JP2014114284A - C-3 substituted chiral succinimide and method of producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of producing a C-3 substituted chiral succinimide which has mild conditions and simple operations, can achieve a good yield and efficiency, and exhibits better application effect.SOLUTION: A 3-alkenylene group substituted succinimide represented by the specified general formula (1) undergoes an asymmetric hydrogenation reaction catalyzed by an iridium chiral catalyst in a solvent under a hydrogen atmosphere, and is thereby converted to a C-3 substituted chiral succinimide represented by the specified general formula (2).

Description

  The present invention relates to a production method and a product thereof in the chemical industry technical field. Specifically, it is a C-3 substituted chiral succinimide and a production method thereof. Here, the production method is a reaction method in which 3-alkenylene group-substituted succinimide is asymmetrically hydrogenated using an iridium catalyst.

  Succinimides and the like are easy to induce further modification due to the diversity of functional groups, and have received wide attention from chemists. Succinimide derivatives with a chiral carbon stereocenter at the C-3 position include many non-peptide nicotinic acetylcholine receptor antagonists MLA, anticonvulsant anticonvulsant pregabalin, anti-HIV, lignan analogs of HSV activity, etc. Succinimide and its analogs are already used as starting materials or synthetic intermediates in the synthesis of certain drugs and natural products because they are important building blocks of biologically active compounds and natural products.

  When the prior art documents were searched, it was found that there were few reports on the chiral synthesis of the C-3 position chiral succinimide derivative. Nigel S. Non-Patent Document 1 describes “A Novel Asymmetric Route to Succinimides and Derived Compounds: Synthesis of the Lignan Lactone (+)-Hinkinin”. -Synthesis of hinokinin). This document reported for the first time that a C-3 trisubstituted chiral succinimide derivative can be obtained through a lithiated alkylation reaction by chiral induction using a chiral alkali sparetine. Tamio Hayashi et al. In Non-Patent Document 2 “Rhodium-Catalyzed Asymmetric Construction of Quaternary Carbon Stereocentric: Ligand-Dependent Regiocondole in the Center. Controlled 1,4-addition reaction of maleimide). In this document, an example of realizing asymmetric synthesis of a C3-aryl group-substituted chiral succinimide derivative by an asymmetric 1,4-addition reaction selectively rhodium-catalyzed in a ligand control region was reported. However, there are few reports on the chiral synthesis of other C3-substituted succinimide derivatives, and no further reports on methods for obtaining such compounds by asymmetric catalytic hydrogenation.

"Chemical Communications" (Chemical Communications) 2004, Vol. 12, pp. 1393-1393 “Journal of the American Chemical Society” (American Chemical Society, Vol. 128, pages 5628-5629)

  The present invention focuses on the above-mentioned insufficient points existing in the prior art, and provides a C-3 substituted chiral succinimide and a method for producing the same. In other words, the present invention provides a reaction method for asymmetric hydrogenation of a 3-alkenylene group-substituted succinimide with an iridium catalyst and a reaction product thereof, which is the first method for asymmetric hydrogenation with an iridium catalyst. To produce a C-3 substituted chiral succinimide compound. The production method of the present invention is mild in conditions and simple in operation, can achieve a good yield and efficiency, and has a better application effect. Moreover, the C-3 substituted chiral succinimide obtained based on this invention is very useful as a starting material or synthetic intermediate of a drug and a natural product.

The present invention is realized by the following technical means.
The present invention relates to a method for producing a C-3 substituted chiral succinimide, the C-3 substituted chiral succinimide is represented by the following general formula (2), and the method for producing the C-3 substituted chiral succinimide is: In the hydrogen atmosphere, the catalyst is catalyzed by an iridium chiral catalyst, and the 3-alkenylene group-substituted succinimide represented by the general formula (1) generates an asymmetric hydrogenation reaction. It is characterized by being converted to the C-3 substituted chiral succinimide represented.

(In the formula, R ¹ is a hydroxy group, an aryl group which may or may not have a substituent, or a carbon number of 1 to 8 which may or may not have a substituent. R ² represents an aryl group that may or may not have a substituent, or a C ¹ to C ⁸ that may or may not have a substituent. Represents an alkyl group, * is a chiral center.)

  In the production method of the present invention, the iridium chiral catalyst is preferably an ionic compound formed by a complex composed of iridium, cyclooctadiene, and a chiral ligand and an anion. In the following, the iridium chiral catalyst is represented as “L · Ir (COD) · X”, where Ir represents iridium, COD represents cyclooctadiene, L represents a chiral ligand, and X represents Represents an anion.

  In the present invention, the chiral ligand L is preferably any one selected from L1, L2, L3, L4, L5, L6, L7, L8, and L9. Here, L1 is a central chiral PN ligand, L2 to L5 are axially unstable PN ligands, L6 is an axial chiral PN ligand, and L7 to L8 are planar chiral PN ligands. Yes, L9 is an axial chiral PP ligand, and their structural formula is as shown below.

In the present invention, the anion X is one selected from chlorine ion, hexafluorophosphate ion, and tetrakis (3,5-bis (trifluoromethyl) phenyl) borate ion (referred to as BAr _F ). It is preferable that

  In the present invention, the solvent is preferably a nonpolar solvent, a polar solvent, or a protic solvent, and specifically, among toluene, benzotrifluoride, dichloromethane, chloroform, dichloroethane, diethyl ether, tetrahydrofuran, and methanol. Any one or more selected is preferable.

Regarding the production method of the present invention, in the general formulas (1) and (2), R ¹ is a phenyl group, a benzyl group, a phenethyl group, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, or an isobutyl group. And preferably represents any one selected from n-butyl and hydroxy groups, and R ² represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, or an isobutyl group. Tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, cyclohexyl group, phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, o-methoxyphenyl group, m-methoxyphenyl Group, p-methoxyphenyl group, 4-piperonyl group, o-fluorophenyl group, m-fluorophenyl group, p-fluorophenyl group, o-chlorophenyl Nyl group, m-chlorophenyl group, p-chlorophenyl group, o-bromophenyl group, m-bromophenyl group, p-bromophenyl group, o-nitrophenyl group, m-nitrophenyl group, p-nitrophenyl group, α -It preferably represents any one selected from among a naphthyl group, a β-naphthyl group and an α-furyl group.

  In the production method of the present invention, the hydrogen atmosphere pressure in the hydrogen atmosphere is preferably 1 to 100 bar.

  Moreover, in the manufacturing method of this invention, it is preferable that reaction temperature is -10 degreeC-40 degreeC, and reaction time is 5 minutes-72 hours.

  In the production method of the present invention, the molar ratio of the iridium chiral catalyst used and the 3-alkenylene group-substituted succinimide represented by the general formula (1) is 1:20 to 1: 10000. preferable.

  The present invention further relates to a C-3 substituted chiral succinimide, and the C-3 substituted chiral succinic acid is preferably a compound represented by the following general formula (2).

(In the formula, R ¹ is a hydroxy group, an aryl group which may or may not have a substituent, or a carbon number of 1 to 8 which may or may not have a substituent. R ² represents an aryl group that may or may not have a substituent, or a C ¹ to C ⁸ that may or may not have a substituent. Represents an alkyl group, * is a chiral center.)

  Based on the production method of the present invention, a 3-alkenylene group-substituted succinimide represented by the general formula (1) is used as a substrate, an asymmetric catalytic hydrogenation with an iridium chiral catalyst, and the general formula (2) A C-3 substituted chiral succinimide is obtained. The production method of the present invention is mild in conditions and simple in operation, can achieve a good yield and efficiency, and has a better application effect. Further, the C-3 substituted chiral succinimide represented by the general formula (2) obtained based on the present invention is very useful as a starting material or synthetic intermediate for drugs and natural products.

  The production method of the present invention can be represented by the following reaction formula.

  Here, the general formula (1) represents a 3-alkenylene group-substituted succinimide which is a substrate of the present invention, and the general formula (2) represents a C-3 substituted chiral succinimide which is a reaction product of the present invention. .

From the above reaction formula, it can be seen that R ¹ and R ² in the general formula (1) and the general formula (2) do not change in the production method of the present invention.

In General Formula (1) and General Formula (2), R ¹ is a hydroxy group, an aryl group that may or may not have a substituent, or a substituent that may or may not have a substituent. Represents an alkyl group having 1 to 8 carbon atoms, and R ² may have an aryl group which may or may not have a substituent, or may or may not have a substituent. Or an alkyl group having 1 to 8 carbon atoms.
Here, examples of the substituent that the alkyl group represented by R ¹ and R ² may have include a hydroxy group, a halogen atom, and an aryl group having 6 to 12 carbon atoms. The aryl group may be further substituted with an alkyl group having 1 to 8 carbon atoms or an alkoxy group having 1 to 8 carbon atoms.
Specifically, examples of the alkyl group which may or may not have the substituent represented by R ¹ and R ² include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n- Alkyl groups such as butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, hexyl group, cyclohexyl group, heptyl group and octyl group, hydroxy groups such as hydroxymethyl group, hydroxyethyl group and hydroxypropyl group Examples thereof include an alkyl group having a group substituent, a halogenated alkyl group such as a chloromethyl group and a chloroethyl group, and an alkyl group substituted with a phenyl group such as a benzyl group.
Examples of the substituent that the aryl group represented by R ¹ and R ² may have include a hydroxy group, a halogen atom, a nitro group, an alkyl group having 1 to 8 carbon atoms, and 1 to 8 carbon atoms. And the like.
Specific examples of the aryl group which may or may not have a substituent represented by R ¹ and R ² include a phenyl group, a hydroxy group-substituted phenyl group, an alkyl group-substituted phenyl group, an alkoxy group. Examples thereof include a group-substituted phenyl group and a halogenated phenyl group.
Here, when the aryl group has a substituent, the substituents may be bonded to each other to form a ring.

Here, R ¹ is a phenyl group (hereinafter referred to as Ph), a benzyl group (hereinafter referred to as Bn), a phenethyl group, a methyl group, an ethyl group (hereinafter referred to as Et), an isopropyl group (hereinafter referred to as iPr), n - (or less nPr) propyl group, an isobutyl group, (hereinafter referred nBu) n-butyl group, hydroxy group, m- tolyl group _{(m-CH 3 C 6 H} 4 -), p- tolyl (p- _{CH 3 C 6 H 4 -)} , m- methoxyphenyl group _{(m-CH 3 OC 6 H} 4 -), p- methoxyphenyl group _{(p-CH 3 OC 6 H} 4 -), 4- piperonyl group (4- piperonyl), m-fluorophenyl group _{(m-FC 6 H 4 -} ), p- fluorophenyl group _{(p-FC 6 H 4 -} ), m- chlorophenyl group _{(m-ClC 6 H 4 -} ), p- chlorophenyl Group (p-C lC ₆ H ₄ -), m- bromophenyl group _{(m-BrC 6 H 4 -} ), p- bromophenyl group _{(p-BrC 6 H 4 -} ), m- nitrophenyl group _(m-O 2 _NC 6 H ₄ -), p-nitrophenyl group _{(p-O 2 NC 6 H} 4 - is preferable to represent any one selected from among) and β- naphthyl group, a phenyl group, a benzyl group, phenethyl group, methyl More preferably, it represents any one selected from a group, an ethyl group, an n-propyl group, an isopropyl group, an isobutyl group, an n-butyl group and a hydroxy group.

R ² is a methyl group, an ethyl group (hereinafter referred to as Et), an n-propyl group (hereinafter referred to as nPr), an isopropyl group (hereinafter referred to as iPr), an n-butyl group, an isobutyl group, or a tert-butyl group (hereinafter referred to as “R”) and tBu), pentyl group, hexyl group, heptyl group, octyl group, a cyclohexyl group (cyclohexyl), phenyl group _{(C 6 H 4 -),} o- tolyl _{(o-CH 3 C 6 H} 4 -), m- tolyl _{(m-CH 3 C 6 H} 4 -), p- tolyl _{(p-CH 3 C 6 H} 4 -), o- methoxyphenyl group _{(o-CH 3 OC 6 H} 4 -), m - methoxyphenyl group _{(m-CH 3 OC 6 H} 4 -), p- methoxyphenyl group _{(p-CH 3 OC 6 H} 4 -), 4- piperonyl group (4-piperonyl), o- fluorophenyl group (o − C ₆ H ₄ -), m- fluorophenyl group _{(m-FC 6 H 4 -} ), p- fluorophenyl group _{(p-FC 6 H 4 -} ), o- chlorophenyl group _{(o-ClC 6 H 4 -} ) , m- chlorophenyl group _{(m-ClC 6 H 4 -} ), p- chlorophenyl group _{(p-ClC 6 H 4 -} ), o- bromophenyl group _{(o-BrC 6 H 4 -} ), m- bromophenyl group ( _{m-BrC 6 H 4 -)} , p- bromophenyl group _{(p-BrC 6 H 4 -} ), o- nitrophenyl group _{(o-O 2 NC 6 H} 4 -), m- nitrophenyl group (m-O ₂ NC ₆ H ₄ —), p-nitrophenyl group (p—O ₂ NC ₆ H ₄ —), α-naphthyl group (α-Naphthyl-), β-naphthyl group (β-Naphthyl-) and α-furyl. Selected from the group (α-furyl) It is preferable to represent any one kind.

  The solvent used in the production method of the present invention is not particularly limited, but it is sufficient that the substrate is dissolved and the reaction does not even occur under the reaction conditions of the production method of the present invention. Specifically, the solvent used in the production method of the present invention may be a nonpolar solvent, a polar solvent or a protic solvent, such as toluene, benzotrifluoride, dichloromethane, chloroform, dichloroethane, diethyl ether, tetrahydrofuran and A solvent selected from methanol is preferred. These solvents may be used alone or in combination of two or more. From the viewpoint of the catalytic effect, a weakly polar solvent such as dichloromethane, chloroform, dichloroethane, diethyl ether, and toluene is more preferable.

  In the production method of the present invention, the molar ratio of the iridium chiral catalyst used during the reaction to the 3-alkenylene group-substituted succinimide represented by the general formula (1) is preferably 1:20 to 1: 10000. From the viewpoint of reaction efficiency, the molar ratio is more preferably 1:50 to 1: 5000, more preferably 1:50 to 1: 2000, and 1:50 to 1: 1000. More preferably, it is still more preferably 1:50 to 1: 500, and particularly preferably 1: 100 to 1: 200.

  In the production method of the present invention, the hydrogen atmosphere pressure in the hydrogen atmosphere is preferably 1 to 100 bar (0.1 to 10.0 MPa). From the viewpoint of reaction efficiency, the hydrogen atmosphere pressure in the hydrogen atmosphere is 5 to 70 bar ( 0.5 to 7.0 MPa) is more preferable, 10 to 50 bar (1.0 to 5.0 MPa) is more preferable, and 15 to 45 bar (1.5 to 4.5 MPa) is preferable. More preferably, the pressure is 20 to 40 bar (2.0 to 4.0 MPa), still more preferably 25 to 35 bar (2.5 to 3.5 MPa).

  In the production method of the present invention, the reaction temperature is preferably −10 ° C. to 40 ° C., and from the viewpoint of reaction efficiency, the reaction temperature is more preferably 0 ° C. to 30 ° C., and 5 ° C. to 30 ° C. More preferably, it is more preferably 10 ° C to 30 ° C, and still more preferably 20 ° C to 30 ° C.

In the production method of the present invention, the reaction time is preferably 5 minutes to 72 hours, and from the viewpoint of the reaction yield, the reaction time is more preferably 10 minutes to 60 hours, and more preferably 1 hour to 48 hours. It is more preferable that the time is 6 hours to 36 hours, and 12 hours to 24 hours is even more preferable.

  A preferred procedure of the production method of the present invention is as follows. First, the iridium chiral catalyst and the 3-alkenylene group-substituted succinimide represented by the general formula (1) are dissolved in a solvent at the above molar ratio, and the resulting solution is put into a sealed pressure vessel such as an autoclave. Next, after sealing the container and substituting the atmosphere in the container with hydrogen, the pressure in the container is maintained in the above range and the temperature is maintained in the above range, and 3 represented by the general formula (1) -Asymmetric hydrogenation reaction of alkenylene group-substituted succinimide.

  Specific examples of the use of the C-3 substituted chiral succinimide of the present invention represented by the general formula (2) include intermediates for producing drugs for anti-HIV drugs and anti-HSV drugs. It is done. Examples of this drug include dibenzylbutanediol lignans.

  In the following, embodiments of the present invention will be described in detail, which are implemented on the basis of the technical means of the present invention and provide detailed embodiments and specific operation processes. The range is not limited to the following examples.

  In the following examples, the 3-alkenylene group-substituted succinimide (that is, the substrate) represented by the general formula (1) is 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h, 1i, 1j, respectively. 1k, 1l, 1m, 1n, 1o, 1p, 1q, 1r, 1s, 1t, 1u, 1v, 1w, 1x, and 1y and by iridium catalyzed asymmetric hydrogenation of these substrates The corresponding reaction products obtained (namely, the C-3 substituted chiral succinimide represented by the general formula (2)) are respectively 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, 2n, 2o, 2p, 2q, 2r, 2s, 2t, 2u, 2v, 2w, 2x, and 2y. In the examples of the present invention, “solid” or “liquid” used to represent the states of these products 2a to 2y refers to a state under normal temperature and normal pressure conditions.

  In the following examples, the yield is a numerical value obtained by calculation based on the following calculation formula.

Theoretically, the enantiomeric excess ratio (hereinafter referred to as “ee value”) is a numerical value obtained by calculation using the following calculation formula.
Enantiomeric excess% = ([S] − [R]) ÷ ([R] + [S]) × 100%
Here, [S] is the amount of the product of the major enantiomer (arbitrary unit), and [R] is the amount of the product of the minor enantiomer (arbitrary unit).

In the following examples, the enantiomeric excess (ie ee value) was measured by HPLC (chiral column). The instrument used for the HPLC analysis was Shimadzu LC-201, and the specific operating conditions are as follows. Using DAICEL CHIRALPAK AD-H, DAICEL CHIRALCEL OD-H or DAICEL CHIRALPAK AS-H chiral column manufactured by Nippon Daicel, the mobile phase is (n-hexane / isopropanol = 90/10 to 95/5), and the mobile phase is The flow rate is 0.5 mL / min, and the measurement wavelength is 210 nm.
Further, in the following examples, each of the synthesized products was subjected to NMR analysis and high-resolution mass spectral analysis. The description after that is omitted.

In an embodiment of the present invention, the instrument used to perform the NMR analysis is a Varian MERCURY plus-400 (400 MHz, ¹ H; 100 MHz, ¹³ C) spectrometer. The instrument used to perform the high resolution mass spectral analysis is a Q-TOF Premier from Waters, USA. The instrument used for optical rotation analysis was a high precision polarimeter AUTOPOL VI of Rudolf, USA, and measurement was performed using 589 nm light in a 50 mm long tube.

[Example 1]
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 20 bar, and the reaction was carried out at 20 ° C. for 5 minutes. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation, and the yield is 100%. The value was 99%.

2a: white solid, mp 90.7-91.5 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.35-7.26 (m, 5H), 7.25-7.21 (m, 3H), 7.13-7.07 (m, 2H), 4 .62 (s, 2H), 3.21-3.10 (m, 2H), 2.90 (dd, J = 13.2, 7.6, 1H), 2.69 (dd, J = 18. 4, 9.0, 1H), 2.44 (dd, J = 18.4, 4.8, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.2, 176.2, 137.1, 135.9, 129.2, 129.0, 128.9, 128.8, 128.1, 127.2 42.6, 41.4, 36.5, 33.3.
High-resolution mass spectrum (Q-TOF Premier): C ₁₈ H ₁₈ NO ₂ (M + H) ⁺ theoretical calculation value 280.1338; actual value 280.1339.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 90/10, 210 nm, 0.5 mL / min. t _R1 = 23.6 min (main peak), t _R2 = 25.2 min (next peak)]; ee = 99%, [α] ²⁰ _D = −74.6 (c = 0.40, CHCl ₃ ).

[Example 2]
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L1 · Ir (COD) · BAr _F ) (19.2 mg, 0.0125 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 15 bar and the reaction was carried out at 0 ° C. for 48 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 99%, ee The value was 90%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 3
Preparation of 2a (R ¹ = Bn, R ² = Ph) Iridium chiral catalyst (L3 · Ir (COD) · BAr _F ) (0.41 mg, 0.00025 mmol) and 1a under the conditions of room temperature (25 ° C.) (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 50 bar and the reaction was carried out at 40 ° C. for 72 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 35%, ee The value was 74%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 4
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L4 · Ir (COD) · BAr _F ) (4.1 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (3.46 g, 12.5 mmol) was dissolved in dry CH ₂ Cl ₂ (30 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 25 bar and reacted at 30 ° C. for 48 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 85%, ee The value was 79%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 5
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L5 · Ir (COD) · BAr _F ) (2.2 mg, 0.00125 mmol) and 1a (R ¹ = Bn, R ² = Ph) (3.46 g, 12.5 mmol) was dissolved in dry CH ₂ Cl ₂ (30 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 70 bar, and the reaction was carried out at −10 ° C. for 72 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 22%, ee The value was 19%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 6
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L6 · Ir (COD) · BAr _F ) (8.6 mg, 0.0050 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 40 bar and the reaction was carried out at 10 ° C. for 48 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 13%, ee The value was 5%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 7
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L7 · Ir (COD) · BAr _F ) (4.1 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 30 bar and the reaction was carried out at 15 ° C. for 12 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 87%, ee The value was 31%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 8
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L8 · Ir (COD) · BAr _F ) (4.2 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 35 bar and reacted at 5 ° C. for 60 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed with ligroin / ethyl acetate as the mobile phase, separating to give the product 2a, yield 93%, ee The value was 54%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 9
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L9 · Ir (COD) · BAr _F ) (8.7 mg, 0.0050 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 45 bar, and the reaction was carried out at 25 ° C. for 10 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 27%, ee The value was 38%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 10
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · PF ₆ ) (2.2 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 13%, ee The value was 51%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 11
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · Cl) (2.0 mg, 0.0025 mmol) and 1a ( R ¹ = Bn, R ² = Ph (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 25 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation, and the yield is 6%. The value was 2%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 12
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry ClCH ₂ CH ₂ Cl (2 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 20 bar, and the reaction was carried out at 20 ° C. for 1 hour. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 13
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry PhCH ₃ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and the reaction was carried out at 23 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase, separating to give the product 2a, yield 52%, ee The value was 84%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 14
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry PhCF ₃ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and the reaction was carried out at 22 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 89%, ee The value was 87%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 15
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry MeOH (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and the reaction was carried out at 21 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 6%, ee The value was 3%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 16
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry Et ₂ O (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and the reaction was carried out at 19 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase, separating to give the product 2a, yield 12%, ee The value was 2%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 17
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry THF (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 16 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 2%, ee The value was 10%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 18
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CHCl ₃ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 16 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2a. The yield is 62%, ee The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 19
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in a mixed solvent of dry CH ₂ Cl ₂ (1 mL) and PhCH ₃ (1 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 20 bar, and the reaction was carried out at 16 ° C. for 12 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 20
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 1 bar and reacted at 40 ° C. for 6 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation, and the yield is 100%. The value was 96%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 21
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 5 bar, and the reaction was carried out at 30 ° C. for 1 hour. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

[Example 22]
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 10 bar and the reaction was carried out at 10 ° C. for 1 hour. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 23
Preparation of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 50 bar and the reaction was carried out at 30 ° C. for 10 minutes. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 24
Production of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (69.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 100 bar, and the reaction was allowed to proceed for 36 hours at −10 ° C. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation, and the yield is 100%. The value was 95%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 25
^{2a (R 1 = Bn, R} 2 = Ph) under the conditions of manufacture at room temperature (25 ° C.) of iridium chiral catalyst _{(L2 · Ir (COD) ·} BAr F) (4.0mg, 0.0025mmol) and, 1a (R ¹ = Bn, R ² = Ph) (138.6 mg, 0.50 mmol) was dissolved in dry CH ₂ Cl ₂ (3 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 29 ° C. for 1 hour. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 26
Production of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (346.6 mg, 1.25 mmol) was dissolved in dry CH ₂ Cl ₂ (6 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 20 bar, and the reaction was carried out at 27 ° C. for 1 hour. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 27
Production of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (693.3 mg, 2.50 mmol) was dissolved in dry CH ₂ Cl ₂ (12 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 28 ° C. for 1.5 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 28
Production of 2a (R ¹ = Bn, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1a (R ¹ = Bn, R ² = Ph) (1.39 g, 5.00 mmol) was dissolved in dry CH ₂ Cl ₂ (20 mL) and placed in an autoclave. The autoclave was closed, replaced with hydrogen three times, the final pressure was maintained at 20 bar, and the reaction was carried out at 28 ° C. for 24 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2a is obtained by separation. The value was 98%.
^The product was confirmed based on the results of ¹ H NMR, ¹³ C NMR, and high resolution mass spectral analysis.

Example 29
Production of 2b (R ¹ = Ph, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1b (R ¹ = Ph, R ² = Ph) (65.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 15 bar and reacted at 0 ° C. for 6 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2b. The value was 96%.

2b: white solid, melting point 130.3-131.2 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.45 (t, J = 7.8, 2H), 7.40-7.32 (m, 3H), 7.29 (d, J = 6.4) 1H), 7.22 (d, J = 7.2, 2H), 7.17 (d, J = 7.2, 2H), 3.36-3.29 (m, 1H), 3.25 ( dd, J = 13.6, 4.4, 1H), 3.08 (dd, J = 13.6, 8.0, 1H), 2.88 (dd, J = 18.4, 8.8, 1H), 2.65 (dd, J = 18.4, 4.8, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 178.5, 175.4, 136.9, 132.1, 129.4, 129.4, 129.8, 128.8, 127.5, 126.7, 41.5, 36.8, 33.5.
High-resolution mass spectrum (Q-TOF Premier): C ₁₇ H ₁₆ NO ₂ (M + H) ⁺ theoretical calculated value 266.1118; found value 266.1178.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 90/10, 210 nm, 0.5 mL / min. t _R1 = 49.5 min (next peak), t _R2 = 54.9 min (main peak)]; ee = 96%, [α] ²⁰ _D = −113.2 (c = 0.30, CHCl ₃ ).

Example 30
Production of 2c (R ¹ = nBu, R ² = Ph) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1c (R ¹ = nBu, R ² = Ph) (60.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2c is obtained by separation, and the yield is 100%. The value was 98%.

2c: colorless liquid.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.33-7.20 (m, 3H), 7.15 (d, J = 6.7, 2H), 3.44 (t, J = 7.6) 2H), 3.18 (dd, J = 13.4, 4.0, 1H), 3.10 (ddd, J = 13.4, 8.9, 4.4, 1H), 2.89 (dd , J = 13.4, 8.3, 1H), 2.66 (dd, J = 18.5, 8.9, 1H), 2.42 (dd, J = 18.5, 4.4, 1H) ), 1.52-1.42 (m, 2H), 1.28-1.16 (m, 2H), 0.89 (t, J = 7.2, 3H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.5, 176.6, 137.2, 129.3, 129.0, 127.3, 41.3, 38.8, 36.7, 33.3 29.9, 20.2, 13.8.
High resolution mass spectrum _{(Q-TOF Premier): C} 15 H 20 NO 2 (M + H) + theoretical calc 246.1494; found 246.1490.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 90/10, 210 nm, 0.5 mL / min. t _R1 = 15.6 min (main peak), t _R2 = 16.5 min (next peak)]; ee = 98%, [α] ²⁰ _D = −63.9 (c = 0.35, CHCl ₃ ).

Example 31
Preparation of 2d (R ¹ = CH ₂ CH ₂ Ph, R ² = Ph) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) under conditions of room temperature (25 ° C) ) And 1d (R ¹ = CH ₂ CH ₂ Ph, R ² = Ph) (72.8 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2d. The yield is 100%, ee The value was 95%.
2d: white solid, mp 61.5-62.0 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.32-7.13 (m, 10H), 3.73-3.69 (m, 2H), 3.16 (dd, J = 13.6, 4. 4, lH), 3.09-3.02 (m, 1H), 2.89-2.72 (m, 3H), 2.62 (dd, J = 18.4, 9.0, 1H), 2.38 (dd, J = 18.4, 4.4, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.2, 176.3, 138.0, 137.4, 129.3, 129.1, 129.0, 128.7, 127.3, 126.9, 41.4, 40.0, 36.7, 33.7, 33.4.
High-resolution mass spectrum (Q-TOF Premier): C ₁₇ H ₁₆ NO ₂ (M + H) ⁺ theoretical calculation value 294.1494;
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 90/10, 210 nm, 0.5 mL / min. t _R1 = 25.1 min (main peak), t _R2 = 27.7 min (next peak)]; ee = 95%, [α] ²⁰ _D = −71.9 (c = 0.40, CHCl ₃ ).

[Example 32]
2e (R ¹ = Bn, R ² = 3-Me—C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1e (R ¹ = Bn, R ² = 3-Me—C ₆ H ₄ ) (72.8 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2e is obtained by separation, and the yield is 100%. The value was 98%.

2e: white solid, mp 69.8-70.9 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.32-7.26 (m, 5H), 7.13 (t, J = 7.2 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.93 (s, 1H), 6.90 (d, J = 7.2 Hz, 1H), 4.62 (d, J = 1.2 Hz, 2H), 3.20-3.05 ( m, 2H), 2.90-2.78 (m, 1H), 2.68 (dd, J = 18.4, 9.2 Hz, 1H), 2.46 (dd, J = 18.4, 4). .8Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.2, 176.3, 138.7, 137.1, 135.9, 130.1, 128.9, 128.1, 128.0, 126.3 42.5, 36.4, 33.4, 21.6.
High-resolution mass spectrum (Q-TOF Premier): C ₁₉ H ₂₀ NO ₂ (M + H) ⁺ theoretical calculation value 294.1494; actual value 294.1488.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 22.9 min (main peak), t _R2 = 24.8 min (next peak)]; ee = 98%, [α] ²⁰ _D = −74.4 (c = 0.40, CHCl ₃ ).

Example 33
2f (R ¹ = Bn, R ² = 4-Me-C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1f (R ¹ = Bn, R ² = 4-Me—C ₆ H ₄ ) (72.8 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase, separating to give the product 2f, yield 100%, ee The value was 99%.

2f: white solid, melting point 91.8-92.7 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.33-7.26 (m, 5H), 7.03 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 4.61 (s, 2H), 3.15-3.08 (m, 2H), 2.90-2.84 (m, 1H), 2.68 (dd, J = 18.4, 8.4 Hz, 1H), 2.44 (dd, J = 18.4, 4.6 Hz, 1H), 2.29 (s, 3H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.3, 176.3, 136.8, 135.9, 133.9, 129.7, 129.2, 128.9, 128.8, 128.1 42.6, 41.4, 36.0, 33.3, 21.2.
High-resolution mass spectrum (Q-TOF Premier): C ₁₉ H ₂₀ NO ₂ (M + H) ⁺ theoretical calculation value 294.1494; actual value 294.1488.
HPLC [DAICEL CHIRALPAK AS-H, hexane / i-PrOH = 90/10, 210 nm, 0.5 mL / min. t _R1 = 35.4 min (main peak), t _R2 = 40.6 min (next peak)]; ee = 99%, [α] ²⁰ _D = −77.9 (c = 0.20, CHCl ₃ ).

Example 34
Production of 2 g (R ¹ = Bn, R ² = 2-MeO—C ₆ H ₄ ) Under conditions of room temperature (25 ° C.), an iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and ¹ g (R ¹ = Bn, R ² = 2-MeO—C ₆ H ₄ ) (76.8 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product is obtained by separation to give 2 g of product with a yield of 100%, ee The value was 84%.

2 g: white solid, melting point 82.0-83.1 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.36-7.26 (m, 5H), 7.22 (td, J = 8.0, 2.0 Hz, 1H), 7.06 (dd, J = 8.0, 1.6 Hz, 1H), 6.85-6.81 (m, 2H), 4.63 (d, J = 0.8 Hz, 2H), 3.79 (s, 3H), 3. 34 (dd, J = 13.2, 4.8 Hz, 1H), 3.21 (m, 1H), 2.75 (dd, J = 13.6, 8.4 Hz, 2H), 2.62 (dd , J = 18.4, 8.8 Hz, 1H), 2.50 (dd, J = 18.4, 4.8 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.6, 176.8, 157.7, 136.1, 131.0, 128.9, 128.8, 128.6, 125.9, 120.9, 110.6, 55.4, 42.5, 40.5, 33.7, 31.4.
High-resolution mass spectrum (Q-TOF Premier): C ₁₉ H ₂₀ NO ₃ (M + H) ⁺ calculated value 310.1443; found value 310.1448.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 34.8 min (main peak), t _R2 = 37.5 min (next peak)]; ee = 84%, [α] ²⁰ _D = −59.9 (c = 0.25, CHCl ₃ ).

Example 35
Preparation of 2h (R ¹ = Bn, R ² = 3-MeO—C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 4.0 mg, at room temperature (25 ° C.)) 0.0025 mmol) and ¹ h (R ¹ = Bn, R ² = 3-MeO—C ₆ H ₄ ) (76.8 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2h is obtained by separation, and the yield is 100%. The value was 97%.

2h: yellow liquid.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31-7.26 (m, 5H), 7.15 (t, J = 7.6 Hz, 1H), 6.76 (ddd, J = 8.0, 2.4, 0.8 Hz, 1H), 6.70-6.65 (m, 2H), 4.62 (s, 2H), 3.74 (s, 3H), 3.19-3.09 ( m, 2H), 2.89-2.82 (m, 2H), 2.69 (dd, J = 18.4, 9.2 Hz, 1H), 2.46 (dd, J = 18.4, 4). .8Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.1, 176.2, 160.0, 138.7, 135.9, 130.0, 128.8, 128.8, 128.1, 121.5, 115.0, 112.5, 55.3, 42.6, 41.4, 36.5, 33.3.
High-resolution mass spectrum (Q-TOF Premier): C ₁₉ H ₂₀ NO ₃ (M + H) ⁺ calculated value 310.1443; found value 310.1439.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 36.5 min (main peak), t _R2 = 40.9 min (next peak)]; ee = 97%, [α] ²⁰ _D = −78.0 (c = 0.15, CHCl ₃ ).

Example 36
2i (R ¹ = Bn, R ² = 4-MeO—C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 4.0 mg, under conditions of room temperature (25 ° C.)) 0.0025 mmol) and 1i (R ¹ = Bn, R ² = 4-MeO—C ₆ H ₄ ) (76.8 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase, and the product 2i is obtained by separation, with a yield of 100%, ee The value was 99%.

2i: White crystals, melting point 86.3-87.0 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31-7.27 (m, 5H), 7.01-6.97 (m, 2H), 6.96-6.71 (m, 2H), 4 .60 (s, 2H), 3.76 (s, 3H), 3.14-3.04 (m, 2H), 2.93-2.87 (m, 1H), 2.68 (dd, J = 18.4, 8.4 Hz, 1H), 2.44 (dd, J = 18.4, 4.4 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.3, 176.3, 158.8, 135.9, 130.3, 128.9, 128.8, 128.8, 128.1, 114.4 55.4, 42.6, 41.5, 35.5, 33.2.
High-resolution mass spectrum (Q-TOF Premier): C ₁₉ H ₂₀ NO ₃ (M + H) ⁺ calculated value 310.1443; found value 310.1445.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 36.3 min (main peak), t _R2 = 41.0 min (next peak)]; ee = 99%, [α] ²⁰ _D = −82.0 (c = 0.40, CHCl ₃ ).

Example 37
2j (R ¹ = Bn, R ² = 4-Piperonyl) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1j (R ¹ = Bn, R ² = 4-Piperonyl) (80.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2j is obtained by separation, with a yield of 100%, ee The value was 99%.

2j: white solid, mp 92.0-92.6 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.32-7.25 (m, 5H), 6.66 (d, J = 7.6 Hz, 1H), 6.60 (d, J = 1.6 Hz, lH), 6.53 (dd, J = 7.6, 1.6 Hz, 1H), 5.93 (d, J = 1.0 Hz, 1H), 5.92 (d, J = 1.0 Hz, 1H) ), 4.62 (d, J = 1.2 Hz, 2H), 3.11-3.02 (m, 2H), 2.88-2.83 (m, 1H), 2.69 (dd, J = 18.4, 8.8 Hz, 1H), 2.45 (dd, J = 18.4, 4.8 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.1, 176.2, 148.1, 146.8, 135.9, 130.6, 128.8, 128.8, 128.1, 122.4 109.6, 108.7, 101.2, 42.6, 41.5, 36.1, 33.2.
High resolution mass spectrum (Q-TOF Premier): Theoretical Calculated ^{_{C 19 H 18 NO 4 (M}} + H) +: 324.1236; Found 324.1231.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 52.2 min (main peak), t _R2 = 58.1 min (next peak)]; ee = 99%, [α] ²⁰ _D = −75.9 (c = 0.40, CHCl ₃ ).

Example 38
Production of 2k (R ¹ = Bn, R ² = 4-F—C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, at room temperature (25 ° C.)) 0.0025 mmol) and 1k (R ¹ = Bn, R ² = 4-F—C ₆ H ₄ ) (64.8 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed with ligroin / ethyl acetate as the mobile phase, separating to give the product 2k, yield 100%, ee The value was 99%.

2k: white crystals, melting point 97.7-98.2 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31-7.26 (m, 5H), 7.06-7.01 (m, 2H), 6.91-6.86 (m, 2H), 4 .60 (s, 2H), 3.15-3.06 (m, 2H), 2.97-2.90 (m, 1H), 2.71 (dd, J = 18.4, 9.2 Hz, 1H), 2.41 (dd, J = 18.4, 4.8 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.0, 176.0, 162.1 (d, J _C-F = 243.9 Hz), 135.8, 132.6 (d, J _C-F = 2 .6 Hz), 130.8 (d, J _C−F = 7.5 Hz), 128.9, 128.9, 128.2, 115.9 (d, J _C−F = 21.2 Hz), 42. 6, 41.3, 35.6, 33.2.
High resolution mass spectrum _{(Q-TOF Premier): C} 18 H 17 NO 2 F (M + H) + theoretical calc 298.1243; found 298.1243.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 28.4 min (main peak), t _R2 = 32.2 min (next peak)]; ee = 99%, [α] ²⁰ _D = −74.5 (c = 0.40, CHCl ₃ ).

Example 39
2l (R ¹ = Bn, R ² = 2-Cl-C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and ¹ l (R ¹ = Bn, R ² = 2—Cl—C ₆ H ₄ ) (77.9 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed with ligroin / ethyl acetate as the mobile phase, separating to give the product 2l, yield 100%, ee The value was 82%.

21: white solid, melting point 87.2-88.0 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.38—7.27 (m, 6H), 7.24-7.12 (m, 3H), 4.65 (s, 2H), 3.46 (dd , J = 14.0, 4.8 Hz, 1H), 3.29-3.21 (m, 1H), 2.88 (dd, J = 14.0, 8.8 Hz, 1H), 2.69 ( dd, J = 18.4, 8.8 Hz, 1H), 2.48 (dd, J = 18.4, 4.8 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 178.9, 176.1, 135.9, 135.4, 134.4, 131.2, 130.1, 129.0, 128.9, 128.8, 128.2, 127.4, 42.7, 40.2, 34.2, 33.6.
High resolution mass spectrum _{(Q-TOF Premier): C} 18 H 17 NO 2 Cl (M + H) + theoretical calc 314.0948; found 314.0940.
HPLC [DAICEL CHIRALPAK AS-H, hexane / i-PrOH = 93/7, 210 nm, 0.5 mL / min. t _R1 = 52.8 min (next peak), t _R2 = 55.7 min (main peak)]; ee = 82%, [α] ²⁰ _D = −45.7 (c = 0.40, CHCl ₃ ).

Example 40
Production of 2m (R ¹ = Bn, R ² = 3-Cl-C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, under conditions of room temperature (25 ° C)) 0.0025 mmol) and ¹ m (R ¹ = Bn, R ² = 3-Cl—C ₆ H ₄ ) (77.9 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2m is obtained by separation, and the yield is 100%. The value was 98%.

2m: white solid, melting point 69.4-70.8 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.33-7.26 (m, 5H), 7.20 (ddd, J = 8.0, 3.6, 1.6 Hz, 1H), 7.17- 7.13 (m, 2H), 6.99-7.96 (m, 1H), 4.62 (d, J = 1.6 Hz, 2H), 3.19-3.08 (m, 2H), 2.91-2.83 (m, 1H), 2.71 (dd, J = 18.4, 9.2 Hz, 1H), 2.40 (dd, J = 18.4, 4.8 Hz, 1H) ;
¹³ C NMR (100 MHz, CDCl ₃ ) δ 178.7, 175.8, 139.3, 135.8, 134.8, 130.3, 129.4, 128.9, 129.9, 128.2 127.5, 127.4, 42.7, 41.2, 36.1, 33.3.
High resolution mass spectrum _{(Q-TOF Premier): C} 18 H 17 NO 2 Cl (M + H) + theoretical calc 314.0948; found 314.0945.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 22.9 min (main peak), t _R2 = 24.8 min (next peak)]; ee = 98%, [α] ²⁰ _D = −59.4 (c = 0.40, CHCl ₃ ).

Example 41
2n (R ¹ = Bn, R ² = 4-Cl—C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and ¹ n (R ¹ = Bn, R ² = 4-Cl—C ₆ H ₄ ) (77.9 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2n is obtained by separation, with a yield of 100%, ee The value was 98%.

2n: white crystals, melting point 117.9-118.6 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.31-7.26 (m, 5H), 7.18-7.14 (m, 2H), 7.02-6.99 (m, 2H), 4 .60 (s, 2H), 3.15-3.06 (m, 2H), 2.96-2.89 (m, lH), 2.71 (dd, J = 18.4, 8.8 Hz, 1H), 2.40 (dd, J = 18.4, 4.8 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 178.8, 175.9, 135.8, 135.3, 133.2, 130.6, 129.1, 128.9, 128.8, 128.2 42.6, 41.1, 35.7, 33.2.
High resolution mass spectrum _{(Q-TOF Premier): C} 18 H 17 NO 2 Cl (M + H) + theoretical calc 314.0948; found 314.0948.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 29.4 min (main peak), t _R2 = 32.2 min (next peak)]; ee = 98%, [α] ²⁰ _D = −71.5 (c = 0.10, CHCl ₃ ).

Example 42
Production of 2o (R ¹ = Bn, R ² = 4-Br—C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, under conditions of room temperature (25 ° C.)) 0.0025 mmol) and 1o (R ¹ = Bn, R ² = 4-Br—C ₆ H ₄ ) (77.9 mg, 0.25 mmol) were dissolved in dry CH ₂ Cl ₂ (2 mL) and autoclaved. Placed inside. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase and separated to give product 2o, yield 100%, ee The value was 95%.

2o: white solid, mp 127.8-128.4 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.33-7.27 (m, 7H), 6.97-6.93 (m, 2H), 4.61 (s, 2H), 3.15-3 .04 (m, 2H), 2.95-2.88 (m, 1H), 2.71 (dd, J = 18.4, 8.8 Hz, 1H), 2.40 (dd, J = 18.0. 4, 4.8 Hz, 1 H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 178.8, 175.8, 135.8, 135.8, 132.1, 131.0, 128.9, 128.8, 128.2, 121.3, 42.7, 41.0, 35.8, 33.2.
High resolution mass spectrum _{(Q-TOF Premier): C} 18 H 17 NO 2 Br (M + H) + theoretical calc 358.0443; found 358.0443.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 30.5 min (main peak), t _R2 = 33.0 min (next peak)]; ee = 95%, [α] ²⁰ _D = −68.6 (c = 0.29, CHCl ₃ ).

Example 43
2p (R ¹ = Bn, R ² = 4-O ₂ N—C ₆ H ₄ ) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4. 0 mg, 0.0025 mmol) and 1p (R ¹ = Bn, R ² = 4-O ₂ N—C ₆ H ₄ ) (80.6 mg, 0.25 mmol) in dried CH ₂ Cl ₂ (2 mL). And then placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2p. The value was 95%.

2p: Pale yellow powder solid, melting point 138.5-139.7 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05-8.01 (m, 2H), 7.30-7.28 (m, 5H), 7.25-7.22 (m, 2H), 4 .60 (d, J = 0.4 Hz, 2H), 3.23-3.15 (m, 2H), 3.11-3.04 (m, 1H), 2.78 (dd, J = 18. 2,8.8 Hz, 1H), 2.44 (dd, J = 18.2, 4.8 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 178.3, 175.4, 147.3, 144.5, 135.7, 130.1, 129.1, 128.8, 128.3, 124.1 42.7, 40.7, 36.2, 33.3.
High resolution mass spectrum _{(Q-TOF Premier): C} 18 H 17 N 2 O 4 (M + H) + theoretical Calculated: 325.1188; Found: 325.1189.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 85/15, 210 nm, 0.5 mL / min. t _R1 = 42.3 min (main peak), t _R2 = 45.1 min (next peak)]; ee = 95%, [α] ²⁰ _D = −62.1 (c = 0.40, CHCl ₃ ).

Example 44
Production of 2q (R ¹ = Bn, R ² = α-Naphthyl) Under the conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1q (R ¹ = Bn, R ² = α-Naphthyl) (81.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2q is obtained by separation, and the yield is 100%. The value was 79%.

2q: white crystals, melting point 123.2-124.6 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 8.06 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H), 7.77 (d, J = 8. 4 Hz, 1H), 7.57-7.49 (m, 2H), 7.39-7.25 (m, 7H), 4.68 (d, J = 2.4 Hz, 2H), 3.98 ( dd, J = 14.0, 4.0 Hz, 1H), 3.34-3.27 (m, 1H), 2.96 (dd, J = 14.6, 10.6 Hz, 1H), 2.59. (Dd, J = 18.4, 9.0 Hz, 1H), 2.48 (dd, J = 18.4, 5.0 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.3, 176.2, 136.0, 134.2, 133.8, 131.7, 129.3, 129.0, 128.9, 128.2 128.2, 127.1, 126.8, 126.2, 125.7, 123.4, 42.7, 40.9, 34.4, 34.3.
High-resolution mass spectrum (Q-TOF Premier) C ₂₂ H ₂₀ NO ₂ (M + H) ⁺ theoretical calculation: 330.1494; found: 330.1486.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 35.1 min (main peak), t _R2 = 38.4 min (next peak)]; ee = 79%, [α] ²⁰ _D = −38.1 (c = 0.40, CHCl ₃ ).

Example 45
Production of 2r (R ¹ = Bn, R ² = β-Naphthyl) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1r (R ¹ = Bn, R ² = β-Naphthyl) (81.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the autoclave gas is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2r is obtained by separation, and the yield is 100%. The value was 97%.
2r: white crystals, melting point 123.6-124.8 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.81-7.78 (m, 1H), 7.74-7.70 (m, 2H), 7.58 (s, 1H), 7.50-7 .44 (m, 2H), 7.30-7.21 (m, 6H), 4.63 (s, 2H), 3.36 (dd, J = 13.9, 4.6 Hz, 1H), 3 .28-3.21 (m, 1H), 3.06 (dd, J = 13.9, 8.4 Hz, 1H), 2.71 (dd, J = 18.4, 9.2 Hz, 1H), 2.51 (dd, J = 18.4, 4.8 Hz, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 179.1, 176.1, 135.8, 134.6, 133.6, 132.6, 128.8, 128.8, 128.8, 128.1 128.0, 127.9, 127.8, 127.2, 126.5, 126.1, 42.6, 41.4, 36.7, 33.4.
High resolution mass spectrum _{(Q-TOF Premier) C 22} H 20 NO 2 (M + H) + theoretical Calculated: 330.1494; Found: 330.1494.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 36.3 min (main peak), t _R2 = 40.7 min (next peak)]; ee = 97%, [α] ²⁰ _D = −72.7 (c = 0.40, CHCl ₃ ).

Example 46
Production of 2s (R ¹ = Bn, R ² = α-Furyl) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1 s (R ¹ = Bn, R ² = α-Furyl) (66.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, and the product 2s is obtained by separation. The value was 97%.

2s: yellow solid, melting point 123.4-124.7 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.35-7.27 (m, 5H), 7.13 (dd, J = 1.6, 0.8 Hz, 1H), 6.20 (dd, J = 3.2, 1.6 Hz, 1H), 6.00 (dd, J = 3.2, 0.8 Hz, 1H), 4.63 (s, 2H), 3.16-3.10 (m, 2H) ), 3.03 (dd, J = 16.4, 8.5 Hz, 1H), 2.79 (dd, J = 18.4, 8.5 Hz, 1H), 2.52 (dd, J = 18.0. 4, 4.8 Hz, 1 H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 178.8, 176.1, 151.1, 142.3, 135.9, 129.0, 128.8, 128.1, 110.5, 107.9, 42.7, 39.4, 33.6, 30.0.
High resolution mass spectrum _{(Q-TOF Premier) C 16} H 16 NO 3 (M + H) + theoretical calc 270.1130; found: 270.1127.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 92/8, 210 nm, 0.5 mL / min. t _R1 = 27.8 min (main peak), t _R2 = 31.7 min (next peak)]; ee = 97%, [α] ²⁰ _D = −36.1 (c = 0.30, CHCl ₃ ).

Example 47
Production of 2t (R ¹ = Bn, R ² = Cyclohexyl) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1t (R ¹ = Bn, R ² = Cyclohexyl) (70.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase, and the product 2t is obtained by separation, with a yield of 100%, ee The value was 88%.

2t: white solid, melting point 73.0-73.8 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.37-7.34 (m, 2H), 7.32-7.24 (m, 3H), 4.63 (d, J = 2.8 Hz, 2H) , 2.89-2.78 (m, 2H), 2.39-2.32 (m, 1H), 1.87-1.80 (m, 1H), 1.71-1.08 (m, 10H), 0.99-0.84 (m, 2H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 180.4, 176.6, 136.1, 129.0, 128.8, 128.1, 42.5, 39.3, 37.9, 35.6 35.2, 34.0, 32.4, 26.6, 26.4, 26.2.
High resolution mass spectrum _{(Q-TOF Premier) C 18} H 24 NO 2 (M + H) + theoretical calc 286.1807; found: 286.1803.
HPLC [DAICEL CHIRALCEL OD-H, hexane / i-PrOH = 95/5, 210 nm, 0.5 mL / min. t _R1 = 31.0 min (main peak), t _R2 = 33.5 min (next peak)]; ee = 88%, [α] ²⁰ _D = −12.3 (c = 0.40, CHCl ₃ ).

Example 48
Production of 2u (R ¹ = Bn, R ² = tBu) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1u (R ¹ = Bn, R ² = tBu) (64.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 48 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase, separating to give the product 2u, yield 79%, ee The value was 40%.

2u: colorless liquid.
¹ H NMR (400 MHz, CDCl ₃ ) δ = 7.38-7.35 (m, 2H), 7.32-7.25 (m, 3H), 4.64 (d, J = 3.6 Hz, 2H) ), 2.92 (dd, J = 18.2, 9.0 Hz, 1H), 2.79-2.72 (m, 1H), 2.42 (dd, J = 18.2, 4.6 Hz, lH), 2.08 (dd, J = 14.2, 2.2 Hz, 1H), 1.27 (dd, J = 13.8, 11.0 Hz, 1H), 0.94 (s, 9H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ = 180.7, 176.6, 136.1, 129.0, 128.8, 128.1, 46.0, 42.7, 37.6, 37.6 31.1, 29.8.
High-resolution mass spectrum (Q-TOF Premier): C ₁₆ H ₂₂ NO ₂ (M + H) ⁺ calculated value: 260.1651; found value 260.1645.
HPLC [DAICEL CHIRALCEL OD-H, hexane / i-PrOH = 95/5, 210 nm, 0.5 mL / min. t _R1 = 30.5 min (next peak), t _R2 = 32.6 min (main peak)]; ee = 40%, [α] ²⁰ _D = −2.8 (c = 0.34, CHCl ₃ ).

Example 49
Production of 2v (R ¹ = Bn, R ² = nPr) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1v (R ¹ = Bn, R ² = nPr) (60.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2v. The value was 95%.
2v: colorless liquid.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.38-7.35 (m, 2H), 7.32-7.24 (m, 3H), 4.64 (d, J = 1.6 Hz, 2H) 2.8.2.74 (m, 2H), 2.44 (dd, J = 17.2, 3.6 Hz, 1H), 1.94-1.86 (m, 1H), 1.54- 1.44 (m, 1H), 1.37-1.24 (m, 5H), 0.88 (t, J = 7.2 Hz, 3H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 180.0, 176.6, 136.1, 128.9, 128.8, 128.1, 42.5, 40.1, 34.6, 31.2, 29.0, 22.6, 14.1.
High resolution mass spectrum _{(Q-TOF Premier) C 15} H 20 NO 2 (M + H) + theoretical calc 246.1494; found: 246.1489.
HPLC [DAICEL CHIRALPAK AS-H, hexane / i-PrOH = 93/7, 210 nm, 0.5 mL / min. t _R1 = 22.4 min (next peak), t _R2 = 23.5 min (main peak)]; ee = 95%, [α] ²⁰ _D = −10.8 (c = 0.23, CHCl ₃ ).

Example 50
Production of 2w (R ¹ = Bn, R ² = iPr) Under conditions of room temperature (25 ° C.), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1w (R ¹ = Bn, R ² = iPr) (60.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. Thereafter, the gas in the autoclave is slowly released, the solvent is removed by rotary evaporation, and silica gel column chromatography is performed using ligroin / ethyl acetate as a mobile phase, followed by separation to obtain the product 2w. The yield is 100%, ee The value was 88%.

2w: white solid, melting point 52.6-53.7 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.38-7.34 (m, 2H), 7.32-7.24 (m, 3H), 4.64 (d, J = 2.4 Hz, 2H) 2.87-2.78 (m, 2H), 2.35 (dd, J = 21.4, 8.2 Hz, 1H), 1.85-1.78 (m, 1H), 1.75- 1.65 (m, 1H), 1.38-1.29 (m, 1H), 0.94 (d, J = 6.4 Hz, 3H), 0.91 (d, J = 6.4 Hz, 3H) );
¹³ C NMR (100 MHz, CDCl ₃ ) δ 180.3, 176.5, 136.1, 128.9, 128.8, 128.1, 42.5, 40.7, 38.6, 35.1 26.3, 23.3, 21.7.
High resolution mass spectrum _{(Q-TOF Premier) C 15} H 20 NO 2 (M + H) + theoretical Calculated: 246.1494; Found: 246.1488.
HPLC [DAICEL CHIRALCEL OD-H, hexane / i-PrOH = 95/5, 210 nm, 0.5 mL / min. t _R1 = 28.0 min (next peak), t _R2 = 30.6 min (main peak)]; ee = 88%, [α] ²⁰ _D = −8.8 (c = 0.40, CHCl ₃ ).

Example 51
Production of 2x (R ¹ = Bn, R ² = Et) Under conditions of room temperature (25 ° C), iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1x (R ¹ = Bn, R ² = Et) (57.3 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and reacted at 20 ° C. for 24 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase and separated to give product 2x, yield 100%, ee The value was 97%.

2x: white solid, mp 39.6-40.8 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.37-7.34 (m, 2H), 7.32-7.24 (m, 3H), 4.64 (d, J = 2.0 Hz, 2H) , 2.86-2.76 (m, 2H), 2.41-2.34 (m, 1H), 1.92-1.84 (m, 1H), 1.52-1.44 (m, 1H), 1.43-1.32 (m, 2H), 0.93 (t, J = 7.6 Hz, 3H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 180.0, 176.6, 136.1, 128.9, 128.8, 128.1, 42.5, 40.0, 34.6, 33.6 20.2, 14.0.
High resolution mass spectrum _{(Q-TOF Premier) C 14} H 18 NO 2 (M + H) + theoretical Calculated: 232.1338; Found: 232.1342.
HPLC [DAICEL CHIRALCEL OD-H, hexane / i-PrOH = 95/5, 210 nm, 0.5 mL / min. t _R1 = 31.2 min (main peak), t _R2 = 32.8 min (next peak)]; ee = 97%, [α] ²⁰ _D = −5.2 (c = 0.23, CHCl ₃ ).

Example 52
Preparation of 2y (R ¹ = OH, R ² = Ph) Iridium chiral catalyst (L2 · Ir (COD) · BAr _F ) (4.0 mg, 0.0025 mmol) and 1y (R ¹ = OH, R ² = Ph) (50.8 mg, 0.25 mmol) was dissolved in dry CH ₂ Cl ₂ (2 mL) and placed in an autoclave. The autoclave was closed and replaced with hydrogen three times, the final pressure was maintained at 20 bar and the reaction was carried out at 20 ° C. for 10 hours. The autoclave gas is then slowly released, the solvent is rotoevaporated, and silica gel column chromatography is performed using ligroin / ethyl acetate as the mobile phase, separating to give the product 2y, yield 100%, ee The value was 96%.

2y: white solid, melting point 138.5-139.5 ° C.
¹ H NMR (400 MHz, CDCl ₃ ) δ 7.32-7.22 (m, 3H), 7.17-7.15 (m, 2H), 3.23 (dd, J = 14.0, 4. 2, 1H), 3.18-7.12 (m, 1H), 2.83 (dd, J = 14.0, 9.4, 1H), 2.68 (dd, J = 18.2, 8 .2, 1H), 2.43 (dd, J = 18.2, 3.8, 1H);
¹³ C NMR (100 MHz, CDCl ₃ ) δ 175.1, 172.5, 136.8, 129.2, 129.2, 127.4, 38.6, 36.4, 30.8.
High resolution mass spectrum _{(Q-TOF Premier) C 11} H 12 NO 3 (M + H) + theoretical Calculated: 206.0817; Found: 206.0818.
HPLC [DAICEL CHIRALPAK AD-H, hexane / i-PrOH = 90/10, 210 nm, 0.5 mL / min. t _R1 = 37.1 min (next peak), t _R2 = 44.2 min (main peak)]; ee = 96%, [α] ²⁰ _D = −68.5 (c = 0.43, CHCl ₃ ).

Claims (12)

In the method for producing a C-3 substituted chiral succinimide,
The C-3 substituted chiral succinimide is represented by the following general formula (2):
The method for producing the C-3 substituted chiral succinimide is catalyzed by an iridium chiral catalyst in a solvent in a hydrogen atmosphere, and the 3-alkenylene group-substituted succinimide represented by the following general formula (1) is asymmetric hydrogenated. A method for producing a C-3 substituted chiral succinimide, which is converted into a C-3 substituted chiral succinimide represented by the following general formula (2) by causing a oxidization reaction.

(In the formula, R ¹ is a hydroxy group, an aryl group which may or may not have a substituent, or a carbon number of 1 to 8 which may or may not have a substituent. R ² represents an aryl group that may or may not have a substituent, or a C ¹ to C ⁸ that may or may not have a substituent. Represents an alkyl group, * is a chiral center.)   2. The C-3 substituted chiral succinimide according to claim 1, wherein the iridium chiral catalyst is an ionic compound formed by a complex composed of iridium, cyclooctadiene, and a chiral ligand and an anion. Manufacturing method. The chiral ligand is any one selected from L1, L2, L3, L4, L5, L6, L7, L8 and L9, and the structural formulas of L1 to L9 are as shown below. The method for producing a C-3-substituted chiral succinimide according to claim 2, wherein:

  The said anion is 1 type chosen from a chlorine ion, a hexafluorophosphate ion, and a tetrakis (3,5-bis (trifluoromethyl) phenyl) borate ion, The Claim 2 or 3 characterized by the above-mentioned. A method for producing the described C-3 substituted chiral succinimide.   The method for producing a C-3-substituted chiral succinimide according to any one of claims 1 to 4, wherein the solvent is a nonpolar solvent, a polar solvent, or a protic solvent.   6. The solvent according to claim 1, wherein the solvent is at least one selected from toluene, benzotrifluoride, dichloromethane, diethyl ether, dichloroethane, chloroform, tetrahydrofuran, and methanol. A method for producing the described C-3 substituted chiral succinimide. R ¹ represents any one selected from phenyl group, benzyl group, phenethyl group, methyl group, ethyl group, n-propyl group, isopropyl group, isobutyl group, n-butyl group and hydroxy group,
R ² is methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, cyclohexyl group, phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, o-methoxyphenyl group, m-methoxyphenyl group, p-methoxyphenyl group, 4-piperonyl group, o-fluorophenyl group, m-fluorophenyl group, p-fluorophenyl group, o-chlorophenyl group, m-chlorophenyl group, p-chlorophenyl group, o-bromophenyl group, m-bromophenyl group, p-bromophenyl group, o-nitrophenyl group, m-nitrophenyl group , P-nitrophenyl group, α-naphthyl group, β-naphthyl group and α-furyl group The method for producing a C-3 substituted chiral succinimide according to any one of claims 1 to 6, wherein:   The method for producing a C-3-substituted chiral succinimide according to any one of claims 1 to 7, wherein a hydrogen atmosphere pressure of the hydrogen atmosphere is 1 to 100 bar.   The molar ratio between the iridium chiral catalyst and the 3-alkenylene group-substituted succinimide represented by the general formula (1) is 1:20 to 1: 10000. 2. A method for producing a C-3 substituted chiral succinimide according to item 1.   The reaction temperature is from -10 ° C to 40 ° C, and the reaction time is from 5 minutes to 72 hours, The production of a C-3 substituted chiral succinimide according to any one of claims 1 to 9, Method. C-3 position substituted chiral succinimide which is a compound represented by following General formula (2).

(In the formula, R ¹ is a hydroxy group, an aryl group which may or may not have a substituent, or a carbon number of 1 to 8 which may or may not have a substituent. R ² represents an aryl group that may or may not have a substituent, or a C ¹ to C ⁸ that may or may not have a substituent. Represents an alkyl group, * is a chiral center.) R ¹ represents any one selected from phenyl group, benzyl group, phenethyl group, methyl group, ethyl group, n-propyl group, isopropyl group, isobutyl group, n-butyl group and hydroxy group,
R ² is methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, cyclohexyl group, phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, o-methoxyphenyl group, m-methoxyphenyl group, p-methoxyphenyl group, 4-piperonyl group, o-fluorophenyl group, m-fluorophenyl group, p-fluorophenyl group, o-chlorophenyl group, m-chlorophenyl group, p-chlorophenyl group, o-bromophenyl group, m-bromophenyl group, p-bromophenyl group, o-nitrophenyl group, m-nitrophenyl group , P-nitrophenyl group, α-naphthyl group, β-naphthyl group and α-furyl group The C-3 substituted chiral succinimide according to claim 11, wherein