JP3399507B2 - New palladium-oxazoline pyrazole complex - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel oxazoline pyrazole compound, palladium-oxazoline pyrazo-
And a catalyst for organic synthesis containing the complex.

[0002]

2. Description of the Related Art Palladium catalysts are useful in various organic synthetic reactions such as carbon-carbon bond forming reactions, oxidation reactions, and reduction reactions, and have been conventionally used mainly as palladium-phosphorus or palladium-arsenic type catalysts. . However, although these catalysts have high activity, they have the problem that they are easily oxidized and thus lose their activity.
Phosphorus and arsenic, which are ligands, have a bad odor and toxicity, which may cause problems such as environmental pollution. Therefore, there is a demand for the development of a paradium catalyst having a ligand that replaces phosphorus or arsenic.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a palladium complex which has a ligand having no bad odor or toxicity in place of phosphorus or arsenic and is excellent in stability and catalytic activity. Further, another object of the present invention is to provide an organic synthetic reaction using a paradium complex having the above characteristics as a catalyst. It is another object of the present invention to provide a compound useful as a ligand having the above characteristics.

[Means for Solving the Problems]

The present inventors have conducted extensive studies to solve the above-mentioned problems, and as a complex capable of exhibiting high catalytic activity in various organic synthetic reactions, a palladium complex having a pyrazole ligand (Japanese Patent Application No. 10-113493). Complex) and a imidazole ligand-containing palladium complex (Japanese Patent Application No. 10-269859)
No.) was provided. These complexes are characterized by having high catalytic activity in the catalytic cyclopropanation reaction of allyl acetate and ketene silyl acetal, which cannot be achieved by conventional palladium complexes.

The present inventors have conducted research to provide a palladium complex having higher catalytic activity and reaction selectivity, and the oxazoline pyrazole compounds represented by the following general formulas (I) and (II) are palladium compounds. It has been found that the palladium complex containing the compound as a ligand can exhibit high catalytic activity in various organic synthesis reactions because it has excellent performance as a stabilizing ligand. In particular, the formula (I
It was found that the palladium complex having an optically active ligand represented by I) can be used as a catalyst for various asymmetric synthesis reactions. The present invention has been completed based on these findings.

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

[Chemical 3] (In the formula, R ¹ represents a lower alkyl group; R ² and R ³ each independently represent a hydrogen atom or a lower alkyl group; R ⁴ represents a hydrogen atom, a lower alkyl group, or a substituent. Which represents a good lower aralkyl group) or a salt thereof; a ligand for a palladium metal represented by the above general formula (I); and the following general formula (II):

[Chemical 4] (In the formula, R ¹¹ represents a lower alkyl group; R ¹² and R ¹³ each independently represent a hydrogen atom or a lower alkyl group; R ¹⁴
Represents a lower alkyl group or a lower aralkyl group which may have a substituent; a wavy line indicates that the carbon atom to which R ¹⁴ is bonded is S-
(Indicated to be in either the R-configuration or the R-configuration)) for the palladium metal.

From another point of view, the present invention provides a palladium complex containing a ligand represented by the above formula (I) or formula (II). According to a preferred embodiment of this complex,
The above palladium complex containing a ligand of formula (I) wherein R ¹ is a tert-butyl group and R ² , R ³ and R ⁴ are hydrogen atoms; R ¹
Is a tert-butyl group, R ² and R ³ are hydrogen atoms, and R
Provided is a palladium complex containing the ligand of the formula (II), wherein ⁴ is an isopropyl group, a tert-butyl group, or a benzyl group; and a catalyst for organic synthesis containing the palladium complex.

This catalyst can be used in a cyclopropanation reaction, and is characterized by having catalytic activity particularly in a cyclopropanation reaction using a ketene silyl acetal. The palladium complex containing the ligand represented by the formula (II) can be used for an asymmetric cyclopropanation reaction.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION In the above general formula (I), R ¹ represents a lower alkyl group, R ² and R ³ each independently represent a hydrogen atom or a lower alkyl group, and R ² and R ³ represent hydrogen. It is preferably an atom. In formula (II), R ¹¹ represents a lower alkyl group, and R ¹² and R ¹³ each independently represent a hydrogen atom or a lower alkyl group, but it is preferable that R ¹² and R ¹³ are hydrogen atoms. 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 two or more linear or branched lower alkyl groups may be substituted on the ring of the cyclic alkyl group. More specifically,
As the 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,
A cyclopropylmethyl group or the like can be used. R ¹
Alternatively, the lower alkyl group represented by R ¹¹ is preferably a bulky alkyl group, and particularly preferably a tert-butyl group.

R ⁴ represents a hydrogen atom, a lower alkyl group or a lower aralkyl group, and R ¹⁴ represents a lower alkyl group or a lower aralkyl group. Substituents may be present on the ring of the aryl ring of the lower aralkyl group represented by these groups.
The number, type, and substitution position of the substituents on the ring are not particularly limited, but when the palladium complex of the present invention is used as a catalyst for organic synthesis, it is used in the reaction so as to enhance the catalytic activity in the reaction. It is desirable to appropriately select from the inert substituents. As the substituent, for example, a lower alkyl group, a lower alkoxy group (methoxy group,
For example, an ethoxy group) and a halogen atom (fluorine atom, chlorine atom, bromine atom, etc.) can be used. R ⁴ or
The lower alkyl group represented by R ¹⁴ is preferably a bulky alkyl group. For example, isopropyl group, isobutyl group, se
A c-butyl group or a tert-butyl group is preferable, and an isopropyl group or a tert-butyl group is more preferable. R ⁴ or R
^The lower aralkyl group represented by ¹⁴ is preferably a benzyl group.

In the compound represented by the formula (I), when R ⁴ is a group other than a hydrogen atom, the carbon atom to which R ⁴ binds is an asymmetric carbon, but is represented by the formula (I). The compound
In addition to the optically active substance in a pure form based on the asymmetric carbon, it may exist as any mixture or racemate of the optically active substance. All of these are included in the compound of the present invention. The compound represented by the formula (II) is an optically active substance, and the wavy line in the formula indicates that the carbon atom to which R ¹⁴ is bonded has either the S-configuration or the R-configuration.

The compound represented by the above formula (I) or formula (II) can exist as an acid addition salt. For example, it is possible to exist in the form of mineral acid salts such as hydrochloride, sulfate, nitrate, etc., organic acid salts such as p-toluenesulfonic acid, methanesulfonic acid, etc., but the kinds of salts are not limited to these. There is no such thing. In addition, the compound or acid addition salt in free form may exist as a hydrate or solvate. Furthermore, the following tautomers are present in the compound represented by the above formula (I) or formula (II) (in the following formula, R ² and R ³ are hydrogen compounds) ), And the ligands of the invention should not be construed as limited to any of these tautomers.

[Chemical 5]

Specific examples of the method for producing the compound represented by the above formula (I) are shown in Examples of the present specification. A person skilled in the art, with reference to the examples herein, a starting compound, a reaction reagent,
It is possible to produce any of the compounds included in the above formula (I) by appropriately selecting reaction conditions and the like, and by appropriately modifying or modifying these methods. Further, the optically active compound represented by the formula (II) can be produced by the asymmetric synthesis, although the racemic compound represented by the formula (I) can be produced and resolved by a usual optical resolution method. You can also One example is shown in the following scheme (wherein R ¹ is a tert-butyl group, R ² and R ³
Represents a compound having a hydrogen atom, and R ¹⁴ is represented as R. In addition, the stereochemistry of a compound shows relative configuration. ).

[0014]

[Chemical 6]

As a representative compound included in the above formula (I), the compound 4a in the above scheme (a compound in which R ¹ is a tert-butyl group and R ² , R ³ and R ⁴ are hydrogen atoms) As a representative compound included in the above formula (II), compound 4b (R ¹ is a tert-butyl group, R ² and R ³ are hydrogen atoms, R ⁴ is an isopropyl group Compound 4c (R ¹ is a tert-butyl group, R ² and R ³
Is a hydrogen atom, R ⁴ is a tert-butyl group), and compound 4d (R ¹ is a tert-butyl group, R ² and R ³ are hydrogen atoms, R ⁴ is a benzyl group Compound)
Can be mentioned. These compounds are odorless solids at room temperature and are stable in air.

The compound represented by the above formula (I) or formula (II) is useful as a ligand for producing a palladium complex. A compound represented by the above formula (I) or (II) and a palladium compound (eg, allylpalladium chloride)
The palladium complex of the present invention can be produced by mixing the above compounds 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) or formula (II), but the kind of this ligand is not particularly limited. . Further, when the palladium complex of the present invention forms a salt, the kind of anion is not particularly limited, and the salt of any form is included in the complex of the present invention. For example, a palladium complex in the form of tetrafluoroborate (complexes 5a to 5d) can be obtained by reacting the compounds 4a to 4d with allylpalladium chloride in the presence of AgBF ₄ .

[0017]

[Chemical 7]

The complex of the present invention can be used as a catalyst for various organic syntheses. Since the complex of the present invention shows high solubility in various organic solvents in the form of a neutral complex,
A wide range of reaction conditions can be applied to various organic reactions. The organic reaction when the complex of the present invention is used as a catalyst is not particularly limited, but it can be used, for example, in a carbon-carbon bond forming reaction, an oxidation reaction, or a reduction reaction. As a characteristic carbon-carbon bond forming reaction carried out using the complex of the present invention, a cyclopropane ring forming reaction can be mentioned.

As shown concretely in the examples of the present specification, the palladium complex of the present invention exhibits catalytic activity in the reaction between ester derivative ketene silyl acetal and allyl acetate, and the cyclopropane compound As the main product. The structure of the 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 addition, in the reaction with cinnamyl acetate, the reaction proceeds stereoselectively to obtain cyclopropane having a trans configuration. Furthermore, the palladium complex having an optically active ligand represented by the formula (II) is useful for the asymmetric cyclopropanation reaction.

When the palladium complex of the present invention is used as a catalyst, the amount used is not particularly limited and may be appropriately selected depending on the type of organic reaction and reaction conditions.
It can be used at a concentration of about 100 mol%, usually 1 to 1
Even with a catalyst amount of about 0 mol%, the product is obtained in high yield. Needless to say, the type of solvent, reaction conditions, type of reagent, etc. can be appropriately selected by those skilled in the art.

[0021]

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 following examples correspond to the compound numbers in the above scheme. Example 1: Production of Ligand Synthesis of Compound 1 A 500 mL three-necked flask was equipped with a dropping funnel and a Dimroth.
After adding sodium hydride (60 wt%, 2.0 g, 50 mmol), replace with argon, and add 25 mL of tetrahydrofuran (THF).
Was added and cooled to 0 ° C. Hydrogen gas was generated when 2,2-dimethylbutan-3-one (5.01 g, 50 mmol) dissolved in 25 mL of THF was slowly added to this suspension. After stirring at 0 ° C for 15 minutes and further stirring at room temperature for 20 minutes, hydrogen gas was completely discharged, and then dimethyl oxalate (8.84 g, 75 mmol) dissolved in 25 mL of THF was added dropwise to the reaction solution. 80 reaction mixture
When the mixture was stirred for 3 hours while heating to ℃, the reaction liquid became reddish brown. After cooling the reaction solution to room temperature, the pH of the aqueous layer was adjusted to 7 to 8 with 10% HCl aqueous solution, and the mixture was extracted with ether. The organic layer was washed successively with saturated aqueous NaHCO ₃ solution and saturated brine, dried and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate / hexane = 1/9) to obtain compound 1 (6.43 g, yield 69%). ¹ H NMR (CDCl ₃ , 300 MHz) δ 14.7 (br, 1H), 6.55 (s,
1H), 3.90 (s, 3H), 1.22 (s, 9H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 209.3, 166.9, 162.7, 9
8.0, 53.0, 41.6, 26.6.

(S) -2-Amino-3-methyl-1-butanol (2.06 g, 20 mmol) was placed in a 200 mL eggplant-shaped flask, and Compound 1 (3.72 g, 20 mmol) was dissolved in 50 mL of ethanol and added. It was After heating to 80 ° C and refluxing for 1 hour, hydrazine 1
A hydrate (10.8 mL) was added to the reaction solution, and the mixture was heated under reflux for 1 hour. After cooling the reaction solution to room temperature, ethanol was distilled off under reduced pressure, and 10 mL of water was added to the residue. The organic matter was extracted with chloroform, the organic layer was dried, and the solvent was evaporated under reduced pressure to give an oily substance (5.96 g).

This oily substance was dissolved in chloroform (50 mL), saturated aqueous NaHCO ₃ solution (20 mL) was added, and the mixture was diluted with diter.
t-Butyldicarbonate (2.14 mL, 10 mmol) was added dropwise and stirred at room temperature. After 3 hours, the reaction mixture was extracted with chloroform, the organic phase was dried, and the solvent was distilled off under reduced pressure. When a small amount of chloroform was added to the residue, white crystals were produced.
The crystals were collected by filtration and dried to obtain compound 2b (1.80 g). Although this product contained a trace amount of impurities, it was directly used in the next reaction. [α] _D ²⁷ : -21.5 ° (c 0.613, MeOH) mp 80-90 ° C Anal. calcd. for C ₁₃ H ₂₃ N ₃ O ₂ ; C: 61.63, H: 9.150,
N: 16.59, Found; C: 55.95, H: 8.42, N: 15.47. ¹ H NMR (CD ₃ OD, 300 MHz) δ 7.85-7.75 (m, 1H), 6.5
2 (br, 1H), 3.90-3.80 (m, 1H), 3.75-3.60 (m, 2
H), 2.08-1.87 (m, 1H), 1.33 (s, 9H), 0.99 (d, 3
H, J = 6.8 Hz), 0.95 (d, 3H, J = 6.8 Hz).

Compound 2b (1.0 g,
3.98 mmol) was added and dissolved in 1,2-dichloroethane. Thionyl chloride (about 0.6 mL) was added to this solution, heated to 40 ° C., and stirred for 1.5 hours. The solvent was removed under reduced pressure, saturated NaHCO ₃ aqueous solution (20 mL) was added to the residue, the organic matter was extracted with chloroform, the organic layer was dried, and the solvent was evaporated under reduced pressure to obtain an oily substance (0.686 g). It was This residue was chromatographed (Fuji Silysia NH, ethyl acetate / hexane = 1
/ 2) to give compound 3b (0.594 g, yield 55%). [α] _D ²⁸ : -25.7 ° (c 0.393, MeOH) mp 124-127 ° C Anal.calcd. for C ₁₃ H ₂₁ N ₃ OCl; C: 57.66, H: 7.817,
N: 15.52, Found; C: 57.14, H: 8.17, N: 15.16. ¹ H NMR (CDCl ₃ , 270 MHz) δ 7.00 (br, 1H), 6.63
(S, 1H), 4.20-4.08 (m, 1H), 3.78 (dd, 1H, J = 4.0,
11.5 Hz), 3.74 (dd, 1H, J = 4.0, 11.5 Hz), 2.13-
1.98 (m, 1H), 1.35 (s, 9H), 1.02 (d, 3H, J = 5.0 H
z), 1.01 (d, 3H, J = 5.0 Hz).

[0025] Compound 3b (0.594
g, 2.18 mmol) and NaOMe (0.294 g, 5.44 mmol) were added, methanol (20 mL) was added and the mixture was heated under reflux for 2 hours, and then methanol was removed under reduced pressure. Water (10 m
L) was added, the organic matter was extracted with chloroform, the organic phase was dried, and the solvent was distilled off under reduced pressure to obtain an oily substance. This residue was purified by chromatography (Fuji Silysia NH, ethyl acetate / hexane = 1/2) to give compound 4b (0.463
g, yield 90%) was obtained. [α] _D ²⁸ : -45.2 ° (c 0.462, MeOH) mp 116-119 ° C Anal. calcd. for C ₁₃ H ₂₁ N ₃ O; C: 66.35, H: 8.9960,
N: 17.86, Found; C: 66.08, H: 9.04, N: 17.63. ¹ H NMR (CDCl ₃ , 300MHz) δ 11.80 (br, 1H), 6.60
(S, 1H), 4.44-4.34 (m, 1H), 4.18-4.06 (m, 2H),
1.95-1.79 (m, 1H), 1.34 (s, 9H), 1.03 (d, 3H, J =
6.8 Hz), 0.92 (d, 3H, J = 6.8 Hz). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 158.2 (br), 103.2, 72.
3, 70.1, 32.7, 31.4, 30.2, 19.0, 18.0.

AgBF ₄ (115 mg,
0.593 mmol) and η ³ -allyl palladium chloride dimer (108 mg, 0.297 mmol) were added, and the atmosphere was replaced with argon. After stirring the mixture for 10 minutes, compound 4b (140 mg, 0.593 mmol)
And stir at 0 ° C for 5 minutes, then add 3 m of dichloromethane.
L was added and the mixture was stirred at room temperature for 1 hour. The insoluble solid was filtered through Celite, the filtrate was concentrated under reduced pressure, and the residue was dried to give a complex.
5b (260 mg, yield 93%) was obtained. 5b: mp 90 ° C (decomp.) Anal.calcd. For C ₁₆ H ₂₆ ON ₃ PdBF ₄ ; C: 40.92, H: 5.5
8, N: 8.95, Found; C: 40.49, H: 5.59, N: 8.71. ¹ H NMR (DMF-d ₇ , 300 MHz, 50 ° C) δ 14.63 (br, 1
H), 6.89 (s, 1H), 5.84 (tt, 1H, J = 7.0, 12.0 H
z), 4.96 (t, 1H, J = 9.3 Hz), 4.86 (dd, 1H, J = 6.8,
9.2Hz), 4.57 (br, 2H), 4.43-4.34 (m, 1H), 3.39
(D, 1H, J = 12.0 Hz), 3.35 (d, 1H, J = 12.0 Hz), 2.
20-2.09 (m, 1H), 1.41 (s, 9H), 0.99 (d, 3H, J = 7.
0 Hz), 0.89 (d, 3H, J = 6.8 Hz). ¹³ C NMR (DMF-d ₇ , 75 MHz, 50 ° C) δ 166.7, 159.4, 14
1.1, 116.7, 103.1, 74.1, 69.6, 62.3, 61.6, 32.3, 3
1.4, 18.3, 15.4.

In the same manner as in the synthesis of 2b, amino alcohol was replaced by 2-aminoethanol, (S) -tert-rucinol, (S) instead of (S) -2-amino-3-methyl-1-butanol, respectively.
Compounds with 2-amino-3-phenyl-1-propanol
2a, compound 2c, and compound 2d were synthesized. Compound 2a mp 141 ° C Anal.calcd. For C ₁₀ H ₁₇ N _3O ; C: 56.85, H: 8.11, N:
19.89, Found; C: 56.54, H: 8.15, N: 20.30. ¹ H NMR (CDCl ₃ , 300 MHz) δ 8.15 (br, 1H), 7.28
(S, 1H), 6.56 (s, 1H), 3.88-3.83 (m, 2H), 3.60
-3.51 (m, 2H), 1.81 (br, 1H), 1.28 (s, 9H). ¹ HN
MR (CD ₃ OD, 270 MHz) δ 8.16 (br), 6.51 (s, 1H),
3.69 (br.t, 2H, J = 5.7 Hz), 3.48 (br.t, 2H, J = 5.7)
Hz), 1.30 (s, 9H). ¹³ C NMR (CD ₃ OD, 67.5 MHz) δ 165.1, 155.8, 147.1,
102.2, 61.6, 42.6, 32.0, 30.5.

Compound 2c Anal.calcd. For C ₁₄ H ₂₅ N ₃ O ₂ : C; 62.9, H; 9.42, N;
15.7. Found: C; 62.31, H; 9.50, N; 15.61. ¹ H NMR (CDCl ₃ , 270 MHz) δ 6.60 (s, 1H), 4.34 (d
d, 1H, J = 8.6, 10.2 Hz), 4.22 (t, 1H, J = 8.5 H
z), 4.04 (dd, 1H, J = 7.9, 10.2 Hz), 1.90-1.35
(Br, 3H), 1.34 (s, 9H), 0.95 (s, 9H). Compound 2d ¹ H NMR (CDCl ₃ , 300 MHz) δ 11.79 (br, 1H), 7.70
(Br, 1H), 7.26-7.14 (m, 5H), 6.52 (s, 1H), 4.5
0-4.37 (m, 1H), 4.30 (br, 1H), 3.79 (dd, 1H, J =
3.3, 11.4 Hz), 3.58 (dd, 1H, J = 5.7, 11.4 Hz), 2.
90-2.72 (m, 2H), 1.28 (s, 9H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 163.0, 154.9, 146.8, 1
37.7, 129.1, 128.6, 126.4, 102.2, 63.6, 52.3, 37.
1, 31.0, 30.0.

Compound 3a and compound 3d were synthesized in the same manner as compound 3b. Compound 3a: mp 158 ° C Anal.calcd. For C ₁₀ H ₁₆ N ₃ ClO; C: 52.29, H: 7.02,
N: 18.29, Found; C: . 51.96, H: 7.03, N: 18.03 1 H NMR (CDCl 3, 300 MHz) δ 7.40 (br, 1H), 6.63
(S, 1H), 3.84-3.63 (m, 4H), 1.34 (s, 9H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 162.7, 155.5, 146.1, 10
2.0, 43.7, 41.0, 31.1, 30.1.Compound 3d ¹ H NMR (CDCl ₃ , 300 MHz) δ 10.92 (br, 1H), 7.34-
7.15 (m, 5H), 6.63 (s, 1H), 4.75-4.60 (m, 1H),
3.71 (dd, 1H, J = 4.2, 11.2 Hz), 3.57 (dd, 1H, J = 3.
5, 11.2 Hz), 3.09-2.94 (m, 2H), 1.34 (s, 9H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 161.9, 155.2, 146.4, 1
36.9, 129.2, 128.7, 126.8, 102.1, 50.4, 46.6, 37.
5, 31.1, 30.1.

When compound 2c is subjected to the same operation as in the synthesis of compound 3b, compound 4c is directly produced. Compound 4c Anal.calcd.for C ₁₄ H ₂₃ N ₃ O: C; 67.4, H; 9.30, N; 1
6.9. Found: C; 66.62, H; 9.30, N; 16.52. ¹ H NMR (CDCl ₃ , 300 MHz) δ 11.9 (br, 1H), 6.60 (s,
1H), 4.33 (dd, 1H, J = 8.6, 10.1 Hz), 4.22 (t, 1
H, J = 7.8 Hz), 4.08 (dd, 1H, J = 7.7, 10.1Hz),
1.32 (s, 9H), 0.97 (s, 9H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 158.07, 103.23, 75.91,
68.74, 34.00, 31.46, 30.29, 30.16, 26.88, 25.62.

Compound 4a and compound 4d were synthesized in the same manner as compound 4b. Compound 4a mp 145 ° C Anal.calcd. For C ₁₀ H ₁₅ N ₃ O; C: 62.15, H: 7.82, N:
21.74, Found; C: 61.92, H: 7.88, N: 21.19. ¹ H NMR (CDCl ₃ , 300 MHz) δ 6.59 (s, 1H), 4.44
(T, 2H, J = 9.5 Hz), 4.07 (t, 2H, J = 9.5 Hz), 1.34
(S, 9H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 159.4, 103.1, 67.6, 54.
6, 31.4, 30.2.

Compound 4d ¹ H NMR (CDCl ₃ , 300 MHz) δ 7.36-7.18 (m, 5H), 6.6
0 (s, 1H), 4.66-4.54 (m, 1H), 4.35 (dd, 1H, J = 8.
4, 9.0 Hz), 4.14 (dd, 1H, J = 7.7, 8.4 Hz), 3.28 (d
d, 1H, J = 5.0, 13.8 Hz), 2.71 (dd, 1H, J = 9.1, 13.8
Hz), 1.35 (s, 9H). ¹³ C NMR (CDCl ₃ , 75 MHz) δ 158.6, 137.8, 129.2, 1
28.6, 126.5, 103.3, 72.0, 67.7, 41.7, 31.4, 30.2.

Similarly to complex 5b, complex 5a and complex 5a, respectively
5c and complex 5d were synthesized. Complex 5a mp 159 ℃ Anal. Calcd. For C ₁₃ H ₂₀ ON ₃ PdBF ₄ ; C: 36.52, H: 4.7
2, N: 9.83, Found; C: 36.42, H: 4.66, N: 9.68. ¹ H NMR (DMSO-d ₆ , 300 MHz) δ 6.81 (s, 1H), 5.77
(M, 1H), 4.82 (brt, 2H, J = 9.5 Hz), 4.45 (br, 2
H), 4.02 (brt, 2H, J = 9.5 Hz), 3.33 (br, 2H), 1.3
2 (s, 9H). ¹ H NMR (CDCl ₃ , 300 MHz, -50 ° C) δ 12.67 (br, 1H),
6.49 (s, 1H), 5.57 (tt, 1H, J = 6.8, 12.4 Hz), 5.
07 (d, 1H, J = 6.8 Hz), 4.94 (dt, 2H, J = 2.2,9.7H
z), 4.23 (d, 1H, J = 6.8 Hz), 4.28-4.05 (m, 2H),
3.42 (d, 2H, J = 12.4 Hz), 3.06 (d, 1H, J = 12.4 H
z), 1.41 (s, 9H).

Complex 5c Anal.calcd. For C ₁₇ H ₂₈ N ₃ OBF ₄ Pd: C; 42.3, H; 5.85,
N; 8.71. Found: C; 40.35, H; 5.57, N; 8.00. ¹³ C NMR (CDCl ₃ , 75 MHz, 40 ° C) δ 166.45, 158.89,
139.93, 115.46, 102.12, 73.60, 73.54, 64.22, 62.3
4, 34.83, 31.73, 29.60, 25.56. ¹ H NMR (DMF-d ₇ , 300MHz, 23 ° C) δ 15.18 (br, 1H),
6.94 (s, 1H), 5.98-5.80 (br, 1H), 5.10 (dd, 1H,
J = 4.4, 9.8 Hz), 4.88 (t, 1H, J = 9.8 Hz), 4.60-4.
44 (br, 2H), 4.17 (dd, 1H, J = 4.4, 9.8 Hz), 3.56-
3.40 (br, 1H), 3.35-3.18 (br, 1H), 1.42 (s, 9H),
1.00 (s, 9H). ¹³ C NMR (DMF-d ₇ , 75 MHz, 23 ° C) δ 167.0, 159.4, 1
40.9, 117.0, 74.8, 73.8, 64.3, 62.7, 32.3, 25.6.

Complex 5d ¹ H NMR (CDCl ₃ , 300 MHz, -20 ° C) δ 12.69 (br, 2
H), 7.42-7.16 (m, 10H), 6.46 (S, 1H), 6.45 (s, 1
H), 5.50 (tt, 1H, J = 7.0, 12.3 Hz), 5.32 (tt, 1H,
J = 6.9, 12.5 Hz), 5.12 (d, 1H, J = 7.0 Hz), 5.05
(D, 1H, J = 6.9 Hz), 4.84 (t, 1H, J = 9.1 Hz), 4.77
(T, 1H, J = 9.2 Hz), 4.67-4.46 (m, 4H), 4.15 (d,
1H, J = 6.9 Hz), 4.03 (d, 1H, J = 6.9 Hz), 3.44 (d,
1H, J = 12.6 Hz), 3.31 (d, 1H, J = 11.1 Hz), 3.15-3.
02 (m, 2H), 2.99-2.88 (m, 3H), 2.78 (d, 1H, J = 1
2.3 Hz), 2.69 (d, 1H, J = 12.3 Hz), 1.41 (s, 18
H).

[0036] In analogy to the synthesis of complex 5b, eta ³ - The use of allyl palladium chloride eta ^{3-1-phenyl-propenyl} palladium chloride dimer instead of dimers,
Complex 6a and complex 6b were obtained.

[0037]

[Chemical 8]

Complex 6a mp 145 ° C Anal. Calcd. For C ₁₉ H ₂₄ ON ₃ PdBF ₄ ; C: 45.08, H: 4.8
0, N: 8.34, Found; C: 44.84, H: 4.78, N: 7.91. ¹ H NMR (CDCl ₃ , 300 MHz, -50 ° C) δ 7.58 (d, 2H, J =
6.8 Hz), 7.50-7.32 (m, 3H), 6.43 (s, 1H), 6.17
-6.02 (m, 1H), 5.12 (br, 1H), 4.60 (d, 1H, J = 13.0
Hz), 4.72-4.55 (m, 2H), 3.53 (d, 1H, J = 12.0 H
z), 3.38-3.22 (m, 1H), 2.58-2.41 (m, 1H), 1.41
(S, 9H). Complex 6b mp 188-193 ℃ (decomp.) Anal. Calcd. For C ₂₂ H ₃₀ ON ₃ PdBF ₄ ; C: 48.42, H: 5.5
4, N: 7.70, Found; C: 48.65, H: 5.60, N: 7.65.

Example 2 Reaction of Allyl Acetate with Ketene Diacetal Pd Complex 5b (23.4 mg, 0.05 mm
ol) and sodium acetate (16.4 mg, 0.2 mmol) were added,
After substituting with argon, 2 mL of DMSO was added. After stirring for 5 minutes, cinnamyl acetate (189 mg, 1 mmol) was added to DMSO 1 m.
Dissolve in L and add, followed by ketene acetal (376 mg, 2
mmol) was added and the mixture was stirred at room temperature for 24 hours. Ether (5 mL) and water (5 mL) were added to the reaction solution, followed by 3 mL of 10% aqueous HCl solution.
In addition, stirring was carried out for 30 minutes at room temperature in order to hydrolyze the remaining ketene acetal. The organic phase is extracted with ether,
It was washed with a saturated aqueous NaHCO ₃ solution and a saturated saline solution, the organic phase was dried, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (ether / hexane = 1/9) to obtain 117 mg of a mixture of compound 9 and compound 10. The mixing ratio was calculated using NMR.

[0040]

[Chemical 9] The mixture of compound 9 and compound 10 was put into a 25-mL flask, and tert-butanol (3 mL) and water (0.5 mL) were added. Osmium tetroxide tert-butanol solution (2.5 wt
%, 0.1 mL) and 4-methylmorpholine N-oxide were added and stirred at room temperature for 2 hours, only the compound having an unsaturated double bond was oxidized. A 10% sodium sulfite aqueous solution was added and the mixture was stirred for 30 minutes, and the organic matter was extracted with ether. The organic phase was washed successively with a 1N-HCl aqueous solution, a saturated NaHCO ₃ aqueous solution and a saturated saline solution, dried and the solvent was distilled off under reduced pressure. The oil obtained was purified by silica gel chromatography (ether / hexane = 1/9) to give pure compound 9 (86 m
g) was obtained. The optical purity was determined by HPLC analysis (Daicel Chemical Industries CHIRALCEL-OJ).

[0041]

[Table 1]

[0042]

The palladium complex of the present invention is stable,
Compared with complexes containing phosphorus or arsenic as a ligand, problems such as malodor are avoided, so it is convenient to handle. Further, it can be used as a catalyst for various organic reactions such as cyclopropanation reaction and is also useful for asymmetric cyclopropanation reaction.

Front page continued (58) Fields surveyed (Int.Cl. ⁷ , DB name) C07D 413/04 C07F 15/00 CA (STN) REGISTRY (STN)

Claims (9)

(57) [Claims] 1. The following general formula (I): (In the formula, R ¹ represents an alkyl group having 1 to 12 carbon atoms; R
² and R ³ are each independently a hydrogen atom or a carbon atom number of 1 to 12.
Represents an alkyl group; R ⁴ is a hydrogen atom, having 1 to 1 carbon atoms
A compound represented by 2 alkyl groups or a benzyl group which may have a substituent) and salts thereof. 2. A ligand for palladium metal represented by the general formula (I) according to claim 1. 3. The following general formula (II): (In the formula, R ¹¹ represents an alkyl group having 1 to 12 carbon atoms;
R ¹² and R ¹³ are each independently a hydrogen atom or a carbon atom of 1
Indicates 12 alkyl groups; R ¹⁴ represents a benzyl group that may have 1 to 12 alkyl group or a substituent carbon atoms; wavy line the carbon atom to which R ¹⁴ is attached is S- arrangement Or R
-Indicates one of the configurations) for the palladium metal. 4. A palladium complex containing the ligand according to claim 2 or 3. 5. The palladium complex according to claim 4, wherein R ¹ is a tert-butyl group and R ² , R ³ and R ⁴ are hydrogen atoms. 6. The palladium complex according to claim 4, wherein R ¹ is a tert-butyl group, R ² and R ³ are hydrogen atoms, and R ⁴ is an isopropyl group, a tert-butyl group, or a benzyl group. 7. A catalyst for cyclopropanation reaction, which comprises the palladium complex according to any one of claims 4 to 6. 8. The catalyst according to claim 7, which has catalytic activity in a cyclopropanation reaction using a ketene silyl acetal. 9. The catalyst according to claim 7, which comprises the ligand according to claim 3 and is used in an asymmetric cyclopropanation reaction.