5-biphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) The chiral 3-aryl (acyl) amine pyridine oxazoline ligand with the structure shown in the formula 1-7 is recorded as 3L7, and the yield is 58 percent.
3L7 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.42(s,1H),8.12(s,1H),7.62(dd,J＝9.1,3.4Hz,1H),7.40–7.26(m,7H),7.21–7.16(m,3H),7.11–7.07(m,1H),5.66–5.47(m,1H),4.82(t,J＝8.7Hz,1H),4.27(dd,J＝8.7,6.4Hz,1H).
example 8
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-8 according to a synthesis scheme shown in figure 8:
intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and S-phenylalaninol (544mg, 3.6mmol) were weighed into a clean dry pear-shaped bottle to whichDissolving in 6mL chlorobenzene, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring under reflux overnight, quenching the reaction system with water, extracting with ethyl acetate (10 mL × 3), washing with saturated sodium chloride solution (10 mL × 2), drying with anhydrous sodium sulfate, evaporating under reduced pressure to remove solvent, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Acetic acid ethyl ester =1: 1) To obtain 3-bromopyridine oxazoline intermediate L8 which is yellow oily and has the yield of 68 percent.
Intermediate L8 (64mg, 0.2mmol), 4, 5-biphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow oil, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1 to 8, which is marked as 3L8, and the yield is 64 percent.
3L8 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.43(s,1H),8.08(s,1H),7.65–7.63(m,1H),7.33(d,J＝8.4Hz,2H),7.28–7.23(m,5H),7.19–7.16(m,3H),7.11–7.08(m,1H),4.67(t,J＝8.4Hz,1H),4.45(t,J＝7.8Hz,1H),4.19-4.15(m,1H),3.08(dd,J＝12.1,4.9Hz,1H),2.85(dd,J＝12.9,5.0Hz,1H).
example 9
3-aryl (acyl) amine pyridine oxazoline chiral ligands of the structures shown in formulas 1-9 were prepared according to the synthetic scheme shown in FIG. 9:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and 1S, 2R-2-amino-diphenylethanol (767mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring overnight under reflux, quenching the reaction system with water, extracting with ethyl acetate (10 mL x 3), washing with saturated sodium chloride solution (10 mL x 2), drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =1: 1) To obtain 3-bromopyridine oxazoline intermediate L9 which is yellow oil with the yield of 43％。
Intermediate L9 (76mg, 0.2mmol), 4, 5-diphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Acetic acid ethyl ester =3: 1) The chiral 3-aryl (acyl) amine pyridine oxazoline ligand with the structure shown in the formula 1-9 is recorded as 3L9, and the yield is 72 percent.
3L9 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ10.47(s,1H),8.16(s,1H),7.72–7.62(m,1H),7.42–7.29(m,12H),7.26–7.19(m,3H),7.16–7.08(m,1H),5.40(d,J＝3.6Hz,2H).
example 10
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-10 according to a synthesis scheme shown in figure 10:
weighing intermediate 3-bromo-2-cyanopyridine (550mg, 3mmol) and R-2-aminobutanol (320mg, 3.6 mmol) in a clean and dry pear-shaped bottle, adding 6mL chlorobenzene to dissolve, adding zinc acetate (110mg, 0.6 mmol) at room temperature, stirring overnight under reflux, quenching the reaction system with water, extracting with ethyl acetate (10 mL x 3), washing with saturated sodium chloride solution (10 mL x 2), drying with anhydrous sodium sulfate, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =1: 1) To obtain 3-bromopyridine oxazoline intermediate L10 which is yellow oily and has the yield of 55 percent.
Intermediate L10 (51mg, 0.2mmol), 4, 5-biphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and aniline (28mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow oily 3-aryl (acyl) amine pyridine-oxazole shown in formula 1-10The yield of the oxazoline chiral ligand is 56 percent and is recorded as 3L 10.
3L10 Nuclear magnetic data: 1 H NMR(500MHz,Chloroform-d)δ13.07(s,1H),9.31(d,J＝6.7Hz,1H),8.42(s,1H),8.15–7.99(m,2H),7.64–7.37(m,4H),4.59(t,J＝9.1Hz,1H),4.50–4.43(m,1H),4.14–4.10(m,1H),1.83–1.69(m,2H),1.07(t,J＝9.0Hz,3H).
13 C NMR(101MHz,Chloroform-d)δ163.9,143.6,138.20134.7,132.3,131.8,128.8,127.9,127.6,126.6,71.8,68.5,29.0,10.6.
example 11
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-11 according to a synthesis scheme shown in figure 11:
intermediate L6 prepared in example 6 (56mg, 0.2mmol), 4, 5-biphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and 4-fluoroaniline (33mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL of 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating solvent under reduced pressure, performing silica gel column chromatography (eluent: V) Petroleum ether /V Acetic acid ethyl ester =3: 1) To obtain yellow solid, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1-11, which is marked as 3L11, and the yield is 72 percent.
3L11 Nuclear magnetic data: 1 H NMR(400MHz,CDCl 3 )δ10.55(s,1H),8.07(dd,J＝4.4,1.4Hz,1H),7.48(dd,J＝8.7,1.5Hz,1H),7.36–7.29(m,1H),7.21–7.10(m,3H),7.05(t,J＝8.6Hz,2H),4.39(dd,J＝9.8,8.3Hz,1H),4.29–4.14(m,2H),0.96(s,9H).
13 C NMR(126MHz,CDCl 3 )δ162.6,159.5(d,J＝242.7Hz),156.5,145.7,138.4,136.0(d,J＝2.6Hz),123.8(d,J＝8.0Hz),116.3(d,J＝22.5Hz),115.4,109.2,76.5,69.3,34.1,26.0.
example 12
3-aryl (acyl) amine pyridine oxazoline chiral ligands of the structures shown in formulas 1-12 were prepared according to the synthetic scheme shown in FIG. 12:
intermediate L6 (56mg, 0.2mmol) prepared in example 6, 4, 5-bis was weighedPhenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and 3-fluoroaniline (33mg, 0.3mmol) in a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) The chiral 3-aryl (acyl) amine pyridine oxazoline ligand with the structure shown in the formula 1-12 is recorded as 3L12, and the yield is 66 percent.
3L12 Nuclear magnetic data: 1 H NMR(500MHz,CDCl 3 )δ10.83(s,1H),8.15(dd,J＝4.3,1.5Hz,1H),7.74(dd,J＝8.6,1.4Hz,1H),7.29(td,J＝8.3,6.6Hz,1H),7.22(dd,J＝8.6,4.3Hz,1H),7.01–6.91(m,2H),6.76(dd,J＝8.3,2.4Hz,1H),4.42(dd,J＝10.0,8.4Hz,1H),4.30–4.17(m,2H),0.98(s,7H).
13 C NMR(126MHz,Chloroform-d)δ163.7(d,J＝245.8Hz),163.5,142.4(d,J＝10.1Hz),142.1,139.3,130.7(d,J＝9.8Hz),129.4,125.96,120.9,116.5(d,J＝2.9Hz),109.9(d,J＝21.3Hz),107.7(d,J＝23.7Hz),76.4,67.8,33.9,26.0.
example 13
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-13 according to a synthesis scheme shown in figure 13:
intermediate L6 (56mg, 0.2mmol) prepared in example 6, 4, 5-bisphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and 2-fluoroaniline (33mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL of 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating solvent under reduced pressure, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow solid, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1-13, which is marked as 3L13, and the yield is 72 percent.
3L13 Nuclear magnetic data: 1 H NMR(400MHz,CDCl 3 )δ10.69(s,1H),8.11(dd,J＝4.4,1.4Hz,1H),7.56-7.53(m,1H),7.41-7.37(m,1H),7.19-6.98(m,4H),4.39(dd,J＝9.3,7.7Hz,1H),4.26–4.17(m,2H),0.95(s,9H).
13 C NMR(101MHz,CDCl 3 )δ163.5,155.5(d,J＝245.9Hz),142.2,139.0,129.4,128.5(d,J＝11.8Hz),125.8,124.3(d,J＝3.8Hz),124.1(d,J＝7.4Hz),122.2(d,J＝1.8Hz),120.4(d,J＝1.2Hz),116.3(d,J＝19.6Hz),76.4,67.8,33.9,25.9.
example 14
3-aryl (acyl) amine pyridine oxazoline chiral ligands of the structures shown in formulas 1-14 were prepared according to the synthetic scheme shown in FIG. 14:
intermediate L6 (56mg, 0.2mmol) prepared in example 6, 4, 5-biphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and 4-methylaniline (32mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Acetic acid ethyl ester =3: 1) Obtaining yellow solid, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in a formula 1-14, and recording as 3L14, wherein the yield is 46%.
3L14 Nuclear magnetic data: 1 H NMR(500MHz,CDCl 3 )δ10.35(s,1H),8.03(dd,J＝4.4,1.4Hz,1H),7.40(dd,J＝8.6,1.4Hz,1H),7.20–7.07(m,3H),6.96–6.84(m,2H),4.39(dd,J＝9.9,8.5Hz,1H),4.28–4.14(m,2H),2.34(s,3H),0.95(s,9H).
13 C NMR(126MHz,CDCl 3 )δ163.7,156.7,144.4,137.9,133.1,128.0,126.0,119.7,114.9,76.5,67.7,55.6,34.0,26.0.
example 15
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-15 according to a synthesis scheme shown in figure 15:
intermediate L6 (56mg, 0.2mmol) prepared in example 6, 4, 5-bisphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and 4-methoxyaniline (37mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Displacing three times, adding 1mL of 1, 4-dioxane, strip at 100 ℃Reacting for 24h, cooling to room temperature, evaporating the solvent under reduced pressure, and performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow oil, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1 to 15, which is marked as 3L15, and the yield is 46 percent.
3L15 Nuclear magnetic data: 1 H NMR(500MHz,CDCl 3 )δ10.53(s,1H),8.05(dd,J＝4.3,1.4Hz,1H),7.57(dd,J＝8.6,1.4Hz,1H),7.17–7.10(m,5H),4.40–4.37(m,1H),4.26–4.17(m,2H),3.81(s,3H),0.96(s,9H).
13 C NMR(126MHz,CDCl 3 )δ163.6,143.5,138.2,137.6,133.5,130.2,128.4,126.0,122.4,120.1,76.5,67.7,33.9,26.0,20.9.
example 16
Preparing 3-aryl (acyl) amine pyridine oxazoline chiral ligands with structures shown in formulas 1-16 according to a synthesis scheme shown in figure 16:
intermediate L6 (56mg, 0.2mmol) prepared in example 6, 4, 5-bisphenylphosphine-9, 9-dimethylxanthene (Xantphos) (14mg, 0.024mmol), palladium acetate (4.5mg, 0.02mmol), cesium carbonate (130mg, 0.4mmol) and 4-chloroaniline (38mg, 0.3mmol) were weighed into a Schlenk reaction flask, N 2 Replacing for three times, adding 1mL 1, 4-dioxane, reacting at 100 deg.C for 24h, cooling to room temperature, evaporating under reduced pressure to remove solvent, performing silica gel column chromatography (eluent: V) Petroleum ether /V Ethyl acetate =3: 1) To obtain yellow solid, namely 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structure shown in formulas 1 to 16, which is marked as 3L16, and the yield is 48 percent.
3L16 Nuclear magnetic data: 1 H NMR(500MHz,CDCl 3 )δ10.25(s,1H),7.92(dd,J＝4.3,1.4Hz,1H),7.54(dd,J＝8.6,1.4Hz,1H),7.31–7.25(m,2H),7.19(dd,J＝8.6,4.3Hz,1H),7.16–7.09(m,2H),4.00–3.90(m,2H),3.71–3.64(m,1H),1.03(s,9H).
13 C NMR(126MHz,CDCl 3 )δ169.1,143.6,138.8,137.6,130.7,129.6,128.8,127.3,123.5,121.8,63.6,60.1,33.8,27.2,27.1.
application example 1
FIG. 17 is a scheme showing the asymmetric addition reaction of arylboronic acids to quinolinones using the 3-ar (acyl) amine pyridine oxazoline chiral ligands prepared in example 11:
palladium trifluoroacetate (1.7 mg, 0.005mmol), 3L11 (3.7 mg, 0.012mmol) and 0.5mL of anhydrous trifluorotoluene were put into a 10mL reaction flask and stirred at 70 ℃ for 2 hours. Phenylboronic acid (22.4 mg, 0.2mmol), water (27. Mu.L, 0.15 mmol), quinolinone (28mg, 0.1mmol) and 0.5mL of anhydrous benzotrifluoride were then added. TLC followed the completion of the reaction, concentrated under reduced pressure, and chromatographed (V petroleum ether: V ethyl acetate = 10) to give a white solid, i.e. an addition product, in 95% yield and 93% ee, which was significantly improved compared to the literature reported addition products of pyridine oxazoline ligand (50% yield and 80% ee). (BrianM. Stoltz, palladium-catalysis A systematic Conjugate additive acidic Acids to Heterocyclic receptors, chem. Eur. J.2013,19, 74-77).
Nuclear magnetic data of addition product: 1 H NMR(400MHz,Chloroform-d)δ7.95(dd,J＝7.8,1.7Hz,1H),7.87(d,J＝8.4Hz,1H),7.55–7.35(m,5H),7.31–7.17(m,5H),7.20–7.09(m,1H),6.30(dd,J＝4.8,3.2Hz,1H),5.52–5.30(m,2H),3.39–3.34(m,2H).
13 C NMR(101MHz,Chloroform-d)δ192.8,154.4,141.6,138.2,135.7,134.7,128.8,128.7,128.6,128.3,127.7,127.0,126.7,125.1,124.5,124.3,68.6,56.2,42.4.
application example 2
FIG. 18 is a schematic diagram showing the asymmetric addition of arylboronic acids to quinolinones catalyzed by a 3-aryl (acyl) amine pyridine oxazoline chiral ligand prepared in example 12:
palladium trifluoroacetate (1.7 mg, 0.005mmol), 3L12 (3.7 mg, 0.012mmol) and 0.5mL of anhydrous trifluorotoluene were put into a 10mL reaction flask and stirred at 70 ℃ for 2 hours. Phenylboronic acid (22.4 mg, 0.2mmol), water (27. Mu.L, 0.15 mmol), quinolinone (28mg, 0.1mmol) and 0.5mL of anhydrous trifluorotoluene were then added. TLC followed by monitoring the completion of the reaction, concentration under reduced pressure, column chromatography (V petroleum ether: V ethyl acetate = 10).
Nuclear magnetic data of addition product: 1 H NMR(400MHz,Chloroform-d)δ7.95(dd,J＝7.8,1.7Hz,1H),7.87(d,J＝8.4Hz,1H),7.55–7.35(m,5H),7.31–7.17(m,5H),7.20–7.09(m,1H),6.30(dd,J＝4.8,3.2Hz,1H),5.52–5.30(m,2H),3.39–3.34(m,2H).
13 C NMR(101MHz,Chloroform-d)δ192.8,154.4,141.6,138.2,135.7,134.7,128.8,128.7,128.6,128.3,127.7,127.0,126.7,125.1,124.5,124.3,68.6,56.2,42.4.
application example 3
FIG. 19 is a schematic diagram showing the asymmetric addition of arylboronic acids to quinolinones catalyzed by a 3-aryl (acyl) amine pyridine oxazoline chiral ligand prepared in example 13:
palladium trifluoroacetate (1.7 mg, 0.005mmol), 3L13 (3.7 mg, 0.012mmol) and 0.5mL of anhydrous trifluorotoluene were put into a 10mL reaction flask and stirred at 70 ℃ for 2 hours. Phenylboronic acid (22.4 mg, 0.2mmol), water (27. Mu.L, 0.15 mmol), quinolinone (28mg, 0.1mmol) and 0.5mL of anhydrous trifluorotoluene were then added. TLC followed by monitoring the completion of the reaction, concentration under reduced pressure, column chromatography (V petroleum ether: V ethyl acetate = 10).
Nuclear magnetic data of addition product: 1 H NMR(400MHz,Chloroform-d)δ7.95(dd,J＝7.8,1.7Hz,1H),7.87(d,J＝8.4Hz,1H),7.55–7.35(m,5H),7.31–7.17(m,5H),7.20–7.09(m,1H),6.30(dd,J＝4.8,3.2Hz,1H),5.52–5.30(m,2H),3.39–3.34(m,2H).
13 C NMR(101MHz,Chloroform-d)δ192.8,154.4,141.6,138.2,135.7,134.7,128.8,128.7,128.6,128.3,127.7,127.0,126.7,125.1,124.5,124.3,68.6,56.2,42.4.
application example 4
FIG. 20 is a scheme showing the asymmetric addition reaction of arylboronic acids to quinolinones using the 3-ar (acyl) amine pyridine oxazoline chiral ligands prepared in example 14:
palladium trifluoroacetate (1.7mg, 0.005mmol), 3L14 (3.7mg, 0.012mmol) and 0.5mL of anhydrous trifluorotoluene were put into a 10mL reaction flask and stirred at 70 ℃ for 2 hours. Phenylboronic acid (22.4 mg, 0.2mmol), water (27. Mu.L, 0.15 mmol), quinolinone (28mg, 0.1mmol) and 0.5mL of anhydrous benzotrifluoride were then added. TLC followed by monitoring the completion of the reaction, concentration under reduced pressure, column chromatography (V petroleum ether: V ethyl acetate = 10).
Nuclear magnetic data of addition product: 1 H NMR(400MHz,Chloroform-d)δ7.95(dd,J＝7.8,1.7Hz,1H),7.87(d,J＝8.4Hz,1H),7.55–7.35(m,5H),7.31–7.17(m,5H),7.20–7.09(m,1H),6.30(dd,J＝4.8,3.2Hz,1H),5.52–5.30(m,2H),3.39–3.34(m,2H).
13 C NMR(101MHz,Chloroform-d)δ192.8,154.4,141.6,138.2,135.7,134.7,128.8,128.7,128.6,128.3,127.7,127.0,126.7,125.1,124.5,124.3,68.6,56.2,42.4.
application example 5
FIG. 21 is a schematic diagram showing the asymmetric addition of arylboronic acids to quinolinones catalyzed by a 3-aryl (acyl) amine pyridine oxazoline chiral ligand prepared in example 15:
palladium trifluoroacetate (1.7mg, 0.005mmol), 3L15 (3.9mg, 0.012mmol) and 0.5mL of anhydrous trifluorotoluene were added to a 10mL reaction flask and stirred at 70 ℃ for 2 hours. Phenylboronic acid (22.4 mg, 0.2mmol), water (27. Mu.L, 0.15 mmol), quinolinone (28mg, 0.1mmol) and 0.5mL of anhydrous benzotrifluoride were then added. TLC followed by monitoring the completion of the reaction, concentration under reduced pressure, column chromatography (V petroleum ether: V ethyl acetate = 10) gave a white solid, i.e. the addition product, in 31% yield and 92% ee value.
Nuclear magnetic data of addition product: 1 H NMR(400MHz,Chloroform-d)δ7.95(dd,J＝7.8,1.7Hz,1H),7.87(d,J＝8.4Hz,1H),7.55–7.35(m,5H),7.31–7.17(m,5H),7.20–7.09(m,1H),6.30(dd,J＝4.8,3.2Hz,1H),5.52–5.30(m,2H),3.39–3.34(m,2H).
13 C NMR(101MHz,Chloroform-d)δ192.8,154.4,141.6,138.2,135.7,134.7,128.8,128.7,128.6,128.3,127.7,127.0,126.7,125.1,124.5,124.3,68.6,56.2,42.4.
application example 6
FIG. 22 is a schematic diagram showing the asymmetric addition of arylboronic acids to quinolinones catalyzed by a 3-aryl (acyl) amine pyridine oxazoline chiral ligand prepared in example 16:
palladium trifluoroacetate (1.7 mg, 0.005mmol), 3L16 (3.9mg, 0.012mmol) and 0.5mL anhydrous trifluorotoluene were added to a 10mL reaction flask, and the mixture was stirred at 70 ℃ for 2 hours. Phenylboronic acid (22.4 mg, 0.2mmol), water (27. Mu.L, 0.15 mmol), quinolinone (28mg, 0.1mmol) and 0.5mL of anhydrous trifluorotoluene were then added. TLC followed by monitoring the completion of the reaction, concentration under reduced pressure, column chromatography (V petroleum ether: V ethyl acetate =10 = 1) gave a white solid, i.e. the addition product, in 78% yield and 82% ee value.
Nuclear magnetic data of addition product: 1 H NMR(400MHz,Chloroform-d)δ7.95(dd,J＝7.8,1.7Hz,1H),7.87(d,J＝8.4Hz,1H),7.55–7.35(m,5H),7.31–7.17(m,5H),7.20–7.09(m,1H),6.30(dd,J＝4.8,3.2Hz,1H),5.52–5.30(m,2H),3.39–3.34(m,2H).
13 C NMR(101MHz,Chloroform-d)δ192.8,154.4,141.6,138.2,135.7,134.7,128.8,128.7,128.6,128.3,127.7,127.0,126.7,125.1,124.5,124.3,68.6,56.2,42.4.
application example 7
The in vitro antibacterial activity evaluation is carried out by adopting a plate hypha growth rate inhibition method, and test strains are selected to be activated on a PDA plate, wherein the test strains comprise rice sheath blight bacteria (Rhizoctonia solani), wheat sheath blight bacteria (Rhizoctonia cerealis), sclerotinia sclerotiorum (Sclerotinia sclerotiorum), wheat gibberellic disease bacteria (Fusarium graminearum), wheat holothurian bacteria (Gaeumanomyces graminis), tomato Botrytis cinerea (Botrytis cinerea), potato late blight bacteria (Phytophthora infestans), phytophthora capsici (Phytophthora capsici), tomato early blight bacteria (Alternaria solani), rice bakanae bacteria (Fusarium fujikurourea), potato stem rot bacteria (Fusarium sulurerum), anthracnose (Colletotrichium cucumarium) and rice blast (Pyricularia oryzae). Preparing a compound into a series of PDA (personal digital assistant) medicine-containing plates with gradient concentration, preparing a test strain into a fungus cake with the diameter of 5mm, placing the fungus cake in the center of a medicine-containing culture dish, culturing at the constant temperature of 25 ℃ until the test strain in a blank control dish grows to be close to the edge of the culture dish, measuring the colony diameter of each medicine-containing plate by using a cross method, calculating the inhibition rate of the compound on hypha growth, and calculating the inhibition rate of the compound on diseases according to a formula shown in a formula I:
Figure BDA0003892260130000231
boscalid (Boscalid) was used as a positive control in the experiment.
The results of the test of the bacteriostatic activity of the 3-aryl (acyl) amine pyridine oxazoline compounds on two agricultural fungi are shown in the table 1.
TABLE 13 bacteriostatic Activity of Arylamidopyridin oxazolines (EC) against two fungi 50 )
Figure BDA0003892260130000232
It can be seen from table 1 that the 3-aryl (amido) aminopyridine oxazoline compounds exhibit moderate to excellent bacteriostatic activity against the two tested pathogenic bacteria. The substituent on oxazoline has certain influence on the bacteriostatic activity, and when the oxazoline substituent is S-benzyl, the substituent has EC on Rhizoctonia solani and Sclerotinia sclerotiorum 50 Respectively 4.98 mu M and 5.23 mu M, and shows certain inhibiting effect on two agricultural fungi.
Similar to the compound 3L16, the 3-aryl (acyl) amine pyridine oxazoline compound with other structures (formula 1-15) provided by the invention also has a multifunctional ligand molecule with chemical catalytic activity and biological pharmacological activity, not only has better bacteriostatic activity on various agricultural pathogenic bacteria, but also can be used for catalyzing asymmetric synthesis reaction and ligand molecule. Has important significance for the research field of biology and chemistry.
Although the present invention has been described in detail with reference to the above embodiments, it is only a part of the embodiments of the present invention, not all of the embodiments, and other embodiments can be obtained without inventive step according to the embodiments, and all of the embodiments belong to the protection scope of the present invention.

Claims (10)

1. A3-aryl (acyl) amine pyridine oxazoline chiral ligand is characterized by having a structural general formula shown in a formula 1:
Figure FDA0003892260120000011
n in the formula 1 is 1 or 0;
r in the formula 1 is
Figure FDA0003892260120000012
Figure FDA0003892260120000013
The above-mentioned
Figure FDA0003892260120000014
R in (1) 1 Comprising C 1 ～C 8 Chain hydrocarbon group, phenyl, substituted phenyl, benzyl, substituted benzyl, naphthyl, methoxy formyl, amido, phenyl substituted amido, benzyl substituted amido, hydroxymethyl, carboxyl and C 1 ～C 6 Carboxylic acid hydrocarbyl ester group of (C) 1 ～C 6 A hydrocarbyl carbonyl, a phenylcarbonyl, a substituted phenylcarbonyl, or a substituted hydroxymethyl;
the above-mentioned
Figure FDA0003892260120000015
R in (1) 2 Including hydrogen, methyl, ethyl, isopropyl, n-butyl, sec-butyl, isobutyl, cyclohexyl, methoxycarbonyl, hydroxymethyl, C 1 ～C 6 A carboxylic acid alkyl ester group, an aryl group or an aryl methylene group;
r in the formula 1 3 Including hydrogen, halogen, C 1 ～C 6 Alkyl, phenyl, arylmethylene, methoxy, phenoxy, alkylcarbonyl, halomethyl, alkoxymethyl, halogen-substituted phenyl, C 1 ～C 6 Hydrocarbyl-substituted phenyl, C 1 ～C 6 Alkoxy-substituted phenyl, C 1 ～C 6 A hydrocarbylamino-substituted phenyl group;
ar in the formula 1 comprisesPhenyl, halophenyl, C 1 ～C 6 Hydrocarbyl-substituted phenyl, C 1 ～C 6 Alkoxy-substituted phenyl, C 1 ～C 6 Hydrocarbylamino-substituted phenyl, C 1 ～C 6 Halogen-substituted hydrocarbyl phenyl, alkylcarbonyl-substituted phenyl, naphthyl, substituted naphthyl, pyridine, substituted pyridine, pyrimidine, substituted pyrimidine, pyrazine, substituted pyrazine, quinoline, substituted quinoline, isoquinoline, substituted isoquinoline, indole, substituted indole, thiazole, substituted thiazole, pyrazole, substituted pyrazole, thiophene, substituted thiophene, furan or substituted furan.
2. The 3-aryl (acyl) amine pyridine oxazoline chiral ligand as recited in claim 1, wherein R is 1 Wherein the substituent on the substituted phenyl group includes C 1 ～C 6 One or more of the alkyl, alkoxy and halogenated alkyl, wherein the number of the substituent groups on the substituted phenyl is 1-5;
the R is 1 Wherein the substituent of the substituted benzyl group is located on the benzene ring, and the substituent of the substituted benzyl group comprises C 1 ～C 6 One or more of alkyl, alkoxy and halogenated alkyl, and the number of the substituent is 1 to 5;
said R is 1 Wherein the substituent of the substituted phenylcarbonyl group is on the benzene ring and includes C 1 ～C 6 One or more of alkyl, alkoxy and halogenated alkyl, and the number of the substituent is 1 to 5;
said R is 1 Wherein the substituent of the substituted hydroxymethyl group is located on a carbon atom of the hydroxymethyl group, and the substituent includes C 1 ～C 6 One or two of hydrocarbyl, phenyl and substituted phenyl.
3. The 3-aryl (acyl) amine pyridine oxazoline chiral ligand as recited in claim 1, wherein R is 3 Including hydrogen, methyl, methoxy, fluoro, chloro or trifluoromethyl.
4. The 3-Ar (acyl) amine pyridine oxazoline-based chiral ligand of claim 1, wherein the Ar comprises:
Figure FDA0003892260120000021
any one of them.
5. 3-aryl (amido) pyridinooxazoline chiral ligands of claim 1 or 2, wherein R is 1 The method comprises the following steps:
Figure FDA0003892260120000022
any one of them.
6. A chiral 3-ar (acyl) amine pyridinoxazoline ligand as claimed in claim 1, wherein R is 2 The method comprises the following steps:
Figure FDA0003892260120000031
any one of them.
7. The 3-aryl (acyl) amine pyridine oxazoline chiral ligand as claimed in any one of claims 1 to 6, which is characterized by having any one of the structures shown in the formulas 1 to 15:
Figure FDA0003892260120000032
8. the method for preparing a 3-aryl (acyl) amine pyridine oxazoline chiral ligand of any one of claims 1 to 7, which is characterized by comprising the following steps:
mixing an amino alcohol compound with a structure shown in a formula 2, a formula 3, a formula 4 or a formula 5, a 3-bromo-2-cyanopyridine compound with a structure shown in a formula 6, an organic zinc catalyst and an organic solvent for cyclization reaction to obtain a 3-bromopyridine oxazoline compound with a structure shown in a formula 7;
Figure FDA0003892260120000033
Figure FDA0003892260120000041
mixing a 3-bromopyridine oxazoline compound with a structure shown in a formula 7, arylamine, a palladium catalyst, an organic phosphine ligand, alkali metal carbonate and an organic solvent to perform C-N cross coupling reaction to obtain a 3-aryl (acyl) amine pyridine oxazoline chiral ligand with a structural general formula shown in a formula 1.
9. The use of the 3-aryl (acyl) amine pyridine oxazoline chiral ligand and the salt thereof acceptable in pesticide chemistry of any one of claims 1 to 7 or the 3-aryl (acyl) amine pyridine oxazoline compound and the salt thereof acceptable in pesticide chemistry prepared by the preparation method of claim 8 as bacteriostatic agents for agricultural pathogenic bacteria.
10. The use of a 3-aryl (acyl) amine pyridine oxazoline chiral ligand as defined in any one of claims 1 to 7 or a 3-aryl (acyl) amine pyridine-oxazoline compound prepared by the preparation method as defined in claim 8 in catalyzing the asymmetric addition reaction of aryl boronic acid to quinolinone.
CN202211263878.5A 2022-10-17 2022-10-17 3-arylamine (acylamino) pyridine oxazoline chiral ligand and preparation and application thereof Pending CN115611878A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202211263878.5A CN115611878A (en) 2022-10-17 2022-10-17 3-arylamine (acylamino) pyridine oxazoline chiral ligand and preparation and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202211263878.5A CN115611878A (en) 2022-10-17 2022-10-17 3-arylamine (acylamino) pyridine oxazoline chiral ligand and preparation and application thereof

Publications (1)

Publication Number Publication Date
CN115611878A true CN115611878A (en) 2023-01-17

Family

ID=84863525

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202211263878.5A Pending CN115611878A (en) 2022-10-17 2022-10-17 3-arylamine (acylamino) pyridine oxazoline chiral ligand and preparation and application thereof

Country Status (1)

Country Link
CN (1) CN115611878A (en)

Similar Documents

Publication Publication Date Title
Moyano et al. Oxazoline-mediated interannular cyclopalladation of ferrocene: chiral palladium (II) catalysts for the enantioselective Aza-Claisen rearrangement
Bashary et al. Design, and facile synthesis of 1, 3 diaryl-3-(arylamino) propan-1-one derivatives as the potential alpha-amylase inhibitors and antioxidants
Han et al. Palladium-catalyzed enantioselective C–H aminocarbonylation: synthesis of chiral isoquinolinones
JP5923105B2 (en) Chiral spiro-pyridylamidophosphine ligand compound, synthesis method thereof and use thereof
Jin et al. Copper-catalysed addition of α-alkyl azaarenes to ethyl glyoxylate via direct C (sp 3)–H activation
Zhang et al. Pd (ii)-catalyzed C (sp 3)–H arylation of amino acid derivatives with click-triazoles as removable directing groups
Vanden Eynden et al. Calcium-promoted Pictet-Spengler reactions of ketones and aldehydes
US9221744B2 (en) Asymmetric catalysts
Warzecha et al. Axial ligand coordination to the C–H amination catalyst Rh2 (esp) 2: a structural and spectroscopic study
Mechler et al. Homo-and Heterobimetallic Pd–, Ag–, and Ni–Hybrid Salen–Bis-NHC Complexes
CN109485602A (en) A kind of chloro- N- of 2- (phenylcarbamoyl) nicotinamide compound and its preparation method and application
Thangavel et al. 1, 4, 7-triazacyclononane ligands bearing tertiary alkyl nitrogen substituents
CN115650980A (en) Oxindole compound and preparation method and application thereof
Martinez-Mingo et al. Overcoming the necessity of γ-substitution in δ-C (sp3)–H arylation: Pd-catalyzed derivatization of α-amino acids
Geiger et al. Recent metal-catalyzed methods for thioether synthesis
Mou et al. Recent Advances in Transition‐Metal‐Catalyzed C− H Functionalization of Ferrocene Amides
Liu et al. New tertiary amine-derived C 2-symmetric chiral pyridine-N, N′-dioxide ligands and their applications in asymmetric catalysis
Zhang et al. Process development and scale-up of fully synthetic tetracycline TP-2758: a potent antibacterial agent with excellent oral bioavailability
Badsara et al. Transition-Metal-Free Syntheses of Pyridine-Containing Thioethers Through Two-Fold C S Bond Formation.
CN112174952B (en) Beta-carboline-oxazoline novel multifunctional ligand beta3Carox, its preparation and application
CN115611878A (en) 3-arylamine (acylamino) pyridine oxazoline chiral ligand and preparation and application thereof
CN112174953A (en) Novel beta-carboline-oxazoline multifunctional ligand beta1Carox, its preparation and application
Brussaard et al. Synthesis and Structural Characterization of Molybdenum (VI) and Iron (II) Coordination Compounds with S-Alkyl-N-methyl-S-(2-pyridyl) sulfoximines and Catalytic Epoxidation Activity of the Molybdenum Complexes
CN113072481B (en) Indolo-cyclobutane skeleton compound, synthesis method and application
CN112812084B (en) Synthetic method of benzofuran compound

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