Process for producing an optically active...

Details Process for producing an optically active... Process for producing an optically active...

2001-03-14

2003-07-22

Nazario-Gonzalez, Porfirio (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heavy metal containing

C556S023000, C556S137000, C502S162000, C568S814000

Reexamination Certificate

active

06596887

ABSTRACT:

FIELD OF THE INVENTION
1. Field of the Invention
The present invention relates to a process of reacting a racemic ruthenium phosphine complex with ½ equivalent of an optically active diamine having chiral asymmetric activity, thereby inactivating one of the enantiomers, adding an optically active diamine derivative to the other portion of the optically active ruthenium-phosphine complex and thus preparing a ruthenium complex having an optically active diphosphine and an optically active diamine derivative coordinated therein; and a process for preparing an optically active alcohol by making use of the complex.
2. Description of the Related Art
It is known that a complex formed of a transition metal atom and an organic ligand is used as an asymmetric reaction catalyst. It is also known that an optically active compound, particularly an axially asymmetric diphosphine ligand compound, is selected as the organic ligand. The axially asymmetric diphosphine ligand compound tends to be very expensive and is therefore disadvantageous for industrial use.
Use of a racemic catalyst, if possible, will be advantageous for the preparation of an inexpensive optically active compound. Two methods are reported for asymmetric synthesis in the presence of a racemic catalyst, that is, (1) a method making use of an asymmetric inactivating agent and (2) a method making use of an asymmetric activating agent.
(1) In “asymmetric inactivating method” which is also called as “chiral poisoning”, one of the enantiomers of a racemic catalyst is subjected to selective complex formation/inactivation and reaction is conducted in the presence of the other enantiomer catalyst. For asymmetric inactivation, enantioselective complex formation is an absolute requirement.
Several reports have so far been made on asymmetric synthesis by using an asymmetric ligand or a metal complex in the racemic form. For example, there is a report in J. M. Brown, et al.,
J. Chem. Soc., Chem. Commun.,
1532(1986) that an optically pure iridium complex in the (S)-form is allowed to act on CHIRAPHOS (2,3-bisdiphenylphosphinobutane) in the racemic form to form a complex with CHIRAPHOS in the (R)-form and then, the remaining CHIRAPHOS in the (S)-form is made use of as a rhodium complex for asymmetric hydrogenation reaction of dehydroamino acid. It is also reported that a chiral ketone is added to a racemic binaphthol-aluminum complex to inactivate the binaphthol-aluminum complex in the (R)-form by forming a complex therewith and then the remaining binaphthol-aluminium complex in the (S)-form takes part in asymmetric Diels-Alder reaction (H. Yamamoto et al.,
J. Am. Chem. Soc.,
111, 789(1989)), or that a methionine-derived phosphine ligand is added as an inactivating agent to a racemic rhodium complex to inactivate one of the enantiomers thereof, whereby asymmetric hydrogenation of dehydroamino acid is conducted (J. W. Faller et al.,
J. Am. Chem. Soc.,
115, 804(1993)).
In the above-described three examples, an enantio-selectivity is not so high, suggesting that an inactivated enantiomer complex is not selectively formed.
(2) “Asymmetric activation” of a racemic catalyst means that an asymmetric activating agent forms a complex selectively with one of the enantiomers of the racemic catalyst, thereby imparting it with higher catalytic activity than that of the catalyst before reaction and in the presence of this catalyst imparted with a higher catalytic activity, catalytic asymmetric synthesis is conducted. Even if an enantioselective complex cannot be formed, there is a diastereiomer relationship between two complexes thus formed, for example, (S)-catalyst/(S)-activating agent and (R)-catalyst/(S)-activating agent so that they must be different each other in catalytic activity. If the difference is large, a high enantio-selectivity can be attained. Mikami, who is one of the present inventors, and et al., reported catalytic asymmetric hydrogenation which is effected by asymmetric activation and can permit attainment of a high enantio-selectivity even in the presence of a racemic BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl)-Ru catalyst (T. Ohkuma et al.,
J. Am. Chem Soc.,
120, 1086(1998)). In this hydrogenation reaction, the asymmetric activating agent forms a complex with each of the enantiomers of the racemic catalyst, thereby forming two activated diastereomer complexes. These two activated complexes in a diastereomeric relation differ largely in catalytic activity and a high enantio-selectivity can be attained, which however depends on the ketone substrate. This method is however accompanied with the problems that a high enantio-selectivity cannot be attained without a large difference between two activated complexes in catalytic activity; and the difference between two activated complexes in catalytic activity depends largely on the ketone substrate to be employed, meaning that the ketone substrate is not generally used.
SUMMARY OF THE INVENTION
The present inventors considered that a more efficient racemic catalyst reaction system can be provided by using two methods for a racemic catalyst, that is, asymmetric activation and asymmetric inactivation in combination and making synergistic use of their merits rather than by using them independently. Described specifically, they considered that if it is possible to inactivate only one of the enantiomers of a racemic catalyst, thereby obtaining only an activated diastereomer complex composed of the other enantiomer, the asymmetric activating method of a racemic BINAP-Ru catalyst improves an enantio-selectivity further and enlarge the application range of its ketone substrate.
With a view toward overcoming the above-described problems, the present inventors have carried out an extensive investigation. As a result, it has been found that an enantio-selectivity as high as that obtained by asymmetric activation of an optically pure catalyst can be attained by an optically active ruthenium-phosphine complex obtained by subjecting one of the enantiomers of a racemic BINAP-Ru complex to complexation and inactivation by using an inactivating agent and then, adding an asymmetric activating agent to form a complex with the other enantiomer; and that in the presence of the above-described complex, hydrogenation reaction of a carbonyl compound proceeds whereby an optically active alcohol is available at a high optical purity and high yield, leading to the completion of the invention.
The following are the aspects of the invention.
1) A process for producing an optically active ruthenium-phosphine complex represented by the following formula (1):
wherein R
5
, R
6
, R
11
and R
12
each independently represents a hydrogen atom, a saturated or unsaturated hydrocarbon group, an aryl group, a urethane group or a sulfonyl group; R
7
, R
8
, R
9
and R
10
are the same or different so that the carbon to which these substituents have been bonded become an asymmetric center and each independently represents a hydrogen atom, an alkyl group, an aromatic monocyclic or polycyclic group, a saturated or unsaturated hydrocarbon group or a cyclic hydrocarbon group; or R
7
or R
8
and R
9
or R
10
may be coupled together to form an alicyclic group so that the carbon bonded thereto becomes an asymmetric center; L represents a bidentate ligand compound of a tertiary phosphine; X represents a halogen atom; and * means chiral center (L* is an optically active substance), which comprises reacting a ruthenium-phosphine complex represented by the following formula (2):
Ru
m
X
n
L
p
A
q
  (2)
wherein X and L have the same meanings as described above (L is a racemic modification); A represents triethylamine (Et
3
N) or dimethylformamide (DMF); and m, n, p and q each stands for an integer and when A represents Et
3
N, m, n, p and q stand for 2, 4, 2 and 1, respectively, and when A represents DMF, m, n, p and q stand for 1, 2, 1 and 2 to 5, respectively; or a ruthenium phosphine complex represented by the following formula (3):
[RuX(D)(L)]X  (3)
wherein, X and L hav

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