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WO2004076459A1 - Compose de bifluorure d'ammonium quaternaire et procede de production de nitroalcool au niveau de ce compose - Google Patents

Compose de bifluorure d'ammonium quaternaire et procede de production de nitroalcool au niveau de ce compose Download PDF

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Publication number
WO2004076459A1
WO2004076459A1 PCT/JP2003/009500 JP0309500W WO2004076459A1 WO 2004076459 A1 WO2004076459 A1 WO 2004076459A1 JP 0309500 W JP0309500 W JP 0309500W WO 2004076459 A1 WO2004076459 A1 WO 2004076459A1
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group
substituted
halogen atom
alkyl group
branched
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Japanese (ja)
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Keiji Maruoka
Takashi Ooi
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Nagase and Co Ltd
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Nagase and Co Ltd
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Priority to JP2004568777A priority Critical patent/JP4593289B2/ja
Priority to AU2003252268A priority patent/AU2003252268A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
    • C07C205/14—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to acyclic carbon atoms
    • C07C205/16—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to acyclic carbon atoms of a carbon skeleton containing six-membered aromatic rings

Definitions

  • the present invention relates to a quaternary ammonium bifluoride compound and a method for producing a nitric alcohol using the same. More specifically, a quaternary catalyst useful as a phase transfer catalyst capable of specifically controlling the configuration of a silylated compound of an etro compound, i.e., a di-alcohol formed by the reaction of a silyl nitrate with an aldehyde compound.
  • the present invention relates to an ammonium bifluoride compound and a method for producing a nitroalcohol using the same, the configuration of which is specifically controlled. Background art
  • nucleophilic reactions caused by organosilicon compounds induced by fluorine ions are regarded as important in organic synthesis due to their good selectivity of the reaction sites.
  • few synthesis examples focus on the stereoselectivity of reaction products.
  • most of the reaction cases using fluorine ions generated from chiral quaternary ammonium fluoride use cinchona alkaloid derivatives as catalysts.
  • the present invention provides the following formula (I):
  • R 5 and R 6 are each independently a hydrogen atom; a straight-chain alkyl group of CC e which may be substituted with a halogen atom; A C 3 -C 6 branched alkyl group which may be substituted; a C 3 -C 6 cyclic alkyl group which may be substituted by a halogen atom; C which may be substituted by a halogen atom
  • a cycloalkyl group of c 3 to c 6 which may be substituted with a halogen atom; a halogen atom, an alkyl group which may be substituted with a halogen atom, or a halogen atom;
  • Ci Cg aralkyl group optionally substituted by alkoxy group;
  • halogen atom optionally substituted Ci C alkyl group optionally substituted by halogen atom, or optionally substituted halogen atom c 1 to c 3 heteroaralkyl group into an optionally substituted alkoxy group;
  • R 5 and R 6 of the compound represented by the above formula (I) are each independently substituted with a C t -C ⁇ alkynole group which may be substituted with a halogen atom. And an aryl group substituted with an aryl group.
  • H 5 and R 6 of the compound represented by the above formula (I) are both 3,5-bis (3,5-ditrifluoromethylphenyl) phenyl. It is.
  • the configuration of the compound represented by the above formula (I) is (S, S) or (R, R).
  • the present invention also provides the following formula ( ⁇ ):
  • R 1 'and R 2' are each independently a hydrogen atom; a straight-chain alkyl group of Ci Cs; C 3 ⁇ C 6 branched alkyl group; a cyclic alkyl group of C 3 -C 6; Ci linear alkenyl group of C 2 ⁇ C 6;; cyclic alkoxy group of c 3 ⁇ C 6; branched-chain alkoxy group c 3 to c 6; straight Zhen alkoxy group cs c 3 to c 6 branched Aruke - Le group; a halo gen atom; cyclic alkynyl groups c 3 ⁇ c 6; c 3 branched alkynyl group to c 6; linear alkyl ⁇ le groups c 2 ⁇ c 6; c 3 cyclic alkenyl group to c 6; a halogen atom, a linear alkyl group of Ci Cs, C 3 ⁇ C '6 branched alkyl group,
  • Cyclic alkyl group of C 6, linear alkoxy group Ci Cs, substituted branched Kusaria alkoxy group or a C 3 ⁇ C 6 cyclic alkoxy heteroaryl groups may be substituted with a group, of c 3 to c 6
  • R 5 and R 6 are each independently a hydrogen atom; a C 1 -C 6 linear alkyl group which may be substituted with a halogen atom; May be c 3 ⁇
  • the configuration of the compound represented by the above formula (1 ′) is (S, S) or (R, R).
  • the present invention also provides a method for producing a quaternary ammonium bifluoride represented by the above formula (I), which comprises the following formula (II):
  • R 5 and R 6 are each independently a hydrogen atom; a C Cs linear alkyl group which may be substituted with a halogen atom; c 3 -c 6 which may be substituted with a halogen atom.
  • N, N-di (Ci ⁇ C 4 alkyl) force Rubamoiru group (wherein, Ji ⁇ 1-4 alkyl group , Which may be the same or different from each other), and X is a chlorine atom, a bromine atom, or an iodine atom). Reacting to obtain an intermediate; and Reacting with an aqueous hydrogen fluoride solution.
  • R 5 and R 6 of the compound represented by the above formula (II) are each independently substituted by a C i -C 4 alkyl group which may be substituted by a halogen atom. And an aryl group substituted with an aryl group.
  • R 5 and R 6 of the compound represented by the above formula (II) are both 3,5-bis (3,5-ditrifluoromethylphenyl) phenyl.
  • the configuration of the compound represented by the above formula (II) is (S, S) or (R, R).
  • the present invention also provides a method for producing a quaternary ammonium bifluoride represented by the above formula (1 ′), which comprises the following formula (II ′):
  • R 1 ′ and R 2 ′ are each independently a hydrogen atom; a linear alkyl group of Ci Cs; a branched alkyl group of C 3 to C 6 ; a cyclic alkynole group of C 3 to Cs; ⁇ to ⁇ 6 linear alkoxy group; C 3 to C 6 branched chain alkoxy group; C 3 to C 6 cyclic alkoxy group; C 2 to C 6 linear alkenyl group; c 3 to c 6 branched chain Aruke - Le group; cyclic alkenyl group C. ⁇ C 6; linear alkynyl of c 2 to c 6 Group; cyclic alkynyl group c 3 to c 6;; branched alkynyl group c 3 to c 6 halo gen atoms; halogen atoms, C j ⁇ linear alkyl group C 6, branched chain alkyl of c 3 to c 6 A group, a C 3 to C 6 cyclic
  • a aryl group which may be substituted with a C 3 -C 6 branched chain alkoxy group or a C 3 -C 6 cyclic alkoxy group; 6 to 6 linear alkyl groups,
  • An aryl group which may be substituted with a halogen atom an aryl group which may be substituted with an alkyl group which may be substituted with an alkyl group; a halogen atom, which may be substituted with a halogen atom; N- (Cj-alkyl), or a heteroaryl group optionally substituted with a 3 alkoxy group which may be substituted with a halogen atom; a (C 1 -C 3 alkoxy) carbyl group; a carbamoyl group; C 4 alkyl) force Rubamoiru groups; and N, N-di (Ci ⁇ C 4 alkyl) force Rubamoiru group (wherein, Ci ⁇ C 4 alkyl group may be the same or different from each other And X is a chlorine atom, a bromine atom, or an iodine atom), and contacting the compound represented by the formula (II) with an ion-exchange resin to obtain an intermediate; and Reacting the
  • the present invention also provides a method for producing a nitro alcohol compound having excellent diastereoselectivity and enantioselectivity, and the method is represented by the above formula (I).
  • either straight-chain alkoxy group of Ci Ce, or branched-chain alkoxy group of C 3 -C 6, or Ararukiruokishi group may be substituted with one Ariru group, straight of C 1 -C 5 chain alkyl group or one linear alkoxy group of Ci ⁇ C 6,, C 3
  • a C 3 -C 5 branched alkyl group which may be substituted by a C 6 -branched alkoxy group, an aralkyloxy group or an aryl group;
  • R 2 , R 3 and R 4 are Each independently represents a C to C 5 linear alkyl group or a C 3 to C 5 branched chain alkyl group) and an aldehyde.
  • the present invention also provides a method for producing a two-mouth alcohol compound which is excellent in diastereoselectivity and enantioselectivity, and comprises a method for producing a quaternary ammonium bifluoride compound represented by the above formula (1).
  • a C 3 -C 5 branched alkyl group which may be substituted by a C 6 -branched alkoxy group, an aralkyloxy group or an aryl group;
  • R 2 , R 3 and R 4 are Each independently represents a C to C 5 linear alkyl group or a C 3 to C 5 branched chain alkyl group) and an aldehyde.
  • straight chain alkyl group of rC Cs includes any straight chain alkyl group having 1 to 6 carbon atoms, and includes, for example, methyl, ethyl, n-propyl, n-butyl, pentyl and hexyl. .
  • C 3 -C 6 branched alkyl group includes any branched alkyl group having 3 to 6 carbon atoms, and includes, for example, isopropynole, sec-butynole, tert-butyl and the like.
  • C 3 -C 6 cyclic alkyl group includes any cyclic alkyl group having 3 to 6 carbon atoms, such as cyclobutyl, cyclopentyl, and cyclohexyl. And so on.
  • di-dialkyl group When simply referred to as “di-dialkyl group”, it means a C i C a straight-chain alkyl group or a C 3 -C 4 branched-chain alkyl group.
  • C 2 -C 6 straight-chain alkenyl group includes any straight-chain alkenyl group having 2 to 6 carbon atoms, such as, for example, ether, propenyl, butenyl, penteninole, and hexyl-. Le.
  • C 3 -C 6 branched alkenyl group includes any branched alkenyl group having 3 to 6 carbon atoms, and includes, for example, isoprobe, 1-methyl-1-propenyl, 1-methylol 2-propeninole, 2-methylinole-1-propenyl, 2-methyl-12-propyl, and the like.
  • C 3 -C 6 cyclic alkenyl group includes any cyclic alkenyl group having 3 to 6 carbon atoms, and includes, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl and the like.
  • C 2 -C 6 straight-chain alkynyl group includes any straight-chain alkynyl group having 2 to 6 carbon atoms, and includes, for example, echul, propiel, butyr, pentiel, and hexyl.
  • C 3 -C 6 branched alkynyl group includes any branched alkynyl group having 3 to 6 carbon atoms, and includes, for example, 1-methyl-12-propynyl and the like.
  • C 3 -C 6 cyclic alkynyl group includes any cyclic alkynyl group having 3 to 6 carbon atoms, and includes, for example, cyclopropyl eturyl, cyclobutyl ethynyl and the like.
  • C i -C 6 linear alkoxy group includes alkoxy groups having any linear alkyl group having 1 to 6 carbon atoms, and includes, for example, methyloxy, ethyloxy, n-propyloxy and the like. .
  • C 3 -C 6 branched alkoxy group refers to any branched chain having 3 to 6 carbon atoms. It includes an alkoxy group having an alkyl group, and includes, for example, isopropyloxy, tert-butyloxy and the like.
  • cyclic alkoxy group of C 3 -C S includes an alkoxy group having any cyclic Al Kill group 3-6 carbon atoms, such as cyclopropyl Petit Ruo alkoxy, consequent opening Penchiruokishi, Kishiruokishi and the consequent opening No.
  • aralkyl group examples include benzyl, phenethyl, and naphthylmethyl.
  • aralkyloxy group examples include benzyloxy, phenethyloxy, and naphthylmethyloxy.
  • heterooaralkyl group examples include pyridylmethyl, indolylmethyl, furylmethyl, chenylmethyl, and pyrrolylmethyl.
  • aryl group examples include phenyl and naphthyl.
  • aryl group substituted with an aryl group which may be substituted with an alkyl group which may be substituted with a halogen atom examples include 3, 5 —Diphenyl, 3,5-di (3,5-di-t-p-inolephene), phenyl, and 3,5-bis- (3,5-bis- (trifluoromethyl) phenyl) phenyl It is.
  • heteroaryl group examples include pyridyl, pyrrolyl, imidazolyl, furyl, indolinole, chenyl, oxazolyl, thiazolyl, and tetrazolyl.
  • halogen examples include chlorine, bromine, iodine and fluorine.
  • a quaternary ammonium bifluoride compound (hereinafter, referred to as a first quaternary ammonium bifluoride compound of the present invention) according to the first embodiment of the present invention is described. explain about.
  • the first quaternary ammonium "F compound of the present invention has the following formula (I):
  • R 5 and R 6 are each independently a hydrogen atom; a linear alkyl group of Ci Ce optionally substituted by a halogen atom; C 3 -C 6 optionally substituted by a halogen atom A branched alkyl group; a C 3 -C 6 cyclic alkyl group optionally substituted with a halogen atom; a C 2 -C 6 linear alkenyl group optionally substituted with a halogen atom; C 3 -C 6 branched alkenyl group which may be substituted; C 3 -C 6 cyclic alkenyl group which may be substituted with a halogen atom; C 2 -C 6 which may be substituted with a halogen atom A straight-chain alkynyl group; a C 3 -C 6 branched alkynyl group optionally substituted with a halogen atom; a C 3 -C 6 cyclic alkyl group optionally substituted with a halogen atom
  • An aryl group optionally substituted with a halogen atom an aryl group substituted with an aryl group optionally substituted with a C i C alkyl group; substituted with a halogen atom or a halogen atom.
  • the first quaternary ammonium bifluoride compound of the present invention represented by the above formula (I) enables the formation of a di-alcohol whose configuration is controlled diastereoselectively and enantioselectively. Useful as a phase transfer catalyst.
  • the first quaternary ammo-dimethylbifluoride compound of the present invention is characterized in that In the compound represented by the formula (I), R 5 and R 6 are each independently substituted with an aryl group which may be substituted with a CC alkyl group which may be substituted with a halogen atom.
  • the quaternary ammonium bifluoride compound is a compound represented by the above formula (I) wherein both R 5 and R 6 are substituted with a C to C 4 alkyl group which may be substituted with a fluorine atom. And an aryl group substituted with an aryl group which may be substituted, and still more preferably a compound which is 3,5-bis (3,5-ditrifluoromethylphenyl) phenyl.
  • the compound represented by the above formula (I) may have a configuration of (S, S) or (R, R).
  • the first quaternary ammonium bifluoride of the present invention represented by the above formula (I) can be produced, for example, as follows.
  • the compound represented by the above formula (II) is not particularly limited to these.
  • the compound represented by the above formula (II) may also have any of the configurations (S, S) and (R, R).
  • the compound represented by the formula (II) can be easily produced by those skilled in the art, for example, according to the method described in JP-A-2001-48866.
  • the ion exchange resin used in the present invention can be arbitrarily selected by those skilled in the art. Specific examples of ion exchange resins that can be used include Amberlyst A26 (OH) (manufactured by Organo Corporation).
  • the contact between the compound represented by the formula (II) and the ion exchange resin may be performed, for example, by dissolving the compound represented by the formula (II) in an appropriate solvent, and filling the solution with the ion exchange resin. This is done by passing through a column.
  • An alcohol solvent is preferable as a solvent that can be used for such a contact.
  • Specific examples of the alcohol solvent include, but are not particularly limited to, methyl alcohol, ethyl alcohol, isopropyl alcohol, and normal propyl alcohol.
  • the amount of the compound represented by the formula (II) and the solvent used in this contact are not particularly limited, and can be appropriately set by those skilled in the art.
  • the obtained first intermediate is reacted using an aqueous solution of hydrogen fluoride, preferably without removing the solvent.
  • the amount of the aqueous hydrogen fluoride solution used in the present invention is not particularly limited, but is preferably at least equal to the amount of the compound represented by the formula (II) used above from the viewpoint of increasing productivity. Hydrogen hydride is selected to react. As a result, the first intermediate is converted into a bifluoride, and the first quaternary ammonium bifluoride compound of the present invention precipitates in the solution. .
  • the first quaternary ammonium bifluoride of the present invention can be produced.
  • a quaternary ammonium bifluoride compound hereinafter, referred to as a second quaternary ammonium bifluoride compound of the present invention
  • the second quaternary ammonium vinyl compound of the present invention has the following formula ( ⁇ ):
  • R 1 ′ and R 2 ′ are each independently a hydrogen atom; Branched chain alkyl group of C 3 -C 6; chain alkyl groups c 3 of to c 6 cyclic alkyl group; a C 3 -C 6 branched-chain alkoxy group; straight chain alkoxy group of C Ce of C 3 ⁇ C 6 straight town Arukininore group C 2 - C 6; cyclic ⁇ Kokishi group; Ji 2 linear Anorekeni of ⁇ Ji 6 ⁇ group; cyclic alkenyl groups of C 3 ⁇ C 6; C 3 ⁇ C 6 branched alkenyl group; cyclic alkynyl group C 3 ⁇ C 6;; C 3 branched alkynyl group ⁇ C 6 halo gen atom; a halogen atom, a linear alkyl group of c 1 to c 6, branched-chain alkyl group of c 3 to c 6, cyclic alkyl group of C 3
  • a heteroaryl group substituted with an aryl group which may be substituted with a C 6 to C 6 branched alkoxy group or a C 3 to C 6 cyclic alkoxy group; or a halogen atom, a C to C 6 straight chain alkyl group, C 3 branched alkyl group ⁇ C 6, c 3 cyclic alkyl group ⁇ C 6, linear alkoxy groups of C t ⁇ C 6, branched Kusaria alkoxy group C 3 -C 6 or C 3,
  • To C 6 may be substituted with a cyclic alkoxy group
  • a heteroaryl group substituted with a teloaryl group, and R 5 and R 6 are the same as defined in the above formula (I).
  • the second quaternary ammonium bifluoride compound of the present invention represented by the formula (1) is combined with the first quaternary ammonium bifluoride compound of the present invention represented by the above formula (I).
  • it is useful as a phase-transfer catalyst which enables the formation of a diastereoselective and enantioselectively controlled configuration-toro alcohol.
  • the compound represented by the above formula (I ′) may have any of the configurations (S, S) and (R, R).
  • the second quaternary ammonium bifluoride compound of the present invention represented by the above formula () can be produced, for example, as follows.
  • the compound represented by the above formula (II ′) is not particularly limited to these.
  • the compound represented by the above formula (II ′) may also have any of the configurations (S, S) and (R, R).
  • the compound represented by the above formula (11,) can be easily produced by those skilled in the art, for example, according to the method described in Japanese Patent Application Laid-Open No. 2002-32692. .
  • the ion exchange resin used to produce the second quaternary ammonium bifluoride compound of the present invention 1 is used to produce the first quaternary ammonium bifluoride compound of the present invention. Further, the contact between the compound represented by the formula (II ′) and the ion-exchange resin is also the same as that of the first quaternary ammonium bifluoride of the present invention. This is carried out in the same manner as when producing a compound.
  • the amount of the aqueous hydrogen fluoride solution used in the present invention is not particularly limited, but is preferably equal to or more than the amount of the compound represented by the formula (II ′) used above from the viewpoint of increasing productivity. Hydrogen fluoride is selected to react. As a result, the second intermediate is converted to a bifluoride, and the second quaternary ammonium bifluoride compound of the present invention precipitates in the solution.
  • the second quaternary ammonium bifluoride of the present invention can be produced.
  • first and second quaternary ammonium fluoride compounds of the present invention all produce diastereoselective and enantioselective nitro alcohols whose configuration is controlled. It is useful as a catalyst (phase transfer catalyst).
  • R is either straight-chain alkoxy group of C i C e, branched Al of C. ⁇ C 6 It may be substituted with a carbonyl group, an aralkyloxy group, or an aryl group,
  • a C 3 -C 5 branched chain alkyl group which may be substituted by a C 6 -branched alkoxy group, an aralkyloxy group or an aryl group;
  • R 2 , R 3 and 'R 4 They are each independently, 0 1 ⁇ Ji 5 linear Arukiru group or 0-3-Ji is a 5 minute ⁇ alkyl group) and a compound represented by the (silyl nitro sulfonate) is reacted with aldehydes.
  • the silyl nitrate represented by the above formula (III) is a silylated nitroalkane.
  • the silyl-tronate can be easily derived by reacting a nitroalkane and a silylating agent by a method commonly used by those skilled in the art.
  • the -troalkanes which can be used are, for example, 112-trohetane, 112-propane, 1-2-trobutane, 3-methinobutane Examples include 1-nitroprononone, 2-methoxy-11-etroetane, 3-pentinoleoxy-112-tropropane, and 2-phenyl-2-trothetane.
  • usable silylating agents include, for example, trialkylhalogenosylane, more specifically, trimethylchlorosilane, triethylchlorosilane, Butylchlorosilane, and t-butyldimethylchlorosilane.
  • trialkylhalogenosylane more specifically, trimethylchlorosilane, triethylchlorosilane, Butylchlorosilane, and t-butyldimethylchlorosilane.
  • the silyl-tronate of the formula (III) used in the method of the present invention can be obtained by using the above-mentioned nitric acid and a silylating agent, for example, through the following reaction:
  • the above nitroalkane, tetrahydrofuran It is prepared separately from butyllithium dissolved in aliphatic hydrocarbons such as pentane, hexane and heptane, and alkyldiamine dissolved in tetrahydrofuran and the like in a ditroalkane solution dissolved in a solvent such as ethyl ether and isopropyl ether.
  • a silylating agent (trialkylsilyl halide) is added while cooling at about -80 ° C, for example. Thereafter, the reaction product is subjected to fractional distillation to obtain the silyl nitrate of the formula (III) used in the method of the present invention.
  • the aldehyde used in the method for producing a nitro alcohol of the present invention is, for example, The following formula (IV):
  • R 7 is a straight-chain alkyl group, a branched alkyl group having 3 to 10 carbon atoms, or an aryl group or an aralkyl group which may have a substituent).
  • aldehyde represented by the formula (IV) include benzaldehyde, 2-naphthaldehyde, phenylacetoaldehyde, -tolualdehyde, p-fluorobenzaldehyde, p- Methoxybenzaldehyde, acetoaldehyde, propioaldehyde, and pentanal.
  • 2-naphthaldehyde and p-tolualdehyde are preferred from the viewpoint of improving both the diastereoselectivity and the enantioselectivity in the reaction step.
  • the first quaternary ammonium bifluoride compound of the present invention represented by the above formula (I) is preferably 0.1 mol. Le 0 / 0-1 0 mole 0/0, more preferably 0. 5 mol. /. It is used in a proportion of 1-5 mol 0/0.
  • the reaction is carried out by reacting the silyl ditronate of the above formula (III), the aldehyde and the first quaternary ammonium bifluoride compound of the present invention represented by the above formula (I) with tetrahydrofuran, ethyl ether, isopropyl ether or the like. It is achieved by charging in a suitable solvent, and stirring and mixing at a low temperature of preferably 100 ° C. to 170 ° C. for 2 hours to 5 hours. After completion of the reaction, an appropriate inorganic acid is added to the reaction mixture, which is then extracted with an extraction solvent such as ethyl ether, isopropyl ether, dichloroethane, and ethyl acetate.
  • an extraction solvent such as ethyl ether, isopropyl ether, dichloroethane, and ethyl acetate.
  • the desired reaction product (nitro alcohol) can be obtained by performing processes such as chromatography.
  • a quaternary ammonium bifluoride compound capable of exhibiting high diastereoselectivity and enantioselectivity as a catalyst, a two-mouth alcohol having a specific steric structure can be produced with high purity. be able to.
  • the first quaternary ammonium bifluoride compound of the present invention was used has been described, but instead of the first quaternary ammonium bifluoride compound, the second quaternary ammonium bifluoride compound of the present invention is used.
  • a quaternary ammonium bifluoride compound may be used.
  • the amount of the silyl nitrate and the aldehyde of the formula (III) and various reaction conditions are the same as described above.
  • the nitro alcohol obtained by the production method of the present invention has, for example, the following formula (V):
  • V may be substituted with a C 1 to C 6 straight-chain alkoxy group, a C 3 to C 6 branched-chain alkoxy group, an aralkyloxy group, or an aryl group, c 1 straight-chain alkyl group to c 5, there Les, linear Arukokishi groups force ,, c 3 of ci ⁇ C 6
  • branched-chain alkoxy group ⁇ C 6, or Ararukiruokishi group may be replacement by or Ariru group, a branched alkyl group of C 3 -C 5; and R 7 is, C ⁇ C i. Straight chain alkyl group, c 3 ⁇ c 1.
  • a silyl nitrate salt of the same compound was obtained in the same manner as in Reference Example 1 except that 31-benzyloxy-12-tropopropane was used instead of nitroethane in Reference Example 1.
  • Table 1 shows the NMR spectrum data of the obtained silylnitronate.
  • the boiling point of the obtained silyl nitronate is 112 ° CZ 0.003 mm
  • Table 2 shows the NMR spectrum data of the obtained Compound (3).
  • Reaction vessel 20 OML, added CH 2 C 1 2 (10 mL ) solution of the compound obtained in Reference Example 3 (3) (1. 7 g , 3 Ommo 1), further acetic acid (6, 0 mL , 0.5M) was added, followed by NCS (8. Og, 6 Ommo 1) and NaI (8.9 g, 6 Ommo 1). After heating the reaction mixture at 100 ° C for 9 hours while stirring, a saturated aqueous solution of sodium sulfite was washed with water until the color of the reaction solution became pale yellow, and extracted twice with ether. Neutralized with saturated aqueous sodium bicarbonate.
  • Table 3 shows the NMR spectrum data of the obtained compound (4).
  • Table 3 NMR spectra of the compound (4)
  • Ar 1 represents 3,5-bistriflurylmethylphenyl
  • a well-dried 10 OmL branched reaction vessel the compound obtained in Reference Example 4 (4) (14.6 g, 23 mmo 1 ) In THF (3 OmL) and cooled to 78 ° C, then add i-PrMgBr (0.83M HF solution, 33 mL, .27.6 mmo1) and raise to 0 ° C. Warm and stir for 0.5 h.
  • B (OH 3 ) 3 (4.OmL, 35 mmo 1) and THF (45 mL) were added to another well-dried 20 OmL three-necked reaction vessel, which was cooled to 178 ° C.
  • Table 4 shows the NMR spectrum data of the obtained compound (5).
  • Table 5 shows the NMR spectrum data of the obtained compound (7).
  • Table 6 shows the NMR spectrum data of the obtained Compound (8).
  • Table 7 shows the NMR spectrum data of the obtained compound (10).
  • the diastereomer ratio of the product obtained above was calculated from the results of -I-NMR analysis.
  • the optical purity was determined using a chiral column (DA I CEL. Chira 1 ak AS) and hexane as the solvent. The measurement was performed using monoisopropyl alcohol (50: 1 (volume ratio)).
  • the HPLC retention time of this 2-((N-Boc-amino) 1-1_phenyl-2-propanol was separately synthesized from (1R, 2S)-(1-) 1-noruefuedrin, which is available as a reagent.
  • (1R, 2S) -2- (NBoc-amino) 1-1Phenyl-11-propanol was compared with the HPLC retention time of the absolute configuration, and (1R, 2S) I found something.
  • Table 8 shows NMR spectrum data of 2- (N-Boc-amino) -1-phenyl-1-propanol obtained above.
  • a tro alcohol having a specific steric structure can be produced with high purity. can do.
  • the quaternary ammonium bifluoride of the present invention and the method for producing nitro alcohol using the quaternary ammonium bifluoride are particularly useful in the production of intermediate substances such as pharmaceuticals and agricultural chemicals.

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Abstract

L'invention concerne un composé de bifluorure d'ammonium quaternaire, et un procédé destiné à produire de façon stéréosélective un nitroalcool au moyen de ce composé. Le composé de bifluorure d'ammonium quaternaire est représenté par la formule (I) suivante. En présence du composé de formule (I), un nitronate de silyle obtenu par silylation d'un composé de nitroalcane est mis en réaction avec un aldéhyde. Ainsi, un nitroalcool hautement sélectionné sur le plan stérique peut être produit.
PCT/JP2003/009500 2003-02-27 2003-07-25 Compose de bifluorure d'ammonium quaternaire et procede de production de nitroalcool au niveau de ce compose Ceased WO2004076459A1 (fr)

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JP2004568777A JP4593289B2 (ja) 2003-02-27 2003-07-25 四級アンモニウムビフルオリド化合物およびそれを用いたニトロアルコールの製造方法
AU2003252268A AU2003252268A1 (en) 2003-02-27 2003-07-25 Quaternary ammonium bifluoride compound and process for producing nitroalcohol with the same

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ES2238020A1 (es) * 2005-04-15 2005-08-01 Universidad Del Pais Vasco Euskal Herriko Unibertsitatea Procedimiento de preparaciones de 1,2-nitroalcoholes opticamente activos.
JP4775915B2 (ja) * 2005-07-29 2011-09-21 長瀬産業株式会社 グアニジン−チオウレア化合物およびそれを用いたニトロアルコールの製造方法
US8367820B2 (en) 2005-03-03 2013-02-05 Nippon Soda Co., Ltd. Optically active ammonium salt compound, production intermediate thereof, and production method thereof

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JP3724046B2 (ja) * 1996-03-19 2005-12-07 チッソ株式会社 不斉合成触媒の調製法
JP2002173492A (ja) * 2000-12-07 2002-06-21 Nagase & Co Ltd 軸不斉を有する光学活性な４級アンモニウム塩とそれを用いたβ−ヒドロキシケトンの立体選択的合成

Non-Patent Citations (1)

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Title
OOI T. ET AL.: "Designer chiral quaternary ammonium bifluorides as an efficient catalyst for asymmetric nitroaldol reaction of silyl nitronates with aromatic aldehydes", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 125, no. 8, 2003, pages 2054 - 2055, XP002982275 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8367820B2 (en) 2005-03-03 2013-02-05 Nippon Soda Co., Ltd. Optically active ammonium salt compound, production intermediate thereof, and production method thereof
JP5296375B2 (ja) * 2005-03-03 2013-09-25 日本曹達株式会社 ２つの軸不斉を有する光学活性アンモニウム塩化合物の製造方法
US8962898B2 (en) 2005-03-03 2015-02-24 Nippon Soda Co., Ltd. Optically active ammonium salt compound, production intermediate thereof, and production method thereof
ES2238020A1 (es) * 2005-04-15 2005-08-01 Universidad Del Pais Vasco Euskal Herriko Unibertsitatea Procedimiento de preparaciones de 1,2-nitroalcoholes opticamente activos.
ES2238020B2 (es) * 2005-04-15 2006-04-01 Universidad Del Pais Vasco Euskal Herriko Unibertsitatea Procedimiento de preparaciones de 1,2-nitroalcoholes opticamente activos.
JP4775915B2 (ja) * 2005-07-29 2011-09-21 長瀬産業株式会社 グアニジン−チオウレア化合物およびそれを用いたニトロアルコールの製造方法

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JPWO2004076459A1 (ja) 2006-06-01
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