WO2024219367A1 - Procédé de production de dérivés d'aryldiadamantylphosphine et procédé de production de dérivés de sel d'aryldiadamantylphosphonium - Google Patents

Procédé de production de dérivés d'aryldiadamantylphosphine et procédé de production de dérivés de sel d'aryldiadamantylphosphonium Download PDF

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WO2024219367A1
WO2024219367A1 PCT/JP2024/015030 JP2024015030W WO2024219367A1 WO 2024219367 A1 WO2024219367 A1 WO 2024219367A1 JP 2024015030 W JP2024015030 W JP 2024015030W WO 2024219367 A1 WO2024219367 A1 WO 2024219367A1
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夏博 佐野
健 田村
恵里 古井
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Nippon Chemical Industrial Co Ltd
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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
    • B01J31/24—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
    • 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
    • B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
    • B01J37/04—Mixing
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds

Definitions

  • the present invention relates to a method for producing an aryldiadamantylphosphine derivative and a method for producing an aryldiadamantylphosphonium salt derivative.
  • Buchwald phosphine ligands include biarylphosphines such as t-BuBrettPhos, RockPhos, BrettPhos, and XPhos.
  • XPhos is a ligand with the structure shown in the following chemical formula (A).
  • AmPhos shown in the following chemical formula (B), is widely known as a ligand for catalysts used in the Suzuki-Miyaura cross-coupling reaction of aryl halides.
  • All of these ligands are phosphine derivatives that have an aryl skeleton and two bulky groups on the phosphorus atom bonded to the aryl skeleton.
  • the adamantyl group is known to be a bulky group, and compared to the t-butyl group, the adamantyl group has a greater electron donating ability, so it is expected that introducing this onto the phosphorus atom will also increase catalytic activity.
  • Non-Patent Document 1 reports that a palladium complex having a ligand, a compound represented by the following chemical formula (C), which has an aryl skeleton and two adamantyl groups as bulky groups on the phosphorus atom, exhibits excellent catalytic activity in cross-coupling reactions and Buchwald-Hartwig reactions.
  • Non-Patent Document 1 proposes a method in which a bromo compound (C1) is reacted with di-1-adamantylphosphine (C2) in the presence of a palladium catalyst (C3) according to the following reaction scheme 1.
  • Non-Patent Document 1 uses a palladium catalyst, it is difficult to remove the palladium catalyst after the reaction, and it is difficult to use this reaction in fields where contamination with palladium metal or the inclusion of palladium in subsequent reactions is undesirable.
  • palladium catalysts are expensive, so this method is not industrially advantageous.
  • an object of the present invention is to provide a method for producing an aryldiadamantylphosphine derivative, in which a diadamantylphosphino group (-P(Ad) 2 ) is introduced into a compound having an aryl skeleton, in a high yield in an industrially advantageous manner without using a palladium catalyst.
  • a bromo compound having an aryl skeleton is lithiated with an alkyllithium and the resulting lithiated product is reacted with diadamantylchlorophosphine, thereby obtaining the desired aryldiadamantylphosphine derivative in high yield without using a palladium catalyst, thereby completing the present invention.
  • the first invention to be provided by the present invention is a method for producing an aryldiadamantylphosphine derivative represented by the following general formula (1): A first step of reacting a bromo compound represented by the following general formula (2) with an alkyl lithium to obtain a lithiated product; and then a second step of reacting the obtained lithiated product with a diadamantylchlorophosphine represented by the following general formula (3).
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • A represents a group selected from an aryl group and a heteroaryl group, and the aryl group and the heteroaryl group may have a substituent.
  • Ad has the same meaning as in general formula (1) above.
  • the second invention provided by the present invention is a method for producing an aryldiadamantylphosphonium salt derivative represented by the following general formula (6), which comprises a third step of reacting an aryldiadamantylphosphine derivative represented by the following general formula (1) with a boric acid compound represented by the following general formula (5).
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • A represents a group selected from an aryl group and a heteroaryl group, and the aryl group and the heteroaryl group may have a substituent.
  • R6 represents a halogen atom, an aryl group, or an aryl heterocyclic group, and the aryl group and the aryl heterocyclic group may have a substituent.
  • the third invention to be provided by the present invention is a method for producing an aryldiadamantylphosphine derivative represented by the following general formula (1), which includes a fourth step of neutralizing an aryldiadamantylphosphonium salt derivative represented by the following general formula (6) with a base.
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • A represents a group selected from an aryl group and a heteroaryl group, and the aryl group and the heteroaryl group may have a substituent.
  • R6 represents a halogen atom, an aryl group, or an aryl heterocyclic group, and the aryl group and the aryl heterocyclic group may have a substituent.
  • the fourth invention that the present invention provides is an aryldiadamantylphosphine derivative represented by the following general formula (1A):
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • R7 represents a linear or branched alkyl group having 1 to 8 carbon atoms.
  • the fifth invention that the present invention provides is an aryldiadamantylphosphonium salt derivative represented by the following general formula (6A):
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • R7 represents a linear or branched alkyl group having 1 to 8 carbon atoms.
  • an aryldiadamantylphosphine derivative which is useful as a ligand for a coupling reaction catalyst, and in which a diadamantylphosphine group (-P(Ad) 2 ) is introduced into a compound having an aryl skeleton, can be produced in high yield by an industrially advantageous method without using a palladium catalyst.
  • the present invention is a method for producing an aryldiadamantylphosphine derivative represented by the following general formula (1).
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • A represents a group selected from an aryl group and a heteroaryl group, and the aryl group and the heteroaryl group may have a substituent.
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group.
  • the substituent in the substituted adamantyl group represents a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • alkyl group having 1 to 4 carbon atoms examples include linear or branched alkyl groups having 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, and n-butyl.
  • alkoxy group having 1 to 4 carbon atoms examples include linear or branched alkoxy groups having 1 to 4 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, and n-butoxy.
  • A represents a group selected from an aryl group and a heteroaryl group.
  • aryl group examples include a phenyl group, a naphthyl group, an anthracene group, a phenanthrene group, a biphenyl group, a terphenyl group, a pyrene group, a perylene group, and a triphenylene group.
  • heteroaryl group examples include sulfur-containing heteroaryl groups such as thiophenyl, thienylenyl, benzothienyl, dibenzothienyl, phenylenedibenzothienylenyl, and dibenzothienylenylphenyl; oxygen-containing heteroaryl groups such as furanyl, benzofuranyl, dibenzofuranyl, phenyldibenzofuranyl, and dibenzofuranylphenyl; nitrogen-containing heteroaryl groups such as pyridyl, pyridylenyl, pyrimidinyl, pyrazyl, quinolyl, isoquinolyl, carbazolyl, 9-phenylcarbazolyl, acridinyl, quinazolyl, quinoxalyl, 1,6-naphthyridinyl, 1,8-naphthyridinyl, and porphyrin; and heteroaryl groups containing two
  • the aryl group and heteroaryl group may have a substituent.
  • substituents include a linear or branched alkyl group having 1 to 24 carbon atoms, a linear or branched alkoxy group having 1 to 24 carbon atoms, a cycloalkyl group having 3 to 24 carbon atoms, a cycloalkyloxy group having 3 to 24 carbon atoms, an alkenyl group having 1 to 24 carbon atoms, an alkynyl group having 1 to 24 carbon atoms, an aryl group having 5 to 24 carbon atoms, an aryloxy group having 5 to 24 carbon atoms, a heteroaryl group having 4 to 24 carbon atoms, an acyl group having 1 to 24 carbon atoms, an amino group having 1 to 24 carbon atoms, a halogeno group, a cyano group, and a nitro group.
  • the hydrogen atoms of these substituents may be further substituted with a halogeno group.
  • halogeno group examples include a fluoro group, a chloro group, a bromo group, and an iodo group.
  • Examples of the linear or branched alkyl group having 1 to 24 carbon atoms include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, a pentyl group, a hexyl group, and an octyl group.
  • Examples of the linear or branched alkoxy group having 1 to 24 carbon atoms include a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a tert-butoxy group, a pentyloxy group, a hexyloxy group, and an octyloxy group.
  • Examples of the cycloalkyl group having 3 to 24 carbon atoms include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
  • the cycloalkyl group may also contain a heteroatom such as S or N.
  • Examples of the cycloalkyloxy group having 3 to 24 carbon atoms include a cyclopropyloxy group, a cyclobutyloxy group, a cyclopentyloxy group, and a cyclohexyloxy group.
  • the cycloalkyloxy group may also contain a heteroatom such as S or N.
  • alkenyl group having 1 to 24 carbon atoms examples include an ethenyl group, a propenyl group, a butenyl group, a pentenyl group, a hexenyl group, and an octenyl group.
  • alkynyl group having 1 to 24 carbon atoms examples include an ethynyl group, a propynyl group, a butynyl group, a pentynyl group, a hexynyl group, and an octynyl group.
  • Examples of the aryl group having 5 to 24 carbon atoms include a phenyl group, a naphthyl group, and a biphenyl group.
  • Examples of the aryloxy group having 5 to 24 carbon atoms include a phenoxy group, a naphthyloxy group, and a biphenyloxy group.
  • heteroaryl group having 4 to 24 carbon atoms examples include a thiophenyl group, a furanyl group, a carbazole group, a benzothiophenyl group, a benzofuranyl group, an indolyl group, a pyrrolyl group, and a pyridyl group.
  • acyl group having 1 to 24 carbon atoms examples include an acetyl group, a propionyl group, a butanoyl group, a pentanoyl group, a heptanoyl group, and groups in which the carbonyl group contained in the acyl group is replaced with an ester group or an amide group.
  • Examples of the amino group having 1 to 24 carbon atoms include a diphenylamino group and a dimethylamino group.
  • a in the general formula (1) is preferably an aryl group represented by the following general formula (4).
  • R 1 to R 5 each independently represent a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group, or a group represented by the general formula: -N(Z 1 )(Z 2 ).
  • Z 1 and Z 2 each independently represent an alkyl group having 1 to 5 carbon atoms.
  • R 1 to R 5 each independently represent a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group, or a group represented by the general formula: -N(Z 1 )(Z 2 ).
  • Z 1 and Z 2 each independently represent an alkyl group having 1 to 5 carbon atoms.
  • alkyl group having 1 to 5 carbon atoms examples include linear or branched alkyl groups having 1 to 5 carbon atoms, such as a methyl group, an ethyl group, an n-propyl group, and an isopropyl group.
  • alkoxy group having 1 to 5 carbon atoms examples include linear or branched alkoxy groups having 1 to 5 carbon atoms, such as a methoxy group, an ethoxy group, an n-propoxy group, and an isopropoxy group.
  • Examples of the alkyl group having 1 to 5 carbon atoms represented by Z 1 and Z 2 in the general formula -N(Z 1 )(Z 2 ) include linear or branched alkyl groups having 1 to 5 carbon atoms, such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, etc.
  • Z 1 and Z 2 may be the same group or different groups.
  • R 1 , R 2 , R 4 and R 5 in the general formula (4) are hydrogen atoms
  • R 3 is an alkyl group having 1 to 3 carbon atoms, such as a methoxy group, an ethoxy group, an n-propyl group or an isopropyl group, or a dimethylamino group.
  • the method for producing an aryldiadamantylphosphine derivative of the present invention includes the following first and second steps.
  • Step 1 A step of reacting a bromo compound represented by the following general formula (2) with an alkyl lithium to obtain a lithiated product.
  • Step 2 A step of reacting the lithiated product obtained in Step 1 with a diadamantylchlorophosphine represented by the following general formula (3).
  • the first step is a step of reacting a bromo compound represented by the following general formula (2) with an alkyl lithium in a solvent to obtain a lithiated product of the bromo compound.
  • a in the formula (2) is a group corresponding to A in the formula (1), and as described above, A represents a group selected from an aryl group and a heteroaryl group, and the aryl group and the heteroaryl group may have a substituent.
  • the preferred groups for A in the formula (2) are as described above.
  • alkyllithium used in the first step examples include methyllithium, n-butyllithium, isopropyllithium, s-butyllithium, t-octyllithium, and t-butyllithium. From the viewpoint of having high nucleophilicity and suppressing side reactions, secondary and tertiary alkyllithiums are preferred. From the viewpoints of ease of handling and industrial availability, s-butyllithium is particularly preferred.
  • the amount of alkyllithium added is preferably 0.7 to 1.3, preferably 0.95 to 1.1, in terms of reactivity, in terms of the molar ratio of alkyllithium to the bromo compound represented by general formula (2) (alkyllithium/bromo compound).
  • the reaction solvent used in the first step is not particularly limited, so long as it can dissolve the bromo compound represented by general formula (2) and the resulting lithiated product, and is inert to the reaction.
  • solvents include tetrahydrofuran, cyclopentyl methyl ether, tert-butyl methyl ether, 1,2-dimethoxyethane, N,N-dimethylformamide, diethyl ether, dibutyl ether, dioxane, hexane, toluene, and the like. These solvents can be used as mixed solvents.
  • tetrahydrofuran is particularly preferred from the viewpoint of the solubility of the lithiated product.
  • the lithiation reaction in the first step is preferably carried out by adding an alkyl lithium to a solution in which the bromo compound represented by general formula (2) is dissolved in a reaction solvent.
  • the reaction temperature in the first step is preferably -200 to 30°C, more preferably -80 to 30°C, from the viewpoint of reactivity.
  • the reaction time in the first step is preferably 15 minutes or more, more preferably 0.5 to 3 hours.
  • the alkyllithium is added at a temperature in the range of ⁇ 80 to ⁇ 10° C., and the reaction is preferably carried out for 0.1 to 5 hours while maintaining the temperature in that range, and more preferably for 0.5 to 2 hours from the viewpoint of reactivity.
  • the solvent may be removed from the reaction solution by distillation or the like in a conventional manner to recover the lithiated product and then purify it.
  • the second step is to react the lithiated product obtained in the first step with diadamantylchlorophosphine represented by the following general formula (3) in a solvent to obtain the desired aryldiadamantylphosphine derivative represented by the general formula (1).
  • Ad in the general formula (3) is a group corresponding to Ad in the general formula (1), and as described above, Ad represents an unsubstituted adamantyl group or an adamantyl group having a substituent.
  • the substituent in the adamantyl group having a substituent is a group selected from alkyl groups and alkoxy groups having 1 to 4 carbon atoms.
  • the preferred groups for Ad in the general formula (3) are as described above.
  • the diadamantyl chlorophosphine represented by the general formula (3) can be produced by a known method. For example, according to the following reaction scheme (2), a diadamantyl phosphine derivative (10) is obtained from phosphorus trichloride (7) and an adamantane derivative (8), and then the diadamantyl phosphine derivative (10) is chlorinated with CCl 4 or COCl 2. (See Phosphorus Sulfur Silicon Relat. Elem., 1995, Vol. 102, Pages 211-215, and JP-A-2004-505091, paragraphs 0041-0046, etc.) A commercially available di-1-adamantyl chlorophosphine may be used.
  • Z3 represents a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms, and t represents an integer of 0 to 3.
  • the reaction of the second step it is preferable to use 1.0 to 10 times, preferably 1.5 to 10.0 times, more preferably 2.0 to 5.0 times the molar amount of the lithiated bromo compound represented by general formula (2) relative to the diadamantylchlorophosphine represented by general formula (3), from the viewpoint of efficiently proceeding with the reaction and obtaining the target product in good yield.
  • the reaction solvent for the second step can be the same as that for the first step, and examples of such solvents include tetrahydrofuran, cyclopentyl methyl ether, tert-butyl methyl ether, 1,2-dimethoxyethane, N,N-dimethylformamide, diethyl ether, dibutyl ether, dioxane, hexane, and toluene. These solvents can be used as a mixed solvent.
  • the reaction in the second step is preferably carried out by adding diadamantylchlorophosphine represented by general formula (3) to the solution containing the lithiated product after completion of the first step.
  • the reaction temperature in the second step is preferably -200 to 100°C, more preferably -80 to 30°C, from the viewpoint of reactivity.
  • the reaction time for the second step is preferably 0.5 hours or more, and more preferably 1 to 4 hours.
  • the desired aryl diadamantyl phosphine derivative represented by the general formula (1) can be obtained by recrystallization, purification using a column, etc., if necessary.
  • the aryl diadamantyl phosphine derivative represented by the general formula (1) is easily oxidized in a solvent or air, it is also possible to carry out the third step described below to temporarily stabilize it as a phosphonium salt, and then carry out the fourth step described below when necessary to prepare the aryl diadamantyl phosphine derivative represented by the general formula (1).
  • the third step of the present invention is a step of reacting an aryldiadamantylphosphine derivative represented by general formula (1) with a boric acid compound represented by general formula (5) in a solvent.
  • the third step produces an aryldiadamantylphosphonium salt derivative represented by the following general formula (6).
  • R6 represents a halogen atom, an aryl group, or an aryl heterocyclic group, and the aryl group and the aryl heterocyclic group may have a substituent.
  • Ad is a group corresponding to Ad in general formula (1)
  • A is a group corresponding to A in general formula (1).
  • R6 represents a halogen atom, an aryl group, or an aryl heterocyclic group.
  • aryl group examples include a phenyl group, a naphthyl group, an anthracene group, a phenanthrene group, a biphenyl group, a terphenyl group, a pyrene group, a perylene group, and a triphenylene group.
  • aryl heterocyclic group examples include a pyridyl group and a thiophenyl group.
  • the aryl group and aryl heterocyclic group may have a substituent.
  • substituents include a linear or branched alkyl group having 1 to 5 carbon atoms and a halogen atom.
  • R6 is preferably a halogen atom, and particularly preferably a fluorine atom.
  • the boric acid compound used in the third step is represented by the following general formula (5).
  • R6 in the formula (5) is a group corresponding to R6 in the formula (6) and represents a halogen atom, an aryl group, or an aryl heterocyclic group, and the aryl group and the aryl heterocyclic group may have a substituent.
  • the preferred groups for R6 in the formula (5) are as described above.
  • the amount of the boric acid compound represented by general formula (5) added is preferably 0.8 to 100 in terms of the molar ratio of the boric acid compound represented by general formula (5) to the aryldiadamantylphosphine derivative represented by general formula (1) (general formula (5)/general formula (1)), and more preferably 2 to 5 from the viewpoint of reactivity.
  • the reaction solvent in the third step can be the same as that in the second step, and examples of such solvents include tetrahydrofuran, cyclopentyl methyl ether, tert-butyl methyl ether, 1,2-dimethoxyethane, N,N-dimethylformamide, diethyl ether, dibutyl ether, dioxane, hexane, and toluene. These solvents can be used as a mixed solvent.
  • the reaction in the third step can be continued without isolating the aryldiadamantylphosphine derivative represented by the general formula (1) by adding saturated saline or the like to the solution containing the aryldiadamantylphosphine derivative represented by the general formula (1) after the completion of the second step, and adding the boric acid compound represented by the general formula (5) to the organic layer separated and recovered.
  • the reaction in the third step may be carried out by adding saturated saline to a solution containing the aryldiadamantylphosphine derivative represented by general formula (1) after the completion of the second step to terminate the reaction, and then adding the boric acid compound represented by general formula (5) without separating and recovering the organic layer.
  • the reaction temperature in the third step is preferably -30 to 80°C, and more preferably -10 to 30°C.
  • the reaction time for the third step is preferably 0.5 hours or more, and more preferably 2 to 5 hours.
  • the solvent is removed from the organic layer by distillation or the like, and purification such as recrystallization is carried out as necessary to obtain the aryldiadamantylphosphonium salt derivative represented by general formula (6).
  • the fourth step is a step in which the aryldiadamantylphosphonium salt derivative obtained in the third step is neutralized with a base to obtain an aryldiadamantylphosphine derivative represented by general formula (1).
  • the neutralization treatment in the fourth step is preferably carried out by adding an aqueous solution containing a base to a solution in which the aryldiadamantylphosphonium salt derivative is dissolved in a solvent.
  • a solvent for dissolving the aryldiadamantylphosphonium salt derivative it is preferable to use a hydrophobic organic solvent, since this allows easy separation from the aqueous layer.
  • solvents include tetrahydrofuran, cyclopentyl methyl ether, tert-butyl methyl ether, 1,2-dimethoxyethane, N,N-dimethylformamide, diethyl ether, dibutyl ether, dioxane, hexane, and toluene.
  • the base used in the fourth step includes alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, and lithium hydroxide, and organic bases such as triethylamine, DBU, and N-ethyldiisopropylamine.
  • the amount of base added is preferably 1 to 100 times the molar amount of the aryl diadamantyl phosphonium salt derivative, and more preferably 2 to 10 times the molar amount.
  • the base can be added in multiple portions to the solution in which the aryl diadamantyl phosphonium salt derivative is dissolved.
  • the temperature of the neutralization treatment in the fourth step is usually -30 to 50°C, preferably -10 to 25°C.
  • the organic layer and the aqueous layer are separated, and the solvent is removed from the organic layer by distillation or the like. If necessary, purification is performed by a conventional method such as recrystallization to obtain the aryldiadamantylphosphine derivative represented by general formula (1).
  • the aryldiadamantylphosphine derivative represented by the general formula (1) obtained by the production method of the present invention is particularly useful as a ligand used in a cross-coupling reaction, and its phosphonium salt not only contributes to stabilization but is also known to be useful as a ligand used in a cross-coupling reaction (see, for example, WO2014/007405 pamphlet, WO2014/007404 pamphlet, etc.).
  • the aryldiadamantylphosphine derivative represented by the general formula (1) and the aryldiadamantylphosphonium salt derivative represented by the general formula (6) obtained by the production method of the present invention are expected to be useful as ligands of catalysts used in coupling reactions such as the Suzuki-Miyaura reaction, the Negishi reaction, the Hiyama reaction, etc.
  • aryl diadamantyl phosphine derivative produced by the present invention is an aryl diadamantyl phosphine derivative represented by the following general formula (1A).
  • the aryl diadamantyl phosphine derivative represented by the general formula (1A) is a novel compound that is particularly expected to be used as a ligand of a catalyst used in coupling reactions such as the Suzuki-Miyaura reaction, the Negishi reaction, and the Hiyama reaction.
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • R7 represents a linear or branched alkyl group having 1 to 8 carbon atoms.
  • Ad represents an unsubstituted adamantyl group or an adamantyl group having a substituent, and the substituent is a group selected from an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.
  • Ad in general formula (1A) is preferably an unsubstituted adamantyl group.
  • Examples of the linear or branched alkyl group having 1 to 8 carbon atoms represented by R7 in the general formula (1A) include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, etc. Among these, a methyl group and an isopropyl group are preferred, and an isopropyl group is particularly preferred from the viewpoints of solubility and industrial availability.
  • aryl diadamantyl phosphonium salt derivative produced by the present invention is an aryl diadamantyl phosphonium salt derivative represented by the following general formula (6A).
  • the aryl diadamantyl phosphonium salt derivative represented by the general formula (1A) is a novel compound that is particularly expected to be used as a ligand of a catalyst used in coupling reactions such as the Suzuki-Miyaura reaction, the Negishi reaction, and the Hiyama reaction.
  • Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is a group selected from an alkyl group and an alkoxy group having 1 to 4 carbon atoms.
  • R7 represents a linear or branched alkyl group having 1 to 8 carbon atoms.
  • Ad represents an unsubstituted adamantyl group or an adamantyl group having a substituent, and the substituent is a group selected from an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms.
  • Ad in general formula (6A) is preferably an unsubstituted adamantyl group.
  • Examples of the linear or branched alkyl group having 1 to 3 carbon atoms represented by R7 in the general formula (6A) include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, etc. Among these, a methyl group and an isopropyl group are preferred, and an isopropyl group is particularly preferred from the viewpoints of solubility and industrial availability.
  • aryldiadamantylphosphine derivatives and aryldiadamantylphosphonium salt derivatives obtained by the production method of the present invention are used as ligands
  • transition metals that can form complexes with these ligands include rhodium, ruthenium, iridium, palladium, nickel, iron, copper, etc., and among these, palladium is particularly preferred.
  • Ad represents a 1-adamantyl group.
  • ⁇ Second step> A solution of 3.00 g (8.91 mmol, 1.0 eq) of di-1-adamantylchlorophosphine (Ad 2 PCl) in 150 mL of deoxygenated THF was added dropwise to the solution. After the addition, the mixture was reacted at ⁇ 78° C. for 1 hour, and then the temperature was gradually raised to ⁇ 10° C. for 3 hours. The conversion rate of Ad 2 PCl was determined by GC and was found to be 98% or more.
  • ⁇ Separation and purification> To the reaction solution, 100 mL of deoxygenated saturated saline was slowly added at -10°C. After stirring for 30 minutes, the aqueous layer was discarded.
  • the solvent was distilled off under reduced pressure, and 200 mL of deoxygenated methanol was added to the residue. The supernatant was removed by decantation filtration, and the remaining solvent was distilled off under reduced pressure to obtain a white solid. The resulting white solid was then recrystallized from deoxygenated THF at ⁇ 10° C. to obtain 2.06 g (4.89 mmol) of purified compound (1a) in a yield of 54.9%.
  • the conversion rate of Ad 2 PCl was determined as follows. A small amount of the reaction mixture was sampled and hydrolyzed with deoxygenated saline. A certain amount of the organic layer was accurately measured, and 2,6-di-tert-butyl-p-cresol was added as an external standard.
  • Ad represents a 1-adamantyl group.
  • Ad represents a 1-adamantyl group.
  • Ad represents a 1-adamantyl group.
  • Ad represents a 1-adamantyl group.
  • Ad represents a 1-adamantyl group.
  • the organic layer was separated at -10°C, 6.0 g of 42% HBF4 aqueous solution was added and stirred for 2 hours, and then stirred at room temperature for a whole day and night.
  • the organic layer was washed three times with 100 mL of saturated saline at room temperature.
  • the solvent was distilled off under reduced pressure to obtain a yellow viscous solid. Recrystallization was performed from 7 times the amount of methanol at -30°C to obtain 2.82 g (5.54 mmol) of a white solid of compound (6a) in a yield of 62.2%.
  • Ad represents a 1-adamantyl group.
  • ⁇ Third step> In the second step of Example 1, 100 ml of deoxygenated saturated saline was added at -10°C to stop the reaction, and then 6.0 g of 42% HBF4 aqueous solution was slowly added at -10°C and stirred at -10°C for 2 hours. Then, the mixture was stirred at room temperature for a whole day and night. The organic layer was washed three times with 100 mL of saturated saline at room temperature. The solvent was distilled off under reduced pressure to obtain a yellow viscous solid. The mixture was recrystallized from 7 times the amount of methanol at -30°C to obtain 2.69 g (5.28 mmol) of white solid compound (6a) in a yield of 59.3%.
  • Ad represents a 1-adamantyl group.
  • ⁇ Fourth step> A 100 mL four-neck flask equipped with a stirrer, a N2 inlet tube, a thermometer, and a dropping tube was charged with a solution of 100 mg (0.196 mmol) of the compound (6a) obtained in Example 6 in 30 mL of deoxygenated toluene, and cooled to -20°C. 30 mL of a 0.1 N deoxygenated NaOH aqueous solution was added dropwise thereto. After stirring at -20°C for 2 hours, the organic layer was separated and washed once with deoxygenated water, and the solvent was distilled off under reduced pressure to obtain 50 mg of a white solid of compound (1a).
  • Ad represents a 1-adamantyl group.
  • Ad represents a 1-adamantyl group.
  • ⁇ Third step> The compound (1b) obtained in the second step of Example 9 was suspended in 400 mL of THF, and 6.0 g of 42% HBF4 aqueous solution was added at -10°C, followed by stirring at -10°C for 2 hours and at room temperature overnight. The organic layer was washed three times with 100 mL of saturated saline at room temperature. The solvent was distilled off under reduced pressure to obtain a white solid. Recrystallization was performed from 10 times the amount of methanol at -10°C to obtain 3.2 g (6.45 mmol) of a white solid of compound (6b) in a yield of 72.4%.
  • Ad represents a 1-adamantyl group.
  • Ad represents a 1-adamantyl group.
  • ⁇ Third step> In the second step of Example 11, 100 ml of deoxygenated saturated saline was added at -10°C to stop the reaction. Then, 6.0 g of 42% HBF4 aqueous solution was slowly added at -10°C, and the mixture was stirred at -10°C for 2 hours and then at room temperature for a whole day and night. The organic layer was washed three times with 100 mL of saturated saline, and the solvent was distilled off under reduced pressure. The crude product was recrystallized from 8 times the amount of methanol at -30°C to obtain 3.00 g (5.72 mmol) of white solid compound (6c) in a yield of 64.2%.

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Abstract

L'invention concerne un procédé à haut rendement, industriellement avantageux pour produire, sans utilisation d'un catalyseur au palladium, un dérivé d'aryldiadamantylphosphine dans lequel un groupe diadamantylphosphine (-P(Ad)2) est introduit dans un composé ayant un squelette aryle. Ce procédé de production de dérivés d'aryldiadamantylphosphine comprend : une première étape consistant à obtenir une substance lithiée par réaction d'un composé bromo avec un alkyllithium ; et une seconde étape consistant à faire réagir ensuite la substance lithiée obtenue avec une diadamantylchlorophosphine.
PCT/JP2024/015030 2023-04-21 2024-04-15 Procédé de production de dérivés d'aryldiadamantylphosphine et procédé de production de dérivés de sel d'aryldiadamantylphosphonium Ceased WO2024219367A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025121285A1 (fr) * 2023-12-05 2025-06-12 日本化学工業株式会社 Complexe phosphine-palladium, catalyseur de polymérisation et procédé de production de polymère aromatique

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019230479A1 (fr) * 2018-05-29 2019-12-05 日本化学工業株式会社 Procédé de production de dérivé de phosphinobenzène borane, procédé de production de dérivé de 1,2-bis(dialkylphosphino)benzène et complexe de métal de transition
CN115385957A (zh) * 2021-05-09 2022-11-25 东莞市均成高新材料有限公司 直线三联芳基膦配体及其过渡金属络合物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019230479A1 (fr) * 2018-05-29 2019-12-05 日本化学工業株式会社 Procédé de production de dérivé de phosphinobenzène borane, procédé de production de dérivé de 1,2-bis(dialkylphosphino)benzène et complexe de métal de transition
CN115385957A (zh) * 2021-05-09 2022-11-25 东莞市均成高新材料有限公司 直线三联芳基膦配体及其过渡金属络合物

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
ÁDÁM SINAI; DÁNIEL CS. SIMKÓ; FRUZSINA SZABÓ; ATTILA PACZAL; TAMÁS GÁTI; ATTILA BÉNYEI; ZOLTÁN NOVÁK; ANDRÁS KOTSCHY: "Aryl‐Diadamantyl Phosphine Ligands in Palladium‐Catalyzed Cross‐Coupling Reactions: Synthesis, Structural Analysis, and Application", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 2020, no. 9, 25 February 2020 (2020-02-25), DE , pages 1122 - 1128, XP072116560, ISSN: 1434-193X, DOI: 10.1002/ejoc.201901834 *
AGUILAR DAVID, FERNÁNDEZ IGNACIO, CUESTA LUCIANO, YAÑEZ-RODRÍGUEZ VÍCTOR, SOLER TATIANA, NAVARRO RAFAEL, URRIOLABEITIA ESTEBAN P.,: "Synthesis, Structure, and Reactivity of N -Benzoyl Iminophosphoranes Ortho Lithiated at the Benzoyl Group", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 75, no. 19, 1 October 2010 (2010-10-01), United States, pages 6452 - 6462, XP093222664, ISSN: 0022-3263, DOI: 10.1021/jo101151s *
DATABASE REGISTRY 14 June 2012 (2012-06-14), ANONYMOUS: "Phosphine, (4-methoxyphenyl)bis(tricyclo[3.3.1.13,7]dec-1-yl)- (CA INDEX NAME)", XP093222681, retrieved from STN Database accession no. 1378030-16-0 *
MATTHEW R. NETHERTON, GREGORY C. FU: "Air-Stable Trialkylphosphonium Salts: Simple, Practical, and Versatile Replacements for Air-Sensitive Trialkylphosphines. Applications in Stoichiometric and Catalytic Processes", ORGANIC LETTERS, vol. 3, no. 26, 1 January 2001 (2001-01-01), US , pages 4295 - 4298, XP002459563, ISSN: 1523-7060, DOI: 10.1021/ol016971g *
PONOMARENKO VADIM I., KRUPENYA DMITRII V., GRACHOVA ELENA V., GINDIN VLADIMIR A., SELIVANOV STANISLAV I., KOSHEVOY IGOR O., TUNIK : "Structure, Stereochemistry and Dynamics of Tetranuclear Polyhydride Clusters Containing Chiral Heterobidentate Phosphanes", ZEITSCHRIFT FUR ANORGANISCHE UND ALLGEMEINE CHEMIE, vol. 635, no. 15, 1 December 2009 (2009-12-01), Hoboken, USA, pages 2515 - 2526, XP093222668, ISSN: 0044-2313, DOI: 10.1002/zaac.200900259 *
SHUNPEI ISHIKAWA, KEI MANABE: "Oligoarene Strategy for Catalyst Development. Hydroxylated Oligoarene-type Phosphines for Palladium-catalyzed Cross Coupling", CHEMISTRY LETTERS, vol. 36, no. 11, 1 January 2007 (2007-01-01), pages 1302 - 1303, XP055157584, ISSN: 03667022, DOI: 10.1246/cl.2007.1302 *
WHEATON CRAIG A., BOW JOHN-PAUL J., STRADIOTTO MARK: "New Phosphine-Functionalized NHC Ligands: Discovery of an Effective Catalyst for the Room-Temperature Amination of Aryl Chlorides with Primary and Secondary Amines", ORGANOMETALLICS, vol. 32, no. 21, 11 November 2013 (2013-11-11), pages 6148 - 6161, XP093222677, ISSN: 0276-7333, DOI: 10.1021/om400684n *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025121285A1 (fr) * 2023-12-05 2025-06-12 日本化学工業株式会社 Complexe phosphine-palladium, catalyseur de polymérisation et procédé de production de polymère aromatique

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