JPS6332333B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for asymmetrically synthesizing optically active homoallylic alcohols. More specifically, the present invention comprises:
A method for asymmetric synthesis of optically active homoallyl alcohols, which comprises reacting an optically active organotin compound represented by the formula () with an aldehyde or an asymmetric ketone in the presence of a Lewis acid, and then hydrolyzing it. It is. However, in the above formula (), R ¹ has a carbon number of 4
~20 carbon atoms selected from saturated chain aliphatic groups, saturated cycloaliphatic groups, unsaturated chain aliphatic groups, unsaturated cycloaliphatic groups, aromatic substituted aliphatic groups, and bonded to tin is an organic group in which at least one carbon atom at the α-position, β-position, or γ-position along the carbon atom chain is an asymmetric carbon atom. R ² is a halogen atom selected from chlorine, bromine, and iodine, or has 1 to 1 carbon atoms.
It is an organic group selected from 12 saturated chain aliphatic groups, saturated cycloaliphatic groups, unsaturated chain aliphatic groups, unsaturated cycloaliphatic groups, aromatic groups, and aromatic substituted aliphatic groups. x and y are 1 to 3 satisfying x+y≦4
is a positive integer. Many organic tin compounds have important uses as reaction reagents for various organic reactions or as catalysts for esterification reactions, ring-opening polymerization reactions of epoxides, etc. However, the organotin compounds conventionally used as reaction reagents and catalysts are only optically inactive compounds, and are used as synthesis reagents and catalysts for so-called asymmetric reactions that preferentially give one optical isomer. had no effect at all. On the other hand, some examples of asymmetric allylation reactions using optically active allyl silicon compounds and allyl boron compounds that exhibit reactivity similar to that of organotin compounds have been found, but in organosilicon compounds, the allyl group is substituted with phenyl. There were many unsatisfactory points, such as being limited to special types, restrictions in handling due to the instability of organic boron compounds in air, and difficulty in reusing reagents. Recently, the present inventors have discovered a novel optically active organotin compound containing both an asymmetric organic group and an allyl group, and have filed a separate application.The present invention relates to the use of these compounds as an allylation reaction reagent for aldehydes or ketones. As a result, they succeeded in obtaining optically active homoallylic alcohols and completed the present invention. Homoallylic alcohols are often important as synthetic intermediates. The optically active organotin compound represented by the formula () of the present invention is produced by the following method. A Grignard reagent is prepared by a conventional method from an organic halide having an optically active organic group represented by the following formula (), and the Grignard reagent is reacted with an allyl-substituted tin halide represented by the following formula () in an appropriate solvent. A group-containing optically active organotin compound is obtained. ^R1X () However, in the above formula (), X is chlorine, bromine,
Represents a halogen atom selected from iodine, and R ¹ is
It is the same as R ¹ in the above formula (). The above formula ()
, X represents a halogen atom selected from chlorine, bromine, and iodine, and R ² is R ² of the above formula ().
is the same as x and y are x in the above formula ()
and y. In the above reaction, examples of the solvent include tetrahydrofuran, diethyl ether, dimethoxyethane, etc., and a suitable reaction temperature of -100 to 120°C is selected. In addition, as another method for producing the compound of formula (),
Known methods (JS Filippo, Jr. et al. J. Am. Chem. Soc.
104, 2831 (1982)) is reacted with bromine to form a tin bromide compound, and this is reacted with allylmagnesium halide or tosylate,
An optically active allyltin compound represented by the following formula () is obtained. (R ¹ )xSn(C ₆ H ₅ ) ₄ −x () However, in the above formulas () and (),
R ¹ is the same as R ¹ in the above formula (), and x is 1
or 2. In the above reaction, the bromination reaction can be carried out in a solvent such as carbon tetrachloride, chloroform, or ether. The reaction temperature is usually in the range of -100 to 120°C. The reaction with the allyl Grignard reagent can be carried out in a solvent such as ether, tetrahydrofuran, dimethoxyethane, etc., and the reaction temperature is usually in the range of -100 to 120°C. In addition, as another method for producing the compound of formula (),
When an optically active diallyltin compound represented by the following formula () is subjected to a disproportionation reaction with an optically active tin halide represented by the following formula (), an optically active monoallyltin compound represented by the following formula () is obtained. (R ¹ ) ₂ Sn (−CH ₂ CH=CH ₂ ) ₂ () (R ¹ ) ₂ SnX ₂ () However, in the above formulas () to (), R ¹ is
It is the same as R ¹ in the above formula (), and also the formula ()
In the formula (), X represents a halogen atom selected from chlorine, bromine, and iodine. The above reaction can be carried out without a solvent or in a solvent such as ether, tetrahydrofuran, chloroform, carbon tetrachloride, benzene, or the like. The reaction temperature is usually in the range of -80 to 120°C. Homoallyl alcohols by asymmetric synthesis of the present invention are produced by the reaction shown by the following formula (). However, in the above formula (), R ³ and R ⁴ are hydrogen atoms, saturated chain aliphatic groups having 1 to 30 carbon atoms, saturated cycloaliphatic groups, unsaturated chain aliphatic groups, unsaturated cycloaliphatic groups. represents mutually different groups selected from a group group, an aromatic group, an aromatic-substituted aliphatic group, a halogen-substituted aliphatic group, and a halogen-substituted aromatic group. Further, R ³ and R ⁴ may form a ring through a carbon-carbon bond. As shown in the above formula (), when an aldehyde or an asymmetric ketone is reacted with an optically active allyltin compound of the formula () and the reactant is subsequently hydrolyzed, the target optically active homoallylic alcohol is obtained. The above reaction can be carried out without a solvent or in a solvent such as ether, dimethoxyethane, dichloromethane, etc. The reaction temperature is usually in the range of -100 to 120°C. The molar ratio of the compound of formula () to the carbonyl compound usually ranges from 0.1 to 10. The reaction is carried out in the presence of a Lewis acid such as boron fluoride etherate, and the equivalent amount of Lewis acid used relative to the carbonyl compound ranges from 0.01 to 10. After the reaction is completed, the optically active substituent can be recovered in a form that can be used repeatedly by subjecting the reaction residue to an appropriate treatment. The present invention will be explained below with reference to Examples. Production example of compound of formula () 1 Diallyltin dibromide was added to 20 ml of a tetrahydrofuran solution of 2-phenylbutylmagnesium chloride prepared from 18.0 g (107 mmol) of (+)-1-chloro-2-phenylbutane (optical purity 97%). 12.8 g (36 mmol) was added at room temperature, stirred at room temperature for 1 hour, and then refluxed for 30 minutes. After adding 100 ml of hexane to the reaction mixture and filtering, the filtrate was concentrated and the resulting oil was distilled to give (-)-diallylbis(2-phenylbutyl)tin ((-)-[C ₂ H ₅ (C ₆ H ₅ ) CHCH ₂ ] ₂ Sn (CH ₂ CH=
15.1 g of CH ₂ ) ₂ ) was obtained (yield 90%, boiling point 210
°C/0.15mmHg, [α] ²³ _D −38.1° (C0.97, benzene)
.
Elemental analysis Actual values: Carbon 67.17%, Hydrogen 7.94%
(Calculated values as C ₂₆ H ₃₆ Sn: 66.83% carbon, hydrogen
7.77%) NMR (CCl ₄ solvent TMS standard δ) 0.69 (6H), 0.87-1.93 (12H), 2.02-2.85 (2H),
4.40~4.88 (4H), 5.16~6.03 (2H), 7.00~7.30
(10H) Production example of compound of formula () 2 (-)-(R)-2-octyltriphenyltin
9.26 g (20 mmol) in 100 ml of carbon tetrachloride solution,
3.36 g (42 mmol) of bromine was added dropwise at 0°C, and the mixture was heated to room temperature.
After reacting for 30 minutes, the solvent was distilled off under reduced pressure, resulting in (-)-2
-9.1 g of octylphenyltin dibromide were obtained (97% yield, [α] ²³ _D -20.1° (C4.00, benzene)). A solution of 9.0 g (19 mmol) of the obtained (-)-2-octylphenyltin dibromide in tetrahydrofuran (40 ml) was added to 9.2 g (76 mmol) of allyl bromide.
After refluxing for 1 hour, 100 ml of hexane was added to the reaction mixture and filtered. The solvent of the filtrate was distilled off under reduced pressure, and the residue was distilled under reduced pressure. Then, (-)-diallyl(2-octyl)phenyltin ((-)-(C ₈ H ₁₇ )(C ₆ H ₅ )Sn
( _CH2CH =CH2 _{)2 )} 6.3g was obtained (yield 85%,
Boiling point 175-180℃/0.2mmHg, [α] ²³ _D −21.2゜(C3.52
,
benzene)). Nuclear magnetic resonance spectrum of (−)-diallyl(2-octyl)phenyltin (CCl ₄ solvent,
TMS standard) and infrared absorption spectrum (thin film method)
are shown in Figures 1 and 2. Production example 3 of compound of formula () (-)-diallylbis(2
-4.6 g (10 mmol) of (-)-bis(2-phenylbutyl)tin dichloride was added to 20 ml of a carbon tetrachloride solution containing 4.7 g (10 mmol) of tin (-)-bis(2-phenylbutyl) at 0°C.
After stirring at room temperature for 1 hour, the solvent was distilled off to give optically active allylbis(2-phenylbutyl)tin chloride ((-)-[C ₂ H ₅ (C ₆ H ₅ )
4.3 g of CHCH ₂ ] ₂ SnCl (CH ₂ CH=CH ₂ ) was obtained (yield 95%). Example 1 (-)-diallylbis(2-phenylbutyl)
20 ml of an ether solution containing 5.05 g (10.8 mmol) of tin and 1.06 ml (5.4 mmol) of a 47% ether solution of boron trifluoride etherate was cooled to -78°C, 0.94 g (16.2 mmol) of propionaldehyde was added, and at this temperature The mixture was stirred for 6.5 hours. The reaction mixture was hydrolyzed with 30 ml of 0.5 N NaOH solution, then washed with 1 N HCl solution and water, dried over magnesium sulfate, the ether was distilled off, and the residue was distilled to give 5-hexen-3-ol 1.02 (yield 63%, [α] ²³ _D −2.97° (C10.7, benzene) %ee 49). The distillation residue of 5-hexen-3-ol was dissolved in 10 ml of acetic anhydride and refluxed for 1 hour, then the acetic anhydride was distilled off under reduced pressure, and the resulting residue was mixed with 1:2 methanol-
Add 3NHCl solution and stir overnight. The reaction solution was extracted with dichloromethane and the solvent was distilled off to obtain bis(2-phenylbutyl)tin dichloride. Two equivalents of allylmagnesium chloride were added to the obtained ether solution of bis(2-phenylbutyl)tin dichloride at -10°C, refluxed for 1 hour, extracted with dichloromethane, and the solvent was distilled off and distilled under reduced pressure to obtain (-). -3.28 g of diallylbis(2-phenylbutyl)tin was recovered (65% recovery rate). Examples 2 to 17 In the same manner as in Example 1, an allylation reaction of a carbonyl compound with an optically active allyltin compound was carried out under the reaction conditions shown in Table 1 to obtain corresponding optically active homoallylic alcohols. The results are shown in Table 1. In addition, in Table 1, in Examples 5 to 17, the yield of the product is the value obtained by separating the product by column chromatography. [Table] Example 18 (-)-diallylbis(2-phenylbutyl)
20 ml of an ether solution containing 5.05 g of tin and 1.06 ml of a 47% solution of boron trifluoride etherate in -78
After cooling to °C, 2.75 g of β-acetylnaphthalene was added as an asymmetric ketone, and the mixture was stirred at the same temperature for 6 hours. The reaction mixture was hydrolyzed by adding 30 ml of 0.5 N NaOH solution, and then washed sequentially with 1 N HCl solution and water.
Dry with magnesium sulfate. Then, the ether is distilled off and the residue is distilled to give 2-(β-naphthyl)
2.40 g of -4-penten-2-ol was obtained (yield 70%, [α] ²³ _D +13.6° (C6.89, benzene),
%
ee30). Example 19 β-acetylnaphthalene as an asymmetric ketone
The desired product, 1.81 g of 2-phenyl-4-penten-2-ol, was obtained in the same manner as in Example 18, except that 1.94 g of acetophenone was used instead of 2.75 g (yield: 69%, [α] ²³ _D +11.4° (C7.85, benzene),
%
ee55).

[Brief explanation of the drawing]

FIG. 1 shows the nuclear magnetic resonance spectrum of (-)-diallyl(2-octyl)phenyltin, and FIG. 2 shows the infrared absorption spectrum of the same substance.

Claims (1)

[Scope of Claims] 1. An optically active homoallylic alcohol characterized in that an optically active organotin compound represented by the following formula () is reacted with an aldehyde or an asymmetric ketone in the presence of a Lewis acid, and then hydrolyzed. Asymmetric synthesis method of the class. However, in the above formula (), R ¹ has 4 carbon atoms
~20 carbon atoms selected from saturated chain aliphatic groups, saturated cycloaliphatic groups, unsaturated chain aliphatic groups, unsaturated cycloaliphatic groups, aromatic substituted aliphatic groups, and bonded to tin is an organic group in which at least one of the carbon atoms at the α-position, β-position, or γ-position along the carbon atom chain is an asymmetric carbon atom. R ² is a halogen atom selected from chlorine, bromine, and iodine, or has 1 to 1 carbon atoms
It is an organic group selected from 12 saturated chain aliphatic groups, saturated cycloaliphatic groups, unsaturated chain aliphatic groups, unsaturated cycloaliphatic groups, aromatic groups, and aromatic substituted aliphatic groups. x and y are 1 to 3 satisfying x+y≦4
is a positive integer.