JP5493346B2 - Ferrocene derivatives and uses thereof - Google Patents

Description

  The present invention relates to a novel ferrocene derivative. The ferrocene derivative of the present invention is useful for an intermediate of a catalyst used for a homogeneous or heterogeneous catalytic reaction.

  Until now, many ferrocene derivatives have been reported (for example, refer nonpatent literature 1). However, there are few reports on 2,1′-dihalogeno-1- (dialkylaminomethyl) ferrocene derivatives or 2-phosphino-1′-halogen-1- (dialkylaminomethyl) ferrocene derivatives (for example, see Patent Document 1). ), 2,1′-dihalogeno-1- (2-dialkylaminoethyl) ferrocene derivative, or 2,1′-dibromo which is a 2-phosphino-1′-halogeno-1- (2-dialkylaminoethyl) ferrocene derivative -1- (2-Dimethylaminoethyl) ferrocene is only known as a raw material for homogeneous or heterogeneous catalysts for (asymmetric) hydrogenation reactions (see, for example, Patent Document 2).

  So far, many palladium-catalyzed ligands have been reported in carbon-carbon bond reactions (also known as Suzuki-Miyaura coupling reactions) or carbon-nitrogen bond reactions (also known as Bichwald-Hartwig reactions). For example, tri (t-butyl) phosphine (see, for example, Patent Document 3 and Non-Patent Document 2), a ferrocene derivative substituted with a dialkylphosphino group (see, for example, Patent Document 4 and Non-Patent Document 3), 2-dicyclohexyl- Examples thereof include carbene derivatives such as 1,1′-biphenyl derivatives (for example, see Patent Document 5), 1,3-bis- (2,6-diisopropylphenyl) imidazolinium salts (for example, see Non-Patent Document 4), and the like. It is done.

  In the homogeneous palladium catalyst comprising the above ligand, the transition metal remains in the reaction system, and thus it has been necessary to repeat recrystallization and / or column chromatography in order to remove the transition metal from the reaction system. In recent years, from the viewpoint of green sustainable chemistry, for example, a microcapsule type catalyst in which a triphenylphosphine derivative is immobilized (see, for example, Patent Document 6), a graft type immobilized catalyst in which a triphenylphosphine derivative is immobilized (for example, a patent) Reference 7), immobilized catalyst with immobilized carbene derivative (for example, see Patent Document 8 and Non-patent Document 5), and microcapsule-type immobilized with 2-dicyclohexylphosphinobiphenyl (also known as Buchwald ligand) immobilized Heterogeneous transition metal catalysts such as fluorination catalysts (see, for example, Patent Document 9) have been reported.

Japanese National Patent Publication No. 11-503439 Special Table 2000-514436 JP 10-139742 A JP 2000-247990 A US 2002/156295 published specification Special table 2004-533928 gazette JP-T-2004-513194 JP 2002-20396 A JP 2008-221089 A Journal of Organometallic Chemistry, 567, 191-198 (1998) Journal of American Chemical Society, 122 (17), 4020-4028 (2000) Journal of American Chemical Society, 130, 6586-6596 (2008) Angew. Chem. Int. Ed. , 46, 2768-2813 (2007) Organic Letters, 10 (8), 1609 (2008) However, in the Suzuki-Miyaura reaction, the heterogeneous catalyst has little elution of transition metal into the reaction system and high reaction activity, but in the Buchwald-Hartwig reaction. However, a result that still satisfies both a low metal elution amount and a high reaction activity has not been obtained (for example, see Patent Document 8). In addition, even when the Buchwald-Hartwig reaction is performed using a microencapsulated catalyst or a graft polymer, sufficient catalytic activity has not yet been obtained (see, for example, Patent Documents 6 and 7).

  Provided is a palladium catalyst or nickel catalyst useful for a carbon-carbon bond reaction or a carbon-nitrogen bond reaction.

  As a result of intensive studies, the present inventors have found that a ligand using a specific ferrocene derivative represented by the general formula (1) and a catalyst thereof are effective for a carbon-carbon bond reaction or a carbon-nitrogen bond reaction. I found out. That is, the present invention relates to a novel ferrocene derivative represented by the general formula (1) and its use.

(In the formula, X represents a halogen atom, Y represents a halogen atom, a dialkylphosphino group or a diarylphosphino group, and Z represents an amino group represented by the following general formula (2) or the following general formula (3). Represents the phosphino group represented.)

(In the formula, R ^{1 to} R ⁴ each independently represent a linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, or an optionally substituted phenyl group or naphthyl group.)
Hereinafter, the present invention will be described in detail.

  In the ferrocene derivative represented by the general formula (1), the substituent X is a halogen atom such as an iodine atom, a chlorine atom, or a bromine atom.

  The substituent Y is a halogen atom, a dialkylphosphino group or a diarylphosphino group. The halogen atom is an iodine atom, a chlorine atom, or a bromine atom. Examples of the dialkylphosphino group include dimethylphosphino group, diethylphosphino group, diisopropylphosphino group, di (t-butyl) phosphino group, t-amyl group, di (cyclohexyl) phosphino group, di (1-adamantyl) phosphino. Group, di (3,5-dimethylphosphino group). Examples of the diarylphosphino group include diphenylphosphino group, bis (2,6-dimethylphenyl) phosphino group, bis (2,4,6-trimethylphenyl) phosphino group, and bis (2,6-diisopropylphenyl) phosphino. Group, bis (2,4,6-triisopropylphenyl) phosphino group, bis (2,6-dimethoxyphenyl) phosphino group, bis (2,4,6-trimethoxyphenyl) phosphino group. Among them, di (cyclohexyl) phosphino group, di (t-butyl) phosphino group, di (1-adamantyl) phosphino group, bis (2,6-dimethylphenyl) phosphino group, bis (2,4,6-trimethylphenyl) Phosphino groups and bromine atoms are effective as substituents for ferrocene derivatives.

R ^{1 to} R ⁴ are each independently a linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, or an optionally substituted phenyl group or naphthyl group.

  Specific examples of the straight-chain, branched or cyclic alkyl group having 1 to 18 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, pentyl group, and amyl group. Hexyl group, 2-hexyl group, cyclohexyl group, 1-adamantyl group, 3,5-dimethyladamantyl group and the like. Examples of the optionally substituted phenyl group or naphthyl group include an alkyl group exemplified above, an alkoxy group having 1 to 6 carbon atoms such as a methoxy group, an ethoxy group, a propoxy group, a butoxy group, and a pentoxy group, and Examples thereof include a phenyl group and a naphthyl group substituted with a phenyl group.

  Specific examples of the substituent Z include a dimethylamino group, a diethylamino group, a di-n-propylamino group, a diisopropylamino group, a di-n-butylamino group, a di-sec-butylamino group, a dicyclohexylamino group, and a dihexylamino group. , An amino group represented by the general formula (2) such as a diphenylamino group, or a diethylphosphino group, a diisopropylphosphino group, a di-n-butylphosphino group, a di-t-butylphosphino group, a dicyclohexylphosphino And a phosphino group represented by the general formula (3) such as a group, a diphenylphosphino group, a di (o-tolyl) phosphino group, a di (m-tolyl) phosphino group and a di (p-tolyl) phosphino group. Of these, a dimethylamino group, a diethylamino group, a dicyclohexylphosphino group, and a diphenylphosphino group are preferable because of ease of synthesis.

  The ferrocene derivative of the present invention can be synthesized from dimethylaminomethylferrocene which is easily available and inexpensive (see the following formula (4)). Specifically, butyllithium and dibromotetrafluoroethane can be reacted with compound 1 to synthesize compound 2 which is a dibromo compound (reference document: Journal of Organometallic Chemistry, 567, 191-198 (1998)). Next, after converting into compound 3 using butyllithium and a chlorophosphine derivative, compound 4 can be synthesized by reacting with a phosphine compound in acetic acid (reference: Inorganic Chemistry Communications, 7, 923- ( 2004)).

(Wherein R ⁵ and R ⁶ each independently represents a linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, or an optionally substituted phenyl group or naphthyl group.)
Next, the method for immobilizing the compound 3 or 4 is not particularly limited. For example, after lithiation of bromine with butyllithium, a formyl form can be synthesized by reacting with dimethylformamide. The resulting formyl form can be introduced with a vinyl group by reacting with a Wittig reagent, or a hydroxymethyl group by treatment with paraformaldehyde. Moreover, a silyl group can be introduce | transduced by making a silyl compound, for example, 3-chloropropyl chlorodimethylsilane, and the said lithio body react.

  The obtained ferrocene derivative having a vinyl group, a hydroxymethyl group, a chloropropyldimethylsilyl group or the like can be immobilized on an organic carrier such as polystyrene by a known method. Moreover, the ferrocene derivative which has a vinyl group can also be microencapsulated by radical polymerization with a styrene derivative.

  The ferrocene derivative represented by the general formula (1) of the present invention is a novel substance, and a ligand derived from this ferrocene derivative is active and palladium eluted in a carbon-carbon bond reaction and a carbon-nitrogen bond reaction. It is a very effective compound in terms of quantity.

  EXAMPLES Hereinafter, although this invention is demonstrated in detail based on an Example, this invention is not limited to these. The analytical instruments and measurement methods used in this example are listed below.

[NMR measurement]
NMR measuring apparatus: VARIAN Gemini-200
[Mass spectrometry]
Mass spectrometer: M-80B manufactured by Hitachi, Ltd.
[Elemental analysis]
Elemental analyzer: Perkin Elmer fully automatic elemental analyzer oxygen flask combustion-IC measurement method: Tosoh ion chromatograph IC-2001
[ICP analysis]
Sample preparation: wet decomposition with sulfuric acid-nitric acid Analyzer: Optima3000DV manufactured by PerkinElmer
Synthesis Example 1 (Synthesis of Fc-2)
Dimethylaminomethylferrocene Fc-1 (9.72 g, 40 mmol) and dehydrated diethyl ether (70 ml) were added to a 300 ml eggplant-shaped flask, and then a 1.6 M n-butyllithium / hexane solution (hereinafter, n-BuLi) was added at room temperature under a nitrogen atmosphere. 27 ml of (abbreviated as solution) was added (44 mmol). After stirring at the same temperature for 2 hours, a solution comprising 30 ml of a previously prepared n-BuLi solution, 5.11 g (44 mmol) of tetramethylethylenediamine and 4 ml of tetrahydrofuran was dropped at room temperature, and the mixture was further stirred for 24 hours. . Thereafter, the reaction solution was cooled to −78 ° C., and 23.1 g (88.9 mmol) of 1.2-dibromotetrafluoroethane was added dropwise. Further, the mixture was stirred at the same temperature for 1 hour and further at room temperature for 2 hours.

70 ml of cold water was added to the reaction solution to complete the reaction. The reaction solution was extracted with ethyl acetate (50 ml × 3 times), and the obtained organic layer was washed with 50 ml of water and subsequently with 50 ml of saturated brine, and then dried over magnesium sulfate. The brown oil obtained by concentrating the organic layer was purified by silica gel chromatography (eluent = acetone) to isolate 8.3 g (yield = 52%) of Fc-2. A ¹ H-NMR chart of Fc-2 is shown in FIG.

¹ H-NMR (CDCl ₃ , ppm): 2.23 (s, 6H), 3.41 (d, J = 3.6 Hz, 2H), 4.09-4.45 (m, 7H)

Example 1 (synthesis of Fc-3)
8.33 g (20.9 mmol) of Fc-2 and 90 ml of dehydrated diethyl ether were charged into a 300 ml eggplant type flask, and 13 ml of n-BuLi solution was added dropwise at -30 to -40 ° C. After stirring at the same temperature for 30 minutes, the reaction solution was cooled to −78 ° C., and 4.75 ml of chloro-di (t-butyl) phosphine was added dropwise with a syringe.

  Then, after stirring at the same temperature for 30 minutes and further at room temperature overnight, 50 ml of cold water was added to complete the reaction. The reaction solution was extracted with ethyl acetate, and the obtained organic layer was washed with 40 ml of water and subsequently with 40 ml of saturated brine, and then dried over magnesium sulfate. The brown oil obtained by concentrating the organic layer was purified by silica gel chromatography (eluent: hexane / ethyl acetate = 1/2 volume ratio) to obtain 2.8 g (yield = 29%) of Fc- 3 was isolated.

A ¹ H-NMR chart of Fc-3 is shown in FIG.

¹ H-NMR (CDCl ₃ , ppm): 0.94 (d, 9H, J = 111 Hz), 1.48 (d, 9H, J = 12.4 Hz), 2.25 (s, 6H), 2. 36 (d, 1H, J = 14.4 Hz), 3.54 (dd, 1H, J = 14, 2.6 Hz), 4.50 (t, 2H, J = 1.6 Hz), 4.31-4 .42 (m, 4H), 4.69 (brs, 1H)
Example 2 (synthesis of Fc-4)
2.8 g (6 mmol) of Fc-3 and 85 ml of dehydrated diethyl ether were added to a 200 ml eggplant type flask. Next, after cooling the reaction solution to −30 to −40 ° C., a 1.6M BuLi hexane solution was added dropwise, and the mixture was aged with stirring at the same temperature for 1 hour. Next, the reaction solution was cooled to −78 ° C. with dry ice / acetone, 0.34 g (11.4 mmol) of paraformaldehyde was added little by little under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 1 hour and further at room temperature for 16 hours. The reaction was terminated by adding 50 ml of cold water. The reaction solution was extracted with ethyl acetate and then purified by silica gel chromatography (eluent = hexane / ethyl acetate = 1/1 volume ratio) to isolate 0.60 g of Fc-4 as a reddish brown oil ( Yield = 24%). Note that Fc-4 showed paramagnetism because it showed a behavior in which the peak became broad in ¹ H-NMR. Since the molecular ion peak of m / e = 417 was shown by FDMS, it was identified as the target product.

Example 3 (Synthesis of 2,1′-dibromo-1- (diphenylphosphinomethyl) ferrocene)
To a 100 ml eggplant-shaped flask, 0.5 g (1.1 mmol) of Fc-3 obtained in Example 1, 0.2 g (1.1 mmol) of diphenylphosphine and 15 ml of acetic acid were added, and the mixture was kept at 100 ° C. for 3 hours under a nitrogen atmosphere. Stir. After cooling, the reaction mixture was concentrated and purified by silica gel chromatography (eluent: hexane / ethyl acetate = 1/2 volume ratio) to obtain 0.34 g of a reddish brown oil. Since the molecular ion peak of m / e = 606 was shown by FDMS, it was identified as the target product.

Example 4 (Synthesis of Fc-5 [immobilization to polystyrene])
Under a nitrogen atmosphere, 0.56 g (1.34 mmol) of Fc-4 synthesized in Example 2 and 80 ml of dehydrated tetrahydrofuran were added to a 100 ml eggplant type flask, and sodium hydride (containing 40% mineral oil) was added. 07 g (1.75 mmol) was added. After stirring the reaction solution at room temperature for 1 hour, macroporous chloromethylated polystyrene (manufactured by Aldrich, 1.2 mmol-Cl / g) was added, and the reaction solution was refluxed for 45 hours. After cooling the reaction solution, 10 ml of water was added, followed by filtration. The obtained immobilized catalyst was washed twice with 10 ml of water, and further washed with methanol and tetrahydrofuran (each 10 ml × 3 times). After vacuum drying, 540 mg of a light red brown granular solid was obtained. As a result of ICP analysis and elemental analysis, the contents of P, Fe and N in Fc-5 were 0.15 mmol / g, 0.22 mmol / g and 0.19 mmol / g, respectively.

Example 5 (Synthesis of Fc-6 [immobilization of palladium acetate])
A 30 ml Schlenk tube was charged with 260.5 mg of Fc-5 synthesized in Example 4, and 34.8 mg of palladium acetate / 2 ml of dehydrated tetrahydrofuran was added. The mixture was heated and stirred at 60 ° C. for 4 hours under a nitrogen atmosphere and cooled to room temperature. The obtained solid was washed with tetrahydrofuran and methanol (each 5 ml × 3 times) and then vacuum-dried. As a result of ICP analysis, the contents of Pd and Fe in Fc-6 were 0.21 mmol / g and 0.18 mmol / g, respectively.

Example 6 (Catalyst performance test in carbon-nitrogen bond reaction)
In a 100 ml eggplant type flask, 125 mg of palladium-immobilized catalyst FC-6 obtained in Example 5 (1 mol% in terms of Pd), 0.39 g (2.5 mmol) of bromobenzene, 0.465 g (5.0 mmol) of aniline, Sodium-t-butoxide 0.48 g (5.0 mmol) and toluene 5 ml were charged and stirred at 100 ° C. for 24 hours under nitrogen. The reaction solution was cooled, 5 ml of water was added, and the reaction solution was filtered. The recovered immobilized catalyst was washed 5 times with 5 ml of toluene. After separating the obtained mother liquor, it was found by gas chromatography analysis by an internal standard method of the organic layer that the target product, N-phenyl-3-toluidine, was obtained in a yield of 95.2%. . Moreover, when the amount of Pd in the reaction solution was analyzed by ICP, it was 4 ppm, and it was found that 6% was eluted with respect to the amount of palladium charged.

Comparative Example 1
When the immobilized catalyst was replaced with 77 mg (1 mol% in terms of Pd) of microcapsule-type catalyst Pd-Encat TOTP30 (manufactured by Wako Pure Chemical Industries, Inc., tris (o-tolyl) phosphine), an experiment similar to Example 6 was performed. The progress of the reaction was hardly recognized.

Comparative Example 2
An experiment similar to that in Example 6 was performed instead of the immobilized catalyst, 104 mg (1 mol% -Pd in terms of palladium), of a catalyst in which carbene precursor and palladium acetate were immobilized on polystyrene. N-phenyl-3-toluidine The yield of was 9.7%.

The synthesis of the carbene precursor and the immobilization of the carbene precursor and palladium acetate on polystyrene were performed according to the method described in Organic Letters, 10 (8), 1609 (2008). A ¹ H-NMR chart of the carbene precursor is shown in FIG. Further, the Pd concentration of the synthesized palladium immobilized catalyst was 2.5 wt% as a result of ICP analysis.

1 shows a ¹ H-NMR chart of Fc-2 synthesized in Synthesis Example 1. 1 shows a ¹ H-NMR chart of Fc-3 synthesized in Example 1. ¹ shows a ¹ H-NMR chart of a carbene precursor (1- (2,4,6-trimethylphenyl) imidazole) synthesized in Comparative Example 2. FIG.

Claims (3)

Carbon - carbon bond reaction or a carbon - a palladium catalyst used in the nitrogen binding reaction, the catalyst is one having immobilized ligands ferrocene derivatives, inorganic or organic carriers represented by the following general formula (1) A palladium catalyst characterized by being.

(Wherein, X represents a halogen atom, Y represents a dialkylphosphino group or diarylphosphino group, Z is represented by the amino group or a group represented by the general formula represented by the following general formula (2) (3) Represents a phosphino group.)

(Wherein R ^{1 to} R ⁴ are each independently a linear, branched or cyclic alkyl group having 1 to 18 carbon atoms, an alkyl group having 1 to 18 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, or (The phenyl group or naphthyl group which the phenyl group may substitute is represented.) The palladium catalyst according to claim 1, wherein the amino group represented by the general formula (2) is a dimethylamino group. Y is di (cyclohexyl) phosphino group, di (t-butyl) phosphino group, di (1-adamantyl) phosphino group, di (2,6-dimethylphenyl) phosphino group, or di (2,4,6-trimethyl) The palladium catalyst according to claim 1, which is a phenyl) phosphino group.

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