JP2832479B2 - Stereochemical inversion method of optically active styrene oxide and preparation of optically active glycol derivative - Google Patents

Description

The present invention relates to a stereochemical inversion method of an optically active styrene oxide and a method for producing an optically active glycol derivative. More specifically, the present invention relates to an optically active styrene oxide with high optical purity and high yield. The present invention relates to a stereochemical inversion method of styrene oxide capable of stereochemical inversion and a method for producing an intermediate thereof.

[Problems to be solved by conventional technology and invention]

Optically active styrene oxide is an extremely important compound as a raw material for synthesizing new materials such as pharmaceuticals, agricultural chemicals, other physiologically active substances, and ferroelectric liquid crystal materials.

Thus, if the preferred optical isomer can be appropriately selected as a raw material for synthesis, the process for obtaining the target compound can be shortened, and the target compound having higher optical purity can be obtained.

In particular, in recent years, the usefulness of optically active substances has been increasing in the field of new materials, and obtaining optically active substances with high optical purity has become a very important issue.

Conventionally, in an alcohol addition reaction to an oxirane compound such as an optically active styrene oxide, for example, SnCl ₄ , BF ₃
A Lewis acid catalyst such as Et ₂ O (Et: ethyl group) is used.

However, when a Lewis acid catalyst is used for the optically active styrene oxide, the compound represented by the following general formula (5) in which the position of addition of the alkoxy group is β is by-produced. The desired optically active glycol derivative having an alkoxy group at the α-position cannot be obtained in good yield, and the obtained optically active glycol derivative (1) undergoes racemization. There was a problem that it could not be obtained.

[However, in the formulas (1) and (2), R ¹ is an allyl group,
An organic group selected from the group consisting of a methallyl group and an alkyl group having 1 to 4 carbon atoms which may have an aryl group as a substituent, and the symbol * represents an asymmetric carbon atom, and the symbol Ph
Represents a phenyl group. In addition, a method of obtaining (S) -styrene oxide using α-chloroacetophenone as a starting material using an optically active catalyst is known (J. Org. Chem. 53 2861 (198)
8)).

However, this method has a problem that it is not practical because a special and expensive reagent is used as a catalyst.

Therefore, as a result of intensive studies to solve the above problems, the present inventors have found that the optically active styrene oxide,
It has been found that the above problem can be solved by using a specific catalyst when the alcohol is subjected to ring-opening addition.

The present invention has been made based on such knowledge,
The purpose is to use an inexpensive catalyst and easily convert both enantiomers of optically active styrene oxide from one ((R) -form or (S) -form) to the other ((S-form) without substantially reducing the optical purity. The present invention provides a stereochemical inversion method of styrene oxide which can be inverted into a)) or (R) form) and a method for producing an optically active glycol derivative which enables to obtain an optically active glycol derivative with high optical purity in a high yield. .

[Means for solving the problem]

The stereochemical inversion method of styrene oxide according to the present invention for achieving the above object has the following five steps (however, step (IV) is a step that is performed as necessary).

<Step (I)> An organotin compound selected from the following (A) group and the following (B)
An optically active glycol derivative represented by the following general formula (1) by ring-opening addition of an alcohol R ¹ OH to an optically active styrene oxide in the presence of a catalyst comprising a thermal condensation product with a phosphate ester selected from the group Manufacturing process.

(A) _{Group: R 'a SnX 4-a} (A-1) R' b SnO c (A-2) R "- (R '2 SnOSnR' 2) -R" (A-3) R 'a SnX represented by _{(RO) 3 P = O (} B-1) < step (II)> above equation (1): _4-a and R _'b complex compound of _{SnO c (a-4) (} B) group A step of reacting the optically active glycol derivative with a sulfonic acid halide in the presence of a base to produce an optically active glycol derivative represented by the following general formula (2).

<Step (III)> The optically active glycol derivative represented by the above formula (2) is
A step of producing an optically active glycol derivative represented by the following general formula (3) by reacting in the presence of an acidic catalyst, a metal catalyst, or a mixed catalyst of an acidic catalyst and a metal catalyst.

<Step (IV)> If necessary, a step of producing an optically active glycol derivative represented by the following general formula (4) by reacting the optically active glycol derivative represented by the above formula (3) with iodide.

<Step (V)> The optically active glycol derivative represented by the above formula (4) is
A step of performing intramolecular ring closure in the presence of a base.

[However, in the formulas (1) and (2), R ¹ is an allyl group,
An organic group selected from the group consisting of a methallyl group and an alkyl group having 1 to 4 carbon atoms which may have an aryl group as a substituent, wherein in the formulas (2) and (3), R ² is a tosyl group , A mesyl group and a benzenesulfonyl group, wherein the symbol * in the formulas (1) to (4) represents an asymmetric carbon atom, and the symbol Ph represents a phenyl group.

Further, in the formulas (A-1) to (A-3), R ′ is an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group having 1 to 12 carbon atoms which may have a substituent. An organic group selected from the group consisting of the formula (A-1)
In the formula, X is an atom or an organic group selected from the group consisting of a halogen atom, an alkoxy group, an aryloxy group, an acyloxy group, and a partial ester residue of phosphoric acid;
In -3), R ″ is R ′ or X in formula (A-1), and the two R ″ s may be the same or different. In the formula (A-1), a is an integer of 1 to 4, and a is 2
When it is an integer of up to 4, R's may be the same or different. When a is 1 or 2, X may be the same or different. In the formula (A-2),
b is 1 or 2; when b is 1, c is 3/2; and when b is 2, c is 1. Further, in the formula (B-1), R
Is hydrogen, an alkyl group having 2 or more carbon atoms, an alkenyl group or a cycloalkyl group, and three R's may be the same or different, but at least one is a group other than a hydrogen atom . In the present invention, in step (I), a thermal condensation product of a specific organotin compound and a specific phosphate is used as a catalyst. As a result, the desired optically active glycol derivatives represented by the above formulas (1) to (3) can be obtained in good yield without lowering the optical purity, and the optical purity can be lowered. The stereochemistry of styrene oxide can be reversed with good yield.

Hereinafter, each step will be described with reference to the following reaction flow sheet, taking as an example a case where an optically active styrene oxide of the (R) form is used as a starting material. However, in the following reaction flow sheet, R ¹ and R ¹ in the above formula (1), R ² has the same meaning as R ² in the formula (2).

<Step (I)> In this step, (R) -styrene oxide is converted to a compound of the general formula R ¹ OH
Is a step of producing an (S) -glycol derivative (represented by (S)-(1) in the reaction flow sheet) by ring-opening addition of an alcohol represented by It is carried out in the presence of a catalyst consisting of a thermal condensation product with a phosphate ester. The starting material (R) -styrene oxide is available from, for example, Aldrich.

R ¹ in the general formula R ¹ OH is an allyl group, an organic group selected from the group consisting of alkyl groups of methallyl groups and substituents as 1-4 carbon atoms which may have an aryl group, such general the alcohol of the formula, for example, _{C 6 H 5 CH 2 OH,} CH 2 = CH-CH 2 OH, CH 2 = C (CH 3) -CH 2 OH, (CH 3) 3 COH, (C 6 H ₅ ) ₂ CHOH and (C ₆ H ₅ ) ₃ COH.

The alcohol R ¹ OH is reacted in the range of 1 to 10 equivalents, preferably 1 to 3 equivalents, to (R) -styrene oxide.

Examples of the organotin compound represented by the general formula (A-1) in the group (A) include (C ₂ H ₅ ) ₄ Sn, (C ₆ H ₅ ) ₄ Sn, (CH ₃ ) ₃ SnF, (C ₄ H ₉ ) ₃ SnCl, (CH ₃ ) ₃ SnBr, (C ₈ H ₁₇ ) ₃ SnCl, (CH ₃ ) ₂ SnF ₂ , (C ₄ H ₉ ) ₂ SnCl ₂ , (C ₁₂ H ₂₃ ) ₂ SnBr ₂ , (C ₄ H ₉ ) ₂ Sn (OCH ₂ CH = CH ₂ ) ₂ (CH ₂ CH = CH ₂ ) Sn (C ₂ H ₅ ) ₃ (C ₄ H ₉ ) ₃ SnOC ₄ H ₉ , (cyclo −C ₆ H ₁₁ ) ₂ Snl ₂ , (C ₄ H ₉ ) SnF ₃ , (C ₈ H ₁₇ ) SnCl ₃ , (C ₈ H ₁₇ ) ₃ SnOCOCH ₃ and (C ₈ H ₁₇ ) ₂ Sn (OCOC ₁₇ H ₃₅ ) ₂ .

Examples of the organotin compound represented by the general formula (A-2) in the group (A) include (CH ₃ ) ₂ SnO, (C ₄ H ₉ ) ₂ SnO, (C ₈ H ₁₇ ) ₂ SnO, (C ₆ H ₅ ) ₂ SnO, CH ₃ SnO _3/2 , and C ₄ H ₉ SnO _3/2 .

As the complex compound of the compound represented by the general formula (A-1) and the compound represented by the general formula (A-2),
For example, (CH ₃ ) ₂ SnO. (C ₂ H ₅ ) ₂ SnBr ₂ , (CH ₃ ) ₂ SnO. (CH ₃ ) ₂ SnCl ₂ , CH ₃ [(CH ₃ ) ₂ SnO] ₂ Cl _3. (CH ₃ ) ₂ SnBr ₂ .

Examples of the organotin compound represented by the general formula (A-3) in the group (A) include (CH ₃ ) ₃ SnOSn (CH ₃ ) ₃ and Cl (C ₄ H ₉ ) ₂ SnOSn (C ₄ H). ₉ ) ₂ Cl, (CH ₃ COO) (C ₆ H ₅ ) ₂ SnO Sn (C ₆ H ₅ ) ₂ (CH ₃ COO).

Examples of the phosphate represented by the general formula (B-1) in the group (B) include (C ₂ H ₅ ) ₃ PO ₄ , (C ₃ H ₇ ) ₃ PO ₄ , and (C ₄ H ₉ ) _{3 PO 4, (C 8 H} 17) 3 PO 4, (CH 2 = CH-CH 2) 3 PO 4, (C 6 H 11) 3 PO 4, (ClCH 2 -CH 2) 3 PO 4, (Cl _{2 C 3 H 5) PO 4} , (C 2 H 5) 2 HPO 4, (C 4 H 9) 2 HPO 4, (C 4 H 9) H 2 PO 4, and the like.

The catalyst in the present invention comprises a mixture of an organotin compound belonging to the group (A) and a phosphoric ester belonging to the group (B) in the range of 150 to 3;
Obtained as a thermal condensation product when heated at 00 ° C. In addition, this condensation may be performed in a solvent as needed.

The organotin compound belonging to the above group (A) and the phosphoric ester belonging to the group (B) are usually reacted at a ratio such that the number ratio of tin atom to phosphorus atom is in the range of 1:10 to 10: 1. I just need.

In the above-mentioned catalyst generation reaction (condensation reaction),
Various relatively simple substances are generated and desorbed by the condensation reaction depending on the types of the components of the group (A) and the components of the group (B).

The obtained thermal condensation product shows different activities depending on the degree of condensation. The optimum degree of condensation of the catalyst in the present invention is:
(A), (B) It depends on the type and ratio of the components selected from both groups, but can be easily determined experimentally.

Those having a high degree of condensation are generally insoluble in solvents, and using such an insoluble catalyst has the advantage that it can be easily removed from the system by mechanical treatment such as after completion of the reaction.

In general, the heat condensation product is soluble in a solvent such as hexane or benzene at the initial stage of condensation, but becomes a polymer and becomes insoluble with the progress of the condensation reaction.

The amount of the catalyst to be used is not particularly limited and can be selected in a wide range, but generally, (R) -styrene oxide
It is preferably in the range of 10 to 1000 parts by weight, more preferably in the range of 100 to 300 parts by weight, per 100 parts by weight.

The reaction temperature in the ring-opening addition reaction in this step is not particularly limited, but is usually preferably in the range of −10 to 100 ° C.

<Step (II)> In this step, the (S) -glycol derivative (shown as (S)-(1) in the reaction flow sheet) obtained in step (I) is reacted with a sulfonic acid halide in the presence of a base. This is a step of forming a (S) -form sulfonic acid ester (represented by (S)-(2) in the reaction flow sheet).

Examples of the sulfonic acid halide include p-toluenesulfonic acid chloride, p-toluenesulfonic acid bromide, p-toluenesulfonic acid iodide, methanesulfonic acid chloride, methanesulfonic acid bromide, methanesulfonic acid iodide, and benzene chloride. Sulfonic acid, brominated benzenesulfonic acid and iodobenzenesulfonic acid are exemplified.

As the base, tertiary amines such as triethylamine and trimethylamine, and pyridine are preferable.

The amount of the sulfonic acid halide to be used is preferably 1 to 10 equivalents, more preferably 1 to 3 equivalents to the alcohol. The amount of the base to be used is preferably 1 to 100 equivalents to the alcohol.

The reaction in this step generally proceeds within the range of −20 to 100 ° C., but preferably within the range of 0 to 70 ° C.

When a solvent is used, it is necessary to use an inert solvent. Among them, pyridine, methylene chloride and chloroform are particularly preferable.

<Step (III)> In this step, (S)-(2) obtained in step (II) is reacted with hydrogen in the presence of a catalyst to form an (S) -glycol derivative ((S) )-(3)).

As the catalyst, an acidic catalyst, a metal catalyst or a mixed catalyst thereof is used. Examples of the acidic catalyst include p-toluenesulfonic acid, benzenesulfonic acid, perchloric acid, sulfuric acid, hydrochloric acid, nitric acid, hydrogen bromide, acetic acid, trifluoroacetic acid,
Examples thereof include trichloroacetic acid, tribromoacetic acid, silica gel, aluminum chloride, titanium tetrachloride, and boron trifluoride. Examples of the metal catalyst include platinum and palladium.

The catalyst, (S) - is appropriately selected according to the kind of the substituents R ¹ of the α-position (2). When the substituent R ¹ is C ₆ H ₅ CH ₂ —, palladium is used, and when the substituent R ¹ is CH ₂ CHCH—CH ₂ — or CH ₂ ＣC
(CH ₃₎ CH ₂ - the mixed catalyst of palladium and p- toluenesulfonic acid or perchloric acid when, substituents R ¹ (C
When H ₃ ) ₃ C-, a mixed acid of trifluoroacetic acid, hydrochloric acid or hydrogen bromide and acetic acid, and when the substituent R ¹ is (C ₆ H ₅ ) ₂ CH-, a mixed catalyst of palladium and aluminum chloride. To (C ₆
When H ₅ ) ₃ C—, acetic acid, trifluoroacetic acid, silica gel or hydrochloric acid is preferably used.

The amount of the catalyst used is determined by the amount of the starting compound (S)-(2)
0.05 to 20 parts by weight, preferably 0.2 to 10 parts by weight per 100 parts by weight
A range of parts by weight is preferred. When a mixed catalyst of an acidic catalyst and a metal catalyst is used, the metal catalyst is preferably used in a range of 0.01 to 1 part by weight based on 100 parts by weight of the acidic catalyst.

In the hydrogenation reaction in this step, as a solvent, water, a single system such as alcohols, alcohols and water,
A mixed solvent such as ethers and water can be used.

Examples of the alcohols include methanol, ethanol, propanol and t-butyl alcohol, and examples of the ethers include ethyl ether, tetrahydrofuran and dioxane. Usually, a single solvent such as methanol, ethanol or water or a mixed solvent of water and methanol or ethanol is suitably used.

The hydrogenation reaction in this step generally proceeds within a range of 0 to 150 ° C, but is preferably performed usually within a range of 15 to 100 ° C.

<Step (IV)> In this step, using (S)-(3) obtained in step (III) with an iodide such as sodium iodide or potassium iodide, β
In this step, i-substituted substituent R ² is substituted as needed. The amount of iodide is preferably from 1 to 30 equivalents to alcohol, more preferably from 3 to 10 equivalents.

The reaction of this step usually proceeds within a range of 0 to 100 ° C. When a solvent is used, an inert solvent must be used, and among them, acetone and benzene are particularly preferable.

<Step (V)> In this step, (S)-(4) obtained in step (IV) was converted to 1.8
-Diazabicyclo [5.4.0] -7-undecene, triethylamine, the other optical isomer of (R) -styrene oxide as a starting material by an intramolecular cyclization reaction in the presence of a base such as sodium hydroxide, ie, (S ) -Step of obtaining styrene oxide. The amount of base is 1 to alcohol
~ 20 equivalents are preferred, and 1-3 equivalents are more preferred.

The reaction of this step usually proceeds within the range of 0 to 70 ° C.
When using a solvent, it is necessary to use an inert solvent,
Of these, dichloroethane and chloroform are particularly preferred.

In addition, (S)-(3) obtained in the step (III) is converted to the step (I)
Even if a direct intramolecular cyclization reaction is carried out in the presence of a base such as sodium hydroxide or potassium hydroxide without passing through V), it is the other optical isomer of the starting material (R) -styrene oxide (S ) -Styrene oxide can be obtained (represented by (VI) in the reaction flow sheet).

The (S) -styrene oxide thus obtained has the optical purity of the raw material (R) -styrene oxide.

Further, the method for producing an optically active glycol derivative (steps (I) to (III)) according to the present invention provides an intermediate for obtaining each enantiomer of optically active styrene oxide having high optical purity, It forms an important intermediate process in the stereochemical inversion method of styrene oxide according to the present invention.

〔Example〕

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the present invention is not limited to the following Examples, and can be implemented by appropriately changing the scope without changing the gist of the present invention. It is.

(A) Synthesis of catalyst In a three-necked flask equipped with a stirrer, a thermometer, and a distillation apparatus, 12.5 g of dibutyltin oxide and 26.6 g of tributyl phosphate were placed, and stirred at 250 ° C. under a nitrogen stream.
The mixture was heated for 20 minutes to distill off the distillate to obtain a solid thermal condensation product as a residue.

(B) Reversal of optical activity of styrene oxide (Example 1) <Step (I)> 217 mg of the thermal condensation product obtained in the above (A) was placed in a reactor as a catalyst, and dried at 150 ° C. for 1 hour under reduced pressure. After the atmosphere in the vessel was replaced with nitrogen, the vessel was cooled to room temperature. Then hexane
5 ml, (R) -styrene oxide (▲ [α] ²² _D ▼ + 45.
120 mg (1 mmol) of 70 c = 1.67 benzene) and 162 mg (1.5 mmol) of benzyl alcohol were added, and the mixture was stirred under heating and reflux for 1 hour. The catalyst was removed by filtration, and the filtrate was concentrated. The residue was subjected to column chromatography (5: 1 = hexane: ethyl acetate) to give 180 mg of (S) -1-benzyloxy-1-phenyl-2-ethanol ((S)-(1)) (yield 79).
%).

 The properties of this product are as follows.

▲ [α] ²² _D ▼ + 86.78 ゜ (c = 2.58 ethanol) ¹ H NMR (CDCl ₃ ) δ2.93 (brs, 1H), 3.55 (dd, 1H, J = 3.7 and 11.7 Hz)
3.68 (dd, 1H, J = 8.4 and 11.7 Hz), 4.38 (ABq, 2H, J = 7.
3Hz), 4.46 (dd, 1H, J = 3.7 and 8.1Hz), 7.27−7.34
(M, 10H). ¹³ C NMR (CDCl ₃ ) δ 67.00, 70.40, 82.10, 126.80, 127.50, 127.60, 127.90,1
28.20, 128.30, 137.80, 138.40. MS m / e228 (M ⁺ ) ee98%: HPLC analysis (Chiralcel OD, 1% isopropanol-hexane) (Example 2) <Step (II)> Obtained in the above step (I) (S) -1-benzyloxy-
To a solution of 123 mg (0.54 mmol) of 1-phenyl-2-ethanol in 5 ml of pyridine was added 309 mg (1.62 mmol) of p-toluenesulfonyl chloride at room temperature, followed by stirring for 4 hours. Then, the mixture was extracted with benzene, the organic layer was washed with water, dried over magnesium sulfate, and concentrated. The residue was subjected to column chromatography (5.1 = hexane: ethyl acetate) to give (S) -1-benzyloxy-1-phenyl-2-
(P-toluenesulfonyloxy) ethane ((S))-
(2)) 183 mg (89% yield) was obtained.

 The properties of this product are as follows.

▲ [α] ²² _D ▼ +66.63 ゜ (c = 2.20 chloroform) ¹ H NMR (CDCl ₃ ) δ 2.41 (s, 3H), 4.09 (dd, 1H, J = 4.0 and 10.6 Hz), 4.1
8 (dd, 1H, J = 8.0 and 10.6Hz), 4.40 (ABq, 2H, J = 11.7H
z), 4.61 (dd, 1H, J = 4.0 and 8.0 Hz), 7.23-7.35 (m, 1
2H), 7.69-7.71 (m, 2H). ¹³ C NMR (CDCl ₃ ) δ 21.50, 70.60, 72.70, 78.60, 126.90, 127.53, 127.55, 12
7.80,128.20,128.50,128.60,129.60,132.90,136.90,13
7.60,144.50. MS m / e274 (M ⁺ -PhCH ₂ OH) (Example 3) <Step (III)> In a glass pressure-resistant reactor, the (S) obtained in the above step (II) was used.
200 mg (5.2 mmol) of -1-benzyloxy-1-phenyl-2- (p-toluenesulfonyloxy) ethane, 5 ml of ethanol and 20 mg of palladium carbon were charged, and hydrogen gas (3 kg / cm ² ) was charged into the vessel. And stirred at room temperature for 72 hours. The reaction mixture was filtered and the filtrate was concentrated. Column chromatography of the residue (5: 1 = hexane: ethyl acetate)
136 mg of (S) -1-phenyl-2- (p-toluenesulfonyloxy) ethanol ((S)-(3))
(89% yield).

The properties of this product are as follows. ¹ H NMR (CDCl ₃ ) δ 2.41 (s, 3H), 3.02 (br s, 1H), 4.01 (dd, 1H, J = 8.0
and 10.0Hz), 4.10 (dd, 1H, J = 4.0 and 10.0Hz), 4.92
(Dd, 1H, J = 4.0 and 8.0Hz), 7.24-7.30 (m, 7H), 7.71
−7.73 (m, 2H). ¹³ C NMR (CDCl ₃ ) δ 21.50,71.60.74.10,126.10,127.80,128.20,128.40,13
0.00,132.40,138.30,144.90. MS m / e274 (M + -H 2 O) ( Example 4) in acetone 15ml solution of <Step (IV)> Sodium iodide 1.57 g (9.6 mmol), the step (III (S) -1-phenyl-
383m of 2- (p-toluenesulfonyloxy) ethanol
g (1.3 mmol) was added, and the mixture was stirred under reflux for 4 hours. Next, after distilling off acetone, ether and water were added. The organic layer was separated, washed successively with an aqueous sodium thiosulfate solution and water, dried over magnesium sulfate, and concentrated. The residue was subjected to column chromatography (5: 1 = hexane: ethyl acetate) to give 276 mg of (S) -2-iodo-1-phenylethanol ((S)-(4)) (yield: 85).
%).

The properties of this product are as follows. ¹ H NMR (CDCl ₃ ) δ 2.91 (br s, 1H), 3.30-3.46 (m, 2H), 4.74 (br t, 1
H), 7.31 (s, 5H ) 0 13 C NMR (CDCl 3) δ15.00,73.80,125.70,128.20,128.50,141.00 HRMS Calcd.for C 8 H 9 OI:. 247.9698.Found:. 247.9720 ( Example 5) <Step (V)> The (S) obtained in the above step (IV) in 10 ml of dichloromethane.
250 mg of 2-iodo-1-phenylethanol (1.0 mmo
l) and 306 mg (2.0 mmol) of 1.8-diazabicyclo [5.4.0] -7-undecene (DBU) were added, and the mixture was stirred at room temperature for 30 minutes.

The reaction mixture was poured into water, the organic layer was separated, washed with water, dried over magnesium sulfate, and concentrated. The residue was subjected to column chromatography (5: 1 = hexane: ethyl acetate) to obtain 143 mg of (S) -styrene oxide (93% yield).

 The properties of this product are as follows.

▲ [α] ²² _D ▼ -45.68 ゜ (c = 1.25 benzene) ¹ H NMR (CDCl ₃ ) δ2.71-2.73 (m, 1H), 3.05-3.08 (m, 1H), 3.75-3.82
(M, 1H), 1.22-7.32 ( m, 5H) 13 C NMR (CDCl 3) δ50.90,52.10,125.30,128.00,128.30,137.40 HRMS Calcd.for C 8 H 8 O:. 120.0575.Found: 120.0558 ee98%: ¹ H NMR analysis in the presence of Eu (hfc) _{3 In the} above example, (R) -styrene oxide was used as the starting material styrene oxide, but (R)
When each of the glycol derivatives of the (R) form and (R) -styrene oxide were produced using the (S) form instead of the isomer, the optical purity was reduced without causing a decrease in the optical purity, as in the above example. The formation of an optical isomer having a high isomer was confirmed.

(Comparative Example 1) (R) -styrene oxide (▲ [α] ²² _D ▼ = 45.70
゜ c = 1.67 benzene) 1.1mol, benzyl alcohol 2.0m
To a hexane solution containing ol, 1.1 mol of SnCl ₄ was added as a catalyst, followed by stirring at room temperature for 30 minutes. Then, an aqueous saturated sodium bicarbonate solution was added thereto. After extraction with dichloromethane, the organic layer was washed with water, dried over magnesium sulfate, and concentrated. The residue was subjected to column chromatography (5: 1 = hexane: ethyl acetate) to obtain the following reaction mixture.

(Comparative Example 2) A reaction mixture shown below was obtained in the same manner as in Comparative Example 1 except that BF ₃ · OEt ₂ was used as a catalyst.

The yield (%) and optical purity (% ee) of the reaction mixture obtained in Comparative Examples 1 and 2 are shown in the following table.

[Effects of the Invention] As described above in detail, the stereochemical inversion method of the optically active styrene oxide according to the present invention can be applied to both enantiomers of the optically active styrene oxide without lowering the optical purity of the starting material styrene oxide. The present invention has excellent unique effects such that the optical activities of the compounds can be reversed with a good yield.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁶ Identification symbol FI // C07B 53/00 C07B 53/00 F 61/00 300 61/00 300 (58) Fields surveyed (Int. Cl. ⁶ , (DB name) C07D 303 / 04,301 / 02,301 / 26 C07C 41 / 02,41 / 03,43 / 178 C07C 309 / 65,309 / 66,309 / 72,309 / 73 C07B 53/00 B01J 31/12

Claims (4)

(57) [Claims] An optically active styrene oxide is added to an alcohol R in the presence of a catalyst comprising a thermal condensation product of an organotin compound selected from the following group (A) and a phosphate ester selected from the following group (B). A step of producing an optically active glycol derivative represented by the following general formula (1) by ring-opening addition of ¹ OH; Reacting the optically active glycol derivative represented by the above formula (1) with a sulfonic acid halide in the presence of a base to produce an optically active glycol derivative represented by the following general formula (2); The optically active glycol derivative represented by the following general formula (3) is reacted with the optically active glycol derivative represented by the above formula (2) in the presence of an acidic catalyst, a metal catalyst or a mixed catalyst of an acidic catalyst and a metal catalyst. A process of manufacturing If necessary, a step of reacting the optically active glycol derivative represented by the above formula (3) with iodide to produce an optically active glycol derivative represented by the following general formula (4); A step of intramolecularly closing the optically active glycol derivative represented by the above formula (3) or (4) in the presence of a base. (A) _{Group: R 'a SnX 4-a} (A-1) R' b SnO c (A-2) R "- (R '2 SnOSnR' 2) -R" (A-3) R 'a SnX _4-a and R _'b complex compound of _{SnO c (a-4) (} B) _{group: (RO) 3 P = O} (B-1) [in the formula (1) and (2), R ¹ Is an allyl group,
An organic group selected from the group consisting of a methallyl group and an alkyl group having 1 to 4 carbon atoms which may have an aryl group as a substituent, wherein in the formulas (2) and (3), R ² is a tosyl group , A mesyl group and a benzenesulfonyl group, wherein the symbol * in the formulas (1) to (4) represents an asymmetric carbon atom, and the symbol Ph represents a phenyl group. Further, in the formulas (A-1) to (A-3), R ′ is an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group having 1 to 12 carbon atoms which may have a substituent. An organic group selected from the group consisting of the formula (A-1)
Wherein X is an atom or group selected from the group consisting of a halogen atom, an alkoxy group, an aryloxy group, an acyloxy group, and a partial ester residue of phosphoric acid, and is represented by the formula (A-
In 3), R ″ is R ′ or X in formula (A-1);
The two R ″ s may be the same or different.
In the formula (A-1), a is an integer of 1 to 4, and a is 2 to 4
R ′ may be the same or different. When a is 1 or 2, X may be the same or different. In the formula (A-2), b is 1
Or 2, when b is 1, c is 3/2, and when b is 2, c is 1. Further, in the formula (B-1), R is hydrogen, an alkyl group having 2 or more carbon atoms, an alkenyl group or a cycloalkyl group, and the three Rs may be the same or different from each other; At least one is a group other than a hydrogen atom. ] 2. The method according to claim 1, wherein the optically active styrene oxide is in the (R) form. 3. The method according to claim 1, wherein the optically active styrene oxide is in the (S) form. 4. An optically active styrene oxide is added to an alcohol R in the presence of a catalyst comprising a thermal condensation product of an organotin compound selected from the following group (A) and a phosphoric acid ester selected from the following group (B). A method for producing an optically active glycol derivative represented by the following general formula (1), wherein ¹ OH is subjected to ring-opening addition. (A) _{Group: R 'a SnX 4-a} (A-1) R' b SnO c (A-2) R "- (R '2 SnOSnR' 2) -R" (A-3) R 'a SnX Complex compound of _4-a and R ′ _b SnO _c (A-4) Group (B): (RO) ₃ P = O (B-1) [wherein, in the formula (1), R ¹ represents an allyl group , An organic group selected from the group consisting of alkyl groups having 1 to 4 carbon atoms which may have an aryl group as a methallyl group and a substituent, the symbol * represents an asymmetric carbon atom, and the symbol Ph is phenyl Represents a group. Further, in the formulas (A-1) to (A-3), R ′ is an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group having 1 to 12 carbon atoms which may have a substituent. An organic group selected from the group consisting of
In -1), X is an atom or group selected from the group consisting of a halogen atom, an alkoxy group, an aryloxy group, an acyloxy group, and a partial ester residue of phosphoric acid. a is an integer of 1 to 4, and when a is an integer of 2 to 4, R ′
May be the same or different. When a is 1 or 2, X may be the same or different. In the formula (A-3), R ″ is R ′ or X in the formula (A-1), and the two R ″ s may be the same or different. In the formula (B-1), R is hydrogen, carbon number 2
The above alkyl group, alkenyl group or cycloalkyl group, and three R's may be the same or different, but at least one is a group other than a hydrogen atom. ]