DE2455444A1 - PROCESS FOR THE PRODUCTION OF CYCLOHEXANONE DERIVATIVES OR CYCLOPENTANONE DERIVATIVES - Google Patents

Description

Dr. F. Zumsiein sen. · Or. Ξ. Aeomsunn Dr. R. Koenigsberger - Dipl.-Fhys. R. Holzbauer - Dr. F. Zumstein jun.

PATENT LAWYERS

TELEPHONE: COLLECTIVE NO. 225341 8 MUNICH 2,

TELEX 529979. BRÄUHAUSSTRASSE 4 / III

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CHECK ACCOUNT: MUNICH 91139

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BANK H. HOUSES

53 / My

Case F2159-K403 (Teijin) / H0

TEIJINLIMITED
Osaka / Japan

Process for the preparation of cyclohexanone derivatives or cyclopentanone derivatives

The invention relates to a method for producing Cyclohexanone derivatives or cyclopentanone derivatives. The invention particularly relates to a method for producing 2,3-disubstituted cyclopentanone derivatives or 2,3-disubstituted cyclohexanone derivatives from substituted or unsubstituted cyclopent ~ 2-en-1-one or unsubstituted or substituted Cyclohex-2-en-i-one.

The 2,3-disubstituted cyclohexanone derivatives or cyclopentantone derivatives, which are produced by the process according to the invention are valuable pharmaceuticals, agricultural chemicals, Perfumes or intermediates therefor such as for steroids, terpenoids, prostaglandins, Jasomon or pyrethroids. In which Process according to the invention, these valuable compounds can be obtained in relatively high yields.

The 2,3-disubstituted cyclohexanone derivatives and 2,3-disubstituted cyclopentanone derivatives, which are produced by the process of the invention can be represented by the following formulas (4-A) and (4-B).

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2,3-disubstituted cyclohexanone derivatives

(4 - A)

2,3-disubstituted cyclopentanone derivatives

(4-B)

In the formulas (4-A) and (4-B) are

R, j, R ₂ , Rz, R ^, Rk, Rg> Ry and R _{Q are} identical or different and each represent a hydrogen atom or a monovalent organic group, where two can be linked together and can form a ring, and

R. and Rg are the same or different and mean one monovalent organic group each.

In the process according to the invention, the cyclohexanone derivatives of the formula (4-A) or the cyclopentanone derivatives of the formula (4-B) are prepared by a process which thereby is marked that one

(A) a cyclohexe.none derivative of the formula in one stage (! -Α) or a cyclopentenone derivative of the formula (1-B)

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(l-A)

R,

(l-B)

wherein R ₁ , R ₂ , R ^ ,. R ^, Rc, Rg, Ry and R _{Q can be the} same or different and each represent a hydrocarbon group or a monovalent organic group and two of these groups can be linked to one another and form a ring,
with an organic copper-lithium compound of the formula (2)

Pii / RV TiV tO \

Rg means a monovalent organic group and wherein the two Rg groups can be the same or different,

Y is a monovalent anion and η is 1 or 2,

or with one. Complex of the organic copper-lithium compound with an organic phosphorus compound in the presence of an aprotic, inert organic medium, and

(b) in a second stage, the product obtained in the first stage with an organic halogen compound of formula (3)

^R A ^X

(3)

ft is a monovalent organic group and S 0 9 8 2 2/1 0 0 Ö

^ 4b5 444

X represent a halogen atom,

in the presence of a nitrogen or sulfur containing polar organic solvent.

According to the above process, in the reaction of the cyclohe3 © .none derivative of the formula (1-A) or the cyclopenteaone derivative of the formula (1-B) with the organic copper-lithium compound of the formula (2), an organic group (R ") is converted into the β-position of the cyclohexejaone derivative of the formula (1-A) or the cyclopentejione derivative of the formula (1-B) is introduced and then the resulting reaction product is reacted with the organic halogen compound (3) in a nitrogen-containing or sulfur-containing aprotic polar organic solvent. The organic group (R.) can be introduced into the α-position of the carbonyl group of the starting materials. The invention thus provides a process for the preparation of 2,3-disubstituted-cyclohexanone derivatives (4-A) or 2,3-disubstituted-cyclopentanone derivatives (4-B) by subsequent introduction of organic groups (R _ß and R.) in the ß-position and α-position of the cyclohexenone derivatives (1-A) and the cyclopentenone derivatives (1-B)

The method according to the invention is explained in more detail below.

(I) First stage

1-1. Cyclohexenone derivatives (1-A):

The cyclohexenone derivative used as the starting material in the first stage of the process of the present invention is a compound represented by the above general formula (1-A). In the formula (1-A), R ₁ to R _{8 represent} a hydrogen atom or a monovalent organic group such as an alkyl, cycloalkyl, alkenyl, alkynyl or aryl group. These groups can be bonded to one another and form a ring. It is easy to see that these organic groups are not reactive with the organic copper-lithium compounds. Preferred monovalent hydrocarbon

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groups are those that contain 1 to 20 carbon atoms, and the ring formed with these groups is preferably 3- to 7-membered.

Typical examples of these compounds are:

(A-1) Cyclohex-2-en-i-one

(A-2) 2-methylcyclohex-2-en-1-one

(A-3) 3-methylcyclohex-2-en-1-one

(A-4) isophorone

(A-5) carvone. ■.

(A-6) 2,3-Dimethylcyclohex-2-en-1-one

(A-7) 2-keto-1-methyl-A ³ -octaline

(A-8) 1-keto-A ² -oetaline

(A-9) 4-ester-3,17-dione
(A-10) 1 (5a) -androstene-3,17-dione
(A-11) 5-Pregnen-3B-ol-7, .20-dione-acetate 1-2. Cyclopentenone derivatives (1-B)

The cyclopentenone derivative of the general formula (1-B) can also as a starting material in the present invention be used. In the formula (1-B), R, j to Rg represent Hydrogen atom or a monovalent organic group such as an alkyl, cycloalkyl, alkenyl, alkynyl or aryl group. These groups can be linked to one another to form a ring be. It can easily be seen that these groups compared to the organic copper-lithium compounds which are described are not reactive. Preferred monovalent organic groups are those which contain 1 to 20 carbon atoms, and the ring formed with these groups is preferably 3- to 7-membered.

Typical examples of these compounds are:

(B-1) Cyclopent-2-en-1-one

(B-2) 3 »4-dimethylcyclopent-2-en-1-one (B-3) 3» 4,4-trimethylcyclopent-2-en-1-one- (B-4) 2-methylcyclopent-2-en-1-one

(B-5) 3-methylcyclopent-2-en-1-one

(B-6) 4-Methyleyclopent-2-en-1-one

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(B-7) 3-Isopropylcyclopent-2-en-1-one (B-8) 2,3,4-trimethylcyclopent-2-en-1-one (B-9) ^ Isopropyl ^^ - dimethylcyclopent ^ -en-i-one (B-r10) 3-Ethyl-2-methylcyclopent-2-en-1-one (B-11) 2,3-Dimethylcyclopent-2-en-1-one 3-methyl-2-amylcyclopent-2-en-1-one

■ i (8) -hydroinden-2-one
(B-14) 8 (9) Hydroinden-1-one

2-hydroinden-1-one

1-3 · Organic copper-lithium compounds (2) According to the process according to the invention, the above cyclohexenone derivatives (1-A) or the above cyclopentenone derivatives (1-B) with the organic copper-lithium compounds of the formula Cu (Ro) LiY ₀ " (2 ) implemented, in which, if the

β η * _— η

Symbols have the meanings given above and η 2 means, the above formula is Cu (R _B ) ₂ * Li (2 ¹ ). This reaction is carried out in the presence of an aprotic inert organic medium. It is believed that as a result of this, the following reactions take place and compounds of formula (L) or (M) are formed:

CuLiR

(L)

CuLiR

• Β

(M)

Examples of R _ß in the general formula (2), by which the organic copper-lithium compound is represented, are alkyl, alkenyl, alkynyl, aralkyl, aralkenyl, aralkynyl, alkoxyalkyl, alkoxyalkenyl and / or alkoxyalkynyl groups .

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Preferred R _ß groups are those which contain 1 to 20 carbon atoms. Examples of Y are chlorine, bromine, iodine and cyano groups.

The organic copper-lithium compound can be easily produced by mixing a corresponding organic lithium compound with a copper (I) salt in an inert medium in a nitrogen atmosphere.

Examples of suitable organic lithium compounds are listed below:

Alkyl-lithium compounds (2-1) methyl-lithium (2-2) ethyl-lithium (2-3) n-propyl-lithium (2-4) i-propyllithium (2-5) n-butyl-lithium (2- 6) t-butyl-lithium (2-7) n-pentyl-lithium

(2-8) n-Hexyl-lithium ~

(2-9) cyclohexyl-lithium (2-10) n-heptyl-lithium (2-11) n-Octyl-lithium (2-12) n-Nonyl "lithium

Alkenyl lithium compounds

(2-13) vinyl-lithium (2-14) 1-prop-cis-i-enyl-lithium (2-15) 1-prop-trans-i-enyl-lithium (2-16) 1-0ct-cis-5-enyl-lithium (2-17) 1-oct-trans-i-enyl-lithium (2-18) 1-oct-cis-i-enyl-lithium (2-19) i-Oct-trans-i-cis-5-dienyl-lithium

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Alkynyl lithium compounds

(2-20) 1-oct-1-ynyl-lithium (2-21) 1-but-i-ynyl-lithium ' (2-22) 1-pent-i-ynyl-lithium (2-23) 1-hex-1-ynyl-lithium (2-24) 1-hept-i-ynyl-lithium (2-25) 1-oct-i-ynyl-lithium.

Aralkyl-lithium compounds (2-26) 1- (8-ehenyl) -octyl-lithium

Aralkenyl lithium compounds

(2-27) 1- (2-phenyl) -vinyl-lithium (2-28) 1- (8-phenyl) -oct-trans-1-enyl-lithium (2-29) 1- (8-phenyl) oct-cis-1-enyl-lithium

Aralkynyl lithium compounds

(2-30) 1- (8-phenyl) -oct-5-ynyl-lithium

Alkoxyaralkyl-lithium compounds

(2-31) 1- (3-tetrahydropyranyloxy) octyl lithium (2-32) 1-bis (3,7-tetrahydropyranyloxy) octyl lithium

Alkoxyalkenyl lithium compounds

(2i-33) 1- (3-Tetrahydropyranyloxy) -oct-trans-1-enyl-lithium (2-34) 1-bis (3,7-tetrahydropyranyloxy) -oct-trans-1-enyl-lithium (2-35) 1- (3-tetrahydropyranyloxy) -oct-trans-i-cis-5-dienyl-

lithium

Alkoxyalkynyl lithium compounds

(2-36) 1- [3- (oc-Ethoxy) ethoxy] -oct-5-ynyl-lithium

Siloxyalkenyl-lithiumΛ compounds

(2-37) 1- (3-t-Butyldimethylsiloxy) -oct-trans-1-enyl-lithium

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The copper (I) salts with the organic lithium compounds can be reacted with the formation of organic copper-lithium compounds (2), for example: Copper (I) chloride, copper (I) bromide, copper (I) iodide and Copper (I) cyanide.

A specific example of the production of the organic copper-lithium compound from the organic lithium compound and the copper (I) salt consists in the fact that the organic Lithium compound with the copper (I) salt at room temperature down to -78 ° C for several hours, for example at -78 ° C for 0.5 hours using an inert medium such as a hydrocarbon (e.g. pentane, hexane or heptane) or an ether (e.g. diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane).

The compound of formula (2) can be used as a complex with a trivalent phosphorus compound such as trialky! Phosphines (e.g. Triethy! Phosphine or tri-n-buty! Phosphine), trialkyl phosphites (e.g. trimethyl phosphite, triisopropyl phosphite or tri-n-butyl phosphite), Triphenylphosphine or hexamethylphosphoric triamide be used. Often the use of the complex results in an increased yield of the end product,

According to the process of the invention, the cyclohexenone derivative of the formula (1-A) or the cyclopentenone derivative is the Formula (1-B) with the above organic copper-lithium compound first implemented in the presence of an aprotic organic medium.

The cyelohexenone derivative or the cyclopentenone derivative and the organic copper-lithium compounds are converted stoichiometrically in equimolar proportions. Generally this will Cyelohexenone derivative or the cyclopentenone derivative in a proportion of 0.5 to 2 mol, preferably 0.8 to 1.2 mol, per mol organic copper-lithium compound is used.

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The reaction temperature is -78 ° to about 50 ⁰ C. However, it is sufficient that the reaction is carried out at room temperature for 10 minutes to 2 hours. The reaction proceeds satisfactorily even when the temperature is lower than the above range, for example when it is -100 ⁰ C.

The reaction is carried out in the presence of an organic medium which is an aprotic organic medium and which is liquid at the reaction temperature and does not react with the reaction reagents. Such aprotic inert organic media include a variety of aprotic inert liquid media including nitrogen-containing or sulfur-containing aprotic polar organic solvents. Examples of these organic media are saturated hydrocarbons such as pentane, hexane, heptane or cyclohexane, aromatic hydrocarbons such as benzene, toluene or xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane or diethylene glycol dimethyl ether, hexamethylphosphoric acid triamide, Ν, Ν,, N, N-dimethylacetamide _; , Dimethyl sulfoxide, suIfolane and N-methy! Pyrrolidone. Inert solvents such as pentane, which are used to produce the organic copper-lithium compounds, can be used directly as aprotic organic solvents. In this case, the starting material, that is, the cyelohexenone derivative (1-A) or the cyclopentenone derivative (1-3B), is added to the reaction system in which the organic copper lithium compound was formed to carry out the reaction.

(II) Second stage

II-1. Reaction agent in the second stage

According to the process according to the invention, the ■ reaction product, obtained by reaction in the first stage with an organic halogen compound of the formula

R _A X (3)

implemented in which

R. is a monovalent organic group and X is a halogen atom,

being in the presence of a nitrogen-containing or sulfur-containing aprotic organic solvent works, the desired 2,3-disubstituted cyclohexanone derivative of the formula "(4-A) - or the 2,3-disubstituted cyclopentanone derivative of the formula (4-B) is formed.

Suitable R. groups are those which have 1 to 20 carbon atoms and chlorine, bromine and iodine are suitable as group X.

Examples of suitable organic halogen compounds are listed below.

3-1. Alkyl halides

Methyl iodide, ethyl iodide, n-propyl iodide, n-butyl iodide, n-amyl iodide, n-hexyl iodide, n-heptyl iodide, n-octyl iodide, n-nonyl iodide, n-decyl iodide, isopropyl iodide, isobutyl iodide, methyl bromide, Ethyl bromide, n-propyl bromide, n-butyl bromide, n-amyl ~ bromide, n-hexyl bromide, n-heptyl bromide, n-octyl bromide, n-nonyl bromide, n-decyl bromide, isopropyl bromide, isobutyl bromide, methyl chloride, Ethyl chloride, n-propyl chloride, n-butyl chloride, n-amyl chloride, n-hexyl chloride, n-heptyl chloride, n-octyl chloride, n-nonyl chloride, n-decyl chloride, isopropyl chloride and isobutyl chloride.

3-2. Cycloalkyl halides

Cyclopentyl iodide, cyclohexyl iodide, cyclopentyl bromide, cyclohexyl bromide, Cyclopentyl chloride and cyclohexyl chloride.

3-3 alkenyl halides

Allyl iodide, 2-butenyl iodide, 3-butenyl iodide, cis-2-pentenyl

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iodide, trans-2-pentenyl iodide, 4-pentenyl iodide, cis-2-hexenyl iodide, trans-2-hexenyl iodide, cis-2-heptenyl iodide, trans-2-heptenyl iodide and the bromides or chlorides corresponding to these iodides.

3 -> - 4. Alkynyl halides

Propargyl iodide, 2-butynyl iodide, 2-pentynyl iodide, 3-pentynyl iodide, 2-hexynyl iodide, 2-heptynyl iodide and these iodides corresponding bromides or chlorides.

3-5- haloalkeny ! Halides

1,3-dichloropropene, 1,3-dichloro-2-butene, 1,3-dichloro-2-pentene, and the iodides or bromides corresponding to these chlorides.

3-6. Alkoxyalkyl halides

Chloromethyl methyl ether, chloromethyl ethyl ether, chloromethyl benzyl ether, Chloräthyi-phenyläther and the iodides or bromides corresponding to these chlorides.

3-7 aralkyl halides

Benzyl chloride, ß-phenetyl chloride, 3-phenylpropyl chloride and the iodides or bromides corresponding to these chlorides.

3-8. Aralkeny! Halides
3-bromo-1-phenyl-1-propene.

3-9 Aralkiny! Halides
3-bromo-1-phenyl-1-propyne.

3-10. Halogen ester

Methyl bromoacetate, ethyl bromoacetate, methyl 3-bromopropionate, Ethyl 2-bromopropionate, methyl 7-bromoheptanate, methyl 7-bromo-2-heptenate and the chlorides or iodides corresponding to these bromides.

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3-11. Haloketones

Bromoacetone, α-bromoacetophenone and the corresponding bromides Iodides or chlorides.

3-12. Halonitriles

Chloroacetonitrile, ß-chloropropionitrile, 6-chlorohexanonitrile, 6-chloro-4-hexenonitrile and the corresponding chlorides Iodides or bromides.

3-13 halogen amides

Chloroacetyl-N, N-diethylamine.

3-14. Halogen acetals

Chloroacetaldehyde dimethylacetal, chloroacetaldehyde diethyl acetal, Chloracetaldehyde-ethylene acetal and the corresponding chlorides Iodides or bromides.

II-2. Second step

It is essential that the implementation of the second stage occur the method according to the invention in the presence of a nitrogen containing 'or sulfur-containing aprotic organic polar solvent is carried out. This leads to a large increase in the yield of the reaction in the second Step.

These nitrogen-containing or sulfur-containing aprotic polar organic solvents can be any inert polar organic solvents that are capable are to dissolve the reaction product formed in the first step and the organic halogen compound of the formula (3). The reactivity of the anion can be increased by carrying out the reaction of the second stage in the presence of such a ^ Solvent carries out, and as a result, the yield decreases in the implementation in the second stage too.

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Suitable nitrogen-containing or sulfur-containing polar organic solvents are those containing 1 to 3 nitrogen or contain sulfur atoms in the molecule and the The reaction system of the second stage are inert.

Examples of preferred nitrogen-containing or sulfur-containing polar organic solvents are hexamethylphosphoric acid triamide, Ν, Ν-dimethylformamide, Ν, Ν-dimethylacetamide, dimethylsulfoxide, formaldehyde-dimethylmercaptal-S-oxide, suIfolane, N-methylpyrrolidone, tetramethylamido-nitrile urea, and dimethyl acetonitrile. Furthermore, more basic aprotic polar organic solvents can also be used with preference, for example tetramethylethylenediamine, tetraethylethylenediamine, triethylenediamine, triethylamine, pyridine, oc, a ^f -dipyridyl, 1,5-diaza-bicyclo [4,3,0] -5 -nonen and 1,5-diaza-bicyclo [5.4.0] -5-undecene.

The inventive reaction of the second stage can be carried out by the reaction product obtained in the first stage with an organic halogen compound of the formula (3) in the presence of the nitrogen-containing or sulfur-containing polar organic solvent at the same temperature as the first stage, for example at a temperature in the range from -100 ° to 50 ⁰ C, mixed well.

To carry out the second stage reaction in the nitrogen containing or sulfur-containing organic solvents, for example, it is practical to carry out the reaction the first stage in such a nitrogen containing or Perform sulfur-containing organic solvent, and the resulting reaction mixture with the organic halogen compound (3) or to mix their solution in an aprotic inert organic solvent. Another method consists in carrying out the first stage reaction in an aprotic inert organic solvent, with the exception of the Nitrogen-containing or sulfur-containing organic

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Solvent, perform the nitrogen-containing or sulfur-containing polar organic solvent to add the resulting reaction mixture and then the mixture with the organic halogen compound (3) or with their Mix the solution in an aprotic inert organic solvent. In short, there is a requirement that the reaction of the second stage in the presence of nitrogen containing or sulfur-containing polar organic Solvent takes place, and if you work in the manner indicated, the yield of end product in the second stage further. be increased.

According to the present invention, the desired cyclopentanone derivative (4-B) can be produced in higher yield by using the reaction product derived from the cyclopentenone derivative (1-B) in the first stage originates to the organic halogen compound of the formula (3) or its solution in an aprotic inert organic Medium in a non-oxidizing atmosphere in the presence of the nitrogen-containing or sulfur-containing aprotic organic solvent is added to the Reaction product with the organic halogen compound. To implement. At this point, it is desirable to make the reaction product of the first stage to the organic one as slowly as possible Add halogen compound (3) or its solution.

A preferred embodiment of the reaction of the second stage in the present invention is that the reaction product of. first stage with about 0.8 to about 5 mol based on the starting material, ie the cyclohexenone derivative or the cyclopentenone derivative, the organic halogen compound (3) or its solution in the presence of about 0.8 to about 10 mol based on the starting material used cyclohexenone or cyclopentenone derivative, the nitrogen-containing or sulfur-containing aprotic polar organic compound is mixed and the mixture usually at a temperature of not more than 50 ⁰ C, preferably 10 to 30 ⁰ C, for a time of about

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30 minutes to about 20 hours. After the reaction, the cyclohexanone derivative (4-A) or the cyclopentanone derivative becomes (4-B) separated and purified, for example, by the following methods.

For example, the reaction product is treated with a basic, strongly electrolytic, aqueous solution, for example an ammoniacal, aqueous, saturated solution of ammonium chloride for about 0.1 to 1 hour hydrolyze the product, and then it is extracted by treatment with an ether such as diethyl ether, a saturated one Hydrocarbon such as pentane or hexane, an aromatic hydrocarbon such as benzene or toluene or a halogenated hydrocarbons such as methylene chloride or chloroform. When the nitrogen containing or sulfur containing aprotic polar organic solvent used in the second stage reaction, a strong one basic compound such as tetramethylethylenediamine, it is preferred to use an acidic aqueous solution such as one dilute aqueous solution of hydrochloric acid instead the above basic, strongly electrolytic, aqueous solution.

The organic phase extracted in this way is then washed well with water or a strongly electrolytic, aqueous solution, Sufficiently dried with anhydrous sodium sulfate and concentrated to obtain a crude product. The cyclohexanone derivative (4-A) or the cyclopentanone derivative (4-B) with high purity can be obtained by processing the crude product purifies by distillation or column chromatography.

As has been described in detail above, the inventive Process for the preparation of the cyclohexanone derivatives (4-A) and the cyclopentanone derivatives (4-B), the valuable Compounds as pharmaceuticals, agricultural chemicals, perfumes and their intermediates are what are called these compounds obtained in high yields and with technical advantage. In particular, the implementations of the first stage and

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the second stage carried out in the same solvent and the technical importance of the process according to the invention is great.

The following examples illustrate the invention without restricting it.

Part A - Synthesis of Cyclohexanone Derivatives

Example A-1

350 mg (50 mmol) of metallic lithium are added to 50 ml of anhydrous diethyl ether and 3.6 g (25 mmol) of methyl iodide are added dropwise at ⁰ ° C. in a nitrogen atmosphere. The mixture is then stirred for 1 to 2 hours, and an ether solution of methyl-lithium is obtained.

The solution is cooled to -78 ° C and a solution of 3.9 g (10 mmol) of a complex of tri-n-butylphosphine with Copper (l) iodide in 20 ml of ether is added dropwise to the solution given. The mixture is stirred for TO minutes, forming a complex of tri-n-butylphosphine with dimethyl-copper-lithium is obtained

960 mg (10 mmol) of cyclohex-2-en-i-one are used with the complex Reacted at room temperature for 1 hour and 5 ml of hexamethylphosphoric acid triamide (abbreviated to HMPA) are added to the reaction mixture and the mixture is stirred for 10 minutes. The reaction mixture turns from yellowish green to black. 3.4 g (20 mmol) of allyl iodide are added to the reaction mixture, so the reaction mixture immediately turns gray.

Stirring is continued overnight (about 15 hours) and after the reaction, about 50 ml of an ammoniacal, saturated, aqueous solution of ammonium chloride is added to the reaction mixture for work-up and this is then extracted with ether. The resulting ether phase is washed with water and dried with anhydrous sodium sulfate,

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3.690 g of a concentrated crude product being obtained. The product is distilled and separated under reduced pressure.

165 mg (1.5 mmol) of 3-methylcyclohexanone (boiling point 102 to 104 ° C./1O4 mmHg) are obtained. The yield is 15% based on the cyclohex-2-en-1-one used as starting material (the yield is calculated in the following on the same basis. The gas chromatographic results (SE30, 10%) of this product correspond to those of an authentic sample of 3-methyl-cyclohexanone.

A further 918 mg (6.0 mmol) of 2-allyl-3-methylcyclohexanone are obtained (Bp. 111 ° C / 122 mmHg) in a yield of 60%.

Infrared absorption (liquid film)
Characteristic absorptions:

3080, 1710, 1645 and 910 cm " ¹

Nuclear magnetic resonance spectrum
(Carbon tetrachloride, <f (ppm)):

1.0 -CH ₃ 3H

1.2-2.5 -CH ₂ - 1 OH

4.8, 5.1, 5.6 -CH = CH ₂ 3 H

Mass spectrum (m / e):

152 (M ⁺ )

Example A-2

A solution of 3.9 g (10 mmol) of a tri-n-butylphosphine complex of copper (l) iodide is added at -78 ° C to an ethereal solution of methyl-lithium, prepared in the same way as in Example A-1 and the mixture is allowed to stand for 15 minutes. Then a solution of 960 mg (10 mmol) of cyclohex-2-en-1-one in 50 ml of ether is added dropwise. The color the reaction mixture changes from white to yellow. The mixture is stirred at room temperature and then over power 3.4 g (20 mmol) of allyl iodide are added, the reaction mixture immediately turns gray. The mixture is stirred for a further day and treated in the same way as in Example A-1,

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to separate and clean the product. 93 mg (0.8 mmol) of 3-methylcyclohexanone are obtained in a yield of B%. 640 mg (4.2 mmol) of 2-allyl-3-methylcyclohexanone are likewise obtained in a yield of 42%.

Example A-3

A solution of 1.9 g (10 mmol) of copper (I) -oodid in 5 ml of HMPA at -78 ⁰ C to a Ä'therlösung of methyl-lithium, prepared as described in Example AI in the same manner, was added and the The mixture is stirred for 10 minutes. Then 960 mg (10 mmol) of cyclohex-2-en-i-one are added and the mixture is stirred for 1 hour at room temperature. The reaction product is worked up, separated and purified by customary methods.

1.520 g of crude product are obtained. Analysis of the product shows that 207 mg (1.8 mmol) of 3-methylcyclohexanone are obtained in a yield of 18% and 739 mg (4.9 mmol) of 2-allyl-3-methylcyclohexaneQn are obtained in a yield of 49%.

Example A-4

960 mg (10 mmol) of cyclohex-2-en-1-one are added to 10 mmol of a tri-n-butylphosphine complex of dimethyl copper-lithium, prepared in the same manner as described in Example A-1, and the mixture is added for 1 hour Room temperature around. Then 5 ml of tetramethylethylenediamine are added and the mixture is stirred for 10 minutes. The color of the reaction mixture changes from yellowish green to whitish green. Then, 3 _f, 4 g (20 mmol) of allyl iodide was added and the reaction mixture is gray. The mixture is stirred further overnight. The product is treated in the same manner as in Example A-1 and the ether extract obtained is washed with sufficiently dilute hydrochloric acid, dried and concentrated. 3 # 016 g of crude product are obtained. The crude product is purified, 194 mg (1.7 mmol) of 3-methylcyclohexanone being obtained in a yield of 17% and 579 mg (3.8 mmol) of 2-allyl-3-methylcyclohexanone in a yield of 38%. .

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Example A-5

To 10 mmol of a tri-n-butylphosphine complex of dimethyl copper-lithium, prepared in the same way as described in Example A-1, 10 mmol (960 mg) of cyclohex-2-en-i-one are added and reacts for 1 hour at room temperature. Then 5 ml of dimethylformamide are added, immediately a precipitate forms. After stirring the mixture well, 3.4 g (20 mmoles) of allyl iodide are added and then the reaction mixture becomes left to stand overnight. The product obtained is worked up and purified according to customary methods. 3.659 g of crude product are obtained. Analysis of the product shows that 106 mg (1.0 mmol) of 3-methylcyclohexanone in one yield of 10% and 448 mg (3 »0 mmol) of 2-allyl-3-methylcyclohexanone were obtained in a yield of 30%.

Example A-6

A Triäthylphosphitkomplex of copper (I) iodide, prepared by stirring 1.9 g (10 mmol) of copper (I) iodide and 1.82 g (10 mmol) of triethyl phosphite at room temperature for 30 minutes, at -78 ⁰ C. to an ethereal solution of methyl-lithium, prepared in the same way as described in Example A-1, added. The mixture is stirred for 30 minutes, a yellowish brown triethyl phosphite complex of dimethyl copper-lithium being formed. 960 mg (10 mmol) of cyclohex-2-en-1-one are added to the mixture and the mixture is stirred at room temperature for 1 hour. The reaction mixture turns yellowish gray. Then 5 ml of HMPA are added and the mixture is stirred for a further 10 minutes and then 3.4 g (20 mmol) of allyl iodide are added, the reaction mixture becoming cream colored. The reaction mixture is stirred further overnight. The reaction mixture is treated in the same way as described in Example A-1 to separate and purify the product. 3.210 g of crude product are obtained and the analysis thereof shows that 52 mg (0.5 mmol) of 3-methylcyclohexanone in a yield of 5% and 843 mg (5.5 mmol) of 2-allyl-3-methylcyclohexanone in a yield of 55% % were obtained.

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Comparative example

10 mmol (96O mg) of cyclohex-2-en-i-one are added to 10 mmol of a tri-n-butylphosphine complex of dimethyl copper-lithium, prepared as described in Example A-1. The reaction is carried out for 1 hour at room temperature. The ether is then evaporated under reduced pressure. 50 ml of dimethoxyethane and 3 »4 g (20 mmol) of allyl iodide are then added and the mixture is stirred overnight at room temperature. The mixture is then worked up and the product is separated off and purified. 1.3.47 g of crude product are obtained. The analysis shows that 260 mg (2.3 mmol) of 3-methylcyclohexanone were obtained in a yield of 2.3% and 244 mg (1.6 mmol) of 2-allyl-3-methylcyclohexanone were obtained in a yield of 16%.

Example A-7

In the same way as in Example A-1, 20 mmol of a tri-n-butylphosphine complex of dimethyl-kiipfer-lithium are reacted with 20 mmol (1.92 g) of cyclohex-2-en-1-one for 1 hour at room temperature. Then 5 ml of HMPA are added and the mixture is stirred for a further 10 minutes. 5.0 g (40 mmol) of 1,3-dichloro-2-butene are added to the reaction mixture and the mixture is stirred overnight at room temperature, then the same treatment is carried out as in Example A-1 in order to separate the product and to clean. 11.70 g of crude product are obtained. The analysis shows that 321 mg (2.9 mmol) of 3-methylcyclohexanone in a yield of 14% and 1.35 g (6.7 mmol) of 2- (3'-chloro-2'-butenyl) -3-methylcyclohexanone were obtained in a yield of 33%. The analytical values of this product are as follows:
Boiling point: 150 ° C / 12O mmHg

Infrared absorption (liquid film) _ ₁ Characteristic absorption: 1710 and 1660 cm. Nuclear magnetic resonance spectrum
[Carbon tetrachloride, S (ppm)]:

1.13 -CH ₃ in the 3-position 3H 1.70 -CH, in the side chain 3H

■ * in the 2 position ■

1,3-2,4 -CH2-1OH

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245SU4

5.54 olefinic protons 1H triplet mass spectrum (m / e): 202 (M)

Example A-8

3.9 g (10 mmol) of a tri-n-butylphosphine complex of Copper (I) iodide is dissolved in 50 ml of anhydrous diethyl ether and 12.8 ml (20 mol) of a 15% strength by weight hexane solution of n-butyl-lithium are added to the solution at -78 ° C. The mixture is stirred for 30 minutes, the mixture turning reddish brown. Then 960 mg (10 mmol) of cyclohex-2-en-1-one is added to the reaction mixture and it turns blackish brown. The reaction mixture is left for an additional hour at room temperature stirred and then 5 ml of HMPA are added, whereby a black precipitate forms. After stirring 2.8 g (20 mmol) of methyl iodide are added to the mixture over a further 10 minutes. The mixture is then for an additional 3 hours stirred at room temperature. The reaction mixture is treated in the same manner as described in Example A-1, wherein 3 »656 g of crude product are obtained.

The crude product is distilled to add the phosphine compound remove, and then the product is separated by column chromatography. 59 mg (0.4 mmol) of 3-n-butylcyclohexanone are obtained, which corresponds to a separately prepared authentic sample of 3-n-butylcyclohexanone. 951 mg are also obtained (5.7 mmol) 2-methyl-3-n-butylcyclohexanone (108-109 ° C / 25 mm Hg) in 5796 yield.

The analytical values of this product are as follows: Infrared absorption (liquid film): 1710 cm "" NMR spectrum [carbon tetrachloride, S (ppm)]: 0.9, 1.0. -CH ₃ 3H χ 2

1.2 to 2.3 -CH ₂ - 14H

Mass spectrum (m / e): 168 (M ⁺ )

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-23- 2455U4

Example A-9

In the same way as described in Example A-8, 10 mmol of a tri-n-butylphosphine complex of di-n-butylcupper-lithium are obtained reacted with 10 mmol (960 mg) Cyciohex-2-en-i-one at room temperature for 1 hour. Then 5 ml HMPA is added and the mixture is stirred for 10 minutes. Then a further 1.8 g (12 mmol) of methyl bromoacetate are added and the reaction is carried out at room temperature for 4 hours. The reaction mixture is worked up in the usual way and the crude product is separated and purified by column chromatography.

556 mg (3.6 mmol) of 3-n-butylcyclohexanone are obtained in one Yield of 36% and also 633 mg (2.8 mmol) of 2-carbomethoxymethyl-3-n-butylcyclohexanone in a yield of 28%.

The analytical values of this product are the following:

Infrared absorption (liquid film) ₁

characteristic absorption: 1735, 1710 and 1170 cm NMR spectrum [carbon tetrachloride, ei (ppm)]: 0.89 - ^: CH ₃ 3H
1.2 to 2.5 -CH £ 16H
3.52 -CH ₃ of OCH ₃ 3H
Mass spectrum (m / e): 226 (M ⁺ )

Example A-10

1.9 g (10 mmol) of copper (I) iodide and 1.82 g (10 mmol) of triethyl phosphite are dissolved in 50 ml of anhydrous diethyl ether and the solution is stirred for 30 minutes at room temperature in a nitrogen atmosphere, a triethyl phosphite complex of copper (I. ) iodide is formed. This solution is cooled to -78 ⁰ C and then 12.8 ml (20 mmol) of a 15 wt be. ^ Hexane solution of n-butyl-lithium added. After stirring for 30 minutes, 96O rag (10 mmol) of cyclohex-2-en-i-one are added and the mixture is stirred for a further hour at room temperature. Then 5 ml of HMPA are added and, after stirring for 10 minutes, 3.6 g (20 mmol) of ethyl β-bromopropionate are added

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added. The mixture is left for another 4 hours at room temperature touched. The reaction mixture is treated in the same manner as described in Example A-1, giving 4.20 g Raw product received. The crude product is separated and purified by column chromatography.

288 mg (1.9 mmol) of 3-n-butylcyclohexanone are obtained in a yield of 19% and also 1.045 g (4.1 mmol) of 2- (2-carboethoxyethyl) -3-n-butylcyclohexanone in a yield of 41%. The analytical values of this product are the following:

Infrared absorption (liquid film): 1735, 1710, 1160-1170 cm " ¹ NMR spectrum [carbon tetrachloride, £ (ppm)]:

0.89 -CH ₃ 3H

1,1 -CH _{3 of} the ester 3H

1.2-2.3 -CH ₂ - 18H

4.0 - ^CH 2 ~ of ^{the ester} 2H

Mass spectrum (m / e): 254 (M)

Example A-11

1.9 g (10 mmoles) of cuprous iodide and 1.24 g (10 mmoles) of trimethyl phosphite are dissolved in 20 ml of anhydrous diethyl ether and the solution is 1 hour at room temperature in a nitrogen atmosphere stirred to prepare a trimethyl phosphite complex of cuprous iodide. This solution is cooled to -78 ° C and then 12.8 ml (20 mmol) of a 15% strength by weight hexane solution of n-butyl-lithium are added. After stirring 960 mg (10mmol) of cyclohex-2-en-1-one are added to the mixture for 30 minutes added and the mixture is stirred for an additional hour at room temperature. Then 5 ml of HMPA are added and the mixture is stirred for 10 minutes. Then 2.3 g (10 mmol) of methyl 7-bromoheptanoate are added and the mixture stirring is continued overnight at room temperature. The reaction mixture is prepared in the same manner as in Example A-1 worked up, giving 4.79 g of crude product. The crude product is separated and purified by column chromatography, whereby 613 mg (4.0 mmol) of 3-n-butylcyclohexanone in a

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A yield of 40% and also 244 mg (0.8 mmol) of 2- (6-carbomethoxyhexyl) -3-n-butylcyclohexanone obtained in a yield of 8%.

The analytical values of this product are as follows: Infrared absorption (liquid film): 1735, 1730, 1170 cm "" ¹ NMR spectrum [carbon tetrachloride, S (ppm)]: 0.9 -CH ₃ 3H

1.1-2.3 - ^CH 2 ^"26H

3.58 -CH _{3 of} the ester 3H

Mass spectrum (m / e): 296 (M ⁺ )

Example A-12

20 mmol of a tri-n-butylphosphine complex of di-n-butylcopper-lithium, prepared in the same way as described in Example A-8, are mixed with 2.76 g (20 mmol) of isophorone- (3,5,5-trimethyl -2-cyclohexanone) reacted for 2 hours at room temperature. Then 5 ml of HMPA are added and the mixture is stirred for a further 10 minutes. Then 4.5 g (50 mmol) of methallyl chloride are added and the mixture is stirred overnight at room temperature. The reaction mixture is treated in the same manner as in Example A-1 to obtain 11.27 g of crude product. The crude product is distilled and separated and purified by column chromatography, 345 mg (1.76 mmol) of 3,5,5-trimethyl-3-n-butylcyclohexanone being obtained in a yield of 9%. In the gas chromatographic analysis (SE 30 10%) this product corresponds to an authentic sample of 3,5,5-trimethyl-3-n-butylcyclohexanone. 990 mg (3.96 mmol) of 2-methallyl-3,5,5-trimethyl-3-n- are also obtained. butylcyclohexanone in a yield of 20%. The analytical values of this product are as follows: Infrared absorption (liquid film): 17-5, 1665.895 cm "* ¹ NMR spectrum [carbon tetrachloride, S (ppm)]: 0.96, 1.0 -CH ₃ 12H
1.2-2.2 -CH ₂ - 13H
2.06 -CH ₃ des methallyls' 3H

4.62 terminal. = CH ₂ 2H

. S098 22/1 Ö0 0

~ 26 -

Mass spectrum (m / e): 250 (M)

Example A-13

20 mmol of a tri-n-butylphosphine complex. of di-n-butyl copper-lithium, prepared in the same way as described in Example A-8, with 3.0 g (20 mmol) of L - (-) - carbon ^ -methyl-S-isopropenyl ^ -cyclohex-enone) 1 hour at room temperature implemented in a nitrogen atmosphere. Then 5 ml HMPA is added and the mixture is stirred for 10 minutes. Then 4.8 g (40 mmol) of propargyl bromide are added and the mixture is stirred overnight at room temperature. The reaction mixture is treated in the same manner as in Example A-1 to obtain 7.55 g of crude product. The raw product is separated off and purified by column chromatography, 2.78 g (13.4 mmol) of 2-methyl-3-n-butyl-5-isopropenylcyclohexanone being obtained obtained in a yield of 67%, which is a separately prepared, authentic sample of 2-methyl-3-n-butyl-isopropenylcyclohexanone according to gas chromatography. 1.08 g (4.4 mmol) of 2-methyl-2-propargyl-3-n-butyl-5-isopropenylcyclohexanone are likewise obtained. The analytical values of this product are the following: Infrared absorption (liquid film): 3300, 2100, 1710, 1645,

895 cm " ¹

Nuclear Magnetic Resonance Spectrum [carbon tetrachloride, S (ppm)]: 0.88, 0.98 -CH ₃ 3H χ 2

1.1-2.2 -CH ₂ - 12H

1.6 end stand. = CH _? 2H

Mass spectrum (m / e): 246 (M)

Example A-14

10 mmol of a tri-n-butylphosphine complex of di-n-butyl copper-lithium, - prepared in the same way as described in Example A-8, with 1.50 g (10 mmol) of D - (+) - carbon (2-methyl-5-isopropenyl-2-cyclohexenone) Reacted 1.5 hours at room temperature in a nitrogen atmosphere. Then v / ground 5 ml of HMPA are added and the mixture is stirred for 10 minutes.

7.1 g (50 mmol) of methyl iodide are also added and the mixture is stirred for 4 hours at room temperature. The mixture is treated in the same manner as in Example A-1 to obtain 4.21 g of crude product. The crude product is distilled to separate and purify it. 126 mg (0.6 mmol) of 2-methyl-3-n-butyl-5-isopropenylcyclohexanone are obtained in a yield of 6% and also 1.72 g (7.7 mmol) of 2,2-dimethyl ^ -n- butyl-S-isopropenylcyclohexanone in a yield of 77%. The analytical values of this product are the following:

Boiling point: 90 to 91 ° C / 0.1 mmHg

Infrared absorption (liquid film): 1710, 1645, 890 cm " ¹ NMR spectrum [carbon tetrachloride, 5 (ppm)]:

0.89 -CH ₃ 3H 0.93 -CH ₃ 3H χ 2 singlet 1.2-1.8 -CH ₂ - 12H 1.71 -CH, of isopropenyl ■ 3H 4.68 terminal. = CH ₂ 2H Mass spectrum (m / e) :. 222 QyI ⁺ ) Example A-I5

A mixture of 950 mg (5 mmol) copper (I) iodide and 820 mg (5 mmol) Hexamethylphosphor-triamid is dissolved in 10 ml of anhydrous diethyl ether and the solution is 30 minutes at room temperature stirred in a nitrogen atmosphere to form a hexamethylphosphorus triamide complex of copper (I) iodide. An ether solution of methyllithium is added to this solution at -78 ° C, prepared from 1.8 g (12.5 mmol) of methyl iodide, 175 mg (25 mmol) of metallic lithium and 20 ml of anhydrous diethyl ether in the same manner as described in Example A-1, and the mixture is stirred for 30 minutes.

480 mg (5 mmol) of cyclohex-2-en-i-one are added and the mixture is reacted at room temperature for 1 hour. The reaction mixture turns from yellowish-green to black. Then 2.5 ml of HMPA are added and the mixture is 10 minutes touched. 1.7 g of allyl iodide are also added and that

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Stirring the mixture was continued overnight. The reaction mixture is worked up in the same way as in Example A-1 and extracted with ether, then washed well with water, dried and concentrated to give 1.317 g of crude product.

37 mg (0.3 mmol) of 3-methylcyclohexanone are obtained in a yield of 6% and likewise 486 mg (3.2 mmol) of 2-allyl-3-methylcyclohexanone in a yield of 64%.

Example A-16

A solution of 76 ml (24 mmol) of 0.32M n-octyl-lithium becomes at -78 ° C to a solution of a complex of 2.29 g (12 mmol) of copper (I) -odide with 2.42 g (12 mmol) of tri-n-butylphosphine in 20 ml of anhydrous diethyl ether are added and the mixture is stirred for 30 minutes. Then 1.26 g (13.2 mmol) of cyclohex-2-en-1-one are obtained added to the reaction mixture and the mixture is stirred for 1 hour. Then 6 ml of HMPA and 4.09 g (239 mmol) of benzyl bromide is added and the mixture is stirred for a further 15 hours at room temperature. After implementation the reaction mixture is worked up in the same manner as in Example A-1, 11.6 g of crude product being obtained. This The crude product is separated off and purified by column chromatography (carrier, silica gel; developing solvent benzene-ethyl acetate) .

250 mg (1.2 mmol) of 3-n-octylcyclohexanone are obtained in one Yield of

2.71 g (9.0 mmol) of 3-n-octyl-2-benzylcyclohexanone are also obtained in a yield of 76%. The analytical values of this product are the following:

Infrared absorption (liquid film)

characteristic absorption: 3000, 1940-1800, 1710, 1600,

730, 700 cm " ¹

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Nuclear Magnetic Resonance Spectrum [carbon tetrachloride, S (ppm)]:

0.83 -CH ₃ 3H.

1.08-2.6 -CH ^ - 24H

7.07 benzene protons 5H

Mass spectrum (m / e): 300 (M)

Part B - Synthesis of Cyclopentenone Derivatives

Example B-1

2.3 g (12 mmol) of copper (I) oxide and 2.4 g (12 mmol) of tri-n-butylphosphine are added to 30 ml of anhydrous diethyl ether and the solution is stirred for about 1 hour at room temperature in a nitrogen atmosphere. The solution is then cooled to -78 ° C. and 12.8 ml (20 mmol) of a 15% strength by weight hexane solution of n-butyl-lithium are added and the mixture is then stirred for a further 30 minutes. Then 820 mg (10 mmol) of cyclopent-2-en-1-one are added and the mixture is further stirred at -78 ° C. for 1 hour. 3.6 g (20 mmol) of hexamethylphosphoric triamide (HMPA abbreviated) are added, and the mixture is stirred for about 10 minutes at -78 ⁰ C. 1.4 g (10 mmol) of methyl iodide are further added and the mixture is stirred for a further 30 minutes at ⁰ ° C. After the reaction, the reaction mixture is treated with about 50 ml of an ammoniacal, saturated, aqueous solution of ammonium chloride and extracted with ether. The ether phase obtained is washed with water and dried with anhydrous sodium sulfate, giving 4.959 g of a concentrated crude product. This crude product is subjected to column chromatography (silica gel) to separate and purify it. 252 ng (1.8 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 18%, according to the gas chromatogram (SE30, 10%), the infrared absorption spectrum and the mass spectrum of a separately produced, authentic sample of 3-η-butylcyclopentanone is equivalent to.

459 ng (3.0 mmol) of 2-methyl-3-n-butylcyclopentanone are also obtained in a yield of 30%. The analytical values

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of this product are the following:

Infrared absorption (liquid film): 1740 cm NMR spectrum [carbon tetrachloride, 6 (ppm)]: 1.07, 1.13 -CH ₃ 3H χ 2
1.4-2.5 -CH ₂ - 12H

Mass spectrum (m / e): 154 (M)

Example B-2

1.9 g (10 mmol) of copper (l) iodide and 2.0 g (10 mmol) of tri-n-butylphosphine are added to 20 ml of anhydrous diethyl ether and the solution is stirred for about 1 hour at room temperature in a nitrogen atmosphere and then to -78 ⁰ C cooled. Then 12.8 ml (20 mmol) of a 15% strength by weight hexane solution of n-r-butyllithium are added and the mixture is stirred for a further 30 minutes. Then 820 mg (10 mmol) of cyclopent-2-en-1-one are added and the mixture is stirred at -78 ° C. for a further 1 hour. Then 5 ml of HMPA are added and the mixture is stirred at -78 ° C. for about 10 minutes. The reaction mixture is warmed to room temperature and gradually added to a solution of 7.1 g (50 mmol) of methyl iodide in 10 ml of ether at room temperature in a nitrogen atmosphere. The mixture is further stirred for 30 minutes and then worked up, extracted, washed and dried in the same manner as in Example B-1 to obtain 3.076 g of a concentrated crude product. The product is separated off and purified by column chromatography (silica gel). 190 mg (1.4 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 14% and also 812 mg (5.2 mmol) of 2-methyl-3-n-butylcyclopentanone in a yield of 52%.

Example B-3

In the same manner as described in Example B-1, 20 mmol n-Butyl-lithium with 820 mg (10 mmol) of cyclopent-2-en-1-one in the presence of 12 mmol of copper (I) iodide implemented. Then 5 ml of HMPA are added and the mixture is 10 minutes at Stirred at room temperature. Then 1.7 g (12 mmol) of methyl

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iodide is added and the mixture is allowed to continue for about 15 hours stirred at room temperature. The reaction mixture is worked up in the same way as described in Example B-1 ", extracted, washed and dried, giving 1.451 g a concentrated crude product is obtained, which is then separated off and purified by column chromatography (silica gel). 12 mg (0.1 mmol) of 3-n-butylcyclopentanone are obtained in one 1% yield. 376 mg (2.4 mmol) of 2-methyl-3-butylcyclopentanone are also obtained in a yield of 24%.

Example B-4

In the same way as described in Example B-1, 20 mmol of n-butyl-lithium with 820 mg (10 mmol) of cyclopent-2-en-1-one in the presence of 12 mmol of a tri-n-butylphosphine complex of copper (I) -iodide implemented. Then 5 ml of tetramethylethylenediamine are added and the mixture is stirred for about 10 minutes at room temperature. The reaction mixture is added to a solution of 7.1 g (50 mmol) of methyl iodide in 10 ml of ether at room temperature in a nitrogen atmosphere. Then the mixture is further stirred for 30 minutes and then worked up, extracted, washed and dried in the same manner as described in Example B-1, whereby 3.898 g of a concentrated crude product is obtained, which is subjected to column chromatography (silica gel) to separate it and clean. 320 mg (2.3 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 23%. 320 mg (2.1 mmol) of 2-methyl-3-n-butylcyclopentanone are likewise obtained in a yield of 21%.

Example B-5 ■

In the same way as described in Example B-2, 20 mmol of n-butyl-lithium are used with 820 mg (10 mmol) of cyclopent-2-ene ion in the presence of 2.62 mg (10 mmol) tripheny! phosphine and 10 mmol of copper (I) iodide reacted. Then 5 ml of dimethyl sulfoxide are added added and the mixture is stirred for about 10 minutes at room temperature. The reaction mixture becomes too

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a solution of 7.1 g (50 mmol) of methyl iodide in 10 ml of ether given at room temperature in a nitrogen atmosphere. then • the mixture is stirred and worked up for a further 30 minutes, extracted, washed, dried and concentrated. The product is subjected to column chromatography (silica gel) to obtain it separate and clean. 360 mg (2.6 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 26%. 250 mg (1.6 mmol) of 2-methyl-3-n-butylcyclopentanone in a yield of 16%.

Example B-6

To be described in the same way as in Example B-2 20 mmol of n-butyl-lithium with 820 mg (10 mmol) of cyclopent-2-en-1-one in the presence of 1.43 g (10 mmol) of copper (I) bromide and 6.2 g (20 mmol) of triphenyl phosphite reacted. Then 5 ml of dimethylformamide are added and the mixture becomes approximately Stirred for 10 minutes at room temperature. The reaction mixture obtained becomes a solution of 7.1 g (50 mmol) of methyl iodide in 10 ml of ether at room temperature in: N atmosphere, given, Stirred for 30 minutes, worked up, extracted, washed, dried, concentrated and subjected to column chromatography, in the same manner as described in Example B-1. 290 mg (2.1 mmol) of 3-n-butylcyclopentanone are obtained in one yield of 21%. A further 220 mg (1.4 mmol) of 2-methyl-3-n-butylcyclopentanone are obtained in a yield of 14%.

Example B-7

0.45 g (5 mmol) of copper (I) cyanide and 10 ml of pyridine are added to 10 ml of anhydrous diethyl ether, and the mixture is stirred for about 1 hour at room temperature in a nitrogen atmosphere. 6.4 ml (10 mmol) of a 15% strength by weight hexane solution of n-butyl-lithium are then added and the mixture is stirred for 30 minutes. Then, 410 mg (5 mmol) of cyclopent-2-en-1-one was added and the mixture is further stirred at -78 ⁰ C for 1 hour. The reaction mixture is warmed to room temperature and gradually becomes a solution of 7.1 g (50 mmol) of methyl

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iodide in 10 ml of Xther at room temperature in a nitrogen atmosphere given. The mixture is stirred for a further 30 minutes and then worked up in the same way as described in Example B-1, extracted, washed, dried, concentrated and separated, giving 130 mg (0.9 mmol) of 3-n-butylcyclopentanone obtained in a yield of 18%. One also obtains 80 mg (0.5 mmol) of 2-methyl-3-n-butylcyclopentanone in a yield of 10%.

Example B-8

2.0 g (10 mmol) are added to 20 ml of anhydrous diethyl ether Tri-n-butylphosphine and 1.9 g (10 mmol) of copper (I) iodide and the mixture is stirred for about 1 hour and then to -78 ° C chilled. Then 12.8 ml (20 mmol) of a 15% strength by weight Hexane solution from n-butyl-lithium is added and the mixture is Stirred for 30 minutes. 820 mg (10 mmol) of cyclopent-2-en-1-one become added and the mixture is stirred at -78 ° C for 1 hour. Then 5 ml of HMPA is added and the mixture becomes approximately Stirred for 10 minutes at -78 ° C * The reaction mixture is then warmed to room temperature. The solution is gradually added dropwise to a solution of 3.06 g (20 mmol) of methyl bromoacetate in 10 ml of ether at room temperature in a nitrogen atmosphere given. The mixture is stirred for an additional 2 hours and then the reaction mixture is made in the same manner as in Example B-1 described worked up, extracted, washed and dried, giving 4.781 g of concentrated crude product obtained, which is separated and chromatographed by column (silica gel) is cleaned. 600 mg (4.3 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 43%. 300 mg (1.4 mmol) of 2-carbomethoxymethyl-3-n-butylcyclopentanone are also obtained. in a yield of 14%. The analytical values of this product are the following:

Infrared absorption (liquid film): 1730-1740, 1160-1120 cm " ¹ NMR spectrum [Carbon tetrachloride, Q (ppm)]: 0.9 -CH, • 3H
1.2-2.4 -CH ₂ - 14H

3,51 -CH _{3 of} the ester 3H '

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Mass spectrum (m / e): 212 (M).

Example B-9

1.24 g (10 mmol) of trimethyl phosphite and 1.9 g (10 mmol) of copper (I) iodide are added to 20 ml of anhydrous diethyl ether and the mixture is stirred for about 1 hour at room temperature in a nitrogen atmosphere. The reaction mixture is then cooled to -78 ° C. and 12.8 ml (20 mmol) of a 15% strength by weight hexane solution of n-butyllithium are added. The mixture is stirred for 30 minutes. Then, 820 mg (10 mmol) of cyclopent-2-en-1-one was added and the mixture is stirred for 1 hour at -78 ^0C. Then 5 ml of HMPA are added and the mixture is stirred at -78 ° C. for 10 minutes. In addition, 1.53 g (10 mmol) of methyl bromoacetate are added and the mixture is ^{stirred at 0} ° C. for 2 hours. The reaction mixture is worked up, extracted, washed, dried and concentrated to give 3.128 g of crude product which is separated off and purified by column chromatography (silica gel). 303 mg (2.2 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 22%. 256 mg (1.2 mmol) of 2-carbomethoxymethyl-3-n-butylcyclopentanone are likewise obtained in a yield of 12%.

Example B-10

4.7 g (12 mmol) of a tri-n-butylphosphine complex of copper (I) iodide and 12.8 ml (20 mmol) of a 15% strength by weight hexane solution of η-butyl are added to 30 ml of anhydrous diethyl ether lithium are then added at -78 ⁰ C in nitrogen atmosphere. The mixture is stirred for 30 minutes at -78 ° C. and then 820 mg (10 mmol) of cyclopent-2-en-1-one are added to ground. The mixture is stirred for a further 2 hours at room temperature. Then 5 ml of HMPA are added and the mixture is stirred for 10 minutes. In addition, 1.84 g (12 mmol) of methyl bromoacetate are added and the mixture is stirred for a further 15 hours at room temperature. The reaction mixture is then worked up, extracted, washed, dried and concentrated to give 3.868 g of crude product which is separated off and baked

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Column chromatography (silica gel) is purified. 282 mg (2.0 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 20%. 97 mg (0.5 mmol) of 2-carbomethoxymethyl-3-n-butylcyclopentanone are also obtained in a yield of 5%.

Example B-11

To 30 ml of anhydrous diethyl ether are added 350 mg (50 mmol) of metallic lithium, and _f 3 6 g (25 mmol) of methyl iodide are added dropwise in a nitrogen atmosphere at ⁰ C O. Then the mixture is stirred for about 2 hours to prepare an ethereal solution of methyl-lithium. The solution is added dropwise to a solution of 1.9 g (10 mmol) of copper (I) iodide in 20 ml of anhydrous diethyl ether at -78 ° C. in a nitrogen atmosphere. The mixture is stirred for a further 30 minutes and 820 mg (10 mmol) of cyclopent-2-en-1-one are added. The reaction temperature is lowered to room temperature and the mixture is further stirred for about 1 hour. The reaction mixture turns from light yellow to yellow. To the reaction mixture is added 5 ml of HMPA and the mixture is stirred for about 10 minutes. The reaction mixture then turns from yellow to brown. A further 3.4 g (20 mmol) of allyl iodide are added and the mixture is stirred for about 15 hours at room temperature. The mixture turns black-brown. The reaction mixture is then worked up, extracted, washed, dried and concentrated in the same manner as described in Example B-1 to obtain 990 mg of crude product, which is subjected to column chromatography (silica gel) to separate and purify it. 30 mg (0.3 mmol) of 3-methylcyclopentanone are obtained in a yield of 3%. This product corresponds in the gas chromatogram (SE30,), infrared absorption spectrum and mass spectrum of a separately prepared, authentic sample of 3-methylcyciopentanone. 100 mg (0.7 mmol) of 2-allyl-3-methylcyclopentanone are likewise obtained in a yield of 1%. The analytical values of this product are the following:

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Infrared absorption (liquid film): 3100, 1740, 1640 cm " ¹ MR spectrum t carbon tetrachloride, β (ppm)]:

1,1 -CH ₃ 3H

1,4-2,4 -CH ₂ - * 8H

4.8, 5.1, 5.7 vinyl group 3H

Mass spectrum (m / e): 138 (M)

Example B-12

280 mg (40 mmol) of metallic lithium are added to 30 ml of anhydrous diethyl ether, and 2.84 g (20 mmol) of methyl iodide are added dropwise at ⁰ ° C. in a nitrogen atmosphere. The mixture is stirred for approximately 3 hours to form methyl-lithium. This solution is added drop-wise at -78 ⁰ C in nitrogen to 20 ml of an ether solution of a copper (l) iodide / tri-n-butylphosphine complex, prepared from 2.09 g (11 mmol) of copper (l) iodide and 2.22 g (11 mmol) of tri-n-butylphosphine are added and the mixture is stirred for 30 minutes. Is added to the mixture 820 mg (10 mmol) of cyclopent-2-en-1 ~ on and the mixture is stirred for 1 hour at -78 ^0C. Further 5 ml of HMPA are added and the mixture is stirred for about 10 minutes. The resulting solution is warmed to room temperature and gradually added dropwise to a solution of 8.40 g (50 mmol) of allyl iodide in 10 ml of ether. The mixture is then stirred for 1 hour at room temperature and then worked up, extracted, washed, dried and concentrated in the same manner as described in Example B-1, giving 5.138 g of crude product which is separated and purified by column chromatography (silica gel). 150 mg (1.5 mmol) of 3-methylcyclopentanone are obtained in a yield of 15%. 350 mg (2.5 mmol) of 2-allyl-3-methylcyclopentanone are likewise obtained in a yield of 25%.

Example B-13

Metallic lithium (140 mg, 20 mmol) is added to 10 ml of anhydrous diethyl ether and 1.42 g (10 mmol) of methyl iodide are added dropwise at ⁰ ° C. in a nitrogen atmosphere.

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The mixture is stirred for about 2 hours to produce methyl-lithium. This solution is added dropwise "at -78 ° C in a nitrogen atmosphere to 10 ml of an ether solution of a trimethylphosphite complex of cuprous iodide, prepared from 2.09 g (11 mmol) of cuprous iodide and 1.36 g (11 mmol) of trimethylphosphite are added, the mixture is stirred for 30 minutes, and 820 mg (10 mmol) of cyclopent-2-en-1-one are added added and the mixture is further stirred for 1 hour at -78 ^0C. Then, 5 ml of HMPA to the mixture and the mixture is stirred for about 5 minutes. This solution is gradually added dropwise to a solution of 1.53 g (20 mmol) Allyl chloride is added to 20 ml of ether and the mixture is stirred for 1 hour at room temperature The reaction mixture is worked up, extracted, washed, dried and concentrated in the same manner as described in Example B-1, 1.099 g of crude product being obtained which can be used for separation and Purification of column chromatography ( Silica gel). 150 mg (1.5 mmol) of 3-methylcyclopentanone are obtained in a yield of 15%. 125 mg (0.9 mmol) of 2-allyl -3-methylcyclopentanone are likewise obtained in a yield of 9%.

Example B-14 '

Described in the same manner as in Example B-13 10 mmol of a methyl-lithium solution prepared and this solution is added dropwise at -78 ° C in a nitrogen atmosphere to a Solution of an HMPA complex of copper (l) iodide, made from 2.09 g (11 mmol) of copper (I) iodide and 1.80 g (11 mmol) of HMPA in 10 ml of ether. The mixture is stirred for 30 minutes. Then 820 mg (10 mmol) of cyclopent-2-en-1-one are added and the The mixture is stirred for a further 1 hour at -78 ° C. Then 5 ml of HMPA are added and the mixture is stirred for about 5 minutes. The mixture is gradually added to a solution of 8.40 g (50 mmol) of allyl iodide in 10 ml of ether and the mixture is stirred for a further 1 hour at room temperature. The reaction mixture is described in the same manner as in Example B-1 worked up, extracted, washed, dried and concentrated, giving 2.574 g of crude product, which for

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Separation and purification of column chromatography (silica gel) is subjected. 210 mg (2.2 mmol) of 3-methylcyclopentanone are obtained in a yield of 22%. 70 mg (0.5 mmol) of 2-allyl-3-methylcyclopentanone are likewise obtained in a yield of

Example 15

1.66 g (10 mmol) of triethyl phosphite and 1.9 g (10 mmol) of copper iodide are added to 20 ml of anhydrous diethyl ether and the solution is stirred for about 1 hour at room temperature in a nitrogen atmosphere. The solution is then cooled to -78 ⁰ C and 12.8 ml (20 mmol) of a 15 wt.% Hexane solution of n-butyl-lithium are added. The mixture is stirred for 30 minutes and 820 mg (10 mmol) of cyclopent-2-en-1-one are added. The mixture is further stirred for 1 hour at -78 ^0C. The reaction mixture is warmed to room temperature. The mixture is gradually added dropwise at room temperature to a solution of 4.72 g (50 mmol) of chloromethyl ethyl ether in 20 ml of ether. The mixture is stirred for a further 1 hour and then worked up, extracted, washed, dried, concentrated and subjected to column chromatography in the same manner as described in Example B-1, 2.936 g of crude product being obtained. Analysis of this product shows that 267 mg (1.9 mmol) of 3-n-butylcyclopentanone were obtained in a yield of 19%. 308 mg (1.6 mmol) of 2-ethoxymethyl-3-n-butylcyclopentanone are likewise obtained in a yield of 16%. The analytical values of this product are as follows: Infrared absorption (liquid film): 1740.1110 cm NMR spectrum [carbon tetrachloride, <£ (ppm)]: 0.98, 1.13 -CH ₃ 3H χ 2

1.2-2.3 -CH ₂ - 12H

3.2-3.6 ~ ^CH 2 "adjacent to 4H

Oxygen atom

Mass spectrum (m / e): 198 (M ⁺ )

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Example B-16

In the same manner as in Example B-2 "can be described 20 mmol of n-butyl-lithium with 820 mg (10 mmol) of cyclopent-2-en-1-one in the presence of 1.9 g (10 mmol) of copper (i) iodide and 2.0 g (10 mmol) of tri-n-butylphosphine reacted. Then 5 ml of HMPA are added and with the reaction product approximately Reacted for 10 minutes at -78 ° C. The reaction mixture will gradually added to a solution of 1.51 g (20 mmol) of chloroacetonitrile in 10 ml of ether and then the mixture is continued Stirred for 2 hours. The reaction mixture is worked up, extracted, washed and washed in the same manner as in Example B-1 dried, giving 4.307 g of concentrated crude product, which is then used for separation and purification by column chromatography (Silica gel) is subjected. 461 mg (3.3 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 33%. 208 mg (1.2 mmol) of 2-cyanomethyl-3-n-butylcyclopentanone are likewise obtained in a yield of 12%. The analytical values of this product are the following:

Infrared absorption (liquid film): 2210, 1740 cm " ^1. 'NMR spectrum [deuterochloroform, S (ppm)]: 0.93 -CH ₃ 3H

1,2-2,3 -CH ₂ - ■ 12H.

2,7 -CH ₂ - the cyanomethyl-2H

group

Example B-17

In the same way as described in Example B-2, 20 mmol of η-butyl-lithium with 820 mg (10 mmol) of cyclopent-2-en-ion in the presence of 1.9 g (10 mmol) of copper (I) iodide and 2.0 g (10 mmol) of tri-n-butylphosphine reacted. Then, 5 ml of HMPA is added and reacted with the .Reaktionsprodukt 10 minutes at -78 ⁰ C. The mixture obtained is added dropwise at room temperature to a solution of 3.1 g (20 mmol) of oc-phenacyl chloride in 20 ml of ether and the mixture is stirred at room temperature for 1 hour. The reaction mixture is worked up, extracted, washed and dried in the same manner as described in Example B-1, wherein

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6.934 g of concentrated crude product is obtained, which is subjected to column chromatography (silica gel) for separation and purification will. 351 mg (2.5 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 25%. 200 mg (0.8 mmol) are also obtained 2-phenacyl-3-n-butylcyclopentanone in a yield of 8%. The analytical values of this product are the following: Infrared absorption (liquid film): 3080, 1740, 1690, 1600,

760, 690 cm " ¹

Nuclear Magnetic Resonance Spectrum [deuterochloroform, O (ppm)]: 0.92 -CH ₃ 3H
1.2-2.3 -CH ₂ - 12H

7.3, 7.8 protons of the 5H
Benzene ring

Mass spectrum (m / e): 258 (M)

Example B-18

In the same way as described in Example B-2, 20 mmol of n-butyl-lithium with 820 mg (10 mmol) of cyclopent-2-en-1-one in the presence of 1.9 g (10 mmol) of copper (l) - iodide and 2.0 g (10 mmol) of tri-n-buty! phosphine reacted. Then, 5 ml of HMPA is added and reacted with the reaction product for 10 minutes at -78 ⁰ C. 3.4 g (20 mmol) of benzyl bromide are further added to this solution and the mixture is stirred at room temperature for 1 hour. The reaction mixture is then worked up, extracted, washed and dried in the same manner as described in Example B-1, 6.559 g of concentrated crude product being obtained, which is subjected to column chromatography (silica gel) for separation and purification. 208 mg (1.5 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 15%. 1.37 g (6.0 mmol) of 2-benzyl-3-n-butylcyclopentanone are likewise obtained in a yield of 60%. The analytical fourths of this product are the following:

Infrared absorption (liquid film): 3040, 1740, 1605, 750,

700 cm " ¹

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Nuclear Magnetic Resonance Spectrum [carbon tetrachloride, (ppm)]: 0.86 -CH _{3 3Η}

1.1-2.2 -CH ₂ - 12Η

2.82 ~ ^CH 2 " ^of benzyl ² H
7.04 protons of the 5H
Benzene ring

Mass spectrum (m / e): 230 (M)

Example B-19 .

In the same way as described in Example B-2, 20 mmol of n-butyl-lithium with 820 mg (10 mmol) of cyclopent-2-en-1-one in the presence of 1.9 g (10 mmol) of copper (I) - iodide and 2.0 g (10 mmol) of tri-n-butylphosphine reacted. Then, 5 ml of HMPA is added and reacted with the reaction product of about 10 minutes at -78 ⁰ C. A further 3.0 g (20 mmol) of Ν, Ν-diethylchloroacetamide are added to the resulting solution and the mixture is stirred for a further 30 minutes at room temperature. The reaction mixture is worked up, extracted, washed and dried in the same manner as described in Example B-1, 6.254 g of concentrated crude product being obtained, which is subjected to column chromatography (silica gel) for separation and purification. 422 mg (3.0 mmol) of 3-n-butylcyclopentanone are obtained in a yield of 30%. 550 mg (2.2 mmol) of oc- (2-oxo-5-n-butylcyclopentyl) -N, N-diethyl acetamide are likewise obtained in a yield of 22%. The analytical values of this product are as follows: Infrared absorption (liquid film): 1740, 1640 cm " ¹ KMR spectrum C carbon tetrachloride, 6 (ppm)]:

0.90 -CH ₃ of ethyl - 3H 1.15 -CH ₃ - of ethyl 6H 3.28 -CH ₂ - adjacent to 4H 2.50 -CH ₀ Carbonyl group e 2H 1.2-2.3 -CH _Q 12H

Mass spectrum (m / e): 253 (M)

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Example B-20

76 ml (23.6 mmol) 0.31M n-octyl-lithium become a solution from a complex of 2.25 g (11.8 mmol) of copper (I) iodide and

2.38 g (11.8 mmol) of tri-n-butylphosphine in 20 ml of anhydrous Diethyl ether is added and the mixture is stirred for 30 minutes. Then 1.06 g (13.0 mmol) of cyclopent-2-en-1-one are added and the mixture is stirred at -78 ° C for 1 hour. 6 ml of HMPA and 4.03 g (23.6 mmol) of benzyl bromide are also added and the mixture is stirred for a further 15 hours at room temperature. After the reaction, the mixture is worked up in the same manner as described in Example B-1, whereby 11.4 g of crude product is obtained which can be used for separation and purification by column chromatography (carrier, silica gel; developing agent Benzene-ethyl acetate) is subjected. 90 mg (0.46 mmole) are obtained 3-n-octylcyclopentanone in a yield of 4%. You get also 1.03 g (3.6 mmol) of 2-benzyl-3-n-octyicyclopentanone in a yield of 31%. The analytical values of this product are the following:

Infrared absorption (liquid film) characteristic absorption: 3000, 1940-1800, 1735, 1600, 700 cm " ¹ NMR spectrum [carbon tetrachloride, S (ppm)]: 0.90 -CH ₃ 3H

1.0 to 2.9 -CH ₂ - 22H
7.10 benzene protons 5H
Mass spectrum (m / e): 286 (M)

Example B-21

A mixture of 1.6 g (6.7 mmol) of trans-1-iodo-i-octene and 5.1 ml (6.7 mmol) of 1.3M n-butyl lithium is 30 minutes at -78 ⁰ C in 6 ml of hexane stirred. The solution obtained is reacted with 1.3 g (3.3 mmol) of tri-n-butylphosphine-copper (I) iodide complex in 20 ml of ether for 20 minutes at -15 to -2O ⁰ C. A solution of 270 mg (3.3 mmol) of cyclopent-2-en-1-one in 5 ml of ether is added to the resulting solution and the mixture is stirred at -78 ° C. for 15 minutes. A solution of 1.8 g (6.8 mmol) of methyl-7-iodo-5-

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heptinat in 5 ml of ether and then 5 ml of HMPA and 5 ml of ether. The mixture is stirred for 1 hour and then worked up in the same manner as described in Example B-1, giving 3.15 g of crude product. This crude product is found to be a complex mixture by thin layer chromatography and gas chromatography. Separation by thin layer chromatography and by analysis by mass fragmentography and gas chromatography and mass spectrum gives 15 mg (0.05 mmol, 2% yield) of 5,6-dehydro-11,15-deoxy-prostaglandin-E ₂ methyl ester.

The analytical values of the product are as follows: Infrared absorption (liquid film) - Characteristic absorption: 3000, 2200, 1735, 1590, 1160, 970 cm " ¹ NMR spectrum [carbon tetrachloride, S (ppm)]:

0.90 -CH ₃ 3H 1-2-1.7 -CH - 12H 1.7-2.6 -CH ₂ - 1OH 2.80 = -CH ₂ - = 2H 3.60 -COOCH, 3H 5.39, 5.49 olefinic 2H Protons Mass spectrum (m / e): 332 (M ⁺ ), 317, 314, 301, 275, 273, 261, 259, 2 93, 163, 140, 121, 109, 91, 79, 67, 55, 41. Z47, 245, 231, 1 ■

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Claims (6)

Patent to claims 1. Process for the preparation of cyclohexanone derivatives or cyclopentanone derivatives of the following formula (4-A) or (4-B) (4-A) R, R R, 5 / Rb j ?. (4-B) FL R / L, Rp f Rz, R / ,, Rn »Rg t Ry and R _{Q can be the} same or different and denote a hydrogen atom or a monovalent organic group, where two of these groups can optionally form a ring, R. denotes a monovalent organic group and Rg denotes a monovalent organic group, characterized in that one (a) a cyclohexenone derivative of the formula (1-A) or a Cyclopentenone derivative of formula (1-B) (1-A) 509822/1000 (l-B) wherein R ₁ to R _{Q have} the definitions given above, with an organic copper-lithium compound of the formula (2) Cu (R _B ). _n LiY ₂ . _n (2) ■ in what Rg has the meaning given above, Y is a monovalent anion and η denotes 1 or 2, and if η denotes 2, the two groups Rg can be the same or different, or with a complex thereof with a trivalent organic phosphorus compound in the presence of an aprotic inert organic medium. and (b) the resulting reaction product with an organic one Halogen compound of formula (3). • ^R A ^X ^) wherein R. has the definition given above and X is a halogen atom, in the presence of a nitrogen-containing one or sulfur-containing aprotic polar organic Reacts solvent. 2. The method according to claim 1, characterized in that R ₁ to R ₈ in the above formulas (1-A), (1-B), (4-A) and (4-B) each have a hydrogen atom, an alkyl , Cycloalkyl, alkenyl, alkynyl or aryl group having 1 to 20 carbon atoms. 3. Method according to claim 1 or 2, characterized in that that R. and Rg in formulas (2), (3), (4-A) and (4-B) each mean organic groups having 1 to 20 carbon atoms. 509822/1000 4. The method according to any one of claims 1 to 3, characterized in that the reactions (a) and (b) are carried out at a temperature of -78 ° to 5O ⁰ C. 5. The method according to any one of claims 1 to 4, characterized in that that the reactions (a) and (b) in the presence of a nitrogen-containing or sulfur-containing aprotic polar organic solvent. 6. Process for the preparation of cyclopentanone derivatives of the formula (4-B) according to one of claims 1 to 5, characterized in that that the reaction product obtained by reacting the cyclopentenone derivative of the formula (1-B) with the organic Copper-lithium compound of the formula (2) or a complex thereof with a trivalent organic phosphorus compound is obtained in the presence of an aprotic inert organic liquid, in a non-oxidizing atmosphere to the organic Halogen compound of the formula (3) or its solution in an aprotic inert organic medium is added. to react the reaction product with the organic halogen compound. 509822/1000