JPS63301844A - Production of optical active arylacetic acid derivative - Google Patents

Abstract

PURPOSE:To obtain the aimed compound in good conversion rate and optical yield, by using a metallic catalyst modified with a specific optically active metallocenylphosphine derivative in producing the titled compound from the corresponding olefin derivative by an asymmetric hydrogen reduction method. CONSTITUTION:A compound expressed by formula I (Ar is formula II or III; R4-R4 are H, lower alkyl or phenyl or further R3 and R4 are halogen, lower alkoxy, etc.) is asymmetrically reduced with hydrogen in the presence of a metallic catalyst modified with an optically active metallocenylphosphine derivative expressed by formula IV (X is CH2, O or NR9; Z is alkylene, CO, COCH2 or CH2CO; Y is OR10 or NR11R12; R5 and R6 are lower alkyl, 5-8C cycloalkyl, aryl, etc.; R7-R12 are H, lower alkyl or NR11R12 which may form a heterocyclic ring; M is Fe, Ru or Os; n is 0 or 1) to advantageously obtain the aimed compound expressed by formula V useful as an intermediate for medicines.agricultural chemicals, etc., in a desired steric configuration. Furthermore, the steric configuration of the aimed compound can be controlled by changing the steric coordination of the catalyst used.

Description

[Detailed Description of the Invention] <Industrial Application Field> The present invention provides a compound of the general formula (1) useful as an intermediate for medicines, agricultural chemicals, etc.
) (In the formula, RI and R1 are hydrogen atoms, lower alkyl groups or phenyl groups, Ar is hydrogen atoms, R3 and R4 are hydrogen atoms, halogen atoms, lower alkyl groups, lower alkoxyl groups, difluoromethoxy groups, trifluoromethyl groups. or phenyl group.) The present invention relates to a method for producing an optically active arylacetic acid derivative represented by

<Prior art> In a method for obtaining optically active aryl acetic acid by an asymmetric hydrogen reduction method, the general formula (N) + − LM (olefin) g X (ff) (in the formula,
M represents a rhodium atom, a ruthenium atom or an iridium atom, and L represents an asymmetric ligand of ferrocenylphosphine or pyridinylphosphine. Also, olefin is 2.5
U.S. Pat.
As the ferrocenylphosphine shown in No. 09.897 specification and used here, in the general formula (V)C formula, R6
and R6 is a lower alkyl group, c.

~8 cycloalkyl group, phenyl group or CsNO3
shows a heterocycle. Q represents a lower alkyl group, an alkenyl group, or C(R' y ) (R'a) Y',
Rte and R'8 represent a hydrogen atom, a lower alkyl group, or an aryl group, and Rf and R6 may be combined to form a cycloalkyl ring.

Y'H hydrogen atom, hydroxyl group, acyloxy group, Z'(R'
+o)! or PRi. R/, , z- is N
,P.

As or sb, R'l (1 and R', 1 represents a hydrogen atom or an alkyl group. (R'1゜) 1 may be a heterocycle containing N or P, and the heterocycle may further be May contain N or 0.

(n represents 0 or 1) An optically active ferrocenylphosphine compound is disclosed.

However, the method using such an optically active ferrocenylphosphine compound is not industrially satisfactory, as the optical yield of the target optically active aryl acetic acid derivative is not necessarily sufficient, and the conversion rate is also low. Ta.

Means for Solving the Problems> Based on the above, the present inventors have conducted intensive studies to solve the above problems and produce optically active arylacetic acid derivatives with a favorable conversion rate and optical yield. By using a metal catalyst modified with an optically active metallocenylphosphine derivative that has a different structure from the metallocenylphosphine described in the previous US patent specification, H It was discovered that an optically active arylacetic acid core conductor having a desired steric configuration can be obtained by selecting the steric configuration of the asymmetric ligand used, and the present invention has been achieved.

That is, the present invention provides an olefin derivative represented by the general formula (11) (wherein R1*R and Ar have the same meanings as above), an olefin derivative represented by the general formula (III) (wherein R and R6 are lower It represents an alkyl group, a cycloalkyl group, an aryl group, or a C6 to C8 heterocycle. R and R11 represent a hydrogen atom or a lower alkyl group. X represents a methylene group, an oxygen atom, or NR, R.

represents a hydrogen atom or a lower alkyl group.

2 is an alkylene group, C=O, O or (,:H2C R7゜, R11 and R11 are hydrogen atoms or lower
1! may be combined to form a heterocycle containing a nitrogen atom, and the heterocycle may further contain an oxygen atom or a nitrogen atom.

M represents Fe, Ru or O8. n is 0 or 1. ) Provides a method for producing an optically active arylacetic acid derivative represented by the general formula (1), characterized in that asymmetric hydrogen reduction is carried out in the presence of a metal catalyst modified with an optically active metallocenylphosphine derivative represented by It is something to do.

In the present invention, general formula ('I) used as a raw material
Examples of olefin derivatives represented by include 2-phenyl-8-methylcrotonic acid, 2-(4-chlorophenyl)-8-methylcrotonic acid, and 2-(4-difluoromethoxyphenyl)-8-methylcrotonic acid. ,2-(4
-isobutylphenyl)-acrylic acid, 2-(4-methoxyphenyl)-3-methylcrotonic acid, 2-phenylacrylic acid, 2-phenyl-8-ethylcrotonic acid, 2
．． 8-diphenylcrotonic acid, 2-(2-naphthyl)-
Examples include 3-methylcrotonic acid and 2-(6-medoxynaphthyl-2)-acrylic acid, which can be produced according to the method described in the above-mentioned US patent.

The optically active metallocenylphosphine derivative used in the present invention is as shown in the general formula (III) above, and a ferrocenylphosphine derivative in which the metal atom M is an iron atom in the general formula (ll[). is preferable,
In addition, as substituents, R3 and R6 are t-butyl group, cyclohexyl group, or phenyl group, R is hydrogen atom, 9 is methyl group, X is NMe, and Z is methylene group, ethylene group, trimethylene group. , tetramethylene R1H
It is more preferably used when and RH each represent a lower alkyl group.

The present invention uses a metal catalyst modified with such a metallocenylphosphine derivative, and transition metals such as rhodium, iridium, or ruthenium are preferably used as the metal component in the metal catalyst.

Specifically, such a catalyst is Rh ((R)-(S)
-BPPP-NMeCH2CHJIlit2) (N8
mouth or C0D) BF4, Rh [(R)-(S)
-BPPP-NMeCH2CH2NEt2) 2c *
o4, Ru, Cla ((R)-(S)-BPPP
-NMeCH, CH, NEt2) z [In the above formula,
(R)-(S)-BPPP-NMeCH2CH2NEt
2 is (R) N-methyl-[2-(diethylamino)
ethyl)-1-((S)-1,2-bis(diphenylphosphino)ferrocenyl]ethylamine, NBD is 2
．． 5-norbornadiene and COD indicate 1,5-cyclooctadiene, respectively. ] etc., and the production of these metal catalysts is described in Bull, C.
hem, Sac, Jpn,, 53.1138 (198
0), ^cc, Chem, Res,, 15.39
5 (19B2L J, Am, Chem, Sac,,
99°6262 (1977) and J, ^m, Ch
ea+, Soc, , 108.6405 (1986)
For example, (R)-(S)-BP
PF-NMeCH, CM, NEt, are (R)-(S)-BPPF-OCOMe and HNMe as shown in the formula below.
It can be produced by reacting CH, -CH, NEt.

In addition, Rh((R)-(S)-BPPF-NMeCH
2CH, NEt2)(NBD)BF, is Rh(NBD
), BF4 in methanol, (R)-(S)-B
React with PPF-NMe CH,CH2NE t2 to form (R)-(S)-BPPF-NMeCH,C
It can be produced by coordination exchange between H, NE t, and NBD.

In the method of the present invention, the amount of catalyst used is 0.001 to 10 mol%, preferably 0.001 to 10 mol%, based on the raw material olefin derivative.
．． 01-1 mol%.

The reaction is usually carried out in a solvent, such as an organic solvent such as methanol, ethanol, isopropanol, butanol, methyl acetate, benzene, toluene, xylene, tetrahydrofuran, or water. +Although mixtures thereof may be mentioned, methanol and ethanol are preferably used.

The amount of such a solvent to be used is usually 1 to 600 times, preferably 10 to 200 times the weight of the raw material olefin derivative.

The hydrogen pressure during the reaction is generally in the range of normal pressure to 500.9/d, but preferably 10 to 150 k
Q/d.

The reaction temperature is 0 to 150°C, preferably 20 to 100°C.
It is.

The reaction time is not particularly limited, but is generally 1 to 20 hours.

It is also possible to add a tertiary amine such as triethylamine, tri-n-propylamine, etc. to the reaction system during the reaction.

When a tertiary amine is used, it is used in an amount of 0.1 to 100 times, preferably 1 to 20 times, the amount of the catalyst.

<Effects of the Invention> Thus, according to the method of the present invention, the optically active arylacetic acid derivative represented by the general formula (1) can be obtained with a good conversion rate and a good optical yield, and the steric coordination of the catalyst used can be obtained. By changing , the configuration of the optically active arylacetic acid derivative to be produced can be controlled.

<Example> The present invention will be explained below using an example of an actual storm.

Example! Rh (NBD)zBF41.9'f (0,005t
(R)(S)-BPPF-NMeCHx
4.5 q (0,00625 mol) of C8NE t2 and 7.5 ml of methanol were charged into an 85 vtl autoclave and dissolved.

Add 211 das of 2-(4-chlorophenyl)-3-methylcrotonic acid to this, and! ! 8 answers, 1 no.

After replacing the hydrogen gas inside the autoclave, the hydrogen pressure was 50kq.
/d and stirred at 80°C for 4 hours.

After the reaction is completed, the autoclave is cooled and the hydrogen is depressurized.
(S)-2-(
218"f of 4-chlorophenyl)-8-methylbutyric acid was obtained.

Conversion rate 100% Selectivity >98% Optical yield 85.4% (10 bodies) The conversion rate, selectivity, and optical yield were calculated by liquid chromatography using an optically active column and optical rotation.

The same applies below.

Also, (R)-(S)-BPPF-NMeCH,CH,
The structure of NEt2 is as follows.

Example 2-1゜(R)-(S)-B P P F-NMe CHz
CHzNE t* (S)-2-(4-chlorophenyl) was reacted and post-treated in the same manner as in Example 1 except that the optically active ferrocenylphosphine derivative shown in Table 1 was used.
-8-methylbutyric acid was obtained. The results are shown in Table-1.

The structure of (R)-(S)-BPPP-W is as follows.

Examples 11 and 12 Reactions and post-treatments were carried out in the same manner as in Example 1, except that the reaction conditions shown in Table 2 were used, and the results shown in Table 2 were obtained.

Example 13 Rh(COD)2c121.2q (0,0025 mmol), AgBF41.0 da (0,005 mmol), (
R)-(S)-BPPF-NMeCH2CH2NE t
24.5 W (0.00625 mmol), 5.1 mmol of triethylamine (0.05 mmol) and 7.5 mmol of ethanol were charged into an 85 g/volume autoclave and dissolved.

2-(4-chlorophenyl)-8-methylcrotonic acid 211 Mf was added to this and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was 50 kq/
d and stirred at 80°C for 4 hours.

After the reaction is completed, the autoclave is cooled and the hydrogen is depressurized.
By distilling off ethanol and further performing alkali extraction, acid precipitation, ether extraction and concentration, (S) -2-(
218 Da of 4-chlorophenyl)-8-methylbutyric acid was obtained.

Conversion rate 100% Selectivity 〉98% Optical yield 890% (bovine body) Example 14 Rh (COD), Cum 1.21q (0,0025 mmol), AgBF, 1.0 Da (0,005 mmol) ,(
S)-(R)-BPPF-NMeCH,CH,NEt,
4.5wy (0,00625 mmol), triethylamine 5,1! (0.05 mmol) and 7.5 ml of methanol were placed in an 85 ml autoclave and dissolved.

To this, 148q (1 mmol) of 2-phenylacrylic acid
was added and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was 50 kg/
d and stirred at room temperature for 16 hours.

After the reaction is completed, the autoclave is cooled and the hydrogen is depressurized.
Methanol was distilled off, and 149.4# of (S)-2-phenylpropionic acid was obtained by further performing alkali extraction, acid precipitation, ether extraction, and concentration.

Conversion rate 100% Selectivity 〉98% Optical yield 80.7% (bovine body) Example 16 Rh, (NBD) m (Jz 1.2 #g (0,002
5 mmol), AgBF41. OW (0,005m
moJ), (R)-(S) (0,00625mmo5)
, triethylamine 5.1'q (0.05 mmol)
and 7.5 ml of methanol were charged into an 85 ysl autoclave and dissolved.

2-(4-chlorophenyl)-8-methylcrotonic acid 21119 (1 mmol)' was added to this and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was 50 kq/
d and stirred at room temperature for 20 hours.

After the reaction, hydrogen was depressurized, methanol was distilled off, and further alkali extraction, acid precipitation, ether extraction and concentration were performed to obtain 21t of (S)-2-(4-chlorophenyl)-8-methylbutyric acid, s da I got it.

Conversion rate 100% Selectivity 〉98% Optical yield 98.8% (+ isomer) Example 16 Rhz CNBD>scl* 1.2%' (0,0
025rnmol), AgBF41.0''I (0
,005mmol), (R)-(S)-(0,0062
5 mmo11), tri x chill yzn 5.1 cape (0,05
mmol) and methanol 7.5 ml to 85*
/ volume autoclave and dissolved. 2-
Phenyl-8-methylcrotonic acid 176T#l (1mm
O1) was added and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was 50 kg/
d and stirred at room temperature for 20 hours.

After the reaction was completed, hydrogen was depressurized, methanol was distilled off, and further alkali extraction, acid precipitation, ether extraction, and &[ were performed to obtain 177 das of (S)-2-phenyl-8-methylbutyric acid.

Conversion rate 100% Selectivity 〉98% Optical yield 95.8% (bovine body) Example 17 Rh, (NBD)tcl* 1.21F (0,002
5mmoe), mmog), triethylamine 5.1
F/(0.05 mmol) and methanol 7.5 t
tl was charged into a 35 txl autoclave and dissolved.

To this was added 206 Da (1 mmo/) of 2-(4-methoxyphenyl)-8-methylcrotonic acid and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was increased to 50%.
d and stirred at room temperature for 20 hours.

After the reaction is completed, hydrogen is removed, methanol is distilled off, and further alkali extraction, acid precipitation, ether extraction and concentration are performed to obtain (S)-2-(4-methoxyphenyl)-8-methylbutyric acid 205.5 capes. I got it.

Conversion rate 100% Selectivity 〉98% Optical yield 91.9% (bovine body) Example 18 Rhz (NBD)*C1* 1.2# (0,0025
mmo/), (0,00625 mmol),) 5.1 w9 (0.05 mmol) of ethylamine and 7.5 ml of methanol were placed in an autoclave having a capacity of 1185 and dissolved.

To this, 2-(2-naphthyl)-8-methylcrotonic acid 2
26 Cape (1 mmo$') was added and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was increased to 50kl/
The mixture was pressurized to d and stirred at 50° C. for 6 hours.

After the reaction, hydrogen was depressurized, methanol was distilled off, and alkali extraction, acid precipitation, ether extraction and concentration were performed to obtain (S)-2-(2-naphthyl)-3-methylbutyric acid 22
Obtained 6 capes.

Conversion rate 100% Selectivity 〉98% Optical yield 91.3% (cow body) Example 19 Rhz(NBD)zC#* 1.2+! 7 (0,00
25mmo[), (0,00625mmo,j), triethylamine 5.181/ (0.05mmol) and meta,/-4-tetrahydrofuran (1:4) mixture (7°5 ml) was charged into an 85ml autoclave and dissolved. did. To this was added 1 mrnoe of 2-phenyl-3-methylcrotonic acid and dissolved.

Mizuya gas ffl inside the autoclave? After that, hydrogen pressure 50k
g/d and stirred at room temperature for 20 hours.

After the reaction was completed, hydrogen was depressurized, the solvent was distilled off, and further alkali extraction, acid precipitation, ether extraction and concentration were performed to obtain (S
)-2-phenyl-3-methylbutyric acid 177M1 was obtained.

Conversion rate 100% Selectivity 〉98% Optical yield 97.6 'y'o (Bovine body) Example 20 Rh, (NBD)z C121,2'9 (0, OO
25 mmo/), AgBF41. llf (0,005
mmo #), (R) = (S) (0,00625 mmo
A mixed solution of 5.1 q (0.05 mmoj) of triethylamine, 5.1 q (0.05 mmoj) of triethylamine, and 7.5 at of a mixture of 1:4 of methanol and ethylamine was charged into an 85 ml autoclave and dissolved. To this, 2-(4-chlorophenyl)-8-
211 Da (1 mmo#) of methyl crotonic acid was added and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was increased to 50%.
d and stirred at room temperature for 20 hours.

After the reaction was completed, hydrogen was depressurized, the solvent was distilled off, and further alkali extraction, acid precipitation, ether extraction and concentration were performed to obtain (S
)-2-(4-chlorophenyl)-8-methylbutyric acid 21
Got BWI.

Conversion rate 100% Selectivity 〉98% Optical yield 97.4% (cow) Example 21 Rhs (NBD) ICA'! 1.2II9(0,0
025 mmol), AgBF41.0! (0,005m
moA, (R)-(0,00625mmol),)
'J-! - Chill 7 ton 5.1WII (0.05m
m01) and methanoltetrahydrofuran (1:4
) 7.6 ml of the mixed solution was charged into an 85 ml autoclave and dissolved. To this, 2-(2-naphthyl)-8-
Methyl crotonic acid 22611F (1 mmol) was added and dissolved.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was 50 kti.
/ci and stirred at room temperature for 65 hours.

After the reaction was completed, hydrogen was depressurized, the solvent was distilled off, and further alkali extraction, acid precipitation, ether extraction and concentration were performed to obtain (S
)-2-(2-naphthyl)-3-methylbutyric acid 226# was obtained.

Conversion rate 100% Selectivity 〉98% Optical yield 96.7% (bovine body) Example 22 Rb2 (NBD)2c4 1.2Mf/(0,002
5mmol), AgBF41.0q (0,005mmol)
/), (S)-(R)-(0,00625mmo/),
Tori x f Lua Mini/2.5III (0,02
5mmol) and methanol 7.5g/85w18
was placed in an autoclave and dissolved.

To this was added 95.11 F (0.5 mmol) of (E)-2-phenyl-8-methyl-2-pentenoic acid and dissolved.

After replacing the inside of the autoclave with hydrogen gas, increase the hydrogen pressure to 100.
/d and stirred at room temperature for 90 hours.

After the reaction, hydrogen was depressurized, methanol was distilled off, and further alkali extraction, acid precipitation, ether extraction and concentration were performed to obtain erythro 2-phenyl-8-methylpentanoic acid 96
．． 0Ml was obtained.

Conversion rate 100% Selectivity 〉98% Optical yield 90.1% (integral) Example 28 Rh, (NBD), C1,1,211F (0,0025
mmo/), AgBF41. O'IF (0,005mm
ol), (S)-(R)-Bppp-NMeca, cu
, N34.5q (0,00625 mmol), triethylamine 5.1! (0.05 mmo4) and 7.5 ml of methanol were placed in a 35 txt autoclave and dissolved. To this was added 288.85W (1 mmol) of 2-phenyl-8-methylcinnamic acid, Eml, t
=.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure (QOkg
/cd and stirred at room temperature for 50 hours.

After the reaction was completed, hydrogen was depressurized, methanol was distilled off, and further alkali extraction, acid precipitation, ether extraction and concentration were performed to obtain 240.2 da of erythro 2.8-diphenylbutyric acid.

Conversion rate 100% Selectivity 〉98% Optical purity 88.2% (integral) Comparative example! Rh (NBD), BF41.91V (0,00
5 mmol), (R)-(S)-BPPF-NMe2B
, 9 W (0,00625 mmol), triethylamine 2.511 F (0,025 t remol) and methanol 7.6 dew l at 85 W! Put it in an autoclave,
dissolve. Add to this 2-(4-chlorophenyl)-8-methylcrotonic acid 211! (1 mmol) and dissolve.

After replacing the inside of the autoclave with hydrogen gas, the hydrogen pressure was 5Qkg.
/d and stirred at 80°C for 4 hours.

After completion of the reaction, post-treatment was carried out in the same manner as in Example 1 to obtain (S)-2-
2121q of (4-chlorophenyl)-3-methylbutyric acid was obtained.

Conversion rate: 100% Selectivity: >98% Optical yield: 15.8% (bovine) The structure of (R)-(S)-BPPF-NMe, Q) is as follows.

Comparative Example 2 Reaction and post-treatment were carried out in the same manner as in Comparative Example 1 except that (S)
-2-(4-chlorophenyl)-8-methylbutyric acid 21
1 Wg was obtained.

Conversion rate 92% Selection rate〉98% Optical yield 25.8% (cow) That's right.

Comparative Example 8 (R)-(S)-BPPF-NMe, (R)-
(S)-2-(4-chlorophenyl)-
8-Methylbutyric acid 212HI was obtained.

Conversion rate 99% Selection rate〉98% It is as follows.

Claims (6)

[Claims] (1) General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, R_1 and R_2 are hydrogen atoms, lower alkyl groups, or phenyl groups, and Ar is ▲Mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ where R_3 and R_4 are hydrogen atoms, halogen atoms, lower alkyl groups, lower alkoxyl groups, difluoromethoxy groups, trifluoromethoxy groups, trifluoromethyl groups. or a phenyl group) is an olefin derivative represented by the general formula (III) ▲ Numerical formula, chemical formula, table, etc. ▼ (III) (In the formula, R_5 and R_6 are lower alkyl groups, C_5
~C_8 cycloalkyl group, aryl group or C_5
~C_6 heterocycle is shown. R_7 and R_8 represent a hydrogen atom or a lower alkyl group. X represents a methylene group, an oxygen atom or NR_9, and R_9 represents a hydrogen atom or a lower alkyl group. Z is an alkylene group, C=O, ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼. Y is OR_1_0 or ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ indicates, and R_1_0 and R_1_2 indicate a hydrogen atom or a lower alkyl group. Or ▲There are mathematical formulas, chemical formulas, tables, etc.▼ is R_1
_1 and R_1_3 may together form a heterocycle containing a nitrogen atom, and the heterocycle may further contain an oxygen atom or a nitrogen atom. M is Fe, Ru
Or indicates Os. n is 0 or 1. ) General formula (I) characterized by asymmetric hydrogen reduction in the presence of a metal catalyst modified with an optically active metallocenylphosphine derivative ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (wherein, R_1, R_2 and Ar have the same meanings as above) A method for producing an optically active arylacetic acid derivative. (2) The production method according to claim 1, wherein the metal component of the metal catalyst is rhodium, iridium, or ruthenium. (3) The production method according to claim 1, wherein in the optically active metallocenylphosphine derivative represented by general formula (III), M is an iron atom. (4) The optically active metallocenylphosphine derivative has general formula (III), where M is an iron atom, R_5 and R
_6 is a t-butyl group, cyclohexyl group or phenyl group, R_7 is a hydrogen atom, R_5 is a methyl group, X is NMe, Z is a methylene group, ethylene group, trimethylene group, tetramethylene group or carbonyl group, Y is ▲There is a mathematical formula, chemical formula, table, etc.▼, R_1_1 and R_1_2 each represent lower alkyl, and R
_1_1 and R_1_2 may together form a heterocycle containing a nitrogen atom, and the heterocycle may further contain an oxygen atom or a nitrogen atom, and n
The manufacturing method according to claim 1, which is a ferrocenylphosphine derivative in which represents 0 or 1. (5) The optically active ferrocenylphosphine derivative is optically active N-methyl-[2-(diethylamino)ethyl]-
The manufacturing method according to claim 4, which is 1-[1',2-bis(diphenylphosphino)ferrocenyl]ethylamine. (6) The optically active ferrocenylphosphine derivative is optically active N-methyl-[2-(hexahydro-1H-azepin-1-yl)ethyl]-1-[1',2-bis(diphenylphosphino)ferrocenyl] The manufacturing method according to claim 4, which is ethylamine.