JPS6365676B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention is based on the formula (): The present invention relates to an organometallic complex containing camphanyl-diphenyl-phosphine, which is a novel chiral compound of phosphines having the formula (R is a methyl group), a method for producing the same, and a homogeneous catalyst produced from the complex.

The uses of chiral trialkylphosphines are well known, and they are particularly well known as excellent ligands. It is also known to form chiral complexes with noble metals, especially rhodium. Such complexes have been effectively used in a variety of asymmetric hydrogenations in homogeneous systems (B.R. James, Homogeneous Hydrogenation, John Wiley, New York, 204-208).
(1973) and Day Valentine et al., Synthesis, p. 329 (1978)).

However, although a large number of trialkylphosphines have been produced and published by many research teams, most of them have serious drawbacks that greatly reduce their industrial utility value. ing. Their disadvantages include, for example, that the raw materials for their production are difficult to obtain and expensive, and that they are difficult to purify, often requiring lengthy purification times or requiring the use of expensive means.・See Day Fritzke et al., Journal of the American Chemical Society, Vol. 99, p. 6562 (1977)). Furthermore, trialkylphosphines generally have low stability and complexes with noble metals are often disappointing.

Therefore, the potential utility of chiral phosphines on an industrial scale is only very limited (U.S. Pat. No. 4,008,281).
Specification, D. S. Knowles et al., Chemical English News (Chem.Eng.
News), vol. 48, p. 41 (1970) and vol. 50, 4
(1972)).

The present inventors have conducted intensive research to find phosphines that overcome the above-mentioned drawbacks, and as a result, a chiral compound having the formula () that can be easily and inexpensively produced from natural camphor via camphanic acid has been found. Asymmetric enantioselection of double bonds that combine with rhodium to form highly stable organometallic complexes that can be cleaved to form chiral compounds, such as carbon-carbon or carbon-tiron. The present invention was completed based on the discovery that this compound has an extremely useful function in enantioselective hydrogenation reactions.

The chiral compound used in the present invention has the general formula (): (wherein, X is a bromine atom, an iodine atom, a p-toluenesulfonyloxy group or a methanesulfonyloxy group, and R is the same as above) and a compound having the general formula (): (wherein Y is a lithium atom, a potassium atom, or a sodium atom) can be obtained by reacting a diphenylphosphine derivative.

This reaction is preferably carried out in the presence of an inert solvent. Examples of the inert solvent include tetrahydrofuran, dioxane, and toluene, with tetrahydrofuran being particularly preferred. The reaction temperature is preferably between -20°C and room temperature, particularly between 0 and 10°C.

The compound having the general formula () is highly reactive and can be used to esterify the alcohol produced by selectively reducing the methyl ester of camphanic acid with, for example, lithium aluminum hydride without breaking the lactone ring structure. Therefore, it can be manufactured.

Camphoric acid or its ester can be obtained from natural camphor (+) via camphoric acid (her.
H. Gerlach, Helvetica Hemica Acta, vol. 51, p. 1587 (1968), V. SUNJIC et al., Croatian Chemical.
Acta (Croat.Chem.Acta), volume 43, page 205,
(1971) and Vol. 45, p. 569 (1973)).

Examples of the compound having the general formula () include camphanyl tosylate, camphanyl bromide, camphanyl iodide, and methanesulfonyloxycamphane. Examples of diphenylphosphine derivatives having the general formula () include lithium-diphenyl-phosphine, potassium-diphenyl-phosphine, and sodium-diphenyl-phosphine.

Camphanyl-diphenyl-phosphine used in the present invention is stable and can be purified by distillation or column chromatography.

The above camphanyl-diphenyl-phosphine is a chiral ligand having the general formula (): M-ClR' ₂ () (where M is a rhodium atom, R' is cyclooctadiene, 1,5-hexadiene or 2,5 −
is norbornadiene) and ionizes to form an anion Z (where Z is ClO ₄ ^- ,
BR ₄ ^- , Cl ^- , Br ^- , or BF ₆ ^- ) to produce the general formula (): [R″ ₂ −M−R′]Z () (where M, R ' and Z are the same as above, and R'' is camphanyl-diphenyl-phosphine having the above formula ().

As the metal complex having the general formula (),
For example, Rh−Cl (cyclooctadiene) ₂ , Rh−
Cl (1,5-hexadiene) ₂ , Rh-Cl (2,5-
Examples include norbornadiene) ₂ . In addition, typical examples of compounds that ionize and generate anions include:
An example is silver perchlorate.

A typical example of the organometallic complex of the present invention having the general formula () is [(camphanyl-diphenyl-phosphine) ₂ -Rh-(2,5-norbornadiene)].ClO ₄ , but this is not the only example. It is not limited.

As far as analysis using current analytical methods is concerned, [(camphanyl-diphenyl-phosphine) ₂ -Rh-
(2,5-norbornadiene)].ClO ₄ is thought to have the following structure.

This organometallic complex has surprising stability and reactivity. Its excellent stability is presumed to be due to the positional relationship between the heteroatom, ie, the phosphorus atom, and the oxygen atom of the lactone ring.

The organometallic complex of the present invention having the general formula () is useful as a chiral homogeneous catalyst. In particular, when it is used in hydrogenation reactions, it acts as a catalyst on chiral or non-chiral compounds that have a double bond that is cleaved to form a chiral compound, and converts it into an asymmetric enantioselective (enantioselective) compound in a homogeneous phase. ) or diastereoselectively hydrogenated. The organometallic complex of the present invention is crystalline and stable.

When using the organometallic complex as a catalyst, it may be used as a crystal, but it is preferable to perform the hydrogenation reaction using a complex prepared on the spot in a reaction system containing the compound to be asymmetrically hydrogenated. It's okay to get old.

Next, the present invention will be explained in detail based on production examples and examples, but the present invention is not limited only to these examples.

Production Example 1 (Production of lactone of (1S,3S)-1-hydroxy-1-hydroxymethyl-2,2,3-trimethylcyclopentane-3-carboxylic acid) Add 32 g of methyl camphoric acid to 250 ml of tetrahydrofuran. 4.2g of lithium aluminum hydride is dissolved and cooled to -10℃.
was added little by little over 60 minutes with stirring under a nitrogen atmosphere. During that time, the temperature of the reaction solution was −10
It was kept at ~-7°C. This state was maintained for another 30 minutes, and then 40 ml of methanol and 14 ml of water were added to eliminate excess lithium aluminum hydride. The obtained hydroxide is filtered, and the obtained filtrate is evaporated under vacuum to obtain the target substance with a melting point of 179-180℃.
I gained 24.6g.

The product was then recrystallized from a diisopropyl ether-ethanol (3:1) mixture.
Infrared absorption spectrum analysis using KBr method, NMR
Spectral and elemental analyzes were performed. The results are shown below.

Infrared absorption spectrum (cm ^-1 ): 3500, 2975, 1755, 1180, 1095, 1035, 907 NMR spectrum (CDCl ₃ , δ value ppm): 0.95 (s, C(CH ₃ ) ₂ ), 1.10 (s, CH ₃ -C),
1.87 (m, CH ₂ - CH ₂ ), 2.60 (broad s,
OH), 3.95 (broad s, CH ₂ OH) Elemental analysis value: C ₁₀ H ₁₆ O ₃ (as 184.0) Calculated value (%): C65.19 H8.75 Actual value (%): C65.31 H8.84 Production Example 2 (Production of lactone of (1S,3S)-1-hydroxy-1-p-toluenesulfonyloxymethyl-2,2,3-trimethylcyclopentane-3-carboxylic acid) Obtained in Production Example 1 19.8 g of the compound obtained was dissolved in 200 ml of anhydrous pyridine and cooled to 0°C. 30.8 g of p-toluenesulfonic acid chloride was added little by little to this solution while stirring. After being left overnight at 0°C, it was poured into 100 ml of water with 600 g of ice floating while stirring. The precipitate was collected by filtration, washed with cold water, and dried to obtain a crude product.

The obtained crude product was recrystallized from 150 ml of 99.8% ethanol to obtain a crystalline white powder with a melting point of 116-117°C.
I gained 33.8g. The results of this analysis are shown below.

Infrared absorption spectrum (KBr method, cm ^-1 ): 2980, 1780, 1360, 1193, 1165, 983, 915,
857, 840, 817, 677, 656 NMR spectrum (CDCl ₃ , δ value ppm): 0.88, 0.93 (s, C(CH ₃ ) ₂ ), 1.08 (S,
CH ₃ ), 1.85 (m, CH ₂ CH ₂ ), 2.50 (s, =C-
CH ₃ ), 4.30 (s, CH ₂ ), 7.80 (m, C ₆ H ₄ ) Elemental analysis value: C ₁₇ H ₂₂ O ₅ S (as 338.41) Calculated value (%): C60.33 H6.55 S9. 48 Actual value (%): C60.41 H6.73 S9.49 Production example 3 ((1S,3S)-1-hydroxy-1-diphenylphosphomethyl-2,2,3-trimethylcyclopentane-3- Production of carboxylic acid lactone (camphanyl-diphenyl-phosphine) 0.36 g of lithium was added little by little to a solution of 6.9 g of triphenylphosphine in 30 ml of tetrahydrofuran under a nitrogen atmosphere. In about 1 hour, the temperature of the reaction solution rose to 30°C, and a reddish color began to appear. The reaction solution, which had returned to room temperature in about 5 hours, was further cooled to -10 DEG C., and while maintaining that temperature, a solution of 2.45 g of t-butyl chloride in 10 ml of tetrahydrofuran was added over 20 minutes. The reaction solution was then heated to reflux for 5 minutes to eliminate phenyllithium, and then cooled to -10°C again. To this (1S,
A solution of 3S)-1-hydroxy-1-p-toluenesulfonyloxymethyl-2,2,3-trimethylcyclopentane-3-carboxylic acid in 30 ml of tetrahydrofuran was added over 90 minutes. The obtained reaction solution was heated at -10℃ for 18
After continued stirring for an hour, the solvent was distilled off under vacuum.

100 ml of benzene and 20 ml of water were added to the remaining oily residue under a nitrogen atmosphere. After stirring for 30 minutes, the organic layer was separated, dried over anhydrous sodium sulphate and evaporated under vacuum. The resulting residue is treated with silica 220
The colorless viscous oily camphanyl-diphenyl-phosphine used in the present invention was purified by passing through a column having 100 g of phosphatide. The results of this analysis are shown below.

Infrared absorption spectrum (film method, cm ^-1 ): 3050, 2960, 1770, 1430, 1392, 1328,
1105, 1080, 1008, 909, 738, 692 NMR spectrum ( _CDCl3 , δ value ppm): 0.93-0.98 (2s, C( _CH3 ) ₂ ), 1.13 (s, C-
_CH3 ), 1.23-2.15 (m, _CH2 - _CH2 ), _δA :
2.75 (J _AX 2Hz), δ _B : 2.35 (J _BX = 2Hz and J _AB
=19.3Hz, -CH ₂ -P(Ph) ₂ ABX system; 8 lines;
2dd) Specific rotation (c = 1.93, CHCl ₃ ): [α] ²⁴ _D = -11.2° Elemental analysis value: C ₂₂ H ₂₅ O ₂ P (as 352.4) Calculated value (%): C74.98 H7.15 Actual value (%): C74.85 H7.18 Example 1 ([(camphanyl-diphenyl-phosphine) ₂
-Rh-2,5-norbornadiene] perchlorate) Add 0.7 ml of 2,5-norbornadiene to a solution of 0.25 g of rhodium chloride (chemical formula RhCl ₃ H ₂ O) dissolved in 4 ml of ethanol-water (5:1). In addition,
When the resulting reaction solution was kept at room temperature for 48 hours, 0.176 g of yellow crystals were obtained, which were collected by filtration. To a solution of 0.137 g (0.3 mmol) of these crystals dissolved in 6 ml of methylene chloride, 0.055 g (0.6 mmol) of 2,5-norbornadiene and then silver perchlorate monohydrate were added under a nitrogen atmosphere. The resulting suspension was kept stirring for 1 hour at room temperature, and silver chloride precipitated. The filtrate from which silver chloride had been filtered off was evaporated to dryness under vacuum. The resulting residue was recrystallized by adding 6 ml of tetrahydrofuran to a melting point of 240°C (decomposition).
pure [Rh-(2,5-norbornadiene)
0.130 g of yellowish-orange crystals of ₂ ].ClO ₄ were obtained.
The results of this analysis are shown below.

NMR spectrum (CDCl ₃ , δ value ppm): 1.55 (broad s, CH ₂ ), 4.20 (broad s,
2-CH), 5.40 (broad s, 4-CH) Then 0.421 g of camphanyl-diphenyl-phosphine was added to 10 ml of degassed anhydrous tetrahydrofuran.
Prepare a solution in which [Rh-(2,5
0.233 g of -norbornadiene) ₂ ].ClO ₄ was added.
The resulting reaction solution was continued to be stirred at room temperature for 1 hour.
Next, 20 ml of degassed n-hexane was added, the mixture was cooled to 0°C, and stirring was continued for an additional 60 minutes. This reaction solution was filtered, washed with n-hexane, and then dried to obtain 0.6 g of the crystalline target product. This one is about 182
It has a melting point of °C and changes its crystal form upon heating. The results of this analysis are shown below.

NMR spectrum (CDCl ₃ , δ value ppm): 0.88 (s, CH ₃ ), 0.91 (s, CH ₃ ), 1.09 (s,
_CH3 ), 1.20-2.30 (m, _CH2 - _CH2 ), 2.60
(broad s, P-CH ₂ ), 3.85 (broad s,
CH), 4.45 and 4.65 (2 broad s, = CH) Elemental analysis value: C ₅₁ H ₆₂ O ₈ ClP ₂ Rh−C ₄ H ₄ O (THF) Calculated value (%): C61.66 H6.21 Actual value (%): C61.35 H6.22 Example 2 (Hydrogenation of α-(3-benzoylphenyl)propenoic acid) Add 100 mg of [Rh-Cl(1,5-hexadiene) ₂ ] to 10 ml of degassed benzene. The dissolved solution was added to a solution of 320 mg of camphanyl-diphenyl-phosphine in 10 ml of degassed benzene. The resulting reaction solution was stirred for 15 minutes and then added to 80 ml of an ethanol solution containing 3 g of α-(3-benzoylphenyl)propenoic acid and 110 mg of triethylamine.

Place the obtained reaction solution in an autoclave and incubate for 70 minutes.
After carrying out the hydrogenation reaction at room temperature under atmospheric pressure for 20 hours, the solvent was distilled off, and the resulting residue was dissolved in 3% sodium hydroxide solution. After filtering this,
The filtrate was acidified to pH 1.0 and then diluted with ether 30
Extracted 3 times with ml. Pour the resulting ether layer into 10ml of water.
The solution was washed twice with water, dehydrated, and the ether was distilled off. Purified by chromatography using silica gel,
An equal amount of (-)-α-(3-benzoylphenyl)propionic acid was added. The results of this analysis are shown below.

Melting point: 92-93°C Specific rotation: [α] ²⁴ _D = -5.65° Example 3 (Hydrogenation of N-benzoyl-dehydrovaline) [(camphanyl-diphenyl-phosphine) ₂
-Rh-2,5-norbornadiene]・ClO ₄・
16 g of N-benzoyl-dehydrovaline and 0.5 ml of triethylamine were added to a suspension of 400 mg of THF in 150 ml of degassed toluene. This mixed solution was placed in an autoclave and washed eight times with hydrogen, followed by a hydrogenation reaction at room temperature for 6 hours under pressure of 30 atmospheres. At the end of the reaction, the reaction solution was evaporated to dryness,
The resulting residue was dissolved in a 2% aqueous sodium hydroxide solution.
ml, and the insoluble portion was filtered off. The resulting filtrate was acidified to pH 2.0 and extracted three times with 200 ml of ethyl acetate. The extract layer was dehydrated over sodium sulfate and then dried under vacuum (0.01 mmHg) using phosphorus pentoxide.

The obtained target substance has a specific optical rotation corresponding to an optical purity of 74%: [α] ²⁴ _D = +37.7° (c = 1.0, CHCl ₃ )
showed that. This was further recrystallized from an aqueous methanol solution to obtain 9.1 g of optically pure (+)-N-benzoylvaline ([α] ²⁴ _D =+51°).

Example 4 (Hydrogenation of Z-α-acetoxycinnamic acid) [(camphanyl-diphenyl-phosphine) ₂ -Rh- 2,5
- norbornadiene].ClO ₄ .THF 0.12 g and triethylamine 0.35 ml were added. The resulting mixture was pressurized to 42 atmospheres in a Parr autoclave and the hydrogenation reaction was carried out at ambient temperature for 30 hours. The obtained product was mixed with methanol-water (1:2.5).
Chromatography on silica gel using as eluent yielded 6.3 g of (+)-α-acetoxy-β-phenylpropionic acid, which was identified by NMR spectroscopy. The specific optical rotation of this product is [α] ²⁴ _D = +27.4° (c = 1.22, methanol)
This corresponded to an optical purity of 82%.

Example 5 (Hydrogenation of 1-acetoxy-1-cyclohexylethene) 1-acetoxy-1-
Dissolve 4.2 g of cyclohexylethene and then dissolve [(camphanyl-diphenyl-phosphine) ₂ −
Rh-2,5-norbornadiene]・ClO ₄・
0.8g of THF was added. This mixed solution was placed in an autoclave, and after being repeatedly washed with hydrogen, the pressure was increased to 25 atm and a hydrogenation reaction was carried out at room temperature for 12 hours. The resulting reaction solution was filtered to remove insoluble portions, and the solvent was concentrated to obtain an oily substance. This was purified by chromatography on a silica gel column using light oil-ethyl acetate (2:1) as the eluent.
4.1 g of (+)-1-acetoxy-1-cyclohexylethane was obtained. The specific optical rotation of this substance is [α] ²⁴ _D =
+94.4° (c=1.05, CHCl ₃ ), corresponding to an optical purity of 86%.

Claims (1)

[Claims] 1 General formula (): [R'' ₂ -M-R']Z () (wherein M is a rhodium atom, R' is cyclooctadiene, 1,5-hexadiene or 2,5 −
Norbornadiene, Z is ClO ₄ ^- , BF ₄ ^- , Cl ^- ,
Br ^- or BF ₆ ^- , R″ is the formula (): (wherein R is a methyl group). 2 General formula (): [R″ ₂ −M−R′]Z () (wherein, M is a rhodium atom, R′ is cyclooctadiene, 1,5-hexadiene, or 2,5-
Norbornadiene, Z is ClO ₄ ^- , BF ₄ ^- , Cl ^- ,
Br ^- or BF ₆ ^- , R″ is the formula (): A homogeneous catalyst comprising an organometallic complex having the formula (wherein R is a methyl group). 3 In the general formula (), M is a rhodium atom, R' is 2,5-norbornadiene, and Z is ClO ₄ ^-
The catalyst according to claim 2, which is 4. The catalyst according to claim 2 or 3, which is used for the asymmetric enantioselective or diastereomer-selective hydrogenation of a double bond that is cleaved to form a chiral compound in a homogeneous phase. . 5 The double bond is a carbon-carbon double bond or a carbon-carbon double bond in a chiral molecule or a non-chiral molecule.
The catalyst according to claim 4, which is a nitrogen double bond. 6 Claims 2 and 3 that are in a crystalline state
5. Catalyst according to item 4 or 5. 7. The catalyst according to claim 2, 3, 4 or 5, which is prepared in situ in a hydrogenation reaction system. 8 Formula (): camphanyl-diphenyl-phosphine having the general formula (): M-ClR' ₂ () (wherein M is a rhodium atom, R' is a cyclooctadiene, 1,5 -hexadiene or 2,5-
is norbornadiene) and ionizes to form an anion Z (where Z is ClO ₄ ^- , BF ₄ ^- ,
Cl ^- , _Br ^- or BF ₆ ^- ). and Z is the same as above, and R'' is camphanyl-diphenyl-phosphine having the above formula ().