Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2003-04-03
2004-08-31
Aulakh, Charanjit S. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C502S171000, C502S150000, C502S160000, C502S200000, C502S349000, C549S295000, C549S300000, C549S311000, C544S064000, C544S089000
Reexamination Certificate
active
06784302
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a method of producing an optically active lactone compound and a Zr(salen) complex suitable for this method.
2. Description of Related Art
The Baeyer-Villiger reaction, i.e. oxidative conversion of carbonyl to ester (or lactone) is of high synthetic value and is widely used in various syntheses. Although many biocatalyzed asymmetric Baeyer-Villiger reactions are known, their chemical versions are still limited in number.
In 1994 is reported copper-catalyzed asymmetric Baeyer-Villiger reaction by Bolm et al (Bolm C., Schlingloff G. and Weickhardt K., Angew. Chem. Int. Ed. Engl. 1994, 33, 1848-1849). In the same year is reported platinum-catalyzed asymmetric Baeyer-Villiger reaction by Strukul et al (Gusso A., Baccin C., Pinna F. and Strukul G., Organometallics, 1994, 13, 3442-3451).
Since then, several catalysts are used in the asymmetric Baeyer-Villiger reaction, and high enantioselectivity is realized in the Baeyer-Villiger reactions of some limited substrates (Bolm C., Luong K. K. and Schlingloff G., Synlett., 1997, 1151-1152; Bolm C., Beckmann O., Cosp A. and Palazzi C., Synlett., 2001, 1461-1463; and Bolm C., Beckmann O. and Palazzi C., Can. J. Chem., 2001, 79, 1593-1597). However, it is strongly demanded to introduce new methodology into the asymmetric Baeyer-Villiger reaction.
The Baeyer-Villiger reaction is a two-step reaction: (i) nucleophilic addition of an oxidizer producing Criegee adduct and (ii) rearrangement of the adduct to ester (or lactone). If a carbonyl compound is a pro-chiral cyclic compound as a starting substance, a product through the Baeyer-Villiger reaction is a pair of enantiomeric lactones.
The stereochemistry of the Baeyer-Villiger reaction is depended by two factors: (i) face selectivity in oxidizer addition and (ii) enantiotopos selectivity in migration. However, as the formation of Criegee adduct is a reversible reaction and the migration of the adduct to lactone is an irreversible reaction and a rate-determining step, topos-selection in the migration step is considered to strongly influence the stereochemistry of the Baeyer-Villiger reaction.
The migration is largely influenced by interaction between &sgr;-orbital of migrating C—C bond and &sgr;*-orbital of O—O bond as mentioned below. For this end, it is considered to achieve a high enantioselectivity if &sgr;-bond and &sgr;*-bond are topos-selectively interacted with each other. Also, it is considered to realize the topos-selective interaction if the Criegee adduct makes a chelate and the chelate conformation is regulated appropriately. Therefore, a metallosalen complex of cis-&bgr; structure is considered to be a catalyst suitable for realizing the topos-selective interaction because it provides two neighboring coordinating sites for the chelate formation and its metal center is chiral.
Based on the above theory, the inventors have reported that Co(salen) complex of square planar geometry does not show any enantioselectivity in the Baeyer-Villiger reaction of 3-substituted cyclobutanone, while Co(salen) complex having a cis-&bgr; structure shows a good enantioselectivity up to an enantiomeric excess of 78%ee (Uchida T. and Katsuki T., Tetrahedron Lett., 2001, 42, 6911-6914).
However, the above result that the enantiomeric excess of the product is not more than 78% ee means that the control of chelate conformation by the Co(salen) complex of cis-&bgr; structure is not sufficient.
SUMMARY OF THE INVENTION
It is, therefore, an object of the invention to provide a method of producing an optically active lactone compound capable of further enhancing the enantiomeric excess. Also, it is another object of the invention to provide a catalyst suitable for the method of producing such a lactone compound.
The inventors have made various studies in order to achieve the above objects and found that a lactone compound can be produced in a higher enantiomeric excess by synthesizing a specified Zr(salen) complex and using such a complex as a catalyst to conduct a Baeyer-Villiger reaction of a cyclic ketone compound.
According to a first aspect of the invention, there is the provision of a method of producing an optically active lactone compound, which comprises using a Zr(salen) complex represented by the following formula (I) or (II):
wherein Ar
1
is an aryl group having a carbon number of 10 to 16 and Y is a phenoxy group or an alkoxy group having a carbon number of 1 to 10 as a catalyst in a solvent, and conducting a Baeyer-Villiger reaction of a cyclic ketone compound with at least one oxidizer selected from the group consisting of hydrogen peroxide, aqueous hydrogen peroxide and urea-hydrogen peroxide adduct (UHP).
The preferable embodiments of the production method according to the invention are as follows.
The Zr(salen) complex is represented by the following formula (III) or (IV):
wherein Ph is a phenyl group and Y is the same meaning as mentioned above.
The symbol Y is a phenoxy group.
The cyclic ketone compound is represented by the following formula (V), (VI), (VII), (VIII) or (IX):
wherein R
1
is a substituted or non-substituted alkyl group having a carbon number of 1 to 20 or a substituted or non-substituted aryl group having a carbon number of 6 to 15,
wherein R
2
is a substituted or non-substituted alkyl group having a carbon number of 1 to 20 or a substituted or non-substituted aryl group having a carbon number of 6 to 15,
wherein n is 0, 1 or 2,
wherein n is 0, 1 or 2.
The cyclic ketone compound is 3-phenyl cyclobutanone, 3-(p-chlorophenyl) cyclobutanone, 3-(p-methoxyphenyl) cyclobutanone or 3-octyl cyclobutanone.
The lactone compound is represented by the following formula (X), (XI), (XII), (XIII), (XIV), (XV) or (XVI):
wherein R
1
is the same meaning as mentioned above,
wherein R
2
is the same meaning as mentioned above,
wherein n is 0, 1 or 2,
wherein n is 0, 1 or 2,
wherein n is 0, 1 or 2,
wherein n is 0, 1 or 2.
The lactone compound is &bgr;-phenyl-&ggr;-butyrolactone, &bgr;-(p-chlorophenyl)-&ggr;-butyrolactone, &bgr;-(p-methoxyphenyl)-&ggr;-butyrolactone or &bgr;-octyl-&ggr;-butyrolactone.
The solvent is a halogenated hydrocarbon. This halogenated hydrocarbon is dichloromethane or chlorobenzene.
The oxidizer is a urea-hydrogen peroxide adduct (UHP).
The lactone compound has an enantiomeric excess of not less than 80%ee.
According to a second aspect of the invention, there is the provision of a Zr(salen) complex represented by the following formula (I) or (II):
wherein Ar
1
and Y are the same meanings as mentioned above.
The preferable embodiments of the second aspect of the invention are as follows.
The Zr(salen) complex is represented by the following formula (III) or (IV):
wherein Ph and Y are the same meanings as mentioned above.
The symbol Y is a phenoxy group.
DETAILED DESCRIPTION OF THE INVENTION
The invention will be described in detail below. The Zr(salen) complex according to the invention is represented by the formula (I) or (II):
wherein Ar
1
is an aryl group having a carbon number of 10 to 16 and Y is phenoxy group or an alkoxy group having a carbon number of 1 to 10.
The complex used in the production method of the invention is important that a metal center is Zr. Although the inventors have examined a Ti(salen) complex having Ti as a metal center among the same Group 4A of the Periodic Table, it has been confirmed that this complex hardly shows a catalytic activity. Because Ti is strong in the oxophilicity as compared with Zr, and when the Ti(salen) complex is treated with hydrogen peroxide or UHP, it produces a peroxy titanium(salen) complex as shown below. Also, the ring-opening of the peroxy Ti(salen) complex is slow.
On the other hand, Zr is weak in the oxophilicity as compared with Ti and Zr—O bond is longer than Ti—O bond, so that it is considered that the ring-opening of peroxy Zr(salen) complex is much easier, or the hydroperoxo group coordinated to the zirconium ion is reluctant to generate a peroxy Zr(salen) complex. Thus, Zr(salen) complexes are expected to
Katsuki Tsutomu
Uchida Tatsuya
Watanabe Akira
Aulakh Charanjit S.
Kyushu University
Oliff & Berridg,e PLC
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