Method for producing optically active amine compound

Abstract

To provide practical production methods for optically active primary and secondary amine compounds that are wide in the application range of substrates and excellent in reaction operativity.SOLUTION: The present invention discloses methods for producing optically active primary and secondary amine compounds by combining the diastereoselective or enantioselective reductive amination reaction of a carbonyl compound by an organic iridium complex catalyst with a specific amino alcohol as an amine source and the oxidative deprotection reaction.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a practical method for producing optically active primary and secondary amine compounds. [Background technology]

[0002] As a method for producing optically active amine compounds, a method of optically resolving a racemic amine compound using an optically active resolving agent is known. However, this method has a problem in that half of the other unnecessary optical isomer is discarded. There is also a method of deriving the desired optically active amine compound from a natural optically active compound as a raw material, but depending on the target structure, it is often difficult to obtain the raw material.

[0003] Many methods for obtaining optically active amine compounds by asymmetric reduction of imine compounds or enamine compounds have been reported. However, it takes time to prepare imine compounds or enamine compounds in advance, and the asymmetric yield is highly dependent on the structure of the substrate, so that the substrates that can be used for the reaction with high asymmetric yield are limited. For example, Patent Document 1 reports a method for producing optically active amine compounds by asymmetric hydrogenation of imine compounds in the presence of an optically active ruthenium catalyst. However, the reaction is limited to substrates that have an aromatic ring next to the imine carbon.

[0004] Although the asymmetric reductive amination reaction, which produces an optically active amine compound in one step by reacting a carbonyl compound with an amine source, is a simple method, the asymmetric yield remains largely dependent on the substrate structure, and many structures remain that cannot be handled by the method. In addition, there are hardly any efficient methods known for catalytic asymmetric reductive amination reactions using optically active catalysts. For example, Patent Document 2 reports an asymmetric reductive amination reaction of ammonium formate and acetophenone in the presence of an optically active iridium catalyst, but the optical purity was only 26% ee at best.

[0005] Diastereoselective reductive amination using an optically active amine as both an asymmetric auxiliary and an amine source can convert a wider range of substrates to optically active amine compounds with high stereoselectivity. Non-Patent Document 1 reports a method in which optically active 1-phenylethylamine is used as an asymmetric auxiliary, and a highly diastereoselective reductive amination reaction is carried out under hydrogenation conditions using a solid catalyst such as Raney Ni, palladium on carbon, or platinum on carbon in the presence of a Lewis acid such as Ti(Oi-Pr)4 or Yb(OAc)3, and the asymmetric auxiliary is deprotected to obtain an optically active amine compound. The same document also reports a method in which optically active tert-butylsulfinamide is used as an asymmetric auxiliary and an amine source, and a highly diastereoselective reductive amination reaction is carried out using DIBAL or L-Selectride in the presence of Ti(OEt)4 at a reaction temperature of -48°C. However, the former method requires an equimolar or more Lewis acid to the substrate, and a large amount of solid catalyst is used. In addition, both the reaction and deprotection are carried out under hydrogenation conditions, which requires special reaction vessels such as pressure cookers. Furthermore, during deprotection from the generated amine compound, not only the phenylethyl group derived from the chiral auxiliary but also the substituent derived from the substrate carbonyl compound may be eliminated, which narrows the range of substrate application. The latter reaction requires extremely low temperatures of -48°C, and uses two equivalents of Lewis acid relative to the substrate and an expensive amine as the chiral auxiliary. For these reasons, both methods cannot be said to be industrially practical production methods in terms of reaction operability, safety, and economy.

[0006] Patent Document 3 reports a method for synthesizing an optically active amine compound by a diastereoselective reductive amination reaction using optically active 1-phenylethylamine as an asymmetric auxiliary and amine source, an optically active iridium complex as a catalyst, and formic acid as a hydrogen source. Although this is a practical reaction, high stereoselectivity can only be obtained for some substrates; for example, in a reaction using β-tetralone as a substrate, the target product can only be obtained with a maximum of 40% de. Furthermore, deprotection of the asymmetric auxiliary is performed by hydrogenation with palladium on carbon, which has the above-mentioned problems. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Patent No. 6173702 [Patent Document 2] Patent No. 6254811 [Patent Document 3] Patent No. 6227889 [Non-patent literature]

[0008] [Non-Patent Document 1] Adv.Synth.Catal.2010,352,753. Summary of the Invention [Problem to be solved by the invention]

[0009] An object of the present invention is to provide a practical method for producing optically active primary and secondary amine compounds which is applicable to a wide range of substrates and has excellent reaction operability. [Means for solving the problem]

[0010] In the course of studying the reductive amination reaction of a carbonyl compound with an amine compound, the present inventors faced the problem that there are substrate structures from which the desired product cannot be obtained with sufficient optical purity by conventional asymmetric reductive amination reactions. Even in diastereoselective reductive amination reactions using optically active amines as chiral auxiliary groups and amine sources, the diastereoselectivity was insufficient depending on the substrate structure. In addition, hydrogenation is used for the deprotection reaction of the chiral auxiliary group, which requires a special reaction vessel such as a pressure kettle, making it difficult to carry out the reaction. Furthermore, there are limitations on the substrate structure required for selective deprotection, which creates major problems in the range of substrate applicability.

[0011] In the course of intensive research, the inventors have found that when a reductive amination reaction of a carbonyl compound is carried out using a specific aminoalcohol as an amine source and a specific organic iridium compound as a catalyst, the reaction proceeds with high diastereoselectivity or enantioselectivity in a wide range of carbonyl compound structures. Furthermore, when a specific aminoalcohol is used as an amine source, the deprotection can be carried out oxidatively by a simple operation, and a special reaction vessel such as a pressure-resistant kettle is not required. In addition, the deprotection conditions are not limited by the above-mentioned substrate structure, so that by combining these, a wide range of optically active primary and secondary amine compounds can be synthesized with high optical purity, and the present invention has been completed.

[0012] That is, the present invention relates to the following. [1] A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) [ka] In the formula, R 1 is a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group in which one or more hydrogen atoms may be substituted with a substituent W, an aryl group having 6 to 22 ring members in which a carbon atom may be substituted with a heteroatom, or a heterocyclyl group having 3 to 20 ring members, W is a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1-C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1-20 sulfenyl group, a C1-20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1-C20 fluoroalkyl group, and two or more Ws are joined together to form one or more rings. Ra, Rb and Rc may be the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members, or an alkylheteroaryl group having 6 to 20 ring members; R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atom may be replaced by a hetero atom, or -C(=O)-ORa, and Ra has the same meaning as defined above. and an amino alcohol represented by the formula: The following general formula (2) [ka] In the formula, R 6 and R 7 are different from each other and each represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acyl group, an ester group bonded at a carbon atom, an amide group bonded at a carbon atom, or a C1-C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be substituted with the substituent W, R 6 and R 7 may be joined together to form a ring; and a carbonyl compound represented by the formula: The following general formula (3) [ka] In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be replaced by the aforementioned substituent W; X is a hydride group or an anionic group; R 8 and R 9 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R 8 or R 9 a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, If j is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (4) [ka] In the formula, Ar, X and R 8 has the same meaning as above, R10 represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 sulfenyl group, a C1 to C20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4, R 8 a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, If l is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (5) [ka] In the formula, Ar and X have the same meanings as above. Y is a nitrogen atom or an oxygen atom, A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted by the substituent W; R 11 represents a C1-C20 sulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb when Y is a nitrogen atom, and one or more hydrogen atoms of these groups may be substituted by the substituent W, and is unsubstituted when Y is an oxygen atom; R 12 , R 13 , R 14 and R 15are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 12 and R 13 and / or R 14 and R 15 may be taken together to form a ring, R 12 or R 13 Either 14 or R 15 may be taken together to form a ring, R 12 Or R 13 and / or R 14 Or R 15 Either of these may be combined with A to form a ring, n is an integer from 0 to 2, or The following general formula (6) [ka] In the formula, Ar and X have the same meanings as above. B is a saturated or unsaturated nitrogen-containing heterocyclic carbene containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted by the substituent W; R 16represents a C1 to C20 sulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 sulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, and one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R 17 , R 18 , R 19 , R 20 and R 21 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 16 , R 17 , R 18 , R 19 and R 20 Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3; with a hydrogen donor compound in the presence of an organic iridium compound represented by the formula: The reaction product has the following general formula (A): [ka] In the formula, R 2 , R 3 , R 4 , and R5 has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

[0013] [2] A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) [ka] In the formula, R 1 is a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group in which one or more hydrogen atoms may be substituted with a substituent W, an aryl group having 6 to 22 ring members in which a carbon atom may be substituted with a heteroatom, or a heterocyclyl group having 3 to 20 ring members, W is a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1-C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1-20 sulfenyl group, a C1-20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1-C20 fluoroalkyl group, and two or more Ws are joined together to form one or more rings. Ra, Rb and Rc may be the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members, or an alkylheteroaryl group having 6 to 20 ring members; R 2 , R 3 , R 4 and R 5are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atom may be replaced by a hetero atom, or -C(=O)-ORa, and Ra has the same meaning as defined above. and an amino alcohol represented by the formula: The following general formula (2) [ka] In the formula, R 6 and R 7 are different from each other and each represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acyl group, an ester group bonded at a carbon atom, an amide group bonded at a carbon atom, or a C1-C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be substituted with the substituent W, R 6 and R 7 may be joined together to form a ring; and a carbonyl compound represented by the formula: The following general formula (7) [ka] In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be replaced by the aforementioned substituent W; X is a hydride group or an anionic group; and an organic iridium compound represented by the formula: The following general formula (8) [ka] In the formula, R 8 and R 9are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R 8 or R 9 a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, If j is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (9) [ka] In the formula, R 8 has the same meaning as above, R 10represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 sulfenyl group, a C1 to C20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4, R 8 a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, If l is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (10) [ka] In the formula, Y is a nitrogen atom or an oxygen atom, A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted by the substituent W; R 11 represents a C1-C20 sulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb when Y is a nitrogen atom, and one or more hydrogen atoms of these groups may be substituted by the substituent W, and is unsubstituted when Y is an oxygen atom; R 12 , R 13 , R 14 and R 15are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 12 and R 13 and / or R 14 and R 15 may be taken together to form a ring, R 12 or R 13 Either 14 or R 15 may be taken together to form a ring, R 12 Or R 13 and / or R 14 Or R 15 Either of these may be combined with A to form a ring, n is an integer from 0 to 2, or The following general formula (11) [ka] In the formula, R 16 represents a C1 to C20 sulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 sulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, and one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R 17 , R 18 , R 19 , R 20 and R 21 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 16 , R 17 , R 18 , R 19 and R 20 Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3, B' is a saturated or unsaturated nitrogen-containing heterocyclic carbene precursor containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted with the substituent W; Z is an anionic group; with a hydrogen donor compound in the presence of an organic compound represented by the formula: The reaction product has the following general formula (A): [ka] In the formula, R 2 , R 3 , R 4 , and R 5 has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

[0014] [3] A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) [ka] In the formula, R 1 is a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group in which one or more hydrogen atoms may be substituted with a substituent W, an aryl group having 6 to 22 ring members in which a carbon atom may be substituted with a heteroatom, or a heterocyclyl group having 3 to 20 ring members, W is a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1-C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1-20 sulfenyl group, a C1-20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1-C20 fluoroalkyl group, and two or more Ws are joined together to form one or more rings. Ra, Rb and Rc may be the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members, or an alkylheteroaryl group having 6 to 20 ring members; R 2 , R 3 , R 4 and R 5 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atom may be replaced by a hetero atom, or -C(=O)-ORa, and Ra has the same meaning as defined above. and an amino alcohol represented by the formula: The following general formula (2) [ka] In the formula, R 6 and R 7 are different from each other and each represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acyl group, an ester group bonded at a carbon atom, an amide group bonded at a carbon atom, or a C1-C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be substituted with the substituent W, R 6 and R 7 may be joined together to form a ring; Carbonyl compounds represented by the formula: A hemiaminal ether, imine or enamine prepared from The following general formula (3) [ka] In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be replaced by the aforementioned substituent W; X is a hydride group or an anionic group; R 8 and R 9 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R 8 or R 9 a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, If j is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (4) [ka] In the formula, Ar, X and R 8 has the same meaning as above, R 10 represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 sulfenyl group, a C1 to C20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4, R 8 a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, If l is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (5) [ka] In the formula, Ar and X have the same meanings as above. Y is a nitrogen atom or an oxygen atom, A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted by the substituent W; R 11 represents a C1-C20 sulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb when Y is a nitrogen atom, and one or more hydrogen atoms of these groups may be substituted by the substituent W, and is unsubstituted when Y is an oxygen atom; R 12 , R 13 , R 14 and R 15 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 12 and R 13 and / or R 14 and R 15 may be taken together to form a ring, R 12 or R 13 Either 14 or R 15 may be taken together to form a ring, R 12 Or R 13 and / or R 14 Or R 15 Either of these may be combined with A to form a ring, n is an integer from 0 to 2, or The following general formula (6) [ka] In the formula, Ar and X have the same meanings as above. B is a saturated or unsaturated nitrogen-containing heterocyclic carbene containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted by the substituent W; R 16 represents a C1 to C20 sulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 sulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, and one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R 17 , R 18 , R 19 , R 20 and R 21 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 16 , R 17 , R 18 , R 19 and R 20Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3; with a hydrogen donor compound in the presence of an organic iridium compound represented by the formula: The reaction product has the following general formula (A): [ka] In the formula, R 2 , R 3 , R 4 , and R 5 has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

[0015] [4] A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) [ka] In the formula, R 1 is a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group in which one or more hydrogen atoms may be substituted with a substituent W, an aryl group having 6 to 22 ring members in which a carbon atom may be substituted with a heteroatom, or a heterocyclyl group having 3 to 20 ring members, W is a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1-C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1-20 sulfenyl group, a C1-20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1-C20 fluoroalkyl group, and two or more Ws are joined together to form one or more rings. Ra, Rb and Rc may be the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members, or an alkylheteroaryl group having 6 to 20 ring members; R 2 , R 3 , R 4 and R 5 are the same or different and each is a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atom may be replaced by a hetero atom, or -C(=O)-ORa, and Ra has the same meaning as above; The following general formula (2) [ka] In the formula, R 6 and R 7 are different from each other and each represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acyl group, an ester group bonded at a carbon atom, an amide group bonded at a carbon atom, or a C1-C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be substituted with the substituent W, R6 and R 7 may be joined together to form a ring; A hemiaminal ether, imine or enamine prepared from a carbonyl compound represented by the formula: The following general formula (7) [ka] In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be replaced by the aforementioned substituent W; X is a hydride group or an anionic group; and an organic iridium compound represented by the formula: The following general formula (8) [ka] In the formula, R 8 and R 9 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R 8 or R 9 a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, If j is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (9) [ka] In the formula, R 8 has the same meaning as above, R 10 represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 sulfenyl group, a C1 to C20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4, R 8 a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, If l is 2 or more, R is 2 or more 8 may be joined together to form one or more rings, The following general formula (10) [ka] In the formula, Y is a nitrogen atom or an oxygen atom, A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted by the substituent W; R 11 represents a C1-C20 sulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb when Y is a nitrogen atom, and one or more hydrogen atoms of these groups may be substituted by the substituent W, and is unsubstituted when Y is an oxygen atom; R 12 , R13 , R 14 and R 15 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 12 and R 13 and / or R 14 and R 15 may be taken together to form a ring, R 12 or R 13 Either 14 or R 15 may be taken together to form a ring, R 12 Or R 13 and / or R 14 Or R 15 Either of these may be combined with A to form a ring, n is an integer of 0 to 2; or The following general formula (11) [ka] In the formula, R 16represents a C1 to C20 sulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 sulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, and one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R 17 , R 18 , R 19 , R 20 and R 21 are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R 16 , R 17 , R 18 , R 19 and R 20 Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3, B' is a saturated or unsaturated nitrogen-containing heterocyclic carbene precursor containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted with the substituent W; Z is an anionic group; with a hydrogen donor compound in the presence of an organic compound represented by the formula: The reaction product has the following general formula (A): [ka] In the formula, R 2 , R 3 , R 4 , and R 5 has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

[0016] [5] The method according to any one of the above [1] to [4], wherein the amino alcohol represented by the general formula (1) is an optically active substance. [6] The method according to any one of the above [1] to [5], wherein the aminoalcohol represented by the general formula (1) is 2-aminoethanol, valinol, 2-amino-1-butanol, leucinol, tert-leucinol, phenylglycinol, phenylalaninol, serine, a serine ester, threonine, or a threonine ester. [7] The method according to any one of [1] to [6] above, wherein n is 0. [8] The method according to any one of [1] to [7] above, wherein m is 1.

[0017] [9] The method according to any one of the above [1] to [8], wherein the organic iridium compound represented by general formula (3), general formula (4), general formula (5) or general formula (6), or the organic compound represented by general formula (8), general formula (9), general formula (10) or general formula (11) is an optically active substance.

[10] The method according to any one of the above [1] to [9], wherein the oxidative deprotection is carried out using periodic acid, a periodate salt or lead tetraacetate as an oxidizing agent.

[11] The method according to any one of the above [1] to

[10] , wherein the hydrogen-donating compound is formic acid or a formate.

[0018]

[12] The method according to any one of the above [1] to

[11] , wherein the carbonyl compound represented by the general formula (2) is 1-indanone, β-tetralone, phenylacetone, pyridylacetone, acetophenone, linear dialkyl ketone, branched dialkyl ketone, cyclohexanone, 3-piperidinone, α-keto acid (keto ester), β-keto acid (keto ester), or γ-keto acid (keto ester), which may have a substituent.

[13] The method according to any one of the above [1] to

[11] , wherein the carbonyl compound represented by the general formula (2) is 5-methoxy-2-tetralone, 5-acetonyl-2-methoxybenzenesulfonamide, 5-acetonyl-7-cyano-1-(3-benzoyloxypropyl)indoline, 3-piperidinone, or 4-cyanoindanone, which may have a substituent. Effect of the Invention

[0019] According to the present invention, by using a specific aminoalcohol as an amine source and a specific organic iridium compound as a catalyst, a reductive amination reaction of a wide range of carbonyl compounds proceeds with high diastereoselectivity or high enantioselectivity. Furthermore, by using a specific aminoalcohol, a deprotection reaction proceeds oxidatively with a simple operation, and optically active primary or secondary amine compounds can be synthesized.

[0020] This makes it possible to produce optically active primary amine compounds, which have been difficult to synthesize with high optical purity in the conventional asymmetric reductive amination reaction of carbonyl compounds using an optically active organometallic complex as a catalyst and an ammonia equivalent as an amine source. In addition, the present invention makes it possible to react carbonyl compounds with high diastereoselectivity, even if the carbonyl compounds have a structure in which diastereoselectivity is insufficient in the diastereoselective reductive amination reaction using an optically active amine as an asymmetric auxiliary group and an amine source. Furthermore, in the conventional method, a hydrogenation reaction is used for the deprotection reaction of the asymmetric auxiliary group, and a special reaction vessel such as a pressure-resistant kettle is required, and there is a restriction on the structure of the substrate. In contrast, in the present invention, both the reduction reaction and the deprotection reaction can be carried out by a simple operation that does not require a special reaction vessel, and the restriction on the substrate structure can be avoided. [Brief description of the drawings]

[0021] [Figure 1] 1 is a reaction formula showing an example of the production method of the present invention. [Diagram 2] 1 shows the structural formulas of carbonyl compounds used in the examples. [Diagram 3] 1 is a structural formula showing an example of an iridium compound used in the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] The present invention will be described in detail below based on preferred embodiments. The present invention is a method for producing an optically active primary or secondary amine compound, comprising the steps of reacting an aminoalcohol represented by general formula (1) described below and a carbonyl compound represented by general formula (2) with a hydrogen-donor compound in the presence of an organic iridium compound represented by general formula (3), general formula (4), general formula (5) or general formula (6), and oxidatively deprotecting a substituent having a 2-hydroxyethyl skeleton on the nitrogen. In the present invention, the "substituent having a 2-hydroxyethyl skeleton on the nitrogen atom" means the moiety represented by the above general formula (A).

[0023] The amino alcohol used in the present invention is represented by the general formula (1): [ka] It is expressed as: In the formula, R 1 is a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group in which one or more hydrogen atoms may be substituted with a substituent W, an aryl group having 6 to 22 ring members in which a carbon atom may be substituted with a heteroatom, or a heterocyclyl group having 3 to 20 ring members.

[0024] In this specification, the term "hydrocarbon group" refers to a group consisting of a carbon skeleton and hydrogen atoms bonded thereto, and includes saturated or unsaturated linear or cyclic hydrocarbon groups. For example, examples of saturated or unsaturated linear hydrocarbon groups include linear or branched alkyl groups, alkenyl groups, and alkynyl groups, while examples of saturated or unsaturated cyclic hydrocarbon groups include cycloalkyl groups, cycloalkenyl groups, cycloalkynyl groups, aryl groups, and groups in which one or more hydrogen atoms of these cyclic hydrocarbon groups are substituted with saturated or unsaturated linear hydrocarbon groups, such as aralkyl groups and arylalkyl groups. In this specification, the alkyl groups, alkenyl groups and alkynyl groups include those having straight or branched chains.

[0025] The substituent W is a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 sulfenyl group, a C1 to C20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group.

[0026] In addition, Ra, Rb and Rc are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members, or an alkylheteroaryl group having 6 to 20 ring members. Specific examples of Ra, Rb, and Rc include, but are not limited to, a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, an n-butyl group, a 2-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, a cyclopentyl group, an n-hexyl group, a cyclohexyl group, a cyclohexylene group, a vinyl group, a propenyl group, a butenyl group, a phenyl group, a toluyl group, a xylyl group, a naphthyl group, a pyridyl group, a furanyl group, a thienyl group, a pyrrolidyl group, a piperidyl group, a benzyl group, and a pyridylmethyl group.

[0027] Specific examples of W include, but are not limited to, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, an n-butyl group, a 2-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, a cyclopentyl group, an n-hexyl group, a cyclohexyl group, a benzyl group, a cyclohexylene group, a vinyl group, a propenyl group, a butenyl group, a phenyl group, a toluyl group, a xylyl group, a naphthyl group, a pyridyl group, a furanyl group, a thienyl group, a pyrrolidyl group, a piperidyl group, a methyl group, a phenyl ... butoxy group, ethoxy group, propoxy group, benzyloxy group, acetyl group, propionyl group, cyclohexanecarbonyl group, benzoyl group, methoxycarbonyl group, ethoxycarbonyl group, tert-butoxycarbonyl group, benzyloxycarbonyl group, acetyloxy group, benzoyloxy group, hydroxyl group, methylamino group, ethylamino group, n-propylamino group, isopropylamino group, dimethylamino group, diethylamino group, di-n-propylamino group, diisopropylamino group,

[0028] Examples of the alkyl group include a carbamoyl group, an N-methylcarbamoyl group, an N,N-dimethylcarbamoyl group, an N-acetylamino group, an N-methyl-N-acetylamino group, an N-benzoylamino group, an N-methyl-N-benzoylamino group, an N-hydroxylamino group, an N-methoxyamino group, a nitro group, a cyano group, a diphenylphosphino group, a dicyclohexylphosphino group, a cyclopropylphosphino group, a cyclobutylphosphino group, a cyclopentylphosphino group, a cyclohexylphosphino group, a methanesulfenyl group, an ethanesulfenyl group, a methanesulfonyl group, an ethanesulfonyl group, a benzenesulfonyl group, a p-toluenesulfonyl group, a trifluoromethanesulfonyl group, a sulfo group, a mercapto group, a methylsilyl group, a dimethylsilyl group, a trimethylsilyl group, a fluorine group, a bromine group, a chlorine group, an iodine group, and a trifluoromethyl group.

[0029] In addition, two or more Ws may join together to form one or more rings. Specific examples of the rings formed include, but are not limited to, cycloalkanes such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, and cycloheptane; aromatic rings such as benzene, naphthalene, and anthracene; aryl-fused cycloalkanes such as indane and tetralin; heteroaromatic rings such as pyrrole, pyridine, pyrazine, pyrimidine, pyridazine, triazine, thiophene, furan, imidazole, oxazole, thiazole, quinoline, benzothiophene, and benzofuran; heterocyclic compounds such as tetrahydrofuran, tetrahydropyran, pyrrolidine, piperidine, coumaran, chroman, indoline, and tetrahydroquinoline; and the like. One or more hydrogen atoms of these rings may be further substituted with a substituent W.

[0030] R 1Specific examples of the alkyl group include, but are not limited to, a hydrogen atom; straight-chain or branched-chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, or dodecyl; fluoroalkyl groups such as a trifluoromethyl group; cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl; unsaturated hydrocarbons such as vinyl or allyl; aralkyl groups such as benzyl; monocyclic or polycyclic aryl groups such as phenyl, naphthyl, anthryl, phenanthryl, or indenyl; and monocyclic or polycyclic heterocyclyl groups such as thienyl, furyl, pyranyl, xanthenyl, pyridyl, pyrrolyl, imidazolinyl, indolyl, carbazoyl, phenanthronyl, pyrrolidyl, or piperidyl, and preferably a hydrogen atom.

[0031] R 2 , R 3 , R 4 and R 5 are the same or different and each is a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by heteroatoms, or -C(=O)-ORa. Ra has the same meaning as above, and R 2 , R 3 , R 4 and R 5Specific examples of include, but are not limited to, a hydrogen atom, a hydrocarbon group such as an alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, heteroaralkyl, aryl, or heteroaryl, a carboxyl group, or an ester group bonded at a carbon atom. Preferred are a hydrogen atom, a saturated chain hydrocarbon group, an aralkyl group, a heteroaralkyl group, an aromatic hydrocarbon group, a heteroaromatic hydrocarbon group, a carboxyl group, or an ester group bonded at a carbon atom, more preferred are a hydrogen atom, a methyl group, an ethyl group, a propyl group, an isopropyl group, an isobutyl group, a 2-butyl group, a tert-butyl group, a benzyl group, a (1H-imidazol-4-yl)methyl group, a (3-indolyl)methyl group, a phenyl group, a hydroxyphenyl group, a carboxyl group, a methoxycarbonyl group, or an ethoxycarbonyl group, and particularly preferred are a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a benzyl group, a phenyl group, a carboxyl group, a methoxycarbonyl group, or an ethoxycarbonyl group.

[0032] More specifically, the aminoalcohol represented by the general formula (1) is, for example, 2-aminoethanol, 2-amino-1-propanol, 2-amino-1-butanol, valinol, leucinol, isoleucinol, tert-leucinol, phenylalaninol, phenylglycinol, histidinol, tryptophanol, tyrosinol, serine, serine ester, threonine, and threonine ester, and preferably 2-aminoethanol, 2-amino-1-propanol, 2-amino-1-butanol, valinol, leucinol, tert-leucinol, phenylalaninol, phenylglycinol, serine, serine ester, threonine, and threonine ester.

[0033] Furthermore, the amino alcohol represented by the general formula (1) may be any of achiral, racemic, and optically active, and is preferably optically active from the viewpoint of stereoselectivity.

[0034] The carbonyl compound used in the present invention is represented by the general formula (2): [ka] It is expressed as: In the formula, R 6 and R 7 are different from each other and are a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acyl group, an ester group bonded at a carbon atom, an amide group bonded at a carbon atom, or a C1-C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be substituted with the substituent W.

[0035] R 6 and R 7 Specific examples of the alkyl group include, but are not limited to, a hydrogen atom, a straight-chain or branched-chain alkyl group such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, or dodecyl, a fluoroalkyl group such as a trifluoromethyl group, a cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, an unsaturated hydrocarbon such as vinyl or allyl, an aralkyl group such as benzyl, phenylethyl, or phenylpropyl, a phenyl, naphthyl, anthryl, or phenanthyl. monocyclic or polycyclic aryl groups such as tolyl and indenyl groups; monocyclic or polycyclic heteroaryl groups such as thienyl, furyl, pyranyl, xanthenyl, pyridyl, pyrrolyl, imidazolinyl, indolyl, carbazoyl, phenanthronyl, pyrrolidyl and piperidyl groups; ester groups such as ferrocenyl group, carboxyl group, methoxycarbonyl group and ethoxycarbonyl group; amide groups such as carbamoyl group, N-methylcarbamoyl group and N,N-dimethylcarbamoyl group; and acyl groups such as acetyl group and benzoyl group.

[0036] Also, R 6 and R 7 may be joined together to form a ring. Specific examples of the ring to be formed include, but are not limited to, cycloalkanes such as cyclopentane, cyclohexane, and cycloheptane; aryl-fused cycloalkanes such as indane and tetralin; and heterocyclic compounds such as tetrahydrofuran, tetrahydropyran, pyrrolidine, piperidine, coumaran, chroman, indoline, and tetrahydroquinoline, and one or more hydrogen atoms of these rings may be substituted with the substituent W.

[0037] More specifically, the carbonyl compound represented by the general formula (2) is preferably, for example, 1-indanone, α-tetralone, β-tetralone, phenylacetone, pyridylacetone, acetophenone, acetonaphthone, propiophenone, linear dialkyl ketone, branched dialkyl ketone, cyclohexanone, pyrrolidinone, piperidinone, α-keto acid (keto ester), β-keto acid (keto ester), γ-keto acid (keto ester), δ-keto acid (keto ester), or the like, which may have a substituent. Particularly preferred are 5-methoxy-2-tetralone, 5-acetonyl-2-methoxybenzenesulfonamide, 5-acetonyl-7-cyano-1-(3-benzoyloxypropyl)indoline, 3-piperidinone, and 4-cyano-1-indanone.

[0038] In addition, in the present invention, an optically active primary or secondary amine compound may be produced by reacting a hemiaminal ether, imine, or enamine prepared from an amino alcohol represented by general formula (1) and a carbonyl compound represented by general formula (2) with a hydrogen donor compound in the presence of an organic iridium compound represented by general formula (3), general formula (4), general formula (5), or general formula (6), and then oxidatively deprotecting the substituent having a 2-hydroxyethyl skeleton on the nitrogen.

[0039] The hemiaminal ether, imine or enamine may be produced in situ or synthesized independently using the aminoalcohol represented by the above general formula (1) and the carbonyl compound represented by the general formula (2) as raw materials.

[0040] The organic iridium compound used in the present invention functions as a catalyst in this method. The organic iridium compound is represented by the general formula (3): [ka] It is expressed as: In the above general formula (3), Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be substituted with the above-mentioned substituent W. Specific examples of Ar include, but are not limited to, an unsubstituted cyclopentadienyl group, a methylcyclopentadienyl group, an ethylcyclopentadienyl group, an isopropylcyclopentadienyl group, a phenylcyclopentadienyl group, a benzylcyclopentadienyl group, a 1,2-dimethylcyclopentadienyl group, a 1,3-dimethylcyclopentadienyl group, a 1,2,3-trimethylcyclopentadienyl group, a 1,2,4-trimethylcyclopentadienyl group, a 1,2,3,4-tetramethylcyclopentadienyl group, a 1,2,3,4,5-pentamethylcyclopentadienyl group (Cp * ), 1,2,3,4,5-pentaphenylcyclopentadienyl group, etc. Among these, 1,2,3,4,5-pentamethylcyclopentadienyl group (Cp * ) and the 1,2,3,4,5-pentaphenylcyclopentadienyl group.

[0041] X is a hydride group or an anionic group. Specific examples of X include, but are not limited to, a hydride group, a hydroxy group, an alkoxy group, a bridged oxo group, a fluorine group, a chlorine group, a bromine group, an iodine group, a tetrafluoroborate group, a tetrahydroborate group, a tetrakispentafluorophenylborate group, a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate group, a hexafluorophosphate group, a hexafluoroantimonate group, a hexachloroantimonate group, a hexafluoroarsenate group, a perchlorate group, an acetoxy group, a benzoyloxy group, a (2,6-dihydroxybenzoyl)oxy group, a (2,5-dihydroxybenzoyl)oxy group, a (3-aminobenzoyl)oxy group, a (2,6-dimethoxybenzoyl)oxy group, a (2,4,6-triisopropylbenzoyl)oxy group,

[0042] Examples of the aryl group include 1-naphthalene carboxylic acid group, 2-naphthalene carboxylic acid group, trifluoroacetoxy group, trifluoromethanesulfonimide group, nitromethyl group, nitroethyl group, toluenesulfonate group, methanesulfonate group, ethanesulfonate group, n-propanesulfonate group, isopropanesulfonate group, n-butanesulfonate group, fluorosulfonate group, fluoromethanesulfonate group, difluoromethanesulfonate group, trifluoromethanesulfonate group, pentafluoroethanesulfonate group, phosphate group, (S)-2,2'-dihydroxy-1,1'-binaphthyl phosphate group, (R)-2,2'-dihydroxy-1,1'-binaphthyl phosphate group, etc. Among these, preferred are hydride group, chlorine group, bromine group, iodine group, tetrafluoroborate group, tetrahydroborate group, and trifluoromethanesulfonate group.

[0043] In addition to the hydride group or anionic group X, Ir may have a neutral molecule that can be coordinated. Specific examples of neutral molecules that can be coordinated to Ir include water, alcohols such as methanol, ethanol, n-propanol, 2-propanol, and 2-methoxyethanol, ethers such as tetrahydrofuran, diethyl ether, diisopropyl ether, cyclopentyl methyl ether, and tert-butyl methyl ether, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethyl sulfoxide, acetone, chloroform, acetonitrile, benzonitrile, pyridine, trialkylphosphines such as trimethylphosphine, triethylphosphine, and tricyclohexylphosphine, and triarylphosphines such as triphenylphosphine. When such neutral molecules are coordinated, they form a cationic complex, and the anionic group exists as a counter anion.

[0044] R 8 and R 9 are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be substituted with the substituent W.

[0045] R 8 and R 9 may be introduced in a plurality of units, and the numbers of substitutions j and k are the same or different and are integers of 0 to 3. When j is 2 or more, 2 or more R 8may be joined together to form one or more rings, such as a phenanthridine ring, an acridine ring, etc. 8 or R 9 A carbon atom in the quinoline ring to which is not bonded may be replaced by a nitrogen atom to form, for example, a naphthyridine ring, a quinoxaline ring, a cinnoline ring, a quinazoline ring, a phthalazine ring, or the like.

[0046] Ra, Rb and Rc have the same meanings as above, R 8 and R 9 Specific examples of the alkyl group include, but are not limited to, a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a 2-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, a cyclopentyl group, an n-hexyl group, a cyclohexyl group, a cyclohexylene group, a vinyl group, a propenyl group, a butenyl group, a phenyl group, a toluyl group, a xylyl group, a naphthyl group, a pyridyl group, a furanyl group, a thienyl group, a pyrrolidyl group, a piperidyl group, a methoxy group, an ethoxy group, a propoxy group, a benzyloxy group, an acetyl group, a propionyl group, a cyclohexanecarbonyl group, a benzoyl group, a methoxycarbonyl group, an ethoxycarbonyl group, an acetyloxy group, a benzoyloxy group, a hydroxyl group,

[0047] methylamino group, ethylamino group, n-propylamino group, isopropylamino group, dimethylamino group, diethylamino group, di-n-propylamino group, diisopropylamino group, carbamoyl group, N-methylcarbamoyl group, N,N-dimethylcarbamoyl group, N-acetylamino group, N-methyl-N-acetylamino group, N-benzoylamino group, N-methyl-N-benzoylamino group, nitro group, cyano group, diphenylphosphino group, dicyclohexylphosphino group, cyclopropylphosphino group, cyclobutylphosphino group, cyclopentylphosphino group, cyclohexylphosphino group, methanesulfenyl group, ethanesulfenyl group, methanesulfonyl group, ethanesulfonyl group, benzenesulfonyl group, p-toluenesulfonyl group, trifluoromethanesulfonyl group,

[0048] Examples of the alkyl group include a sulfo group, a mercapto group, a methylsilyl group, a dimethylsilyl group, a trimethylsilyl group, a fluorine group, a bromine group, a chlorine group, an iodine group, and a trifluoromethyl group. 8 and R 9 is preferably a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a phenyl group, a methoxy group, an ethoxy group, a propoxy group, a benzyloxy group, a hydroxyl group, a dimethylamino group, a diethylamino group, a nitro group, a cyano group, a fluorine group, or a trifluoromethyl group, and particularly preferably a hydrogen atom, a methyl group, an isopropyl group, a methoxy group, an ethoxy group, a hydroxyl group, a dimethylamino group, a nitro group, or a trifluoromethyl group. The organic iridium compound represented by the general formula (3) may be either a racemic or optically active compound.

[0049] The organic iridium compound used in the present invention is represented by the general formula (4): [ka] It is expressed as: In the formula, Ar, X and R 8 has the same meaning as above. R 8 may be introduced in a plurality of units, and the number of substitutions l is an integer of 0 to 4. When l is 2 or more, 2 or more R 8 may be joined together to form one or more rings, such as a quinoline ring, an isoquinoline ring, etc. 8 A carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom to form, for example, a pyridazine ring, a pyrazine ring, a pyrimidine ring, a triazine ring, or the like.

[0050] R 10represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 sulfenyl group, a C1 to C20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be substituted by the substituent W.

[0051] Ra, Rb and Rc have the same meanings as above, R 10 Specific examples of the aryl group include, but are not limited to, a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a 2-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, a cyclopentyl group, an n-hexyl group, a cyclohexyl group, a cyclohexylene group, a vinyl group, a propenyl group, a butenyl group, a phenyl group, a toluyl group, a xylyl group, a diethylphenyl group, a diisopropylphenyl group, a 4-methoxyphenyl group, a 4-dimethylaminophenyl group, and a 4-hydroxyphenyl group. , naphthyl group, pyridyl group, furanyl group, thienyl group, pyrrolidyl group, piperidyl group, methoxy group, ethoxy group, propoxy group, benzyloxy group, acetyl group, propionyl group, cyclohexanecarbonyl group, benzoyl group, methoxycarbonyl group, ethoxycarbonyl group, acetyloxy group, benzoyloxy group, hydroxyl group, methylamino group, ethylamino group, n-propylamino group, isopropylamino group, dimethylamino group, diethylamino group, di-n-propylamino group, diisopropylamino group,

[0052] Examples of the alkyl group include a carbamoyl group, an N-methylcarbamoyl group, an N,N-dimethylcarbamoyl group, an N-acetylamino group, an N-methyl-N-acetylamino group, an N-benzoylamino group, an N-methyl-N-benzoylamino group, a nitro group, a cyano group, a diphenylphosphino group, a dicyclohexylphosphino group, a cyclopropylphosphino group, a cyclobutylphosphino group, a cyclopentylphosphino group, a cyclohexylphosphino group, a methanesulfenyl group, an ethanesulfenyl group, a methanesulfonyl group, an ethanesulfonyl group, a benzenesulfonyl group, a p-toluenesulfonyl group, a trifluoromethanesulfonyl group, a sulfo group, a mercapto group, a methylsilyl group, a dimethylsilyl group, a trimethylsilyl group, a fluorine group, a bromine group, a chlorine group, an iodine group, and a trifluoromethyl group.

[0053] Preferred are a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a phenyl group, a toluyl group, a xylyl group, a diisopropylphenyl group, a 4-methoxyphenyl group, a 4-dimethylaminophenyl group, a 4-hydroxyphenyl group, a 4-trifluoromethylphenyl group, a 4-cyanophenyl group, a 4-fluorophenyl group, and a 4-nitrophenyl group, and particularly preferred are a hydrogen atom, a methyl group, a phenyl group, a p-toluyl group, a 2,6-xylyl group, a 2,6-diisopropylphenyl group, a 4-methoxyphenyl group, a 4-dimethylaminophenyl group, a 4-hydroxyphenyl group, a 4-trifluoromethylphenyl group, and a 4-nitrophenyl group. The organic iridium compound represented by the general formula (4) may be either a racemic or optically active compound.

[0054] The organic iridium compound used in the present invention is represented by the general formula (5): [ka] It is expressed as: In the formula, Ar and X have the same meanings as defined above. Y is a nitrogen atom or an oxygen atom, and in either case is bound to iridium by forming a covalent bond. A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted with the substituent W described above. A may be a monocyclic group or a polycyclic group. The number of ring members in each ring constituting A is, for example, 4 to 8, and preferably 5 to 6, but is not limited thereto.

[0055] Specific examples of A include nitrogen-containing aromatic rings such as pyridine, pyridazine, pyrazine, pyrimidine, triazine, and tetrazine; nitrogen-containing polycyclic aromatic rings such as quinoline, isoquinoline, quinazoline, quinoxaline, acridine, phthalazine, and naphthyridine; 5-membered nitrogen-containing aromatic rings such as imidazole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, triazole, and tetrazole; 5-membered nitrogen-containing non-aromatic rings such as azetidine, pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine, pyrazoline, oxadoline, indoline, and isoindoline; and 6-membered nitrogen-containing non-aromatic rings such as piperidine, piperazine, morpholine, quinuclidine, 5,6,7,8-tetrahydroquinoline, and 5,6,7,8-tetrahydroisoquinoline. Among these, from the viewpoints of reactivity and catalytic activity, pyridine, quinoline, isoquinoline, 5,6,7,8-tetrahydroquinoline, and 5,6,7,8-tetrahydroisoquinoline are preferred, and pyridine, isoquinoline, and 5,6,7,8-tetrahydroisoquinoline are particularly preferred.

[0056] R 11 When Y is a nitrogen atom, it is a C1 to C20 sulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb, and one or more hydrogen atoms of these groups may be substituted by the substituent W. R 11Specific examples of the sulfonyl group include, but are not limited to, a methanesulfonyl group (Ms), an ethanesulfonyl group (Es), an n-propylsulfonyl group, an isopropylsulfonyl group, an n-butylsulfonyl group, an isobutylsulfonyl group, an n-pentylsulfonyl group, a cyclopentylsulfonyl group, a 1-octanesulfonyl group, a 1-hexadecanesulfonyl group, an o-toluenesulfonyl group, an m-toluenesulfonyl group, a p-toluenesulfonyl group (Ts), a benzenesulfonyl group, a 2,6-dimethylbenzenesulfonyl group, a 3,5-dimethylbenzenesulfonyl group, and a 2,6-dimethylbenzenesulfonyl group. sulfonyl group, 2,4,6-trimethylbenzenesulfonyl group, 2,4,6-triisopropylbenzenesulfonyl group, 4-cyanobenzenesulfonyl group, 2-nitrobenzenesulfonyl group, 3-nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group, 2,4-dinitrobenzenesulfonyl group, 2-(trifluoromethyl)benzenesulfonyl group, 4-(trifluoromethyl)benzenesulfonyl group, 3,5-bis(trifluoromethyl)benzenesulfonyl group, 4-chlorobenzenesulfonyl group, 2,4-dichlorobenzenesulfonyl group,

[0057] 4-Fluorobenzenesulfonyl group, 3,4,5-trifluorobenzenesulfonyl group, 2,3,4,5,6-pentafluorobenzenesulfonyl group, 4-methoxybenzenesulfonyl group, (+)-10-camphorsulfonyl group, (-)-10-camphorsulfonyl group, pyridine-3-sulfonyl group, trichloromethanesulfonyl group, trifluoromethanesulfonyl group, 2,2,2-trifluoroethanesulfonyl group, 4-hydroxybenzenesulfonyl group, 4-biphenylsulfonyl group, Phenylbenzenesulfonyl group, benzylsulfonyl group (-SO2Bn), acetyl group, propionyl group, isopropylcarbonyl group, tert-butylcarbonyl group, benzoyl group, trifluoroacetyl group, trichloroacetyl group, pentafluoropropionyl group, 3,3,3-trifluoropropionyl group, methoxycarbonyl group, ethoxycarbonyl group, isopropyloxycarbonyl group, tert-butoxycarbonyl group (Boc), phenoxycarbonyl group,

[0058] Carbamoyl group, N-methylcarbamoyl group, N-ethylcarbamoyl group, N-isopropylcarbamoyl group, N-tert-butylcarbonyl group, N-trifluoromethylcarbamoyl group, N-phenylcarbamoyl group, N-(4-fluorophenyl)carbamoyl group, N-(4-cyanophenyl)carbamoyl group, N-(4-nitrophenyl)carbamoyl group, N-(4-trifluoromethylphenyl)carbamoyl group, N-(3,5-bis(trifluoromethyl)phenyl)carbamoyl group, Examples of such an alkyl group include an N-(3,5-difluorophenyl)carbamoyl group, an N-(3,4,5-trifluorophenyl)carbamoyl group, and the like. Preferred are a methanesulfonyl group, an ethanesulfonyl group, a p-toluenesulfonyl group, a benzenesulfonyl group, a 4-fluorobenzenesulfonyl group, a benzylsulfonyl group, an acetyl group, a trifluoroacetyl group, and an N-phenylcarbamoyl group, and particularly preferred is a methanesulfonyl group. R 11 is unsubstituted when Y is an oxygen atom.

[0059] R 12 , R 13 , R 14 and R 15 are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be substituted with the substituent W.

[0060] Ra, Rb and Rc have the same meanings as above, R 12 , R 13 , R 14 and R15 Specific examples of the alkyl group include, but are not limited to, a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a 2-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, a cyclopentyl group, an n-hexyl group, a cyclohexyl group, a 2,6-dimethylcyclohexyl group, a 2,2,6,6-tetramethylcyclohexyl group, a cyclohexylene group, a vinyl group, a propenyl group, a butenyl group, a phenyl group, a toluyl group, a xylyl group, a mesityl group, a pentamethylphenyl group, a 4-methoxyphenyl group, a 3,5-diphenylphenyl group, a 4-methoxyphenyl group, a 5-phenyl ... Methoxyphenyl group, 2,6-dimethoxyphenyl group, 4-dimethylaminophenyl group, 4-hydroxyphenyl group, naphthyl group, anthracenyl group, fluorenyl group, phenalenyl group, phenanthrenyl group, indenyl group, pyridyl group, furanyl group, thienyl group, pyrrolidyl group, piperidyl group, methoxy group, ethoxy group, propoxy group, benzyloxy group, acetyl group, propionyl group, cyclohexanecarbonyl group, benzoyl group, methoxycarbonyl group, ethoxycarbonyl group, acetyloxy group, benzoyloxy group, hydroxyl group,

[0061] methylamino group, ethylamino group, n-propylamino group, isopropylamino group, dimethylamino group, diethylamino group, di-n-propylamino group, diisopropylamino group, carbamoyl group, N-methylcarbamoyl group, N,N-dimethylcarbamoyl group, N-acetylamino group, N-methyl-N-acetylamino group, N-benzoylamino group, N-methyl-N-benzoylamino group, nitro group, cyano group, diphenylphosphino group, dicyclohexylphosphino group, cyclopropylphosphino group, cyclobutylphosphino group, cyclopentylphosphino group, cyclohexylphosphino group, methanesulfenyl group, ethanesulfenyl group, benzenesulfonyl group, p-toluenesulfonyl group, trifluoromethanesulfonyl group, sulfo group, mercapto group, methylsilyl group, dimethylsilyl group, trimethylsilyl group,

[0062] Examples of the alkyl group include a fluorine group, a bromine group, a chlorine group, an iodine group, and a trifluoromethyl group. Preferred are a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, an isobutyl group, a tert-butyl group, a cyclohexyl group, a phenyl group, a toluyl group, a xylyl group, a mesityl group, a pentamethylphenyl group, a 4-methoxyphenyl group, a 3,5-dimethoxyphenyl group, a 2,6-dimethoxyphenyl group, a 4-dimethylaminophenyl group, a 4-hydroxyphenyl group, a naphthyl group, an anthracenyl group, a fluorenyl group, a phenalenyl group, a phenanthrenyl group, an indenyl group, a methoxy group, a benzyloxy group, and a hydroxyl group, and particularly preferred are a hydrogen atom, a methyl group, an isopropyl group, a phenyl group, a p-toluyl group, a 3,5-xylyl group, a 2,6-xylyl group, a 2,4,6-mesityl group, and a pentamethylphenyl group.

[0063] R 12 and R 13 and / or R 14 and R 15 may be joined together to form a ring. R 12 or R 13 Either 14 or R 15 may be combined with either of them to form a ring, and when the ring formed is an aromatic compound, R 12 and R 13 and the carbon to which R is bonded 14 and R 15 The carbon atom to which R is bonded forms a double bond, and R is not involved in ring formation. 12 or R 13 and R 14 or R 15 is unsubstituted. The ring thus formed is not particularly limited, but examples thereof include a cycloalkane ring, a cycloalkene ring, a cycloalkyne ring, an aromatic ring, a hetero ring, a cyclic ketone, a lactone ring, a lactam ring, a carbamate ring, a urea ring, and a thiourea ring. One or more hydrogen atoms in these groups may be substituted with the substituent W. The number of ring members in these rings is not particularly limited, but may be, for example, 3 to 20, preferably 3 to 12, and more preferably 4 to 8. Specific examples of such rings include, but are not limited to, a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a cycloheptane ring, a cyclooctane ring, a benzene ring, a naphthalene ring, a pyran ring, a furan ring, a pyrrole ring, an imidazoline ring, an imidazole ring, an imidazolidine ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyrrolidine ring, a piperidine ring, a piperazine ring, a morpholine ring, β-lactam, γ-lactam, and δ-lactam.

[0064] R 12 Or R 13 and / or R 14 Or R 15 Either one of these may be combined with A to form a ring. The ring thus formed is not particularly limited, but examples thereof include quinoline, quinazoline, quinoxaline, acridine, naphthyridine, indole, benzimidazole, indazole, benzoxazole, benzothiazole, benzotriazole, 5,6,7,8-tetrahydroquinoline, and 2,3-cyclopentenopyridine. n is an integer of 0 to 2, and is preferably 0. R 12 and R 13 and / or R 14 and R 15 The carbon atom to which is bonded may be an asymmetric carbon. The organic iridium compound represented by the general formula (5) may be either a racemic or optically active compound.

[0065] Furthermore, the organic iridium compound used in the present invention is represented by the general formula (6): [ka] It can be expressed as: In the formula, Ar and X have the same meanings as above. B is a saturated or unsaturated nitrogen-containing heterocyclic carbene containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted with the substituent W described above. The heterocycle constituting B is composed of at least a heterocycle having a carbene structure. The heterocycle having a carbene structure contains two nitrogen atoms and one or more carbon atoms as ring members, and is composed so that one carbon atom is sandwiched between the two nitrogen atoms and the carbon atom forms a carbene structure. This allows B to be coordinated to Ir as a carbene ligand.

[0066] B may be a monocyclic or polycyclic group. When B is a monocyclic group, B is a heteromonocyclic group having only the above-mentioned heterocycle having a carbene structure as a ring structure. On the other hand, when B is a polycyclic group, B contains one or more rings in addition to the heterocycle having the above-mentioned carbene structure. In this case, each ring can be bonded to each other by spiro bonding or condensation, or formed by bridging other rings. Preferably, each ring is bonded to each other by condensation.

[0067] The heterocycle containing the carbene structure can be saturated or unsaturated. The heterocycle having a carbene structure is composed of two nitrogen atoms and one or more carbon atoms, and may further contain one or more heteroatoms as ring members, such as nitrogen, oxygen and sulfur atoms. Examples of the heterocycle having a carbene structure include, but are not limited to, carbene rings such as an imidazole ring, an imidazoline ring, an imidazolidine ring, a 1,2,4-triazole ring, a tetrazole ring, an oxazoline ring, an oxazole ring, an oxazolidine ring, a thiazoline ring, a thiazole ring, a thiazolidine ring, etc. In particular, it is preferable that B is a monocyclic or polycyclic carbene containing an imidazole ring, an imidazoline ring, or an imidazolidine ring as the heterocycle having a carbene structure. In addition, the rings in B other than the heterocycle having a carbene structure can each be saturated or unsaturated. In addition, the rings other than the heterocycle having a carbene structure in B may be either hydrocarbon rings or heterocycles. When the ring is a heterocycle, the ring contains one or more heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom.

[0068] The number of ring members in each ring constituting B is not limited to, but is, for example, 4 to 8, and preferably 4 to 6. In particular, the number of ring members in the heterocycle having a carbene structure is preferably 4 to 6, and more preferably 5. Specific examples of B include carbene rings such as monocyclic heteroaromatic rings such as an imidazole ring, a 1,2,4-triazole ring, and a tetrazole ring; monocyclic non-aromatic heterocyclic rings such as an imidazoline ring and an imidazolidine ring; and polycyclic heteroaromatic rings such as a benzimidazole ring, a purine ring, and a pteridine ring. Among the above, from the viewpoints of reactivity and catalytic activity, an imidazole ring or a carbene ring of an imidazoline ring is preferred, and a carbene ring of an imidazole ring is more preferred.

[0069] R 16R is a C1 to C20 sulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, and one or more hydrogen atoms of these groups may be replaced by the substituent W. 16 Specific examples of the benzenesulfonyl group include, but are not limited to, a methanesulfonyl group (Ms), an ethanesulfonyl group (Es), an n-propylsulfonyl group, an isopropylsulfonyl group, an n-butylsulfonyl group, an isobutylsulfonyl group, an n-pentylsulfonyl group, a cyclopentylsulfonyl group, a 1-octanesulfonyl group, a 1-hexadecanesulfonyl group, an o-toluenesulfonyl group, an m-toluenesulfonyl group, a p-toluenesulfonyl group (Ts), a benzenesulfonyl group, a 2,6-dimethylbenzenesulfonyl group, a 3,5-dimethylbenzenesulfonyl group, a 2,4,6-trimethylbenzenesulfonyl group, a 2,4,6- triisopropylbenzenesulfonyl group, 4-cyanobenzenesulfonyl group, 2-nitrobenzenesulfonyl group, 3-nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group, 2,4-dinitrobenzenesulfonyl group, 2-(trifluoromethyl)benzenesulfonyl group, 4-(trifluoromethyl)benzenesulfonyl group, 3,5-bis(trifluoromethyl)benzenesulfonyl group, 4-chlorobenzenesulfonyl group, 2,4-dichlorobenzenesulfonyl group, 4-fluorobenzenesulfonyl group, 3,4,5-trifluorobenzenesulfonyl group, 2,3,4,5,6-pentafluorobenzenesulfonyl group,

[0070] 4-Methoxybenzenesulfonyl group, (+)-10-camphorsulfonyl group, (-)-10-camphorsulfonyl group, pyridine-3-sulfonyl group, trichloromethanesulfonyl group, trifluoromethanesulfonyl group, 2,2,2-trifluoroethanesulfonyl group, 4-hydroxybenzenesulfonyl group, 4-biphenylbenzenesulfonyl group, benzylsulfonyl group (-SO2Bn), acetyl group, propionyl group, isopropylcarbonyl group, tert-butylcarbonyl group, benzoyl group, trifluoroacetyl group, trichloroacetyl group, pentafluoropropionyl group, 3,3,3-trifluoropropionyl group, methoxycarbonyl group, ethoxycarbonyl group, isopropyloxycarbonyl group, tert-butoxycarbonyl group (Boc), a phenoxycarbonyl group, a carbamoyl group, an N-methylcarbamoyl group, an N-ethylcarbamoyl group, an N-isopropylcarbamoyl group, an N-tert-butylcarbonyl group, an N-trifluoromethylcarbamoyl group, an N-phenylcarbamoyl group, an N-(4-fluorophenyl)carbamoyl group, an N-(4-cyanophenyl)carbamoyl group, an N-(4-nitrophenyl)carbamoyl group, an N-(4-trifluoromethylphenyl)carbamoyl group, an N-(3,5-bis(trifluoromethyl)phenyl)carbamoyl group, an N-(3,5-difluorophenyl)carbamoyl group, an N-(3,4,5-trifluorophenyl)carbamoyl group, a thiocarbamoyl group, an N-methylthiocarbamoyl group, an N-phenylthiocarbamoyl group,

[0071] Examples of such groups include a trifluoromethyl group, a pentafluoroethyl group, a phenyl group, a 4-nitrophenyl group, a 4-cyanophenyl group, a 4-fluorophenyl group, a 3,5-difluorophenyl group, a 3,4,5-trifluorophenyl group, a 4-(trifluoromethyl)phenyl group, a 3,5-bis(trifluoromethyl)phenyl group, and a pentafluorophenyl group. Preferred are a methanesulfonyl group, an ethanesulfonyl group, a p-toluenesulfonyl group, a benzenesulfonyl group, a benzylsulfonyl group, an acetyl group, a trifluoroacetyl group, and an N-phenylcarbamoyl group.

[0072] R 17 , R 18 , R 19 , R 20 and R 21 are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced with heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to 20 sulfenyl group, a C1 to 20 sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be substituted with the substituent W.

[0073] Ra, Rb and Rc have the same meanings as above, R 17 , R 18 , R 19 , R 20 and R 21Specific examples of the alkyl group include, but are not limited to, a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a 2-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, a cyclopentyl group, an n-hexyl group, a cyclohexyl group, a 2,6-dimethylcyclohexyl group, a 2,2,6,6-tetramethylcyclohexyl group, a cyclohexylene group, a vinyl group, a propenyl group, a butenyl group, a phenyl group, a toluyl group, a xylyl group, a mesityl group, a pentamethylphenyl group, a 4-methoxyphenyl group, a 3,5-diphenylphenyl group, a 4-methoxyphenyl group, a 5-phenyl ... Methoxyphenyl group, 2,6-dimethoxyphenyl group, 4-dimethylaminophenyl group, 4-hydroxyphenyl group, naphthyl group, anthracenyl group, fluorenyl group, phenalenyl group, phenanthrenyl group, indenyl group, pyridyl group, furanyl group, thienyl group, pyrrolidyl group, piperidyl group, methoxy group, ethoxy group, propoxy group, benzyloxy group, acetyl group, propionyl group, cyclohexanecarbonyl group, benzoyl group, methoxycarbonyl group, ethoxycarbonyl group, acetyloxy group, benzoyloxy group, hydroxyl group,

[0074] methylamino group, ethylamino group, n-propylamino group, isopropylamino group, dimethylamino group, diethylamino group, di-n-propylamino group, diisopropylamino group, carbamoyl group, N-methylcarbamoyl group, N,N-dimethylcarbamoyl group, N-acetylamino group, N-methyl-N-acetylamino group, N-benzoylamino group, N-methyl-N-benzoylamino group, nitro group, cyano group, diphenylphosphino group, dicyclohexylphosphino group, cyclopropylphosphino group, cyclobutylphosphino group, cyclopentylphosphino group, cyclohexylphosphino group, methanesulfenyl group, ethanesulfenyl group, methanesulfonyl group, ethanesulfonyl group, benzenesulfonyl group, p-toluenesulfonyl group, trifluoromethanesulfonyl group, sulfo group,

[0075] Examples of the aryl group include a mercapto group, a methylsilyl group, a dimethylsilyl group, a trimethylsilyl group, a fluorine group, a bromine group, a chlorine group, an iodine group, and a trifluoromethyl group. Preferred are a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, an isobutyl group, a tert-butyl group, a cyclohexyl group, a phenyl group, a toluyl group, a xylyl group, a mesityl group, a pentamethylphenyl group, a 4-methoxyphenyl group, a 3,5-dimethoxyphenyl group, a 2,6-dimethoxyphenyl group, a 4-dimethylaminophenyl group, a 4-hydroxyphenyl group, a naphthyl group, an anthracenyl group, a fluorenyl group, a phenalenyl group, a phenanthrenyl group, and an indenyl group, and particularly preferred are a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a phenyl group, a p-toluyl group, a 3,5-xylyl group, a 2,6-xylyl group, a 2,4,6-mesityl group, and a pentamethylphenyl group.

[0076] Among the above-mentioned substituents, R 16 , R 17 , R 18 , R 19 and R 20 Two or more groups selected from the group consisting of may be joined together to form one or more rings. The ring thus formed is not particularly limited, but examples thereof include a cycloalkane ring, a cycloalkene ring, a cycloalkyne ring, an aromatic ring, a hetero ring, a cyclic ketone, a lactone ring, a lactam ring, a carbamate ring, a urea ring, and a thiourea ring. One or more hydrogen atoms in these groups may be substituted with the substituent W. The number of ring members in these rings is not particularly limited, but may be, for example, 3 to 20, preferably 3 to 12, and more preferably 4 to 8. Specific examples of such rings include, but are not limited to, a cyclopropane ring, a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, a cycloheptane ring, a cyclooctane ring, a cyclopentanone ring, a cyclohexanone ring, a cycloheptanone ring, a cyclooctanone ring, a benzene ring, a pyran ring, a furan ring, a pyrrole ring, an imidazoline ring, an imidazole ring, an imidazolidine ring, a pyridine ring, a pyrimidine ring, a pyrazine ring, a pyrrolidine ring, a piperidine ring, a piperazine ring, a morpholine ring, a β-lactam, a γ-lactam, a δ-lactam, a 2-oxazolidinone ring, a 2-imidanolidinone ring, a tetrahydro-2-pyrimidinone ring, a 2-imidazolidinone ring, a tetrahydro-2-pyrimidinethione ring, and the like.

[0077] In particular, R 16 and R 17 and / or R 18 That is, R 16 and R 17 , R 16 and R 18 or R 16 and R 17 and R 18 are preferably taken together to form a ring. In such a case, the ring formed is preferably a lactam ring, a heterocycle, a carbamate ring, a urea ring, or a thiourea ring, and more preferably a γ-lactam, a 2-oxazolidinone ring, a 2-imidanolidinone ring, a tetrahydro-2-pyrimidinone ring, a 2-imidazolidinone ring, or a tetrahydro-2-pyrimidinethione ring. m is an integer of 0 to 3, and is preferably 1. R 17 and R 18 and / or R 19 and R 20 The carbon atom to which is bonded may be an asymmetric carbon. The organic iridium compound represented by the general formula (6) may be either a racemic or optically active compound.

[0078] In the present invention, an optically active primary or secondary amine compound can also be produced by reacting an aminoalcohol represented by the above-mentioned general formula (1) and a carbonyl compound represented by the general formula (2) with a hydrogen donor compound in the presence of an organic iridium compound represented by the general formula (7) and an organic compound represented by the general formula (8), general formula (9), general formula (10) or general formula (11), and then oxidatively deprotecting the substituent having a 2-hydroxyethyl skeleton on the nitrogen.

[0079] Furthermore, it is also possible to produce an optically active primary or secondary amine compound by reacting a hemiaminal ether, imine or enamine prepared from an aminoalcohol represented by the above-mentioned general formula (1) and a carbonyl compound represented by the general formula (2) with a hydrogen donor compound in the presence of an organic iridium compound represented by the below-mentioned general formula (7) and an organic compound represented by the general formula (8), general formula (9), general formula (10) or general formula (11), and then oxidatively deprotecting the substituent having a 2-hydroxyethyl skeleton on the nitrogen. That is, an organic iridium compound represented by general formula (7) and an organic compound represented by general formula (8), general formula (9), general formula (10) or general formula (11) form an organic iridium compound corresponding to general formula (3), general formula (4), general formula (5) or general formula (6), respectively, in the reaction system, and function as a catalyst. Furthermore, the organic compound represented by the general formula (11) may be reacted with, for example, silver(I) oxide or copper(I) oxide to prepare a corresponding organic silver compound or organic copper compound, which may then be reacted with the organic iridium compound represented by the general formula (7). In this case, an organic iridium compound corresponding to the general formula (6) is also formed in the reaction system, and functions as a catalyst.

[0080] The organic iridium compound used in the present invention is represented by the general formula (7) [ka] wherein Ar and X have the same meanings as defined above. The organic compound used in the present invention is General formula (8), [ka] General formula (9), [ka] General formula (10), [ka] Or general formula (11) [ka] It is expressed as:

[0081] In these formulas, R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , j, k, l, A, Y, n, and m have the same meanings as above. B' is a saturated or unsaturated nitrogen-containing heterocyclic carbene precursor containing at least two nitrogen atoms, one or more hydrogen atoms of which may be substituted by the substituent W, and becomes the above-mentioned saturated or unsaturated nitrogen-containing heterocyclic carbene B by eliminating a proton on the carbon atom sandwiched between the two nitrogen atoms. In other words, B' has the same meaning as that obtained by replacing the carbene in the above-mentioned B with a carbene precursor.

[0082] Z is an anionic group, and specific examples thereof include, but are not limited to, a fluorine group, a chlorine group, a bromine group, an iodine group, a tetrafluoroborate group, a tetrahydroborate group, a tetrakispentafluorophenylborate group, a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate group, a hexafluorophosphate group, a hexafluoroantimonate group, a hexachloroantimonate group, a hexafluoroarsenate group, a perchlorate group, an acetoxy group, a benzoyloxy group, a (2,6-dihydroxybenzoyl)oxy group, a (2,5-dihydroxybenzoyl)oxy group, a (3-aminobenzoyl)oxy group, a (2,6-dimethoxybenzoyl)oxy group, a (2,4,6-triisopropylbenzoyl)oxy group, a 1-naphthalenecarboxylic acid group, a 2-naphthalenecarboxylic acid group,

[0083] Examples of such groups include trifluoroacetoxy, trifluoromethanesulfonimide, toluenesulfonate, methanesulfonate, ethanesulfonate, n-propanesulfonate, isopropanesulfonate, n-butanesulfonate, fluorosulfonate, fluoromethanesulfonate, difluoromethanesulfonate, trifluoromethanesulfonate, pentafluoroethanesulfonate, phosphate, (S)-2,2'-dihydroxy-1,1'-binaphthyl phosphate, (R)-2,2'-dihydroxy-1,1'-binaphthyl phosphate, etc. Among these, preferred are chlorine, bromine, iodine, tetrafluoroborate, tetrahydroborate, p-toluenesulfonate, methanesulfonate, and trifluoromethanesulfonate. The organic compound represented by the general formula (8), the general formula (9), the general formula (10) or the general formula (11) may be achiral, racemic or optically active.

[0084] The hydrogen-donating compound in the present invention means a compound capable of donating hydrogen by thermal action or catalytic action, and the type of such a hydrogen-donating compound is not particularly limited. Suitable hydrogen-donating compounds include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol, 1-pentanol, cyclopentyl alcohol, 1-hexanol, cyclohexyl alcohol, benzyl alcohol, formic acid, sodium formate, potassium formate, lithium formate, and ammonium formate, and can be used alone or in combination. In terms of reactivity and economy, formic acid, formate salts, methanol, ethanol, and 2-propanol are preferred.

[0085] The amount of the hydrogen donating compound used can be 1 to 30 equivalents relative to the carbonyl compound, but is preferably 1 to 10 equivalents in terms of reactivity and economy. When a formate such as sodium formate, potassium formate, lithium formate, or ammonium formate is used as the hydrogen donating compound, a phase transfer catalyst may be added as necessary to carry out the reaction. Any salt having a long-chain alkyl ammonium cation may be used as the phase transfer catalyst, but tetrabutylammonium salt is preferred in terms of reactivity and economy. In many cases, the addition of a phase transfer catalyst has the effect of improving the reaction rate. The amount of the phase transfer catalyst added is usually in the range of 0.001 to 10 molar equivalents relative to the carbonyl compound, but is preferably 0.01 to 0.1 molar equivalents in terms of reactivity and economy.

[0086] The amount of the amino alcohol used is usually 1 to 30 equivalents relative to the carbonyl compound, but from the standpoint of reactivity and economic efficiency, it is preferably 1 to 10 equivalents. It can also be used as an amino alcohol salt.

[0087] The amount of the organic iridium compound used, expressed as the molar ratio of the carbonyl compound to the organic iridium compound, S / C (substrate / catalyst molar ratio), varies greatly depending on the structure of the carbonyl compound, the type and concentration of the organic iridium compound, the reaction temperature, the type of hydrogen-donating compound, etc., but can be in the range of S / C = 10 to 10,000,000, preferably in the range of S / C = 100 to 1,000,000.

[0088] In the reaction of the first step of the present invention, that is, the reaction of an amino alcohol with a carbonyl compound or the reaction of a hemiaminal ether, an imine or an enamine, a suitable reaction solvent can be used in consideration of the physical and chemical properties of the substrate, the product, the organic iridium compound and the hydrogen donor compound. Protic solvents, aprotic solvents, ionic liquids, water and buffer solutions can be used alone or in combination. In terms of reactivity and economy, water, methanol, ethanol, 2-propanol, ethylene glycol, ethyl acetate, propyl acetate, butyl acetate, tetrahydrofuran, tert-butyl methyl ether, diisopropyl ether, ethylene glycol dimethyl ether, acetonitrile, toluene, chloroform and methylene chloride are preferred.

[0089] The reaction temperature in the first step is preferably about −20° C. to 100° C., taking into consideration the solubility and reactivity of the substrate and product, and economic efficiency, and is more preferably 20° C. to 80° C. The reaction time varies depending on reaction conditions such as S / C, substrate concentration, and temperature, but the reaction is completed within a few minutes to 100 hours.

[0090] In the second step of the present invention, a substituent having a 2-hydroxyethyl skeleton on the nitrogen, i.e., the reaction product of the first step, is represented by the following general formula (A): [ka] In the formula, R 2 , R 3 , R 4 , and R 5has the same meaning as in general formula (1), The oxidative deprotection reaction of the site represented by is achieved by oxidative cleavage of the carbon-carbon bond of the 2-amino-1-ethanol skeleton followed by hydrolysis. As an oxidizing agent for driving this reaction, an oxidizing agent used in the oxidative cleavage of 1,2-diols can be used, and is not particularly limited in type, but for example, periodic acid, periodate such as sodium periodate, potassium periodate, and ammonium periodate, lead tetraacetate, hypervalent iodine compounds such as (diacetoxyiodo)benzene and Dess-Martin periodinane, sodium hypochlorite, etc. can be used alone or in combination. In consideration of reactivity and economic efficiency, periodic acid, periodate, lead tetraacetate, and Dess-Martin periodinane are preferred. The amount of the oxidizing agent used may be 1 to 30 equivalents relative to the carbonyl compound, but from the standpoints of reactivity and economy, it is preferably 1 to 10 equivalents.

[0091] In the second step, a reaction solvent can be appropriately used in consideration of the physical and chemical properties of the substrate, product, and oxidizing agent. It is preferable to use a solvent according to the properties of the oxidizing agent used, and protic solvents, aprotic solvents, ionic liquids, water, and buffer solutions can be used alone or in combination. The reaction temperature in the second step is also appropriately selected in consideration of the physical and chemical properties and reactivity of the substrate, product and oxidizing agent, and economic efficiency. It is particularly preferable to select the temperature according to the properties of the oxidizing agent used. The reaction can usually be carried out at about -78°C to 100°C. The reaction time varies depending on reaction conditions such as the properties and amount of the oxidizing agent, the substrate concentration and temperature, but the reaction is completed within a few minutes to 100 hours.

[0092] The optically active primary or secondary amine compound thus produced can be purified by known methods such as acid-base extraction, column chromatography, distillation, salification, recrystallization, etc., or by a suitable combination of these methods. The reaction format of the above reaction is not particularly limited, and the reaction can be carried out in any of a batch system, a continuous system, and a flow reactor. EXAMPLES

[0093] The present invention will be described in more detail below with reference to examples. Of course, the present invention is not limited to the following examples. In the following examples, the substrates, reactants, solvents, etc. used in the reactions were purchased reagents unless otherwise specified. NMR was measured using a JNM-ECX400P (400 MHz, JEOL). 1 H-NMR was performed using tetramethylsilane (TMS) as an internal standard, and its signal was set to δ = 0 (δ is a chemical shift). In addition, coumarin or 1,3,5-trimethoxybenzene was used as an internal standard to calculate the reaction yield. GC was performed using a 7890B (Agilent Technologies) column, CP-chirasil-DEX CB (25 m × 0.25 mm × 0.25 μm, Agilent Technologies). HPLC was performed using 1260Infinity and 1260InfinityII (Agilent Technologies). The columns and eluents used were CROWNPAK CR-I(+) (150mm×3mmφ×5μm, Daicel) and aqueous perchloric acid / acetonitrile, CROWNPAK CR-I(-) (150mm×3mmφ×5μm, Daicel) and aqueous trifluoroacetic acid / acetonitrile, CHIRALCEL OD-H (250mm×4.6mmφ×5μm, Daicel) and hexane / 2-propanol, or CHIRALPAK AD-H (250mm×4.6mmφ×5μm, Daicel) and ethanol / diethylamine or hexane / 2-propanol / triethylamine.

[0094] Cp * IrCl (N-(4-dimethylaminophenyl)-4-dimethylaminopyridine-2-carboxylic acid amidate) (Ir-PA), Cp *IrCl(4-dimethylamino-8-quinolinolate) (Ir-QN) was used as a purchased reagent. Cp * IrCl (N-(1-phenyl-1-(3,5-dimethyl-4-methoxy-2-pyridyl)ethyl) methanesulfonamidate) (Ir-PSA36), and Ir-PSAs 4, 5, 7, 14, 15, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 35, 38, 39, and 40 were synthesized with reference to the method described in Japanese Patent No. 6227889. Cp * IrCl(2-(2-pyridyl)phenolate) (Ir-PP) was synthesized with reference to the method described in Japanese Patent No. 5719115. Cp * IrCl (5-((3,4,5-triethyl-4-imidazolin-2-ylidene-1-yl)methyl)-1-pyrrolidinate-2-one) (Ir-CA) was synthesized with reference to the method described in Japanese Patent No. 6254811.

[0095] [Comparative Example 1] Synthesis of (S)-2-amino-5-methoxytetralin 5-Methoxy-2-tetralone (1.85 g, 10.5 mmol) and (S)-valinol (1.25 g, 12.1 mmol) were placed in a Schlenk flask and replaced with argon. Acetonitrile (21 mL) and anhydrous magnesium sulfate (1.85 g) were added and stirred at 60°C for 15 hours. The reaction solution was filtered through Celite and concentrated under reduced pressure to obtain 2.85 g of spiro[5-methoxytetralin-2,2'-[4]-isopropyloxazolidine]. 1.31 g of the product was placed in a Schlenk flask and purged with argon. The product was dissolved in methanol (18 mL) and cooled to -20°C. Sodium borohydride (284 mg) was added at -20°C, and the mixture was stirred for 19 hours while warming to room temperature. The reaction mixture was quenched by adding 1M hydrochloric acid, concentrated under reduced pressure, and methanol was distilled off. A saturated aqueous solution of sodium bicarbonate was added, stirred, and extracted three times with ethyl acetate. The ethyl acetate phases were combined, washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 1.45 g of (S)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin. NMR analysis showed that the product was produced in a yield of 99%, but the diastereoselectivity was only 9% de. The entire product was dissolved in methanol (6 mL), water (7 mL), and 40% methylamine aqueous solution (2 mL), and orthoperiodic acid (1.5 g) was added and stirred for 17 hours. After concentrating under reduced pressure to remove methanol, water was added and stirred, and the mixture was extracted three times with ethyl acetate. The ethyl acetate phases were combined, washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.42 g of (S)-2-amino-5-methoxytetralin. HPLC analysis showed that the optical purity was only 8% ee.

[0096] [Comparative Example 2] Synthesis of (S)-2-amino-5-methoxytetralin An autoclave was charged with 10% palladium / carbon (65 mg) and purged with argon. After adding a solution of 1.31 g of spiro[5-methoxytetralin-2,2'-[4]-isopropyloxazolidine] synthesized in the same manner as in Comparative Example 1 dissolved in methanol (10 mL), the autoclave was purged with hydrogen gas three times. The autoclave was pressurized with hydrogen gas to 0.5 MPa and vigorously stirred at 40°C for 22 hours. After carefully releasing the hydrogen gas, the reaction solution was filtered through Celite and concentrated under reduced pressure to obtain 1.43 g of (S)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin. NMR analysis showed that the yield was 63% and the diastereoselectivity was only 16% de. The entire product was dissolved in methanol (6 mL), water (7 mL), and 40% methylamine aqueous solution (2 mL), and orthoperiodic acid (1.5 g) was added and stirred for 18 hours. After concentrating under reduced pressure to remove methanol, water was added and stirred, and the mixture was extracted three times with ethyl acetate. The ethyl acetate phases were combined, washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.41 g of (S)-2-amino-5-methoxytetralin. HPLC analysis showed that the optical purity was only 15% ee.

[0097] [Example 1] Synthesis of (S)-2-amino-5-methoxytetralin (S)-mandelate 5-Methoxy-2-tetralone (150g, 850mmol) was charged into a reaction vessel and replaced with argon. (S)-Valinol (101g, 978mmol), methanol (850mL), and formic acid (117g, 2.55mol) were added and stirred for about 10 minutes, after which Ir-PSA36 (118mg, 170μmol) was added and vigorously stirred for 18 hours at 40℃ under argon flow. The reaction solution was concentrated under reduced pressure to remove methanol, then neutralized with aqueous sodium bicarbonate and extracted with MTBE. The MTBE phase was washed with water, and the solvent was removed under reduced pressure to obtain (S)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin. The diastereoselectivity of the reaction was 83%de by HPLC analysis. The product was salified, recrystallized, and purified to a diastereomeric excess of 99%de, and then a portion of it (230mmol) was placed in a reaction vessel and dissolved in methanol (154mL), water (154mL), and 40% aqueous methylamine solution (230mL). The mixture was cooled to 10°C, sodium periodate (128g, 597mmol) was added, and the mixture was stirred for 22 hours. An aqueous sodium hydroxide solution was added to the reaction mixture, which was then stirred and extracted with ethyl acetate. The ethyl acetate phase was washed with water and concentrated under reduced pressure to remove the ethyl acetate. The residue was dissolved in 2-propanol, and then (S)-mandelic acid was added to salify it, and the resulting precipitate was collected by filtration. The obtained crystals were dried under reduced pressure to obtain 74g of (S)-2-amino-5-methoxytetralin·(S)-mandelate with a diastereomeric excess of 99%de, with a total yield of 73%. 1 H NMR(DMSO-d6,400MHz)δ1.61(m,1H),2.06(m,1H),2.44-2.53(m,1H),2.70(dd, 1H,J=10.1,16.0Hz),2.80(m,1H),2.96(dd,1H,J=4.1,16.0Hz),3.29(m,1H),3 .4(br,1H),3.76(s,3H),4.50(s,1H),6.67(d,1H,J=7.8Hz),6.77(d,1H,J=7.8 Hz),7.10(t,1H,J=7.8Hz),7.14(m,1H),7.21(m,2H),7.35(m,2H),7.5(br,3H). 13 C NMR(DMSO-d6,100MHz)δ21.3,26.8,33.6,46.1,55.2,73.4,107.8,121.0,123.3,126.0,126.2,126.6,127.3,134.2,143.7,156.7,174.3.

[0098] [Example 2] Synthesis of (S)-2-amino-5-methoxytetralin First, (S)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin was synthesized. 5-Methoxy-2-tetralone (881 mg, 5 mmol) and (S)-valinol (619 mg, 6 mmol) were placed in a Schlenk flask and replaced with argon. Methanol (5 mL) and formic acid (566 μL, 15 mmol) were added and stirred for about 1 minute, after which Ir-PSA36 (6.96 mg, 10 μmol) was added and vigorously stirred for 18 hours at 40°C under an argon stream. The reaction solution was neutralized by adding an aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined ethyl acetate phase was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the product. NMR analysis showed that (S)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin was produced in a yield of 95%. 1H NMR(CDCl3,400MHz)δ0.91(d,3H,J=6.8Hz),0.96(d,3H,J=6.8Hz),1.51(m,1H),1.80(m,1H),2.10(m,1H),2.51-2.65(m,3H),2.8 6-3.03(m,3H),3.29(dd,1H,J=7.2,10.4Hz),3.60(dd,1H,J=4.8,10.8Hz),3.81(s,3H),6.66-6.71(m,2H),7.09(t,1H,J=8.0Hz).

[0099] The entire amount of the target product obtained was dissolved in methanol (15 mL), water (15 mL), and 40% methylamine aqueous solution (5 mL), and orthoperiodic acid (3.76 g, 16.5 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was diluted with water, extracted with ethyl acetate, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain (S)-2-amino-5-methoxytetralin. Its optical purity was 84% ​​ee by HPLC analysis.

[0100] [Examples 3 to 26] Synthesis of (S)-2-amino-5-methoxytetralin Except for changing the organic iridium compound used as the catalyst, (S)-2-amino-5-methoxytetralin was synthesized in the same manner as in Example 2. The results are shown in Table 1. In the table, "yield" indicates the reaction yield of the first step, and "ee" indicates the optical purity of the final product. [Table 1]

[0101] [Examples 27 to 29] Synthesis of (S)-2-amino-5-methoxytetralin (S)-2-Amino-5-methoxytetralin was synthesized in the same manner as in Example 2, except that the amino alcohol used as the amine source was changed. The results are shown in Table 2. In the table, yield indicates the reaction yield of the first step, and ee indicates the optical purity of the final product. [Table 2]

[0102] [Example 30] Synthesis of (R)-2-amino-5-methoxytetralin First, (R)-N-((R)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin was synthesized as follows. 5-Methoxy-2-tetralone (881 mg, 5 mmol) and (R)-valinol (619 mg, 6 mmol) were placed in a Schlenk flask and replaced with argon. Methanol (5 mL) and formic acid (566 μL, 15 mmol) were added and stirred for about 1 minute, after which Ir-PSA28 (6.38 mg, 10 μmol) was added and vigorously stirred at 40°C for 18 hours under an argon stream. The reaction solution was neutralized by adding an aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined ethyl acetate phase was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the product. NMR analysis showed that (R)-N-((R)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin was produced in a yield of 70%.

[0103] The entire amount of the target product obtained was dissolved in methanol (15 mL) and 40% methylamine aqueous solution (5 mL), and orthoperiodic acid (3.76 g, 16.5 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was diluted with water, extracted with ethyl acetate, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain (R)-2-amino-5-methoxytetralin. The optical purity was 32% ee by HPLC analysis.

[0104] [Example 31] Synthesis of (R)-N-acetyl-1-(2-methoxyphenyl)-2-propylamine First, (R)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-1-(2-methoxyphenyl)-2-propylamine was synthesized as follows. (S)-Valinol (619 mg, 6 mmol) was placed in a Schlenk flask and argon was substituted. Methanol (5 mL), (2-methoxyphenyl)acetone (767 μL, 5 mmol), and formic acid (566 μL, 15 mmol) were added and stirred for about 1 minute, after which Ir-PSA18 (6.66 mg, 10 μmol) was added and vigorously stirred for 18 hours at 40°C under an argon stream. The reaction solution was neutralized by adding an aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined ethyl acetate phase was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 1.36 g of product. NMR analysis showed that (R)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-1-(2-methoxyphenyl)-2-propylamine was quantitatively produced. 1 H NMR(CDCl3,400MHz)δ0.91(d,3H,J=6.8Hz),0.96(d,3H,J=7.2Hz),1.08(m,3H),1.79(m,1H),2.47(dd,1H),2.54( m,1H),2.88(dd,1H),2.99(m,1H),3.25(dd,1H),3.48(dd,1H),3.82(s,3H),6.84-6.93(m,2H),7.10-7.22(m,2H).

[0105] 251 mg of the target product obtained was dissolved in methanol (3 mL), water (3 mL), and 40% methylamine aqueous solution (1 mL), and orthoperiodic acid (752 mg, 3.3 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was diluted with water, extracted with ethyl acetate, washed with saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain (R)-1-(2-methoxyphenyl)-2-propylamine. Furthermore, the entire amount of the obtained compound was dissolved in methylene chloride (5 mL), triethylamine (210 μL) and acetic anhydride (113 μL, 1.2 mmol) were added, and the mixture was stirred at room temperature for 18 hours. A saturated ammonium chloride aqueous solution was added to the reaction solution, and the mixture was stirred, and extracted three times with methylene chloride. The methylene chloride phase was combined and dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain (R)-N-acetyl-1-(2-methoxyphenyl)-2-propylamine for measuring the optical purity. HPLC analysis revealed that the optical purity was 86% ee.

[0106] [Examples 32-33] Synthesis of N-acetyl-1-(2-methoxyphenyl)-2-propylamine 1-(2-Methoxyphenyl)-2-propylamine was obtained in the same manner as in Example 31, except that Ir-PSA7 was used as the organic iridium compound serving as the catalyst, and (S)-phenylglycinol or (R)-phenylglycinol was used as the amino alcohol serving as the amine source. Furthermore, N-acetyl-1-(2-methoxyphenyl)-2-propylamine was synthesized for measuring the optical purity. The results are shown in Table 3. In the table, yield denotes the reaction yield of the first step, and ee denotes the optical purity of the final product. [Table 3]

[0107] [Example 34] Synthesis of N-benzoyl-1-(4-chlorophenyl)-2-propylamine First, N-((R)-2-hydroxyl-1-phenylethyl)-1-(4-chlorophenyl)-2-propylamine formate was synthesized as follows. (4-Chlorophenyl)acetone (200 mg, 1.19 mmol) and (R)-phenylglycinol (195 mg, 1.42 mmol) were placed in a Schlenk flask and replaced with argon. Methanol (1.2 mL) and formic acid (135 μL, 3.56 mmol) were added and stirred for about 1 minute, after which Ir-PSA18 (1.6 mg, 2.4 μmol) was added and stirred vigorously at 40°C for 18 hours under an argon stream. The reaction solution was concentrated under reduced pressure to obtain the product. NMR analysis showed that N-((R)-2-hydroxyl-1-phenylethyl)-1-(4-chlorophenyl)-2-propylamine formate was quantitatively produced. 1 H NMR(CDCl3,400MHz)δ1.17(d,3H,J=6.4Hz),2.61(dd,1H),3.02(m,1H),3.12(dd,1H ),3.90(dd,1H),4.03(dd,1H),4.41(dd,1H),6.83(m,2H),6.9(br,2H),7.18(m,2H), 7.43-7.56(m,5H),8.57(s,1H).

[0108] The target product was neutralized by adding an aqueous potassium hydroxide solution and extracted with methylene chloride. The methylene chloride phase was concentrated under reduced pressure to obtain the target product in free form. Half of the target product in free form was dissolved in methanol (1.8 mL) and 40% aqueous methylamine solution (0.6 mL), and an aqueous solution of orthoperiodic acid (446 mg, 3.3 mmol) dissolved in water (1.8 mL) was added and stirred at room temperature for 18 hours. The reaction solution was extracted with methylene chloride and dried over anhydrous sodium sulfate to obtain a 1-(4-chlorophenyl)-2-propylamine / methylene chloride solution. Furthermore, triethylamine (62 μL) and benzoyl chloride (35 μL, 297 μmol) were added to half of the obtained solution and stirred at room temperature for 30 minutes. A saturated aqueous sodium bicarbonate solution was added to the reaction solution, stirred, and extracted with methylene chloride. The methylene chloride phase was concentrated under reduced pressure to obtain N-benzoyl-1-(4-chlorophenyl)-2-propylamine for measuring the optical purity, which was 97% ee by HPLC analysis.

[0109] [Example 35] Synthesis of N-benzoyl-1-(4-chlorophenyl)-2-propylamine The reaction was carried out in the same manner as in Example 34, except that Ir-PA was used as the organic iridium compound catalyst. First, N-((R)-2-hydroxyl-1-phenylethyl)-1-(4-chlorophenyl)-2-propylamine formate was quantitatively obtained. Then, a 1-(4-chlorophenyl)-2-propylamine / methylene chloride solution was obtained. Furthermore, to measure the optical purity, N-benzoyl-1-(4-chlorophenyl)-2-propylamine was synthesized, and its optical purity was 80% ee.

[0110] [Example 36] Synthesis of N-benzoyl-1-(4-methylphenyl)-2-propylamine The reaction was carried out in the same manner as in Example 34 except that (4-methylphenyl)acetone was used as the carbonyl compound substrate, and N-((R)-2-hydroxyl-1-phenylethyl)-1-(4-methylphenyl)-2-propylamine formate was quantitatively obtained. 1 H NMR(CDCl3,400MHz)δ1.17(d,3H,J=6.4Hz),2.28(s,3H),2.60(dd,1H),3.02(m,1H) ,3.10(dd,1H),3.89(dd,1H),4.02(dd,1H),4.40(dd,1H),6.81(m,2H),7.03(m,2H), 7.40-7.56(m,5H),8.62(s,1H). Then, 1-(4-methylphenyl)-2-propylamine / methylene chloride solution was obtained. Furthermore, in order to measure the optical purity, N-benzoyl-1-(4-methylphenyl)-2-propylamine was synthesized, and the optical purity was 96% ee.

[0111] [Example 37] Synthesis of N-benzoyl-1-(4-methylphenyl)-2-propylamine The reaction was carried out in the same manner as in Example 36, except that Ir-CA was used as the organic iridium compound catalyst, and (S)-phenylglycinol was used as the amino alcohol source amine, and N-((S)-2-hydroxyl-1-phenylethyl)-1-(4-methylphenyl)-2-propylamine formate was obtained in a yield of 94%. Then, a 1-(4-methylphenyl)-2-propylamine / methylene chloride solution was obtained. Furthermore, to measure the optical purity, N-benzoyl-1-(4-methylphenyl)-2-propylamine was synthesized, and its optical purity was 87% ee.

[0112] [Example 38] Synthesis of N-benzoyl-1-(4-pyridyl)-2-propylamine First, N-((S)-2-(1-hydroxyl-3-methylbutyl))-1-(4-pyridyl)-2-propylamine formate was synthesized as follows. In an argon-purged Schlenk flask, (4-pyridyl)acetone (200 mg, 1.48 mmol), (S)-valinol (244 mg, 1.78 mmol), methanol (1.48 mL), and formic acid (110 μL, 2.96 mmol) were charged and stirred for about 1 minute. Ir-PSA36 (5.2 mg, 7.4 μmol) was then added and stirred vigorously for 18 hours at 40°C under an argon stream. The reaction solution was concentrated under reduced pressure to obtain the product. NMR analysis showed that N-((S)-2-(1-hydroxyl-3-methylbutyl))-1-(4-pyridyl)-2-propylamine formate was quantitatively produced. 1 H NMR(CDCl3,400MHz)δ0.95(d,3H),0.99(d,3H),1.12(d,3H),1.86(m,1H),2.58(dd,1H),2.64(m,1 H),2.98(dd,1H),3.18(m,1H),3.47(dd,1H),3.59(dd,1H),7.14(m,2H),8.51(m,2H),8.6(br,1H).

[0113] The target product was neutralized by adding an aqueous potassium hydroxide solution and extracted with methylene chloride. The methylene chloride phase was concentrated under reduced pressure to obtain the target product in free form. Half of the target product in free form was dissolved in methanol (2.2 mL) and 40% aqueous methylamine solution (735 μL), and an aqueous solution of orthoperiodic acid (552 mg, 2.42 mmol) dissolved in water (2.2 mL) was added and stirred at room temperature for 18 hours. The reaction solution was extracted with methylene chloride, washed with a saturated aqueous sodium chloride solution, and then dried over anhydrous sodium sulfate to obtain a 1-(4-pyridyl)-2-propylamine / methylene chloride solution. Furthermore, triethylamine (80 μL) and benzoyl chloride (43 μL, 370 μmol) were added to half of the obtained solution and stirred at room temperature for 2 hours. A saturated aqueous sodium bicarbonate solution was added to the reaction solution, stirred, and extracted with methylene chloride. The methylene chloride phase was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain N-benzoyl-1-(4-pyridyl)-2-propylamine for measuring the optical purity, which was 95% ee by HPLC analysis.

[0114] [Example 39] Synthesis of N-benzoyl-1-phenyl-2-butylamine The reaction was carried out in the same manner as in Example 38 using 1-phenyl-2-butanone as the carbonyl compound substrate, (R)-phenylglycinol as the aminoalcohol source, and Ir-PSA18 as the organic iridium compound catalyst, to obtain N-((R)-2-hydroxyl-1-phenylethyl)-1-phenyl-2-butylamine formate in 94% yield. 1 H NMR(CDCl3,400MHz)δ0.85(d,3H),1.47(m,2H),2.71-2.78(m,2H),2.92(dd,1H) ,3.69-3.79(m,2H),4.02(dd,1H),7.08(m,2H),7.19-7.40(m,8H),8.5(br,1H). Then, a 1-phenyl-2-butylamine / methylene chloride solution was obtained. Furthermore, in order to measure the optical purity, N-benzoyl-1-phenyl-2-butylamine was synthesized, and the optical purity was 83% ee.

[0115] [Example 40] Synthesis of (R)-2-methoxy-5-(2-aminopropyl)benzenesulfonamide First, (R)-2-methoxy-5-(2-(N-((S)-2-hydroxyl-1-phenylethyl)aminopropyl)benzenesulfonamide formate was synthesized as follows. 5-Acetonyl-2-methoxybenzenesulfonamide (730 mg, 3 mmol) and (S)-phenylglycinol (494 mg, 3.6 mmol) were placed in a Schlenk flask and replaced with argon. Methanol (3 mL) and formic acid (453 μL, 12 mmol) were added and stirred for about 1 minute, after which Ir-PSA36 (2.1 mg, 3 μmol) was added and stirred vigorously at 40°C for 18 hours under an argon stream. The reaction solution was concentrated under reduced pressure to remove the methanol, and the product was obtained. NMR analysis showed that (R)-2-methoxy-5-(2-(N-((S)-2-hydroxyl-1-phenylethyl)aminopropyl)benzenesulfonamide formate was formed in 94% yield. 1 H NMR(DMSO-d6,400MHz)δ0.77(d,3H,J=6.4Hz),2.39(dd,1H),2.57(m,1H),2.86(dd,1H),3.34(dd,1H),3.4 5(dd,1H),3.84(s,3H),3.92(dd,1H),7.0(br,2H),7.06(d,1H,J=8.0Hz),7.20-7.44(m,7H),8.26(s,1H).

[0116] The entire amount of the target product obtained was neutralized by adding aqueous sodium hydroxide solution and extracted three times with methylene chloride. The methylene chloride phases were combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 438 mg of (R)-2-methoxy-5-(2-(N-((S)-2-hydroxyl-1-phenylethyl)aminopropyl)benzenesulfonamide. The entire amount of the product was dissolved in methanol (4.2 mL), water (4.2 mL), and 40% aqueous methylamine solution (1.3 mL), and orthoperiodic acid (978 mg, 4.3 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was concentrated to dryness to obtain (R)-2-methoxy-5-(2-aminopropyl)benzenesulfonamide. Its optical purity was 95% ee by HPLC analysis.

[0117] [Example 41] Synthesis of (R)-2-methoxy-5-(2-aminopropyl)benzenesulfonamide The reaction was carried out in the same manner as in Example 40, except that (S)-valinol was used as the amino alcohol, the amine source, and (R)-2-methoxy-5-(2-(N-((S)-2-(1-hydroxyl-3-methylbutyl))aminopropyl)benzenesulfonamide formate was obtained in 69% yield. Furthermore, (R)-2-methoxy-5-(2-aminopropyl)benzenesulfonamide was synthesized, and its optical purity was 97% ee.

[0118] [Example 42] Synthesis of (R)-N-acetyl-1-phenylethylamine First, (R)-N-((R)-2-hydroxyl-1-phenylethyl)-1-phenylethylamine was synthesized as follows. Acetophenone (233μL, 2mmol), (R)-phenylglycinol (329mg, 2.4mmol), methanol (2mL), and formic acid (226μL, 6mmol) were charged into an argon-substituted Schlenk flask and stirred for about 1 minute. Ir-PSA18 (6.66mg, 10μmol) was then added and stirred vigorously for 18 hours at 40℃ under an argon stream. The reaction solution was neutralized with an aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The combined ethyl acetate phase was washed with water and then with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 443mg of product. NMR analysis showed that (R)-N-((R)-2-hydroxyl-1-phenylethyl)-1-phenylethylamine was produced in a yield of 75%. 1 H NMR(CDCl3,400MHz)δ1.32(d,3H,J=6.4Hz),2.52(br,1H),3.48-3.57(m,3H),3.64(q,1H,J=6.8Hz),7.19-7.38(m,10H).

[0119] The entire amount of the target product obtained was dissolved in methanol (6 ml), water (6 mL), and 40% methylamine aqueous solution (2 mL), and orthoperiodic acid (1.5 g, 6.6 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was extracted three times with methylene chloride. The methylene chloride phases were combined, washed with water and then with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain (R)-1-phenylethylamine. Furthermore, the entire amount of the product was dissolved in methylene chloride (5 mL), and triethylamine (277 μL) and acetic anhydride (189 μL, 2 mmol) were added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was quenched by adding a saturated aqueous sodium bicarbonate solution, and extracted three times with methylene chloride. The methylene chloride phases were combined, washed with water and then with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain (R)-N-acetyl-1-phenylethylamine for measuring the optical purity. GC analysis revealed that the optical purity was 93% ee.

[0120] [Example 43] Synthesis of 1-(2-chlorophenyl)ethylamine First, N-((R)-2-hydroxyl-1-phenylethyl)-1-(2-chlorophenyl)ethylamine was synthesized as follows. In an argon-substituted Schlenk flask, 2'-chloroacetophenone (650μL, 5mmol), (R)-phenylglycinol (823mg, 6mmol), methanol (5mL), and formic acid (566μL, 15mmol) were charged and stirred for about 1 minute, after which Ir-QN (5.5mg, 10μmol) was added and vigorously stirred for 18 hours at 40℃ under an argon stream. The reaction solution was neutralized by adding an aqueous sodium bicarbonate solution and extracted with methylene chloride. The methylene chloride phase was washed with a saturated aqueous sodium chloride solution, and the solvent was distilled off to obtain the product. NMR analysis showed that N-((R)-2-hydroxyl-1-phenylethyl)-1-(2-chlorophenyl)ethylamine was produced in a yield of 46%. The diastereomer excess was 90%de. The residue was purified by silica gel column chromatography using hexane / ethyl acetate as an eluent to obtain 574mg of the target product. 1 H NMR(CDCl3,400MHz)δ1.30(d,3H,J=6.4Hz),3.49-3.62(m,3H),4.16(q,1H,J=6.4Hz),7.18-7.35(m,8H),7.54(m,1H).

[0121] 100 mg of the obtained target product was dissolved in methanol (810 μl), THF (90 μL), water (0.9 mL), and 40% aqueous methylamine solution (0.36 mL), and orthoperiodic acid (298 mg, 1.3 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was diluted with water and extracted twice with ethyl acetate. The ethyl acetate phases were combined, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 1-(2-chlorophenyl)ethylamine. The optical purity was 86% ee by HPLC analysis.

[0122] [Example 44] Synthesis of 1-(2-chlorophenyl)ethylamine First, N-((R)-2-hydroxyl-1-phenylethyl)-1-(2-chlorophenyl)ethylamine was synthesized as follows. 2'-Chloroacetophenone (650μL, 5mmol), (R)-phenylglycinol (823mg, 6mmol), toluene, and p-toluenesulfonic acid monohydrate (48mg, 0.25mmol) were charged into an argon-substituted Schlenk tube, and a Dean-Stark trap was attached and the mixture was heated and refluxed for 18 hours. Toluene was distilled off under reduced pressure, and methanol (5mL) and formic acid (566μL, 15mmol) were added to the mixture, which was stirred for about 1 minute, and then Ir-QN (5.5mg, 10μmol) was added and stirred vigorously at 40℃ for 18 hours under an argon stream. The reaction solution was neutralized by adding an aqueous sodium bicarbonate solution and extracted with methylene chloride. The methylene chloride phase was washed with a saturated aqueous sodium chloride solution, and the solvent was distilled off to obtain 1.32g of the product. NMR analysis revealed that N-((R)-2-hydroxyl-1-phenylethyl)-1-(2-chlorophenyl)ethylamine was produced in 72% yield with a diastereomeric excess of 88%de.

[0123] The entire amount of the target product obtained was dissolved in methanol (8.1 ml), THF (0.9 mL), water (9 mL), and 40% aqueous methylamine solution (3.6 mL), and orthoperiodic acid (2.98 g, 13 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was diluted with water and extracted twice with ethyl acetate. The ethyl acetate phases were combined, dried over anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography using hexane / ethyl acetate as an eluent to obtain 481 mg of 1-(2-chlorophenyl)ethylamine. The optical purity was 92% ee by HPLC analysis.

[0124] [Example 45] Synthesis of (S)-N-acetyl-2-octylamine First, (S)-N-((R)-2-(1-hydroxyl-3-methylbutyl))-2-octylamine was synthesized as follows. Ir-PSA18 (1.33 mg, 2 μmol) was placed in a Schlenk flask and replaced with argon. 2-Octanone (156 μL, 1 mmol), (R)-valinol (124 mg, 1.2 mmol), methanol (1 mL), and formic acid (116 μL, 3 mmol) were added and vigorously stirred at 40°C for 18 hours under argon flow. The reaction solution was concentrated under reduced pressure to remove the methanol, and then neutralized with an aqueous sodium hydroxide solution and extracted twice with methylene chloride. The methylene chloride phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed to obtain 210 mg of product. NMR analysis showed that (S)-N-((R)-2-(1-hydroxyl-3-methylbutyl))-2-octylamine was produced in a yield of 94%. 1 H NMR(CDCl3,400MHz)δ0.86-0.92(m,3H),0.90(d,3H,J=6.8Hz),0.95(d,3H,J=6.8Hz),1.04(d,3H, J=6.4Hz),1.20-1.46(m,10H),1.75(m,1H),2.44(m,1H),2.64(m,1H),3.28(dd,1H),3.52(dd,1H).

[0125] The entire amount of the target product obtained was dissolved in methanol (3 mL), water (3 mL), and 40% methylamine aqueous solution (1 mL), and orthoperiodic acid (752 mg, 3.3 mmol) was added and stirred for 68 hours. Aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was stirred and extracted with methylene chloride. The methylene chloride phase was washed with saturated aqueous sodium thiosulfate solution, then dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain (S)-2-octylamine. Furthermore, the entire amount of the product was dissolved in methylene chloride, and triethylamine (600 μL), DMAP (14 mg), and acetic anhydride (400 μL, 4.2 mmol) were added, and the mixture was stirred at room temperature for 47 hours. Aqueous ammonium chloride solution was added to the reaction solution, and the mixture was stirred, and then extracted with methylene chloride. The methylene chloride phase was dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain (S)-N-acetyl-2-octylamine for measuring the optical purity. GC analysis revealed that the optical purity was 49% ee.

[0126] [Example 46] Synthesis of N-benzoyl-2-methyl-4-heptylamine Ir-PSA18 (3.33 mg, 5 μmol) and (R)-phenylglycinol (165 mg, 1.2 mmol) were placed in a Schlenk flask and replaced with argon. 2-Methyl-4-heptanone (158 μL, 1 mmol), methanol (1 mL), and formic acid (116 μL, 3 mmol) were added and vigorously stirred at 40°C for 18 hours under argon flow. The reaction solution was concentrated under reduced pressure to remove the methanol, then neutralized with an aqueous sodium hydroxide solution and extracted with methylene chloride. The methylene chloride phase was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed to obtain 128 mg of product. NMR analysis showed that N-((R)-2-hydroxyl-1-phenylethyl)-2-methyl-4-heptylamine was produced in a yield of 35%.

[0127] The entire product was dissolved in methanol (6 mL), water (3 mL), and 40% methylamine aqueous solution (1 mL), and orthoperiodic acid (752 mg, 3.3 mmol) was added and stirred for 21 hours. Aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was stirred and extracted twice with methylene chloride. The methylene chloride phases were combined, washed with saturated aqueous sodium thiosulfate solution, dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain 2-methyl-4-heptylamine. Furthermore, the entire product was dissolved in methylene chloride and triethylamine (348 μL), and benzoyl chloride (232 μL) was added dropwise under ice cooling, and the mixture was warmed to room temperature and stirred for 68 hours. Aqueous sodium hydroxide solution was added to the reaction solution to quench it, and the mixture was extracted with methylene chloride. The methylene chloride phase was washed with water, dried with anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography using hexane / ethyl acetate as an eluent to obtain 55 mg of the product. The produced N-benzoyl-2-methyl-4-heptylamine was analyzed for its optical purity by NMR analysis, and its optical purity was 71% ee by HPLC analysis. 1H NMR(CDCl3,400MHz)δ0.92-0.99(m,9H),1.33-1.60(m,6H),1.69(m,1H),4.27(m,1H),5.72(br.d,1H),7.41-7.52(m,3H),7.76(m,2H).

[0128] [Example 47] Synthesis of N-benzoyl-3,3-dimethylcyclohexylamine First, N-((R)-2-hydroxyl-1-phenylethyl)-3,3-dimethylcyclohexylamine was synthesized as follows. Ir-PSA18 (1.33 mg, 2 μmol) and (R)-phenylglycinol (165 mg, 1.2 mmol) were placed in a Schlenk flask and replaced with argon. 3,3-Dimethylcyclohexanone (139 μL, 1 mmol), methanol (1 mL), and formic acid (116 μL, 3 mmol) were added and vigorously stirred at 40°C for 18 hours under argon flow. The reaction solution was concentrated under reduced pressure to remove the methanol, then neutralized with an aqueous sodium hydroxide solution and extracted twice with methylene chloride. The methylene chloride phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed to obtain the product. NMR analysis showed that N-((R)-2-hydroxyl-1-phenylethyl)-3,3-dimethylcyclohexylamine was produced in a yield of 92%. 1 H NMR(CDCl3,400MHz)δ0.77(s,3H),0.84-0.97(m,2H),0.91(s,3H),1.05(m,1H),1.27-1 .74(m,5H),2.53(m,1H),3.43(dd,1H),3.65(dd,1H),3.87(dd,1H),7.25-7.34(m,5H).

[0129] The entire product was dissolved in methanol (6 mL), water (3 mL), and 40% methylamine aqueous solution (1 mL), and orthoperiodic acid (752 mg, 3.3 mmol) was added and stirred for 51 hours. Aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was stirred and extracted twice with methylene chloride. The methylene chloride phases were combined, washed with saturated aqueous sodium thiosulfate solution, dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain 3,3-dimethylcyclohexylamine. Furthermore, the entire product was dissolved in methylene chloride and triethylamine (488 μL), and benzoyl chloride (395 μL) was added dropwise under ice cooling, and the mixture was warmed to room temperature and stirred for 68 hours. Aqueous sodium hydroxide solution was added to the reaction solution to quench it, and the mixture was extracted with methylene chloride. The methylene chloride phase was washed with water, dried with anhydrous sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography using hexane / ethyl acetate as an eluent to obtain 183 mg of N-benzoyl-3,3-dimethylcyclohexylamine for measuring the optical purity, which was 87% ee by HPLC analysis.

[0130] [Example 48] Synthesis of (S)-2-amino-3-phenylpropionic acid First, (S)-N-((R)-2-(1-hydroxyl-3-methylbutyl))-2-amino-3-phenylpropionic acid formate was synthesized as follows. Phenylpyruvic acid (492 mg, 3 mmol) and (R)-valinol (371 mg, 3.6 mmol) were placed in a Schlenk flask and replaced with argon. Methanol (3 mL) and formic acid (340 μL, 9 mmol) were added and stirred for about 1 minute, after which Ir-PSA36 (4.2 mg, 6 μmol) was added and stirred vigorously at 40°C for 18 hours under an argon stream. The reaction solution was concentrated under reduced pressure to remove the methanol, yielding 793 mg of product. NMR analysis revealed that (S)-N-((R)-2-(1-hydroxyl-3-methylbutyl))-2-amino-3-phenylpropionic acid formate was formed in a yield of 43%. 1H NMR(DMSO-d6,400MHz)δ0.62(d,3H,J=6.9Hz),0.71(d,3H,J=6.9Hz),1.61(m,1H),2.25(m,1H),2.62(dd,1H,J=8.7,13.7Hz), 7.73(dd,1H,J=8.2,13.3Hz),3.23(dd,1H,J=7.3,11.0Hz),3.36-3.40(m,2H),3.84(dd,1H,J=3.7,8.7Hz),7.13-7.27(m,5H).

[0131] The total amount of the target product obtained was dissolved in methanol (9.6 mL), water (8.1 mL), and 40% methylamine aqueous solution (4.5 mL), and orthoperiodic acid (2.26 g, 9.9 mmol) was added and vigorously stirred at room temperature for 16 hours. The reaction solution was concentrated to dryness to obtain (S)-2-amino-3-phenylpropionic acid. The optical purity was 97% ee by HPLC analysis.

[0132] [Example 49] Synthesis of (S)-2-amino-4-phenylbutyric acid First, (S)-N-((R)-2-hydroxyl-1-phenylethyl)-2-amino-4-phenylbutyric acid formate was synthesized as follows. 2-Oxo-4-phenylbutyric acid (535 mg, 3 mmol) and (R)-phenylglycinol (494 mg, 3.6 mmol) were placed in a Schlenk flask and replaced with argon. Methanol (3 mL) and formic acid (340 μL, 9 mmol) were added and stirred for about 1 minute, after which Ir-PSA36 (4.2 mg, 6 μmol) was added and stirred vigorously at 40°C for 18 hours under an argon stream. The reaction solution was concentrated under reduced pressure to remove the methanol, yielding 984 mg of product. NMR analysis showed that (S)-N-((R)-2-hydroxyl-1-phenylethyl)-2-amino-4-phenylbutyric acid formate was formed in a yield of 68%. The total amount of the target product obtained was dissolved in methanol (9.6 mL), water (8.1 mL), and 40% aqueous methylamine solution (4.5 mL), and orthoperiodic acid (2.26 g, 9.9 mmol) was added and vigorously stirred at room temperature for 16 hours. The reaction solution was concentrated to dryness to obtain (S)-2-amino-4-phenylbutyric acid. The optical purity was 94% ee by HPLC analysis.

[0133] [Example 50] Synthesis of methyl N-benzoyl-4-aminovalerate First, N-((S)-2-(1-hydroxyl-3-methylbutyl))-4-aminovaleric acid formate was synthesized as follows. In an argon-purged Schlenk flask, levulinic acid (200 mg, 1.72 mmol), (R)-valinol (213 mg, 2.07 mmol), methanol (1.73 mL), and formic acid (195 μL, 5.17 mmol) were charged and stirred for about 1 minute, after which Ir-PSA18 (2.3 mg, 3.5 μmol) was added and the mixture was stirred vigorously at 40°C for 18 hours under an argon stream. The reaction solution was concentrated under reduced pressure to obtain the product. NMR analysis showed that N-((S)-2-(1-hydroxyl-3-methylbutyl))-4-aminovaleric acid formate was produced in a yield of 92%. 1 H NMR(CDCl3,400MHz)δ1.04(d,3H),1.09(d,3H),1.37(d,3H),1.81-2.15(m,3H) ,2.42(m,1H),2.52(m,1H),2.93(m,1H),3.54(m,1H),3.83(m,1H),3.92(m,1H).

[0134] Half of the target product was dissolved in methanol (2.6 mL) and 40% methylamine aqueous solution (0.86 mL), and an aqueous solution of orthoperiodic acid (648 mg, 2.84 mmol) dissolved in water (2.6 mL) was added and stirred at room temperature for 18 hours. Methylene chloride was added to the reaction solution, and the mixture was stirred and separated to obtain the aqueous layer. The aqueous layer was concentrated under reduced pressure to remove some of the water, and then passed through a cation exchange resin (Amberlite CG-50, Organo), concentrated under reduced pressure, and dried. 1M hydrogen chloride / methanol solution (3 mL) was added and stirred, and the resulting precipitate was removed by filtration, and the mixture was concentrated and dried to obtain methyl 4-aminovalerate hydrochloride. Furthermore, triethylamine (100 μL) and benzoyl chloride (50 μL, 431 μmol) were added to half of the obtained salt, and the mixture was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution, and the mixture was stirred and extracted with methylene chloride. The methylene chloride phase was concentrated under reduced pressure to obtain methyl N-benzoyl-4-aminovalerate for measuring the optical purity, which was 68% ee by HPLC analysis.

[0135] [Example 51] Synthesis of methyl N-((S)-2-hydroxyl-1-phenylethyl)-3-aminovalerate Ir-PSA18 (3.33 mg, 5 μmol) and (S)-phenylglycinol (165 mg, 1.2 mmol) were placed in a Schlenk flask and replaced with argon. Methyl 3-oxovalerate (124 μL, 1 mmol), methanol (1 mL), and formic acid (116 μL, 3 mmol) were added and vigorously stirred at 40°C for 18 hours under argon flow. The reaction solution was concentrated under reduced pressure to remove the methanol, then neutralized with an aqueous sodium hydroxide solution and extracted twice with MTBE. The MTBE phase was combined and washed with water, and the solvent was removed by distillation to obtain 210 mg of product. NMR analysis showed that N-((S)-2-hydroxyl-1-phenylethyl)-3-aminomethyl valerate was produced in a yield of 41%. 1H NMR(CDCl3,400MHz)δ0.84(t,3H,J=7.2Hz),1.37-1.53(m,2H),2.36(dd,1H),2.49(dd,1 H),2.90(m,1H),3.48(m,1H),3.65(m,1H),3.69(s,3H),3.87(m,1H),7.26-7.38(m,5H).

[0136] [Example 52] Synthesis of N-acetyl-2-propylcyclohexylamine Ir-PSA18 (3.33 mg, 5 μmol) and (R)-phenylglycinol (165 mg, 1.2 mmol) were placed in a Schlenk flask and replaced with argon. 2-Propylcyclohexanone (154 μL, 1 mmol), methanol (1 mL), and formic acid (116 μL, 3 mmol) were added and vigorously stirred at 40°C for 18 hours under argon flow. The reaction solution was concentrated under reduced pressure to remove the methanol, then neutralized with an aqueous sodium hydroxide solution and extracted twice with MTBE. The MTBE phase was combined and washed with water, and the solvent was removed by distillation to obtain 229 mg of product. NMR analysis showed that N-((R)-2-hydroxyl-1-phenylethyl)-2-propylcyclohexylamine was produced in a yield of 70%. 1 H NMR(CDCl3,400MHz)δ0.94(t,3H),1.17-1.58(m,13H),2.66(m,1H),3.06(br,1H),3.44(dd,1H),3.65(m,1H),3.78(m,1H),7.25-7.36(m,5H). The entire amount of the target product obtained was dissolved in methanol (6 mL), water (3 mL), and 40% methylamine aqueous solution (1 mL), and orthoperiodic acid (752 mg, 3.3 mmol) was added and stirred for 19 hours. Aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was stirred and extracted with methylene chloride. The methylene chloride phase was washed with saturated aqueous sodium thiosulfate solution, then dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain 2-propylcyclohexylamine. Furthermore, the entire amount of the product was dissolved in methylene chloride, and triethylamine (130 μL) and acetic anhydride (95 μL, 1 mmol) were added and the mixture was stirred at room temperature for 3 hours. The reaction solution was quenched by adding aqueous sodium hydroxide solution, and then extracted with MTBE. The MTBE phase was washed with water, and the solvent was distilled off to obtain N-acetyl-2-propylcyclohexylamine for measuring the optical purity. GC analysis showed that the diastereomeric ratio was 88:12, and the optical purity of the major was 98% ee.

[0137] [Example 53] Synthesis of 3-(acetylamino)-1-tert-butoxycarbonylpiperidine First, 1-tert-butoxycarbonyl-3-(((S)-2-(1-hydroxyl-3-methylbutyl))amino)piperidine was synthesized as follows. Ir-PSA18 (1.33 mg, 2 μmol) and N-Boc-3-piperidinone (199 mg, 1 mmol) were placed in a Schlenk flask and replaced with argon. (R)-Valinol (124 mg, 1.2 mmol), methanol (1 mL), and formic acid (116 μL, 3 mmol) were added and vigorously stirred under argon at 40°C for 18 hours. The reaction solution was concentrated under reduced pressure to remove the methanol, then neutralized with an aqueous sodium hydroxide solution and extracted twice with MTBE. The MTBE phase was combined and washed with water, and the solvent was removed by distillation to obtain 305 mg of product. NMR analysis showed that 1-tert-butoxycarbonyl-3-(((S)-2-(1-hydroxyl-3-methylbutyl))amino)piperidine was produced in a yield of 91%. The entire amount of the target product obtained was dissolved in methanol (3 mL), water (3 mL), and 40% methylamine aqueous solution (1 mL), and orthoperiodic acid (752 mg, 3.3 mmol) was added and stirred for 16 hours. Aqueous sodium hydroxide solution was added to the reaction solution, and the mixture was stirred and extracted with methylene chloride. The methylene chloride phase was washed with saturated aqueous sodium thiosulfate solution, then dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain 1-tert-butoxycarbonyl-3-aminopiperidine. Furthermore, the entire amount of the product was dissolved in methylene chloride, and triethylamine (708 μL) and acetic anhydride (400 μL, 4.2 mmol) were added, and the mixture was stirred at room temperature for 18 hours. The reaction solution was quenched by adding an aqueous sodium hydroxide solution, and then extracted with methylene chloride. The methylene chloride phase was dried with anhydrous sodium sulfate, and the solvent was distilled off to obtain 3-(acetylamino)-1-tert-butoxycarbonylpiperidine for measuring the optical purity. GC analysis revealed that the optical purity was 50% ee.

[0138] [Example 54] Synthesis of (S)-2-amino-5-methoxytetralin First, (S)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin was synthesized as follows. 5-Methoxy-2-tetralone (3.54g, 20mmol) and (S)-valinol (2.48g, 24mmol) were placed in a Schlenk flask and replaced with argon. Chloroform (40mL) and anhydrous magnesium sulfate (3.52g) were added and stirred under reflux for 17 hours. The reaction solution was filtered through Celite and concentrated under reduced pressure to obtain 5.12g of spiro[5-methoxytetralin-2,2'-[4]-isopropyloxazolidine]. The obtained spiro[5-methoxytetralin-2,2′-[4]-isopropyloxazolidine] (1.31 g) was placed in a Schlenk flask and replaced with argon. Acetonitrile (5 mL) and formic acid (566 μL, 15 mmol) were added and stirred for about 1 minute, then Ir-PSA4 (6.52 mg, 10 μmol) was added and stirred vigorously at 40°C for 18 hours under argon flow. The reaction solution was neutralized by adding an aqueous sodium bicarbonate solution and extracted three times with ethyl acetate. The ethyl acetate phase was combined, washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the product. NMR analysis showed that (S)-N-((S)-2-(1-hydroxyl-3-methylbutyl))-2-amino-5-methoxytetralin was produced in a yield of 91%.

[0139] The entire amount of the target product obtained was dissolved in methanol (15 mL), water (15 mL), and 40% methylamine aqueous solution (5 mL), and orthoperiodic acid (3.76 g, 16.5 mmol) was added and vigorously stirred at room temperature for 64 hours. The reaction solution was diluted with water, extracted with ethyl acetate, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain (S)-2-amino-5-methoxytetralin. Its optical purity was 63% ee by HPLC analysis.

[0140] [Example 55] Synthesis of 1-amino-4-cyanoindan First, N-((R)-2-hydroxyl-1-phenylethyl)-1-amino-4-cyanoindan was synthesized as follows. 4-Cyano-1-indanone (157 mg, 1 mmol) and (R)-phenylglycinol (165 mg, 1.2 mmol) were placed in a Schlenk flask and replaced with argon. Methylene chloride (1 mL) and formic acid (113 μL, 3 mmol) were added and stirred for about 1 minute, after which Ir-PSA18 (1.33 mg, 2 μmol) was added and vigorously stirred for 18 hours at 40°C under an argon stream. The reaction solution was neutralized by adding an aqueous sodium bicarbonate solution and extracted with methylene chloride. The methylene chloride phase was washed with a saturated aqueous sodium chloride solution, and the solvent was distilled off to obtain the product. NMR analysis showed that N-((R)-2-hydroxyl-1-phenylethyl)-1-amino-4-cyanoindan was produced in a yield of 90%. The entire amount of the target product obtained was dissolved in methanol (2 mL), THF (225 μL), water (2.2 mL), and 40% aqueous methylamine solution (0.9 mL), and orthoperiodic acid (739 mg, 3.2 mmol) was added and vigorously stirred at room temperature for 18 hours. The reaction solution was diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 1-amino-4-cyanoindan. The optical purity was 99% ee by HPLC analysis. 1 H NMR(CDCl3,400MHz)δ1.77(m,1H),2.60(m,1H),2.96(m,1H),3.18(m,1H),4.42(t, 1H,J=7.2Hz),7.32(t,1H,J=7.6Hz),7.49(d,1H,J=7.6Hz),7.56(d,1H,J=7.6Hz).

Claims

1. A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) 【Chemistry 1】 In the formula, R １ represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by heteroatoms, or a heterocyclyl group having 3 to 20 ring members, in which one or more hydrogen atoms are optionally substituted by a substituent W, W is a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group; two or more Ws together form 1 or two or more rings may be formed, and Ra, Rb and Rc are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members or an alkylheteroaryl group having 6 to 20 ring members; R ２ , R ３ , R ４ and R ５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by a heteroatom, or -C(=O)-ORa, where Ra has the same meaning as defined above. and an amino alcohol represented by the formula: The following general formula (2) 【Chemistry 2】 In the formula, R ６ and R ７ are different from each other and each is a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acetyl group, a benzoyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a carbamoyl group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R ６ and R ７ may be joined together to form a ring; and a carbonyl compound represented by the formula: The following general formula (3) 【Chemistry 3】 In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be substituted by the substituent W. X is a hydride group or an anionic group; R ８ and R ９ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R ８ Or R ９ a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, When j is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (4) 【Chemistry 4】 In the formula, Ar, X and R ８ has the same meaning as above, R １０ represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4; R ８ a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, When l is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (5) 【Chemistry 5】 In the formula, Ar and X have the same meanings as defined above. Y is a nitrogen atom or an oxygen atom; A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted with the substituent W; R １１ represents, when Y is a nitrogen atom, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb, in which one or more hydrogen atoms may be substituted with the substituent W, and is unsubstituted when Y is an oxygen atom; R １２ , R １３ , R １４ and R １５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １２ and R １３ and / or R １４ and R １５ may be taken together to form a ring, R １２ Or R １３ Either １４ Or R １５ may be taken together to form a ring, R １２ Or R １３ and / or R １４ Or R １５ Either one of the groups may be combined with A to form a ring, n is an integer from 0 to 2; or The following general formula (6) 【Chemistry 6】 In the formula, Ar and X have the same meanings as above. B is a saturated or unsaturated nitrogen-containing heterocyclic carbene containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted with the substituent W; R １６ represents a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R １７ , R １８ , R １９ , R ２０ and R ２１ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １６ , R １７ , R １８ , R １９ and R ２０ Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3; with a hydrogen donor compound in the presence of an organic iridium compound represented by the formula: The reaction product is represented by the following general formula (A): 【Chemistry 7】 In the formula, R ２ , R ３ , R ４ , and R ５ has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

2. A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) 【Chemistry 8】 In the formula, R １ represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by heteroatoms, or a heterocyclyl group having 3 to 20 ring members, one or more hydrogen atoms of these groups may be replaced by the substituent W, W is a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group; two or more Ws together form 1 or two or more rings may be formed, and Ra, Rb and Rc are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members or an alkylheteroaryl group having 6 to 20 ring members; R ２ , R ３ , R ４ and R ５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by a heteroatom, or -C(=O)-ORa, where Ra has the same meaning as defined above. and an amino alcohol represented by the formula: The following general formula (2) 【Chemistry 9】 In the formula, R ６ and R ７ are different from each other and each is a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acetyl group, a benzoyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a carbamoyl group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R ６ and R ７ may be joined together to form a ring; and a carbonyl compound represented by the formula: The following general formula (7) 【Chemistry 10】 In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be substituted by the substituent W. X is a hydride group or an anionic group; and an organic iridium compound represented by the formula: The following general formula (8) 【Chemistry 11】 In the formula, R ８ and R ９ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R ８ Or R ９ a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, When j is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (9) 【Chemistry 12】 In the formula, R ８ has the same meaning as above, R １０ represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4; R ８ a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, When l is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (10) 【Chemistry 13】 In the formula, Y is a nitrogen atom or an oxygen atom, A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted with the substituent W; R １１ represents, when Y is a nitrogen atom, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb, in which one or more hydrogen atoms may be substituted with the substituent W, and is unsubstituted when Y is an oxygen atom; R １２ , R １３ , R １４ and R １５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １２ and R １３ and / or R １４ and R １５ may be taken together to form a ring, R １２ Or R １３ Either １４ Or R １５ may be taken together to form a ring, R １２ Or R １３ and / or R １４ Or R １５ Either one of the groups may be combined with A to form a ring, n is an integer from 0 to 2, or The following general formula (11) 【Chemistry 14】 In the formula, R １６ represents a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R １７ , R １８ , R １９ , R ２０ and R ２１ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １６ , R １７ , R １８ , R １９ and R ２０ Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3, B' is a saturated or unsaturated nitrogen-containing heterocyclic carbene precursor containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted with the substituent W; Z is an anionic group; with a hydrogen donor compound in the presence of an organic compound represented by the formula: The reaction product is represented by the following general formula (A): 【Chemistry 15】 In the formula, R ２ , R ３ , R ４ , and R ５ has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

3. A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) 【Chemistry 16】 In the formula, R １ represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by heteroatoms, or a heterocyclyl group having 3 to 20 ring members, one or more hydrogen atoms of these groups may be replaced by the substituent W, W is a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group; two or more Ws together form 1 or two or more rings may be formed, and Ra, Rb and Rc are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members or an alkylheteroaryl group having 6 to 20 ring members; R ２ , R ３ , R ４ and R ５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by a heteroatom, or -C(=O)-ORa, where Ra has the same meaning as defined above. and an amino alcohol represented by the formula: The following general formula (2) 【Chemistry 17】 In the formula, R ６ and R ７ are different from each other and each is a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acetyl group, a benzoyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a carbamoyl group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R ６ and R ７ may be joined together to form a ring; Carbonyl compounds represented by the formula: A hemiaminal ether, imine or enamine prepared from The following general formula (3) 【Chemistry 18】 In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be substituted by the substituent W. X is a hydride group or an anionic group; R ８ and R ９ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R ８ Or R ９ a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, When j is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (4) 【Chemistry 19】 In the formula, Ar, X and R ８ has the same meaning as above, R １０ represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4; R ８ a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, When l is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (5) 【Chemistry 20】 In the formula, Ar and X have the same meanings as defined above. Y is a nitrogen atom or an oxygen atom; A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted with the substituent W; R １１ represents, when Y is a nitrogen atom, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb, in which one or more hydrogen atoms may be substituted with the substituent W, and is unsubstituted when Y is an oxygen atom; R １２ , R １３ , R １４ and R １５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １２ and R １３ and / or R １４ and R １５ may be taken together to form a ring, R １２ Or R １３ Either １４ Or R １５ may be taken together to form a ring, R １２ Or R １３ and / or R １４ Or R １５ Either one of the groups may be combined with A to form a ring, n is an integer from 0 to 2, or The following general formula (6) 【Chemistry 21】 In the formula, Ar and X have the same meanings as above. B is a saturated or unsaturated nitrogen-containing heterocyclic carbene containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted with the substituent W; R １６ represents a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R １７ , R １８ , R １９ , R ２０ and R ２１ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １６ , R １７ , R １８ , R １９ and R ２０ Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3; with a hydrogen donor compound in the presence of an organic iridium compound represented by the formula: The reaction product is represented by the following general formula (A): 【Chemical 22】 In the formula, R ２ , R ３ , R ４ , and R ５ has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

4. A method for producing an optically active primary or secondary amine compound, comprising the steps of: The following general formula (1) 【Chemistry 23】 In the formula, R １ represents a hydrogen atom, a C1-C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atoms may be replaced by heteroatoms, or a heterocyclyl group having 3 to 20 ring members, in which one or more hydrogen atoms are optionally substituted by a substituent W, W is a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group; two or more Ws together form 1 or two or more rings may be formed, and Ra, Rb and Rc are the same or different and each represent a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, an aralkyl group having 6 to 20 ring members, a heteroaralkyl group having 6 to 20 ring members, an alkylaryl group having 6 to 20 ring members or an alkylheteroaryl group having 6 to 20 ring members; R ２ , R ３ , R ４ and R ５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 22 ring members whose carbon atom may be replaced by a hetero atom, or -C(=O)-ORa, where Ra has the same meaning as defined above; The following general formula (2) 【Chemistry 24】 In the formula, R ６ and R ７ are different from each other and each is a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, an acetyl group, a benzoyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a carbamoyl group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R ６ and R ７ may be joined together to form a ring; A hemiaminal ether, imine or enamine prepared from a carbonyl compound represented by the formula: The following general formula (7) 【Chemistry 25】 In the formula, Ar is a cyclopentadienyl group in which one or more hydrogen atoms may be substituted by the substituent W. X is a hydride group or an anionic group; and an organic iridium compound represented by the formula: The following general formula (8) 【Chemistry 26】 In the formula, R ８ and R ９ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, j and k are the same or different and are integers from 0 to 3; R ８ Or R ９ a carbon atom in the quinoline ring to which is not attached may be replaced by a nitrogen atom, When j is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (9) 【Chemical 27】 In the formula, R ８ has the same meaning as above, R １０ represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by heteroatoms, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, l is an integer from 0 to 4; R ８ a carbon atom in the pyridine ring to which is not bonded may be replaced by a nitrogen atom, When l is 2 or more, 2 or more R ８ may be joined together to form one or more rings, The following general formula (10) 【Chemistry 28】 In the formula, Y is a nitrogen atom or an oxygen atom, A is a saturated or unsaturated heterocycle containing at least one nitrogen atom, in which one or more hydrogen atoms may be substituted with the substituent W; R １１ represents, when Y is a nitrogen atom, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra or -C(=O)-NRaRb, in which one or more hydrogen atoms may be substituted with the substituent W, and is unsubstituted when Y is an oxygen atom; R １２ , R １３ , R １４ and R １５ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １２ and R １３ and / or R １４ and R １５ may be taken together to form a ring, R １２ Or R １３ Either １４ Or R １５ may be taken together to form a ring, R １２ Or R １３ and / or R １４ Or R １５ Either one of the groups may be combined with A to form a ring, n is an integer from 0 to 2; or The following general formula (11) 【Chemical formula 29】 In the formula, R １６ represents a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, -C(=O)-Ra, -C(=O)-ORa, -C(=O)-NRaRb, -C(=S)-NRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 fluoroalkyl group, or an aryl group having 6 to 20 ring members in which a carbon atom may be replaced by a heteroatom, one or more hydrogen atoms of these groups are optionally substituted by the substituent W, R １７ , R １８ , R １９ , R ２０ and R ２１ are the same or different and each represents a hydrogen atom, a C1 to C20 saturated or unsaturated hydrocarbon group, an aryl group having 6 to 20 ring members whose carbon atoms may be replaced by a heteroatom, a heterocyclyl group having 3 to 20 ring members, a C1 to C20 alkoxy group, -C(=O)-Ra, -C(=O)-ORa, -OC(=O)-Ra, a hydroxyl group, -NRaRb, -C(=O)-NRaRb, -NRa-C(=O)-Rb, a nitro group, a cyano group, -PRaRb, a C1 to C20 alkylsulfenyl group, a C1 to C20 alkylsulfonyl group, a benzenesulfonyl group, a sulfo group, a mercapto group, -SiRaRbRc, a halogen group, or a C1 to C20 fluoroalkyl group, and one or more hydrogen atoms of these groups may be replaced by the substituent W, Ra, Rb and Rc have the same meanings as above, R １６ , R １７ , R １８ , R １９ and R ２０ Two or more groups selected from the group consisting of may be joined together to form one or more rings, m is an integer of 0 to 3, B' is a saturated or unsaturated nitrogen-containing heterocyclic carbene precursor containing at least two nitrogen atoms, in which one or more hydrogen atoms may be substituted with the substituent W; Z is an anionic group; with a hydrogen donor compound in the presence of an organic compound represented by the formula: The reaction product is represented by the following general formula (A): 【Chemistry 30】 In the formula, R ２ , R ３ , R ４ , and R ５ has the same meaning as in general formula (1), a step of oxidatively deprotecting the moiety represented by The method according to claim 1, further comprising:

5. The method according to any one of claims 1 to 4, wherein the amino alcohol represented by the general formula (1) is an optically active substance.

6. The method according to any one of claims 1 to 5, wherein the aminoalcohol represented by general formula (1) is 2-aminoethanol, valinol, 2-amino-1-butanol, leucinol, tert-leucinol, phenylglycinol, phenylalaninol, serine, a serine ester, threonine, or a threonine ester.

7. The method according to any one of claims 1 to 6, wherein n is 0.

8. The method according to any one of claims 1 to 7, wherein m is 1.

9. The method according to any one of claims 1 to 8, wherein the organic iridium compound represented by general formula (3), general formula (4), general formula (5), or general formula (6), or the organic compound represented by general formula (8), general formula (9), general formula (10), or general formula (11) is an optically active substance.

10. The process according to any one of claims 1 to 9, wherein the oxidative deprotection is carried out using periodic acid, periodate or lead tetraacetate as oxidizing agent.

11. The method according to any one of claims 1 to 10, wherein the hydrogen donating compound is formic acid or a formate.

12. The method according to any one of claims 1 to 11, wherein the carbonyl compound represented by general formula (2) is 1-indanone, β-tetralone, phenylacetone, pyridylacetone, acetophenone, linear dialkyl ketone, branched dialkyl ketone, cyclohexanone, 3-piperidinone, α-keto acid (keto ester), β-keto acid (keto ester), or γ-keto acid (keto ester), which may have a substituent.

13. The method according to any one of claims 1 to 11, wherein the carbonyl compound represented by the general formula (2) is 5-methoxy-2-tetralone, 5-acetonyl-2-methoxybenzenesulfonamide, 5-acetonyl-7-cyano-1-(3-benzoyloxypropyl)indoline, 3-piperidinone, or 4-cyanoindanone, each of which may have a substituent.

Images