Claims
- 1. A method of producing an epoxide from an olefin comprising:
contacting an oxidizing agent with an olefin in the presence of a chiral ketone under conditions sufficient to produce an epoxide from the olefin, wherein the chiral ketone is selected from the group consisting of a compound of the formula: 41 or a derivative thereof which is capable of converting to the chiral ketone of Formula I under the reaction conditions, wherein
bonds a and b are of cis-configuration relative to each other; n is 0 or 1; X is selected from the group consisting of O and CR7R8, where R7 and R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl and heteroalkyl, or R7 together with R4 together with the atoms to which they are attached to form an optionally substituted heterocyclyl; each of R1 and R2 is independently selected from the group consisting of hydrogen or alkyl, or R1 and R2 together with atoms to which they are attached to form a cycloalkyl; R3 is selected from the group consisting of hydrogen and OR9, where R9 is a hydroxyl protecting group or aryl group; R5 is alkylene; R4 is hydrogen or a hydroxy protecting group; and R6 is hydrogen, alkyl, or —ORa, where Ra is hydrogen or a hydroxy protecting group; or R4 and R6 together with the atoms to which they are attached to form an optionally substituted heterocyclyl.
- 2. The method of claim 1, wherein R4 and R6 or R4 and R7 together with the atoms to which they are attached to form an optionally substituted heterocyclyl.
- 3. The method of claim 1, wherein R3 is hydrogen.
- 4. The method of claim 3, wherein X is O or CH2.
- 5. The method of claim 1, wherein the chiral ketone is of the formula:
- 6. The method of claim 5, wherein the chiral ketone is of the formula:
- 7. The method of claim 6, wherein each of R1 and R2 is independently hydrogen or C1-C4 alkyl or R1 and R2 together with the atoms to which they are attached to form cyclopentyl, cyclohexyl or cycloheptyl.
- 8. The method of claim 7, wherein R10 and R11 are C1-C4 alkyl or R10 and R11 together with the atoms to which they are attached to form cyclopentyl, cyclohexyl or cycloheptyl.
- 9. The method of claim 8, wherein the chiral ketone is of the formula:
- 10. The method of claim 1, wherein the oxidizing agent comprises a peracid, an oxidizer derived from a mixture of hydrogen peroxide and a nitrile compound, potassium peroxomonosulfate, sodium perborate, or a mixture thereof.
- 11. The method of claim 1, wherein the oxidizing agent is potassium peroxomonosulfate or is derived from a mixture comprising a nitrile compound and hydrogen peroxide.
- 12. The method of claim 1 further comprising maintaining the pH of the reaction mixture at from about pH 10 to about pH 14.
- 13. The method of claim 1, wherein the epoxide is an enol ester epoxide and said method further comprises stereoselectively producing an α-acyloxy carbonyl compound from the enol ester epoxide, said α-acyloxy carbonyl producing step comprising:
contacting the enol ester epoxide with an acid catalyst under conditions sufficient to stereoselectively produce the α-acyloxy carbonyl compound.
- 14. The method of claim 13, wherein the α-acyloxy carbonyl is produced with inversion of stereochemistry.
- 15. The method of claim 13, wherein the α-acyloxy carbonyl is produced with retention of stereochemistry.
- 16. A method for stereoselectively producing an α-acyloxy carbonyl compound from an enol ester olefin comprising:
(a) contacting an oxidizing agent with the enol ester olefin in the presence of a chiral ketone under conditions sufficient to produce an enol ester epoxide from the enol ester olefin, wherein the chiral ketone is selected from the group consisting of a compound of the formula: 45or a derivative thereof which is capable of converting to the chiral ketone of Formula I under the reaction conditions, wherein
bonds a and b are of cis-configuration relative to each other; n is 0 or 1; X is selected from the group consisting of O and CR7R8, where R7 and R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl and heteroalkyl, or R7 together with R4 together with the atoms to which they are attached to form an optionally substituted heterocyclyl; each of R1 and R2 is independently selected from the group consisting of hydrogen or alkyl, or R1 and R2 together with atoms to which they are attached to form a cycloalkyl; R3 is selected from the group consisting of hydrogen and OR9, where R9 is a hydroxyl protecting group or aryl; R5 is alkylene; R4 is hydrogen or a hydroxy protecting group; and R6 is hydrogen, alkyl, or —ORa, where Ra is hydrogen or a hydroxy protecting group; or R4 and R6 together with the atoms to which they are attached to form an optionally substituted heterocyclyl; and (b) contacting the enol ester epoxide with an acid catalyst under conditions sufficient to stereoselectively produce the α-acyloxy carbonyl compound.
- 17. The method of claim 16, wherein the α-acyloxy carbonyl is produced with inversion of stereochemistry.
- 18. The method of claim 16, wherein the α-acyloxy carbonyl is produced with retention of stereochemistry.
- 19. The method of claim 16, wherein the chiral ketone is of the formula:
- 20. A method for increasing a relative concentration of at least one stereoisomer of a compound having at least one olefinic moiety, from a stereoisomer mixture of the compound, said method comprising:
contacting an oxidizing agent with the stereoisomer mixture of the compound in the presence of a chiral ketone to producing an epoxide of at least one stereoisomer of the compound at a relatively higher rate than an epoxide of another stereoisomer of the compound, wherein the chiral ketone is selected from the group consisting of a compound of the formula: 47 or a derivative thereof which is capable of converting to the chiral ketone of Formula I under the reaction conditions, wherein
bonds a and b are of cis-configuration relative to each other; +P2 n is 0 or 1;
X is selected from the group consisting of O and CR7R8, where R7 and R8 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl and heteroalkyl, or R7 together with R4 together with the atoms to which they are attached to form an optionally substituted heterocyclyl; each of R1 and R2 is independently selected from the group consisting of hydrogen or alkyl, or R1 and R2 together with atoms to which they are attached to form a cycloalkyl; R3 is selected from the group consisting of hydrogen and OR9, where R9 is a hydroxyl protecting group or aryl; R5 is alkylene; R4 is hydrogen or a hydroxy protecting group; and R6 is hydrogen, alkyl, or —ORa, where Ra is hydrogen or a hydroxy protecting group; or R4 and R6 together with the atoms to which they are attached to form an optionally substituted heterocyclyl.
- 21. The method of claim 20, wherein the stereoisomer mixture comprises a geometrical isomer of the olefin moiety.
- 22. The method of claim 20, wherein the compound further comprises at least one chiral center.
- 23. The method of claim 22, wherein the stereoisomer mixture comprises a stereoisomer of the chiral center.
- 24. The method of claim 23, wherein said stereoisomer mixture is a racemic mixture.
- 25. The method of claim 20, wherein the chiral ketone is of the formula:
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a Continuation-In-Part of U.S. patent application Ser. No. 09/284,054, filed Apr. 6, 1999, which is a U.S. National Phase Patent Application of PCT Patent Application No. PCT/US97/18310, filed Oct. 8, 1997, which claims the priority benefit of U.S. Provisional Patent Application No. 60/028,009, filed Oct. 8, 1996. This application is also a Continuation-In-Part of U.S. patent application Ser. No. 09/673,335, filed Oct. 13, 2000, which is a U.S. National Phase Patent Application of PCT Patent Application No. PCT/US99/08418, filed Apr. 16, 1999, which claims the priority benefit of U.S. Provisional Patent Application No. 60/082,029, filed Apr. 16, 1998. This application is also a Continuation-In-Part of U.S. patent application Ser. Nos. 09/663,390, filed Aug. 10, 2000 and 09/534,419, filed Mar. 23, 2000, which claim the priority benefits of U.S. Provisional Patent Application Nos. 60/148,904, filed Aug. 13, 1999, and 60/125,687, filed Mar. 23, 1999, respectively. All of the above patent applications are incorporated herein by reference in their entirety.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH
[0002] The U.S. Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of Grant No. CHE-9875497 awarded by National Science Foundation and Grant Nos. GM55704-01 and GM59705-01 awarded by the National Institutes of Health.
Provisional Applications (4)
|
Number |
Date |
Country |
|
60028009 |
Oct 1996 |
US |
|
60082029 |
Apr 1998 |
US |
|
60148904 |
Aug 1999 |
US |
|
60125687 |
Mar 1999 |
US |
Continuation in Parts (4)
|
Number |
Date |
Country |
Parent |
09284054 |
Apr 1999 |
US |
Child |
10041953 |
Jan 2002 |
US |
Parent |
09673335 |
Dec 2000 |
US |
Child |
10041953 |
Jan 2002 |
US |
Parent |
09663390 |
Aug 2000 |
US |
Child |
10041953 |
Jan 2002 |
US |
Parent |
09534419 |
Mar 2000 |
US |
Child |
10041953 |
Jan 2002 |
US |