JP2006151947A - Method for producing linear compound by dimerization reaction of terminal olefin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for efficiently producing a linear compound by the dimerization reaction of a terminal olefin. <P>SOLUTION: This method for efficiently producing the linear compound represented by the general formula: R<SP>4</SP>CH<SB>2</SB>CH=CHCH<SB>2</SB>CH<SB>2</SB>CH<SB>2</SB>R<SP>4</SP>(R<SP>4</SP>is a hydrocarbon group having two or more carbon atoms) comprises dimerizing a terminal olefin represented by the general formula: CH<SB>2</SB>=CHCH<SB>2</SB>R<SP>4</SP>in the presence of a complex represented by general formula 1 (R<SP>1</SP>to R<SP>3</SP>are each identically or differently a hydrocarbon group, a halogen atom or the like; X is a halogen atom or the like) as a catalyst. Exaltone and muscone can efficiently be synthesized from the produced dimer. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a method capable of preferentially producing a linear compound by a dimerization reaction of a terminal olefin. Furthermore, Exalton and Muscon can be manufactured using this manufacturing method.

Musk is widely used as a fragrance in perfumes and cosmetics. However, because natural musk is taken from musk deer, etc., its commercial use is almost impossible under the “Convention on the International Trade of Endangered Wild Animal and Plant Species” (Washington Convention). Therefore, artificial musks such as nitro musk are widely used as an alternative.
Muscon (Chemical Formula 2, R = Me) and Exalton (Chemical Formula 2, R = H), which are fragrance components of natural musk, have a unique structure of 15-membered rings, and are therefore difficult to synthesize. In recent years, several synthesis methods have been reported, but all of them are expensive due to the use of multi-step synthesis methods and long-chain compounds that are difficult to obtain, and are not suitable for industrial synthesis. Therefore, an efficient synthesis method is required.

It was Ziegler in Germany that succeeded in the first total synthesis of Muscon (Non-patent Document 1). A chain compound having a nitrile group at both ends was cyclized by intramolecular Thrope reaction using lithium amide as a catalyst under highly diluted conditions.
The key to the synthesis of musks such as exalton is to efficiently obtain 16-carbon compounds as cyclization raw materials. Thus, as a method for synthesizing a long-chain compound such as a 16-carbon compound, it has been considered to couple easily available 8-carbon compounds to a double carbon chain.
As such a carbon-carbon bond forming reaction, a Heck reaction (Non-patent document 2), a Suzuki coupling reaction (Non-patent document 3), an olefin metathesis reaction using a Grubbs catalyst (Non-patent document 4), and the like have been studied. However, in particular, as a technique close to the present invention, 2-butene diene using a biiminopyridyl complex which is a transition metal complex having various transition metals such as a Ti-Al-based metal such as a Ziegler-Natta catalyst as a central metal. Quantification reactions have been reported (Non-Patent Documents 5 and 6).

K. Ziegler and K. Weber, Ann. Chem., 512, 164 (1938) I. -I.I. Kim et al., J. Org. Chem., 46, 1067 (1981) N. Miyaura et al., J. Am. Chem. Soc., 107, 972 (1985) Amab K. Chatterjee, et al., J. Am. Chem. Soc., 125, 11360 (2003) Brooke L. Small et al., U. S. Patent, US 6291733 B1 (2001) Brooke L. Small, Organometallics, 22, 3178 (2003)

そのためムスクの合成のための環化原料である１６炭素化合物を効率よく合成するためには、オレフィンの末端同士でカップリングさせるhead to head型（linear体が得られる。）とオレフィンの末端と内部でカップリングするhead to tail型（branched体が得られる。）の位置選択性を制御する必要がある。
本発明は、このようなビスイミノピリジル錯体触媒を用いた末端オレフィンの二量化反応において線状化合物（linear体）を効率よく合成し、併せてエキザルトンやムスコンを効率よく合成する方法を提供することを目的とする。 In the dimerization reaction of 1-butene using a biiminopyridyl complex as a catalyst (Non-patent Documents 5 and 6), the reaction has regioselectivity as shown in the following formula (wherein the wavy line is cis or trans or (The same shall apply hereinafter.)

Therefore, in order to efficiently synthesize a 16-carbon compound, which is a cyclization raw material for musk synthesis, a head-to-head type (linear body is obtained) in which olefin ends are coupled to each other, an olefin end and an internal portion are obtained. It is necessary to control the position selectivity of the head to tail type (branched body is obtained) that is coupled with.
The present invention provides a method for efficiently synthesizing a linear compound (linear body) in a dimerization reaction of a terminal olefin using such a bisiminopyridyl complex catalyst, and also efficiently synthesizing exalton and muscone. With the goal.

  The present inventors focused on the bisiminopyridyl complex catalyst, and as a result of examining the catalyst ligand and the central metal, as a result of appropriately selecting the central metal, the steric three-dimensional structure around the catalytic central metal of the bisiminopyridyl complex. It has been found that by selecting a ligand having a control ability, a linear compound can be efficiently synthesized in a dimerization reaction of a terminal olefin, and the present invention has been completed.

(式中、Ｒ^１は、それぞれ同じであっても異なってもよく、炭化水素基を表し、Ｒ^２は、それぞれ同じであっても異なってもよく、水素原子又は炭化水素基を表し、Ｒ^３は、それぞれ同じであっても異なってもよく、水素原子、炭化水素基又はハロゲン原子を表し、Ｘは、それぞれ同じであっても異なってもよく、ハロゲン原子又はアルキル基を表す。)で表される錯体を触媒として、一般式
ＣＨ_２＝ＣＨＣＨ_２Ｒ^４
(式中、Ｒ^４は炭素数２以上の炭化水素基を表す。)で表される末端オレフィンを二量化することにより、一般式
Ｒ^４ＣＨ_２ＣＨ＝ＣＨＣＨ_２ＣＨ_２ＣＨ_２Ｒ^４
で表される線状化合物を製造する方法である。 That is, the present invention has the general formula

(Wherein R ¹ may be the same or different and each represents a hydrocarbon group, R ² may be the same or different and each represents a hydrogen atom or a hydrocarbon group; ³ may be the same or different and each represents a hydrogen atom, a hydrocarbon group or a halogen atom, and X may be the same or different and each represents a halogen atom or an alkyl group. Using the represented complex as a catalyst, the general formula CH ₂ ═CHCH ₂ R ⁴
(Wherein R ⁴ represents a hydrocarbon group having 2 or more carbon atoms.) By dimerizing the terminal olefin represented by the general formula: R ⁴ CH ₂ CH═CHCH ₂ CH ₂ CH ₂ R ⁴
Is a method for producing a linear compound represented by the formula:

In the present invention, the above R ⁴ is — (CH ₂ ) ₅ OY.
(In the formula, Y represents a hydrogen atom or a hydroxyl-protecting group).
Furthermore, the present invention is the use of this exalton for the production of muscone.

Ｒ^１は、それぞれ同じであっても異なってもよく、炭化水素基、好ましくはアルキル基を表す。より好ましくは炭素数が１〜３のアルキル基を表す。Ｒ^２は、それぞれ同じであっても異なってもよく、水素原子又は炭化水素基、好ましくは水素原子又はアルキル基を表す。Ｒ^３は、それぞれ同じであっても異なってもよく、水素原子、炭化水素基又はハロゲン原子、好ましくはハロゲン原子，より好ましくは塩素原子又は臭素原子を表す。炭化水素基としては、好ましくは炭素数が１〜３のアルキル基である。
Ｘは、それぞれ同じであっても異なってもよく、ハロゲン原子又はアルキル基、好ましくはハロゲン原子、より好ましくは塩素原子又は臭素原子を表す。アルキル基としてはメチル基が好ましい。
その他上記化合物（化１）のベンゼン環はアルキル基やアリール基などの置換基を有していてもよい。 The catalyst of the present invention is represented by the following formula.

R ¹ may be the same or different and each represents a hydrocarbon group, preferably an alkyl group. More preferably, it represents an alkyl group having 1 to 3 carbon atoms. R ² may be the same or different and each represents a hydrogen atom or a hydrocarbon group, preferably a hydrogen atom or an alkyl group. R ³ may be the same or different and each represents a hydrogen atom, a hydrocarbon group or a halogen atom, preferably a halogen atom, more preferably a chlorine atom or a bromine atom. The hydrocarbon group is preferably an alkyl group having 1 to 3 carbon atoms.
X may be the same or different and each represents a halogen atom or an alkyl group, preferably a halogen atom, more preferably a chlorine atom or a bromine atom. The alkyl group is preferably a methyl group.
In addition, the benzene ring of the above compound (Chemical Formula 1) may have a substituent such as an alkyl group or an aryl group.

The present invention is a complex of cobalt and the above ligand. Complex formation can be performed by dissolving a ligand and a cobalt salt in an organic solvent usually at room temperature.
In the present invention, by using cobalt as the transition metal, the selectivity of the linear compound can be remarkably improved when the terminal olefin is dimerized as compared with the case where other transition metals are used.

In the present invention, the terminal olefin is dimerized using the catalyst.
The terminal olefin as a substrate is represented by the following formula.
CH ₂ = CHCH ₂ R ⁴
R ⁴ represents a hydrocarbon group having 2 or more carbon atoms, preferably an alkyl group having 2 to 15 carbon atoms, more preferably an alkyl group having 3 to 5 carbon atoms.
The solvent is not particularly limited as long as it is an organic solvent, but toluene and MAO are preferably used.
The concentration of the catalyst is preferably 0.01 to 0.2M.
The reaction temperature is usually from −25 ° C. to room temperature, and the reaction time is 30 minutes or longer.

As a result of this reaction, a linear compound represented by the following formula is preferentially produced.
R ⁴ CH ₂ CH═CHCH ₂ CH ₂ CH ₂ R ⁴
In this reaction, a side chain compound represented by the following formula is also produced, but the yield is low.
R ⁴ CH ₂ CH═CHCH (CH ₃ ) CH ₂ R ⁴
At this stage, only the linear compound may be purified and used by known means.
The linear compound thus obtained is useful as a raw material for various compounds. As an example, a method for producing Exalton and Muscon is shown below.

(1) Exaltone can be produced by the following steps.
(i) R ⁴ in the above general formula is — (CH ₂ ) ₅ OY
(Wherein Y represents a hydrogen atom or a protecting group for a hydroxyl group) is dimerized. As this protecting group, benzyl group, t-butyl group, i-propyl group, silyl group, acetyl group, RCO- group (R represents a hydrocarbon group) and the like can be used.
For example, 7-octen-1-ol is reacted with benzyl bromide using sodium hydride or the like to protect the hydroxyl group. The obtained benzyl ether is reacted with the catalyst of the present invention in the presence of MAO (Methylaluminoxane) in an organic solvent such as toluene to dimerize. A linear compound (linear body) is preferentially obtained by the method of the present invention. You may refine | purify a linear compound as needed.

(ii) The resulting linear compound is hydrogenated. For example, the dimer is hydrogenated with Pd—C or the like. At the same time, the protecting group may be deprotected. As a result, 1,16-hexadecanediol is obtained.
(iii) A halogenating agent is allowed to act on this to produce an acid halide to produce β-lactone.
For example, the above diol is oxidized by a Jones oxidation method or the like to form a dicarboxylic acid, and the dicarboxylic acid is derived into an acid halide by thionyl chloride, oxalyl chloride, or the like. This reaction is preferably carried out in a water-free and argon atmosphere because the acid halide that is usually produced is unstable in the air. Moreover, since this reaction hardly causes a side reaction, it can be used in the next reaction as a crude product.
The resulting acid halide is reacted with DABCO (1,4-diazabicyclo [2,2,2] octane) to produce β-lactone. The acid halide solution is preferably added dropwise to the highly diluted solution of DABCO over a long period of time. Instead of DABCO, nitrogen-containing cyclic compounds such as N-methylpyrrolidone, 4- (dimethylamino) pyridine and quinuclidine, aliphatic amines such as tetramethylethyldiamine, and the like may be used.

(iv) The obtained β-lactone is decarboxylated under acidic conditions. As a result, exalton is generated. In order to efficiently perform this decarboxylation, it is preferable to carry out under acidic conditions using silica gel. That is, by bringing β-lactone into contact with silica gel in the presence of an oxidizing agent such as trichloromethane, mild oxidation conditions are obtained and decarboxylation proceeds easily. For example, hydrolysis and decarboxylation are performed by passing the solution containing β-lactone through silica gel column chromatography containing trichloroethane several times.

(2) Muscone from exalton can be produced by the following process. Cyclopentadecanone (exalton) is brominated to synthesize 2-bromocyclopentadecanone. This is dehydrobromated (HBr) with a base such as triethylamine to lead to an α, β unsaturated ketone, and by ketalization using 1,4-di-O-methyl-D-threitol as the diol component (E) -Α, β-unsaturated ketals are obtained. The (E) -α, β-unsaturated ketal is treated with an excess of Simmons-Smith reagent under diethyl ether reflux to give the cyclopropane ketal diastereomer. This diastereomer is hydrolyzed to obtain an aromatic bicycloketone. The cyclopropane ring of this bicycloketone is reduced and opened, and the resulting alcohol is oxidized to obtain muscone.

The following examples illustrate the invention but are not intended to limit the invention.
The catalyst ligand was synthesized by iminating with various amines using 2,6-diacetylpyridine as a starting material.
Production Example 1
In this production example, a 2,6-bis (imino) pyridyl ligand (Compound 1) was synthesized.
The reaction vessel (50 ml eggplant flask) was heated under vacuum in advance under water-free conditions, and the reaction solvent was also dried. Under an argon gas atmosphere, 1.26 g and 1.24 ml (13.5 mmol) of aniline were added to a mixed solution of 0.49 g (3.0 mmol) of 2,6-diacetylpyridine and 20 ml of methylene chloride. To this reaction solution, 5 drops of formic acid (97%) was added and stirred at room temperature for 40 hours. The reaction solution was concentrated with an evaporator and dried in vacuum. Thereafter, the reaction flask was cooled to −40 ° C. in a freezer. Yellow crystals were precipitated by gradually adding methanol cooled in an ice bath to the reaction flask. The crystals were filtered off with suction and washed with methanol cooled in an ice bath. The crystals were vacuum-dried to obtain 0.65 g (Y. 68%) of yellow crystals.
¹ H-NMR (CDCL ₃ ) δ ppm 2.41 (s, 6H), 6.85 (d, J = 7.9Hz, 4H), 7.12 (t, J = 7.3Hz, 2H), 7.38 (t, J = 7.3Hz, 4H), 7.88 (t, J = 7.9Hz, 1H), 8.34 (d, J = 7.9Hz, 2H)

The following ligand (compound 2-8) was produced by the same reaction while appropriately changing the substituent of pyridine.

Analytical data of the produced 2,6-bis (imino) pyridyl ligand (compound 2) is shown below.
¹ H-NMR (CDCL ₃ ) δ ppm 2.13 (s, 6H), 2.34 (s, 6H), 6.69 (d, J = 6.6Hz, 2H), 7.03 (t, J = 7.3Hz, 2H), 7.21 ( m, 4H), 7.89 (t, J = 7.9Hz, 1H), 8.41 (d, J = 7.9Hz, 2H)
Analytical data of the produced 2,6-bis (imino) pyridyl ligand (Compound 3) is shown below.
¹ H-NMR (CDCL ₃ ) δ ppm 2.01 (s, 6H), 2.34 (s, 12H), 6.59 (d, J = 7.9Hz, 2H), 7.02 (t, J = 7.9Hz, 4H), 7.87 ( t, J = 7.9Hz, 1H), 8.38 (d, J = 7.9Hz, 2H)
Analytical data of the produced 2,6-bis (imino) pyridyl ligand (Compound 4) is shown below.
¹ H-NMR (CDCL ₃ ) δ ppm 2.11 (s, 6H), 2.34 (s, 6H), 6.63 (d, J = 8.6Hz, 2H), 7.20 (t, J = 8.6Hz, 4H), 7.90 ( t, J = 7.9Hz, 1H), 8.38 (d, J = 7.9Hz, 2H)
¹³ C-NMR (CDCL ₃ ) δ ppm 167.4, 155.0, 136.8, 130.1, 128.4, 126.3, 122.3, 119.3, 17.8, 16.5
Analytical data of the produced 2,6-bis (imino) pyridyl ligand (Compound 5) is shown below.
¹ H-NMR (CDCL ₃ ) δ ppm 1.16 (t, J = 7.9Hz, 6H), 2.37 (s, 6H), 2.52 (q, J = 7.9Hz, 4H), 6.67 (d, J = 7.9Hz, 2H), 7.02 (dt, J = 19.8, 7.9Hz, 6H), 7.89 (t, J = 7.9Hz, 1H), 8.40 (d, J = 7.9Hz, 2H)
Analytical data of the produced 2,6-bis (imino) pyridyl ligand (Compound 6) is shown below.
¹ H-NMR (CDCL ₃ ) δ ppm 1.15 (t, J = 7.25, 6H), 2.36 (s, 6H), 2.48 (q, J = 7.25, 4H), 6.55 (d, J = 8.6Hz, 2H) , 7.32 (dd, J = 8.6, 2.0Hz, 2H), 7.39 (d, J = 2.0Hz, 2H), 7.90 (t, J = 7.9Hz, 1H), 8.38 (d, J = 7.9Hz, 2H)
¹³ C-NMR (CDCL ₃ ) δ ppm 167.1, 155.0, 148.1, 136.8, 135.7, 131.4, 129.1, 122.3, 119.8, 116.6, 24.7, 16.5, 13.9
Analytical data of the produced 2,6-bis (imino) pyridyl ligand (Compound 7) is shown below.
¹ H-NMR (CDCL ₃ ) δ ppm 1.20 (d, J = 7.3Hz, 12H), 2.39 (s, 6H), 2.52 (dq, J = 6.9, 7.3Hz, 2H), 6.65 (d, J = 7.9 Hz, 2H), 7.02 (m, 6H), 7.90 (t, J = 7.9Hz, 1H), 8.41 (d, J = 7.9Hz, 2H)
The analytical data of the produced 2,6-bis (imino) pyridyl ligand (Compound 8) are shown below.
¹ H-NMR (CDCL ₃ ) δ ppm 2.41 (s, 6H), 6.85 (d, J = 7.3Hz, 2H), 7.47 (m, 6H), 7.65 (d, J = 8.6Hz, 2H), 7.82 ( d, J = 8.6Hz, 2H), 7.88 (d, J = 7.9Hz, 2H), 8.00 (t, J = 7.9Hz, 1H), 8.60 (d, J = 7.9Hz, 2H)

Production Example 2
In this production example, a complex of each ligand produced in Production Example 1 and cobalt was produced.
The reaction vessel (10 ml eggplant flask) was preliminarily heated under vacuum and in water-free conditions, and the reaction solvent was also dried. Under an argon gas atmosphere, 0.25 mmol of cobalt (II) chloride hexahydrate (CoCl ₂ .6H ₂ O) was added to a mixed solution of 0.3 mmol of the bisiminopyridyl ligand and 3 ml of THF. When the mixture is stirred at room temperature for 5 minutes, blue-violet crystals are precipitated. Ether is added to the reaction vessel to completely precipitate the crystals. The solvent is removed by suction filtration and washed with ether and n-pentane. The crystals were vacuum-dried to obtain blue-violet crystals with a yield of 87 to 96%.

Production Example 3
In this production example, a complex of each ligand produced in Production Example 1 and iron was produced.
The reaction vessel (10 ml eggplant flask) was preliminarily heated under vacuum and in water-free conditions, and the reaction solvent was also dried. Under an argon gas atmosphere, 0.25 mmol of ferrous chloride tetrahydrate (FeCl ₂ .4H ₂ O) was added to a mixed solution of 0.3 mmol of the bisiminopyridyl ligand and 3 ml of THF. When the mixture is stirred at room temperature for 5 minutes, blue-violet crystals are precipitated. Ether is added to the reaction vessel to completely precipitate the crystals. The solvent is removed by suction filtration and washed with ether and n-pentane. The crystals were vacuum-dried to obtain blue-violet crystals with a yield of 90-100%.

In this example, the dimerization reaction of 1-octene was performed using the catalyst (Co catalyst) obtained in Production Example 2 above.
The reaction vessel (10 ml eggplant flask) was preliminarily heated under vacuum and in water-free conditions. Under an argon gas atmosphere, 2.0 × 10 ⁻³ mol of each catalyst and 10 mmol of 1-octene mixed solution were stirred at room temperature for several minutes. To the reaction solution, 0.4 ml of 10% MAO toluene solution was added and stirred at room temperature (or 0, -40, -78 ° C) for 30 minutes. The reaction solution is gradually added to a beaker containing water to complete the reaction. At this time, aluminum hydroxide was produced as an inorganic salt, and thus it was removed by suction filtration, and the filtrate was extracted with hexane. The dimer was obtained in a yield of 24-78% by concentrating with an evaporator, purifying by silica gel column chromatography (hexane, 20 times), and vacuum drying. In addition, olefins were hydrogenated to determine regioselectivity. 10 wt% of 10% Pd—C was added to the dimer, 10 ml of ethyl acetate was added, and the mixture was stirred in a hydrogen gas atmosphere for 1 day. Since this reaction proceeds quantitatively, it does not affect the regioselectivity of the reaction. This reaction product was confirmed by ¹ H-NMR to confirm that the olefin was completely hydrogenated. Regioselectivity was calculated by GC14A. GC conditions (INJ: 250 ° C, DET: 250 ° C, COL INIT.TEMP: 200 ° C, COL INIT.TIME: 3min, COL PROG.RATE: 10 ° C, COL FINAL.TEMP: 250 ° C, COL FINAL.TIME: 20min ) Linear detection time: 7-8mim, branched: 6-7min

The results are shown in the table below.

Compared with the case where the Fe catalyst of Comparative Example 1 described later was used, when the Co catalyst of this example was used, the yield was low, but the linear body was given almost regioselectively.
In Entry1,2,5,6, the control by the size of the solid was examined directly. When R ¹ was H, almost no dimer was obtained. This is considered to be because it is not controlled because it is too small three-dimensionally and gives a product in which the raw material olefin is isomerized.
In Entry2,5,7, the dimer was obtained in the best yield for entry5. Through these reactions, the regioselectivity kept high selectivity.
For R ³ , the yield was high in the case of electron withdrawing halogen.

Comparative Example 1
In this comparative example, 1-octene dimerization reaction was performed under the same conditions as in Example 1 using the catalyst (Fe catalyst) obtained in Production Example 3 above. The results are shown in the table below.

  When Fe is used as the central metal, dimerization proceeds with a good yield, but a side chain compound (branched) is produced in a high yield, and the yield of the target linear compound (linear) is as in Example 1. The position selectivity was not high.

In this example, exalton was synthesized.
Using a 200 ml eggplant flask, a mixed solution of 17.0 g, 20 ml (0.135 mol) of 7-octenal (compound 32) and 70 ml of ethanol was cooled with an ice bath in a nitrogen gas atmosphere. To the mixed solution, 2.55 g (0.068 mol) of sodium borohydride was added little by little, and then stirred for 45 minutes. The reaction solution was neutralized with 1N hydrochloric acid, and the produced inorganic salt was removed by suction filtration. The filtrate was extracted with ethyl acetate and concentrated by an evaporator. The product was purified by silica gel column chromatography (hexane / ethyl acetate = 5/1, 50 times) to obtain 14.0 g (Y. 81%) of 7-octen-1-ol (compound 33).
¹ H-NMR (CDCL ₃ ) δ ppm 1.36 (bs, 6H), 1.57 (bs, 3H), 2.04 (t, J = 6.6Hz, 2H)
3.63 (t, J = 6.6Hz, 2H), 4.97 (m, 2H), 5.81 (tdq, J = 20.1, 17.1, 3.3Hz, 1H)
IR (neat) cm ^-1 638, 728, 911, 996, 1058, 1463, 1642, 2858, 2930, 3078, 3332

The reaction vessel (200 ml two-necked eggplant flask) was preliminarily heated under vacuum and in water-free conditions, and the reaction solvent was also dried. Since sodium hydride is a mixture with oil, it was used after washing with hexane. Under a nitrogen gas atmosphere, a mixed solution of 0.96 g (40 mmol) of sodium hydride and 100 ml of THF was cooled with an ice bath. While maintaining the mixed solution at 0 ° C., 5.13 g (40 mmol) of 7-octen-1-ol was added dropwise over 30 minutes. Subsequently, 3.42 g and 2.40 ml (20 mmol) of benzyl bromide were added dropwise to the mixed solution. Raised to room temperature and stirred for one day. While cooling with an ice bath, 0.1N hydrochloric acid was added to the reaction mixture until it became weakly acidic. Since an inorganic salt was formed, it was removed by suction filtration, and the filtrate was extracted with ether and concentrated. The product was purified by silica gel column chromatography (hexane / ethyl acetate = 9/1, 50 times) to obtain 7.26 g (Y. 98%) of 7-octenylbenzyl ether (Compound 34).
¹ H-NMR (CDCL ₃ ) δ ppm 1.34 (bs, 6H), 1.62 (m, 2H), 2.04 (m, 2H), 3.46 (t, J = 6.6Hz, 2H), 4.50 (s, 2H), 4.97 (m, 2H), 5.81 (tdq, J = 20.8, 16.8, 3.3Hz, 1H), 7.31 (m, 5H)
IR (neat) cm ^-1 698, 735, 910, 995, 1029, 1104, 1204, 1362, 1455, 1496, 1640, 2856, 2931, 2976, 3031, 3066, 3480

The above reaction formula is shown below.

The reaction vessel (100 ml eggplant flask) was previously heated under vacuum and in a water-free condition, and the reaction solvent was also dried. Under an argon gas atmosphere, a mixed solution of 70.68 mg (0.15 mmol) of the catalyst (19), 16.37 g of benzyl octenyl ether (34) and 17.79 ml (75 mmol) was stirred at −25 ° C. for several minutes. Slowly added 31.5 ml of 10% MAO and stirred for 30 minutes. The reaction solution is gradually added to a beaker containing water to complete the reaction. At this time, aluminum hydroxide was produced as an inorganic salt, and thus it was removed by suction filtration, and the filtrate was extracted with hexane. Concentrated by an evaporator and purified by silica gel column chromatography (hexane / ethyl acetate = 9/1, 50 times) to obtain 6.55 g (Y. 40%) of colorless liquid benzoyloctenyl ether dimer (compound 35). .
Regioselectivity was measured by GC14A after the next stage olefin hydrogenation and deprotection. In addition, since the reaction at the next stage proceeds quantitatively, the change in the position selectivity of the reaction does not change even after the next reaction.
¹ H-NMR (CDCL ₃ ) δ ppm 1.36 (m, 8H), 1.61 (t, J = 5.9Hz, 8H), 2.01 (m, 4H), 3.46 (t, J = 6.6Hz, 4H), 4.50 ( s, 2H), 5.41 (m, 2H), 7.32 (m, 10H)

The above reaction formula is shown below.

The reaction vessel used was a 200 ml eggplant flask. 150 ml of EtOH is added to a mixed solution of 6.55 g (15 mmol) of dimer and 2 g of 10% Pd—C. The mixed solution is stirred for 1 day under a hydrogen gas atmosphere. At this time, the reaction time is adjusted until the benzyl protection is completely removed by TLC. If the reaction is not completed at this time, Pd-C and hydrogen gas are added. This olefin hydrogenation and deprotection proceeds almost quantitatively. The reaction product is filtered through celite and concentrated. Since crystals were precipitated, the crystals were washed with hexane, and 3.87 g (quant.) Of white crystals (1,16-hexadecanediol (compound 36)) were obtained by suction filtration. It was 100% linear by GC14A.
¹ H-NMR (CDCL3) δ ppm 1.26 (bs, 22H), 1.58 (bs, 8H), 3.63 (m, 4H)
IR (neat) cm ^-1 692, 720, 732, 1028, 1044, 1062, 1072, 1124, 1409, 1462, 1473, 1560, 1646, 2850, 2919, 3286
mp 91.7-92.4 ° C (lit. 92.0-93.0 ° C)
GC conditions (INJ: 250 ° C, DET: 250 ° C, COL INIT.TEMP: 200 ° C, COL INIT.TIME: 3min, COL PROG.RATE: 10 ° C, COL FINAL.TEMP: 250 ° C, COL FINAL.TIME: 20min ) Linear detection time: 29min

Jones reagent was prepared as follows. To a reaction vessel (20 ml eggplant flask), 1.8 g (17.8 mmol) of chromium trioxide and 5.6 ml of water were added. The mixture was cooled in an ice bath and 1.61 ml of 95% sulfuric acid was added dropwise. The solid in the reaction vessel was completely dissolved by ultrasonic waves.
To a 200 ml eggplant flask, add 0.77 g (2.96 mmol) of 1,16-hexadecanediol and 110 ml of acetone. The solids were completely dissolved by ultrasonic waves, and the Jones reagent prepared above was added dropwise while maintaining the reaction system at 20 ° C. After dropping, the mixture is stirred for 4 hours. After the reaction, it is concentrated to remove acetone. In the residue, a blue chrome solid and white crystals remain. Water was added thereto to completely dissolve chromium. The aqueous chromium solution and white crystals are separated by suction filtration, and the crystals are further washed with water. The obtained crystals were dissolved in tetrahydrofuran (so that a saturated solution of THF was obtained). Further, when hexane was added, white crystals were precipitated again, which was filtered and dried under vacuum to obtain 0.77 g (Y. 91%) of hexadecanoic acid (Compound 37).
¹ H-NMR (d6DMSO) δ ppm 1.24 (bs, 20H), 1.52 (bs, 4H), 2.17 (t, J = 7.3Hz, 4H) (Aldrich date base and H of carboxylic acid cannot be detected)
IR (neat) cm ^-1 548, 685, 724, 939, 1184, 1216, 1258, 1298, 1431, 1468, 1701, 2689, 2851, 2919
mp 120.1-122.9 ° C (lit. 122.0-124.0 ° C)

The reaction vessel (50 ml eggplant flask) was heated in advance under vacuum and in water-free conditions. Thionyl chloride used for the reaction was purified by atmospheric distillation. (B.p. 77.5 ° C) Under a nitrogen gas atmosphere, the temperature of a mixed solution of hexadecanedioic acid (37) 1.01 g (3.5 mmol) and thionyl chloride (14.0 mmol) was slowly increased over 30 minutes, and refluxed for 2 hours. Stir. By concentration, thionyl chloride was distilled off to obtain 1.13 g (Y. 99%) of a crude acid chloride product (acid chloride (compound 38)). Since this reaction hardly caused side reactions, the composition organism was used in the next step.
¹ H-NMR (CDCL ₃ ) δ ppm 1.27 (s, 20H), 1.70 (t, J = 7.3Hz, 4H), 2.88 (t, J = 7.3Hz, 4H)
IR (neat) cm ^-1 571, 595, 692, 726, 955, 1136, 1404, 1466, 1803, 2855, 2928

The above reaction formula is shown below.

The reaction vessel (200 ml eggplant flask) was preliminarily heated under vacuum and under water-free conditions, and the reaction solvent was also dried. DABCO used was purified by recrystallization from ether. A 0.07M solution of DABCO (0.10 g, 0.31 mmol) in THF (60 ml) is heated to 40 ° C. 0.09M of THF solution (acid chloride 0.31 mmol / THF 3.5 ml) of acid chloride 0.100 g was added dropwise with a microfeeder over 4 hours. After dropping, the mixture was stirred for 30 minutes and neutralized with hydrochloric acid. The mixture was extracted with ether, dried over magnesium sulfate, filtered to remove magnesium sulfate, and concentrated. Silica gel column chromatography (chloroform / hexane 1: 1, 100 times) was performed to obtain β-lactone (Compound 41) at 0.054 g (Y. 70%).
¹ H-NMR (CDCL ₃ ) δ ppm 0.85-2.41 (m, 24H), 4.05 (bs, 1H), 4.68 (dd, J = 10.6, 4.0Hz, 1H)

β-lactone 0.054 g (0.25 mmol) was subjected to silica gel column chromatography (chloroform, 50 times) several times to obtain exalton (compound 2) at 0.054 g (Y. 96%).
¹ H-NMR (CDCL ₃ ) δ ppm 1.30 (m, 20H), 1.65 (t, J = 7.3Hz, 4H), 2.42 (t, J = 7.3Hz, 4H)
IR (neat) cm ^-1 711, 734, 1079, 1127, 1153, 1215, 1286, 1368, 1409, 1460, 1712, 2856, 2934

The above reaction formula is shown below.

Claims (6)

General formula

(Wherein R ¹ may be the same or different and each represents a hydrocarbon group, R ² may be the same or different and each represents a hydrogen atom or a hydrocarbon group; ³ may be the same or different and each represents a hydrogen atom, a hydrocarbon group or a halogen atom, and X may be the same or different and each represents a halogen atom or an alkyl group. Using the represented complex as a catalyst, the general formula CH ₂ ═CHCH ₂ R ⁴
(Wherein R ⁴ represents a hydrocarbon group having 2 or more carbon atoms.) By dimerizing the terminal olefin represented by the general formula: R ⁴ CH ₂ CH═CHCH ₂ CH ₂ CH ₂ R ⁴
The manufacturing method of the linear compound represented by these. The method according to claim 1, wherein R ¹ represents an alkyl group, R ³ represents a halogen atom, and X represents a halogen atom. General formula R ⁴ CH ₂ CH═CHCH ₂ CH ₂ CH ₂ R ⁴
(In the formula, R ⁴ represents a hydrocarbon group having 2 or more carbon atoms.) A linear compound represented by the formula (1) is hydrogenated, and a halogenating agent is allowed to act on this to produce an acid halide to convert β-lactone. A method for producing a cyclic compound comprising producing and decarboxylating this β-lactone under acidic conditions. The manufacturing method of claim 3, wherein ^{R 4} is - _{(CH 2)} 5 OY
(Wherein Y represents a hydrogen atom or a hydroxyl-protecting group). The method for producing exalton according to claim 4, wherein the linear compound is produced by the method according to claim 1. Use of the exalton produced in claim 4 or 5 for the production of muscone.