JP2000095790A - Novel palladium-imidazole complex - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel palladium-imidazole complex that has no bad smell and no toxicity and is useful as a ligand for palladium complex having excellent stability and high catalytic activity. SOLUTION: This novel compound is represented by the formula [R1 and R2 are each H, a lower alkyl; R3 is a (substituted)2-pyridinyl]. This compound can be prepared by the process described in a literature (Synthesis, 489, 1980, Hughey IV, J.L., et al). This novel compound is mixed with a palladium compound, for example, allylpalladium chloride in an inert solvent for example, dichloromethane or the like to give a palladium complex, which is useful for organic synthetic reactions for example, cyclopropanation reaction or the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel palladium
The present invention relates to an imidazole complex and a catalyst for organic synthesis containing the complex.

[0002]

2. Description of the Related Art A palladium catalyst is useful in various organic synthesis reactions such as a carbon-carbon bond forming reaction, an oxidation reaction, and a reduction reaction, and has been conventionally mainly used as a palladium-phosphorus or palladium-arsenic type catalyst. . However, although these catalysts have high activity, they have a problem that they are easily oxidized and thus easily lose their activity.
Since the ligands phosphorus and arsenic have a bad smell and toxicity, they may cause problems such as environmental pollution. Therefore, there is a need for the development of a palladium catalyst having a ligand replacing phosphorus and arsenic.

[0003]

An object of the present invention is to provide a palladium complex which has a non-odorous or nontoxic ligand in place of phosphorus or arsenic and has excellent stability and catalytic activity. Another object of the present invention is to provide an organic synthesis reaction using a palladium complex having the above characteristics as a catalyst.

[0004]

The present inventors have intensively studied to solve the above-mentioned problems, but palladium-pyridinylpyrazole complex is useful as a catalyst having the above-mentioned characteristics, They have found that they have high catalytic activity in organic synthesis reactions (Japanese Patent Application No. 10-113493). The present inventors conducted further research to solve the above problems,
A palladium complex containing an imidazole compound represented by the following formula (I) as a ligand has the above characteristics, and the complex has excellent catalytic activity and selectivity in an organic synthesis reaction such as a cyclopropanation reaction. Was found to be able to demonstrate. The present invention has been completed based on these findings.

That is, the present invention provides the following general formula (I):

Embedded image (Wherein, R ¹ and R ² each independently represent a hydrogen atom or a lower alkyl group, and R ³ represents a substituted or unsubstituted 2-pyridinyl group) a ligand for palladium metal; A palladium complex comprising the ligand is provided. Further, a catalyst for organic synthesis containing the complex, preferably a catalyst for carbon-carbon bond, more preferably a catalyst for forming cyclopropane is provided. The catalyst of the present invention has catalytic activity in, for example, a cyclopropanation reaction using ketene silyl acetal. In another aspect, the present invention provides a cyclopropanation reaction using the above catalyst.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION In the above general formula (I), R ¹ and R
² each independently represents a hydrogen atom or a lower alkyl group. It is preferred that R ¹ and R ² are simultaneously hydrogen atoms, but either or both of R ¹ and R ² may be lower alkyl groups. When both are lower alkyl groups, they may be the same or different. As the lower alkyl group, a linear, branched or cyclic alkyl group having 1 to 12 carbon atoms, preferably about 1 to 6 carbon atoms, or an alkyl group which is a combination thereof can be used. One or more linear or branched lower alkyl groups may be substituted on the ring of the cyclic alkyl group. More specifically, as a lower alkyl group, methyl group, ethyl group, n-propyl group, isopropyl group, cyclopropyl group, n-butyl group, sec-butyl group, tert-butyl group, cyclobutyl group, cyclopropylmethyl Groups can be used.

R ³ represents a substituted or unsubstituted 2-pyridinyl group. When the 2-pyridinyl group has a substituent, the number, type, and position of the substituent on the ring are not particularly limited,
When the palladium complex of the present invention is used as a catalyst for organic synthesis, it is desirable to appropriately select from the substituents that are inert in the reaction so as to enhance the catalytic activity in the target reaction. As the substituent, for example, a lower alkyl group, a lower alkoxy group (such as a methoxy group or an ethoxy group), a halogen atom (such as a fluorine atom, a chlorine atom, or a bromine atom) can be used. The substitution position is preferably at the 6-position. R ³ is preferably an unsubstituted 2-pyridinyl group or a 6-lower alkyl-2-pyridinyl group, and particularly preferably an unsubstituted 2-pyridinyl group or 6-methyl-2-pyridinyl group.

[0008] The compound represented by the above formula (I) has tautomers, and the compound is coordinated to palladium metal as shown in the following Examples to form the palladium of the present invention. It is considered to form a complex (in the following formula, a compound in which R ³ is an unsubstituted 2-pyridyl group is shown). However, the ligand of the present invention should not be interpreted as being limited to any of these tautomers.

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Some of the compounds represented by the above formula (I) are known and can be produced according to the methods described in the literature (JL Hughey IV, S. Knapp, H. Schugar, Synthes).
is, 489, 1980). According to the methods described in the above-mentioned publications, by appropriately selecting starting compounds, reaction reagents, reaction conditions, and the like, and by appropriately modifying or modifying the method, a compound included in the above formula (I) Can be manufactured.

As a typical compound included in the above formula (I), compound Ia (R ¹ and R ² are hydrogen atoms and R ³ is unsubstituted)
A compound which is a 2-pyridinyl group) and a compound Ib (R ¹ and R ²
Is a hydrogen atom, and R ³ is a 6-methyl-2-pyridinyl group). These compounds are odorless solids at room temperature and are stable in air.

The palladium complex of the present invention can be produced by mixing the compound represented by the above formula (I) and a palladium compound (for example, allyl palladium chloride) in an inert solvent. The palladium complex of the present invention usually has one ligand in addition to the compound represented by the above formula (I), but the kind of the ligand is not particularly limited. When the palladium complex of the present invention forms a salt, the type of anion is not particularly limited, and any form of salt is included in the complex of the present invention.

For example, a palladium complex in the form of tetrafluoroborate (complex 2a or 2b) is obtained by reacting the above-mentioned compound 1a or compound Ib with allyl palladium chloride in the presence of AgBF ₄ . The complex in the form of tetrafluoroborate (cationic) can be converted into the neutral complex 3a or 3b by further treatment with a base. Both such cationic and neutral complexes are included within the scope of the present invention.

[0013]

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The complex of the present invention can be used as various organic synthesis catalysts. Since the complex of the present invention exhibits high solubility in various organic solvents in the form of a neutral complex,
A wide range of reaction conditions can be applied in various organic reactions. The organic reaction in the case where the complex of the present invention is used as a catalyst is not particularly limited. For example, the organic reaction can be used for a carbon-carbon bond forming reaction, an oxidation reaction, a reduction reaction, or the like. As a characteristic carbon-carbon bond forming reaction performed using the complex of the present invention, a reaction for forming a cyclopropane ring can be exemplified.

As specifically shown in the examples of the present specification, the palladium complex 2a or 2b of the present invention exhibits catalytic activity in the reaction of the ester derivative ketene silyl acetal with allyl acetate, The cyclopropane compound is given as the main product. The structure of ketene silyl acetal that can be used in the method of the present invention is not particularly limited, and those skilled in the art can select an appropriate compound. Representative ketene silyl acetals are illustrated in the examples herein. In the reaction with cinnamyl acetate, the reaction proceeds stereoselectively, and cyclopropane having a trans configuration is obtained. The amount used when the palladium complex of the present invention is used as a catalyst is not particularly limited and can be appropriately selected depending on the type of organic reaction and reaction conditions, for example, 0.01 to 100 mol%.
It can be used at a moderate concentration. Needless to say, the type of solvent, reaction conditions, type of reagent, and the like can be appropriately selected by those skilled in the art.

[0016]

The present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited to these examples. The compound numbers in the examples correspond to the compound numbers in the above scheme. Example 1: Preparation of compound 1b Literature (Hughey IV, JL, et al., Synthesis, 489, 198)
According to the production of compound 1a described in 0), compound 1b was obtained in a yield of 56% using 3-methyl-2-cyanopyridine as a starting compound. ¹ H NMR (300 MHz, CDCl ₃ ) δ 11.1 (br, 1H), 8.37 (b
rd, 1H, J = 4.8 Hz), 7.59 (br.d, 1H, J = 7.6 Hz),
7.30 (s, 1H), 7.15 (m, 1H), 7.11 (s, 1H), 2.85
(s, 3H). ¹³ C NMR (75 MHz, CDCl ₃ ) δ 147.2, 146.21, 145.93,
139.87, 131.79, 130.31, 122.56, 116.45, 20.88.mp 121 ° C Anal.Found: C, 67.72; H, 5.69; N, 26.19% .Calcd.
for C, 67.91; H, 5.70; N, 26.40%.

Example 2 Production of Palladium Complex (Complex 2) AgBF ₄ (278 mg, 1.428 mmo) was placed in a 100 mL brown three-necked flask.
l) and η ³ -allylpalladiumchloride dimer (261 mg, 0.7
14 mmol), the reaction system was purged with argon, cooled to 0 ° C., and 40 mL of dichloromethane was added. The reaction mixture
After stirring for 10 minutes, compound 1a (208 mg, 1.42
(8 mmol) was added as a solid. The reaction mixture is allowed to
After stirring for minutes, the mixture was returned to room temperature and further stirred for 1 hour. 40 mL of methanol was added to the reaction vessel, the insoluble solid was filtered through celite, the filtrate was concentrated under reduced pressure, and the residue was dried to obtain complex 2a.
Was obtained (515 mg, yield 95%).

¹ H NMR (600 MHz, CD ₃ OD: CD ₂ Cl ₂ = 1: 1)
δ 8.75 (br.d, 1H, J = 5.4 Hz), 8.19 (ddd, 1H, J
= 7.8, 7.8, 1.5 Hz), 8.08 (br.d, 1H, J = 7.8 Hz),
7.60 (ddd, 1H, J = 7.8, 5.4, 1.5 Hz), 7.43 (d, 1H,
J = 1.0 Hz), 7.31 (d, 1H, J = 1.0 Hz), 5.85 (tt, 1
H, J = 12.7, 6.3 Hz), 4.41 (br, 1H), 4.35 (br, 1
. H), 3.48 (br, 1H), 3.30 (br, 1H) 13 C NMR (150 MHz, CD 3 OD: CD 2 Cl 2 = 1: 1) δ 15
4.98, 148.45, 147.91, 141.63, 131.45, 127.09, 121.
86, 121.29, 118.46, 63.60, 58.31.mp 220 ° C (decomp.) Anal Calcd. For C ₁₁ H ₁₂ N ₃ PdBF ₄ : C, 34.82; H, 3.19;
N, 11.07; Found: C, 34.52; H, 3.11; N, 10.79.

Similarly, a complex was prepared from compound 1b (233 mg).
2b was obtained (565 mg, 83% yield). ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.10 (br), 8.75 (br.
d, J = 5.1 Hz), 8.10 (br.d, J = 7.7 Hz), 7.71 (br.
s), 7.57 (dd, J = 7.7, 5.1 Hz), 7.54 (br.s), 5.90
(tt, J = 12.1, 6.6 Hz), 4.39 (syn 2H, d, J = 6.6 H
z), 3.36 (anti 2H, d, J = 12.1 Hz), 2.69 (Me, br.
^{s). 13 C NMR (150} MHz, DMSO-d 6) δ 152.53, 146.36, 144.
98, 143.14, 132.32, 130.42, 125.94, 122.51, 118.0
4, 60.81, 19.66

EXAMPLE 3 Preparation of Palladium Complex (Complex 3)_ThreeAfter stirring in an aqueous solution, extract with dichloromethane.
And extract was dried over anhydrous MgSO _FourAfter drying with, the complex 3a is concentrated.
Obtained.¹ H NMR (600 MHz, CD_ThreeOD: CD_TwoCl_Two = 1: 1) δ 8.46
(br.d, 1H, J = 5.4 Hz), 7.93 (br.d, 1H, J = 8.3 H
z), 7.88 (ddd, 1H, J = 8.3, 8.3, 1.5 Hz), 7.18 (dd
d, 1H, J = 8.3, 5.4, 1.0 Hz), 7.14 (br.s, 1H), 7.1
0 (br.s, 1H), 5.67 (tt, 1H, J = 12.7, 6.8 Hz), 4.13
 (d, 1H, J = 6.8 Hz), 4.03 (d, 1H, J = 6.8 Hz), 3.2
6 (d, 1H, J = 12.7 Hz), 3.03 (d, 1H, J = 12.7 Hz).¹³ C NMR (150 MHz, CD_ThreeOD: CD_TwoCl_Two = 1: 1) δ 154.7
6, 153.97, 153.51, 140.15, 130.99, 130.81, 122.92,
 119.94, 116.47, 61.68, 54.38.

Similarly, complex 3b was obtained from complex 2b (202 mg) (147 mg, 94% yield). ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 8.49 (d, J = 5.4 Hz),
7.81 (d, J = 7.8 Hz), 7.15 (dd, J = 7.8, 5.4 Hz),
7.09 (s), 7.08 (s), 5.72 (m), 4.05 (syn 2H, br), 3.
28 (anti 1H, br), 2.96 (anti 1H, br), 2.76 (Me,
s). ¹³ C NMR (150 MHz, DMSO-d ₆ ) δ 154.63, 151.16, 150.
55, 141.68, 130.79, 130.61, 129.64, 121.18, 115.9
0, 62.00, 53.22, 19.84.mp 138 ° C Anal Calcd. For C ₁₂ H ₁₃ N ₃ Pd: C, 47.16; H, 4.29; N,
13.75; Pd, 34.81 Found: C, 47.17; H, 4.22; N, 1
3.71; Pd, 34.79.

Example 4: Cyclopropanation reaction

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The palladium complex 2a (19 mg, 0.05 mmol) of the present invention and sodium acetate (1
6.4 mg, 0.2 mmol), and the reaction system was purged with argon, and then 2 mL of DMSO was added. After stirring the reaction mixture for 5 minutes, allyl acetate (100 mg, 1 mmol) dissolved in 1 mL of DMSO was added. Next, ketene acetal (429 mg, 2 mm
ol) was dissolved in 1 mL of DMSO and added, and stirring was continued at room temperature. As a result, the reaction solution changed from colorless to pale yellow. The progress of the reaction was monitored by gas chromatography, and the reaction was terminated when the formation of compounds 6a and 7a was stopped (90 ° C at room temperature).
After stirring for a minute, Pd black precipitate was formed, and the reaction was completed).

To the reaction solution, 5 mL of ether and 5 mL of water were added, followed by 3 mL of a 10% aqueous HCl solution, and the mixture was stirred at room temperature for 30 minutes to hydrolyze the remaining ketene acetal. The organic layer was extracted with ether, and washed with a saturated aqueous solution of NaHCO ₃ and a saturated saline solution. The organic layer was dried (MgSO ₄ ), filtered, and the filtrate was concentrated under reduced pressure. The oily substance having a relatively low boiling point was removed by distillation, and the residue was purified by silica gel chromatography using an ether-hexane (1: 9) solvent to obtain a mixture of compound 6a and compound 7a. Was done. When the mixture ratio of the products was calculated by using gas chromatography and NMR, the formation ratio of compound 6a: compound 7a was 23: 1. Pure compound
6a was isolated by the method described in the example of Japanese Patent Application No. 10-113493. Similarly, when palladium complex 2b was used, the formation ratio of compound 6a to compound 7a was 44: 1.

Example 5: Cyclopropanation reaction Compound 6b and compound 7b were produced in the same manner as in Example 4 above, using catalyst 2a or 2b.

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Compound 6b ¹ H NMR (500 MHz, CDCl ₃ ) δ 4.08 (q, 2H), 1.21 (t, 3
H), 1.01 (s, 3H ), 1.00 (m, 1H), 0.35-0.22 (m, 4H). 13 C NMR (125.8 MHz, CDCl 3), δ 177.9, 60.2, 41.1,
22.9, 19.5, 14.5, 0.70.MS, m / z (relative intensity) 156 (M ⁺ , 3.3), 141 (1
7.5), 128 (6.6), 113 (9.9), 110 (10.4), 100 (24.
8), 83 (100), 67 (11.6), 55 (99.3).

Similarly, Compound 6c and Compound 7c were produced using Catalyst 2a or 2b.

Embedded image

Compound 6c ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.29 (t, 2H), 7.18 (t, 1
H), 7.13 (d, 2H), 4.17 (m, 2H), 1.99 (s, 3H), 1.93
(ddd, 1H, J = 5.0, 5.7, 9.2 Hz), 1.39 (ddd, 1H, J-5.
0, 5.7, 8.7 Hz), 1.26 (t, 3H, J = 7.1 Hz), 1.20 (s,
3H), 1.01 (ddd, 1H, J = 5.5, 5.7, 8.7 Hz), 0.90 (ddd,
1H, J = 5.5, 5.7, 9.2 Hz). 13 C NMR (125.8 MHz, CDCl 3) δ 177.3, 143.0, 128.2,
126.1, 125.4, 60.4, 41.5, 31.1, 23.2 (2C), 19.1,
14.2, 11.3. Anal.Found: C, 77.27; H, 8.85% .Calcd for C ₁₅ H ₂₀ O
₂ : C, 77.55; H, 8.69%.

[0029]

The palladium complex of the present invention is stable,
It is convenient to handle since problems such as bad smell are avoided as compared with complexes containing phosphorus or arsenic as a ligand. Further, it can be used as a catalyst for various organic reactions such as cyclopropanation reaction, and is particularly useful as a catalyst having excellent selectivity in cyclopropanation reaction.

Continued on the front page F term (reference) 4C063 AA01 BB01 CC25 DD12 EE10 4G069 AA15 BA27A BA27B BC72A BC72B BE13A BE38A BE38B CB65 4H050 AA01 AA03 AB40 WB14 WB21

Claims (6)

[Claims] 1. The following general formula (I): (Wherein, R ¹ and R ² each independently represent a hydrogen atom or a lower alkyl group, and R ³ represents a substituted or unsubstituted 2-pyridinyl group). 2. A palladium complex containing the ligand represented by the general formula (I) according to claim 1. 3. R ¹ and R ² are hydrogen atoms, and R ³ is unsubstituted
The palladium complex according to claim 2, which is a 2-pyridinyl group or a 6-methyl-2-pyridinyl group. 4. A catalyst for organic synthesis comprising the palladium complex according to claim 2 or 3. 5. The method according to claim 4, which is used in a cyclopropanation reaction.
The catalyst according to the above. 6. The catalyst according to claim 5, which has catalytic activity in a cyclopropanation reaction using ketene silyl acetal.