JP5099932B2 - Carbon-carbon bond formation reaction using fluorenone imine - Google Patents

Description

  The present invention particularly relates to an efficient carbon-carbon bond forming reaction using fluorenone imine.

  A technique using a nitroalkane as an equivalent has been developed for a nucleophilic reaction using a simple alkylamine.

Kobayashi, S .; Yazaki, R .; Seki, K .; Yamashita, Y. Angew. Chem. Int. Ed. 2008, 47, 5613. Rosini, G .; Ballini, R. Synthesis, 1988, 833. Westermann, B. Angew. Chem. Int. Ed. 2003, 42, 151.

  Numerous nucleophilic reactions using simple alkylamines have been developed. However, the conventional methods require a cumbersome reduction operation when converting to an amino group after the reaction.

  By the way, fluorenone imine has an effect of extremely stabilizing an anion generated on the α-position carbon of the nitrogen atom. As a result, even when a weak base is used, deprotonation easily occurs. Therefore, it was thought that it was applicable to the reaction using various substituted alkylamines. The present inventor has previously proposed an efficient Mannich-type reaction of a glycine derivative and a phosphonic acid analog using fluorenone imine. However, this proposal limited the substrate.

  Therefore, the problem to be solved by the present invention is to provide a diamine analog or amino alcohol analog efficiently.

The study for solving the above-mentioned problems has been intensively promoted. In other words, the development of Mannich-type reaction by the activation of simple alkylamine was intensively pursued. As a result, simple alkylamines protected as, for example, fluorenone imine (eg, benzylamine, ethylamine, methylamine, etc.) have been found to add efficiently and highly diastereoselectively to imines. The protected 1,2 diamine obtained by this reaction was easily led to the free 1,2 diamine by acid hydrolysis treatment.

  Based on the above findings, the present invention has been achieved.

That is, the above problem is
A reaction method for producing a carbon-carbon bond, comprising:
This is solved by a reaction method characterized by reacting a compound represented by the following general formula [I] with a compound represented by the following general formula [II] to produce a diamine analog.

Also, a reaction method for generating a carbon-carbon bond,
Reacting a compound represented by the following general formula [I] with a compound represented by the following general formula [II] in the presence of an optically active quaternary ammonium salt to form a diamine analog. It is solved by a reaction method characterized by

一般式［Ｉ］中、Ｒ^１，Ｒ^２は、Ｈまたは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^１とＲ^２とは、同一でも、異なるものでも良い。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、Ｈ、Ｆ，Ｃｌ，Ｂｒ，Ｉ、炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）、Ｏ，Ｓ又はＮ（Ｏ，Ｓ，Ｎは、置換基を有する場合と、水素原子のみ有する場合とが有る。）である。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、全てが同一でも、異なるものでも良い。 Formula [I]

In the general formula [I], R ¹ and R ² are H or a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). R ¹ and R ² may be the same or different. R ³ , R ⁴ , R ⁵ and R ⁶ are H, F, Cl, Br, I, a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). ), O, S or N (O, S, N may have a substituent or only a hydrogen atom). R ³ , R ⁴ , R ⁵ and R ⁶ may all be the same or different.

一般式［ＩＩ］中、Ｒ^７，Ｒ^８は、Ｈまたは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^９は、ＣＯＯＲ，ＳＯ_２Ｒ又はＰＯＲ_２（Ｒは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。））である。 Formula [II]

In general formula [II], R ⁷ and R ⁸ are H or a hydrocarbon group (the hydrocarbon group may or may not have a substituent). R ⁹ is COOR, SO ₂ R or POR ₂ (R is a hydrocarbon group (the hydrocarbon group may or may not have a substituent)).

In addition, the above problem is
A reaction method for producing a carbon-carbon bond, comprising:
This is solved by a reaction method characterized by reacting a compound represented by the following general formula [I] with a compound represented by the following general formula [III] to produce an amino alcohol analog.

一般式［Ｉ］中、Ｒ^１，Ｒ^２は、Ｈまたは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^１とＲ^２とは、同一でも、異なるものでも良い。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、Ｈ、Ｆ，Ｃｌ，Ｂｒ，Ｉ、炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）、Ｏ，Ｓ又はＮ（Ｏ，Ｓ，Ｎは、置換基を有する場合と、水素原子のみ有する場合とが有る。）である。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、全てが同一でも、異なるものでも良い。 Formula [I]

In the general formula [I], R ¹ and R ² are H or a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). R ¹ and R ² may be the same or different. R ³ , R ⁴ , R ⁵ and R ⁶ are H, F, Cl, Br, I, a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). ), O, S or N (O, S, N may have a substituent or only a hydrogen atom). R ³ , R ⁴ , R ⁵ and R ⁶ may all be the same or different.

一般式［ＩＩＩ］中、Ｒ^１０は炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^１１はＨまたは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^１０とＲ^１１とは、同一でも、異なるものでも良い。 Formula [III]

In general formula [III], R ¹⁰ is a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). R ¹¹ is H or a hydrocarbon group (the hydrocarbon group may or may not have a substituent). R ¹⁰ and R ¹¹ may be the same or different.

  By the present invention (carbon-carbon bond formation reaction using an alkylamine protected with a fluorenylidene group as a carbon nucleophile), 1,2-diamine analogs and amino alcohols were efficiently obtained. For example, it can be directly converted to the target amino group by hydrolysis by acid treatment without undergoing a reduction operation. For example, compared to the case of using nitroalkane, there is no need for a reduction operation for obtaining an amino group after the reaction, which is advantageous in terms of energy. From this, a useful object useful in the field of fine chemicals such as pharmaceuticals was efficiently obtained.

The present invention is a reaction method for producing a carbon-carbon bond. This method is particularly a method of producing a diamine analog. And it is the method of producing | generating the compound represented by the following general formula [X] by making the compound represented by the following general formula [I] and the compound represented by the following general formula [II] react. .
Formula [X]

一般式［Ｉ］中、Ｒ^１，Ｒ^２は、Ｈまたは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^１とＲ^２とは、同一でも、異なるものでも良い。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、Ｈ、Ｆ，Ｃｌ，Ｂｒ，Ｉ、炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）、Ｏ，Ｓ又はＮ（Ｏ，Ｓ，Ｎは、置換基を有する場合と、水素原子のみ有する場合とが有る。）である。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、全てが同一でも、異なるものでも良い。
上記Ｒ^１，Ｒ^２，Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６の炭化水素基は、好ましくは、炭素数が１〜１０のものである。そして、アルキル基、アリール基、アルケニル基、又はアラルキル基が好ましい。好ましいアルキル基は炭素数が１〜６のものである。特に好ましいアルキル基は、メチル基、エチル基、プロピル基、ｉ−プロピル基、ブチル基、ｔ−ブチル基である。好ましいアリール基は炭素数が６〜１０のものである。特に好ましいアリール基は、フェニル基、ナフチル基（例えば、1−naphthyl,2−naphthyl）である。好ましいアルケニル基は炭素数が３〜９のものである。特に好ましいアルケニル基はビニル基、メチルビニル基（例えば、2−methylvinyl）である。好ましいアラルキル基は炭素数が７〜１０のものである。特に好ましいアラルキル基は、例えばベンジル基（Ｂｎ）やアルキルナフチル基（例えば、1−naphthylmethyl,2−naphthylmethyl）である。前記アルキル基、アリール基、アルケニル基、アラルキル基は、置換基を有する場合と、置換基を有さない場合とが有る。この置換基としては、例えばＦ，Ｃｌ，Ｂｒ，Ｉ，ＣＮ等が挙げられる。アルキル基も挙げられる。Ｒ^１，Ｒ^２は、特に、前記アルキル基、アリール基、アルケニル基、アラルキル基の置換基として、前記以外にも、アセタール基、ｔ−ブチルジメチルシリルオキシ基などのトリアルキルシリルオキシ基、エトキシカルボニル基などのアルコキシカルボニル基も挙げられる。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、上記した基の他にも、例えばＯ，Ｓ又はＮ（Ｏ，Ｓ，Ｎは、置換基を有する場合と、置換基を有さない場合とが有る。）であっても良い。この場合の置換基としては、例えば炭素数が１〜１０のアルキルが挙げられる。従って、Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、ＭｅＯ，ＭｅＳ，Ｍｅ_２Ｎ等であっても良い。これ等のＲＯ，ＲＳ，Ｒ_２Ｎ（Ｒ＝アルキル基）は好ましい。 Formula [I]

In the general formula [I], R ¹ and R ² are H or a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). R ¹ and R ² may be the same or different. R ³ , R ⁴ , R ⁵ and R ⁶ are H, F, Cl, Br, I, a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). ), O, S or N (O, S, N may have a substituent or only a hydrogen atom). R ³ , R ⁴ , R ⁵ and R ⁶ may all be the same or different.
The hydrocarbon group for R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ is preferably one having 1 to 10 carbon atoms. An alkyl group, an aryl group, an alkenyl group, or an aralkyl group is preferable. Preferred alkyl groups are those having 1 to 6 carbon atoms. Particularly preferred alkyl groups are a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, and a t-butyl group. Preferred aryl groups are those having 6 to 10 carbon atoms. Particularly preferred aryl groups are a phenyl group and a naphthyl group (for example, 1-naphthyl, 2-naphthyl). Preferred alkenyl groups are those having 3 to 9 carbon atoms. Particularly preferred alkenyl groups are a vinyl group and a methylvinyl group (for example, 2-methylvinyl). Preferred aralkyl groups are those having 7 to 10 carbon atoms. Particularly preferred aralkyl groups are, for example, a benzyl group (Bn) and an alkyl naphthyl group (for example, 1-naphthylmethyl, 2-naphthylmethyl). The alkyl group, aryl group, alkenyl group, and aralkyl group may have a substituent or may not have a substituent. Examples of this substituent include F, Cl, Br, I, and CN. An alkyl group is also mentioned. In particular, R ¹ and R ² can be used as substituents for the alkyl group, aryl group, alkenyl group, and aralkyl group, as well as trialkylsilyloxy groups such as acetal group and t-butyldimethylsilyloxy group, ethoxy Also included are alkoxycarbonyl groups such as carbonyl groups. R ³ , R ⁴ , R ⁵ , and R ⁶ may be, for example, O, S, or N (where O, S, and N have a substituent and a case that does not have a substituent, in addition to the above-described groups. May be present). Examples of the substituent in this case include alkyl having 1 to 10 carbon atoms. Therefore, R ³ , R ⁴ , R ⁵ , R ⁶ may be MeO, MeS, Me ₂ N, or the like. These RO, RS, and R ₂ N (R = alkyl group) are preferable.

一般式［ＩＩ］中、Ｒ^７，Ｒ^８は、Ｈまたは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^９は、ＣＯＯＲ，ＳＯ_２Ｒ又はＰＯＲ_２（Ｒは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。））である。
上記Ｒ^７，Ｒ^８の炭化水素基は、好ましくは、炭素数が１〜１０のものである。そして、アルキル基、アリール基、アルケニル基、又はアラルキル基が好ましい。好ましいアルキル基は炭素数が１〜６のものである。特に好ましいアルキル基は、メチル基、エチル基、プロピル基、ｉ−プロピル基、ブチル基、ｔ−ブチル基である。好ましいアリール基は炭素数が６〜１０のものである。特に好ましいアリール基は、フェニル基、ナフチル基（例えば、1−naphthyl,2−naphthyl）である。好ましいアルケニル基は炭素数が３〜９のものである。特に好ましいアルケニル基はビニル基、メチルビニル基（例えば、2−methylvinyl）である。好ましいアラルキル基は炭素数が７〜１０のものである。特に好ましいアラルキル基は、例えばベンジル基や1−naphthylmethyl,2−naphthylmethyl等のアルキルナフチル基である。前記アルキル基、アリール基、アルケニル基、アラルキル基は、置換基を有する場合と、置換基を有さない場合とが有る。この置換基としては、例えばＦ，Ｃｌ，Ｂｒ，Ｉ，ＣＮ等が挙げられる。炭素数が１〜１０のアルキル基も挙げられる。Ｒ^７とＲ^８とは、同一でも、異なるものでも良い。尚、Ｒ^７，Ｒ^８の少なくとも一方は炭化水素基であることが好ましい。
上記Ｒ^９は、ＣＯＯＲ，ＳＯ_２Ｒ又はＰＯＲ_２（Ｒは炭化水素基）である。この炭化水素基Ｒは、好ましくは、炭素数が１〜１０のものである。そして、アルキル基、アリール基、アルケニル基、又はアラルキル基が好ましい。好ましいアルキル基は炭素数が１〜６のものである。特に好ましいアルキル基は、メチル基、エチル基、プロピル基、ｉ−プロピル基、ブチル基、ｔ−ブチル基である。好ましいアリール基は炭素数が６〜１０のものである。特に好ましいアリール基は、フェニル基、ナフチル基（例えば、1−naphthyl,2−naphthyl）である。好ましいアルケニル基は炭素数が３〜９のものである。特に好ましいアルケニル基はビニル基、メチルビニル基（例えば、2−methylvinyl）である。好ましいアラルキル基は炭素数が７〜１０のものである。特に好ましいアラルキル基は、例えばベンジル基や1−naphthylmethyl,2−naphthylmethyl等のアルキルナフチル基である。前記アルキル基、アリール基、アルケニル基、アラルキル基は、置換基を有する場合と、置換基を有さない場合とが有る。この置換基としては、例えばＦ，Ｃｌ，Ｂｒ，Ｉ，ＣＮ等が挙げられる。炭素数が１〜１０のアルキル基も挙げられる。 Formula [II]

In general formula [II], R ⁷ and R ⁸ are H or a hydrocarbon group (the hydrocarbon group may or may not have a substituent). R ⁹ is COOR, SO ₂ R or POR ₂ (R is a hydrocarbon group (the hydrocarbon group may or may not have a substituent)).
The hydrocarbon groups for R ⁷ and R ⁸ are preferably those having 1 to 10 carbon atoms. An alkyl group, an aryl group, an alkenyl group, or an aralkyl group is preferable. Preferred alkyl groups are those having 1 to 6 carbon atoms. Particularly preferred alkyl groups are a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, and a t-butyl group. Preferred aryl groups are those having 6 to 10 carbon atoms. Particularly preferred aryl groups are a phenyl group and a naphthyl group (for example, 1-naphthyl, 2-naphthyl). Preferred alkenyl groups are those having 3 to 9 carbon atoms. Particularly preferred alkenyl groups are a vinyl group and a methylvinyl group (for example, 2-methylvinyl). Preferred aralkyl groups are those having 7 to 10 carbon atoms. Particularly preferred aralkyl groups are alkyl naphthyl groups such as benzyl group and 1-naphthylmethyl, 2-naphthylmethyl. The alkyl group, aryl group, alkenyl group, and aralkyl group may have a substituent or may not have a substituent. Examples of this substituent include F, Cl, Br, I, and CN. An alkyl group having 1 to 10 carbon atoms is also included. R ⁷ and R ⁸ may be the same or different. In addition, it is preferable that at least one of R ⁷ and R ⁸ is a hydrocarbon group.
R ⁹ is COOR, SO ₂ R or POR ₂ (R is a hydrocarbon group). The hydrocarbon group R preferably has 1 to 10 carbon atoms. An alkyl group, an aryl group, an alkenyl group, or an aralkyl group is preferable. Preferred alkyl groups are those having 1 to 6 carbon atoms. Particularly preferred alkyl groups are a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, and a t-butyl group. Preferred aryl groups are those having 6 to 10 carbon atoms. Particularly preferred aryl groups are a phenyl group and a naphthyl group (for example, 1-naphthyl, 2-naphthyl). Preferred alkenyl groups are those having 3 to 9 carbon atoms. Particularly preferred alkenyl groups are a vinyl group and a methylvinyl group (for example, 2-methylvinyl). Preferred aralkyl groups are those having 7 to 10 carbon atoms. Particularly preferred aralkyl groups are alkyl naphthyl groups such as benzyl group and 1-naphthylmethyl, 2-naphthylmethyl. The alkyl group, aryl group, alkenyl group, and aralkyl group may have a substituent or may not have a substituent. Examples of this substituent include F, Cl, Br, I, and CN. An alkyl group having 1 to 10 carbon atoms is also included.

  The present invention is a reaction method for producing a carbon-carbon bond. This method is particularly a method of producing a diamine analog. Then, in the presence of an optically active quaternary ammonium salt, the compound represented by the above general formula [I] is reacted with the compound represented by the above general formula [II].

一般式［ＩＶ］中、Ｒ^１２は炭化水素基である。好ましくは炭素数が１〜１０のアルキル基である。又は、炭素数が７〜１１のアラルキル基である。Ｒ^１３は炭化水素基である。好ましくは炭素数が１〜１０のアルキル基またはアルケニル基である。Ｒ^１４は炭化水素基（置換基を持つ場合と、置換基を持たない場合とが有る。）である。例えば、アルキル基、アリール基、アルケニル基、アラルキル基などである。好ましいアルキル基は炭素数が１〜６のものである。好ましいアリール基は炭素数が６〜１０のものである。好ましいアルケニル基は炭素数が３〜９のものである。好ましいアラルキル基は炭素数が７〜１１のものである。前記アルキル基、アリール基、アルケニル基、アラルキル基は、置換基を有する場合と、置換基を有さない場合とが有る。Ｒ^１５，Ｒ^１６，Ｒ^１７，Ｒ^１８はＨ又は炭化水素基である。この炭化水素基は、好ましくは、炭素数が１〜１０のものである。そして、アルキル基、アリール基、アルケニル基、又はアラルキル基が好ましい。好ましいアルキル基は炭素数が１〜６のものである。特に好ましいアルキル基は、メチル基、エチル基、プロピル基、ｉ−プロピル基、ブチル基、ｔ−ブチル基である。好ましいアリール基は炭素数が６〜１０のものである。特に好ましいアリール基は、フェニル基、ナフチル基（例えば、1−naphthyl,2−naphthyl）である。好ましいアルケニル基は炭素数が３〜９のものである。特に好ましいアルケニル基はビニル基、メチルビニル基（例えば、2−methylvinyl）である。好ましいアラルキル基は炭素数が７〜１０のものである。特に好ましいアラルキル基は、例えばベンジル基（Ｂｎ）やアルキルナフチル基（例えば、1−naphthylmethyl,2−naphthylmethyl）である。前記アルキル基、アリール基、アルケニル基、アラルキル基は、置換基を有する場合と、置換基を有さない場合とが有る。この置換基としては、例えばＦ，Ｃｌ，Ｂｒ，Ｉ，ＣＮ等が挙げられる。アルキル基も挙げられる。上記した基の他にも、例えばＯ，Ｓ又はＮ（Ｏ，Ｓ，Ｎは、置換基を有する場合と、置換基を有さない場合とが有る。）であっても良い。この場合の置換基としては、例えば炭素数が１〜１０のアルキルが挙げられる。従って、Ｒ^１５，Ｒ^１６，Ｒ^１７，Ｒ^１８は、ＭｅＯ，ＭｅＳ，Ｍｅ_２Ｎ等であっても良い。これ等のＲＯ，ＲＳ，Ｒ_２Ｎ（Ｒ＝アルキル基）は好ましい。 The optically active quaternary ammonium salt is particularly preferably a compound having a structure represented by the following general formula [IV].
Formula [IV]

In the general formula [IV], R ¹² is a hydrocarbon group. Preferably it is a C1-C10 alkyl group. Or, it is an aralkyl group having 7 to 11 carbon atoms. R ¹³ is a hydrocarbon group. Preferably it is a C1-C10 alkyl group or alkenyl group. R ¹⁴ is a hydrocarbon group (which may or may not have a substituent). For example, an alkyl group, an aryl group, an alkenyl group, an aralkyl group, and the like. Preferred alkyl groups are those having 1 to 6 carbon atoms. Preferred aryl groups are those having 6 to 10 carbon atoms. Preferred alkenyl groups are those having 3 to 9 carbon atoms. Preferred aralkyl groups are those having 7 to 11 carbon atoms. The alkyl group, aryl group, alkenyl group, and aralkyl group may have a substituent or may not have a substituent. R ¹⁵ , R ¹⁶ , R ¹⁷ , and R ¹⁸ are H or a hydrocarbon group. This hydrocarbon group preferably has 1 to 10 carbon atoms. An alkyl group, an aryl group, an alkenyl group, or an aralkyl group is preferable. Preferred alkyl groups are those having 1 to 6 carbon atoms. Particularly preferred alkyl groups are a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, and a t-butyl group. Preferred aryl groups are those having 6 to 10 carbon atoms. Particularly preferred aryl groups are a phenyl group and a naphthyl group (for example, 1-naphthyl, 2-naphthyl). Preferred alkenyl groups are those having 3 to 9 carbon atoms. Particularly preferred alkenyl groups are a vinyl group and a methylvinyl group (for example, 2-methylvinyl). Preferred aralkyl groups are those having 7 to 10 carbon atoms. Particularly preferred aralkyl groups are, for example, a benzyl group (Bn) and an alkyl naphthyl group (for example, 1-naphthylmethyl, 2-naphthylmethyl). The alkyl group, aryl group, alkenyl group, and aralkyl group may have a substituent or may not have a substituent. Examples of this substituent include F, Cl, Br, I, and CN. An alkyl group is also mentioned. In addition to the above-described groups, for example, O, S, or N (O, S, and N may have a substituent or may not have a substituent) may be used. Examples of the substituent in this case include alkyl having 1 to 10 carbon atoms. Therefore, R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ may be MeO, MeS, Me ₂ N, or the like. These RO, RS, and R ₂ N (R = alkyl group) are preferable.

The present invention is a reaction method for producing a carbon-carbon bond. This method is in particular a method for producing amino alcohol analogs. And it is the method of producing | generating the compound represented by the following general formula [Y] by making the compound represented by the following general formula [I], and the compound represented by the following general formula [III] react. .
General formula [Y]

一般式［Ｉ］中、Ｒ^１，Ｒ^２は、Ｈまたは炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）である。Ｒ^１とＲ^２とは、同一でも、異なるものでも良い。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、Ｈ、Ｆ，Ｃｌ，Ｂｒ，Ｉ、炭化水素基（炭化水素基は、置換基を有する場合と、置換基を有さない場合とが有る。）、Ｏ，Ｓ又はＮ（Ｏ，Ｓ，Ｎは、置換基を有する場合と、水素原子のみ有する場合とが有る。）である。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、全てが同一でも、異なるものでも良い。
上記Ｒ^１，Ｒ^２，Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６の炭化水素基は、好ましくは、炭素数が１〜１０のものである。そして、アルキル基、アリール基、アルケニル基、又はアラルキル基が好ましい。好ましいアルキル基は炭素数が１〜６のものである。特に好ましいアルキル基は、メチル基、エチル基、プロピル基、ｉ−プロピル基、ブチル基、ｔ−ブチル基である。好ましいアリール基は炭素数が６〜１０のものである。特に好ましいアリール基は、フェニル基、ナフチル基（例えば、1−naphthyl,2−naphthyl）である。好ましいアルケニル基は炭素数が３〜９のものである。特に好ましいアルケニル基はビニル基、メチルビニル基（例えば、2−methylvinyl）である。好ましいアラルキル基は炭素数が７〜１０のものである。特に好ましいアラルキル基は、例えばベンジル基（Ｂｎ）やアルキルナフチル基（例えば、1−naphthylmethyl,2−naphthylmethyl）である。前記アルキル基、アリール基、アルケニル基、アラルキル基は、置換基を有する場合と、置換基を有さない場合とが有る。この置換基としては、例えばＦ，Ｃｌ，Ｂｒ，Ｉ，ＣＮ等が挙げられる。アルキル基も挙げられる。Ｒ^１，Ｒ^２は、特に、前記アルキル基、アリール基、アルケニル基、アラルキル基の置換基として、前記以外にも、アセタール基、ｔ−ブチルジメチルシリルオキシ基などのトリアルキルシリルオキシ基、エトキシカルボニル基などのアルコキシカルボニル基も挙げられる。Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、上記した基の他にも、例えばＯ，Ｓ又はＮ（Ｏ，Ｓ，Ｎは、置換基を有する場合と、置換基を有さない場合とが有る。）であっても良い。この場合の置換基としては、例えば炭素数が１〜１０のアルキルが挙げられる。従って、Ｒ^３，Ｒ^４，Ｒ^５，Ｒ^６は、ＭｅＯ，ＭｅＳ，Ｍｅ_２Ｎ等であっても良い。これ等のＲＯ，ＲＳ，Ｒ_２Ｎ（Ｒ＝アルキル基）は好ましい。 Formula [I]

In the general formula [I], R ¹ and R ² are H or a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). R ¹ and R ² may be the same or different. R ³ , R ⁴ , R ⁵ and R ⁶ are H, F, Cl, Br, I, a hydrocarbon group (the hydrocarbon group may have a substituent or may not have a substituent). ), O, S or N (O, S, N may have a substituent or only a hydrogen atom). R ³ , R ⁴ , R ⁵ and R ⁶ may all be the same or different.
The hydrocarbon group for R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ is preferably one having 1 to 10 carbon atoms. An alkyl group, an aryl group, an alkenyl group, or an aralkyl group is preferable. Preferred alkyl groups are those having 1 to 6 carbon atoms. Particularly preferred alkyl groups are a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, and a t-butyl group. Preferred aryl groups are those having 6 to 10 carbon atoms. Particularly preferred aryl groups are a phenyl group and a naphthyl group (for example, 1-naphthyl, 2-naphthyl). Preferred alkenyl groups are those having 3 to 9 carbon atoms. Particularly preferred alkenyl groups are a vinyl group and a methylvinyl group (for example, 2-methylvinyl). Preferred aralkyl groups are those having 7 to 10 carbon atoms. Particularly preferred aralkyl groups are, for example, a benzyl group (Bn) and an alkyl naphthyl group (for example, 1-naphthylmethyl, 2-naphthylmethyl). The alkyl group, aryl group, alkenyl group, and aralkyl group may have a substituent or may not have a substituent. Examples of this substituent include F, Cl, Br, I, and CN. An alkyl group is also mentioned. In particular, R ¹ and R ² can be used as substituents for the alkyl group, aryl group, alkenyl group, and aralkyl group, as well as trialkylsilyloxy groups such as acetal group and t-butyldimethylsilyloxy group, ethoxy Also included are alkoxycarbonyl groups such as carbonyl groups. R ³ , R ⁴ , R ⁵ , and R ⁶ may be, for example, O, S, or N (where O, S, and N have a substituent and a case that does not have a substituent, in addition to the above-described groups. May be present). Examples of the substituent in this case include alkyl having 1 to 10 carbon atoms. Therefore, R ³ , R ⁴ , R ⁵ , R ⁶ may be MeO, MeS, Me ₂ N, or the like. These RO, RS, and R ₂ N (R = alkyl group) are preferable.

一般式［ＩＩＩ］中、Ｒ^１０は炭化水素基である。Ｒ^１１はＨまたは炭化水素基である。
この炭化水素基は、好ましくは、炭素数が１〜１０のものである。そして、アルキル基、アリール基、アルケニル基、又はアラルキル基が好ましい。好ましいアルキル基は炭素数が１〜６のものである。特に好ましいアルキル基は、メチル基、エチル基、プロピル基、ｉ−プロピル基、ブチル基、ｔ−ブチル基である。好ましいアリール基は炭素数が６〜１０のものである。特に好ましいアリール基は、フェニル基、ナフチル基（例えば、1−naphthyl,2−naphthyl）である。好ましいアルケニル基は炭素数が３〜９のものである。特に好ましいアルケニル基はビニル基、メチルビニル基（例えば、2−methylvinyl）である。好ましいアラルキル基は炭素数が７〜１０のものである。特に好ましいアラルキル基は、例えばアルキルナフチル基（例えば、1−naphthylmethyl,2−naphthylmethyl）やベンジル基（Ｂｎ）である。前記アルキル基、アリール基、アルケニル基、アラルキル基は、置換基を有する場合と、置換基を有さない場合とが有る。この置換基としては、例えばＦ，Ｃｌ，Ｂｒ，Ｉ，ＣＮ等が挙げられる。炭素数が１〜１０のアルキル基も挙げられる。Ｒ^１０とＲ^１１とが共に炭化水素基である場合、これ等は、同一でも、異なるものでも良い。Ｒ^１０とＲ^１１とは繋がっていても良い。 Formula [III]

In the general formula [III], R ¹⁰ is a hydrocarbon group. R ¹¹ is H or a hydrocarbon group.
This hydrocarbon group preferably has 1 to 10 carbon atoms. An alkyl group, an aryl group, an alkenyl group, or an aralkyl group is preferable. Preferred alkyl groups are those having 1 to 6 carbon atoms. Particularly preferred alkyl groups are a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, and a t-butyl group. Preferred aryl groups are those having 6 to 10 carbon atoms. Particularly preferred aryl groups are a phenyl group and a naphthyl group (for example, 1-naphthyl, 2-naphthyl). Preferred alkenyl groups are those having 3 to 9 carbon atoms. Particularly preferred alkenyl groups are a vinyl group and a methylvinyl group (for example, 2-methylvinyl). Preferred aralkyl groups are those having 7 to 10 carbon atoms. Particularly preferred aralkyl groups are, for example, alkyl naphthyl groups (for example, 1-naphthylmethyl, 2-naphthylmethyl) and benzyl groups (Bn). The alkyl group, aryl group, alkenyl group, and aralkyl group may have a substituent or may not have a substituent. Examples of this substituent include F, Cl, Br, I, and CN. An alkyl group having 1 to 10 carbon atoms is also included. When R ¹⁰ and R ¹¹ are both hydrocarbon groups, these may be the same or different. R ¹⁰ and R ¹¹ may be connected.

  Hereinafter, the present invention will be described with specific examples. However, the present invention may be anything as long as it does not depart from the above technical idea. That is, there are no restrictions on the following embodiments.

本実施例では、ＤＰＰ−ｉｍｉｎｅとＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅとの反応について述べる。
乾燥反応容器内に、アルゴン雰囲気下で、ＫＯ^ｔＢｕ（０．０１０ｍｍｏｌ）と１８−ｃｒｏｗｎ−６（０．０１１ｍｍｏｌ）とが入れられた。この後、無水ジエチルエーテル（０．２ｍｌ）がシリンジで加えられた。そして、室温下で１０分間の攪拌が行われた。攪拌後、０℃に冷却された。この後、上記構造式のＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅ ２（０．２ｍｍｏｌ）の無水ジエチルエーテル溶液（０．６ｍｌ）が添加された。そして、１０分間の攪拌が行われた。攪拌後、上記構造式のＤＰＰ−ｉｍｉｎｅ １（０．２４ｍｍｏｌ）の無水ジクロロメタン（ＤＣＭ）溶液（０．２ｍｌ）が添加された。添加後、薄紫色の反応溶液が２０時間に亘って攪拌された。攪拌後、飽和塩化アンモニウム（１０ｍｌ）が添加された。これにより反応が停止した。この後、常法による後処理が行なわれ、粗生成物が得られた。この粗生成物がシリカゲル薄層クロマトグラフィ（シリカゲル薄層クロマトグラフィは、ヘキサンと酢酸エチルとトリエチルアミンの混合液で処理）で精製された。この結果、上記反応式で示された構造で下記に示される特性の目的物が得られた。このジアミンの収率は８７％であった。ｓｙｎ／ａｎｔｉは９８／２であった。

[Method of synthesizing diamine]
[Mannich-type reaction using alkylamine protected as fluorenone imine]

In this example, a reaction between DPP-imine and Fluoroneine is described.
In a dry reaction vessel, KO ^t Bu (0.010 mmol) and 18-crown-6 (0.011 mmol) were placed under an argon atmosphere. After this, anhydrous diethyl ether (0.2 ml) was added via syringe. And stirring for 10 minutes was performed at room temperature. After stirring, it was cooled to 0 ° C. After this, an anhydrous diethyl ether solution (0.6 ml) of Fluoroneone 2 (0.2 mmol) of the above structural formula was added. Then, stirring was performed for 10 minutes. After stirring, a solution of DPP-imine 1 (0.24 mmol) of the above structural formula in anhydrous dichloromethane (DCM) (0.2 ml) was added. After the addition, the light purple reaction solution was stirred for 20 hours. After stirring, saturated ammonium chloride (10 ml) was added. This stopped the reaction. Thereafter, a post-treatment by a conventional method was performed, and a crude product was obtained. This crude product was purified by silica gel thin layer chromatography (silica gel thin layer chromatography was treated with a mixture of hexane, ethyl acetate and triethylamine). As a result, an object having the characteristics shown below was obtained with the structure shown in the above reaction formula. The yield of this diamine was 87%. The syn / anti was 98/2.

本実施例でも、ＤＰＰ−ｉｍｉｎｅとＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅとの反応について述べる。
乾燥反応容器内に、アルゴン雰囲気下で、ＫＯ^ｔＢｕ（０．０２０ｍｍｏｌ）と１８−ｃｒｏｗｎ−６（０．０２２ｍｍｏｌ）とが入れられた。この後、無水ジエチルエーテル（０．２ｍｌ）がシリンジで加えられた。そして、室温下で１０分間の攪拌が行われた。攪拌後、０℃に冷却された。この後、上記構造式のＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅ ３（０．２４ｍｍｏｌ）の無水ジエチルエーテル溶液（０．６ｍｌ）が添加された。そして、１０分間の攪拌が行われた。攪拌後、上記構造式のＤＰＰ−ｉｍｉｎｅ １（０．２４ｍｍｏｌ）の無水ジクロロメタン（ＤＣＭ）溶液（０．２ｍｌ）が添加された。添加後、淡青色の反応溶液が２０時間に亘って攪拌された。攪拌後、飽和塩化アンモニウム水溶液が添加された。これにより反応が停止した。この後、常法による後処理が行なわれ、粗生成物が得られた。この粗生成物がシリカゲル薄層クロマトグラフィ（シリカゲル薄層クロマトグラフィは、ヘキサンと酢酸エチルとトリエチルアミンの混合液で処理）で精製された。この結果、上記反応式で示された構造で下記に示される特性の目的物が得られた。このジアミンの収率は９３％であった。ｓｙｎ／ａｎｔｉは９７／３であった。

In this example, the reaction between DPP-imine and Fluoroneone will be described.
In a dry reaction vessel, KO ^t Bu (0.020 mmol) and 18-crown-6 (0.022 mmol) were placed under an argon atmosphere. After this, anhydrous diethyl ether (0.2 ml) was added via syringe. And stirring for 10 minutes was performed at room temperature. After stirring, it was cooled to 0 ° C. After this, an anhydrous diethyl ether solution (0.6 ml) of Fluoroneine 3 (0.24 mmol) of the above structural formula was added. Then, stirring was performed for 10 minutes. After stirring, a solution of DPP-imine 1 (0.24 mmol) of the above structural formula in anhydrous dichloromethane (DCM) (0.2 ml) was added. After the addition, the light blue reaction solution was stirred for 20 hours. After stirring, saturated aqueous ammonium chloride solution was added. This stopped the reaction. Thereafter, a post-treatment by a conventional method was performed, and a crude product was obtained. This crude product was purified by silica gel thin layer chromatography (silica gel thin layer chromatography was treated with a mixture of hexane, ethyl acetate and triethylamine). As a result, an object having the characteristics shown below was obtained with the structure shown in the above reaction formula. The yield of this diamine was 93%. The syn / anti was 97/3.

本実施例でも、ＤＰＰ−ｉｍｉｎｅとＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅとの反応について述べる。
乾燥反応容器内に、アルゴン雰囲気下で、ＫＯ^ｔＢｕ（０．０２０ｍｍｏｌ）と２，６−ｄｉｍｅｔｈｙｌｐｈｅｎｏｌ（０．０２４ｍｍｏｌ）とが入れられた。この後、無水ジメチルホルムアミド（ＤＭＦ ０．２ｍｌ）がシリンジで加えられた。そして、室温下で３０分間の攪拌が行われた。攪拌後、０℃に冷却された。この後、上記構造式のＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅ ４（０．２ｍｍｏｌ）の無水ＤＭＦ溶液（０．１ｍｌ）が添加された。そして、１０分間の攪拌が行われた。攪拌後、上記構造式のＤＰＰ−ｉｍｉｎｅ １（０．２４ｍｍｏｌ）の無水ＤＭＦ溶液（０．２ｍｌ）が添加された。添加後、暗褐色の反応溶液が２０時間に亘って攪拌された。攪拌後、飽和塩化アンモニウム水溶液が添加された。これにより反応が停止した。この後、常法による後処理が行なわれ、粗生成物が得られた。この粗生成物がシリカゲル薄層クロマトグラフィ（シリカゲル薄層クロマトグラフィは、ヘキサンと酢酸エチルとトリエチルアミンの混合液で処理）で精製された。この結果、上記反応式で示された構造で下記に示される特性の目的物が得られた。このジアミンの収率は８６％であった。

In this example, the reaction between DPP-imine and Fluoroneone will be described.
In a dry reaction vessel, KO ^t Bu (0.020 mmol) and 2,6-dimethylphenol (0.024 mmol) were placed under an argon atmosphere. After this, anhydrous dimethylformamide (DMF 0.2 ml) was added via syringe. And stirring for 30 minutes was performed at room temperature. After stirring, it was cooled to 0 ° C. Thereafter, an anhydrous DMF solution (0.1 ml) of Fluoroneine 4 (0.2 mmol) having the above structural formula was added. Then, stirring was performed for 10 minutes. After stirring, an anhydrous DMF solution (0.2 ml) of DPP-imine 1 (0.24 mmol) having the above structural formula was added. After the addition, the dark brown reaction solution was stirred for 20 hours. After stirring, saturated aqueous ammonium chloride solution was added. This stopped the reaction. Thereafter, a post-treatment by a conventional method was performed, and a crude product was obtained. This crude product was purified by silica gel thin layer chromatography (silica gel thin layer chromatography was treated with a mixture of hexane, ethyl acetate and triethylamine). As a result, an object having the characteristics shown below was obtained with the structure shown in the above reaction formula. The yield of this diamine was 86%.

本実施例でも、ＤＰＰ−ｉｍｉｎｅとＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅとの反応について述べる。
乾燥反応容器内に、アルゴン雰囲気下で、四級アンモニウム塩Ａ（５．８ｍｇ：５ｍｏｌ％）と、炭酸セシウム（Ｃｓ_２ＣＯ_３，３３ｍｇ：０．１０ｍｍｏｌ）と、ＤＰＰイミン５（３４ｍｇ：０．１１ｍｍｏｌ）と、無水エーテル（Ｅｔ_２Ｏ，０．８ｍＬ）とが入れられた。この後、室温下で、１０分間の攪拌が行われた。この後、フルオレノンイミン６（２７ｍｇ：０．１０ｍｍｏｌ）の無水エーテル溶液（０．２ｍＬ）が加えられた。そして、攪拌が室温下で１５時間行われた。この後、反応溶液を塩化メチレン（ＣＨ_２Ｃｌ_２）で希釈した。そして、反応液がセライトろ過され、減圧下で濃縮処理された。そして、分取用薄層シリカゲルクロマトグラフィにより精製が行われた。この結果、上記反応式で示された構造で下記に示される特性の目的物が得られた。このジアミンの収率は９４％（５４ｍｇ：０．０９４ｍｍｏｌ）であった。前記実施例にあっては、ｓｙｎ／ａｎｔｉが９８／２，９７／３であったのに対して、本実施例では、光学活性な第四級アンモニウム塩が触媒として用いられたことから、ｓｙｎ／ａｎｔｉは７８／２２であった。尚、ジアステレオ比は^１Ｈ−ＮＭＲ分析によって決定された。

In this example, the reaction between DPP-imine and Fluoroneone will be described.
In a dry reaction vessel, under an argon atmosphere, quaternary ammonium salt A (5.8 mg: 5 mol%), cesium carbonate (Cs ₂ CO ₃ , 33 mg: 0.10 mmol), and DPP imine 5 (34 mg: 0.00). 11 mmol) and anhydrous ether (Et ₂ O, 0.8 mL). Thereafter, stirring was performed at room temperature for 10 minutes. After this, a solution of fluorenone imine 6 (27 mg: 0.10 mmol) in anhydrous ether (0.2 mL) was added. And stirring was performed at room temperature for 15 hours. After this time, the reaction solution was diluted with methylene chloride (CH ₂ Cl ₂ ). The reaction solution was filtered through Celite and concentrated under reduced pressure. Purification was performed by preparative thin layer silica gel chromatography. As a result, an object having the characteristics shown below was obtained with the structure shown in the above reaction formula. The yield of this diamine was 94% (54 mg: 0.094 mmol). In the above example, syn / anti was 98/2, 97/3, whereas in this example, an optically active quaternary ammonium salt was used as a catalyst. / Anti was 78/22. The diastereo ratio was determined by ¹ H-NMR analysis.

Compound of general formula [I] (R ¹ = Bn, R ² = R ³ = R ⁴ = R ⁵ = R ⁶ = H) instead of the compound of general formula [I] [II] used in the above Examples And a compound of the general formula [II] (R ⁷ = Ph, R ⁸ = H, R ⁹ = ^t BuOCO) are used, the general formula [I] (R ¹ = Bn, R ² = R ³ = R ⁴ = R ⁵ = R ⁶ = H) and a compound of the general formula [II] (R ⁷ = p-MeOPh, R ⁸ = H, R ⁹ = Ph ₂ P (O)) Compounds of general formula [I] (R ¹ = Bn, R ² = R ³ = R ⁴ = R ⁵ = R ⁶ = H) and general formula [II] (R ⁷ = p-Cl, R ⁸ = H, R Even when a compound of ⁹ = Ph ₂ P (O)) was used, the same results as in the above examples were obtained.

本実施例では、ベンズアルデヒドとＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅとの反応について述べる。
乾燥反応容器内に、アルゴン雰囲気下で、ＫＯ^ｔＢｕ（０．０２０ｍｍｏｌ）と１８−ｃｒｏｗｎ−６（０．０２２ｍｍｏｌ）とが入れられた。この後、無水ジエチルエーテル（０．２ｍｌ）がシリンジで加えられた。そして、室温下で１０分間の攪拌が行われた。攪拌後、０℃に冷却された。この後、上記構造式のＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅ（０．２ｍｍｏｌ）の無水ジエチルエーテル溶液（０．６ｍｌ）が添加された。そして、１０分間の攪拌が行われた。攪拌後、ベンズアルデヒド（０．２４ｍｍｏｌ）の無水ジエチルエーテル溶液（０．２ｍｌ）が添加された。添加後、薄紫色の反応溶液が２０時間に亘って攪拌された。攪拌後、飽和塩化アンモニウム（１０ｍｌ）が添加された。これにより反応が停止した。この後、常法による後処理が行なわれ、粗生成物が得られた。この粗生成物がシリカゲル薄層クロマトグラフィ（シリカゲル薄層クロマトグラフィは、ヘキサンと酢酸エチルとトリエチルアミンの混合液で処理）で精製された。この結果、上記反応式で示された構造で下記に示される特性の目的物が得られた。このアミノアルコールの収率は３３％（ＮＭＲ収率）であった。又、約１：１のジアステレオ混合物であった。

[Method of synthesizing amino alcohol]
[Reaction of benzaldehyde with Fluoroneone]

In this example, the reaction between benzaldehyde and Fluoroneone will be described.
In a dry reaction vessel, KO ^t Bu (0.020 mmol) and 18-crown-6 (0.022 mmol) were placed under an argon atmosphere. After this, anhydrous diethyl ether (0.2 ml) was added via syringe. And stirring for 10 minutes was performed at room temperature. After stirring, it was cooled to 0 ° C. Thereafter, a solution of fluorene imine (0.2 mmol) having the above structural formula in anhydrous diethyl ether (0.6 ml) was added. Then, stirring was performed for 10 minutes. After stirring, benzaldehyde (0.24 mmol) in anhydrous diethyl ether (0.2 ml) was added. After the addition, the light purple reaction solution was stirred for 20 hours. After stirring, saturated ammonium chloride (10 ml) was added. This stopped the reaction. Thereafter, a post-treatment by a conventional method was performed, and a crude product was obtained. This crude product was purified by silica gel thin layer chromatography (silica gel thin layer chromatography was treated with a mixture of hexane, ethyl acetate and triethylamine). As a result, an object having the characteristics shown below was obtained with the structure shown in the above reaction formula. The yield of this amino alcohol was 33% (NMR yield). It was a diastereomeric mixture of about 1: 1.

本実施例では、１，４−付加反応について述べる。
乾燥反応容器内に、アルゴン雰囲気下で、ＫＯ^ｔＢｕ（０．０２０ｍｍｏｌ）と上記化合物Ａ（０．０２４ｍｍｏｌ）とが入れられた。この後、ＤＭＦ（０．２ｍｌ）がシリンジで加えられた。そして、室温下で３０分間の攪拌が行われた。攪拌後、０℃に冷却された。この後、上記構造式のＦｌｕｏｒｅｎｏｎｅ ｉｍｉｎｅ２（０．２ｍｍｏｌ）のＤＭＦ溶液（０．３ｍｌ）が添加された。そして、１０分間の攪拌が行われた。攪拌後、カルコン１（０．２２ｍｍｏｌ）のＴＨＦ溶液（０．５ｍｌ）が添加された。添加後、濃紫色の反応溶液が２４時間に亘って攪拌された。攪拌後、飽和塩化アンモニウムが添加された。これにより反応が停止した。この後、常法による後処理が行なわれ、粗生成物が得られた。収率はジベンジルを内部標準として^１Ｈ ＮＭＲで決定された。

尚、上記化合物（カルコン１）は下記の一般式で表される化合物の場合も同様であった。

この一般式中、Ｒ^１９，Ｒ^２０，Ｒ^２１，Ｒ^２２はＨ又は炭化水素基（置換基を有する場合でも有さない場合でも良い。）である。但し、Ｒ^２２は、−ＯＲ，−ＳＲ，−ＮＲ_２（Ｒは置換基を有することも有る炭化水素基）であっても良い。

In this example, the 1,4-addition reaction is described.
In a dry reaction vessel, KO ^t Bu (0.020 mmol) and the compound A (0.024 mmol) were placed under an argon atmosphere. After this, DMF (0.2 ml) was added via syringe. And stirring for 30 minutes was performed at room temperature. After stirring, it was cooled to 0 ° C. Thereafter, a DMF solution (0.3 ml) of Fluoroneine 2 (0.2 mmol) having the above structural formula was added. Then, stirring was performed for 10 minutes. After stirring, a solution of chalcone 1 (0.22 mmol) in THF (0.5 ml) was added. After the addition, the deep purple reaction solution was stirred for 24 hours. After stirring, saturated ammonium chloride was added. This stopped the reaction. Thereafter, a post-treatment by a conventional method was performed, and a crude product was obtained. The yield was determined by ¹ H NMR using dibenzyl as an internal standard.

In addition, the said compound (chalcone 1) was the same also in the case of the compound represented by the following general formula.

In this general formula, R ¹⁹ , R ²⁰ , R ²¹ and R ²² are H or a hydrocarbon group (which may or may not have a substituent). However, R ²² may be —OR, —SR, —NR ₂ (R is a hydrocarbon group which may have a substituent).

Claims (8)

A method for producing a compound represented by the following general formula [X] ,
A compound represented by the following general formula [I] and a compound represented by the following general formula [II] are reacted in the presence of an optically active quaternary ammonium salt to give the following general formula [ X] is produced | generated, The method characterized by the above-mentioned.
Formula [I]

[In General Formula [I], R ¹ and R ² are H or a hydrocarbon group having 1 to 10 carbon atoms . R ¹ and R ² may be the same or different. R ³ , R ⁴ , R ⁵ , and R ⁶ are H or a hydrocarbon group having 1 to 10 carbon atoms . R ³ , R ⁴ , R ⁵ and R ⁶ may all be the same or different. ]
Formula [II]

[In General Formula [II], R ⁷ and R ⁸ are H or a hydrocarbon group having 1 to 10 carbon atoms . R ⁹ is COOR, SO ₂ R or POR ₂ (R is a hydrocarbon group having 1 to 10 carbon atoms ). ]
Formula [X]

The hydrocarbon group of R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ^{6 in} the general formula [I] is an alkyl group, an aryl group, an alkenyl group, or an aralkyl group, the method of. The method according to claim 1, wherein the hydrocarbon group of R ⁷ and R ⁸ in the general formula [II] is an alkyl group, an aryl group, an alkenyl group, or an aralkyl group. The method according to claim 1, wherein the hydrocarbon group represented by R ⁹ in the general formula [II] is an alkyl group, an aryl group, an alkenyl group, or an aralkyl group. The method according to claim 1, wherein the optically active quaternary ammonium salt is a compound having a structure represented by the following general formula [IV].
Formula [IV]

[In the general formula [IV], R ¹² , R ¹³ and R ¹⁴ are hydrocarbon groups. R ¹⁵ , R ¹⁶ , R ¹⁷ , and R ¹⁸ are H or a hydrocarbon group. ] A method for producing a compound represented by the following general formula [Y] ,
A compound represented by the following general formula [I] is reacted with a compound represented by the following general formula [III] to produce a compound represented by the following general formula [Y]. how to.
Formula [I]

[In General Formula [I], R ¹ and R ² are H or a hydrocarbon group having 1 to 10 carbon atoms . R ¹ and R ² may be the same or different. R ³ , R ⁴ , R ⁵ , and R ⁶ are H or a hydrocarbon group having 1 to 10 carbon atoms . R ³ , R ⁴ , R ⁵ and R ⁶ may all be the same or different. ]
Formula [III]

[In General Formula [III], R ¹⁰ is a hydrocarbon group having 1 to 10 carbon atoms . R ¹¹ is H or a hydrocarbon group having 1 to 10 carbon atoms . R ¹⁰ and R ¹¹ may be the same or different. ]
General formula [Y]

The hydrocarbon group of R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ^{6 in} the general formula [I] is an alkyl group, an aryl group, an alkenyl group, or an aralkyl group, the method of. The method according to claim 6, wherein the hydrocarbon group of R ¹⁰ and R ¹¹ in the general formula [III] is an alkyl group, an aryl group, an alkenyl group, or an aralkyl group.