JPH08245668A - Asymmetric epoxidation catalyst - Google Patents

Abstract

PURPOSE: To obtain a new compound useful as an asymmetric epoxidation reaction catalyst and capable of giving an optically active epoxy derivative useful for medicines and as an intermediate for the medicines in high yield by asymmetrically epoxidizing an olefin having no adjacent functional groups and useful for an asymmetric epoxidation catalyst. CONSTITUTION: This asymmetric epoxidation catalyst is an optically active manganese complex of formula I or formula II (R<1> is a 1-4C alkyl, a substituted silyl, etc.; R is H, phenyl, etc.; X<-> is an anionic pair capable of forming a salt; Y is H, a halogen, etc.). E.g. this epoxidation catalyst can be obtained by bringing one hydroxyl group of S-(-)-binaphtol into a triflate with N- phenyltrifluoromethanesulfoneimide, replacing the triflate with a phenyl Grignard reagent and successively methoxymethylating, lithiating, formylating and demethoxymethylating to obtain a salicylaldehyde compound of formula III, which is then reacted with the compound of formula IV obtained from (R)-(+)-3- methylcyclohexanone as a starting material.

Description

Detailed Description of the Invention

[0001]

The present invention relates to an optically active benzopyran compound effective for the treatment of hypertension, asthma, etc.
The present invention relates to a method for producing an optically active epoxy compound, which is an important intermediate in medicine.

[0002]

2. Description of the Related Art Recently, a catalytic asymmetric epoxidation reaction using an optically active manganese complex has been found, and an efficient method for producing an optically active epoxy compound using an olefin compound having no neighboring functional group as a raw material. Is being watched as. For example, a method for producing Jacobsen described in JP-A-5-507645 and JP-A-5-3018.
No. 78, EP-A-535377, and Japanese Patent Application No. 6-41076 (filed on Mar. 11, 1994), there are manufacturing methods such as Katsuki.

Unlike the racemate resolution method, these methods solve the problem that the enantiomer on the unnecessary side is wasted because the optically active epoxy compound is obtained from the prochiral olefin compound, and the olefin used as the raw material is eliminated. Depending on the type, it is an efficient production method because it gives good chemical yield and optical yield.

[0004]

However, the above-mentioned catalysts do not always give good results for the production of all optically active epoxy derivatives, and there are still many active studies to improve them. Is the current situation.

[0005]

Means for Solving the Problems As a result of diligent studies to find an asymmetric catalyst capable of obtaining an optically active epoxy compound from an olefin having no neighboring functional group in a high asymmetric yield, the present inventors have found that The invention was completed. That is, the present invention provides the formula [I] or the formula [I ′]

[0006]

[Chemical 11]

[Wherein R ¹ is a C ₁ -C ₄ alkyl group, C
₁ -C ₄ alkoxy group, means a substituted silyl group. R is a hydrogen atom, a C ₁ -C ₄ alkyl group, a phenyl group (the phenyl group is a halogen atom, a C ₁ -C ₄ alkyl group, C ₁
It may be substituted with a C ₄ alkoxy group. ), And a substituted silyl group.

[0008] X ^- is meant an anion pair which may form salts. Y represents a hydrogen atom, a halogen atom, C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group, a nitro group or a cyano group. ] An optically active manganese complex represented by the formula [I
I]

[0009]

[Chemical 12]

[In the formula, R ² and R ³ are each independently a hydrogen atom, a cyano group, a nitro group, a tosylamino group,
An amino group which may be protected by a protecting group such as a benzylamino group, a halogen atom, a C ₁ -C ₄ alkyl group, a C _1-
C ₄ alkoxy group, halogeno C ₁ -C ₄ alkyl group, carboxy group, formyl group, C ₁ -C ₄ alkanoyl group,
Aroyl groups, halogeno C ₁ -C ₄ alkanoyl group, a carbamoyl group, C ₁ -C ₄ alkylsulfinyl group, an arylsulfinyl group, C ₁ -C ₄ alkylsulfonyl group, an arylsulfonyl group, aminosulfonyl group, a mono- or di-C ₁ To C ₄ alkylaminosulfonyl group.

R ⁴ is a hydrogen atom, a C ₁ -C ₄ alkyl group,
Means C ₁ -C ₄ alkoxy group. R ⁵ is C _{1 to} C ₄
An alkyl group, a C ₁ -C ₄ alkoxy group, a phenyl group (the phenyl group is a halogen atom, a C ₁ -C ₄ alkyl group,
It may be substituted with a C ₁ -C ₄ alkoxy group. ) Means.

Or R ⁴ and R ⁵ together

[0013]

[Chemical 13]

(R ⁶ , R ⁷ , R ⁸ and R ⁹ each independently represent a hydrogen atom or a C ₁ -C ₄ alkyl group). ] The asymmetric epoxidation reaction is carried out with respect to the olefin compound represented by the formula [1] using the optically active manganese complex represented by the formula [I] or [I '] as a catalyst.

[0015]

Embedded image

(Wherein R ² , R ³ , R ⁴ and R ⁵ are the same as above. The absolute coordination of the carbon atom indicated by * means R or S.) Method for producing compound, formula [IV]

[0017]

[Chemical 15]

(In the formula, R ² and R ³ are each independently a hydrogen atom, a cyano group, a nitro group, a tosylamino group,
An amino group which may be protected by a protecting group such as a benzylamino group, a halogen atom, a C ₁ -C ₄ alkyl group, a C _1-
C ₄ alkoxy group, halogeno C ₁ -C ₄ alkyl group, carboxy group, formyl group, C ₁ -C ₄ alkanoyl group,
Aroyl groups, halogeno C ₁ -C ₄ alkanoyl group, a carbamoyl group, C ₁ -C ₄ alkylsulfinyl group, an arylsulfinyl group, C ₁ -C ₄ alkylsulfonyl group, an arylsulfonyl group, aminosulfonyl group, a mono- or di-C ₁ To C ₄ alkylaminosulfonyl group.

R ⁶ and R ⁷ each independently represent a hydrogen atom or a C ₁ -C ₄ alkyl group. ), The asymmetric epoxidation reaction is carried out using either the optically active manganese complex represented by the formula [I] or [I '] of claim 1 as a catalyst, and the benzopyran derivative represented by the formula [V]

[0020]

Embedded image

(In the formula, R ² , R ³ , R ⁶ and R ⁷ are the same as described above. The absolute coordination of the carbon atom represented by * means R or S.) Method for producing benzopyran compound, formula [VI]

[0022]

[Chemical 17]

(In the formula, R ⁶ and R ⁷ are each independently a hydrogen atom or a C ₁ -C ₄ alkyl group.) The indene compound represented by the formula [I] ] Or an optically active manganese complex represented by [I ′] is used as a catalyst to carry out an asymmetric epoxidation reaction,

[0024]

Embedded image

(Wherein R ⁶ and R ⁷ are the same as above, and the absolute coordination of the carbon atom represented by * means R or S), and a method for producing an optically active epoxyindene compound, Formula (VIII)

[0026]

[Chemical 19]

The indene represented by the formula [IX] is subjected to an asymmetric epoxidation reaction by using either the optically active manganese complex represented by the formula [I] or [I '] of claim 1 as a catalyst. ]

[0028]

Embedded image

(Is the absolute coordination of the carbon atom indicated by * an R?
Means S. ) Optically active epoxy indene represented by
Of the manufacturing method of. Hereinafter, the formula [I],
[I '], [II], [III], [IV], [V], [V
I], [VII] substituents R, R¹, R², R³, R^Four, R
^Five, R⁶, R⁷, R⁸, R⁹, X ^-And about Y
I do.

The C ₁ -C ₄ alkyl group includes a methyl group, an ethyl group, an n-propyl group, an i-propyl group and an n-
Examples thereof include a butyl group, an i-butyl group, a sec-butyl group and a t-butyl group. The C ₁ -C ₄ alkoxy group, a methoxy group, an ethoxy group, n- propoxy group, i-
Propoxy group, n-butoxy group, i-butoxy group, se
Examples thereof include c-butoxy group and t-butoxy group.

Examples of the substituted silyl group include trimethylsilyl group, triethylsilyl group, tri-n-propylsilyl group, tri-i-propylsilyl group, tri-n-butylsilyl group, tri-i-butylsilyl group and dimethylethylsilyl group. , Dimethyl-n-propylsilyl group, dimethyl-
n-butylsilyl group, dimethyl-i-butylsilyl group,
A dimethyl-t-butyl silyl group etc. are mentioned.

Examples of the amino group which may be protected by a protecting group include a tosylamino group, a benzylamino group, an acylamino group and an alkoxyamino group. Examples of the acylamino group include an acetylamino group, a propionylamino group and a benzoylamino group. As the alkoxyamino group, a methoxycarbonylamino group,
Ethoxycarbonylamino group, n-propoxycarbonylamino group, i-propoxycarbonylamino group, n-
Butoxycarbonylamino group, i-butoxycarbonylamino group, sec-butoxycarbonylamino group, t-
Examples thereof include butoxycarbonylamino group.

Examples of the C ₁ -C ₄ alkanoyl group include an acetyl group and a propionyl group. Examples of the aroyl group include benzoyl group, o-toluoyl group, m-toluoyl group, p-toluoyl group, and naphthoyl group. As the C ₁ -C ₄ alkylsulfinyl group, a methylsulfinyl group, an ethylsulfinyl group, an n-propylsulfinyl group, an i-propylsulfinyl group, an n-
Butylsulfinyl group, i-butylsulfinyl group, s
Examples thereof include an ec-butylsulfinyl group and a t-butylsulfinyl group.

Examples of the arylsulfinyl group include a benzenesulfinyl group, an o-toluenesulfinyl group, and a m-
Examples thereof include a toluenesulfinyl group and a p-toluenesulfinyl group. As the C ₁ -C ₄ alkylsulfonyl group, a methylsulfonyl group, an ethylsulfonyl group, n-
Propylsulfonyl group, i-propylsulfonyl group, n
-Butylsulfonyl group, i-butylsulfonyl group, se
Examples thereof include c-butylsulfonyl group and t-butylsulfonyl group.

Examples of the arylsulfonyl group include benzenesulfonyl group, o-toluenesulfonyl group, m-toluenesulfonyl group, p-toluenesulfonyl group and the like. Examples of the mono- or di-C ₁ -C ₄ alkylaminosulfonyl group include methylaminosulfonyl group, dimethylaminosulfonyl group, ethylaminosulfonyl group, diethylaminosulfonyl group, n-propylaminosulfonyl group, di-n-propylaminosulfonyl group, etc. Is mentioned.

Examples of the halogen atom include a fluorine atom, a chlorine atom and a bromine atom. Examples of the halogeno C ₁ -C ₄ alkyl group include a trifluoromethyl group, a monochloromethyl group and a pentafluoroethyl group. Examples of the halogeno C ₁ -C ₄ alkanoyl group include a trifluoroacetyl group, a monoacetyl group, a pentafluoropropionyl group and the like.

Halogen atom, C ₁ -C ₄ alkyl group, C
Examples of the phenyl group which may be substituted with a _{1 to} C ₄ alkoxy group include a fluorophenyl group, a chlorophenyl group,
Bromophenyl group, tolyl group, ethylphenyl group, t-
Butylphenyl group, 3,5-dimethylphenyl group, o-
Methoxyphenyl group, m-methoxyphenyl group, p-methoxyphenyl group and the like can be mentioned.

As the anion pair capable of forming a salt, monovalent OH ⁻ , F ⁻ , Cl ⁻ , Br ⁻ , I ⁻ , CH ₃ CO _{2 are used.
^{-, PF 6 -, ClO 4}} -, BF 4 -, 2 -valent C
Examples thereof include O ₃ ²⁻ , SO ₄ ²⁻ , trivalent PO ₄ ³⁻ ion and the like. Incidentally, manganese, which is the central metal of the optically active manganese complex of the formula [I] or [I '], can take an oxidation state of monovalent to pentavalent.

Representative synthetic examples of the optically active manganese complex of the formula [I] or [I '] will be described below. Schemes 1 and 2
And 3 include [I] [R ¹ = Me (methyl group), R = P
h (phenyl group), Y = H, X ^- = ^- OAc (acetate ion)] is shown as an example, but since [I] and [I '] have an antipodal relationship with each other, [I' ] [R ¹ = Me, R
= Ph, Y = H, X ^- = ^- OAc], the optically active binaphthol compound and the diamine compound which are the starting materials may be changed to those having the opposite configurations.

Synthesis of a salicylaldehyde compound from an optically active binaphthol compound having a molecular asymmetry has already been reported in Tetrahedron, 50, (41), 1182.
It can be obtained by the method described on page 7, 1994. That is, S-(−)-binaphthol is reacted with N-phenyltrifluoromethanesulfonimide in the presence of (a) collidine to form one hydroxyl group as triflate, and (b) chloride [1,2-bis (diphenyl) chloride. Phosphino) ethane] nickel (II) is used as a catalyst to replace the phenyl Grignard reagent.

Then, (c) under basic conditions, methoxymethylated with chloromethyl methyl ether, and then (d) t-
The target salicylaldehyde compound is synthesized through lithiation with butyl lithium, (e) formylation with dimethylformamide, and (f) demethoxymethylation with trimethylsilyl bromide. The compound having a different R portion may be synthesized by changing the type of Grignard reagent in the step (b). (See Scheme 1) Scheme 1

[0042]

[Chemical 21]

[In the formula, Tf ₂ NPh is N-phenyltrifluoromethanesulfonimide, PhMgBr is phenylmagnesium bromide, and NiCl ₂ (dppe) is [1,2-bis (diphenylphosphino) ethane] nickel (II) chloride. , MOMCl means chloromethyl methyl ether, (i-Pr) ₂ NEt means diisopropylethylamine, t-BuLi means tertiary butyllithium, DMF means dimethylformamide, and TMSBr means trimethylsilyl bromide. ] The other raw material, the diamine compound, is (R)
A known method from-(+)-3-methylcyclohexanone [Journal, American, Chemical, Society (J. Am. Chem. Soc.), 86, 465, 1964.
Year) to synthesize (+)-trans-2,5-dimethylcyclohexanone.

That is, 3-methylcyclohexanone was reacted with diethyl oxalate in the presence of (g) NaOEt to give glyoxylate, and (h) decarbonylated to give β.
-Ketoester and (i) methyl iodide is reacted in the presence of NaOEt to give dimethylcyclohexanone. Next, (j) tosylhydrazone is reacted with (k) methyllithium to give dimethylcyclohexene, and (l) iodine chloride is reacted with sodium azide to synthesize an iodoazide compound.

Further, this is reduced with (m) LAH,
(N) Tosylate to tosyl aziridine. Next, (o) sodium azide is used to obtain an azide, (p) catalytic hydrogenation to give a diamine, (q) tosylation to give ditosylamine, and finally (r) reduction to synthesize the desired diamine compound. . (See Scheme 2) Scheme 2

[0046]

[Chemical formula 22]

[Wherein (CO₂Et)₂Is oxalate
Til, MeI is methyl iodide, H ₂NNHTs are
Silhydrazine, MeLi methyllithium, LA
H is lithium aluminum hydride, TsCl is chloride
Tosyl, Et₃N means triethylamine, respectively
It However, the synthetic method of the diamine compound is the substituent R¹Depending on the type of
Therefore, it is not limited to this method.
There is no.

The salicylaldehyde compound and the diamine compound thus obtained are mixed with an alcohol solvent such as ethanol and methanol, a nitrile solvent such as acetonitrile and propionitrile, a halogen solvent such as dichloromethane and chloroform, benzene, and the like. In an aromatic hydrocarbon solvent such as toluene, an ether solvent such as tetrahydrofuran or diethyl ether, a hydrocarbon solvent such as hexane or heptane, an amide solvent such as dimethylformamide, dimethylacetamide or N-methylpyrrolidone. Mix to form an imine compound.

Preferred solvents are ethanol, methanol, acetonitrile, dichloromethane, toluene,
Examples thereof include dimethylformamide. At this time, if necessary, a dehydrating agent such as anhydrous magnesium sulfate, boric acid anhydride, or molecular sieve in an equimolar amount or more may coexist. Alternatively, the produced water may be removed by azeotropic dehydration with a solvent.

The reaction temperature is not particularly limited and is -2.
The temperature can be from 0 ° C to the boiling point of the solvent used, but it is preferably in the range of 0 ° C to 50 ° C. The imine compound does not necessarily have to be taken out from the reaction system, and can be continuously carried out with the next manganese complex synthesis. The obtained imine compound is an alcohol solvent such as ethanol or methanol, a nitrile solvent such as acetonitrile or propionitrile, a halogen solvent such as dichloromethane or chloroform, an amide solvent such as dimethylformamide, dimethylacetamide, or N-methylpyrrolidone. It is dissolved or suspended in a solvent such as a solvent, and 0.5 molar equivalent to 10 molar equivalents, preferably 0.8 molar equivalent to 2 molar equivalents of manganese acetate are added and the reaction is carried out in the presence of oxygen. Active manganese complex [I] [R ¹ = Me, R = Ph,
Y = H, X ^- = ^- OAc] can be obtained.

If [0051] is ^necessary, - OAc ions Cl ^-,
It is also possible to replace it with other anions such as PF ₆ ⁻ . For example, by adding equimolar amount or more of lithium chloride to the reaction system, exchange with Cl ⁻ ion can be performed. Preferred solvents include ethanol, methanol, acetonitrile, dichloromethane, dimethylformamide and the like.

The reaction temperature is not particularly limited, and is -2.
The temperature can be from 0 ° C to the boiling point of the solvent used, but it is preferably in the range of 0 ° C to 50 ° C. Oxygen is supplied by blowing a large excess of air or oxygen gas into the reaction system or by stirring in an open system in the atmosphere. (See Scheme 3) Scheme 3

[0053]

[Chemical formula 23]

[0054] [In the ^formula, Ph, - OAc have the same meanings as defined above. Next, a specific method of the asymmetric epoxidation reaction will be described.

[0055]

[Chemical formula 24]

The amount of the optically active manganese complex represented by the formula [I] or [I '] used as the asymmetric catalyst is based on the starting olefins of the formula [II], [IV] and [VI]. And usually in the range of 0.1 mol% to 5 mol%. Examples of the oxidizing agent include iodosylbenzene, 2-iodosylbenzoic acid, sodium hypochlorite, tetrabutylammonium periodate, hydrogen peroxide, oxygen, air and the like.

The amount of the oxidizing agent used is usually in the range of 1 to 10 equivalents, preferably 1 to 3 equivalents, based on the starting olefin compound. When air or oxygen gas is used as the oxidant, it is supplied by blowing a large excess of air or oxygen gas into the reaction system or by stirring in an open system in the atmosphere.

As the reaction solvent, water, acetonitrile,
Examples thereof include dichloromethane, dichloroethane, ethyl acetate, methyl isobutyl ketone, chlorobenzene, and mixed solvents thereof. In particular, when the oxidizing agent is sodium hypochlorite, it may be preferable to carry out in a two-phase system such as water and dichloromethane.

In the reaction system, pyridine-N-oxide, 4
A component having a coordinating ability can be made to coexist with a manganese complex such as -phenylpyridine-N-oxide, lutidine-N-oxide, picoline-N-oxide and 2-methylimidazole. There is no particular limitation on the amount of the component having the coordination ability used. Reaction temperature is usually -50 ° C to 50 ° C
Is preferably in the range of -20 ° C to 25 ° C.

After completion of the reaction, the target solvent can be isolated by concentrating the organic solvent under reduced pressure and separating it by silica gel column chromatography or distillation. The optical purity of the obtained optically active epoxy compound can be analyzed by an optically active chromatography column or optical rotation.

[0061]

INDUSTRIAL APPLICABILITY The optically active manganese complex catalyst of the formula [I] or the formula [I '] of the present invention has the formula [I] having no neighboring functional group.
I], olefins of formula [IV] and formula [VI] and indene are asymmetrically epoxidized, and formula [III], formula [V] and formula [VII] useful as pharmaceuticals and intermediates thereof with high asymmetric yield. And an optically active epoxy derivative of the formula [IX].

[0062]

[Synthesis of Optically Active Diamine Compound (R = Me)]

[0063]

[Chemical 25]

[In the formula, H ₂ NNHTs is tosylhydrazine, EtOH is ethanol, MeLi is methyllithium, Et ₂ O is diethyl ether, LAH is lithium aluminum hydride, TsCl is tosyl chloride and Et ₃ N. Means triethylamine and DMF means dimethylformamide. ] Synthesis of 1 In a solution of (+)-trans-2,5-dimethylcyclohexanone (1.24 g, 9.84 mmol) in ethanol (14 ml), tosylhydrazine (2.01 g, 10.
(8 mmol) was added and the mixture was reacted at room temperature for 3 hours.

After concentrating the reaction mixture, the residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 9/1). Yield of 1 (yield): 1.8 g (62%). White crystals. Synthesis of 2 in a diethyl ether solution (24.4 ml) of 1 (1.8 g, 6.1 mmol) in methyllithium (10.5 ml,
1.4 M, 14.6 mmol) was added dropwise at room temperature over 30 minutes. After the dropping, the mixture was reacted at room temperature for 24 hours.

After the reaction, a small amount of water was added to stop the reaction.
The reaction mixture was extracted with diethyl ether, the organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by Kugel distillation (boiling point: 130-135 ° C). Yield of 2 (yield): 335 mg (50%). Colorless transparent liquid.

[0067] ^{IR (KBr): 3009,1650,1456,1369cm -1 1} HNMR (270MHz, CDCl 3): 5.56 (s, 2H), 2.30-2.13 (m, 2H),
1.98-1.83 (m, 2H), 1.36-1.20 (m, 2H), 1.05 (d, 6H, J = 6.9H
z) 3 synthesis Sodium azide (496 mg, 7.63 mmol) in acetonitrile solution (1.5 ml) was added to iodine chloride (56
An acetonitrile solution (0.5 ml) of 0 mg, 3.45 mmol) was added dropwise at room temperature.

Furthermore, 2 (335 mg, 3.
An acetonitrile solution (0.5 ml) of (05 mmol) was added dropwise at room temperature. The mixture was reacted as it was at room temperature for 18 hours.
The reaction mixture was poured into water to stop the reaction, and the mixture was extracted with diethyl ether. The organic layer was washed with saturated aqueous sodium thiosulfate, further washed with water, dried over anhydrous magnesium sulfate, and then concentrated.

The residue was purified by silica gel column chromatography (eluting solvent: hexane). Yield of 3 (yield): 520 mg (61%). Colorless transparent liquid. ^{IR (KBr): 2097,1654,1259cm -1 1} HNMR (270MHz, CDCl 3): 4.77 (dd, 1H, J = 2.6,2.0Hz), 4.54
(dd, 1H, J = 3.0,2.0Hz) 2.73-2.64 (m, 1H), 1.61-1.18 (m, 5
H), 1.00 (d, 3H, J = 6.6Hz), 0.92 (d, 3H, J = 5.9Hz) [α] _D ²⁴ : + 12.8 ° (C 1.0, CHCl ₃ ) 4 synthetic lithium aluminum hydride ( 146 mg, 3.
To a diethyl ether solution (7.8 ml) of 8 mmol), a diethyl ether solution (3 ml) of 3 (520 mg, 1.86 mmol) was added dropwise at 0 ° C. over 20 minutes.

The temperature was raised to room temperature and the mixture was stirred for 15 hours. 20%
Aqueous sodium hydroxide was added and stirred for 1 hour to stop the reaction. The reaction mixture was filtered and the organic layer was separated, dried over anhydrous magnesium sulfate and then concentrated. The residue was dissolved in dichloromethane (5.2 ml), triethylamine (260 μl) and tosyl chloride (416 mg) were added, and the mixture was stirred at room temperature for 12 hours.

After concentrating the reaction mixture, the residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 19/1). Yield of 4 (yield): 228 mg (44%). Colorless transparent liquid. IR (KBr): 2928, 1599, 1157, 934, 849cm ^{-1 1} HNMR (400MHz, CDCl ₃ ): 7.82 (d, 2H, J = 8.1Hz), 7.32 (d, 2
H, J = 8.1Hz), 2.84 (dd, 1H, J = 7.3,2.9Hz), 2.77 (d, 1H, J =
7.3Hz), 2.44 (s, 3H), 1.85-1.72 (m, 2H), 1.61-1.58 (m, 1
H), 1.33-1.29 (m, 1H), 1.06 (d, 3H, J = 6.8Hz), 1.02-0.92
(m, 1H), 0.84-0.74 (m, 1H), 0.72 (d, 3H, J = 6.8Hz) [α] _D ²⁴ : +3.6 ° (C 0.6, CHCl ₃ ) HRMS (FAB): m / z [as C ₁₅ H ₂₁ O ₂ NS] Calculated value: 279.4001 Analysis value: 280.1371 (M + H) ⁺ 5 Synthesis 4 (228 mg, 0.82 mmol) in dimethylformamide solution (4.1 ml) sodium azide (107 ml)
(mg, 1.64 mmol) was added and the mixture was reacted at room temperature for 7 hours.

After the reaction was stopped by adding water, the reaction mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate, and then concentrated. The residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 9/1). Yield of 5 (yield): 225 mg (85%). White crystals.

IR (KBr): 3292, 2963, 2100, 1599, 816,
^{667, 590, 552cm -1 1 HNMR} (400MHz, CDCl 3): 7.77 (d, 2H, J = 8.1Hz), 7.32 (d, 2
H, J = 8.1Hz), 4.62 (d, 1H, J = 7.6Hz), 3.58 (dd, 1H, J = 2.9,
2.4Hz), 3.27 (ddd, 1H, J = 7.6,3.4,2.4Hz), 2.44 (s, 3H),
1.89-1.80 (m, 2H), 1.45-1.33 (m, 2H), 1.26-1.16 (m, 1H),
0.94 (d, 3H, J = 6.8Hz), 0.97-0.85 (m, 1H), 0.53 (d, 3H, J =
6.8Hz) [α] _D ²⁴ : + 88.8 ° (C 1.0, CHCl ₃ ) HRMS (FAB): m / z [as C ₁₅ H ₂₂ O ₂ N ₄ S] Calculated value: 322.4282 Analytical value: 323.1542 (M Synthesis of + H) ⁺ 6 Palladium-carbon (20 mg) was added to an ethyl acetate solution (3.5 ml) of 5 (225 mg, 0.7 mmol), and catalytic reduction with hydrogen was performed at room temperature under normal pressure.

After 1 hour, the reaction mixture was filtered through Celite and then concentrated. The residue was dissolved in dichloromethane (3.5 ml) and triethylamine (117 μl, 0.77 mm
ol) and tosyl chloride (147 mg, 0.77 mm)
was added and reacted at room temperature for 12 hours. After the reaction mixture was concentrated, the residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 8/2).

Yield of 6 (yield): 116 mg (37
%). White crystals. IR (KBr): 3294, 2962, 1597, 937, 814, 669, 592, 55
^{3cm -1 1 HNMR (400MHz, CD} 2 Cl 2): 7.75 (d, 4H, J = 8.1), 7.34 (d, 4H,
J = 8.1Hz), 4.42 (d, 2H, J = 6.3Hz), 3.30 (dd, 2H, J = 6.3,2.3
Hz), 2.45 (s, 6H), 1.89-1.82 (m, 2H), 1.42-1.39 (m, 2H),
0.96-0.90 (m, 2H), 0.44 (d, 6H, J = 6.8Hz) [α] _D ²⁴ : +194.1 ° (C 0.17, CHCl ₃ ) HRMS (FAB): m / z [C ₂₂ H ₃₀ O ₄ N ₂ as S _2] calculated: 450.6154 analysis value: 451.1725 (M ⁺ H) + example 1 [an optically active manganese complex ([I-1]: R ¹ = Me, R
= Ph, Y = H, X ⁻ = PF ₆ ⁻ )]

[0076]

[Chemical formula 26]

[In the formula, Ph is phenyl, Cp ₂ Fe.
PF ₆ means ferroscenium hexafluorophosphate. ] Liquid ammonia solution of lithium (30 mg, 4.3 mmol) was cooled to -78 ° C and 6 (10 mg, 0.02).
A tetrahydrofuran solution (1 ml) of 2 mmol) was added, and the mixture was reacted at −78 ° C. for 1 hour.

The reaction mixture was warmed to room temperature and a small amount of water was added to stop the reaction. Ethanol (3 ml) and salicylaldehyde compound 7 (17 mg, 0.044 mmol)
Was added and reacted at room temperature for 13 hours. The reaction mixture was filtered then concentrated. The residue was dissolved in acetonitrile (2 ml) and manganese acetate tetrahydrate (8.6 mg, 0.03
(5 mmol) was added and the mixture was stirred at room temperature for 2 hours.

Further, an acetonitrile solution (2 ml) of ferroscenium hexafluorophosphate (12 mg, 0.035 mmol) was added, and the mixture was reacted at room temperature for 12 hours. The reaction mixture was concentrated and then purified by silica gel column chromatography (eluting solvent: dichloromethane / methanol = 10/1). Yield of manganese complex [I-1] (yield): 8 mg (22
%).

IR (KBr): 3448, 2923, 2862, 1606, 145
8,1419,1326,1161,1093,845,669 cm ^-1 Example 2 [Epoxidation of benzopyran compound]

[0081]

[Chemical 27]

Raw material benzopyran compound (10.5 m
g, 0.04 mmol) and manganese complex [I-1]
(1.05 mg, 1.0 μmol) and 4-phenylpyridine-N-oxide (1.7 mg, 10 μmol) were dissolved in dichloromethane (0.25 ml), cooled to 0 ° C., and sodium hypochlorite (0 0.34 ml, 200
μmol) was added.

After reacting at 0 ° C. for 1 hour, the reaction mixture was separated and further extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 8/2). Yield of epoxide (yield): 7.0 mg (63%). Asymmetric yield: 99.7% ee (DAICEL CHIRAL
CEL OJ, hexane / isopropanol = 1/1
Flow rate = 0.5 ml / min). Yellow crystals. Examples 3 to 5 [Epoxidation of various olefins] In the same manner as in Example 2, with respect to various olefins, the compound of the present invention [I-1] was used as a catalyst, and iodosylbenzene (P
hIO), the test results when asymmetric epoxidation with sodium hypochlorite in dichloromethane are shown in the table below.

[0084]

[Chemical 28]

Reference Examples 2 to 5 The following table shows the results of the asymmetric epoxidation reaction of olefins using the manganese complexes shown below as catalysts.

[0086]

[Chemical 29]

[0087]

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Claims (5)

[Claims] 1. A formula [I] or a formula [I ′] Wherein, R ¹ is C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group, it means a substituted silyl group. R is a hydrogen atom, C
₁ -C ₄ alkyl group, a phenyl group (the phenyl group, a halogen atom, C ₁ -C ₄ alkyl group, optionally substituted by C ₁ -C ₄ alkoxy group.), Refers to substituted silyl group. X ⁻ means an anion pair capable of forming a salt.
Y is a hydrogen atom, a halogen atom, a C ₁ -C ₄ alkyl group,
C ₁ -C ₄ alkoxy group means a nitro group or a cyano group. ] The optically active manganese complex represented by these. 2. A formula [II]: [In the formula, R ² and R ³ are each independently a hydrogen atom,
Amino group which may be protected by a protecting group such as cyano group, nitro group, tosylamino group, benzylamino group, halogen atom, C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group, halogeno C ₁ -C ₄ alkyl group, carboxy group, formyl group, C ₁ -C ₄ alkanoyl group, aroyl group, halogeno C ₁ -C ₄ alkanoyl group, carbamoyl group, C
₁ -C ₄ alkylsulfinyl group, an arylsulfinyl group, C ₁ -C ₄ alkylsulfonyl group, an arylsulfonyl group, aminosulfonyl group, a mono- or di-C ₁ -C ₄
It means an alkylaminosulfonyl group. R ⁴ denotes a hydrogen atom, C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group. R ⁵ is a C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group, a phenyl group (wherein the phenyl group is substituted with a halogen atom, a C ₁ -C ₄ alkyl group, a C ₁ -C ₄ alkoxy group, Also means). Or R ⁴ and R
⁵ together [Chemical 3] (R ⁶ , R ⁷ , R ⁸ and R ⁹ each independently represent a hydrogen atom or a C ₁ -C ₄ alkyl group). ] The asymmetric epoxidation reaction is carried out on the olefin compound represented by the formula [III] using the optically active manganese complex represented by the formula [I] or [I '] as a catalyst. [Chemical 4] (In the formula, R ² , R ³ , R ⁴ and R ⁵ are the same as above. Absolute coordination of carbon atom represented by * means R or S.) Production of optically active epoxy compound Law. 3. A formula [IV]: (In the formula, R ² and R ³ are each independently a hydrogen atom,
Amino group which may be protected by a protecting group such as cyano group, nitro group, tosylamino group, benzylamino group, halogen atom, C ₁ -C ₄ alkyl group, C ₁ -C ₄ alkoxy group, halogeno C ₁ -C ₄ alkyl group, carboxy group, formyl group, C ₁ -C ₄ alkanoyl group, aroyl group, halogeno C ₁ -C ₄ alkanoyl group, carbamoyl group, C
₁ -C ₄ alkylsulfinyl group, an arylsulfinyl group, C ₁ -C ₄ alkylsulfonyl group, an arylsulfonyl group, aminosulfonyl group, a mono- or di-C ₁ -C ₄
It means an alkylaminosulfonyl group. R ⁶ and R ⁷
Each independently represent a hydrogen atom or a C ₁ -C ₄ alkyl group. ), The asymmetric epoxidation reaction is carried out using the optically active manganese complex represented by the formula [I] or [I '] of claim 1 as a catalyst, and the benzopyran derivative represented by the formula [V] [Chemical 6] (In the formula, R ² , R ³ , R ⁶ and R ⁷ are the same as above. The absolute coordination of the carbon atom represented by * means R or S.) Manufacturing method. 4. The formula [VI]: (In the formula, R ⁶ and R ⁷ are each independently a hydrogen atom,
Means C ₁ -C ₄ alkyl group. ) To the indene compound represented by the formula [I] or [I '] according to claim 1.
The asymmetric epoxidation reaction is carried out using any of the optically active manganese complex represented by (In the formula, R ⁶ and R ⁷ are the same as above. The absolute coordination of the carbon atom represented by * means R or S.) The process for producing an optically active epoxyindene compound. 5. A compound represented by the formula [VIII]: The indene represented by the formula [IX] is prepared by performing an asymmetric epoxidation reaction using either the optically active manganese complex represented by the formula [I] or [I '] of claim 1 as a catalyst. (Absolute coordination of carbon atom indicated by * means R or S.) A method for producing an optically active epoxyindene.