WO2020175631A1 - Procédé de réduction d'un composé hydrocarboné insaturé - Google Patents

Procédé de réduction d'un composé hydrocarboné insaturé Download PDF

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WO2020175631A1
WO2020175631A1 PCT/JP2020/008069 JP2020008069W WO2020175631A1 WO 2020175631 A1 WO2020175631 A1 WO 2020175631A1 JP 2020008069 W JP2020008069 W JP 2020008069W WO 2020175631 A1 WO2020175631 A1 WO 2020175631A1
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group
compound
general formula
unsaturated hydrocarbon
reaction
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PCT/JP2020/008069
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Japanese (ja)
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坪内源
片山裕美子
村上吉明
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株式会社神鋼環境ソリューション
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds

Definitions

  • the present invention relates to a method for reducing unsaturated hydrocarbon compounds.
  • Birch (8 _) reduction and catalytic hydrogenation reduction are known as methods for reducing unsaturated hydrocarbon compounds.
  • the Birch reduction is a method of reducing an unsaturated hydrocarbon compound by reacting the unsaturated hydrocarbon compound with an alkali metal simple substance such as metallic sodium or metallic lithium in liquid ammonia. When a single alkali metal is put into liquid ammonia, the alkali metal dissolves and turns into ions. The outermost shell electrons of the dissolved alkali metal move to the solvent, and the electrons are surrounded by the solvent to be in the form of solvated electrons.
  • the Birch reduction utilizes the strong reducing power of this solvated electron. When the Birch reduction is applied to the internal alkyne compound as an unsaturated hydrocarbon compound, it can be reduced to a 3 ⁇ -alkene compound.
  • Catalytic hydrogenation reduction includes a method in which an unsaturated hydrocarbon compound reacts with hydrogen in the presence of a palladium or platinum catalyst to reduce the unsaturated hydrocarbon compound.
  • catalytic hydrogenation reduction with a palladium or platinum catalyst reduces the corresponding alkane compound, but the reduction is stopped at the alkene compound stage by adjusting the activity of the catalyst. be able to.
  • the reduction reaction of the alkyne compound can be stopped in the first step, and the corresponding alkene compound is produced.
  • the Lindlar catalyst can be prepared by treating palladium supported on calcium carbonate with quinoline and lead acetate. When the Lindlar catalyst is applied to an internal alkyne compound as an unsaturated hydrocarbon compound, it can be reduced to the corresponding __-alkene compound, which is different from the Birch reduction in stereoselectivity. ⁇ 2020/175631 2
  • Patent Document 1 discloses that under argon, bis(pinacolato)diboron Anhydrous containing Then, tetradeca-7-yne, which is an alkyne compound, was added to the mixture, and the mixture was reacted at 80° for 1 hour to cause a diboration reaction, which was reduced to the corresponding alkene compound (())- It has been reported that 2,2'-(tetradec-7-ene-7,8-diyl)bis(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolen) was obtained. .. Similarly, it has been reported that the diboration reaction proceeds also for alkyne compounds of 2-butyne and 3-hexyne. As described above, according to the method described in Patent Document 1, the internal alkyne compound can be reduced to the corresponding O_13-alkene compound.
  • a borated alkene compound for example, an alkyl borate prepared by a reaction of styrene and 9-borabicyclo[3.3.1]nonane dimer ((9 ⁇ ) 2 ) is tributyl
  • a method of reacting with an alkyne compound such as ethyl 3-phenylpropionate in the presence of a phosphine (hereinafter sometimes abbreviated as "84") catalyst has been reported (see Non-Patent Document 2). thing) . It is reported that the resulting borated alkene compound has a substituent introduced at the 3-position.
  • a diboronated alkene compound or a diboronated alkane compound is included.
  • Organic boron compounds are used in the total synthesis of natural products, medical and agricultural chemicals, electronic materials such as liquid crystals and organic EL, and organic synthetic reactions of a wide variety of functional materials such as intermediates thereof.
  • the diboronated alkene compound produced in Patent Document 1 is also used as a synthetic intermediate for semiconductor materials.
  • the organoboron compound bortezmib ixazomib has been developed as a therapeutic agent for multiple myeloma
  • tavaborole is an antifungal agent
  • crisaborole has been developed as a therapeutic agent for atopic dermatitis. Attention has been paid to various physiological activities of organic boron compounds.
  • Patent Document 1 International Publication No. 2015/097078
  • Non-Patent Document 1 Yuki Nagashima et al., "Trans-Diborylation of Alkynes: Pseudo-Intramo lecu lar Strategy Utilizing a Propargy 11 c Alcohol Unit", J. Am. Chem. Soc., 2014, 136 (24 ), pp 8532-8535
  • Non-Patent Document 2 Kazunor i Nagao et al., "Phosphine-Catalyzed Ant i-Carbobora ion of Alkynoates with Alkyl-, Alkenyl-, and Ary Iboranes", J. Am. Chem. Soc., 2014, 136 (30). , pp 10605-10608
  • the Birch reduction uses liquid ammonia (boiling point: 33°C) that is cooled to below the boiling point and liquefied, and is usually performed at a low temperature of -35°C or lower. Equipment for cooling is required. Moreover, ammonia used as a solvent is highly toxic. When a metal mass such as a simple substance of alkali metal is used, it may be difficult to form a uniform reaction system due to local heat generation. Therefore, the cost burden such as equipment for perch reduction, safety management, and energy cost will increase. ⁇ 2020/175631 4 ⁇ (: 171? 2020 /008069
  • catalytic hydrogenation reduction and the method described in Patent Document 1 using a platinum catalyst all use very expensive catalysts such as palladium and platinum, and therefore the cost is increased. To do.
  • industrial use requires complicated steps for catalyst recovery and regeneration, which increases the number of steps and complicates the steps.
  • palladium is a rare metal among precious metals, so there is a problem in terms of sustainability.
  • catalytic hydrogenation is not an alternative to Birch reduction because of its stereoselectivity when adapted to internal alkynes, and vice versa.
  • Non-Patent Document 1 there is also a problem that a device and equipment suitable for handling are required so that it can be suitably used as a base (for example, in Japan, the It is designated as a Class 3 pyrophoric substance and a water-prohibiting substance.).
  • Grignard reagent and NaH also have a problem that they require careful handling from the viewpoint of stability and danger of the reagent. It is also used as a catalyst in the method described in Non-Patent Document 2. Also has the problem that it is spontaneously ignitable, and similarly, it requires equipment and facilities suitable for handling (for example, in Japan, it is designated as a Class 4 flammable liquid by the Fire Service Law). ..
  • an unsaturated hydrocarbon compound can be reduced easily in a small number of steps without using a device that requires complicated temperature control or safety control, or a reagent that requires careful handling or an expensive reagent. It is desired to build a technology that can.
  • the unsaturated hydrocarbon compound can be easily and inexpensively and efficiently reduced with a small number of steps by using reagents that are easy to handle and handle.
  • the degree of reduction can be controlled by reacting with a diboronic acid ester compound or a boric acid ester compound.
  • organic boron compounds such as diboron alkene compounds and diboron alkene compounds obtained as a result of reduction of unsaturated hydrocarbon compounds by such a reduction method are used in organic synthesis reactions of a wide variety of functional materials. It is something. The present inventors have completed the present invention based on these findings.
  • the present invention relates to a method for reducing an unsaturated hydrocarbon compound, which comprises: a reaction solvent containing an alkali metal dispersed in a dispersion solvent;
  • [ ⁇ , [ ⁇ , are each independently an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic group.
  • a heterocyclic group ⁇ 2020/175631 6 ⁇ (:171? 2020 /008069
  • the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, it does not require complicated temperature control or safety control, and does not require expensive reagents or reagents that require careful handling. Therefore, unsaturated hydrocarbon compounds can be reduced inexpensively and efficiently in a short time with a small number of steps using reagents that are easy to obtain and handle, which is very economically and industrially advantageous. is there.
  • Alkali metals, especially sodium, are metals that are extremely widely distributed on the globe, so the reduction method of this configuration is also a method with excellent sustainability. Furthermore, organoboron compounds such as diboron alkane compounds obtained as a result of reduction of unsaturated hydrocarbon compounds by the reduction method of the present construction are used in organic synthesis reactions of a wide variety of functional materials. .. Therefore, the reduction method of this configuration can be applied to a wide variety of natural products such as total synthesis, medical and agricultural chemicals, electronic materials such as liquid crystals and organic compounds, and intermediates thereof. ⁇ 2020/175631 7 ⁇ (:171? 2020 /008069
  • Another characteristic configuration is that in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent,
  • (3 ⁇ 4 (3 ⁇ 4 ⁇ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group An alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic heterocyclic group, and may be bonded to each other to form a ring].
  • the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, complicated temperature control and safety control are not required, and expensive reagents and reagents that require careful handling are not required. Therefore, by using reagents that are easy to obtain and handle, the unsaturated hydrocarbon compound can be reduced inexpensively and efficiently in a small number of steps in a short time, which is very economical and industrially advantageous. Is.
  • Alkali metals, especially sodium, are metals that are extremely widely distributed on the earth, so the reduction method of this configuration is also excellent in sustainability.
  • the organic boron compounds such as diboron alkene compounds obtained as a result of the reduction of unsaturated hydrocarbon compounds by the reduction method of the present constitution are used in the organic synthesis reaction of a wide variety of functional materials. .. Therefore, the reduction method of this configuration is used for the total synthesis of natural products, organic and pharmaceutical compounds, electronic materials such as liquid crystals and organic compounds, and organic synthesis reactions of various functional materials such as intermediates thereof. Can be used for.
  • Another characteristic configuration is that in the presence of a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent,
  • the unsaturated hydrocarbon compound can be reduced under mild conditions by using the dispersion in which the alkali metal is dispersed in the dispersion solvent. Therefore, complicated temperature control and safety control are not required, and expensive reagents and reagents that require careful handling are not required. Therefore, by using reagents that are easy to obtain and handle, the unsaturated hydrocarbon compound can be reduced inexpensively and efficiently in a small number of steps in a short time, which is very economical and industrially advantageous. Is.
  • Alkali metals, especially sodium, are metals that are extremely widely distributed on the earth, so the reduction method of this configuration is also excellent in sustainability. Furthermore, organoboron compounds such as diboron alkane compounds obtained as a result of the reduction of unsaturated hydrocarbon compounds by the reduction method of this configuration are used in organic synthesis reactions of a wide variety of functional materials. .. Therefore, the reduction method of this configuration is used for the total synthesis of natural products, organic and pharmaceutical compounds, electronic materials such as liquid crystals and organic compounds, and organic synthesis reactions of various functional materials such as intermediates thereof. Can be used for.
  • Another characteristic configuration is that the molar ratio of the dispersion obtained by dispersing the alkali metal in a dispersion solvent to the unsaturated hydrocarbon compound is 2 or more and 4 or less. ⁇ 2020/175631 1 1 ⁇ (: 171? 2020 /008069
  • the unsaturated hydrocarbon compound can be reduced more efficiently by optimizing the amount of the dispersion in which the alkali metal is dispersed in the dispersion solvent.
  • FIG. 1 is a diagram summarizing synthesis conditions and results of Example 1 — 1 (reduction reaction of diphenylacetylene (1)).
  • FIG. 2 is a diagram summarizing synthesis conditions of Example 1-2 (reduction reaction of bis(4-methoxyphenyl)acetylene (1)).
  • FIG. 3 is a diagram summarizing synthesis conditions of Example 1 — 1 3 (reduction reaction of diphenylacetylene (2)).
  • FIG. 4 is a diagram summarizing synthesis conditions of Example 1 — 14 (reduction reaction of diphenylacetylene (3)).
  • FIG. 5 is a diagram summarizing synthesis conditions and results of Example 2 — 1 (reduction reaction of diphenylacetylene (4)).
  • FIG. 6 is a diagram summarizing the synthesis conditions of Example 2-2 (reduction reaction of diphenylacetylene (5)).
  • FIG. 7 is a diagram summarizing synthesis conditions of Example 2-9 (reduction reaction of diphenylacetylene (6)).
  • FIG. 8 is a diagram outlining the synthesis conditions for Example 2 — 16 (reduction reaction of 1-phenyl-...!-hexyne).
  • FIG. 9 is a diagram summarizing synthesis conditions and results of Example 3 — 1 (reduction reaction of _ — stilbene).
  • FIG. 10 is a diagram summarizing the synthesis conditions of Example 3-2 (reduction reaction of 3 ⁇ 4 -methoxystilbene).
  • FIG. 11 is a diagram summarizing the synthesis conditions for Example 3 — 18 (stilbene (isomer mixture) reduction reaction (2) ).
  • FIG. 12 is a diagram summarizing synthesis conditions and results of Example 4 (styrene reduction reaction). ⁇ 2020/175631 12 ⁇ (:171? 2020 /008069
  • FIG. 13 is a diagram summarizing synthesis conditions and results of Example 5 (reduction reaction of phenanthrene).
  • FIG. 14 is a diagram summarizing the synthesis conditions of Example 6 (reduction reaction of 4-methoxyphenylarene).
  • the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is an alkyne compound having one or more carbon-carbon triple bonds in the molecule, converting the carbon-carbon triple bond into a single bond, and reducing it to the corresponding alkane compound. Including the method.
  • an alkyne compound which is an unsaturated hydrocarbon compound represented by the general formula and a diboronic acid ester represented by the general formula 114 It includes a step of reducing the unsaturated hydrocarbon compound by reacting with a compound.
  • examples of the unsaturated hydrocarbon compound to be reduced include an alkyne compound containing one or more carbon-carbon triple bonds in the molecule. it can.
  • An alkyne compound is a terminal alkyne compound in which at least one of two carbon atoms forming a carbon-carbon triple bond is bonded to a hydrogen atom, but both carbon atoms form a carbon atom forming a carbon-carbon triple bond. In addition to the bond with, it may be an internal alkyne compound bonded to a group other than a hydrogen atom.
  • the alkyne compound represented by the general formula I 3 are each independently a hydrogen atom or an aliphatic group which may have a substituent that does not react with an alkyl metal.
  • Hydrocarbon group alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, fat Cyclic heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cyclo An alkylamino group, an arylamino group, an aralkylamino group, a moon heterocyclic heterocyclic amino group, an aromatic heterocyclic amino group, or a silyl group, which has a substituent reactive with an alkali metal, This is not preferable because a dispersion in which a substituent and sodium are dispersed in a dispersion solvent reacts with each other to induce a
  • the aliphatic hydrocarbon group may be linear or branched, or saturated or unsaturated.
  • the chain length is also not particularly limited.
  • the substituent is not particularly limited as long as it does not react with an alkali metal.
  • Examples of the aliphatic hydrocarbon group include, but are not limited to, preferably an alkyl group having 1 to 20 carbon atoms, particularly preferably an alkyl group having 3 to 20 carbon atoms, an alkenyl group, and an alkynyl group. To be done. Therefore, an unsaturated hydrocarbon compound containing two or more carbon-carbon triple bonds in the molecule can also be a target of reduction in the method for reducing an unsaturated hydrocarbon compound according to this embodiment.
  • the aliphatic hydrocarbon group includes, specifically, as an alkyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, an isoptyl group, and a -butyl group.
  • alkenyl group examples include, but are not limited to, an ethenyl group, a probenyl group, a butenyl group, a pentenyl group, a hexenyl group, a heptenyl group and an octenyl group.
  • alkynyl group examples include, but are not limited to, an ethynyl group, a propynyl group, afugyl group, a pentynyl group, a heptynyl group and an octynyl group.
  • the aliphatic hydrocarbon group may further have a substituent.
  • the substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other.
  • an aliphatic which may have a substituent ⁇ 2020/175631 15 ⁇ (:171? 2020 /008069
  • Hydrocarbon group alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic group Formula heterocyclic oxy group, aromatic heterocyclic oxy group, alkylthio group, cycloalkylthio group, arylthio group, aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkyl Examples thereof include, but are not limited to, an amino group, an arylamino group, an aralkylamino group, an alicyclic heterocyclic amino group, an aromatic heterocyclic amino group, and a silyl group.
  • the aliphatic hydrocarbon group is the same as the above-mentioned ones, such as an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, an aromatic heterocyclic group, a halogen atom, an alkoxy group.
  • the number of ring members is not particularly limited, regardless of whether the bond between ring-constituting atoms is saturated or unsaturated. Moreover, not only a single ring but also a ring having a ring assembly such as a condensed ring or a spit ring is included.
  • the alicyclic hydrocarbon group is not limited to these, but preferably has 3 to 10 carbon atoms, particularly preferably 3 to 7 cycloalkyl groups, preferably 4 to 10 carbon atoms, Particularly preferred are 4 to 7 cycloalkenyl groups, cycloalkynyl groups and the like.
  • cycloalkyl group examples include, but are not limited to, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group.
  • cycloalkenyl group examples include, but are not limited to, a cyclopropenyl group, a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group, a cycloheptenyl group, a cyclooctenyl group and the like.
  • a cycloalkynyl group ⁇ 2020/175631 16 ⁇ (:171? 2020/008069
  • Examples thereof include, but are not limited to, cyclooctynyl group and the like.
  • the alicyclic hydrocarbon group may have a substituent.
  • the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other.
  • the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
  • the alicyclic heterocyclic group is a non-aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only a single ring but also those having a ring assembly such as a condensed ring or a spiro ring are included.
  • the bond between ring members may be saturated or unsaturated, and the number of ring members is not particularly limited.
  • the heteroatom is not particularly limited as long as it does not react with sodium as a ring-constituting atom.
  • the number of heteroatoms is not particularly limited, and the position of heteroatoms is also not limited.
  • Preferred examples of the hetero atom include an oxygen atom, a nitrogen atom, a sulfur atom and the like.
  • an alicyclic heterocyclic group having preferably 2 to 7 carbon atoms, particularly preferably 2 to 5 carbon atoms, and preferably 1 to 5 and particularly preferably 1 to 3 heteroatoms. Is mentioned.
  • it when it has a plurality of heteroatoms, it may be the same kind of atoms or different kinds of atoms.
  • the alicyclic heterocyclic group includes a nitrogen-containing alicyclic heterocyclic group such as a monocyclic four-membered ring azetidinyl group, a five-membered ring pyrrolidinyl group, a six-membered ring piperidyl group, and a piperazinyl group.
  • a nitrogen-containing alicyclic heterocyclic group such as a monocyclic four-membered ring azetidinyl group, a five-membered ring pyrrolidinyl group, a six-membered ring piperidyl group, and a piperazinyl group.
  • An oxygen-containing alicyclic compound cyclic group such as a monocyclic three-membered cyclic oxiranyl group, a four-membered cyclic oxetanyl group, a five-membered cyclic tetrahydrofuryl group, a six-membered tetrahydropyranyl group, Sulfur-containing alicyclic heterocyclic groups such as monocyclic five-membered tetrahydrothiophenyl groups, nitrogen-containing oxygen alicyclic heterocyclic groups such as monocyclic six-membered morpholinyl groups, monocyclic Examples thereof include nitrogen-containing sulfur alicyclic heterocyclic groups such as 6-membered thiomorpholinyl groups, but are not limited thereto.
  • the alicyclic heterocycle may further have a substituent.
  • the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different. ⁇ 2020/175631 17 ⁇ (: 171? 2020/008069
  • the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
  • the aromatic hydrocarbon group is not particularly limited as long as it has an aromatic ring. Not only a single ring but also those having a ring assembly such as a condensed ring or a spiro ring are included. There is no particular limitation on the number of members. For example, an aromatic hydrocarbon group having preferably 6 to 22, and particularly preferably 6 to 14 carbon atoms can be mentioned.
  • Aromatic hydrocarbon groups include monocyclic six-membered ring phenyl groups, etc., bicyclic naphthyl groups, pentalenyl groups, indenyl groups, azulenyl groups, etc., tricyclic biphenylenyl groups, indacenyl groups, acenaphthylenyl groups, fluorenyl groups.
  • phenalenyl group, phenanthryl group, anthryl group, etc. tetracyclic fluoranthenyl, aceanthrylenyl group, triphenylenyl group, pyrenyl group, naphthacenyl group, etc., pentacyclic perylenyl group, tetraphenylenyl group, etc.
  • examples include, but are not limited to, a hexacyclic pentacenyl group and the like, a heptcyclic rubicenyl group, a coronenyl group, a heptacenyl group, and the like. Particularly preferred is a phenyl group.
  • the aromatic hydrocarbon group may further have a substituent.
  • the substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other.
  • the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
  • the aromatic heterocyclic group is an aromatic heterocyclic group having one or more heteroatoms as ring-constituting atoms. Not only a single ring, but also those having a ring assembly such as a condensed ring or a spiro ring are included.
  • the number of ring members is also not particularly limited.
  • the heteroatom is not particularly limited as long as it does not react with sodium as a ring-constituting atom.
  • the number of heteroatoms is not particularly limited, and the position of heteroatoms is also not limited.
  • Preferred examples of the hetero atom include oxygen atom, nitrogen atom, sulfur atom and the like.
  • an aromatic compound having 1 to 5 carbon atoms, particularly preferably 3 to 5 carbon atoms, and preferably 1 to 4 heteroatoms, particularly preferably 1 to 3 heteroatoms.
  • Heterocyclic groups may be mentioned.
  • the atoms may be the same or different.
  • examples of the monocyclic aromatic heterocyclic group include a 5-membered pyrrolyl group, a pyrazolyl group, a pyridyl group, an imidazolyl group, a 6-membered pyrazinyl group, a pyrimidinyl group, a pyridazinyl group.
  • nitrogen-containing aromatic heterocyclic groups five-membered furyl groups and other oxygen-containing aromatic heterocyclic groups, five-membered cyclic cenyl groups and other oxygen-containing aromatic heterocyclic groups, and five-membered oxazolyl groups Group, an isoxazolyl group, a nitrogen-containing oxygen aromatic heterocyclic group such as a flazanyl group, a five-membered thiazolyl group, a nitrogen-containing sulfur aromatic heterocyclic group such as an isothiazolyl group, and the like, but are not limited to these. Absent.
  • Examples of the polycyclic aromatic heterocyclic group include a bicyclic indolizinyl group, an isoindolyl group, an indolyl group, an indazolyl group, a purinyl group, an isoquinolyl group, a quinolyl group, a phthalazinyl group, a naphthyridinyl group, a quinoxalinyl group, Nitrogen-containing aromatic heterocyclic groups such as quinazolinyl groups, cinnolinyl groups, tricyclic carbazolyl groups, carborinyl groups, phenatridinyl groups, acridinyl groups, perimidinyl groups, phenanthrolinyl groups, phenazinyl groups, and bicyclic benzofuranyl groups.
  • Oxygen-containing aromatic heterocyclic groups such as isobenzofuranyl group, benzopyranyl group, sulfur-containing aromatic heterocyclic groups such as bicyclic benzocenyl group, tricyclic thianthrenyl group, and bicyclic benzoxazolyl Group, benzoisoxazolyl group and other nitrogen-containing oxygen aromatic heterocyclic groups, bicyclic benzothiazolyl group, benzoisothiazolyl group, tricyclic phenothiazinyl group and other nitrogen-containing sulfur aromatic heterocyclic groups, three Examples thereof include, but are not limited to, oxygen-containing sulfur aromatic heterocyclic groups such as cyclic phenoxathinyl groups.
  • the aromatic heterocyclic group may further have a substituent.
  • the substituent may have one or a plurality of substituents, and when having a plurality of substituents, they may be the same or different from each other.
  • the position of the substituent is also not particularly limited. Examples of the substituent include the same groups as those exemplified as the substituent of the aliphatic hydrocarbon group. ⁇ 2020/175631 19 ⁇ (:171? 2020 /008069
  • halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • the alkoxy group is preferably an alkoxy group having 1 to 10 carbon atoms, and specific examples thereof include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a pentyloxy group and a hexyloxy group.
  • the cycloalkoxy group is preferably a cyclobropoxy group having 3 to 10 carbon atoms, and examples thereof include a cyclobutoxy group, a cyclopentyloxy group and a cyclohexyloxy group.
  • the aryloxy group is preferably an aryloxy group having 6 to 20 carbon atoms, and specific examples thereof include a phenyloxy group and a naphthyloxy group, but the aryloxy group is not limited thereto.
  • the aralkyloxy group is preferably an aralkyloxy group having 7 to 11 carbon atoms, and specific examples thereof include a benzyloxy group and a phenethyloxy group.
  • Examples of the alicyclic heterocyclic oxy group and the aromatic heterocyclic oxy group include the alicyclic heterocyclic group and aromatic heterocyclic group shown above as the heterocyclic moiety. In addition, these may further have a substituent.
  • the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other.
  • the position of the substituent is also not particularly limited. Examples of the substituent are the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
  • the alkylthio group is preferably an alkylthio group having 1 to 20 carbon atoms, and examples thereof include a methylthio group, an ethylthio group, a propylthio group, a pentylthio group, a pentylthio group, and a hexylthio group. Not something to do.
  • Examples of the cycloalkylthio group include cycloalkylthio groups having 3 to 10 carbon atoms, and specific examples thereof include a cyclopropylthio group, a cyclobutylthio group, a cyclopentylthio group, and a cyclohexylthio group. It is not limited to.
  • the arylthio group is preferably an arylthio group having 6 to 20 carbon atoms, and specific examples thereof include a phenylthio group and a naphthylthio group, but the arylthio group is not limited thereto.
  • the aralkylthio group is ⁇ 2020/175631 20 ⁇ (:171? 2020 /008069
  • Preferable examples are aralkylthio groups having 7 to 11 carbon atoms, and specific examples thereof include a benzylthio group and a phenethylthio group, but the aralkylthio group is not limited thereto.
  • Examples of the alicyclic heterocyclic thio group and the aromatic heterocyclic thio group include the alicyclic heterocyclic group and aromatic heterocyclic group represented by the above as the heterocyclic moiety. Moreover, these may further have a substituent.
  • the substituents may have one or a plurality of substituents, and when they have a plurality of substituents, they may be the same or different from each other.
  • the position of the substituent is also not particularly limited. Examples of the substituent include the same as those exemplified as the substituent of the aliphatic hydrocarbon group.
  • the silyl group is a substitution of, on the silicon, three or more aliphatic hydrocarbon groups, alicyclic hydrocarbon groups, alicyclic heterocyclic groups, aromatic hydrocarbon groups, aromatic heterocyclic groups, and the like. It is a monovalent group having a group. Substituents such as an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group and an aromatic heterocyclic group may be the same as those mentioned above.
  • a dimethylsilyl group a diphenylsilyl group, a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a dimethyl-1-butylsilyl group, and a diphenyl-1-butylsilyl group. ..
  • [0046] may be the same group or different groups.
  • the carbon-carbon triple bond is not particularly limited, and the ring formed by the bond that can form part of the ring is exemplified by cycloalkyne ring such as cyclooctyne ring. be able to.
  • the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment specifically includes diphenylacetylene, phenylacetylene, and 1-phenyl-1-propyne. , 1-phenyl-1-butyne, 1-phenyl-1-pentyne, 1-phenyl-!!-hexyne, 1-phenyl-2-(trimethylsilyl)acetylene, 1-phenyl-2-acetyl(acetyl), Bis (trimethylsilyl) acetylene, 2-phenyl-1-ethynylboronic acid pinacola ⁇ 2020/175631 21
  • the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment a commercially available one may be used, or a method known in the art may be used. You may use what was manufactured.
  • the diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment is represented by the following general formula 1.
  • [ ⁇ , [ ⁇ , are each independently an aliphatic hydrocarbon group which may have a substituent that does not react with an alkali metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or an aromatic group. It is a heterocyclic group.
  • aliphatic hydrocarbon group alicyclic hydrocarbon group, alicyclic heterocyclic group, aromatic hydrocarbon group, and aromatic heterocyclic group, those mentioned above can be exemplified.
  • Examples include, but are not limited to, a heptane-2,3-diyl group, where a ring structure composed of a boron atom, two oxygen atoms bonded to it, and an atom bonded to each oxygen atom is used. , Preferably having 4 to 8 ring members.
  • the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure are bonded to each other to form a further cyclic structure. You may.
  • diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment specifically, bis(pinacolato)diboron (4, 4, 4', 4', 5, 5 , 5', 5'-Octamethyl-2,2'-bi-1,3,2-dioxapororane), bis(neopentylglycolate)diborone (5,5,5,5,5-tetramethyl-2,2 ,-Bi-1,3,2-dioxaborinane), bis(hexylene glycolate)diborone (4,4,4',4',6,6'-hexamethyl-2,2'-bi-1,3,3 2-dioxaborinane), bis(catecholate) diborone (2,2'-bi -1,3,2-benzodioxaporol), 2-(4,4,5,5-tetramethyl-1 ,3,2 -Dioxaborolan-2-yl)-2,3
  • the diboronic acid ester compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment may be a commercially available one, or may be one produced by a method known in the art. May be used.
  • the dispersion obtained by dispersing an alkali metal in a dispersion solvent used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is a dispersion of an alkali metal as fine particles in an insoluble solvent, or an alkali metal. Is dispersed in an insoluble solvent in a liquid state.
  • the alkali metal include sodium, potassium, lithium and alloys containing these metals.
  • the average particle size of the fine particles is preferably less than 10 111, and particularly preferably less than 5 111.
  • the average particle diameter was represented by the diameter of a sphere having a projected area equivalent to the projected area obtained by image analysis of a micrograph. ⁇ 2020/175631 23 ⁇ (: 171? 2020 /008069
  • a dispersion prepared by dispersing an alkali metal in a dispersion solvent may be abbreviated as “30”. It is an abbreviation for Sod i um, and is labeled with a symbol because a dispersion using sodium as an alkali metal is used in the examples described below. However, the sign of does not exclude alkali metals other than sodium.
  • the concentration of the alkali metal contained in [0057] is not particularly limited, but for example, 5 The following can be illustrated.
  • any solvent known in the art can be used as long as the alkali metal can be dispersed as fine particles or the alkali metal can be dispersed in a liquid state in an insoluble solvent.
  • mineral oils such as normal paraffinic solvents such as normal decane, normal hexane, normal heptane, and normal pentane, aromatic solvents such as xylene and toluene, heterocyclic compound solvents such as tetrahydrothiophene, and mixed solvents thereof.
  • mineral oils such as normal paraffinic solvents such as normal decane, normal hexane, normal heptane, and normal pentane
  • aromatic solvents such as xylene and toluene
  • heterocyclic compound solvents such as tetrahydrothiophene, and mixed solvents thereof.
  • a solvent used as a reaction solvent a solvent known in the technical field may be used as long as it does not inhibit the reaction in the reduction method. it can.
  • an aprotic polar solvent is preferable.
  • an ether solvent a paraffin solvent such as normal paraffin solvent or cycloparaffin solvent, an aromatic solvent, an amine solvent, or a heterocyclic compound solvent can be used.
  • ether solvents cyclic ethers ⁇ 2020/175631 24 ⁇ (:171? 2020 /008069
  • a solvent is preferable, and tetrahydrofuran (hereinafter sometimes abbreviated as “Cho #”) or the like can be preferably used.
  • the paraffinic solvent cyclohexane, normal hexane, normal decane and the like are particularly preferable.
  • the aromatic solvent xylene, toluene, benzene and the like are preferable.
  • Ethylenediamine and the like can be preferably used as the amine solvent.
  • Tetrahydrothiophene or the like can be used as the solvent for the heterocyclic compound. Further, these may be used alone or in combination of two or more and used as a mixed solvent.
  • the dispersion solvent and the reaction solvent may be of the same kind or different kinds.
  • the reaction temperature in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is not particularly limited, and an unsaturated hydrocarbon compound to be reduced, a diboronic acid ester compound, It can be appropriately set depending on the kind and amount of the reaction solvent, the reaction pressure and the like.
  • the reaction temperature is preferably set to a temperature that does not exceed the boiling point of the reaction solvent.
  • the reaction temperature can be set at a high temperature because it becomes higher than the boiling point under atmospheric pressure under pressure.
  • the reaction can be carried out at room temperature, preferably 0 to 100 ° , particularly preferably 0 to 80 ° , and further preferably 0 to 50 ° . It is not necessary to provide a temperature control means for special heating or cooling, but a temperature control means may be provided if necessary.
  • the reaction time in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is not particularly limited, and is an unsaturated hydrocarbon compound to be reduced, a diboronic acid ester compound, It may be appropriately set according to the kind and amount of the reaction solvent, the reaction pressure, the reaction temperature, and the like. Usually, it is carried out for 15 minutes to 24 hours, preferably 20 minutes to 6 hours.
  • the unsaturated hydrocarbon compound reduction method according to the present embodiment is preferably carried out in an inert gas atmosphere filled with argon gas, nitrogen gas, or the like.
  • the unsaturated hydrocarbon compound is reacted in a molar ratio of 1: 2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting in this amount, the unsaturated hydrocarbon compound can be efficiently reduced. on the other hand, If the amount is too large, post-treatment that remains after the reaction may be required, which may complicate the operation.
  • unsaturated hydrocarbon The molar ratio of the diboronic acid ester compound is 1: 2 to 2.2: 1 to 1.
  • the substance amount of It means the amount of the substance contained in alkaline metal equivalent.
  • the unsaturated hydrocarbon compound reduction method further includes 2-propanol, methanol, ethanol, butanol, phenol, 2,2,2-trifluoroethanol, 1, 1, 1,
  • the reduction reaction may be carried out by adding a lower alcohol such as 3,3,3-hexafluoro-2-propanol or a phenol or the like.
  • a lower alcohol such as 3,3,3-hexafluoro-2-propanol or a phenol or the like.
  • the triple bond of the unsaturated hydrocarbon compound can be reduced to a single bond.
  • the boron ester can be bonded to the site of reduction of the unsaturated hydrocarbon compound.
  • unsaturated hydrocarbon compounds It may be added 15 to 30 minutes after reacting the diboronic acid ester compound.
  • an alkyne compound which is an unsaturated hydrocarbon compound to be reduced is reduced to a corresponding diborated alkane compound represented by the following general formula III 3.
  • the boron-boron single bond) of the diboronic acid ester is cleaved, and the alkyne that is the unsaturated hydrocarbon compound to be reduced is
  • the carbon-carbon triple bond of the compound one boryl group derived from diboronic acid ester and one hydrogen atom are added to each carbon atom constituting the triple bond. This reduces the alkyne compound to the corresponding diboronated alkane compound.
  • the alkane compound obtained by the method for reducing an unsaturated hydrocarbon compound according to the present embodiment is obtained as a stereoisomer, but when a reaction is carried out by adding a lower alcohol such as 2-propanol, a (13, 23) form, When the (, 2(3 ⁇ 4) form is reacted with phenol, the (, 23) form and the (13, 21 ⁇ ) form are preferentially obtained.
  • the reduced alkane compound may be purified by a purification means known in the art.
  • the reduced alkane compound is subjected to an extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated solution obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
  • the unsaturated hydrocarbon compound reduction method according to the present embodiment is an alkyne compound having one or more carbon-carbon triple bonds in the molecule, wherein the carbon-carbon triple bond is converted into a double bond and reduced to the corresponding alkene compound. Including how to do.
  • a dispersion prepared by dispersing an alkali metal in a dispersion solvent in a reaction solvent an alkyne compound which is an unsaturated hydrocarbon compound represented by the general formula and a borate ester represented by the general formula 114 It includes a step of reducing the unsaturated hydrocarbon compound by reacting with a compound.
  • the unsaturated hydrocarbon compound to be reduced as in the above [1], one or more carbon-carbon triple bonds in the molecule are included.
  • the alkyne compound include: Alkyne ⁇ 2020/175631 27 ⁇ (:171? 2020 /008069
  • the compound is a terminal alkyne compound in which at least one of two carbon atoms forming a carbon-carbon triple bond is bonded to a hydrogen atom, both carbon atoms are bonded to a carbon atom forming a carbon-carbon triple bond.
  • it may be an internal alkyne compound bonded to a group other than a hydrogen atom.
  • a hydrogen atom an aliphatic hydrocarbon group which may have a substituent which does not react with an alkyl metal, an alicyclic hydrocarbon group, an alicyclic heterocyclic group, an aromatic hydrocarbon group, or , Aromatic heterocyclic group, halogen atom, alkoxy group, cycloalkoxy group, aryloxy group, aralkyloxy group, alicyclic heterocyclic oxy group, aromatic compound ring oxy group, alkylthio group, cycloalkylthio group, arylthio group , Aralkylthio group, alicyclic heterocyclic thio group, aromatic heterocyclic thio group, alkylamino group, cycloalkylamino group, arylamino group, aralkylamino group, alicyclic heterocyclic amino group, aromatic heterocycle An amino group and a silyl
  • the alkyne compound is represented by the general formula [1] above, terms in can as the alkyne compound represented by the general formula and the same description, and thus, the Oyobi is in the general formula, and the formula I 3 Can be equivalent to
  • ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment is represented by the following general formula 114. ⁇ 0 2020/1756 31 28 ⁇ (: 17 2020 /008069
  • 1 ⁇ , (3 ⁇ 4 ⁇ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group
  • aromatic heterocyclic group those described in the above item [1] can be exemplified.
  • ⁇ and 1 b are both may be combined to form a ring, presence bonded as groups independently without binding to one another and two oxygen atoms bonded to the boron atom and a boron atom bonded to each other There is no particular restriction on the position.
  • 1,1,2,2-tetramethylethylene group which is a group forming a pinacol ring, 1,1,2-trimethylpropylene group, 2,2-dimethylpropylene group, propylene Group, ⁇ -phenylene group, 1-(4-methoxyphenyl)-2,2-dimethylethylene group, (112( ⁇ 33,5-2,6,6-trimethylbicyclo[3.1.1]]heptane
  • Examples include, but are not limited to, a boron atom, two oxygen atoms bonded to it, and a cyclic structure composed of atoms bonded to each oxygen atom is a ring.
  • the number of members is preferably 4 to 8.
  • the atom forming the cyclic structure may have a substituent, and even if the substituents introduced into the cyclic structure are bonded to each other to form a further cyclic structure. Good.
  • ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment include trimethyl borate (trimethoxyborane). ⁇ 2020/175631 29 ⁇ (:171? 2020 /008069
  • Triethyl borate (triethoxyborane), tripropyl borate, triisopropyl borate, tributyl borate, trihexyl borate, trioctyl borate, tridecyl borate, tritetradecyl borate, trioctadecyl borate, etc.
  • Boric acid trialkyl esters, triphenyl borate, tri-borate triaryl esters such as boric acid triethanolamine, boric acid triisopropanolamine, tris(trimethylsilyl)borate having silyloxy group Acid triesters are mentioned.
  • pinacol ethoxyboronate (2-ethoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane)
  • pinacol isopropoxyboronate (2-isopropoxy-4,4,5,5) -Tetramethyl-1 ,3,2-dioxaborolane
  • pinacol methoxyboronate (2-methoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane)
  • trimethoxyborane examples thereof include catechol borate, neopentyl glycol borate, and biscyclohexyl diol borate. Particularly preferably, trimethoxyborane can be used
  • reaction solvent used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment the reaction solvent described in the above item [1] can be exemplified.
  • reaction conditions such as reaction temperature, reaction time, reaction atmosphere, etc. in the method for reducing unsaturated hydrocarbon compounds according to the present embodiment, and the conditions described in the above item [1] are exemplified. can do
  • the unsaturated hydrocarbon compound to be reduced the boric acid ester compound, and the type of reaction solvent, etc. It can be set appropriately according to the amount and the like.
  • the unsaturated hydrocarbon compound is reacted in a molar ratio of 1:2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting with this amount, unsaturated hydrocarbon compounds can be efficiently returned. ⁇ 2020/175631 30 boxes (:171? 2020 /008069
  • the substance amount of It means the mass of the substance contained in terms of alkali metal.
  • the unsaturated hydrocarbon compound reduction method according to the present embodiment may be further post-treated with a dihydric alcohol such as pinacol or neopentyl glycol, or potassium hydrogen fluoride.
  • a dihydric alcohol such as pinacol or neopentyl glycol, or potassium hydrogen fluoride.
  • the -0( ⁇ group of the borate ester compound is protected by divalent alcohol or potassium hydrogen fluoride, and boric acid or boroxine generated by the reaction of the borate ester compound with the water in the reaction system.
  • borate triesters such as trimethyl borate are used as borate ester
  • pinacol is added to obtain a borated alkene compound with a pinacol boryl group.
  • such a dihydric alcohol or the like it is preferably performed after adding the borate ester compound.
  • the alkyne compound that is the unsaturated hydrocarbon compound to be reduced is reduced to the corresponding diboronated alkene compound represented by the following general formula 11. ..
  • the boron-oxygen single bond of 1 in the borate ester -O) bond is cleaved to reduce ⁇ 2020/175631 31 ⁇ (: 171? 2020 /008069
  • the alkyne compound which is the target unsaturated hydrocarbon compound
  • one boryl group derived from borate ester is added to each carbon constituting the triple bond.
  • the alkyne compound is reduced to the corresponding alkene compound.
  • the alkyne compound is an internal alkyne compound
  • the alkene compound formed is one in which a boryl group is introduced into the __13 type.
  • the reduced alkene compound may be purified by a purification means known in the art.
  • the reduced alkane compound is subjected to an extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated solution obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
  • the unsaturated hydrocarbon compound reduction method according to the present embodiment is an alkene compound containing one or more carbon-carbon double bonds in the molecule, the carbon-carbon double bond is converted into a single bond, and the corresponding alkane compound is converted to the corresponding alkane compound. Including a method of reducing.
  • examples of unsaturated hydrocarbon compounds to be reduced include alkene compounds containing one or more carbon-carbon double bonds in the molecule. It is possible to reduce a substance containing two or more carbon-carbon double bonds.
  • the alkene compound at least one of the two carbon atoms forming the carbon-carbon double bond is bonded only to the hydrogen atom except the bond to the carbon atom forming the carbon-carbon double bond, and is bonded to another group. Even if the terminal alkene compound is not present, both carbon atoms form a carbon-carbon double bond. ⁇ 0 2020/175631 32 ⁇ (: 17 2020 /008069
  • an internal alkene compound bonded with a group other than a hydrogen atom may be used.
  • the arrangement of these groups is not limited to the general arrangement (including type 0). Even the £ placement Including the mold).
  • I is the general formula.
  • the carbon-carbon double bond can form a part of the ring by forming a ring by bonding with the or.
  • they may exist as independent groups without being bonded to each other.
  • the ring formed by the bond of and or is not particularly limited, and examples thereof include a cycloalkene ring such as a cyclohexene ring and an aromatic ring such as a benzene ring.
  • a cycloalkene ring such as a cyclohexene ring
  • an aromatic ring such as a benzene ring.
  • the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure may be bonded to each other to form a further cyclic structure.
  • ( ⁇ and ( ⁇ may be bonded to each other to form a ring, or may be present as independent groups without being bonded to each other.
  • the ring formed by the bond is not particularly limited, and examples thereof include a cycloalkane ring such as a cyclohexane ring and a cycloalkene ring such as a cyclohexene ring. Also, similarly, they may be bonded to each other to form a ring, or they may exist as groups independent of each other. Further, the atom forming the cyclic structure may have a substituent, and the substituents introduced into the cyclic structure may be bonded to each other to form a further cyclic structure.
  • the unsaturated hydrocarbon compound to be reduced in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment a commercially available one may be used, or the unsaturated hydrocarbon compound may be prepared by a method known in the art. You may use what was manufactured.
  • the unsaturated hydrocarbon compound according to the present embodiment is used as a target of reduction in the reduction method. ⁇ 2020/175631 34 ⁇ (:171? 2020 /008069
  • saturated hydrocarbon compound examples include styrene, ⁇ _-stilbene, 3-stilbene, /3-methylstyrene, /3-ethylstyrene, /3-propylstyrene, /3-butylstyrene and /3-pentyl.
  • Styrene /3-hexylstyrene, ⁇ -methylstyrene, ⁇ -ethylstyrene, Propyl styrene, Petit Styrene, Pentyl styrene, Hexylstyrene, 1-methyl-1,2-diphenylethylene, 1,2,3-triphenylethylene, indene, 1,2-dihydronaphthalene, butadiene, isoprene, 1,3-cyclohexagen, norbornene, norbornadiene, etc. Can be mentioned.
  • the ester borate compound used in the method for reducing an unsaturated hydrocarbon compound according to the present embodiment has the following general formula II. As shown in.
  • 1 ⁇ , (3 ⁇ 4 ⁇ Oyobi are each independently of the alkali metals and does not react with an aliphatic substituted hydrocarbon group, an alicyclic hydrocarbon group, an alicyclic heterocyclic A group, an aromatic hydrocarbon group, or an aromatic heterocyclic group.
  • the boric acid ester compound shown in can be equivalent to the boric acid ester compound represented by the general formula described in the section [2] above, and therefore can be represented by the general formula II.
  • trimethoxyborane can be used.
  • reaction solvent used in the method for reducing an unsaturated hydrocarbon compound according to this embodiment the reaction solvent described in the above item [1] can be exemplified.
  • reaction conditions such as reaction temperature, reaction time, reaction atmosphere, etc. in the method for reducing unsaturated hydrocarbon compounds according to the present embodiment. ⁇ 2020/175631 35 ⁇ (: 171? 2020 /008069
  • the unsaturated hydrocarbon compound to be reduced In the method for reducing an unsaturated hydrocarbon compound according to the present embodiment and the amount of the boric acid ester compound used, the unsaturated hydrocarbon compound to be reduced, the boric acid ester compound, and the type of reaction solvent and the like, It can be set appropriately according to the amount and the like.
  • the unsaturated hydrocarbon compound is reacted in a molar ratio of 1:2 or more. More preferably, the reaction is carried out at 1:2 or more and 1:4 or less. By reacting in this amount, the unsaturated hydrocarbon compound can be efficiently recovered.
  • the amount is too large, post-treatment that remains after the reaction becomes necessary, and the operation may be complicated.
  • the substance amount of It means the mass of the substance contained in terms of alkali metal.
  • lithium iodide may be added. This has the effect of improving the yield and stereoselectivity of the product. When adding such lithium iodide, It is preferable to add before adding.
  • the method for reducing an unsaturated hydrocarbon compound according to the present embodiment further includes 1 ⁇ 1, 1 ⁇ 1, 1 ⁇ 1', 1 ⁇ 1'-tetramethylethylenediamine (chome 1 ⁇ 8), triethylamine, etc.
  • the amines may be added. This improves the product yield and diastereoselectivity.
  • Is preferably added before the addition of.
  • a post-treatment with a dihydric alcohol such as pinacol or neopentyl glycol or potassium hydrogen fluoride may be further performed.
  • a dihydric alcohol such as pinacol or neopentyl glycol or potassium hydrogen fluoride
  • the 0 ( ⁇ group of the borate ester compound is protected by a divalent alcohol or potassium hydrogen fluoride, and boric acid, boroxine, etc., which are generated by reacting the borate ester compound with water in the reaction system.
  • a boric acid triester such as trimethyl borate
  • An alkene compound borated by a ruboryl group can be obtained. Further, when such a dihydric alcohol is added, it is preferable to add it after adding the borate ester compound.
  • the alkyne compound that is the unsaturated hydrocarbon compound to be reduced is represented by the following general formula III. Is reduced to the corresponding diboronated alkene compound shown in.
  • the ⁇ bond of 1 of boric acid ester is cleaved, and the alkene compound which is the unsaturated hydrocarbon compound to be reduced is
  • the alkene compound which is the unsaturated hydrocarbon compound to be reduced is
  • one boryl group derived from borate ester is added to each carbon atom constituting the double bond.
  • the alkene compound is reduced to the corresponding alkane compound.
  • the internal alkene is used as the raw material, a mixture of the (1, 2) form and the (, 2(3 ⁇ 4) form is obtained diastereoselectively from both __13 type and “3 type” alkenes.
  • the reduced alkane compound may be purified by a purification means known in the art.
  • the reduced alkane compound is subjected to extraction treatment using an organic solvent such as ethyl acetate as an extraction solvent, and the concentrated extract obtained is concentrated and applied to a purified carrier such as silica gel chromatography. Can be purified with.
  • Example [0105] Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.
  • SD in the following examples a dispersion in which metallic sodium is dispersed as fine particles in normal paraffin oil is used, and the substance amount of SD is a numerical value in terms of metallic sodium contained in SD.
  • Lithium iodide (0.27 g. 2.0 mmol), bis(4-methoxyphenyl)acetylene (0.24 g, 1.0 mmol) and bis(pinacolato)diborone (0.25 g, 1.0 mmol) were placed in a glass test tube containing a stir bar. And add nitrogen gas to the test tube. ⁇ 2020/175631 38 ⁇ (: 171? 2020 /008069
  • the collected organic layer was dehydrated with sodium sulfate, and then all volatile compounds were removed with a mouth rotary evaporator.
  • the ratio of the compound 82 and the compound 82 in the product was 75:25.
  • Substrate General formula (1) General formula (2) (Examples 1 to 4) Reduction reaction of bis(2-methoxyphenyl)acetylene Example 1 except that the substrate was changed to bis(2-methoxyphenyl)acetylene (the following formula) (0.24 9 , 1.0 1111110 0) -When the reaction was performed under the same conditions as in -2, the product was obtained as a white solid, 0.31 9 (0.62 111 111 ⁇ 62%). 1 ⁇ (determined by 3 ⁇ 4, the general formula (1) in the product) And the mass ratio of the compounds represented by the general formula (2) was 74:26.
  • Example 1-5 Reduction reaction of bis (2-methylphenyl) acetylene (1)
  • the reaction was performed under the same conditions as in 1-2, the product was obtained as a white solid, 0.37 9 (0.79 111 111 ⁇ then 79%).
  • the amount ratio of the compounds represented by the general formula (1) and the compound represented by the general formula (2) in the product was 70:30, respectively.
  • Example 1_2 The reaction was carried out under the same conditions as in Example 1_2 except that the substrate was changed to 2-(phenylethynyl)naphthalene (the following formula) (0.239, 1.011111100) and the reaction temperature in the first step was changed to 0 ° .
  • the product was obtained as a white solid, 0.32 9 (0.65 111111 ⁇ then 65%).
  • 1 H-stain (determined by 3 ⁇ 4, respectively, according to the general formula (1) and the general formula (2) in the product)
  • the mass ratio of the represented compounds was 89:11. [Chemical 22]
  • Example 1_2 The reaction was carried out under the same conditions as in Example 1_2 except that the substrate was changed to 1-(4-methylsulfanylphenyl)-2-phenylenylacetylene (the following formula) (0.22 g, 1.0 mmol).
  • the product was obtained as a white solid in an amount of 0.23 g (0.49 mm ⁇ U 49%).
  • the mass ratio of the compounds represented by the general formula (1) and the general formula (2) in the product was 95:5.
  • Substrate 1 - phenyl - 2 - (trimethylsilyl) acetylene (the following formulas) (0.17 9, 1.0, the reaction temperature in the first stage was changed to 0 °, also 2 - using hexanol - propanol in cash forte 1 Other than that, when the reaction was performed under the same conditions as in Examples 1 and 2, the product was 0.31 9 (0.73 111 111 ⁇ and 73%) as a white solid.
  • the general formula in the product The mass ratio of the compounds represented by 1) and general formula (2) was 46:54, respectively.
  • Example 1_ except that the substrate was changed to 1-phenyl-2-(triisopropylsilyl)acetylene (the following formula) (0 ⁇ 25 g, 0.95 mmol) and the reaction temperature in the first step was changed to 0°C.
  • Lithium iodide (0.27 g, 2.0 mmol), diphenylacetylene (0.18 g, 1.0 mmol) and bis(pinacolato)diboron (0.25 g, 1.0 mmol) were added to a glass test tube containing a stir bar and tested. The inside of the tube was replaced with nitrogen gas. After cooling the test tube to 0 °C in an ice bath, THF (3.6 mL) and N, N, N', N'-tetramethylethylenediamine (0.4 mL) were added, and SD (9.9 M) was added to the mixture. , 0.20 mL, 2.0 mmol) was added dropwise.
  • Diphenylacetylene (0.18 9 , 1.0 11111101) and bis(pinacolato)diboron (0.25 9 , 1.0 11111100) were added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas. After cooling to 0 ° , use the # (3.
  • Tetramethylethylenediamine (0.4 ⁇ !) was added, and (9.9 11/1, 0.20 111 and 2.0 11111100) was added dropwise to this mixture. After completion of the addition, the mixture was stirred at 0° for 30 minutes and then 1,3- Dichloropropane (0.19 111 and 2.0 11111101) was added, and the reaction solution was heated to 60 ° and stirred for 5 hours.
  • Lithium iodide (0.27 g, 2.0 mmol), diphenylacetylene (0.18 g, 1.0 mmol) and bis(pinacolato)diboron (0.25 g, 1.0 mmol) were added to a glass test tube containing a stir bar and tested. The inside of the tube was replaced with nitrogen gas. After cooling the test tube to 0 °C in an ice bath, THF (3.6 mL) and N, N, N', N'-tetramethylethylenediamine (0.4 mL) were added, and SD (9.9 M) was added to the mixture. , 0.20 mL, 2.0 mmol) was added dropwise.
  • Example 2-4 Reduction reaction of bis(2-methoxyphenyl)acetylene (2) Using bis(2-methoxyphenyl)acetylene (the following formula) (0.24 9 , 1.0 1111110 [) as a substrate, one step When the reaction was performed under the same conditions as in Example 2_2 except that the eye reaction temperature was changed to room temperature, the compound represented by the general formula (3) was obtained as a white solid in an amount of 0.30 9 (0.60 11111101, 60%). Was given.
  • Example 2-5 Reduction reaction of 1-phenyl-2464-butylacetylene (2) Substrate 1-phenyl-2-diamine 6"1;-butylacetylene (the following formula) (0.15 9, 0 ⁇ 94 11111101), the reaction was conducted under the same conditions as in Example 2_2 except that the reaction temperature in the first step was changed to room temperature. As a result, the compound represented by the general formula (3) was found to be 0.32 9 (0.
  • Example 2-2 The reaction was carried out under the same conditions as in Example 2-2 except that the substrate was changed to 1-phenyl-2-(trimethylsilyl)acetylene (the following formula) (0.17 9 and 1.0), and was expressed by the general formula (3).
  • the compound was obtained as a white solid in 0.37 9 (0.861 ⁇ 0 and 86%).
  • Example 2 _ 2 The reaction was carried out under the same conditions as in Example 2 _ 2 except that the substrate was changed to 1-phenyl-2-(triisopropylsilyl)acetylene (the following formula) (0 25 g, 0.95 mmol), and the general formula (3 0.39 g (0.76 mm ⁇ U 76%) was obtained as a white solid.
  • the substance ratio was 75:25.
  • the compound represented by () was obtained in a yield of 83%.
  • Example 2-15 Reduction reaction of 2-(phenylethynyl)naphthalene (3)
  • the substrate was changed to 2-(phenylethynyl)naphthalene (the following formula) (0.23 9, 1.0 11111100)
  • the reaction was performed under the same conditions as in Example 2_9, the compound represented by the general formula (4) was obtained (the yield was 55%).
  • Example 2_1 was used except for some conditions.
  • Anhydrous lithium iodide (0.33 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas.
  • the test tube was cooled to 0 ° C in an ice bath, and then THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.4 mL), cis-stilbene (ci s- 1,2-diphenylethene) (0.18 mL, 1.0 mmol) and trimethoxyborane (0.67 mU 6.0 mmol) were added. SD (9.2 M, 0.27 mU 2.5 mmol) was added dropwise to this mixture.
  • Anhydrous lithium iodide (0.34 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas.
  • the test tube was cooled to 0 ° C in an ice bath, followed by THF (3.6 mL), N, N, N', N'-tetramethylethylenediamine (0.
  • Example 3-3 to 3_15 examples in which the reaction was performed under the same conditions as in Example 3_2 except for some conditions will be described.
  • the product in each of the following examples is represented by the general formula (5) and the general formula (6) (below) corresponding to the substrate in each example.
  • the substrate can be a cis form, a trans form, or a mixture of isomers. ⁇ 2020/1756 31 53 2020 /008069
  • Substrate Toxistilbene (the following formula) (0.10 9 ,0.49
  • the product was 0.15 9 (0.31 1111110, 64%) as a white solid.
  • the ratio of the compounds represented by the general formula (5) and the compound represented by the general formula (6) in the product was 94:6.
  • the amount ratio of the compounds represented by the general formula (5) and the compound represented by the general formula (6) in the product was 93:7.
  • the product was obtained as a white solid, 0.34 9 (0.74111111 ⁇ 74%) 1 ⁇ (determined by 3 ⁇ 4, represented by the general formula (5) and general formula (6) in the product, respectively)
  • the mass ratio of the compounds was 92:8.
  • heterogeneous mixture E/Z 67/33, 0.20 g, 0.99 mmol
  • the product was obtained as a colorless liquid, 0.26 9 (0.51 1 ⁇ 0, 53%).
  • the 1 H ratio (determined by 3 ⁇ 4, the ratio of the amount of the compound represented by the general formula (5) and the amount of the compound represented by the general formula (6) in the product was 50:50, respectively.
  • the substrate is 1,2-dihydronaphthalene (the following formula) (0.13 9, 1.0
  • Compound 11/1 was obtained as a colorless liquid in an amount of 0.17 9 (0.441111110, 44%).
  • Substrate )-2-Pinacolatoboryl styrene (the following formula) (0.18 9 ,1.03
  • the reaction was performed under the same conditions as in Example 3_2 except that 10 11111101 was used as the trimethoxyborane, and the compound 1 ⁇ 1 was obtained as a white solid in an amount of 0.31 9 (0.641111110, 62%). ..
  • Anhydrous lithium iodide (0.34 g, 2.5 mmol) was added to a glass test tube containing a stir bar, and the inside of the test tube was replaced with nitrogen gas.
  • THF 4.0 mL
  • trimetoxyborane (0.11 mL, 1.0 mmol) were added.
  • the test tube was cooled to -78 °C with dry ice/acetone, and SD (10.0 M, 0.25 mL, 2.5 mmol) was added dropwise to this mixture.
  • Examples 3 _ 19 and 3-20 below examples in which the reaction was performed under the same conditions as in Example 3-18 except for some conditions will be described.
  • the product in each of the following examples is represented by the general formula (7) and the general formula (8) (below) corresponding to the substrate in each example.
  • the substrate is either a 3 ⁇ body or a mixture of isomers.
  • Example 3 _ 18 The reaction was performed under the same conditions as in Example 3 _ 18 except that the substrate was changed to 3-stilbene (0.18 9, 1.01 1111110 ⁇ ) and methyl iodide was changed to butyl iodide (0.55, 3.0 11111100). 0.14 9 (0.39 1 ⁇ then 39%) was obtained as a white solid.
  • 1 H (determined by 3 ⁇ 4, represented by the general formula (7) and general formula (8) in the product, respectively) The mass ratio of these compounds was 10:90.
  • Example 3 (Example 3 _ 20) Reduction reaction of stilbene (mixture of isomers) (3)
  • the present invention relates to all technical fields in which reduction of unsaturated hydrocarbon compounds is required, in particular, total synthesis of natural products, medical and agricultural chemicals, and electronic materials such as liquid crystal and organic! , It is a useful technology in organic synthesis technology of various functional materials such as intermediates.

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Abstract

La présente invention concerne un procédé de réduction d'un composé hydrocarboné insaturé par réaction d'un composé alcyne, qui est un composé hydrocarboné insaturé, avec un composé ester d'acide diboronique ou un composé ester d'acide borique, ou par réaction d'un composé alcène, qui est un composé hydrocarboné insaturé, avec un composé ester d'acide borique, de telles réactions étant réalisées dans un solvant de réaction et en présence d'une dispersion d'un métal alcalin dispersé dans un solvant de dispersion.
PCT/JP2020/008069 2019-02-28 2020-02-27 Procédé de réduction d'un composé hydrocarboné insaturé WO2020175631A1 (fr)

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CN106146543A (zh) * 2015-04-27 2016-11-23 中国科学院上海有机化学研究所 过渡金属络合物、手性α-氨基三级硼酸酯及其制备方法

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CN106146543A (zh) * 2015-04-27 2016-11-23 中国科学院上海有机化学研究所 过渡金属络合物、手性α-氨基三级硼酸酯及其制备方法

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
AN, JIE ET AL.: "Evaluating a Sodium Dispersion Reagent for the Bouveault- Blanc Reduction of Esters", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 79, no. 14, 2014, pages 6743 - 6747, XP055735661, ISSN: 1520-6904, DOI: 10.1021/jo501093g *
FARRE, ALBERT ET AL.: "Developing a Bench-Scale Green Diboration Reaction toward Industrial Application", SYNTHESIS, vol. 49, no. 21, 2017, pages 4775 - 4782, XP055735658, ISSN: 1437-210X, DOI: 10.1055/s-0036-1590912 *
FURUKAWA, TAKAYUKI ET AL.: "C-H borylation by platinum catalysis", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 90, no. 3, 2017, pages 332 - 342, XP055735657, ISSN: 0009-2673, DOI: :10.1246/bcsj.20160391 *
LILLO, VANESA ET AL.: "A valuable, inexpensive Cul/N-heterocyclic carbene catalyst for the selective diboration of styrene", CHEMISTRY - A EUROPEAN JOURNAL, vol. 13, no. 9, 2007, pages 2614 - 2621, XP055735659, ISSN: 0947-6539, DOI: 10.1002/chem.200601146 *
TAKAHASHI, FUMIYA ET AL.: "Diborative Reduction of Alkynes to 1,2- Diboryl-1,2-Dimetalloalkanes: Its Application for the Synthesis of Diverse 1,2-Bis(boronate)s", ORGANIC LETTERS, vol. 21, no. 12, 12 June 2019 (2019-06-12), pages 4739 - 4744, XP055735662, ISSN: 1523-7052, DOI: 10.1021/acs.orglett.9b01622 *

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