JP2002535395A - Epoxidation method using amine catalyst - Google Patents

Abstract

  (57) [Summary] A method for epoxidizing an alkene comprising reacting an alkene with an oxidizing agent in the presence of a catalyst, wherein the catalyst is an amine represented by the formula (I), wherein T is R represents hydrogen or a group represented by formula (a);¹, R², R³, R ⁴, R⁵And R⁶Each independently represents hydrogen, an optionally substituted alkyl, an optionally substituted aryl group, a heterocyclyl or an optionally substituted aralkyl group, wherein the substituent of the above group is , Alkyl, aryl, heterocyclyl, hydroxy, alkoxy or group NR^sR^t(Where R^sAnd R^tIs each independently up to three groups selected from hydrogen, alkyl or alkylcarbonyl),⁷Represents hydrogen, alkyl, aryl or aralkyl; or T represents R¹Is R²Represents a group represented by the formula (a) which represents an optionally substituted alkylene chain containing 2 to 6 carbon atoms, wherein the alkylene chain is an oxygen atom or a group NR^p(Where R^pIs hydrogen or alkyl), and any substituent of any carbon atom of the alkylene chain may be hydroxy, alkoxy, oxo or a group NR.^sR^t(Where R^sAnd R^tEach independently represents hydrogen, alkyl or alkylcarbonyl), or a substituent on any two adjacent carbon atoms of the alkylene chain is a carbon atom to which they are attached. With R to form an alicyclic, aryl or heterocyclic ring;³, R⁴, R⁵, R⁶And R⁷Is the same as defined above.] Embedded image Embedded image

Description

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a novel method, in particular, to a method for epoxidizing non-functionalized alkenes.

Catalytic asymmetric epoxidation of non-functionalized alkenes using metal complexes (eg, Mn, Jaco
bsen, International Patent Application, Publication No. WO 91/14694) is now well established.
Recently, non-metallic epoxy compounds such as peroxides, peracids, dioxiranes and oxaziridine have been shown to have improved enantioselectivity. Above all,
The dioxiranes (prepared from the corresponding carbohydrates) of Shi et al. (Journal Organic Chemistry, 1997, Vol. 62, no. 8, pp 2328-2329) may have good enantioselectivity with good product yield. Indicated.

[0003] Asymmetric epoxidation is also described in Aggarwal (Chemical Communications, 1996, no. 2).
(A) and Hanquet (Tetrahedron Lette).
rs, 1993, Vol. 34, no. 45, pp 7271-7274), and is known to be carried out using a complex oxaziridinium salt catalyst prepared from a condensed ring amine complex such as (B). Being:

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Recently, Armstrong et al. (Synlett, 1997, No. 9, pp 1075-1076) , the epoxidation of unfunctionalized alkenes, presence, exocyclic iminium salts derived from pyrrolidine Oxone ^R (C) Has been demonstrated to be able to be performed in high yield using:

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The inventors have now surprisingly found that the epoxidation of non-functionalized alkenes is efficient and optionally asymmetric, using a series of simple amines as catalysts and without the need for complex catalysts. It was found that this could be done. Furthermore, the catalyst cycle used is simple and robust, establishing the use of readily available and inexpensive reagents and environmentally safe solvents.

The present invention is a process for epoxidizing an alkene, comprising reacting an alkene with an oxidizing agent in the presence of a catalyst, wherein the catalyst comprises a compound of formula (I):

Embedded image [Wherein T is hydrogen or formula (a):

Embedded image Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are each independently hydrogen, an optionally substituted alkyl, an optionally substituted aryl group, Represents a heterocyclyl or an aralkyl group which may be substituted, wherein a substituent of the above-mentioned group is alkyl, aryl, heterocyclyl, hydroxy, alkoxy or a group N
Up to three groups selected from R ^s R ^t, wherein R ^s and R ^t each independently represent hydrogen, alkyl or alkylcarbonyl, and R ⁷ is hydrogen,
T represents a group represented by the above formula (a), wherein R ¹ together with R ² represents an optionally substituted alkylene chain containing 2 to 6 carbon atoms. Wherein the alkylene chain may have an oxygen atom or a group NR ^p (where R ^p is hydrogen or alkyl) interposed in the middle, and may have any substituent at any carbon atom of the alkylene chain. Is selected from hydroxy, alkoxy, oxo or the group NR ^s R ^t, wherein R ^s and R ^t each independently represent hydrogen, alkyl or alkylcarbonyl, or Substituents on any two adjacent carbon atoms, taken together with the carbon atom to which they are attached, to form an alicyclic, aryl, or heterocyclic ring; R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are the same as defined above.]

When R ¹ together with R ² represents an optionally substituted alkylene chain, it is suitably an optionally substituted alkylene chain containing 2 or 3 carbon atoms.

In one embodiment of the compounds of the formula (I), T represents a group of the formula (a) as defined above, wherein R ¹ together with R ² are substituted as defined above. Represents an optionally substituted alkylene chain, and R ⁵ represents an optionally substituted alkyl, an optionally substituted aryl group, a heterocyclyl, or an optionally substituted aralkyl group, wherein The substituents of the groups mentioned are up to three groups selected from alkyl, aryl, heterocyclyl, hydroxy or alkoxy, R ⁷ represents hydrogen, alkyl, aryl or aralkyl, R ³ , R ⁴ and R ⁶ each independently represents hydrogen. Suitably, R ⁵ represents an optionally substituted alkyl, heterocyclyl, or an optionally substituted aralkyl group, wherein said substituent is alkyl, aryl, heterocyclyl, hydroxy or Selected from alkoxy groups.

When R ⁵ is an optionally substituted alkyl, especially an optionally substituted C _1-6 alkyl, a specific substituent includes alkoxy, for example,
Methoxy. When R ⁵ is heterocyclyl, particular heterocyclyl group, pyridyl and the like, for example, a 3-pyridyl.

[0010] Suitably, R ⁵ represents an optionally substituted aralkyl group. Preferably,
R ⁵ represents an optionally substituted bisarylalkyl, in particular bisarylmethyl. Examples of the substituent of R ⁵ include hydroxy and alkoxy groups. Examples of R ⁵ include diphenylhydroxymethyl and diphenylmethyl. A preferred R ⁵ group is a diphenylmethyl group.

When R ¹ together with R ² represents an optionally substituted alkylene chain as defined above, R ³ , R ⁴ , R ⁶ and R ⁷ suitably represent hydrogen; ⁵ represents an aralkyl group which may be substituted.

In one particular form of the method, the catalyst is of the formula (IIa) or (IIb)
:

Embedded image [Wherein, R ⁵ , R ⁶ and R ⁷ are the same as defined above, and X ¹ is CH ₂ , O ₂
Or NX ⁴ , wherein X ⁴ is hydrogen, alkyl, alkylcarbonyl,
Represents an alkoxycarbonyl, an aryl, or an aralkyl, each of R ³ and R ⁴ is the same as defined above, X ² is independently the same as the definition of R ² , and X ³ is independently R 3 ³ define the same or where, X ² and R ³ are each independently, represent hydrogen, X ³ and R ⁴ are cycloaliphatic or together with the carbon atoms to which they are attached Which forms a heterocyclic ring].

[0013] In one preferred form of the method, the catalyst is of the formula (IIc):

Embedded image [Wherein, R ⁷ is the same as defined in formula (I), R ⁸ and R ⁹ each independently represent an alkyl or, preferably, an aryl group, and R ¹⁰ represents hydrogen, hydroxy Or m represents an integer, and m represents an integer of 1 or 2.]

Suitably, R ⁷ represents hydrogen, C _1-6 alkyl or benzyl. Preferably, R ⁷ represents hydrogen. Suitably, R ⁸ represents aryl, especially phenyl. Suitably, R ⁹ represents aryl, especially phenyl. Suitably, R ⁸ and R ⁹ each independently represent phenyl. Suitably, R ¹⁰ represents hydrogen. Suitably, m is an integer 1.

Examples of amines of formula (I) include:

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Examples of amines of formula (IIa) and (IIb) include:

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Examples of amines of the formula (IIc) include:

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Preferred amines include (S)-(−)-2- (diphenylhydroxymethyl) pyrrolidine and (S)-(−)-2- (diphenylmethyl) pyrrolidine.

The epoxidation reaction is carried out using any suitable method, whereby an alkene, preferably a prochiral alkene, an oxidizing agent and a compound of formula (I) are reacted to obtain the desired epoxide; Suitably, the reaction is carried out in an organic solvent such as acetonitrile, or in an organic solvent / water mixture such as aqueous acetonitrile, at a temperature ranging from low to medium to high, for example, -20 ° C to 50 ° C, Preferably, it is performed at room temperature.

As mentioned above, the epoxidation of the alkene can be performed in an asymmetric manner. This is generally done by using a chiral amine catalyst.

Suitable prochiral alkenes include trans-stilbene, 1-methylcyclohex-1-ene, 1-phenylcyclohex-1-ene, styrene, α-methylstyrene, β-methylstyrene and indene. Can be Suitable prochiral alkenes also include chromene. Further alkenes include methylenecyclohexene, octahydronaphthalene, norbornylene, limonene and kalen.

Suitable oxidizing agents include conventional oxidizing systems using methods similar to those used for preparing known compounds, suitably nucleophilic systems such as Oxone (KHS
O ₅ ), sodium bicarbonate, acetonitrile / water, for example, Hanquet et al. (Tetra
hedron Leters, 1993, Vol. 34, no. 45, pp 7271-7274).

[0023] Suitable oxidizing agents are nucleophilic agents. One particularly suitable nucleophilic nucleic agent ^is provided by Oxone R (KHSO _5), and mixtures of sodium bicarbonate. Aqueous acetonitrile is a suitable reaction solvent when Oxone ^R / NaHCO ₃ is determined nucleic acid agent. Suitably, the reaction is performed in the presence of a base such as sodium bicarbonate.

In one preferred form of the method, the oxidation is performed in the presence of a second base, for example, a mild organic base, for example, pyridine, 2,6-lutidine and triethylamine.

Suitably, the molar ratio of the compound of formula (I) to the prochiral alkene is in the range of 100-0.01 mol%, preferably in the range of 1-10 mol%, for example 5 Mol%.

[0026] Suitable aryl groups are phenyl or naphthyl. As used herein, an alkyl group, whether alone or as part of another group such as an alkoxy or aralkyl group, has 1-6 carbon atoms.
And an alkyl group having a straight or branched carbon chain, such as a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl group.

As used herein, the “alicyclic group” includes an alicyclic ring having 4 to 12 carbon atoms, particularly 4 to 6 carbon atoms. Suitable heterocyclyl groups include aromatic heterocyclyl groups which are substituted or unsubstituted monocyclic or fused rings having 5 to 7 ring atoms, suitably 6 ring atoms. The atoms in each ring include up to 4, in particular 1 or 2, heteroatoms selected from oxygen, sulfur or nitrogen. An example of a heterocyclic ring is a pyridyl ring.

The compounds of the formula (I) are generally known, commercially available compounds: for example, the compounds of the formula (II) in which the group CR ⁸ R ⁹ R ¹⁰ is diarylmethylhydroxy are described in DJ Mathre ( editor I. Shinkai, Organic Synthesis, 1997, Vol. 7
4, pp 50-71). Group CR ⁸
A compound of the formula (II) wherein R ⁹ R ¹⁰ is diarylmethylmethoxy is
D Enders (Bulletin des Societes Chimiques Belges, 1988, Vol. 97, No. 8-9
, pp 691-704). Further, the compound represented by the formula (II) in which the group CR ⁸ R ⁹ R ¹⁰ is diarylmethyl is a compound represented by the formula:
It can be prepared using the method disclosed by O'Hagan et al. (Tetrahedron: Asymmetry, 1997, Vol. 8, No. 1, pp. 149-153).

The following examples illustrate the invention but do not limit it in any way.

EXAMPLES General Epoxidation Method Using One Bath Method Amine (I) (0.05 mmol) in CH ₃ CN: H ₂ O (95: 5) (1 m
l) The solution in alkene 2 (0.5 mmol), NaHCO ₃ (5 mm
ol), was added Oxone ^R (0.6mmol). Within 2 hours, the reaction was diluted with water, extracted with ethyl acetate, dried (MgSO ₄ ) and concentrated in vacuo. The crude material was purified (HPLC or flash chromatography) to give the desired epoxide.

Example 1 Stoichiometric Epoxidation of 1-Phenylcyclohex-1-ene (S)-(−)-2- (diphenylhydroxymethyl) pyrrolidine 1 (25 mg, 0
.1 mmol) in CH ₃ CN: H ₂ O (95: 5) (1 ml) was added successively to 1-phenylcyclohex-1-ene 2 (15 □ l, 0.11 mmol),
NaHCO ₃ (90 mg, 1.1 mmol), Oxone ^R (81 mg, 0.13
mmol) was added. After 1 hour, the reaction was diluted with water and extracted with ethyl acetate (
Conversion> 99%, GC), dried (MgSO ₄ ) and concentrated in vacuo. The crude material was purified by flash chromatography, eluting with ethyl acetate: petrol (2:98), to give the desired 1-phenylcyclohex-1-eneoxide 3 (18
mg, 90%, 72% ee (S, S)): GC □ -CycloDex 1
20, 30 m, oven temperature 130 ° C, injector temperature 200 ° C, detector temperature 250 ° C, PSI 20, retention time 12.8 minutes (S, S) and 13.13 minutes (R, R
).

[0032]

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Example 2 Catalytic Epoxidation of 1-Phenylcyclohex-1-ene (S)-(−)-2- () in CH ₃ CN: H ₂ O (95: 5) (0.5 ml) Diphenylmethyl) pyrrolidine 4 (1 mg, 0.0042 mmol), 1-phenylcyclohex-1-ene 2 (67 μl, 0.42 mmol), NaHCO ₃ (330 m
g, 3.9 mmol) and Oxone ^R (300mg, 0.50mmol) except as described above. After 40 minutes, the reaction was diluted and worked up as described above: conversion by GC> 99%, 57% ee.

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Example 3 Catalytic Epoxidation of 1-Phenylcyclohex-1-ene (S)-(−)-(Diphenylmethyl) pyrrolidine 4 (5 mg) in CH ₃ CN: H ₂ O (95: 5) , 0.021 mmol), 1-phenylcyclohex-1-ene 2 (67 μl, 0.424 mmol), NaHCO ₃ (330 mg, 3.9 mmol)
l), pyridine (17μl, 0.21mmol) and Oxone ^R (500m
g, 0.84 mmol), except that the method of Example 1 was repeated. After 2 hours, the reaction was diluted with water, extracted with CHCl ₃ (conversion> 99% by NMR [nitrobenzene as internal standard]), dried (Na ₂ SO ₄ ) and concentrated in vacuo. The crude material was purified according to the above (Example 1) to give 64 mg (88%, 57% ee (S, S)) of 1-phenylcyclohex-1-ene oxide. In Table 1, "
"Diols" are hydrolysis by-products derived from the desired epoxide product.

[0035]

[Table 1]

[0036]^a Alkene (0.424 mmol; C_substrate= 0.848 mol / L), 5
% Amine, 2 eq Oxone, 10 eq NaHCO₃, CD₃CN: D
₂0.5 ml O (95: 5), 0.5 equiv of pyridine, 4 hours at room temperature.^bOne equivalent
Pyridine.^cThe rest are alkenes.^dInternal standard (nitrobenzene) ¹ Yield measured by 1 H-NMR.^eChiral HPLC using OD chiral column
Enantioselectivity as measured by and correlated with literature data.^fTwo hours later
Conversion.

──────────────────────────────────────────────────続 き Continuation of front page (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE ), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID , IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW (72 ) Inventor Ballinder Kumar Agarwal United Kingdom, S3.7 HIF, Sheffield, Department of Chemistry, University of Sheffield F-term (Reference) 4C048 AA04 BB02 BC01 CC01 UU03 XX05 4G069 AA06 BA21B BE13B BE20B CB07 CB73 DA02 4H039 CA63 CC40

Claims (21)

[Claims] 1. An alkene epoxidation process comprising reacting an alkene with an oxidizing agent in the presence of a catalyst, wherein the catalyst is of the formula (I): [Wherein T is hydrogen or formula (a): Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are each independently hydrogen, an optionally substituted alkyl, an optionally substituted aryl group, Represents a heterocyclyl or an optionally substituted aralkyl group, wherein the substituent of the group is alkyl, aryl, heterocyclyl, hydroxy, alkoxy or a group NR ^s R ^t (where R ^s and R ^t is independently up to three groups selected from hydrogen, alkyl or alkylcarbonyl), and R ⁷ represents hydrogen, alkyl, aryl or aralkyl; or T is R ¹ There represents a group represented by the above formula represents an alkylene chain substituted containing from 2 to 6 carbon atoms together with R ² (a), the alkylene chain is an oxygen atom or a group ^(Wherein, R ^p is hydrogen or alkyl as) R p may have Nde inserted during the optional substituents of the carbon atoms of any of the alkylene chain, hydroxy, alkoxy, oxo or a group NR ^s R ^t wherein R ^s and R ^t each independently represent hydrogen, alkyl or alkylcarbonyl, or a substitution on any two adjacent carbon atoms of the alkylene chain. The radicals together with the carbon atom to which they are attached form an alicyclic, aryl or heterocyclic ring; R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are as defined above] A method characterized by being an amine represented by the formula: 2. The process according to claim 1, wherein in the compound of the formula (I), R ¹ together with R ² represents an optionally substituted alkylene chain containing 2 or 3 carbon atoms. . 3. A compound of formula (I) wherein T is as defined above in formula (a)
) Represents a group represented by¹Is R²Together with
Represents an alkylene chain;⁵Is an optionally substituted alkyl,
Optionally substituted aryl, heterocyclyl or optionally substituted aralkyl
(Where the substituents of the above groups are alkyl, aryl, heterocyclyl)
Up to three groups selected from cryl, hydroxy or alkoxy), R ⁷ Represents hydrogen, alkyl, aryl or aralkyl;³, R⁴And R⁶ The method according to claim 1 or 2, wherein each independently represents hydrogen. 4. The method according to claim 1, wherein in the compound of the formula (I), R ⁵ is a diphenylmethyl group. 5. The compound of the formula (I) is a compound of the formula (IIa) or (IIb)
: [Wherein, R ⁵ , R ⁶ and R ⁷ are the same as defined in any one of claims 1 to 4, and X ¹ is CH ₂ , O or NX ⁴ , wherein X ⁴ is , Hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, aryl, aralkyl, each of R ³ and R ⁴ is the same as defined in any one of claims 1 to 4, and X ² is independently R ^And X ³ is independently the same as defined for R ³ , or X ² and R ³ each independently represent hydrogen, and X ³ and R ⁴ are , Together with the carbon atom to which they are attached, to form an alicyclic or heterocyclic ring]. 6. A compound of the formula (I) having the formula (IIc): [Wherein, R ⁷ is the same as defined in formula (I), R ⁸ and R ⁹ each independently represent an alkyl or, preferably, an aryl group, and R ¹⁰ represents hydrogen, hydroxy Or m represents alkoxy and m represents an integer of 1 or 2.] The method according to claim 1, wherein 7. The process according to claim 1, wherein in the compound of formula (I), R ⁷ represents hydrogen. 8. The method according to claim 1, wherein in the compound of the formula (I), R ⁸ and R ⁹ each independently represent phenyl. 9. The method according to claim 1, wherein in the compound of the formula (I), R ¹⁰ represents hydrogen. 10. The method according to claim 1, wherein m is an integer of 1 in the compound represented by the formula (I). 11. A compound represented by the formula (I): The method of claim 1, wherein the method is selected from the group consisting of: 12. A compound represented by formula (IIa) or (IIb): The method of claim 5, wherein the method is selected from the group consisting of: 13. A compound represented by the formula (IIc): 7. The method of claim 6, wherein the method is selected from the group consisting of: 14. The compound represented by the formula (I) is (S)-(−)-2- (diphenylhydroxymethyl) pyrrolidine or (S)-(−)-2- (diphenylmethyl) pyrrolidine. The method of claim 1. 15. The method according to claim 1, wherein the oxidizing agent is a nucleophilic agent. 16. The method according to claim 1, wherein the reaction is carried out in the presence of a base. 17. The method of claim 1 wherein the oxidizing agent is Oxone ^R (KHSO _5), and mixtures of sodium bicarbonate. 18. The method according to claim 1, wherein the oxidation is performed in the presence of a second base. 19. The method according to claim 18, wherein the second base is pyridine, 2,6-lutidine or triethylamine. 20. The process according to claim 1, wherein the molar ratio of the compound of formula (I) to the prochiral alkene is in the range of 1 to 10 mol%. 21. The process according to claim 1, wherein the molar ratio of the compound of the formula (I) to the prochiral alkene is 5 mol%.