JPS6232758B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel compound, an optically active alkyl diphosphine compound, and a method for producing the same, and more particularly, it relates to an optically active alkyl diphosphine compound having the following general formula (a) or (b).

【formula】

[Formula] (In the formula, R represents a lower alkyl group or a cyclohexyl group.) Optically active alkyl diphosphine compounds represented by the formula and methods for producing these compounds include (-)-
Alternatively, (+)-1,4-ditosyl-2,3-O-isopropylidene-threitol is reacted with an alkali metal fluoride to form (+)- or (-)-2,3-O
-isopropylidene-2,3-dihydroxy-
The present invention relates to a method for producing a desired product by reacting 1,4-difluorobutane with an alkali metal alkyl phosphide or an alkali metal cyclohexyl phosphide. In recent years, many transition metal complexes have been synthesized, and since noble metal complexes are particularly stable and easy to handle, many synthetic studies have been reported. in 1965
The synthesis of tris(triphenylphosphine)halorhodium was reported by Wilkinson et al. and Bennett et al. (JAOsborn, G. Wilkinson, JFYong,
Chem, Commun, 1965, 17; MABennett, P.
A.Longstaff, Chem, ind., 1965, 846.) At the same time, it was found that it had a high activity as a homogeneous reduction catalyst, which was not found in previous complexes. It has been found that it acts as a catalyst. In general, reports on the application of this type of catalyst and organic synthesis reactions have been published one after another, and among them, optically active chelated diphosphine is used in the asymmetric synthesis catalytic reaction using transition metal complexes in the synthesis of optically active compounds. have been reported to be effective ligands. All of these phosphines contain at least one phosphorus atom.
It has aryl substitutions. For example, it has been reported that phosphines with strong basicity become more active catalysts in the hydrogen ring group of carbonyl compounds (RR Schrock, JAOsborn, J.
Chem.Soc., Chem.Commun., 1970, 567), and rhodium and (-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane. There is a research report on the hydrogenation of precursors such as alanine and phenylalanine using complex salts (HBKagan, TPDang, J. Amer.
Chem.Soc., 94 , 6429 (1972)). While continuing research on catalysts for asymmetric synthesis reactions, the present inventor discovered a novel compound represented by the above general formula (a) or (b) among optically active diphosphines, and used this compound as a ligand. It was confirmed that the rhodium complex salt obtained above has excellent properties as a catalyst, and an advantageous method for producing the same was discovered, thereby completing the present invention. The compound of the present invention can be produced, for example, by the steps shown in the following reaction formula. In the formula, Ts represents a tosyl group, R represents a lower alkyl group or a cyclohexyl group, and M represents an alkali metal. 1,4-Ditosyl-2,3-O-isopropylidene-threitol () can be easily obtained from known literature using natural L-(+)tartaric acid as a starting material (LJRubin, HALordy, HO
L. Fischer, J. Amer. Chem. Soc., 74 , 425
(1952)). (+)-2・3-O-isopropylidene-2・
3-dihydroxy-1,4-difluorobutane () is produced by reacting ditosylate () with excess alkali metal fluoride such as anhydrous potassium fluoride in a solvent such as anhydrous diethylene glycol under reduced pressure. It can be obtained by 10mmHg when diethylene glycol is used as a solvent
Heat at around 130°C under reduced pressure back and forth, and continue heating until no distillate remains. The distilled oily substance is extracted using ether etc. in a conventional manner, dried, and purified by distillation under reduced pressure to obtain (+)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-difluoro. A colorless liquid of butane () is obtained. The next step, that is, the reaction between difluoride () and alkali metal alkyl phosphide or alkali metal cyclohexyl phosphide (), proceeds smoothly at room temperature in dioxane or a mixed solvent of dioxane and tetrahydrofuran, resulting in the formation of the desired optically active alkyl phosphide. Diphosphine () can be obtained. That is, dioxane or a mixture of dioxane and tetrahydrofuran is used as a solvent, an alkali metal alkyl phosphide or alkali metal cyclohexyl phosphide () is suspended in this, and a solution of difluoride () dissolved in the solvent is gradually added to this. After addition, stirring was continued for about one day at room temperature to complete the reaction. As alkali metal alkyl phosphides, the alkali metal is lithium, sodium,
potassium, and the alkyl group is methyl, ethyl,
Selected from compounds that are propyl, isopropyl, butyl, and isobutyl. Moreover, a compound having a cyclohexyl group instead of an alkyl group may also be used. The appropriate amount of alkali metal alkyl phosphide or alkali metal cyclohexyl phosphide used in the method of the present invention is 2 to 3 times the mole of difluoride (). After the reaction is complete, add a small amount of water and stir to eliminate reactivity.
The solvent is removed by distillation under reduced pressure, the residue is mixed with ether and water, the organic layer is separated, the aqueous layer is combined with the liquid extracted with ether, and the mixture is dried using anhydrous sodium sulfate or the like. Distillation under reduced pressure yields alkyl diphosphine (a). When these alkyldiphosphines () are converted into sulfides or carbon disulfide adducts, they form crystalline compounds that are stable in the air, can be subjected to elemental analysis, and can be purified based on this property. can. For example (-)-2・3-O
-isopropylidene-2,3-dihydroxy-
1,4-bis(diethylphosphino)butane and (-)-2,3-O-isopropylidene-2.
3-dihydroxy-1,4-bis(diisopropylphosphino)butane reacts with sulfur in benzene solution and can readily form a solid disulfide that is stable in air. Also (-)-
In the case of 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(dicyclohexylphosphino)butane, ether and excess carbon disulfide were added to the ether extract obtained during the above synthesis process. When added and reacted, a brown-red carbon disulfide adduct is produced. This is purified by recrystallization from an ethanol-carbon disulfide mixed solvent. When this carbon disulfide adduct is suspended in absolute ethanol and refluxed for 1 hour in a nitrogen stream, the initial brown-red color gradually disappears to obtain a colorless solution. This was purified to high purity by distilling it under reduced pressure (-)-
2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(dicyclohexylphosphino)butane can be obtained. In the production of aryl homologs which are generally known compounds, such as (-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane, ditosylate () and an alkali metal diaryl phosphide to obtain the desired product,
The reaction of ditosylate () with an alkali metal alkyl phosphide or an alkali metal cyclohexyl phosphide does not produce any corresponding diphosphine. That is, ditosylate () and lithium diethyl phosphide do not react even when heated in tetrahydrofuran and kept under reflux for 24 hours.
In addition, the reaction of a compound in which fluorine in difluoride () is replaced with iodine, bromine, or chlorine and an alkali metal alkyl phosphide or alkali metal cyclohexyl phosphide produces alkyl diphosphine (), but the yield is low. It is very bad and produces by-products of unknown structure in addition to tetraalkyl diphosphanes. In the production process of the present invention, (+)- or (-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4
- It is important to use difluorobutane (). Instead of using natural L-(+)tartaric acid as a starting material, if unnatural D-(-)tartaric acid is used as a starting material, the enantiomer of the compound shown in formula (a) above can be obtained as the enantiomer of formula (b). The compounds can be obtained by synthetic routes similar to those described above. The optically active alkyl diphosphine compounds (a) and (b) of the present invention form optically active complexes as transition metal ligands, and these complexes exhibit excellent catalytic activity in organic synthesis reactions, especially asymmetric synthesis. It shows. For example, in the synthesis of optically active citronellal, which is an important compound in the fragrance industry,
There is a reaction in which optically active citronellal is obtained by converting neryl diethylamine into optically active citral enamine using an optically active catalyst and hydrolyzing this. A catalyst is created by the reaction, and this is applied to this reaction to achieve optical purity of approximately
It was confirmed that 85% optically active citronellal was obtained. Next, the present invention will be explained in detail with reference to Examples. Example 1 (-)-2.3-O-isopropylidene-2.3
-Production of dihydroxy-1,4-bis(diethylphosphino)butane (-)-1,4-ditosyl-2,3-O-isopropylidene-threitol 25.0g (53.0m
mol) and anhydrous potassium fluoride 12.9g (222m
mol) in 52 ml of anhydrous diethylene glycol, and the mixture was heated and stirred at 130°C under reduced pressure of 11 to 12 mmHg. Heating was continued until the distillate disappeared over a period of 4 hours, and the oily distillate was collected in a cold container. next,
After adding 50 ml of water to this, it was extracted with ether, then dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and distilled under reduced pressure to form a colorless oil (+)-2.3-O.
-isopropylidene-2,3-dihydroxy-
5.5 g of 1,4-difluorobutane was obtained. The yield was 63% based on ditosylate. The properties and analytical values of this substance are as follows. Boiling point: 56-57℃/16mmHg [α] ²⁵ _D = +23.4° (C = 1.64, CHCl ₃ ) Elemental analysis value: (C ₇ H ₁₂ O ₂ F ₂ ) C H Calculated value (%) 50.60 7.28 Actual measurement Value (%) 49.87 7.31 ¹ H=NMR (CDCl ₃ , 60MHz): δ1.45 (s, 6H, CH ₃ ), 4.13 (m, 2H,

[Formula] ), 4.50 (dd, J _HH = 3.5Hz, J _HF = 57Hz,
4H, -CH2 _- ^F19F -NMR ( _CDCl3 , _56MHz ): δ (upfield from _C6F6 ) 68 (dt, ² J _HF = 49
Hz, ³ J _HF = 21Hz) Next, 5.65g of lithium diethylphosphine synthesized from diethylphosphine and butyllithium.
(58.9 mmol) was suspended in 170 ml of dioxane and stirred, and the above-obtained (+)-2.3-O
-isopropylidene-2,3-dihydroxy-
1,4-difluorobutane 3.34g (2.01mmol)
A solution of 5 ml of dioxane was added. Although the lithium diethyl phosphide gradually melted and generated a slight heat, stirring was continued at room temperature for 22 hours to complete the reaction. Next, after adding 2 to 3 drops of water and stirring, the dioxane was removed under reduced pressure, the remaining oil was extracted with a mixture of 75 ml of ether and 35 ml of water, the organic layer was separated, and the aqueous layer was further extracted with ether. This and the organic layer were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the obtained oil was distilled under high vacuum to obtain (-)-2,3-O-isopropylidene-
5.1 g of 2,3-dihydroxy-1,4-bis(diethylphosphino)butane was obtained. This is a yield of 83% based on difluoride. The properties and analytical values of this substance are as follows. Boiling point: 90-91℃/10 ^-3 mmHg [α] ²⁰ _D = -25.5° (C = 6.63, CHCl ₃ ) ¹ H-NMR: CDCl ₃ , δp.pmfrom TMS 1.04 (dt, J _PH 14Hz, J _HH 8Hz, PCH ₂ C H ₃ ) 1.19 (s, 〓C(C H ₃ ) ₂ ), 1.20 (m, PC
H ₂ CH ₃ ) 1.70 (d, CHC H ₂ P), 3.86 (m,

[Formula]) Furthermore, a solution of 308.9 mg (1.0 mmol) of (-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diethylphosphino)butane dissolved in 1.5 ml of benzene , sulfur 64.9 mg (2.0
mmol) was added dropwise to a suspension of 2 ml of benzene at room temperature while stirring. An exothermic reaction occurs, giving a colorless solution. When 6 ml of n-hexane is gradually added to this, a white precipitate is formed. Separate this, wash with 1 mol of n-hexane, and then
Recrystallized from 2.2 ml of hexane (1:2) mixture (-)-2,3-O-isopropylidene-2,3-
Dihydroxy-1,4-bis(diethylphosphino)butane disulfide was obtained. The properties and analytical values of this substance are as follows. Melting point: 134-136°C [α] ²⁰ _D = -30.6° (C = 1.59, CHCl ₃ ) Elemental analysis value: (C ₁₅ H ₃₂ O ₂ P ₂ S ₂ ) C H Calculated value (%) 48.64 8.71 Actual value (%) 48.35 8.52 ¹ H-NMR: CDCl ₃ , (δp.pmfrom TMS) 1.22 (m, PCH ₂ CH ₃ ), 1.40 (s, 〓C
(CH ₃ ) ₂ ) 2.00 (m, PC H ₂ CH ₃ +CHC H ₂ P), 4.3 (m,

[Formula]) Example 2 (-)-2,3-O-isopropylidene-2,3
-Production of dihydroxy-1,4-bis(diisopropylphosphino)butane First, 6.10 g (51.6
ml) in 30 ml of n-hexane, and add an n-hexane solution containing 1.6 mol of butyllithium at room temperature.
34 ml was added dropwise, and the mixture was refluxed for 3 hours. After filtering the supernatant and washing the resulting white precipitate with n-hexane,
Dry under reduced pressure. The lithium diisopropyl phosphide thus obtained was suspended in 150 ml of dioxane, and (+)-2,3-O-isopropylidene-2,3- produced in Example 1 was added to the suspension.
Dihydroxy-1,4-difluorobutane 3.58g
(21.5 mmol) was added. Stirred at room temperature for 24 hours. After the reaction was completed, a small amount of water was added and stirred, and then the dioxane was removed under reduced pressure, the resulting oil was extracted with a mixture of 80 ml of ether and 40 ml of water, and the organic layer was separated. The aqueous layer was further extracted with ether, this and the organic layer were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the oil was distilled under high vacuum (-)-
2.61 g of 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diisopropylphosphino)butane was obtained. This was a yield of 33% based on difluoride. The properties of this thing are as follows. Boiling point: 125-131°/10 ^-3 mmHg [α] ²⁰ _D = -31.0° (C = 2.97, C ₆ H ₆ ) Further, in the same manner as in Example 1, it was treated with sulfur in benzene to obtain (-)-2.・3-O-isopropylidene-2,3-hydroxy-1,4-bis(diisopropylphosphino)butane disulfide was prepared and subjected to nuclear magnetic resonance absorption analysis.The results are as follows. ¹ H-NMR: CDCl ₃ (δp.pmfrom TMS) 1.30 (dd, PCH ( CH ₃ ) ₂ , 1.40 (s, 〓C
(CH ₃ ) ₂ ), 2.10 (m, CH ₂ PC H ), 4.30
(brm,

[Formula]) Example 3 (-)-2,3-O-isopropylidene-2,3
-Production of dihydroxy-1,4-bis(dicyclohexylphosphino)butane First, 5.70g (20m
mol) in 70 ml of n-hexane, 21 ml of an n-hexane solution containing 34 mmol of butyllithium was added at room temperature, and the mixture was refluxed for 2 hours. The formed precipitate was filtered, washed with n-hexane, and then dried under reduced pressure to obtain 5.7 g (28 mmol) of lithium dicyclohexyl phosphide as a pale yellow solid.
This was suspended in 80 ml of dioxane, and (+)-2,3-O-isopropylidene-2,3-dihydroxy-1,4 prepared according to Example 1 was added to the suspension.
- A solution of 1.9 g (11 mmol) of difluorobutane in dioxane was added dropwise at room temperature over a period of 10 minutes.
The suspension gradually dissolved and became a green-yellow mixture after 2 hours. Furthermore, after stirring at room temperature for 20 hours,
After terminating the reaction by adding 5 ml of methanol and stirring, the volatile components were removed under reduced pressure and extracted with a mixture of 100 ml of ether and 100 ml of water. Separate the organic layer;
The aqueous layer was further extracted with ether, and this was combined with the organic layer, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to a volume of 50 ml. This carbon disulfide
When 1.3 ml is added, a brown precipitate forms immediately. This was filtered, washed with ether, and dried under reduced pressure to obtain 4.0 g of a crude product. This was recrystallized using a mixed solvent of ethanol-benzene-carbon disulfide, hexane-benzene-carbon disulfide, and ethanol-carbon disulfide sequentially to (-)-2.3-O-isopropylidene-2.3. 2.6 g of carbon disulfide adduct of -dihydroxy-1,4-bis(dicyclohexylphosphino)butane was obtained. The yield was 34% based on difluoride. The melting point and elemental analysis values of this product are as follows. Melting point: 106-107℃ Elemental analysis value: (C ₃₃ H ₅₆ O ₂ P ₂ S ₂ ) C H Calculated value (%) 58.72 8.36 Actual value (%) 58.67 8.32 Next, carbon disulfide adduct was suspended in ethanol. After refluxing for 1 hour in a nitrogen stream, it was evaporated to dryness under reduced pressure to give a colorless (-)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-
Bis(dicyclohexylphosphino)butane 2.4
I got g. The yield for difluoride is
It was 33%. The properties and analytical values of this substance are as follows. Melting point: 90-92°C (measured using a sealed tube filled with nitrogen) [α] ²⁴ _D = -24.1° (C = 0.97, benzene) ¹ H = NMR: C ₆ H ₆ (δp.pmfrom TMS) 1.50 (s, 〓C( _CH3 ) ₂ ), 0.9-2.2 (complex peaks, cyclohexyl,
CH2 _- P) 4.0(m,

【formula】)

Claims (1)

[Claims] 1. An optically active alkyl diphosphine compound represented by the following general formula (a) or (b) [Formula] [Formula] (wherein R represents a lower alkyl group or a cyclohexyl group) . 2 (-)-2・3-O-isopropylidene-
The optically active alkyl diphosphine compound according to claim 1, which is 2,3-dihydroxy-1,4-bis(diethylphosphino)butane. 3 (-)-2・3-O-isopropylidene-
The optically active alkyl diphosphine compound according to claim 1, which is 2,3-dihydroxy-1,4-bis(diisopropylphosphino)butane. 4 (-)-2・3-O-isopropylidene-
The optically active alkyl diphosphine compound according to claim 1, which is 2,3-dihydroxy-1,4-bis(dicyclohexylphosphino)butane. 5 (-)- or (+)-1.4-ditosyl-2.
3-O-isopropylidene-threitol is reacted with an alkali metal fluoride (+)- or (-)-
2,3-O-isopropylidene-2,3-dihydroxy-1,4-difluorobutane and reacted with an alkali metal alkyl phosphide or alkali metal cyclohexyl phosphide to obtain the following general formula (a) or (b) Production of an optically active alkyldiphosphine compound characterized by obtaining an optically active alkylphosphine compound represented by [Formula] [Formula] (wherein R represents a lower alkyl group or a cyclohexyl group) Method.