JPWO2009051025A1 - Catalysts for phosphorus-containing compounds and sulfur-containing compounds - Google Patents

Abstract

An object of the present invention is to provide a method for producing an alkenyl phosphorus compound using a hydrogenated phosphonic acid ester, a hydrogenated phosphinic acid ester or a disubstituted phosphine oxide as a starting material and using an inexpensive catalyst. Complex compounds represented by [HNi (PR1R2R3) 2] + X- or [HNi (R1R2P (CH2) xPR4R5)] + X- (wherein R1, R2, R3, R4 and R5 are each independently substituted) Or an unsubstituted hydrocarbon group, X is an anion of an acid (eg, an inorganic or organic acid) that is a hydride donor, and x is a positive integer.

Description

  The present invention relates to a cationic nickel hydride complex and a method for producing the same. The present invention also relates to the production of alkenyl phosphorus compounds (eg, vinyl phosphonic acid esters) and alkenyl sulfide compounds (eg, phenyl vinyl sulfide) using this complex. It is known that such an alkenyl phosphorus compound has its basic skeleton found in nature and exhibits physiological activity by acting with an enzyme or the like. This compound is also an extremely useful compound that can be easily converted into tertiary phosphine and the like widely used as an auxiliary ligand for various catalytic reactions. Furthermore, the compounds are a group of compounds that are highly useful in the synthesis of fine chemicals, such as easily reacting with nucleophiles and radical species, and can also be used in Horner-Wittig reactions. In addition, these compounds are used as non-halogen flame retardants for polymers and plastics.

  As a method for synthesizing such an alkenyl phosphorus compound with the formation of a carbon-phosphorus bond, a corresponding alkenyl halide compound is synthesized by hydrogenated phosphinic acid ester and disubstituted phosphine oxide (hereinafter these phosphorus compounds are collectively referred to as P A method of substituting with -H compound) is conceivable. However, in this method, it is necessary to add a base for capturing the hydrogen halide generated simultaneously with the reaction, thereby producing a large amount of a hydrogen halide salt. Moreover, the alkenyl halide compound which is the starting material is not always easily available industrially and generally has toxicity. For this reason, this method is not considered to be an industrially advantageous method. On the other hand, although the manufacturing method of the alkenyl phosphorus compound by addition of a P-H compound to acetylene using a catalyst is also reported recently (patent documents 1-5 = Japanese Patent Nos. 2775426, 2777985, 2849712). No. 3, No. 3007984, No. 3041396, etc.) are all methods using an expensive palladium or rhodium catalyst.

  Further, Patent Documents 6 to 9 (Japanese Patent Application Laid-Open Nos. 2004-026655, 2004-075688, Japanese Patent Application Laid-Open No. 2005-232060, and Japanese Patent Application Laid-Open No. 2005-232060) are known as addition of P—H by zero-valent Ni. Further, Patent Documents 10 to 12 (Special Tables 2001-518905, Special Tables 2002-518507, and JP-A-2005-132841) are also known.

  Patent Document 13 (Japanese Patent Application Laid-Open No. 2005-068096) is known as addition of S—H by zero-valent Ni.

As for the cationic complex nickel hydride, only the coordinated saturated [HNi (PR ₃ ) ₄ ] ⁺ X ^−, that is, the pentacoordinate one having four phosphine ligands has been known (Non-patents) Literature 1-4 (The organic chemistry of nickel, by PW Jolly and G. Wilke, Vol. 1, Academic Press, 1974, chapter IV, US 67-68223; J. Am. Chem. Soc. 1970, 92, 4217; J. Am. Chem. Soc. 1970, 92, 6777; 1970, 92, 67, 1991, 30, 394; 85; 1972, 94, 2994.)). These cationic complexes are industrially used for transfer of olefins and polymerization catalysts for dienes.
Japanese Patent No. 2775426 Japanese Patent No. 2777985 Japanese Patent No. 2849712 Japanese Patent No. 3007984 Patent No. 3041396 JP2004026665 JP2004-077568 JP-A-2005-232067 JP-A-2005-232060 Special table 2001-518905 Special table 2002-518507 JP-A-2005-132841 JP 2005-068096 A The organic chemistry of nickel, by p. W. Jolly and G. Wilke, Vol. 1, Academic Press, 1974, chapter IV; US 67-682623; Inorganic Chemistry, 1970, 9, 392; Inorganic Chemistry, 1970, 9, 394; 1991, 30, 2005; Am. Chem. Soc. 1970, 92, 4217 J. et al. Am. Chem. Soc. 1970, 92, 4217 J. et al. Am. Chem. Soc. 1970, 92, 6777; 1970, 92, 6785; 1972, 94, 2994.

  In the production of vinyl phosphorus and vinyl sulfides, a neutral nickel catalyst having a zero-valent phosphine as a ligand is used (Patent Documents 6 to 13, etc.). These catalyst systems generally require 4 equivalents or more of phosphine to nickel in order to obtain high catalytic activity. However, since phosphines are expensive, there is a demand for the appearance of a catalyst that uses a small amount of phosphine and can withstand an industrial scale. In addition, since these zero-valent nickel catalysts that are conventionally used are oxidized immediately when exposed to air, the handling thereof must be performed in an oxygen-free atmosphere, and the operation is complicated.

As a result of intensive studies, the present inventors have investigated the reaction with acid (for example, inorganic acid or organic acid) HX that is a hydride donor using Ni (PR ³ ) ₄ . It was unexpectedly found that the complex [HNi (PR ₃ ) ₂ ] ⁺ X ⁻ is quantitatively generated, and [HNi (PR ¹ R ² R ³ ) ₂ ] ⁺ X ⁻ or [HNi (R ¹ R ² P ( CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ (wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently substituted or substituted A hydrocarbon group, X is an anion of an acid (for example, an inorganic acid or an organic acid) that is a hydride donor, and x is a positive integer.) I found it. These cationic complexes are characterized in that they can be handled in air. Therefore, it has the characteristic that it can be actually sold as a product for industrial use.

  Specifically, the present invention provides a cationic nickel hydride complex and a method for producing the same. The present invention also provides a catalytic reaction using the above cationic complex (production of vinyl phosphorus and vinyl sulfide by P—H addition + S—H addition reaction).

As a specific chemical formula of the compound of the present invention, [HNi (PR ¹ R ² R ³ ) ₂ ] ⁺ X ⁻ or [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, and X is a hydride donor An anion of an acid (for example, an inorganic acid or an organic acid, and x is a positive integer).

Can be mentioned. Here, regarding phosphine PR ₃ (wherein R is a hydrocarbon group or a derivative thereof as defined herein): R of phosphine PR ₃ does not necessarily have to be the same. Further, it may be a chelate type such as R ₂ P (CH ₂ ) × PR ₂ (however, in this case, it is 1 instead of 2).
X: Inorganic oxoacid anion OY, specifically, O—P (O) (OH) ₂ , O—S (O) ₂ (OH), O—P (O) Ph ₂ (where Ph is a phenyl group ), O—P (O) (OR) ₂ (wherein R is a hydrocarbon group or a derivative thereof as defined herein), ClO ₄ , RCO _{2 and the} like (ie, inorganic And oxo acid radicals (after removal of H of OH).

  In the metal complex catalyzed reaction, generally, the higher the coordination unsaturated, the higher the activity. That is, it is expected that the smaller the number of phosphine ligands, the higher the catalytic activity. Moreover, since the usage-amount of expensive phosphines can be saved, it can be said that it is a preferable aspect as an industrial process.

Accordingly, the present invention provides the following.
(1) a complex compound represented by [HNi (PR ¹ R ² R ³ ) ₂ ] ⁺ X ⁻ or [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid which is a hydride donor, and x Is a positive integer.)
(2) The complex compound according to the above item, wherein the hydrocarbon group is selected from the group consisting of an alkyl group, an aryl group, a cycloalkyl group, an allyl group, an alkenyl group, and an aralkyl group.
(3) The hydrocarbon group is selected from the group consisting of a C1-C6 alkyl group, a C3-C8 aryl group, a C3-C8 cycloalkyl group, a C3-C8 allyl group, a C2-C6 alkenyl group, and a C3-C8 aralkyl group. The complex compound according to the above item.
(4) The complex compound according to the above item, wherein the hydrocarbon group is independently selected from the group consisting of a methyl group, an ethyl group and a phenyl group.
(5) In the complex compound, the hydrocarbon group is [HNi (PR ¹ R ² R ³ ) ₂ ] ⁺ X ⁻ in which the hydrocarbon group is a C1-C2 alkyl group or a C6 aryl group, or the hydrocarbon group is The complex compound according to the above item, which is a C1 alkyl group and x is 2 [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ .
(6) The complex compound according to the above item, wherein the acid that is the hydride donor is an inorganic acid or an organic acid.
(7) The complex compound according to the above item, wherein the acid that is the hydride donor is an inorganic acid.
(8) The complex compound according to the above item, wherein the acid that is the hydride donor is an organic acid.
(9) The complex compound according to the above item, wherein the anion of the acid which is the hydride donor is an inorganic oxoacid anion.
(10) an anion of the hydride donor and is acid, acetate ion, sulfate ion, phosphate _{^{ion, - O-P (O)}} (OH) 2, - O-S (O) 2 (OH), - _{^{O-P (O) R 6}} 2, - O-P (O) (oR 6) 2 and _{^{ClO 4 -, R 6 CO 2}} - is selected from the group consisting of, ^{R 6} are each independently a substituted The complex compound according to the above item, which is a substituted or unsubstituted hydrocarbon group.
(11) wherein the acid is a hydride donor, acetate ion, sulfate ion, phosphate _{^{ion, - O-P (O)}} (C 6 H 5) 2 and _{^{- O-P (O) (}} C 6 H 5 O The complex compound according to the above item, selected from the group consisting of ₂ ).
(12) The acid as the hydride donor is H ₃ PO ₄ , H ₂ SO ₄ , (C ₆ H ₅ O) ₂ PO ₂ H, or (C ₆ H ₅ ) ₂ PO ₂ H. The complex compound described.
(13) A catalyst composition for producing an alkenylphosphonic acid ester compound or an alkenyl sulfide compound comprising the complex compound described in the above item.
(14) Zero valent nickel or a nickel precursor that is easily reduced to zero valence in the system, PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ), and HX (here Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, and X is an anion of an acid which is a hydride donor. , X is a positive integer).
(15) Item 14 wherein the zero-valent nickel or the nickel precursor easily reduced to zero-valent in the system is bis (1,5-cyclooctadiene) nickel (O) (Ni (cod) ₂ ) A mixture or combination as described in.
(16) The mixture or combination according to item 14, further having the characteristics according to any one of items 2 to 12.
(17) Zero-valent nickel or a nickel precursor that is easily reduced to zero valence in the system, PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ), and HX (here Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, and X is an anion of an acid which is a hydride donor. , X is a positive integer)) or mixtures thereof in the manufacture of alkenylphosphonic acid ester compounds or alkenyl sulfide compounds.
(18) A catalyst or catalyst raw material for producing an alkenylphosphonic acid ester compound or alkenyl sulfide compound, comprising the mixture or combination according to item 17.
(19) A compound represented by Ni (PR ¹ R ² R ³ ) ₄ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ , and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid which is a hydride donor, and x is a positive integer. ) Mixture or combination with.
(20) The mixture or combination according to item 19, further having the characteristics according to any one of items 2 to 12.
(21) a compound represented by Ni (PR ¹ R ² R ³ ) ₄ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ , and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid which is a hydride donor, and x is a positive integer. ) In the production of alkenylphosphonic acid ester compounds or alkenyl sulfide compounds.
(22) A catalyst or catalyst raw material for the production of an alkenylphosphonic acid ester compound or an alkenyl sulfide compound comprising the mixture or combination described in the above item.
(23) Alkenylphosphonic acid ester compound (R ^a1 O) (R ^a2 O) P (O) —R ^b
(Wherein R ^a1 and R ^a2 are each independently substituted or unsubstituted hydrocarbon groups or together form a cyclic hydrocarbon group, and R ^b is substituted or substituted. Alkenyl sulfide compound R ^c S—R ^b
Wherein R ^c is a substituted or unsubstituted hydrocarbon group and R ^b is a substituted or unsubstituted alkenyl group, comprising:
A) Phosphonate compound (R ^a1 O) (R ^a2 O) P (O) H or sulfide compound R ^c SH, and the general formula (2)
R ^b1 (C≡CR ^b2 ) _n (2)
(In the formula, n is 1 or 2, and R ^b1 is a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, aralkyl group, heteroaryl group, alkenyl group, when n is 1. An alkoxy group, an aryloxy group, or a silyl group, when n is 2, an alkylene group, a cycloalkylene group, an arylene group, an aralkylene group, a heteroarylene group, an alkenylene group, an alkylenedioxy group, an aryleneoxy group, or a silyl group And a complex compound according to Item 1 or a mixture or combination according to Item 11 or 16 is added simultaneously or sequentially to a reaction system with the acetylene compound represented by R ^b2 represents a hydrogen atom. Mixing to produce the alkenylphosphonic acid ester compound or alkenyl sulfide compound It encompasses methods.
(24) In the step A), bis (1,5-cyclooctanediene) nickel (O), the PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ and a hydride donor The method according to the above item, comprising reacting the phosphonic acid ester compound or sulfide compound with the alkyne compound in the presence of an acid.
(25) The method according to the above item, which comprises a step of removing the PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ after the step A).
(26) A step of removing the PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ by subjecting the reaction system to heating and decompression under a nitrogen stream after the step A). The method according to the above item, comprising:
(27) The method according to the above item, which comprises a step of deactivating the nickel catalyst after the step B).
(28) The method according to the above item, comprising a step of oxidizing the nickel catalyst or phosphine by performing air blowing stirring after the step B).
(29) The method according to the above item, further comprising, after the step C), a step of D) filtering off the alkenylphosphonic acid ester compound or alkenyl sulfide compound.
(30) The method according to the above item, comprising a step of concentrating and purifying the filtrate obtained by the filtration after the step D) by distillation.
(31) A raw material for producing an alkenylphosphonic acid ester compound or alkenyl sulfide compound produced by the method described in the above item.

  Accordingly, these and other advantages of the invention will be apparent upon reading the following detailed description.

  The present invention provides high yields of alkenyl phosphorus compounds (alkenyl phosphonic acid esters, alkenyl phosphinic acid esters and alkenyl phosphine oxide compounds) useful as synthetic intermediates for physiologically active substances such as pharmaceuticals and agricultural chemicals and ligands for catalyst preparation. And a highly practical manufacturing method. The method for synthesizing an alkenyl phosphorus compound of the present invention uses a relatively inexpensive nickel complex catalyst as a catalyst, and converts a P—H compound (hydrogenated phosphonate, hydrogenated phosphinate, and disubstituted phosphine oxide) to acetylene. It can be synthesized simply, safely and efficiently simply by reacting, and the product can be easily separated and purified. Therefore, the present invention has a great industrial effect.

  The method for producing an alkenylphosphonic acid ester compound or alkenyl sulfide compound of the present invention is characterized in that the amount of catalyst used is remarkably reduced and easy to handle as compared with the case where a conventional catalyst is used. That is, in the conventional catalyst, about 5 mole percent of the catalyst is used with respect to the reaction substrate in order to obtain the alkenylphosphonic acid ester compound or alkenyl sulfide compound in a high yield. However, the use of such expensive catalysts is far from the industrial scale. When the catalyst of the present invention was used, a high yield of 90% or more, and in most cases 95% or more was achieved when the amount of the catalyst used was about 0.5 mole percent. With such a yield, production commensurate with the industrial scale can be performed. Also for toxic and expensive phosphine ligands, conventional catalysts generally have a nickel to phosphorus ratio of 1 to 4, whereas in the present invention a nickel to phosphorus ratio of 1 to 2 is sufficient. It is. Furthermore, the conventional catalyst is deactivated immediately in the air, whereas the present catalyst can be handled easily even in the air, so that it can be used conveniently.

  The present invention will be described below. Throughout this specification, it should be understood that the singular forms also include the plural concept unless specifically stated otherwise. Thus, it should be understood that singular articles (eg, “a”, “an”, “the”, etc. in the case of English) also include the plural concept unless otherwise stated. In addition, it is to be understood that the terms used in the present specification are used in the meaning normally used in the art unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.

(Definition of terms)
The definitions of terms particularly used in the present specification are described below.

  In the present specification, the term “complex compound” or “complex” is used interchangeably, and is used in the meaning commonly used in the art, and is coordinated around an atom or ion of a metal element or metal-like element. A group in which children (atoms, atomic groups, molecules, or ions) are combined. In addition to complex ions and salts, non-electrolytes such as nickel-carbonyl (four carbon monoxide molecules coordinate to nickel atoms) are also included.

  In the present specification, the “hydrocarbon” is used in a normal meaning used in the art, and refers to an arbitrary substance in which carbon and hydrogen are bonded or a derivative thereof. When a substituent is bonded, it may be particularly referred to as a substituted (substituted) hydrocarbon.

  As used herein, “substitution” refers to replacement of a specific hydrogen atom in an organic compound with another atom or atomic group.

  In the present specification, the “substituent” refers to an atom or a functional group substituted with another in a chemical structure.

As used herein, “acid that is a hydride donor” refers to any acid that can donate hydride (H ⁺ ), and typically includes inorganic and organic acids.

  In the present specification, “inorganic acid” is a generic term for inorganic compounds having acid properties. Contains hydrochloric acid, sulfuric acid, and nitric acid.

  In the present specification, the “organic acid” is a general term for organic compounds having acid properties. Carboxylic acids (eg acetic acid, benzoic acid, salicylic acid) are included. Preferably acetic acid is used.

  In the present specification, the “anion” is a general term for ions having a negative charge.

  In the present specification, unless otherwise specified, substitution is the substitution of one or more hydrogen atoms in a certain organic compound or substituent with another atom or atomic group, or a double bond or triple bond. That means. It is possible to remove one hydrogen atom and replace it with a monovalent substituent, or combine with a single bond to form a double bond, and remove two hydrogen atoms to form a divalent substituent. It can be substituted or combined with a single bond to form a triple bond.

  Examples of the substituent in the present invention include alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, alkoxy, carbocyclic group, heterocyclic group, halogen, hydroxy, thiol, cyano, nitro, amino, carboxy, carbamoyl, acyl, acylamino, Examples include, but are not limited to, thiocarboxy, amide, substituted carbonyl, substituted thiocarbonyl, substituted sulfonyl, or substituted sulfinyl. Such a substituent can be appropriately used in the present invention when designing an amino acid.

  Preferably, when a plurality of substituents are present, each may be independently a hydrogen atom or alkyl, but not all of the plurality of substituents are hydrogen atoms. More preferably, independently when there are multiple substituents, each may be independently selected from the group consisting of hydrogen and C1-C6 alkyl. The substituents may all have a substituent other than hydrogen, but preferably have at least one hydrogen, more preferably 2 to n (where n is the number of substituents) hydrogen. obtain. It may be preferred that the number of hydrogens in the substituent is large. This is because a large substituent group or a polar substituent group may have a hindrance to the effect of the present invention (particularly, interaction with an aldehyde group). Accordingly, the substituent other than hydrogen may preferably be C1-C6 alkyl, C1-C5 alkyl, C1-C4 alkyl, C1-C3 alkyl, C1-C2 alkyl, methyl and the like. However, since the effect of the present invention may be enhanced, it may be preferable to have a large substituent.

  In the present specification, C1, C2,..., Cn represent the number of carbon atoms (where n represents an arbitrary positive integer). Therefore, C1 is used to represent a substituent having 1 carbon.

As used herein, “alkyl” refers to a monovalent group formed by loss of one hydrogen atom from an aliphatic hydrocarbon (alkane) such as methane, ethane, or propane, and is generally represented by C _n H _{2n + 1} −. Where n is a positive integer. Alkyl can be linear or branched. In the present specification, the “substituted alkyl” refers to an alkyl in which H of the alkyl is substituted with a substituent specified below. Specific examples thereof include C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl. C1-C11 alkyl or C1-C12 alkyl, C1-C2 substituted alkyl, C1-C3 substituted alkyl, C1-C4 substituted alkyl, C1-C5 substituted alkyl, C1-C6 substituted alkyl C1-C7 substituted alkyl, C1-C8 substituted alkyl, C1-C9 substituted alkyl, C1-C10 substituted alkyl, C1-C11 substituted alkyl or C1-C12 substituted alkyl obtain. Here, for example, C1-C10 alkyl means linear or branched alkyl having 1 to 10 carbon atoms, methyl (CH _3- ), ethyl (C ₂ H _5- ), n-propyl. _{(CH 3 CH 2 CH 2 -} ), isopropyl _{((CH 3) 2 CH -} ), n- butyl _{(CH 3 CH 2 CH 2 CH} 2 -), n- pentyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 -), n-hexyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 CH 2 -), n- heptyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 CH 2 CH 2 -), n- octyl _(CH 3 CH _{2 CH 2 CH 2 CH 2 CH} 2 CH 2 CH 2 -), n- nonyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 CH 2 CH 2 CH 2 CH 2 -), n- decyl _(CH 3 CH 2 CH ₂ C _{H 2 CH 2 CH 2 CH 2} CH 2 CH 2 CH 2 -), - C (CH 3) 2 CH 2 CH 2 CH (CH 3) 2, -CH 2 CH (CH 3) such as ₂ are exemplified. In addition, for example, C1-C10 substituted alkyl refers to C1-C10 alkyl, in which one or more hydrogen atoms are substituted with a substituent.

  As used herein, “optionally substituted alkyl” means that either “alkyl” or “substituted alkyl” as defined above may be used.

As used herein, “alkylene” refers to a divalent group formed by losing two hydrogen atoms from an aliphatic hydrocarbon (alkane) such as methylene, ethylene, propylene, and is generally represented by —C _n H _2n —. Where n is a positive integer. The alkylene can be straight or branched. As used herein, “substituted alkylene” refers to an alkylene in which H of alkylene is substituted with a substituent specified below. Specific examples thereof include C1-C2 alkylene, C1-C3 alkylene, C1-C4 alkylene, C1-C5 alkylene, C1-C6 alkylene, C1-C7 alkylene, C1-C8 alkylene, C1-C9 alkylene, C1-C10 alkylene. C1-C11 alkylene or C1-C12 alkylene, C1-C2 substituted alkylene, C1-C3 substituted alkylene, C1-C4 substituted alkylene, C1-C5 substituted alkylene, C1-C6 substituted alkylene C1-C7 substituted alkylene, C1-C8 substituted alkylene, C1-C9 substituted alkylene, C1-C10 substituted alkylene, C1-C11 substituted alkylene or C1-C12 substituted alkylene obtain. Here, for example, C1-C10 alkylene means linear or branched alkylene having 1 to 10 carbon atoms, methylene (—CH ₂ —), ethylene (—C ₂ H ₄ —), n - propylene _{(-CH 2 CH 2 CH 2 -} ), isopropylene _{(- (CH 3) 2 C} -), n- butylene _{(-CH 2 CH 2 CH 2 CH} 2 -), n- pentylene _(-CH 2 CH _{2 CH 2 CH 2 CH 2 -} ), n- hexylene _{(-CH 2 CH 2 CH 2 CH} 2 CH 2 CH 2 -), n- heptylene _{(-CH 2 CH 2 CH 2 CH} 2 CH 2 CH 2 CH 2 - ), N-octylene (—CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ —), n-nonylene (—CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -), n-decylene _{(-CH 2 CH 2 CH 2 CH} 2 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 -), - CH 2 C (CH 3) 2 - and the like are exemplified. Further, for example, C1-C10 substituted alkylene refers to C1-C10 alkylene, in which one or more hydrogen atoms are substituted with a substituent. In the present specification, “alkylene” may contain one or more atoms selected from an oxygen atom and a sulfur atom.

  As used herein, “optionally substituted alkylene” means that either “alkylene” or “substituted alkylene” as defined above may be used.

  As used herein, “cycloalkyl” refers to alkyl having a cyclic structure. “Substituted cycloalkyl” refers to a cycloalkyl in which H of the cycloalkyl is substituted by the substituent specified below. Specific examples include C3-C4 cycloalkyl, C3-C5 cycloalkyl, C3-C6 cycloalkyl, C3-C7 cycloalkyl, C3-C8 cycloalkyl, C3-C9 cycloalkyl, C3-C10 cycloalkyl, C3-C11. Cycloalkyl, C3-C12 cycloalkyl, C3-C4 substituted cycloalkyl, C3-C5 substituted cycloalkyl, C3-C6 substituted cycloalkyl, C3-C7 substituted cycloalkyl, C3-C8 substituted Cycloalkyl, C3-C9 substituted cycloalkyl, C3-C10 substituted cycloalkyl, C3-C11 substituted cycloalkyl or C3-C12 substituted cycloalkyl. For example, cycloalkyl is exemplified by cyclopropyl, cyclohexyl and the like.

  In the present specification, the “optionally substituted cycloalkyl” means either “cycloalkyl” or “substituted cycloalkyl” as defined above.

In the present specification, “alkenyl” refers to a monovalent group produced by losing one hydrogen atom from an aliphatic hydrocarbon having one double bond in the molecule, and is generally represented by C _n H _2n−1 —. (Where n is a positive integer greater than or equal to 2). “Substituted alkenyl” refers to alkenyl in which H of alkenyl is substituted by the substituent specified below. Specific examples include C2-C3 alkenyl, C2-C4 alkenyl, C2-C5 alkenyl, C2-C6 alkenyl, C2-C7 alkenyl, C2-C8 alkenyl, C2-C9 alkenyl, C2-C10 alkenyl, C2-C11 alkenyl or C2-C12 alkenyl, C2-C3 substituted alkenyl, C2-C4 substituted alkenyl, C2-C5 substituted alkenyl, C2-C6 substituted alkenyl, C2-C7 substituted alkenyl, C2-C8 substituted Alkenyl, C2-C9 substituted alkenyl, C2-C10 substituted alkenyl, C2-C11 substituted alkenyl or C2-C12 substituted alkenyl. Here, for example, is C2~C10 alkyl means a straight or branched alkenyl containing 2 to 10 carbon atoms, vinyl _(CH 2 = CH-), allyl _{(CH 2 = CHCH 2 -)} , CH ₃ CH═CH— and the like are exemplified. Also, for example, C2-C10 substituted alkenyl refers to C2-C10 alkenyl, in which one or more hydrogen atoms are substituted with substituents.

  As used herein, “optionally substituted alkenyl” means that either “alkenyl” or “substituted alkenyl” as defined above may be used.

In the present specification, “alkenylene” refers to a divalent group formed by losing two hydrogen atoms from an aliphatic hydrocarbon having one double bond in the molecule, and is generally —C _n H _2n-2 —. (Where n is a positive integer greater than or equal to 2). “Substituted alkenylene” refers to alkenylene in which H of alkenylene is substituted by the substituent specified below. Specific examples include C2-C25 alkenylene or C2-C25 substituted alkenylene, especially C2-C3 alkenylene, C2-C4 alkenylene, C2-C5 alkenylene, C2-C6 alkenylene, C2-C7 alkenylene, C2 -C8 alkenylene, C2-C9 alkenylene, C2-C10 alkenylene, C2-C11 alkenylene or C2-C12 alkenylene, C2-C3-substituted alkenylene, C2-C4-substituted alkenylene, C2-C5-substituted alkenylene, C2- C6-substituted alkenylene, C2-C7 substituted alkenylene, C2-C8 substituted alkenylene, C2-C9 substituted alkenylene, C2-C10 substituted alkenylene, C2-C11 substituted alkenylene or C2~C12 substituted alkenylene are preferred. Here, for example, is C2~C10 alkyl means a straight or branched alkenylene including 2-10 carbon _{atoms, -CH = CH -, - CH} = CHCH 2 -, - (CH 3) C = CH- and the like are exemplified. Further, for example, C2-C10 substituted alkenylene refers to C2-C10 alkenylene, in which one or more hydrogen atoms are substituted with substituents. As used herein, “alkenylene” may contain one or more atoms selected from an oxygen atom and a sulfur atom.

  As used herein, “optionally substituted alkenylene” means that either “alkenylene” or “substituted alkenylene” as defined above may be used.

  As used herein, “cycloalkenyl” refers to alkenyl having a cyclic structure. “Substituted cycloalkenyl” refers to cycloalkenyl in which H of cycloalkenyl is substituted by the substituent specified below. Specific examples include C3-C4 cycloalkenyl, C3-C5 cycloalkenyl, C3-C6 cycloalkenyl, C3-C7 cycloalkenyl, C3-C8 cycloalkenyl, C3-C9 cycloalkenyl, C3-C10 cycloalkenyl, C3-C11. Cycloalkenyl, C3-C12 cycloalkenyl, C3-C4 substituted cycloalkenyl, C3-C5 substituted cycloalkenyl, C3-C6 substituted cycloalkenyl, C3-C7 substituted cycloalkenyl, C3-C8 substituted Cycloalkenyl, C3-C9 substituted cycloalkenyl, C3-C10 substituted cycloalkenyl, C3-C11 substituted cycloalkenyl or C3-C12 substituted cycloalkenyl. For example, preferable cycloalkenyl includes 1-cyclopentenyl, 2-cyclohexenyl and the like.

  In the present specification, “optionally substituted cycloalkenyl” means either “cycloalkenyl” or “substituted cycloalkenyl” as defined above.

As used herein, “alkynyl” refers to a monovalent group formed by losing one hydrogen atom from an aliphatic hydrocarbon having one triple bond in the molecule, such as acetylene, and is generally C _n H _{2n −3} − (where n is a positive integer of 2 or more). “Substituted alkynyl” refers to alkynyl in which H of alkynyl is substituted by the substituent specified below. Specific examples include C2-C3 alkynyl, C2-C4 alkynyl, C2-C5 alkynyl, C2-C6 alkynyl, C2-C7 alkynyl, C2-C8 alkynyl, C2-C9 alkynyl, C2-C10 alkynyl, C2-C11 alkynyl, C2-C12 alkynyl, C2-C3 substituted alkynyl, C2-C4 substituted alkynyl, C2-C5 substituted alkynyl, C2-C6 substituted alkynyl, C2-C7 substituted alkynyl, C2-C8 substituted Alkynyl, C2-C9 substituted alkynyl, C2-C10 substituted alkynyl, C2-C11 substituted alkynyl or C2-C12 substituted alkynyl. Here, for example, C2 to C10 alkynyl means, for example, a linear or branched alkynyl containing 2 to 10 carbon atoms, such as ethynyl (CH≡C—), 1-propynyl (CH ₃ C≡C -) Etc. are exemplified. In addition, for example, C2-C10 substituted alkynyl refers to C2-C10 alkynyl, in which one or more hydrogen atoms are substituted with a substituent.

  As used herein, “optionally substituted alkynyl” means that either “alkynyl” or “substituted alkynyl” as defined above may be used.

As used herein, “alkoxy” refers to a monovalent group generated by loss of a hydrogen atom of a hydroxy group of an alcohol, and is generally represented by C _n H _{2n + 1} O— (where n is 1 or more). Is an integer). “Substituted alkoxy” refers to alkoxy in which H of alkoxy is substituted by a substituent specified below. Specific examples include C1-C2 alkoxy, C1-C3 alkoxy, C1-C4 alkoxy, C1-C5 alkoxy, C1-C6 alkoxy, C1-C7 alkoxy, C1-C8 alkoxy, C1-C9 alkoxy, C1-C10 alkoxy, C1-C11 alkoxy, C1-C12 alkoxy, C1-C2-substituted alkoxy, C1-C3-substituted alkoxy, C1-C4-substituted alkoxy, C1-C5-substituted alkoxy, C1-C6-substituted alkoxy, C1-C7 substituted alkoxy, C1-C8 substituted alkoxy, C1-C9 substituted alkoxy, C1-C10 substituted alkoxy, C1-C11 substituted alkoxy or C1-C12 substituted alkoxy . Here, for example, C1-C10 alkoxy means linear or branched alkoxy containing 1 to 10 carbon atoms, and includes methoxy (CH ₃ O—), ethoxy (C ₂ H ₅ O—), An example is n-propoxy (CH ₃ CH ₂ CH ₂ O—).

  In the present specification, “optionally substituted alkoxy” means either “alkoxy” or “substituted alkoxy” as defined above.

  As used herein, “heterocycle (group)” refers to a group having a cyclic structure including carbon and heteroatoms. Here, the hetero atom is selected from the group consisting of O, S and N, and may be the same or different, and may be contained in one or more than one. Heterocyclic groups can be aromatic or non-aromatic and can be monocyclic or polycyclic. The heterocyclic group may be substituted.

  In the present specification, the “optionally substituted heterocycle (group)” may be either the “heterocycle (group)” or “substituted heterocycle (group)” defined above. Means.

  As used herein, “alcohol” refers to an organic compound in which one or more hydrogen atoms of an aliphatic hydrocarbon are substituted with a hydroxyl group. In the present specification, it is also expressed as ROH. Here, R is an alkyl group. Preferably R may be C1-C6 alkyl. Examples of the alcohol include, but are not limited to, methanol, ethanol, 1-propanol, 2-propanol and the like.

  In this specification, the “carbocyclic group” is a group containing a cyclic structure containing only carbon, and the above-mentioned “cycloalkyl”, “substituted cycloalkyl”, “cycloalkenyl”, “substituted cyclo A group other than “alkenyl”. The carbocyclic group can be aromatic or non-aromatic and can be monocyclic or polycyclic. The “substituted carbocyclic group” refers to a carbocyclic group in which H of the carbocyclic group is substituted with a substituent specified below. Specific examples include C3-C4 carbocyclic group, C3-C5 carbocyclic group, C3-C6 carbocyclic group, C3-C7 carbocyclic group, C3-C8 carbocyclic group, C3-C9 carbocyclic group, C3-C10. Carbocyclic group, C3-C11 carbocyclic group, C3-C12 carbocyclic group, C3-C4-substituted carbocyclic group, C3-C5-substituted carbocyclic group, C3-C6-substituted carbocyclic group, C3- C7 substituted carbocyclic group, C3-C8 substituted carbocyclic group, C3-C9 substituted carbocyclic group, C3-C10 substituted carbocyclic group, C3-C11 substituted carbocyclic group or C3- It can be a C12 substituted carbocyclic group. The carbocyclic group can also be a C4-C7 carbocyclic group or a C4-C7 substituted carbocyclic group. Examples of the carbocyclic group include those in which one hydrogen atom is deleted from the phenyl group. Here, the hydrogen deletion position may be any position chemically possible, and may be on an aromatic ring or a non-aromatic ring.

  In the present specification, the “optionally substituted carbocyclic group” means that any of the above-defined “carbocyclic group” or “substituted carbocyclic group” may be used.

As used herein, “aryl” refers to a group formed by leaving one hydrogen atom bonded to an aromatic hydrocarbon ring, and is included in the present specification as a carbocyclic group. From benzene, phenyl group (C ₆ H _5- ), from toluene, tolyl group (CH ₃ C ₆ H ₄ -)-, from xylene, xylyl group ((CH ₃ ) ₂ C ₆ H _3- ), from naphthalene A naphthyl group (C ₁₀ H ₈ —) is derived.

  As used herein, “heterocyclic group” refers to a group having a cyclic structure including carbon and heteroatoms. Here, the heteroatoms are selected from the group consisting of O, S and N, and may be the same or different, and may be contained in one or more than one. Heterocyclic groups can be aromatic or non-aromatic and can be monocyclic or polycyclic. The “substituted heterocyclic group” refers to a heterocyclic group in which H of the heterocyclic group is substituted with a substituent specified below. Specific examples include C3-C4 carbocyclic group, C3-C5 carbocyclic group, C3-C6 carbocyclic group, C3-C7 carbocyclic group, C3-C8 carbocyclic group, C3-C9 carbocyclic group, C3-C10. Carbocyclic group, C3-C11 carbocyclic group, C3-C12 carbocyclic group, C3-C4-substituted carbocyclic group, C3-C5-substituted carbocyclic group, C3-C6-substituted carbocyclic group, C3- C7 substituted carbocyclic group, C3-C8 substituted carbocyclic group, C3-C9 substituted carbocyclic group, C3-C10 substituted carbocyclic group, C3-C11 substituted carbocyclic group or C3- One or more carbon atoms of the C12 substituted carbocyclic group may be substituted with a heteroatom. Heterocyclic groups can also be those in which one or more heteroatoms are substituted for the carbon atoms of a C4-C7 carbocyclic group or a C4-C7 substituted carbocyclic group. Examples of the heterocyclic group include thienyl group, pyrrolyl group, furyl group, imidazolyl group, and pyridyl group. The hydrogen deletion position may be any chemically possible position, and may be on an aromatic ring or a non-aromatic ring.

  In this specification, a carbocyclic group or heterocyclic group may be substituted with a divalent substituent in addition to being substituted with a monovalent substituent as defined below. Such divalent substitutions can be oxo substitutions (= O) or thioxo substitutions (= S).

  In this specification, “halogen” refers to fluorine (F), chlorine (Cl), bromine (Br), iodine (I), etc. belonging to group 17 of the periodic table (called group 17 in the recent definition). A monovalent group of an element.

  As used herein, “hydroxy” refers to a group represented by —OH. “Substituted hydroxy” refers to a hydroxy in which H is substituted with a substituent as defined below.

  In the present specification, the “thiol” is a group (mercapto group) in which an oxygen atom of a hydroxy group is substituted with a sulfur atom, and is represented by —SH. “Substituted thiol” refers to a group in which H of mercapto is substituted with a substituent defined below.

As used herein, “cyano” refers to a group represented by —CN. “Nitro” refers to a group represented by —NO ₂ . “Amino” refers to a group represented by —NH ₂ . “Substituted amino” refers to amino substituted with H as defined below.

  In this specification, “carboxy” refers to a group represented by —COOH. “Substituted carboxy” refers to a carboxy H substituted with a substituent as defined below.

  As used herein, “thiocarboxy” refers to a group in which an oxygen atom of a carboxy group is substituted with a sulfur atom, and may be represented by —C (═S) OH, —C (═O) SH, or —CSSH. “Substituted thiocarboxy” refers to thiocarboxy H substituted with the substituents defined below.

As used herein, “acyl” refers to a monovalent group formed by removing OH from a carboxylic acid. Representative examples of the acyl group include acetyl (CH ₃ CO—), benzoyl (C ₆ H ₅ CO—), and the like. “Substituted acyl” refers to an acyl hydrogen substituted with a substituent as defined below.

In the present specification, “amide” is a group obtained by substituting hydrogen of ammonia with an acid group (acyl group), and is preferably represented by —CONH ₂ . “Substituted amide” refers to a substituted amide.

  As used herein, “carbonyl” refers to a generic term for a substance including — (C═O) — which is a characteristic group of aldehyde and ketone. “Substituted carbonyl” means a carbonyl group substituted with a substituent selected below.

  In this specification, “thiocarbonyl” is a group in which an oxygen atom in carbonyl is substituted with a sulfur atom, and includes a characteristic group — (C═S) —. Thiocarbonyl includes thioketones and thioaldehydes. “Substituted thiocarbonyl” means thiocarbonyl substituted with a substituent selected below.

As used herein, “sulfonyl” refers to a generic term for a substance including a characteristic group —SO ₂ —. “Substituted sulfonyl” means a sulfonyl substituted with a substituent selected below.

  As used herein, “sulfinyl” is a generic term for a substance including a characteristic group —SO—. “Substituted sulfinyl” means sulfinyl substituted with a substituent selected below.

As used herein, “alkenylphosphonic acid ester compound”
(R ^a1 O) (R ^a2 O) P (O) —R ^b
(Wherein R ^a1 and R ^a2 are each independently substituted or unsubstituted hydrocarbon groups or together form a cyclic hydrocarbon group, and R ^b is substituted or substituted. No alkenyl group). It is known that an alkenyl phosphorus compound has its basic skeleton found in nature and exhibits physiological activity by acting with an enzyme or the like. This compound is also an extremely useful compound that can be easily converted into tertiary phosphine and the like widely used as an auxiliary ligand for various catalytic reactions. Furthermore, the compounds are a group of compounds that are highly useful in the synthesis of fine chemicals, such as easily reacting with nucleophiles and radical species, and can also be used in Horner-Wittig reactions.

As used herein, “alkenyl sulfide compound”
R ^c S-R ^b
Where R ^c is a substituted or unsubstituted hydrocarbon group and R ^b is a substituted or unsubstituted alkenyl group. Alkenyl sulfide compounds easily react with various nucleophiles and radical species, are widely used in the synthesis of pharmaceuticals and natural compounds, and are highly useful in the synthesis of fine chemicals.

As used herein, “zero-valent nickel or nickel precursor that is easily reduced to zero valence in the system” refers to a zero-valent nickel compound or any nickel compound that is easily reduced to zero valence. Originally, examples of the zero-valent nickel compound include bis (1,5-cyclooctadiene) nickel (O) (also expressed as Ni (cod) ₂ in this specification), nickel carbonyl, and the like. It is not limited to. Specific examples of nickel complexes containing a phosphine or phosphite ligand include tetrakis (triphenylphosphine) nickel, tetrakis (diphenylmethylphosphine) nickel, tetrakis (dimethylphenylphosphine) nickel, tetrakis (triethylphosphine) nickel, Tetrakis (triphenyl phosphite) nickel and the like can be mentioned, but are not limited to this, and examples of the combination of precursors that can be easily reduced to zero valence include, for example, zero valence in a reaction system. It is also possible to use precursors that are converted into A precursor that easily gives a highly active zero-valent nickel catalyst by reaction with an organometallic reagent such as Grignard or organolithium in the reaction system can also be used. Specific examples of such precursors include dichlorobis (triphenylphosphine) nickel, dichlorobis (diphenylmethylphosphine) nickel, dichlorobis (dimethylphenylphosphine) nickel and the like. These precursors interact with organometallic reagents such as Grignard reagents and organolithiums to reduce polyvalent nickel and generate zero-valent nickel. Similarly, a zero-valent nickel catalyst can be prepared by reacting a mixture of a divalent nickel compound such as nickel acetylacetonate and a phosphine or phosphite with a reducing agent such as organoaluminum or LiAlH _4. it can.

As used herein, “cationic nickel hydride complex” refers to any hydride complex of nickel having a positive charge. [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ^{− and the} like also belong to this category.

(Description of Preferred Embodiment)
Hereinafter, preferred embodiments of the present invention will be described. The embodiments provided below are provided for a better understanding of the present invention, and the scope of the present invention should not be limited to the following description. Therefore, it is obvious that those skilled in the art can make appropriate modifications within the scope of the present invention with reference to the description in the present specification.

(Complex compound)
In one aspect, the present _{^{invention, [HNi (PR 1 R 2}} R 3) 2] + X - indicated by the ^- or ^{_{[HNi (R 1 R 2 P}} (CH 2) x PR 4 R 5)] + X A complex compound (wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, and X is a hydride donor acid ( For example, an anion of an inorganic acid or an organic acid), and x is a positive integer. Examples of the hydrocarbon group used in the present invention include an alkyl group, a cycloalkyl group, an allyl group, an aryl group, and an aralkyl group.

  As the number of carbon atoms of the hydrocarbon group, any number can be used as long as it has a catalytic action.

  For example, when an alkyl group is used as a substituent, it preferably has 18 or less carbon atoms, more preferably 6 or less, even more preferably 3 or less, even more preferably 2 or less, and most preferably 1 (ie Methyl group). Once it has been found that an alkyl group-substituted product acts as a catalyst having one or another carbon number, the one substituted with an alkyl group having any carbon number also acts as a catalyst. It is understood. The theoretical explanation is that we do not want to be bound by this, but the bond between metallic nickel and phosphine is the formation of sigma bonds associated with the unpaired electron of phosphine to nickel and the phosphine of electrons on nickel. Since the trivalent phosphine having an unpaired electron basically has the above function and exhibits similar behavior, the catalytic action is alkyl. It is unlikely that it depends on the number of carbon atoms.

  For example, when an aryl group is used as a substituent, preferably it has 18 or less carbon atoms, more preferably 12 or less, even more preferably 8 or less, even more preferably 7 or less, and most preferably 6 (ie Phenyl group). Once it has been found that an aryl group-substituted product having a carbon number of 6 or another carbon number acts as a catalyst, those substituted with an aryl group of any carbon number also act as a catalyst. It is understood. The theoretical explanation is that we do not want to be bound by this, but the bond between metallic nickel and phosphine is the formation of sigma bonds associated with the unpaired electron of phosphine to nickel and the phosphine of electrons on nickel. Since the trivalent phosphine having an unpaired electron basically has the above function and exhibits similar behavior, the catalytic action is alkyl. It is unlikely that it depends on the number of carbon atoms.

  Moreover, if it is a hydrocarbon group, even if it is another kind, it can replace, and it understands that a substituted body acts as a catalyst.

In the present invention, R ¹ , R ² , R ³ , R ⁴ and R ⁵ may be the same or different from each other. Catalysts containing the same have the advantage that they are easy to synthesize, but the catalysts are almost the same whether they are all the same or mixed with different substituents. ing. Also, the advantages that R ¹ , R ² , R ³ , R ⁴ and R ⁵ are the same as each other include that these phosphines can be synthesized relatively easily, and therefore the catalyst is cheaper. . On the other hand, the advantage of different R ¹ , R ² , R ³ , R ⁴ and R ⁵ is that the physical properties of phosphines are easily controlled, and by using phosphines having different substituents such as reaction selectivity, Advantages such as easier control.

  Moreover, as a substituent of the complex compound of this invention, a cycloalkyl group, an allyl group, an alkenyl group, an aralkyl group etc. other than an alkyl group and an aryl group can be used. Once it is found that the alkyl group or aryl group substituent acts as a catalyst, it is understood that those substituted with cycloalkyl groups, allyl groups, alkenyl groups, and aralkyl groups also act as catalysts. Is done. The theoretical explanation is that we do not want to be bound by this, but the bond between metallic nickel and phosphine is the formation of sigma bonds associated with the unpaired electron of phosphine to nickel and the phosphine of electrons on nickel. Since the trivalent phosphine having an unpaired electron basically has the above function and exhibits similar behavior, the catalytic action is alkyl. It is unlikely that it depends on the number of carbon atoms.

  In a preferred embodiment, the hydrocarbon group can be a methyl group, an ethyl group, a phenyl group, or the like. Although not wishing to be bound by theory, the reasons why it is preferable to use a catalyst containing these methyl, ethyl, and phenyl groups are simple handling, easy synthesis, and catalytic reactivity. It is expensive.

In one embodiment, complex compound of the present invention, hydrocarbon group is C1~C2 alkyl group, or a C6 aryl group _{^{[HNi (PR 1 R 2 R}} 3) 2] + X - or where the The hydrocarbon group is a C1 alkyl group and x is 2 [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ . Although not wishing to be bound by theory, the reasons why it is preferable to use these specific catalysts include simple handling, easy synthesis, and high catalytic reactivity.

  In the present specification, it is understood that any acid can be used as X. For example, in one embodiment, the anion of an acid that is a hydride donor can be an inorganic oxoacid anion.

In a preferred embodiment, the anion of the acid, which is a hydride donor, sulfate ion, phosphate _{^{ion, - O-P (O)}} R 6 2, - O-P (O) (OR 6) 2, ClO 4 - , R ⁶ CO ₂ ^{— and the} like.

  And once a particular acid (eg, phosphoric acid, etc.) has been found to act as a catalyst, it is understood that a catalyst comprising any acid belonging to this group also acts as a catalyst.

In a more preferred embodiment, the anion of an inorganic acid, sulphate, _{^{phosphate, - O-P (O)}} R 6 2, - O-P (O) and the like ^(OR _{6) 2.}

In a preferred embodiment, the inorganic acid can be H ₃ PO ₄ , H ₂ SO ₄ , (C ₆ H ₅ O) ₂ PO ₂ H or (C ₆ H ₅ ) ₂ O ₂ H.

  In a preferred embodiment, the organic acid can be acetic acid, benzoic acid, salicylic acid, more preferably acetic acid.

In one embodiment, it is understood that any combination of X and R ^{1 to} R ⁵ can be used.

Examples of the alkyl group when R ^{1 to} R ⁵ are alkyl groups include alkyl groups having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Specific examples thereof include, for example, a methyl group, an ethyl group, and n -Or iso-propyl group, n-, iso-, sec- or tert-butyl group, n-pentyl group, n-hexyl group and the like can be mentioned.

Examples of the cycloalkyl group when R ^{1 to} R ⁵ are cycloalkyl groups include cycloalkyl groups having 3 to 12 carbon atoms, preferably 5 to 12 carbon atoms, and specific examples thereof include, for example, a cyclopentyl group and cyclohexyl group. Group, cyclooctyl group, cyclododecyl group and the like.

Examples of the aryl group in the case where R ^{1 to} R ⁵ are aryl groups include aryl groups having 6 to 14 carbon atoms, preferably 6 to 10 carbon atoms. Specific examples thereof include a phenyl group and a naphthyl group. Furthermore, those substitution products (tolyl group, xylyl group, benzylphenyl group, etc.) are also included.

Examples of the aralkyl group in the case where R ^{1 to} R ⁵ are aralkyl groups include aralkyl groups having 7 to 15 carbon atoms, preferably 7 to 11 carbon atoms, and specific examples thereof include, for example, benzyl group, phenethyl group, naphthylmethyl. Groups and the like.

The alkyl group, cycloalkyl group, aryl group or aralkyl group represented by R ^{1 to} R ⁵ is a substituent inert to the reaction, for example, methoxy group, methoxycarbonyl group, cyano group, dimethylamino group, fluoro group, chloro group. It may be substituted with a group, a hydroxy group or the like.

  Specific examples of the phosphinic acid used in the present invention include diphenylphosphinic acid and dimethylphosphinic acid. The amount used is equimolar or less, preferably 0.1 to 10 mol% with respect to the P—H compound used.

  The reaction is not particularly required to use a solvent, but can be carried out in a solvent if necessary. Solvents include hydrocarbon solvents such as toluene and xylene, ether solvents such as dioxane, tetrahydrofuran (THF), diisopropyl ether and dimethoxyethane, ester solvents such as ethyl acetate and butyl acetate, and ketones such as acetone and methyl ethyl ketone. Various solvents such as nitrile solvents such as acetonitrile and propiononitrile and amide solvents such as N, N-dimethylformamide (DMF) can be used. Moreover, these can also be used individually or in mixture of 2 or more types.

As specific compounds, for example (where Me represents a methyl group, Et represents an ethyl group, and Ph represents a phenyl group), Ni (PMe ₃ ) ₄ , [HNi (PMe ₃ ) ₂ ] ⁺ (H ₂ PO ₄ ) ⁻ , [HNi (PMe ₃ ) ₂ ] ⁺ (H ₂ PO ₄ ) ⁻ , [HNi (PMe ₃ ) ₂ ] ⁺ (HSO ₄ ) ^{_{-, [HNi (PMe 3)}} 2] + [PO 2 (OC 6 H 5) 2] -, [HNi (PMe 3) 2] + [PO 2 (C 6 H 5) 2] -, [HNi (PPhMe ₂ ) ₂ ] ⁺ (H ₂ PO ₄ ) ⁻ , [HNi (PEt ₃ ) ₂ ] ⁺ (H ₂ PO ₄ ) ⁻ , [HNi (PMe ₃ ) ₂ ] ⁺ ((Ph ₂ PO ₂ ) ⁻ , [ HNi (PMe ₃ ) ₂ ] ⁺ ((PhO) ₂ PO ₂ ) ⁻ , [HNi (PMe ₃ ) ₂ ] ⁺ (HSO ₄ ) ⁻ , [HNi (PMe ₃ ) ₂ ] ⁺ (H ₂ PO ₄ ) ^{− and the} like.

(Catalyst production example)
The method for producing the catalyst of the present invention is generalized as follows.

_{^{([HNi (PR 1 R 2}} R 3) 2] + X - case)
In the present invention, [HNi (PR ¹ R ² R ³ ) ₂ ] ⁺ X ⁻ represents R ¹ R ² R ³ is an alkyl group, an aryl group, a cycloalkyl group, an allyl group, an alkenyl group, an aralkyl group, etc. sulfate ions as phosphate ^{_{ions, - O-P (O)}} R 6 2, - O-P (O) (OR 6) 2, ClO 4 -, R 6 CO 2 -, even be produced it can. That is, at 0 ° C., with stirring, an acid (eg, inorganic or organic acid) that is a hydride donor in a solvent (eg, THF, 5 mL) solution of Ni (PR ¹ R ² R ³ ) ₄ (eg, 1 mmol). ) HX (eg 1 mmol) was added. It is confirmed that precipitation (for example, yellow precipitation) occurs immediately. For example, the precipitate can be filtered, washed with a solvent (eg, THF and pentane), and the resulting solid can be vacuum dried to obtain [HNi (PR ¹ R ² R ³ ) ₂ ] ⁺ X ^−. it can.

^{_{([HNi (R 1 R 2}} P (CH 2) x PR 4 R 5)] + X - case)
[HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ^{− of the} present invention can also be produced in the same manner, in addition to an alkyl group and an aryl group, a cycloalkyl group and an allyl group. , an alkenyl group, an aralkyl group, sulfate ions as X, phosphate ^{_{ions, - O-P (O)}} R 6 2, - O-P (O) (OR 6) 2, ClO 4 -, R 6 CO 2 - However, it can be manufactured as follows.

Acid (eg, hydride donor) in a solution of Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ (eg, 1 mmol) in a solvent (eg, THF, 5 mL) with stirring at zero degrees Inorganic or organic acid) HX (eg 1 mmol) is added. Precipitation occurs immediately. [([HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] by filtering the precipitate, washing with a solvent (eg, THF and pentane) and drying the resulting solid in vacuo. ⁺ X ^- is obtained.
_{^{[HNi (PR 1 R 2 R}} 3) 2] + X - and _{^{[HNi (R 1 R 2 P}} (CH 2) x PR 4 R 5)] + X - , the solution Ni ^{(PR 1 R} 2 ^{R 3} ) ₂ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) and HX are in equilibrium, and the equilibrium is markedly Ni (PR ¹ R ² R ³ ) ₂ or Ni (R ¹ R ² P ( CH ₂₎ when biased to _x PR ⁴ R ⁵⁾ and HX is a pure _{^{[HNi (PR 1 R 2 R}} 3) 2] + X - or _{^{[HNi (R 1 R 2 P}} (CH 2) x PR 4 R 5) There may be cases where it is difficult to isolate ⁺ X ⁻ , but even in that case, the present invention can be carried out by supplying the raw materials. Thus, it is contemplated that the present invention also covers any combination or mixture of materials that produces a catalyst that is primarily present in solution. In this case, each component present in the combination or mixture of these materials and raw materials should have a molar ratio to be present as a catalyst (for example, zero-valent nickel: PR ¹ R ² R ³ : HX = 1: 2: 1; Ni ( PMe ₃ ) ₄ + H ₃ PO ₄ (1 equivalent); Ni (cod) ₂ + 2.0PMe ₃ + 1.0H ₃ PO ₄ etc.).

In the case of [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ , it is produced only in the reaction system when the material is put into the reaction system, but there are some which are difficult to separate. sell. Even in such a case, [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ itself is produced, and the above set of materials is provided as a catalyst thereof. May be. In this case, it is preferable that each component which exists in the combination or mixture of these materials and raw materials is provided by the molar ratio which should exist as a catalyst.

Accordingly, the present invention relates to zero valent nickel or a nickel precursor that is easily reduced to zero valence in the system (eg, bis (1,5-cyclooctadiene) nickel (O) (Ni (cod) ₂ )), PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently A mixture with a substituted or unsubstituted hydrocarbon group, X is an anion of an acid (eg, an inorganic or organic acid) that is a hydride donor, and x is a positive integer. Provide a combination. This mixture or combination is useful because it reacts to produce the catalyst of the present invention.

Alternatively, the present invention relates to a compound represented by Ni (PR ¹ R ² R ³ ) ₄ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, and X is the shadow of an acid (eg, an inorganic or organic acid) that is a hydride donor. An ion and x is a positive integer). This mixture or combination is useful because it reacts to produce the catalyst of the present invention.

(Catalyst composition for production of alkenylphosphonic acid ester compound or alkenyl sulfide compound)
The present invention also provides a catalyst composition for the production of an alkenyl phosphonic acid ester compound or an alkenyl sulfide compound comprising the complex compound of the present invention. Here, it is understood that any form described in the “complex compound” can be used as the catalyst composition.

The invention also relates to zero valent nickel or a nickel precursor that is easily reduced to zero valence in the system (eg, bis (1,5-cyclooctadiene) nickel (O) (Ni (cod) ₂ ) and PR. ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently substituted Or a mixture or combination with an anion of an acid (eg, an inorganic or organic acid) that is a hydride donor and x is a positive integer. A catalyst composition for the production of an alkenylphosphonic acid ester compound or an alkenyl sulfide compound is provided. That is, zero-valent nickel or a nickel precursor that is easily reduced to zero valence in the system (for example, bis (1,5-cyclooctadiene) nickel (O) (Ni (cod) ₂ )) and PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently substituted or A mixture or combination with an unsubstituted hydrocarbon group, X is an anion of an acid (eg, an inorganic or organic acid) that is a hydride donor, and x is a positive integer. It can be used in the production of phosphonate compounds or alkenyl sulfide compounds. Accordingly, zero-valent nickel or a nickel precursor that is easily reduced to zero valence in the system (eg, bis (1,5-cyclooctadiene) nickel (O) (Ni (cod) ₂ )) and PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently substituted or A mixture or combination with an unsubstituted hydrocarbon group, X is an anion of an acid (eg, an inorganic or organic acid) that is a hydride donor, and x is a positive integer. It can be referred to as a catalyst or a catalyst raw material for the production of a phosphonic acid ester compound or an alkenyl sulfide compound. Here, "catalyst raw material" refers to any substance that becomes a catalyst when reacted or mixed. Here, it is understood that any form described in the “complex compound” can be used as the catalyst composition.

Alternatively, the present invention relates to a compound represented by Ni (PR ¹ R ² R ³ ) ₄ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, and X is the shadow of an acid (eg, an inorganic or organic acid) that is a hydride donor. A catalyst composition comprising a mixture or a combination thereof, wherein x is a positive integer. That is, a compound represented by Ni (PR ¹ R ² R ³ ) ₄ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid (eg, an inorganic or organic acid) that is a hydride donor; x is a positive integer)) or a combination thereof can be used as a catalyst or catalyst raw material in the production of alkenylphosphonic acid ester compounds or alkenyl sulfide compounds. Here, it is understood that any form described in the “complex compound” can be used as the catalyst composition.

  If necessary, the catalyst composition of the present invention may be added with a material that dissolves the catalyst composition in addition to the complex compound of the present invention or the material that forms the complex compound in the reaction system. Specific examples thereof include water, alcohols such as methanol and ethanol, DMSO dimethyl sulfone oxide, DMF dimethylformamide, and the like, but are not limited thereto. Toluene, pentane, hexane, diethyl ether, and acetone may be added, but are not limited thereto. The reasons why these may be added include the reason that the performance of the catalyst is not impaired by the presence of these, while there is an advantage that it can be handled more easily by using a solution.

(Production of alkenylphosphonic acid ester compound or alkenyl sulfide compound)
In another aspect, the present invention provides an alkenylphosphonic acid ester compound (R ^a1 O) (R ^a2 O) P (O) —R ^b
(Wherein R ^a1 and R ^a2 are each independently substituted or unsubstituted hydrocarbon groups or together form a cyclic hydrocarbon group, and R ^b is substituted or substituted. Alkenyl sulfide compound R ^c S—R ^b
Wherein R ^c is a substituted or unsubstituted hydrocarbon group and R ^b is a substituted or unsubstituted alkenyl group, comprising:
A) Phosphonate compound (R ^a1 O) (R ^a2 O) P (O) H or sulfide compound R ^c SH, and the general formula (2)
R ^b1 (C≡CR ^b2 ) _n (2)
(In the formula, n is 1 or 2, and R ^b1 is a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, aralkyl group, heteroaryl group, alkenyl group, when n is 1. An alkoxy group, an aryloxy group, or a silyl group, when n is 2, an alkylene group, a cycloalkylene group, an arylene group, an aralkylene group, a heteroarylene group, an alkenylene group, an alkylenedioxy group, an aryleneoxy group, or a silyl group R ^b2 represents a hydrogen atom.) The complex compound of the present invention or a mixture or combination of the present invention is added simultaneously or sequentially to the reaction system with the acetylene compound represented by Provided is a method comprising the step of producing a phosphonate ester compound or an alkenyl sulfide compound .

Here, in Step A, the phosphonic acid ester compound (R ^a1 O) (R ^a2 O) P (O) H or sulfide compound R ^c SH as the material and the acetylene compound as the other material are mixed in the reaction system. Then, the reaction can proceed by simultaneously or sequentially adding the catalyst composition of the present invention or the raw material thereof to produce an alkenylphosphonic acid ester compound or alkenyl sulfide compound.

  Here, any reaction conditions can be used, but a normal temperature of −20 ° C. to 150 ° C., a concentration of 0.01 M to 20 M, a type of solvent, etc .: a solvent may or may not be used. The reaction can proceed. For example, various solvents can be used, and preferred examples include nonpolar solvents such as hexane and toluene. Examples of preferable conditions include a temperature of 0 ° C. to 150 ° C., a concentration of 0.01 M to 2 M, and toluene. Can be mentioned.

  The reaction is not particularly required to use a solvent, but can be carried out in a solvent if necessary. Solvents include hydrocarbon solvents such as toluene and xylene, ether solvents such as dioxane, tetrahydrofuran (THF), diisopropyl ether and dimethoxyethane, ester solvents such as ethyl acetate and butyl acetate, and ketones such as acetone and methyl ethyl ketone. Various solvents such as nitrile solvents such as acetonitrile and propiononitrile and amide solvents such as N, N-dimethylformamide (DMF) can be used. Moreover, these can also be used individually or in mixture of 2 or more types.

  The reaction temperature is generally selected from the range of −20 ° C. to 300 ° C., preferably 0 ° C. to 150 ° C., because the reaction does not proceed at an advantageous rate at too low temperature and the catalyst decomposes at too high temperature. It is carried out in the range. The reaction time varies depending on the kind of acetylene compound and P—H compound to be used, reaction temperature and other reaction conditions, but is usually about several hours to several tens of hours.

  Although this reaction proceeds even in the presence of oxygen, such as in the air, the catalytically active species that act in this reaction system are sensitive to oxygen, so the reaction should be carried out in an inert gas atmosphere such as nitrogen, argon, or methane. preferable. Separation of the product from the reaction mixture is readily accomplished by chromatography, distillation, recrystallization and the like.

In one embodiment, in step A), bis (1,5-cyclooctanediene) nickel (O) and said PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ and hydride The phosphonic acid ester compound or sulfide compound and the alkyne compound can be reacted in the presence of a donor acid (for example, an inorganic acid or an organic acid). Any timing can be adopted as the timing of adding the catalyst or catalyst raw material as long as it functions as a catalyst. It is preferable to be simultaneous, but it is not limited to this.

  The method for producing an alkenylphosphonic acid ester compound or alkenyl sulfide compound of the present invention is characterized in that the amount of catalyst used is remarkably reduced and easy to handle as compared with the case where a conventional catalyst is used. That is, in the conventional catalyst, about 5 mole percent of the catalyst is used with respect to the reaction substrate in order to obtain the alkenylphosphonic acid ester compound or alkenyl sulfide compound in a high yield. However, the use of such expensive catalysts is far from the industrial scale. When the catalyst of the present invention was used, a high yield of 90% or more, and in most cases 95% or more was achieved when the amount of the catalyst used was about 0.5 mole percent. With such a yield, production commensurate with the industrial scale can be performed. Also for toxic and expensive phosphine ligands, conventional catalysts generally have a nickel to phosphorus ratio of 1 to 4, whereas in the present invention a nickel to phosphorus ratio of 1 to 2 is sufficient. It is. Furthermore, the conventional catalyst is deactivated immediately in the air, whereas the present catalyst can be handled easily even in the air, so that it can be used conveniently.

  It is known that an alkenyl phosphorus compound has its basic skeleton found in nature and exhibits physiological activity by acting with an enzyme or the like. This compound is also an extremely useful compound that can be easily converted into tertiary phosphine and the like widely used as an auxiliary ligand for various catalytic reactions. Furthermore, the compounds are a group of compounds that are highly useful in the synthesis of fine chemicals, such as easily reacting with nucleophiles and radical species, and can also be used in Horner-Wittig reactions.

  Therefore, it should be said that it is highly valuable that the production efficiency of such highly useful compounds has been greatly increased.

  In another aspect, the present invention also provides an alkenyl phosphonic acid ester compound or an alkenyl sulfide compound or a raw material for producing the same or a composition containing them. Since the raw material for producing the alkenylphosphonic acid ester compound or alkenyl sulfide compound obtained according to the present invention is obtained by a method having a remarkably excellent yield, it has an effect that impurities are reduced. . Accordingly, it can be said that the raw material for producing the alkenylphosphonic acid ester compound or alkenyl sulfide compound produced by the method of the present invention has never been a substance (mixture) in the state of production, and the use of the raw material as a raw material itself is novel. It can be said that. The production raw material of the present invention preferably includes 90% or more of the alkenylphosphonic acid ester compound or alkenyl sulfide compound, and can be said to be one of the features that the catalyst of the present invention is included in an amount recognizable. .

  References such as scientific literature, patents and patent applications cited herein are hereby incorporated by reference in their entirety to the same extent as if each was specifically described.

  Hereinafter, although an example explains the composition of the present invention in detail, the present invention is not limited to this. The reagents used in the following were commercially available unless otherwise specified.

    Examples of the present invention will be described below, but the present invention is not limited thereto. The reagents used below were either purchased from Aldrich, Tokyo Kasei, or Wako Pure Chemical Industries, or were manufactured by a conventional method (J. Am. Chem. Soc. 1970, vol. 92, page 2296).

Example 1
(Experimental example)
To a solution of Ni (PMe ₃ ) ₄ (1 mmol (mmol)) in THF (5 mL) at 0 ° C. with stirring, a solution of phosphoric acid (1 mmol (mmol)) in THF (2 ml) was added. A yellow precipitate immediately formed. The precipitate was filtered under nitrogen, washed with THF and pentane, and the solid was dried in vacuo. Quantitatively (308 mg) [HNi (PMe ₃ ) ₂ ] ⁺ (H ₂ PO ₄ ) ⁻ was obtained. This complex is a new one not known so far. The structure was determined as follows.

(result)
Elemental analysis: calculated C, 23.33%; H, 6.85%. Measurement: C, 23.63%; H, 6.91%.
¹ H NMR (DMSO-d6): δ 7.23 (bs, 2H), 1.62 (s, 18H), −16.9 (s, 1H, H—Ni)
³¹ P NMR (DMSO-d6): δ1.5 (H ₂ PO ₄ ), −16.8 (PMe ₃ ) (Note that the integration ratio of signals of δ1.5 and −16.8 is 1: 2.) .
The corresponding various [HNi (PR ₃ ) ₂ ] ⁺ X− were quantitatively obtained by reacting the different nickel complexes shown in the same method with an acid that is a hydride donor.

(Table 1: Synthesis of [HNi (PR ₃ ) ₂ ] ⁺ X ⁻ by reaction of Ni (PR ₃ ) ₄ and an inorganic acid which is a hydride donor)

(Examples 2 to 4: Catalytic reaction using a cationic complex)
These complexes exhibit high catalytic activity for the following addition reactions.

(procedure)
(MeO) ₂ P (O) H 1 mmol and 1-octyne 1 mmol were mixed, and 0.5 mol% of the catalyst of the present invention or a catalyst (Ni (PMe ₃ ) ₄ ) as a comparative example was mixed, Were reacted in 1M tetrahydrofuran (THF) to obtain the following compounds 1 and 2. The reaction time and yield at that time are shown below.

(result)
The catalyst composition of the present invention was found to have a higher yield and higher product selectivity than neutral Ni (PMe ₃ ) ₄ . The results are summarized in the following table.

The above examples are all examples of isolated [HNi (PR ₃ ) ₂ ] ⁺ X ⁻ , but are generated in the system in an actual reaction system, for example, PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) + hydride donor acid (eg, inorganic or organic acid), or zero valent nickel such as (Ni (cod) ₂ ) or easily zero valent in the system nickel precursor ⁺ PR ^{1 R} 2 R ^3, or ^{_{R 1 R 2 P (CH 2}} ) x PR 4 R 5) + acid hydrido donor is reduced to (e.g., inorganic acids or organic acids) combination or mixture of such Are also contemplated to be within the scope of the present invention.

(Manufacturing comparative example)
A. Comparative Example for Production of Vinylphosphonic Acid Diethyl Ester (Comparative Example A-1)
To the reaction apparatus, 6.45 mL of diethyl phosphite and 50 mL of toluene were added, and 4.5 mL of Ni (PMe3) ₄ (2.25 mol% with respect to diethyl phosphite) was added and reacted while blowing acetylene gas. The residue was purified by distillation to obtain 2.44 g (yield 29.7%) of vinylphosphonic acid diethyl ester.

(Comparative Example A-2)
6.45 mL of diethyl phosphite, 12.9 mL of toluene, and 0.15 g of phosphoric acid were added to the reactor, and Ni (PMe ₃ ) ₄ 3.98 mL (2 mol% with respect to diethyl phosphite) was added while blowing acetylene gas. Added and allowed to react. The residue was purified by distillation to obtain 7.16 g (yield 87.7%) of vinylphosphonic acid diethyl ester.

(Comparative example B. Comparative example of vinylphosphonic acid dimethyl ester production)
(Comparative Example B-1)
13.8 mL of dimethyl phosphite and 150 mL of toluene were added to the reactor, and 6 mL of Ni (PMe ₃ ) ₄ (1 mol% with respect to dimethyl phosphite) was added and reacted while blowing acetylene gas. Purification by distillation gave 9.86 g (yield 48.3%) of vinylphosphonic acid diethyl ester.

(Examples 5 to 23: other combinations)
Addition reactions to various PH compounds and acetylenes were carried out in the same procedure as in Examples 2-4. The results are summarized in the following table as Examples 5-23.

  (result)

  As described above, whether the catalyst of the present invention is used alone or in combination or as a mixture, it should be 90% or more as long as the catalyst produced in the reaction system is desired. Is understood.

(Examples 24-35: other combinations)
Further examples of addition reactions to various P—H compounds and acetylenes were carried out in the same procedure as in Examples 2-4. Hereinafter, as Examples 24 to 35, combinations of catalysts and reaction systems within the scope of the present invention different from those of Examples 1 to 23 will be described.

(result)
Even in the combinations described in Table 4, the same high yield reaction as in Examples 1 to 23 occurred. In fact, a yield of 91% was observed in Example 26 and 90% in Example 32.

(For organic acids)
Examples 36-38 were carried out in the same experiment using organic acids as acids. In Examples 36-38, an experiment similar to the case of an inorganic acid was performed except that an organic acid was used as the acid.

  As described above, even when an organic acid is used instead of an inorganic acid, the catalyst of the present invention is produced in a reaction system whether used alone or as a combination or mixture. As long as the catalyst is desired, it is understood that it is above 90%.

(Summary)
As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, this invention should not be limited and limited to this embodiment. It is understood that the scope of the present invention should be construed only by the claims. It is understood that those skilled in the art can implement an equivalent range based on the description of the present invention and the common general technical knowledge from the description of specific preferred embodiments of the present invention. Patents, patent applications, and documents cited herein should be incorporated by reference in their entirety, as if the contents themselves were specifically described herein. Understood.

  The present invention is also an extremely useful compound that can be easily converted into tertiary phosphine and the like widely used as an auxiliary ligand for various catalytic reactions. In addition, this compound can easily react with nucleophiles and radical species, and can be used for Horner-Wittig reaction, etc., achieving efficient production of a group of compounds that are highly useful in the synthesis of fine chemicals. To do.

  The present invention provides high yields of alkenyl phosphorus compounds (alkenyl phosphonic acid esters, alkenyl phosphinic acid esters and alkenyl phosphine oxide compounds) useful as synthetic intermediates for physiologically active substances such as pharmaceuticals and agricultural chemicals and ligands for catalyst preparation. And a highly practical manufacturing method. The method for synthesizing an alkenyl phosphorus compound of the present invention uses a relatively inexpensive nickel complex catalyst as a catalyst, and converts a P—H compound (hydrogenated phosphonate, hydrogenated phosphinate, and disubstituted phosphine oxide) to acetylene. It can be synthesized simply, safely and efficiently simply by reacting, and the product can be easily separated and purified. Therefore, the present invention has a great industrial effect.

  Therefore, it finds applicability in all industries using this phosphorus compound or sulfur compound.

Claims (31)

A complex compound represented by [HNi (PR ¹ R ² R ³ ) ₂ ] ⁺ X ⁻ or [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ (wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid which is a hydride donor, and x is a positive An integer.) The complex compound according to claim 1, wherein the hydrocarbon group is selected from the group consisting of an alkyl group, an aryl group, a cycloalkyl group, an allyl group, an alkenyl group, and an aralkyl group. The hydrocarbon group is selected from the group consisting of a C1-C6 alkyl group, a C3-C8 aryl group, a C3-C8 cycloalkyl group, a C3-C8 allyl group, a C2-C6 alkenyl group, and a C3-C8 aralkyl group. The complex compound according to claim 1. The complex compound according to claim 1, wherein the hydrocarbon group is independently selected from the group consisting of a methyl group, an ethyl group, and a phenyl group. Said complex compound, said hydrocarbon group is C1~C2 alkyl or C6 aryl group _{^{[HNi (PR 1 R 2 R}} 3) 2] + X, - a is or said hydrocarbon group is C1 alkyl The complex compound according to claim 1, wherein x is 2 [HNi (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ )] ⁺ X ⁻ . The complex compound according to claim 1, wherein the acid that is the hydride donor is an inorganic acid or an organic acid. The complex compound according to claim 1, wherein the acid that is the hydride donor is an inorganic acid. The complex compound according to claim 1, wherein the acid that is the hydride donor is an organic acid. The complex compound according to claim 1, wherein an anion of the acid that is the hydride donor is an inorganic oxoacid anion. The anion of the hydride donor and is acid, acetate ion, sulfate ion, phosphate _{^{ion, - O-P (O)}} (OH) 2, - O-S (O) 2 (OH), - O-P _{^{(O) R 6 2, -}} O-P (O) (oR 6) 2 and _{^{ClO 4 -, R 6 CO 2}} - is selected from the group consisting of, ^{R 6} is or independently substituted The complex compound according to claim 1, which is an unsubstituted hydrocarbon group. Wherein the acid is a hydride donor, acetate ion, sulfate ion, phosphate ^ion, - from _{O-P (O) (C} 6 H 5 O) 2 - O-P (O) (C 6 H 5) 2 and The complex compound according to claim 1, which is selected from the group consisting of: 2. The acid according to claim 1, wherein the acid that is the hydride donor is H ₃ PO ₄ , H ₂ SO ₄ , (C ₆ H ₅ O) ₂ PO ₂ H, or (C ₆ H ₅ ) ₂ PO ₂ H. Complex compound. The catalyst composition for manufacture of the alkenyl phosphonic acid ester compound or alkenyl sulfide compound containing the complex compound of Claim 1. Zero valent nickel or a nickel precursor that is easily reduced to zero valence in the system, PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ), and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid which is a hydride donor, and x is Is a positive integer). 15. The zerovalent nickel or nickel precursor that is easily reduced to zerovalent in the system is bis (1,5-cyclooctadiene) nickel (O) (Ni (cod) ₂ ). A mixture or combination of. 15. A mixture or combination according to claim 14, further comprising the features of any one of claims 2-12. Zero valent nickel or a nickel precursor that is easily reduced to zero valence in the system, PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ), and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid which is a hydride donor, and x is And a mixture or combination thereof in the manufacture of alkenylphosphonic acid ester compounds or alkenyl sulfide compounds. A catalyst or catalyst raw material for the production of an alkenylphosphonic acid ester compound or an alkenyl sulfide compound comprising the mixture or combination according to claim 17. A compound represented by Ni (PR ¹ R ² R ³ ) ₄ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ , and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid that is a hydride donor, and x is a positive integer. Mixture or combination. 20. A mixture or combination according to claim 19 further comprising the features of any one of claims 2-12. A compound represented by Ni (PR ¹ R ² R ³ ) ₄ or Ni (R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ ) ₂ , and HX (where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a substituted or unsubstituted hydrocarbon group, X is an anion of an acid that is a hydride donor, and x is a positive integer. Use in the manufacture of phosphonate compounds or alkenyl sulfide compounds. A catalyst or catalyst raw material for the production of an alkenylphosphonic acid ester compound or an alkenyl sulfide compound comprising the mixture or combination according to claim 19. Alkenylphosphonic acid ester compound (R ^a1 O) (R ^a2 O) P (O) —R ^b
(Wherein R ^a1 and R ^a2 are each independently substituted or unsubstituted hydrocarbon groups or together form a cyclic hydrocarbon group, and R ^b is substituted or substituted. Alkenyl sulfide compound R ^c S—R ^b
Wherein R ^c is a substituted or unsubstituted hydrocarbon group and R ^b is a substituted or unsubstituted alkenyl group, comprising:
A) Phosphonate compound (R ^a1 O) (R ^a2 O) P (O) H or sulfide compound R ^c SH, and the general formula (2)
R ^b1 (C≡CR ^b2 ) _n (2)
(In the formula, n is 1 or 2, and R ^b1 is a substituted or unsubstituted alkyl group, cycloalkyl group, aryl group, aralkyl group, heteroaryl group, alkenyl group, when n is 1. An alkoxy group, an aryloxy group, or a silyl group, when n is 2, an alkylene group, a cycloalkylene group, an arylene group, an aralkylene group, a heteroarylene group, an alkenylene group, an alkylenedioxy group, an aryleneoxy group, or a silyl group .R ^b2 indicating the range group is a hydrogen atom. the reaction system with the acetylene compound represented by), the mixture or combination simultaneously or sequentially according to the complex compound or claim 11 or 16 according to claim 1 In addition, mixing to produce the alkenylphosphonic acid ester compound or alkenyl sulfide compound Including the extent, method. In the step A), bis (1,5-cyclooctanediene) nickel (O) and the PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ⁵ and an acid that is a hydride donor 24. The method of claim 23 comprising reacting the phosphonic acid ester compound or sulfide compound with the alkyne compound in the presence of. After the step A), B) method according to the ^PR 1 ^R 2 ^{R 3,} or _{^{R 1 R 2 P (CH 2}} ) x PR 4 comprising removing ^{R 5,} claim 23. After the step A), the reaction system is subjected to heating and decompression under a nitrogen stream to remove the PR ¹ R ² R ³ or R ¹ R ² P (CH ₂ ) _x PR ⁴ R ^5. 24. The method of claim 23. 26. The method of claim 25, comprising after step B) C) deactivating the nickel catalyst. 26. The method according to claim 25, comprising a step of oxidizing the nickel catalyst or phosphine after the step B) by stirring with blowing air. 28. The method of claim 27, further comprising, after step C), D) filtering off the alkenylphosphonic acid ester compound or alkenyl sulfide compound. 30. The method according to claim 29, comprising a step of concentrating and purifying the filtrate obtained by the filtration after the step D) by distillation. A raw material for producing an alkenylphosphonic acid ester compound or alkenyl sulfide compound produced by the method according to claim 23.