JP2010235595A - Method of preparing alkylated indoles - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method whereby indoles that are alkylated at position 2 or 3 can be prepared in a high yield using a wide range of starting materials and without requiring any special apparatus. <P>SOLUTION: The method for preparing a compound represented by Formula (3) comprises reacting the indoles represented by Formula (1), a compound represented by Formula (2) (wherein R<SP>1</SP>and R<SP>2</SP>are each independently a hydrogen atom, aliphatic group, aryl group, heteroaryl group, arylalkyl group, alkylaryl group or trialkylsilyl group; R<SP>3</SP>is a monovalent group other than a hydrogen atom; R<SP>4</SP>and R<SP>5</SP>are each independently a hydrogen atom or optionally substituted alkyl group, aryl group or heteroaryl group, provided that they may be bound to each other to form a ring; m is integer of 0-4, provided that when m is 2-4, the plurality of R<SP>3</SP>may be identical to or different from each other) and a hydride donor. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a process for producing alkylated indoles. More specifically, the present invention relates to a method for producing an indole having an alkylated 2-position or 3-position by selectively alkylating the 2-position or 3-position of the indole. In the present invention, “alkylation” in “alkylation of indoles” refers to “introducing an alkyl group or a substituted alkyl group in which a part of its hydrogen atoms are substituted with a substituent”.

Since indole derivatives have a heterocyclic skeleton, they are important as intermediates for pharmaceuticals, various chemical products, highly functional materials and the like, and are very important compounds.
Indoles can be given new physical properties by, for example, substituting at least a part of hydrogen atoms with various substituents. For the purposes described above, indoles have a desired function. It has been studied to design the structure of a class of derivatives.

Among the indole derivatives, for alkyl indoles in which the hydrogen atom bonded to the carbon atom is substituted with an alkyl group, various methods for alkylating the 3-position of indoles have been studied.
For example, Non-Patent Document 1 discloses a method of alkylating the 3-position of indoles by reacting the indoles with an alkene while heating with microwave irradiation in the presence of a gold catalyst.
Non-Patent Document 2 discloses a method of alkylating the 3-position of indoles by reacting the indoles with an alkene at a high pressure of 50 psi in the presence of a platinum chloride catalyst.

Ming-Zhong Wang et. al. Chem. Eur. J. et al. , 14, 8353-8364 (2008) Zhibin Zhang et. al. Chem. Commun. 3717-3719 (2006).

However, the method described in Non-Patent Document 1 has a problem in that a special apparatus is required to irradiate microwaves. In addition, the reaction temperature is high, and by reacting under such severe conditions, a large amount of by-products such as a part of the alkyl group undergoes a transfer reaction or reacts at a site other than the target of the alkene. Therefore, there is a problem that the yield of the desired target product is lowered. Furthermore, in order to obtain the target product with a relatively good yield, the alkene that can be used has a limited structure such as a structure having an aromatic skeleton other than the terminal, and the usable raw materials are limited. There was a problem that it was.
On the other hand, the method described in Non-Patent Document 2 has a problem in that a special apparatus is required because the reaction is performed under high pressure. Also, the reaction temperature is high, and by reacting under such severe conditions, a large amount of by-products such as a part of the alkyl group undergoes a transfer reaction, resulting in a decrease in the yield of the desired target product. There was a problem of doing.

  The present invention has been made in view of the above circumstances, and provides a method that does not require a special apparatus, can use a wide range of raw materials, and can produce indoles in which the 2- or 3-position is alkylated in a high yield. The task is to do.

To solve the above problem,
The present invention provides the following general formula (3), characterized in that an indole represented by the following general formula (1), a compound represented by the following general formula (2), and a hydride donor are reacted. Methods for producing the compounds represented are provided.

(Wherein R ¹ and R ² are each independently a hydrogen atom, aliphatic group, aryl group, heteroaryl group, arylalkyl group, alkylaryl group or trialkylsilyl group; R ³ is a group other than a hydrogen atom; Each of R ⁴ and R ⁵ independently represents a hydrogen atom, or an alkyl group, aryl group or heteroaryl group which may have a substituent, and is bonded to each other to form a ring. M is an integer of 0 to 4; when m is 2 to 4, a plurality of R ³ may be the same or different.

  Further, the present invention provides the following general formula (7), characterized by reacting an indole represented by the following general formula (6), a compound represented by the following general formula (2), and a hydride donor. The method of manufacturing the compound represented by this is provided.

Wherein R ¹ is a hydrogen atom, aliphatic group, aryl group, heteroaryl group, arylalkyl group, alkylaryl group or trialkylsilyl group; R ^{2 ′} is an aliphatic group, aryl group, heteroaryl group , An arylalkyl group, an alkylaryl group or a trialkylsilyl group; R ³ is a monovalent group other than a hydrogen atom; R ⁴ and R ⁵ each independently have a hydrogen atom or a substituent; A good alkyl group, aryl group or heteroaryl group, which may be bonded to each other to form a ring; m is an integer of 0 to 4; R ³ may be the same as or different from each other.)

In the production method of the present invention, R ¹ is preferably a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an aryl group or heteroaryl group having 6 to 12 carbon atoms.
In the production method of the present invention, when the compound (1) is used, the R ² is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an aryl group or heteroaryl group having 6 to 12 carbon atoms, When using the said compound (6), it is preferable that said R2 ^' is a C1-C6 alkyl group, a C6-C12 aryl group, or heteroaryl group.
In the production method of the present invention, R ⁴ and R ⁵ are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 8 carbon atoms, an aryl group having 6 to 12 carbon atoms, or A heteroaryl group having 2 to 11 carbon atoms is preferred.
In the production method of the present invention, the hydride donor is preferably a silane compound or a stannane compound.
In the production method of the present invention, it is further preferable to react using a Lewis acid catalyst.
In the production method of the present invention, the Lewis acid catalyst is preferably a metal sulfonate or a metal sulfonimide.

  According to the present invention, a special apparatus is unnecessary, a wide range of raw materials can be used, and indole having an alkylated 2- or 3-position can be produced with high yield.

The present invention will be described in detail below.
[Method for producing indole having alkylation at 3-position]
The method for producing a compound represented by the following general formula (3) of the present invention (hereinafter abbreviated as compound (3)) is an indole represented by the following general formula (1) (hereinafter abbreviated as compound (1)). And a compound represented by the following general formula (2) (hereinafter abbreviated as compound (2)) and a hydride donor. That is, an alkyl group is introduced with high selectivity at the 3-position of the compound (1).

(Wherein R ¹ and R ² are each independently a hydrogen atom, aliphatic group, aryl group, heteroaryl group, arylalkyl group, alkylaryl group or trialkylsilyl group; R ³ is a group other than a hydrogen atom; Each of R ⁴ and R ⁵ independently represents a hydrogen atom, or an alkyl group, aryl group or heteroaryl group which may have a substituent, and is bonded to each other to form a ring. M is an integer of 0 to 4; when m is 2 to 4, a plurality of R ³ may be the same or different.

<Compound (1)>
In the compound (1), R ¹ and R ² are each independently a hydrogen atom, an aliphatic group, an aryl group, a heteroaryl group, an arylalkyl group, an alkylaryl group, or a trialkylsilyl group.
The aliphatic group in R ¹ and R ² may be linear, branched or cyclic, and is preferably linear or branched.
Examples of the linear or branched aliphatic group include an alkyl group, an alkenyl group, and an alkynyl group, and examples of the cyclic aliphatic group include a cycloalkyl group, a cycloalkenyl group, and a cycloalkynyl group.

As the alkyl group in the aliphatic group of R ¹ and R ² , an alkyl group having 1 to 8 carbon atoms is preferable. Specifically, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, Examples include isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl and n-octyl. Of these, an alkyl group having 1 to 6 carbon atoms is more preferable, and an alkyl group having 1 to 3 carbon atoms is particularly preferable.
The alkenyl group or alkynyl group in the aliphatic group for R ¹ is an unsaturated bond formed between the carbon atom bonded to the 1st nitrogen atom constituting the indole ring and the carbon atom adjacent to the carbon atom. It is preferable that the number of unsaturated bonds is smaller.
The alkenyl group or alkynyl group in the aliphatic group for R ² is an unsaturated bond formed between the carbon atom bonded to the carbon atom at the 2-position constituting the indole ring and the carbon atom adjacent to the carbon atom. It is preferable that the number of unsaturated bonds is smaller.

The cyclic aliphatic group for R ¹ and R ² may be either a monocyclic structure or a polycyclic structure.
The cycloalkyl group in the cyclic aliphatic group represented by R ¹ and R ² preferably has 5 to 10 carbon atoms.
The cycloalkenyl group or cycloalkynyl group in the cyclic aliphatic group of R ¹ is such that the unsaturated bond between carbon atoms is separated from the carbon atom bonded to the nitrogen atom at the 1-position constituting the indole ring. Preferably, the smaller the number of unsaturated bonds, the better.
The cycloalkenyl group or cycloalkynyl group in the cyclic aliphatic group represented by R ² is such that the unsaturated bond between carbon atoms is separated from the carbon atom bonded to the carbon atom at the 2-position constituting the indole ring. Preferably, the smaller the number of unsaturated bonds, the better.

The aryl group in R ¹ and R ² may be either a monocyclic structure or a polycyclic structure, but is preferably a monocyclic structure. The aryl group preferably has 6 to 12 carbon atoms, and more preferably a phenyl group.
Examples of the arylalkyl group in R ¹ and R ² include a monovalent group in which the aryl group is bonded to an alkylene group, and the alkylene group includes one alkyl group in the aliphatic group of R ¹ and R ² . Examples thereof include a group excluding a hydrogen atom.
The alkylaryl group for R ¹ or R ^2, wherein one of the hydrogen atoms of the aryl group can be exemplified a monovalent group substituted with an alkyl group, as the alkyl group, the aliphatic group of R ¹ and R ² The same thing as the alkyl group in can be illustrated.
In the aryl group in R ¹ and R ² , one or more hydrogen atoms on the benzene ring may be substituted with a substituent such as an alkyl group, but are preferably not substituted.

The heteroaryl group in R ¹ and R ^2, one of the aryl group for R ¹ and R ^2, a group of one or more is replaced with a heteroatom of the carbon atoms constituting the aromatic ring can be exemplified. Here, examples of the hetero atom include an oxygen atom, a sulfur atom, and a nitrogen atom. The number of carbon atoms substituted with a heteroatom is not particularly limited, but is preferably one.
The heteroaryl group in R ¹ and R ² preferably has 6 to 12 carbon atoms.

The trialkylsilyl group in R ¹ and R ² is preferably a trimethylsilyl group, a triethylsilyl group or a triisopropylsilyl group.

Among the above, R ¹ is preferably a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an aryl group or a heteroaryl group having 6 to 12 carbon atoms, and a hydrogen atom or an alkyl group having 1 to 3 carbon atoms. It is more preferable that
R ² is preferably a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an aryl group or a heteroaryl group having 6 to 12 carbon atoms, a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or phenyl. More preferably, it is a group.

In the compound (1), R ³ is a monovalent group other than a hydrogen atom.
The monovalent group in R ³ may be a single atom or a group composed of a plurality of atoms.
Examples of the monovalent group of R ³ include the same aliphatic groups, aryl groups, heteroaryl groups, arylalkyl groups, alkylaryl groups, and trialkylsilyl groups as those of R ¹ and R ² . In addition to these, alkoxy groups, alkenyloxy groups, aryloxy groups, arylalkyloxy groups, alkylaryloxy groups, hydroxyl groups, and halogen atoms can be exemplified.

The alkoxy group in R ³ may be linear, branched or cyclic, and the linear or branched alkyl group or the cycloalkyl group in R ¹ and R ² is a group in which an oxygen atom is bonded. Can be illustrated. Of these, an alkoxy group having 1 to 6 carbon atoms is particularly preferable.
Similarly, the alkenyloxy group in R ³ may be linear, branched or cyclic, and the linear or branched alkenyl group or cycloalkenyl group in R ¹ and R ² is an oxygen atom. A bonded group can be exemplified.
Examples of the aryloxy group, arylalkyloxy group, and alkylaryloxy group in R ³ include groups in which the aryl group, arylalkyl group, and alkylaryl group in R ¹ and R ² are each bonded to an oxygen atom.
Examples of the halogen atom in R ³ include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

The monovalent group illustrated here may have a substituent. Here, having a substituent means that at least a part of carbon atoms constituting the monovalent group is substituted with a group other than carbon atoms, or at least one of hydrogen atoms constituting the monovalent group. The part is substituted with a group other than a hydrogen atom. And both the hydrogen atom and the carbon atom may be substituted with a substituent. Here, the number of substituents is not particularly limited.
Examples of the substituent for substituting the carbon atom include heteroatoms such as oxygen atom, nitrogen atom, sulfur atom and boron atom.
As a substituent which substitutes a hydrogen atom, a C1-C3 alkyl group or an alkoxy group can be illustrated as a preferable thing.

In the compound (1), m is an integer of 0 to 4, preferably 0 to 2, and more preferably 0 or 1.
When m is 2 to 4, the plurality of R ³ may be the same as or different from each other. That is, all R ³ may be the same, some R ³ may be different from each other, or all R ³ may be different from each other.
When m is 1 to 4, the bonding position of R ^{3 to} the indole ring is not particularly limited. For example, when m is 1, R ³ is bonded to the 5-position carbon atom of the indole ring. Preferably it is.

  Particularly preferred examples of the compound (1) include those represented by the following formulas (1101) to (1112) and (1201) to (1212).

  In particular, the compound (1) represented by the formulas (1110) to (1112) and (1210) to (1212) has an organoboron moiety, and is useful as a carbon-carbon bond forming reaction. It is suitable as a raw material for Suzuki-Miyaura coupling) and is extremely useful in industry.

  Although the usage-amount of a compound (1) should just adjust suitably according to the kind etc. of a compound (2), it is preferable that it is usually 1-4 times mole amount of a compound (2), and 1-3 times The molar amount is more preferable, and the molar amount is particularly preferably 1 to 2 times.

<Compound (2)>
In the compound (2), R ⁴ and R ⁵ are each independently a hydrogen atom or an optionally substituted alkyl group, aryl group or heteroaryl group, and bonded to each other to form R ⁴ , R 5 ⁵ and a carbon atom to which R ⁴ and R ⁵ are respectively bonded may form a ring.
The alkyl group in R ⁴ and R ⁵ may be any of linear, branched and cyclic, and specifically, an alkyl group having 1 to 8 carbon atoms is preferable, and more specifically, a methyl group, Ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, cyclopentyl Group, cyclohexyl group, cycloheptyl group, cyclooctyl group, cyclopentylmethyl group, 1-cyclopentylethyl group, cyclohexylmethyl group and 1-cyclohexylethyl group.
Among these, a C1-C8 alkyl group is preferable and a C1-C6 alkyl group is more preferable.

The aryl group in R ⁴ and R ⁵ may be either a monocyclic structure or a polycyclic structure, but preferably has 6 to 12 carbon atoms, preferably a monocyclic structure, and particularly preferably a phenyl group.

The heteroaryl group for R ⁴ and R ^5, one of the aryl group for R ⁴ and R ^5, groups in which one or more is replaced with a heteroatom of the carbon atoms constituting the aromatic ring can be exemplified. Here, examples of the hetero atom include an oxygen atom, a sulfur atom, and a nitrogen atom. The number of carbon atoms substituted with a heteroatom is not particularly limited, but is preferably one.
The heteroaryl group in R ⁴ and R ⁵ preferably has a total number of carbon atoms and hetero atoms of 6 to 12. The heteroaryl group preferably has 2 to 11 carbon atoms.
Preferable examples of the heteroaryl group in R ⁴ and R ⁵ include a thienyl group.

When R ⁴ and R ⁵ are bonded to each other to form a ring, the ring may be either a monocyclic structure or a polycyclic structure.
The number of carbon atoms in the ring (the number of carbon atoms in R ^4, the number of carbon atoms in R ⁵ , the number of carbon atoms to which R ⁴ is bonded (ie, “1”)) and the number of carbon atoms to which R ⁵ is bonded ( That is, the total of “1”) is preferably 6 to 15, and more preferably 7 to 12.
If a cycloalkyne compound in which R ⁴ and R ⁵ are bonded to each other to form a ring is used as the compound (2), a cycloalkyl group can also be easily introduced.

The alkyl group, aryl group or heteroaryl group in R ⁴ and R ⁵ may have a substituent. Here, “the alkyl group, aryl group or heteroaryl group has a substituent” means that at least a part of the hydrogen atoms constituting the alkyl group, aryl group or heteroaryl group is substituted with a group other than a hydrogen atom. Or at least a part of the carbon atoms constituting the alkyl group, aryl group or heteroaryl group is substituted with a group other than carbon atoms. And both the hydrogen atom and the carbon atom may be substituted with a substituent.

Examples of the substituent that substitutes a hydrogen atom in R ⁴ and R ⁵ include an alkyl group, an aryl group, an alkylcarbonyloxy group, a trialkylsilyloxy group, a phthalimidoyl group, a hydroxyl group, a cyano group, and a halogen atom.
Examples of the alkyl group and aryl group as substituents for R ⁴ and R ⁵ are the same as the alkyl group and aryl group for R ¹ and R ² .
Examples of the alkyl group in the alkylcarbonyloxy group as a substituent in R ⁴ and R ⁵ include the same alkyl groups as those in R ¹ and R ² .
Examples of the trialkylsilyloxy group as a substituent in R ⁴ and R ⁵ include a trimethylsilyloxy group, a triethylsilyloxy group, and a triisopropylsilyloxy group.
Examples of the halogen atom as a substituent in R ⁴ and R ⁵ include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

The number of substituents for substituting a hydrogen atom is not particularly limited and can be arbitrarily adjusted according to the types of R ⁴ and R ⁵ , but the smaller the number, the more preferably 0 or 1.
Further, the position of the hydrogen atom substituted with the substituent is not particularly limited, but it is usually preferable that it is farther from the triple bond of the compound (2). For example, in the case of an alkyl group, the carbon atom forming the triple bond It is particularly preferred that the hydrogen atom bonded to the terminal carbon atom on the opposite side to is substituted with the above substituent.

  Preferred examples of the substituent for substituting a hydrogen atom include a phenyl group, a hydroxyl group, a cyano group, and a phthalimidoyl group.

Examples of the substituent for substituting the carbon atom in R ⁴ and R ⁵ include a carbonyl group (—C (═O) —), an ester bond (—C (═O) —O—), an amide bond (—NH—C ( = O)-), heteroatoms can be exemplified. Examples of the hetero atom include an oxygen atom, a nitrogen atom, a sulfur atom, a boron atom, and a silicon atom.
The number of substituents substituting the carbon atom is not particularly limited and can be arbitrarily adjusted according to the types of R ⁴ and R ⁵ , but the smaller the number, the better.
Further, the position of the carbon atom substituted with the substituent is not particularly limited, but it is usually preferable that the position is farther from the triple bond of the compound (2).

  As a preferable substituent for substituting a carbon atom, a hetero atom can be exemplified.

R ⁴ and R ⁵ are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 8 carbon atoms, an aryl group having 6 to 12 carbon atoms, or a heteroaryl group having 2 to 11 carbon atoms. It is preferable that

<Hydride donor>
The hydride donor may be any known hydride donor as long as it can donate hydride (H ⁻ ) in the reaction system. Preferable examples include silane compounds and stannane compounds.

Examples of the silane compound include alkyl silane, alkoxy silane, aryl silane, and alkyl aryl silane.
Examples of the alkyl silane include diethyl silane ((CH ₃ CH ₂ ) ₂ SiH ₂ ), dimethyl ethyl silane (CH ₃ CH ₂ (CH ₃ ) ₂ SiH), and dimethyl isopropyl silane ((CH ₃ ) ₂ CH (CH ₃ ) _2. SiH), tert-butyl dimethylsilane _{((CH 3) 3 C (} CH 3) 2 SiH), diethyl isopropyl silane _{((CH 3) 2 CH (} CH 3 CH 2) 2 SiH), cyclohexyl dimethylsilane _(C 6 H ₁₁ (CH ₃ ) ₂ SiH), tri (n-propyl) silane ((CH ₃ CH ₂ CH ₂ ) ₃ SiH), triethylsilane ((CH ₃ CH ₂ ) ₃ SiH), triisopropylsilane (((CH ₃ ) ₂ CH) ₃ SiH), tris (trimethylsilyl) silane (((CH ₃ ) ₃ Si) ₃ S iH) can be exemplified.
Examples of the alkoxysilane include trimethoxysilane ((CH ₃ O) ₃ SiH) and triethoxysilane ((CH ₃ CH ₂ O) ₃ SiH).
Examples of the aryl silane include phenyl silane (C ₆ H ₅ SiH ₃ ), diphenyl silane ((C ₆ H ₅ ) ₂ SiH ₂ ), and triphenyl silane ((C ₆ H ₅ ) ₃ SiH).
Examples of the alkylarylsilane include phenylmethylsilane (C ₆ H ₅ (CH ₃ ) SiH ₂ ), phenyldimethylsilane (C ₆ H ₅ (CH ₃ ) ₂ SiH), and diphenylmethylsilane ((C ₆ H ₅ ) ₂ CH. ₃ SiH).
Among these, as the silane compound, alkylarylsilane or arylsilane is preferable, and diphenylmethylsilane or triphenylsilane is particularly preferable.

Examples of the stannane compound include alkylstannane and arylstannane.
Examples of the alkyl stannane include trialkyl stannanes such as tri (n-butyl) stannane ((CH ₃ CH ₂ CH ₂ CH ₂ ) ₃ SnH).
Examples of the aryl stannane include triaryl stannanes such as triphenyl stannane ((C ₆ H ₅ ) ₃ SnH).

  Although the usage-amount of a hydride donor should just be adjusted suitably according to the kind etc. of a compound (1) and (2), it is preferable that it is usually 1 to 4 times mole amount of a compound (2). It is more preferably ˜3 times the molar amount, and particularly preferably 1 to 2 times the molar amount.

  A hydride donor may be used individually by 1 type, and may use 2 or more types together. When two or more kinds are used in combination, the combination and ratio may be appropriately selected according to the purpose. However, in the present invention, it is preferable to use one kind alone.

<Lewis acid catalyst>
In the present invention, in addition to the compound (1), the compound (2) and the hydride donor, it is preferable to further react using a Lewis acid catalyst. By using the Lewis acid catalyst, the compound (3) or (3 ′) can be obtained more rapidly and in a high yield.
The Lewis acid catalyst may be a known one, and among them, metal sulfonate or metal sulfonimide is preferable.

Examples of the metal sulfonate include a compound represented by the following general formula (41) (hereinafter abbreviated as M (OTf) _n ) and a compound represented by the following general formula (42) (hereinafter abbreviated as M (ONf) _n ). Can be exemplified.
An example of the metal sulfonimide is a compound represented by the following general formula (43) (hereinafter abbreviated as M (NTf ₂ ) _n ). These are all known compounds.

  (In the formula, M is a metal atom; n is an integer of 1 or more.)

In the formula, M is a metal atom, and preferred examples include indium (In), zinc (Zn), copper (Cu), silver (Ag), gold (Au), bismuth (Bi), zirconium (Zr), Examples include scandium (Sc), mercury (Hg), gallium (Ga), iron (Fe), and hafnium (Hf).
n is an integer of 1 or more, and is determined by the type of M.

In the present invention, examples of preferable metal sulfonates include those in which M is indium (In), and particularly preferable examples include In (OTf) ₃ and In (ONf) ₃ .
Then, as the preferred metals sulfonimide, M can be exemplified those in which indium _{(In), In (NTf 2} ) 3 can be exemplified as particularly preferable.

  The amount of the Lewis acid catalyst used may be appropriately adjusted according to the types of the compounds (1) and (2), but is usually preferably 5 to 60 mol% based on the compound (2). 10 to 50 mol% is more preferable, and 10 to 40 mol% is particularly preferable.

  A Lewis acid catalyst may be used individually by 1 type, and may use 2 or more types together. When two or more kinds are used in combination, the combination and ratio may be appropriately selected according to the purpose.

<Other reaction conditions>

In the present invention, in addition to the compound (1), the compound (2), the hydride donor, and the Lewis acid catalyst, other components may be used and reacted as long as the effects of the present invention are not hindered. good.
For example, when a small amount of water coexists, the progress of the side reaction may be suppressed and the yield of the compound (3) may be improved. Although the usage-amount of water should just be adjusted suitably, normally it is preferable that it is 0.05-3 times mole amount of a compound (2), and it is more preferable that it is 0.1-2 times mole amount.
Furthermore, when using a compound unstable to water, such as the compound (1) represented by the formulas (1110) to (1112) and (1210) to (1212), a dehydrating agent is used. It is good to use together. As the dehydrating agent, known ones such as anhydrous magnesium sulfate can be used, and the amount used can be arbitrarily adjusted.

In the present invention, the reaction solvent can be appropriately selected from those that do not interfere with the reaction in consideration of the types of the compound (1), the compound (2), and the hydride donor. Of these, ethers, alkyl halides or benzenes are preferred.
Examples of ethers include 1,4-dioxane, dimethoxyethane, tetrahydrofuran, diethyl ether and dibutyl ether. As the halogenated alkyls, 1,2-dichloroethane can be exemplified as a preferable one. And as benzene, chlorobenzene can be illustrated as a preferable thing. Of these, chlorobenzene is particularly preferred.

  A reaction solvent may be used individually by 1 type, and may use 2 or more types together as a mixed solvent. When two or more kinds are used in combination, the combination and ratio may be appropriately selected according to the purpose.

In the present invention, for example, the compound (1), the compound (2) and a hydride donor, more preferably a Lewis acid catalyst are mixed in a reaction solvent in the presence of other components as necessary, and reacted. Thus, compound (3) is obtained.
The reaction temperature may be appropriately adjusted and is not particularly limited, but is usually preferably 10 to 90 ° C.
The reaction time may be appropriately adjusted according to other reaction conditions such as the reaction temperature, but usually 0.5 to 130 hours are preferable.

Furthermore, in the present invention, the compound (1) and the compound (2), more preferably a Lewis acid catalyst, are mixed in a reaction solvent in the presence of other components as necessary to carry out the first stage reaction. The compound (3) can also be obtained by applying a two-stage reaction in which the hydride donor is added to the same reaction vessel and the second-stage reaction is performed. In this case, in the first stage reaction, the compound (1) and the compound (2) react to produce an alkene derivative as an intermediate, but the alkene derivative is relatively stable, This may be taken out and subjected to the necessary treatment, and then the second stage reaction may be performed.
The temperature during the first stage reaction and the second stage reaction may be the same as described above. The reaction temperature may be changed between the first stage and the second stage, and the reaction may be performed while changing the reaction temperature in either the first stage or the second stage.
Moreover, it is preferable to adjust reaction time so that it may become the same as the above with the sum total of the 1st step and the 2nd step.
The raw materials such as compound (1), compound (2), hydride donor and Lewis acid catalyst, and the amount of reaction solvent used may be the same as described above.

  In the present invention, after completion of the reaction, the compound (3) can be taken out by a known method. That is, if necessary, after performing post-treatment such as filtration, washing, extraction, pH adjustment, dehydration, concentration, etc., the compound (3) may be taken out by crystallization, column chromatography or the like. Further, the extracted compound (3) may be further purified by repeating crystallization, column chromatography and the like.

  In the conventional alkylation reaction of indoles, an alkyl group can be introduced at the 3-position. However, since microwave irradiation and pressurization are required, a special apparatus is required, and the yield of the target product is further reduced. The raw material which is low and can be used may be limited. On the other hand, in the present invention, a special apparatus is unnecessary, a wide range of raw materials can be used, the reaction conditions are mild, and indole having an alkylated 3-position can be produced in a high yield. The present invention provides the first method for highly selectively alkylating the 3-position of indoles by chemical reaction.

In the present invention, the reaction is presumed to proceed as follows. Here, an example in which a Lewis acid catalyst containing metal (M) (hereinafter abbreviated as “cat.M”) is used will be described.
cat. By reacting compound (1) with compound (2) in the presence of M, it is considered that compound (5), which is an alkene derivative, is first produced. The compound (5) is produced by reacting the compound (1) and the compound (2) one molecule at a time, and is relatively stable, so that the production of by-products is suppressed. At this time, which of the two carbon atoms forming the triple bond of compound (2) preferentially reacts with compound (1) depends on the combination of R ⁴ and R ⁵ of compound (2). It is determined. Usually, a carbon atom having a functional group having a high electron donating ability reacts preferentially with the compound (1). For example, when either one of R ⁴ and R ⁵ is a hydrogen atom, this selectivity is further improved. Here, the case where the carbon atom to which R ⁴ is bonded reacts with the compound (1) is shown. And compound (5) is further cat. It reacts with hydride (H ⁻ ) in the presence of M to produce the target compound (3). These reactions proceed under mild conditions. For example, side reactions such as transfer reactions of alkyl groups are suppressed, so that the 3-position of compound (1) can be highly selectively alkylated with high yield. The compound (3) is obtained at a rate.

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and m are the same as above).

Compound (3), depending on the type, by performing an additional reaction, it can be converted to R ^1. This reaction is generally known as a reaction for converting a protecting group of a nitrogen atom constituting a heterocyclic ring, and a known method can be appropriately selected. For example, the reaction for converting R ¹ which is a group other than a hydrogen atom to a hydrogen atom is a deprotection reaction, for example, the reaction for converting R ¹ from a benzyl group (—Bn) to a hydrogen atom (debenzylation reaction). Is mentioned.

For example, in the present invention, when the compound (1) in which R ¹ is a hydrogen atom is used and the yield of the compound (3) is not improved for some reason, R ¹ is a group other than a hydrogen atom. After obtaining the corresponding compound (3) using the compound, the compound (3) is subjected to a deprotection reaction, and R ¹ is converted to a hydrogen atom, whereby the desired product can be obtained.

[Method for producing indole having alkylation at 2-position]
The method for producing a compound represented by the following general formula (7) of the present invention (hereinafter abbreviated as compound (7)) is an indole represented by the following general formula (6) (hereinafter referred to as compound (6)). (Abbreviated), a compound (2), and a hydride donor are reacted. That is, an alkyl group is introduced with high selectivity at the 2-position of the compound (7).

Wherein R ¹ is a hydrogen atom, aliphatic group, aryl group, heteroaryl group, arylalkyl group, alkylaryl group or trialkylsilyl group; R ^{2 ′} is an aliphatic group, aryl group, heteroaryl group , An arylalkyl group, an alkylaryl group or a trialkylsilyl group; R ³ is a monovalent group other than a hydrogen atom; R ⁴ and R ⁵ each independently have a hydrogen atom or a substituent; A good alkyl group, aryl group or heteroaryl group, which may be bonded to each other to form a ring; m is an integer of 0 to 4; R ³ may be the same as or different from each other.)

^{Wherein, R 1, R 3, R} 4, R 5, m ^{is, R} 1, ^{R 3} in Formula (1) ~ (3), R 4, R 5, is the same as m.
R ^{2 ′} is an aliphatic group, an aryl group, a heteroaryl group, an arylalkyl group, an alkylaryl group or a trialkylsilyl group, except that it is not a hydrogen atom, R in the general formula (1) ^Same as ² .

Compound (6) is bonded instead R ^{2 'to} R ² in the indole ring, the binding position is in except a 3-position carbon atoms of not 2-position carbon atom constituting the indole ring, compound ( Same as 1).
And the manufacturing method of a compound (7) is the same as the manufacturing method of a compound (3) except using a compound (6) instead of a compound (1).

Hereinafter, the present invention will be described in more detail with reference to specific examples. However, the present invention is not limited to the following examples. In addition, the usage-amount (mol%) of the Lewis' acid catalyst shown below is the quantity on the basis of a compound (2) all. “Mmol” represents 10 ⁻³ mol. Furthermore, each abbreviation shows the following groups, respectively.
Ph: phenyl group n-Hex: n-hexyl group t-Bu: tert-butyl group PI: phthalimidoyl group 3-Thi: 3-thienyl group

Example 1
As shown in Tables 1 and 2, R ¹ and R ² are hydrogen atoms, m is 0 (1) (0.6 mmol), R ⁴ is an n-hexyl group, and R ⁵ is a hydrogen atom. Compound (2) (0.4 mmol), diphenylmethylsilane (0.6 mmol) and In (NTf ₂ ) ₃ (30 mol%) were mixed in chlorobenzene (0.4 ml) and reacted at 45 ° C. for 24 hours. The product was purified by silica gel column chromatography, and the target compound (3101) was taken out. In Table 2, “Yield (%)” indicates the isolated yield (%) of the target product based on the compound (2).
The NMR data of the obtained compound (3101) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.86 (t, J = 7.2 Hz, 3 H), 1.12-1.42 (m, 8 H), 1.34 (d, J = 6.9 Hz, 3 H), 1.55 -1.67 (m, 1 H), 1.71-1.86 (m, 1 H), 3.02 (sext, J = 6.9 Hz, 1 H), 6.95 (dd, J = 2.3, 0.6 Hz, 1 H), 7.09 (ddd , J = 8.0, 6.9, 1.1 Hz, 1 H), 7.17 (ddd, J = 8.3, 7.2, 1.2 Hz, 1 H), 7.35 (dt, J = 8.0, 1.2 Hz, 1 H), 7.65 (dd, J = 8.0, 1.2 Hz, 1 H), 7.87 (bs, 1 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δ ppm: 14.1, 21.4, 22.7, 27.7, 29.5, 30.8, 31.9, 37.7, 111.1, 118.9, 119.4, 119.8, 121.7, 122.9, 126.9, 136.5.

(Example 2)
Compound (3102) was obtained in the same manner as in Example 1 except that the reaction was performed under the conditions shown in Tables 1 and 2.
The NMR data of the obtained compound (3102) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.83 (t, J = 6.9 Hz, 3 H), 1.06-1.33 (m, 8 H), 1.38 (d, J = 7.5 Hz, 3 H), 1.62 -1.76 (m, 1 H), 1.77-1.90 (m, 1 H), 2.36 (s, 3 H), 2.87-2.97 (m, 1 H), 7.02 (ddd, J = 8.0, 6.9, 1.1 Hz, 1 H), 7.07 (ddd, J = 8.0, 6.9, 1.2 Hz, 1 H), 7.25 (d, J = 8.0 Hz, 1 H), 7.62 (d, J = 7.5 Hz, 1 H), 7.62 (bs , 1 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δ ppm: 12.2, 14.1, 21.3, 22.7, 28.3, 29.4, 31.3, 31.9, 37.1, 110.2, 116.7 118.6, 119.5, 120.5, 127.5, 129.9, 135.4.

Example 3
Compound (3103) was obtained in the same manner as in Example 1 except that the reaction was carried out under the conditions shown in Tables 1 and 2.
The NMR data of the obtained compound (3103) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.79 (t, J = 6.9 Hz, 3 H), 1.05-1.23 (m, 8 H), 1.45 (d, J = 7.5 Hz, 3 H), 1.66 -1.82 (m, 1 H), 1.84-2.00 (m, 1 H), 3.09-3.18 (m, 1 H), 7.09 (ddd, J = 8.0, 6.9, 1.1 Hz, 1 H), 7.18 (ddd, J = 8.0, 6.9, 1.1 Hz, 1 H), 7.34-7.40 (m, 2 H), 7.42-7.53 (m, 4 H), 7.79 (dd, J = 8.0, 1.2 Hz, 1 H), 7.89 ( bs, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δ ppm: 14.1, 21.5, 22.7, 28.3, 29.3, 31.1, 31.2, 36.9, 110.9, 118.4, 119.0 120.9, 121.8, 127.4, 127.6, 128.6, 128.8, 133.8, 134.2, 136.3.

Example 4
Compound (3104) was obtained in the same manner as in Example 1 except that the reaction was carried out under the conditions shown in Tables 1 and 2. In the compound (1), m is 1 and R ³ is bonded to the 5-position carbon atom of the indole ring.
The NMR data of the obtained compound (3104) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.84 (t, J = 6.9 Hz, 3 H), 1.04-1.34 (m, 8 H), 1.37 (d, J = 7.5 Hz, 3H), 1.63- 1.74 (m, 1 H), 1.77-1.87 (m, 1 H), 3.22 (s, 3 H), 2.83-2.94 (m, 1 H), 3.85 (s, 3 H), 6.74 (dd, J = 8.6, 2.3 Hz, 1 H), 7.08 (d, J = 2.3 Hz, 1 H), 7.14 (d, J = 8.6 Hz, 1 H), 7.52 (bs, 1H).

(Example 5)
Compound (3105) was obtained in the same manner as in Example 1 except that the reaction was carried out under the conditions shown in Tables 1 and 2. Incidentally, in the compound (1), m is 1, R ³ is attached to the 5-position carbon atom of the indole ring.
The NMR data of the obtained compound (3105) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.86 (t, J = 7.2 Hz, 3 H), 1.15-1.37 (m, 8 H), 1.31 (d, J = 6.9 Hz, 3 H), 1.52 -1.66 (m, 1 H), 1.67-1.79 (m, 1 H), 2.96 (sext, J = 6.9 Hz, 1 H), 6.95 (d, J = 2.3 Hz, 1 H), 7.22 (d, J = 8.5 Hz, 1 H), 7.23-7.29 (m, 1 H), 7.75 (d, J = 1.7 Hz, 1 H), 7.92 (bs, 1 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δ ppm: 14.1, 21.4, 22.7, 27.6, 29.5, 30.7, 31.9, 37.6, 112.3, 112.5, 121.1, 122.0, 122.7, 124.6, 128.7, 135.1.

(Example 6)
Compound (3201) was obtained in the same manner as in Example 1 except that the reaction was performed under the conditions shown in Tables 1 and 2.
The NMR data of the obtained compound (3201) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.86 (t, J = 6.9 Hz, 3 H), 1.19-1.39 (m, 8 H), 1.33 (d, J = 6.9 Hz, 3 H), 1.55 -1.64 (m, 1 H), 1.71-1.82 (m, 1 H), 3.01 (sext, J = 7.0 Hz, 1 H), 6.74 (s, 3 H), 6.79 (s, 1 H), 7.08 ( ddd, J = 8.0, 6.9, 1.2 Hz, 1 H), 7.20 (ddd, J = 8.3, 7.2, 1.2 Hz, 1 H), 7.28 (d, J = 8.6 Hz, 1 H), 7.63 (ddd, J = 8.1, 1.2, 1.2 Hz, 1 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δ ppm: 14.1, 21.6, 22.7, 27.8, 29.5, 30.8, 31.9, 32.6, 37.9, 109.1, 118.3, 119.5, 121.3, 121.4, 124.7, 127.3, 137.1.

(Example 7)
Compound (3106) was obtained in the same manner as in Example 1 except that 0.2 mmol of water was added to the reaction system and the reaction was performed under the conditions shown in Tables 1 and 2.
The NMR data of the obtained compound (3106) are shown below.
^{1 H-NMR (500 MHz,} CDCl 3) δppm: 1.77 (d, J = 6.9 Hz, 3 H), 2.34 (s, 3 H), 4.42 (q, J = 7.4, 1H), 6.97 (ddd, J = 8.0, 6.9, 1.2 Hz, 1 H), 7.06 (ddd, J = 8.0, 6.9, 1.2 Hz, 1 H), 7.15 (tt, J = 7.2, 1.5 Hz, 1 H), 7.22-7.29 (m, 3 H), 7.31-7.36 (m, 2 H), 7.39 (dd, J = 8.1, 1.2 Hz, 1 H), 7.71 (bs, 1H).

(Example 8)
Compound (3202) was obtained in the same manner as in Example 1 except that 1.2 mmol of anhydrous magnesium sulfate was added to the reaction system and the reaction was performed under the conditions shown in Tables 1 and 2. In the compound (1), m is 1 and R ³ is bonded to the 5-position carbon atom of the indole ring.
The NMR data of the obtained compound (3202) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 1.35 (d, J = 1.7 Hz, 12 H), 1.69 (d, J = 7.5 Hz, 3 H), 3.72 (s, 3 H), 4.47 (q , J = 7.3 Hz, 1 H), 6,69 (s, 1 H), 7.18 (tt, J = 7.2, 1.6 Hz 1 H), 7.23-7.36 (m, 5 H), 7.64 (dd, J = 8.0, 1.2 Hz, 1 H), 8.05 (bs, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δppm: 22.8, 24.9, 30.9, 32.6, 36.3, 83.3, 108.5, 121.3, 125.8, 126.1, 127.0, 127.1, 127.5, 127.9, 128.2, 139.1, 146.7.

Example 9
Compound (3203) was obtained in the same manner as in Example 1 except that the reaction was performed under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3203) are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ) δppm: 0.93 (s, 9 H), 1.29 (d, J = 7.3 Hz, 3 H), 2.92 (q, J = 7.3 Hz, 1 H), 3.76 (s , 3 H), 6.80 (s, 1 H), 7.07 (ddd, J = 7.8, 6.9, 0.9 Hz, 1 H), 7.18 (ddd, J = 8.0, 7.1, 0.9 Hz, 1 H), 7.26 (dt , J = 8.2, 0.9 Hz, 1 H), 7.62 (dt, J = 8.2, 0.9 Hz, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δ ppm: 17.0, 28.0, 32.6, 34.3, 40.5, 108.9, 118.3, 119.1, 120.0, 121.0, 126.4, 128.9, 136.3.

(Example 10)
Compound (3204) was obtained in the same manner as in Example 1 except that the reaction was carried out under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3204) are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ) δppm: 1.45 (d, J = 6.9 Hz, 3 H), 2.08 (s, 3 H), 3.01 (dd, J = 13.3, 7.3 Hz, 1 H), 3.07 (dd, J = 13.3, 7.3 Hz, 1 H), 3.21 (sext, J = 7.3 Hz, 1 H), 3.58 (s, 3 H), 6.96-7.04 (m, 2 H), 7.07 (ddd, J = 7.8, 6.9, 0.9 Hz, 1 H), 7.09-7.21 (m, 4 H), 7.22-7.28 (m, 1 H), 7.75 (dd, J = 7.8, 0.9 Hz, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δppm: 10.8, 20.7, 29.4, 34.4, 43.7, 108.7, 114.9, 118.3, 119.5, 120.1, 125.5, 126.3, 127.9, 129.0, 132.3, 136.9, 141.9.

(Example 11)
The reaction was conducted in the same manner as in Example 1 except that the conditions shown in Tables 3 and 4 were used. In addition to the same reaction as in Example 1, the reaction with the hydroxyl group contained in R ⁴ of compound (2) was performed. Compound (3206) was obtained by dehydrogenation reaction with a hydride donor in the system.
The NMR data of the obtained compound (3206) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.60 (s, 3 H), 1.31 (d, J = 6.9 Hz, 3 H), 1.32-1.45 (m, 2 H), 1.51-1.63 (m, 3 H), 1.68-1.78 (m, 1 H), 2.99 (sext, J = 7.0 Hz, 1 H), 3.66 (t, J = 6.9 Hz, 2 H), 6.76 (s, 3 H), 7.06 ( ddd, J = 8.0, 6.9, 1.2 Hz, 1 H), 7.20 (ddd, J = 8.0, 6.9, 1.2 Hz, 1 H), 7.27 (dd, J = 8.0, 1.2 Hz, 1 H), 7.30-7.44 (m, 6 H) 7.56 (dd, J = 8.1, 1.2 Hz, 3 H) 7.60 (dd, J = 8.0, 1.2 Hz, 1 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δppm: -3.05, 21.6, 23.9, 30.7, 32.5, 32.7, 37.6, 63.5, 109.1, 118.3, 119.4, 121.1, 121.3, 124.8, 127.2, 127.8, 129.7, 134.3, 136.3, 137.1.

(Example 12)
In Example 11, the compound (3206) was obtained. To obtain the compound (3205), the reaction was performed as follows.
That is, compound (3205) was obtained in the same manner as in Example 1 except that 0.8 mmol of water was added to the reaction system and the reaction was performed under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3205) are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ) δppm: 1.17 (s, 1 H), 1.34 (d, J = 7.3 Hz, 3 H), 1.36-1.47 (m, 2 H), 1.52-1.62 (m, 2 H), 1.62-1.70 (m, 1 H), 1.75-1.86 (m, 1 H), 3.03 (sext, J = 6.9 Hz, 1 H), 3.60 (t, J = 6.4 Hz, 2 H), 3.70 (s, 3 H), 6.80 (s, 1 H), 7.08 (ddd, J = 8.2, 6.9, 0.9 Hz, 1 H), 7.20 (ddd, J = 8.2, 6.9, 0.9 Hz, 1 H), 7.28 (dt, J = 8.2, 0.9 Hz, 1 H), 7.62 (dt, J = 7.8, 0.9 Hz, 1 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δ ppm: 21.6, 23.9, 30.8, 32.6, 33.0, 37.6, 63.0, 109.2, 118.4, 119.4, 120.9, 121.3, 124.5, 127.2, 137.1.

(Example 13)
Compound (3207) was obtained in the same manner as in Example 1 except that the reaction was performed under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3207) are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ) δppm: 1.37 (d, J = 7.3 Hz, 3 H), 1.60-1.73 (m, 2 H), 1.75-1.94 (m, 2 H), 2.33 (td, J = 7.1, 1.4 Hz, 2 H), 3.07 (sext, J = 7.1 Hz, 1 H), 3.75 (s, 3 H), 6.82 (s, 1 H), 7.09 (ddd, J = 8.2, 6.9, 0.9 Hz, 1 H), 7.22 (ddd, J = 8.3, 7.0, 0.9 Hz, 1 H), 7.30 (dt, J = 8.3, 0.9 Hz, 1 H), 7.60 (dt, J = 8.3, 0.9 Hz, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δ ppm: 17.3, 21.8, 23.6, 30.4, 32.6, 36.7, 109.3, 118.6, 119.2, 119.6, 119.8, 121.5, 125.0, 127.0, 137.2.

(Example 14)
Compound (3208) was obtained in the same manner as in Example 1 except that the reaction was carried out under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3208) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 1.34 (d, J = 6.9 Hz, 3 H), 1.63-1.86 (m, 4 H), 3.06 (sext, J = 6.8 Hz, 1 H), 3.63 -3.69 (m, 2 H), 3.73 (s, 3 H), 6.80 (d, J = 6.8 Hz, 1 H), 7.04 (ddd, J = 8.3, 7.3, 1.0 Hz, 1 H), 7.17 (ddd , J = 8.0, 7.1, 1.1 Hz, 1 H), 7.25 (d, J = 7.5 Hz, 1 H), 7.59 (ddd, J = 8.1, 7.1, 1.1 Hz, 1 H), 7.67-7.71 (m, 2 H), 7.79-7.83 (m, 2 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δ ppm: 21.7, 26.7, 30.5, 32.6, 34.8, 38.2, 119.2, 118.4, 119.4, 120.3, 121.3, 123.1, 125.0, 127.1, 132.1, 133.8, 137.1.

(Example 15)
Compound (3209) was obtained in the same manner as in Example 1 except that 0.2 mmol of water was added to the reaction system and the reaction was performed under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3209) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 1.78 (d, J = 7.5 Hz, 3 H), 2.33 (s, 3 H), 3.65 (s, 3 H), 4.45 (q, J = 7.3 Hz , 1 H), 6.96 (t, J = 7.4 Hz, 1 H), 7.07-7.17 (m, 2 H), 7.22-7.27 (m, 3 H), 7.34 (dd, J = 8.1, 1.2, Hz, 2 H), 7.40 (dd, J = 8.1, 1.2 Hz, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δ ppm: 10.6, 20.7, 29.5, 35.7, 108.6, 115.4, 118.5, 119.3, 120.2, 125.5, 126.7, 127.3, 128.1, 132.5, 136.7, 146.3.

(Example 16)
Compound (3210) was obtained in the same manner as in Example 1 except that 0.2 mmol of water was added to the reaction system and the reaction was performed under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3210) are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ) δppm: 1.74 (d, J = 7.4 Hz, 3 H), 2.32 (s, 3 H), 3.65 (s, 3 H), 4.40 (qd, J = 7.3, 1.4 Hz, 1 H), 6.90 (dd, J = 5.0, 1.4 Hz, 1 H), 6.96 (ddd, J = 7.9, 6.9, 0.92 Hz, 1 H), 7.02 (quint, J = 1.4 Hz, 1 H ), 7.06 (ddd, J = 7.9, 6.9, 0.9 Hz, 1 H), 7.18 (dd, J = 5.4, 3.2 Hz, 1 H), 7.24 (dt, J = 8.3, 0.9 Hz, 1 H), 7.32 (dt, J = 8.0, 0.9 Hz, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δ ppm: 10.4, 21.1, 29.4, 32.0, 108.6, 115.1, 118.5, 119.2, 119.2, 120.3, 125.0, 126.5, 128.4, 132.2, 136.7, 147.6.

(Example 17)
Compound (3211) was obtained in the same manner as in Example 1 except that the reaction was performed under the conditions shown in Tables 3 and 4.
The NMR data of the obtained compound (3211) are shown below.
¹ H-NMR (500 MHz, CDCl ₃ ) δppm: 0.94 (t, J = 7.5 Hz, 3 H), 1.97-2.07 (m, 1 H), 2.15-2.26 (m, 1 H), 3.74 (s, 3 H), 4.05 (t, J = 7.5 Hz, 1 H), 6.86 (s, 1 H), 7.00 (ddd, J = 8.0, 7.4, 1.2 Hz, 1 H), 7.12-7.20 (m, 2 H ), 7.22-7.34 (m, 4 H), 7.44 (dd, J = 8.1, 1.2 Hz, 1 H).
¹³ C-NMR (125 MHz, CDCl ₃ ) δ ppm: 12.9, 29.2, 32.7, 44.8, 109.0, 118.6, 119.0, 119.6, 121.4, 125.8, 125.8, 127.5, 128.0, 128.2, 137.2, 145.5.

(Example 18)
As shown in Tables 5 and 6, compound (6) (0.48 mmol) in which R ¹ is a hydrogen atom, R ^{2 ′} is a phenyl group and m is 0, R ⁴ is an n-hexyl group, and R ⁵ is Compound (2) (0.4 mmol) which is a hydrogen atom, diphenylmethylsilane (0.6 mmol) and In (NTf ₂ ) ₃ (30 mol%) were mixed in chlorobenzene (0.4 ml), and the mixture was stirred at 70 ° C. for 7 hours. After the reaction, purification was performed by silica gel column chromatography to take out the target compound (7101).
The NMR data of the obtained compound (7101) are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ) δppm: 0.81 (t, J = 6.9 Hz, 3 H), 1.07-1.28 (m, 8 H), 1.33 (d, J = 6.8 Hz, 3 H), 1.55 -1.70 (m, 2 H), 3.21 (sext, J = 7.2 Hz, 1 H), 7.10 (ddd, J = 7.8, 6.9, 0.9 Hz, 1 H), 7.17 (ddd, J = 8.2, 6.9, 0.9 Hz, 1 H), 7.27-7.34 (m, 1 H), 7.36 (dt, J = 8.2, 0.9 Hz, 1 H), 7.41-7.51 (m, 4 H), 7.58 (dt, J = 7.8, 0.9 Hz, 1 H), 7.94 (bs, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δppm: 14.0, 21.5, 22.6, 27.5, 29.2, 30.5, 31.7, 37.4, 110.4, 114.3, 118.9, 119.8, 121.5, 126.0, 128.0, 128.4, 129.9, 135.2, 135.5 , 140.3.

(Example 19)
Compound (7102) was obtained in the same manner as in Example 18, except that 0.2 mmol of water was added to the reaction system, and the reaction was performed under the conditions shown in Tables 5 and 6.
The NMR data of the obtained compound (7102) are shown below.
¹ H-NMR (400 MHz, CDCl ₃ ) δppm: 1.70 (d, J = 7.3 Hz, 3 H), 4.62 (q, J = 7.3 Hz, 1 H), 7.10 (ddd, J = 8.0, 7.1, 0.9 Hz, 1 H), 7.17 (ddd, J = 8.0, 7.1, 0.9 Hz, 1 H), 7.20-7.37 (m, 6 H), 7.40-7.55 (m, 5 H), 7.62 (dt, J = 7.8 , 0.9 Hz, 1 H), 7.82 (bs, 1 H).
¹³ C-NMR (100 MHz, CDCl ₃ ) δ ppm: 20.6, 35.6, 110.6, 114.6, 119.2, 120.0, 121.8, 126.2, 126.5, 127.2, 127.9, 128.5, 128.6, 129.7, 135.1, 135.3, 138.7, 143.8.

  The present invention can be used for the manufacture of pharmaceuticals, various chemical products, highly functional materials and the like.

Claims (8)

A compound represented by the following general formula (3), characterized by reacting an indole represented by the following general formula (1), a compound represented by the following general formula (2), and a hydride donor: Manufacturing method.

(Wherein R ¹ and R ² are each independently a hydrogen atom, aliphatic group, aryl group, heteroaryl group, arylalkyl group, alkylaryl group or trialkylsilyl group; R ³ is a group other than a hydrogen atom; Each of R ⁴ and R ⁵ independently represents a hydrogen atom, or an alkyl group, aryl group or heteroaryl group which may have a substituent, and is bonded to each other to form a ring. M is an integer of 0 to 4; when m is 2 to 4, a plurality of R ³ may be the same or different. A compound represented by the following general formula (7), characterized by reacting an indole represented by the following general formula (6), a compound represented by the following general formula (2), and a hydride donor: Manufacturing method.

Wherein R ¹ is a hydrogen atom, aliphatic group, aryl group, heteroaryl group, arylalkyl group, alkylaryl group or trialkylsilyl group; R ^{2 ′} is an aliphatic group, aryl group, heteroaryl group , An arylalkyl group, an alkylaryl group or a trialkylsilyl group; R ³ is a monovalent group other than a hydrogen atom; R ⁴ and R ⁵ each independently have a hydrogen atom or a substituent; A good alkyl group, aryl group or heteroaryl group, which may be bonded to each other to form a ring; m is an integer of 0 to 4; R ³ may be the same as or different from each other.) 3. The method for producing a compound according to claim ¹ , wherein R ¹ is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an aryl group or heteroaryl group having 6 to 12 carbon atoms. When the compound (1) is used, the R ² is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or an aryl group or heteroaryl group having 6 to 12 carbon atoms, and the compound (6) is used. In this case, the compound according to any one of claims 1 to 3, wherein R ^{2 '} is an alkyl group having 1 to 6 carbon atoms, or an aryl group or heteroaryl group having 6 to 12 carbon atoms. Manufacturing method. R ⁴ and R ⁵ are each independently a hydrogen atom, an optionally substituted alkyl group having 1 to 8 carbon atoms, an aryl group having 6 to 12 carbon atoms, or a heteroaryl having 2 to 11 carbon atoms. It is group, The manufacturing method of the compound as described in any one of Claims 1-4 characterized by the above-mentioned.   The said hydride donor is a silane compound or a stannane compound, The manufacturing method of the compound as described in any one of Claims 1-5 characterized by the above-mentioned.   Furthermore, it reacts using a Lewis' acid catalyst, The manufacturing method of the compound as described in any one of Claims 1-6 characterized by the above-mentioned.   The method for producing a compound according to claim 7, wherein the Lewis acid catalyst is a metal sulfonate or a metal sulfonimide.