JP5172249B2 - Composite metal catalyst - Google Patents

Description

  The present invention relates to a composite metal catalyst and a method for producing an α, β-unsaturated carbonyl compound using the catalyst.

The α, β-unsaturated carbonyl compounds represented by the general formula (2) are widely used as important synthetic intermediates such as pharmaceuticals, agricultural chemicals, cosmetics and functional organic materials. As one of the most useful synthesis methods of the α, β-unsaturated carbonyl compound, there is a method in which the hydroxyl group is rearranged from the propargyl alcohol compound represented by the general formula (1). Conventionally, as a catalyst for proceeding the rearrangement reaction, vanadium, molybdenum or tungsten oxo compounds (Non-patent Document 1), a catalyst in which a titanium compound and a copper salt or a silver salt are combined (Non-patent Document 2), a mercury salt (non-patent document 1). Patent Document 3), gold salts (Non-Patent Documents 4 and 5), composite metal catalysts in which a gold compound and a silver salt are combined (Non-Patent Document 6), and the like are known. These methods need to be performed at a high temperature, cannot be applied to primary and secondary propargyl alcohol compounds, or require a long time of 12 hours or more to complete the reaction, and are not always satisfactory. It was. In addition, a method using a catalyst composed of perrhenate and arylsulfonic acid is known (Patent Document 1, Non-Patent Document 7), but a side reaction of a dehydration reaction may proceed depending on a substrate.
JP 5-97758 Tetrahedron, 1977, volume 33, p1775-1783. Tetrahedron Letters, 1988, Vol. 29, p6253-6256. Organic Letters, 2006, Vol. 8, p447--450. Organic Letters, 2006, Vol. 8, p4027--4029. Journal of the American Chemical Society, 2005, 127, p14180-14181. Organic Letters, 2005, Volume 7, p4129-4132. Chemistry Letters, 1991, p1413-1416.

  The present invention provides a method for producing an α, β-unsaturated carbonyl compound in high yield from a propargyl alcohol compound in a short time at room temperature by developing a catalyst for solving the above problems. To do. The present invention also provides a method for synthesizing important synthetic intermediates such as various pharmaceuticals, agricultural chemicals, cosmetics and functional organic materials.

  The present inventor has proposed that a composite metal catalyst comprising a combination of three metal compounds, a transition metal compound, a gold compound and a silver compound, performs a rearrangement reaction from a propargyl alcohol compound to an α, β-unsaturated carbonyl compound at a temperature near room temperature. Was completed in a short period of time, and was found to be applicable to a wide range of substrates including primary and secondary propargyl alcohol compounds, and was not accompanied by side reactions of dehydration reaction, thereby completing the present invention.

That is, the present invention
(1) a composite metal catalyst in which three kinds of metal compounds of a transition metal compound, a gold compound and a silver compound are combined;
(2) By the catalyst of claim 1, the general formula (1),

(Wherein R ¹ and R ² are the same or different and have a hydrogen atom, a lower alkyl group which may have a substituent, a lower alkenyl group which may have a substituent, or a substituent. A lower alkynyl group which may have a substituent, an aryl group which may have a substituent, an aralkyl group which may have a substituent, a heteroaryl group which may have a substituent, and a substituent. Represents a lower alkoxy group which may be substituted, or a silyl group which may have a substituent, or each alkyl group of R ¹ and R ² is bonded to each other to form an aliphatic monocyclic ring or an aliphatic heterocyclic monocyclic ring. In addition, an aromatic ring may be condensed to the same single ring, and R ³ is a hydrogen atom, a lower alkyl group which may have a substituent, or a lower alkenyl which may have a substituent. Group, optionally substituted lower alkynyl group, substituted An aryl group which may have a substituent, an aralkyl group which may have a substituent, a heteroaryl group which may have a substituent, a lower alkoxy group which may have a substituent, a substituent An aryloxy group which may have a substituent, a heteroaryloxy group which may have a substituent, a lower alkylthio group which may have a substituent, an arylthio group which may have a substituent, A heteroarylthio group which may have a substituent, an amino group which may have a substituent, an acylamino group which may have a substituent, a carbamoyl group which may have a substituent, A silyl group which may have a substituent, a silyloxy group which may have a substituent, an acyl group which may have a substituent, an acyloxy group which may have a substituent, a substituent The lower a Job aryloxycarbonyl group which may have a substituent aryloxycarbonyl group which may have a substituent heteroaryloxy group, a halogen atom, a nitro group, a cyano group. Or R ² and R ³ may be bonded to each other to form an aliphatic monocyclic ring or an aliphatic heterocyclic monocyclic ring, and the monocyclic ring may be condensed with an aromatic ring). General formula (2), characterized in that

(Wherein R ¹ , R ² and R ³ are the same as above), a method for producing an α, β-unsaturated carbonyl compound represented by:
Etc.

  According to the present invention, various propargyl alcohols including secondary propargyl alcohol can be rearranged to produce an α, β-unsaturated carbonyl compound at room temperature in a high yield. The present invention can also be applied to primary and secondary propargyl alcohols that could not be applied conventionally. Since it proceeds with a small amount of catalyst of usually 0.005 to 0.01 equivalent, it is economically effective.

The composite metal catalyst of the present invention is a catalyst in which three kinds of metal compounds of transition metal compound, gold compound and silver compound are combined (hereinafter sometimes referred to as the catalyst of the present invention).
Examples of the transition metal compound in the present invention include compounds containing various transition metals, preferably VO (OSiPh ₃ ) ₃ , VO [OSi (C ₆ H ₄ -p-Cl) ₃ ] ₃ , VO [OSi (C ₆ H ₄ -p-CF ₃ ) ₃ ] ₃ , VO (OEt) ₃ , VO (OC ₃ H ₇ ) ₃ , VO (OCH (CH ₃ ) ₂ ) ₃ , VO (OPh) ₃ , VOSO ₄ , VOPO ₄ , VOAsO ₄ , VO (acac) ₂ , VO (CH ₃ COCH ₂ COPh) ₂ , VO (CF ₃ COCH ₂ COCF ₃ ) ₂ , VO, VO ₂ , V ₂ O ₃ , V ₂ O ₄ , V ₂ O ₅ , VOCl ₃ , VOCl ₂ (OEt), VOF ₃ , VO (OAc) ₂ , VO (oxalate), MoO ₂ (acac) ₂ , MoO ₂ (tBuCOCH ₂ COtBu) ₂ , H ₄ SiO ₄ / 12MoO ₃ , H ₃ (PMo ₁₂ O ₄₀ ), Na ₃ (PMo ₁₂ O ₄₀ ), (NH ₄ ) ₃ (PMo ₁₂ O ₄₀ ), MoO ₂ (OSiPh ₃ ) ₂ , MoO ₂ , MoO ₃ , MoOCl ₄ , MoO ₂ Cl ₂ , Bu ₄ NReO ₄ , CH ₃ ReO ₃ , HReO ₄ , ReO ₂ , ReO ₃ , Re ₂ O ₇ , ReO ₃ (OSiPh ₃ ), ReO ₃ (OSiMe ₃ ), ReOCl ₃ (PPh ₃ ) ₂ , TiO ( acac) ₂ , Ti (OBu) ₄ , Ti (OBu) ₂ (acac) ₂ , TiCl ₄ , Cp ₂ TiCl ₂ , Ti (OEt) ₄ , Ti (OC ₃ H ₇ ) ₄ , WO ₂ , WO ₃ , H ₃ (PW ₁₂ O ₄₀ ), WO ₂ Cl ₂ , WOCl ₄ , H ₄ (Si W ₁₂ O ₄₀ ) etc. Here, Ph is phenyl (C ₆ H ₅ ), Et is ethyl (C ₂ H ₅ ), acac is acetylacetone (CH ₃ COCH ₂ COCH ₃ ), Ac is acetyl (COCH ₃ ), Me is methyl (CH ₃ ) , Bu represents butyl (CH ₂ CH ₂ CH ₂ CH ₃ ), and tBu represents tert-butyl (C (CH ₃ ) ₃ )) (the same applies hereinafter).

Examples of the gold compound in the present invention include various compounds including gold, preferably AuCl, AuCl ₃ , NaAuCl ₄ HAuCl ₄ , AuBr ₃ , HAuBr ₄ , AuCl (PMe ₃ ), AuCl (PEt ₃ ), AuCl (PPh ₃ ), AuCl [P (C ₆ H ₄ -p-CF ₃ ) ₃ ], AuCl ₃ (pyridine), Au ₂ Cl ₂ (dppm), AuCl [P (tBu) ₂ (o-biphenyl)], [(Ph ₃ PAu) ₃ O] BF ₄ , AgCl (SMe ₂ ) and the like. Here, dppm represents bis (diphenylphosphino) methane.

The silver compound in the present invention, various compounds containing silver and the like, preferably _{AgOTf, AgClO 4, AgBF 4,} AgPF 6, AgSbF 6, AgOAc, AgOCOCF 3, AgNTf 2, AgOTs, AgOMs like. Here, Tf represents trifluoromethanesulfonyl (CF ₃ SO ₂ ), Ts represents p-toluenesulfonyl (p-CH ₃ —C ₆ H ₄ —SO ₂ ), and Ms represents methanesulfonyl (CH ₃ SO ₂ ) The same).

  As a mixing ratio of these three types of metal compounds, the molar ratio of transition metal compound: gold compound: silver compound is usually 1: 0.01-100: 0.01-100, preferably 1: 0.1-10: 0.1-10. is there.

  The propargyl alcohol compounds used in the present invention are primary, secondary and tertiary propargyl alcohols represented by the following formula (1).

As the lower alkyl group of the lower alkyl group which may have a substituent represented by R ^{1 to} R ³ , a linear or branched alkyl group having 1 to 20 carbon atoms such as a methyl group, an ethyl group, Propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl Group, etc. are mentioned, but it is not limited to this. Preferably it is a C1-C10 linear or branched alkyl group.

Examples of the lower alkenyl group of the lower alkenyl group optionally having a substituent represented by R ^{1 to} R ³ include a linear or branched alkenyl group having 1 to 20 carbon atoms such as a vinyl group, a propenyl group, Examples include, but are not limited to, an allyl group, a butenyl group, a pentenyl group, and a hexenyl group. A straight chain or branched alkenyl group having 1 to 10 carbon atoms is preferred.

As the lower alkynyl group of the lower alkynyl group optionally having a substituent represented by R ^{1 to} R ³ , a linear or branched alkenyl group having 1 to 20 carbon atoms such as ethynyl group, propynyl group, A butynyl group, a pentynyl group, a hexynyl group, and the like are exemplified, but the present invention is not limited thereto. Preferably it is a C1-C10 linear or branched alkynyl group.

Examples of the aryl group of the aryl group that may have a substituent represented by R ^{1 to} R ³ include, but are not limited to, a phenyl group, a 1-naphthyl group, a 2-naphthyl group, and the like.

As the aralkyl group of the aralkyl group which may have a substituent represented by R ^{1 to} R ³ , a benzyl group, an o-methylbenzyl group, an m-methylbenzyl group, a p-methylbenzyl group, 2-phenylethyl Group, 3-phenylpropyl group, 1-naphthylmethyl group and the like, but are not limited thereto.

Examples of the heteroaryl group of the heteroaryl group which may have a substituent represented by R ^{1 to} R ³ include a furyl group, a pyrrolyl group, a pyridyl group, an indolyl group, a quinolyl group, an isoquinolyl group, and a thienyl group. However, it is not limited to this.

Examples of the lower alkoxy group of the lower alkoxy group which may have a substituent represented by R ^{1 to} R ³ include, but are not limited to, a methoxy group, an ethoxy group, a propoxy group, and a butoxy group.

Examples of the silyl group which may have a substituent represented by R ^{1 to} R ³ include a trimethylsilyl group, a triethylsilyl group, a tert-butyldimethylsilyl group, a triisopropylsilyl group, and a dimethylphenylsilyl group. Not limited to this.

The alkyl groups of R ¹ and R ² may be bonded to each other to form an aliphatic monocyclic ring or an aliphatic heterocyclic monocyclic ring, and the monocyclic ring may be condensed with an aromatic ring. Examples of the ring or aliphatic heteromonocycle include cyclopropane, cyclobutane, cyclopentane, cyclohexane, tetrahydrofuran, pyrrolidine, piperidine, tetrahydrothiophene, indane, tetralin, dihydrobenzofuran, indoline, and the like.

The aryloxy group of the aryloxy group which may have a substituent represented by R ³ includes, but is not limited to, a phenyloxy group, a 1-naphthyloxy group, a 2-naphthyloxy group, and the like. .

The heteroaryloxy group of the heteroaryloxy group optionally having a substituent represented by R ³ is a furyloxy group, a pyrrolyloxy group, a pyridyloxy group, an indolyloxy group, a quinolyloxy group, or an isoquinolyloxy group. A thienyloxy group and the like, but is not limited thereto.

Examples of the lower alkylthio group of the lower alkylthio group which may have a substituent represented by R ³ include, but are not limited to, a methylthio group, an ethylthio group, a propylthio group, and a butylthio group.

Examples of the arylthio group of the arylthio group which may have a substituent represented by R ³ include, but are not limited to, a phenylthio group, a 1-naphthylthio group, a 2-naphthylthio group, and the like.

Examples of the heteroarylthio group of the heteroarylthio group which may have a substituent represented by R ³ include a furylthio group, a pyrrolylthio group, a pyridylthio group, an indolylthio group, a quinolylthio group, an isoquinolylthio group, and a thienylthio group. However, it is not limited to this.

The amino group of the amino group which may have a substituent represented by R ³ is a methylamino group, a dimethylamino group, an ethylamino group, a diethylamino group, a phenylamino group, a benzylamino group, a pyrrolidino group, a piperidino group However, it is not limited to this.

Examples of the acylamino group of the acylamino group which may have a substituent represented by R ³ include, but are not limited to, N-formylamino group, N-acetylamino group, N-benzoylamino group and the like. .

The carbamoyl group of the carbamoyl group which may have a substituent represented by R ³ is N-methylcarbamoyl group, N, N-dimethylcarbamoyl group, N-ethylcarbamoyl group, N, N-diethylcarbamoyl group, Examples thereof include, but are not limited to, an N-phenylcarbamoyl group and an N-benzylcarbamoyl group.

The silyloxy group of the silyloxy group which may have a substituent represented by R ³ is a trimethylsilyl group, a triethylsilyloxy group, a tert-butyldimethylsilyloxy group, a triisopropylsilyloxy group, a dimethylphenylsilyloxy group, or the like However, it is not limited to this.

Examples of the acyl group that may have a substituent represented by R ³ include, but are not limited to, a formyl group, an acetyl group, a propanoyl group, and a benzoyl group.

Examples of the acyloxy group of the acyloxy group which may have a substituent represented by R ³ include, but are not limited to, a formyloxy group, an acetyloxy group, and a propanoyloxy group.

Examples of the lower alkoxycarbonyl group of the lower alkoxycarbonyl group which may have a substituent represented by R ³ include, but are not limited to, a methoxycarbonyl group, an ethoxycarbonyl group, and a propoxycarbonyl group.

Examples of the aryloxycarbonyl group of the aryloxycarbonyl group which may have a substituent represented by R ³ include a phenoxycarbonyl group, a 1-naphthyloxycarbonyl group, a 2-naphthyloxycarbonyl group, and the like. Not limited to.

The heteroaryloxycarbonyl group of the heteroaryloxycarbonyl group which may have a substituent represented by R ³ is a furyloxycarbonyl group, a pyrrolyloxycarbonyl group, a pyridyloxycarbonyl group, an indolyloxycarbonyl group, Examples include, but are not limited to, quinolyloxycarbonyl group, isoquinolyloxycarbonyl group, thienyloxycarbonyl group, and the like.

  Throughout this specification, alkyl groups, alkenyl groups, alkynyl groups, aryl groups, aralkyl groups, heteroaryl groups, aliphatic monocyclic groups, heterocyclic groups, alkoxy groups, aryloxy groups, heteroaryloxy groups, alkylthio groups, Any of arylthio group, heteroarylthio group, amino group, acylamino group, carbamoyl group, silyl group, silyloxy group, acyl group, acyloxy group, alkoxycarbonyl group, aryloxycarbonyl group, heteroaryloxycarbonyl group, etc. can be substituted. It may have a substituent at any position, and examples of the substituent include a lower alkyl group which may have a substituent, a lower alkenyl group which may have a substituent, and a substituent. Optionally having a lower alkynyl group, optionally having an aryl group, having a substituent An aralkyl group which may have a substituent, a heteroaryl group which may have a substituent, a lower alkoxy group which may have a substituent, an aryloxy group which may have a substituent, and a substituent A heteroaryl group which may have a substituent, a lower alkylthio group which may have a substituent, an arylthio group which may have a substituent, a heteroarylthio group which may have a substituent, a substituent A carbamoyl group which may have a substituent, an acylcarbamoyl group which may have a substituent, a silyl group which may have a substituent, a silyloxy group which may have a substituent, an acyl group, an acyloxy Group, optionally substituted lower alkoxycarbonyl group, optionally substituted aryloxycarbonyl group, optionally substituted heteroaryloxycarbonyl , Halogen atom, nitro group, cyano group, cyanato group, and isocyanato group.

In the present invention, an α, β-unsaturated carbonyl compound represented by the general formula (2) (wherein R ¹ , R ² and R ³ are the same as above) is obtained.

  The organic solvent used for the conversion reaction from the general formula (1) to the general formula (2) of the present invention is not particularly limited, but preferably ethers such as diethyl ether, diisopropyl ether, t-butyl methyl ether, and tetrahydrofuran. Hydrocarbon solvents such as pentane, hexane and heptane; aromatic solvents such as benzene, toluene and xylene; ester solvents such as methyl acetate, ethyl acetate and propyl acetate; dichloromethane, 1,2-dichloroethane, chloroform and the like Halogen solvents; ketone solvents such as acetone, methyl ethyl ketone and cyclohexanone; nitrile solvents such as acetonitrile and propionitrile; nitro solvents such as nitromethane and nitroethane.

  The equivalent amount of the composite metal catalyst used in the reaction is, as far as the transition metal compound contained in the composite metal catalyst is concerned, the molar ratio of propargyl alcohol: transition metal compound is usually 1: 0.0001 to 0.3, preferably 1: 0.001 to 0.1. is there.

  Although the reaction can be carried out under pressure, it is usually carried out at normal pressure. In the case of normal pressure reaction, the reaction temperature can be carried out between −50 ° C. and the boiling point of the solvent, preferably 0 ° C. to 50 ° C.

  The concentration of the substrate, ie propargyl alcohol, in the reaction solution is usually 0.01 to 30% by weight, preferably 0.1 to 10% by weight.

  The time required for the conversion reaction from propargyl alcohol to the α, β-unsaturated carbonyl compound using the catalyst of the present invention is usually 10 minutes to 5 hours.

  Hereinafter, the present invention will be specifically described by way of examples showing a method for producing an α, β-unsaturated carbonyl compound from propargyl alcohol using the catalyst of the present invention, but the present invention is not limited to these examples. Absent.

Example 1

To a solution of 5-Phenyl-2-pentyn-1-ol (100 mg, 0.62 mmol) in toluene (1.6 mL), MoO ₂ (acac) ₂ (2.1 mg, 0.0064 mmol), AuCl (PPh ₃ ) (3.1 mg, 0.0063 mmol) and AgOTf (1.6 mg, 0.0063 mmol) were sequentially added, and the mixture was stirred at room temperature for 30 minutes. A saturated aqueous ammonium chloride solution and diethyl ether were added to the reaction solution, and the organic layer was separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by column chromatography (hexane / Et ₂ O = 10: 1) to obtain 5-phenyl-1-penten-3-one (93 mg, 93%).

(Examples 2 to 19)
Reaction was carried out in the same manner as in Example 1 for propargyl alcohol compounds having various R ¹ , R ² and R ³ . The results are shown in Table 1.

(Table 1)

Claims (1)

At least one selected from MoO ₂ (acac) ₂ , MoO ₂ (tBuCOCH ₂ COtBu) ₂ , MoO ₂ (OSiPh ₃ ) ₂ , and MoO ₂ Cl ₂ (where acac is acetylacetone (CH ₃ COCH ₂ COCH ₃ ), tBu is tert-butyl (C (CH ₃ ) ₃ ), Ph is phenyl (C ₆ H ₅ )) transition metal compound, AuCl (PMe ₃ ), AuCl (PEt ₃ ), AuCl (PPh ₃ ) , AuCl [P (C ₆ H ₄ -p-CF ₃ ) ₃ ], and AuCl [P (tBu) ₂ (o-biphenyl)] (where Me is methyl (CH ₃ ), Et is ethyl (C ₂ H _5), Ph is phenyl (C ₆ H _5), tBu is butyl tert (C (CH ₃₎ represents a ₃₎₎ gold _{compounds, AgOTf, AgClO 4, AgBF 4} , AgPF _{6, AgSbF 6, AgOAc, AgOCOCF} 3, AgNTf 2, AgOTs, and at least one selected from AgOMs (where, Tf is trifluoromethanesulfonyl (CF ₃ SO _2), Ac is acetyl (COCH _3), Ts Is p-toluenesulfonyl (p-CH ₃ -C ₆ H ₄ -SO ₂ ), Ms is methanesulfonyl (CH ₃ SO ₂ ) ) General formula (1) consisting of three metal compounds of silver compound
(In the formula, R ¹ and R ² are the same or different and each represents a hydrogen atom , a lower alkyl group , a lower alkenyl group , a lower alkynyl group , an aryl group , an aralkyl group , a heteroaryl group , a lower alkoxy group , or a silyl group. Alternatively, each alkyl group of R ¹ and R ² may be bonded to each other to form an aliphatic monocyclic ring or an aliphatic heterocyclic monocyclic ring, and an aromatic ring may be condensed with the monocyclic ring. ³ represents hydrogen atom , lower alkyl group , lower alkenyl group , lower alkynyl group , aryl group , aralkyl group , heteroaryl group , lower alkoxy group , aryloxy group , heteroaryloxy group , lower alkylthio group , arylthio group , heteroarylthio Group , amino group , acylamino group , carbamoyl group , silyl group , silyloxy group , acyl group , acyloxy group , lower alkoxy Represents a cicarbonyl group , an aryloxycarbonyl group , a heteroaryloxycarbonyl group, a halogen atom, a nitro group, or a cyano group, or each alkyl group of R ² and R ³ is bonded to each other to form an aliphatic monocycle or an aliphatic heterocycle A monocyclic ring may be formed, and an aromatic ring may be condensed to the monocyclic ring) to transfer a propargyl alcohol compound represented by the general formula (2),
(Where R ¹ , R ² And R ³ Is the same as above. The composite metal catalyst used for the reaction which synthesize | combines the (alpha), (beta)-unsaturated carbonyl compound shown by this.