JPH06247928A - Production of alpha, beta-substituted cyclopentanone derivative - Google Patents

Abstract

PURPOSE:To obtain the subject compound as an intermediate for prostaglandins in a high yield and through short steps under neutral and mild conditions without troubles such as preparing unstable anionic reagent (s). CONSTITUTION:The compound of formula V can be obtained by reaction, in the presence of a radical generator, between (A) a substituted cyclopentanone derivative of formula {X is (alphaOZ, beta-H) or (alpha-H, beta-OZ) (Z is OH-protecting group), Y is (-alpha-H, beta-R) or (alpha-R, beta-H) [ R is formula II (T is CH2CH2 or CH=CH; (j) and (k) each 0-2; R<0> is H, alkyl or alkoxy; R<1> is alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, phenoxy, etc.)]} and (B) a compound of formula III [A is halogen or formula IV (R<x> is H, alkyl, aryl, etc.); R<2>-R<8> are each H, alkyl or alkoxyl; R<9> is H, alkyl, halogen, CN, NH2, etc.; U is T, CidenticalC, phenylene, etc.; (l) is 1-7; (m), (p) and (r) are each 0 or 1; (n), (q) and (s) are each 0-5; X<1> and X<2> are each 0 or S; Z<1> is CN, OH, H, halogen, etc.], followed by, if desired, hydrolysis.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to α, which is useful as an intermediate for medical and agricultural chemicals, particularly as a synthetic intermediate for prostaglandins.
The present invention relates to a method for producing a β-substituted cyclopentanone derivative.

[0002]

PRIOR ART AND PROBLEM TO BE SOLVED BY THE INVENTION α, β
-Substituted cyclopentanone derivatives have attracted attention as intermediates for medical and agricultural chemicals, and are particularly useful as synthetic intermediates for prostaglandins having strong physiological activity. Conventionally, as one of the reactions for producing prostaglandins, a prostaglandin F by a conjugate addition reaction represented by the following formula
₂ The synthesis method of α is known [J. Stark et al., Journal American Chemical Society (JA
m. Chem. Soc. ), 97, 4745, 626
0, (1975)].

[0003]

[Chemical 6]

The method for synthesizing the prostaglandin F ₂ α is characterized in that the yield from the compound (IV) is high, and the α chain portion can be freely changed by selecting a reagent for conjugate addition. ing. However, the conventionally known conjugated addition reagents include CO ₂ R ¹² , CN, and
OCOR ¹³ (wherein R ¹² and R ¹³ represent the same or different alkyl groups having 1 to 6 carbon atoms) or the like and cannot contain a group that easily reacts with an organometallic agent, and thus, Such substituents were formed by conversion. For example, also in the synthesis of the above prostaglandin F ₂ α,
The CH (CH ₃ ) OC ₂ H ₅ group is released to convert it to an alcohol, and this is further oxidized with a toxic chromium-based oxidant to induce a carboxylic acid. There were various problems.

On the other hand, there is a method of using an organozinc reagent as a method of using a conjugated addition reagent having a substituent which cannot be directly introduced as described above and which can directly introduce such a substituent [Sato et al., JP-A-02- 184487].

[0006]

[Chemical 7]

The method described above is a powerful method that solves many of the problems of the G-Stark method. However, since the reaction of the organozinc reagent is also an anion reaction, it is not possible to include a compound having a reactive hydrogen atom such as OH and COOH as a substituent. Also, both methods have partial structures due to anion reaction.

[0008]

[Chemical 8]

A substance which easily causes β-elimination, such as

[0010]

[Chemical 9]

A material such as Michael which is easy to add,

[0012]

[Chemical 10]

In the case of containing a compound which is likely to be an allene as described above, the reagent cannot be prepared or a side reaction is likely to occur.
Furthermore, it is necessary to prevent mixing of water and oxygen, and in general, extremely low temperatures are required in many cases, and there are special know-hows for preparation of reagents, which may lead to failure.

The present invention has been made in view of the above circumstances, and is useful as an intermediate for prostaglandins,
PROBLEM TO BE SOLVED: To provide a method for efficiently producing an α, β-cyclopentanone derivative which can be industrially advantageously induced into a prostaglandin in a short process without inconvenience such as using an unstable anionic reaction reagent. With the goal.

[0015]

Means and Actions for Solving the Problems The present inventors have
As a result of intensive studies to achieve the above object, the following general formula [I]

[0016]

[Chemical 11]

[Wherein, X represents (α-OZ, β-H) or (α-H, β-OZ), and Z represents a hydroxyl-protecting group. Y is (α-H, β-R) or (α-R, β-
H) and R is

[0018]

[Chemical 12]

In the group represented by, T is CH ₂ CH ₂ or CH
A group selected from ═CH, j and k each independently represent an integer of 0, 1 or 2, and R ⁰ represents (2-k) hydrogen atoms, an alkyl group having 1 to 4 carbon atoms or 1 to 2 carbon atoms. 4 alkoxy group, R ¹ is an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, a phenyl group,
Phenoxy group, phenyl group or phenoxy group substituted by "halogen atom, trifluoromethyl group, alkyl group having 1 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms", or -BD (B is the number of carbon atoms 1 to 4 is an alkylene group, D is a phenyl group, a phenoxy group, "a halogen atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a phenyl group or a phenoxy group". It represents a substituted phenyl group or phenoxy group or a cycloalkyl group having 5 to 7 carbon atoms.)
And Z'represents a protective group for a hydroxyl group which is the same as or different from Z described above. ] And substituted cyclopentanone derivative represented by the general formula [II] _{^{A (CR 2 R 3) l}} X 1 m (CR 4 R 5) n U p (CR 6 R 7) q X 2 r (CR 8 R ⁹ ) _s Z ¹ [II] [wherein A is a halogen atom or

[0020]

[Chemical 13]

(R ^X represents a hydrogen atom, an alkyl group having 1 to 9 carbon atoms, an aralkyl group or an aryl group),
R < ² >, R < ³ >, R < ⁴ >, R < ⁵ >, R < ⁶ >, R < ⁷ > and R <^8> are each independently a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or 1 to 4 carbon atoms.
4 is an alkoxy group, R ⁹ is a hydrogen atom and has 1 to 1 carbon atoms.
An alkyl group having 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a halogen atom, CN, NH ₂ , OH or —COOR ^a ( ^Ra is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkenyl having 2 to 6 carbon atoms). Group is shown), U is CH ₂ CH ₂ , CH═C
H, C≡C, C = C = C or a group selected from phenylene groups, l is an integer of 1 to 7, m, p and r are each an integer of 0 or 1, and n, q and s are each 0. Indicates an integer of ˜5. X ¹ and X ² each represent an oxygen atom or a sulfur atom, and Z ¹ is CO ₂ R ^y , CN, OH, OCOR ^z or CO.
NR ^b R ^c (R ^b and R ^c are each a hydrogen atom and a carbon number of 1 to
6 represents an alkyl group having 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a benzyl group or a phenyl group. ), A hydrogen atom, a halogen atom, or a group selected from a substituted or unsubstituted aromatic group, wherein R ^y and R ^z are a hydrogen atom and a carbon number of 1 to 6, respectively.
Represents an alkyl group or an alkenyl group having 2 to 6 carbon atoms. ] With an organic radical precursor represented by, in the presence of a radical generator such as tin hydride and azobisisobutyronitrile or trialkylborane, zinc-copper complex, and subject to hydrolysis if necessary. Therefore, in the organic radical precursor, a hydroxyl group, a carboxyl group, β-
Even if a group such as an oxa group, an α, β-unsaturated ester group or a β-triple bond is contained, these groups can be directly introduced without any trouble, and a toxic reaction reagent such as a chromium-based oxidizing agent is used. Without the following general formula [III]

[0022]

[Chemical 14]

[Wherein, W represents (α-OQ, β-H) or (α-H, β-OQ), and Q represents a hydrogen atom or a protective group for the same hydroxyl group as Z.] Also, V is (α-H, β-
R) or (α-R, β-H), and R is

[0024]

[Chemical 15]

In the group represented by, T, R ⁰ , j and k have the same meanings as described above, and Q'represents a hydrogen atom or the same hydroxyl-protecting group as Z '. Also, X ¹ , X ² , U, R ² , R ³ , R
⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Z ¹ , l, m, n, p,
q, r and s have the same meanings as described above. The present invention has been completed by finding that an α, β-substituted cyclopentanone derivative represented by the following formula can be obtained.

Therefore, according to the present invention, the substituted cyclopentanone represented by the above formula [I] and the organic radical precursor represented by the above formula [II] are reacted in the presence of a radical generator and optionally hydrolyzed. A method for producing an α, β-substituted cyclopentanone derivative represented by the above formula [III] is provided.

The present invention will be described in more detail below. In the method for producing an α, β-substituted cyclopentanone derivative of the present invention, the general formula which is the first starting material is

[0028]

[Chemical 16]

The substituted cyclopentanone derivative represented by is a known compound and can be produced by various methods such as the method described in JP-A-2-128. Here, in the general formula [I], X and Y are as described above, and X is (α-OZ, β-H) or (α
-H, β-OZ), Y is (α-H, β-R) or (α-
R, β-H), Z is a hydroxyl protecting group, and R is

[0030]

[Chemical 17]

In the group represented by, T is CH ₂ CH ₂ or CH
A group selected from ═CH, j and k each independently represent an integer of 0, 1 or 2, and R ⁰ represents (2-k) hydrogen atoms, an alkyl group having 1 to 4 carbon atoms or 1 to 2 carbon atoms. 4 alkoxy group, R ¹ is an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, a phenyl group,
Phenoxy group, phenyl group or phenoxy group substituted by "halogen atom, trifluoromethyl group, alkyl group having 1 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms", or -BD (B is the number of carbon atoms 1 to 4 is an alkylene group, D is a phenyl group, a phenoxy group, "a halogen atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a phenyl group or a phenoxy group". It represents a substituted phenyl group or phenoxy group or a cycloalkyl group having 5 to 7 carbon atoms.)
And Z'is a protective group for a hydroxyl group,
In this case, the protective groups for the hydroxyl groups of Z and Z ′ include trialkylsilyl groups (eg trimethylsilyl group, t-butyldimethylsilyl group), alkoxyalkyl groups (eg methoxymethyl group), aralkyloxyalkyl groups (eg benzyloxy group). Examples thereof include a methyl group), a trityl group, and a tetrahydropyranyl (THP) group. Z and Z ′ may be the same or different from each other. When k is 2, two Z'groups may be combined to form an alkylene group (eg, ethylene group, 1,1,2,2-tetramethylethylene group). or,

[0032]

[Chemical 18]

R ¹ is preferably one having 1 to 10 carbon atoms, specifically, methyl group, n-propyl group, n
-Substituted or unsubstituted alkyl groups such as pentyl group, phenoxymethyl group, 3- (t-butyldimethylsilyloxy) -2-hexyl group; vinyl group, allyl group, 2-penten-1-yl group, 4- Phenyl-2-butene-1-
A substituted or unsubstituted alkenyl group such as an yl group; 1-butynyl group, 1-hexynyl group, 2-pentynyl group, 5-
A substituted or unsubstituted alkynyl group such as (ethoxyethyloxy) -2-pentyn-1-yl group; a phenyl group,
Examples thereof include substituted or unsubstituted aryl groups such as 3-trifluoromethylphenyl group.

In this case, when the intermediate of prostaglandins is obtained, R

[0035]

[Chemical 19]

The group represented by

[0037]

[Chemical 20]

(In the formula, Z ″ represents a hydroxyl-protecting group and may be the same as or different from the above-mentioned hydroxyl-protecting group Z.

[0039]

[Chemical 21]

Represents a single bond or a double bond, and R ¹⁰ represents an alkyl group having 1 to ¹⁰ carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, and 2-1 to 2 carbon atoms.
0 alkynyl group, phenyl group, phenoxy group, phenyl group or phenoxy group substituted by "halogen atom, trifluoromethyl group, alkyl group having 1 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms", or- BD (B
Is an alkylene group having 1 to 4 carbon atoms, D is a phenyl group, a phenoxy group, a "halogen atom, a trifluoromethyl group,
A phenyl group or a phenoxy group substituted with an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a phenyl group or a phenoxy group or a cycloalkyl group having 5 to 7 carbon atoms, and R ⁴ is hydrogen. An atom, a methyl group, an ethyl group, a methoxy group, an ethoxy group and the like are shown. It is preferable that it is a group represented by these. R ¹⁰ is a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-
Butyl group, i-butyl group, t-butyl group, amyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, 2-methylhexyl group, 2-methyl-2-hexyl group, 2-hexyl group , Cyclopentyl group, cyclohexyl group, cyclohexylmethyl group, hexa-4-yn-2
-Yl group, hepta-4-in-2-yl group, 2,6-dimethyl-hepta-5-en-1-yl group, penta-1-
En-1-yl group, penta-2-en-1-yl group, hexa-1-en-2-yl group, 3-ethoxy-2-methyl-propan-2-yl group, ethoxyethyl group, 5- Methoxyhexyl group, 2- (trimethylsilyloxy)-
2-hexyl group, halogenated methyl group, halogenated n-
Butyl group, halogenated n-pentyl group, halogenated nonyl group, phenyl group, benzyl group, halogenated phenyl group, n-pentyloxymethyl group, 1-ethoxy-2-
Methyl-propan-2-yl group, phenoxymethyl group,
Benzyloxymethyl group, p-chlorphenoxymethyl group, 2-phenylethyl group, benzyloxyethyl group, p
-Fluorophenoxymethyl group, phenylacetylenyl group, m-chlorphenoxymethyl group, m-trifluoromethyl-phenoxymethyl group, 1-butyl-cyclopropyl group, 3-ethyl-cyclopentyl group, benzothiophen-5-yl Group, a 2-octenyl group, a 3-methoxycarbonylpropyl group, a vinyl group, and the like, and examples of Z ″ include the same protecting groups as the above Z.

Next, the organic radical precursor, which is the second starting material in the production method of the present invention, has the general formula [II] A (CR ² R ³ ) _l X ¹ _m (CR ⁴ R ⁵ ) _{n Up} (CR ⁶ R ⁷ ) _q X ² _r (CR ⁸ R ⁹ ) _s Z ¹ [II], wherein A, U, l, m in the formula [II],
n, p, q, r, s, R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ ,
R ⁸ , R ⁹ , X ¹ , X ² and Z ¹ are as described above, A is a halogen atom, or

[0042]

[Chemical formula 22]

(R ^X represents a hydrogen atom, an alkyl group having 1 to 9 carbon atoms, an aralkyl group or an aryl group), and U is CH ₂ CH ₂ , CH = CH, C≡C, C = C = C. Or a group selected from a phenylene group, l is an integer of 1 to 7,
m, p and r are integers of 0 or 1 respectively, n, q and s
Each represents an integer of 0 to 5. X ¹ and X ² each represent an oxygen atom or a sulfur atom, Z ¹ is CO ₂ R ^y , C
N, OH, OCOR ^z , CONR ^b R ^c (R ^b and R ^c are each a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, and 1 carbon atom)
6 represents an alkoxy group, a benzyl group or a phenyl group. ), A hydrogen atom, a halogen atom, or a group selected from a substituted or unsubstituted aromatic group, R ^y and R ^z are each a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkenyl having 2 to 6 carbon atoms. Indicates a group. In this case, R ² in the formula
The total number of carbon atoms excluding R ⁹ and Z ¹ is preferably within the range of 1 to 10.

The substituted or unsubstituted aromatic group among the substituents represented by Z ¹ includes "a halogen atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, and 1 to 6 carbon atoms".
6 alkoxy groups, CO ₂ R ^d , CN, OH, OCOR ^e
Or CONR ^f R ^g (R ^d and R ^e are each a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkenyl group having 2 to 6 carbon atoms. R ^f and R ^g are each a hydrogen atom and 1 to 6 carbon atoms.
6 represents an alkyl group having 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a benzyl group or a phenyl group. ) ", Which may be substituted with phenyl group, naphthyl group, thienyl group, furyl group, pyrrolyl group, imidazolyl group, pyrazolyl group, isothiazolyl group, isoxazolyl group, pyridyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, indolyl group ,
Examples thereof include a quinolyl group and a quinoxalinyl group.

The halogen atom of A is a chlorine atom, a bromine atom or an iodine atom,

[0046]

[Chemical formula 23]

Examples of R ^X include a hydrogen atom, an alkyl group such as methyl, ethyl, propyl, butyl, t-butyl and octyl, an aralkyl group such as a benzyl group, and an aryl group such as a phenyl group.

Concretely, as the organic radical precursor of the above formula [II], when these formulas are represented by AR ⁵ , R ⁵ is methyl group, ethyl group, n-propyl group, n-
Butyl group, t-butyl group,

[0049]

[Chemical formula 24]

[0050]

[Chemical 25]

[0051]

[Chemical formula 26]

And the like. In the above formula, ⁱ Pr is i-propyl group, ⁿ Bu is n-butyl group, ^t B
u is a tert-butyl group.

A is

[0054]

[Chemical 27]

The compound of formula (I) can be prepared by a known method (for example, DHRB) from the corresponding alcohol (R ⁵ OH).
arton et al., Synthesis, 1981 , 74.
3. ).

[0056]

[Chemical 28]

In the production method of the present invention, the substituted cyclopentanone derivative represented by the general formula [I] is reacted with the organic radical precursor represented by the general formula [II] in the presence of a radical generator, and optionally hydrolyzed. By decomposing, the general formula [III]

[0058]

[Chemical 29]

An α, β-substituted cyclopentanone derivative represented by is synthesized. Here, the above general formula [II
I], W, V, U, X ¹ , X ² , R ² , R ³ , R ⁴ ,
R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , Z ¹ , l, m, n, p, q,
r and s are as described above, and W is (α-OQ, β-H).
Or (α-H, β-OQ), V represents (α-H, β-R) or (α-R, β-H), Q is a hydrogen atom or a protective group of the same hydroxyl group as Z, and R is

[0060]

[Chemical 30]

In the group represented by, T is CH ₂ CH ₂ or CH
A group selected from ═CH, j and k each independently represent an integer of 0, 1 or 2, and R ⁰ represents (2-k) hydrogen atoms, an alkyl group having 1 to 4 carbon atoms or 1 to 2 carbon atoms. 4 alkoxy group, R ¹ is an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, an alkynyl group having 2 to 10 carbon atoms, a phenyl group,
Phenoxy group, phenyl group or phenoxy group substituted by "halogen atom, trifluoromethyl group, alkyl group having 1 to 6 carbon atoms, alkoxy group having 1 to 6 carbon atoms", or -BD (B is the number of carbon atoms 1 to 4 is an alkylene group, D is a phenyl group, a phenoxy group, "a halogen atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a phenyl group or a phenoxy group". It represents a substituted phenyl group or phenoxy group or a cycloalkyl group having 5 to 7 carbon atoms.)
Wherein Q'is a hydrogen atom or the same hydroxyl group-protecting group as Z '. X ¹ and X ² are each a nitrogen atom,
Represents an oxygen atom or a sulfur atom, Z ¹ is CO ₂ R ^y , C
N, OH, OCOR ^z , CONR ^b R ^c (R ^b and R ^c are each a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, and 1 carbon atom)
6 represents an alkoxy group, a benzyl group or a phenyl group. ), A hydrogen atom, a halogen atom, or a group selected from a substituted or unsubstituted aromatic group, R ^y and R ^z are each a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkenyl having 2 to 6 carbon atoms. Represents a group, l is an integer of 1 to 7, m,
p and r each represent an integer of 0 or 1, and n, q, and s each represent an integer of 0 to 5.

In this case, the protective groups for the hydroxyl groups of Q and Q'and

[0063]

[Chemical 31]

Examples of R ⁰ and R ¹ are the same as those represented by Z, Z ′, R ⁰ and R ¹ of the above-mentioned general formula [I]. When the cyclopentanone derivative [III] is used as an intermediate for the production of prostaglandins,

[0065]

[Chemical 32]

The base is

[0067]

[Chemical 33]

(However, in the formula, R ¹⁰ , R ¹¹ , Z ',

[0069]

[Chemical 34]

Is preferably the same as defined above).

In the reaction between the substituted cyclopentanone derivative [I] and the organic radical precursor [II], the organic radical precursor [II] is the substituted cyclopentanone derivative [I].
It is preferable to use 0.5 to 10 equivalents, especially 1 to 5 equivalents.

The radical generator is used as a radical initiation catalyst. Examples of the radical generator include peroxides such as benzoyl peroxide, acetyl peroxide, t-butyl hydroperoxide, cumene hydroperoxide and potassium peroxodisulfate. Examples include azo compounds such as azobisisobutyronitrile and azobiscyclohexanecarbonitrile, or alkylborane compounds such as trimethylborane, triethylborane and tributylborane, and zinc powder treated with a copper salt or ammonium salt and ultrasonic waves. it can.

When a peroxide, an azo compound or an alkylborane compound is used as the radical generator, it is used in a catalytic amount to several equivalents, preferably 0.05 to 2 equivalents, relative to the organic radical precursor [II]. . Further, as a radical reducing agent, a tin hydride compound such as tributyl sushydride, triphenyl tin hydride, dibutyl tin hydride or diphenyl tin hydride is used in 0 to excess amount, preferably 1
Use ~ 5 equivalents. The reaction in this case can be carried out using a solvent, and the solvent used may be one that does not inhibit the reaction, and is preferably benzene, toluene, a benzene solvent such as xylene, cyclohexane, hexane, or pentane. Such hydrocarbon-based solvents and mixed solvents thereof. The reaction temperature is generally -100 ° C to the reflux temperature of the solvent, preferably -50 to 100 ° C. Especially when a borane compound is used, the reaction proceeds even at a low temperature. The reaction time is usually 10 minutes to 24 hours.

Further, when zinc is used as a radical generator, zinc powder is prepared from a copper salt such as copper iodide, copper bromide or copper chloride, or ammonium chloride, ammonium acetate, ammonium sulfate, tetramethylammonium chloride, The organic radical precursor [II] can be reacted by treating with an ammonium salt such as tetraethylammonium bromide and ultrasonic waves. An excess amount of zinc, preferably 1 to 5 equivalents, and a catalytic amount, preferably 0.05 to 2 equivalents, of copper salt or ammonium salt relative to the organic radical precursor [II] are used. As the reaction solvent, water,
Alcohols such as methanol, ethanol, isopropanol, butanol, ether, tetrahydrofuran,
An ether such as dioxane, a polar solvent such as acetonitrile, dimethylformamide, dimethylsulfoxide, or a mixed solvent thereof can be used. The reaction temperature is −20 to 80 ° C., preferably 10 to 25 ° C.,
The reaction time is 30 minutes to 24 hours.

When it is necessary to hydrolyze the obtained reaction product, usual hydrolysis conditions can be adopted. For example, in the case of ester, sodium hydroxide,
In addition to hydrolysis with an alkali hydroxide such as lithium hydroxide or potassium hydroxide, a method using a hydrolase or a microorganism can be used. Further, in the case of hydrolyzing the nitrile or removing the protective group for the hydroxyl group, hydrolysis with an acid such as sulfuric acid, hydrochloric acid or phosphoric acid may be employed in addition to the above-mentioned alkaline hydrolysis.

[0076]

According to the production method of the present invention, an α, β-substituted cyclopentanone derivative useful as an intermediate for pharmaceuticals, particularly as a synthetic intermediate for prostaglandins, particularly the following formula [IIIa]

[0077]

[Chemical 35]

(However, in the formula, Z, Z ', U, T, X ¹ ,
X ² , Z ¹ , R ⁰ , R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ ,
R ⁸ , R ⁹ , k, l, m, n, p, q, r and s have the same meanings as described above. ) The compound shown in) has no inconveniences such as preparing an unstable anion reagent, paying attention to contamination of water and oxygen, and using a toxic reaction reagent. That is, it can be manufactured industrially advantageously.

Hereinafter, the present invention will be described more specifically with reference to Examples, but the present invention is not limited to the following Examples. In the following examples, THF is tetrahydrofuran, Me is a methyl group, Et is an ethyl group, ⁿ Bu is n.
-Butyl group, ^t Bu is t-butyl group, TBS is ^t BuM
The eSi group and AIBN represent azobisisobutyronitrile.

[0080]

【Example】

Example 1

[0082]

[Chemical 36]

Tributyltin hydride (1.08 ml) was added to a solution of methylenecyclopentanone (1) (465 mg, 1 mmol) and allyl 6-iodohexanoate (2) (1.14 g, 4 mmol) in benzene (10 ml) under an argon atmosphere. , 4 mmol) and AIBN (8.2 m
g, 0.05 mmol) was added at room temperature, and the mixture was heated to 80 ° C. and stirred for 4 hours. After cooling to room temperature, the reaction solution was filtered through a silica gel short column, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain compound (3) (368 mg, yield 61%) and compound (4) (72 mg, yield 12%).

Compound (3) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.02 (2s, 12H), 0.05 (2s, 12)
H), 0.87 (2s, 18H), 0.89 (2s, 18H), 0.70-1.00 (m, 3
H), 1.02-1.81 (m, 18H), 1.85-2.03 (m, 1H), 2.08-2.25
(m, 3H), 2.44 (dt, J = 10.7, 7.2Hz, 1H), 2.63 (dd, J =
6.9, 18.2Hz, 1H), 3.98-4.09 (m, 1H), 4.11-4.25 (m, 1
H), 4.63 (d, J = 5.0Hz, 2H), 5.15-5.40 (m, 2H), 5.45-
5.64 (m, 2H), 5.82 (d, J = 15.4Hz, 1H), 5.87-6.13 (m, 1
H). ¹³ C-nmr (75MHz, CDCl ₃ ):-4.71, -4.67, -4.6, -4.2, 14.
2, 18.0, 18.2, 20.0, 23.1, 25.8, 25.9, 26.4, 27.5,
28.2, 29.17, 29.23, 32.0, 36.9, 46.3, 47.5, 53.2,
53.5, 64.7, 71.1, 73.2, 117.9, 121.0, 128.9, 132.
4, 136.3, 149.4, 166.1, 215.7.IR (neat): 775, 835, 1100, 1250, 1360, 1460, 1650, 1
725, 1740, 2855, 2930. [α] _D ²⁰ -40.3 ° (c = 2.45, CHCl ₃ ).

Compound (4) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.00 (4s, 12H), 0.03 (4s, 12)
H), 0.06 (4s, 12H), 0.08 (4s, 12H), 0.87 (2s, 18H),
0.88 (2s, 18H), 0.80-0.96 (m, 3H), 1.03-1.75 (m, 18H),
2.22 (d, J = 18.8Hz, 1H), 2.31 (t, J = 7.6Hz, 2H), 2.41
(dd, J = 18.8, 5.1Hz, 1H), 2.56-2.66 (m, 1H), 2.85-2.
94 (m, 1H), 3.96-4.06 (m, 1H), 4.20 (d, J = 5.2Hz, 1H),
4.57 (dt, J = 5.7, 1.4Hz, 1H), 5.07 (dd, J = 10.3, 15.1
Hz, 1H), 5.22 (ddt, J = 1.4, 10.4, 1.2Hz, 1H), 5.30 (d
dt, J = 1.5, 16.4, 1.5Hz, 1H), 5.58 (dd, J = 15.1, 6.6H
z, 1H), 5.92 (ddt, J = 10.4, 16.4, 5.7Hz, 1H).

Example 2 Compound (1) (465 mg, 1 mm under an argon atmosphere)
ol) and the compound (2) (1.14 g, 4 mmol) in toluene (1 ml) at 0 ° C., tributyltin hydride (1.08 ml, 4 mmol) and triethylborane (2M hexane solution, 0.1 mmol) were added, Stirred at 0 ° C. for 3 hours. By treating in the same manner as in Example 1, 16.7: 1 of compounds (3) and (4) (calculated from ¹ H-nmr).
410 mg (yield 68%) of the mixture was obtained.

Example 3 In Example 2, when the reaction temperature was 20 ° C., 416 mg (yield 69%) of a 11.1: 1 mixture of the compounds (3) and (4) was obtained.

Example 4 A solution of zinc powder (584 mg, 8.93 mmol) and copper iodide (357 mg, 1.88 mmol) in ethanol-water (9: 1, 16.3 ml) was sonicated for 5 minutes. In this solution, compound (1) (465 mg, 1 mmo
1) and a solution of the compound (2) (1.14 g, 4 mmol) in ethanol-water (9: 1, 4 ml) were added, and the mixture was added at 18 ° C for 6
Sonicated for hours. Saturated saline (15 ml) was added and the mixture was extracted with ether and purified in the same manner as in Example 1 to give 362 mg of a 10: 1 mixture of compounds (3) and (4) (yield 6
0%) was obtained.

Example 5

[0090]

[Chemical 37]

In the same manner as in Example 1, compound (6) (yield 55%) and compound (7) (yield 10%) were obtained from compound (1) and compound (5).

Compound (6) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.02 (2s, 12H), 0.05 (2s, 12)
H), 0.87 (2s, 18H), 0.89 (2s, 18H), 0.82-0.95 (m, 3
H), 1.17-1.68 (m, 18H), 1.87-1.97 (m, 1H), 2.17 (dd,
J = 8.2, 18.3Hz, 1H), 2.28 (t, J = 7.5Hz, 2H), 2.44 (dt,
J = 11.0, 7.5Hz, 1H), 2.62 (ddd, J = 18.3, 1.2, 6.9Hz,
1H), 3.66 (s, 3H), 3.99-4.14 (m, 2H), 5.50 (dd, J = 7.
7, 15.4Hz, 1H), 5.59 (dd, J = 15.4, 4.8Hz, 1H). ¹³ C-nmr (75MHz, CDCl ₃ ):-4.6, -4.5, -4.2, 14.1, 18.1,
18.3, 22.7, 25.0, 25.1, 25.8, 25.9, 26.7, 27.8, 2
9.0, 29.5, 31.9, 34.1, 38.6, 47.6, 51.4, 53.3, 53.
9, 72.7, 128.7, 136.2, 174.0, 216.0. [Α] _D ²¹ -41.4 ° (c = 2.60, CHCl ₃ ).

Compound (7) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.00 (4s, 12H), 0.02 (4s, 12)
H), 0.06 (4s, 12H), 0.09 (4s, 12H), 0.87 (2s, 18H),
0.88 (2s, 18H), 0.82-0.97 (m, 3H), 1.02-1.78 (m, 18H),
2.23 (d, J = 18.9Hz, 1H), 2.29 (t, J = 7.5Hz, 2H), 2.41
(dd, J = 18.9, 5.1Hz, 1H), 2.56-2.66 (m, 1H), 2.85-2.
95 (m, 1H), 3.66 (s, 3H), 3.97-4.05 (m, 1H), 4.21 (d,
J = 5.3Hz, 1H), 5.07 (dd, J = 10.4, 15.0Hz, 1H), 5.59 (d
d, J = 15.0, 6.3Hz, 1H).

Example 6

[0095]

[Chemical 38]

In the same manner as in Example 1, a 5: 1 mixture of compound (9) and compound (10) (yield 50%) was obtained from compound (1) and compound (8).

Compound (9) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.02 (3s, 12H), 0.05 (3s, 12)
H), 0.06 (3s, 12H), 0.87 (2s, 18H), 0.89 (2s, 18H),
0.81-0.96 (m, 3H), 1.15-1.68 (m, 18H), 1.84-1.92 (m,
1H), 2.17 (dd, J = 8.2, 18.4Hz, 1H), 2.32 (t, J = 7.4Hz,
2H), 2.44 (dt, J = 11.0, 7.7Hz, 1H), 2.62 (ddd, J = 18.
4, 1.1, 7.1Hz, 1H), 3.98-4.14 (m, 2H), 5.50 (dd, J =
7.2, 15.4Hz, 1H), 5.59 (dd, J = 15.4, 4.9Hz, 1H). ¹³ C-nmr (75MHz, CDCl ₃ ):-4.6, -4.5, -4.2, 14.1, 18.1,
18.3, 22.7, 24.7, 25.1, 25.8, 26.0, 26.7, 27.8, 2
8.9, 29.5, 31.9, 34.0, 38.6, 47.6, 53.4, 53.9, 72.
7, 73.2, 128.7, 136.2, 179.4, 216.1.

Example 7 In the same manner as in Example 4, a 10: 1 mixture of compound (9) and (10) (yield 32%) was obtained from compound (1) and compound (8).

Example 8

[0100]

[Chemical Formula 39]

In the same manner as in Example 1, compound (12) (yield 61%) and compound (13) (yield 12%) were obtained from compound (1) and compound (11).

Compound (12) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.01 (2s, 12H), 0.05 (2s, 12
H), 0.87 (2s, 18H), 0.89 (2s, 18H), 0.80-0.95 (m, 3
H), 1.14-1.80 (m, 14H), 1.87-1.99 (m, 1H), 2.17 (dd,
J = 8.2, 18.2Hz, 1H), 2.30 (t, J = 6.7Hz, 2H), 2.43 (dt,
J = 10.9, 7.6Hz, 1H), 2.63 (dd, J = 18.2, 6.8Hz, 1H),
3.74 (s, 3H), 3.98-4.13 (m, 2H), 5.50 (dd, J = 7.6, 15.4
Hz, 1H), 5.61 (dd, J = 15.4, 4.7Hz, 1H). ¹³ C-nmr (75MHz, CDCl ₃ ):-4.7, -4.6, -4.3, 14.0, 18.0,
18.2, 18.5, 22.6, 25.1, 25.8, 25.9, 26.2, 27.3, 2
7.8, 31.8, 38.5, 47.5, 52.5, 53.5, 53.6, 72.6, 72.
9, 73.2, 89.5, 128.6, 136.5, 154.2, 215.9. [Α] _D ²² −36.0 ° (c = 1.33, CHCl ₃ )

Compound (13) ¹ H-nmr (300MHz, CDCl ₃ , δ): 0.00 (4s, 12H), 0.03 (4s, 12)
H), 0.06 (4s, 12H), 0.09 (4s, 12H), 0.87 (2s, 18H),
0.89 (2s, 18H), 0.75-0.95 (m, 3H), 1.05-1.80 (m, 14H),
2.23 (d, J = 19.7Hz, 1H), 2.33 (t, J = 7.1Hz, 2H), 2.42
(dd, J = 19.7, 5.1Hz, 1H), 2.56-2.68 (m, 1H), 2.87-2.
96 (m, 1H), 3.75 (s, 3H), 3.98-4.07 (m, 1H), 4.21 (d,
J = 5.6Hz, 1H), 5.07 (dd, J = 9.8, 14.9Hz, 1H), 5.61 (d
d, J = 14.9, 7.1Hz, 1H).

Example 9 Compound (1) and compound (11) were prepared in the same manner as in Example 2.
From the above, a 15.8: 1 mixture (yield 70%) of the compounds (12) and (13) was obtained.

Example 10 In the same manner as in Example 3, the compound (1) and the compound (11) were used.
From this, a 10.8: 1 mixture of compounds (12) and (13) (yield 71%) was obtained.

Example 11

[0107]

[Chemical 40]

In the same manner as in Example 1, compound (15) (yield 65%) and compound (16) (yield 10%) were obtained from compound (1) and compound (14).

Compound (15) ¹ H-nmr (300MHz, CDCl ₃ , δ): 0.00 (2s, 12H), 0.04 (2s, 12
H), 0.86 (2s, 18H), 0.88 (2s, 18H), 0.82-0.95 (m, 3
H), 1.20-1.75 (m, 12H), 1.90-1.99 (m, 1H), 2.16 (dd,
J = 8.1, 18.2Hz, 1H), 2.44 (dt, J = 7.6, 11.0Hz, 1H),
2.55 (t, J = 6.6Hz, 2H), 2.61 (dd, J = 18.2, 7.1Hz, 1H),
3.38 (t, J = 6.0Hz, 2H), 3.65 (t, J = 6.6Hz, 2H), 3.67
(s, 3H), 4.00-4.12 (m, 2H), 5.49 (dd, J = 7.7, 15.5Hz,
1H), 5.59 (dd, J = 4.9, 15.5Hz, 1H). ¹³ C-nmr (75MHz, CDCl ₃ ):-4.7, -4.6, -4.3, 14.0, 18.0,
18.2, 22.6, 24.5, 25.0, 25.8, 25.9, 26.8, 31.8, 3
4.9, 38.5, 47.5, 51.6, 53.4, 53.5, 65.9, 71.0, 72.
6, 73.2, 128.6, 136.4, 172.0, 215.9.IR (neat): 770, 830, 1110, 1250, 1360, 1460, 1740, 2
^{_{850, 2940. [α] D 23}} -36.3 ° (c = 3.65, CHCl 3)

Compound (16) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.00 (4s, 12H), 0.02 (4s, 12)
H), 0.06 (4s, 12H), 0.08 (4s, 12H), 0.87 (s, 18H), 0.
80-0.97 (m, 3H), 1.03-1.80 (m, 12H), 2.21 (d, J = 19.2H
z, 1H), 2.41 (dd, J = 19.2, 5.2Hz, 1H), 2.57 (t, J = 6.6
Hz, 2H), 2.56-2.69 (m, 1H), 2.86-2.95 (m, 1H), 3.38
(t, J = 6.8Hz, 1H), 3.66 (t, J = 6.6Hz, 1H), 3.69 (s, 3
H), 3.97-4.05 (m, 1H), 4.20 (d, J = 5.6Hz, 1H), 5.07 (d
d, J = 10.3, 15.4Hz, 1H), 5.59 (dd, J = 15.4, 6.1Hz, 1
H).

Example 12 Compound (1) and compound (14) were prepared in the same manner as in Example 2.
Thus, a 14.2: 1 mixture (yield 70%) of the compounds (15) and (16) was obtained.

Example 13 Compound (1) and compound (14) were prepared in the same manner as in Example 3.
Thus, a 10.4: 1 mixture of compounds (15) and (16) (yield 65%) was obtained.

Example 14

[0114]

[Chemical 41]

Compound (18) (yield 33%) and compound (19) (yield 9%) were obtained from compound (1) and compound (17) in the same manner as in Example 1.

Compound (18) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.03 (2s, 12H), 0.05 (2s, 12)
H), 0.87 (2s, 18H), 0.90 (2s, 18H), 0.80-0.94 (m, 3
H), 1.20-1.80 (m, 10H), 2.04-2.12 (m, 1H), 2.19 (dd,
J = 8.2, 18.4Hz, 1H), 2.24-2.31 (m, 1H), 2.38-2.53 (m,
6H), 2.63 (ddd, J = 18.4, 1.1, 7.0Hz, 1H), 3.68 (s, 3
H), 4.01-4.14 (m, 2H), 5.51 (dd, 7.9, 15.4Hz, 1H),
5.63 (dd, J = 5.0, 15.4Hz, 1H). ¹³ C-nmr (75MHz, CDCl ₃ ):-4.7, -4.6, -4.3, 14.0, 14.7,
16.5, 18.0, 18.2, 22.6, 25.0, 25.8, 25.9, 27.5, 3
1.9, 33.8, 38.5, 47.4, 51.7, 52.3, 53.6, 72.6, 73.
2, 78.9, 80.2, 128.5, 136.6, 172.5, 215.7.IR (neat): 770, 830, 1090, 1240, 1360, 1460, 1735, 2
320, 2850, 2930. [α] _D ²³ −46.0 ° (c = 0.78, CHCl ₃ ).

Compound (19) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.00 (4s, 12H), 0.02 (4s, 12)
H), 0.06 (4s, 12H), 0.09 (4s, 12H), 0.87 (2s, 18H),
0.89 (2s, 18H), 0.80-0.98 (m, 3H), 1.05-1.60 (m, 8H),
2.25 (d, J = 17.3Hz, 1H), 2.35-2.55 (m 7H), 2.85-2.98
(m, 2H), 3.68 (s, 3H), 3.97-4.04 (m, 1H), 4.21 (d, J =
5.6Hz, 1H), 5.07 (dd, J = 8.4, 14.5Hz, 1H), 5.50 (dd, J
= 14.5, 6.6Hz, 1H).

Example 15 Compound (1) and compound (17) were prepared in the same manner as in Example 3.
From this, a 10.1: 1 mixture of compounds (18) and (19) (yield 39%) was obtained.

Example 16

[0120]

[Chemical 42]

In the same manner as in Example 1, compound (22) (yield 60%) and compound (23) (yield 12%) were obtained from compound (20) and compound (21).

Compound (22) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.02 (4s, 12H), 0.04 (4s, 12)
H), 0.05 (4s, 12H), 0.06 (4s, 12H), 0.87 (2s, 18H),
0.89 (2s, 18H), 0.75-0.97 (m, 6H), 1.00-1.80 (m, 15H),
1.87-2.00 (m, 1H), 2.08-2.24 (m, 3H), 2.44 (dt, J = 1
0.9, 7.1Hz, 1H), 2.62 (ddd, J = 1.1, 6.9, 18.2Hz, 1H),
3.98-4.09 (m, 1H), 4.13-4.22 (m, 1H), 4.62 (dt, J = 5.
6, 1.4Hz, 2H), 5.23 (ddt, J = 1.3, 10.4, 1.2Hz, 1H),
5.32 (ddt, J = 1.6, 17.2, 1.5Hz, 1H), 5.50 (dd, J = 6.5,
15.4Hz, 1H), 5.57 (dd, J = 15.4, 5.2Hz, 1H), 5.82 (dt,
J = 15.6, 1.5Hz, 1H), 5.93 (ddt, 10.4, 17.2, 5.6Hz,
1H), 6.96 (dt, J = 15.6, 6.9Hz, 1H). ¹³ C-nmr (75MHz, CDCl ₃ ):-4.6, -4.5, -4.1, 14.2, 18.1,
20.1, 23.1, 25.8, 26.0, 26.5, 27.7, 28.3, 29.2, 2
9.3, 32.1, 36.9, 46.3, 47.6, 53.3, 53.6, 64.9, 71.
1, 73.3, 117.9, 120.9, 128.8, 132.3, 136.2, 149.4,
166.1, 215.8. [Α] _D ²⁰ −34.2 ° (c = 3.50, CHCl ₃ ).

Compound (23) ¹ H-nmr (300MHz, CDCl ₃ , δ): 0.00 (4s, 12H), 0.02 (4s, 12)
H), 0.06 (4s, 12H), 0.08 (4s, 12H), 0.87 (2s, 18H),
0.89 (2s, 18H), 0.78-0.95 (m, 15H), 2.12-2.28 (m, 3H),
2.41 (dd, J = 4.7, 19.1Hz, 1H), 2.56-2.68 (m 1H), 2.8
6-2.94 (m, 1H), 4.00-4.14 (m, 1H), 4.21 (d, J = 5.1Hz,
1H), 4.63 (d, J = 5.6Hz, 2H), 5.07 (dd, J = 10.3, 15.4H
z, 1H), 5.24 (d, J = 10.3Hz, 1H), 5.32 (d, J = 16.4Hz, 1
H), 5.57 (dd, J = 15.4, 7.5Hz, 1H), 5.83 (d, J = 15.6Hz,
1H), 5.95 (ddt, J = 10.3, 16.4, 5.6Hz, 1H), 6.97 (dt,
J = 15.6, 5.6Hz, 1H).

Example 17 In the same manner as in Example 2, the compound (20) and the compound (2
From 1), a 14.7: 1 mixture (yield 65%) of the compounds (22) and (23) was obtained.

Example 18 In the same manner as in Example 3, the compound (20) and the compound (2
From 1), a 9.6: 1 mixture (yield 70%) of the compounds (22) and (23) was obtained.

Example 19

[0127]

[Chemical 43]

In the same manner as in Example 1, compound (25) (yield 64%) and compound (26) (yield 14%) were obtained from compound (24) and compound (5).

Compound (25) ¹ H-nmr (300 MHz, CDCl ₃ , δ): 0.04 (2s, 15H), 0.10 (2s, 15)
H), 0.87 (s, 9H), 0.92 (t, J = 7.1Hz, 3H), 1.16 (2s, 3
H), 1.17 (2s, 3H), 1.15-1.69 (m, 16H), 1.86-1.99 (m,
1H), 2.12-2.32 (m, 3H), 2.26 (t, J = 7.5Hz, 2H), 2.35-
2.47 (m, 1H), 2.55-2.67 (m, 1H), 3.66 (s, 3H), 3.95-
4.06 (m, 1H), 5.25-5.37 (m, 1H), 5.52-5.69 (m, 1H).

Claims (4)

[Claims] 1. A compound represented by the general formula [I]: [Wherein X is (α-OZ, β-H) or (α-H,
β-OZ), and Z represents a hydroxyl-protecting group. Also, Y
Represents (α-H, β-R) or (α-R, β-H),
R is In the group represented by, T is a group selected from CH ₂ CH ₂ or CH═CH, j and k are each independently an integer of 0, 1 or 2, and R ⁰ is (2-k) hydrogen atoms. , Carbon number 1-4
The alkyl group or the alkoxy group having 1 to 4 carbon atoms of R ¹
Is an alkyl group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, and 2 carbon atoms
Alkynyl group, phenyl group, phenoxy group,
"Halogen atom, trifluoromethyl group, carbon number 1-6
Alkyl group, C1-C6 alkoxy group "substituted phenyl group or phenoxy group, or -B-
D (B is an alkylene group having 1 to 4 carbon atoms, D is a phenyl group, a phenoxy group, "a halogen atom, a trifluoromethyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, phenyl Group or phenoxy group "substituted with a phenyl group or a phenoxy group or a carbon number of 5 to 7
Represents a cycloalkyl group. ) Represents a group represented by
Z'represents a protective group for a hydroxyl group which is the same as or different from Z described above. ] And substituted cyclopentanone derivative represented by the general formula [II] _{^{A (CR 2 R 3) l}} X 1 m (CR 4 R 5) n U p (CR 6 R 7) q X 2 r (CR 8 R ⁹ ) _s Z ¹ [II] [wherein A is a halogen atom or (R ^X represents a hydrogen atom, an alkyl group having 1 to 9 carbon atoms, an aralkyl group or an aryl group), and R ² , R ³ and R
⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ are each independently a hydrogen atom,
R ⁹ represents an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, R ⁹ represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a halogen atom, C
N, NH ₂ , OH or —COOR ^a (R ^a represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkenyl group having 2 to 6 carbon atoms), U is CH ₂ CH ₂ , CH═CH, C≡
C, C = C = C or a group selected from phenylene groups, l is an integer of 1 to 7, m, p and r are each an integer of 0 or 1, n, q and s are each an integer of 0 to 5 Indicates. X ¹ and X ² each represent an oxygen atom or a sulfur atom, and Z ¹ represents CO ₂ R ^y , CN, OH, OCOR ^z , CONR.
^b R ^c (R ^b and R ^c each represent a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a benzyl group or a phenyl group), a hydrogen atom, a halogen atom,
Or a group selected from a substituted or unsubstituted aromatic group, R ^y and R ^z each represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an alkenyl group having 2 to 6 carbon atoms. ] An organic radical precursor represented by the formula] is reacted in the presence of a radical generator and optionally hydrolyzed. [Wherein W is (α-OQ, β-H) or (α-H,
β-OQ), and Q represents a hydrogen atom or the same hydroxyl-protecting group as Z. V is (α-H, β-R) or (α-
R, β-H), where R is In the group represented by, T, R ⁰ , j and k have the same meanings as described above, and Q ′ represents a hydrogen atom or the same hydroxyl group-protecting group as Z ′. Also, X ¹ , X ² , U, R ² , R ³ , R ⁴ , R ⁵ ,
R ⁶ , R ⁷ , R ⁸ , R ⁹ , Z ¹ , l, m, n, p, q, r and s have the same meanings as described above. ], Α-β-
A method for producing a substituted cyclopentanone derivative. 2. The method according to claim 1, wherein the radical generator is a peroxide, an azo compound or an alkylborane compound. 3. The method according to claim 2, wherein the reaction is further carried out by using a tin hydride compound together with the radical generator. 4. The method according to claim 1, wherein the radical generator is zinc treated with a copper salt or an ammonium salt by ultrasonic waves.