EP1147099A1 - Epoxidation process using amine catalysts - Google Patents

Epoxidation process using amine catalysts

Info

Publication number
EP1147099A1
EP1147099A1 EP00901253A EP00901253A EP1147099A1 EP 1147099 A1 EP1147099 A1 EP 1147099A1 EP 00901253 A EP00901253 A EP 00901253A EP 00901253 A EP00901253 A EP 00901253A EP 1147099 A1 EP1147099 A1 EP 1147099A1
Authority
EP
European Patent Office
Prior art keywords
formula
process according
alkyl
compound
optionally substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00901253A
Other languages
German (de)
French (fr)
Inventor
Mauro Francesco Alessio Uni. Sheffield ADAMO
Varinder Kumar Uni. Sheffield AGGARWAL
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Sheffield
Original Assignee
University of Sheffield
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Sheffield filed Critical University of Sheffield
Publication of EP1147099A1 publication Critical patent/EP1147099A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D301/00—Preparation of oxiranes
    • C07D301/02—Synthesis of the oxirane ring
    • C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
    • C07D301/14—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D301/00—Preparation of oxiranes
    • C07D301/02—Synthesis of the oxirane ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/04—Compounds containing oxirane rings containing only hydrogen and carbon atoms in addition to the ring oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • This invention relates to a novel process and in particular a process for the epoxidation of unfunctionalised alkenes.
  • Asymmetric epoxidations are also known to proceed using complex oxaziridinium salt catalysts which are themselves prepared from complex, fused-ring amines, such as those disclosed by Aggarwal (A) (Chemical Communications, 1996, no. 2, pp 191-192) and Hanquet (B) (Tetrahedron Letters, 1993, Vol. 34, no. 45, pp 7271-7274):
  • the invention provides a process for the epoxidation of an alkene, which process comprises reacting an alkene with an oxidising agent in the presence of a catalyst, characterised in that the catalyst is an amine of formula (I):
  • T represents hydrogen or a moiety of formula (a):
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 each independently represents hydrogen, optionally substituted alkyl, an optionally substituted aryl group, heterocyclyl or an optionally substituted aralkyl group wherein substituents for the above mentioned groups are selected from up to three of alkyl, aryl, heterocycyl, hydroxy, alkoxy or a group NR s R l wherein R s and R l each independently represent hydrogen, alkyl or alkylcarbonyl and R 7 represents hydrogen, alkyl, aryl or aralkyl; or T represents a moiety (a) wherein R 1 together with R 2 represents an optionally substituted alkylene chain comprising 2 to 6 carbon atoms the alkylene chain being optionally interrupted with an oxygen atom or a group NRP wherein RP is hydrogen or alkyl, and wherein optional substituents for any carbon atom of the alkylene chain are selected from hydroxy, alkoxy, oxo or
  • R 1 together with R 2 represents an optionally substituted alkylene chain, it is suitably an optionally substituted alkylene chain comprising 2 or 3 carbon atoms.
  • T represents a moiety of the above defined formula (a)
  • R 1 together with R 2 represents an optionally substituted alkylene chain as defined above
  • R ⁇ represents optionally substituted alkyl, an optionally substituted aryl group, heterocyclyl or an optionally substituted aralkyl group wherein substituents for the above mentioned groups are selected from up to three of alkyl, aryl, heterocycyl, hydroxy or alkoxy
  • R 7 represents hydrogen, alkyl, aryl or aralkyl and R 3 , R 4 and R 6 each independently represents hydrogen.
  • R ⁇ represents optionally substituted alkyl, heterocyclyl or an optionally substituted aralkyl group wherein the substituents are selected from an alkyl, aryl, heterocycyl, hydroxy or alkoxy group.
  • R5 is optionally substituted alkyl, especially optionally substituted C ⁇ .
  • ⁇ alkyl particular substituents include alkoxy, for example methoxy.
  • R5 is heterocyclyl
  • particular heterocycyl groups include pyridyl for example a 3-pyridyl group.
  • R ⁇ represents an optionally substituted aralkyl group.
  • R 5 represents optionally substituted bisarylalkyl especially bisarylmethyl.
  • substituents for R 5 include hydroxy and alkoxy groups.
  • R 5 examples include diphenylhydroxymethyl and diphenylmethyl.
  • R 5 group is a diphenylmethyl group.
  • R 1 together with R 2 represents the above defined optionally substituted alkylene chain
  • R 3 , R 4 , R 6 and R 7 suitably represent hydrogen and R ⁇ represents an optionally substituted aralkyl group.
  • the catalyst is an amine of formula (Ila) or (lib):
  • R 5 , R 6 and R 7 are as defined above
  • X 1 is CH2, O or N ⁇ 4, wherein X ⁇ represents hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, aryl, aralkyl and either R 3 and R 4 are as defined above
  • X 2 independently represents any value of R 2 and X 3 independently represents any value of R 3 or X 2 and R 3 each independently represent hydrogen and X 3 and R 4 together with the carbon atoms to which they are attached form an alicyclic or heterocylic ring.
  • the catalyst is an amine of formula (lie):
  • R ⁇ is as defined in formula (I) and R& and R ⁇ each independently represents an alkyl or, preferably, an aryl group and RlO represents hydrogen, hydroxy or alkoxy and m is an integer 1 or 2.
  • R ⁇ represents hydrogen, Cj. alkyl or benzyl
  • R ⁇ represents hydrogen.
  • R ⁇ represents aryl, especially phenyl.
  • R ⁇ represents aryl, especially phenyl.
  • R ⁇ and R ⁇ each independently represents phenyl.
  • R ⁇ represents hydrogen
  • n is an integer 1.
  • amines of formula (I) include:
  • Examples of amines of formulae (Ha) and (lib) include:
  • amines of formula (He) include:
  • Preferred amines include (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine and (S)-(-)-2-(diphenylmethyl)pyrrolidine.
  • the epoxidation reaction may be carried out using any suitable procedure wherein the alkene, preferably a prochiral alkene, the oxidising agent and the compound of formula (I) are allowed to react thereby providing the required 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 low to medium-elevated temperature such as a temperature in the range -20°C to 50°C, preferably at ambient temperature.
  • the epoxidation of the alkene can proceed in an asymmetric manner. This is generally effected by use of an chiral amine catalyst.
  • Suitable prochiral alkenes include tra/u-stilbene, 1-methylcyclohex-l-ene, 1- phenylcyclo hex-1-ene, styrene, ⁇ -methylstyrene, ⁇ -methylstyrene and indene. Suitable prochiral alkenes also include chromenes.
  • Additional alkenes include methylenecyclohexene, octahydronapthalene, norbornylene, limonene and carene.
  • Suitable oxidising agent include conventional oxidising systems, suitably nucleophilic oxidising systems, such as Oxone (KHSO5), sodium bicarbonate, acetonitrile/water, using methods analogous to those used to prepare known compounds, for example the oxidising agents disclosed by Hanquet et al. (Tetrahedron Letters, 1993, Vol. 34, no. 45, pp 7271-7274).
  • KHSO5 nucleophilic oxidising systems
  • sodium bicarbonate sodium bicarbonate
  • acetonitrile/water using methods analogous to those used to prepare known compounds, for example the oxidising agents disclosed by Hanquet et al. (Tetrahedron Letters, 1993, Vol. 34, no. 45, pp 7271-7274).
  • a suitable oxidising agent is a nucleophilic oxidising agent.
  • One particularly suitable nucleophilic oxidising agent is provided by a mixture of Oxone® (KHSO5) and sodium bicarbonate.
  • Aqueous acetonitrile is an apt reaction solvent when Oxone®/NaHC ⁇ 3 is the nucleophilic oxidising agent.
  • the reaction is carried out in the presence of a base such as sodium bicarbonate.
  • a base such as sodium bicarbonate.
  • the oxidation is carried out in the presence of a second base, such as a mild organic base for example pyridine, 2, 6-lutidine and triethylamine.
  • the molar ratio of the compound of formula (I) to the prochiral alkene is in the range 100 to 0.01 mol %, preferably from 1 to 10 mol %, for example 5 mol %.
  • a suitable aryl group is a phenyl group or a naphthyl group.
  • alkyl groups are alkyl groups having straight or branched carbon chains, containing 1 to 6 carbon atoms, e.g. methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl or tert-butyl groups.
  • 'alicyclic group' includes alicyclic rings of 4 to 12 carbon atoms, especially 4 to 6 carbon atoms.
  • Suitable heterocyclyl groups include substituted or unsubstituted, single or fused ring aromatic heterocyclyl groups having 5 to 7 ring atoms, suitably 6 ring atoms, said ring atoms comprising up to 4 hetero atoms in each ring, especially 1 or 2, selected from oxygen, sulphur or nitrogen.
  • An example of a heterocyclic ring is a pyridyl ring.
  • the compounds of formula (I) are generally known, commercially available compounds:
  • the compounds of formula (II) wherein the moiety CR8R9R10 is diarylmethylhydroxy may be prepared using methods disclosed by D. J. Mathre (editor I. Shinkai, Organic Synthesis, 1997, Vol. 74, pp 50-71).
  • the compounds of formula (II) wherein the moiety CR8R9R10 is diarylmethylmethoxy are prepared by using methods disclosed by D Enders (Bulletin des Societes Chimiques Beiges, 1988, Vol. 97, No. 8-9, pp 691-704).
  • compounds of formula (II) wherein the moiety CR ⁇ R ⁇ RIO is diarylmethyl may be prepared using methods disclosed by D. O ⁇ agan et al (Tetrahedron: Asymmetry, 1997, Vol. 8, No. 1, pp.149-153).
  • the crude material was purified via flash chromatography eluting with ethyl acetate:petrol (2:98), to give the desired 1- phenylcyclohex-1-ene oxide 3, 18 mgs, 90%, 72% e.e. (S,S) by GC D-CycloDex 120, 30m, oven temperature 130°C, injector temperature 200°C, detector temperature 250°C, PSI 20, retention time 12.8 min (S,S) and 13.13 min (R,R).
  • Example 2 Catalytic epoxidation of 1-Phenylcyclohex-l-ene As above except; (S)-(-)-2-(diphenylmethyl)pyrrolidine 4 (1 mg, 0.0042mmol) in CH 3 CN:H 2 O (95:5) (0.5 ml), 1-phenylcyclohex-l-ene 2 (67 ⁇ l, 0.42 mmol), NaHCO 3 (330 mg, 3.9 mmol), and Oxone® (300 mg, 0.50 mmol). After 40 mins the reaction was diluted and work up as described previously, >99% conversion by GC, 57% e.e.
  • Example 1 The crude material was purified as described previously (example 1) to give 64 mg of 1-phenylcyclohex-l-ene oxide 88%, 57%ee (S,S).
  • the 'dioP referenced in Table 1 is a hydrolysis by-product derived from the desired epoxide product.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Epoxy Compounds (AREA)
  • Catalysts (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

A process for the epoxidation of an alkene, which process comprises reaction of an alkene with an oxidising agent in the presence of a catalyst, characterised in that the catalyst is an amine of formula (I), wherein T represents hydrogen or a moiety of formula (a); R?1, R2, R3, R4, R5 and R6¿ each independently represents hydrogen, optionally substituted alkyl, an optionally substituted aryl group, heterocyclyl or an optionally substituted aralkyl group wherein substituents for the above mentioned groups are selected from up to three of alkyl, aryl, heterocycyl, hydroxy, alkoxy or a group NRsRt wherein R?s and Rt¿ each independently represents hydrogen, alkyl or alkylcarbonyl and R7 represents hydrogen, alkyl, aryl or aralkyl; or T represents a moiety (a) wherein R1 together with R2 represents an optionally substituted alkylene chain comprising 2 to 6 carbon atoms the alkylene chain being optionally interrupted with an oxygen atom or a group NRp wherein Rp is hydrogen or alkyl, and wherein optional substituents for any carbon atom of the alkylene chain are selected from hydroxy, alkoxy, oxo or a group NRsRt wherein R?s and Rt¿ each independently represents hydrogen, alkyl or alkylcarbonyl or substituents on any two adjacent carbon atoms of the chain together with the carbon atoms to which they are attached form an alicyclic, aryl or heterocyclic ring; and R?3, R4, R5, R6 and R7¿ are as defined above.

Description

EPOXIDATION PROCESS USING AMINE CATALYSTS
This invention relates to a novel process and in particular a process for the epoxidation of unfunctionalised alkenes.
The catalytic asymmetric epoxidation of unfunctionalised alkenes using metal complexes (e.g. Mn, Jacobsen, International Patent Application, Publication Number WO/91/14694) is now well established. Recently, non-metallic epoxidates such as peroxides, peracids, dioxiranes and oxaziridines have shown improved enantioselectivity. Notably, the dioxiranes (prepared from the corresponding carbohydrates) of Shi et al (Journal Organic Chemistry, 1997, Vol. 62, no. 8, pp 2328-2329) have shown good enantioselectivity with good product yields.
Asymmetric epoxidations are also known to proceed using complex oxaziridinium salt catalysts which are themselves prepared from complex, fused-ring amines, such as those disclosed by Aggarwal (A) (Chemical Communications, 1996, no. 2, pp 191-192) and Hanquet (B) (Tetrahedron Letters, 1993, Vol. 34, no. 45, pp 7271-7274):
Recently, Armstrong et al (Synlett, 1997, No. 9, pp 1075-1076) has shown that an epoxidat:on of unfunctionalised alkenes can also be effected in excellent yields using an exocyclic iminium salt (C), derived from pyrrolidine, in the presence of Oxone®.
(C)
We have now surprisingly discovered that the epoxidation of unfunctionalised alkenes can proceed efficiently and, if required, asymmetrically using a series of simple amines as catalysts and without the need for complex catalysts. Furthermore, the catalytic cycle employed is simple and robust, enabling the use of readily available and cheap reagents as well as environmentally safe solvents. Accordingly, the invention provides a process for the epoxidation of an alkene, which process comprises reacting an alkene with an oxidising agent in the presence of a catalyst, characterised in that the catalyst is an amine of formula (I):
(I)
wherein T represents hydrogen or a moiety of formula (a):
(a)
R1, R2, R3, R4, R5 and R6 each independently represents hydrogen, optionally substituted alkyl, an optionally substituted aryl group, heterocyclyl or an optionally substituted aralkyl group wherein substituents for the above mentioned groups are selected from up to three of alkyl, aryl, heterocycyl, hydroxy, alkoxy or a group NRsRl wherein Rs and Rl each independently represent hydrogen, alkyl or alkylcarbonyl and R7 represents hydrogen, alkyl, aryl or aralkyl; or T represents a moiety (a) wherein R1 together with R2 represents an optionally substituted alkylene chain comprising 2 to 6 carbon atoms the alkylene chain being optionally interrupted with an oxygen atom or a group NRP wherein RP is hydrogen or alkyl, and wherein optional substituents for any carbon atom of the alkylene chain are selected from hydroxy, alkoxy, oxo or a group NRsRl wherein Rs and Rl each independently represent hydrogen, alkyl or alkylcarbonyl or substituents on any two adjacent carbon atoms of the chain together with the carbon atoms to which they are attached form an alicyclic, aryl or heterocyclic ring; and R3, R4, R5 , R6 and R7 are as defined above.
When R1 together with R2 represents an optionally substituted alkylene chain, it is suitably an optionally substituted alkylene chain comprising 2 or 3 carbon atoms. In one aspect of the compounds of formula (I), T represents a moiety of the above defined formula (a), R1 together with R2 represents an optionally substituted alkylene chain as defined above, R^ represents optionally substituted alkyl, an optionally substituted aryl group, heterocyclyl or an optionally substituted aralkyl group wherein substituents for the above mentioned groups are selected from up to three of alkyl, aryl, heterocycyl, hydroxy or alkoxy and R7 represents hydrogen, alkyl, aryl or aralkyl and R3, R4 and R6 each independently represents hydrogen. Suitably, R^ represents optionally substituted alkyl, heterocyclyl or an optionally substituted aralkyl group wherein the substituents are selected from an alkyl, aryl, heterocycyl, hydroxy or alkoxy group. When R5 is optionally substituted alkyl, especially optionally substituted C\.β alkyl, particular substituents include alkoxy, for example methoxy.
When R5 is heterocyclyl, particular heterocycyl groups include pyridyl for example a 3-pyridyl group. Suitably, R^ represents an optionally substituted aralkyl group.
Preferably, R5 represents optionally substituted bisarylalkyl especially bisarylmethyl.
Examples of substituents for R5 include hydroxy and alkoxy groups.
Examples of R5 include diphenylhydroxymethyl and diphenylmethyl.
A preferred R5 group is a diphenylmethyl group. When R1 together with R2 represents the above defined optionally substituted alkylene chain, R3, R4, R6 and R7 suitably represent hydrogen and R^ represents an optionally substituted aralkyl group.
In one particular form of the process, the catalyst is an amine of formula (Ila) or (lib):
(Ha) (lib)
wherein R5 , R6 and R7 are as defined above, X1 is CH2, O or Nχ4, wherein X^ represents hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, aryl, aralkyl and either R3 and R4 are as defined above, X2 independently represents any value of R2 and X3 independently represents any value of R3 or X2 and R3 each independently represent hydrogen and X3 and R4 together with the carbon atoms to which they are attached form an alicyclic or heterocylic ring.
In one preferred form of the process, the catalyst is an amine of formula (lie):
(lie)
wherein R^ is as defined in formula (I) and R& and R^ each independently represents an alkyl or, preferably, an aryl group and RlO represents hydrogen, hydroxy or alkoxy and m is an integer 1 or 2.
Suitably, R^ represents hydrogen, Cj. alkyl or benzyl,
Preferably, R^ represents hydrogen. Suitably, R^ represents aryl, especially phenyl.
Suitably, R^ represents aryl, especially phenyl.
Suitably, R^ and R^ each independently represents phenyl.
Suitably, R^ represents hydrogen.
Suitably, m is an integer 1.
Examples of amines of formula (I) include:
Examples of amines of formulae (Ha) and (lib) include:
Examples of amines of formula (He) include:
Preferred amines include (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine and (S)-(-)-2-(diphenylmethyl)pyrrolidine.
The epoxidation reaction may be carried out using any suitable procedure wherein the alkene, preferably a prochiral alkene, the oxidising agent and the compound of formula (I) are allowed to react thereby providing the required 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 low to medium-elevated temperature such as a temperature in the range -20°C to 50°C, preferably at ambient temperature. As indicated above the epoxidation of the alkene can proceed in an asymmetric manner. This is generally effected by use of an chiral amine catalyst.
Suitable prochiral alkenes include tra/u-stilbene, 1-methylcyclohex-l-ene, 1- phenylcyclo hex-1-ene, styrene, α-methylstyrene, β-methylstyrene and indene. Suitable prochiral alkenes also include chromenes.
Additional alkenes include methylenecyclohexene, octahydronapthalene, norbornylene, limonene and carene.
Suitable oxidising agent include conventional oxidising systems, suitably nucleophilic oxidising systems, such as Oxone (KHSO5), sodium bicarbonate, acetonitrile/water, using methods analogous to those used to prepare known compounds, for example the oxidising agents disclosed by Hanquet et al. (Tetrahedron Letters, 1993, Vol. 34, no. 45, pp 7271-7274).
A suitable oxidising agent is a nucleophilic oxidising agent. One particularly suitable nucleophilic oxidising agent is provided by a mixture of Oxone® (KHSO5) and sodium bicarbonate.
Aqueous acetonitrile is an apt reaction solvent when Oxone®/NaHCθ3 is the nucleophilic oxidising agent.
Suitably, the reaction is carried out in the presence of a base such as sodium bicarbonate. In one preferred form of the process, the oxidation is carried out in the presence of a second base, such as 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 100 to 0.01 mol %, preferably from 1 to 10 mol %, for example 5 mol %. A suitable aryl group is a phenyl group or a naphthyl group.
As used herein, alkyl groups, whether present alone or as part of other groups such as alkoxy or aralkyl groups, are alkyl groups having straight or branched carbon chains, containing 1 to 6 carbon atoms, e.g. methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl or tert-butyl groups. As used herein, 'alicyclic group' includes alicyclic rings of 4 to 12 carbon atoms, especially 4 to 6 carbon atoms.
Suitable heterocyclyl groups include substituted or unsubstituted, single or fused ring aromatic heterocyclyl groups having 5 to 7 ring atoms, suitably 6 ring atoms, said ring atoms comprising up to 4 hetero atoms in each ring, especially 1 or 2, selected from oxygen, sulphur or nitrogen. An example of a heterocyclic ring is a pyridyl ring.
The compounds of formula (I) are generally known, commercially available compounds: For example the compounds of formula (II) wherein the moiety CR8R9R10 is diarylmethylhydroxy, may be prepared using methods disclosed by D. J. Mathre (editor I. Shinkai, Organic Synthesis, 1997, Vol. 74, pp 50-71). The compounds of formula (II) wherein the moiety CR8R9R10 is diarylmethylmethoxy, are prepared by using methods disclosed by D Enders (Bulletin des Societes Chimiques Beiges, 1988, Vol. 97, No. 8-9, pp 691-704). Also, compounds of formula (II) wherein the moiety CR^R^RIO is diarylmethyl may be prepared using methods disclosed by D. OΗagan 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 procedure using one pot method
To a solution of amine (I) (0.05 mmol) in CH3CN:H2O (95:5) (1 ml) were added sequentially alkene 2 (0.5 mmol), NaHCO3 (5 mmol), Oxone® (0.6 mmol). Within 2 hrs the reaction was diluted with water and extracted with ethyl acetate, dried (MgSO4), concentrated in vacuo. The crude material was purified (HPLC or flash chromatography) to give the desired epoxide.
Example 1: Stoichiometric epoxidation of 1-Phenylcyclohex-l-ene
To a solution of (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine 1 (25 mg, 0.1 mmol) in CH3CN:H2θ (95:5) (1 ml) were added sequentially 1-phenylcyclohex-l-ene 2 (15 Dl, 0.11 mmol), NaHCO3 (90 mg, 1.1 mmol), Oxone® (81 mg, 0.13 mmol). After 1 hr the reaction was diluted with water and extracted with ethyl acetate, (>99% conversion, GC), dried (MgSO4) and concentrated in vacuo. The crude material was purified via flash chromatography eluting with ethyl acetate:petrol (2:98), to give the desired 1- phenylcyclohex-1-ene oxide 3, 18 mgs, 90%, 72% e.e. (S,S) by GC D-CycloDex 120, 30m, oven temperature 130°C, injector temperature 200°C, detector temperature 250°C, PSI 20, retention time 12.8 min (S,S) and 13.13 min (R,R).
Oxone, 10 eq. NaHCO3
Example 2: Catalytic epoxidation of 1-Phenylcyclohex-l-ene As above except; (S)-(-)-2-(diphenylmethyl)pyrrolidine 4 (1 mg, 0.0042mmol) in CH3CN:H2O (95:5) (0.5 ml), 1-phenylcyclohex-l-ene 2 (67 μl, 0.42 mmol), NaHCO3 (330 mg, 3.9 mmol), and Oxone® (300 mg, 0.50 mmol). After 40 mins the reaction was diluted and work up as described previously, >99% conversion by GC, 57% e.e.
2 Oxone, 10 eq. NaHCO3 3 Example 3: Catalytic Epoxidation of 1-phenylcyclohex-l-ene.
The procedure of example 1 was repeated except that (S)-(-)-(diphenylmethyl)pyrrolidine 4 (5 mg, 0.021 mmol) in CH3CN:H2O (95:5), 1-phenylcyclohex-l-ene 2 (67 μl, 0.424 mmol) NaHCO3 (330mg, 3.9mmol), pyridine (17 μl, 0.21 mmol) and Oxone® (500 mg, 0.84 mmol). After 2h the reaction was diluted with water, extracted with CHC13 (>99 % conversion by NMR [nitrobenzene as Internal Standard]), dried (Na.SO4) and concentrated in vacuo. The crude material was purified as described previously (example 1) to give 64 mg of 1-phenylcyclohex-l-ene oxide 88%, 57%ee (S,S). The 'dioP referenced in Table 1 is a hydrolysis by-product derived from the desired epoxide product.
Table 1: Alkene epoxidation using 5 mol % of Amine"
aAlkene (0.424 mmol; Csubstrat = 0.848 mol/L), 5 mol % amine, 2eq Oxone, 10 eq NaHCO3, 0.5ml CD3CN:D2O (95:5), 0.5 eq. pyridine, 4h, it. b 1 eq. pyridine. c Remainder is alkene. d Yields determined by Η-NMR relative to an internal standard (nitrobenzene). e Enantioselectivities determined by chiral HPLC using an OD chiral column and correlated with literature data. f Conversion after 2h.

Claims

Claims:
1. A process for the epoxidation of an alkene, which process comprises reacting an alkene with an oxidising agent in the presence of a catalyst, characterised in that the catalyst is an amine of formula (I):
(I)
wherein T represents hydrogen or a moiety of formula (a):
(a)
R1, R2, R3, R4, R5 and R6 each independently represents hydrogen, optionally substituted alkyl, an optionally substituted aryl group, heterocyclyl or an optionally substituted aralkyl group wherein substituents for the above mentioned groups are selected from up to three of alkyl, aryl, heterocycyl, hydroxy, alkoxy or a group NRsRl wherein Rs and Rl each independently represent hydrogen, alkyl or alkylcarbonyl and R7 represents hydrogen, alkyl, aryl or aralkyl; or T represents a moiety (a) wherein R1 together with R2 represents an optionally substituted alkylene chain comprising 2 to 6 carbon atoms the alkylene chain being optionally interrupted with an oxygen atom or a group NRP wherein RP is hydrogen or alkyl, and wherein optional substituents for any carbon atom of the alkylene chain are selected from hydroxy, alkoxy, oxo or a group NRsRl wherein Rs and Rl each independently represent hydrogen, alkyl or alkylcarbonyl or substituents on any two adjacent carbon atoms of the chain together with the carbon atoms to which they are attached form an alicyclic, aryl or heterocyclic ring; and R3, R4, R5 , R6 and R7 are as defined above.A suitable oxidising agent is a nucleophilic oxidising agent.
2. A process according to claim 1, wherein in the compound of formula (I) R1 together with R2 represents an optionally substituted alkylene chain comprising 2 or 3 carbon atoms.
3. A process according to claim 1 or claim 2, wherein in the compound of formula (I) T represents a moiety of the above defined formula (a), R1 together with R2 represents an optionally substituted alkylene chain as defined above, R^ represents optionally substituted alkyl, an optionally substituted aryl group, heterocyclyl or an optionally substituted aralkyl group wherein substituents for the above mentioned groups are selected from up to three of alkyl, aryl, heterocycyl, hydroxy or alkoxy and R7 represents hydrogen, alkyl, aryl or aralkyl and R3, R4 and R6 each independently represents hydrogen.
4. A process according to any one of claims 1 to 3, wherein in the compound of formula (I) R5 group is a diphenylmethyl group.
5. A process according to claim 1 , wherein the compound of formula (I) is an amine of formula (Ila) or (lib):
wherein R5 , R6 and R7 are as defined in any preceeding claim, X1 is CH2, O or
NX^, wherein X^ represents hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, aryl, aralkyl and either R3 and R4 are as defined in any preceeding claim, X2 independently represents any value of R2 and X3 independently represents any value of R3 or X2 and R3 each independently represent hydrogen and X3 and R4 together with the carbon atoms to which they are attached form an alicyclic or heterocylic ring.
6. A process according to claim 1 , wherein the compound of formula (I) is an amine of formula (He):
(lie)
wherein R^ is as defined in formula (I) and R° and R each independently represents an alkyl or, preferably, an aryl group and R 0 represents hydrogen, hydroxy or alkoxy and m is an integer 1 or 2.
7. A process according to any one of claims 1 to 6, wherein in the compound of formula (I) R^ represents hydrogen.
8. A process according to any one of claims 1 to 7, wherein in the compound of formula (I) R^ and R^ each independently represents phenyl.
9. A process according to any one of claims 1 to 8, wherein in the compound of formula (I) R^ represents hydrogen.
10. A process according to any one of claims 1 to 9, wherein in the compound of formula (I) m is an integer 1.
11. A process according to claim 1 , wherein in the compound of formula (I) is selected from the list consisting of:
12. A process according to claim 5, wherein in the compound of formulae (Ha) and (lib) ) is selected from the list consisting of:
13. A process according to claim 6, wherein in the compound of formulae (He) is selected from the list consisting of:
14. A process according to claim 1 , wherein in the compound of formula (I) is (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine or (S)-(-)-2-(diphenylmethyl)pyrrolidine.
15. A process according to claim 1 , wherein the oxidising agent is a nucleophilic oxidising agent.
16. A process according to claim 1, wherein the reaction is carried out in the presence of a base.
17. A process according to claim 1, wherein the oxidising agent is a mixture of
Oxone® (KHSO5) and sodium bicarbonate.
18. A process according to claim 1, wherein the oxidation is carried out in the presence of a second base.
19. A process according to claim 18, wherein the second base is pyridine, 2, 6-lutidine or triethylamine.
20. A process according to claim 1 , wherein the molar ratio of the compound of formula (I) to the prochiral alkene is in the range of from 1 to 10 mol %.
21. A process according to claim 1 , wherein the molar ratio of the compound of formula (I) to the prochiral alkene is 5 mol %.
EP00901253A 1999-01-29 2000-01-28 Epoxidation process using amine catalysts Withdrawn EP1147099A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9902055.4A GB9902055D0 (en) 1999-01-29 1999-01-29 Novel process
GB9902055 1999-01-29
PCT/GB2000/000258 WO2000044735A1 (en) 1999-01-29 2000-01-28 Epoxidation process using amine catalysts

Publications (1)

Publication Number Publication Date
EP1147099A1 true EP1147099A1 (en) 2001-10-24

Family

ID=10846780

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00901253A Withdrawn EP1147099A1 (en) 1999-01-29 2000-01-28 Epoxidation process using amine catalysts

Country Status (5)

Country Link
EP (1) EP1147099A1 (en)
JP (1) JP2002535395A (en)
AU (1) AU2120800A (en)
GB (1) GB9902055D0 (en)
WO (1) WO2000044735A1 (en)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4024165A (en) * 1976-06-29 1977-05-17 Shell Oil Company Process for the epoxidation of olefins
US5274139A (en) * 1993-02-26 1993-12-28 University Of Florida Method for effective reaction between oxygen and organic substance utilizing regenerable hydroperioxide oxidant

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0044735A1 *

Also Published As

Publication number Publication date
AU2120800A (en) 2000-08-18
GB9902055D0 (en) 1999-03-24
WO2000044735A1 (en) 2000-08-03
JP2002535395A (en) 2002-10-22

Similar Documents

Publication Publication Date Title
Ito et al. What is the origin of highly asymmetric induction by a chiral (salen) manganese (III) complex? Design of a conformationally fixed complex and its application to asymmetric epoxidation of 2, 2-dimethylchromenes
HU910847D0 (en) Process for producing chloro-triazole derivatives
KR100565964B1 (en) Epoxide Manufacturing Method
KR20160097230A (en) Bicyclic alkyl compounds and synthesis
Tohma et al. Novel catalytic asymmetric sulfoxidation in water using the hypervalent iodine reagent iodoxybenzene
Yang et al. A rapid and divergent access to chiral azacyclic nucleoside analogues via highly enantioselective 1, 3-dipolar cycloaddition of β-nucleobase substituted acrylates
Das et al. Polyaniline supported cobalt (II) catalyst: Oxidation of alkenes with molecular oxygen
EA005209B1 (en) Phase transfer catalyzed glycosidation of an indolocarbazole
Davis et al. Chiral sulfamides: synthesis of optically active 2-sulfamyloxaziridines. High enantioselectivity in the asymmetric oxidation of sulfides to sulfoxides
KR19990036258A (en) Dinaphtha zephinium salts useful as enantiomeric selective epoxidation catalysts
EP0928787A1 (en) Process for the preparation of 3-amino-pyrrolidine derivatives
WO2000044735A1 (en) Epoxidation process using amine catalysts
WO2001021617A1 (en) Process for preparing sulfoxide compounds
US20030195366A1 (en) Epoxidation process using amine catalysts
CN116199572B (en) Method for alpha-bromination of iron-catalyzed ketone
CA2565013C (en) Method for producing pentacyclic taxans
US5763623A (en) Process for catalytic epoxidation of olefinic compounds, novel cyclic ketone catalysts useful in said process
CN111943893B (en) Synthesis method of 4, 7-diazaspiro [2,5] octane compound
CN118638038B (en) N-axis chiral indole amide compound and synthesis method thereof
Bandini et al. Synthesis of Perhydrooxazinones from 2-Aza-3-Trimethylsilyloxy-1, 3-Butadiene. A General Route to 3, 3-Disubstituted-β-Hydroxy Acids
Gaudinet-Hamann et al. A convenient synthesis of bis-tetraazamacrocycles
KR950032179A (en) Improved Mass Synthesis of Azapyrone
KR20200088080A (en) fabrication method of 3,4-Dihydropyranones and the 3,4-Dihydropyranones
EP0120094B1 (en) Azetidinone compounds
CHENGDU One Enzyme–Two Variants: Enantioselective Synthesis of Fused Lactones Giving Access to Two Enantiomers

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010717

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

17Q First examination report despatched

Effective date: 20011206

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20040218