WO2007105657A1 - Méthode de synthèse d'un composé oligomère par réaction de couplage croisé - Google Patents

Méthode de synthèse d'un composé oligomère par réaction de couplage croisé Download PDF

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WO2007105657A1
WO2007105657A1 PCT/JP2007/054729 JP2007054729W WO2007105657A1 WO 2007105657 A1 WO2007105657 A1 WO 2007105657A1 JP 2007054729 W JP2007054729 W JP 2007054729W WO 2007105657 A1 WO2007105657 A1 WO 2007105657A1
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group
compound
cross
boronic acid
coupling
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PCT/JP2007/054729
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Japanese (ja)
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Michinori Suginome
Kosho Hojo
Hiroyoshi Noguchi
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Kyoto University
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Priority to JP2008505123A priority Critical patent/JP4929468B2/ja
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    • 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
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
    • B01J31/2243—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
    • 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
    • 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
    • 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
    • B01J2531/847—Nickel

Definitions

  • the present invention relates to a novel method for synthesizing oligomeric compounds using a cross-coupling reaction. Specifically, the present invention relates to a method for precisely synthesizing a wide variety of oligomeric compounds using a reaction in which an organic boron compound and an organic halogen compound are cross-coupled in the presence of a Group 10 transition metal catalyst.
  • Conjugated aromatic oligomers are useful for functional material chemistry! It is a group of compounds that attract the most attention. Although conjugated aromatic oligomers have a small molecular weight, they can exhibit a conjugated length equivalent to that of the corresponding conjugated polymer, and can be imparted with new functions by precise molecular design. Therefore, it has great potential as various functional materials.
  • the properties of these compounds are synthetic methods that can faithfully reproduce the molecular design determined by the control of the degree of polymerization and the support of theoretical chemistry, which depends heavily on the type and number of functional groups incorporated in the monomer unit. Establishment is required. It is also desirable to develop a reaction system that can perform high-throughput rapid synthesis of many candidate compounds.
  • the Suzuki Ichiura coupling using palladium which is a Group 10 transition metal, as a catalyst is one of the most frequently used techniques in the synthesis of conjugated aromatic polymers.
  • a bifunctional monomer having both a boron moiety and a halogen moiety on an aromatic ring is used, and a polymer having a high degree of polymerization can be obtained by using an appropriate palladium catalyst (for example, non-patent documents 1 to 4). 3).
  • an organic boronic acid A and a bifunctional monomer B having both a boric acid moiety and a halogen moiety in the molecule are mixed with a conventional Suzuki-Minoura at a molar ratio of 1: 1.
  • Coupling When to conditions reaction will be homopolymers one B n of the polymer A- B n and B having an organic group derived from A to end to produce a wide molecular weight distribution, is not suitable for precise synthesis of co-oligomer.
  • Non-Patent Document l Chem. Rev. 1995, 95, 2457
  • Non-Patent Document 2 Polymer, 1989, 30, 1060.
  • Non-Patent Document 3 J. Polym. Sci. Part A: Polym. Chem., 2001, 39, 1533.
  • An object of the present invention is to provide a method for producing a highly versatile oligomer compound efficiently and precisely using a cross-coupling reaction having excellent versatility.
  • the present invention has shown that, for example, as shown in FIG. 2, the rogen-substituted arylboronic acid (B) is not affected by the palladium catalyst and is masked. After conversion to a compound ( ⁇ ′) having a modified boronic acid group (indicated by one B (M))
  • the compound ( ⁇ ') and the organic boronic acid compound ( ⁇ ) are cross-coupled with a palladium catalyst, followed by removing the masking group ( ⁇ ) on the boron to regenerate the boronic acid group, and further masking. It was found that an oligomer (A—B—C—D) having a single chemical structure and molecular weight can be precisely synthesized by reacting with a compound (C ′) having a boronic acid group and repeating this step. . As a result of further research based on this knowledge, the present invention has been completed.
  • the present invention provides the following oligomer compound production method and the like.
  • Item 1 A method for producing a cross-coupling compound, wherein a compound having a boronic acid group or a boronic acid ester group, a leaving group, and masking are performed in the presence of a group 10 transition metal catalyst.
  • a production method comprising cross-coupling a compound having a boronic acid group in a molecule.
  • a 1 and A 2 are the same or different, optionally substituted aromatic rings, optionally substituted heteroaromatic rings, or optionally substituted alkenes;
  • Y 2 Represents a divalent group coordinated with at least one nitrogen atom to a boron atom, and p represents an integer of 1 or more.
  • R 1 is the same or different and represents a hydrogen atom, an alkyl group or an aryl group or a group in which two R 1 are bonded to each other, and A 1 and p are the same as described above.
  • R 10 , R 11 R 2 °, R 21 , R 3 °, R 4 °, R 5 °, R 51 , R 6 °, R 61 , R 7 R 80 , R 9 ° and R 100 is the same or different and represents a hydrogen atom, an alkyl group, an alkyl group, an aryl group or an aralkyl group, R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 22 , R 23 , R 24 , R 25 , R 31 , R 32 , R 33 , R 34 , R
  • R 74, R 75, R 76, R 81, R 82, R 83 , R 84 , R 91 , R 92 , R 10 ⁇ R 102 , R 103 and R 104 are the same or different and each represents a hydrogen atom, an alkyl group or an aryl group, or two bonded to adjacent carbon atoms. Alkyl groups may be combined to form a ring. )
  • Item 3 The production method according to Item 2, which is a divalent group represented by:
  • R 10 , R n , R 12 , R 13 , R ′′, R 15 , R 16 and R 17 are the same as described above.
  • Item 4 The production method according to Item 3, which is a divalent group represented by:
  • Item 5 The production method according to any one of Items 2 to 4, wherein the Group 10 transition metal catalyst is a palladium catalyst or a nickel catalyst.
  • Item 6 is a norogen atom, TfO—, TsO—, MsO— or (R ′ O) P (0) 0— (wherein , R ′ represents a hydrogen atom or an alkyl group.
  • X 2 is a norogen atom, TfO—, TsO—, MsO— or (R ′ O) P (0) 0— (wherein , R ′ represents a hydrogen atom or an alkyl group.
  • Item 7 An aromatic ring which may be substituted by the same or different A 1 or A 2 or substituted !, may! /, Or a heteroaromatic ring. The manufacturing method as described.
  • Item 8 A method for producing a cross-coupling compound, comprising:
  • the manufacturing method characterized by including.
  • Item 9 A method for producing an oligomer compound, comprising:
  • the manufacturing method characterized by including.
  • Item 10 The method according to Item 9, wherein the step (i) and the step (ii) are repeated twice or more.
  • X 2 represents a leaving group
  • a 2 represents an optionally substituted aromatic ring, an optionally substituted heteroaromatic ring, or an optionally substituted alkene
  • Y 2 Is against the boron atom A divalent group coordinated by at least one nitrogen atom.
  • n represents an integer of 1 or more
  • Y n + 1 represents a divalent group coordinated with at least one nitrogen atom to the boron atom.
  • ⁇ represents an integer of 1 or more.
  • n represents an integer of 1 or more
  • R n + 1 is the same or different and is a hydrogen atom, an alkyl group or an aryl group, or two R n + 1 represents a bonded group, and p represents an integer of 1 or more.
  • X 2 represents a leaving group
  • a 2 represents an optionally substituted aromatic ring, an optionally substituted heteroaromatic ring, or an optionally substituted alkene
  • Y 2 represents a divalent group coordinated by at least one nitrogen atom to the boron atom.
  • a bidentate ligand compound having a coordination site of at least one nitrogen atom and a compound represented by the formula:
  • Item 15 A method for producing a cross-coupling compound, comprising a compound having a leaving group, a boronic acid group or a boronic ester group, and a masked boronic acid in the presence of a Group 10 transition metal catalyst.
  • a production method comprising cross-coupling with a compound having a group in a molecule.
  • a 1 and A 2 are the same or different and each represents an optionally substituted aromatic ring, an optionally substituted heteroaromatic ring, or an optionally substituted alkene;
  • Y 2 Represents a divalent group coordinated to a boron atom by at least one nitrogen atom, and q represents an integer of 1 or more.
  • R 1 is the same or different and is a hydrogen atom, an alkyl group or an aryl group, or a group in which two R 1 are bonded to each other, and A 2 and Y 2 are the same as above. )
  • Item 16 The production method according to Item 15, wherein the compound represented by the formula is cross-coupled.
  • R 10 , R 11 R 2 °, R 21 , R 3 °, R 4 °, R 5 °, R 51 , R 6 °, R 61 , R 7 °, R 8 °, R 9 ° and R 10 ° are the same or different and each represents a hydrogen atom, an alkyl group, an alkyl group, an aryl group or an aralkyl group.
  • R 74 , R 75 , R 76 , R 81 , R 82 , R 83 , R 84 , R 91 , R 92 , R 102 , R 103 and R 104 are the same or different and each represents a hydrogen atom, an alkyl group or an aryl group, or two alkyl groups bonded to adjacent carbon atoms are bonded to form a ring. Moyo. )
  • Item 17 The production method according to Item 16, which is a divalent group represented by:
  • Item 18 The production method according to Item 17, which is a divalent group represented by:
  • Item 19 The Item 15-18, wherein the Group 10 transition metal catalyst is a palladium catalyst or a nickel catalyst! The manufacturing method according to any of the above.
  • X 2 is a norogen atom, TfO—, TsO—, MsO— or (R ′ O) P (0) 0— (formula
  • R ′ represents a hydrogen atom or an alkyl group.
  • a 1 or A 2 are the same or different and is a an aromatic ring or a substituted also be substituted!, Be O, sections 16 to 20 is a heteroaromatic ring, according to any deviation Production method.
  • Item 22 A method for producing a cross-coupling compound, comprising:
  • the manufacturing method characterized by including.
  • Item 23 A method for producing an oligomeric compound comprising:
  • the manufacturing method characterized by including.
  • Item 24 The production method according to Item 23, wherein the cross-coupling compound obtained in the step (iii) is further used as a raw material in the step (ii).
  • a production method characterized by repeating the steps (ii) and (iii) two or more times.
  • R 1 is the same or different and is a hydrogen atom, an alkyl group or an aryl group, or a group in which two R 1 are bonded to each other, and A 2 is an optionally substituted fragrance.
  • a ring, an optionally substituted heteroaromatic ring, or an optionally substituted alkene, and Y 2 represents a divalent group coordinated by at least one nitrogen atom to the boron atom.
  • R 1 is the same or different and is a hydrogen atom, an alkyl group or an aryl group, or a group in which two R 1 are bonded to each other, and A 2 is an optionally substituted fragrance.
  • a ring, an optionally substituted heteroaromatic ring, or an optionally substituted alkene, and Y 2 represents a divalent group coordinated by at least one nitrogen atom to the boron atom.
  • R 1 is the same as defined above.
  • a production method comprising reacting a compound represented by the formula:
  • Item 27 A method for producing a cross-coupling compound, wherein a compound having a leaving group bonded to a solid phase carrier in the presence of a Group 10 transition metal catalyst, and a boronic acid group or a boronic acid ester group And a cross-coupling with a compound having a masked boronic acid group in the molecule.
  • P represents a solid phase carrier
  • Z represents —O— or —NH—
  • a 1 and A 2 are the same or different aromatic rings, which may be substituted, A heteroaromatic ring which may be substituted, or may be an alkene
  • Y 2 represents a divalent group coordinated by at least one nitrogen atom to a boron atom
  • q is 1 or more Indicates an integer.
  • R 1 is the same or different and is a hydrogen atom, an alkyl group or an aryl group, or a group in which two R 1 are bonded to each other, and A 2 and Y 2 are the same as above.
  • Item 28 The production method according to Item 27, wherein the compound represented by the formula is cross-coupled.
  • ⁇ represents a solid phase carrier
  • ⁇ represents — ⁇ — or — ⁇ —
  • ⁇ 2 are the same or different aromatic rings that may be substituted, which may be substituted.
  • Heteroaromatic ring, or substituted may represent an alkene
  • ⁇ 2 represents a divalent group coordinated with at least one nitrogen atom to the boron atom
  • q represents an integer of 1 or more Indicates.
  • —AB Y ⁇ +1 (lb)
  • P represents a solid phase carrier
  • Z represents —O— or —NH—
  • Ai A 11 may be the same or different, an optionally substituted aromatic ring, which may be substituted.
  • a heteroaromatic ring, or substituted, may represent an alkene
  • Y 2 represents a divalent group coordinated by at least one nitrogen atom to a boron atom
  • q is an integer of 1 or more Indicates.
  • Item 31 A method for producing a cross-coupling compound, comprising:
  • the manufacturing method characterized by including.
  • Item 32 A method for producing an oligomeric compound comprising:
  • the manufacturing method characterized by including.
  • Item 33 The production method according to Item 32, further comprising the solid phase obtained in the step (iii) A process for producing a cross-coupling compound combined with a carrier is used as a raw material in the step (ii), and the series of steps (ii) and (iii) is repeated twice or more.
  • Item 34 The production method according to Item 33, wherein the cross-coupling compound bound to the solid support obtained in the step (iii) is eliminated in the presence of a Group 10 transition metal catalyst.
  • a production method comprising removing a solid phase carrier after reacting with a compound having a group.
  • the oligomeric compound produced in the present invention has at least 2 selected from the group consisting of an optionally substituted aromatic ring, substituted !, a heteroaromatic ring, and a substituted alkene force.
  • the single bond is formed by a cross-coupling reaction using a group 10 transition metal.
  • n represents an integer of 1 or more
  • Y n + 1 represents a divalent group coordinated with at least one nitrogen atom to the boron atom.
  • ⁇ represents an integer of 1 or more.
  • ⁇ is not particularly limited as long as it is an integer of 1 or more.
  • ⁇ is an integer from 1 to 20
  • ⁇ is not particularly limited as long as it is an integer of 1 or more.
  • ⁇ is an integer of 1 to 6, and further an integer of 1 to 3.
  • the oligomer compound is represented by the general formula ( ⁇ ):
  • the aromatic ring of the optionally substituted aromatic ring represented by- +1 includes a single ring or a condensed ring of two or more rings, for example, a benzene ring, a naphthalene ring, an anthracene ring , Phenanthrene ring, fluorene ring and the like.
  • Examples of the substituent which may have a substituent on the aromatic ring include, for example, an alkyl group (for example, Cl to 10 alkyl group), an alkyl group (for example, C2 to 10 alkenyl).
  • -Alkyl group alkyl group (for example, C2-10 alkyl group), alkoxy group (for example, Cl-10 alkyloxy group), hydroxyl group, amino group, mono- or dialkylamino group, carboxyl group, alkoxycarbo -Group (for example, Cl to 10 alkoxy carbo group), cyan group, nitro group, group containing kaine (for example, trialkylsilyl group), acyl group (for example, acetyl group, formyl group), amino carbo- Group, aryl group (for example, phenyl group), heteroaryl group (for example, pyridyl group, pyrrolyl group, furyl group, etc.), group containing phosphorus atom (for example,
  • the monoheteroaromatic ring includes, for example, a pyridine ring, a pyrazine ring, a pyrimidine ring, a pyridazine ring, a pyrrole ring, an imidazole ring, a pyrazole ring, an isoxazole ring, an isothiazole ring, a thiophene ring, and a furan ring.
  • bicyclic heteroaromatic ring examples include benzofuran ring, isobenzofuran ring, indolizine ring, isoindole ring, indole ring, purine ring, isoquinoline ring, quinoline ring, phthalazine ring, naphthyridine ring, quinoxaline ring, A quinazoline ring, a cinnoline ring, etc. are mentioned.
  • tricyclic heteroaromatic ring examples include a phenanthridine ring, an atalidine ring, a phenantorin ring, and a phenazine ring.
  • Examples of the substituent which may have a substituent on the heteroaromatic ring include, for example, Alkyl groups (eg Cl-10 alkyl groups), alkyl groups (eg C2-10 alkyl groups), alkyl groups (eg C2-10 alkyl groups), alkoxy groups (eg C1 To 10 alkoxy groups), hydroxyl groups, amino groups, mono- or dialkylamino groups, carboxyl groups, alkoxy carb groups (for example, Cl to 10 alkoxy carbo groups), cyan groups, nitro groups, and groups containing silicon ( For example, trialkylsilyl group), acyl group (for example, acetyl group, formyl group), aminocarbonyl group, aryl group (for example, fullyl group), heteroaryl group (for example, pyridyl group, pyrrolyl group, furyl) Group), a group containing a phosphorus atom (for example, dialkylphosphino group, dialylphosphino group
  • the heteroaromatic ring may have 1 to 3 substituents selected from these groups.
  • the alkene of the optionally substituted alkene represented by A 1 to An + 1 is a C2 to 10 linear, branched or cyclic alkene.
  • the alkene may have one or two or more carbon-carbon double bonds, and when the double bond has a substituent, it is trans or cis, or E or Z. It may be a geometric isomer. When the double bond has two or more, the double bond may or may not be conjugated.
  • Examples of the chain alkene include ethylene, propene, butadiene and the like.
  • Examples of the cyclic alkene include cyclopentene, cyclohexene, cyclopentagen, cyclohexagen, cyclohexabutadiene and the like.
  • metal atoms metal atoms
  • Cyclic alkenes containing (boron atom, silicon atom, germanium atom, etc.) in the ring may be used, and examples thereof include silole (silacyclopentagen), bolol, and gelmol.
  • the alkene may have a substituent.
  • substituents include an alkyl group (for example, Cl to 10 alkyl group) and an alkenyl group (for example, C2 to 10 alkenyl). Group), an alkyl group (for example, C2-10 alkyl group), an alkoxy group (for example, Cl-10 alkoxy group), a hydroxyl group, an amino group, a mono- or dialkylamino group, a carboxyl group, an alkoxycarbon.
  • Groups for example, Cl to 10 alkoxy carbo groups), cyan groups, nitro groups , A group containing a cage (for example, a trialkylsilyl group), an acyl group (for example, an acetyl group, a formyl group), an aminocarbonyl group, an aryl group (for example, a phenyl group), a heteroaryl group (for example, a pyridyl group) , A pyrrolyl group, a furyl group, etc.), a group containing a phosphorus atom (for example, a dialkylphosphino group, a diarylphosphino group, a dialkylphosphoryl group, a diarylphosphoryl group, a dialkoxyphosphoryl group, a diallyloxy group) Phosphoryl group), a group containing a sulfur atom (for example, chenyl group, sulfo group, sulfino group, sulfeno group) and the
  • the size of type and n in the above-eight 11 "can be appropriately selected depending on applications for such oligomeric compounds produced. Further, ⁇ eight 11 Both connected by single bond However, the single bond usually has a carbon (sp 2 ) -carbon (sp 2 ) bond strength.
  • the divalent group that coordinates with the boron atom represented by Y n + 1 by at least one nitrogen atom has two nitrogen atoms that can coordinate with the boron atom.
  • R 74, R 75, R 76, R 81, R 82, R 83 , R 84 , R 91 , R 92 , R 10 ⁇ R 102 , R 103 and R 104 are the same or different and each represents a hydrogen atom, an alkyl group or an aryl group, or two bonded to adjacent carbon atoms. Alkyl groups may be combined to form a ring. )
  • R 10, R 11 R 2 ° , R 21, R 3 °, R 4 °, R 5 °, R 51, R 6 °, R 61, R 7 °, R 8 °, R 9 ° And R 10 ° are preferably a hydrogen atom, an alkyl group of Cl to 6 (for example, a methyl group, an ethyl group, or an isopropyl group), an alkenyl group of C2 to 10 (for example, a bur group, an aryl group, Crotyl group), C 6-10 aryl group (for example, phenol group, tolyl group) or C 7-10 aralkyl group (for example, benzyl group, phenethyl group).
  • an alkyl group of Cl to 6 for example, a methyl group, an ethyl group, or an isopropyl group
  • an alkenyl group of C2 to 10 for example, a bur group, an aryl group, Crotyl group
  • R 12 , R 13 , R ", R 15 , R 16 , R 17 , R 22 , R 23 , R 25 , R 31 , R 32 , R 33 , R 34 , R '', R 42 , R 43 , R 44 , R 52 , R 53 , R 54 , R 55 , R 62 , R 63 , R 64 , R 65 , R 66 , R 67 , R 71 , R 72 , R 73 , R 7 5, R 76, R 81, R 82, R 83, R 84, R 91, R 92, R 102 , R 103 and R 104 are preferably a hydrogen atom, an alkyl group (especially a methyl group) or a fur group of Cl to 6, or a formula (a,) to (!
  • spiro ring such as a cyclopentane ring or cyclopentane.
  • a ring, a cyclohexane ring, a cycloheptane ring or the like may be formed.
  • examples of the divalent group represented by (a ′) include those in which R 1C) and R 11 are the same or different and are a hydrogen atom or a methyl group.
  • R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are all exemplified by hydrogen atoms.
  • Examples of the divalent group represented by (b ') include those in which R 21 and R 3 are the same or different and are a hydrogen atom or a methyl group.
  • R 22 , R 23 , R 24 and R 25 are all hydrogen atoms, or R 22 and R 25 are hydrogen atoms and R 23 and R 24 carbyl groups are exemplified.
  • Examples of the divalent group represented by (c ') include those in which R 3G is a hydrogen atom or a methyl group. Further, R 31 , R 32 , R 33 and R 34 are all exemplified by hydrogen atoms.
  • Examples of the divalent group represented by (d ') include those in which R4G is a hydrogen atom or a methyl group. Further, R 41 , R 42 , R 43 and R 44 are all exemplified by hydrogen atoms.
  • Examples of the divalent group represented by (e ') include those in which R 5 and R 51 are a hydrogen atom, a methyl group or a phenyl group.
  • R 52 , R 53 , R 54 and R 55 are all hydrogen atoms, R 52 and R 54 are hydrogen atoms and R 53 and R 55 are phenol groups, or R 52 and R 55 Examples are those in which 54 forms a ring as — (CH 2) — and R 53 and R 55 are hydrogen atoms.
  • Examples of the divalent group represented by () include those in which R 6G and R 61 are a hydrogen atom or a methyl group.
  • Examples of R 62 , R 63 , R 64 , R 65 , R 66 and R 67 are all hydrogen atoms.
  • Examples of the divalent group represented by (g ') include those in which R 7 is a hydrogen atom or a methyl group.
  • R 71 , R 72 , R 73 , R 74 , R 75 and R 76 are all hydrogen atoms.
  • Examples of the divalent group represented by (h ') include those in which R 8 is a hydrogen atom or a methyl group.
  • R 81 , R 82 , R 83 and R 84 are all hydrogen atoms, or R 81 and R 82 are hydrogen atoms and R 83 and R 84 are methyl groups.
  • Examples of the divalent group represented by (1 ') include those in which R 9 is a hydrogen atom or a methyl group.
  • R 91 and R 92 are both hydrogen atoms.
  • Examples of the divalent group represented by ( ⁇ ) include those in which R 1CK) is a hydrogen atom or a methyl group.
  • R 10 ⁇ R 1G2 , R 1G3 and R 1G4 are all hydrogen atoms, all are methyl groups, or R 1G1 and R 1G2 are hydrogen atoms and R 1G3 and R 1G4 cation groups Is illustrated.
  • the divalent group represented by (a ′) is more preferred.
  • oligomer compound of the present invention include:
  • n represents an integer of 1 or more
  • Y n + 1 represents at least one nitrogen atom with respect to the boron atom, which may be the same or differently substituted aromatic ring, optionally substituted heteroaromatic ring, or optionally substituted alkene Represents a divalent group coordinated with q
  • q represents an integer of 1 or more.
  • n, ⁇ + 1 and Y n + 1 are the same as above.
  • q is not particularly limited as long as it is an integer of 1 or more.
  • q is an integer of 1 to 6, and further an integer of 1 to 3.
  • oligomer compound of the present invention include, for example, the general formula (lb):
  • ⁇ represents a solid phase carrier
  • ⁇ represents — ⁇ — or — ⁇ —
  • Ai A 11 may be the same or different aromatic ring, which may be substituted, or may be substituted.
  • Y n + 1 represents a divalent group coordinated by at least one nitrogen atom to a boron atom
  • q represents an integer of 1 or more. Show.
  • the compound represented by these is mentioned.
  • n The definitions of Y n + 1 and q are the same as above.
  • a compound having a boronic acid group or a boronic ester group in the presence of a group 10 transition metal catalyst, and a compound having a leaving group and a masked boronic acid group in the molecule is characterized by cross coupling.
  • step (i) and the step (ii) two or more times, a plurality of cross-force pulling reactions can be performed to extend the oligomeric compound.
  • steps (i) and (ii) once or twice or more, the chemical structure and molecular weight are uniform without forming a conventional homopolymer with a random degree of polymerization as shown in FIG. Oligomer compounds can be produced efficiently ( Figure 2).
  • n represents an integer of 1 or more
  • -+ 2 are the same or different, optionally substituted aromatic rings, optionally substituted heteroaromatic rings, or optionally substituted alkenes.
  • Y 2 to Y n + 1 are the same or different and represent a divalent group coordinated with at least one nitrogen atom to the boron atom
  • ⁇ 2 to ⁇ ⁇ + 2 are the same or different and are leaving groups ! ⁇ ⁇ "Is the same or different and is a hydrogen atom, an alkyl group or an aryl group, or a group in which two R's are bonded to each other, and ⁇ represents an integer of 1 or more.
  • -6 alkyl groups are exemplified, and examples of aryl groups include a phenyl group, a tolyl group, and the like. Is exemplified.
  • an alkylene group particularly a C2-6 alkylene group
  • a 1,2 diphenylene group and the like are exemplified.
  • the alkylene group include a divalent alkylene group obtained by removing two hydroxyl groups from a dihydric alcohol such as ethylene glycol, propylene glycol, and pinacol.
  • the group represented by the formula: —B iOR 1 ) or the formula: —B (OR n + 1 ) includes boron.
  • the leaving groups represented by X 2 to X n + 2 include halogen atoms (especially chlorine, bromine and iodine atoms), triflate (one OTf), tosylate (one OTs), mesylate (one OMs ), One OP (O) (OR ′) (wherein R ′ represents a hydrogen atom or an alkyl group).
  • halogen atoms especially chlorine, bromine and iodine atoms
  • triflate one OTf
  • tosylate one OTs
  • mesylate one OMs
  • One OP (O) OR ′
  • R ′ represents a hydrogen atom or an alkyl group
  • step (i) in the presence of a Group 10 transition metal catalyst, a compound having a boronic acid group or a boronic ester group is cross-coupled with a compound having a leaving group and a masked boronic acid group in the molecule.
  • a cross-coupling compound is obtained.
  • Examples of the compound having a boronic acid group or a boronic acid ester group include compounds represented by the general formula (1).
  • a powerful compound is good if it has at least one boronic acid group or boronic acid ester group (group represented by one B (OR 1 )) in the molecule.
  • this is a compound used as the base point of the oligomer compound of this invention.
  • This compound can be directly subjected to this reaction to extend an oligomer by a liquid phase method.
  • the oligomer can be extended by the solid phase method after binding and supporting the solid phase carrier using the functional group on A 1 .
  • the compound having a leaving group and a masked boronic acid group in the molecule may be represented by the general formula:
  • the compound shown by (2) is mentioned.
  • the powerful compound has a leaving group (X 2 ) and a boronic acid group masked with a divalent group (Y 2 ) in the molecule.
  • the leaving group (X 2 ) Of these, bromine atom, iodine atom, and OTf are preferable.
  • the divalent group (Y 2 ) masking the boronic acid group include any of the groups (a ′) to (; j ′) described above.
  • R a represents an alkyl group or an aryl group.
  • ⁇ and ⁇ are the same as those described above, and X 2 and the boron atom may be substituted with an offset carbon on the ring, respectively. ,.
  • Examples of the alkyl group represented by R a include Cl to 10 linear, branched or cyclic alkyl groups, and specifically include methyl, ethyl, propyl, isopropyl, butyl, isopropyl, sbutyl, pentyl, Hexyl, heptyl, octyl and the like are exemplified.
  • Examples of aryl groups include phenyl, tolyl, naphthyl, and anthryl. The above aromatic ring or heteroaromatic ring may have the above-mentioned substituents!
  • X 2 is preferably a bromine atom, an iodine atom, or —OTf. Particularly preferred is a bromine atom or an iodine atom.
  • Preferable Y 2 includes a divalent group represented by the above (a,), R 10 , R 11 , R 12 , R
  • R 14 , R 15 , R 16 and R 17 all derived from 1,8-diaminonaphthalene, which is a hydrogen atom, that is, the formula:
  • a compound having a leaving group and a masked boronic acid group in the molecule for example, a compound represented by the general formula
  • the compound having a leaving group and a masked boronic acid group in the molecule includes a compound having a boronic acid group and a bidentate ligand compound having a coordination site of at least one nitrogen atom. It can be produced by dehydration condensation with (masking compound).
  • the compound represented by the general formula (2) includes a compound having a boronic acid group represented by the general formula (2 ′) and the following general formulas (a) to (j): [0155] [Chemical 36]
  • any of the compounds represented by (masking compound) can be produced by reacting any of the compounds represented by (masking compound).
  • a catalyst for example, It can be produced by reacting in the presence of (para-toluenesulfonic acid).
  • the reaction can be carried out while removing water azeotropically using a Gene's Stark apparatus or the like. After completion of the reaction, it is purified by column chromatography, recrystallization, etc. to obtain the compound represented by the general formula (2).
  • the compounds represented by the general formulas (5), (8), (11), (14)... Can be produced in the same manner.
  • the compound represented by the general formula (2 ′) can be easily produced by those skilled in the art.
  • the Group 10 transition metal catalyst used in step (i) includes a palladium catalyst or a nickel catalyst.
  • the noradium catalyst is not particularly limited as long as it is a commonly used 0-valent or divalent catalyst.
  • palladium bromide, palladium chloride, palladium iodide, paradium cyanide, palladium acetate, palladium trifluoroacetate, Palladium cetylacetonate [Pd (acac)], diacetate bis (triphenylphosphine) palladium
  • Triphenylphosphine palladium [Pd (PPh)], dichloro [1,2-bis (diphenylphosphine)
  • a phosphine-based catalyst such as hum is preferred.
  • bis (tri tert-butylphosphine) paradium is preferable.
  • a palladium catalyst prepared from the above palladium catalyst and a ligand can also be used in the cross-coupling reaction system.
  • the ligand include triphenylphosphine, trimethylphosphine, triethylphosphine, tri (n-butyl) phosphine, tri (tert-butyl) phosphine, di (tert-butyl) methylphosphine, tri (i-propyl).
  • Phosphine tricyclohexylphosphine, tri (o-tolyl) phosphine, tri (2-furyl) phosphine.
  • phosphines such as Pd (OAc), Pd (dba), Pd (dba)
  • a phosphine ligand such as palladium catalyst and tri (tert-butyl) phosphine, (2-biphenyl) dicyclohexylphosphine, certain! /, Or triphenylphosphine is preferable.
  • the nickel catalyst is not particularly limited as long as it is a normally used 0-valent or divalent catalyst.
  • a normally used 0-valent or divalent catalyst for example, [NiCl (dppf) + BuLi (reducing agent)], [NiCl (dppf)], [ NiCl (dppe
  • IMes is a compound shown below.
  • the amount of the Group 10 transition metal catalyst used is the amount of the raw material boronic acid group or boronic acid ester group.
  • the compound (compound represented by the general formula (1)) is about 0.0001 to 1 mol, preferably about 0.001 to 0.5 mol, more preferably about 0.001 to 0 mol, per 1 mol of the compound. 2 It is about mono.
  • the amount of the ligand used is determined by the amount of the compound having a boronic acid group or a boronic ester group as a raw material (represented by the general formula (1)).
  • the compound is about 0.0001 to 1 mol, preferably about 0.001 to 0.5 mol, and more preferably about 0.001 to 0.2 mol with respect to 1 mol.
  • the amount of the ligand used may be about 1 to 10 mol, preferably about 1 to 4 mol, per 1 mol of Group 10 transition metal atom in the catalyst.
  • an active agent for boron atom is added.
  • the boron atom activator is not particularly limited as long as it is a reagent capable of forming an art complex on boron in the Suzuki-Kajiura cross-coupling reaction.
  • potassium fluoride, cesium fluoride, sodium hydroxide examples include potassium hydroxide, sodium methoxide, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, and potassium phosphate.
  • they are cesium fluoride, cesium carbonate, or potassium phosphate.
  • the amount of the boron atom activator used is 0.5 to 5.0 moles with respect to 1 mole of the compound having the boronic acid group or boronic ester group of the raw material (the compound represented by the general formula (1)).
  • the degree is preferably about 1.0 to 3.0 moles.
  • the reaction solvent for the cross-coupling reaction is not particularly limited as long as it does not affect the reaction, as long as it is appropriately selected depending on the type of catalyst, the type of raw material compound, and the like.
  • water aromatic hydrocarbons such as toluene, xylene and benzene; esters such as methyl acetate, ethyl acetate and butyl acetate; ethers such as jetyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diisopropyl ether
  • Halogenated hydrocarbons such as methyl chloride, chloroform, dichloromethane, dichloroethane and dibromoethane
  • Ketones such as acetone and methylethylketone
  • Amides such as dimethylformamide and dimethylacetamide
  • Toryls alcohols such as methanol, ethanol, isopropyl alcohol; dimethyl sulfoxide and the like.
  • the reaction temperature for this reaction can be usually about 0 to 120 ° C, preferably about 20 to 80 ° C. If the reaction temperature is too high, it is difficult to control the reaction, and if the reaction temperature is too low, the reaction rate becomes slow.
  • the reaction time varies depending on the reaction temperature, reaction substrate, type 10 transition metal catalyst, and the like, and is usually 1 minute to 24 hours, preferably 10 minutes to 3 hours. Reaction time is significantly shortened by irradiation with ultrasonic waves and microwaves.
  • the crude product is purified using a known purification means such as column chromatography or recrystallization to obtain a cross-coupling compound (for example, a compound represented by the general formula (3)).
  • a cross-coupling compound for example, a compound represented by the general formula (3).
  • the other step (i) shown in the reaction scheme can also be reacted in the same manner as described above.
  • step (ii) the masking group of the boronic acid group is removed from the cross-coupling compound obtained in (i) above, and the cross-coupling compound having a boronic acid group or a boronic acid ester group is removed. Get things. Further, this is provided as a raw material for the step (i).
  • the masking group (Y 2 ) of the boronic acid group can usually be removed by solvolysis in the presence of an acid. Specifically, it can be carried out by treating the compound represented by the general formula (3) with an acid in a solvent.
  • acids include protic acids such as sulfuric acid, hydrochloric acid, nitric acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid, and Lewis acids such as zinc chloride, silyl triflate, aluminum chloride, titanium tetrachloride, and tetraisopropoxy titanium. An acid etc. are mentioned.
  • Solvolysis can usually be carried out at room temperature (about 10-30 ° C) for about 1-5 hours.
  • the masked boronic acid group is usually hydrolyzed and converted to a boronic acid group by reacting in a solvent containing water in the presence of an acid. Further, the masked boronic acid group does not contain water, and is reacted with an alcohol (corresponding to the above-mentioned RH) in the presence of an acid in the reaction system to cause alcoholysis and to generate a boronic acid group derived from the alcohol. Converted to an ester group. For example, when a masked boronic acid group is reacted with an acid in methanol, a boronic acid dimethyl ester group (—B (OMe)) is obtained, and a diazo such as pinacol is obtained.
  • a boronic acid dimethyl ester group —B (OMe)
  • the boronic acid pinacol ester group (one B (pin)) is obtained.
  • the crude product is purified using a known purification means such as column chromatography. Then, a cross-coupling compound (for example, a compound represented by the general formula (4)) having a boronic acid group or a boronic ester group is obtained. This restores the reactivity of the Group 10 transition metal catalyst.
  • a cross-coupling compound for example, a compound represented by the general formula (4)
  • the masking compound (for example, the compounds represented by the general formulas (a) to (j)) removed by the solvolysis is a cross-coupled having a boronic acid group or a boronic ester group.
  • the aqueous layer can be recovered by separating it from the aqueous phase by making the aqueous layer basic or by adjusting the pH to a predetermined value with a buffer solution.
  • the masking compound is a compound represented by the general formula (a) (particularly 1,8-diamineaminophthalene)
  • the desired compound represented by the general formula (4) is recovered after the recovery.
  • the aqueous layer can be recovered by making it basic (for example, NaOH aqueous solution).
  • the recovered masking compound can be used, for example, as a raw material for producing a compound represented by the formula (5), (8), (11), (14) or the like.
  • the obtained cross-coupling compound (for example, the compound represented by the general formula (4)) having a boronic acid group or a boronic acid ester group is a Group 10 transition metal catalyst of the above step (i). It can be used for the cross-coupling step.
  • the coupling partner is a compound having a leaving group and a masked boronic acid group in the molecule (for example, a compound represented by the general formula (5)). It may be the same as or different from the compound used (for example, the compound represented by the general formula (2)).
  • the production method can be produced by reacting the corresponding compound having a boronic acid group with any one of the general formulas (a) to (j) as described in the above step (i).
  • the cross-coupling reaction and the removal of the masking group are repeated to extend the carbon-carbon bond, and the oligomeric compound has a uniform chemical structure.
  • the compound represented by the general formula (I) is produced by performing the above steps (i) and (ii) n times (n is an integer of 1 or more, particularly an integer of 2 or more).
  • the resulting oligomeric compound represented by the general formula (I) is subjected to solvolysis using the general formula: R n + 1 OH in the same manner as in the above step (ii) to give the general formula (II It can also be an oligomeric compound represented by
  • the oligomer compound represented by the general formula (II) is subjected to a cross-coupling reaction with the compound represented by the general formula (15).
  • the oligomeric compound represented can be obtained.
  • a n + 2 has the same meaning as A n + 2, and may be the same or different! /.
  • a homooligomer can be produced if the structure of the compound having a leaving group and a masked boronic acid group in the molecule is the same in each repeating step.
  • a co-oligomer can be produced by changing the structure of the compound (for example, by changing the compound represented by the formula (5), (8), (11), (14), etc.). In this way, various oligomer compounds can be synthesized. For example, see Figure 3.
  • Solid phase synthesis refers to a method of synthesizing a compound on a solid phase carrier by binding the compound on a solid phase carrier (mainly polystyrene resin: particles of 100 to 500 mesh). Since the carrier is insoluble in the solvent, the reagent after the reaction can be removed simply by washing with the solvent, and the target compound remains on the carrier. That is, the post-reaction after reaction is simple, there is no need for purification of intermediates, and there are many advantages compared to the conventional liquid phase synthesis where the synthesis speed is high. By applying the production method of the present invention to solid phase synthesis, automatic synthesis becomes extremely easy.
  • a 1 of the compound represented by the formula (1) which is the raw material compound of the present invention, is bound to a predetermined solid phase carrier, and the cross-coupling and unmasking group of the present invention are repeated. , to extend the oligomeric compounds on a solid support followed by cutting the solid phase carrier and a 1, it can be prepared oligomeric compound.
  • a compound having a leaving group in the presence of a group 10 transition metal catalyst, a compound having a boronic acid group or a boronic acid ester group and a masked polonic acid group in the molecule Is cross-coupled.
  • a cross-coupling compound having a boronic acid group or a phosphonic acid ester group obtained in (ii) above in the presence of a Group 10 transition metal catalyst, a leaving group and a masked boron A step of cross-coupling with a compound having a ronic acid group in the molecule to obtain a cross-coupling compound.
  • the cross-coupling compound obtained in the step (iii) is used as a raw material in the step (ii), and the series of the steps (ii) and (iii) is performed twice.
  • an oligomeric compound extended by the coupling reaction can be obtained.
  • an oligomer compound having a uniform chemical structure and molecular weight can be efficiently produced.
  • the leaving group represented by X includes halogen atoms (especially chlorine, bromine and iodine atoms), triflate (one OTf), tosylate (one OTs), mesylate (one OMs), one OP (O) ( OR ') (where R'
  • 2 represents a hydrogen atom or an alkyl group. ) And the like. Preferred are bromine atom, iodine atom, and OTf.
  • Examples of the compound having a leaving group include compounds represented by the general formula (la). Are either commercially available or can be readily produced by those skilled in the art.
  • Examples of the compound having a boronic acid group or a boronic acid ester group and a masked boronic acid group in the molecule include compounds represented by the general formula (2a). This is because a compound having a leaving group and a masked boronic acid group used as raw materials in step (i) of the first method in the presence of a group 10 transition metal catalyst (for example, in the general formula (2) And a bisboronic acid ester compound (compound represented by the general formula (20)) or a hydroboronic acid ester compound (compound represented by the general formula (21)). I'll do it.
  • reaction conditions a known method can be employed.
  • the compound represented by the general formula (2) is added to a compound (dioxane, etc.), a palladium catalyst (Pd (dba), etc.), a base ( Potassium acetate, etc.)
  • a compound having a leaving group (a compound represented by the general formula (la)) and a compound having a boronic acid group or a boronic acid ester group and a masked boronic acid group (represented by the general formula (2a)).
  • a compound having a leaving group (a compound represented by the general formula (la)) and a compound having a boronic acid group or a boronic acid ester group and a masked boronic acid group (represented by the general formula (2a)).
  • step (i) of the first method can be carried out in the same manner or in accordance with step (i) of the first method.
  • purification is performed using a known purification means to obtain a cross-coupling compound (compound represented by the general formula (3a)).
  • the resulting cross-coupling compound (compound represented by the general formula (3a)) is obtained by removing the boronic acid group masking group and having a boronic acid group or a boronic acid ester group.
  • the step of obtaining (the compound represented by the general formula (4a)) can be carried out in the same manner or according to the step (ii) of the first method.
  • a cross-coupling compound (compound represented by the general formula (4a)) having a boronic acid group or a boronic ester group, a leaving group, and a maskin A compound (a compound represented by the general formula (5)) having a bonded boronic acid group in the molecule.
  • the step of obtaining a cross-coupling compound by the coupling can be carried out in the same manner as or similar to step (i) of the first method.
  • oligomer compound can be produced.
  • the compound represented by the general formula (la) is produced by performing the steps (ii) and (iii) n times (n is an integer of 1 or more, particularly an integer of 2 or more).
  • the resulting oligomer compound represented by the general formula (la) is subjected to solvolysis using the general formula: R n + 1 OH in the same manner as in the above step (ii) to give the general formula (Ila) It can also be an oligomer compound represented by In the same manner as in the above step (i), the oligomer compound represented by the general formula (Ila) is subjected to a cross-coupling reaction with the compound represented by the general formula (15). The oligomeric compound represented can be obtained.
  • a homo-oligomer can be produced if the structure of the compound having a leaving group and a masked boronic acid group in the molecule is the same in each repeating step.
  • a co-oligomer can be produced by changing the structure of the compound (for example, by changing the compound represented by the formula (5), (8), (11), (14), etc.). In this way, various oligomer compounds can be synthesized.
  • Solid phase synthesis refers to a method of synthesizing a compound on a solid phase carrier by binding the compound on a solid phase carrier (mainly polystyrene resin: particles of 100 to 500 mesh). Since the carrier is insoluble in the solvent, the reagent after the reaction can be removed simply by washing with the solvent, and the target compound remains on the carrier. That is, the post-reaction after reaction is simple, there is no need for purification of intermediates, and there are many advantages compared to the conventional liquid phase synthesis where the synthesis speed is high. By applying the production method of the present invention to solid phase synthesis, automatic synthesis becomes extremely easy.
  • a 1 of the compound represented by the formula (la), which is the raw material mixture of the present invention, is converted into a predetermined solid.
  • the oligomeric compound is produced by extending the oligomeric compound on the solid phase carrier by repeating the cross-coupling and unmasking group of the present invention by binding to the phase carrier and then cleaving the solid phase carrier. Can do.
  • P represents a solid phase carrier
  • Z represents —O— or —NH—
  • Ai A 11 may be the same or different, optionally substituted aromatic ring, optionally substituted.
  • ⁇ 2 to ⁇ ⁇ + 1 represents a divalent group coordinated with at least one nitrogen atom to the boron atom
  • 1 ⁇ to + 1 is the same or different and is a hydrogen atom
  • R represents an alkyl group
  • q represents an integer of 1 or more.
  • Examples of the solid phase represented by P include polystyrene and polystyrene Z polyethylene glycol copolymer.
  • Wang resin, Wang-PEG regin (all manufactured by Watanabe Chemical Co., Ltd.), ArgoGel-Wang, ArgoPore (all manufactured by Argonaut Co.), etc. are easily available as commercial products.
  • Examples of the alkyl group represented by R include Cl-3 alkyl groups such as methyl and ethyl.
  • step (i) in the presence of a Group 10 transition metal catalyst, a compound having a leaving group bonded to a solid support (a compound represented by the general formula (lb)), a boronic acid group or a boronic ester group, and A cross-coupling compound (general formula (2)) bonded to a solid support by cross-coupling with a compound having a masked boronic acid group in the molecule (compound represented by general formula (2a)).
  • a compound represented by 3b) is obtained.
  • This step can be performed in the same manner as or similar to step (i) of the first method.
  • step (ii) the cross-coupling compound (compound represented by general formula (3b)) obtained in (i) above is removed.
  • the boronic acid group masking group is removed and bound to the solid support.
  • a cross-coupling compound (compound represented by the general formula (4b)) having a boronic acid group or a boronic acid ester group is obtained. This step can be performed in the same manner or according to step (ii) of the first method.
  • a cross-coupling compound having a boronic acid group or a boronic ester group bonded to the solid phase carrier obtained in (ii) above (general formula (4b) Compound) and a compound having a leaving group and a masked boronic acid group in the molecule (compound represented by the general formula (5)) were cross-coupled and bound to a solid phase carrier.
  • a cross-coupling compound (compound represented by the general formula (6b)) is obtained. This step can be carried out in the same manner or according to step (i) of the first method.
  • a cross-coupling compound (compound represented by the general formula (6b)) bound to the solid support obtained in the step (iii) is used as a raw material in the step (ii).
  • the series of steps (ii) and (i ii) can be repeated twice or more.
  • the resulting cross-coupling compound bound to the solid phase carrier represented by the general formula (lb) is obtained using the general formula: R n + 1 OH in the same manner as in the above step (ii). It can also be solvolyzed to give an oligomer compound bound to a solid phase carrier represented by the general formula (lib).
  • the oligomeric compound bound to the solid phase carrier represented by the general formula (lib) is subjected to a cross-coupling reaction with the compound represented by the general formula (15) in the same manner as in the above step (i), and the general formula (15) It is possible to obtain an oligomeric compound bound to a solid phase carrier represented by Illb).
  • An oligomer compound represented by (IVb) is obtained.
  • the method for removing the solid phase carrier is not particularly limited. A known method can be adopted.
  • Z is a group represented by —O—
  • the ester is hydrolyzed with an aqueous alkali metal solution, and then (trimethylsilyl) diazomethane (TMSCHN) or the like is added.
  • TMSCHN trimethylsilyl diazomethane
  • an oligomer compound By converting into an oligomer compound, an oligomer compound can be obtained.
  • an oligomer compound bonded between sp 2 carbons can be synthesized easily and precisely.
  • the production method of the present invention includes pharmaceuticals, dyes, pigments, catalysts, organic semiconductor materials for organic transistors (oligothiophene compounds, etc.), organic light-emitting materials including those for organic EL, electron transport material for organic EL, organic solar It is extremely useful for the synthesis of oligomeric compounds that are useful as various functional materials such as batteries, liquid crystal molecular materials, conductive materials, nonlinear optical materials, and optical filters. It is also useful as a tool for searching for further functional materials.
  • an oligomeric compound can be produced efficiently and precisely using the Suzuki Ichinomiyaura cross-coupling reaction having excellent versatility.
  • oligomeric (polymer) compounds with a single molecular weight and high selectivity.
  • it is a manufacturing method suitable for precision synthesis using an automatic synthesizer, and various functional materials can be adjusted at low cost and in large quantities. And can be developed in various fields.
  • Figure 1 Shows a method for synthesizing oligomeric compounds using the conventional Suzuki-Kajiura cross coupling.
  • FIG. 2 shows a method for synthesizing oligomeric compounds using the Suzuki-Kajiura cross coupling of the present invention.
  • FIG. 3 shows production examples of homo-oligomer compounds and co-oligomer compounds using the production method of the present invention.

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Abstract

La présente invention concerne une méthode permettant d'obtenir de façon efficace et précise un composé oligomère par réaction de couplage croisé de Suzuki-Miyaura, ladite méthode étant très polyvalente. Cette méthode de production d'un composé oligomère est caractérisée en ce qu'elle inclut : une étape (i) dans laquelle un composé portant un groupement acide borique ou un groupement ester borique et un composé portant un groupement partant et un groupement acide borique masqué sont soumis à couplage croisé en présence d'un catalyseur de métal de transition du Groupe 10 pour obtenir un produit de couplage croisé ; et une étape (ii) dans laquelle le groupement masquant du groupement acide borique est éliminé du produit de couplage croisé obtenu en (i) ci-avant pour obtenir un produit de couplage croisé portant un groupement acide borique ou un groupement ester borique, ce composé étant soumis au titre de produit de départ à l'étape (i).
PCT/JP2007/054729 2006-03-10 2007-03-09 Méthode de synthèse d'un composé oligomère par réaction de couplage croisé WO2007105657A1 (fr)

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CN102086179B (zh) * 2009-12-07 2013-04-17 温州大学 一种联芳基化合物的合成方法
JP2013527858A (ja) * 2010-03-31 2013-07-04 中国石油化工股▲ふん▼有限公司 エチレンのオリゴマー化のための触媒組成物およびオリゴマー化のプロセス
JP2014189647A (ja) * 2013-03-27 2014-10-06 Orient Chemical Industries Co Ltd チエノチオフェン−ベンゾジチオフェン共重合体の製造方法
WO2015024938A1 (fr) * 2013-08-20 2015-02-26 Saudi Basic Industries Corporation Procédé de préparation de ligands 2,2'-bis-indényl biphényle et de leurs complexes métallocènes
JP2015168671A (ja) * 2014-03-10 2015-09-28 学校法人明治大学 有機ホウ素化合物及びその製造方法

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JP2012530739A (ja) * 2009-06-26 2012-12-06 プライム ユーロピアン テラペウティカルズ ソシエタ ペル アチオニ アリールピリジニル化合物の調製方法
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JP2013527858A (ja) * 2010-03-31 2013-07-04 中国石油化工股▲ふん▼有限公司 エチレンのオリゴマー化のための触媒組成物およびオリゴマー化のプロセス
JP2014189647A (ja) * 2013-03-27 2014-10-06 Orient Chemical Industries Co Ltd チエノチオフェン−ベンゾジチオフェン共重合体の製造方法
WO2015024938A1 (fr) * 2013-08-20 2015-02-26 Saudi Basic Industries Corporation Procédé de préparation de ligands 2,2'-bis-indényl biphényle et de leurs complexes métallocènes
CN105452260A (zh) * 2013-08-20 2016-03-30 沙特基础工业公司 制备2,2’-双-茚基联苯配体和它们的茂金属络合物的方法
JP2016531125A (ja) * 2013-08-20 2016-10-06 サウディ ベーシック インダストリーズ コーポレイション ２，２’−ビスインデニルビフェニル配位子の調製方法およびそのメタロセン錯体
US9828447B2 (en) 2013-08-20 2017-11-28 Saudi Basic Industries Corporation Process for the preparation of 2,2′-bis-indenyl biphenyl ligands and their metallocene complexes
EA032159B1 (ru) * 2013-08-20 2019-04-30 Сауди Бейсик Индастриз Корпорейшн Способ получения 2,2'-бис-инденилбифенильных лигандов и их металлоценовых комплексов
JP2015168671A (ja) * 2014-03-10 2015-09-28 学校法人明治大学 有機ホウ素化合物及びその製造方法

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