Method for producing aryl diadamantylphosphine derivatives

Abstract

To provide a method for producing aryldiadamantylphosphine derivatives, obtained by introducing a diadamantylphosphine group (-P(Ad)2) into a compound having an aryl skeleton, in a highly industrially advantageous manner and in high yield, without the use of a palladium catalyst. [Solution] A method for producing an aryldiadamantylphosphine derivative, comprising: a lithiation step of reacting a bromo compound with alkyllithium to obtain a lithide; and a reaction crystallization step of reacting the obtained lithide with diadamantylchlorophosphine in a solvent to produce and precipitate an aryldiadamantylphosphine derivative.

Description

[Technical Field]

[0001] This invention relates to a method for producing aryl diadamantylphosphine derivatives. [Background technology]

[0002] A group led by Professor Buchwald at the Massachusetts Institute of Technology proposed a series of electron-rich and bulky phosphines (e.g., Patent Documents 1-3). These are called Buchwald phosphine ligands, and their function in generating various CC, CN, and CO bonds has attracted attention. Known biarylphosphines such as t-BuBrettPhos, RockPhos, BrettPhos, and XPhos are Buchwald phosphine ligands. For example, XPhos is a ligand with the structure shown in the following chemical formula (A).

[0003] Furthermore, AmPhos, represented by the chemical formula (B) below, is widely known as a ligand for catalysts used in reactions such as the Suzuki-Miyaura cross-coupling reaction of aryl halides.

[0004] These ligands all have an aryl skeleton and are phosphine derivatives having two bulky groups on the phosphorus atom bonded to the aryl skeleton.

[0005] [ka]

[0006] The adamantyl group is known for being bulky, and when compared to the t-butyl group, the adamantyl group has greater electron-donating ability. It is therefore expected that introducing it onto a phosphorus atom will increase catalytic activity.

[0007] Non-Patent Document 1 reports that a palladium complex having a compound represented by the following chemical formula (C) having an aryl skeleton and having two adamantyl groups as bulky groups on a phosphorus atom as a ligand exhibits excellent catalytic activity in cross-coupling reactions and Buchwald-Hartwig reactions.

[0008]

Chemical Formula

[0009] As a method for introducing a diadamantylphosphino group (-P(Ad)2) into an aryl skeleton, Non-Patent Document 1 proposes a method of reacting a bromo compound (C1) and di-1-adamantylphosphine (C2) in the presence of a palladium catalyst (C3) according to the following reaction scheme 1.

[0010]

Chemical Formula

[0011] However, since the method of 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 that dislike contamination of palladium metal and incorporation of palladium in subsequent reactions. In addition, palladium catalysts are expensive and not an industrially advantageous method.

Prior Art Documents

Patent Documents

[0012]

Patent Document 1

Patent Document 2

Patent Document 3

Non-Patent Documents

[0013] [Non-Patent Document 1] European Journal of Organic Chemistry,2020,1122-1128 [Overview of the Initiative] [Problems that the invention aims to solve]

[0014] In other words, the object of the present invention is to provide a method for producing aryldiadamantylphosphine derivatives, obtained by introducing a diadamantylphosphine group (-P(Ad)2) into a compound having an aryl skeleton, in a highly industrially advantageous manner and in high yield, without the use of a palladium catalyst. [Means for solving the problem]

[0015] In view of the above circumstances, the present inventors have conducted extensive research and have found that, in a method for introducing a diadamantylphosphin group (-P(Ad)2) into a compound having an aryl skeleton, by providing a reaction crystallization step in which a bromo compound having an aryl skeleton is lithified with alkyllithium, and the resulting lithified product is reacted with diadamantylchlorophosphin to produce and precipitate an aryldiadamantylphosphin derivative represented by general formula (1), the desired aryldiadamantylphosphin derivative can be obtained in high yield without using a palladium catalyst, thus completing the present invention.

[0016] In other words, the invention to be provided by the present invention is a method for producing an aryl diadamantylphosphine derivative represented by the following general formula (1), [ka] (In the formula, Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, wherein the substituent is selected from alkyl and alkoxy groups having 1 to 4 carbon atoms. A represents a group selected from aryl and heteroaryl groups, wherein the aryl and heteroaryl groups may have substituents.) A lithiation step to obtain a lithide by reacting a bromo compound represented by the following general formula (2) with alkyllithium, [ka] (In the formula, A is equivalent to that in the general formula (1) above.) Next, a reaction crystallization step is performed in which the obtained lithiate is reacted with diadamantylchlorophosphine represented by the following general formula (3) in a solvent to produce and precipitate an aryl diadamantylphosphine derivative represented by the general formula (1). This is a method for producing aryl diadamantylphosphine derivatives, characterized by having the following characteristics. [ka] (In the formula, Ad is equivalent to the general formula (1) above.) [Effects of the Invention]

[0017] According to the present invention, aryldiadamantylphosphine derivatives, which are useful as ligands for coupling reaction catalysts, can be produced in high yield by an industrially advantageous method without the use of a palladium catalyst, by introducing a diadamantylphosphine group (-P(Ad)2) into a compound having an aryl skeleton. [Modes for carrying out the invention]

[0018] The present invention will be described below based on preferred embodiments.

[0019] The present invention relates to a method for producing an aryl diadamantylphosphine derivative represented by the following general formula (1).

[0020] [ka] (In the formula, Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, wherein the substituent is selected from alkyl and alkoxy groups having 1 to 4 carbon atoms. A represents a group selected from aryl and heteroaryl groups, wherein the aryl and heteroaryl groups may have substituents.)

[0021] In general formula (1), Ad represents an unsubstituted adamantyl group or a substituted adamantyl group. The substituent in the substituted adamantyl group represents a group selected from alkyl groups and alkoxy groups having 1 to 4 carbon atoms.

[0022] Examples of the C1-C4 alkyl groups include linear or branched alkyl groups having C1-C4, such as methyl, ethyl, n-propyl, isopropyl, and n-butyl groups. Examples of the C1-C4 alkoxy groups include linear or branched alkoxy groups having C1-C4, such as methoxy, ethoxy, n-propoxy, isopropoxy, and n-butoxy groups.

[0023] In general formula (1), A represents a group selected from aryl groups and heteroaryl groups.

[0024] Examples of the aryl group include phenyl, naphthyl, anthracene, phenanthrene, biphenyl, terphenyl, pyrene, perylene, and triphenylene groups.

[0025] Examples of the aforementioned heteroaryl groups include sulfur-containing heteroaryl groups such as thiophenyl group, thienylenyl group, benzothienyl group, dibenzothienyl group, phenylenedibenzothienylenyl group, and dibenzothienylenylphenyl group; oxygen-containing heteroaryl groups such as furanyl group, benzofuranyl group, dibenzofuranyl group, phenyldibenzofuranyl group, and dibenzofuranylphenyl group; nitrogen-containing heteroaryl groups such as pyridyl group, pyridylenyl group, pyrimidinyl group, pyrazyl group, quinolyl group, isoquinolyl group, carbazolyl group, 9-phenylcarbazolyl group, acridinyl group, quinazolyl group, quinoxalyl group, 1,6-naphthilidinyl group, 1,8-naphthilidinyl group, and porphyrin group; and heteroaryl groups containing two or more heteroatoms (e.g., nitrogen and sulfur), such as benzothiazolyl group.

[0026] The aryl group and heteroaryl group may have substituents. Examples of substituents include linear or branched alkyl groups having 1 to 24 carbon atoms, linear or branched alkoxy groups having 1 to 24 carbon atoms, cycloalkyl groups having 3 to 24 carbon atoms, cycloalkyloxy groups having 3 to 24 carbon atoms, alkenyl groups having 1 to 24 carbon atoms, alkynyl groups having 1 to 24 carbon atoms, aryl groups having 5 to 24 carbon atoms, aryloxy groups having 5 to 24 carbon atoms, heteroaryl groups having 4 to 24 carbon atoms, acyl groups having 1 to 24 carbon atoms, amino groups having 1 to 24 carbon atoms, halogeno groups, cyano groups, and nitro groups. These substituents may further have hydrogen atoms substituted with halogeno groups.

[0027] Examples of the halogen group include a fluoro group, a chloro group, a bromo group, and an iodine group.

[0028] Examples of the linear or branched alkyl groups having 1 to 24 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, and octyl groups.

[0029] Examples of the linear or branched alkoxy groups having 1 to 24 carbon atoms include methoxy groups, ethoxy groups, n-propoxy groups, isopropoxy groups, n-butoxy groups, isobutoxy groups, tert-butoxy groups, pentyloxy groups, hexyloxy groups, and octyloxy groups.

[0030] Examples of the cycloalkyl groups having 3 to 24 carbon atoms include cyclopropyl groups, cyclobutyl groups, cyclopentyl groups, and cyclohexyl groups. Furthermore, the cycloalkyl groups may contain heteroatoms such as S and N.

[0031] Examples of the cycloalkyloxy group having 3 to 24 carbon atoms include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, and cyclohexyloxy groups. The cycloalkyloxy group may also contain heteroatoms such as S and N.

[0032] Examples of the C1-C24 alkenyl group include ethenyl, propenyl, butenyl, pentenyl, hexenyl, and octenyl groups.

[0033] Examples of the alkynyl group having 1 to 24 carbon atoms include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and octinyl groups.

[0034] Examples of the aryl group having 5 to 24 carbon atoms include the phenyl group, the naphthyl group, and the biphenyl group.

[0035] Examples of the aryloxy group having 5 to 24 carbon atoms include a phenoxy group, a naphthyloxy group, and a biphenyloxy group.

[0036] Examples of the heteroaryl groups having 4 to 24 carbon atoms include thiophenyl, furanyl, carbazole, benzothiophenyl, benzofuranyl, indolyl, pyrrolyl, and pyridyl groups.

[0037] Examples of the acyl group having 1 to 24 carbon atoms include an acetyl group, a propionyl group, a butanoyl group, a pentanoyl group, a heptanoyl group, and a group in which a carbonyl group contained in the acyl group is substituted with an ester group or an amide group.

[0038] Examples of the amino group having 1 to 24 carbon atoms include a diphenylamino group and a dimethylamino group.

[0039] In the production method of the present invention, A in the general formula (1) is preferably an aryl group represented by the following general formula (4).

[0040]

Chemical formula

[0041] In the formula of the general formula (4), R 1 ~R 5 each independently represents 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 represents an alkyl group having 1 to 5 carbon atoms.

[0042] Examples of the alkyl group having 1 to 5 carbon atoms 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.

[0043] Examples of the alkoxy groups having 1 to 5 carbon atoms include linear or branched alkoxy groups having 1 to 5 carbon atoms, such as methoxy groups, ethoxy groups, n-propoxy groups, and isopropoxy groups.

[0044] The general formula: -N(Z 1 )(Z 2 Z in the formula 1 and Z 2 Examples of C1-C5 alkyl groups represented by Z include linear or branched alkyl groups having C1-C5, such as methyl, ethyl, n-propyl, and isopropyl groups. 1 and Z 2 These may be the same group or different groups.

[0045] In the manufacturing method of the present invention, R in the general formula (4) 1 , R 2 , R 4 and R 5 is a hydrogen atom, and R 3 It is particularly preferable, from the viewpoint of solubility and catalytic activity, that the group be a C1-C3 alkyl group such as a methoxy group, ethoxy group, n-propyl group, or isopropyl group, or a dimethylamino group.

[0046] Particularly preferred compounds obtained by the manufacturing method of the present invention include aryl diadamantylphosphine derivatives represented by the following general formula (1A). [ka] (In the formula, Z 1 and Z 2 Each of these independently represents an alkyl group having 1 to 5 carbon atoms.

[0047] The present invention provides a method for producing aryl diadamantylphosphine derivatives, comprising the following lithiation step and reaction crystallization step.

[0048] Lithiation step: A step in which a bromo compound represented by the following general formula (2) is reacted with alkyllithium to obtain a lithide. Reaction crystallization step: A step in which the lithiated product obtained in the lithiation step is reacted with diadamantylchlorophosphine represented by the following general formula (3) in a solvent to produce and precipitate an aryl diadamantylphosphine derivative represented by the general formula (1).

[0049] The lithiation step involves reacting a bromo compound represented by the following general formula (2) with alkyllithium in a solvent to obtain a lithiated product of the bromo compound.

[0050] [ka]

[0051] In general formula (2), A corresponds to the group A in general formula (1), and as described above, A represents a group selected from aryl groups and heteroaryl groups, and the aryl group and heteroaryl group may have substituents. The preferred group for A in general formula (2) is as described above.

[0052] Examples of alkyllithium used in the lithiation process include methyllithium, n-butyllithium, isopropyllithium, s-butyllithium, t-octyllithium, and t-butyllithium. From the viewpoint of handling and industrial availability, n-butyllithium is particularly preferred.

[0053] From the viewpoint of reactivity, the amount of alkyllithium added should preferably be such that the molar ratio of alkyllithium to the bromo compound represented by general formula (2) (alkyllithium / bromo compound) is 0.9 to 1.5, more preferably 0.95 to 1.3.

[0054] The reaction solvent used in the lithiation step is not particularly limited, as long as it can dissolve the bromo compound represented by general formula (2) and the resulting lithiated product, and is inert to the reaction. Examples of such solvents include tetrahydrofuran (THF), cyclopentyl methyl ether (CPME), 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. In the production method of the present invention, when producing an aryl diadamantylphosphine derivative represented by general formula (1A), it is preferable to include cyclopentyl methyl ether from the viewpoint that it can be used as a solvent in the reaction crystallization step described later. It is particularly preferable to use a mixed solvent of cyclopentyl methyl ether and tetrahydrofuran.

[0055] The lithiation reaction in the lithiation step is preferably carried out by adding alkyllithium to a solution in which a bromo compound represented by general formula (2) is dissolved in a reaction solvent.

[0056] The reaction temperature for the lithiation step is preferably -40 to 10°C, more preferably -20 to 0°C, from the viewpoint of reactivity.

[0057] The reaction time for the lithiation step is preferably 15 minutes or more, and more preferably 0.5 to 3 hours. In the manufacturing method of the present invention, the addition of alkyllithium is preferably carried out in the range of -40 to 10°C, and the reaction is further carried out for 15 minutes to 5 hours while maintaining that temperature range, and more preferably for 0.5 to 3 hours from the viewpoint of reactivity.

[0058] After the lithiation reaction is complete, the solvent may be removed from the reaction solution by distillation or other conventional methods to recover the lithiated product and purify it. However, in the present invention, it is preferable from an industrial standpoint to proceed directly to the reaction crystallization step without recovering the lithiated product after the lithiation reaction is complete.

[0059] The reaction crystallization step involves reacting the lithiated product obtained in the lithiation step with diadamantylchlorophosphine represented by the following general formula (3) in a solvent to produce and precipitate an aryl diadamantylphosphine derivative represented by the general formula (1).

[0060] [ka]

[0061] In general formula (3), Ad corresponds to the Ad in general formula (1), and as described above, Ad represents an unsubstituted adamantyl group or a substituted adamantyl group. The substituent in the substituted adamantyl group is selected from alkyl groups and alkoxy groups having 1 to 4 carbon atoms. The preferred group for Ad in general formula (3) is as described above.

[0062] Diadamantylchlorophosphine, represented by general formula (3), can be produced by known methods. For example, according to the reaction scheme (2) below, a diadamantylphosphine derivative (10) can be obtained from phosphorus trichloride (7) and an adamantane derivative (8), and then the diadamantylphosphine derivative (10) can be produced by chlorinating it with CCl4 or COCl2 (see Phosporus Sulfur Silicon Relat. Elem., 1995, Vol. 102, Pages 211-215, and paragraphs 0041-0046 of Japanese Patent Publication No. 2004-505091, etc.). Alternatively, commercially available di-1-adamantylchlorophosphine may be used.

[0063] [ka] (In the formula, Z 3 (where 't' represents a group selected from alkyl and alkoxy groups having 1 to 4 carbon atoms. 't' represents an integer from 0 to 3.)

[0064] In the reaction crystallization step, it is preferable to prepare two solutions: solution A, which is obtained by dissolving the lithiated product obtained in the lithiation step in a solvent, and solution B, which is obtained by dissolving diadamantylchlorophosphine represented by general formula (3) in a solvent, and then add solution B to solution A to carry out the reaction.

[0065] In the manufacturing method of the present invention, the solvents used in solution A and solution B are those that, after the addition of solution B, can dissolve the lithide and the diadamantylchlorophosphine represented by general formula (3), and can generate and precipitate the aryldiadamantylphosphine derivative represented by general formula (1) obtained by the reaction.

[0066] Solution A is a solution in which a lithide is dissolved in a solvent. Suitable solvents for dissolving the lithide in Solution A depend on the type of lithide being dissolved, but examples 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 also be used as a mixed solvent.

[0067] From the viewpoint of improving reactivity, the concentration of the lithide in solution A is preferably 8-16 wt%, more preferably 10-14 wt%.

[0068] In the manufacturing method of the present invention, it is preferable from the viewpoint of industrial advantage to use the reaction solution after the lithiation step as is for solution A.

[0069] Solution B is a solution obtained by dissolving diadamantylchlorophosphine represented by general formula (3) in a solvent. Examples of solvents that dissolve diadamantylchlorophosphine represented by general formula (3) in Solution B 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 also be used as a mixed solvent.

[0070] In the production method of the present invention, particularly when producing an aryl diadamantylphosphine derivative represented by general formula (1A), it is preferable from the viewpoint of suppressing the generation of by-products that solutions A and B contain at least cyclopentyl methyl ether as a solvent. Furthermore, from the viewpoint of suppressing the generation of by-products, it is preferable to prepare solutions A and B such that the reaction solution (solution A + solution B) after adding solution B to solution A contains 10 to 40 parts by mass, preferably 20 to 30 parts by mass, of a solvent other than cyclopentyl methyl ether per 100 parts by mass of cyclopentyl methyl ether. Furthermore, when producing the aryl diadamantylphosphine derivative represented by general formula (1A), it is preferable to use a mixed solvent of cyclopentyl methyl ether and tetrahydrofuran as the solvent in solution A, and to use cyclopentyl methyl ether as the solvent in solution B, particularly from the viewpoint of suppressing the generation of by-products.

[0071] In the reaction crystallization step, it is preferable to add solution B in an amount of 1.3 to 3.0 moles, preferably 1.4 to 2.5 moles, and more preferably 1.5 to 2.0 moles, of the lythiolated bromo compound represented by general formula (2) relative to the diadamantylchlorophosphine represented by general formula (3), from the viewpoint of efficiently carrying out the reaction and obtaining the target product in good yield.

[0072] In the reaction crystallization step, the addition of solution B is carried out at a temperature range of -40 to 10°C, preferably -20 to 0°C, and the reaction is further carried out for 0.5 to 5 hours while maintaining that temperature range, and more preferably for 1 to 3 hours from the viewpoint of reactivity.

[0073] After the reaction crystallization step is complete, water, a water-soluble solvent, or a mixed solvent of water and a water-soluble solvent is added to the reaction solution to quench it. The reaction solvent is then removed by distillation or other means to recover the target product, and if necessary, recrystallization, column chromatography, or other purification methods are performed to obtain the desired aryl diadamantylphosphine derivative represented by general formula (1).

[0074] The aryl diadamantylphosphine derivative represented by general formula (1) obtained by the production method of the present invention is particularly useful as a ligand for cross-coupling reactions, and is especially expected to be used as a ligand for catalysts in coupling reactions such as the Suzuki-Miyaura reaction, the Negishi reaction, and the Hiyama reaction. [Examples]

[0075] The present invention will be described below with reference to examples, but the present invention is not limited to these examples. {Example 1} [ka] (In the formula, Ad represents a 1-adamantyl group.) <Lithiation process> In a 300 mL four-necked flask equipped with a stirrer, nitrogen inlet tube, thermometer, and dropping tube, 6.00 g (30.0 mmol, 1.80 eq) of 4-bromo-N,N-dimethylaniline, 5.70 g of anhydrous tetrahydrofuran (THF), and 24.00 g of anhydrous cyclopentyl methyl ether (CPME) were weighed out and cooled to -15°C. A solution of n-BuLi hexane (1.6 mol / L, 15.36 g, 36.0 mmol) was added dropwise, and the mixture was allowed to react for 15 minutes to obtain a solution containing the lithiate. <Reaction and crystallization process> 5.62 g (16.7 mmol, 1.0 eq) of di-1-adamantylchlorophosphine (Ad2PCl) in 55.00 g of anhydrous cyclopentyl methyl ether (CPME) solution was added dropwise to the solution containing the lithiated compound. After addition, the mixture was reacted at -15°C for 1 hour to obtain a solution containing precipitate. The conversion rate of Ad2PCl was determined by GC to be over 98%. 50.00 g of pure water was slowly added to the solution containing the precipitate after the reaction at -10°C. After stirring for 30 minutes, the aqueous layer was discarded. The solvent was removed by distillation under reduced pressure, and 30.00 g of deoxygenated methanol was added to the residue at 25°C. The mixture was filtered to obtain 6.46 g (15.3 mmol) of a white solid in 91.6% yield. <Identification data for the obtained white solid (compound (1a))> 1H-NMR(THF-d8):δ7.58(br , 1H)、7.30(br , 1H)、6.72~6.50(m , 2H)、2.95(s , 6H)、2.12~1.62(m , 30H) 31 P-NMR(THF-d8):δ38.9 MS(DI-EI):m / z 421(M+) IR(ATR):2897、2844、2810、1596、1510、1445、1361、1229、1201、1098、811、532 cm -1

Claims

1. A method for producing an aryl diadamantylphosphine derivative represented by the following general formula (1), 【Chemistry 1】 (In the formula, Ad represents an unsubstituted adamantyl group or a substituted adamantyl group, and the substituent is selected from alkyl groups and alkoxy groups having 1 to 4 carbon atoms. A represents a group selected from aryl groups and heteroaryl groups, and the aryl group and heteroaryl group may have substituents.) A lithiation step to obtain a lithide by reacting a bromo compound represented by the following general formula (2) with alkyllithium, 【Chemistry 2】 (In the formula, A is equivalent to that in the general formula (1) above.) Next, a reaction crystallization step is performed in which the obtained lithiate is reacted with diadamantylchlorophosphine represented by the following general formula (3) in a solvent to produce and precipitate an aryl diadamantylphosphine derivative represented by the general formula (1). A method for producing an aryl diadamantylphosphine derivative, characterized by having the following: 【Transformation 3】 (In the formula, Ad is equivalent to that in the general formula (1) above.)

2. A method for producing an aryldiadamantylphosphine derivative according to claim 1, wherein Ad in the general formula (1) is an unsubstituted adamantyl group and A is an aryl group represented by the following general formula (4). 【Chemistry 4】 (In the formula, R １ ~R ５ Each of these independently comprises a hydrogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group, or a group with the general formula: -N(Z １ ) (Z ２ This indicates the group represented by ). １ and Z ２ Each of these independently represents an alkyl group having 1 to 5 carbon atoms.

3. A method for producing an aryldiadamantylphosphine derivative according to claim 1 or 2, wherein the alkyllithium is n-butyllithium.

4. A method for producing an aryl diadamantylphosphine derivative according to claim 1 or 2, wherein the reaction temperature of the lithio step is -40 to 10°C.

5. A method for producing an aryl diadamantylphosphine derivative according to claim 1 or 2, wherein the reaction temperature of the reaction crystallization step is -40 to 10°C.

6. A method for producing aryladamantylphosphine according to claim 1 or 2, wherein in the reaction crystallization step, a lithide of a bromo compound represented by general formula (2) is reacted with diadamantylchlorophosphine represented by general formula (3) in an amount of 1.3 to 3.0 molars.

7. A method for producing aryladamantylphosphine according to claim 1 or 2, characterized in that the aryldiadamantylphosphine derivative represented by the general formula (1) is represented by the following general formula (1A). 【Transformation 5】 (In the formula, Z １ and Z ２ Each of these independently represents an alkyl group having 1 to 5 carbon atoms.

8. The method for producing an aryl diadamantyl fin derivative according to claim 7, characterized in that the reaction crystallization step involves preparing solution A, which is obtained by dissolving the lithiated product obtained in the lithiation step in a solvent, and solution B, which is obtained by dissolving diadamantylchlorophosphine represented by general formula (3) in a solvent, and then adding solution B to solution A to carry out the reaction.

9. The method for producing an aryl diadamantylphosphine derivative according to claim 8, characterized in that the aforementioned liquids A and B each contain at least cyclopentyl methyl ether.

10. The method for producing an aryl diadamantylphosphine derivative according to claim 8, characterized in that the solvent of solution A is a mixed solvent of cyclopentyl methyl ether and tetrahydrofuran.

11. The method for producing an aryl diadamantylphosphine derivative according to claim 8, characterized in that the solvent of the aforementioned solution B is cyclopentyl methyl ether.

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