JP2013139417A - Bis-imidazolidine pincer complex and bis-imidazolidine pincer catalyst, and methods for preparing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To establish a method for synthesizing a bis-imidazolidine pincer complex.SOLUTION: The bis-imidazolidine pincer complex is represented by formula (1) (wherein Rand Rare each CH, -(CH)- or Ph; Ris H, CHSO, CHCHSO, CHSO, CHCO, CHCO, CH, CH, CHPh or Ph; Ris H,Bu, CH, Br or NO; X is Cl, Br, I, OTf, ClO, BFor PF; M is Pd, Ni, Rh, Ir or Ru; and Ph is an aromatic ring).

Description

  The present invention relates to a bisimidazolidine pincer type complex, a bisimidazolidine pincer type catalyst, and a method for producing them.

  A biopolymer having an optically active amino acid or sugar as a basic structural unit constructs a highly asymmetric space, and a drug using the biopolymer as a receptor needs to have optical activity. Such a method for synthesizing an optically active substance is called an asymmetric synthesis method. Among the asymmetric synthesis methods, a catalytically capable of synthesizing a theoretically infinite optically active substance from a small amount of an asymmetric source. Asymmetric synthesis methods are extremely useful and important.

  At present, catalytic asymmetric synthesis is achieved by using various metal catalysts. As asymmetric ligands that realize useful catalytic asymmetric reactions, the development of C2 symmetric optically active bisoxazolines and optically active imidazoline ligands described in Non-Patent Documents 1 to 3 below have been reported.

  In addition, the pincer complex has a remarkable complex stability as compared with a conventional organometallic compound, and on the other hand, many new physical properties and reactions have been achieved since the environment around the metal can be easily controlled. Among them, the development of optically active pincer type complexes is reported in the following Non-Patent Documents 4 and 5 and Patent Document 1 below as asymmetric catalysts.

Myung-Jong Jin et al., “Highly enantioselective Pd-catalyzed allyl lysing using new chiral ferrhoside phosphinimididine ligands” Chem. Comm. 2006, 663-664. Geon-Jong Kim et al. “New enantioselective chiral imidazolidine ligands for Pd-catalyzed asymmetry allylation” Tetrahedron. Lett. 2003, 1971-1974 Takayoshi Arai et al. “Chiral Bis (imidazolidine) pyridine-Cu (OTf) 2: Catalytic Asymmetric Endo-Selective [3 + 2] Cycloaddition of Imino Essr. Am. Chem. Soc. 2010, 5338-5339. ” Yasuhiro Uozumi et al., “NCN Pincer Palladium Complexes: Ther Preparation via a Ligand Induction Route and Theatrical Properties” Am. Chem. Soc. 2005, 12273-12281. Mao-Ping Soff et al. “Chiral NCN Pincer Pt (II) and Pd (II) Complexes with cit cit citrate citrate, 1,3 bis (2′-imidazolinyl) citrate citrate citrate. "Organometallics. 2009, 3369-3380.

JP 2010-188267 A

However, while optically active bisimidazoline pincer type complexes are known, there are no reports of bisimidazolidine pincer type complexes.

  Therefore, in view of the above problems, the present invention introduces a bisimidazolidine skeleton into a pincer complex, which is more complex than a bisimidazoline pincer complex and has a characteristic asymmetry having a proton on nitrogen coordinated to a metal. The purpose is to build a reaction and realize a practical metal complex catalyst.

  The present inventors have been diligently studying the above problems, and based on the report of Uozumi et al., Synthesized an aromatic palladium compound having a dialdehyde group and reacted with a monoalkylated optically active diamine. Thus, the pincer type neutral complex was successfully obtained, and the present invention was completed. Furthermore, it was possible to make a cationic complex by the action of silver trifluoromethanesulfonate.

That is, the complex according to one aspect of the present invention is represented by the following chemical formula (1).

In the above formula (1), R ¹ and R ² are any of CH ₃ , — (CH ₂ ) ₄ — and Ph, and R ³ is H, CH ₃ SO ₂ , CH ₃ C ₆ H ₄ SO _2. , C ₆ H ₅ SO ₂ , CH ₃ CO, C ₆ H ₅ CO, CH ₃ , C ₂ H ₅ , CH ₂ Ph, and Ph, and R ⁴ is H, ^t Bu, CH ₃ , One of Br and NO ₂ , X is one of Cl, Br, I, OTf, ClO ₄ , BF ₄ , and PF ₆ , and M is Pd, Ni, Rh, Ir, and Ru. Either. Here, Ph represents an aromatic ring.

A catalyst according to another aspect of the present invention is represented by the following chemical formula (1).

In the above formula (1), R ¹ and R ² are any of CH ₃ , — (CH ₂ ) ₄ — and Ph, and R ³ is H, CH ₃ SO ₂ , CH ₃ C ₆ H ₄ SO _2. , C ₆ H ₅ SO ₂ , CH ₃ CO, C ₆ H ₅ CO, CH ₃ , C ₂ H ₅ , CH ₂ Ph, and Ph, and R ⁴ is H, ^t Bu, CH ₃ , One of Br and NO ₂ , X is one of Cl, Br, I, OTf, ClO ₄ , BF ₄ , and PF ₆ , and M is Pd, Ni, Rh, Ir, and Ru. Either. Here, Ph represents an aromatic ring.

  In addition, the catalyst according to the present invention can be suitably used for the Michael reaction.

  According to the production method of the present invention, a bisimidazolidine pincer complex can be synthesized in three to four steps. By changing the substituent, counter anion, and metal species of the optically active diamine, it is possible to provide a complex having a high degree of freedom of coordination field and a catalytic reaction using the same due to electronic effects and steric effects. In addition, a more complex coordination field can be constructed.

  As described above, according to the present invention, a characteristic asymmetric reaction having a proton on nitrogen coordinated to a metal, which is more complicated than that of a bisimidazoline pincer complex, is constructed, and a practical metal complex and catalyst, and a method for producing the same. Can be provided.

  Embodiments of the present invention will be described below with reference to the drawings. However, the present invention can be implemented in many different modes and is not limited to the embodiments shown below.

The bisimidazolidine pincer complex (hereinafter also referred to as “the complex”) according to the present embodiment is represented by the above chemical formula (1). This complex has an optically active diamine as a building unit.

In the above formula (1), R ¹ and R ² are any of CH ₃ , — (CH ₂ ) ₄ — and Ph, and R ³ is H, CH ₃ SO ₂ , CH ₃ C ₆ H ₄ SO _2. , C ₆ H ₅ SO ₂ , CH ₃ CO, C ₆ H ₅ CO, CH ₃ , C ₂ H ₅ , CH ₂ Ph, and Ph, and R ⁴ is H, ^t Bu, CH ₃ , One of Br and NO ₂ , X is one of Cl, Br, I, OTf, ClO ₄ , BF ₄ , and PF ₆ , and M is Pd, Ni, Rh, Ir, and Ru. Either. Here, Ph represents an aromatic ring.

  This complex is white fine particles at room temperature in the air, and can be stored for 1 month or longer in a cool and dark place. Moreover, it is soluble in organic solvents, such as tetrahydrofuran, a methylene chloride, and chloroform, and these can be used for a catalyst asymmetric reaction as a solvent.

  This complex can be used as a catalyst as described above, and can be used for, for example, a 1,4-addition reaction. As described above, this catalyst is more practical than a bisimidazoline pincer complex, and is a practical catalyst because it builds a characteristic asymmetric reaction having a proton on nitrogen coordinated to a metal.

  The complex is not limited as long as it can be synthesized. For example, a diamine and a chloride of (2,6-diformylphenyl) bis (triphenylphosphine) metal species are reacted in an oxygen atmosphere. Can be built with.

In addition, one NH on the imidazolidine ring is changed to CH ₃ SO ₂ , CH ₃ C ₆ H ₄ SO ₂ , C ₆ H ₅ SO ₂ , CH ₃ CO, C ₆ H ₅ CO, CH ₃ , C ₂ H ₅ , By substituting with CH ₂ Ph, Ph, etc., coordination ability and coordination field complexity can be changed by electronic and steric effects. Here, Ph represents an aromatic ring.

Specifically, the complex according to this embodiment can be synthesized by the following method.

  According to this embodiment, synthesis of a bisimidazolidine pincer complex having versatility and versatility can be achieved, and a catalyst using a coordination field with a high degree of freedom can be provided.

  Here, the complex which concerns on the said embodiment was actually synthesize | combined, and the effect was confirmed. This will be specifically described below.

Example 1
In this example, a bisimidazolidine pincer complex represented by the following formula (4) was synthesized.

Synthesis of [(1S, 2S) -N-benzyl-1,2-diphenylethane-1,2-diamine] (1):

  First, dimethylformamide (25 ml) was placed in an eggplant flask containing activated MS 4Å (2.5 g) and purged with argon. Thereafter, (1S, 2S) -1,2-diphenylethane-1,2-diamine (1 g, 5 mmol) and cesium hydroxide monohydrate (836 mg) and benzyl chloride (690 μl) were added in this order, and the mixture was stirred at 35 ° C. did. Then, after stirring for 24 hours or more, MS was removed by filtration with filter paper, 1N aqueous sodium hydroxide solution was added, and extraction was performed in the order of ethyl acetate, water, and brine. The organic layer was dried over dead glass and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent 1: 1 n-hexane / ethyl acetate to ethyl acetate) to obtain the target compound (1) as a yellow oil in a yield of 46%. The device data of (1) is shown below.

¹ H NMR (400 MHz, CDCl ₃ ) δ 3.47 (d, J = 13.5 Hz, 1H), 3.67 (d, J = 13.5 Hz, 1H), 3.76 (d, J = 7. 3Hz, 1H), 4.01 (d, J = 7.3 Hz, 1H), 7.09-7.31 (m, 15H, aromatic);
¹³ C NMR (125 MHz, CDCl ₃ ): δ 51.4, 61.8, 68.8, 126.8, 126.9, 127.02, 127.03, 128.0, 128.07, 128.09 , 128.3, 140.2, 140.6, 141.2, 143.5;
FT / IR 3375, 3311, 3060, 3026, 2904, 2837, 1601, 1493, 1452, 762, 696 cm ^-1 ;
[Α] _D ²⁰ = −7.5 ° (c = 1.23, CHCl ₃ );
_{HRMS (FAB +) calcd for C} 21 H 23 N 2 (M + + H) 303.1861: found 303.1873.

Synthesis of [(2,6-bis ((4S, 5S) -1-benzyl-4,5-diphenylimidazolidin-2-yl) -4-tert-butylphenyl) palladium (II) chloride] (4):

  According to the report of Uozumi et al. Described in Non-Patent Document 4, (3) was obtained. Then, under an oxygen atmosphere, (3) (427.83 mg, 0.5 mmol) and (1) (453.62 mg, 1.5 mmol) were mixed in acetonitrile (15.15 ml) and stirred with relux for 2 days. did. Next, the mixture was allowed to cool to room temperature, and the precipitate was washed with methanol and diethyl ether. As a result, white fine particles (4) were obtained in a yield of 26.1%. The device data of (4) was as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 1.15 (s, 9H), 3.87 (d, 2H), 4.02 (d, 2H), 4.10 (t, 2H), 4.34 ( m, 2H), 4.85 (m, 2H), 5.57 (d, 2H), 6.70 (s, 2H), 7.13-7.34 (m, 32H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 31.54, 34.75, 58.17, 73.80, 77.67, 89.14, 121.38, 127.52, 127.67, 128.09, 128.17, 128.49, 128.57, 128.63, 129.54, 134.81, 138.17, 138.61, 146.25, 147.29;
FT / IR 3201.26, 293.56, 2853.17, 1376.93 cm ^-1 ;
[Α] _D ²⁰ = −77.5 (c = 1.00, CHCl ₃ );
_{FTMS (ESI +) calcd for C} 54 H 53 N 4 Pd (M + -Cl) 863.3300; found 863.3311.

As a result, a complex represented by the following structural formula (4) could be obtained.

(Example 2)
In this example, the triflate body (5), which is a cationic complex, was synthesized by treating (4) in the above example with a silver salt. Specific description will be given below.

Synthesis of [(2,6-bis ((4S, 5S) -1-benzyl-4,5-diphenylimidlizin-2-yl) -4-tert-butylphenyl) (trifluoromethylsulfonyxy) palladium (II)] (5):

  Under argon atmosphere, a mixture of silver trifluoromethanesulfonate (98.27 mg, 0.383 mmol) and (4) (218.20 mg, 0.255 mmol) in methylene chloride (10.2 ml) and water (1.03 ml). Stir in solvent for 24 hours. The mixture was filtered through Celite, washed with methylene chloride, and then concentrated under reduced pressure to obtain 99% yield of pale yellow fine particles (5). The device data of the above formula (5) is as follows.

¹ H NMR (400 MHz, CDCl ₃ ) δ 1.11 (s, 9H), 3.95 (br, 2H), 4.02 (d, 2H), 4.21 (br, 4H), 5.60 ( d, 2H), 6.54 (br, 2H), 7.10-7.39 (m, 30H, aromatic);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 0.98, 31.5, 34.8, 58.9, 73.8, 77.4, 87.9, 121.7, 127.5, 127.6, 127.7, 128.1, 128.3, 128.7, 129.8, 132.0, 134.3, 138.5, 138.6, 146.8, 148.2;
FT / IR 3194.51, 292.36, 2853.17, 1376.93 cm ^-1 ;
^{_{[Α] D 20 = -122.4 (}} c = 1.00, CHCl 3).

(Example 3)
Next, the effect of the complex obtained in Example 1 as a catalyst was confirmed. Specifically, (4) obtained in Example 1 was applied to catalytic asymmetric Michael reaction.

(Confirmation of Michael reaction using (4) as catalyst)

The reaction was carried out by reacting 41.65 mg of trans-chalcone dissolved in 1 ml of anhydrous tetrahydrofuran, 19.81 mg of malononitrile, and 16.80 mg of sodium hydrogen carbonate in the presence of 5 mol% of the catalyst (4) at 0 ° C. for 48 hours. As a result, 0.022 g of the following compound (6) was obtained. The yield of (6) was 40%, and the enantiomeric excess was 38% ee.

  The asymmetric synthesis reaction using the other catalyst of (6) is described in, for example, “Wei Wang et al.“ Organocatalytic Energetic Conjugate Additions to Enones ”“ J. Am. Chem. Soc. Has been.

  As described above, according to this example, it was confirmed that a useful catalyst capable of performing an asymmetric Michael reaction could be realized.

  The catalyst provided by the present invention can perform asymmetric reaction and has industrial applicability because it has sufficient stability to withstand industrialization.

Claims (3)

A complex represented by the following formula (1).
(However, R ¹ and R ² are any of CH ₃ , — (CH ₂ ) ₄ —, and Ph, and R ³ is H, CH ₃ SO ₂ , CH ₃ C ₆ H ₄ SO ₂ , C ₆ H. ₅ SO ₂ , CH ₃ CO, C ₆ H ₅ CO, CH ₃ , C ₂ H ₅ , CH ₂ Ph, and Ph, and R ⁴ is H, ^t Bu, CH ₃ , Br, and It is any of NO ₂ , X is any of Cl, Br, I, OTf, ClO ₄ , BF ₄ , and PF ₆ , and M is any of Pd, Ni, Rh, Ir, and Ru Here, Ph represents an aromatic ring.) A catalyst represented by the following formula (1).
(However, R ¹ and R ² are any of CH ₃ , — (CH ₂ ) ₄ —, and Ph, and R ³ is H, CH ₃ SO ₂ , CH ₃ C ₆ H ₄ SO ₂ , C ₆ H. ₅ SO ₂ , CH ₃ CO, C ₆ H ₅ CO, CH ₃ , C ₂ H ₅ , CH ₂ Ph, and Ph, and R ⁴ is H, ^t Bu, CH ₃ , Br, and It is any of NO ₂ , X is any of Cl, Br, I, OTf, ClO ₄ , BF ₄ , and PF ₆ , and M is any of Pd, Ni, Rh, Ir, and Ru Here, Ph represents an aromatic ring.)   The catalyst according to claim 2, which is used for 1,4-addition reaction.