Novel 3-substituted vinyl sulfoximine derivatives, method for producing the same, and stereoselective method for producing 3-substituted alkenes using the same

Abstract

To provide 3-substituted vinyl sulfoximine derivatives useful for the stereoselective synthesis of 3-substituted alkenes.SOLUTION: The present invention relates to a compound represented by formula (I) in the figure [where each symbol is as defined in the specification], or a salt thereof, and to a method for producing the same. The present invention also relates to a stereoselective method for producing a 3-substituted alkene via a cross-coupling reaction using the compound of formula (I).SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a novel 3-substituted vinylsulfoximine derivative or a salt thereof, which is a precursor useful for the regioselective and stereoselective synthesis of 3-substituted alkenes, a method for producing the same, and a method for producing a stereoselective 3-substituted alkene using the same.

Background Art

[0002] 3-Substituted alkenes are structures contained in many pharmaceuticals and organic functional molecules. However, for 3-substituted alkenes with different substituents, regioselective and stereoselective synthesis is difficult, and there is currently no highly versatile synthesis method.

[0003] As a synthesis method for 3-substituted alkenes, the cross-coupling reaction is one of the effective methods. However, the biggest problem is that it is not easy to obtain the starting compound, 3-substituted vinyl (pseudo) halides, and there are limitations on the starting compounds that can be used.

[0004] The known synthesis methods for 3-substituted vinyl (pseudo) halides are specifically classified into four types: (a) a conversion reaction from a classical carbonyl group (Shapiro reaction), (b) a conversion reaction by cross-coupling from 1,1-dihalides (for example, Non-Patent Document 1), (c) a conversion reaction by addition to an alkyne (hydrohalogenation reaction) (for example, Non-Patent Documents 2 and 3), and (d) a conversion reaction by olefin metathesis (cross-metathesis) (for example, Non-Patent Documents 4 and 5).

[0005] However, in any of the above synthesis methods, there are problems in either the regioselectivity and / or stereoselectivity of the obtained 3-substituted alkene, or the availability of reaction reagents, catalysts, and starting compounds. Therefore, it is difficult to call them universal synthesis methods.

[0006] On the other hand, Non-Patent Document 6 discloses the following formula:

[0007]

Chemical Formula

[0008] (The definitions of the symbols in the formula are as described in Non-Patent Document 6.) Examples have been reported in which a cross-coupling reaction using a specific 3-substituted vinylsulfoximine represented by the formula as a pseudo-halide is used to convert it to a 3-substituted alkene. However, in Non-Patent Document 6, the reaction substrates are limited, and since it is difficult to obtain other 3-substituted vinylsulfoximines, this finding has not been directly utilized for the synthesis of other 3-substituted alkenes thereafter.

[0009] In fact, although several synthesis examples of 2-substituted vinylsulfoximines in which the α-position is a hydrogen atom are known (Non-Patent Documents 7 to 10), as synthesis examples of 3-substituted vinylsulfoximines, almost none are known other than the specific compounds described in Non-Patent Document 6.

Prior Art Documents

Non-Patent Documents

[0010]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Non-Patent Document 10

Summary of the Invention

Problems to be Solved by the Invention

[0011] An object of the present invention is to provide a 3-substituted vinyl (pseudo)halide which is a useful precursor for the regioselective and stereoselective synthesis of 3-substituted alkenes.

Means for Solving the Problems

[0012] As a result of intensive studies to solve the above problems, the present inventors have found that a compound represented by the following formula (I) or a salt thereof, that is, a 3-substituted vinylsulfoximine derivative, can be easily prepared, and that the 3-substituted vinylsulfoximine derivative is useful as a synthetic precursor for 3-substituted alkenes, thus completing the present invention.

[0013] That is, the present invention includes the aspects exemplified below.

[0014] [1] Formula (I):

[0015]

Chemical formula

[0016] [In the formula, R 1 is a C 1-6 alkyl group, a C 3-8 cycloalkyl group, each of which may be substituted with one or more substituents selected from the substituent group a,6-14 represents an aryl group or an aromatic heterocyclic group; R 2 is a halogen atom, or a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 1-6 alkylsulfenyl group, an acyl group, a C 6-14 represents an aryl group or an aromatic heterocyclic group; R 3 is a C 6-14 aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from substituent group a; and R is a hydrogen atom, or a C 1-6 alkyl group. (Substituent group a) halogen atom; cyano group; nitro group; C 1-6 alkyl group; C 1-6 haloalkyl group; C 1-6 alkoxy group; C 1-6 haloalkoxy group; C 2-6 alkynyl group; di(C 1-6 alkyl)phosphoryl group; di(C 6-10 aryl)phosphoryl group; C 1-6 alkylsulfonyl group; C 1-6 haloalkylsulfonyl group; C 1-6 alkyl-carbonyl group; C 1-6 alkoxy-carbonyl group; C 6-14 aryl-carbonyl group; C 1-6 haloalkyl-carbonyl group; C 1-6 haloalkoxy-carbonyl group; C 1-6 Alkylsulfonyloxy group; C 1-6 Haloalkylsulfonyloxy group; C 1-6 Alkyl - carbonyloxy group; C 1-6 Alkoxy - carbonyloxy group; C 1-6 Haloalkyl - carbonyloxy group; C 1-6 Haloalkoxy - carbonyloxy group; (i) Halogen atom, (ii) DiC 1-6 Alkylamino group, (iii) C 1-6 Alkoxy group, and (iv) C 1-6 Haloalkoxy group Optionally substituted with one or two C 1-6 Alkyl groups Optionally substituted carbamoyl group; (i) Halogen atom, (ii) C 1-6 Alkyl group, (iii) C 1-6 Haloalkyl group, (iv) C 1-6 Alkoxy group, (v) C 1-6 Haloalkoxy group, (vi) C 1-6 Alkylsulfonyl group, (vii) C 1-6 Haloalkylsulfonyl group, (viii) C 1-6 Alkyl - carbonyl group, (ix) C 1-6 Alkoxy - carbonyl group, (x) C 1-6 Haloalkyl - carbonyl group, (xi) C 1-6 Haloalkoxy - carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of optionally substituted by 6-14 an aryl group; (i) a halogen atom, (ii) a C 1-6 alkyl group, (iii) a C 1-6 haloalkyl group, (iv) a C 1-6 alkoxy group, (v) a C 1-6 haloalkoxy group, (vi) a C 1-6 alkylsulfonyl group, (vii) a C 1-6 haloalkylsulfonyl group, (viii) a C 1-6 alkyl-carbonyl group, (ix) a C 1-6 alkoxy-carbonyl group, (x) a C 1-6 haloalkyl-carbonyl group, (xi) a C 1-6 haloalkoxy-carbonyl group, and (xii) a nitro group One to three substituents selected from the group consisting of optionally substituted by 6-14 an aryloxy group; (i) a halogen atom, (ii) a C 1-6 alkyl group, (iii) a C 1-6 haloalkyl group, (iv) a C 1-6 alkoxy group, (v) a C 1-6 haloalkoxy group, (vi) a C 1-6 alkylsulfonyl group, (vii) a C 1-6 haloalkylsulfonyl group, (viii) a C 1-6 alkyl-carbonyl group, (ix) a C 1-6 alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 6-14 arylsulfonyloxy group; (i) a halogen atom, (ii) C 1-6 alkyl group, (iii) C 1-6 haloalkyl group, (iv) C 1-6 alkoxy group, (v) C 1-6 haloalkoxy group, (vi) C 1-6 alkylsulfonyl group, (vii) C 1-6 haloalkylsulfonyl group, (viii) C 1-6 alkyl-carbonyl group, (ix) C 1-6 alkoxy-carbonyl group, (x) C 1-6 haloalkyl-carbonyl group, (xi) C 1-6 haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 7-18 aralkyl group; (i) a halogen atom, (ii) C 1-6 alkyl group, (iii) C 1-6 haloalkyl group, (iv) C 1-6 alkoxy group, (v) C 1-6 haloalkoxy group, (vi) C 1-6 alkylsulfonyl group, (vii) C1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 7-18 an aralkyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 3-8 a cycloalkyl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted with C 3-8 a cycloalkyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted with a 5- to 14-membered aromatic heterocyclic group; and (i) a halogen atom, (ii) C 1-6 Alkyl groups, (iii) C 1-6 Haloalkyl groups, (iv) C 1-6 Alkoxy groups, (v) C 1-6 haloalkoxy groups, (vi) C 1-6 Alkylsulfonyl groups, (vii) C 1-6 haloalkylsulfonyl groups, (viii) C 1-6 Alkyl-carbonyl groups, (ix) C 1-6 Alkoxy-carbonyl groups, (x) C 1-6 haloalkyl-carbonyl groups, (xi) C 1-6 haloalkoxy-carbonyl groups, and (xii) Nitro group One to three substituents selected from the group consisting of and a 3- to 14-membered non-aromatic heterocyclic group optionally substituted with (hereinafter, also referred to as "the compound of the present invention"), or a salt thereof,

[0017] [2] R 1 each of which may be substituted with one or more substituents selected from the substituent group a; C 1-4 Alkyl group, C 3-6 Cycloalkyl group or C 6-10 is an aryl group; R 2 each of which may be substituted with a fluorine atom or one or more substituents selected from the substituent group a; C 1-4 Alkyl group, C 3-6 Cycloalkyl groups, C 6-10 an aryl group or a 5- to 14-membered aromatic heterocyclic group; R 3 each of which may be substituted with one or more substituents selected from the substituent group a; C6-10 an aryl group or a 5- to 14-membered aromatic heterocyclic group; and R is a hydrogen atom or a C 1-4 alkyl group, the compound according to [1] above, or a salt thereof,

[0018] [3] R 1 is (i) a halogen atom, (ii) a cyano group, (iii) a C 1-4 alkoxy group, (iv) a C 1-4 haloalkoxy group, (v) a C 3-8 cycloalkyl group, and (vi) a C 6-10 aryl group selected from the group consisting of one or more substituents optionally substituted with a C 1-4 alkyl group, or (i) a halogen atom, (ii) a cyano group, (iii) a C 1-4 alkyl group, (iv) a C 1-4 haloalkyl group, (v) a C 1-4 alkoxy group, (vi) a C 1-4 haloalkoxy group, and (vii) a nitro group selected from the group consisting of one or more substituents optionally substituted phenyl group; R 2 is a fluorine atom, (i) a halogen atom, (ii) a cyano group, (iii) a C 1-4 alkoxy group, (iv) a C 1-4 haloalkoxy group, (v) a C 3-6 cycloalkyl group, (vi) a C 6-10an aryl group, and (vii) C 2-4 an alkynyl group one or more substituents selected from the group consisting of optionally substituted C 1-4 alkyl group, or (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 alkyl group, (iv) C 1-4 haloalkyl group, (v) C 1-4 alkoxy group, (vi) C 1-4 haloalkoxy group, and (vii) a nitro group one or more substituents selected from the group consisting of an optionally substituted phenyl group; R 3 is (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 alkyl group, (iv) C 1-4 haloalkyl group, (v) C 1-4 alkoxy group, (vi) C 1-4 haloalkoxy group, (vii) (a) a halogen atom, (b) C 1-4 alkyl group, (c) C 1-4 haloalkyl group, (d) C 1-4 alkoxy group, (e) C 1-4 haloalkoxy group, (f) C 1-4 alkylsulfonyl group, (g) C 1-4 haloalkylsulfonyl group, (h) C 1-4 alkyl-carbonyl group, (i) C 1-4an alkoxy-carbonyl group, (j) C 1-4 a haloalkyl-carbonyl group, and (k) C 1-4 a haloalkoxy-carbonyl group selected from the group consisting of one to three substituents which may be substituted benzyl group, and (viii) a nitro group, selected from the group consisting of one or more substituents which may be substituted with each, a phenyl group or a 5- to 14-membered aromatic heterocyclic group; and R is a hydrogen atom, or a methyl group a compound according to the above [1], or a salt thereof,

[0019] [4] In the presence of a base, formula (1):

[0020]

Chemical formula

[0021] [wherein, R 1 is a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 6-14 aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from substituent group a; R 2 is a halogen atom, or a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 1-6 alkylsulfenyl group, an acyl group, a C 6-14 aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from substituent group a; and PG is a C 1-6 alkyl-carbonyl group, a C 6-14Represents an aryl-carbonyl group or an aromatic heterocyclic-carbonyl group. (Substituent group a) Halogen atom; Cyano group; Nitro group; C 1-6 Alkyl group; C 1-6 Haloalkyl group; C 1-6 Alkoxy group; C 1-6 Haloalkoxy group; C 2-6 Alkynyl group; Di(C 1-6 Alkyl)phosphoryl group; Di(C 6-10 Aryl)phosphoryl group; C 1-6 Alkylsulfonyl group; C 1-6 Haloalkylsulfonyl group; C 1-6 Alkyl-carbonyl group; C 1-6 Alkoxy-carbonyl group; C 6-14 Aryl-carbonyl group; C 1-6 Haloalkyl-carbonyl group; C 1-6 Haloalkoxy-carbonyl group; C 1-6 Alkylsulfonyloxy group; C 1-6 Haloalkylsulfonyloxy group; C 1-6 Alkyl-carbonyloxy group; C 1-6 Alkoxy-carbonyloxy group; C 1-6 Haloalkyl-carbonyloxy group; C 1-6 Haloalkoxy-carbonyloxy group; (i) Halogen atom, (ii) DiC 1-6 Alkylamino group, (iii) C 1-6an alkoxy group, and (iv) C 1-6 a haloalkoxy group optionally substituted with one or two C 1-6 alkyl groups optionally substituted carbamoyl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group optionally substituted with one to three substituents selected from the group consisting of 6-14 a C aryl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 6-14 an aryloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 6-14 an arylsulfonyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 7-18 an aralkyl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 7-18 an aralkyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group selected from the group consisting of one to three substituents which may be substituted on the C 3-8 cycloalkyl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) nitro group 1 to 3 substituents selected from the group consisting of optionally substituted by 3-8 cycloalkyloxy group; (i) halogen atom, (ii) C 1-6 alkyl group, (iii) C 1-6 haloalkyl group, (iv) C 1-6 alkoxy group, (v) C 1-6 haloalkoxy group, (vi) C 1-6 alkylsulfonyl group, (vii) C 1-6 haloalkylsulfonyl group, (viii) C 1-6 alkyl-carbonyl group, (ix) C 1-6 alkoxy-carbonyl group, (x) C 1-6 haloalkyl-carbonyl group, (xi) C 1-6 haloalkoxy-carbonyl group, and (xii) nitro group 1 to 3 substituents selected from the group consisting of optionally substituted by a 5- to 14-membered aromatic heterocyclic group; and (i) halogen atom, (ii) C 1-6 alkyl group, (iii) C 1-6 haloalkyl group, (iv) C 1-6 alkoxy group, (v) C 1-6 haloalkoxy group, (vi) C 1-6 alkylsulfonyl group, (vii) C 1-6 haloalkylsulfonyl group, (viii) C 1-6 alkyl-carbonyl group, (ix) C 1-6An alkoxy-carbonyl group, (x) C 1-6 A haloalkyl-carbonyl group, (xi) C 1-6 A haloalkoxy-carbonyl group, and (xii) A nitro group One to three substituents selected from the group consisting of A 3- to 14-membered non-aromatic heterocyclic group which may be substituted with A compound represented by the formula (2):

[0022]

Chemical formula

[0023] (In the formula, R 3 represents an aryl group or an aromatic heterocyclic group which may each be substituted with one or more substituents selected from the above-mentioned substituent group a, and is a C 6-14 aryl group or an aromatic heterocyclic group.) A process for reacting a compound represented by the formula (I):

[0024]

Chemical formula

[0025] (In the formula, R represents a hydrogen atom or a C 1-6 alkyl group, and the other symbols have the same meanings as described above.) A method for producing a compound represented by the formula (I) or a salt thereof,

[0026] [5] The production method according to the above [4], wherein the base is sodium hydride or potassium hydride,

[0027] [6] The formula (I):

[0028]

Chemical formula

[0029] [wherein, R 1 represents an optionally substituted C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 6-14 aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; R 2 represents a halogen atom, or an optionally substituted C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 1-6 alkylsulfenyl group, an acyl group, a C 6-14 aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; R 3 represents an optionally substituted C 6-14 aryl group or an aromatic heterocyclic group; and R represents a C 1-6 alkyl group. (Substituent group a) Halogen atom; Cyano group; Nitro group; C 1-6 alkyl group; C 1-6 haloalkyl group; C 1-6 alkoxy group; C 1-6 haloalkoxy group; C 2-6 alkynyl group; Di(C 1-6 alkyl)phosphoryl group; Di(C 6-10 aryl)phosphoryl group; C 1-6 alkylsulfonyl group; C 1-6 haloalkylsulfonyl group; C 1-6 alkyl-carbonyl group; C 1-6 alkoxy-carbonyl group; C 6-14Aryl-carbonyl group; C 1-6 Haloalkyl-carbonyl group; C 1-6 Haloalkoxy-carbonyl group; C 1-6 Alkylsulfonyloxy group; C 1-6 Haloalkylsulfonyloxy group; C 1-6 Alkyl-carbonyloxy group; C 1-6 Alkoxy-carbonyloxy group; C 1-6 Haloalkyl-carbonyloxy group; C 1-6 Haloalkoxy-carbonyloxy group; (i) A halogen atom, (ii) DiC 1-6 Alkylamino group, (iii) C 1-6 Alkoxy group, and (iv) C 1-6 Haloalkoxy group Optionally substituted with one or two C 1-6 Alkyl groups, and optionally substituted carbamoyl group; (i) A halogen atom, (ii) C 1-6 Alkyl group, (iii) C 1-6 Haloalkyl group, (iv) C 1-6 Alkoxy group, (v) C 1-6 Haloalkoxy group, (vi) C 1-6 Alkylsulfonyl group, (vii) C 1-6 Haloalkylsulfonyl group, (viii) C 1-6 Alkyl-carbonyl group, (ix) C 1-6 Alkoxy-carbonyl group, (x) C 1-6 Haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of a C 6-14 aryl group which may be substituted; (i) a halogen atom, (ii) a C 1-6 alkyl group, (iii) a C 1-6 haloalkyl group, (iv) a C 1-6 alkoxy group, (v) a C 1-6 haloalkoxy group, (vi) a C 1-6 alkylsulfonyl group, (vii) a C 1-6 haloalkylsulfonyl group, (viii) a C 1-6 alkyl-carbonyl group, (ix) a C 1-6 alkoxy-carbonyl group, (x) a C 1-6 haloalkyl-carbonyl group, (xi) a C 1-6 haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of a C 6-14 aryloxy group which may be substituted; (i) a halogen atom, (ii) a C 1-6 alkyl group, (iii) a C 1-6 haloalkyl group, (iv) a C 1-6 alkoxy group, (v) a C 1-6 haloalkoxy group, (vi) a C 1-6 alkylsulfonyl group, (vii) a C 1-6 haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of C 6-14 an arylsulfonyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of C 7-18 an aralkyl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 7-18 an aralkyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 3-8 a cycloalkyl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group selected from the group consisting of 1 to 3 substituents with which a C 3-8 cycloalkyloxy group may be substituted; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) nitro group 1 to 3 substituents selected from the group consisting of a 5- to 14-membered aromatic heterocyclic group which may be substituted with; and (i) a halogen atom,[ (ii) C 1-6 alkyl group,[ (iii) C 1-6 haloalkyl group,[ (iv) C 1-6 alkoxy group,[ (v) C 1-6 haloalkoxy group,[ (vi) C 1-6 alkylsulfonyl group,[ (vii) C 1-6 haloalkylsulfonyl group,[ (viii) C 1-6 alkyl-carbonyl group,[ (ix) C 1-6 alkoxy-carbonyl group,[ (x) C 1-6 haloalkyl-carbonyl group,[ (xi) C 1-6 haloalkoxy-carbonyl group, and (xii) nitro group 1 to 3 substituents selected from the group consisting of a 3- to 14-membered non-aromatic heterocyclic group which may be substituted with.] A compound represented by or a salt thereof, in the presence of a palladium catalyst and a ligand, of formula (3):

[0030]

Chemical formula

[0031] (In the formula, R 4 is a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 6-14It represents an aryl group or an aromatic heterocyclic group.) A step of subjecting a boronic acid compound represented by the formula to a cross-coupling reaction, formula (II):

[0032] [Chemical formula]

[0033] (Each symbol in the formula has the same meaning as described above.) A method for producing a trisubstituted alkene represented by

[0034] [7] The production method according to [6] above, wherein the palladium catalyst is palladium acetate

[0035] [8] The production method according to [6] or [7] above, wherein the ligand is 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (RuPhos) or 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyldicyclohexyl (2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (SPhos) And so on [Advantages of the Invention]

[0036] According to the present invention, a novel trisubstituted vinylsulfoximine derivative represented by the above formula (I), which is a useful precursor for the regioselective and stereoselective synthesis of trisubstituted alkenes, a method for producing the same, and a simple and stereoselective method for producing a trisubstituted alkene using the same can be provided. Further, according to the present invention, the stereochemistry of the trisubstituted alkene produced by the cross-coupling reaction can be controlled (maintained) according to the stereochemistry (E-form or Z-form) of the compound (I) used. [Modes for Carrying Out the Invention]

[0037] Hereinafter, the definitions of the groups used in the present specification will be described in detail. Unless otherwise specified, the groups have the following definitions.

[0038] In this specification, a compound represented by a formula is indicated by attaching the formula number to the "compound". For example, the compound represented by formula (I) is indicated as "compound (I)". In this specification, the numerical range represented by "~" or "-" means a numerical range with the numbers before and after "~" or "-" as the lower limit value or the upper limit value. In this specification, when a numerical range is attached to the element symbol "C" before and after "-" and shown as the name of an arbitrary group, each arbitrary group with an integer number of carbon atoms with the numbers before and after "-" as the lower limit value or the upper limit value is indicated. For example, an alkyl group having 1 to 4 carbon atoms may be indicated as "C 1-4 alkyl group", which indicates -CH3, -C2H5, -C3H7, -C4H9, etc. respectively. The same applies to other groups.

[0039] In this specification, the "halogen atom" means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

[0040] In this specification, "C 1-6 alkyl group" means a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms. "C 1-6 alkyl group" includes, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, etc.

[0041] In this specification, "C 1-4 alkyl group" means a linear or branched saturated hydrocarbon group having 1 to 4 carbon atoms. "C 1-4 alkyl group" includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl.

[0042] In this specification, "C 1-6 alkoxy group" means a group of the formula R’O- (where R’ is C 1-6represents an alkyl group.) represents a group. "C" 1-6 Examples of the "alkoxy group" include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, and the like.

[0043] In this specification, "C" 1-4 The "alkoxy group" means a group represented by the formula R'O- (where R' represents a C 1-4 alkyl group.). "C" 1-4 Examples of the "alkoxy group" include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, and tert-butoxy.

[0044] In this specification, "C" 1-6 The "haloalkyl group" means a group in which one or more hydrogen atoms in the "C" 1-6 alkyl group are substituted with halogen atoms. Examples of the "C" 1-6 haloalkyl group include fluoromethyl, difluoromethyl, trifluoromethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 2,2,3,3-tetrafluoropropyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, 6,6,6-trifluorohexyl, and the like.

[0045] In this specification, "C" 1-6 The "alkylsulfenyl group" means a group represented by the formula R'S- (where R' represents a C 1-6 alkyl group.). "C" 1-6Examples of the "alkylsulfenyl group" include methylsulfenyl, ethylsulfenyl, propylsulfenyl, isopropylsulfenyl, butylsulfenyl, isobutylsulfenyl, sec-butylsulfenyl, tert-butylsulfenyl, pentylsulfenyl, isopentylsulfenyl, neopentylsulfenyl, hexylsulfenyl, and the like.

[0046] In this specification, "C" 1-6 The "alkylsulfonyl group" means a group represented by the formula R'S(=O)2- (wherein R' represents a C 1-6 alkyl group). "C" 1-6 Examples of the "alkylsulfonyl group" include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl, isohexylsulfonyl, 1,1-dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl, 2-ethylbutylsulfonyl, and the like.

[0047] In this specification, "C" 1-6 The "haloalkylsulfonyl group" means a group represented by the formula R'S(=O)2- (wherein R' represents a C 1-6 haloalkyl group). "C" 1-6Examples of the "haloalkylsulfonyl group" include fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, 2-chloroethylsulfonyl, 2-bromoethylsulfonyl, 2-iodoethylsulfonyl, 2-fluoroethylsulfonyl, 2,2-difluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl, pentafluoroethylsulfonyl, 2,2,3,3-tetrafluoropropylsulfonyl, 3,3,3-trifluoropropylsulfonyl, 4,4,4-trifluorobutylsulfonyl, 5,5,5-trifluoropentylsulfonyl, 6,6,6-trifluorohexylsulfonyl, and the like.

[0048] In this specification, "C 1-6 The "alkyl-carbonyl group" means a group represented by the formula R'C(O)- (wherein R' represents a C 1-6 alkyl group).) 1-6 Examples of the "alkyl-carbonyl group" include methylcarbonyl (acetyl), ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, isopentylcarbonyl, neopentylcarbonyl, hexylcarbonyl, and the like.

[0049] In this specification, "C 1-6 The "haloalkoxy group" means a group in which one or more hydrogen atoms in the "C 1-6 alkoxy group" are substituted with halogen atoms. Examples of the "C 1-6 haloalkoxy group" include fluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, trifluoromethoxy, 2-chloroethoxy, 2-bromoethoxy, 2-iodoethoxy, difluoromethoxy, perfluoroethoxy, perfluoropropoxy, perfluoroisopropoxy, 5,5,5-trifluoropentyl, 6,6,6-trifluorohexyl, and the like. Among them, the C 1-4 haloalkoxy group is preferred.

[0050] In this specification, "C 1-6 alkoxy-carbonyl group" means a group represented by the formula R'OC(O)- (wherein R' represents a C 1-6 alkyl group).) 1-6 Examples of the "C

[0051] In this specification, "C 2-6 alkenyl group" means a monovalent group obtained by removing one hydrogen atom from any carbon atom of a linear or branched alkene having 2 to 6 carbon atoms. "C 2-6 Examples of the "alkenyl group" include vinyl, 1-propenyl, allyl, isopropenyl, butenyl, isobutenyl, etc.

[0052] In this specification, "C 2-6 alkynyl group" means a monovalent group obtained by removing one hydrogen atom from any carbon atom of a linear or branched alkyne having 2 to 6 carbon atoms. "C 2-6 Examples of the "alkynyl group" include ethynyl, propargyl, 3-butynyl, 2-butynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, etc.

[0053] In this specification, "C 3-8 cycloalkyl group" means a cyclic saturated hydrocarbon group having 3 to 8 carbon atoms. "C 3-8 Examples of the "cycloalkyl group" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl.

[0054] In this specification, "C 3-8 cycloalkyloxy group" means a group in which a "C 3-8 cycloalkyl group" is bonded to an oxygen atom. "C3-8 Examples of the "cycloalkyloxy group" include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, and cyclooctyloxy.

[0055] In this specification, "C" 6-14 The "aryl (group)" means a monocyclic or polycyclic (condensed) hydrocarbon group exhibiting aromaticity. "C" 6-14 Examples of the "aryl (group)" include phenyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-anthryl, fluorenyl, and the like.

[0056] In this specification, "C" 6-14 The "aryloxy group" means a group in which the "C" 6-14 "aryl (group)" is bonded to an oxygen atom. "C" 6-14 Examples of the "aryloxy group" include phenyloxy, 1-naphthyloxy, 2-naphthyloxy, biphenylyloxy, 2-anthryloxy, and the like.

[0057] In this specification, "C" 6-14 The "aryl-carbonyl group" means a group represented by the formula R'C(O)- (where R' represents a C 6-14 aryl group). "C" 6-14 Examples of the "aryl-carbonyl group" include phenylcarbonyl, 1-naphthylcarbonyl, 2-naphthylcarbonyl, biphenylylcarbonyl, 2-anthrylcarbonyl, and the like.

[0058] In this specification, "C" 6-14 The "arylsulfonyloxy group" means a group represented by the formula R'S(=O)2-O- (where R' represents a C 6-14 aryl group). "C" 6-14 Examples of the "arylsulfonyloxy group" include phenylsulfonyloxy, 1-naphthylsulfonyloxy, 2-naphthylsulfonyloxy, biphenylylsulfonyloxy, 2-anthrylsulfonyloxy, and the like.

[0059] In this specification, the "aromatic heterocyclic-carbonyl group" means a group represented by the formula R'C(O)- (wherein R' represents an aromatic heterocyclic group). Examples of the "aromatic heterocyclic-carbonyl group" include pyridylcarbonyl, thienylcarbonyl, furylcarbonyl, pyrazylcarbonyl, quinolylcarbonyl, indolylcarbonyl, and the like.

[0060] In this specification, "C 7-18 aralkyl (group)" means a group in which an "C 1-4 alkyl group" is substituted with an "C 6-14 aryl group". Examples of the "C 7-18 aralkyl (group)" include benzyl, 1-phenylethyl, 2-phenylethyl, (naphthyl-1-yl)methyl, (naphthyl-2-yl)methyl, 1-(naphthyl-1-yl)ethyl, 1-(naphthyl-2-yl)ethyl, 2-(naphthyl-1-yl)ethyl, 2-(naphthyl-2-yl)ethyl, biphenylylmethyl, and the like.

[0061] In this specification, "C 7-18 aralkyloxy group" means a group in which an "C 7-18 aralkyl (group)" is bonded to an oxygen atom. Examples of the "C 7-18 aralkyloxy group" include benzyloxy, phenethyloxy, naphthylmethyloxy, biphenylylmethyloxy, and the like.

[0062] In this specification, the "acyl group" means a formyl group, a linear or branched alkyl-carbonyl group, or an aryl-carbonyl group, and although the carbon number range is not particularly limited, preferably, it is a formyl group, a C 1-6 alkyl-carbonyl group, or a C 6-14 aryl-carbonyl group. Preferred specific examples of the acyl (group) include formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl (pivaloyl), hexanoyl, heptanoyl, benzoyl, 1-naphthoyl, 2-naphthoyl, and the like.

[0063] In this specification, "a carbamoyl group which may be substituted with one or two C 1-6 alkyl groups" means a group in which one or two hydrogen atoms of the carbamoyl group (-CONH2) are each independently substituted with a "C 1-6 alkyl group". Examples of "a carbamoyl group which may be substituted with one or two C 1-6 alkyl groups" include methylcarbamoyl, dimethylcarbamoyl, ethylcarbamoyl, diethylcarbamoyl, and the like.

[0064] In this specification, "a diC 1-6 alkylamino group" means a group in which two hydrogen atoms of the amino group (-NH2) are each independently substituted with a "C 1-6 alkyl group". Examples of "a diC 1-6 alkylamino group" include dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, dipentylamino, dihexylamino, and the like.

[0065] In this specification, "a di(C 1-6 alkyl)phosphoryl group" means a group represented by the formula (R'O)2P(=O)- (wherein the two R's each independently represent a C 1-6 alkyl group). Examples of "a di(C 1-6 alkyl)phosphoryl group" include dimethylphosphoryl, diethylphosphoryl, dipropylphosphoryl, diisopropylphosphoryl, dibutylphosphoryl, dipentylphosphoryl, dihexylphosphoryl, and the like.

[0066] In this specification, "a di(C 6-10 aryl)phosphoryl group" means a group represented by the formula (R'O)2P(=O)- (wherein the two R's each independently represent a C 6-10 aryl group). Examples of "a di(C 6-10 aryl)phosphoryl group" include diphenylphosphoryl, di(1-naphthyl)phosphoryl, di(2-naphthyl)phosphoryl, and the like.

[0067] In the present specification, examples of the "aromatic heterocyclic group" include 5- to 14-membered aromatic heterocyclic groups containing 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms, and oxygen atoms in addition to carbon atoms as ring-constituting atoms.

[0068] Preferable examples of the "5- to 14-membered aromatic heterocyclic group" include 5- or 6-membered monocyclic aromatic heterocyclic groups such as thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, triazolyl, tetrazolyl, triazinyl, etc.; 8- to 14-membered condensed aromatic heterocyclic groups (condensed polycyclic (preferably bicyclic or tricyclic) aromatic heterocyclic groups) such as benzothiophenyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, imidazopyridyl, thienopyridyl, furopyridyl, pyrrolopyridyl, pyrazolopyridyl, oxazolopyridyl, thiazolopyridyl, imidazopyrazinyl, imidazopyrimidinyl, thienopyrimidinyl, furopyrimidinyl, pyrrolopyrimidinyl, pyrazolopyrimidinyl, oxazolopyrimidinyl, thiazolopyrimidinyl, pyrazolotriazinyl, naphtho[2,3-b]thienyl, phenoxathiinyl, indolyl, isoindolyl, 1H-indazolyl, purinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, etc.

[0069] In the present specification, examples of the "non-aromatic heterocyclic group" include 3- to 14-membered non-aromatic heterocyclic groups containing 1 to 4 heteroatoms selected from nitrogen atoms, sulfur atoms, and oxygen atoms in addition to carbon atoms as ring-constituting atoms.

[0070] Preferable examples of the "3- to 14-membered non-aromatic heterocyclic group" include 3- to 10-membered monocyclic non-aromatic heterocyclic groups (preferably 5- to 8-membered monocyclic non-aromatic heterocyclic groups) such as aziridinyl, oxiranyl, thiiranyl, azetidinyl, oxetanyl, thietanyl, tetrahydrothienyl, tetrahydrofuryl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, oxazolinyl, oxazolidinyl, pyrazolinyl, pyrazolidinyl, thiazolinyl, thiazolidinyl, tetrahydroisothiazolyl, tetrahydrooxazolyl, tetrahydroisoxazolyl, piperidyl, piperazinyl, tetrahydropyridyl, dihydropyridyl, dihydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, azepanyl, diazepanyl, azepinyl, oxepanyl, azocanyl, diazocanyl, etc.; 8- to 14-membered fused non-aromatic heterocyclic groups (fused polycyclic (preferably bicyclic) non-aromatic heterocyclic groups) such as tetrahydrotriazolopyridyl, tetrahydrotriazolopyrazinyl, tetrahydropyrazolopyrazinyl, dihydropyrazolopyrrolyl, dihydropyrazolopyrazinyl, tetrahydropyrazolopyridyl, tetrahydroimidazolopyridyl, dihydroimidazolopyridyl, dihydroimidazolopyrrolyl, tetrahydroimidazolopyrazinyl, dihydropyrimidopyrrolyl, dihydropyridopyrrolyl, tetrahydropyridopyridyl, tetrahydrooxazolopyrazinyl, tetrahydropyridopyridyl, tetrahydrotriazolodiazepinyl, octahydro-1,4-oxazinopyrazinyl, dihydrobenzofuranyl, dihydrobenzimidazolyl, dihydrobenzoxazolyl, dihydrobenzothiazolyl, dihydrobenzisothiazolyl, dihydronaphtho[2,3-b]thienyl, tetrahydroisoquinolyl, dihydroisoquinolyl, tetrahydroquinolyl, 4H-quinolizinyl, indolinyl, isoindolinyl, tetrahydrothieno[2,3-c]pyridyl, dihydrothiazolo[4,5-c]pyridyl, dihydrothiazolo[5,4-c]pyridyl, tetrahydrobenzazepinyl, tetrahydroquinoxalinyl, tetrahydrophenanthridinyl, hexahydrophenothiazinyl, hexahydrophenoxazinyl, tetrahydrophthalazinyl, tetrahydronaphthyridinyl, dihydronaphthyridinyl, tetrahydroquinazolinyl, tetrahydrocinnolinyl, tetrahydrocarbazolyl, tetrahydro-β-carbolinyl, tetrahydroacridinyl, tetrahydrophenazinyl, tetrahydrothioxanthenyl, octahydroisoquinolyl, etc. are mentioned.

[0071] In the present specification, the "aromatic heterocyclic-carbonyl group" means a group represented by the formula R'C(O)- (wherein R' represents an aromatic heterocyclic group). Examples of the "aromatic heterocyclic-carbonyl group" include pyridylcarbonyl, thienylcarbonyl, furylcarbonyl, pyrazylcarbonyl, quinolylcarbonyl, indolylcarbonyl, etc.

[0072] As used herein, "optionally substituted" means unsubstituted or substituted with a specific substituent at any replaceable position (any hydrogen atom is replaced with a substituent). When not otherwise specified, the "substituent" refers to a substituent selected from the following (Substituent Group a).

[0073] (Substituent Group a) Halogen atom; Cyano group; Nitro group; C 1-6 Alkyl group; C 1-6 Haloalkyl group; C 1-6 Alkoxy group; C 1-6 Haloalkoxy group; C 2-6 Alkynyl group; Di(C 1-6 Alkyl)phosphoryl group; Di(C 6-10 Aryl)phosphoryl group; C 1-6 Alkylsulfonyl group; C 1-6 Haloalkylsulfonyl group; C 1-6 Alkyl-carbonyl group; C 1-6 Alkoxy-carbonyl group; C 6-14 Aryl-carbonyl group; C 1-6 Haloalkyl-carbonyl group; C 1-6 Haloalkoxy-carbonyl group; C 1-6 Alkylsulfonyloxy group; C 1-6 Haloalkylsulfonyloxy group; C 1-6 Alkyl-carbonyl-oxy group; C 1-6 Alkoxy-carbonyl-oxy group; C 1-6 Haloalkyl-carbonyl-oxy group; C1-6 Haloalkoxy - carbonyloxy group; (i) A halogen atom, (ii) DiC 1-6 Alkylamino group, (iii) C 1-6 Alkoxy group, and (iv) C 1-6 Haloalkoxy group Optionally substituted with one or two C 1-6 Alkyl groups Optionally substituted carbamoyl group; (i) A halogen atom, (ii) C 1-6 Alkyl group, (iii) C 1-6 Haloalkyl group, (iv) C 1-6 Alkoxy group, (v) C 1-6 Haloalkoxy group, (vi) C 1-6 Alkylsulfonyl group, (vii) C 1-6 Haloalkylsulfonyl group, (viii) C 1-6 Alkyl - carbonyl group, (ix) C 1-6 Alkoxy - carbonyl group, (x) C 1-6 Haloalkyl - carbonyl group, (xi) C 1-6 Haloalkoxy - carbonyl group, and (xii) Nitro group Optionally substituted with one to three substituents selected from the group consisting of Optionally substituted C 6-14 Aryl group; (i) A halogen atom, (ii) C 1-6 Alkyl group, (iii) C 1-6 Haloalkyl group, (iv) C 1-6 Alkoxy group, (v) C1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 6-14 an aryloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted C 6-14 an arylsulfonyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group selected from the group consisting of 1 to 3 substituents which may be substituted on a C 7-18 aralkyl group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) nitro group 1 to 3 substituents selected from the group consisting of optionally substituted with C 7-18 aralkyloxy group; (i) halogen atom, (ii) C 1-6 alkyl group, (iii) C 1-6 haloalkyl group, (iv) C 1-6 alkoxy group, (v) C 1-6 haloalkoxy group, (vi) C 1-6 alkylsulfonyl group, (vii) C 1-6 haloalkylsulfonyl group, (viii) C 1-6 alkyl-carbonyl group, (ix) C 1-6 alkoxy-carbonyl group, (x) C 1-6 haloalkyl-carbonyl group, (xi) C 1-6 haloalkoxy-carbonyl group, and (xii) nitro group 1 to 3 substituents selected from the group consisting of optionally substituted with C 3-8 cycloalkyl group; (i) halogen atom, (ii) C 1-6 alkyl group, (iii) C 1-6 haloalkyl group, (iv) C 1-6 alkoxy group, (v) C 1-6 haloalkoxy group, (vi) C 1-6 alkylsulfonyl group, (vii) C 1-6 haloalkylsulfonyl group, (viii) C 1-6 alkyl-carbonyl group, (ix) C 1-6an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted by 3-8 a cycloalkyloxy group; (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group one to three substituents selected from the group consisting of optionally substituted by (i) a halogen atom, (ii) C 1-6 an alkyl group, (iii) C 1-6 a haloalkyl group, (iv) C 1-6 an alkoxy group, (v) C 1-6 a haloalkoxy group, (vi) C 1-6 an alkylsulfonyl group, (vii) C 1-6 a haloalkylsulfonyl group, (viii) C 1-6 an alkyl-carbonyl group, (ix) C 1-6 an alkoxy-carbonyl group, (x) C 1-6 a haloalkyl-carbonyl group, (xi) C 1-6 a haloalkoxy-carbonyl group, and (xii) a nitro group from 1 to 3 substituents selected from the group consisting of a 3- to 14-membered non-aromatic heterocyclic group which may be substituted.

[0074] The number of substituents is not particularly limited as long as it is a substitutable number, but is usually 1 to 5, preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different from each other.

[0075] In the present specification, "its salt" refers to a salt when a compound has an acidic group or a basic group and can be made into a basic salt or an acidic salt by reacting with a base or an acid.

[0076] Examples of the "basic salt" include alkali metal salts such as sodium salt, potassium salt, and lithium salt; alkaline earth metal salts such as magnesium salt and calcium salt; organic base salts such as N-methylmorpholine salt, triethylamine salt, tributylamine salt, diisopropylethylamine salt, dicyclohexylamine salt, N-methylpiperidine salt, pyridine salt, 4-pyrrolidinopyridine salt, and picoline salt; and amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate salt, and aspartate salt. Preferably, it is an alkali metal salt.

[0077] Examples of the "acid salt" include hydrohalide salts such as hydrogen fluoride salt, hydrochloride salt, hydrobromide salt, hydroiodide salt, etc., inorganic acid salts such as nitrate salt, perchlorate salt, sulfate salt, phosphate salt; lower alkane sulfonate salts such as methanesulfonate salt, trifluoromethanesulfonate salt, ethanesulfonate salt, aryl sulfonate salts such as benzenesulfonate salt, p-toluenesulfonate salt, organic acid salts such as acetate salt, malate salt, fumarate salt, succinate salt, citrate salt, ascorbate salt, tartrate salt, oxalate salt, maleate salt; amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate salt, aspartate salt, etc. Preferably, it is a hydrohalide salt (particularly, hydrochloride salt).

[0078] In this specification, the "pseudohalide" means a compound substituted with a substituent (pseudohalogeno group) known to be capable of substitution reaction in the same manner as a halide. The pseudohalogeno group is not particularly limited as long as it is a substituent known to cause the substitution reaction. For example, sulfonyloxy groups such as trifluoromethanesulfonyloxy group, methanesulfonyloxy group, p-toluenesulfonyloxy group; acyloxy groups such as acetoxy group; cyano group; isocyanate group; thiocyanate group; isothiocyanate group, etc. The compound (I) of the present invention is also one of the pseudohalides.

[0079] In this specification, the "3-substituted alkene" means a compound in which three of the four groups on the two carbon atoms constituting the alkene are substituted with groups other than hydrogen atoms.

[0080] (Compound (I) of the present invention) Hereinafter, each group in the formula (I) of the compound (I) will be described.

[0081] The compound (I) is represented by the formula (I), and the formula (I) is The following formula (I-E):

[0082]

Chemical formula

[0083] (Each symbol in the formula has the same meaning as described above.) a compound represented by the formula, or a salt thereof, and the following formula (I-Z):

[0084] [Chemical formula]

[0085] (Each symbol in the formula has the same meaning as described above.) represents either a compound represented by the formula (I-E), or a salt thereof, a compound represented by the formula (I-Z), or a salt thereof, or a mixture of isomers containing them in any ratio. Therefore, compound (I) includes a compound represented by the formula (I-E), or a salt thereof, a compound represented by the formula (I-Z), or a salt thereof, and a mixture of isomers thereof.

[0086] R 1 is a C alkyl group, a C cycloalkyl group, a C aryl group, or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the group of substituents a. 1-6 alkyl group, C 3-8 cycloalkyl group, C 6-14 aryl group or aromatic heterocyclic group.

[0087] R 1 is preferably a C alkyl group, a C cycloalkyl group, or a C aryl group, each of which may be substituted with one or more substituents selected from the group of substituents a. 1-4 alkyl group, C 3-6 cycloalkyl group or C 6-10 aryl group, more preferably (i) a halogen atom, (ii) a cyano group, (iii) a C alkoxy group, 1-4 alkoxy group, (iv) a C haloalkoxy group, 1-4 haloalkoxy group, (v) a C cycloalkyl group, and 3-8 cycloalkyl group, and (vi) a C aryl group 6-10 aryl group One or more substituents selected from the group consisting of optionally substituted with C 1-4 an alkyl group, or (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 a haloalkyl group, (v) C 1-4 an alkoxy group, (vi) C 1-4 a haloalkoxy group, and (vii) a nitro group One or more substituents selected from the group consisting of an optionally substituted phenyl group, more preferably, (i) a cyano group, (ii) C 1-4 an alkyl group, (iii) C 1-4 an alkoxy group, and (vi) a nitro group One or more substituents selected from the group consisting of an optionally substituted phenyl group.

[0088] R 2 is a halogen atom, or a C 1-6 alkyl group, C 3-8 cycloalkyl group, C 1-6 alkoxy group, C 1-6 alkylsulfenyl group, acyl group, C 6-14 aryl group or aromatic heterocyclic group, each optionally substituted with one or more substituents selected from the substituent group a.

[0089] R 2 is preferably a fluorine atom, or a C 1-4 alkyl group, C 3-6 cycloalkyl group, C 6-10an aryl group or a 5- to 14-membered aromatic heterocyclic group, more preferably, a fluorine atom, (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkoxy group, (iv) C 1-4 a haloalkoxy group, (v) C 3-6 a cycloalkyl group, (vi) C 6-10 an aryl group, and (vii) C 2-4 an alkynyl group selected from the group consisting of one or more substituents optionally substituted C 1-4 an alkyl group, or (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 a haloalkyl group, (v) C 1-4 an alkoxy group, (vi) C 1-4 a haloalkoxy group, and (vii) a nitro group selected from the group consisting of one or more substituents optionally substituted phenyl group, even more preferably, a fluorine atom, (i) a fluorine atom, (ii) a cyano group, (iii) C 1-4 an alkoxy group, (iv) C 3-6 a cycloalkyl group, (v) C 6-10 an aryl group, and (vi) C 2-4 an alkynyl group selected from the group consisting of one or more substituents optionally substituted C1-4 an alkyl group, or (i) a fluorine atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 an alkoxy group, and (v) a nitro group and is a phenyl group optionally substituted with one or more substituents selected from the group consisting of (hereinafter referred to as "substituent group a").

[0090] R 3 represents a C 6-14 aryl group or an aromatic heterocyclic group, each optionally substituted with one or more substituents selected from the substituent group a.

[0091] R 3 is preferably a C 6-10 aryl group or a 5- to 14-membered aromatic heterocyclic group, each optionally substituted with one or more substituents selected from the substituent group a, more preferably (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 a haloalkyl group, (v) C 1-4 an alkoxy group, (vi) C 1-4 a haloalkoxy group, (vii) (a) a halogen atom, (b) C 1-4 an alkyl group, (c) C 1-4 a haloalkyl group, (d) C 1-4 an alkoxy group, (e) C 1-4 a haloalkoxy group, (f) C 1-4 an alkylsulfonyl group, (g) C 1-4a haloalkylsulfonyl group, (h) C 1-4 an alkyl-carbonyl group, (i) C 1-4 an alkoxy-carbonyl group (j) C 1-4 a haloalkyl-carbonyl group, and (k) C 1-4 a haloalkoxy-carbonyl group one to three substituents selected from the group consisting of a benzyl group which may be substituted, and (viii) a nitro group, one or more substituents selected from the group consisting of each of which may be substituted, a phenyl group or a 5- to 14-membered aromatic heterocyclic group, more preferably, (i) a fluorine atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 an alkoxy group, (v) (a) a halogen atom, (b) C 1-4 an alkyl group, (c) C 1-4 a haloalkyl group, (d) C 1-4 an alkoxy group, (e) C 1-4 a haloalkoxy group, (f) C 1-4 an alkylsulfonyl group, (g) C 1-4 a haloalkylsulfonyl group, (h) C 1-4 an alkyl-carbonyl group, (i) C 1-4 an alkoxy-carbonyl group (j) C 1-4 a haloalkyl-carbonyl group, and (k) C 1-4 a haloalkoxy-carbonyl group one to three substituents selected from the group consisting of a benzyl group which may be replaced, and (vi) a nitro group, one or more substituents selected from the group consisting of each of which may be replaced by

[0092] R is a hydrogen atom or a C 1-6 alkyl group.

[0093] R is preferably a hydrogen atom or a C 1-4 alkyl group, more preferably a hydrogen atom or a methyl group.

[0094] As the compound (I), the following compounds are preferred. [Compound (IA)] R 1 is a C 1-4 alkyl group, a C 3-6 cycloalkyl group or a C 6-10 aryl group, each of which may be replaced by one or more substituents selected from the above-mentioned substituent group a, R 2 is a fluorine atom or a C 1-4 alkyl group, a C 3-6 cycloalkyl group, a C 6-10 aryl group or a 5- to 14-membered aromatic heterocyclic group, each of which may be replaced by one or more substituents selected from the above-mentioned substituent group a, R 3 is a C 6-10 aryl group or a 5- to 14-membered aromatic heterocyclic group, each of which may be replaced by one or more substituents selected from the above-mentioned substituent group a, and R is a hydrogen atom or a C 1-4 alkyl group, Compound (I) or a salt thereof.

[0095] [Compound (IB)] R 1 is (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkoxy group, (iv) C 1-4 a haloalkoxy group, (v) C 3-8 a cycloalkyl group, and (vi) C 6-10 an aryl group one or more substituents selected from the group consisting of a C 1-4 alkyl group which may be substituted, or (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 a haloalkyl group, (v) C 1-4 an alkoxy group, (vi) C 1-4 a haloalkoxy group, and (vii) a nitro group one or more substituents selected from the group consisting of a phenyl group which may be substituted, R 2 is a fluorine atom, (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkoxy group, (iv) C 1-4 a haloalkoxy group, (v) C 3-6 a cycloalkyl group, (vi) C 6-10 an aryl group, and (vii) C 2-4 an alkynyl group one or more substituents selected from the group consisting of a C 1-4 alkyl group which may be substituted, or (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 a haloalkyl group, (v) C 1-4 an alkoxy group, (vi) C 1-4 a haloalkoxy group, and (vii) a nitro group one or more substituents selected from the group consisting of a phenyl group which may be substituted, R 3 is (i) a halogen atom, (ii) a cyano group, (iii) C 1-4 an alkyl group, (iv) C 1-4 a haloalkyl group, (v) C 1-4 an alkoxy group, (vi) C 1-4 a haloalkoxy group, (vii) (a) a halogen atom, (b) C 1-4 an alkyl group, (c) C 1-4 a haloalkyl group, (d) C 1-4 an alkoxy group, (e) C 1-4 a haloalkoxy group, (f) C 1-4 an alkylsulfonyl group, (g) C 1-4 a haloalkylsulfonyl group, (h) C 1-4 an alkyl-carbonyl group, (i) C 1-4 an alkoxy-carbonyl group (j) C 1-4 a haloalkyl-carbonyl group, and (k) C 1-4 a haloalkoxy-carbonyl group one to three substituents selected from the group consisting of a benzyl group which may be substituted, and (viii) a nitro group, one or more substituents selected from the group consisting of a phenyl group or a 5- to 14-membered aromatic heterocyclic group, each of which may be substituted with R is a hydrogen atom or a methyl group, compound (I) or a salt thereof.

[0096] [Compound (IC)] R 1 is (i) a cyano group, (ii) a C 1-4 alkyl group, (iii) a C 1-4 alkoxy group, and (vi) a nitro group one or more substituents selected from the group consisting of a phenyl group which may be substituted with R 2 is a fluorine atom, (i) a fluorine atom, (ii) a cyano group, (iii) a C 1-4 alkoxy group, (iv) a C 3-6 cycloalkyl group, (v) a C 6-10 aryl group, and (vi) a C 2-4 alkynyl group one or more substituents selected from the group consisting of a C 1-4 alkyl group which may be substituted with (i) a fluorine atom, (ii) a cyano group, (iii) a C 1-4 alkyl group, (iv) a C 1-4 alkoxy group, and (v) a nitro group one or more substituents selected from the group consisting of a phenyl group which may be substituted with R3 is (i) a fluorine atom, (ii) a cyano group, (iii) a C 1-4 alkyl group, (iv) a C 1-4 alkoxy group, (v) (a) a halogen atom, (b) a C 1-4 alkyl group, (c) a C 1-4 haloalkyl group, (d) a C 1-4 alkoxy group, (e) a C 1-4 haloalkoxy group, (f) a C 1-4 alkylsulfonyl group, (g) a C 1-4 haloalkylsulfonyl group, (h) a C 1-4 alkyl-carbonyl group, (i) a C 1-4 alkoxy-carbonyl group (j) a C 1-4 haloalkyl-carbonyl group, and (k) a C 1-4 haloalkoxy-carbonyl group a benzyl group optionally substituted with 1 to 3 substituents selected from the group consisting of and (vi) a nitro group, one or more substituents selected from the group consisting of each optionally substituted with a phenyl group, a pyridyl group or an indolyl group, and R is a hydrogen atom or a methyl group, Compound (I) or a salt thereof.

[0097] Specific examples of preferred Compound (I) are the compounds of Examples 1 to 10 described later.

[0098] When the compound (I) has isomers such as tautomers, optical isomers, stereoisomers, positional isomers, rotational isomers, etc., any one of the isomers or a mixture thereof is included in the compound of the present invention. Further, when optical isomers are present in the compound (I), the optical isomers resolved from the racemate are also included in the compound (I). The compound (I) may be a solvate (e.g., hydrate, ethanol solvate, dimethyl sulfoxide solvate, etc.) or a non-solvate, and any of them is included in the compound (I).

[0099] The compound (I) may be a compound labeled or substituted with isotopes (e.g., 2 H, 3 H, 13 C, 14 C, 15 N, 18 F, 32 P, 35 S, 123 I, 125 I, 131 I, etc.).

[0100] The compound (I) or a salt thereof may be a crystal, and the crystal form may be a single crystal or a mixture of multiple crystal forms.

[0101] (Method for producing the compound of the present invention (compound (I))) Hereinafter, a method for producing the compound (I) or a salt thereof (hereinafter, also referred to as "method for producing the compound (I)") will be described. As an example of the method for producing the compound (I), typical production methods are described below, but the production method is not limited thereto. The compound (I) can be produced by the following production methods, Examples 1 to 8 described later, or methods analogous thereto.

[0102] The starting compounds, reagents, and the obtained compounds used in the steps in the following production methods may each form a salt. Examples of such salts include the same salts as those described above. When the obtained compound (I) is a free compound, it can be converted into the desired salt by a known method. Conversely, when the obtained compound (I) is a salt, it can be converted into the free form or another desired type of salt by a known method.

[0103] In this specification, the content of all non-patent documents or references explicitly cited can all be cited here as part of this specification.

[0104] [Production Method] (Step 1) The production method of compound (I) is a method of obtaining compound (I) by subjecting compound (1) described in the following scheme as a starting material to a reaction with compound (2) in the presence of a base.

[0105] [Chemical Formula]

[0106] (Each symbol in the formula has the same meaning as described above.)

[0107] This step is a step of producing compound (I) (compound (I) in which R is a hydrogen atom) by reacting compound (1) with compound (2) in a solvent in the presence of a base.

[0108] The solvent to be used is not particularly limited as long as it does not affect the reaction, but preferably, for example, aromatic hydrocarbons such as benzene, toluene, xylene, etc.; ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, etc.; amides such as N,N-dimethylformamide; mixed solvents containing a plurality of the above organic solvents in an arbitrary ratio, etc. are mentioned, and preferably, it is N,N-dimethylformamide.

[0109] The bases to be used are not particularly limited. For example, organic bases such as 1,8-diazabicyclo[5.4.0]-7-undecene; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate; alkaline earth metal carbonates such as magnesium carbonate; alkali metal hydroxides such as sodium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide; metal alkoxides such as sodium tert-butoxide, potassium tert-butoxide; metal amides such as lithium diisopropylamide, sodium hexamethyldisilazide; organometallic compounds such as tert-butyllithium; metal hydrides such as potassium hydride, sodium hydride, etc. Among them, preferably, sodium hydride or potassium hydride is used. The amount of the base used is usually 1.5 to 3 moles, preferably 2 moles, per 1 mole of compound (1).

[0110] Compound (1) can be prepared from commercially available products (sulfides or sulfoxides) by the methods described in the reference examples below, methods known per se (for example, see Chem. Commun., 2017, 53, 348 - 351; Org. Lett., 2023, 25, 7529 - 7534; Angew. Chem. Int. Ed., 2016, 55, 7203 - 7207, etc.), or by methods analogous thereto. Specifically, for example, in the presence of ammonium carbamate, sulfides are reacted with iodobenzene diacetate, converted to the corresponding sulfoximine, and then a protecting group (PG) is introduced onto the nitrogen atom to produce compound (1).

[0111] Compound (2) can be preferably used as a commercially available product as it is or synthesized by a method known per se. The amount of compound (2) used is usually 1.5 to 3 moles, preferably 2 moles, per 1 mole of compound (1).

[0112] The reaction temperature is usually 0°C to 60°C, preferably room temperature (15°C to 30°C).

[0113] The reaction time is usually 1 to 8 hours, preferably 2 to 4 hours.

[0114] In the production method of the present invention, since the sulfoximino group is a bulky group, after the condensation of compound (1) and compound (2), the protecting group (PG) on the nitrogen atom has the following formula:

[0115]

Chemical formula

[0116] (In the formula, R 0 represents a C 1-6 alkyl group, a C 6-14 aryl group or an aromatic heterocyclic group, and the other symbols have the same meanings as described above.) Since it is presumed that the elimination reaction from the 1,5-carbonyl transfer via the intermediate represented by proceeds, the resulting compound (I) selectively forms almost only the E-isomer (E / Z => 99:1).

[0117] On the other hand, when the protecting group (PG) on the nitrogen atom is a group other than the -C(=O)R 0 (that is, a C 1-6 alkyl-carbonyl group, a C 6-14 aryl-carbonyl group or an aromatic heterocyclic-carbonyl group which may be each substituted with one or more substituents selected from the above-mentioned substituent group a), for example, when PG is a hydrogen atom or a methyl group, or when the =N-PG group in formula (1) is =O), the reaction in this step does not proceed.

[0118] (Step 2) For the compound (I) in which R in the formula (I) is a C 1-6 alkyl group, the compound (I) obtained in the above step 1 (the compound in which R in formula (I) is a hydrogen atom) is reacted with a compound of the formula:

[0119]

Chemical formula

[0120] (In the formula, X represents a halogen atom, and R represents a C 1-6 alkyl group.) It can be produced by reacting a compound represented by

[0121] The amount of R-X used is usually 1 to 3 moles, preferably 1.1 to 1.5 moles, per 1 mole of compound (I) (a compound in which R in formula (I) is a hydrogen atom).

[0122] Examples of the solvent used include the same solvents as in Step 1 above, and preferably tetrahydrofuran.

[0123] Examples of the base used include the same bases as in Step 1 above, and among them, preferably sodium hydride or potassium hydride. The amount of the base used is usually 1 to 3 moles, preferably 1.1 to 1.5 moles, per 1 mole of compound (I) (a compound in which R in formula (I) is a hydrogen atom).

[0124] The compound (I) obtained by the above production method can be isolated and purified by known means, such as solvent extraction, liquid conversion, phase transfer, crystallization, recrystallization, chromatography, etc.

[0125] When compound (I) contains optical isomers, stereoisomers, positional isomers, or rotational isomers, these are also contained as compound (I), and each can be obtained as a single product by synthetic methods and separation methods known per se. For example, when optical isomers exist in compound (I), the optical isomers separated from the compound are also included in compound (I).

[0126] (Method for producing a stereoselective 3-substituted alkene using the compound (compound (I)) of the present invention) Hereinafter, the conversion reaction of compound (I) or a salt thereof to 3-substituted alkene (compound (II)) will be described.

[0127] This process can be carried out by a cross-coupling reaction (Suzuki-Miyaura cross-coupling reaction) between compound (I) and compound (3) in a solvent that does not affect the reaction, in the presence of a palladium catalyst and a ligand.

[0128] [Chemical formula]

[0129] (In the formula, R represents a C 1-6 alkyl group, and each of the other symbols has the same meaning as described above.)

[0130] Compound (I) can be produced by the above production method (production method of compound (I)) or a method analogous thereto. As compound (3), a commercially available product can be used, or it can be produced by a method known per se [for example, the methods described in "Advanced Organic Chemistry, 4th Ed." (written by Jerry March), "Comprehensive Organic Transformations, 2nd Ed." (written by Richard C. Larock)] or methods analogous thereto. It can be produced. The amount of compound (3) used is usually 1 to 3 moles per 1 mole of compound (I).

[0131] Examples of the palladium catalyst include palladium(II) acetate, palladium(II) chloride, dichlorobis(tricyclohexylphosphine)palladium(II), tris(dibenzylideneacetone)dipalladium(0), bis(dibenzylideneacetone)palladium(0) (Pd2(dba)3), tetrakis(triphenylphosphine)palladium(0), palladium(II) chloride - diphenylphosphinoferrocene (PdCl2(dppf)), PdCl2(dppf) dichloromethane complex, palladium on carbon (0), bis(triphenylphosphine)palladium dichloride, etc. Among them, palladium(II) acetate is preferred.

[0132] As the ligand, 1,1'-bis(diphenylphosphino)ferrocene (dppf), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)ferrocene (QPhos), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (RuPhos), 3,6-dimethoxy-2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (BrettPhos), tri-t-butylphosphine, tricyclohexylphosphine, [4-(N,N-dimethylamino)phenyl]di-tert-butylphosphine (AmPhos), (S)-1-[(RP)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (JosiPhos) and other phosphine ligands; N-heterocyclic carbene (NHC) ligands (e.g., 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr), 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene (IMes), 1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene (SIPr), 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene (SIMes), etc.) and the like can be mentioned. Among them, 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (RuPhos) or 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos) is preferred.

[0133] The usage amount of the palladium catalyst is usually 0.01 mol to 1 mol, preferably 0.05 mol to 0.1 mol, relative to 1 mol of the compound (I).

[0134] The usage amount of the ligand is usually 0.05 mol to 1 mol, preferably 0.1 mol to 0.4 mol, relative to 1 mol of the compound (I).

[0135] Examples of the solvent include THF, toluene, and dimethoxyethane. The preferred solvent is THF. The reaction temperature is, for example, from 0°C to 60°C, preferably room temperature (15°C to 30°C).

[0136] In this step, the reaction also proceeds stereoselectively, and compound (II) is produced with E-selectivity (e.g., E / Z > 97:3).

[0137] Also, according to the results of Test Example 2 described later, if this step is carried out using the Z-isomer as compound (I), compound (II) is produced with Z-selectivity.

[0138] The method for producing a 3-substituted alkene of the present invention can convert a sulfoximino group as a pseudo-halogeno group into various substituents using the Suzuki-Miyaura cross-coupling reaction. In fact, there is a wide variety of commercially available compounds as compound (3), and there are also many compounds with known synthetic methods. As a result, since various types of compound (3) can be easily obtained, according to this production method, depending on the stereochemistry (E-isomer or Z-isomer) of compound (I) used, various types of 3-substituted alkenes (compound (II)) can be stereoselectively and simply synthesized.

Examples

[0139] Hereinafter, the present invention will be described with reference to reference examples, examples, and test examples, but the present invention is not limited thereto. The nuclear magnetic resonance spectrum (NMR) was measured using AVANCE III 400 manufactured by Bruker. 1 1H-NMR was measured at 400 MHz using deuterated chloroform as a solvent and tetramethylsilane as a reference. 1Data on 1H-NMR are reported as chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = double doublet, dt = double triplet, dq = double quartet, tt = triple triplet, ddt = double double triplet, brs = broad singlet), coupling constant (Hz), integration, and assignment. High-resolution mass spectrometry (HRMS) was measured using a micrOTOF II manufactured by Bruker. The raw material compounds, reagents, solvents, etc. used in the following reference examples and examples are known compounds unless otherwise specified. Commercially available products were used as they were, or were synthesized and identified according to known methods (e.g., Chem. Commun., 2017, 53, 348-351; Org. Lett., 2023, 25, 7529-7534; Angew. Chem. Int. Ed., 2016, 55, 7203-7207, etc.) or methods analogous thereto. were used.

[0140] % indicates mol / mol% for yield, and weight% for others unless otherwise specified. Room temperature indicates a temperature of 15 °C to 30 °C unless otherwise specified. Other abbreviations used in the text have the following meanings. THF: tetrahydrofuran DMF: N,N-dimethylformamide RuPhos: 2-dicyclohexylphosphino-2’,6’-diisopropoxybiphenyl CDCl3: deuterated chloroform

[0141] Reference Example 1: Synthesis of N-(ethyl(oxo)phenyl)-λ 6 -sulfanylidene)pivalamide (Compound (1-1))

[0142]

Chemical Structure

[0143] Project 1 S-Ethyl-S-phenyl-sulfoximine

[0144] [Chemical formula]

[0145] According to the method described in the literature (Chem. Commun., 2017, 53, 348 - 351.), in a 200 mL eggplant flask, ammonium carbamate (100 mmol, 7.88 g) and iodobenzene diacetate (125 mmol, 40.3 g) were added to a methanol (120 mL) solution of ethyl phenyl sulfide (50 mmol, 6.76 mL), and the mixture was stirred at room temperature for 1 hour. After distilling off the solvent of the reaction mixture under reduced pressure, the residue was purified by Biotage Selekt (SEL - 2SV), Rening Cartridges 80 g (FSRN - M800E - 0080) (hexane:ethyl acetate = 10:1 to 0:100) to obtain S - ethyl - S - phenyl - sulfoximine (5.58 g; yield: 66%). The various spectra of the obtained compound were consistent with the literature values (Org. Lett., 2023, 25, 7529 - 7534). It was

[0146] Project 2 N-(Ethyl(oxo)phenyl)-λ 6 -sulfanylidene)pivalamide (Compound (1 - 1))

[0147] [Chemical formula]

[0148] In a 200 mL eggplant flask, triethylamine (82.5 mmol, 6.39 mL) and pivaloyl chloride (40 mmol, 4.82 mL) were added to a chloroform (100 mL) solution of S - ethyl - S - phenyl - sulfoximine (33 mmol, 5.58 g) obtained in Project 1, and the mixture was stirred at room temperature for 16 hours. Water (50 mL) was added to the reaction mixture Then, the reaction was stopped, and the mixture was extracted with chloroform (3 × 30 mL). The organic phase was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by Biotage Selekt (SEL-2SV), Rening Cartridges 80 g (FSRN-M800E-0080) (hexane:ethyl acetate = 10:1 to 4:96) to obtain the title compound (5.52 g; yield: 66%) as a white solid. 1 1H NMR (400 MHz, CDCl3): δ 7.93 - 7.91 (dt, J = 7.3, 1.2 Hz, 2H), 7.68 - 7.64 (tt, J = 7.3, 1.2 Hz, 1H), 7.58 (tt, J = 7.3, 1.2 Hz, 2H), 3.54 (dq, J = 21.5, 7.3 Hz, 1H), 3.43 (dq, J = 21.5, 7.3 Hz, 1H), 1.24 (s, 9H), 1.22 (t, J = 7.3 Hz, 3H); HRMS: 253.1135 (Fw. 253.1137).

[0149] Reference Example 2: Synthesis of N-(ethyl(oxo)phenyl)-λ 6 -sulfanylidene)acetamide (Compound (1-2))

[0150]

Chemical Structure

[0151] By using acetyl chloride instead of pivaloyl chloride in Step 2 of Reference Example 1, the title compound (yield: 73%) was obtained. The various spectra of the obtained compound were consistent with the literature values (Org. Lett., 2022, 24, 2733 - 2737).

[0152] Reference Example 3: Synthesis of N-(benzyl(oxo)phenyl)-λ 6 -sulfanylidene)pivalamide (Compound (1-3))

[0153]

Chemical Structure

[0154] Instead of S-ethyl-S-phenyl-sulfoximine in Step 2 of Reference Example 1, S-benzyl-S-phenyl-sulfoximine was used to obtain the title compound (yield: 66%) as a white solid. 1 H NMR (400 MHz, CDCl3): δ7.62-7.59 (m, 3H), 7.45 (t, J = 7.8 Hz, 2H), 7.30 (t, J = 7.5 Hz, 1H), 7.20 (t, J = 7.6 Hz, 2H), 6.93 (d, J = 7.6 Hz, 2H), 4.91 (d, J = 13.7 Hz, 1H), 4.65 (d, J = 13.7 Hz, 1H), 1.23 (s, 9H); HRMS: 315.1290 (Fw. 315.1293).

[0155] Reference Example 4: Synthesis of N-(5-hexyn-1-yl(oxo)phenyl)-λ 6 -sulfanylidene)pivalamide (Compound (1-4))

[0156]

Chemical Structure

[0157] Instead of S-ethyl-S-phenyl-sulfoximine in Step 2 of Reference Example 1, S-5-hexyn-1-yl-S-phenyl-sulfoximine was used to obtain the title compound (yield: 74%) as a white solid. 11H NMR (400 MHz, CDCl3): δ 7.95 - 7.93 (m, 2H), 7.71 - 7.66 (tt, J = 7.3, 1.2 Hz, 1H), 7.63 - 7.59 (m, 2H), 3.54 - 3.43 (m, 2H), 2.20 (td, J = 7.0, 2.7 Hz, 2H), 1.92 (t, J = 2.7 Hz, 1H), 1.89 - 1.70 (m, 2H), 1.30 - 1.27 (m, 2H), 1.26 (s, 9H); HRMS: 305.4361 (Fw. 305.4360).

[0158] Reference Example 5: Synthesis of N-(fluoromethyl(oxo)phenyl)-λ 6 -sulfanylidene)pivalamide (Compound (1 - 5))

[0159]

Chemical Structure

[0160] By using S-fluoromethyl-S-phenyl-sulfoximine instead of S-ethyl-S-phenyl-sulfoximine in Step 2 of Reference Example 1, the title compound (yield: 66%) was obtained as a white solid. 1 1H NMR (400 MHz, CDCl3): δ 8.01 (dt, J = 7.3, 1.5 Hz, 2H), 7.74 (tt, J = 7.3, 1.5 Hz, 1H), 7.63 (dt, J = 7.3, 1.5 Hz, 1H), 5.83 (dd, J = 47.2, 9.1 Hz, 1H), 5.36 (dd, J = 47.2, 9.1 Hz, 1H), 1.27 (s, 9H); HRMS: 257.0887 (Fw. 257.0886).

[0161] Reference Example 6: Synthesis of S-fluoromethyl-S-phenyl-sulfoximine

[0162] [Chemistry]

[0163] According to the method described in the literature (Angew. Chem. Int. Ed., 2016, 55, 7203 - 7207), the title compound (yield: 74%) was obtained from S - fluoromethyl - S - phenyl - sulfoxide. The various spectra of the obtained compound were consistent with the literature values (Angew. Chem. Int. Ed., 2016, 55, 7203 - 7207).

[0164] Example 1: Synthesis of [(1E) - 1 - methyl - 2 - (4 - methoxyphenyl)ethenyl]phenylsulfoximine (Compound (I - 1))

[0165] [Chemistry]

[0166] To a solution of the compound (1 - 1) (0.20 mmol, 50.6 mg) obtained in Reference Example 1 in DMF (2.0 mL), sodium hydride (60%, dispersed in liquid paraffin) (0.40 mmol, 16.0 mg) and p - anisaldehyde (Compound (2 - 1)) (48 μL) were added, and the mixture was stirred at room temperature for 3 hours. Water (2.0 mL) was added to the reaction mixture to stop the reaction, and after extraction with ethyl acetate (10 mL), the organic layer was washed twice with water (10 mL) three times to remove DMF. After drying the organic layer over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by Biotage Selekt (SEL - 2SV), Rening Cartridges 80 g (FSRN - M800E - 0080) (gradient with a ratio of hexane:ethyl acetate from 95:5 to 3:2), and the title compound (Compound (I - 1)) (yield: 47.1 mg; yield: 82%; E:Z = 98:2) was obtained as a colorless oil. 11H NMR (400 MHz, CDCl3): δ 8.00 (d, J = 7.1 Hz, 2H), 7.82 (brs, 1H), 7.58 - 7.48 (m, 3H), 7.37 (d, J = 8.8 Hz, 2H), 6.92 (m, J = 8.8 Hz, 2H), 3.81 (s, 3H), 2.84 (brs, 1H), 2.15 (d, J = 1.2 Hz, 3H); HRMS: 287.0978 (Fw. 287.0980).

[0167] Example 2: Synthesis of [(1E)-1-methyl-2-(4-fluorophenyl)ethenyl]phenylsulfoximine (Compound (I-2))

[0168]

Chem.

[0169] According to the method described in Example 1, by using Compound (1-3) instead of Compound (1-1) and 4-fluorobenzaldehyde (Compound (2-2)) instead of Compound (2-1), the title compound (Compound (I-2)) (yield at 15 mmol scale: 60%) was obtained as a white solid. 1 1H NMR (400 MHz, CDCl3): δ 7.95 (s, 1H), 7.74 - 7.71 (m, 2H), 7.55 - 7.50 (m, 1H), 7.42 - 7.35 (m, 3H), 7.29 (dd, J = 8.1, 6.8 Hz, 2H), 7.04 - 7.00 (m, 2H), 6.97 - 6.94 (m, 2H), 6.87 - 6.81 (m, 2H), 2.87 (s, 1H); HRMS: 337.0935 (Fw. 337.0937).

[0170] Example 3: Synthesis of [N-methyl-(1E)-1-methyl-2-(4-fluorophenyl)ethenyl]phenylsulfoximine (Compound (I-3))

[0171] [Chem.]

[0172] To a solution of the compound (I-2) (3.5 mmol, 1.18 g) obtained in Example 2 and sodium hydride (60%, dispersed in liquid paraffin) (4.2 mmol, 168 mg) in dehydrated THF (50 mL), methyl iodide (5.3 mmol, 326 μL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction was stopped by adding water (50 mL), and the mixture was extracted three times with ethyl acetate (50 mL) and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by Biotage Selekt (SEL-2SV), Rening Cartridges 80 g (FSRN-M800E-0080) (gradient with a ratio of hexane:ethyl acetate = 95:5 to 40%) to obtain the title compound (compound (I-3)) (yield: 1.10 g; yield: 89% (E:Z = 99:1)) as a white solid. 1 H NMR (400 MHz, CDCl3): δ 7.90 (s, 1H), 7.65 (dt, J = 8.6, 1.2 Hz, 2H), 7.45 (tt, J = 9.3, 1.2 Hz, 1H), 7.38 - 7.31 (m, 3H), 7.28 - 7.24 (m, 2H), 7.03 (ddt, J = 8.8, 5.4, 2.0 Hz, 2H), 6.92 (dd, J = 7.8, 1.5 Hz, 2H), 6.86 - 6.82 (tt, J = 8.8, 2.0 Hz, 2H), 2.95 (s, 3H); HRMS: 304.1260 (Fw. 304.1263).

[0173] Examples 4 - 9 According to the methods described in Examples 1 to 3, by using the corresponding Compound (1) and Compound (2) instead of Compound (1-1) or Compound (1-3), and Compound (2-1) or Compound (2-2), Compounds (Compound (I-4) to Compound (I-10)) of Examples 4 to 10 were synthesized respectively. Table 1 below shows the chemical structures and physical property data of Compound (I-4) to Compound (I-9).

[0174]

Table 1

[0175] Example 10: Synthesis of (Z)-(2-(4-fluorophenyl)-1-phenylvinyl)(methylimino)(phenyl)-λ 6 -sulfanone (Compound (I-10))

[0176]

Chemical formula

[0177] Compound (I-3) (2.0 mmol, 702 mg) obtained in Example 3 was dissolved in acetone (20 mL), and stirred at room temperature for 6 hours under a nitrogen atmosphere while irradiating light with a wavelength of 250 to 650 nm. The reaction solution was concentrated under reduced pressure using an evaporator, and the residue was purified by Biotage Selekt (SEL-2SV), Rening Cartridges 80 g (FSRN-M800E-0080) (using only hexane) to obtain the title compound (Compound (I-10)) (yield: 85.8 mg; yield: 12% (E:Z = 1:>99)) as a white solid. m.p. 149.6 - 150.4 °C; 11H NMR (400 MHz, CDCl3) δ 7.57 (dd, J = 8.4, 1.2 Hz, 2H), 7.53 (ddd, J = 8.8, 5.4, 0.7 Hz, 2H), 7.38 (dd, J = 7.3, 7.3 Hz, 1H), 7.30 - 7.22 (m, 7H), 7.06 (s, 1H), 7.02 (dd, J = 8.7, 8.6 Hz, 2H), 2.91 (s, 3H); 13 13C{ 1 1H} NMR (101 MHz, CDCl3) δ 162.7 (d, J = 249.4 Hz), 142.9, 139.9, 138.7, 137.1, 132.2, 131.6 (d, J = 8.1 Hz), 129.9 (Overlapping two peaks), 129.1, 128.3, 128.2, 127.9, 114.7 (d, J = 22.0 Hz), 30.1; 19 19F{ 1 1H} NMR (376 MHz, CDCl3) δ -112.4; HRMS (APCI) m / z ([M+H] + ) calcd for C 21 18H 19 19FNOS: 352.1154, found: 352.1166.

[0178] Test Example 1: Cross - coupling reaction of compound (I) and organoboron compound (compound (3)) in the presence of a palladium catalyst

[0179]

Chemical Structure

[0180] The compound (I-3) (0.20 mmol, 70.4 mg) obtained in Example 3, 4-methoxyphenylboronic acid (Compound (3-1)) (0.6 mmol, 91.2 mg), potassium carbonate (0.4 mmol, 55.3 mg), RuPhos (20 μmol, 9.4 mg) and palladium acetate (20 μmol, 4.4 mg) were placed in a 20 mL vial and stirred in dehydrated THF (2.0 mL) at 60 °C for 16 hours under a nitrogen atmosphere. Water (2.0 mL) was added to stop the reaction, and the mixture was extracted three times with ethyl acetate (10 mL). The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified using Biotage Selekt (SEL-2SV), Rening Cartridges 80 g (FSRNM800E-0080) (with hexane only) to obtain Compound (II-1) (yield: 51.7 mg; yield: 85% (E:Z = 99:1)). 1 H NMR (400 MHz, CDCl3): δ8.02-7.99 (dt, J = 6.9, 1.5 Hz, 2H), 7.83 (s, 1H), 7.60 (tt, J = 7.3, 1.2 Hz, 1H), 7.54 (tt, J = 6.9, 1.5 Hz, 2H), 7.41-7.36 (ddt, J = 8.7, 5.4, 2.0 Hz, 2H), 7.12-7.07 (tt, J = 8.7, 2.0 Hz, 2H), 2.13 (d, J = 1.5 Hz, 3H); HRMS: 304.1260 (Fw. 304.1263).

[0181] Under the same reaction conditions as in Test Example 1, by using various boronic acid compounds, it is possible to stereoselectively synthesize various 3-substituted alkenes having corresponding various substituents.

[0182] Test Example 2: Cross-coupling reaction between the Z-isomer of Compound (I) and the organoboron compound (Compound (3)) (stereoretentive coupling reaction)

[0183]

Chemical formula

[0184] The compound (I-10) (0.20 mmol, 70.4 mg) obtained in Example 10, 4-methoxyphenylboronic acid (Compound (3-1)) (0.6 mmol, 91.2 mg), potassium carbonate (0.4 mmol, 55.3 mg), RuPhos (20 μmol, 9.4 mg) and palladium acetate (20 μmol, 4.4 mg) were placed in a 20 mL vial and stirred in dehydrated THF (2.0 mL) at 60 °C for 16 hours under a nitrogen atmosphere. Water (2.0 mL) was added to stop the reaction, and the mixture was extracted three times with ethyl acetate (10 mL). The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by Biotage Selekt (SEL-2SV), Rening Cartridges 10 g (FSRNM800E-0080) (using only hexane) to obtain Compound (II-2) (yield: 41.3 mg; yield: 68% (E:Z = 11:89)) as a colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.34-7.28 (m, 5H), 7.11 (d, J = 8.8 Hz, 2H), 7.03 (dd, J = 8.6, 5.6 Hz, 2H), 6.89-6.81 (m, 5H), 3.85 (s, 3H); 13 C{ 1 H} NMR (101 MHz, CDCl3) δ 161.3 (d, J = 247.2 Hz), 159.0, 143.6, 142.1, 133.7 (d, J = 3.7 Hz), 131.6, 131.0 (d, J = 8.1 Hz), 128.7, 128.2, 127.6, 127.5, 126.5, 114.9 (d, J = 21.3 Hz), 114.1, 55.2; 19 F{ 1 H} NMR (376 MHz, CDCl3) δ -115.0; HRMS (APCI) m / z ([M+H] + ) calcd for C 21 H 18FO: 305.1336, found: 305.1327.

[0185] From the results of Test Examples 1 and 2, it was confirmed that the stereochemistry of the trisubstituted alkene produced in the cross-coupling reaction can be retained depending on the stereochemistry (E-form or Z-form) of the compound (I) used. Since the cross-coupling reaction is extremely versatile in the field of organic synthetic chemistry, various types of boronic acid compounds have been readily available as commercial products or known compounds. Therefore, the cross-coupling reaction using the compound (I) of the present invention is useful as a novel synthetic method for stereoselective trisubstituted alkenes.

Industrial Applicability

[0186] According to the present invention, it is possible to provide a novel 3-substituted vinylsulfoximine derivative (compound (I)) which is a useful precursor for the regioselective and stereoselective synthesis of a 3-substituted alkene (compound (II)), a method for producing the same, and a simple and stereoselective method for producing a 3-substituted alkene (compound (II)) using the same. Further, according to the present invention, the stereochemistry of the 3-substituted alkene produced in the cross-coupling reaction can be controlled (retained) depending on the stereochemistry (E-form or Z-form) of the compound (I) used.

Claims

1. Formula (I): 【Chemical 1】 [wherein, R １ is a C １－６ alkyl group, a C ３－８ cycloalkyl group, a C ６－１４ aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; R ２ represents a halogen atom, or a C １－６ alkyl group, a C ３－８ cycloalkyl group, a C １－６ alkoxy group, a C １－６ alkylsulfenyl group, an acyl group, a C ６－１４ aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; R ３ represents a C ６－１４ aryl group or an aromatic heterocyclic group, which may each be substituted with one or more substituents selected from the substituent group a; and R represents a hydrogen atom or a C １－６ alkyl group. (Substituent group a) Halogen atom; Cyano group; Nitro group; C １－６ alkyl group; C １－６ Haloalkyl group; C １－６ alkoxy group; C １－６ haloalkoxy group; C ２－６ alkynyl group; Di(C １－６ alkyl)phosphoryl group; Di(C ６－１０ aryl)phosphoryl group; C １－６ alkylsulfonyl group; C １－６ Haloalkylsulfonyl group; C １－６ alkyl-carbonyl group; C １－６ alkoxy-carbonyl group; C ６－１４ aryl-carbonyl group; C １－６ haloalkyl-carbonyl group; C １－６ haloalkoxy-carbonyl group; C １－６ alkylsulfonyloxy group; C １－６ haloalkylsulfonyloxy group; C １－６ alkyl-carbonyloxy group; C １－６ alkoxy-carbonyloxy group; C １－６ haloalkyl-carbonyloxy group; C １－６ haloalkoxy - carbonyloxy group; (i) Halogen atom, (ii) DiC １－６ alkylamino group, (iii) C １－６ an alkoxy group, and (iv) C １－６ Haloalkoxy group One or two C's which may be substituted with a substituent selected from the group consisting of １－６ alkyl group Optionally substituted carbamoyl group; (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of C which may be replaced ６－１４ aryl group; (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of C which may be replaced ６－１４ an aryloxy group; (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of C which may be replaced ６－１４ an arylsulfonyloxy group; (i) Halogen atom, (ii) C １－６ alkyl group (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of C which may be replaced ７－１８ an aralkyl group; (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of C which may be replaced ７－１８ an aralkyloxy group; (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ Haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of C which may be replaced ３－８ cycloalkyl group; (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of C which may be replaced ３－８ cycloalkyloxy group; (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of Optionally substituted 5- to 14-membered aromatic heterocyclic group; and (i) Halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) Nitro group One to three substituents selected from the group consisting of Optionally substituted 3- to 14-membered non-aromatic heterocyclic group.] A compound represented by or a salt thereof.

2. R １ is a C １－４ alkyl group, a C ３－６ cycloalkyl group or a C ６－１０ aryl group, each of which may be substituted with one or more substituents selected from the substituent group a; R ２ is a fluorine atom, or a C １－４ alkyl group, a C ３－６ cycloalkyl group, a C ６－１０ aryl group or a 5- to 14-membered aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; R ３ is a C ６－１０ aryl group or a 5- to 14-membered aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; and R is a hydrogen atom or C １－４ The compound according to claim 1, or a salt thereof, wherein R is an alkyl group.

3. R １ is (i) Halogen atom, (ii) Cyano group, (iii) C １－４ an alkoxy group, (iv) C １－４ haloalkoxy group, (v) C ３－８ cycloalkyl group, and (vi) C ６－１０ aryl group One or more substituents selected from the group consisting of C which may be replaced １－４ an alkyl group, or (i) Halogen atom, (ii) Cyano group, (iii) C １－４ alkyl group, (iv) C １－４ haloalkyl group, (v) C １－４ an alkoxy group (vi) C １－４ haloalkoxy group, and (vii) Nitro group One or more substituents selected from the group consisting of Optionally substituted phenyl group; R ２ is Fluorine atom, (i) Halogen atom, (ii) Cyano group, (iii) C １－４ an alkoxy group, (iv) C １－４ haloalkoxy group, (v) C ３－６ cycloalkyl group, (vi) C ６－１０ an aryl group, and (vii) C ２－４ alkynyl group One or more substituents selected from the group consisting of C which may be replaced １－４ an alkyl group, or (i) Halogen atom, (ii) Cyano group, (iii) C １－４ alkyl group, (iv) C １－４ haloalkyl group, (v) C １－４ an alkoxy group, (vi) C １－４ haloalkoxy group, and (vii) Nitro group One or more substituents selected from the group consisting of Optionally substituted phenyl group; R ３ is (i) Halogen atom, (ii) Cyano group, (iii) C １－４ alkyl group (iv) C １－４ haloalkyl group, (v) C １－４ an alkoxy group, (vi) C １－４ haloalkoxy group, (vii) (a) Halogen atom, (b) C １－４ alkyl group, (c) C １－４ haloalkyl group (d) C １－４ an alkoxy group (e) C １－４ haloalkoxy group, (f) C １－４ alkylsulfonyl group, (g) C １－４ haloalkylsulfonyl group, (h) C １－４ alkyl-carbonyl group, (i) C １－４ an alkoxy-carbonyl group, (j) C １－４ haloalkyl-carbonyl group, and (k) C １－４ Haloalkoxy-carbonyl group One to three substituents selected from the group consisting of Optionally substituted benzyl group, and (viii) Nitro group, One or more substituents selected from the group consisting of Optionally substituted phenyl group or 5- to 14-membered aromatic heterocyclic group; and R is a hydrogen atom or a methyl group The compound according to Claim 1 or a salt thereof.

4. In the presence of a base, formula (1): 【Chemical 2】 [wherein, R １ is a C １－６ alkyl group, a C ３－８ cycloalkyl group, a C ６－１４ aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; R ２ represents a halogen atom, or a C １－６ alkyl group, a C ３－８ cycloalkyl group, a C １－６ alkoxy group, a C １－６ alkylsulfenyl group, an acyl group, a C ６－１４ aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; and PG is a C which may be each substituted with one or more substituents selected from the substituent group a １－６ alkyl-carbonyl group, C ６－１４ aryl-carbonyl group or aromatic heterocyclic-carbonyl group. (Substituent group a) Halogen atom; Cyano group; Nitro group; C １－６ alkyl group; C １－６ Haloalkyl group; C １－６ alkoxy group; C １－６ haloalkoxy group; C ２－６ alkynyl group; Di(C １－６ alkyl) phosphoryl group; Di(C ６－１０ aryl)phosphoryl group; C １－６ alkylsulfonyl group; C １－６ Haloalkylsulfonyl group; C １－６ alkyl-carbonyl group; C １－６ alkoxy-carbonyl group; C ６－１４ aryl-carbonyl group; C １－６ Haloalkyl-carbonyl group; C １－６ haloalkoxy-carbonyl group; C １－６ alkylsulfonyloxy group; C １－６ Haloalkylsulfonyloxy group; C １－６ alkyl-carbonyloxy group; C １－６ alkoxy-carbonyloxy group; C １－６ Haloalkyl - carbonyloxy group; C １－６ haloalkoxy - carbonyloxy group; (i) a halogen atom, (ii) DiC １－６ alkylamino group, (iii) C １－６ an alkoxy group, and (iv) C １－６ Haloalkoxy group One or two C's which may be substituted with a substituent selected from the group consisting of １－６ alkyl group a carbamoyl group which may be substituted; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ６－１４ aryl group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ６－１４ aryloxy group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ６－１４ an arylsulfonyloxy group; (i) a halogen atom, (ii) C １－６ alkyl group (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ７－１８ aralkyl group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ７－１８ an aralkyloxy group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ３－８ cycloalkyl group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ Haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ３－８ cycloalkyloxy group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of a 5- to 14-membered aromatic heterocyclic group which may be substituted; and (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of a 3- to 14-membered non-aromatic heterocyclic group which may be substituted. ] A process for producing a compound represented by formula (I): 【Chemical Formula 3】 (wherein R ３ represents a C ６－１４ aryl group or an aromatic heterocyclic group which may each be substituted with one or more substituents selected from the group of substituents a).) which comprises reacting a compound represented by formula (2): 【Chemical Formula 4】 (In the formula, R represents a hydrogen atom or a C １－６ alkyl group, with a compound represented by formula (I): Other symbols have the same meanings as described above. ) A method for producing a compound represented by formula (I): or a salt thereof, according to claim 4, wherein the base is sodium hydride or potassium hydride.

6. Formula (I): 【Chemical Formula 5】 [In the formula, R １ represents an optionally substituted C １－６ alkyl group, a C ３－８ cycloalkyl group, a C ６－１４ aryl group or an aromatic heterocyclic group, which may be substituted with one or more substituents selected from the substituent group a; R ２ represents a halogen atom, or a C １－６ alkyl group, a C ３－８ cycloalkyl group, a C １－６ alkoxy group, a C １－６ alkylsulfenyl group, an acyl group, a C ６－１４ aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the substituent group a; R ３ represents a C ６－１４ aryl group or an aromatic heterocyclic group, which may each be substituted with one or more substituents selected from the substituent group a; and R is C １－６ which represents an alkyl group. (Substituent group a) a halogen atom; a cyano group; a nitro group; C １－６ alkyl group; C １－６ Haloalkyl group; C １－６ alkoxy group; C １－６ haloalkoxy group; C ２－６ alkynyl group; Di(C １－６ alkyl) phosphoryl group; Di(C ６－１０ aryl)phosphoryl group; C １－６ alkylsulfonyl group; C １－６ haloalkylsulfonyl group; C １－６ alkyl-carbonyl group; C １－６ alkoxy-carbonyl group; C ６－１４ aryl-carbonyl group; C １－６ Haloalkyl-carbonyl group; C １－６ haloalkoxy-carbonyl group; C １－６ alkylsulfonyloxy group; C １－６ Haloalkylsulfonyloxy group; C １－６ alkyl-carbonyloxy group; C １－６ alkoxy - carbonyloxy group; C １－６ haloalkyl-carbonyloxy group; C １－６ haloalkoxy - carbonyloxy group; (i) a halogen atom, (ii) DiC １－６ alkylamino group, (iii) C １－６ an alkoxy group, and (iv) C １－６ Haloalkoxy group One or two C's which may be substituted with a substituent selected from the group consisting of １－６ alkyl group a carbamoyl group which may be substituted; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ６－１４ aryl group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ６－１４ an aryloxy group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ６－１４ an arylsulfonyloxy group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ７－１８ an aralkyl group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ７－１８ an aralkyloxy group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ３－８ cycloalkyl group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of C which may be replaced ３－８ a cycloalkyloxy group; (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group (v) C １－６ haloalkoxy group, (vi) C １－６ an alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group 1 to 3 substituents selected from the group consisting of A 5- to 14-membered aromatic heterocyclic group which may be substituted with; and (i) a halogen atom, (ii) C １－６ alkyl group, (iii) C １－６ haloalkyl group, (iv) C １－６ an alkoxy group, (v) C １－６ haloalkoxy group, (vi) C １－６ alkylsulfonyl group, (vii) C １－６ haloalkylsulfonyl group, (viii) C １－６ alkyl-carbonyl group, (ix) C １－６ alkoxy-carbonyl group, (x) C １－６ haloalkyl-carbonyl group, (xi) C １－６ haloalkoxy-carbonyl group, and (xii) a nitro group One to three substituents selected from the group consisting of A 3- to 14-membered non-aromatic heterocyclic group which may be substituted with. ] A compound represented by or a salt thereof is subjected to a cross-coupling reaction with a boronic acid compound represented by formula (3): [Chemical Formula 6] (wherein R ４ represents a C １－６ alkyl group, a C ３－８ cycloalkyl group, a C ２－６ alkenyl group, a C ２－６ alkynyl group, a C ６－１４ aryl group or an aromatic heterocyclic group, each of which may be substituted with one or more substituents selected from the group of substituents a).) in the presence of a palladium catalyst and a ligand, the method for producing a trisubstituted alkene represented by formula (II): [Chemical Formula 7] (Each symbol in the formula has the same meaning as described above.) (In the formula, each symbol has the same meaning as described above.)

7. The production method according to claim 6, wherein the palladium catalyst is palladium acetate.

8. The production method according to claim 6 or 7, wherein the ligand is 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (RuPhos), or 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyldicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (SPhos).

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