CN113735914A - Ferrocene derivative metalloid organic complex and preparation method and application thereof - Google Patents

Ferrocene derivative metalloid organic complex and preparation method and application thereof Download PDF

Info

Publication number
CN113735914A
CN113735914A CN202110973993.0A CN202110973993A CN113735914A CN 113735914 A CN113735914 A CN 113735914A CN 202110973993 A CN202110973993 A CN 202110973993A CN 113735914 A CN113735914 A CN 113735914A
Authority
CN
China
Prior art keywords
organic complex
ligand
ferrocene derivative
solvent
metalloid organic
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.)
Granted
Application number
CN202110973993.0A
Other languages
Chinese (zh)
Other versions
CN113735914B (en
Inventor
邢祥友
徐星军
尤义鹏
潘玉鹏
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.)
Southwest University of Science and Technology
Original Assignee
Southwest University of Science and 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 Southwest University of Science and Technology filed Critical Southwest University of Science and Technology
Priority to CN202110973993.0A priority Critical patent/CN113735914B/en
Publication of CN113735914A publication Critical patent/CN113735914A/en
Application granted granted Critical
Publication of CN113735914B publication Critical patent/CN113735914B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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
    • B01J31/18—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
    • B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
    • B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
    • 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
    • B01J31/22—Organic complexes
    • B01J31/2282—Unsaturated compounds used as ligands
    • B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
    • 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
    • B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • 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
    • 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
    • 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
    • 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
    • C07D213/60—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 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
    • C07D213/61—Halogen atoms or nitro radicals
    • 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
    • C07D215/12—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/18—Aralkyl radicals
    • C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon 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
    • B01J2531/821—Ruthenium
    • 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
    • B01J2531/84—Metals of the iron group
    • B01J2531/842—Iron
    • 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)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Catalysts (AREA)

Abstract

The invention relates to the technical field of organic synthesis, in particular to a ferrocene derivative metalloid organic complex and a preparation method and application thereof. The ferrocene derivative metalloid organic complex is shown as a formula I, and the structure of the ferrocene derivative metalloid organic complex contains a pincer-shaped ligand, so that the ferrocene derivative metalloid organic complex has higher stability and longer service life; meanwhile, the ferrocene derivative metalloid organic complex has high catalytic activity, and the preparation of the chiral compound can be efficiently and rapidly realized only by 0.001 mol% -0.01 mol% of the dosage; and the central metal of the ferrocene derivative metalloid organic complex is ruthenium, so the method has low economic cost and has an industrial popularization prospect.

Description

Ferrocene derivative metalloid organic complex and preparation method and application thereof
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a ferrocene derivative metalloid organic complex and a preparation method and application thereof.
Background
Chiral compounds play a significant role in the pharmaceutical and material synthesis industry, and particularly in the field of medicine, nearly half of common medicines have chirality, and more than 2/3 are chiral medicines in new medicines developed at present. The chiral secondary alcohol is a very important chiral compound, is also a key intermediate for synthesizing a plurality of other chiral compounds, and has wide application value in both academia and industry. Among chiral secondary alcohols, particularly secondary alcohols having similar steric hindrance and electric property of two substituents, such as aryl-substituted, heteroaryl-substituted chiral secondary alcohol compounds, have important applications in the field of new medicines. Although chemists have developed various asymmetric synthesis methods for such compounds, the reduction of the corresponding carbonyl compounds by direct asymmetric hydrogenation to produce such chiral secondary alcohols with high stereoselectivity remains a great challenge and success cases remain rare. Therefore, the development of an efficient and universal method for preparing the chiral secondary alcohol with similar steric hindrance and electric property of the substituent group by asymmetrically hydrogenating and reducing the ketone carbonyl compound has very important significance in synthesis and industrial application.
At present, asymmetric hydrogenation for reducing carbonyl compounds to prepare chiral secondary alcohols mainly comprises two routes: one is high-pressure hydrogenation asymmetric reduction, and the other is transfer hydrogenation asymmetric reduction. Generally, a high-efficiency catalyst for high-pressure hydrogenation asymmetric reduction can achieve a conversion number (TON) of up to 20 ten thousand, so that the catalyst is frequently used in industrial production, but has the defects of high price of chiral diphosphorus ligand, harsh reaction conditions and the like. The catalyst for transfer hydrogenation asymmetric reduction developed at present has the defects of low catalytic activity, large dosage, high price and the like.
Disclosure of Invention
Based on the above, there is a need for a ferrocene derivative metalloid organic complex and a preparation method thereof, which can be used as a catalyst for asymmetric reduction to prepare a chiral alcohol compound and have the advantages of high catalytic activity, low dosage, low cost and the like.
In one aspect of the present invention, a ferrocene derivative metalloid organic complex is provided, which has a structure as shown in formula I:
Figure BDA0003226659590000011
wherein R is1Selected from straight-chain alkyl and cycloalkyl with 1-6 carbon atoms, or branched-chain alkyl and cycloalkyl with 3-6 carbon atoms;
R2independently for each occurrence, is selected from substituted or unsubstituted phenyl, substituted or unsubstituted benzo nitrogen-containing heterocyclic groups;
R3each occurrence is independently selected from-H, straight-chain alkyl with 1-6 carbon atoms, alkoxy, halogen group, hydroxyl, acyl, or branched-chain alkyl with 3-6 carbon atoms, alkoxy, substituted or unsubstituted phenyl, and R3With pyridine attached theretoWith or without looping.
The ferrocene derivative metalloid organic complex structure provided by the invention contains the pincer-shaped ligand, so that the ferrocene derivative metalloid organic complex structure has higher stability and longer service life; meanwhile, the ferrocene derivative metalloid organic complex has high catalytic activity, and the preparation of the chiral compound can be efficiently and rapidly realized only by 0.001 mol% -0.01 mol% of the dosage; and the central metal of the ferrocene derivative metalloid organic complex is ruthenium, so the method has low economic cost and has an industrial popularization prospect.
In some embodiments, the R is1Is selected from-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2(CH2)2CH3Cyclopropyl, cyclopentyl or cyclohexyl.
In some embodiments, the R is2Each occurrence is independently selected from C6H5-、3-OMe-C6H5-、4-TMS-C6H5-、4-MeO-C6H5-、4-F-C6H5-、4-Cl-C6H5-、4-I-C6H5-、3,5-(C(CH3)3)2-C6H3-、3,4,5-(OMe)3-C6H2-、3,4,5-(CF3)3-C6H2-、3,4,5-(F)3-C6H2-、3,5-(CF3)2-C6H3-、3,4-(CF3)2-C6H3-、3-OMe-C6H4-、3,5-(OMe)2-C6H3-、3,5-(i-Pr)2-C6H3-, 1, 3-benzodioxolyl, benzimidazolyl or benzoxazinyl.
In some embodiments, the R is3Each occurrence is independently selected from the group consisting of-H, MeO-, EtO-, i-Pr-, C6H5-、3-OMe-C6H5-、4-TMS-C6H5-、4-MeO-C6H5-、4-F-C6H5-、4-Cl-C6H5-、4-I-C6H5-、3,5-(C(CH3)3)2-C6H3-、3,4,5-(OMe)3-C6H2-、3,4,5-(CF3)3-C6H2-、3,4,5-(F)3-C6H2-、3,5-(CF3)2-C6H3-、3,4-(CF3)2-C6H3-、3-OMe-C6H4-、3,5-(OMe)2-C6H3-、3,5-(i-Pr)2-C6H3-、-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2(CH2)2CH3-F, -Cl, -Br, -I, -OH, -C (═ O) Me, -C (═ O) Et, or-C (═ O)iPr。
In some embodiments, the R is2In each occurrence, the same groups are selected.
In another aspect of the present invention, a preparation method of the ferrocene derivative metalloid organic complex is further provided, which comprises the following steps:
reacting the precursor with a first ligand in a first solvent to prepare an intermediate;
reacting the intermediate with a second ligand in a second solvent to prepare a ferrocene derivative metalloid organic complex;
wherein the precursor is tris (triphenylphosphine) ruthenium dichloride, and the first solvent and the second solvent are both alcohol solvents;
the first ligand has a structure as shown in formula II:
Figure BDA0003226659590000021
the second ligand has a structure as shown in formula III:
Figure BDA0003226659590000031
wherein R is1～R3As defined in any of the previous embodiments.
In some embodiments, the first ligand is selected from the group consisting of:
Figure BDA0003226659590000032
Figure BDA0003226659590000041
in some embodiments, the second ligand is selected from the group consisting of:
Figure BDA0003226659590000042
in some embodiments, the conditions for reacting the precursor with the first ligand in the first solvent are: reacting for 2-4 h at 60-90 ℃; and/or
The conditions for reacting the intermediate with the second ligand in the second solvent are as follows: reacting for 9-16 h at 110-130 ℃ in the presence of alkali, wherein the alkali is selected from triethylamine, dimethylamine, diethylamine or pyridine and the like.
In some embodiments of the present invention, the substrate is,
the molar ratio of the precursor to the first ligand is 1: (1-1.2); and/or
The molar ratio of the intermediate to the second ligand is 1: (1-1.2); and/or
The molar ratio of the intermediate to the base is 1: (2-3); and/or
The molar ratio of the precursor to the first solvent is 1: (1-10); and/or
The molar ratio of the intermediate to the second solvent is 1: (1-10).
In another aspect of the invention, the application of the ferrocene derivative metalloid organic complex in preparing chiral alcohol compounds is also provided.
Detailed Description
In order that the invention may be more fully understood, reference will now be made to the accompanying examples. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the invention, "a plurality" means at least two, e.g., two, three, etc., unless explicitly specified otherwise. In the description of the present invention, "a plurality" means at least one, e.g., one, two, etc., unless specifically limited otherwise.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
In the present invention, the technical features described in the open type include a closed technical solution composed of the listed features, and also include an open technical solution including the listed features.
In the present invention, the numerical intervals are regarded as continuous, and include the minimum and maximum values of the range and each value between the minimum and maximum values, unless otherwise specified. Further, when a range refers to an integer, each integer between the minimum and maximum values of the range is included. Further, when multiple range-describing features or characteristics are provided, the ranges may be combined. In other words, unless otherwise indicated, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein.
The temperature parameter in the present invention is not particularly limited, and may be a constant temperature treatment or a treatment within a certain temperature range. The constant temperature process allows the temperature to fluctuate within the accuracy of the instrument control.
In the present invention, Me represents a methyl group, Et represents an ethyl group, Bn represents a benzyl group, Ph represents a phenyl group,tbu or t-Bu represents tert-butyl, i-Pr oriPr represents isopropyl group, Fc represents ferrocene, halogen represents F, Cl, Br or I, and the atom at the position is chiral atom.
In the present invention, the expression "each occurrence of a group of a certain number is independently selected from … …" means: when a plurality of groups with the same code number exist in the compound structure at the same time, the groups with the same code number respectively specifically refer to the selection of which groups are independent from each other and are not influenced, namely, the groups with the same code number can be the same or different in the compound structure. For example, in formula I, "R2Independently for each occurrence, is selected from substituted or unsubstituted phenyl, and substituted or unsubstituted benzo nitrogen-containing heterocyclic group "represents: in formula I, four R's are attached to the phosphorus atom2The radicals may simultaneously be unsubstituted phenyl; or two of R2The radicals being unsubstituted phenyl, two of which R2The group is an unsubstituted benzo nitrogen-containing heterocyclic group; and also three of R2The radicals being substituted phenyl radicals in which one R is2The benzo nitrogen-containing heterocyclic group … … whose group is substituted is here by way of example only and does not list all possibilities for combination and is not considered as a substituent for R in formula I2To four R2Specific references to groups may be by definition in various combinations.
In one aspect of the present invention, a ferrocene derivative metalloid organic complex is provided, which has a structure as shown in formula I:
Figure BDA0003226659590000061
wherein R is1Selected from straight-chain alkyl and cycloalkyl with 1-6 carbon atoms, or branched-chain alkyl and cycloalkyl with 3-6 carbon atoms;
R2independently for each occurrence, is selected from substituted or unsubstituted phenyl, substituted or unsubstituted benzo nitrogen-containing heterocyclic groups;
when R is2When the substituent is a substituted phenyl group, the substituent can be substituted by one or more substituents with 1-5 carbon atoms, and the substituents with 1-5 carbon atoms are specifically alkyl, alkoxy, alkyl silicon base, halogen group or trifluoromethyl;
R3each occurrence is independently selected from-H, straight-chain alkyl with 1-6 carbon atoms, alkoxy, halogen group, hydroxyl, acyl, or branched-chain alkyl with 3-6 carbon atoms, alkoxy, substituted or unsubstituted phenyl, and R3With the pyridine ring to which it is attached, either cyclized or not; it can be understood that R3When the pyridine ring is connected with the substituted or unsubstituted phenyl, the substituted or unsubstituted phenyl is selected;
when R is3When substituted phenyl, it may be substituted with one or more substituents having 1 to 5 carbon atoms, and the substituents having 1 to 5 carbon atoms are specifically alkyl, alkoxy, halogen or trifluoromethyl;
the dotted line in formula I indicates that there may or may not be a bond. When bonded, the pyridine ring is fused to a naphthalene ring backbone; when not bonded, the ortho position of the pyridine ring is substituted with a benzene ring skeleton.
The ferrocene derivative metalloid organic complex structure provided by the invention contains the pincer-shaped ligand, so that the ferrocene derivative metalloid organic complex structure has higher stability and longer service life; meanwhile, the ferrocene derivative metalloid organic complex has high catalytic activity, and the preparation of the chiral compound can be efficiently and rapidly realized only by 0.001 mol% -0.01 mol% of the dosage; and the central metal of the ferrocene derivative metalloid organic complex is ruthenium, so the method has low economic cost and has an industrial popularization prospect.
In some embodiments, R1Is selected from-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2(CH2)2CH3Cyclopropyl, cyclopentyl or cyclohexyl.
In some embodiments, R2Each occurrence is independently selected from C6H5-、3-OMe-C6H5-、4-TMS-C6H5-、4-MeO-C6H5-、4-F-C6H5-、4-Cl-C6H5-、4-I-C6H5-、3,5-(C(CH3)3)2-C6H3-、3,4,5-(OMe)3-C6H2-、3,4,5-(CF3)3-C6H2-、3,4,5-(F)3-C6H2-、3,5-(CF3)2-C6H3-、3,4-(CF3)2-C6H3-、3-OMe-C6H4-、3,5-(OMe)2-C6H3-、3,5-(i-Pr)2-C6H3-, 1, 3-benzodioxolyl, benzimidazolyl or benzoxazinyl.
In some embodiments, the R is3Each occurrence is independently selected from the group consisting of-H, MeO-, EtO-, i-Pr-, C6H5-、3-OMe-C6H5-、4-TMS-C6H5-、4-MeO-C6H5-、4-F-C6H5-、4-Cl-C6H5-、4-I-C6H5-、3,5-(C(CH3)3)2-C6H3-、3,4,5-(OMe)3-C6H2-、3,4,5-(CF3)3-C6H2-、3,4,5-(F)3-C6H2-、3,5-(CF3)2-C6H3-、3,4-(CF3)2-C6H3-、3-OMe-C6H4-、3,5-(OMe)2-C6H3-、3,5-(i-Pr)2-C6H3-、-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2(CH2)2CH3-F, -Cl, -Br, -I, -OH, -C (═ O) Me, -C (═ O) Et, or-C (═ O)iPr。
In some embodiments, R2In each occurrence, the same groups are selected.
In some embodiments, the aforementioned ferrocene derivative metalloid organic complex is specifically the following compound:
Figure BDA0003226659590000071
Figure BDA0003226659590000081
in another aspect of the present invention, a preparation method of the ferrocene derivative metalloid organic complex is further provided, which comprises the following steps:
reacting the precursor with a first ligand in a first solvent to prepare an intermediate;
reacting the intermediate with a second ligand in a second solvent to prepare a ferrocene derivative metalloid organic complex;
wherein the precursor is ruthenium (triphenyl phosphine) dichloride, and the first solvent and the second solvent are alcohol solvents; preferably, the alcohol solvent is methanol or isopropanol, and the alcohol solvent can not only fully dissolve the solute, but also promote the reaction;
the first ligand has a structure as shown in formula II:
Figure BDA0003226659590000082
the second ligand has a structure as shown in formula III:
Figure BDA0003226659590000083
the dotted line in formula III indicates that there may or may not be a bond. When bonded, the second ligand has a benzoquinoline skeleton, and when not bonded, the second ligand has a 2-phenylpyridine skeleton.
Wherein R is1～R3As defined in any of the previous embodiments.
In some embodiments, the first ligand is selected from the group consisting of:
Figure BDA0003226659590000084
Figure BDA0003226659590000091
the chiral diphosphine ligand is replaced by the achiral diphosphine ligand, and the chiral elements of the diamine ligand are retained and adjusted to control the chirality of the catalytic asymmetric reaction, so that the difficulty and the cost for synthesizing the chiral ferrocene derivative metalloid organic complex are greatly reduced.
In some embodiments, the second ligand is selected from the group consisting of:
Figure BDA0003226659590000101
in some embodiments, the conditions under which the precursor is reacted with the first ligand in the first solvent are: reacting for 2-4 h at 60-90 ℃; optionally, the conditions for reacting the precursor with the first ligand in the first solvent are: reacting for 3 hours at 70-80 ℃;
in some embodiments, the conditions under which the intermediate is reacted with the second ligand in the second solvent are: reacting for 9-16 h at 110-130 ℃ in the presence of a base, and optionally reacting the intermediate with a second ligand in a second solvent under the conditions of: reacting for 12-14 h at 120 ℃ in the presence of alkali; the base is selected from triethylamine, ethylamine, dimethylamine, diethylamine or pyridine, etc.
In some embodiments, the molar ratio of precursor to first ligand is 1: (1-1.2), optionally, the molar ratio of the precursor to the first ligand may be, for example, 1: 1.1; within a preset range, the precursor and the first ligand can react more fully.
In some embodiments, the molar ratio of intermediate to second ligand is 1: (1-1.2), optionally, the molar ratio of the intermediate to the second ligand may be, for example, 1: 1.1; within a predetermined range, the intermediate and the second ligand can react more fully.
In some embodiments, the molar ratio of intermediate to base is 1: (2-3), optionally, the molar ratio of the intermediate to the base may be, for example, 1: 2.5; the amount of base used is such that the intermediate reacts more fully with the second ligand.
In some embodiments, the molar ratio of precursor to first solvent is 1: (1-10), optionally, the molar ratio of the precursor to the first solvent may also be, for example, 1:3, 1:5, or 1: 8; setting the molar ratio of the precursor to the first solvent in the above range may satisfy the dissolution of the precursor and the different first ligands in the first solvent.
In some embodiments, the molar ratio of intermediate to second solvent is 1: (1-10), optionally, the molar ratio of the intermediate to the second solvent may also be, for example, 1:3, 1:5, or 1: 8; setting the molar ratio of the intermediate to the second solvent to the above range may satisfy the dissolution of the intermediate and the different second ligand in the second solvent.
In some embodiments, preferably, after the precursor is reacted with the first ligand in the first solvent, the obtained reaction solution is filtered, and then the filtrate is concentrated to obtain a first solid, and then the first solid is recrystallized to obtain an intermediate.
Preferably, the solvent for the recrystallization of the first solid can adopt dichloromethane and n-hexane, and the volume ratio of the dichloromethane to the n-hexane is (1-2): (1-5). By setting the volume ratio of dichloromethane to n-hexane to the above range, the recrystallization effect can be improved, and the purity of the obtained intermediate is high.
In some embodiments, preferably, after the intermediate reacts with the second ligand in the second solvent, the obtained reaction solution is filtered, and then the filtrate is concentrated to obtain a second solid, and then the second solid is recrystallized to obtain the ferrocene derivative metalloid organic complex.
Preferably, the solvent for recrystallization of the second solid can adopt dichloromethane and diethyl ether, and the volume ratio of the dichloromethane to the diethyl ether is 1: (1-20). The volume ratio of the dichloromethane to the ether is set to be in the range, so that the recrystallization effect is better, and the obtained ferrocene derivative metalloid organic complex has high purity.
Further preferably, before the second solid is recrystallized, a step of washing the second solid is further included. The washing solvent adopts n-hexane and/or n-pentane, and the washing can remove partial reaction byproducts.
In another aspect of the invention, the application of the ferrocene derivative metalloid organic complex in preparing chiral alcohol compounds is also provided.
Specifically, when the ferrocene derivative metalloid organic complex is used as a catalyst for preparing a chiral alcohol compound, the method comprises the following steps:
and reacting the ketone compound, the ferrocene derivative metalloid organic complex and the alkali in a third solvent for 15-90 min at the temperature of 20-30 ℃ to prepare the chiral alcohol compound.
In some embodiments, preferably, the ketone compound is selected from the following compounds:
Figure BDA0003226659590000111
Figure BDA0003226659590000121
in some embodiments, the base is selected from potassium tert-butoxide, sodium hydroxide or potassium hydroxide.
In some embodiments, the third solvent is a pure solvent, preferably isopropanol; the alcohol solvent has good solubility to each reactant in the system, can be used as a hydrogen source to catalyze the reduction of carbon-containing unsaturated bonds in organic matters, realizes transfer hydrogenation asymmetric reduction, and has the advantages of good selectivity, mild action conditions, high atom economy and the like.
In some embodiments, the molar ratio of the ferrocene derivative metalloid organic complex to the ketone compound is (0.001-0.01): 100, optionally, the molar ratio of ferrocene derivative metalloid organic complex to ketone compound is 0.002: 100. 0.005: 100 or 0.008: 100.
in some embodiments, the molar ratio of base to ketone compound is (1-15): 100, alternatively, the molar ratio of base to ketone compound is 2: 100. 5: 100 or 10: 100.
in some embodiments, a reaction solution obtained by reacting the ketone compound, the ferrocene derivative metalloid organic complex and the base in the third solvent is filtered, and then the filtrate is sequentially washed, dried and distilled to obtain the chiral alcohol compound. The washing solution was saturated saline, and the drying agent was anhydrous sodium sulfate.
In some embodiments, preferably, the crude product obtained by distillation is recrystallized by using n-hexane and ethyl acetate as solvents in a volume ratio of (5-20): 1.
the preparation of chiral alcohol by using the ferrocene derivative metalloid organic complex can be realized by short-time reaction at room temperature, the reaction condition is mild, the catalyst feeding amount is small, the conversion number is high (up to 10 ten thousand), the post-treatment is simple, the ee value of the obtained chiral alcohol is high (85-99 percent), and the application prospect is wide.
The present invention will be described in further detail with reference to specific examples and comparative examples. It is understood that the following examples are more specific to the apparatus and materials used, and in other embodiments, are not limited thereto. The following examples, unless otherwise specified, do not contain other components not specifically indicated except for inevitable impurities.
Example 1
Examples 1 to 1
The preparation process of the ferrocene derivative metalloid organic complex of the embodiment is as follows:
(1) under the protection of argon, tris (triphenylphosphine) ruthenium (II) dichloride and methoxy-substituted dppf ligand in a molar ratio of 1:1 are added
Figure BDA0003226659590000131
Dissolving in isopropanol, heating at 90 ℃ for 2 hours to obtain a first reaction liquid, filtering the first reaction liquid to obtain a first filtrate, carrying out reduced pressure distillation on the first filtrate to obtain a first solid, washing the first solid with n-pentane, removing generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the dichloromethane, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
(2) The intermediate obtained in the above step is mixed with a ligand CNN10
Figure BDA0003226659590000132
Dissolving in isopropanol, heating at 90 ℃ for 2 hours to obtain a first reaction liquid, filtering the first reaction liquid to obtain a first filtrate, carrying out reduced pressure distillation on the first filtrate to obtain a first solid, washing the first solid with n-pentane, removing generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the dichloromethane, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
Performing nuclear magnetic test on the ferrocene derivative metalloid organic complex by adopting a Bruker Avance 400 nuclear magnetic resonance tester, wherein the test result is as follows:
1H NMR(400MHz,CDCl3):δ8.61(t,J＝4.0Hz,1H),8.43(t,J＝8.8Hz,2H),8.00(t,J＝8.5Hz,2H),7.62(d,J＝9.0Hz,1H),7.59–7.44(m,7H),7.41(s,1H),7.31(d,J＝8.9Hz,1H),7.03(d,J＝7.8Hz,2H),6.86(d,J＝8.1Hz,2H),6.69(dd,J＝9.0,1.2Hz,2H),5.93(s,2H),5.79(d,J＝7.4Hz,2H),5.36(s,1H),5.32(dd,J＝3.6,2.5Hz,7H),4.80(s,1H),4.29(d,J＝1.3Hz,1H),4.24–4.17(m,2H),4.11(s,1H),3.88(d,J＝2.7Hz,3H),3.87(s,3H),3.83–3.79(m,1H),3.74(s,3H),3.47(s,3H),3.40(dd,J＝12.4,4.2Hz,1H),3.23(s,1H),2.50(d,J＝4.5Hz,1H).
13C NMR(151MHz,CD2Cl2):δ161.9,160.4,160.3,158.8,156.0,154.5,147.1,147.0,146.3,139.7,139.7,139.3,135.5,135.3,134.2,134.0,133.97,131.5,131.3,130.4,130.3,129.0,128.7,126.8,126.5,126.2,125.6,125.3,123.0,120.4,120.4,119.1,113.8,113.7,113.66,113.6,112.2,112.1,111.5,88.3,88.1,88.0,87.7,77.5,77.4,77.2,77.1,76.0,74.2,74.2,73.6,73.5,72.3,69.7,69.7,69.6,69.6,69.1,69.1,56.0,55.8,55.6,55.3,35.5,28.1.
31P NMR(243MHz,CD2Cl2):δ58.02(d,J＝37.8Hz),42.15(d,J＝36.7Hz).
HRMS(ESI+):calculated for C62H59ClFeN2O4P2Ru[M-Cl]+:1115.2337,found 1115.2338.
the experimental data show that the ferrocene derivative metalloid organic complex 1 with the following structure is successfully prepared:
Figure BDA0003226659590000141
examples 1 to 2
The preparation process of the ferrocene derivative metalloid organic complex of the embodiment is as follows:
(1) under the protection of argon, tris (triphenylphosphine) ruthenium (II) dichloride and dppf ligand in a molar ratio of 1:1 are added
Figure BDA0003226659590000142
Dissolving isopropanol, heating at 90 deg.C for 2 hr to obtain first reaction solution, filtering to obtain first filtrate, and reducing the first filtrateAnd carrying out pressure distillation to obtain a first solid, washing the first solid with n-pentane to remove generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the first solid, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
(2) The intermediate obtained in the above step is mixed with a ligand CNN9
Figure BDA0003226659590000143
Dissolving in isopropanol, heating at 90 ℃ for 2 hours to obtain a first reaction liquid, filtering the first reaction liquid to obtain a first filtrate, carrying out reduced pressure distillation on the first filtrate to obtain a first solid, washing the first solid with n-pentane, removing generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the dichloromethane, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
Performing nuclear magnetic test on the obtained ferrocene derivative metalloid organic complex, wherein the test result is as follows:
1H NMR(400MHz,CD2Cl2):δ8.68(d,J＝6.0Hz,1H),8.60(t,J＝8.3Hz,2H),8.19(t,J＝8.4Hz,2H),7.69–7.45(m,13H),7.43–7.18(m,7H),7.05(s,1H),6.61(t,J＝7.3Hz,1H),6.30(t,J＝7.0Hz,2H),6.06(d,J＝8.1Hz,2H),5.47(s,1H),5.37(d,J＝4.6Hz,2H),4.93(s,1H),4.37(s,1H),4.28(s,1H),4.24(s,1H),4.14(s,1H),3.88(s,1H),3.76(t,J＝10.9Hz,1H),3.58(d,J＝11.0Hz,1H),3.29(s,1H),2.10(d,J＝9.5Hz,2H),1.76(d,J＝32.0Hz,3H),1.62(d,J＝12.5Hz,1H),1.33(dd,J＝13.6,5.9Hz,3H),1.21–1.05(m,3H),0.93(dd,J＝13.6,7.0Hz,2H).
13C NMR(101MHz,CD2Cl2):δ155.8,153.3,146.5,146.3,146.2,143.5,139.4,139.1,138.5,137.8,137.7,1345.0,134.6,133.7,133.3,132.1,132.0,130.3,129.8,129.4,128.6,128.5,128.3,128.2,127.7,127.61,127.5,126.6,126.4,126.3,125.2,122.5,1120.0,118.6,117.6,87.5,77.1,77.0,76.6,76.5,75.6,73.8,73.8,73.0,69.2,68.7,66.9,39.7,30.2,26.6,26.3,26.0,25.7,22.3,13.8.
31P NMR(162MHz,CD2Cl2):δ60.81(d,J＝36.1Hz),45.01(d,J＝36.1Hz).
HRMS(ESI+):calculated for C60H53ClFeN2P2Ru[M-Cl]+:1021.2071,found 1021.2072.
the experimental data show that the ferrocene derivative metalloid organic complex 2 with the following structure is successfully prepared:
Figure BDA0003226659590000151
examples 1 to 3
Under the protection of argon, tris (triphenylphosphine) ruthenium (II) dichloride and methoxy-substituted dppf ligand in a molar ratio of 1:1 are added
Figure BDA0003226659590000152
Dissolving in isopropanol, heating at 90 ℃ for 2 hours to obtain a first reaction liquid, filtering the first reaction liquid to obtain a first filtrate, carrying out reduced pressure distillation on the first filtrate to obtain a first solid, washing the first solid with n-pentane, removing generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the dichloromethane, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
(2) The intermediate obtained in the above step is mixed with a ligand CNN10
Figure BDA0003226659590000161
Dissolving in isopropanol, heating at 90 ℃ for 2 hours to obtain a first reaction liquid, filtering the first reaction liquid to obtain a first filtrate, carrying out reduced pressure distillation on the first filtrate to obtain a first solid, washing the first solid with n-pentane, removing generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the dichloromethane, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
Performing nuclear magnetic test on the ferrocene derivative metalloid organic complex by adopting a Bruker Avance 400 nuclear magnetic resonance tester, wherein the test result is as follows:
1H NMR(600MHz,CDCl3):δ8.61(t,J＝4.0Hz,1H),8.43(t,J＝8.8Hz,2H),8.00(t,J＝8.5Hz,2H),7.62(d,J＝9.0Hz,1H),7.59–7.44(m,7H),7.41(s,1H),7.31(d,J＝8.9Hz,1H),7.03(d,J＝7.8Hz,2H),6.91–6.83(m,4H),6.80–6.73(m,4H),6.69(dd,J＝6.0,1.3Hz,4H),5.94(dd,J＝9.4,1.4Hz,6H),4.80(s,1H),4.33–4.23(m,4H),3.99(d,J＝1.8Hz,4H),3.74(s,3H),3.83–3.79(m,1H),3.74(s,3H),3.47(s,3H),3.40(dd,J＝12.4,4.2Hz,1H),3.23(s,1H),2.50(d,J＝4.5Hz,1H).
13C NMR(151MHz,CD2Cl2):δ161.9,160.4,160.3,158.8,156.0,154.5,147.1,147.0,146.3,139.7,139.7,139.3,135.5,135.3,134.2,134.0,133.97,131.5,131.3,130.4,130.3,129.0,128.7,126.8,126.5,126.2,125.6,125.3,123.0,120.4,120.4,119.1,113.8,113.7,113.66,113.6,112.2,112.1,111.5,88.3,88.1,88.0,87.7,77.5,77.4,77.2,77.1,76.0,74.2,74.2,73.6,73.5,72.3,69.7,69.7,69.6,69.6,69.1,69.1,56.0,55.8,55.6,55.3,35.5,28.1.
31P NMR(162MHz,CD2Cl2):δ60.81(d,J＝36.1Hz),45.01(d,J＝36.1Hz).
HRMS(ESI+):calculated for C64H55ClFeN2O10P2Ru[M-Cl]+:1231.1725,found 1231.1724.
the experimental data show that the ferrocene derivative metalloid organic complex 3 with the following structure is successfully prepared:
Figure BDA0003226659590000162
examples 1 to 4
(1) Under the protection of argon, tris (triphenylphosphine) ruthenium (II) dichloride and dppf ligand in a molar ratio of 1:1 are added
Figure BDA0003226659590000163
Dissolving in isopropanol, heating at 90 deg.C for 2 hr to obtain first reaction solution, and filtering to obtain second reaction solutionAnd (3) carrying out reduced pressure distillation on the first filtrate to obtain a first solid, washing the first solid with n-pentane to remove generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the dichloromethane, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
(2) The intermediate obtained in the above step is mixed with a ligand CNN18
Figure BDA0003226659590000171
Dissolving in isopropanol, heating at 90 ℃ for 2 hours to obtain a first reaction liquid, filtering the first reaction liquid to obtain a first filtrate, carrying out reduced pressure distillation on the first filtrate to obtain a first solid, washing the first solid with n-pentane, removing generated triphenylphosphine, dissolving the first solid in dichloromethane, adding n-hexane into the dichloromethane, and recrystallizing to obtain an intermediate, wherein the volume ratio of the dichloromethane to the n-hexane is 1: 1.
Performing nuclear magnetic test on the obtained ferrocene derivative metalloid organic complex, wherein the test result is as follows:
1H NMR(400MHz,CD2Cl2):δ8.61(t,J＝4.0Hz,1H),8.43(t,J＝8.8Hz,2H),8.00(t,J＝8.5Hz,2H),7.62(d,J＝9.0Hz,1H),7.59–7.44(m,7H),7.41(s,1H),7.31(d,J＝8.9Hz,1H),7.03(d,J＝7.8Hz,2H),6.86(d,J＝8.1Hz,2H),6.69(dd,J＝9.0,1.2Hz,2H),5.93(s,2H),5.79(d,J＝7.4Hz,2H),5.36(s,1H),5.32(dd,J＝3.6,2.5Hz,7H),4.80(s,1H),4.29(d,J＝1.3Hz,1H),4.24–4.17(m,2H),4.11(s,1H),3.88(d,J＝2.7Hz,3H),3.87(s,3H),3.83–3.79(m,1H),3.74(s,3H),3.47(s,3H).
13C NMR(101MHz,CD2Cl2):δ161.9,160.4,160.3,158.8,156.0,154.5,147.1,147.0,146.3,139.7,139.7,139.3,135.5,135.3,134.2,134.0,133.97,131.5,131.3,130.4,130.3,129.0,128.7,126.8,126.5,126.2,125.6,125.3,123.0,120.4,120.4,119.1,113.8,113.7,113.66,113.6,112.2,112.1,111.5,88.3,88.1,88.0,87.7,77.5,77.4,77.2,77.1,76.0,74.2,74.2,73.6,73.5,72.3,69.7,69.7,69.6,69.6,69.1,69.1,56.0,55.8,55.6,55.3,35.5,28.1.
31P NMR(162MHz,CD2Cl2):δ60.81(d,J＝36.1Hz),45.01(d,J＝36.1Hz).
HRMS(ESI+):calculated for C59H55ClFeN2OP2Ru[M-Cl]+:1027.2183,found 1027.2181.
the experimental data show that the ferrocene derivative metalloid organic complex 2 with the following structure is successfully prepared:
Figure BDA0003226659590000172
example 2-1 to example 2-32
Example 2-1 to example 2-18 are examples in which the ferrocene derivative metalloid organic complex prepared in example 1-1 is used to catalyze a ketone compound to obtain a chiral alcohol compound, and example 2-19 to example 2-32 are examples in which the ferrocene derivative metalloid organic complex prepared in example 1-2 is used to catalyze a ketone compound to obtain a chiral alcohol compound. The method comprises the following specific steps:
dissolving a ferrocene derivative metalloid organic complex and potassium tert-butoxide in a mixed solvent of isopropanol, uniformly mixing, adding a ketone compound, stirring at room temperature for 2min to obtain a reaction solution, wherein the mole percentage of the ferrocene derivative metalloid organic complex to the ketone compound is 0.001-0.01%, and the mole percentage of the potassium tert-butoxide to the ketone compound is 1.5-2.0%, filtering the reaction solution to obtain an organic filtrate, adding saturated saline solution into the organic filtrate to wash the organic filtrate, and then adding anhydrous sodium sulfate to dry the organic filtrate; and filtering the washed and dried organic filtrate to obtain filtrate. And carrying out reduced pressure distillation on the filtrate to obtain the product chiral alcohol compound.
Specific parameters in the processes for preparing alcohol compounds in examples 2-1 to 2-32 are shown in table 2:
TABLE 2 Nuclear magnetic data and Mass Spectrometry data of chiral alcohol Compounds obtained in the examples
Figure BDA0003226659590000181
Figure BDA0003226659590000191
Figure BDA0003226659590000201
Figure BDA0003226659590000211
Figure BDA0003226659590000221
Figure BDA0003226659590000231
The experimental result shows that the ferrocene derivative metalloid organic complex provided by the invention has high catalytic activity, and the ferrocene derivative metalloid organic complex provided by the invention is used for catalyzing the ketone compound to carry out hydrogenation transfer, so that the obtained alcohol compound has high yield and chirality, and the ee value is more than 85%.
Comparative examples 1 to 1
Comparative example 1-1 the procedure for preparing a catalyst was similar to that of example 1-1, except that the second ligand in comparative example 1-1 was NH in the ligand CNN102One hydrogen of (a) is substituted by methyl. The catalyst obtained in comparative example 1-1 has the following structural formula, wherein Ar is phenyl group and Me is methyl group:
Figure BDA0003226659590000241
comparative example 2-1
The chiral alcohol compound of comparative example 2-1 was prepared in a similar manner to example 2-1, except that the catalyst used in comparative example 2-1 was the catalyst prepared in comparative example 1-1. However, the results showed that the chiral alcohol could not be produced using the catalyst prepared in comparative example 1-1, and the reaction did not occur.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the patent of the invention is subject to the appended claims, and the description can be used for explaining the contents of the claims.

Claims (10)

1. A ferrocene derivative metalloid organic complex is characterized by having a structure shown as formula I:
Figure FDA0003226659580000011
wherein R is1Selected from straight-chain alkyl and cycloalkyl with 1-6 carbon atoms, or branched-chain alkyl and cycloalkyl with 3-6 carbon atoms;
R2independently for each occurrence, is selected from substituted or unsubstituted phenyl, substituted or unsubstituted benzo nitrogen-containing heterocyclic groups;
R3each occurrence is independently selected from-H, straight-chain alkyl with 1-6 carbon atoms, alkoxy, halogen group, hydroxyl and acyl, or branched-chain alkyl with 3-6 carbon atoms and alkoxy, and the substituent or the substituent is not selectedSubstituted phenyl, and R3With or without a ring being formed with the pyridine ring to which it is attached.
2. A ferrocene derivative metalloid organic complex as claimed in claim 1, wherein R is1Is selected from-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2(CH2)2CH3Cyclopropyl, cyclopentyl or cyclohexyl.
3. A ferrocene derivative metalloid organic complex as claimed in claim 1, wherein R is2Each occurrence is independently selected from C6H5-、3-OMe-C6H5-、4-TMS-C6H5-、4-MeO-C6H5-、4-F-C6H5-、4-Cl-C6H5-、4-I-C6H5-、3,5-(C(CH3)3)2-C6H3-、3,4,5-(OMe)3-C6H2-、3,4,5-(CF3)3-C6H2-、3,4,5-(F)3-C6H2-、3,5-(CF3)2-C6H3-、3,4-(CF3)2-C6H3-、3-OMe-C6H4-、3,5-(OMe)2-C6H3-、3,5-(i-Pr)2-C6H3-, 1, 3-benzodioxolyl, benzimidazolyl or benzoxazinyl.
4. A ferrocene derivative metalloid organic complex as claimed in claim 1, wherein R is3Each occurrence is independently selected from-H, MeO-, EtO-,iPr-、C6H5-、3-OMe-C6H5-、4-TMS-C6H5-、4-MeO-C6H5-、4-F-C6H5-、4-Cl-C6H5-、4-I-C6H5-、3,5-(C(CH3)3)2-C6H3-、3,4,5-(OMe)3-C6H2-、3,4,5-(CF3)3-C6H2-、3,4,5-(F)3-C6H2-、3,5-(CF3)2-C6H3-、3,4-(CF3)2-C6H3-、3-OMe-C6H4-、3,5-(OMe)2-C6H3-、3,5-(i-Pr)2-C6H3-、-CH3、-CH2CH3、-CH2CH2CH3、-CH(CH3)2、-C(CH3)3、-CH2(CH2)2CH3-F, -Cl, -Br, -I, -OH, -C (═ O) Me, -C (═ O) Et, or-C (═ O)iPr。
5. A ferrocene derivative metalloid organic complex according to any one of claims 1 to 4, wherein R is2In each occurrence, the same groups are selected.
6. A method for preparing a ferrocene derivative metalloid organic complex according to any one of claims 1 to 5, comprising the steps of:
reacting the precursor with a first ligand in a first solvent to prepare an intermediate;
reacting the intermediate with a second ligand in a second solvent to prepare a ferrocene derivative metalloid organic complex;
wherein the precursor is tris (triphenylphosphine) ruthenium dichloride, and the first solvent and the second solvent are both alcohol solvents;
the first ligand has a structure as shown in formula II:
Figure FDA0003226659580000021
the second ligand has a structure as shown in formula III:
Figure FDA0003226659580000022
wherein R is1～R3The definition of (A) is as defined in any one of claims 1 to 5.
7. The method of claim 6, wherein the first ligand is selected from the group consisting of:
Figure FDA0003226659580000023
Figure FDA0003226659580000031
and/or
The second ligand is selected from the following compounds:
Figure FDA0003226659580000032
Figure FDA0003226659580000041
8. the method according to any one of claims 6 to 7, wherein the conditions for reacting the precursor with the first ligand in the first solvent are as follows: reacting for 2-4 h at 60-90 ℃; and/or
The conditions for reacting the intermediate with the second ligand in the second solvent are as follows: reacting for 9-16 h at 110-130 ℃ in the presence of alkali, wherein the alkali is selected from triethylamine, ethylamine, dimethylamine, diethylamine or pyridine.
9. The method according to claim 8,
the molar ratio of the precursor to the first ligand is 1: (1-1.2); and/or
The molar ratio of the intermediate to the second ligand is 1: (1-1.2); and/or
The molar ratio of the intermediate to the base is 1: (2-3); and/or
The molar ratio of the precursor to the first solvent is 1: (1-10); and/or
The molar ratio of the intermediate to the second solvent is 1: (1-10).
10. The use of a ferrocene derivative metalloid organic complex as claimed in any one of claims 1 to 5 in the preparation of chiral alcohol compounds.
CN202110973993.0A 2021-08-24 2021-08-24 Ferrocene derivative metal organic complex and preparation method and application thereof Active CN113735914B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110973993.0A CN113735914B (en) 2021-08-24 2021-08-24 Ferrocene derivative metal organic complex and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110973993.0A CN113735914B (en) 2021-08-24 2021-08-24 Ferrocene derivative metal organic complex and preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN113735914A true CN113735914A (en) 2021-12-03
CN113735914B CN113735914B (en) 2023-05-12

Family

ID=78732573

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110973993.0A Active CN113735914B (en) 2021-08-24 2021-08-24 Ferrocene derivative metal organic complex and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN113735914B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100152448A1 (en) * 2007-07-11 2010-06-17 Pierluigi Rigo Ligands of the benzo [h] quinoline class and transition metal complexes containing them and use of said complexes as catalysts
CN107667093A (en) * 2015-06-03 2018-02-06 庄信万丰股份有限公司 Benzo [h] quinoline part and its complex compound

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100152448A1 (en) * 2007-07-11 2010-06-17 Pierluigi Rigo Ligands of the benzo [h] quinoline class and transition metal complexes containing them and use of said complexes as catalysts
CN101784526A (en) * 2007-07-11 2010-07-21 乌迪内大学 New benzo [h] quinoline part and contain the transition metal complex of this part and this complex compound as the purposes of catalyzer
CN107667093A (en) * 2015-06-03 2018-02-06 庄信万丰股份有限公司 Benzo [h] quinoline part and its complex compound

Also Published As

Publication number Publication date
CN113735914B (en) 2023-05-12

Similar Documents

Publication Publication Date Title
WO2012065571A1 (en) Chiral spiro-pyridylamidophosphine ligand compound, synthesis method therefor and application thereof
İmik et al. Synthesis and investigation of catalytic activity of phenylene–And biphenylene bridged bimetallic Palladium-PEPPSI complexes
CN112824422B (en) Chiral ferrocene-indole diphosphine ligand as well as preparation method and application thereof
Ruan et al. Catalytic Asymmetric Alkynylation and Arylation of Aldehydes by an H8‐Binaphthyl‐Based Amino Alcohol Ligand
CN112264105B (en) Supported palladium catalyst for synthesis of substituted ketone and bisphenol F
CN111718372B (en) Axial chiral phosphine-alkene ligand and preparation method and application thereof
CN113735914B (en) Ferrocene derivative metal organic complex and preparation method and application thereof
CN112920033A (en) Preparation method of o-alkynyl phenylcyclobutanone and preparation method of naphthalenone
Li et al. Practical allylation with unactivated allylic alcohols under mild conditions
JP3789508B2 (en) Optically active asymmetric diphosphine and method for obtaining optically active substance in the presence of the compound
JP6065259B2 (en) Method for producing optically active amines
CN112675920B (en) Mono-chiral center catalyst, preparation thereof and method for catalytically synthesizing chiral alcohol compound and chiral alpha-allyl alcohol
JP5208939B2 (en) 2,2 ', 6,6'-tetrasubstituted aminophosphine ligand and method for synthesis thereof
WO2017193288A1 (en) Synthesis of phosphine ligands bearing tunable linkage: methods of their use in catalysis
CN109666044B (en) Organophosphorus compound based on [2.2] p-cyclophane alkyl skeleton and intermediate, preparation method and application thereof
CN114539319B (en) Chiral phosphine-dicyclophosphoramidite ligand and preparation method and application thereof
CN113511984B (en) Preparation method and application of beta-azido acid and beta-amino acid compound
Fan et al. Rhodium catalyzed asymmetric Pauson-Khand reaction using SDP ligands
JP2005518339A (en) Process for producing enantiomerically rich N-acyl-β-amino acid derivatives by enantioselective hydrogenation of the corresponding (Z) enamide
CN112824424B (en) Chiral ferrocene-imidazole diphosphine ligand and synthesis method and application thereof
CN108997431B (en) Synthesis method and application of p-xylene glycol derived bidentate phosphite ligand
CN109776400B (en) Preparation method of (R) -phenyl (pyridine-2-yl) methanol derivative
CN115025814B (en) Universal chiral catalyst and preparation method thereof
EP2070903A1 (en) Microwave-assisted ring opening reaction
JP5081146B2 (en) Process for producing 1,2-phenylethane compounds using atom transfer radical coupling 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
GR01 Patent grant
GR01 Patent grant