JP3277065B2 - Phosphine compounds, complexes using the same as ligands, methods for producing optically active aldehydes using them, and 4-[(R) -1'-formylethyl] azetidin-2-one derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a phosphine compound, and more particularly to a phosphine compound which can be used as a useful catalyst in an asymmetric hydroformylation reaction by combining with a transition metal such as rhodium, and the use of the compound and the transition metal. The present invention relates to a method for producing an optically active aldehyde, a method for producing an antibiotic intermediate using the same, and an intermediate thereof.

[0002]

2. Description of the Related Art Numerous reports have been made on transition metal complexes which can be used in organic synthesis reactions, for example, complexes used as catalysts in asymmetric hydrogenation reactions, asymmetric hydrosilylation reactions, asymmetric hydroformylation reactions, and the like. I have. Of these, complexes in which an optically active tertiary phosphine is coordinated with a transition metal such as rhodium or ruthenium often have excellent performance as a catalyst for an asymmetric synthesis reaction, and in order to further enhance the performance of this catalyst. In the meantime, phosphine compounds having a special structure have been developed so far (edited by The Chemical Society of Japan, Chemistry Review 32, "Chemistry of Organic Metals", pp. 237-238, Showa 5)
7 years).

[0003] Among them, attention is focused on asymmetric hydroformylation reaction using a transition metal-phosphine complex. For example, the following techniques are known. J. Org. Che
m., 46, 4422 (1981) include optically active 2,3.
-O-diisopropylidene-2,3-dihydroxy-1,
4-bis (diphenylphosphino) butane (hereinafter referred to as DIO
P) as a ligand, a reaction using a rhodium complex described in Bull. Chem. Soc. Jpn., 52, 2
605 (1979) has an optically active bidentate phosphine (D
The reaction using a rhodium complex having IOP or the like as a ligand is further carried out by Tetrahedron Asymmetry.
Y, 10, 693 (1990) discloses an asymmetric hydroformylation reaction of methyl acetamidoacrylate using a rhodium complex having DIOP or the like as a ligand.

On the other hand, as a complex having an optically active tertiary phosphite as a ligand, Tetrahedron A
Symmetry, 3,583 (1992) describes a bis (triarylphosphite) having an optically active binaphthyl skeleton. An asymmetric hydroformylation reaction of vinyl acetate using a rhodium complex having this as a ligand is described. Are known.

By the way, the following formula (VI) which is an important intermediate of a carbapenem antibacterial agent which has been actively developed in recent years:
I)

Embedded image (Wherein, R ¹ represents a hydrogen atom or a hydroxyl protecting group, R ²
Represents a hydrogen atom or an amino protecting group).
[(R) -1′-carboxyethyl] azetidine-2-
The development of a method for producing an on-derivative is also being actively pursued. Conventional carbapenems having no substituent at the 1-position have the drawback that they are chemically unstable at high concentrations and are easily metabolized by renal dehydropeptidase.
However, it is known that the introduction of an alkyl group having a β configuration at the 1-position increases the stability to renal dehydropeptidase, and enables single use without using a renal dehydropeptidase inhibitor. There are many reports on the method of synthesizing this compound (VII).

Embedded image (Wherein R ¹ and R ² have the same meanings as described above) of 4-acetoxyazetidin-2-one derivative
On the other hand, there is known a method of performing a carbon increase reaction with various nucleophiles. Another known method for synthesizing the compound represented by the formula (VII) is represented by the general formula (IX):

Embedded image (Wherein R ¹ has the same meaning as described above), wherein the compound represented by the general formula (X) is alkylated using a base such as lithium diisopropylamide.

Embedded image (Wherein, R ¹ and R ² have the same meanings as described above, and R ¹⁰
Represents an alkyl group, a carboxyl group or an alkoxycarbonyl group), a method of catalytically reducing an exomethylene group of a compound represented by the formula (I), or asymmetric reduction using a specific catalyst. However, in most cases, the compound of the general formula (VII) obtained by the above method is obtained as a compound in which its stereoisomers, that is, α-form and β-form are mixed at a specific ratio.

[0006]

As described above, a large number of special phosphine compounds have been developed to provide a catalyst having higher performance as a catalyst for an asymmetric hydroformylation reaction. Depending on the reaction and the reaction, there may be cases where the selectivity and the asymmetric yield cannot be sufficiently satisfied, and the development of a new phosphine compound which gives higher regioselectivity and an asymmetric yield than conventional catalysts and the transition metal- A phosphine complex has been desired.

Further, there is a demand for a method for efficiently producing a compound (VII) having a methyl group having a β-configuration or a precursor thereof, which is highly useful as an intermediate of carbapenems known as an excellent antibacterial agent. I was

[0008]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that a phosphine compound having an optically active biphenol or binaphthols as a skeleton is used as a ligand. Has been found to be significantly superior in the asymmetric yield and the regioselectivity in the asymmetric hydroformylation reaction as compared with the conventionally known transition metal-optically active phosphine complex.

Further, various optically active aldehydes can be easily synthesized by using this catalyst, and by utilizing this catalyst, the compound (VII) which is an important intermediate of carbapenems as an antibiotic can be easily obtained. The present inventors have found that a compound that can be derived can be synthesized and completed the present invention.

Therefore, an object of the present invention is to provide the following general formula (1)

Embedded image (Wherein R ⁴ and R ⁴ ′ are the same or different and each represent a hydrogen atom,
R ³ represents a lower alkyl group or a lower alkoxy group;
R ³ ′, R ⁹ and R ⁹ ′ are the same or different,
A hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, or a ring may be formed by R ³ and R ⁴ , or R ³ ′ and R ⁴ ′. R ⁵ and R ⁶ are the same or different and represent a phenyl group which may be substituted with lower alkyl, halogen or lower alkoxy, and R ⁷ and R ⁸ are the same or different and are substituted with lower alkyl, lower alkoxy or halogen. Or a phenyl group, or R ⁷ and R ⁸
May form a divalent hydrocarbon group) or a phosphine compound represented by the following general formula (2)

Embedded image(Where R¹⁴, R¹⁴'Are the same or different,
A lower alkyl group or a lower alkoxy group;
¹³, R¹³', R¹⁹And R¹⁹'Are the same or different
Is a hydrogen atom, a lower alkyl group or a lower alkoxy
Represents a group or a halogen atom. R^Fifteen, R¹⁶Are the same or
Differently, a lower alkyl, a halogen atom or a lower
A phenyl group which may be substituted with alkoxy,
¹⁷And R¹⁸ Are the same or different and are lower alkyl, lower
Phenyl which may be substituted with secondary alkoxy or halogen
Or R¹⁷And R¹⁸Forms a divalent hydrocarbon group with
Phosphine compounds represented by
Transition metal-phosphite having a phosphine compound of the formula
To provide a complex.

Another object of the present invention is to provide a complex of the phosphine compound with a transition metal such as rhodium, or a catalyst represented by the following general formula (3) Q ¹ -CH ＣＨCH—Q ² wherein Q 1 represents a hydrogen atom or a lower alkyl group;
Q2 is a lower alkyl group, a lower alkoxy group, a halogen atom, a lower alkylcarbonyloxy group, a cyano group, a carboxyl group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a phthalimide group, an acetylamino group,
Benzoylamino group, mono-lower alkylamino group, di-lower alkylamino group, benzoyl group; lower alkyl, lower alkoxy, phenyl group optionally substituted with halogen; lower alkyl, lower alkoxy, optionally substituted with halogen A naphthyl group or a group represented by the following general formula (4):

Embedded image (Wherein R ¹ represents a hydrogen atom or a hydroxyl-protecting group), or Q ¹ and Q ^{2 represent the following} formula (5)

Embedded image (Wherein, n represents 1 or 2). The method for producing optically active aldehydes comprises hydroformylating an olefin represented by the formula: is there.

Further, another object of the present invention is to provide a compound represented by the following general formula (7) produced by using the above-mentioned hydroformylation reaction.

Embedded image (Wherein, R ¹ has the same meaning as described above). 4-[(R) -1′-formylethyl] azetidine-2
-One derivatives are provided.

In the present specification, a lower alkyl group means a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group.
A butyl group and the like are meant, a halogen atom is a chlorine atom, a bromine atom, an iodine atom and a fluorine atom, and a lower alkoxy group is a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, sec
-Butoxy group, tert-butoxy group and the like.

In the present specification, the bivalent hydrocarbon group includes a biphenyl group, a biphenyl group having a substituent,
Binaphthyl group, binaphthyl group having a substituent, bianthryl group, bianthril group having a substituent, biphenanthryl group, biarylene group such as biphenanthryl group having a substituent, or ethylene group, trimethylene group , Tetramethylene group, pentamethylene group, 1,4-dimethyltetramethylene group, 1,3-butadienylene group, 1,4-
It means a linear or branched, saturated or unsaturated alkylene group having 2 to 6 carbon atoms, such as a dimethyl-1,3-butadienylene group.

The phosphine compound (1) of the present invention is produced, for example, by a method represented by the following reaction formula.

Embedded image (Wherein Tf represents a trifluoromethanesulfonyl group)

That is, Tetrahedron Le
tt., 31, 6321-6324, (1990), and reacting 1,1'-bi-2-naphthol with trifluoromethanesulfonic anhydride to give 2,2'-bis (trifluoromethanesulfonyloxy ) -1,1′-binaphthyl, and in the presence of a palladium complex catalyst,
The phosphine oxide is reacted to give 2-diphenylphosphinyl-2'-trifluoromethanesulfonyloxy-1,1'-binaphthyl, which is then reduced with trichlorosilane in the presence of triethylamine and then hydrolyzed to give 2 -Diphenylphosphino-2'-hydroxy-1,1'-binaphthyl is reacted with chlorophosphite separately synthesized in the presence of triethylamine to obtain the phosphine compound (1) of the present invention.

The phosphine compound (1) of the present invention thus obtained is, for example, as shown in Table 1 or Table 2 below.
And the like.

[0018]

[Table 1]

[0019]

[Table 2]

The skeleton of the phosphine compound (1) of the present invention includes an optically active compound and a racemic compound, and the present invention includes any of these compounds.

The obtained phosphine compound of the present invention (1)
Can be combined with a transition metal to prepare a complex having the phosphine compound (1) of the present invention as a ligand. Examples of transition metals include rhodium, ruthenium, iridium, platinum and the like, with rhodium being preferred. Hereinafter, using rhodium as an example, a complex having the phosphine compound (1) of the present invention as a ligand (hereinafter, referred to as “rhodium-optically active phosphine complex”) will be described.

Formation of rhodium-optically active phosphine complex
Compounds used as complex precursors for
For example, for example, RhCl_Three, RhBr_Three, RhI_Three, R
h_TwoO_Three, Rh (OAc)_Three(Hereinafter, the acetyl group will be referred to
Abbreviated), [Rh (O_TwoC₇H_Fifteen )_Two]_Two, Rh (acac)
_Three(Hereinafter acetylacetonate is abbreviated as acac), R
h_Four(CO)₁₂, Rh₆(CO)₁₆, [Rh (COD) C
l]_Two (Hereinafter, 1,5-cyclooctadiene is referred to as COD.
Abbreviated), [Rh (COD) Br]_Two, [Rh (COD)
I]_Two, [Rh (COD) OAc]_Two, [Rh (COD)
OCOC (CH_Three)_Three]_Two, [Rh (NBD) Cl]_Two 
(Hereinafter, norbornadiene is abbreviated as NBD), [Rh
(NBD) Br]_Two, [Rh (NBD) I]_Two, [Rh
(NBD) OAc]_Two, [Rh (NBD) OCOC (C
H_Three)_Three]_Two, Rh (COD) (acac), Rh (NB
D) (acac),

Rh (CO) ₂ (acac), [Rh (C
O) ₂ Cl] ₂ , [Rh (CO) ₂ Br] ₂ , [Rh (C
O) ₂ I] ₂ , Rh (CO) ₂ (Cp) (hereinafter, 1,3-cyclopentadiene is abbreviated as CP), Rh (CO) ₂ (t
mCp) (hereinafter 1,2,3,4-tetramethyl-1,3-
Cyclopentadiene is abbreviated as tmCp), [Rh (C
O) (tmCp) ₂ ], Rh (C ₂ H ₄ ) ₂ (acac),
[Rh (C ₂ H ₄ ) ₂ Cl] ₂ , [Rh (C ₂ H ₄ ) ₂ B]
r] ₂ , [Rh (C ₂ H ₄ ) ₂ I] ₂ , [Rh (C ₂ H ₄ )
₂ (tmCp)], RhCl (PPh ₃ ) ₃ (hereinafter the phenyl group is abbreviated as Ph), RhBr (PPh ₃ ) ₃ , RhI
(PPh ₃ ) ₃ , RhH (CO) (PPh ₃ ) ₃ , RhH
(PPh ₃ ) ₃ ,

RhH (P (i-Pr) ₃ ) ₃ (hereinafter the isopropyl group is abbreviated as i-Pr), RhHCl ₂ (PP
_{h 3) 2, RhHCl 2 (} AsPh 3) 2, RhHCl 2 (S
bPh ₃ ) ₂ , RhH ₂ Cl (PPh ₃ ) ₂ , RhH ₂ Br
(PPh ₃ ) ₂ , RhH ₂ I (PPh ₃ ) ₂ , Rh (OA
c) (CO) (PCp ₃ ) ₂ , Rh (OCOPh) (C
O) (PCp ₃ ) ₂ , Rh (ClO ₄ ) (CO) (PC
p ₃ ) ₂ , Rh (Cl) (CO) (PCp ₃ ) ₂ , Rh (C
l) (CO) (PBu ₃ ) ₂ , Rh (Cl) (CO) (P
Ph ₃ ) ₂ , Rh (I) (CO) (PCp ₃ ) ₂ , [RhH
{P (Oi-Pr) ₃ } ₂ ] ₂ , Rh (C ₅ H ₇ O ₂ ) (C
₂ H _4),

[Rh (COD)_Two] BF_Four, [Rh (CO
D) (CH_ThreeCN)_Two] BF_Four, [Rh (COD) (Ph_Two
PC_FourH₈PPh_Three)] BF_Four, [Rh (C₇H₈) (Ph_Two
PC_FiveH_TenPPh_Two)] BF_Four, [Rh (C₇H₈) [PP
h_Two(O-C₆H_FourOCH_Three)_Two]_Two ] BF_Four, [Rh (CO
D) (PPh_Three)_Two] PF₆, Rh (COD) (AsP
h_Three)_Two] ClO_Four, [Rh (NBD) (PPh_Three)_Two] C
10_Four, [RhH_Two(PPh_Three)_Two(AcCH_Three) (C_TwoH_Five
OH)] ClO_Four, [RhH_Two(PPh_Three)_Two(CH_ThreeC
N)_Two] ClO_Four, [RhH_Two(PPh_Three)_Two(C_TwoH_FiveO
H)_Two] ClO_Four, [RhCl_Two(N_-C_FiveH₁(C
H_Three)_Four)]_Two, Rh (Cp) (PPh_Three)_Two, [Rh (t
mCp) (CH_ThreeCN)_Three] (PF₆)_Two, Rh_TwoCl_Two(N
-C_ThreeH_Five)_Four, Rh (n-C_ThreeH_Five)_Three And the like.

The rhodium compound of the present invention can be obtained by mixing these rhodium compounds with the phosphine compound (1) of the present invention in a suitable solvent. Examples of the solvent used here include: hydrocarbons such as toluene, benzene, hexane, heptane, isooctane, and decane; ethers such as diethyl ether and tetrahydrofuran; ketones such as acetone and methyl ethyl ketone; and lower alcohols such as methanol and ethanol; Esters such as ethyl acetate and the like, methylene chloride and the like are exemplified, and toluene and methylene chloride are preferred. The rhodium-phosphine complex of the present invention usually contains one Rh atom in the complex.
Mononuclear complex, but may be a dinuclear complex having two or more Rh atoms.

Although only rhodium has been described above, the corresponding transition metal-phosphine complex can be obtained in the same manner for ruthenium, iridium and platinum.

An optically active aldehyde can be produced by adding the transition metal-phosphine complex obtained as described above as a catalyst to the reaction system of the hydroformylation reaction. Also, an optically active aldehyde can be produced by hydroformylating an olefin with a transition metal compound in the presence of the phosphine compound (1) of the present invention.

That is, even when the transition metal-phosphine complex prepared in advance as described above is used, the transition metal compound and the phosphine compound of the present invention are mixed in a reaction solvent without using the same. Even in the case of carrying out the conversion reaction, the reaction proceeds via a transition metal-phosphine complex, and both methods give an optically active aldehyde.

This is clear from the following facts. For example, when Rh (CO) ₂ (acac) and a phosphine compound of the present invention (abbreviated as phos) are reacted one by one in a solvent such as methylene chloride, two COs are obtained.
(Carbon monoxide) and the phosphine compound undergo ligand exchange to form a Rh (acac) (phos) type complex. When this complex was isolated and ³¹ P-NMR was measured,
Two signals are shown. Rh (CO) ₂ (aca
When one equivalent of c) and 2.5 equivalents of phos are similarly treated in a solvent and ³¹ P-NMR is measured, two signals of phos itself are observed in addition to the two signals of the above complex.

On the other hand, under the conditions of the hydroformylation reaction (Rh
1 equivalent of (CO) ₂ (acac), 2.5 equivalents of phos;
However prior to the addition of carbon monoxide and hydrogen) in ³¹ P-
Since NMR also shows the signal of the complex and the signal of phos in the same manner as above, Rh (aca
c) The reaction proceeds via (phos).

From this, it is understood that a transition metal-phosphine complex is formed even when the transition metal and the phosphine complex (1) are separately added to the system.

The olefins hydroformylated with the above transition metal-phosphine complex include, for example, the following, but are not limited thereto.

Vinyl chloride, vinyl bromide, vinyl iodide,
1-propene, 1-butene, 1-pentene, 1-hexene, 3,3-dimethyl-1-butene, N-vinylphthalimide, vinyl acetate, vinyl propionate, vinyl valerate, acrylonitrile, acrylic acid, methyl acrylate , Ethyl acrylate, butyl acrylate, t-butyl acrylate, methyl vinyl ether, ethyl vinyl ether
Ter, butyl vinyl ether, t-butyl vinyl ether, 3-buten-2-one, 1-buten-3-one,
-Hepten-3-one, 4,4-dimethyl-1-penten-3-one, 1-phenyl-2-propen-1-one, N-vinylacetamide, N-vinylbenzamide,

Methylvinylamine, ethylvinylamine, butylvinylamine, dimethylvinylamine, diethylvinylamine, dibutylvinylamine, styrene,
Chlorostyrene, bromostyrene, methylstyrene, 4
-T-butylstyrene, 4-isobutylstyrene, methoxystyrene, ethoxystyrene, vinylnaphthalene,
2-methoxy-6-vinylnaphthalene, 1-chloro-1
-Propene, 1-bromo-1-propene, 2-butene,
2-pentene, 2-hexene, 2-heptene,

1-propenyl acetate, 1-propenyl cyanide, crotonic acid, methyl crotonate, butyl crotonate, methyl 1-propenyl ether, 3-pentene-2
-One, 2-octen-4-one, N-2-pentenylacetamide, methyl 2-propenylamine, butyl 2
-Propenylamine, dimethyl 2-propenylamine,
Dibutyl 2-propenylamine, 4- (2-propenyl) chlorobenzene, 4- (2-propenyl) toluene, 4- (2-propenyl) butylbenzene, (1′R,
3S, 4R) -3- (1 '-(Pro-1) oxy) ethyl-4-vinylazetidin-2-one, indene, 1,
2-dihydronaphthalene.

Here, Pro-1 is defined by the above general formula (4)
In represents R ¹ in the formula represented as R ^1, a hydrogen atom,
Or trimethylsilyl, triethylsilyl, isopropyldimethylsilyl, tert-butyldimethylsilyl, (triphenylmethyl) dimethylsilyl, tert
Substituted silyl groups such as -butyldiphenylsilyl, methyldiisopropylsilyl, methyldi-tert-butylsilyl, tribenzylsilyl, tri (p-tolyl) silyl, triisopropylsilyl, triphenylsilyl,

Acyl groups such as formyl, benzoylformyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, methoxyacetyl, phenoxyacetyl, p-chlorophenoxyacetyl, benzoyl, benzyloxycarbonyl, ethoxycarbonyl, benzyl , Benzhydryl, aralkyl groups such as triphenylmethyl group, and the like; and among them, a hydrogen atom, trimethylsilyl, tert-butyldimethylsilyl, benzyloxycarbonyl, ethoxycarbonyl, acetyl, benzyl, benzhydryl And triphenylmethyl are preferred.

In the hydroformylation method of the present invention, the phosphine compound of the present invention and a compound of a metal selected from rhodium, ruthenium, iridium and platinum are separately added as catalysts to a reaction system, or rhodium, ruthenium, iridium and platinum are added. The transition metal-phosphine complex of the present invention formed from a compound of a metal selected from the above and the phosphine compound of the present invention is added to the reaction system as a catalyst.

The concentration of the catalyst in the reaction system is 0.000 as metal atom in the metal compound per liter of liquid phase.
1 to 1000 mg, preferably 0.001 to 100 m
g, and in phosphine is 1 to 5 times, preferably 2 to 4 times the number of moles of metal atoms.
Used in double the amount.

The hydroformylation method of the present invention can be carried out without using a reaction solvent, but it is usually preferable to carry out the reaction in the presence of a reaction solvent. As the reaction solvent,
Any one that does not adversely affect the reaction can be used, and particularly preferred are hydrocarbons.Specifically, hexane, heptane, octane, isooctane, nonane, decane, cyclohexane, cyclopentane, benzene, toluene, Xylene, mesitylene and the like can be mentioned.

In addition, ethers such as diisopropyl ether, dibutyl ether, tetrahydrofuran, dimethoxyethane, diethylene glycol dimethyl ether, diisobutyl ketone, methyl isobutyl ketone,
Ketones such as acetone and methyl ethyl ketone, esters such as ethyl acetate, butyl butyrate and butyl benzoate, methanol, ethanol, butanol and tert-butanol
And alcohols such as alcohol. These solvents can be used alone or in combination of two or more.

In general, in the hydroformylation reaction, a method of coexisting water in the reaction system is preferred in order to enhance the catalytic activity. In the present invention, water can coexist during the reaction. There is no particular limitation on the amount of water to be added, but the effect is weak when the amount is extremely small, and the effect levels off even when the amount is extremely large. Usually, if the amount of water added is 0.001 to 1000 times the weight of the substrate olefin, the reaction rate may be increased.

In the process of the present invention, various additives other than water can be added for the purpose of improving the activity, regioselectivity and stereoselectivity of the catalyst. Examples of such additives include phosphorus compounds such as triethyl phosphine oxide, triphenyl phosphine oxide, tributyl phosphine oxide, triethyl phosphite, tributyl phosphite, and triphenyl phosphite, and carboxylic acids such as acetic acid, propionic acid, and pivalic acid. Can be

As the reaction conditions for carrying out the hydroformylation reaction of the present invention, the reaction temperature is usually -20 ° C to 2 ° C.
The temperature is preferably 50 ° C, more preferably 10 to 150 ° C.
The lower the reaction temperature, the better from the viewpoint of the thermal stability of the aldehyde to be produced, and the higher the reaction temperature, the better. The reaction pressure is in the range of 5 to 200 kg / cm ² , more preferably 20 to 150 kg / cm ² . The molar ratio of the mixture of the raw material carbon monoxide and hydrogen is usually 10 to 10.
It is in the range of 0.1, more preferably in the range of 4-0.2.

As long as the mixing ratio of carbon monoxide and hydrogen maintains such a ratio, the mixture can be diluted with another gas inert to the reaction. As the diluent gas, methane,
Nitrogen, argon, helium, carbon dioxide, or the like is used alone or in combination.

Further, compounds which can be advantageously produced using the hydroformylation method of the present invention include:
The following general formula (7)

Embedded image (Wherein R ¹ has the same meaning as described above)
-[(R) -1'-formylethyl] azetidine-2-
On derivatives.

This compound has the following general formula (6)

Embedded image (Wherein R1 has the same meaning as described above) as a starting material, and can be obtained with high asymmetric yield and regioselectivity by using the hydroformylation method of the present invention. .

The compound represented by the general formula (6), which is a starting material, is described in, for example, Liebig Ann. Chem., 53
9-560 (1974).

That is, the following formula (XII)

Embedded image (Wherein R ¹ represents the same meaning as described above) to a 4-acetoxyazetidin-2-one derivative in a soluble solvent such as acetone-water, methanol, or water-methanol. By reacting sodium benzenesulfinate, sodium p-toluenesulfinate or the corresponding potassium salt or lithium salt, the following general formula (XIII)

Embedded image (Wherein, R ¹ has the same meaning as described above, and Ar represents a phenyl group which may be substituted with a halogen atom or a lower alkyl group, etc.).
J. Chem. Soc. Chem. Commn., 19
80, 736-738, by reacting an organic vinyl compound, for example, a vinylating agent such as vinyl magnesium chloride, vinyl magnesium bromide, vinyl magnesium iodide, divinyl magnesium, vinyl lithium, vinyl zinc chloride, divinyl zinc, or the like. Can easily be obtained.

The compound (6) thus obtained is subjected to a hydroformylation reaction using the transition metal-phosphine complex of the present invention or both of the phosphine of the present invention and the transition metal compound as catalysts. The compound of the general formula (7) is obtained.

The absolute configuration of the skeleton of the phosphine compound of the present invention used here is the (R) configuration, and on the corresponding phosphite side, this moiety is derived from an axially asymmetric type diol. In this case, it is necessary that the absolute configuration of this compound be the (S) configuration, so that the absolute configuration of the 1′-formyl group in the resulting compound of the general formula (7) is (R) configuration, that is, β-isomer is efficiently obtained This is an essential condition.

The compound of the general formula (7) obtained by subjecting the compound (6) thus obtained to the hydroformylation reaction of the present invention is subjected to ordinary oxidation, for example, Jones' reaction. By oxidizing by oxidation or the like, the formyl group can be easily converted into a carboxyl group, and the oxidized compound (VII) becomes an important intermediate of a carbapenem antibiotic.

According to the present invention, double bonds of various compounds can be stereospecifically converted into aldehyde groups. As described above, the hydroformylation reaction of the present invention is of great significance in chemical synthesis because optically active aldehydes used as pharmaceuticals, agricultural chemicals, flavors, etc., or intermediates thereof can be easily synthesized in a high asymmetric yield. It is.

[0055]

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

The following instruments were used for measuring the physicochemical properties in the examples. Nuclear magnetic resonance spectrum (NMR): EX-270 (manufactured by JEOL), AM-400 (manufactured by Bruker) Internal standard substance ¹ H; tetramethylsilane external standard substance ³¹ P; 85% phosphoric acid Optical purity: GC- 15A gas chromatography (manufactured by Shimadzu Corporation) column; chiral capillary column CHROMPACK β-236M Chemical purity: Hitachi-263-30 gas chromatography (manufactured by Hitachi, Ltd.) Optical rotation: DIP-360 (manufactured by JASCO Corporation)

Example 1 (S) -3,3'-Dichloro-2,2 ', 4,4'-tetramethyl-6-diphenylphosphinobiphenyl-6'-yloxy ((R) -1,1 '-Binaphthalene-2,2'-diyldioxy) phosphine and (R) -3,3'-dichloro-2,2', 4,4'-tetramethyl-6-diphenylphosphinobiphenyl-6'-yloxy (( R) -1,
Preparation of 1'-binaphthalene-2,2'-diyldioxy) phosphine:

(1) (±) -3,3'-dichloro-2,
2 ', 4,4'-tetramethylbiphenyl-6,6'-dio-
(Hereinafter referred to as "Compound A"): 4-Chloro-3,5-xylenol (10 g) in a flask (70.
0 mmol) and iron chloride hexahydrate 37.8 g (140 mm
ol) and reacted at 80 ° C. for 16 hours. After the completion of the reaction, the reaction mixture was treated with 300 ml of 1N hydrochloric acid, and then extracted three times with 250 ml of dichloromethane. The obtained organic layer was washed with a saturated aqueous solution of sodium bicarbonate 500
After washing with water and 500 ml of saturated saline, the mixture was concentrated and recrystallized from hexane / chloroform to obtain 3.32 g of the title compound A. Yield 30%.

Melting point: 231-233 ° C. ¹ H-NMR (CDCl ₃ ) δ: 2.05 (s, 6H),
2.41 (s, 6H), 4.57 (s, 2H), 6.84 (s,
2H)

(2) (±) -3,3'-dichloro-2,
Production of 2 ′, 4,4′-tetramethyl-6,6′-bis (trifluoromethanesulfonyloxy) biphenyl (hereinafter referred to as “compound B”): Obtained in step (1) in a flask under an argon stream. 6.22 g of the obtained compound A (20.0 mo
l) 4.72 g (44.0 mmol) of 2,6-lutidine
And 732 mg of 4-dimethylaminopyridine (6.0
0 mmol) was dissolved in 30 ml of dichloromethane, and 12.4 g of trifluoromethanesulfonic anhydride was added to this solution.
(44.0 mmol) was added at 0 ° C., and the reaction was allowed to proceed for 1 hour. After completion of the reaction, the solvent was distilled off, and the residue was purified by column chromatography (hexane / chloroform = 1: 1) to obtain 10.9 g of the title compound B.
95% yield.

Melting point: 90-91 ° C. ¹ H-NMR (CDCl ₃ ) δ: 2.14 (s, 6H),
2.50 (s, 6H), 7.17 (s, 2H)

(3) (±) -3,3'-dichloro-2,
Production of 2 ′, 4,4′-tetramethyl-6-diphenylphosphinyl-6′-trifluoromethanesulfonyloxybiphenyl (hereinafter referred to as “compound C”): In a flask under an argon stream, (2) Compound B obtained in 11.
44 g (19.9 mmol) and 8.05 g (39.8 mmol) of diphenylphosphine oxide are dissolved in 980 ml of dimethyl sulfoxide, and 821 mg (1.9 mg) of 1,3-bis (diphenylphosphino) propane is added to this solution.
9 mmol) and 15.3 ml of diisopropylamine
Was added over 20 minutes, followed by stirring at 90 ° C. for 60 hours.

After completion of the reaction, 120 ml of water was added to the reaction mixture.
And extracted twice with 250 ml of ether. The obtained organic layer was washed with 200 ml of water, 200 ml of 1N-hydrochloric acid, 200 ml of a saturated aqueous solution of sodium hydrogen carbonate, and saturated saline.
Washed in order of 200 ml and dried over magnesium sulfate. After drying, column chromatography (hexane /
The residue was purified by ethyl acetate (1: 1) to obtain 7.77 g of the title compound C. Yield 62%.

Melting point: 159-160 ° C. ³¹ P-NMR (CDCl ³ ) δ: 27.75

(4) (±) -3,3'-dichloro-2,
Production of 2 ', 4,4'-tetramethyl-6-diphenylphosphino-6'-hydroxybiphenyl (hereinafter referred to as "compound D"): Compound C obtained in (3) above in a flask 7.32 g (11.7 mmol) and 47.2 g (467 mmol) of triethylamine in xylene 400
dissolved in 6 ml of trichlorosilane.
(467 mmol) was added dropwise at 0 ° C. Subsequently, the reaction solution was stirred at 120 ° C. for 35 hours. Further, 200 ml of a saturated aqueous solution of sodium hydroxide was carefully added dropwise to this solution at 0 ° C., followed by stirring at 60 ° C. for 2 hours. After completion of the reaction, the reaction mixture was extracted twice with 150 ml of toluene.
The mixture was washed with 0 ml twice and dried over magnesium sulfate.

After drying, the solvent was distilled off to obtain 7.46 g of a residue. Subsequently, a solution obtained by dissolving 7.46 g of the residue in 130 ml of tetrahydrofuran was added to the flask, and a 44 ml aqueous solution of 5.87 g (140 mmol) of lithium hydroxide monohydrate was added thereto, followed by stirring at 30 ° C. for 15 hours.
After completion of the reaction, 200 ml of 1N hydrochloric acid was added to the reaction mixture, and the mixture was extracted twice with 200 ml of ether. The obtained organic layer was washed with 300 ml of water and 250 ml of saturated saline,
Dried over magnesium sulfate. After drying, the solvent was distilled off, and the residue was purified by column chromatography (hexane / ethyl acetate = 12: 1 to 3: 1) to obtain 5.05 g of the title compound D. Yield 90% (from compound C).

Melting point: 71-79 ° C. ³¹ P-NMR (CDCl ₃ ) δ: -13.37

(5) (R) -1,1'-binaphthalene-
2,2′-diyldioxychlorophosphine (hereinafter, referred to as “compound E”) and (S) -1,1′-binaphthalene-2,2′-diyldioxychlorophosphine (hereinafter, referred to as “compound E”)
Production of “Compound F”): 50 m under a stream of argon
(R) -1,1'-bi-2 in a flask equipped with a 1-liter reflux condenser.
-Naphthol (4.94 g, 17.3 mmol) and phosphorus trichloride (104 g, 757 mmol) were added, and the mixture was heated under reflux for 17 hours. After returning to room temperature, unreacted phosphorus trichloride was distilled off under reduced pressure to obtain a residue. Was. Subsequently, the residue was subjected to azeotropic distillation twice with 50 ml of toluene under reduced pressure, the residue was dissolved in benzene, and lyophilized under reduced pressure to obtain 5.56 g of the title compound E as a white solid. Yield 92%.

³¹ P-NMR (CDCl ₃ ) δ: 178.8 Similarly, Compound F was quantitatively obtained.

(6) (S) -3,3'-dichloro-2,
2 ', 4,4'-Tetramethyl-6-diphenylphosphinobiphenyl-6'-yloxy ((R) -1,1'-binaphthalene-2,2'-diyldioxy) phosphine (hereinafter, (S, R) -Biphemphos) and (R) -3,3'-dichloro-2,2 ', 4,4'-tetramethyl-6-diphenylphosphinobiphenyl-6'-yloxy ((R) -1,1'-Binaphthalene-2,2'-diyldioxy) phosphine (hereinafter referred to as (R, R) -bip
hemphos):

In a flask, 756 mg of compound D (1.58
mmol) and 1336 mg (3.81 mm) of compound E
ol) was dissolved in 40 ml of toluene, and 386 mg (3.81 mmol) of triethylamine was added thereto at 0 ° C., and the mixture was stirred at room temperature for 42 hours, followed by adding 50 ml of water to stop the reaction. After liquid separation with 50 ml of ether, the obtained organic layer was washed twice with 80 ml of water and once with 80 ml of saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a crude product. This was subjected to column chromatography (hexane / dichloromethane = 20: 1 to 1).
(S, R) -biphemphos
395 mg (yield 32%) and (R, R) -biphe
259 mg (21% yield) of mphos was obtained.

(S, R) -biphemphos Melting point: 155 to 162 ° C. Optical rotation: [α] _D ²⁵ = -281 ° (C 1.0, toluene) ³¹ P-NMR (toluene-d ₈ ) δ: -13.4 (d, J
(pp = 35.14 Hz), 146.7 (d) Thin layer chromatography: Rf 0.47 (hexane / dichloromethane = 1: 1)

(R, R) -biphemphos Melting point: 153-159 ° C. Optical rotation: [α] _D ²² = −252 ° (C 1.0, toluene) ³¹ P-NMR (toluene-d ₈ ) δ: -12.6 (d, J
pp = 12.2 Hz), 145.8 (d) Thin layer chromatography: Rf 0.42 (hexane / dichloromethane = 1: 1)

Example 2 In the same manner as in Example 1, the isomer (R) -3,3'-
Dichloro-2,2 ', 4,4'-tetramethyl-6-diphenylphosphinobiphenyl-6'-yloxy ((S)
-1,1'-binaphthalene-2,2'-diyldioxy) phosphine (hereinafter abbreviated as (R, S) -biphemphos) and (S) -3,3'-dichloro-2,2 ', 4,
4′-tetramethyl-6-diphenylphosphinobiphenyl-6′-yloxy ((S) -1,1′-binaphthalene-2,2′-diyldioxy) phosphine (hereinafter, referred to as
(S, S) -biphemphos).

(R, S) -biphemphos Melting point: 153-158 ° C. Optical rotation: [α] _D ²¹ = 273 ° (C 1.0, toluene) ³¹ P-NMR (toluene-d ₈ ) δ:- 13.3 (d, J
pp = 36.6 Hz), 146.8 (d) Thin layer chromatography: Rf 0.47 (hexane / dichloromethane = 1: 1)

(S, S) -biphemphos Melting point: 147-151 ° C. Optical rotation: [α] _D ²¹ = 253 ° (C 1.0, toluene) ³¹ P-NMR (toluene-d ₈ ) δ:- 12.6 (d, J
pp = 13.8 Hz), 145.8 (d) Thin layer chromatography: Rf 0.42 (hexane / dichloromethane = 1: 1)

Example 3 (R) -2-diphenylphosphino-1,1'-biphenyl-2'-yloxy ((R) -1,1'-binaphthalene-2,2'-diyldioxy) phosphine and ( S)-
2-diphenylphosphino-1,1'-biphenyl-2 '
-Yloxy ((R) -1,1'-binaphthalene-2,2 '
Preparation of -diyldioxy) phosphine:

(1) 2,2′-bis (trifluoromethanesulfonyloxy) biphenyl (hereinafter referred to as “compound B ′”
The title compound B 'was obtained in the same manner as in Example 1 (2). 96% yield. Melting point: 33-34 ° C Thin layer chromatography: Rf 0.67 (hexane / ethyl acetate = 7: 3)

(2) 2-diphenylphosphinyl-2 '
-Production of trifluoromethanesulfonyloxybiphenyl (hereinafter, referred to as "compound C '"): The title compound C' was obtained in the same manner as in Example 1 (3). 79% yield. Melting point: 123-124 ° C. ³¹ P-NMR (CDCl ₃ ) δ: 27.78 ¹⁹ F-NMR (CDCl ₃ ) δ: −6.05

(3) 2-diphenylphosphino-2'-
Hydroxybiphenyl (hereinafter referred to as "Compound D '")
In the same manner as in Example 1 (4), the title compound D ′ was prepared in a yield of 6
Obtained at 0%. Melting point: 122-123 ° C ³¹ P-NMR (CDCl ₃ ) δ: -12.01

(4) (R) -2-diphenylphosphino-1,1′-biphenyl-2′-yloxy ((R) -1,
1'-binaphthalene-2,2'-diyldioxy) phosphine and (S) -2-diphenylphosphino-1,1 '
Production of -biphenyl-2'-yloxy ((R) -1,1'-binaphthalene-2,2'-diyldioxy) phosphine: (R) -2-diphenylphosphino in the same manner as in Example 1 (6). -1,1'-biphenyl-2'-yloxy ((R) -1,1'-binaphthalene-2,2'-diyldioxy) phosphine (hereinafter, (R, R) -H-biph
emphos) and (S) -2-diphenylphosphino-1,1′-biphenyl-2′-yloxy ((R) -1,1′-binaphthalene-2,2′-diyldioxy) phosphine (hereinafter referred to as ( (S, R) -H-biphe
mphos) (S, R) -H-biph
emphos / (R, R) -H-biphemphos
= 55: 45). Yield 62%.

Melting point of mixture: 150-156 ° C. Optical rotation of mixture: [α] _D ²² = 324 ° (C 1.0, toluene)

(S, R) -H-biphemphos ³¹ P-NMR (toluene-d ₈ ) δ: -11.9 (d, J
(pp = 35.1 Hz), 146.77 (d). (R, R) -H-biphemphos ³¹ P-NMR (toluene-d ₈ ) δ: −11.5 (d, J
(pp = 21.4 Hz), 146.81 (d)

Example 4 (R) -2-diphenylphosphino-5,5 ′, 6,6 ′,
Synthesis of 7,7 ', 8,8'-octahydro-1,1'-binaphthalen-2'-yloxy-((S) -1,1'-binaphthalene-2,2'-diyldioxy) phosphine: (1) Synthesis of (R) -5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,1'-bi-2-naphthol: 200 m
(R) -2,2'-dihydroxy-
3.00 g (10.5 mmol) of 1,1′-binaphthyl,
360 mg of platinum dioxide and 75 ml of acetic acid were added,
After stirring at 3 atm of hydrogen pressure and 5 ° C for 18 hours, the hydrogen pressure was increased to 1 atm.
The mixture was stirred at 0 atm and 18 ° C for 7 days, added with ethyl acetate, and filtered through Celite. Water was added to the obtained filtrate, and the mixture was separated. The obtained organic layer was washed twice with a saturated aqueous solution of sodium bicarbonate and separated. The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. 3.03 g of the title compound was obtained. 98% yield,
Optical purity of 99% ee or more.

(2) (R) -2,2′-bis (trifluoromethanesulfonyloxy) -5,5 ′, 6,6 ′, 7,7 ′,
Synthesis of 8,8'-octahydro-1,1'-binaphthyl: 5
26 ml of methylene chloride in a 0 ml four-necked flask,
5.15 g of (R) -5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,1'-bi-2-naphthol (17.4 mm
ol) 2,6-Toluidine 5.58 g (52.2 mmol)
l) and 0.955 g of 4-dimethylaminopyridine
(7.83 mmol) was dissolved in this solution at 0 ° C. at 14.7 g of trifluoromethanesulfonic anhydride (54.7 g).
2.2 mmol) are added. The mixture was stirred at room temperature for 23 hours to complete the reaction.

After completion of the reaction, the solvent was distilled off, and the residue was purified by silica gel column chromatography using methylene chloride as a developing solvent to give (R) -2,2'-bis (trifluoromethanesulfonyloxy) -5,5. ', 6,6', 7,7 ', 8,
9.36 g of 8'-octahydro-1,1'-binaphthyl was obtained. Yield 100%.

(3) (R) -2-diphenylphosphinyl-2'-trifluoromethanesulfonyloxy-
5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,1'
Synthesis of Binaphthyl In a 50 ml flask, (R) -2,2′-bis (trifluoromethanesulfonyloxy) -5,5 ′, 6,6 ′, 7,7 prepared in (2) above under an argon stream. ', 8,8'-octahydro-1,1'-binaphthyl 2.68 g (4.98 g)
mmol) and 1.99 g of diphenylphosphine oxide
(9.82 mmol) in 20 ml of dimethyl sulfoxide
And palladium acetate 110 mg in this solution
(0.491 mmol), ethyldiisopropylamine
5.1 ml and sodium formate 33 mg (0.491 mm
ol) and stirred at room temperature for 20 minutes.

Next, the solution was stirred at 90 ° C. for 19 hours, then returned to room temperature, 250 ml of ether and 150 ml of water were added, and the mixture was stirred and separated. After liquid separation, the organic layer was washed four times with 125 ml of water, and then washed with 125 ml of 5% diluted hydrochloric acid.
Twice with 50 ml of water, once with 125 ml of a saturated aqueous sodium hydrogen carbonate solution, and finally with 125 ml of saturated saline.
And washed. After the obtained organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off, the residue was purified by silica gel column chromatography using a toluene / acetonitrile = 3/1 mixture (solvent ratio, the same applies hereinafter) as a developing solvent. Thereby, 1.37 g of the title compound was obtained. Yield 83%.

(4) (R) -2-diphenylphosphino-2'-hydroxy-5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,1'-binaphthyl Synthesis: 50ml of 4
(R) -2-diphenylphosphinyl-
2'-trifluoromethanesulfonyloxy-5,5 ',
6,6 ′, 7,7 ′, 8,8′-octahydro-1,1′-binaphthyl 318.7 mg (0.664 mmol) in xylene
Dissolved in 22 ml of triethylamine.
1 g (12 mmol) and 1.62 g of trichlorosilane
(12 mmol) was added. This mixture was stirred at 120 ° C. for 17 hours. After the temperature of the reaction solution was returned to room temperature, 4.4 ml of 35% sodium hydroxide was carefully added, and the mixture was stirred for another 2 hours and then separated.

After liquid separation, the organic layer was washed twice with 30 ml of saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain a crude product. This crude product was dissolved in 7 ml of tetrahydrofuran, and 335 mg (7.98 mmol) of lithium hydroxide was added therein.
Was added to 2.4 ml of water, and the mixture was added at room temperature for 15 minutes.
Stirred for hours. 50 ml of ether and 5% diluted hydrochloric acid 15
The organic layer was washed twice with water, dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was treated with a mixed solution of hexane / ethyl acetate = 5/1 as a developing solvent. Purification by silica gel column chromatography gave 105.4 mg of the title compound. Yield 51
%.

(5) (S) -1,1'-binaphthalene-
Synthesis of 2,2′-diyldioxychlorophosphine: (S) -1,1′-2 was placed in a 50 ml flask under a stream of argon.
-Binaphthole (4.94 g, 17.3 mmol) and phosphorus trichloride (11.3 g, 830 mmol) were added, and the mixture was heated under reflux for 4 hours, returned to room temperature, and unreacted phosphorus trichloride was distilled off under reduced pressure. 5.56 g of the title compound as white crystals were obtained. Yield 92%.

(6) (R) -2-diphenylphosphino-5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,
1′-binaphthalen-2′-yloxy-((S) -1,
Synthesis of 1'-binaphthalene-2,2'-diyldioxy) phosphine: (R) -2-diphenylphosphino-2'-hydroxy-5,5 ', 6,6',
7,7 ', 8,8'-octahydro-1,1'-binaphthyl
0.294 g (0.946 mmol) and (S) -1,1-
Take 662 mg (1.89 mmol) of binaphthalene-2,2'-diyldioxychlorophosphine and add ether 3
Dissolved in 0 ml. 191 mg (1.89 mmol) of triethylamine was added thereto at 0 ° C.
After stirring for an hour, 20 ml of water was added to stop the reaction.

After liquid separation, the obtained organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a crude product. This was purified by silica gel column chromatography using a mixture of hexane / dichloromethane = 1/1 as a developing solvent to give (R) -2-diphenylphosphino-5,5 ′,
6,6 ′, 7,7 ′, 8,8′-octahydro-1,1′-binaphthalen-2′-yloxy-((S) -1,1′-binaphthalene-2,2′-diyldioxy) phosphine ( Less than,
(R), (S) -OcH-BINAPHOS) were obtained as white crystals in 719.4 mg. Yield 98%.

³¹ P-NMR (CDCl ₃ ) δ: -15.0
(D, J = 42.7 Hz), 146.8 (d, J = 42.7H)
z) ³¹ P-NMR (toluene-d ₈ ) δ: 50.4 (dd, J
pp = 87.0 Hz, JRh-p = 174.0 Hz), 1
60.2 (dd, JRh-p = 328.1 Hz)

Example 5 (R) -2-diphenylphosphino-5,5 ′, 6,6 ′,
7,7 ', 8,8'-octahydro-1,1'-binaphthalen-2'-yloxy-((S) -5,5', 6,6 ', 7,7',
8,8'-octahydro-1,1'-binaphthalene-2,2 '
Synthesis of -diyldioxy) phosphine: (1) (S) -5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,1'-binaphthalene-2,2'-diyldi Synthesis of oxychlorophosphine: 50 ml under a stream of argon
(S) -5,5 ', 6,6', 7,7 ', 8,8'-
Octahydro-1,1'-bi-2-naphthol 5.12 g
(17.3 mmol) and 11.3 g (830) of phosphorus trichloride
mmol), and the mixture was heated under reflux for 4 hours, returned to room temperature, and unreacted phosphorus trichloride was distilled off under reduced pressure to obtain 5.7 g of the title compound as white crystals. Yield 92%.

(2) (R) -2-diphenylphosphino-5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,
1'-binaphthalen-2'-yloxy-((S) -5,
Synthesis of 5 ′, 6,6 ′, 7,7 ′, 8,8′-octahydro-1,1′-binaphthalene-2,2′-diyldioxy) phosphine: (S) -1 in Example 1 (6) , 1-Binaphthalene-2,2'-diyldioxychlorophosphine was converted to (S) -5,5 ', 6,6', 7,7 ', 8,8'-octahydro-1,1'-binaphthalene-2 The title compound (hereinafter referred to as (R), (S)-(OcH) ₂ ) was prepared in the same manner as in Example 1 (6) except that the compound was changed to 2,2'-diyldioxychlorophosphine.
-BINAPHOS) in 91% yield. ³¹ P-NMR (CDCl ₃ ) δ: -14.7 (d, J = 3
9.7 Hz), 138.3 (d, J = 39.7 Hz)

Example 6 Synthesis of (R) -2-diphenylphosphino-1,1'-binaphthalen-2'-yloxy ((S) -1,1'-binaphthalene-2,2'-diyldioxy) phosphine : (1) Synthesis of (R) -2,2'-bis (trifluoromethanesulfonyloxy) -1,1'-binaphthyl: Example 4
In (2), (R) -5,5 ', 6,6', 7,7 ', 8,8
-The same operation as in Example 4 (2) was carried out except that (R) -1,1'-bi-2-naphthol was used instead of octahydro-1,1'-bi-2-naphthol. 9.56 g of the title compound were obtained. Yield 100%.

(2) (R) -2-diphenylphosphinyl-2'-trifluoromethanesulfonyloxy-1,
Synthesis of 1′-binaphthyl: In Example 4 (3),
(R) -2,2′-bis (trifluoromethanesulfonyloxy) -5,5 ′, 6,6 ′, 7,7 ′, 8,8′-octahydro-1,1′-binaphthyl ) -2,2′-Bis (trifluoromethanesulfonyloxy) -1,1′-
Except that binaphthyl was used, the same operation as in Example 4 (3) was performed to obtain 2.51 g of the title compound. Yield 83%.

(3) Synthesis of (R) -2-diphenylphosphino-2'-hydroxy-1,1'-binaphthyl: (R) -2-diphenylphosphinyl-2 'in Example 4 (4) -Hydroxy-5,5 ', 6,6', 7,7 ', 8,8'-
(R)-in place of octahydro-1,1'-binaphthyl
2-diphenylphosphinyl-2'-hydroxy-1,
By operating in the same manner as in Example 4 (4) except that 1′-binaphthyl was used, 153 mg of the title compound was obtained. Yield 51
%.

(4) (R) -2-diphenylphosphino-1,1′-binaphthalen-2′-yloxy-((S)
Synthesis of -1,1'-binaphthalene-2,2'-diyldioxy) phosphine: In Example 4 (6), (R) -2
-Diphenylphosphino-2'-hydroxy-5,5 ',
(R) -2-diphenylphosphino-in place of 6,6 ', 7,7', 8,8'-octahydro-1,1'-binaphthyl
The same procedure as in Example 4 (6) was repeated except that 2′-hydroxy-1,1′-binaphthyl was used.
712 mg of (R, S) -BINAPHOS was obtained. Yield 98%.

Example 7 Preparation of (R) -2-diphenylphosphino-1,1'-binaphthalen-2'-yloxy-((S) -10,10'-biphenanthrene-9,9'-diyldioxy) phosphine Synthesis: (1) (S) -10,10'-biphenanthrene-9,9 '
Synthesis of -diyldioxychlorophosphine: Example 4
Example 4 (5) except that (S) -10,10'-bi-9-phenanthrole was used in place of (S) -1,1'-bi-2-naphthol in (5). The same operation as in 4) was performed to obtain 1.05 g of the title compound. 90% yield.

(2) (R) -2-diphenylphosphino-1,1'-binaphthalen-2'-yloxy-((S)
Synthesis of -10,10'-biphenanthrene-9,9'-diyldioxy) phosphine: In Example 4 (6),
Performed except that (S) -10,10'-biphenanthrene-9,9'-diyldioxychlorophosphine was used instead of (S) -1,1-binaphthalene-2,2'-diyldioxychlorophosphine. The same procedure as in Example 4 (6) was performed to obtain 726 mg of the title compound. 95% yield. ³¹ P-NMR (C ₆ D ₆ ) δ: 148.05 (d, J = 2
(1.4 Hz), -13.34 (d, J = 21.4 Hz)

Example 8 Rh (acac) [(S, R) -biphempho
Preparation of 39.7 mg (0.0) of (S, R) -biphemphos of Example 1 in a 20 ml Schlenk tube.
5mmol) and Rh (acac) ₂ (CO) ₂ 12.8m
g (0.05 mmol) and dissolve in 5 ml of benzene. After the reaction solution was stirred at room temperature for 5 minutes, the solvent was distilled off under reduced pressure and Rh (acac) [(S, R) -biphe
mphos] was obtained as a yellow solid. Yield 100%.

Example 9 Rh (acac) [(R, R) -biphempho
s]: (S, R) -biphemph of Example 8
Rh (acac) was operated in the same manner as in Example 8 except that (R, R) -biphemphos was used instead of os.
[(R, R) -biphemphos] was obtained in 100% yield.

Example 10 Rh (acac) [(S, R) -H-biphemph
os]: (S, R) -biphemp of Example 8
(±, R) -H-biphempho instead of hos
Rh (ac) was operated in the same manner as in Example 8 except for using s.
ac) [(S, R) -H-biphemphos] with 1
Obtained in a yield of 00%.

Example 11 Rh (acac) [(R, S) -OcH-BINAPH
OS]: (S, R) -biphemp of Example 8
(R, S) -OcHBINAPHOS instead of hos
Rh (aca) was operated in the same manner as in Example 8 except that
c) [(R, S) -OcH-BINAPHOS]
Obtained in 0% yield.

Example 12 Rh (acac) [(S, R) -OcH-BINAPH
OS]: (S, R) -biphemp of Example 8
(S, R) -OcHBINAPHOS instead of hos
Rh (aca) was operated in the same manner as in Example 8 except that
c) [(S, R) -OcH-BINAPHOS]
Obtained in 0% yield.

Example 13 Rh (acac) [(R, S)-(OcH) ₂ -BINA
PHOS]: (S, R) -biphe of Example 8
(R, S)-(OcH) ₂ -BIN instead of mphos
The same operation as in Example 8 was carried out except that APHOS was used.
h (acac) [(R, S)-(OcH) _2- BINAP
HOS] was obtained in 100% yield.

Examples 14 to 25 In the same manner as in Examples 3 to 13, phosphine compounds and complexes as shown in Tables 3 and 4 were obtained.

[0110]

[Table 3]

[0111]

[Table 4]

Example 26 Production of (S)-(+)-2-phenylpropanal:
(S, R) -biphem in 50 ml autoclave
phos 38.7 mg (0.0488 mmol), Rh
(Acac) (CO) ₂ 3.1 mg (0.012 mmol)
1) and styrene 1250 mg (12.0 mmol)
Was added, and 50 atm of hydrogen and 50 atm of carbon monoxide were added, followed by stirring at 60 ° C for 42 hours.

The conversion and the production ratio of the product were ¹ H-NM.
It was measured by R (internal standard: diphenylmethane).
The optical purity was measured by gas chromatography after converting the produced optically active aldehyde into a carboxylic acid by Jones oxidation. As a result, the conversion of styrene was 1
At 00%, 2-phenylpropanal / 3-phenylpropanal = 9: 1. The asymmetric yield of 2-phenylpropanal was 94% ee, which was (S)-(+)-2-phenylpropanal.

Examples 27 to 33 According to Example 26, a hydroformylation reaction was carried out.
The results in Table 5 were obtained.

[0115]

Embedded image

[0116]

[Table 5]

EXAMPLE 34 Preparation of 2-acetoxypropanal: 50 ml of ethanol
761 mg of vinyl acetate (8.84 mmol)
l), Rh (acac) ((R, S) -OcH-BIN
APHOS) 8.6 mg (0.00884 mmol),
8.3 ml of benzene was added, 50 atm of carbon monoxide was added to 50 atm of hydrogen pressure, and the mixture was stirred at 60 ° C. for 44 hours.
As a result, the conversion of vinyl acetate was 72%. The compound produced in this reaction was a mixture of 88.6% of 2-acetoxypropanal and 11.4% of 3-acetoxypropanal. The asymmetric yield of 2-acetoxypropanal was 90% ee.

Examples 35 to 39 The same procedures as in Example 33 were carried out except that the olefins and the phosphine compound as a ligand were changed to obtain optically active aldehydes shown in Table 6 below.

[0119]

Embedded image

[0120]

[Table 6]

Example 40 (R) -2-[(3S, 4R) -3-[(R) -1-t
-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propanal: Rh (ac
ac) [(R, S) -BINAPOS] 9.3 mg
(0.01 mmol), (R, S) -BINAPHOS
8 mg (0.01 mmol) and (1R, 3S, 4R)
-Vinyl azetidin-2-one 510 mg (2 mmol
l) was placed in an autoclave of 100 ml, the inside of the vessel was sufficiently replaced with nitrogen, and 5 ml of toluene was added.
To this, carbon dioxide was pressurized at 50 kg / cm ² , and then hydrogen was pressurized so that the total pressure became 100 kg / cm ² . Thereafter, the mixture was heated to 60 ° C. in an oil bath and reacted for 48 hours with vigorous stirring.

After standing at room temperature, excess carbon monoxide and hydrogen were discharged, toluene was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain (R) -2-[(3S, 4R) -3-[(R) -1-t
-Butyldimethylsilyloxyethyl] -2-oxoazetidin-4-yl] propanal and (S) -2-
[(3S, 4R) -3-[(R) -1-t-butyldimethylsilyloxyethyl] -2-oxoazetidine-4
513 mg of a 94/6 mixture of [-yl] propanal were obtained. 90% yield.

The ratio of 2 (R) / 2 (S) was determined by ¹ H-NMR based on the integral ratio of aldehyde protons.
The mixture which was further subjected to Jones oxidation and led to the corresponding carboxylic acid was sampled by HPLC (Inertsil ODS-2, eluent: acetonitrile-H ₂ O 6/4, pH = 2.3 (phosphoric acid)). Was determined by comparison.

(2 (R) form) ¹ H-NMR (400 MHz, CDCl ₃ ) δ: 0.07
(S, 3H), 0.08 (s, 3H), 0.88 (s, 9H),
1.22 (d, J = 7.3 Hz, 3H), 1.24 (d, J =
6.3 Hz, 3H), 2.68 (m, 1H), 3.94 (d
d, J = 5.4, 2.4 Hz, 1H), 4.20 (m, 1H),
5.98 (s, 1H), 9.81 (d, J = 1.1 Hz, 1
H)

Examples 41 to 47 The same treatment as in Example 40 was performed except that the catalyst was changed as shown in Table 7. Table 7 shows the results.

[0126]

[Table 7] Examples 48 to 50 The same treatment as in Example 40 was performed except that the solvent was changed as shown in Table 8. Table 8 shows the results.

[0127]

[0128]

By using the phosphine compound of the present invention and a transition metal compound or the transition metal-phosphine complex of the phosphine compound of the present invention and a transition metal compound as a catalyst for a hydroformylation reaction, high regioselectivity and high stereoselectivity can be obtained. Optically active aldehydes can be obtained. that's all

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ Identification code FI C07F 15/00 C07F 15/00 F C07B 53/00 B // C07B 53/00 61/00 300 61/00 300 C07D 205/08 K C07D 477/00 487/04 134 (72) Inventor Yasushi Kato 1-4-11 Nishi-Hachiman, Hiratsuka-shi, Kanagawa Pref. Fine Chemical Research Laboratory (72) Inventor Noboru Sayo 1-Nishi-Hachiman, Hiratsuka-shi, Kanagawa 4-11 Takasago International industry Co., Ltd. Fine Chemicals research house (72) inventor Yunlin Hidenori Hiratsuka, Kanagawa Prefecture Nishiyawata 1-4-11 Takasago International industry Co., Ltd. Fine Chemicals research house (58) investigated the field (Int.Cl. ⁷ , DB name) C07D 205/08 C07F 9/50 C07F 15/00 C07D 477/00 CA (STN) REGISTRY (STN)

Claims (12)

(57) [Claims] [Claim 1] The following general formula (1) (Wherein R ⁴ and R ⁴ ′ are the same or different and each represent a hydrogen atom,
R ³ represents a lower alkyl group or a lower alkoxy group;
R ³ ′, R ⁹ and R ⁹ ′ are the same or different,
A hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, or a ring may be formed by R ³ and R ⁴ , or R ³ ′ and R ⁴ ′. R ⁵ and R ⁶ are the same or different and represent a phenyl group which may be substituted with lower alkyl, halogen or lower alkoxy, and R ⁷ and R ⁸ are the same or different and are substituted with lower alkyl, lower alkoxy or halogen. Or a phenyl group, or R ⁷ and R ⁸
May form a divalent hydrocarbon group.) 2. The following general formula (2): (Wherein R ¹⁴ and R ¹⁴ ′ are the same or different and each represent a hydrogen atom, a lower alkyl group or a lower alkoxy group;
¹³ , R ¹³ ′, R ¹⁹ and R ¹⁹ ′ are the same or different and each represent a hydrogen atom, a lower alkyl group, a lower alkoxy group or a halogen atom. R ¹⁵ and R ¹⁶ are the same or different, lower alkyl, a halogen or a lower alkoxy which may be substituted phenyl group, R ¹⁷ and R
¹⁸ is the same or different and represents a lower alkyl, a lower alkoxy, a phenyl group optionally substituted with halogen,
R ¹⁷ and R ¹⁸ may form a divalent hydrocarbon group). 3. A transition metal-phosphine complex comprising a transition metal selected from rhodium, ruthenium, iridium and platinum and the phosphine compound according to claim 1 as a ligand. 4. The following general formula (1): (Wherein, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ³ ′,
R ⁴ ′ and R ⁹ ′ have the same meanings as described above) and rhodium, ruthenium,
A complex with a metal selected from iridium and platinum is prepared in advance, and this complex is used as a catalyst for a hydroformylation reaction in the following general formula (3): Q ¹ —CH ＝ CH—Q ² [wherein Q ¹ is a hydrogen atom Or a lower alkyl group,
Q ² is a lower alkyl group, a lower alkoxy group, a halogen atom, a lower alkylcarbonyloxy group, a cyano group, a carboxyl group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a phthalimide group, an acetylamino group,
Benzoylamino group, mono-lower alkylamino group, di-lower alkylamino group, benzoyl group; lower alkyl, lower alkoxy, phenyl group optionally substituted with halogen; lower alkyl, lower alkoxy, optionally substituted with halogen A group representing a naphthyl group or a group represented by the following general formula (4): (Wherein R ¹ represents a hydrogen atom or a hydroxyl-protecting group), or Q ¹ and Q ^{2 represent the following} formula (5): (Wherein, n represents 1 or 2). A process for producing optically active aldehydes, comprising hydroformylating an olefin represented by the formula: 5. The following general formula (1): (Wherein, R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ³ ′,
R ⁴ ′ and R ⁹ ′ have the same meanings as described above), and a metal compound of a metal selected from rhodium, ruthenium, iridium and platinum as a catalyst. A process for producing optically active aldehydes, comprising hydroformylating an olefin represented by Q ¹ -CH = CH-Q ² (wherein Q ¹ and Q ² have the above-mentioned meanings). 6. An olefin represented by the following general formula (6): (Wherein R ¹ has the same meaning as described above). The method for producing an optically active aldehyde according to claim 4, wherein 7. The olefin is represented by the following general formula (6): (Wherein R ¹ has the same meaning as described above). The method for producing an optically active aldehyde according to claim 5, wherein 8. A transition metal phosphine complex having a transition metal selected from rhodium, ruthenium, iridium and platinum and the phosphine compound according to claim 2 as a ligand. 9. The following general formula (2): (Wherein, R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ ,
R ¹³ ′, R ¹⁴ ′ and R ¹⁹ ′ have the same meaning as described above) and rhodium, ruthenium,
A complex with a metal selected from iridium and platinum is prepared in advance, and this complex is used as a catalyst for a hydroformylation reaction in the following general formula (3): Q ¹ —CH ＝ CH—Q ² (wherein Q ¹ and Q ² Wherein the olefins represented by the formula are hydroformylated. 10. The following general formula (2): (Wherein, R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ ,
R ¹³ ′, R ¹⁴ ′ and R ¹⁹ ′ have the same meaning as described above) and a metal compound of a metal selected from rhodium, ruthenium, iridium and platinum as a catalyst. Production of an optically active aldehyde characterized by hydroformylating an olefin represented by the formula (3) Q ¹ —CHＣＨCH—Q ² (wherein Q ¹ and Q ² have the above-mentioned meanings) Method. An olefin is represented by the following general formula (6): (Wherein R ¹ has the same meaning as described above). The method for producing an optically active aldehyde according to claim 9, wherein An olefin is represented by the following general formula (6): (Wherein R ¹ has the same meaning as described above). The method for producing an optically active aldehyde according to claim 10, wherein