JPH0866195A - Production of optically active (3) (1,1')ferrocenophane compound - Google Patents

Abstract

PURPOSE: To easily obtain an optically active [3](1,1')ferrocenophane compound useful as e.g. a modifier for organometallic complex catalysts without the need of resolving the racemic form, by reducing a racemic (1,1')ferrocenophane compound in the presence of bread yeast. CONSTITUTION: A racemic [3](1,1')ferrocenophane compound of formula I e.g. 5-formyl[3](1,1')ferrocenophane} is dissolved in ethanol; the resultant solution is added to a medium where bread yeast is in culture followed by agitation at 30 deg.C for one hour to carry out a reduction followed by adding ether to the system to terminate the reaction, followed by filtration; the resultant filtrate is subjected to ether extraction, and the resultant extract liquid is dehydrated and the ether is distilled off, and the residual liquid is then subjected to silica gel column chromatography to effect purification, thus obtaining the objective optically active hydroxymethyl[3](1,1')ferrocenophane compound of formula II and optically active formyl[3](1,1')ferrocenophane compound of formula III, each useful as e.g. a modifier for organometallic complex catalysts.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing optically active [3] (1,1 ′) ferrocenophanes represented by the general formulas (II) and (III). It is known that optically active ferrocenes are used for modification of asymmetric reducing metal complex catalysts. (T. Hayashi, et. A
l., Bull.Chem.Soc. Jpn., 53 , 1138 (1980).) Optically active [3] (1,1 ') ferrocenophanes have similar applications as modifiers for organometallic complex catalysts. Can be considered.

[0002]

BACKGROUND OF THE INVENTION Optically active [3] (1,1 ') ferrocenophanes are known to be 5- and 6-hydroxymethyl compounds, 5- and 6-carboxy compounds, 5- and 6-formyl compounds. And the like, all of which are optically active 5-- produced by optical resolution of racemates.
And 6-carboxy [3] (1,1 ') ferrocenophane as a starting material,
alk, O.Hofer, K.Schoegl, Monatsch. Chem., 100 , 624
(1969).) The production method by fermentation using baker's yeast, lipase, esterase, etc. is not yet known.

[0003]

Conventional optical activity [3]
The production method of (1,1 ′) ferrocenophanes has been produced by a complicated method of optical resolution of a racemate, but the present invention provides 5- and 6-formyl [3] (1,
The present invention provides a method for producing optically active [3] (1,1 ′) ferrocenophanes by a simple method by asymmetric reduction reaction of 1 ′) ferrocenophan with baker's yeast.

[0004]

That is, the present invention is characterized in that a racemic [3] (1,1 ′) ferrocenophan compound represented by the general formula (I) is reduced in the presence of baker's yeast. Optically active hydroxymethyl [3] (1,
1 ') ferrocenophanes (II) and optically active formyl [3] (1,1') ferrocenophanes (III)
Is a manufacturing method.

[Chemical 4] (I)

[Chemical 5] (II)

[Chemical 6] (III)

The specific examples of [3] (1,1 ') ferrocenophanes which can be produced by the present invention are (+)-5-
Hydroxymethyl [3] (1,1 ′) ferrocenophane, (−)-5-hydroxymethyl [3] (1,1 ′)
Ferrocenophane, (+)-6-hydroxymethyl [3] (1,1 ′) ferrocenophane, (−)-6-hydroxymethyl [3] (1,1 ′) ferrocenophane,
(+)-5-formyl [3] (1,1 ′) ferrocenophane, (−)-5-formyl [3] (1,1 ′) ferrocenophane, (+)-6-formyl [3] (1,1 ')
Ferrocenophane, (-)-6-formyl [3] (1,
1 ') ferrocenophane, etc.

The racemic 5- or 6-formyl [3] (1,1 ') ferrocenophanes of the general formula (I) used as the starting material of the present invention can be produced by a known method.
(H.Falk, O.Hofer, K.Schoegl, Monatsch. Chem., 100 , 6
24 (1969). That is, [3] (1,1 ′) ferrocenophane was reacted with N, N-diphenylcarbamyl chloride by the Friedel-Crafts reaction to give 5- and 6-carboxy [3] (1 , 1 ') Ferrocenophane and further esterified to give 5- and 6-alkoxycarbonyl [3] (1, 1') ferrocenophane, then reduced with lithium aluminum hydride and further oxidized with active manganese dioxide. By doing so, 5- and 6-formyl [3] (1,1 ′) ferrocenophane can be easily produced.

As the baker's yeast used in the present invention, either commercially available pressed baker's yeast or dried baker's yeast can be used, and immobilized baker's yeast immobilized on a polymer compound can also be used. The reaction is usually carried out in a water solvent, but when the immobilized baker's yeast is used, lower alcohols such as ethanol and isopropanol, and hydrocarbon solvents such as toluene and hexane can also be used. The amount of the solvent used is preferably about 0.25 to 10 times that of the raw material. The pH of the solution is 5.5 so that the activity of baker's yeast can be derived.
It is desirable to adjust to the range of 7.5 to 7.5. It is preferable to add sugars such as ethanol, glucose, and sucrose as an energy source for baker's yeast. The reaction temperature is in the range of 10 to 50 ° C., particularly room temperature to 40
It is better to react in the range of ° C.

To describe one embodiment of the present invention, there is a method in which baker's yeast is first suspended in an aqueous glucose solution for fermentation, and then an ethanol solution of the starting material (I) is gradually added dropwise to react. is there. The reaction is completed in about several hours to several tens of hours, depending on the starting material and the state of baker's yeast. After completion of the reaction, the bacterial cells are filtered off, the solvent is removed, and the product is purified by column chromatography or the like to obtain the optically active alcohols (II) and optically active aldehydes (III) of interest. .

By the asymmetric reduction reaction of the aldehyde compound (I) by such baker's yeast, the racemic material (I) as a raw material is obtained.
One of the photochemically active substances is selectively reduced,
The optically active alcohol (II) is produced as a reduction product, and the other one of the raw material compounds, which is an optically active aldehyde (III), remains as a reduction residue, so that the two optically active compounds are simultaneously formed. can get. Further, the obtained reduction residue aldehyde (III) is chemically reduced with sodium borohydride or the like to give an optically active alcohol having a configuration opposite to that of the previously obtained optically active alcohol (II). You can Moreover, when the reduction product (II) is oxidized with active manganese dioxide, it can be easily led to an optically active aldehyde having a configuration opposite to that of the aldehyde derivative (III) obtained as a reduction residue.

Hereinafter, the present invention will be described in more detail with reference to examples.

【Example】

Example 1 5-Formyl [3] (1,1 ′) ferrocenophane par
Reduced by yeast 45 g of D-glucose was dissolved in 570 ml of distilled water, and 3
While stirring at 0 ° C., 45 g of dried baker's yeast (manufactured by Oriental Yeast Co., Ltd.) was added little by little, and stirring was continued for 20 minutes while fermentation was continued. 5-formyl [3]
A solution prepared by dissolving 570 mg of (1,1 ′) ferrocenophane in 10 ml of ethanol was added dropwise, and the mixture was stirred at 30 ° C. for 1 hour. After 120 ml of ether was added to stop the reaction and the mixture was filtered, the filtrate was extracted with ether. The extract was dehydrated, ether was distilled off, and the remaining liquid was hexane / ether (5: 1).
Was used as an eluent and purified by a column chromatography method using a silica gel column. From the first eluate (-)-
(4R, 5S) -5-formyl [3] (1,1 ′) ferrocenophane {dark orange oil, [α] _D ²⁰ 38.1 °,
Yield 37%} was obtained. From the second eluate (+)-(4S,
5R) -5-Hydroxymethyl [3] (1,1 ′) ferrocenophane {yellow crystal, mp 71-74 ° C., [α] _D
²⁰ + 24.7 ° (reference value [α] _D ²⁰ + 34 °), ee
73%} was obtained. Example 2 6-formyl [3] (1,1 ′) ferrocenophane par
6-formyl [3] (1,1 ') ferrocenophan 50 reduced by yeast
Using 0 mg as a starting material, the reaction was carried out in the same manner as in Example 1 under other conditions (however, the reaction time was 2 hours), and (-)-
(4S, 6R) -6-formyl [3] (1,1 ') ferrocenophane {orange crystal, mp 72-79 ° C, [α] _D
²⁰ -295 ° (literature value [α] _D ²⁰ -360 °), ee
82%, yield 20.7%} and (-)-(4R, 6
S) -6-Hydroxymethyl [3] (1,1 ′) ferrocenophane {orange oil, [α] _D ²⁰ -30.0 °, yield 13%} was obtained.

According to the present invention, racemic [3] (1,
1 ′) One of the optically active isomers of the ferrocenophan compound can be selectively reduced, and two kinds of optically active isomers can be obtained by separating the obtained reduction product and the reduction residue. .

Claims (1)

[Claims] 1. An optically active hydroxymethyl [3] which is characterized by reducing a racemic [3] (1,1 ′) ferrocenophan compound represented by the following general formula (I) in the presence of baker's yeast. (1,1 ') Ferrocenophanes (I
I) and a method for producing optically active formyl [3] (1,1 ′) ferrocenophanes (III). Embedded image (I) (II) (III)