JP2000109436A - Improved production of cross coupling compound using phosphine oxide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a cross coupling compound by a method of extremely improved yield by subjecting an organotin compound, an organic electrophilic agent and a specific phosphine oxide to a cross coupling reaction in the presence of a palladium catalyst. SOLUTION: An organotin compound (a compound in which at least one of four substituent groups bonded to a tin atom is an aryl, a heteroaryl, an aralkyl or an alkynyl), an organic electrophilic agent [(a hetero)aryl halide, an aralkyl halide, an alkynyl halide, an acid halide, etc.], and a phosphine oxide of the formula; R3P=O (R is a lower alkyl or an aryl) are subjected to a cross coupling reaction in the presence of a palladium catalyst [e.g. tetrakis(triphenylphosphine)palladium (0)]. The reaction is carried out in a solvent such as preferably an aliphatic or aromatic hydrocarbon, ether, nitrile, amide, etc., at 0-200 deg.C for 1 hour to 5 days.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a cross-coupling reaction using an organotin compound and an organic electrophile in the presence of a palladium catalyst. The present invention relates to a method for producing a novel cross-coupling compound.

[0002]

2. Description of the Related Art Among various carbon-carbon formation reactions, a palladium-catalyzed cross-coupling reaction has a mild reaction condition, is tolerant to many functional groups, and has a regio- and stereoselectivity. Because of its high cost, it is a synthesis method that has been used frequently.

[0003] In particular, the reaction between an organotin compound and various organic electrophiles is known as the Stille reaction, and the organotin compound can coexist with many functional groups among the organometallic species, and is sensitive to oxygen and moisture. Because it is stable and difficult to decompose, it is much easier to handle than other organometallic species, and since a variety of organotin compounds are provided, there are a huge number of reports (Review: John K. Stille, Angew. Chem. I
nt. Ed. Engl., 25, 508, 1986; Terence N. Mitchell,
Synthesis, 803, 1992).

However, it is not known to use phosphine oxide for this reaction.

[0005]

DISCLOSURE OF THE INVENTION The present inventors have conducted intensive research on the cross-coupling reaction using an organotin compound and an organic electrophile in the presence of a palladium catalyst for many years. The inventors have found that the use of phosphine oxides leads to significant yield improvements and have completed the present invention.

Still another object of the present invention is to provide a method of using a phosphine oxide in a cross-coupling reaction between an organotin compound and an organic electrophile in the presence of a palladium catalyst. is there.

[0007]

The process for producing a novel cross-coupling compound according to the present invention comprises a cross-coupling reaction using an organotin compound and an organic electrophile in the presence of a palladium catalyst. A phosphine oxide having R ₃ P ＝ O (wherein R represents a lower alkyl group or an aryl group);
The novel method of the present invention relates to a cross-coupling reaction using an organotin compound and an organic electrophile in the presence of a palladium catalyst, further comprising a phosphine oxide having the general formula R ₃ P ＰO (where R is , A lower alkyl group or an aryl group.).

Here, the palladium catalyst refers to a catalyst containing palladium, and if so, there is no particular limitation.
For example, tetrakis (triphenylphosphine) palladium (0), bis [1,2-bis (diphenylphosphino) ethane] palladium (0), bis [o-phenylenebis (diethylphosphino) ethane (diphenylphosphino) palladium (0), bis (cycloocta-1,5-
Diene) palladium (0), palladium carbon, palladium black, palladium (II) acetate, palladium (II) acetoacetate, palladium (II) chloride, palladium (II) cyanide, palladium (II) trifluoroacetate, [1, 2
-Bis (diphenylphosphino) ethane] dichloropalladium (II), bis (acetonitrile) dichloropalladium (II), bis (acetate) bis (triphenylphosphine) palladium (II), bis (benzonitrile)
Dichloropalladium (II), [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (I
I), (2,2′-bipyridine) dichloropalladium (I
I), (bicyclo [2,2,1] hepta-2,5-diene) dichloropalladium (II), dichloro (1,5-cyclooctadiene) palladium (II), dichlorobis (triphenylphosphine) dichloropalladium ( II)
Palladium catalysts such as tetrakis (triphenylphosphine) palladium (0) and bis [1,2-bis (diphenylphosphino)] are preferred.
Ethane] palladium (0), bis [o-phenylenebis (diethylphosphino) ethane (diphenylphosphino) palladium (0), bis (cycloocta-1,5-
Diene) palladium (0), palladium (II) acetate, palladium (II) acetoacetate, palladium (II) chloride, palladium (II) trifluoroacetate, [1,2-bis (diphenylphosphino) ethane] dichloropalladium ( I
I), bis (acetonitrile) dichloropalladium (I
I), bis (acetate) bis (triphenylphosphine) palladium (II) and dichlorobis (triphenylphosphine) dichloropalladium (II), more preferably tetrakis (triphenylphosphine) palladium (0), bis [ 1,2-bis (diphenylphosphino) ethane] palladium (0), [1,2-bis (diphenylphosphino) ethane] dichloropalladium (II)
And dichlorobis (triphenylphosphine) dichloropalladium (II).

The organic tin compound is a compound in which at least one of the four substituents bonded to a tin atom is an aryl group, a heteroaryl group, an aralkyl group or an alkynyl group. The aryl group is the same as the aryl group in the definition of R, and the heteroaryl group is a 5- to 7-membered heteroaromatic group containing 1 to 3 sulfur atoms, oxygen atoms and / or nitrogen atoms. For example, groups such as furyl, thienyl, pyrrolyl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl Can be mentioned.

The above “5- to 7-membered heteroaromatic group” is
May be fused with another cyclic group, for example, isobenzofuranyl, chromenil, xanthenyl, phenoxathiinyl, indolizinyl, isoindolyl, indolyl,
Examples include groups such as indazolyl, purinyl, quinolidinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, carbazolyl, carbolinyl, acridinyl, isoindolinyl.

The aralkyl group refers to a group in which the above "aryl group" is bonded to the following "lower alkyl group".
Benzyl, α-naphthylmethyl, β-naphthylmethyl,
Examples include groups having high rearrangement activity such as indenylmethyl, phenanthrenylmethyl, anthracenylmethyl, diphenylmethyl, and triphenylmethyl.

The alkynyl group includes, for example, ethynyl, 2
-Propynyl, 1-methyl-2-propynyl, 2-methyl-2-propynyl, 2-ethyl-2-propynyl, 2
-Butynyl, 1-methyl-2-butynyl, 2-methyl-
2-butynyl, 1-ethyl-2-butynyl, 3-butynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butynyl, 2-pentynyl, 1
-Methyl-2-pentynyl, 2-methyl-2-pentynyl, 3-pentynyl, 1-methyl-3-pentynyl, 2
-Methyl-3-pentynyl, 4-pentynyl, 1-methyl-4-pentynyl, 2-methyl-4-pentynyl, 2
-Hexynyl, 3-hexynyl, 4-hexynyl, 5-
A straight-chain or branched-chain alkynyl group having 2 to 6 carbon atoms such as hexynyl can be mentioned.
From 4 to 4 linear or branched alkynyl groups.

The organic electrophile includes aryl halide, heteroaryl halide, aralkyl halide or alkynyl halide or its equivalent,
Alternatively, it represents an acid halide, and the aryl halide is the above "aryl group" and a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom (preferably a bromine atom and an iodine atom). Represents a group bonded to

The term "heteroaryl halide" means a group wherein the above "heteroaryl group" and the above "halogen atom" are bonded.

The term "aralkyl halide" refers to a group in which the "aralkyl group" and the "halogen atom" are bonded.

The term "alkynyl halide" refers to a group in which the "alkynyl group" and the "halogen atom" are bonded.

The equivalent means a derivative in which the above-mentioned halogen atom is another leaving group. Such a leaving group is not particularly limited as long as it is a group which usually leaves as a nucleophilic residue. But not preferably, an alkylcarbonyloxy group such as acetyloxy; a lower alkoxycarbonyloxy group such as methoxycarbonyloxy or ethoxycarbonyloxy; a chloroacetyloxy, dichloroacetyloxy, trichloroacetyloxy, or trifluoroacetyloxy group. Halogenated alkylcarbonyloxy group; lower alkanesulfonyloxy group such as methanesulfonyloxy and ethanesulfonyloxy; halogeno lower alkanesulfonyloxy group such as trifluoromethanesulfonyloxy and pentafluoroethanesulfonyloxy; Examples thereof include arylsulfonyloxy groups such as nyloxy, p-toluenesulfonyloxy, and p-nitrobenzenesulfonyloxy, and more preferably a lower alkanesulfonyloxy group or a halogeno lower alkanesulfonyloxy group, which is most preferable. Is a halogeno lower alkane sulfonyloxy group.

The acid halide refers to a halide of a carboxylic acid, and specific examples thereof include aliphatic acyl halides such as acetyl chloride, propionyl chloride, butyryl bromide, valeryl chloride, and hexanoyl chloride; Methoxycarbonyl chloride, methoxycarbonyl bromide, ethoxycarbonyl chloride, propoxycarbonyl chloride, butoxycarbonyl chloride, lower alkoxycarbonyl halide such as hexyloxycarbonyl chloride or benzoyl chloride, benzoyl bromide, arylcarbonyl halide such as naphthoyl chloride Acyl halides can be mentioned.

The lower alkyl group in the definition of R includes, for example, methyl, ethyl, n-propyl, isopropyl,
n-butyl, isobutyl, s-butyl, tert-butyl,
n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methylpentyl,
-Methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl A straight-chain or branched alkyl group having 1 to 6 carbon atoms such as, 2-ethylbutyl, and preferably a straight-chain or branched alkyl group having 1 to 4 carbon atoms.

The aryl group in the definition of R includes, for example, an aromatic hydrocarbon group having 5 to 14 carbon atoms such as phenyl, indenyl, naphthyl, phenanthrenyl, and anthracenyl. is there.

The "aryl group" may be condensed with a cycloalkyl group having 3 to 10 carbon atoms, and examples thereof include groups such as 2-indanyl.

The group may have 1 to 4 substituents on the ring of the aryl group. Examples of the substituent include an "aryl group"; an amino group; A substituted amino group; a nitro group; a cyano group; a carboxylic acid residue which may be substituted with the above “lower alkyl”, “halogeno lower alkyl” or “aralkyl” to form an ester; a carbamoyl group Methylcarbamoyl, ethylcarbamoyl, n-propylcarbamoyl,
Isopropylcarbamoyl, n-butylcarbamoyl,
Isobutylcarbamoyl, s-butylcarbamoyl, te
rt-butylcarbamoyl, n-pentylcarbamoyl,
Isopentylcarbamoyl, 2-methylbutylcarbamoyl, neopentylcarbamoyl, n-hexylcarbamoyl, 4-methylpentylcarbamoyl, 3-methylpentylcarbamoyl, 2-methylpentylcarbamoyl, 3,3-dimethylbutylcarbamoyl, 2,2-dimethyl Butylcarbamoyl, 1,1-dimethylbutylcarbamoyl, 1,2-dimethylbutylcarbamoyl,
1,3-dimethylbutylcarbamoyl, 2,3-dimethylbutylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, di-n-propylcarbamoyl, diisopropylcarbamoyl, di-n-butylcarbamoyl, diisobutylcarbamoyl, di-s-butylcarbamoyl, di- A lower alkyl-substituted carbamoyl group substituted with a linear or branched alkyl group having 1 to 6 carbon atoms such as tert-butylcarbamoyl (preferably having 1 to 4 carbon atoms);
A carbamoyl group substituted by two alkyl groups, more preferably methylcarbamoyl and dimethylcarbamoyl. A halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom; the above-mentioned "lower alkyl group"; the below-mentioned "lower alkoxy group"; trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, dibromomethyl, fluoro Methyl, 2,2,2-trichloroethyl, 2,2,2-trifluoroethyl, 2-bromoethyl, 2-chloroethyl, 2-fluoroethyl, 2,2-
Halogeno lower alkyl groups such as dibromoethyl; alkylcarbonyl groups such as formyl, acetyl, propionyl, butyryl, isobutyryl, pivaloyl, valeryl, isovaleryl, octanoyl, lauroyl, myristoyl, tridecanoyl, palmitoyl, stearoyl, chloroacetyl, dichloroacetyl, Halogenated alkylcarbonyl groups such as trichloroacetyl and trifluoroacetyl, lower alkoxyalkylcarbonyl groups such as methoxyacetyl, (E) -2-methyl-2
-An aliphatic acyl group such as an unsaturated alkylcarbonyl group such as butenoyl; and an alkylenedioxy group having 1 to 4 carbon atoms such as methylenedioxy, ethylenedioxy and propylenedioxy. In
A lower alkyl group and a halogen atom.

The group is preferably an aryl group such as phenyl or naphthyl; 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl,
-Bromophenyl, 3-bromophenyl, 4-bromophenyl, 3,5-difluorophenyl, 2,5-difluorophenyl, 2,6-difluorophenyl, 2,4-
Difluorophenyl, 3,5-dibromophenyl, 2,
5-dibromophenyl, 2,6-dichlorophenyl,
2,4-dichlorophenyl, 2,3,6-trifluorophenyl, 2,3,4-trifluorophenyl, 3,
4,5-trifluorophenyl, 2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl,
2,3,6-tribromophenyl, 2,3,4-tribromophenyl, 3,4,5-tribromophenyl, 2,
5,6-trichlorophenyl, 2,4,6-trichlorophenyl, 1-fluoro-2-naphthyl, 2-fluoro-1-naphthyl, 3-fluoro-1-naphthyl, 1-chloro-2-naphthyl, 2- Chloro-1-naphthyl, 3-
Bromo-1-naphthyl, 3,8-difluoro-1-naphthyl, 2,3-difluoro-1-naphthyl, 4,8-difluoro-1-naphthyl, 5,6-difluoro-1-naphthyl, 3,8- Dichloro-1-naphthyl, 2,3-dichloro-1-naphthyl, 4,8-dibromo-1-naphthyl, 5,6-dibromo-1-naphthyl, 2,3,6-trifluoro-1-naphthyl, , 3,4-trifluoro-1-naphthyl, 3,4,5-trifluoro-1-naphthyl, 4,5,6-trifluoro-1-naphthyl, 2,
Aryl groups substituted with halogen atoms such as 4,8-trifluoro-1-naphthyl; 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-trichloromethylphenyl, 3 -Dichloromethylphenyl, 4-trichloromethylphenyl, 2-tribromomethylphenyl, 3-dibromomethylphenyl, 4-dibromomethylphenyl,
3,5-bistrifluoromethylphenyl, 2,5-bistrifluoromethylphenyl, 2,6-bistrifluoromethylphenyl, 2,4-bistrifluoromethylphenyl, 3,5-bistribromomethylphenyl,
2,5-bisdibromomethylphenyl, 2,6-bisdichloromethylmethylphenyl, 2,4-bisdichloromethylphenyl, 2,3,6-tristrifluoromethylphenyl, 2,3,4-tristrifluoromethyl Phenyl, 3,4,5-tristrifluoromethylphenyl, 2,5,6-tristrifluoromethylphenyl,
2,4,6-tristrifluoromethylphenyl, 2,
3,6-tristribromomethylphenyl, 2,3,4
-Trisdibromomethylphenyl, 3,4,5-tristribromomethylphenyl, 2,5,6-trisdichloromethylmethylphenyl, 2,4,6-trisdichloromethylphenyl, 1-trifluoromethyl-2-naphthyl 2-trifluoromethyl-1-naphthyl, 3-trifluoromethyl-1-naphthyl, 1-trichloromethyl-2-naphthyl, 2-dichloromethyl-1-naphthyl,
3-tribromomethyl-1-naphthyl, 3,8-bistrifluoromethyl-1-naphthyl, 2,3-bistrifluoromethyl-1-naphthyl, 4,8-bistrifluoromethyl-1-naphthyl, 5,6- Bistrifluoromethyl-1-naphthyl, 3,8-bistrichloromethyl-
1-naphthyl, 2,3-bisdichloromethyl-1-naphthyl, 4,8-bisdibromomethyl-1-naphthyl,
5,6-bistribromomethyl-1-naphthyl, 2,
3,6-tristrifluoromethyl-1-naphthyl,
2,3,4-tristrifluoromethyl-1-naphthyl, 3,4,5-tristrifluoromethyl-1-naphthyl, 4,5,6-tristrifluoromethyl-1-naphthyl, 2,4,8 -Tristrifluoromethyl-1-
Aryl groups substituted with halogenated lower alkyl groups such as naphthyl; 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-propylphenyl, 4-ethylphenyl, 2-butylphenyl , 3-pentylphenyl, 4-pentylphenyl,
3,5-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 2,4-dimethylphenyl, 3,5-dibutylphenyl, 2,5-dipentylphenyl, 2,6-dipropylmethylphenyl , 2, 4
-Dipropylphenyl, 2,3,6-trimethylphenyl, 2,3,4-trimethylphenyl, 3,4,5-trimethylphenyl, 2,5,6-trimethylphenyl,
2,4,6-trimethylphenyl, 2,3,6-tributylphenyl, 2,3,4-tripentylphenyl,
3,4,5-tributylphenyl, 2,5,6-tripropylmethylphenyl, 2,4,6-tripropylphenyl, 1-methyl-2-naphthyl, 2-methyl-1-naphthyl, 3-methyl- 1-naphthyl, 1-ethyl-2-
Naphthyl, 2-propyl-1-naphthyl, 3-butyl-
1-naphthyl, 3,8-dimethyl-1-naphthyl, 2,
3-dimethyl-1-naphthyl, 4,8-dimethyl-1-
Naphthyl, 5,6-dimethyl-1-naphthyl, 3,8-
Diethyl-1-naphthyl, 2,3-dipropyl-1-naphthyl, 4,8-dipentyl-1-naphthyl, 5,6-
Dibutyl-1-naphthyl, 2,3,6-trimethyl-1
-Naphthyl, 2,3,4-trimethyl-1-naphthyl,
3,4,5-trimethyl-1-naphthyl, 4,5,6-
Trimethyl-1-naphthyl, 2,4,8-trimethyl-
Aryl groups substituted with lower alkyl groups such as 1-naphthyl; 2-vinylphenyl, 3-vinylphenyl,
-Vinylphenyl, 2-butenylphenyl, 3-pentenylphenyl, 4-pentenylphenyl, 3,5-divinylphenyl, 2,5-divinylphenyl, 2,6-dipropenylmethylphenyl, 2,4-dipropenylphenyl , 2,3,6-trivinylphenyl, 2,3,4-
Tripentenylphenyl, 3,4,5-tributenylphenyl, 2,5,6-tripropenylphenyl, 2,
4,6-tripropenylphenyl, 1-vinyl-2-naphthyl, 2-propenyl-1-naphthyl, 3-vinyl-
1-naphthyl, 3,8-divinyl-1-naphthyl, 2,
Aryl groups substituted by lower alkenyl groups such as 3-dipropenyl-1-naphthyl, 4,8-dipentenyl-1-naphthyl, 5,6-dibutenyl-1-naphthyl; 2
-Ethynylphenyl, 3-propynylphenyl, 4-ethynylphenyl, 2-butynylphenyl, 3-pentynylphenyl, 4-pentynylphenyl, 3,5-dibutynylphenyl, 2,5-dipentynylphenyl, 2 , 6
Aryl groups substituted with lower alkynyl groups such as -dipropynylmethylphenyl, 2,4-dipropynylphenyl; 2-methoxyphenyl, 3-methoxyphenyl,
4-methoxyphenyl, 2-ethoxyphenyl, 3-propoxyphenyl, 4-ethoxyphenyl, 2-butoxyphenyl, 3-pentoxyphenyl, 4-pentoxyphenyl, 3,5-dimethoxyphenyl, 2,5-dimethoxyphenyl , 2,6-dimethoxyphenyl, 2,4
-Dimethoxyphenyl, 3,5-dibutoxyphenyl,
2,5-dipentoxyphenyl, 2,6-dipropoxymethoxyphenyl, 2,4-dipropoxyphenyl,
2,3,6-trimethoxyphenyl, 2,3,4-trimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2,5,6-trimethoxyphenyl, 2,4,6-
Trimethoxyphenyl, 2,3,6-tributoxyphenyl, 2,3,4-tripentoxyphenyl, 3,4
5-tributoxyphenyl, 2,5,6-tripropoxyphenyl, 2,4,6-tripropoxyphenyl, 1
-Methoxy-2-naphthyl, 2-methoxy-1-naphthyl, 3-methoxy-1-naphthyl, 1-ethoxy-2-
Naphthyl, 2-propoxy-1-naphthyl, 3-butoxy-1-naphthyl, 3,8-dimethoxy-1-naphthyl, 2,3-dimethoxy-1-naphthyl, 4,8-dimethoxy-1-naphthyl, 5, 6-dimethoxy-1-naphthyl, 3,8-diethoxy-1-naphthyl, 2,3-dipropoxy-1-naphthyl, 4,8-dipentoxy-1
-Naphthyl, 5,6-dibutoxy-1-naphthyl, 2,
3,6-trimethoxy-1-naphthyl, 2,3,4-trimethoxy-1-naphthyl, 3,4,5-trimethoxy-1-naphthyl, 4,5,6-trimethoxy-1-naphthyl, 2,4 Aryl group substituted with a lower alkoxy group such as 8-trimethoxy-1-naphthyl; 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, 3,5-diaminophenyl, 2,5-diaminophenyl, 2,6-diaminophenyl, 2,4-diaminophenyl, 2,3,6-triaminophenyl, 2,3,4
-Triaminophenyl, 3,4,5-triaminophenyl, 2,5,6-triaminophenyl, 2,4,6-triaminophenyl, 1-amino-2-naphthyl, 2-amino-1-naphthyl , 3-amino-1-naphthyl, 3,
8-diamino-1-naphthyl, 2,3-diamino-1-
Naphthyl, 4,8-diamino-1-naphthyl, 5,6-
Diamino-1-naphthyl, 2,3,6-triamino-1
-Naphthyl, 2,3,4-triamino-1-naphthyl,
3,4,5-triamino-1-naphthyl, 4,5,6-
Triamino-1-naphthyl, 2,4,8-triamino-
Aryl groups substituted with amino groups such as 1-naphthyl; 2- (methylamino) phenyl, 3- (methylamino) phenyl, 4- (methylamino) phenyl, 2-
(Ethylamino) phenyl, 3- (ethylamino) phenyl, 4- (ethylamino) phenyl, 2- (propylamino) phenyl, 3- (propylamino) phenyl,
4- (propylamino) phenyl, 2- (dimethylamino) phenyl, 3- (dimethylamino) phenyl, 4-
(Dimethylamino) phenyl, 2- (diethylamino)
Phenyl, 3- (diethylamino) phenyl, 4- (diethylamino) phenyl, 3,5-bis (methylamino) phenyl, 2,5-bis (methylamino) phenyl, 2,6-bis (methylamino) phenyl, , 4-
Bis (methylamino) phenyl, 3,5-bis (dimethylamino) phenyl, 2,5-bis (dimethylamino)
Phenyl, 2,6-bis (dimethylamino) phenyl,
2,4-bis (dimethylamino) phenyl, 1- (methylamino) -2-naphthyl, 2- (methylamino) -1
-Naphthyl, 3- (methylamino) -1-naphthyl, 1
-(Dimethylamino) -2-naphthyl, 2- (dimethylamino) -1-naphthyl, 3- (dimethylamino) -1
-An aryl group substituted with an amino group substituted with a lower alkyl group such as naphthyl; 2-nitrophenyl, 3-
Nitrophenyl, 4-nitrophenyl, 3,5-dinitrophenyl, 2,5-dinitrophenyl, 2,6-dinitrophenyl, 2,4-dinitrophenyl, 2,3,6
-Trinitrophenyl, 2,3,4-trinitrophenyl, 3,4,5-trinitrophenyl, 2,5,6-trinitrophenyl, 2,4,6-trinitrophenyl,
1-nitro-2-naphthyl, 2-nitro-1-naphthyl, 3-nitro-1-naphthyl, 3,8-dinitro-1
-Naphthyl, 2,3-dinitro-1-naphthyl, 4,8
Dinitro-1-naphthyl, 5,6-dinitro-1-naphthyl, 2,3,6-trinitro-1-naphthyl, 2,
3,4-trinitro-1-naphthyl, 3,4,5-trinitro-1-naphthyl, 4,5,6-trinitro-1-
Aryl groups substituted by nitro groups such as naphthyl, 2,4,8-trinitro-1-naphthyl; 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3,
5-dicyanophenyl, 2,5-dicyanophenyl,
2,6-dicyanophenyl, 2,4-dicyanophenyl, 2,3,6-tricyanophenyl, 2,3,4-tricyanophenyl, 3,4,5-tricyanophenyl,
2,5,6-tricyanophenyl, 2,4,6-tricyanophenyl, 1-cyano-2-naphthyl, 2-cyano-1-naphthyl, 3-cyano-1-naphthyl, 3,8-
Dicyano-1-naphthyl, 2,3-dicyano-1-naphthyl, 4,8-dicyano-1-naphthyl, 5,6-dicyano-1-naphthyl, 2,3,6-tricyano-1-naphthyl, 2, 3,4-tricyano-1-naphthyl, 3,
4,5-tricyano-1-naphthyl, 4,5,6-tricyano-1-naphthyl, 2,4,8-tricyano-1-
An aryl group substituted with a cyano group such as naphthyl; 2
-Acetylphenyl, 3-acetylphenyl, 4-acetylphenyl, 3,5-diacetylphenyl, 2,5-
Diacetylphenyl, 2,6-diacetylphenyl,
2,4-diacetylphenyl, 2,3,6-tripropionylphenyl, 2,3,4-tripropionylphenyl, 3,4,5-tripropionylphenyl, 2,5
6-Tributyrylphenyl, 2,4,6-Tributyrylphenyl, 1-acetyl-2-naphthyl, 2-acetyl-1-naphthyl, 3-acetyl-1-naphthyl, 3,8
-Diacetyl-l-naphthyl, 2,3-dipropionyl-l-naphthyl, 4,8-dibutyryl-l-naphthyl,
5,6-dibutyryl-1-naphthyl, 2,3,6-triacetyl-1-naphthyl, 2,3,4-triacetyl-
1-naphthyl, 3,4,5-tripropionyl-1-naphthyl, 4,5,6-tributyryl-1-naphthyl,
Aryl group substituted with an aliphatic acyl group such as 2,4,8-tributyryl-1-naphthyl; 2-carboxyphenyl, 3-carboxyphenyl, 4-carboxyphenyl, 3,5-dicarboxyphenyl, 5-dicarboxyphenyl, 2,6-dicarboxyphenyl, 2,
An aryl group substituted with a carboxy group such as 4-dicarboxyphenyl; 2-carbamoylphenyl, 3-carbamoylphenyl, 4-carbamoylphenyl, 3,
5-dicarbamoylphenyl, 2,5-dicarbamoylphenyl, 2,6-dicarbamoylphenyl, 2,4-
An aryl group substituted with a carbamoyl group such as dicarbamoylphenyl; and an aryl group substituted with an alkylenedioxy group such as 3,4-methylenedioxyphenyl.

The starting compound of the present invention has an asymmetric carbon in the molecule, and there are stereoisomers each having R-coordination and S-coordination. Are included in the present invention.

[0025]

DETAILED DESCRIPTION OF THE INVENTION The reaction of the present invention is preferably carried out in a solvent.

The solvent is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Examples thereof include aliphatic hydrocarbons such as hexane and heptane; benzene, toluene and xylene. Aromatic hydrocarbons such as; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether; nitriles such as acetonitrile, propionitrile, isobutyronitrile; formamide;
Examples include amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidinone, and hexamethylphosphorotriamide.

[0027] The reaction temperature is from 0 ° C to 200 ° C, preferably from 50 ° C to 150 ° C.

The reaction time mainly depends on the reaction temperature, the starting compound,
Although it depends on the type of reagent, additive or solvent used, it is usually 1 hour to 5 days, preferably 5 hours to 24 hours.

Hereinafter, the present invention will be described more specifically with reference to Examples and Reference Examples.

[0030]

[Example] Cross-coupling using palladium catalyst
Effect of Phosphine Oxide on Reaction As shown in the table below, a reaction for producing a cross-coupling compound using a raw material compound was examined under the following conditions.

<Condition A> Organotin compound: organic electrophile: Pd (PPh ₃ ) ₄ : potassium carbonate = 1: 2: 0.1: 2 (in dioxane solvent) <Condition B> Organotin compound: organic parent Electronic agent: Pd (PPh ₃ ) ₄ : potassium carbonate: Ph ₃ PO = 1: 3: 0.1: 2: 1 (in dioxane solvent)

[0032]

[Table 1]

As is evident from Table 1, in all the examples, when phosphine oxide was added as an additive, a remarkable improvement in yield was observed.

[0034]

Example 1 1,4-Dimethoxy-2- [4-methoxy
-3- (2,3,4,6-tetra-O-acetyl-β-
D-galactopyranosyl) benzyl] -5- (2-phthal
Luimide-2-deoxy-3,4,6-tri-O-ace
Tyl -β-D-glucopyranosyl) benzene <Reaction under Condition A> 1,4-Dimethoxy-2- (2-phthalimido-2-deoxy-3,4,6) disclosed in Japanese Patent Application No. 9-288847. -Tri-O-acetyl-β
-D-glucopyranosyl) -5-tri-n-butylstannylbenzene (107 mg, 0.127 mmol), 4-bromomethyl-1-methoxy- obtained in Reference Example 1.
2- (2,3,4,6-tetra-O-acetyl-β-D
-Galactopyranosyl) benzene (202 mg, 0.3
80 mmol), tetrakistriphenylphosphinepalladium (17.5 mg, 0.015 mmol), and potassium carbonate (39 mg, 0.28 mmol) were added to 1,
It was dissolved in 4-dioxane and heated under reflux for 7 hours under a nitrogen stream. Add ethyl acetate (15 ml), wash with saturated aqueous potassium fluoride solution, dry over magnesium sulfate,
The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (ethyl acetate: hexane = 1: 1) to give the target compound in an amount of 22% (28 mg, 0.028 mm).
ol). <Reaction under Condition B> 1,4-Dimethoxy-2- (2-phthalimido-2-deoxy-3,4,6-tri-O-acetyl-β disclosed in Japanese Patent Application No. 9-288847.
-D-glucopyranosyl) -5-tri-n-butylstannylbenzene (107.8 mg, 0.128 mmol)
l), 4-bromomethyl-1-methoxy-2- (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) benzene obtained in Reference Example 1 (208 m
g, 0.391 mmol), tetrakistriphenylphosphine palladium (18.8 mg, 0.016 mmol)
l), potassium carbonate (38 mg, 0.27 mmol),
And triphenylphosphine oxide (37 mg,
0.13 mmol) in 1,4-dioxane,
The mixture was heated and refluxed for 7 hours under a nitrogen stream. Ethyl acetate (15m
l) was added, washed with a saturated aqueous potassium fluoride solution, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (ethyl acetate: hexane = 1: 1) to give the target compound at 82%.
(106 mg, 0.105 mmol). Melting point: 110-111 ° C. TLC R _f : 0.18 (hexane: ethyl acetate =
1: 1) ¹ H-nuclear magnetic resonance spectrum (270 MHz, CDCl
₃ ) δ ppm: 7.84-7.81 (1H, m), 7.71-7.63 (3H, m), 7.24 (1H, d, J = 1.9 Hz), 6.92 ( 1H, dd, J = 8.5, 1.9 Hz), 6.70 (1H, d, J = 8.5 Hz), 6.32 (1H, s), 6.12 (1H, t, J = 10) 5.0 Hz), 5.66 (1H, d, J = 10.0 Hz), 5.49 (1H, d, J = 3.3 Hz), 5.42 (1H, t, J = 10.0 Hz), 5 3.29 (1H, t, J = 10.0 Hz), 5.18 (1H, dd, J = 10.0, 3.3 Hz), 4.84 (1H, d, J = 10.0 Hz), 4. 64 (1H, t, J = 10.0 Hz), 4.33 (1H, dd, J = 12.4, 4.7 Hz), 4.22-4.00 (4H, m), 3.88 (1H , D, J = 15.6 Hz), 3.87-3.78 (1H, m), 3.81 (3H, s), 3.78 (3H, s), 3.72 (1H, d, J = 15.5 Hz) ), 3.35 (3H, s), 2.19 (3H, s), 2.09 (3H, s), 2.07 (3H, s), 2.02 (3H, s), 1.97. (3H, s), 1.87 (3H, s), 1.68 (3H, s). Infrared absorption spectrum (KBr tablet, cm ^-1 ): 3480,
2939, 2839, 1752, 1721, 1506. High resolution (FAB) mass spectrum: Calculated value: C ₅₀ H ₅₅ O ₂₁ N: [M] ⁺ = 1005.326
7, actual value: 1005.3239. Specific rotation: [α] ²³ _D = -11 ° (c = 0.55, CH
₂ Cl ₂ ).

[0035]

Example 2 1,4-Dimethoxy-2- [4-methoxy
-3- (2,3,4,6-tetra-O-acetyl-β-
D-galactopyranosyl) benzyl] -5- (2,3
4-tri-O-acetyl-β-L-rhamnopyranosyl)
Benzene <Reaction under Condition A> 1,4-Dimethoxy-2- (2,3,4-tri-O-acetyl-β-L-rhamnopyranosyl) -5 disclosed in Japanese Patent Application No. 9-288847. −
Tri-n-butylstannylbenzene (98 mg, 0.1
4 mmol), 4-bromomethyl-1-methoxy-2- (2,3,4,6-tetra-O-) obtained in Reference Example 1.
Acetyl-β-D-galactopyranosyl) benzene (2
Using 24 mg, 0.42 mmol), the reaction was carried out according to the method of condition A of Example 1 to obtain 28% of the target compound (3%).
3 mg, 0.039 mmol). <Reaction under condition B> 1,4-Dimethoxy-2- (2,3,4-tri-O-acetyl-β-L-rhamnopyranosyl) -5-5- disclosed in Japanese Patent Application No. 9-288847.
Tri-n-butylstannylbenzene (72.9 mg,
0.104 mmol) and 4-bromomethyl-1-methoxy-2- (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) benzene obtained in Reference Example 1 (166 mg). , 0.313 mmol) and triphenylphosphine oxide (30 mg, 0.11 m
The reaction was carried out according to the method of condition B of Example 1 to give 76% of the target compound (68 mg, 0.080 m
mol). TLC R _f : 0.40 (hexane: ethyl acetate =
1: 1). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl
₃ ) δ ppm: 7.31 (1H, d, J = 1.6 Hz), 7.06-6.98 (2H, m), 6.73 (1H, d, J = 8.3 Hz), 52 (1H, s), 5.53 (1H, d, J = 3.6 Hz), 5.51 (1H, d, J = 3.2 Hz), 5.48 (1H, t, J = 10.0 Hz) ), 5.25 (1H, dd, J = 9.9, 3.6 Hz), 5.20 (1H, dd, J = 10.0, 3.2 Hz), 5.15 (1H, t, J = 9.9 Hz), 5.01 (1H, s), 4.88 (1H, d, J = 10.0 Hz), 4.20-4.01 (3H, m), 3.79 (6H, s) , 3.79-3.71 (2H, m), 3.71 (3H, s), 3.76-3.65 (1H, m), 2.21 (3H, s), 2.08 (3H , S), 2.03 (3 H, s), 1.99 (3H, s), 1.98 (3H, s), 1.93 (3H, s), 1.72 (3H, s), 1.32 (1H, d, J = 6.2 Hz). Infrared absorption spectrum (KBr tablet, cm ^-1 ): 3469,
2939, 2858, 1751, 1505. High resolution (FAB) mass spectrum: Calculated value: C ₄₂ H ₅₂ O ₁₉ Na: [M + Na] ⁺ = 883,
3000. Found: 883.3030. Specific rotation: [α] ²³ _D = + 19.9 ° (c = 1.83,
CH ₂ Cl ₂ ).

[0036]

Example 3 1,3-Dimethoxy-4- [4-methoxy
-3- (2,3,4,6-tetra-O-acetyl-β-
D-galactopyranosyl) benzyl] -6- (methyl
5-acetamido-3,5-dideoxy-4,7,8,
9-tetra-O-acetyl-α-D-glycero-D-g
Lact-2-nonulopyranosylonate ) benzene <Reaction under condition A> 1,3-Dimethoxy-4- (methyl 5-acetamido-3,5-dideoxy) disclosed in Japanese Patent Application No. 9-288847. -4,7,8,9-Tetra-O-acetyl-α-D-glycero-D-galact-2-nonulopyranosylonate) -6-tri-n-butylstannylbenzene (86 mg, 0.096 mmol)
l), 4-bromomethyl-1-methoxy-2- (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) benzene (157 m) obtained in Reference Example 1.
g, 0.30 mmol), and the reaction was carried out according to the method of condition A of Example 1, but the target compound was not obtained. <Reaction under Condition B> 1,3-Dimethoxy-4- (methyl-5-acetamido-3,5-dideoxy-4,7,8,9-tetra-) disclosed in Japanese Patent Application No. 9-288847. O-acetyl-α-D-glycero-D-galact-2-nonulopyranosylonate) -6-tri-n-butylstannylbenzene (89 mg, 0.099 mmol)
l), 4-bromomethyl-1-methoxy-2- (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) benzene obtained in Reference Example 1 (160 m
g, 0.30 mmol) and triphenylphosphine oxide (15 mg, 0.054 mmol), and the reaction was carried out according to the method of Condition B of Example 1 to obtain the target compound in 63% (67 mg, 0.063 mmol). Was. Melting point: 115-118 ° C. TLC _Rf : 0.44 (ethyl acetate). ¹ H-nuclear magnetic resonance spectrum (270 MHz, CDCl
₃ ) δ ppm: 7.36 (1H, d, J = 2.0 Hz), 7.30 (1H, s), 7.07 (1H, dd, J = 8.5, 2.0 Hz), 6. 80 (1H, d, J = 8.5 Hz), 6.38 (1H, s), 5.55-5.19 (7H, m), 4.88 (1H, d, J = 9.8 Hz), 4.41 (1H, dd, J = 12.3, 2.8 Hz), 4.22-4.04 (5H, m), 3.94 (1H, d, J = 15.1 Hz), 3.86 -3.78 (2H, m), 3.81 (3H, s), 3.73 (3H, s), 3.70 (3H, s), 2.89 (1H, dd, J = 13.2) , 5.1 Hz), 2.23 (3H, s), 2.12 (3H, s), 2.07 (3H, s), 2.03 (3H, s), 2.01 (3H, s) , 2.00 (6H, s) 1.89 (3H, s), 1.78 (1H, dd, J = 13.2,11.6H
z), 1.73 (3H, s). Infrared absorption spectrum (KBr tablet, cm ^-1 ): 3384,
2953, 2935, 1750, 1688, 1505. High resolution (FAB) mass spectrum: Calculated: C ₅₀ H ₆₄ O ₂₄ N] [M + H] ⁺ = 1062,3
818. Obtained: 1062, 3812. Specific rotation: [α] ²³ _D = -14 ° (c = 0.23, CH
₂ Cl ₂ ).

[0037]

Example 4 1,4-Dimethoxy-2- [4-methoxy
-3- (2,3,4,6-tetra-O-acetyl-β-
D-galactopyranosyl) benzyl] -5- (2,3
4-tri-O-acetyl-β-L-rhamnopyranosyl)
Benzene <Reaction under Condition B> 1,4-Dimethoxy-2- (2,3,4-tri-O-acetyl-β-L-rhamnopyranosyl) -5 disclosed in Japanese Patent Application No. 9-288847. −
Tri-n-butylstannylbenzene (144.1 mgm
g, 0.210 mmol), 4-bromomethyl-1-methoxy-2- (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl) benzene obtained in Reference Example 1 ( 337 mg, 0.633 mmol) and triphenylphosphine oxide (59 mg, 0.21
The reaction was carried out according to the method of condition B of Example 1 to obtain 76% of the target compound (135 mg, 0.15
9 mmol). Melting point: 84-85 ° C. TLC R _f : 0.43 (hexane: ethyl acetate =
2: 3). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl
₃ ) δ ppm: 7.30 (1H, d, J = 1.3 Hz), 7.00 (1H, dd, J = 8.6, 1.2 Hz), 6.86 (1H, s), 6. 74 (1H, d, J = 8.6 Hz), 6.57 (1H, s), 5.51 (1H, d, J = 2.7 Hz), 5.43 (1H, t, J = 9.8 Hz) ), 5.35 (1H, t, J = 9.2 Hz), 5.30 (1H, t, J = 9.2 Hz), 5.20 (1H, dd, J = 9.8, 2.7 Hz) , 5.18-5.12 (1H, m), 4.88 (1H, d, J = 9.8 Hz), 4.83 (1H, d, J = 9.2 Hz), 4.22-4. 03 (4H, m), 3.93 (1H, d, J = 15.5 Hz), 3.84 (1H, d, J = 15.5 Hz), 3.80 (3H, s), 3.79 ( 3H, s), 3.72 3H, s), 3.46 (1H, t, J = 10.8 Hz), 2.21 (3H, s), 2.06 (3H, s), 2.04 (3H, s), 2.03 (3H, s), 1.98 (3H, s), 1.78 (3H, s), 1.73 (3H, s). Infrared absorption spectrum (KBr tablet, cm ^-1 ): 2944,
2859, 1753, 1506. High resolution (FAB) mass spectrum: Calculated: C ₄₁ H ₅₀ O ₁₉ Na: [M + Na] ⁺ = 869,
2844. Obtained: 869, 2868. Specific rotation: [α] ²³ _D = -21 ° (c = 0.41, CH
₂ Cl ₂ ).

[0038]

Example 5 1,3-Dimethoxy-4- [4-methoxy
-3- (2,3,4-tri-O-acetyl-β-L-fu
Copyranosyl) benzyl] -6- (methyl 5-aceto
Amido-3,5-dideoxy-4,7,8,9-tetra
-O-acetyl-α-D-glycero-D-galacto-2
- Bruno Nuro Pila Noshiro sulfonate) benzene disclosed in Japanese Patent Application 9- No. 288,847 Publication <Reaction conditions B>, 1,3-dimethoxy-4- (methyl 5-acetamido-3,5-dideoxy -4, 7,8,9-Tetra-O-acetyl-α-D-glycero-D-galact-2-nonulopyranosylonate) -6-tri-n-butylstannylbenzene (140 mg, 0.156 mmol)
l), 4-bromomethyl-1-methoxy-2- (2,3,4-tri-O-acetyl-β- obtained in Reference Example 2.
L-fucopyranosyl) benzene (204 mg, 0.43
mmol) and triphenylphosphine oxide (22 mg, 0.079 mmol), and the reaction was carried out according to the method of condition B in Example 1.
(120 mg, 0.119 mmol). Melting point: 115-118 ° C. TLC _Rf : 0.44 (ethyl acetate). ¹ H-nuclear magnetic resonance spectrum (400 MHz, CDCl
₃ ) δ ppm: 7.37 (1H, d, J = 2.0 Hz), 7.30 (1H, s), 7.03 (1H, dd, J = 8.3, 2.0 Hz), 6. 79 (1H, d, J = 8.3 Hz), 6.38 (1H, s), 5.52 (1H, t, J = 8.3 Hz), 5.45 (1H, dt, J = 11.0) , 5.0 Hz), 5.36-5.33 (2H, m), 5.25-5.18 (3H, m), 4.84 (1H, d, J = 9.9 Hz), 4.43 (1H, dd, J = 12.2, 2.6 Hz), 4.19 (1H, dd, J = 12.2, 6.6 Hz), 4.10 (1H, q, J = 10.3 Hz), 3.96 (1H, q, J = 6.3 Hz), 3.92 (1H, d, J = 16.8 Hz), 3.88-3.81 (2H, m), 3.81 (6H, s) ), 3.74 ( H, s), 3.70 (3H, s), 2.91 (1H, dd, J = 13.3, 5.1 Hz), 2.26 (3H, s), 2.12 (3H, s) , 2.07 (3H, s), 2.00 (3H, s), 1.99 (3H, s), 1.98 (6H, s), 1.89 (3H, s), 1.80 ( 1H, t, J = 13.3 Hz), 1.74 (3H, s), 1.21 (3H, d, J = 6.4 Hz). Infrared absorption spectrum (KBr tablet, cm ^-1 ): 3465,
3377, 2938, 2856, 1748, 1720,
1612. High resolution (FAB) mass spectrum: Calculated: C ₄₈ H ₆₁ O ₂₂ NNa: [M + Na] ⁺ = 102
6,3583. Obtained: 1026, 3557. Specific rotation: [α] ²³ _D = + 5.3 ° (c = 0.32, C
H ₂ Cl _2).

[0039]

Reference Example 1 4-bromomethyl-1-methoxy-2-
(2,3,4,6-tetra-O-acetyl-β-D-Ga
Lactopyranosyl) benzene (organic parent of Examples 1-4)
Electronic Agent) 4-Methyl-1-methoxy-2- (2,3,4,6-tetra- ) disclosed in JP-A-9-143190
O-acetyl-β-D-galactopyranosyl) benzene (454.3 mg, 1.00 mmol) was added to carbon tetrachloride 1
0 ml, and dissolved in N-brominated succinimide (198 m
g, 1.11 mmol) and AIBN (small amount) were added, and the mixture was heated under reflux for 2 hours under a nitrogen stream. The solvent is distilled off under reduced pressure,
The obtained residue was purified by silica gel chromatography (ethyl acetate: hexane = 1: 3) to give the desired compound in 74%.
% (390 mg, 0.735 mmol). Melting point: 42-45 [deg.] C. TLC R _f : 0.20 (hexane: ethyl acetate =
1: 1). ¹ H-nuclear magnetic resonance spectrum (270 MHz, CDCl
₃ ) δ ppm: 7.59 (1H, d, J = 2.3 Hz), 7.34 (1H, dd, J = 8.5, 2.3 Hz), 6.83 (1H, d, J = 8) 5.5 Hz), 5.52 (1H, d, J = 3.3 Hz), 5.47 (1H, t, J = 10.0 Hz), 5.21 (1H, dd, J = 10.0, 3. 3 Hz), 4.88 (1H, d, J = 10.0 Hz), 4.50 (2H, s), 4.23-4.03 (3H, m), 3.85 (3H, s), 2 .23 (3H, s), 2.04 (3H, s), 1.99 (3H, s), 1.78 (3H, s). High resolution (FAB) mass spectrum: Calculated value: C ₂₂ H ₂₈ O ₁₀ Br] [M + H] ⁺ = 531,0
865. Obtained value: 531,0845. Specific rotation: [α] ²³ _D = −2.12 ° (c = 1.37,
CH ₂ Cl ₂ ).

[0040]

Reference Example 2 4-bromomethyl-1-methoxy-2-
(2,3,4-tri-O-acetyl-β-L-fucopyra
Nosyl) benzene (organic electrophile of Example 5) 4-Methyl-1-methoxy-2- (2,3,4-tri-O-acetyl-β disclosed in JP-A-9-143190 -L-fucopyranosyl) benzene (2.27
g, 5.74 mmol) and reacted according to the method of Reference Example 1 to give 65% of the target compound (1.77 g, 3.75 g).
73 mmol). Melting point: 48-50 [deg.] C. TLC R _f : 0.20 (hexane: ethyl acetate =
1: 1). ¹ H-nuclear magnetic resonance spectrum (270 MHz, CDCl
₃ ) δ ppm: 7.48 (1H, d, J = 2.4 Hz), 7.32 (1H, dd, J = 8.6, 2.2 Hz), 6.82 (1H, d, J = 8) 6.6 Hz), 5.46 (1 H, t, J = 9.8 Hz), 5.36 (1 H, d, J = 3.3 Hz), 5.21 (1 H, dd, J = 9.8, 3. 2. 3 Hz), 4.86 (1 H, d, J = 9.8 Hz), 4.53 (1 H, d, J = 10.2 Hz), 4.49 (1 H, d, J = 10.2 Hz), 96 (1H, q, J = 6.5 Hz), 3.84 (3H, s), 2.26 (3H, s), 1.99 (3H, s), 1.77 (3H, s), 1 .23 (1H, d, J = 6.5 Hz). High resolution (FAB) mass spectrum: Calculated value: C ₂₀ H ₂₆ O ₁₈ Br: [M + H] ⁺ = 473,0
811. Obtained: 473,0811. Specific rotation: [α] ²³ _D = + 18.4 ° (c = 0.70)
0, CH ₂ Cl ₂ ).

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4H006 AA02 AC20 AC24 BA25 BA32 BA44 BA46 BA47 BA48 BA53 BB11 BB15 BB20 BB21 BB24 BB25 4H039 CA19 CD20

Claims (2)

[Claims] In a cross-coupling reaction using an organotin compound and an organic electrophile in the presence of a palladium catalyst, a phosphine oxide having the general formula R ₃ P ＝ O wherein R is a lower alkyl A cross-coupling compound). 2. In a cross-coupling reaction using an organotin compound and an organic electrophile in the presence of a palladium catalyst, a phosphine oxide having the general formula R ₃ P ＝ O, wherein R is a lower alkyl Or an aryl group).