CH640505A5 - Process for preparing carboxylic acid esters cyclopropane racemic, structure and trans new compound obtained. - Google Patents

Description

640 505

2

2. Claims according to claim 1, characterized in

in that the strong base used is chosen from the group formed

1. Process for the preparation of alkyl esters of cyclopropa- acids with alkali alcoholates, alkali hydrides, necarboxylic alkali amides, of formula (I): and alkylllithians.

H1 5 3. Preparation process according to claim 1, characterized

~~ ^ \ C = CH H in that the condensation of the aldehyde ester and ylides is effected

c c / ... killed in a solvent or a mixture of solvents chosen in the

2 y / \ y group consisting of dimethyl sulfoxide, dimethoxyethane,

H P. COOR dimethylformamide, hexamethylphosphorotriamide, hydrocarbons

/ \ io aliphatic bures, monocyclic aromatic hydrocarbons and

H3 b cycloalkanes.

,. 4. Preparation process according to claim 1, characterized

racemic, of trans structure, in which R, and R2 represent in œ that] a strong base is, e butyilithium and that one carries out the con-

an alkyl radical containing from 1 to 6 carbon atoms or else densification of the aldehyde ester and of the ylide at -80 + 10 ° C in the t-

Rt and R2 together represent, with the carbon atom to which they 1S trahydrofuran are linked, a carbon homocycle comprising from 3 to 6 atoms of Le Spiro. [2,4] -heptane-2- (2-methyl-H-Propenyl) -l-carbon carboXylate, R3 and R4 represent an alkyl radical comprising from 1 to ^ methyl

6 carbon atoms or else R3 and R4 represent together, with

the carbon atom to which they are linked, a carbon homocycle comprising from 3 to 6 carbon atoms, it being understood however that the 20 The present invention relates to a process for the preparation of substituents R ,, R2, R3 and R4 may not be identical between them of d-alkyl esters of racemic cyclopropanecarboxylic acids of ni represent, with the carbon atom to which they are linked, the same trans homocycle structure and R represents an alkyl radical comprising from 1 to 6 The invention more specifically for subject a preparation process

carbon atoms, characterized in that a ration salt is reacted with d> alkyl esters of cyclopropanecarboxylic acids, of phosphomum, of formula (IIA): formula (I). ^

Hedge r "\ c = ch

; CH-L ($) 3 (IIa) ^ / \ -c- (I)

/ H

R

in which Hai represents a chlorine, bromine or iodfi atom, in an amount corresponding to approximately 1 Eq, relative to the aldehyde-ester subsequently used, with a strong base, to obtain the ylide of formula (IIB ):

30

COOR

racemic, of trans structure, in which R! and R2 represent an alkyl radical comprising from 1 to 6 carbon atoms or else Rt and R2 represent together, with the carbon atom to which they R, 33 are bonded, a carbon homocycle comprising from 3 to 6 atoms

\ © © carbon, R3 and R4 represent an alkyl radical comprising from 1 to

- = (<P) 3 (IIB) 6 carbon atoms or else R3 and R4 together represent, with r2 • the carbon atom to which they are linked, a carbon homocycle comprising 3 to 6 carbon atoms, it being understood however, that reacts this ylide on 1 aldehyde-ester of formula (III): 40 substances rj> r2i r3 and R4 cannot be identical with each other

O nor represent, with the carbon atom to which they are linked, the same

It is homocycle and R represents an alkyl radical comprising from 1 to 6

H —C .H carbon atoms, characterized in that a phosphonium salt of formula (IIA) is reacted: .C = C (III) 45 F A '

/ \ Hai © r.

H C-OR \ ©

il; ch-p = (o>) 3 (iiA)

° „/

R

• 2

in which the double bond is of configuration (Z) or (E), in order to obtain an intermediate condensation product (X), submits a salt in which the halide has a chlorine, bromine or phosphonium atom of formula (IVA): iodine <in an amount corresponding to about 1 Eq, compared to

the aldehyde-ester subsequently put at stake, with a strong base, for Hai © R3. obtain the ylide of formula (IIB):

CH-P = (<5) 3 (IVa) 55 Rl r Q 0

r4 C-P = (®) 3 (IIb)

in which Hai represents a chlorine, bromine or r2 atom

iodine, in an amount corresponding to approximately 1 Eq relative to

the aldehyde ester (III), with the action of a strong base, in order to obtain the ylide eo reacts this ylide with the aldehyde ester of formula (III):

(ivb): o r3v ii

\ e © H-C. H

/ c-p-m '> - <

^ 4 / \

H C-OR

which is reacted on the intermediate condensation product (X), ||

previously obtained. O

3

640 505

in which the double bond is of configuration (Z) or (E), for which the addition, whether it is carried out on the aldehyde carbonyl or on obtaining an intermediate condensation product (X), subjects a salt to the double bond alkyl 4-oxo-2-butenoate, forced-phosphonium lead of formula (IVA): ment to the desired molecule (see Belgian patent N ° 827651).

In the process of the present invention, it is a question of fixing selectively

Hal © R,

\

a ylure:

ych-P = (®) s (iva) r.,

/ \ e ©

r / ^ c-P (®) 3

in which Hai represents a chlorine, bromine or R2 atom

iodine, in an amount corresponding to approximately 1 Eq relative to i °.

„. ,,,, ^, TIT. ,. ,,,. . „On aldehydic carbonyl then a different ylide:

laldehyde-ester (III), with the action of a strong base, to obtain 1 ylure n

(ivb): R3 R3

\ © ® \ e ©

^ C — P = (®) 3 (IVB) ^ C-P (0>) 3

R 15 Of

K4 R4

which is reacted on the intermediate condensation product (X), on the ethylenic double bond of the aldehyde-ester (III).

previously obtained. The success of such an operation was, a priori, very problematic.

In formula (I), ri, r2 on the one hand and r3, r4 on the other hand that can represent a methyl, ethyl, linear propyl radical or if) indeed> phosphorus ylides (IIB) and (IVB) react with branched, linear or branched butyl, linear or branched pentyl, hexyl of similar velocities on the aldehyde carbonyl and on the linear or branched double or else the radicals rj, r2 on the one hand and r3, r4 bonding of the aldehyde-ester (III), the desired compound is not obtained

on the other hand can represent, with the carbon atoms aux- cb £ but with complex mixtures of compounds comprising to which they are linked, a cyclopropyl, cyclobutyl, cyclopentyl radical, the same carbon atom of the substitutions on the one hand by the radi-

cyclohexyl and r can represent a methyl, ethyl, .propyl radical 25 cals Rj and and on the other hand by the radicals r3 and r4.

linear or branched, linear or branched butyl, linear pentyl or sij on the other hand, as is the case in the process of the present branched, linear or branched hexyl. invention, the aldehyde carbonyl of the starting compound (III) is

Among the compounds of formula (I) which the process of the invention is more reactive with respect to the phosphorus ylides which the double bond makes it possible to prepare, mention will be made particularly of spiro [2,4] -heptane-ethylenic, obtains an intermediate of formula:

Methyl 2- (2-methyl-1-propenyl) -1-carboxylate, which is a 30

new compound and, as such, is part of the invention. Ri.

The strong base which is reacted on the phosphide halide - C - CH H

nium in order to form the ylide is preferably chosen from the group /

consisting of alkaline alcoholates, alkaline hydrides, amides - R2 .C = C. (X)

alkaline res and alkoyllithians. "/ \

J H C OR

According to a preferred embodiment of the method of the invention, the | T

strong base is butyllithium. q

The aldehyde ester and the ylide are condensed in an organic solvent or in a mixture of. organic solvents. whose double bonds, according to the data in the literature,

These solvents are advantageously chosen from the group constituted 40 can be the object, on the part of the ylide:

with dimethylsulfoxide, dimethoxyethane, dimethylforma- ^

mide, hexamethylphosphorotriamide, aliphatic hydrocarbons 3 \ ^ q $

monocyclic aromatic hydrocarbons and cyclo-C — P (®) 3

alkanes. /

According to a preferred embodiment of the method of the invention, the 45 4

organic solvent used is tetrahydrofuran. simultaneously from an attack 1,2 and 1,4 or selectively from an

To prepare, in situ, the desired ylures, preference is given to attack 1,2 and to attack 1,4.

a slight strong base defect compared to the phosphide halide - this is how, often, the attack by a carbanion of a nium system used and the aldehyde ester and conjugated ethylenic double bonds, analogous to that which ylures, preferably at - 80 + 10 ° C. 50 includes the intermediary (X), can be done indifferently in 1,2

One can indifferently use, in all the reactions of or 1,4 [see, for example, Cyril S.F. Tang and Henry Rapoport in: “J.

process of the invention, an aldehyde ester derived from maleic acid-Org. Chem. ”, Vol. 38, No. 16 (1973) or William G. Dauben and Alan that (double bond of configuration Z) is an aldehyde-ester derivative p. Kozikowski in: "Tetrahedron Letters", N ° 38, pp. 3711-3714

fumaric acid (double bond of configuration E). (1973)]. This attack can also be carried out either selectively

The method of the invention makes it possible to obtain, by total synthesis, 55 in [see, for example, E.J. Corey and Manfred Jautelat in: “J. Am.

in a reaction step, comprising the successive introduction of Chem. Soc. ”, 89, 3912, 3914 (1967)], or selectively in 1.4 [see,

two different phosphorus ylides, esters of cyclopropane acids - for example, D.E. Ames and R.E. Bowman in: "J. Chem. Soc. ",

racemic carboxylics (I), of trans structure, having subsp 329 (1950)].

titers Ri, R2 and R3, R4, different on the unsaturated side chain n was therefore impossible, taking into account the data of the prior art

and on the cyclopropane cycle; many of these esters (I) are unable to predict whether the expected reaction leading to the compounds (I)

transferable by another route. desired would take place or if other reactions of the same type did not

A process for the total synthesis of acid esters was already known to take place simultaneously or preferentially. The racemic transchrysanthemic process (case in which R! = R2 = R4 = the invention therefore presents a remarkable original character,

methyl), but this process involved only one type of phos ylide- The esters of formula (I) can be used as an intermediate-

phorus of formula: H3C 65 res in the synthesis of generally well known compounds having

C P <1) 1 notably remarkable insecticidal properties.

S ~ ^ '3 The following examples illustrate the invention, without however the

H3C limit.

640 505

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Example 1:

Racemic methyl transspiro- [2,4] -heptane-2- (2-methyl-1-propenyl) -l-carboxylate a) Isopropylidenetriphenylphosphonium s ylide solution

In 120 cm3 of tetrahydrofuran, 14 g of triphenylisopropylphosphonium iodide are introduced, slowly added, under a nitrogen atmosphere, 1.98 g of butyllithium in solution in hexane and observes the characteristic coloring of the ylide (solution A) .

10

b) Cyclopentylidenemethyltriphenylphosphonium ylide solution

In 120 cm3 of tetrahydrofuran, 13.8 g of pentylidenemethyltriphenylphosphonium bromide are introduced, slowly added, under a nitrogen atmosphere, 1.98 g of butyllithium in solution in hexane and observes the characteristic coloring of the ylide (so- 15 • issue B).

c) Reaction

In the solution of ylide obtained in paragraph a (solution A), the following is introduced, drop by drop, while maintaining the temperature at 20

—78 ° C, 3.42 g of methyl l-formylbut-2-enoate, observes a total and instantaneous discoloration of the ylide solution, add, drop by drop, at - 78 ° C, the ylide solution obtained in paragraph b (solution B), allows the temperature of the reaction mixture to rise, observes a sudden discoloration at -30 ° C, stirred for 2 h at 25 ° C, added 10 cm3 of water, stirred, extracted the aqueous phase with ether,

wash the organic phase with water, with a saturated aqueous solution of sodium chloride, dry, concentrate to dryness by distillation under reduced pressure, chromatograph the residue on silica gel, eluting with a mixture of ether and pentane (5 / 95) and obtains 3.3 g of methyl spiro- [2,4] - (2-methyl-1-propenyl) -1-carboxylate.

Example 2:

Racemic methyl trans-2,2-dimethyl-3-cyclopentylidenemethylcyclopropane-1-carboxy-late

The ylide solutions (solutions A and B) are prepared as in paragraphs a and b of Example 1.

3.42 g of l-formylbut-2-enoate are introduced dropwise into the ylide solution obtained in paragraph b of Example 1 (solution B), while maintaining the temperature at -78 ° C. methyl, observe a total and instantaneous discoloration of the ylide solution, add, drop by drop, at -78 ° C the ylide solution obtained in paragraph a of Example 1 (solution A), allow the temperature of the reaction mixture, observe abrupt discoloration at - 30 ° C, stir for 2 h at 20 ° C, add 10 cm3 of water, stir, extract the aqueous phase with ether, wash the organic phase with water using a saturated aqueous sodium chloride solution, dry, concentrated to dryness by distillation under reduced pressure, chromatograph the residue on silica gel, eluting with a mixture of ether and pentane (5/95) and obtained 2.8 g of 2 , Methyl-2-dimethyl-3-cyclopentylidenemethylcycloprop-ane-1-carboxylate.

R