TW201945373A - Optically active rare earth complex, asymmetric catalyst formed from said complex, and method for producing optically active organic compound using said asymmetric catalyst - Google Patents

Abstract

This invention addresses the problem of providing an optically active rare earth complex which can be used as an asymmetric catalyst that is not deactivated by a trace of water, that can be stored, and that requires no heating or drying prior to use. This invention solves the problem by providing the optically active rare earth complex represented by general formula (1).

Description

Optically active rare earth complex, asymmetric catalyst formed from the complex, and method for producing optically active organic compound using the asymmetric catalyst

The present invention relates to a novel optically active rare earth complex, an asymmetric catalyst formed from the optically active rare earth complex, and a method for producing an optically active organic compound using the asymmetric catalyst.

In recent years, with regard to industrial chemical synthesis, attention has been paid to methods that take environmental considerations into consideration. Attention has been paid to synthesis methods using "catalysts" which can be carried out under mild conditions and with high efficiency. Generally difficult chemical reactions. Among them, an "optically active organometallic catalyst" containing a metal and an optically active ligand is particularly important because it has the ability to synthesize a large amount of useful optically active compounds from a small amount of catalyst.

As an optically active organic metal catalyst, there is an optically active catalyst using a rare earth element as a central metal. The so-called rare earth elements are a general term for thallium, yttrium, and 15 elements (lanthanoid) with atomic number 57 (lanthanum: La) to 71 (lutetium: Lu). The rare earth element has the characteristics described below, and therefore functions as a special catalyst that cannot be replaced by an optically active organometallic catalyst having an element other than the rare earth element as a center metal.
(1) Both have high coordination tolerance, so that free catalyst design can be realized.
(2) Since both have high coordination tolerance, they can also be applied to reactions with high coordination and using a multifunctional matrix.
(3) Although the chemical properties are similar to each other, the Lewis acidity and ionic radius are slightly different, so the catalyst can be optimized by changing the lanthanide element used depending on the ligand, substrate, and reaction type.

The present inventors have reported catalytic asymmetry of trans-1-methoxy-3- (trimethylsiloxy) -1,3-butadiene (siloxydiene) using an optically active lanthanide catalyst Asymmetric Diels-Alder Reaction (Non-patent documents 1 to 4). Trans-1-methoxy-3- (trimethylsiloxy) -1,3-butadiene has also been reported to show high reactivity in the Diels-Adel reaction and can be converted from the reaction product It is a useful compound, but because it is easily decomposed, there are few examples of reports of catalytic asymmetric reactions. However, the optically active lanthanide catalyst promotes the Diels-Adel reaction of trans-1-methoxy-3- (trimethylsiloxy) -1,3-butadiene and is provided in high yields. High optical purity product.

However, in the case of an optically active lanthanide catalyst, if moisture is present during preparation, the formation of an active complex is hindered. In addition, since the optically active lanthanide catalyst is deactivated by moisture even in the case of an active complex, there are problems as described below (Non-Patent Document 4).
(1) The catalyst cannot be stored and needs to be prepared as required.
(2) If the catalyst is not dried, the yield and enantioselectivity will decrease sharply. Therefore, it is necessary to heat and dry the catalyst under high reduced pressure when preparing the catalyst.
(3) When heating and drying the catalyst, a high vacuum device, a high-purity inert gas, and a heating bath are required.
(4) The preparation of the catalyst and the reaction using it need to be performed under strict anhydrous conditions.
[Prior Art Literature]
[Non-patent literature]

Non-Patent Document 1: Sudo Y (Y Sudo), D Shirasaki, Harada S (S Harada), Nishida A (A Nishida); Electron-deficient olefins catalyzed by Yb (III) -BINAMIDE complex Highly Enantioselective Diels-Alder Reactions of Danishefsky Type Dienes with Electron-Deficient Alkenes Catalyzed by Yb (III) -BINAMIDE Complexes "Journal of the American Chemical Society"; 2008, 130, 12588-12589.
Non-Patent Document 2: Harada S (S Harada), Morikawa T (T Morikawa), Nishida A (A Nishida); Chirality catalyzed by the Diels-Adel reaction of silyloxy vinyl indole ' Complex: Chiral Holmium Complex Catalyzed Diels-Alder Reaction of Silyloxyvinylindoles: Stereoselective Synthesis of Hydrocarbazoles; "Organic Letters"; 2013, 15, 5314-5317.
Non-Patent Document 3: Harada S (S Harada), Nakashima S (S Nakashima), Yamada W (W Yamada), Morikawa T (T Morikawa), Nishida A (A Nishida); Silyloxydiene containing a pyrrolidine ring Catalytic and Enantioselective Diels-Adel Reactions and Their Applications in the Construction of Chiral Tri-tetracyclic Skeletons TO THE CONSTRUCTION OF CHIRAL TRI-AND TETRACYCLIC SKELETONS); "Heterocycles"; 2017, 95, 872-893.
Non-Patent Document 4: Masayoshi Harada, Takahiro Morikawa, Shiyooka Hiraoka, and Atsuji Nishida; Development of a catalytic asymmetric Diels-Alder reaction of an electron-rich diene using an optically active rare-earth complex; "Journal of Organic Synthetic Chemistry"; 2013, 71, 818-829.

[Problems to be Solved by the Invention]

An object of the present invention is to provide an optically active rare-earth complex that can be used as an asymmetric catalyst that does not deactivate in the case of a small amount of moisture, can be stored, and does not require heating and drying before use.
[Means for solving problems]

Means for solving the problems of the present invention are as follows.
An optically active rare-earth complex, which is represented by the following general formula (1).
[Chemical 1]

(Where,
R each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a phenyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms or a halogen atom, A cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group which may be substituted with an alkyl group having 1 to 6 carbon atoms or a halogen atom or a phenyl group, and an alkyne group which may be substituted with an alkyl group having 1 to 6 carbon atoms or a halogen atom or a phenyl group A nitro group, a alkoxy group having 1 to 6 carbon atoms, and a cyano group which may be substituted by a halogen atom,
n is an integer from 1 to 6, methylene in the ring may be substituted by -C = C-, -C≡C-, -CO-, -CO-O-, -O-, -S-, -NH- ,
Z represents any of N, O, and S,
Ln represents a rare earth element,
X represents a halogen atom, a trifluoromethanesulfonyloxy group, a bis (trifluoromethanesulfonyl) amine group, a nitrate group, or an acetate group, which may be the same or different)
2. The optically active rare earth complex according to 1., wherein Z is N.
3. The optically active rare-earth complex according to 1. or 2., wherein n is 3 or 4.
4. The optically active rare earth complex according to any one of 1. to 3., wherein X is a halogen atom, a trifluoromethanesulfonyloxy group, or a bis (trifluoromethanesulfonyl) amino group.
5. An asymmetric catalyst formed from the optically active rare-earth complex according to any one of 1. to 4.
6. A method for producing an optically active organic compound, characterized by using an asymmetric catalyst as described in 5 ..
7. The method for producing an optically active organic compound according to 6., wherein a 6-membered ring compound is produced by adding a dienephile to a diene compound.
[Effect of the invention]

The optically active rare-earth complex of the present invention does not require special experimental equipment such as a high vacuum device, a high-purity inert gas, and a heating bath, and can be produced by ordinary experimental operations. This optically active rare-earth complex can be used as an asymmetric catalyst when producing an optically active organic compound.
The asymmetric catalyst of the present invention formed from the optically active rare earth complex does not deactivate with a small amount of water, and therefore can be stored and used as a solid reagent. The asymmetric catalyst of the present invention does not need to be heated and dried before use, and therefore, it is possible to achieve efficiency and cost reduction of operations in the production of optically active organic compounds. With the asymmetric catalyst of the present invention, an optically active organic compound can be produced with high yield and high selectivity. In particular, the asymmetric catalyst of the present invention can be used as a catalyst for the Diels-Adel reaction, and is suitably used in the production of optically active 6-membered ring compounds.

The present invention relates to an optically active rare earth complex, which is represented by the following general formula (1).

[Chemical 2]

In the general formula (1),
R each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a phenyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms or a halogen atom, A cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group which may be substituted with an alkyl group having 1 to 6 carbon atoms or a halogen atom or a phenyl group, and an alkyne group which may be substituted with an alkyl group having 1 to 6 carbon atoms or a halogen atom or a phenyl group A nitro group, a alkoxy group having 1 to 6 carbon atoms, and a cyano group which may be substituted with a halogen atom.
n is an integer from 1 to 6, methylene in the ring may be substituted by -C = C-, -C≡C-, -CO-, -CO-O-, -O-, -S-, -NH- .
Z represents any of N, O, and S,
Ln represents a rare earth element.
X represents a halogen atom, a trifluoromethanesulfonyloxy group, a bis (trifluoromethanesulfonyl) amino group, a nitrate group, or an acetate group, and may be the same or different.

In the optically active rare earth complex of the present invention represented by the general formula (1),
R is preferably a hydrogen atom, a halogen atom, an alkyl group having 1 to 4 carbon atoms which may be substituted with a halogen atom, a phenyl group which may be substituted with an alkyl group having 1 to 4 carbon atoms or a halogen atom, or 1 to 4 carbon atoms. Alkyl or phenyl substituted alkenyl, alkynyl substituted with alkyl or phenyl having 1 to 4 carbon atoms, nitro, alkoxy having 1 to 4 carbon or cyano group, more preferably a hydrogen atom , A halogen atom, a phenyl group, an alkynyl group which may be substituted with an alkyl group having 1 to 4 carbon atoms or a phenyl group, a nitro group, and an alkoxy group having 1 to 4 carbon atoms, further preferably a hydrogen atom.

n is preferably an integer of 2 to 6, more preferably an integer of 3 to 5, and even more preferably 3 or 4. Specifically, cyclopentane, cyclohexane, and 4-cyclohexene are preferable.

Z represents any of N, O, and S. When Z is N, the bond to the bipyridine structure side is a double bond. When Z is O or S, the bond to the bipyridine structure side. Is a single key. Z can be selected according to its compatibility with the rare-earth element used in the complex. Since Z tends to show higher stereoselectivity, Z is preferably N.

Rare earth elements are preferably yttrium and 15 elements (lanthanides) with atomic numbers 57 (lanthanum: La) to 71 (rhenium: Lu), more preferably atomic numbers 62 (rhenium: Sm) to 71 (rhenium: Lu) 's 10 elements, and further preferably 钐, 釓,', 镱, 镏.

X is preferably a halogen atom, a trifluoromethanesulfonyloxy group, a bis (trifluoromethanesulfonyl) amino group, more preferably a trifluoromethanesulfonyloxy group, a bis (trifluoromethanesulfonyl) amino group, Further preferred is trifluoromethanesulfonyloxy.

The optically active rare earth complex of the present invention can be prepared by combining a bis-imino-bis-bipyridine type asymmetric ligand (hereinafter referred to as ImBpy) synthesized from a chiral diamine with a rare earth metal salt in an organic compound. It is prepared by mixing in a solvent. The preparation of the complex does not require anhydrous operation, and can be performed in the presence of the atmosphere. The method for producing the optically active rare earth complex of the present invention is not limited to this method.

ImBpy used in the present invention can be produced according to, for example, a production method shown below, but is not limited to this method.

"Manufacturing method of ImBpy where Z is N"
[Chemical 3]

"Manufacturing method of ImBpy with Z being O"
[Chemical 4]

"Manufacturing method of ImBpy where Z is S"
[Chemical 5]

ImBpy used in the present invention is not particularly limited as long as it satisfies the ligand structure in the optically active rare-earth complex shown in the general formula (1). For example, when Z is N Examples include ImBpy1 to ImBpy3 shown in the following general formulas (2) to (4). In addition, when Z is O or S, a structure corresponding to each of ImBpy1 to ImBpy3 can be listed. As an example, ImBpy4 is shown in the following general formula (5). Any of the compounds represented by the general formulae (2) to (5) can be synthesized from raw materials that can be purchased inexpensively.

[Chemical 6]

[Chemical 7]

[Chemical 8]

[Chemical 9]

The optically active rare earth complex of the present invention can be used as an asymmetric catalyst in the production of an optically active organic compound. The optically active rare-earth complex of the present invention can be stored in the air while maintaining a solid state, and can be used as an asymmetric catalyst without being deactivated in the case of a trace amount of water.
The asymmetric catalyst of the present invention can be used in the production of an optically active organic compound, for example, it can be used as a Diels-Adel reaction for producing a 6-membered ring compound by adding a diene to a diene. , 1,3-dipole moment addition cyclization reaction, nitro-aldol reaction (aldol) reaction, carbonyl-ene reaction, 1,4-addition reaction, Streka (Strecker) reaction, epoxidation reaction of conjugated ketene and other asymmetric catalysts.
Examples

"Synthesis example 1"
ImBpy1 to ImBpy4 were synthesized from a commercially available cyclic chiral diamine by the above-mentioned method. The yields were 86%, 52%, 42%, and 54%, respectively.

「Synthesis example 2」
ImBpy1 to ImBpy4 are mixed with a rare earth metal salt in acetonitrile, and the solvent is distilled off to obtain an optically active rare earth complex.
The obtained optically active rare-earth complexes and the measured physical properties are shown in Table 1. In addition, no physical properties were measured for Nos. 1 to 4, 15 to 18, 20, and 21, but it was confirmed that they can be used as catalysts as shown in Table 2 below.

[Table 1]

Regarding the optically active rare earth complex No. 7 synthesized above, a single crystal was prepared from a mixed solvent of acetonitrile and diethyl ether, and X-ray structure analysis was performed. The complex structure is shown in FIG. 1. For complex No. 19, a single crystal was prepared from a mixed solvent of acetonitrile and diethyl ether in the same manner, and X-ray crystal structure analysis was performed. The complex structure is shown in FIG. 2.
The optically active rare-earth complex of the present invention can be confirmed to have a structure of a rare-earth metal in which the ligand is spirally wound around the center. With this helical structure, the ease of approaching the active point of the forward chiral compound differs, so the optically active rare earth complex of the present invention functions as an asymmetric catalyst.

"Usage example 1"
Using the synthesized optically active rare earth complexes Nos. 1 to 5, 7, and 10 to 21 as asymmetric catalysts, the following reactions were performed. In addition, as a comparative example, an optically active lanthanide catalyst described in Non-Patent Document 3 (sulfonyl imine triflate and the following (R) -bisthiourea and 1,8-bis The azabicyclo [5.4.0] -undec-7-ene (1,8-Diazabicyclo [5.4.0] undec-7-ene (DBU) three-component chiral ((Ho) catalyst)) performs the same reaction. Furthermore, the optically active rare earth complex No. 7 and the optically active lanthanide catalyst described in Non-Patent Document 3 were reacted in the same manner by using those synthesized and stored in the atmosphere for 24 hours. The reaction conditions are as follows.
Catalyst amount: 10 mol%
Reaction temperature: 0 ° C for Nos. 1 to 5, 7, 10 to 21, and -20 ° C for comparative examples
Reaction time: 4 hours for Nos. 1 to 5, 7, 10 to 18, 5 hours for Nos. 19 to 21, and 30 minutes for the comparative example.
The results are shown in Table 2.

[Chemical 10]

[Chemical 11]

[Table 2]

"result"
As for the conventional optically active lanthanide catalyst as a comparative example, if it is a catalyst immediately after preparation, the reaction proceeds with high optical selectivity, but the catalyst after storage undergoes a reaction, but the yield is greatly reduced (96%-> 45%), and stereoselectivity was largely unrepresented (4%).
It was confirmed that the optically active rare earth complex of the present invention has high optical selectivity. In addition, after the optically active rare-earth complex of the present invention is stored in the air, the yield and optical selectivity are not substantially changed.

The optically active rare-earth complex of the present invention has the same activity as the previous optically active lanthanide catalyst, and can be stored in the air without being deactivated in water, and does not need to be dried by heating before use. Therefore, the optically active rare-earth complex of the present invention can be directly processed as a solid reagent when it is intended to be used, and the efficiency and cost of the operation can be achieved.

"Use case 2"
The optically active rare earth complex No. 13 synthesized above was stored in the atmosphere and room temperature for 12 hours, 2 days, 7 days, 21 days, and 30 days after synthesis. Judge Adel reaction. In addition, as a comparative example, the solution prior to the solvent distillation during the synthesis of the asymmetric catalyst of No. 13 was directly added to the reaction solution, and the same reaction was performed. The reaction conditions and the results are shown in Table 3.

[Chemical 12]

[table 3]

"result"
It was confirmed that the optically active rare earth complex of the present invention has high optical selectivity. In addition, after the optically active rare earth complex of the present invention was stored in the air for 30 days, the yield and optical selectivity were not substantially changed, and the catalyst equivalent to that of the comparative example immediately after preparation and without the removal of solvent by distillation was maintained active.

no

FIG. 1 is a diagram showing a structure of an optically active rare earth complex (ZBN of ImBpy-1 and gadolinium triflate) of the present invention.

FIG. 2 is a view showing a structure of an optically active rare-earth complex of Z of O (a complex of ImBpy-4 and rhenium triflate) according to the present invention.

Claims (7)

An optically active rare earth complex, which is represented by the following general formula (1): (Wherein R each independently represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms which may be substituted with a halogen atom, a phenyl group which may be substituted with an alkyl group having 1 to 10 carbon atoms or a halogen atom, A cycloalkyl group having 3 to 8 carbon atoms substituted with a halogen atom, an alkenyl group which may be substituted with an alkyl group having 1 to 6 carbon atoms or a halogen atom or a phenyl group, an alkyl group having 1 to 6 carbon atoms or a halogen atom or a benzene group Group substituted alkynyl, nitro, 1-6-carbon alkoxy, cyano which can be substituted by halogen atoms, n is an integer of 1-6, methylene in the ring may be -C = C- , -C≡C-, -CO-, -CO-O-, -O-, -S-, -NH-, Z represents any of N, O, S, Ln represents a rare earth element, X represents Halogen atom, trifluoromethanesulfonyloxy, bis (trifluoromethanesulfonyl) amine, nitrate, and acetate may be the same or different). The optically active rare-earth complex according to item 1 of the scope of patent application, wherein Z is N. The optically active rare-earth complex according to item 1 or item 2 of the patent application scope, wherein n is 3 or 4. The optically active rare earth complex according to any one of claims 1 to 3, wherein X is a halogen atom, trifluoromethanesulfonyloxy, bis (trifluoromethanesulfonyl) amine base. An asymmetric catalyst formed from the optically active rare earth complex according to any one of claims 1 to 4 of the scope of patent application. A method for manufacturing an optically active organic compound, which is characterized by using an asymmetric catalyst as described in item 5 of the patent application scope. The method for producing an optically active organic compound according to item 6 of the scope of patent application, wherein a 6-membered ring compound is produced by adding a diene compound to a diene compound.