Catalytic asymmetric epoxidation

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C549S333000, C549S334000, C549S525000, C549S529000, C549S531000

Reexamination Certificate

active

06348608

ABSTRACT:

FIELD OF THE INVENTION
The present invention is directed to a catalytic asymmetric epoxidation of olefins by contacting an oxidizing agent to a mixture of a cyclic chiral ketone and an olefin.
BACKGROUND OF THE INVENTION
Epoxides are very important chiral building blocks for the synthesis of enantiomerically pure complex molecules. Asymmetric epoxidation of olefins presents a powerful strategy for the synthesis of enantiomerically enriched epoxides. Great success has been achieved in the epoxidation of allylic alcohols, unfunctionalized cis-olefins, and conjugated trisubstituted olefins. However, the epoxidation of trans-olefins bearing no allylic alcohol group with high enantiomeric excess still remains a challenging problem.
Among many other powerful epoxidation methods chiral dioxiranes generated in situ from Oxone® (potassium peroxomonosulfate) and a chiral ketone have appeared to be promising reagents for asymmetric epoxidations, particularly for trans-olefins bearing no allylic alcohol groups. Since the first asymmetric epoxidation of olefins with dioxirane were reported in 1984, significant progress has been made in the area. A C
2
symmetric cyclic chiral ketone derived from 1,1′-binaphthyl-2,2′-dicarboxylic acid has been used as a catalyst to achieve high enantioselectivity for the epoxidation of trans-4,4′-disubstituted stilbenes. This cyclic chiral ketone, however, is expensive and not readily available. In addition, the utility of this cyclic chiral ketone is limited to certain substrates.
Therefore, there is a need for an inexpensive, readily available, and general asymmetric epoxidation catalyst which can epoxidize a variety of olefins with high enantioselectivity.
SUMMARY OF THE INVENTION
Present invention provides a chiral ketone and a method of producing an epoxide from an olefin. The method includes adding a solution comprising an oxidizing agent to a reaction solution comprising a chiral ketone and an olefin under conditions effective to generate an epoxide; and separating the epoxide from the reaction solution. The chiral ketone is selected from the group consisting of compounds of the formula:
wherein
W, X, Y and Z are independently CR
9
R
10
, O, NR
11
, S, Se, Si or P;
l, m, n and p are independently an integer from 0 to 3;
R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
7
, R
8
, R
9
and R
10
are independently hydrogen, halide, hydroxyl, nitro, thio, or alkyl, alkoxy, aryl, silyl, siloxy, carbonyl, carboxylate, ester, amino, sulfinyl, sulfonyl, sulfate, sulfite, phosphate or phosphite groups containing from 1 to about 20 carbon atoms, or two or more R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
7
, R
8
, R
9
and R
10
are linked to form 3 to about 10 membered cyclic moiety containing 1 to about 20 carbon atoms; and
R
11
is hydrogen, oxygen or alkyl, sulfonyl, alkoxy or carbonyl groups containing from 1 to about 20 carbon atoms.
Preferably a chiral ketone is selected from the group consisting of the compound of the formula:
wherein preferably, m is 0, Y is O or CR
9
R
10
, n and p are 1, and Z is CR
9
R
10
.
Preferably two or more R
1
, R
2
, R
3
, R
4
, R
5
, R
6
, R
7
, R
8
, R
9
and R
10
, are linked to form 3 to about 10 membered cyclic moiety containing 1 to about 20 carbon atoms, more preferably R
1
and R
2
are linked to form a moiety of the formula:
—O—C(CH
2
CH
3
)
2
—O—CH
2
— or —O—C(CH
3
)
2
—O—CH
2
—.
Alternatively, R
1
and R
7
are linked to form a moiety of the formula —O—C(CH
3
)
2
—O—, —O—C(CH
2
CH
3
)
2
—O—, or —C(CH
3
)
2
—.
Preferably R
3
and R
6
are linked to form a moiety of the formula —O—C(CH
3
)
2
—O— or a moiety of the formula —O—C(CH
2
CH
3
)
2
—O—. Preferably R
4
, R
5
, R
9
and R
10
are independently hydrogen, halide or alkoxy, carboxyl or alkyl groups having 1 to about 20 carbon atoms. More preferably, R
4
, R
5
and R
10
are hydrogen and R
9
is hydrogen, halide, or alkoxy, carboxyl, sulfinyl or alkyl groups having 1 to about 20 carbon atoms.
Preferably the ketone is derived from a carbohydrate, quinic acid or carvone. More preferably the ketone is derived from a group consisting of carvone, inositol, quinic acid, (D)-fructose, (L)-fructose, (D)-arabinose, (L)-arabinose and (L)-sorbose.
Preferably the epoxidation reaction is affected by adding an oxidizing agent selected from the group consisting of peracids, hydrogen peroxide, sodium hypochlorite, potassium peroxomonosulfate, sodium perborate and hypofluoride (HOF). Preferably the epoxidation reaction is affected at pH of from about 5 to about 14 by adding a base, more preferably at pH of from 10 to about 14, and most preferably at pH of from 10 to about 12.
In another embodiment of the present invention, a method of producing an epoxide from an olefin by contacting with a chiral dioxirane is provided. The chiral dioxirane is produced by contacting the corresponding chiral ketone with an oxidizing agent.
The present invention further includes


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patent: 5414078 (1995-05-01), Liotta et al.
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Kroutil et al., “Developm

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