WO2012150208A1 - Use of substituted benzyl alcohol esters of cyclopropanecarboxylic acid for controlling insecticide-resistant insects - Google Patents

Abstract

The present application relates to the use of substituted benzyl alcohol esters of cyclopropanecarboxylic acid for controlling insecticide-resistant insects.

Description

 Use of substituted benzyl alcohol esters of cyclopropanecarboxylic acid for controlling insecticide-resistant insects

The present application relates to the use of substituted benzyl alcohol esters of cyclopropanecarboxylic acid for controlling insecticide-resistant insects. Resistance can be defined as an "inheritable change in the sensitivity of a pest population that is reflected in the repeated failure of a product to achieve the expected level of control when used against the pest species, according to the manufacturer's instructions." (Insecticide Resistance Action Committee, IRAC, www Cross resistance occurs when resistance to one insecticide also leads to resistance to another insecticide, even if the insect has not come into contact with the latter due to the size and rapid generation sequence of populations of animal pests the risk of developing insecticide resistance, especially if insecticides are used incorrectly or too highly.

After introduction of synthetic organic insecticides in the 1940s, eg. DDT, it did not take long before the first cases of resistance were observed and already in 1947 resistance to DDT in houseflies was confirmed. Two to 20 years after the introduction of each new insecticide class (cyclodienes, organophosphates, carbamates, formamidines, pyrethroids, spinosyns, neonicotinoids, and even Bacillus thuringensis), resistance was found in a number of key pest species (www, irac-online, or g).

There are several mechanisms of resistance development. The most common is metabolic resistance. For example, resistant insects can detoxify or destroy the insecticide faster, or they excrete it faster than normal sensitive insects. Insects use their internal enzyme systems to break down insecticides. Resistant insects have increased levels or more efficient forms of these enzymes. In addition to their higher efficiency, these enzymes can also have a broad spectrum of activity, ie reduce several different insecticides. Metabolic resistance depends on the structure of the drug. Therefore, metabolic resistance is most likely to be disrupted by drugs of different chemical structure. The second most common mechanism of resistance is a change in the target structure (protein, receptor, ion channel, etc.) of the insecticide. The insecticidal action is reduced by a change in the binding site, these are usually point mutations that are inherited to the coming generations. In addition, there is still resistance through behavioral change (resistant insects recognize the danger and avoid the insecticide) and penetration resistance (the outer shell of the insect develops barriers that slow down the penetration of insecticides into the body of insects). Frequently one finds in resistant pests also a combination of several of these resistance mechanisms. - -

Insecticide resistance management (IRM) is an important agricultural task and is recommended as a critical component of integrated pest management (IPM). The most important measure under the IRM is to reduce the selection pressure in favor of resistant pests. This is achieved by using different chemical classes of insecticides and different mechanisms of action in turn, which slows down the development of resistance or can be completely prevented.

Whether a resistance mechanism responsible for the resistance of a pest to a particular insecticide makes this pest resistant to a new insecticide (cross-resistance) is difficult to predict due to the various mechanisms of resistance. In particular, in cases where the mechanism of action of the novel insecticide is unknown or in which resistance is mediated by mechanisms other than alteration of the binding site, for example by metabolic resistance, it is difficult to predict cross-resistance. There is therefore a great need for methods for the control of animal pests in relation to one or more classes of insecticides, in particular cyclodienes, organophosphates, carbamates, formamidines, pyrethroids, spinosynes, neonicotinoids, insect growth regulators and antifeedants (substances which prevent a pest from eating) are resistant.

The object of the present invention was to provide a class of compounds for controlling insecticide-resistant insects, in particular from the family of Culicidae. The problem is solved, as well as other tasks not explicitly mentioned, which can be derived or deduced from the relationships discussed herein, by the use of the compounds of the formula

(I)

worin

wherein

Q is a radical of the formula (L I)

stands in which is alkyl, alkoxy, haloalkyl, alkylthio, alkylsulfoxyl, alkylsulfonyl, haloalkoxy, haloalkylthio, haloalkylsulfoxyl, haloalkylsulfonyl, alkylamino, dialkylamino, cyano, halogen or hydroxy and p is a number from 0 to 2, optionally substituted hetaryl, preferably pyridine-2 -yl or pyridin-3-yl, or for one of the radicals from the series

steht, worin der Pfeil die Bindung zum benachbarten Ring markiert,

where the arrow marks the bond to the adjacent ring,

Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, Fluorine, bromine, chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino, is methyl, cyano, halogen or haloalkyl, preferably halogen is fluorine, preferably haloalkyl is fluoromethyl, and Yi and Y ₂ are each independently halogen or haloalkyl, preferably halogen is selected from the group of bromine or chlorine, preferably haloalkyl is trifluoromethyl, for controlling insecticide-resistant insects.

Depending on the nature of the substituents, the compounds of the formula (I) can also be present in different compositions as optical isomers or mixtures of isomers, which can optionally be separated in a customary manner.

Possible configuration of the compounds of the formula (I) are described by the formulas (I-a) to (I-d) shown below:

(I-c) (I-d) in which the radicals Yi, Y2, and Q have the abovementioned meanings.

The compounds of the formulas (I-a), (I-b), (I-c) or (I-d) can be present both as mixtures and in the form of their pure isomers. If desired, mixtures of the compounds of the formulas (I-a), (I-b), (Ic) or (I-d) can be separated by physical methods, for example by chromatographic methods.

For reasons of clarity, only the structural formula (I) without the above-described stereochemistry will be shown in the following. However, this includes that the compound in question may optionally be present as isomer mixture (I-a), (I-b), (I-c) or (I-d) or in the other isomeric form.

in welcher Furthermore, it has been found that the novel compounds of the formula (I) can be obtained when compounds of the general formula (II)

in which

Yi and Y2 are each independently halogen or haloalkyl, preferably halogen is selected from the group of bromine or chlorine, preferably haloalkyl is trifluoromethyl and

LG for an in situ generated nucleofuge leaving group, is, a) in a first reaction step with compounds of the general formula (ΠΙ-Α)

in welcher

in which

Hal is halogen, such as iodine or bromine, preferably iodine,

Z is alkyl, alkoxy, haloalkyl, alkylthio, alkylsulfoxyl, alkylsulfonyl, haloalkoxy, haloalkylthio, haloalkylsulfoxyl, haloalkylsulfonyl, alkylamino, dialkylamino, cyano, halogen or hydroxy and p is a number from 0 to 2,

R 2 is methyl, cyano, halogen or haloalkyl, preferably halogen is fluorine, preferably haloalkyl is fluoromethyl, if appropriate in the presence of a suitable acid binder and if appropriate in the presence of a suitable diluent to give compounds of the general formula (IA) - -

 (I-A)

in which

Hal is halogen, such as iodine or bromine, preferably iodine,

Z and p have the meaning given above,

in welcher R _{2 is} methyl, cyano, halogen or haloalkyl, preferably halogen is fluorine, haloalkyl is preferably reacted for fluoromethyl, which is then reacted in a second reaction step in a coupling reaction with (hetero) arylboronic acids (R = H) or their derivatives (R = Alkylene) of the general formula (IV)

in which

R is hydrogen or alkylene and

Ri is optionally substituted hetaryl, preferably pyridin-2-yl or pyridin-3-yl, or one of the radicals from the series

steht, worin der Pfeil die Bindung zum benachbarten Ring markiert,

where the arrow marks the bond to the adjacent ring,

Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halogenocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfmyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, fluoro, Bromine, chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino are optionally reacted in the presence of a suitable transition metal catalyst and optionally in the presence of a suitable diluent, or

b) with compounds of the general formula

 (III-B) in which

Z, p and Ri have the meaning given above, R _{2 is} methyl, cyano, halogen or haloalkyl, preferably halogen is fluorine, preferably haloalkyl is fluoromethyl, if appropriate in the presence of a suitable acid binder and optionally in the presence of a suitable diluent. Finally, it has been found that the novel compounds of the formula (I) have pronounced biological properties and, above all, for controlling animal pests, in particular insects, arachnids and nematodes, which are used in agriculture, in forestry, in the protection of stored products and materials, and on the hygiene sector are suitable.

The compounds of the invention are generally defined by the formula (I). Preferred substituents or ranges of the radicals listed in the formulas mentioned above and below are explained below.

In a preferred embodiment, the compound has the general formula (1-2)

is alkyl, alkoxy, haloalkyl, alkylthio, alkylsulfoxyl, alkylsulfonyl, haloalkoxy, haloalkylthio, haloalkylsulfoxyl, haloalkylsulfonyl, alkylamino, dialkylamino, cyano, halogen or hydroxy and p is a number from 0 to 2, Ri is one of the radicals from line

- -

steht, worin der Pfeil die Bindung zum benachbarten Ring markiert, bevorzugt Ri für einen der Reste ausgewählt aus der Gruppe (A), (B), (C), (D), (F), (G), (H), (M) und (T) steht und

in which the arrow marks the bond to the adjacent ring, preferably R 1 represents one of the radicals selected from the group (A), (B), (C), (D), (F), (G), (H), (M) and (T) stands and

Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halogenocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, fluoro, Bromine, chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino and

R _{2 is} methyl, fluorine or fluoromethyl,

Yi and Y _{2 are} bromine, chlorine or trifluoromethyl.

In a particularly preferred embodiment, the compounds have the general formula (1.3) or (1.4):

in welcher - - für Alkyl, Alkoxy, Halogenalkyl, Alkylthio, Alkylsulfoxyl, Alkylsulfonyl, Halogenalkoxy, Halo- genalkylthio, Halogenalkylsulfoxyl, Halogenalkylsulfonyl, Alkylamino, Dialkylamino, Cyan, Halogen oder Hydroxy steht und p eine Zahl von 0 bis 2 ist, für einen der Reste aus der Reihe

in which - - is alkyl, alkoxy, haloalkyl, alkylthio, alkylsulfoxyl, alkylsulfonyl, haloalkoxy, halo genalkylthio, haloalkylsulfoxyl, haloalkylsulfonyl, alkylamino, dialkylamino, cyano, halogen or hydroxy and p is a number from 0 to 2, for one of the radicals the series

steht, worin der Pfeil die Bindung zum benachbarten Ring markiert, bevorzugt Ri für einen der Reste ausgewählt aus der Gruppe (A), (B), (C), (D), (F), (G), (H), (M) und (T) steht und

in which the arrow marks the bond to the adjacent ring, preferably R 1 represents one of the radicals selected from the group (A), (B), (C), (D), (F), (G), (H), (M) and (T) stands and

Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halogenocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfmyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, fluorine, bromine, Chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino,

R 2 is methyl, fluorine or fluoromethyl. In a very particularly preferred embodiment, the compounds have the general formula (1.5) or (1.6)

for one of the leftovers

steht, worin der Pfeil die Bindung zum benachbarten Ring markiert, bevorzugt Ri für einen der Reste ausgewählt aus der Gruppe (A), (B), (C), (D), (F), (G), (H), (M) und (T) steht und

in which the arrow marks the bond to the adjacent ring, preferably R 1 represents one of the radicals selected from the group (A), (B), (C), (D), (F), (G), (H), (M) and (T) stands and

Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halogenocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfmyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, fluoro, Bromine, chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino and

R _{2 is} methyl, fluorine or fluoromethyl. In a further preferred embodiment, the compound has the general formula (1.7)

in which

Ri for one of the leftovers

steht, worin der Pfeil die Bindung zum benachbarten Ring markiert und

wherein the arrow marks the bond to the adjacent ring and

Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halogenocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfmyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, fluoro, Bromine, chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino, stands for methyl, fluorine or fluoromethyl and

Yi and Y _{2 are} bromine, chlorine or trifluoromethyl. - -

In a particularly preferred embodiment, the compounds have the general formula (1.8) and (1.9),

 (1.8) (1.9) in which

Ri for one of the leftovers

steht, bevorzugt Ri für einen der Reste ausgewählt aus der Gruppe (A), (B), (C), (D), (F), (G), (H), (M) und (T) steht, worin der Pfeil die Bindung zum benachbarten Ring markiert und

Ri preferably represents one of the radicals selected from the group consisting of (A), (B), (C), (D), (F), (G), (H), (M) and (T), in which the arrow marks the binding to the adjacent ring and

Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halogenocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfmyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, fluoro, Bromine, chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino, preferably stand for fluorine and

R _{2 is} methyl, fluorine or fluoromethyl. Further very particularly preferred substituents of the radicals listed in the compounds of the formula (I) are explained in Table 1.

 Table 1: Very particularly preferred compounds of the formula (I)

- 5 -

- 5 -

- - Very particularly preferred compounds of the formula (LI) are the following compounds:

- -

Erfindungsgemäß besonders bevorzugt werden Verbindungen der Formel (I), in welchen eine Kombination der vorstehend als besonders bevorzugt aufgeführten Bedeutungen vorliegt.

Particular preference according to the invention is given to compounds of the formula (I) in which a combination of the meanings listed above as being particularly preferred is present.

Very particular preference according to the invention is given to compounds of the formula (I) which contain a combination of the meanings given above as being very particularly preferred.

If Y 1, Y 2, M, p, R 1 and R 2 have the meanings given above, then the compounds of the formula (I) according to the invention can be prepared according to the reaction steps A to D according to Methods I and II shown in Reaction Scheme I.

- 7 -

Reaction scheme I

Is in the inventive method for the preparation of the novel compounds of formula (I) according to Method I as the compound of formula (II), the (lR, 3R) -3- (2,2-dibromoethyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride and used as the compound of the formula (III-A, R2 = F, Hal = I, p = 1, Z = H), for example (2-fluoro-3-iodo-phenyl) -methanol, is obtained by the preparation process (step D) first a compound of the formula (IA, R ₂ = F, Hal = I, p = 1, Z = H), for example, the (1R, 3R) -3- (2,2-dibromoethyl) -2,2-dimethyl cyclopropanecarboxylic acid 2-fluoro-3-iodo-benzyl ester (see Reaction Scheme II). Reaction scheme II

The subsequent second reaction step with the (1R, 3R) -3- (2,2-dibromoethyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2-fluoro-3-iodo-benzyl ester using a compound of the formula (A-4) , For example, 4-trifluoromethylphenyl-boronic acid, according to the manufacturing method (step E) is represented by the reaction scheme V mentioned below (see Preparation Examples, Example 1).

If, however, in the process according to the invention for the preparation of the novel compounds of the formula (I) according to method II as the compound of the formula (II) the (1R, 3R) -3- (2,2-dibromoethyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride and as the compound of the formula (III-B, R2 = F, p = 1, Z = H, Ri = 3,5-difluorophenyl), for example (2-fluoro-3 ', 5'-difluoro-1, -biphenyl] methanol, the preparation process (stage D) can be represented by the reaction scheme III (see Preparation Examples, Example 35).

Reaction scheme III

The compounds required as starting materials for preparing the process according to the invention (stage D, E) are generally defined by the formulas (II) and (III-B) / (III-A).

In these formulas (II) and (III-B) / (III-A) Yi, Y ₂ , Z, p, Ri and R _{2 are} preferably those radicals which have already been described in connection with the description of the compounds of the general formula (I) are mentioned as preferred substituents.

The compounds of formula (II) may, for. T. commercially or by literature methods according to the reaction scheme I (step C, method I, II) are obtained from the corresponding 2,2-dimethyl-cyclopropanecarboxylic acids (A-l) (see also Preparation Example 1, step D).

For example, the cyclopropanecarboxylic acids (Al) are known: Yi, Y 2 = Br, 3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (DE-OS 2544150), (IR, 3R) -3- (2 , 2-dibromo-ethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (M. Elliott et al., Pestic. Sci. 1975, 6, 537-542), (1R, 3S) - 3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (GB 1,446,304), (IS, 3S) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (DE-OS 2544150), for Yi = CF3; Y 2 = Cl, 3- (2-chloro-3,3,3-trifluoro-1-propen-1-yl) -2,2-dimethyl-cyclopropanecarboxylic acid (GB 2085000), (IR, 3R) -3- [( l) -2-chloro-3,3,3-trifluoro-1-propen-1-yl] -2,2-dimethyl-cyclopropane-carboxylic acid, trans-2> - {2-cor-3,3,3 trifluoro-1-propen-1-yl) -2,2-dimethyl-cyclopropane-carboxylic acid and (1S, 3S) -3- (2-chloro-3,3,3-trifluoro-1-propen-1-yl ) -2,2-dimethyl-cyclopropane-carboxylic acid, (DE-OS 2802962).

In the formulas (II) and LG, LG stands for an in situ generated nucleofuge leaving group ("Leaving Group"). - -

Examples of compounds of the formula (II) having a nucleofugic leaving group LG are known; For example, the cyclopropanecarboxylic acid halides (II): with LG = Cl and Yi, Y2 = Br, 3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanoic acid chloride (DE-OS 2544150), (lR, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanoic acid chloride (US 4,342,770); with LG = Br and Yi, Y2 = Br, (1R-cw) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanoic acid bromide (FR 2407200); with LG = F and Yi, Y2 = Br, (IR-di ') - 3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropane-acid fluoride (FR 2407200); with LG = Cl and Yi = CF ₃ ; Y ₂ = Cl, 3- (2-chloro-3,3,3-trifluoro-1-propen-1-yl) -2,2-dimethylcyclopropanecarboxylic acid chloride (S.J.Xue et al., Yingyong Huaxue 2004, 21, 319-321; ref CAS 131: 190516, 2004), (IR, 3R) -3 - [(1 Z) -2-chloro-3,3,3-trifluoro-1-propen-1-yl] - 2,2-dimethylcyclopropanecarboxylic acid chloride (WO 2003/053905).

Alternatively, the reaction of compounds of the formula (II) with the compounds of the formula (III-B) / (III-A) can also be carried out in the presence of a coupling agent for the carboxylic acid and optionally in the presence of a basic reaction auxiliary in one of the diluents given below , Suitable coupling agents for carrying out the preparation process are all those which are suitable for the preparation of an amide bond (cf., for example, Houben-Weyl, Methoden der Organischen Chemie, Volume 15/2; Bodansky et al., Peptide Synthesis 2 ^nd ed. (Wiley & Sons, New York 1976) or Gross, Meienhofer, The Peptides: Analysis, Synthesis, Biology (Academic Press, New York 1979).

Some of the compounds of the formula (III-B) / (III-A) are known or can be prepared by methods known from the literature in accordance with Reaction Scheme I (stages A and B, see Preparation Example 1 or Steps A, E and B; Production Example 35).

If, for example, in the compounds of the formula (III-B) the radical R 1 is aryl or hetaryl, the radical R _{2 is} fluorine or fluoromethyl (-CH ₂ -F) and Z and p have the meaning mentioned above, this is correspondingly substituted 2-fluoro-benzyl alcohols or 2-fluoromethyl-benzyl alcohols.

If, for example, in the compounds of the formula (ΙΠ-Α) Z and p have the abovementioned meaning, they are correspondingly substituted 2-fluoro-3-halogeno-benzyl alcohols or 2-fluoromethyl-3-halo-benzyl alcohols.

For example, compounds of the general formula (III-B) which are known are 2,4,5,6-tetrafluoro- [1,1-biphenyl] -3-methanol (US Pat. No. 4,329,518), 2,4,6-trifluoro [ 1, 1'-biphenyl] -3-methanol (US 4,402,973), 2-fluoro-2 ', 6'-dimethyl- [1, 1'-biphenyl] -3-methanol (WO 2007/123225) or 2-fluoro 3 ', 5'-difluoro [1, 1'-biphenyl] -3-methanol (see Preparation Example 35, Method II, Step B). - -

In addition, as compounds of general formula (ΠΙ-Α) known: (2-fluoro-3-iodo-phenyl) methanol (WO 2009/132774), (2-fluoro-3-iodo-4-methyl-phenyl) methanol (US Pat. No. 7,759,337), (4-chloro-2-fluoro-3-iodo-phenyl) -methanol (WO 2006/094187) and 2,4-difluoro-3-iodo-phenyl) -methanol (cf. Preparation Example 1, Method I, Stage B). The compounds of the formula (III-B) / (III-A) can be obtained by known preparation methods, for example by reduction of the ester function from optionally substituted benzenecarboxylic acid esters (A-5) or from optionally substituted 3-halobenzoic acids (A-3).

Suitable reducing agents for the reduction of a carbonyl group are a wide variety of hydrogenating reagents, such as alkali metal hydrides, in particular sodium borohydride (NaBH i), lithium borohydride (L1BH4), lithium aluminum hydride (L1AIH4), lithium triethylborohydride (Li [Et3BH]), lithium tricarboxylic (Li [, yeoBu3BH], sodium bis (2-methoxyethoxy) aluminum hydride, alkylaluminum hydrides, in particular diisobutylaluminum hydride (DIBAL-H), or tetramethylammonium triacetoxyborohydride, inter alia, in question (see H. de Koning, WN Houben-Weyl E 21, p 1953 and references therein). of course, a "borohydride resin", for example "borohydride on Amberlite ^® IRA-406", are used for the hydrogenation (cf.. AR Sande et al. Tetrahedron Lett. 1984, 25, 3501).

However, preference is given to using alkali metal hydrides, in particular sodium borohydride (NaBH4) or lithium borohydride (L1BH4) (compare Preparation Example 1, Stage A).

If, for example, in the compounds (A-5) the radical R 1 is aryl or hetaryl and / or in the compounds (A-3) Z and p have the meaning mentioned above, these are correspondingly substituted 2-halo-benzoic acid esters (R ₂ = halogen) or 2-haloalkyl-benzoic acid ester (R ₂ = halomethyl), which can be obtained by known preparation methods.

For example, the halogenated benzoic acid esters of the formula (A-5), 2,3 ', 5'-trifluoro [l, - biphenyl] -3-carboxylic acid methyl ester (R ₂ = F), 6-fluoro-2-fluoromethyl [l , 1'-biphenyl] -3-carboxylic acid methyl ester (R ₂ = CH ₂ -F) and 2-bromomethyl-6-fluoro- [l, r-biphenyl] -3-carboxylic acid methyl ester (R ₂ = CH ₂ - Br) in the preparation examples.

Furthermore, the 2-haloalkyl-benzoic acid esters (R ₂ = halomethyl), in particular the 2-bromomethyl-benzoic acid ester (R ₂ = CH ₂ -Br) and 2-fluoromethyl-benzoic acid ester (R ₂ = CH ₂ -F), according to the Reaction scheme IV can be obtained. - -

Reaction scheme IV

In this case, the 2-bromomethyl-benzoic acid esters of the formulas (A-3a) and (A-5a) are first prepared from the optionally substituted 2-methyl-benzoic acid esters of the formulas (A-6) and (A-7) by means of radical bromination, the then in the presence of a suitable fluorinating agent in the 2-bromomethyl-benzoic acid ester of the formulas (A-3b) and (A-5b) can be converted (see Preparation Examples).

In a typical reaction of the radical halogenation, a suitable halogenating agent such as sodium hypochlorite (Hai = chlorine), N-halo-succinimide (Hai = bromine, chlorine) or chloramine-T (Hai = chlorine) with optionally substituted 2-methyl benzoic acid esters of the formulas (A-6) and (A-7) in one or more diluents and in the presence of a suitable catalyst, for example UV light, peroxides, azo-fc-isobuyronitrile (AIBN) or zirconium (IV) chloride (ZrC ) (see reaction scheme IV).

For the preparation of the 2-bromomethyl-benzoic acid esters of the formulas (A-3b) and (A-5b) it is preferred to use N-bromosuccinimide (NB S) and catalysts such as Azo in halogenated aromatic solvents, for example trifluorotoloul, and in the presence of the halogenating agent bis-isobuyronitrile (AIBN) or zirconium (IV) chloride (ZrCl) at 100 ° C to 105 ° C.

Certain substituted 2-methylbenzoic acid esters of the formulas (A-6) and (A-7) have already been disclosed, for example: 2-methyl-6- (methylsulfonyl) - [1,1'-biphenyl] -3-carboxylic acid methyl ester (JP 11193259) or 2-methyl-4- (methylsulfonyl) -3- (2-thienyl) benzoic acid methyl ester (WO 9626193). In addition, the preparation of the 6-fluoro-2-methyl- [l, l'-biphenyl] -3-carboxylic acid methyl ester in Preparation Example 54 is described.

The optionally substituted 2-fluoro-benzoic acid esters (A-5) are selected from the halogenated benzoic acid esters of the formula (A-3, Hai = I) and the (hetero) arylboronic acids (R = H) or their derivatives (R = alkylene) of the formula (A-4), for example by means of a suitable coupling reaction, for example the palladium-catalyzed cross-coupling (Suzuki coupling; H.-J. Wang et al., Tetrahedron Lett. 2005, 46, 2631-2634 and references cited therein), in the presence of suitable transition metal catalysts (compare Preparation Example 35, Method II, Step E).

In an analogous manner and using a suitable coupling reaction (eg Suzuki coupling in the presence of suitable transition metal catalysts, see Reaction Scheme I, Stefe E), the compounds of general formula (I) can also be prepared from the compounds of general formula (IA) and the (hetero) arylboronic acids (R = H) or their derivatives (R = alkylene) of the formula (A-4).

In the process according to the invention for preparing the novel compounds of the formula (I) according to Method I as compound of the formula (IA), the (1R, 3R) -3- (2,2-dibromoethyl) -2,2-dimethylcyclopropanecarboxylic acid 2-fluoro-3-iodo-benzyl ester (see Reaction Scheme II) and 4-trifluoromethylphenylboronic acid used as the compound of formula (A-4), according to step E, the (1R, 3R) -3 (2,2- Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoro-4'-trifluoromethyl- [1, Γ-biphenyl] -3-yl) methyl ester (see Reaction Scheme V and Preparation Examples, Example 1).

Reaction scheme V

The used (hetero) arylboronic acids (R = H) or their derivatives (R = alkylene) of the formula (A-4) are commercially available or can be obtained by known preparation methods.

Known halogenated benzoic acid esters of the formula (A-3) are, for example: for R2 = F, 2-fluoro-3-iodo-4-methylbenzoic acid methyl ester (WO 1010/030592), 2,4,5-trifluoro-3-iodo ethyl benzoate (WO 98/07682) and methyl 2,6-difluoro-3-iodo-benzoate (WO 2009/076747); for R ₂ = CH ₂ -Br, 2-bromomethyl-3-iodo-benzoic acid methyl ester (WO 2007/090068). In addition, preparation routes for 2-fluoro-3-iodo-benzoic acid methyl ester and 2-fluoro-methyl-3-iodo-benzoic acid methyl ester are described in the Preparatory Examples.

The preparation of the halogenated benzoic acid esters of the formula (A-3) is possible by known process methods from optionally substituted 3-halobenzoic acids of the general formula (A-2), for example by means of an esterification reaction (compare also Preparation Example 1, Step A) ,

Certain substituted benzoic acid esters of the formula (A-2) have already become known, for example: 2-fluoro-3-iodobenzoic acid (WO 2009/132774), 2,6-difluoro-3-iodo-benzoic acid (M. Sato et al. , J. Med. Chem. 2009, 52, 4869-4882), 2,4,5-trifluoro-3-iodo-benzoic acid (EP-A 357 047). In addition, the preparation of 2-fluoro-3-iodo-benzoic acid in Preparation Example 1 is described. - -

Alternatively, the preparation of the halogenated benzoic acid esters of the formula (A-3) can of course also be prepared by known procedures from optionally substituted 3-aminobenzoic acid esters of the general formula (A-8), for example by means of the known Sandmeyer reaction (cf. B. Houben-Weyl, Methods of Organic Chemistry, Volume VIII, page 311) possible (see reaction scheme VI). Reaction scheme VI

In general, it is advantageous to carry out the preparation methods I and II according to the invention in the presence of diluents. Diluents are advantageously used in such an amount that the reaction mixture remains easy to stir throughout the process. Suitable diluents for carrying out the process according to the invention are all inert organic solvents.

Examples are: halogenated hydrocarbons, in particular chlorohydrocarbons, such as tetraethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichlorethylene, pentachloroethane, difluorobenzene, 1, 2-dichloroethane, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene, trichlorobenzene; Alcohols such as methanol, ethanol, isopropanol, butanol; Ethers, such as ethyl propyl ether, methyl tert-butyl ether, n-butyl ether, anisole, phenol, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl ether and polyether of Ethylene oxide and / or propylene oxide; Amines such as trimethyl, triethyl, tripropyl, tributylamine, N-methylmorpholine, pyridine and tetramethylenediamine; Nitrocarbons such as nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene, o-nitrotoluene; Nitriles, such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile, m-chlorobenzonitrile, and also compounds such as tetrahydrothiophene dioxide and dimethyl sulfoxide, tetramethylene sulfoxide, dipropyl sulfoxide, benzylmethyl sulfoxide, diisobutyl sulfoxide, dibutyl sulfoxide, diiso amyl sulfoxide; Sulfones such as dimethyl, diethyl, dipropyl, dibutyl, diphenyl, dihexyl, methylethyl, ethylpropyl, ethylisobutyl and pentamethylene sulfone; aliphatic, cycloaliphatic or aromatic hydrocarbons, such as pentane, hexane, heptane, octane, nonane and technical hydrocarbons; For example, so-called white spirits with components with boiling points in the range, for example, from 40 ° C to 250 ° C, cymene, gasoline fractions within a boiling interval of 70 ° C to 190 ° C, cyclohexane, methylcyclohexane, petroleum ether, ligroin, octane, benzene, toluene, chlorobenzene , Bromobenzene, nitrobenzene, xylene; Esters such as methyl, ethyl, butyl, isobutyl acetate, as well as dimethyl, dibutyl, ethylenecarbonate; Amides such as hexamethylenephosphoric triamide, formamide, N-methylformamide, N, N-dimethylformamide, NN-dipropylformamide, NN-dibutylformamide, N-methylpyrrolidine, N-methyl- - - caprolactam, 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidine, octylpyrrolidone, octylcaprolactam, 1,3-dimethyl-2-imidazolinedione, N-formyl-piperidine, NN'- l, 4-diformyl-piperazine; Ketones such as acetone, acetophenone, methyl ethyl ketone, methyl butyl ketone.

Mixtures of the solvents and diluents mentioned can also be used for the processes according to the invention.

Preferred diluents for carrying out the process according to the invention are halogenated hydrocarbons, in particular chlorohydrocarbons, such as tetraethylene, tetrachloroethane, dichloroprone, methylene chloride, dichlorobutane or chloroform, in particular methylene chloride.

The preparation of compounds of the formula (I) according to the preparation processes is carried out by reacting compounds of the formula (II) in the presence of compounds of the formula (IA) [Method I] or of the formula (III-B) [Method II], optionally in The presence of an acid binder and, if appropriate, be reacted in one of the diluents mentioned.

The reaction time is generally 10 minutes to 48 hours. The reaction takes place at temperatures between -10 ° C. and + 200 ° C., preferably between + 10 ° C. and 120 ° C., more preferably at room temperature.

It can be worked under normal pressure in principle. Preferably, working at atmospheric pressure or at pressures up to 15 bar and optionally under a protective gas atmosphere (nitrogen, helium or argon).

For carrying out the process according to the invention, in general from 0.5 to 4.0 mol, preferably from 0.7 to 3.0 mol, particularly preferably from 1.0 to 2.0 mol, of compounds of the formula ## STR3 ## per mole of compound of the general formula (II) (IA) [Method I] or the formula (III-B) [Method II] used.

Furthermore, it is advantageous to carry out the preparation process in the presence of basic reaction auxiliaries (acid binders).

As basic reaction auxiliaries for carrying out the process according to the invention, it is possible to use all suitable acid binders, such as amines, in particular tertiary amines and also alkali metal and alkaline earth metal compounds.

Examples include the hydroxides, hydrides, oxides and carbonates of lithium, sodium, potassium, magnesium, calcium and barium, as well as further basic compounds such as amidine bases or guanidine bis-ene 7-methyl-l, 5,7-triaza- bicyclo (4.4.0) dec-5-ene (MTBD); Diazabicyclo (4.3.0) nonene (DBN), diazabicyclo (2.2.2) octane (DABCO), 1,8-diazabicyclo (5.4.0) undecene (DBU), cyclohexyltetrabutyl-guanidine (CyTBG), cyclohexyltetramethylguanidine (CyTMG) , Ν, Ν, Ν, Ν-tetramethyl-l, 8-naphthalenediamine, pentamethylpiperidine, tertiary amines such as triethylamine, trimethyl - 5 - amine, tribenzylamine, triisopropylamine, tributylamine, tricyclohexylamine, triamylamine, trihexylamine, N, N-dimethylaniline, Ν, Ν-dimethyl-toluidine, N, N-dimethyl-p-aminopyridine, N-methyl-pyrrolidine, N-methyl -piperidine, N-methyl-imidazole, N-methyl-pyrazole, N-methyl-morpholine, N-methyl-hexamethylenediamine, pyridine, 4-pyrrolidinopyridine, 4-dimethylaminopyridine, quinoline, α-picoline, β-picoline, isoquinoline , Pyrimidine, acridine, Ν, Ν, Ν ', Ν'-tetramethylenediamine, Ν, Ν', Ν'-tetraethylenediamine, quinoxaline, N-propyl-diisopropylamine, N-ethyl-diisopropylamine, N, N'-dimethyl-cyclohexylamine, 2,6-lutidine, 2,4-lutidine or triethyldiamine.

Preferably tertiary amines such as trimethylamine, triethylamine, N-ethyl-N, N-diisopropylamine or aromatic amines such as pyridine, 4-pyrrolidinopyridine, 4-dimethylamino-pyridine, quinoline, a-picoline, ß-picoline, in particular pyridine use.

The preparation of compounds of the formula (I) according to Preparation Method I (Step E) is carried out by reacting compounds of the formula (IA) in the presence of compounds of the formula (A-4) by means of a palladium-catalyzed cross-coupling reaction (Suzuki coupling), in the presence of suitable transition metal catalysts and in the presence of one of the specified diluents.

The reaction time is generally 10 minutes to 48 hours. The reaction takes place at temperatures between -10 ° C and + 200 ° C, preferably between + 10 ° C and 150 ° C, more preferably 60 ° C to 120 ° C.

It can be worked under normal pressure in principle. Preference is given to working at atmospheric pressure or at pressures of up to 15 bar and, if appropriate, under a protective gas atmosphere (nitrogen, helium or argon).

For carrying out the process according to the invention, in general from 0.5 to 4.0 mol, preferably from 0.7 to 3.0 mol, particularly preferably from 1.0 to 2.0 mol, of compounds of the formula ## STR9 ## per mole of compound of the general formula (IA) (A-4). Furthermore, to carry out the process according to the invention per mole of compound of the general formula (I-A) generally 0.01 to 0.04 mol, preferably 0.01 to 0.03 mol, particularly preferably 0.02 mol of transition metal catalyst.

Particular preference is given to using suitable palladium catalysts, for example palladium (II) acetate [Pd (ac) 2] or [1,1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) [PdCb (dppf)].

In the case of palladium-catalyzed cross-coupling (Suzuki coupling) with palladium (II) acetate [Pd (ac) 2], it is advantageous to carry this out in the presence of triarylphosphines, for example triphenylphosphine. to lead. In general, from 0.01 to 0.07 mol, preferably from 0.02 to 0.06 mol, particularly preferably from 0.04 to 0.05 mol, of triphenylphosphine are used per mole of compound of the general formula (IA).

Furthermore, it is advantageous to carry out the palladium-catalyzed cross-coupling (Suzuki coupling) in the presence of suitable alkali metal salts, for example potassium phosphate.

After completion of the reaction, the entire reaction mixture is concentrated. The products obtained after working up can be purified in a customary manner by recrystallization, vacuum distillation or column chromatography (see also the Preparation Examples).

Depending on the nature of the substituents, the compounds according to the invention can be present as geometric and / or as optically active isomers or corresponding isomer mixtures in different compositions. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers or geometric isomers. The invention thus comprises pure stereoisomers as well as any mixtures of these isomers.

The compounds of the invention may optionally be present in different polymorphic forms or as a mixture of different polymorphic forms. Both the pure polymorphs and the polymorph mixtures are the subject of the invention and can be used according to the invention.

Depending on the nature of the substituents, the compounds according to the invention can be present as geometrical and / or as optically active isomers or corresponding isomer mixtures in a different composition. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers or geometric isomers. The invention thus comprises pure stereoisomers as well as any mixtures of these isomers.

The active compounds according to the invention are suitable for plant protection, favorable warm-blooded toxicity and good environmental compatibility for the protection of plants and plant organs, for increasing crop yields, improving the quality of the crop and for controlling animal pests, in particular insects, arachnids, helminths, nematodes and molluscs found in agriculture, horticulture, livestock, forests, gardens and recreational facilities, in supplies and materials, and in the hygiene sector. They can preferably be used as crop protection agents. They are effective against normally sensitive and resistant species as well as against all or individual stages of development. The above mentioned pests include:

From the order of the Anoplura (Phthiraptera) eg Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Trichodectes spp. - 7 -

Pests of the Arthropoda strain, in particular of the class Arachnida, e.g. Acarus spp., Aceria sheldoni, Aculops spp., Aculus spp., Amblyomma spp., Amphitetranychus viennensis, Argas spp., Boophilus spp., Brevipalpus spp., Bryobia graminum, Bryobia praetiosa, Centruroides spp., Chorioptes spp. Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermacentor spp., Eotetranychus spp., Epitrimerus pyri, Eutetranychus spp., Eriophyes spp., Glycyphagus domesticus, Halotydeus destructor, Hemitarsonemus spp., Hyalomma spp., Ixodes spp., Latro- dectus spp., Loxosceles spp., Metatetranychus spp., Neutrombicula autumnalis, Nuphersa spp., Oligonychus spp., Ornithodorus spp., Ornithonyssus spp., Panonychus spp., Phyllocoptruta oleivora, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus Spp., Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus, Steneotarsonemus spp., Steneotarsonemus spinki, Tarsonemus spp., Tetranychus spp., Trombicula alfreddugesi, Vaejovis spp., Vasates lycopersici.

From the genus of Chilopoda, e.g. Geophilus spp., Scutigera spp.

From the order or class of collembola e.g. Onychiurus armatus.

From the class of Diplopoda e.g. Blaniulus guttulatus. From the class of Insecta, e.g. from the order of the Blattodea e.g. Blattella asahinai, Blattella germanica, Blatta orientalis, Leucophaea maderae, Panchlora spp., Parcoblatta spp., Periplaneta spp., Supella longipalpa.

From the order Coleoptera eg Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Agelastica alni, Agriotes spp., Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp., Anthrenus spp., Apion spp., Apogonia spp , Atomaria spp., Attagenus spp., Bruchidius obtectus, Bruchus spp., Cassida spp., Cerotoma trifurcata, Ceutorrhynchus spp., Chaetocnema spp., Cleonus mendicus, Conoderus spp., Cosmopolites spp., Costelytra zealandica, Ctenicera spp. Curculio spp., Cryptolestes ferruginus, Cryptorhynchus lapathi, Cylindrocopturus spp., Dermestes spp., Diabrotica spp., Dichocrocis spp., Dicladispa armigera, Diloboderus spp., Epilachna spp., Epitrix spp., Faustinus spp., Gibbium psylloides, Gnathocerus cornutus , Hellula and alis, Heterronychus arator, Heteronyx spp., Hylamorpha elegans, Hylotrupes bajulus, Hypera postica, Hypomeces squamosus, Hypothenemus spp., Lachnosterna consanguinea, Lasioderma serricorne, Latheticus oryzae, Lathridi spp., Lema spp., Leptinotarsa decemlineata, Leucoptera spp., Lissorhoptrus oryzophilus, Lixus spp., Luperodes spp., Lyctus spp., Megascelis spp., Melanotus spp., Meligethes aeneus, Melolontha spp., Migdolus spp. , Monochamus spp., Naupactus xanthographus, Necrobia spp., Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorrhynchus spp., Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Phyllophaga helleri, Phyllotreta spp., Popillia japonica, Premnotrypes spp , Prostephanus truncatus, Psylliodes spp., Ptinus spp., Rhizobius ventralis, Rhizopertha dominica, Sitophilus spp., Sitophilus oryzae, Sphenophorus spp., Stegobium paniceum, Sterile - Nechus spp., Symphyletes spp., Tanymecus spp., Tenebrio molitor, Tenebrioides mauretanicus, Tribolium spp., Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp.

From the order of Diptera e.g. Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Asphondylia spp., Bactrocera spp., Bibio hortulanus, Calliphora erythrocephala, Calliphora vicina, Cerititis capitata, Chironomus spp., Chrysomyia spp., Chrysops spp , Chrysozona pluvialis, Cochliomyia spp., Contarinia spp., Cordylobia anthropophaga, Cricotopus sylvestris, Culex spp., Culicoides spp., Culiseta spp., Cuterebra spp., Dacus oleae, Dasyneura spp., Delia spp., Dermatobia hominis, Drosophila Spp., Echinocnemus spp., Fannia spp., Gasterophilus spp., Glossina spp., Haematopota spp., Hydrellia spp., Hydrellia griseola, Hylemya spp., Hippobosca spp., Hypoderma spp., Liriomyza spp. Lucilla spp. Lutzomyia spp., Mansonia spp., Musca spp., Oestrus spp., Oscinella frit, Paratanytarsus spp., Paralauterbombiella subcincta, Pegomyia spp., Phlebotomus spp., Phorbia spp., Phormia spp., Piophila casei, Prodiplosis spp., Psila rosae, Rhagoletis spp., Sarcophaga spp., Simulium spp, Stomoxys spp., Tabanus spp., Tetanops spp ., Tipula spp ..

From the order of Heteroptera, e.g. Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocris spp., Campylomma livida, Cavelerius spp., Cimex spp., Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp ., Eusystus spp., Eurygaster spp., Heliopeltis spp., Horcias nobilellus, Leptocorisa spp., Leptocorisa varicornis, Leptoglossus phyllopus, Lygus spp., Macropes excavatus, Miridae, Monaionion atratum, Nezara spp., Oebalus spp. , Pentomidae, Piesma quadrata, Piezodorus spp., Psallus spp., Pseudacysta persea, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp.

From the order of Homoptera, for example, Acizzia acaciaebaileyanae, Acizzia dodonaeae, Acizzia uncidae, Acrida turrita, Acyrthosipon spp., Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleyrodes proletella, Aleurolobus barodensis, Aleurothrixus floccosus, Allocaridara malayensis, Amrasca spp , Anuraphis cardui, Aonidiella spp., Aphanostigma piri, Aphis spp., Arboridia apicalis, Arytainilla spp., Aspidiella spp., Aspidiotus spp., Atanus spp., Aulacorthum solani, Bemisia tabaci, Blastopsylla occidentalis, Boreioglycaspis melaleucae, Brachycaudus helichrysi, Brachycolus spp., Brevicoryne brassicae, Cacopsylla spp., Calligypona marginata, Carneocephala fulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., Chaetosiphon fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chondracris rosea, Chromaphis juglandicola, Chrysomphalus ficus, Cicadulina mbila, Coccomytilus halli, Coccus spp., Cryptomyzus ribis, Cryptoneossa spp., Ctenarytaina spp., Dalbulus spp., Dialeurodes citri, Diaph orina citri ,, Diaspis spp., Drosicha spp., Dysaphis spp., Dysmicoccus spp., Empoasca spp., Eriosoma spp., Erythroneura spp., Eucalyptolyma spp., Euphyllura spp., Euscelis bilobatus, Ferrisia spp., Geococcus coffeae, Glycaspis spp., Heteropsylla cubana, Heteropsylla spinulosa, Homalodisca coagulata, Hyalopterus arundinis, Icerya spp., Idiocerus spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp., Lepidosaphes spp., Lipaphis erysimi, Macrosiphum spp., Macrosteies facifrons, Mahanarva spp., Melanaphis sacchari, Metcalfiella spp., Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus - spp., Nasonovia ribisnigri, Nephotettix spp., Nettigoniclla spectra, Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Oxya chinensis, Pachypsylla spp., Parabemisia myricae, Paratrioza spp., Parlatoria spp., Pemphigus spp., Peregrinus maidis, Phenacoccus spp., Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp., Pinnaspis aspidistrae, Planococcus spp., Prosopidopsylla flava, Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp., Psyllopsis spp., Psylla spp., Pteromalus spp., Pyrilla spp , Quadraspidiotus spp., Quesada gigas, Rastrococcus spp., Rhopalosiphum spp., Saissetia spp., Scaphoidus titanus, Schizaphis graminum, Selenaspidus articulatus, Sogata spp., Sogatella furcifera, Sogatodes spp., Stictocephala festina, Siphoninus phillyreae, Tenalaphara malayensis, Tetrago- nocephela spp., Tinocallis caryaefoliae, Tomaspis spp., Toxoptera spp., Trialeurodes vaporariorum Trioza spp., Typhlocyba spp., Unaspis spp., Viteus vitifolii, Zygina spp.

From the order of Hymenoptera e.g. Acromyrmex spp., Athalia spp., Atta spp., Diprion spp., Hoplo- campa spp., Lasius spp., Monomorium pharaonis, Sirex spp., Solenopsis invicta, Tapinoma spp., Uracus spp., Vespa spp., Xeris spp ..

From the order of isopods e.g. Armadillidium vulgare, Oniscus asellus, Porcellio scaber. From the order of Isoptera e.g. Coptotermes spp., Cornitermes cumulans, Cryptotermes spp., Incisperses spp., Microtermes obesi, Odontotermes spp., Reticulitermes spp.

From the order of Lepidoptera, for example, Achroia grisella, Acronica major, Adoxophyes spp., Aedia leucomelas, Agrotis spp., Alabama spp., Amyelois transitella, Anarsia spp., Anticarsia spp., Argyroploce spp., Barathra brassicae, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cecececia spp., Caloptilia theivora, Capua reticulana, Carpocapsa pomonella, Carposina niponensis, Cheimatobia brumata, Chilo spp., Choristoneura spp., Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrope cis medinalis, Cnephasia spp., Conopomorpha spp., Conotrachelus spp., Copitarsia spp., Cydia spp., Dalaca noctuides, Diaphania spp., Diatraea saccharalis, Earias spp., Ecdytolopha aurantium, Elasmotpus lignosellus, Eidana saccharina, Ephestia spp , Epinotia spp., Epiphyas postvittana, Etiella spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia spp., Galleria mellonella, Gracillaria spp., Grapholitha spp., Hedylepta spp., Helicoverpa spp., Heliothis spp., yard mannophila pseudopetella, Homoeosoma spp., Homona spp., Hyponomeuta padella, Kakivoria flavofasciata, Laphygma spp., Laspeyresia molesta, Leucinodes orbonalis, Leucoptera spp., Lithocolletis spp., Lithophane antennata, Lobesia spp., Loxagrotis albicosta, Lymantria spp., Lyonetia spp., Malacosoma neustria, Maruca testulalis, Mamstra brassicae, melanitis leda, Mocis spp., Monopis obviella, Mythimna separata, Nemapogon cloacellus, Nymphula spp., Oiketicus spp., Oria spp., Orthaga spp., Ostrinia spp., Oulema oryzae, Panolis flammea, Parnara spp., Pectinophora spp., Perileucoptera spp., Phthorimaea spp., Phyllocnis citrella, Phyllonorycter spp., Pieris spp., Platynota stultana, Plodia interpunctella, Plusia spp., Plutella xylostella, Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp., Pseudaletia unipuncta, Pseudoplusia includens, Pyrausta nubilalis, Rachiplusia nu, Schoenobius spp., Scirpophaga spp., Scirpophaga - innotata, Scotia segetum, Sesamia spp., Sesamia inferens, Sparganothis spp., Spodoptera spp., Spodopterra praefica, Stathmopoda spp., Stomopteryx subsecivella, Synanthedon spp., Tecia solanivora, Thermesia gemmatalis, Tinea cloacella, Tinea pellionella, Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp., Tryporyza incertulas, Tuta absoluta, Virachola spp. From the order of Orthoptera or Saltatoria eg Acheta domesticus, Dichroplus spp., Gryllotalpa spp., Hieroglyphus spp., Locusta spp. , Melanoplus spp., Schistocerca gregaria.

From the order of Phthiraptera e.g. Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Phylloera vastatrix, Phtirus pubis, Trichodectes spp.

From the order of Psocoptera e.g. Lepinotus spp., Liposcelis spp. From the order of siphonaptera e.g. Ceratophyllus spp., Ctenocephalides spp., Pulex irritans, Tunga penetrans, Xenopsylla cheopsis.

From the order of Thysanoptera e.g. Anaphothrips obscurus, Baliothrips biformis, Drepanothrips reuteri, Enneothrips havens, Frankliniella spp., Heliothrips spp., Hercinothrips femoralis, Rhiprophorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamomi, Thrips spp .. From the order of Zygentoma (= Thysanura), e.g. , Ctenolepisma spp., Lepisma saccharina, Lepis- modes inquilinus, Thermobia domestica.

From the class of Symphyla e.g. Scutigerella spp ..

Pests of the Mollusca strain, in particular of the bivalve class, e.g. Dreissena spp., As well as from the class Gastropoda e.g. Arion spp., Biomphalaria spp., Bulinus spp., Deroceras spp., Galba spp., Lymnaea spp., Oncomelania spp., Pomacea spp., Succinea spp.

Animal parasites from the strains of Plathelminthes and Nematoda, eg Ancylostoma duodenale, Ancylostoma ceylanicum, Acylostoma braziliensis, Ancylostoma spp., Ascaris spp., Brugia malayi, Brugia timori, Bunostomum spp., Chabertia spp., Clonorchis spp., Cooperia spp. , Dicrocoelium spp, Dictyocollus filaria, Diphyllobothrium latum, Dracunculus medinensis, Echinococcus granulosus, Echinococcus multilocularis, Enterobius vermicularis, Faciola spp., Haemonchus spp., Heterakis spp., Hymenolepis nana, Hyostrongulus spp., Loa Loa, Nematodirus spp. Oesophagostomum spp., Opisthorchis spp., Onchocerca volvulus, Ostertagia spp., Paragonimus spp., Schistosomes spp, Strongyloides fuelleborni, Strongyloides stercoralis, Stronyloides spp., Taenia saginata, Taenia solium, Trichinella spiralis, Trichinella nativa, Trichinella britovi, Trichinella nelsoni, Trichinella pseudopsiralis, Trichostrongulus spp., Trichuris trichuria, Wuchereria bancrofti. - -

Plant pests from the strain of Nematoda, i. plant parasitic nematodes, in particular Aphelenchoides spp., Bursaphelenchus spp., Ditylenchus spp., Globodera spp., Heterodera spp., Longidorus spp., Meloidogyne spp., Pratylenchus spp., Radopholus spp., Trichodorus spp., Tylenchulus spp, Xiphinema Spp., Helicotylenchus spp., Tylenchorhynchus spp., Scutellonema spp., Paratrichodorus spp., Meloinema spp., Paraphelenchus spp., Aglenchus spp., Belonolaimus spp., Nacobbus spp, Rotylenchus spp., Rotylenchus spp., Neotylenchus spp , Paraphelenchus spp., Dolichodorus spp., Hoplolaimus spp., Punctodera spp., Criconemella spp., Quinisulcius spp., Hemicycliophora spp., Anguina spp., Subanguina spp., Hemicriconemoides spp., Psilenchus spp., Pseudohalenchus spp ., Criconemoides spp., Cacopaurus spp. Furthermore, the order of coccidia can be determined from the sub-kingdom of protozoa Fight Eimeria spp.

Preference is given to the use of the compounds according to the invention for combating pyrethroid-resistant insects from the family of CuUcidae, Muscidae or Blattidae. Particularly preferred is the use of the compounds according to the invention for combating pyrethroid-resistant insects from the family of CuUcidae. Preference is given to insects of the Cuucidae family selected from the genera Aedes aegypti, Aedes albopictus, Anopheles stephensi, Culex quinquefasciatus, Anopheles albimanus, Anopheles funestus, Anopheles gambiae, Culex pipiens pallens, Anopheles minimus, Anopheles arabiensis and Anopheles sacharovi. The insects are particularly preferably selected from the group of the genera Culex quinquefasciatus and Anopheles gambiae. The compounds according to the invention can also be used in certain concentrations or application rates as herbicides, safeners, growth regulators or agents for improving plant properties, or as microbicides, for example as fungicides, antimycotics, bactericides, viricides (including anti-viral agents) or as anti-MLO agents (Mycoplasma -like-organism) and RLO (Rickettsia-like-organism). They can also be used as intermediates or precursors for the synthesis of other active ingredients.

The active compounds can be converted into the customary formulations, such as solutions, emulsions, wettable powders, water- and oil-based suspensions, powders, dusts, pastes, soluble powders, soluble granules, scattering granules, suspension-emulsion concentrates, active substance-impregnated natural products, active ingredient Impregnated synthetic materials, fertilizers and Feinstverkapselungen in polymeric materials.

These formulations are prepared in a known manner, for example by mixing the active compounds with extenders, ie liquid solvents and / or solid carriers, optionally with the use of surface-active agents, ie emulsifiers and / or dispersants and / or foaming agents. The preparation of the formulations is carried out either in suitable systems or before or during use.

Excipients which can be used are those which are suitable for imparting special properties to the composition itself and / or preparations derived therefrom (for example spray liquor, seed dressing), such as certain technical properties and / or specific biological properties. Typical auxiliaries are: extenders, solvents and carriers.

As extender, e.g. Water, polar and non-polar organic chemical liquids e.g. from the classes of aromatic and non-aromatic hydrocarbons (such as paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes), alcohols and polyols (which may also be substituted, etherified and / or esterified), ketones (such as acetone , Cyclohexanone), esters (including fats and oils) and (poly) ethers, the simple and substituted amines, amides, lactams (such as N-alkylpyrrolidones) and lactones, the sulfones and sulfoxides (such as dimethyl sulfoxide).

In the case of using water as extender, for example, organic solvents can also be used as auxiliary solvents. Suitable liquid solvents are essentially: aromatics, such as xylene, toluene, or alkylnaphthalenes, chlorinated aromatics and chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example petroleum fractions, mineral and vegetable oils, alcohols such as butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents such as dimethyl sulfoxide, and water. Suitable solid carriers are: for example, ammonium salts and ground natural minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as finely divided silica, alumina and silicates, as solid carriers for granules: eg broken and fractionated natural rocks such as calcite, marble, pumice, sepiolite, dolomite and synthetic granules of inorganic and organic flours and granules of organic material such as paper, sawdust, coconut shells, corn cobs and tobacco stalks; suitable emulsifiers and / or foam formers are: for example nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers, alkylsulfonates, alkyl sulfates, arylsulfonates and protein hydrolysates; suitable dispersants are nonionic and / or ionic substances, for example from the classes of alcohol POE and / or POP ethers, acid and / or POPPOE esters, alkylaryl and / or POP POE ethers, fatty and / or POP-POE adducts, POE and / or POP polyol derivatives, POE and / or POP sorbitan or sugar adducts, alkyl or aryl sulfates, sulfonates and phosphates or the corresponding PO ether adducts. Further suitable oligo- or polymers, for example starting from vinylic monomers of Acrylic acid, from EO and / or PO alone or in combination with, for example, (poly) alcohols or (poly) amine. Furthermore, find use lignin and its sulfonic acid derivatives, simple and modified celluloses, aromatic and / or aliphatic sulfonic acids and their adducts with formaldehyde.

Adhesives such as carboxymethylcellulose, natural and synthetic powdery, granular or latex-like polymers can be used in the formulations, such as gum arabic, polyvinyl alcohol, polyvinyl acetate, as well as natural phospholipids such as cephalins and lecithins and synthetic phospholipids.

Dyes such as inorganic pigments, e.g. Iron oxide, titanium oxide, ferrocyan blue and organic dyes such as alizarin, azo and metal phthalocyanine dyes and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

Other additives may be fragrances, mineral or vegetable optionally modified oils, waxes and nutrients (also trace nutrients), such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

Stabilizers such as cold stabilizers, preservatives, antioxidants, light stabilizers or other agents which improve the chemical and / or physical stability can also be present.

The formulations generally contain between 0.01 and 98% by weight of active ingredient, preferably between 0.5 and 90%.

The active ingredient according to the invention can be present in its commercial formulations and in the formulations prepared from these formulations in admixture with other active ingredients such as insecticides, attractants, sterilants, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers or semiochemicals.

A mixture with other known active substances, such as herbicides, fertilizers, growth regulators, safeners, semiochemicals, or with agents for improving the plant properties is possible.

The active compounds according to the invention can furthermore be present in the form of insecticides in their commercial formulations and in the formulations prepared from these formulations in admixture with synergists. Synergists are compounds which increase the effect of the active ingredients without the added synergist itself having to be active. The active compounds according to the invention can also be used as insecticides in their commercial formulations and in the formulations prepared from these formulations in mixtures with inhibitors that reduce degradation of the active ingredient after application in the environment of the plant, on the surface of plant parts or in plant tissues.

The active ingredient content of the application forms prepared from the commercial formulations can vary widely. The active ingredient concentration of the application forms can be from 0.00000001 up to 95% by weight of active compound, preferably between 0.00001 and 1% by weight.

The application is done in a custom forms adapted to the application.

According to the invention, all plants and parts of plants can be treated. In this context, plants are understood as meaning all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants). Crop plants can be plants that can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the transgenic plants and including the plant protectable or non-protectable plant varieties. Plant parts are to be understood as meaning all aboveground and underground parts and organs of the plants, such as shoot, leaf, flower and root, by way of example leaves, needles, stems, stems, flowers, fruiting bodies, fruits and seeds and roots, tubers and rhizomes. The plant parts also include crops and vegetative and generative propagation material, such as cuttings, tubers, rhizomes, offshoots and seeds.

The treatment according to the invention of the plants and plant parts with the active ingredients is carried out directly or by acting on their environment, habitat or storage space according to the usual treatment methods, e.g. by dipping, spraying, evaporating, atomizing, spreading, brushing, injecting and in propagating material, in particular in seeds, further by single or multilayer coating.

As already mentioned above, according to the invention all plants and their parts can be treated. In a preferred embodiment, wild-type or plant species obtained by conventional biological breeding methods, such as crossing or protoplast fusion, and plant cultivars and their parts are treated. In a further preferred embodiment, transgenic plants and plant cultivars which have been obtained by genetic engineering methods, if appropriate in combination with conventional methods (Genetically Modified Organisms), and their parts are treated. The terms "parts" or "parts of plants" or "plant parts" have been explained above.

It is particularly preferred according to the invention to treat plants of the respective commercially available or in use plant cultivars. Plant varieties are understood as meaning plants with new traits that have been bred either by conventional breeding, by mutagenesis or by recombinant DNA techniques. These can be varieties, biotypes and genotypes. ₅

Depending on the plant species or plant cultivars, their location and growth conditions (soils, climate, vegetation period, diet), the treatment according to the invention may also give rise to superadditive ("synergistic") effects. For example, reduced application rates and / or enhancements of the spectrum of action and / or an increase in the effect of the substances and agents that can be used according to the invention, better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering efficiency, easier harvesting, acceleration of ripeness, higher crop yields, higher quality and / or higher nutritional value of the harvested products, higher shelf life and / or machinability of the harvested products possible, which go beyond the actual expected effects. The preferred plants or plant varieties to be treated according to the invention to be treated include all plants which, as a result of the genetic engineering modification, obtained genetic material which gives these plants particularly advantageous valuable properties ("traits"). Examples of such properties are better plant growth, increased tolerance to high or low temperatures, increased tolerance to dryness or to bottoms salt, increased flowering, easier harvesting, acceleration of ripeness, higher crop yields, higher quality and / or higher nutritional value of the harvested products , higher shelf life and / or workability of the harvested products. Further and particularly emphasized examples of such properties are an increased defense of the plants against animal and microbial pests, as against insects, mites, phytopathogenic fungi, bacteria and / or viruses as well as an increased tolerance of the plants against certain herbicidal active substances. Examples of transgenic plants are the important crops such as cereals (wheat, rice), corn, soybeans, potatoes, sugar beets, tomatoes, peas and other vegetables, cotton, tobacco, oilseed rape and fruit plants (with the fruits apples, pears, citrus fruits and Grapes), with special emphasis on maize, soya, potato, cotton, tobacco and oilseed rape. Traits which are particularly emphasized are the increased defense of the plants against insects, arachnids, nematodes and snails by toxins which are formed in the plants, in particular those which are produced by the genetic material from Bacillus thuringiensis (for example by the genes CrylA (cf. a), CrylA (b), CrylA (c), CryllA, Cryll-IA, CryIIIB2, Cry9c Cry2Ab, Cry3Bb and CrylF and combinations thereof) are produced in the plants (hereinafter "Bt plants"). Traits also highlight the increased defense of plants against fungi, bacteria and viruses by systemic acquired resistance (SAR), systemin, phytoalexins, elicitors and resistance genes and correspondingly expressed proteins and toxins. Traits which are furthermore particularly emphasized are the increased tolerance of the plants to certain herbicidal active compounds, for example imidazolines, sulfonylureas, glyphosate or phosphinotricin (eg "PAT" gene). The genes conferring the desired properties ("traits") can also occur in combinations with one another in the transgenic plants. Examples of "Bt plants" are maize varieties, cotton varieties, soya bean varieties and potato varieties which are sold under the trade names YIELD GARD ^® (eg - 5b -

Corn, cotton, soybeans), KnockOut ^® (for example maize), StarLink ^® (for example maize), Bollgard ^® (cotton), nucleic COTN ^® (cotton) and NewLeaf ^® (potato). Examples of herbicide-tolerant plants are maize varieties, cotton varieties and soybean varieties may be mentioned, under the trade names Roundup Ready ^® (tolerance to glyphosate, for example maize, cotton, soya bean), Liberty Link ^® (tolerance to phosphinotricin, for example oilseed rape), IMI ^® (Tolerance to imidazolinone) and STS ^® (tolerance to sulfonylureas eg corn). As herbicide-resistant (conventionally grown on herbicide tolerance) plants are also sold under the name Clearfield ^® varieties (eg corn). Of course, these statements also apply to future or future marketed plant varieties with these or future developed genetic traits.

The listed plants can be treated particularly advantageously according to the invention with the compounds of the general formula (I) or the active substance mixtures according to the invention. The preferred ranges given above for the active compounds or mixtures also apply to the treatment of these plants. Particularly emphasized is the plant treatment with the compounds or mixtures specifically mentioned in the present text.

- 7 - Production examples

Example 1 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro-4'-trifluoromethyl- [1, Γ -biphenyl] -3-yl) methyl ester

a-1) Stufe A (Methode I, II): 2-Fluor-3-iod-benzoesäuremethylester

a-1) Step A (Method I, II): 2-fluoro-3-iodo-benzoic acid methyl ester

1. Schritt: 2-Fluor-3-iod-benzoesäure (vgl. auch WO 2009/132774)

1st step: 2-fluoro-3-iodo-benzoic acid (see also WO 2009/132774)

To a stirred solution of 3.39 g (4.1 ml, 24.0 mmol) of 2,2,6,6-tetramethylpiperidine in 60 ml of tetrahydrofuran (THF) at -20 ° C under a protective gas atmosphere (nitrogen) 15 mL (24, 0 mmol) of a 1.6 M solution of n-butyllithium in hexane. The resulting reaction mixture was stirred for a further 30 minutes at this temperature. Subsequently, the reaction mixture was cooled to -78 ° C and treated with 4.48 g (2.4 ml, 20.0 mmol) of 1-iodo-2-fluorobenzene. The reaction mixture was stirred for a further 2 hours at -78 ° C. Thereafter, the reaction mixture was carefully mixed with an excess freshly crushed dry ice (solid carbon dioxide) (quenching to -50 ° C). Subsequently, the reaction mixture was brought to room temperature within 30 minutes. Thereafter, the solvent was removed in vacuo and the remaining residue was mixed with 50 ml of water. The aqueous phase was first washed twice with 20 mL diethyl ether and then acidified to pH = 1 with 4 M hydrochloric acid. It was then extracted three times with 50 ml of diethyl ether. The combined extracts were dried over sodium sulfate and concentrated in vacuo. After complete removal of the total solvent, 4.8 g (90% of theory) of 2-fluoro-3-iodobenzoic acid remain as a colorless, crystalline solid which can be used for the esterification reaction without further purification.

2nd step: 2-fluoro-3-iodo-benzoic acid methyl ester

To a stirred solution of 4.80 g (18.0 mmol) of 2-fluoro-3-iodo-benzoic acid (see step 1) in 100 mL of dichloromethane was added 2.54 g (1.7 mL, 20 mmol) of oxalyl chloride and two drops of N, N-dimethylformamide (DMF). The reaction mixture was allowed to stand at room temperature for about 3 hours - - Stirred and then quenched with 10 ml of methanol. Thereafter, all solvents and the excess of oxalyl chloride were removed in vacuo and the remaining residue was dissolved in 100 ml of diethyl ether and washed with saturated 25 ml of sodium bicarbonate solution and petroleum ether. Thereafter, the reaction solution was dried over sodium sulfate and the organic phase was concentrated in vacuo. The crude product was purified by flash chromatography using 15% ethyl acetate in hexane. This gives 4.22 (84% of theory) of 2-fluoro-3-iodo-benzoic acid methyl ester as a white solid. a-2) Step A (method L II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester

 1st step: methyl 2-bromomethyl-3-iodobenzoate (see also WO 2007/090068)

To a stirred solution of 5.21 g (29.3 mmol) of N-bromo-succinimide (NBS) in 210 mL of α, α, α-trifluorotoluene was added under protective gas atmosphere (nitrogen) successively 297 mg (1.273 mmol) of zirconium Convene (IV) chloride (ZrC) and 7.34 g (26.6 mmol) of 3-iodo-2-methyl-benzoic acid methyl ester given. Subsequently, the reaction mixture was stirred for 24 hours at 105-108 ° C at reflux. After addition of saturated sodium bicarbonate solution (quenching), it was extracted three times with 50 ml of dichloromethane. The combined organic phases were dried over magnesium sulfate, concentrated in vacuo and purified by flash chromatography using 5% ethyl acetate in hexane. This gives 7.82 g (83% of theory) of 2-bromomethyl-3-iodo-benzoic acid methyl ester as a colorless solid.

2nd step: 2-fluoromethyl-3-iodo-benzoic acid methyl ester

73.44 mL (73.44 mmol) of tetra-n-butylammonium fluoride (TBAF, 1.0 M in THF) was added under a protective gas atmosphere (nitrogen) to a stirred solution of 1.18 g (33.4 mmol) 2-bromomethyl-3 iodo-benzoic acid ester (see step 1) in THF. Thereafter, the reaction mixture was stirred at room temperature for 24 hours. The solvent was then removed in vacuo and the remaining residue was purified by flash chromatography using 5% ethyl acetate in hexane. This gives 6.32 g (64% of theory) of methyl 2-fluoromethyl-3-iodobenzoate as a white solid. - - a-3) Step A (Method I, II): 6-Fluoro-3-iodo-2-methyl-benzoic acid methyl ester

 1st step: 6-fluoro-3-iodo-2-methyl-benzoic acid (compare preparation of 2-fluoro-3-iodo-benzoic acid,

WO 2009/132774)

 2nd step: methyl 6-fluoro-3-iodo-2-methylbenzoate (compare preparation of methyl 2-fluoro-3-iodobenzoate)

B (Method I): (2-fluoro-3-iodophenyl) methanol (see also WO 2009/132774)

 To a stirred solution of 4.34 g (15.5 mmol) 2-fluoro-3-iodo-benzoic acid methyl ester (step A) in 50 mL toluene at room temperature under a protective gas atmosphere (nitrogen) 7.8 mL (15.5 mmol) a 2.0 M solution of lithium borohydride in tetrahydrofuran (THF). Subsequently, the entire reaction mixture was stirred at 100 ° C for 30 minutes. Thereafter, 10 mL of an IM hydrochloric acid solution was added and the solvents were separated. The remaining residue was dissolved in 50 mL diethyl ether and washed successively with 20 mL saturated sodium thiosulfate solution, 20 mL saturated sodium bicarbonate solution and brine. The organic phase was dried over sodium sulfate, filtered off and concentrated in vacuo. The resulting 2-fluoro-3-iodo-phenyl) methanol can be used without further purification for the subsequent reaction.

B (Method I): (2,6-difluoro-3-iodophenyl) methanol

(2,6-Difluoro-3-iodo-phenyl) methanol was prepared analogously from 2,6-difluoro-3-iodo-benzoic acid methyl ester (cf., WO 2009/076747) by means of lithium borohydride reduction in toluene / tetrahydrofuran in 87%. iger yield (ie theory) as a colorless, crystalline solid. b-3) Step B (Method I): (2-fluoromethyl-3-iodo-phenyl) -methanol

To a stirred solution of 5.84 g (19.85 mmol) of 2-fluoromethyl-3-iodo-benzoic acid methyl ester (step A) in 150 mL diethyl ether 661 mg lithium aluminum hydride were added at -42 ° C under a protective gas atmosphere (nitrogen) and the reaction mixture was stirred at this temperature. After two hours, the reaction mixture was quenched with hydrochloric acid solution and then extracted three times with 75 mL of diethyl ether. The organic phase was dried over magnesium sulfate, filtered off, concentrated in vacuo and purified by flash chromatography using a gradient (ethyl acetate / n-hexane). This gives 3.48 g (66% of theory) of (2-fluoromethyl-3-iodo-phenyl) methanol as a colorless solid. b-4) Step B (Method I): 2-fluoromethyl-6-fluoro- [l, r-biphenyl] -methanol (see Preparation of

 (2-fluoromethyl-3-iodo-phenyl) -methanol; Yield obtained via reaction stages / step 5 and reduction: 48% d. Theory)

c) Step C (method I. II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarb

 Chloride (see also US Pat.

 6.20 g (20.0 mmol) of (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (compare also M. Eliott et al, Pesticide Sci., 6, 537- 542, 1975) were dissolved in 100 mL of dry dichloromethane

and under inert gas atmosphere (nitrogen) with 2.67 g (21.0 mmol) of oxalyl chloride and a catalytic amount (2 drops) of DMF. After three hours of stirring at room temperature, the solvent was removed in vacuo and the crude (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride (yellowish oil) for the next reaction step (Step E). used. - - d-1) Step D (Method I): (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethylcyclopropanecarb

2

 The (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride obtained in stage C was stirred in 40 ml of dichloromethane and admixed with 3.16 g (40 mmol) of pyridine. Subsequently, the reaction mixture was further stirred for one hour at room temperature and then treated with a solution of 4.56 g (18.1 mmol) (2-fluoro-3-iodo-phenyl) methanol (step C) in 20 mL dichloromethane. Thereafter, the reaction mixture was stirred for about 18 hours at room temperature. Subsequently, the solvent and excess pyridine were removed in vacuo. The remaining residue was dissolved in 100 ml of diethyl ether and washed successively with 50 ml of water, 50 ml of saturated sodium bicarbonate solution and saturated brine. The organic phase was dried over sodium sulfate and concentrated after filtration in vacuo. The remaining crude product was purified by flash chromatography (silica gel eluent: 2% ethyl acetate in hexane). (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2-fluoro-3-iodo-benzyl ester is obtained as a colorless solid.

Yield: 77% (ie theory)

ES HRMS: m / z found: 554.8268.

Ci ₅ Hi ₄ 0 ₂ F ²³ Na ⁷⁹ Br ⁸¹ Br ¹²⁷ I [M + Na] ⁺ calcd: 554.8267. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.73 (ddd, J = 7.7, 5.9, 1.7 Hz, 1H), 7.36 (ddd, J = 7.7, 6.8, 1.6 Hz, 1H), 6.92 (t, J = 7.8 Hz, 1H), 6.76 (d, J = 8.5 Hz, 1H), 5.17 (dd, J = 3.7, 1.2 Hz, 2H), 1.98 (t, J = 8.5 Hz, 1H), 1.90 (d, J = 8.5 Hz, 1H), 1.27 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.47, 161.40, 158.94, 139.97, 139.95, 133.70, 131.07, 131.04, 126.24, 126.20, 124.55, 124.38, 89.99, 82.07, 81.81, 60.63, 60.59, 36.20, 32.09, 28.74, 28.20, 15.45 ppm. d-2) Step D (Method I): (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2-fluoro-3-iodo-benzyl ester

- -

- -

The (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid 2-fluoro-3-iodo-benzyl ester was prepared in an analogous manner from (1R, 3R) -3 - (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride and (3-2-fluoro-3-iodo-phenyl) methanol.

ES HRMS: m / z found: 498.9552. Ci6Hi ₄ 0 ₂ F ₄ ²³ Na ³⁵ Cl ¹²⁷ I calculated: 498.9561. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.66-7.63 (1H, m), 7.28-7.24 (1H, m), 6.84 (1H, J = 7.9Hz, d), 6.82 (1H, J = 5.3Hz , d), 5.13-5.05 (2H, m), 2.18 (1H, J = 8.5Hz, t), 1.95 (1H, J = 8.4Hz, d), 1.29 (6H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 171.5, 140.1, 131.1, 130.3, 126.2, 82.0, 81.8, 60.8, 33.1, 31.4, 29.3, 28.7, 21.4, 15.3, 14.6 ppm. d-3) Step D (Method I): -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

The (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid 2,6-difluoro-3-iodo-benzyl ester was prepared in an analogous manner from (1R, 3R) -3 - (2,2-Dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride and (2,6-difluoro-3-iodo-phenyl) methanol.

Yield: 66% (ie theory)

ES HRMS: m / z found: 570.8176

Ci ₅ Hi302F2 ²³ Na ⁷⁹ Br ₂ ¹²⁷ I calculated: 570.8176. ¹ H NMR (400MHz, CDCl 3): δ 7.76-7.71 (1H, m), 6.81 (1H, t, J = 8.7Hz), 6.78 (1H, d, J = 8.6Hz), 5.24 (1H, d, J = 12.0 Hz), 5.19 (1H, d, J = 12.1 Hz), 1.99 (1H, t, J = 8.4 Hz), 1.86 (1H, d, J = 8.5 Hz), 1.27 (3H, s), 1.24 ( 3H, s) ppm

¹³ C NMR (100 MHz, CDCl 3) δ 170.3, 163.7, 162.4, 161.1, 159.9, 140.1, 140.0, 133.7, 1 14.0, 1 13.7, 113.5, 113.3, 113.1, 90.0, 75.6, 75.3, 54.6, 36.2, 32.1, 28.7, 28.1, 15.5 ppm. d-4) Step D (Method I): (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2,6-difluoro-3-iodo-benzyl ester - -

The (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid 2,6-difluoro-3-iodobenzyl ester was prepared in an analogous manner (IR, 3R). -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride and (2,6-difluoro-3-iodo-phenyl) -methanol. ES HRMS: m / z found: 516.9451.

Ci6Hi30 ₂ F ₅ ²³ Na ³⁵ Cl ¹²⁷ I calculated: 516.9451.

^L H NMR (400MHz, CDC1 _3): δ 7.76-7.71 (1H, m), 6.92 (1H, d, J = 10.3 Hz), 6.81 (1H, t, J = 10.0 Hz), 5.25 (1H, d, J = 12.1 Hz), 5.20 (1H, d, J = 12.0 Hz), 2.20 (1H, t, J = 8.5 Hz), 1.99 (1H, d, J = 8.4 Hz), 1.30 (3H, s), 1.29 (3H, s) ppm. ¹³ C NMR (100 MHz, CDCl 3) δ 170.1, 163.7, 162.4, 161.1, 159.9, 140.2, 140.1, 130.2, 124.8, 122.8, 122.5, 122.1, 119.4, 1 16.8, 1 14.0, 1 13.9, 113.7, 113.3, 1 13.1, 1 12.9, 75.5, 75.2, 60.8, 54.7, 33.1, 31.4, 29.3, 28.7, 15.3 ppm. d-5) Step D (Method I): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid

2-fluoromethyl-3-iodo-benzyl ester

The (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid 2-fluoromethyl-3-iodobenzyl ester was prepared in an analogous manner from (1R, 3R) -3- ( 2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride and (2-fluoromethyl-3-iodo-phenyl) methanol as a colorless solid.

Yield: 79% (theory)

ES HRMS: found [M + Na] ⁺ , 566.8452.

Ci6Hi60 ₂ F ²³ Na ⁷⁹ Br ₂ ¹²⁷ I calculates 566.8444.

'H NMR (400 MHz, CDCl3) δ: 7.89 (1H, d, J = 7.8 Hz), 7.42 (1H, d, J = 7.7 Hz), 7.08 (1H, dd, J = 7.8 and 7.7 Hz), 6.75 (1H, d, J = 8.5 Hz), 5.65 (2H, d, JH-F = 47.7 Hz), 5.25 (2H, m), 1.98 (1H, dd, J = 8.4 and 8.5 Hz), 1.90 (1H, d, J = 8.45 Hz), 1.25 (3H, s), 1.24 (3H, s) ppm. ¹³ C NMR (100 MHz, CDC13) δ: 15.48, 28.29, 28.77, 32.12, 36.22, 64.34, 85.14, 86.79, 90.05, 130.49, 131.70, 131.73, 133.72, 136.82, 138.07, 140.61, 170.39 ppm. d-6) Step D (Method I): (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2-fluoromethyl-3-iodo-benzyl ester

The (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid 2-fluoromethyl-3-iodo-benzyl ester was prepared in an analogous manner from (1R, 3R) -3 - (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclo-propanecarboxylic acid chloride and (2-fluoromethyl-3-iodo-phenyl) methanol.

ES HRMS: found [M + Na] ⁺ , 512.9695. Ci7Hi ₆ 0 ₂ F4 ²³ Na ³⁵ Cr ²⁷ I calculates 512.9717.

'H NMR (400 MHz, CDC1 ₃₎ δ: 7.89 (1H, d, J = 7.8 Hz), 7:41 (1H, d, J = 7.7 Hz), 7:07 (1H, dd, J = 7.8 and 7.7 Hz), 6.91 (1H, d, J = 9.0 Hz), 5.65 (2H, d, JH-F = 47.7 Hz), 5.26 (2H, m), 2.19 (1H, dd, J = 8.5 and 9.0 Hz), 2.03 (1H , d, J = 8.5 Hz), 1.29 (3H, s), 1.28 (3H, s) ppm.

¹³ C NMR (100 MHz, CDC13) δ: 15.30, 28.72, 29.40, 31.46, 33.16, 64.51, 85.15, 86.80, 130.31, 130.35, 130.51, 131.67, 131.71, 136.71, 136.86, 137.88, 140.70, 170.20 ppm. e) Step E (Method I): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-fluoro-4'-trifluoromethyl [1, Γ -biphenyl] -3-yl) methyl ester

To a solution of 543 mg (1.0 mmol) of (lR, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2-fluoro-3-iodo-benzyl ester in 20 mL toluene 4.5 mg (0.02 mmol) of palladium (II) acetate, 13.1 mg (0.05 mmol) of triphenylphosphine, 0.85 g (4.0 mmol) of potassium phosphate and 235 mg (1.2 mmol ) Added 4-trifluoromethylphenylboronic acid. Thereafter, the reaction mixture was degassed and stirred at 70 ° C for 6 hours. Subsequently, the resulting reaction mixture was forced through a silica gel-loaded filter to remove the palladium catalyst and the inorganic salts. The crude product obtained as a pale yellow oil was purified by flash chromatography (silica gel eluent: 3% ethyl acetate in n-hexane). (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid (2-methyl-4'-trifluoromethyl) - [1, Γ-biphenyl] -3-yl is obtained ) methylester.

Yield: 56% (theory) - 5 -

ES HRMS: m / z found

C ₂₂ Hi ₈ 0 ₂ F ₄ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 572.9487. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.71 (d, J = 8.6 Hz, 2H), 7.66 (d, J = 8.2 Hz, 2H), 7.46 - 7.39 (m, 2H), 7.26 (t, J = 7.6 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 5.25 (d, J = 0.9 Hz, 2H), 1.99 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz , 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl3) δ 170.56, 159.46, 156.96, 139.45, 133.77, 131.29, 130.82, 129.84, 128.39, 128.26, 125.83, 124.90, 124.61, 124.46, 89.94, 60.62, 36.19, 32.17, 28.76, 28.15, 15.47 ppm.

In an analogous manner, examples 2 to 4 were obtained by means of Suzuki coupling (stage E, method I).

Example 2 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro-4'-trifluoromethoxy- [1, Γ -biphenyl] -3-yl) methyl ester

Output: 82% (ie theory)

ES HRMS: m / z found: 588.9464.

C ₂₂ Hi80 ₃ F ₄ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 588.9436. ¹ H NMR (400 MHz, CDCl 3) δ 7.57 (dd, J = 8.7, 1.6 Hz, 2H), 7.40 (t, J = 7.3 Hz, 2H), 7.30 (d, J = 8.8 Hz, 2H), 7.24 ( t, J = 7.6 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 5.24 (s, 2H), 1.99 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.58, 159.42, 156.93, 149.28, 134.48, 133.79, 131.31, 130.90, 130.43, 128.41, 124.80, 124.49, 124.33, 121.32, 89.91, 60.65, 36.18, 32.17, 28.76, 28.14, 15.47 ppm. Example 3 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro-3'-trifluoromethyl- [1, Γ -biphenyl] -3-yl) methyl ester

Output: 71% (ie theory) - -

ES HRMS: m / z found 572.9466.

C ₂₂ Hi ₈ 0 ₂ F ₄ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ requires 572.9487. ¹ H NMR NMR (400 MHz, CDCl ₃ ) δ 7.80 (s, 1H), 7.74 (d, J = 7.3 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.57 (t, J = 7.7 Hz , 1H), 7.43 (t, J = 7.3 Hz, 2H), 7.26 (t, J = 7.7 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 5.24 (s, 2H), 1.99 (t , J = 8.4 Hz, 1H), 1.92 (d, J = 8.4 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.57, 159.45, 156.96, 136.60, 133.78, 132.80, 131.53, 131.33, 131.21, 130.77, 129.36, 128.34, 126.27, 124.95, 124.59, 124.43, 89.93, 60.64, 36.19, 32.17, 28.76, 28.15, 15.47 ppm.

In an analogous manner, 6 hours of reaction time at 75 ° C by means of Suzuki coupling (step E, method I), the examples 4 were obtained.

Example 4 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2, 3 '-difluoro [1, 1'-biphenyl] -3-yl) methyl ester

Yield: 81% (i.e., theory) ES HRMS: m / z found: 522.9507.

C ₂ iHi ₈ O ₂ F ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 522.9519. ¹ H NMR (400 MHz, CDCl 3) δ 7.44-7.37 (m, 3H), 7.32 (ddd, J = 7.7, 2.7, 1.5 Hz, 1H), 7.26 (d, J = 4.3 Hz, 1H), 7.22 (i.e. , J = 7.6 Hz, 1H), 7.08 (tdd, J = 8.4, 2.6, 1.1 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 5.24 (s, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDCl 3) δ 170.58, 164.36, 161.92, 159.43, 156.93, 137.92, 133.80, 131.27, 130.51, 130.30, 128.43, 125.18, 124.77, 124.48, 1 16.39, 115.03, 89.91, 60.72, 36.18, 32.18 , 28.77, 28.13, 15.48 ppm.

In an analogous manner, 4 hours reaction time at 70 ° C by means of Suzuki coupling (step E, method I) was obtained Examples 5. Example 5 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro-3'-trifluoromethoxy- [1, Γ -biphenyl] -3-yl) methyl ester

Output: 80% (ie theory)

ES HRMS: m / z found: 588.9449.

C22H1803F4 ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 588.9436. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.51-7.46 (m, 2H), 7.44-7.39 (m, 3H), 7.28-7.22 (m, 2H), 6.79 (d, J = 8.4 Hz, 1H), 5.24 (s, 2H), 1.99 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDC13) δ 170.59, 159.42, 156.92, 149.68, 137.76, 133.79, 131.27, 130.69, 130.21, 128.11, 127.89, 124.90, 124.40, 122.18, 120.66, 119.63, 89.91, 60.62, 36.19, 32.17, 28.76, 28.17, 15.47 ppm.

In an analogous manner, the Example 6 was obtained at 16 hours reaction time at 70 ° C by means of Suzuki coupling (step E, method I).

Example 6 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoro-3-thienoyl)

2-yl) -benzyl ester

Output: 45% (ie theory)

ES HRMS: m / z found: 510.9169.

Ci ₉ Hi ₇ 0 ₂ F ²³ NaS ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 510.9177. ¹ H NMR (400 MHz, CDCl 3) δ 7.62 (td, J = 7.6, 1.7 Hz, 1H), 7.49 (dt, J = 3.7, 1.3 Hz, 1H), 7.38 (dd, J = 5.1, 1.1 Hz, 1H ), 7.30 (td, J = 7.2, 1.7 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 7.13 (ddd, J = 5.0, 3.7, 0.8 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 5.23 (dd, J = 4.2, 1.3 Hz, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.91 (d, J = 8.4 Hz, 1H), 1.28 (s, 3H) , 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.59, 158.85, 156.34, 139.97, 137.09, 133.82, 129.50, 128.12, 127.01, 126.43, 124.77, 124.45, 122.83, 89.90, 60.73, 36.17, 32.19, 28.77, 28.14, 15.49 ppm , - -

In an analogous manner, examples 7 were obtained at 70 ° C. for 20 hours reaction time by means of Suzuki coupling (stage E, method I).

Example 7 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoro-4'-chloro [1, 1'-biphenyl] -3-yl) methyl ester

Yield: 62% (ie theory)

ES HRMS: m / z found: 538.9224.

C ₂ iHi ₈ O ₂ F ²³ Na ³⁵ Cl ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 538.9223. ^l H NMR (400 MHz, CDC1 ₃₎ δ 7:49 (d, J = 1.6 Hz, 1H), 7:47 (d, J = 1.5 Hz, 1H), 7:44 to 7:42 (m, 1H), 7:42 to 7:36 (m, 3H), 7.22 (t, J = 7.6 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 5.23 (s, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.91 (d, J = 8.5 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.58, 159.42, 156.93, 134.36, 134.25, 133.80, 131.24, 130.75, 130.33, 129.10, 128.60, 124.77, 124.46, 89.91, 60.72, 36.18, 32.18, 28.77, 28.13, 15.48 ppm ,

In an analogous manner, examples 8 were obtained at 18 hours reaction time at 100 ° C by means of Suzuki coupling (stage E, method I).

Example 8 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoro-2'-trifluoromethoxy- [1, Γ -biphenyl] -3-yl) methyl ester

Yield: 32% (i.e., theory) ES HRMS: m / z found: 588.9427.

C22Hi ₈ 03F ₄ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calculates 588.9436. Ή NMR (400 MHz, CDC1 ₃ ) δ 7.48 - 7.28 (m, 6H), 7.23 (t, J = 7.6 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 5.23 (d, J = 6.2 Hz, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.91 (d, J = 8.4 Hz, 1H), 1.27 (s, 3H), 1.25 (s, 3H) ppm.

In an analogous manner, examples 9 to 11 were obtained at a reaction time of 24 hours at 70 ° C. by means of a Suzuki coupling (stage E, method I).

Example 9 (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro-4'-chloro- [1, Γ -biphenyl] -3-yl) methylester

Yield: 43% (of theory) ES HRMS: m / z found: 483.0521

C22Hi80 ₂ F ₄ ²³ Na ³⁵ Cl2 calculated: 483.0518.

'H NMR (400 MHz, CDCl 3): δ 7.41-7.28 (6H, m), 7.18-7.12 (1H, m), 6.85 (1H, d, J = 9.4Hz), 5.18 (2H, s), 2.11 ( 1H, t, J = 8.6Hz), 1.97 (1H, d, J = 8.3Hz), 1.23 (6H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.4, 134.3, 131.4, 130.7, 130.3, 129.1, 128.5, 124.8, 124.1, 66.3, 60.9, 33.2, 31.4, 29.3, 28.8, 15.3 ppm.

Example 10 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,3'-difluoro [1, 1'-biphenyl] -3-yl) methyl ester

Yield: 19% (i.e., theory) ES HRMS: m / z found: 467.0808.

C22Hi80 ₂ F ₅ ²³ Na ³⁵ Cl calculated: 467.0813.

'H NMR (400 MHz, CDCl3): δ 7.35-7.12 (6H, m), 7.02-6.97 (1H, m), 6.86 (1H, d, J = 8.8Hz), 5.16 (2H, s), 2.11 ( 1H, t, J = 8.7Hz), 1.97 (1H, d, J = 8.4Hz), 1.23 (s, 6H) ppm. - 5 -

¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.4, 164.4, 161.9, 159.5, 157.0, 137.8, 131.4, 130.5, 125.0, 124.2, 116.8, 115.1, 66.3, 60.9, 33.2, 31.4, 29.2, 28.7, 15.5 ppm.

Example 11 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,4'-difluoro [1, 1'-biphenyl] -3-yl) methyl ester

Output: 32% (ie theory)

ES HRMS: m / z found 467.0806.

C22Hi80 ₂ F ₅ ²³ Na ³⁵ Cl calculated 467.0813.

'H NMR (400 MHz, CDCl 3): δ 7.26-7.12 (3H, m), 7.41-7.34 (2H, m), 7.54-7.49 (2H, m), 6.92 (1H, d, J = 8.6Hz), 5.27 (2H, s), 2.19 (1H, t, J = 8.6Hz), 2.05 (1H, s), 1.31-1.24 (m, 6H) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.4, 131.6, 130.1, 124.7, 124.1, 116.0, 115.8, 60.9, 33.2, 32.0, 31.4, 29.2, 28.8, 23.1, 21.4, 15.3, 14.5 ppm.

Using 2 mol% of [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 24 hours of reaction time at 70 ° C., the reaction was carried out by means of Suzuki coupling (stage E, method I). Examples 12 to 17 are obtained.

Example 12 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2, 2'-difluoro-

[1, 1'-biphenyl] -3-yl) methyl ester

Yield: 37% (of theory) ES HRMS: m / z found: 522.9504

C2iHi ₈ 02F ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 522.9519. ¹ H NMR (400 MHz, CDCl 3) δ 7.47 - 7.34 (m, 4H), 7.28 - 7.13 (m, 3H), 6.80 (d, J = 8.4 Hz, 1H), 5.24 (d, J = 3.2 Hz, 2H ), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm. ₅

¹³ C NMR (101 MHz, CDCl ₃ ) δ 170.63, 161.46, 159.61, 158.98, 157.11, 133.84, 132.30, 131.99, 130.75, 130.39, 128.08, 124.49, 124.41, 124.05, 123.46, 116.34, 89.84, 60.74, 36.16, 32.20 , 28.77, 28.14, 15.47 ppm.

Example 13 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2, 3 ', 4', 5'-tetrafluoro- [1, Γ -biphenyl] -3 - yl) methylester

Yield: 44% (ie theory)

ES HRMS: m / z found: 558.9353.

C ₂ iHi60 ₂ F ₄ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 558.9330. 'H NMR (400 MHz, CDCl3) δ 7.43 (td, J = 7.3, 1.8 Hz, 1H), 7.36 (td, J = 7.6, 1.8 Hz, 1H), 7.28 - 7.15 (m, 3H), 6.78 (i.e. , J = 8.5 Hz, 1H), 5.23 (d, J = 1.0 Hz, 2H), 1.99 (t, J = 8.5 Hz, 1H), 1.92 (d, J = 8.4 Hz, 1H), 1.29 (s, 3H ), 1.26 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.54, 160.20, 159.95, 159.24, 156.74, 150.34, 150.21, 138.60, 133.72, 131.10, 130.89, 126.84, 124.99, 124.64, 113.59, 89.98, 60.51, 36.22, 32.13, 28.76, 28.19, 15.46 ppm. Example 14 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,2 ', 4'-trifluoro [1, 1'-biphenyl] -3-yl) methylester

Yield: 33% (ie theory)

ES HRMS: m / z found: 540.9420. C ₂ iHi ₇ O ₂ F3 ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 540.9425. ¹ H NMR (400 MHz, CDCl 3) δ 7.43 (td, J = 7.2, 1.7 Hz, 1H), 7.40-7.32 (m, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.01-6.89 (m , 2H), 6.79 (d, J = 8.4 Hz, 1H), 5.23 (s, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.4 Hz, 1H), 1.28 (s , 3H), 1.25 (s, 3H) ppm. - 5 -

¹³ C NMR (101 MHz, CDCl ₃ ) δ 170.58, 163.68, 162.04, 161.68, 161.55, 159.57, 157.07, 146.30, 133.80, 132.71, 132.17, 130.84, 129.93, 124.49, 124.17, 1 1 1.91, 1 1 1.70, 89.88 , 60.60, 36.17, 32.18, 28.76, 28.14, 15.47 ppm.

Example 15 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro- (4'-ethynyl) - [1,1'-biphenyl] -3-yl ) methylester

Yield: 13% (ie theory)

ES HRMS: m / z found: 528.9615.

C ₂ 3Hi ₉ O ₂ F ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 528.9613. ¹ H NMR (400 MHz, CDCl 3) δ 7.62-7.46 (m, 4H), 7.45-7.31 (m, 2H), 7.23 (t, J = 7.6 Hz, 1H), 6.79 (d, J = 8.4 Hz, 1H ), 5.23 (s, 2H), 3.14 (s, 1H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.28 (s, 3H), 1.25 (s , 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.59, 160.30, 156.98, 136.28, 133.80, 132.62, 132.40, 131.28, 130.96, 130.44, 129.40, 127.74, 124.81, 89.89, 83.77, 78.35, 60.69, 36.17, 32.18, 28.77, 28.13, 15.48 ppm. Example 16 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,2'-difluoro [1, 1'-biphenyl] -3-yl) methyl ester

Yield: 25% (ie theory)

ES HRMS: m / z found 467.0811,

C22Hi80 ₂ F ₅ ²³ Na ³⁵ Cl calculated 467.0813.

'H NMR (400 MHz, CDCl3): δ 7.42-7.27 (5H, m), 7.19-7.07 (2H, m), 6.85 (1H, t, J = 8.4Hz), 5.16 (2H, s), 2.11 ( lH, t, J = 9.1Hz), 1.97 (1H, d, J = 7.1Hz), 1.23 (6H, s) ppm. - 5 -

¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.4, 132.4, 132.0, 130.7, 130.4, 129.1, 126.2, 124.5, 116.3, 116.1, 66.3, 60.9, 33.1, 31.4, 29.2, 28.7, 15.7, 15.3 ppm.

Example 17 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,2 ', 4'-trifluoro [1, Γ -biphenyl] -3-yl ) methylester

Output: 16% (ie theory)

ES HRMS: m / z found: 485.0706.

C22Hi ₇ 0 ₂ F6 ²³ Na ³⁵ Cl calculated: 485.0719. ¹ H NMR (400 MHz, CDCl 3): δ 7.45-7.33 (3H, m), 7.26-7.21 (1H, m), 7.00-6.91 (3H, m), 5.16 (2H, s), 2.18 (1H, t , J = 8.9Hz), 2.05 (1H, s), 1.31 (6H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 168.6, 157.9, 130.6, 129.2, 128.6, 122.8, 122.2, 1 10.2, 109.9, 102.9, 59.1, 43.5, 31.5, 29.7, 27.4, 27.0, 19.7, 13.6, 12.9 ppm.

Using 2 mol% of [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 24 hours of reaction time at 75 ° C., the reaction was carried out by means of Suzuki coupling (stage E, method I) obtained Example 18.

- 5 -

Example 18 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro-2'-trifluoromethyl- [1, Γ -biphenyl] -3-yl) methyl ester

Yield: 40% (i.e., theory) ES HRMS: m / z found: 572.9478.

C ₂₂ Hi80 ₂ F ₄ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 572.9487. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.78 (dd, J = 7.7, 0.7 Hz, 1H), 7.60 (dd, J = 7.5, 6.8 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H) , 7.44 (td, J = 7.1, 1.9 Hz, 1H), 7.35 (d, J = 7.5 Hz, 1H), 7.28 - 7.22 (m, 1H), 7.19 (t, J = 7.6 Hz, 1H), 6.79 ( d, J = 8.4 Hz, 1H), 5.22 (s, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.27 (s, 3H), 1.25 ( s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.62, 159.40, 156.93, 134.52, 133.85, 133.70, 132.49, 131.99, 131.77, 130.75, 129.90, 129.60, 128.67, 127.45, 126.57, 123.77, 89.82, 60.54, 36.15, 32.19, 28.76, 28.13, 15.44 ppm.

Using 2 mol% [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 6 hours of reaction time at 70 ° C., the reaction was carried out by means of Suzuki coupling (stage E, method I). Example 19 was obtained.

Example 19 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,2 ', 4'-trifluoro [1, 1'-biphenyl] -3-yl) methylester

Ausb.: 56 % (d. Theorie)

Yield: 56% (theory)

ES HRMS: m / z found: 540.9412. C ₂ iHi ₇ O ₂ F3 ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 540.9425. ¹ H NMR (400 MHz, CDCl 3) δ 7.44-7.34 (m, 3H), 7.30-7.19 (m, 3H), 6.78 (d, J = 8.4 Hz, 1H), 5.23 (d, J = 1.2 Hz, 2H ), 1.99 (t, J = 8.5 Hz, 1H), 1.92 (d, J = 8.4 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm. ¹³ CNMR (101 MHz, CDC1 ₃ ) δ 170.56, 163.61, 159.33, 156.84, 154.77, 151.80, 149.28, 139.95, 133.77, 131.14, 130.54, 125.59, 124.88, 124.58, 118.69, 118.47, 117.65, 89.93, 60.53, 36.19, 32.16, 28.77, 28.15, 15.47 ppm.

Analogously, Suzuki coupling (Step E, Method I) was prepared from (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2,6-difluoro-3-iodo-b enzylester and the corresponding arylboronic acids in the presence of 2 mol% [l, l-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl2 (dppf)), potassium phosphate and 16 hours reaction time at 70 ° C in toluene, Examples 20 and 21 ,

Example 20 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6,2'-trifluoro [1, 1'-biphenyl] -3-yl) methyl ester

Ausb.:28%(d. Theory)

ES HRMS: m / z found: 538.9465.

C2iHi ₇ 02F3 ²³ Na ⁷⁹ Br ₂ calculates: 538.9445. ¹ H NMR (400MHz, CDCl 3): δ 7.35-7.27 (3H, m), 7.19-7.08 (2H, m), 6.97 (1H, t, J = 8.6Hz), 6.73 (1H, d, J = 8.4Hz ), 5.23 (1H, d, J = 11.9 Hz), 5.18 (1H, d, J = 11.9 Hz), 1.90 (1H, t, J = 8.4 Hz), 1.80 (1H, d, J = 8.4 Hz), 1.20 (3H, s), 1.16 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.4, 163.1, 161.4, 160.7, 160.4, 158.9, 157.8, 133.8, 133.0, 131.9, 130.6, 130.5, 124.6, 122.9, 122.7, 120.4, 120.2, 116.4, 116.2, 112.7, 112.5, 112.3, 111.9, 111.7, 89.8, 54.6, 36.1, 32.1, 28.7, 28.1, 15.5 ppm.

- 5 -

Example 21 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6,2 ', 4'-tetrafluoro [1, Γ -biphenyl] -3-yl ) methylester

Yield: 15% (i.e., theory) ES HRMS: m / z found: 556.9371.

C2iHi602F ₄ ²³ Na ⁷⁹ Br ₂ Calculated: 556.9351. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.38 (2H, quin, J = 7.9 Hz), 7.05 (1H, t J = 8.6 Hz), 7.00 (2H, m), 6.80 (1H, d, J = 8.5 Hz), 5.29 (2H, dd, J = 18.5, 11.9 Hz), 1.98 (1H, t, J = 8.4 Hz), 1.87 (1H, d, J = 8.5 Hz), 1.27 (3H, s), 1.23 ( 3H, s) ppm. ¹³ C NMR (100 MHz, CDCl 3) δ 170.4, 164.7, 163.3, 162.1, 161.1, 160.7, 160.4, 159.1, 157.8, 133.8, 132.8, 1 12.8, 1 12.6, 1 12.4, 1 12.1, 1 1 1.9, 105.0, 104.7, 104.5, 90.0, 54.6, 36.2, 32.1, 28.7, 28.2, 15.5 ppm.

Using 2 mol% [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 16 hours reaction time in 1,4-dioxane at 70 ° C., reactions were carried out by means of Suzuki coupling (cf. Step E, Method I) Examples 22 and 23 were obtained.

Example 22 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,6,2'-trifluoro [1, Γ -biphenyl] -3-yl) methylester

Yield: 44% (i.e., theory) ES HRMS: m / z found: 485.0722.

C22Hi ₇ 0 ₂ F6 ²³ Na ³⁵ Cl calculated: 485.0719. ¹ H NMR (400MHz, CDCl 3): δ 7.42-7.33 (3H, m), 7.25-7.14 (2H, m), 7.04 (1H, t, J = 8.6Hz), 6.95 (1H, d, J = 9.5Hz ), 5.31 (1H, d, J = 12.0 Hz), 5.26 (1H, d, J = 11.9 Hz), 2.19 (1H, t, J = 9.2 Hz), 2.01 (1H, d, J = 8.4 Hz), 1.30 (3H, s), 1.28 (3H, s) ppm. _5?

¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.2, 163.2, 161.4, 160.7, 160.4, 159.0, 157.9, 133.1, 131.9, 130.6, 130.5, 130.4, 124.9, 122.9, 122.7, 122.4, 122.2, 122.0, 120.4, 120.3 , 119.5, 116.4, 116.2, 112.5, 112.3, 112.1, 111.9, 111.7 54.6, 33.2, 31.4, 29.2, 28.7, 15.3 ppm.

Example 23 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,6,2 ', 4'-tetrafluoro [1, 1'-biphenyl] - 3-yl) methylester

Output: 45% (ie theory)

ES HRMS: m / z found: 503.0606.

C22Hi60 ₂ F ₇ ²³ Na ³⁵ Cl calculated: 503.0625. ¹ H NMR (400 MHz, CDCl 3): δ 7.39-7.30 (2H, m), 7.04-6.90 (4H, m), 5.30 (1H, d, J = 12.0 Hz), 5.26 (1H, d, J = 12.0 Hz ), 2.19 (1H, t, J = 8.6 Hz), 2.01 (1H, d, J = 8.4 Hz), 1.30 (3H, s), 1.28 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.2, 164.7, 163.2, 162.2, 161.7, 160.7, 160.4, 159.2, 157.9, 133.0, 132.7, 132.0, 131.9, 130.4, 124.9, 124.6, 122.4, 122.2, 122.1, 121.7, 119.5, 119.4, 1 19.0, 1 18.9, 1 16.8, 116.4, 116.2, 112.7, 1 12.5, 1 12.3, 1 12.1, 11 1.8, 105.0, 104.7, 104.5, 54.7, 33.2, 31.4, 29.2, 28.7, 15.3 ppm.

Using 2 mol% of palladium (II) acetate (Pd (ac) 2), 5 mol% of triphenylphosphine and 6 hours of reaction time in toluene at 70 ° C Suzuki coupling (Step E, Method I) Examples 24 and 27 receive.

Example 24 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,6,4'-trifluoro-1- ', 1'-biphenyl] -3-yl) methyl ester

Yield: 50% (ie theory)

ES HRMS: m / z found: 538.9439. - 5 -

C2iHi ₇ 02F3 ²³ Na ⁷⁹ Br ₂ calculates: 538.9445.

'H NMR (400MHZ, CDC1 ₃ ): δ 7.41 (2H, t, J = 7.0 Hz), 7.35 (1H, dt, J = 8.7, 6.4 Hz), 7.09 (2H, t, J = 8.7 Hz), 6.96 (1H, t, J = 8.6 Hz), 6.73 (1H, d, J = 8.5 Hz), 5.19 (2H, m), 1.91 (1H, t, J = 8.5 Hz), 1.80 (1H, d, J = 8.4 Hz), 1.20 (3H, s), 1.16 (3H, s) ppm. ¹³ C NMR (100 MHz, CDCl 3) δ 170.4, 164.2, 162.7, 161.7, 160.2, 160.1, 157.6, 133.8, 132.0, 131.1, 131.0, 125.1, 125.0, 124.9, 116.1, 1 15.9, 112.8, 112.7, 112.5, 1 12.1, 111.9, 89.9, 54.6, 36.1, 32.1, 28.7, 28.1, 15.5 ppm.

Example 25 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,6,3'-trifluoro-

[1, 1'-biphenyl] -3-yl) methyl ester

Yield: 24% (ie theory)

ES HRMS: m / z found: 538.9440.

C2iHi ₇ 02F3 ²³ Na ⁷⁹ Br ₂ calculates: 538.9445. ¹ H NMR (400MHz, CDCl 3): δ 7.46-7.39 (2H, m), 7.30-7.21 (2H, m), 7.11 (2H, t, J = 8.4Hz), 6.05 (1H, t, J = 8.6Hz ), 6.80 (1H, d, J = 8.5 Hz), 5.27 (1H, s), 5.25 (1H, s), 1.99 (1H, t, J = 8.5 Hz), 1.88 (1H, d, J = 8.5 Hz ), 1.28 (3H, s), 1.24 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.5, 164.4, 161.9, 160.4, 160.2, 158.7, 157.7, 137.2, 137.1, 133.8, 132.0, 130.5, 125.1, 116.6, 116.3, 115.4, 1 15.2, 113.0, 112.8, 112.6 , 112.3, 112.1, 89.9, 54.6, 36.2, 32.1, 28.8, 28.2, 15.5 ppm. Example 26 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro-4'-chloro [1,1'-biphenyl] -3-yl ) methylester

Yield: 38% (ie theory)

ES HRMS: m / z found: 554.9174. - 5 -

C2iHi ₇ 02F3 ²³ Na ³⁵ Cr ⁹ Br ₂ Calculated: 554.9150. ¹ H NMR (400MHz, CDC1 ₃ ): δ 7.46-7.37 (5H, m), 7.04 (1H, t, J = 8.6Hz), 6.80 (1H, d, J = 8.5Hz), 5.26 (2H, m) , 1.98 (1H, t, J = 8.5 Hz), 1.87 (1H, d, J = 8.5 Hz), 1.28 (3H, s), 1.23 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.5, 162.8, 160.3, 160.1, 157.6, 134.4, 133.8, 133.6, 132.0, 130.7, 129.2, 124.9, 124.7, 112.9, 112.7, 112.5, 112.2, 112.0, 89.9, 54.6, 36.2, 32.1, 28.8, 28.2, 15.5 ppm.

Example 27 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,6,4'-trifluoro [1, Γ -biphenyl] -3-yl) methylester

Yield: 80% (i.e., theory) ES HRMS: m / z found: 485.0697.

C22Hi ₇ 0 ₂ F6 ²³ Na ³⁵ Cl calculated: 485.0719.

'H NMR (400MHZ, CDCl3): δ 7.48 (2H, t, J = 8.5 Hz), 7.42 (1H, m), 7.15 (2H, t, J = 8.6 Hz), 7.03 (1H, t, J = 8.6 Hz), 6.95 (1H, d, J = 9.5 Hz), 5.30 (1H, d, J = 11.9 Hz), 5.25 (1H, d, J = 11.9 Hz), 2.20 (1H, t, J = 8.7 Hz) , 2.02 (1H, d, J = 8.4 Hz), 1.31 (3H, s), 1.28 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.3, 164.2, 162.7, 161.7, 160.2, 160.0, 157.6, 132.1, 131.1, 130.4, 125.1, 125.0, 122.7, 122.4, 122.2, 122.0, 121.6, 119.5, 1 16.1, 1 15.9, 112.7, 12.3, 112.2, 112.0, 54.8, 33.2, 31.4, 29.3, 28.7, 15.3 ppm.

Using 2 mol% of tetrakis (triphenylphosphine) palladium (Pd (PPh3) i) and 6 hours of reaction time in toluene at 70 ° C, Examples 28 and 29 were obtained by Suzuki coupling (Step E, Method I). - -

Example 28 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,6,3'-trifluoro [1, Γ -biphenyl] -3-yl) methylester

Yield: 15% (ie theory)

ES HRMS: m / z found: 485.0721. C22Hi ₇ 0 ₂ F6 ²³ Na ³⁵ Cl calculated: 485.0719. ¹ H NMR (400MHz, CDC1 ₃ ): δ 7.46-7.39 (2H, m), 7.29-7.20 (2H, m), 7.11 (2H, t, J = 8.4Hz), 7.05 (1H, t, J = 8.6 Hz), 6.94 (1H, d, J = 9.4 Hz), 5.31 (1H, d, J = 11.9 Hz), 5.26 (1H, d, J = 11.9 Hz), 2.20 (1H, t, J = 8.5 Hz) , 2.01 (1H, d, J = 8.4 Hz), 1.31 (3H, s), 1.29 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.2, 164.4, 162.9, 161.9, 160.3, 160.2, 157.6, 137.2, 137.1, 132.1, 130.5, 125.0, 122.4, 122.2, 122.0, 1 19.5, 116.5, 116.3, 115.4, 115.2 , 112.8, 112.6, 1 12.4, 1 12.3, 1 12.1, 54.7, 33.2, 31.4, 29.3, 28.8, 15.4 ppm.

Example 29 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro-4'-chloro [1, Γ -biphenyl] -3 - yl) methylester

Yield: 23% (ie theory)

ES HRMS: m / z found 501.0423.

C22Hi70 ₂ F ₅ ²³ Na ³⁵ Cl2 calculates 501.0423. ¹ H NMR (400MHz, CDCl 3): δ 7.45-7.37 (5H, m), 7.04 (1H, t, J = 8.6Hz), 6.93 (1H, d, J = 9.5Hz), 5.31 (2H, m), 2.19 (lH, t, J = 8.5 Hz), 2.01 (1H, d, J = 8.4 Hz), 1.31 (3H, s), 1.28 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.2, 162.8, 160.3, 160.1, 157.5, 134.5, 133.5, 132.0, 130.6, 130.3, 129.2, 124.9, 124.8, 122.8, 122.4, 122.0, 1 19.5, 112.7, 112.5, 112.4 , 112.3, 112.0, 54.7, 33.2, 31.4, 29.2, 28.7, 15.3 ppm. - -

Analogously, Suzuki coupling (Step E, Method I) was prepared from (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 2-fluoromethyl-3-iodo-benzyl ester and corresponding arylboronic acids in the presence of 2 mol% palladium (II) acetate (Pd (ac) 2), 5 mol% triphenylpine potassium phosphate and 6 hours reaction time at 70 ° C in toluene, Examples 30 and 35.

Example 30 (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoromethyl-4'-fluoro- [1, Γ -biphenyl] -3-yl) methylester

Yield: 81% (ie theory)

ES HRMS: m / z found: 481.0977.

C ₂ 3H ₂ oO ₂ F ₅ ²³ Na ³⁵ Cl calcd: 481.0970. ¹ H NMR (400 MHz, CDCl ₃ ): δ 7.49-7.43 (2H, m), 7.36-7.31 (3H, m), 7.15 (2H, t, J = 8.6 Hz), 6.94 (1H, d, J = 9.3 Hz), 5.40 (1H, s), 5.39 (1H, d, J = 13.0 Hz), 5.34 (1H, d, J = 13.0 Hz) 5.28 (1H, s), 2.21 (1H, t, J = 8.6 Hz ), 2.07 (1H, d, J = 8.4 Hz), 1.30 (6H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.4, 164.1, 161.7, 144.0, 137.3, 136.4, 131.9, 131.6, 131.5, 131.1, 130.4, 130.0, 129.5, 122.4, 122.2, 122.0, 1 19.5, 115.8, 1 15.5, 80.2, 78.6, 64.3, 33.3, 31.4, 29.3, 28.8, 15.4 ppm.

Example 31 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-3'-fluoro- [1, Γ -biphenyl] -3-yl) methylester

Yield: 9% (ie theory)

ES HRMS: m / z found: 481.0966.

C23H ₂ o02F ₅ ²³ Na ³⁵ Cl calculated: 481.0970. ¹ H NMR (400MHz, CDCl 3): δ 7.50-7.32 (4H, m), 7.16-7.08 (3H, m), 6.94 (1H, d, J = 9.4Hz), 5.42 (1H, s), 5.40 (1H, d, J = 13.0 Hz), 5.35 (1H, d, J = 13.0 Hz) 5.30 (1H, s), 2.21 (1H, t, J = 8.7 Hz), 2.07 (1H, d , J = 8.3 Hz), 1.30 (6H, s) ppm.

¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.3, 164.1, 161.7, 143.6, 142.6, 137.3, 131.7, 131.6, 130.9, 130.4, 130.2, 130.1, 129.7, 125.8, 122.4, 122.2, 122.0, 117.1, 116.9, 1 15.1, 114.9, 80.1, 78.5, 64.2, 33.3, 31.4, 29.2, 28.8, 15.4 ppm.

Example 32 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-4'-chloro [1, Γ -biphenyl] -3-yl) methylester

Yield: 21% (of theory) ES HRMS: m / z found: 497.0674.

C23H ₂ OO ₂ F ₄ ²³ Na ³⁵ Cl 2 Calculated: 497.0674. ¹ H NMR (400MHz, CDCl 3): δ 7.50-7.40 (4H, m), 7.33-7.30 (3H, m), 6.94 (1H, d, J = 9.4Hz), 5.40 (1H, s), 5.39 (1H , d, J = 13.0 Hz), 5.34 (1H, d, J = 13.0 Hz) 5.28 (1H, s), 2.21 (1H, t, J = 8.6 Hz), 2.06 (1H, d, J = 8.4 Hz) , 1.30 (6H, s) ppm. ¹³ C NMR (100 MHz, CDCl 3) δ 170.3, 143.8, 138.9, 137.4, 134.3, 131.8, 131.6, 131.2, 131.0, 130.4, 130.1, 129.7, 128.9, 122.4, 122.2, 122.1, 119.5, 80.1, 78.5, 64.3, 33.3, 31.4, 29.3, 28.8, 15.3 ppm.

Example 33 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-2'-fluoro- [1, Γ -biphenyl] -3-yl) methylester

Ausb.: 30 % (d. Theorie)

Yield: 30% (ie theory)

ES HRMS: m / z found: 481.0951. C23H ₂ o02F ₅ ²³ Na ³⁵ Cl calculated: 481.0970. ¹ H NMR (400 MHz, CDCl 3): δ Ί 52-1 1 (3H, m), 7.33 (2H, t, J = 7.5 Hz), 7.25 1H, t, J = 7.5 Hz), 7.18 (1H, t, J = 9.0 Hz), 6.96 (1H, d, J = 9.4 Hz), 5.49 (1H, s), 5.40 (1H, d, J = 13.0 Hz), 5.35 (1H, d, J = 13.0 Hz) 5.21 (1H, s), 2.21 (1H, t, J = 8.9 Hz), 2.07 (1H, d, J = 8.4 Hz), 1.30 (6H, s) ppm.

¹³ C NMR (100 MHz, CDCl ₃ ) δ 170.4, 161.1, 158.7, 137.7, 137.0, 132.8, 132.7, 132.4, 131.4, 130.9, 130.5, 130.3, 129.9, 129.8, 127.9, 127.7, 124.6, 122.4, 122.2, 122.0 , 1 19.5, 1 16.2, 115.9, 80.6, 78.9, 64.3, 33.3, 31.4, 29.3, 28.8, 15.3 ppm.

Example 34 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-4'-fluoro- [1, Γ -biphenyl] -3-yl) methylester

Yield: 21% (i.e., theory) ES HRMS: m / z found: 499.0897.

C23Hi90 ₂ F ₆ ²³ Calculated Na ³⁵ Cl: 499.0875. ¹ H NMR (400MHz, CDCl 3): δ 7.53-7.45 (2H, m), 7.32 (2H, q, J = 8.4Hz), 7.00 (3H, m), 5.47 (1H, s), 5.38 (1H, d , J = 13.0 Hz), 5.34 (1H, d, J = 13.0 Hz), 5.17 (1H, s), 2.22 (1H, t, J = 8.9 Hz), 2.07 (1H, d, J = 8.4 Hz), 1.30 (6H, s) ppm. ¹³ C NMR (100 MHz, CDCl 3) δ 170.3, 164.4, 162.0, 161.3, 158.8, 137.1, 136.9, 133.2, 133.1, 132.9, 132.8, 131.5, 130.4, 130.1, 129.9, 123.9, 123.8, 122.5, 122.2, 122.1, 121.7, 119.5, 1 16.7, 1 11.9, 1 11.7, 104.7, 104.5, 104.2, 80.4, 78.7, 64.2, 33.3, 31.4, 29.3, 28.8, 15.3 ppm.

Example 35 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2, 3 ', 5'-trifluoro) - [1,1'-biphenyl] -3-yl ) methylester

a) Stufe A (Methode II): 2-Fluor-3-iod-benzoesäuremethylester (bekannt aus Stufe A, Methode I) b) Stufe E (Methode II): 2, 3',5'-Trifluor-[l, -biphenyl]-3-carbonsäuremethylester - -

a) Step A (Method II): 2-fluoro-3-iodo-benzoic acid methyl ester (known from Step A, Method I) b) Step E (Method II): 2, 3 ', 5'-trifluoro [l, - biphenyl] -3-carbonsäuremethylester - -

To a solution of 560 mg (2.0 mmol) of 2-fluoro-3-iodo-benzoic acid methyl ester in 20 mL of toluene, 36.6 mg (0.05 mmol) of [l, l-bis (diphenylphosphino) ferrocenes] dichloropalladium (II ) (PdCl2 (dppf)), 1.70 g (8.0 mmol) of potassium phosphate and 488 mg (3.0 mmol) of 3,5-difluorophenylboronic acid. Subsequently, the reaction mixture was degassed and stirred at 100 ° C for 24 hours. Thereafter, the resulting reaction mixture was forced through a silica gel-loaded filter to remove the palladium catalyst and the inorganic salts. The crude product obtained was purified by flash chromatography (silica gel, eluent: 3% ethyl acetate in n-hexane). This gives 229 mg (43% of theory) of methyl 3 ', 5'-difluoro-2-methyl- [l, -biphenyl] -3-carboxylate, which can be reduced. c) Step B (Method II): (2, 3 ', 5'-trifluoro [1, 1'-biphenyl] methanol, see Step B, Method I

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure- (2, 3',5'-trifluor-[l,l '-biphenyl]-3-yl)methylester; vgl. Stufe D , Methode I

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2, 3 ', 5'-trifluoro [1, l' -] biphenyl] -3-yl) methylester; see. Stage D, Method I

Yield: 79% (theory)

ES HRMS: m / z found: 540.9413.

C2iHi ₇ 0 ₂ F3 ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 540.9425. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.45-7.37 (m, 2H), 7.25 - 7.21 (m, 1H), 7.12-7.05 (m, 2H), 6.83 (t, J = 8.9, 2.3 Hz, 1H ), 6.78 (d, J = 8.4 Hz, 1H), 5.23 (s, 2H), 1.99 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.28 (s, 3H ), 1.26 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.54, 164.48, 162.15, 159.32, 156.81, 138.83, 133.75, 131.04, 124.94, 124.71, 112.60, 106.69, 103.64, 99.99, 89.96, 60.57, 36.20, 32.15, 28.76, 28.15, 15.47 ppm. - 5

 In an analogous manner, the examples and 53 were obtained by means of stage D, method II (compare also stage D, method I).

Example 36 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,2 ', 3'-trifluoro) - [1,1'-biphenyl] -3-yl) methylester

a) Stufe A (Methode II): 2-Fluor-3-iod-benzoesäuremethylester (bekannt aus Stufe A, Methode I) b) Stufe E (Methode II) : 2, 2 ' ,3 ' -Trifluor- [ 1 , 1 ' -biphenyl] -3 -carbonsäuremethylester; vgl. Stufe E,

a) Step A (Method II): 2-Fluoro-3-iodo-benzoic acid methyl ester (known from Step A, Method I) b) Step E (Method II): 2, 2 ', 3'-trifluoro [1, 1 '-biphenyl] -3-carboxylic acid methyl ester; see. Level E,

 Method II; Example 35; Yield obtained: 45% (theory)

c) Stufe B (Methode II): (2, 2',3'-Trifluor-[l,l '-biphenyl]methanol; vgl. Stufe B, Methode I;

c) Step B (Method II): (2, 2 ', 3'-trifluoro [1, 1'-biphenyl] methanol, see Step B, Method I;

 Yield obtained: 88% (of theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure- (2, 2',3'-trifluor-[l,l '-biphenyl]-3-yl)methylester; vg l . S tu fe D , Methode I

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2, 2 ', 3'-trifluoro [1, l' -] biphenyl] -3-yl) methylester; see . S tu fe D, method I

Yield: 70% (ie theory)

ES HRMS: m / z found: 540.9387.

C ₂ iHi ₇ 0 ₂ F ₃ ^ij Na W ¹ Br [M + Naf calculated: 540.9425. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.46 (td, J = 7.1, 1.9 Hz, 1H), 7.37 (td, J = 7.6, 1.8 Hz, 1H), 7.26 (d, J = 3.2 Hz, 1H) , 7.13 (d, J = 3.0 Hz, 1H), 7.14 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDCl ₃ ) δ 170.57, 159.40, 156.91, 133.80, 132.06, 131.22, 128.96, 126.66, 124.59, 124.37, 124.30, 124.14, 122.07, 117.52, 117.35, 89.90, 60.60, 36.17, 32.18, 28.75 , 28.12, 15.46 ppm.

Example 37 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2, 2 ', 5'-trifluoro) - [1,1'-biphenyl] -3-yl ) methylester

a) Stufe A (Methode II): 2-Fluor-3-iod-benzoesäuremethylester (bekannt aus Stufe A, Methode I) b) Stufe E (Methode II): 2, 2',5'-Trifluor-[l, -biphenyl]-3-carbonsäuremethylester; vgl. Stufe E,

a) Step A (Method II): 2-fluoro-3-iodo-benzoic acid methyl ester (known from Step A, Method I) b) Step E (Method II): 2, 2 ', 5'-trifluoro [l, - biphenyl] -3-carbonsäuremethylester; see. Level E,

 Method II; Example 35; Yield obtained: 50% (theory)

c) Stufe B (Methode II): (2, 2',5'-Trifluor-[l,l '-biphenyl]methanol; vgl. Stufe B, Methode I;

c) Step B (Method II): (2, 2 ', 5'-trifluoro [1, 1'-biphenyl] methanol, see Step B, Method I;

 Yield obtained: 90% (of theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2, 2 ', 5'-trifluoro [l, 1'-biphenyl] -3-yl) methyl ester; see. Stage D, Method I

Yield: 83% (ie theory)

ES HRMS: m / z found: 540.9447.

C2iHi ₇ 0 ₂ F3 ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 540.9425. _n

- 67 - ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.45 (td, J = 7.2, 1.8 Hz, 1H), 7.37 (t, J = 6.6 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H ), 7.17 - 7.03 (m, 3H), 6.79 (d, J = 8.4 Hz, 1H), 5.24 (s, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz , 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.56, 159.47, 156.97, 133.79, 132.04, 131.22, 124.57, 124.31, 123.18, 118.47, 118.21, 117.42, 117.17, 116.83, 116.59, 89.91, 60.53, 36.17, 32.17, 28.75, 28.13, 15.46 ppm.

Example 38 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2, 4'-difluoro) - [1, 1'-biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 2-Fluor-3-iod-benzoesäuremethylester (bekannt aus Stufe A, Methode I) b) Stufe E (Methode II): 2, 4 "-Difluor-[ 1,1 '-biphenyl] -3 -carbonsäuremethylester; vgl. Stufe E,

a) Step A (Method II): 2-Fluoro-3-iodo-benzoic acid methyl ester (known from Step A, Method I) b) Step E (Method II): 2,4 '-difluoro- [1,1'-biphenyl ] -3-carboxylic acid methyl ester, see step E,

 Method II; Example 35; Yield obtained: 78% (of theory)

c) Stufe B (Methode II): (2, 4'-Difluor-[l,l '-biphenyl]methanol; vgl. Stufe B, Methode I; erhaltene Ausbeute: 90 % (d. Theorie)

c) Step B (Method II): (2, 4'-difluoro [1, 1'-biphenyl] methanol, see Step B, Method I, Yield obtained: 90% (of theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2, 4'-difluoro [1,1'-biphenyl] -3-yl) methyl ester; see. Stage D, Method I

Yield: 75% (i.e., theory) ES HRMS: m / z found: 522.9432. C2iHi ₈ 0 ₂ F2 ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 522.9519. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.53, 7.53, 7.52, 7.52, 7.51, 7.51, 7.50, 7.50, 7.41, 7.41, 7.39, 7.39, 7.37, 7.37, 7.36, 7.35, 7.24, 7.22, 7.20, 7.16 , 7.14, 7.12, 6.80, 6.78, 5.23, 2.00, 1.98, 1.96, 1.93, 1.91, 1.28, 1.25 ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.60, 159.43, 156.95, 133.81, 131.36, 131.19, 131.1 1, 130.07, 124.71, 124.36, 124.21, 1 15.97, 1 15.76, 89.87, 60.78, 36.17, 32.18, 28.77, 28.14 , 15.48 ppm.

Example 39 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoro [l, 1'-biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 2-Fluor-3-iod-benzoesäuremethylester (bekannt aus Stufe A, Methode I) b) Stufe E (Methode II): 2-Fluor-[l , l '-biphenyl] -3 -carbonsäuremethylester; vgl. Stufe E, Methode II; Beispiel 35; erhaltene Ausbeute: 95 % (d. Theorie)

a) Step A (Method II): 2-Fluoro-3-iodo-benzoic acid methyl ester (known from Step A, Method I) b) Step E (Method II): 2-Fluoro [1, 1'-biphenyl] -3 -carboxylate; see. Stage E, Method II; Example 35; Yield obtained: 95% (of theory)

c) Stufe B (Methode II): (2-Fluor-[l , l '-biphenyl]methanol; vgl. Stufe B, Methode I; erhaltene

c) Step B (Method II): (2-Fluoro [1, 1'-biphenyl] methanol, see Step B, Method I;

 Yield: 99% (theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-Fluoro [1, 1'-biphenyl] -3-yl) methyl ester; see. Stage D, Method I

Y. : 91% (of theory) ES HRMS: m / z found: 504.9589. C ₂ iHi ₉ 0 ₂ F ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 504.9613. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.56 (t, J = 1.6 Hz, 1H), 7.54 (dd, J = 2.6, 1.4 Hz, 1H), 7.48-7.42 (m, 3H), 7.41-7.35 ( m, 2H), 7.22 (t, J = 7.6 Hz, 1H), 6.80 (d, J = 8.4 Hz, 1H), 5.24 (s, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 ( d, J = 8.5 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.62, 159.54, 157.05, 135.85, 133.85, 131.54, 129.95, 129.52, 128.87, 128.23, 124.68, 124.26, 124.11, 89.86, 60.86, 36.16, 32.21, 28.78, 28.11, 15.49 ppm ,

Example 40 (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid i

 [1, 1'-biphenyl] -3-yl) methyl ester

Yield: 89% (of theory) ES HRMS: m / z found: 449.0919.

C22Hi90 ₂ F ₄ ²³ Na ³⁵ Cl [M + Na] ⁺ calculated: 449.0907. ¹ H NMR (400 MHz, CDCl 3) δ 7.55 (t, J = 1.6 Hz, 1H), 7.54 (dd, J = 2.7, 1.4 Hz, 1H), 7.49-7.43 (m, 3H), 7.42-7.34 (m , 2H), 7.22 (t, J = 7.6 Hz, 1H), 6.94 (dd, J = 9.4, 1.0 Hz, 1H), 5.24 (dd, J = 3.5, 1.2 Hz, 2H), 2.19 (t, J = 8.5 Hz, 1H), 2.05 (d, J = 8.4 Hz, 1H), 1.31 (s, 3H), 1.30 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDCl 3) δ 170.41, 159.58, 157.09, 135.80, 131.66, 130.41, 130.04, 129.50, 128.87, 128.25, 127.59, 124.68, 124.06, 122.16, 119.47, 61.00, 33.26, 31.39, 29.21, 28.77, 15.34 ppm.

Example 41 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,3 ', 5'-trifluoro [1, Γ -biphenyl] -3-yl ) methylester

a) Stufe A (Methode II): 2-Fluor-3-iod-benzoesäuremethylester (bekannt aus Stufe A, Methode I) b) Stufe E (Methode II): 2, 3',5'-Trifluor-[l, -biphenyl]-3-carbonsäuremethylester; vgl. Stufe E,

a) Step A (Method II): 2-fluoro-3-iodo-benzoic acid methyl ester (known from Step A, Method I) b) Step E (Method II): 2, 3 ', 5'-trifluoro [l, - biphenyl] -3-carbonsäuremethylester; see. Level E,

Method II; Example 35; Yield obtained: 43% (theory) - 7 -

c) Stufe B (Methode II): (2, 3',5'-Trifluor-[l,l '-biphenyl]methanol; vgl. Stufe B, Methode I;

c) Step B (Method II): (2, 3 ', 5'-trifluoro [1, 1'-biphenyl] methanol, see Step B, Method I;

 Yield obtained: 95% (of theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2, 3 ', 5'-trifluoro [l, l'-biphenyl] -3-yl) methyl ester; see. Stage D, Method I

Yield: 50% (ie theory)

ES HRMS: m / z found: 485.0703. C22H1803F5 ²³ Na ³⁵ Cl [M + Na] ⁺ calcd: 485.0719. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.44-7.38 (m, 2H), 7.24 (t, J = 7.6 Hz, 1H), 7.13-7.04 (m, 2H), 6.92 (dd, J = 9.4, 1.0 Hz, 1H), 6.84 (tt, J = 8.9, 2.3 Hz, 1H), 5.24 (s, 2H), 2.19 (t, J = 8.5 Hz, 1H), 2.05 (d, J = 8.4 Hz, 1H), 1.31 (s, 3H), 1.30 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.34, 164.49, 162.15, 159.39, 156.45, 138.87, 131.06, 130.31, 126.52, 124.94, 124.49, 122.15, 119.69, 112.33, 106.16, 103.67, 98.81, 60.78, 33.20, 31.43, 29.25, 28.76, 15.33 ppm.

Example 42 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro [1, 1'-biphenyl] -3-yl) methyl ester

- 7 - a) Stufe A (Methode II): 2,6-Difluor-3-iod-benzoesäuremethylester (bekannt aus

- 7 - a) Step A (Method II): 2,6-Difluoro-3-iodo-benzoic acid methyl ester (known from

 WO 2009/076747) b) Stage E (Method II): 2,6-difluoro [1-biphenyl] -3-carboxylic acid methyl ester; see. step

 method II; Example 35; Yield obtained: 91% (of theory)

c) Stufe B (Methode II): 2,6-Difluor [l,l '-biphenyl]-methanol; vgl. Stufe B, Methode I; erhaltene

c) Step B (Method II): 2,6-difluoro [1, 1'-biphenyl] methanol; see. Stage B, Method I; obtained

 Yield: 96% (theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure- (2,6-difluor-[l,l '-biphenyl]-3-yl)methylester; vgl. Stufe D, Methode I; Ausb.: 87 % (d. Theorie)

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro [1, 1'-biphenyl] -3 yl) methylester; see. Stage D, Method I; Yield: 87% (ie theory)

ES HRMS: m / z calculated: 522.9515.

C21H1802F2 ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ found: 522.9519. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.54-7.35 (m, 6H), 7.01 (td, J = 8.7, 1.4 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H), 5.26 (d, J = 6.3 Hz, 2H), 1.96 (t, J = 8.5 Hz, 1H), 1.86 (d, J = 8.4 Hz, 1H), 1.28 (s, 3H), 1.23 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.46, 162.64, 162.57, 160.14, 160.07, 135.17, 133.81, 132.09, 131.99, 129.39, 129.36, 128.97, 128.33, 125.87, 89.85, 54.65, 36.13, 32.08, 28.74, 28.11, 15.47 ppm.

Example 43 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro [1,1'-biphenyl] -3-yl) methyl ester

Output: 80% (ie theory) - 7 -

ES HRMS: m / z found

C22Hi80 ₂ F ₅ ²³ Na ³⁵ Cl [M + Na] ⁺ Calculated: 467.0813.

1H NMR (400 MHz, CDC13) δ 7.53-7.35 (m, 6H), 7.01 (td, J = 8.6, 1.4 Hz, 1H), 6.93 (dd, J = 9.4, 0.9 Hz, 1H), 5.27 (d, J = 7.3 Hz, 2H), 2.17 (t, J = 8.9 Hz, 1H), 2.00 (d, J = 8.4 Hz, 1H), 1.30 (s, 3H), 1.28 (s, 3H) ppm.

13C NMR (101 MHz, CDC13) δ 170.24, 162.65, 160.12, 157.60, 157.22, 135.13, 132.18, 132.08, 130.39, 129.36, 129.34, 128.98, 128.35, 125.90, 122.16, 119.46, 54.80, 33.18, 31.36, 29.20, 28.75 , 15.34 ppm.

Example 44 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro-3-thien-2-yl) benzyl ester

a) Stufe A (Methode II): 2,6-Difluor-3-iod-benzoesäuremethylester (bekannt aus

a) Step A (Method II): 2,6-Difluoro-3-iodo-benzoic acid methyl ester (known from

 WO 2009/076747) b) Step E (Method II): 2,6-Difluoro-3-thien-2-yl-benzoic acid methyl ester; see. Level E, method

 II; Example 35; Yield obtained: 48% (theory)

c) Stufe B (Methode II): (2,6-Difluor-3-thien-2-yl)benzylalkohol; vgl. Stufe B, Methode I; erhaltene Ausbeute: 99 % (d. Theorie)

c) Step B (Method II): (2,6-Difluoro-3-thien-2-yl) benzyl alcohol; see. Stage B, Method I; Yield obtained: 99% (of theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure- (2,6-difluor-3-thien-2-yl)benzylester; vgl. Stufe D, Methode I; Ausb.: 85 % (d. Theorie) - 7 -

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro-3-thien-2-yl) benzyl ester; see. Stage D, Method I; Yield: 85% (ie theory) - 7 -

ES HRMS: m / z found

Ci9Hi ₆ 02F ₂ ²³ NaS ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 528.9083.

'H NMR (400 MHz, CDC1 ₃ ) δ 7.61 (td, J = 8.7, 6.2 Hz, 1H), 7.43 (d, J = 3.7 Hz, 1H), 7.38 (dd, J = 5.1, 0.8 Hz, 1H) , 7.12 (dd, J = 4.7, 4.1 Hz, 1H), 6.97 (td, J = 8.7, 1.3 Hz, 1H), 6.80 (d, J = 8.5 Hz, 1H), 5.26 (d, J = 8.7 Hz, 2H), 1.96 (t, J = 8.5 Hz, 1H), 1.86 (d, J = 8.5 Hz, 1H), 1.28 (s, 3H), 1.23 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.42, 162.24, 159.73, 159.54, 157.03, 136.33, 133.78, 130.26, 128.16, 127.62, 126.80, 126.74, 126.31, 126.28, 89.90, 54.51, 36.15, 32.06, 28.73, 28.15, 15.47 ppm.

Example 45 -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2,6-

Yield: 75% (ie theory)

ES HRMS: mz found: 473.0370.

C2oHi60 ₂ F ₅ ²³ NaS ³⁵ Cl [M + Na] ⁺ calcd: 473.0377. ^l H NMR (400 MHz, CDCl3) δ 7.62 (td, J = 8.7, 6.2 Hz, 1H), 7:42 (d, J = 3.6 Hz, 1H), 7:38 (d, J = 4.8 Hz, 1H), 7.15 - 7.09 (m, 1H), 6.98 (dd, J = 8.6, 1.1 Hz, 1H), 6.93 (d, J = 10.2 Hz, 1H), 5.26 (d, J = 9.0 Hz, 2H), 2.17 (t, J = 8.9 Hz, 1H), 2.00 (d, J = 8.4 Hz, 1H), 1.31 (s, 3H), 1.28 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.21, 162.29, 159.78, 159.50, 156.93, 136.27, 130.38, 130.32, 128.16, 127.61, 126.80, 126.74, 126.34, 126.31, 122.17, 119.47, 54.66, 33.14, 31.39, 29.24, 28.74, 15.33 ppm.

- 7 -

Example 46 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoromethyl-3-thien-2-yl) benzyl ester

a) Stufe A (Methode II): 2-Fluormethyl-3-iod-benzoesäuremethylester (bekannt aus Stufe A,

a) Step A (Method II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester (known from Step A,

 Method I) b) Step E (Method II): 2-fluoromethyl-3-thien-2-yl-benzoic acid methyl ester; see. Level E,

 Method II; Example 35; Yield obtained: 79% (of theory)

c) Stufe B (Methode II): (2-Fluormethyl-3-thien-2-yl)benzylalkohol; vgl. Stufe B, Methode I;

c) Step B (Method II): (2-fluoromethyl-3-thien-2-yl) benzyl alcohol; see. Stage B, Method I;

 Yield obtained: 87% (theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure- (2-fluormethyl-3-thien-2-yl)benzylester; vgl. Stufe D, Methode I; Ausb.: 95 % (d. Theorie)

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoromethyl-3-thien-2-yl) benzyl ester; see. Stage D, Method I; Output: 95% (ie theory)

ES HRMS: m / z found: 524.9330. C2oHi ₉ 0 ₂ F ²³ Na ⁷⁹ SBr ⁸¹ Br [M + Na] ⁺ calcd: 524.9334.

'H NMR (400 MHz, CDCb) δ 7.51 - 7.41 (m, 3H), 7.40 (dd, J = 5.1, 1.2 Hz, 1H), 7.17 (dd, J = 3.5, 1.2 Hz, 1H), 7.12 (dd , J = 5.1, 3.5 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 5.49 (d, J = 48.1 Hz, 2H), 5.34 (dd, J = 8.0, 1.4 Hz, 2H), 1.98 (t, J = 8.4Hz, 1H), 1.92 (d, J = 8.4Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.52, 141.18, 137.65, 137.38, 133.79, 132.37, 132.23, 131.86, 129.90, 128.51, 127.93, 126.77, 89.92, 80.17, 78.55, 64.17, 36.17, 32.22, 28.76, 28.16, 15.48 ppm. Example 47 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-3-thien-2-yl) benzyl ester

Yield: 86% (of theory) ES HRMS: m / z found: 469.0619.

C2iHi ₉ O ₂ F ₄ ²³ NaS ³⁵ Cl [M + Na] ⁺ calcd: 469.0628.

'H NMR (400 MHz, CDC1 ₃ ) δ 7.52-7.43 (m, 3H), 7.40 (dd, J = 5.1, 1.2 Hz, 1H), 7.17 (dd, J = 3.5, 1.2 Hz, 1H), 7.12 ( dd, J = 5.1, 3.5 Hz, 1H), 6.93 (d, J = 9.5 Hz, 1H), 5.49 (d, J = 48.1 Hz, 2H), 5.34 (dd, J = 10.6, 1.4 Hz, 2H), 2.19 (t, J = 8.8 Hz, 1H), 2.05 (d, J = 8.4 Hz, 1H), 1.30 (s, 6H) ppm. ¹³ C NMR (101 MHz, CDCl 3) δ 170.31, 141.14, 137.43, 137.38, 132.41, 132.26, 131.95, 130.31, 129.91, 128.51, 127.93, 126.80, 122.07, 119.46, 80.15, 78.53, 64.36, 33.26, 31.42, 29.26, 28.76, 15.33 ppm.

(1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoromethyl- [1,1'-biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 2-Fluormethyl-3-iod-benzoesäuremethylester (bekannt aus Stufe A,

a) Step A (Method II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester (known from Step A,

 Method I) b) Step E (Method II): 2-fluoromethyl- [1,1'-biphenyl] -3-carboxylic acid methyl ester; see. Level E,

 Method II; Example 35; Yield obtained: 97% (of theory)

c) Stufe B (Methode II): 2-Fluormethyl- [1,1 ' -biphenyl] -methanol; vgl. Stufe B, Methode I; erhaltene Ausbeute: 89 % (d. Theorie) - 7 -

c) Step B (Method II): 2-fluoromethyl- [1,1'-biphenyl] -methanol; see. Stage B, Method I; Yield obtained: 89% (of theory) - 7 -

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-fluoromethyl- [l, -biphenyl] -3-yl) methyl ester; see. Stage D, Method I; Yield: 97% (i.e., theory) ES HRMS: m / z found: 518.9776.

C22H _{2 2} i0 F ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calculated: 518.9770.

'H NMR (400 MHz, CDC1 ₃ ) δ 7.66-7.31 (m, 8H), 6.79 (d, J = 8.3 Hz, 1H), 5.38 (d, J = 48.1 Hz, 2H), 5.35 (dd, J = 5.3, 1.5 Hz, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.4 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDC13) δ 170.58, 144.85, 140.50, 137.35, 133.84, 131.74, 131.60, 130.99, 129.94, 129.25, 128.66, 127.97, 89.87, 80.36, 78.74, 64.17, 36.16, 32.25, 28.78, 28.14, 15.50 ppm.

Example 49 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl- [1, Γ -biphenyl] -3-yl) methyl ester

Ausb.: 82 % (d. Theorie)

Output: 82% (ie theory)

ES HRMS: m / z found: 463.1051. C23H2i0 ₂ F ₄ ²³ Na ³⁵ Cl [M + Na] ⁺ Calculated: 463.1064.

'H NMR (400 MHz, CDCl3) δ 7.66-7.31 (m, 8H), 6.79 (d, J = 8.3 Hz, 1H), 5.38 (d, J = 48.1 Hz, 2H), 5.35 (dd, J = 5.3 , 1.5 Hz, 2H), 1.98 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.4 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDC13) δ 170.58, 144.85, 140.50, 137.35, 133.84, 131.74, 131.60, 130.99, 129.94, 129.25, 128.66, 127.97, 89.87, 80.36, 78.74, 64.17, 36.16, 32.25, 28.78, 28.14, 15.50 ppm. Example 50 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoromethyl-4'-fluoro- [1,1'-biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 2-Fluormethyl-3-iod-benzoesäuremethylester (bekannt aus Stufe A,

a) Step A (Method II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester (known from Step A,

 Method I) b) Step E (Method II): 2-fluoromethyl-4'-fluoro [1,1'-biphenyl] -3-carboxylic acid methyl ester; see.

 Stage E, Method II; Example 35; Yield obtained: 97% (of theory)

c) Stufe B (Methode II): 2-Fluormethyl-4'-fluor[l,l '-biphenyl]-methanol; vgl. Stufe B, Methode I;

c) Step B (Method II): 2-fluoromethyl-4'-fluoro [1,1'-biphenyl] -methanol; see. Stage B, Method I;

 Yield obtained: 84% (theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-fluoromethyl-4'-fluoro- [l, -biphenyl] -3-yl) methyl ester; see. Stage D, Method I; Yield: 99% (i.e., theory) ES HRMS: m / z found: [M + Na] ⁺ , 534.9692.

C22H ₂ o02F2 ²³ Na ⁷⁹ Br ₂ calculated: 534.9696. ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.39 (2H, m), 7.26 (2H, m), 7.05 (2H, m), 6.71 (1H, d, J = 8.4 Hz), 5.27 (2H, d , ff-i- = 48.1 Hz), 5.26 (2H, m), 1.90 (1H, t, J = 8.4 Hz), 1.86 (1H, d, J = 8.4 Hz), 1.2 (3H, s), 1.17 ( 3H, s) ppm. ¹³ C NMR (100 MHz, CDC13) δ: 14.04, 26.69, 27.32, 30.78, 34.72, 62.66, 77.15, 78.77, 88.47, 114.06, 114.28, 127.96, 128.54, 129.56, 130.06, 130.16, 132.36, 136.01, 136.04, 142.42 , 142.46, 169.10 ppm. - 7 -

Example 51 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-3'-fluoro- [1, 1'-biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 2-Fluormethyl-3-iod-benzoesäuremethylester (bekannt aus Stufe A,

a) Step A (Method II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester (known from Step A,

 Method I) b) Step E (Method II): 2-fluoromethyl-3'-fluoro [1,1'-biphenyl] -3-carboxylic acid methyl ester; see.

 Stage E, Method II; Example 35; Yield obtained: 99% (of theory)

c) Stufe B (Methode II): 2-Fluormethyl-3'-fluor[l,l '-biphenyl]-methanol; vgl. Stufe B, Methode

c) Step B (Method II): 2-fluoromethyl-3'-fluoro [1,1'-biphenyl] -methanol; see. Level B, method

 I; Yield obtained: 85% (theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-fluoromethyl-3'-fluoro- [l, -biphenyl] -3-yl) methyl ester; see. Stage D, Method I; Yield: 75% (i.e., theory) ES HRMS: m / z found: [M + Na] ⁺ , 534.9697.

C22H ₂ o02F2 ²³ Na ⁷⁹ Br ₂ calculated: 534.9696.

^L H NMR (400 MHz, CDC1 ₃₎ δ: 7.49 (2H, m), 7:41 (1H, m), 7:33 (1H, d, J = 7.5 Hz), 7.16 (1H, d, J = 7.5 Hz), 7.11 (2H, m), 6.79 (1H, d, J = 8.3 Hz), 5.37 (2H, d, J _H -F = 48.0 Hz), 5.35 (2H, m), 1.99 (1H, dd, J = 8.3 and 8.4 Hz), 1.93 (1H, d, J = 8.4 Hz), 1.28 (3H, s), 1.25 (3H, s) ppm. ¹³ C NMR (100 MHz, CDC13) δ: 15.48, 28.15, 28.76, 32.22, 36.17, 64.05, 78.49, 80.12, 89.92, 114.85, 115.06, 116.86, 117.08, 125.75, 129.66, 129.69, 130.02, 130.06, 130.14, 130.22 , 130.77, 133.79, 137.50, 164.12, 170.54 ppm. - 7 - lR, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-2'-fluoro- [1, 1'-biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 2-Fluormethyl-3-iod-benzoesäuremethylester (bekannt aus Stufe A,

a) Step A (Method II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester (known from Step A,

 Method I) b) Step E (Method II): 2-fluoromethyl-2'-fluoro [1-biphenyl] -3-carboxylic acid methyl ester; see.

 Stage E, Method II; Example 35; Yield obtained: 96% (of theory)

c) Stufe B (Methode II): 2-Fluormethyl-2'-fluor[l,l '-biphenyl]-methanol; vgl. Stufe B, Methode

c) Step B (Method II): 2-fluoromethyl-2'-fluoro [1,1'-biphenyl] -methanol; see. Level B, method

 I; Yield obtained: 91% (of theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-fluoromethyl-2'-fluoro [l, -biphenyl] -3-yl) methyl ester; see. Stage D, Method I; Yield: 91% (ie theory)

ES FTRMS: m / z found [M + Na] ⁺ , 534.9720.

C22H ₂ o02F2 ²³ Na ⁷⁹ Br ₂ calculated 534.9696. ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.52 (1H, d, J = 7.4 Hz), 7.48 (1H, dd, J = 7.4 and 7.6 Hz), 7.40 (1H, m), 7.32 (2H, m ), 7.23 (1H, t, J = 7.6 Hz), 7.16 (1H, m), 6.81 (1H, d, J = 8.2), 5.19-5.49 (4H, m), 1.99 (1H, dd, J = 8.2 and 8.4 Hz), 1.94 (1H, d, J = 8.4 Hz), 1.28 (3H, s), 1.26 (3H, s) ppm.

¹³ C NMR (100 MHz, CDC13) δ: 15.48, 28.13, 28.77, 32.24, 36.16, 64.06, 78.93, 80.57, 89.88, 115.94, 116.16, 124.51, 124.55, 129.75, 129.79, 130.21, 130.29, 131.29, 132.39, 133.84 , 137.17 137.63, 137.67, 170.57 ppm. - -

(1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoromethyl-2 ', 4'-difluoro [1,1'-biphenyl] -3-yl) methylester

a) Stufe A (Methode II): 2-Fluormethyl-3-iod-benzoesäuremethylester (bekannt aus Stufe A,

a) Step A (Method II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester (known from Step A,

 Method I) b) Step E (Method II): methyl 2-fluoromethyl-2 ', 4'-difluoro [1, 1'-biphenyl] -3-carboxylate;

 see. Stage E, Method II; Example 35; Yield obtained: 89% (of theory)

c) Stufe B (Methode II): 2-Fluormethyl-2',4'-difluor[l,l '-biphenyl]-methanol; vgl. Stufe B, Methode I; erhaltene Ausbeute: 92 % (d. Theorie)

c) Step B (Method II): 2-fluoromethyl-2 ', 4'-difluoro [1, 1'-biphenyl] -methanol; see. Stage B, Method I; Yield obtained: 92% (theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-fluoromethyl-2 ', 4'-difluoro [l, 1'-biphenyl] -3-yl) methyl ester; see. Stage D, Method I; Y. : 84% (ie theory)

ES HRMS: m / z found: [M + Na] ⁺ , 552.9603.

C22Hi902F ₃ ²³ Na ⁷⁹ Br ₂ Calculated: 552.9602. ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.53 (1H, m), 7.48 (1H, m), 7.30 (2H, m), 6.95 (2H, m), 6.79 (1H, d, J = 8.26 Hz ), 5.18-5.48 (4H, m), 1.99 (1H, dd, J = 8.26 and 8.4 Hz), 1.93 (1H, dJ = 8.4 Hz), 1.28 (3H, s), 1.26 (3H, s) ppm , -

¹³ C NMR (100 MHz, CDC13) δ: 15.46, 28.15, 28.76, 32.21, 36.16, 64.00, 78.74, 80.39, 89.91, 111.68, 111.72, 111.89, 111.93, 129.86, 129.90, 130.03, 131.41, 132.70, 132.85, 133.04 , 133.09, 133.14, 133.17, 133.80, 136.82, 136.86, 137.31, 170.54 ppm.

Example 54 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-fluoromethyl-4'-chloro- [1, Γ -biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 2-Fluormethyl-3-iod-benzoesäuremethylester (bekannt aus Stufe A,

a) Step A (Method II): 2-fluoromethyl-3-iodo-benzoic acid methyl ester (known from Step A,

 Method I) b) Step E (Method II): 2-fluoromethyl-4'-chloro [1,1'-biphenyl] -3-carboxylic acid methyl ester; see.

 Stage E, Method II; Example 35; Yield obtained: 95% (of theory)

c) Stufe B (Methode II): 2-Fluormethyl-4' -chlor [Ι,Γ -biphenyl] -methanol; vgl. Stufe B, Methode

c) Step B (Method II): 2-fluoromethyl-4'-chloro [Ι, Γ-biphenyl] -methanol; see. Level B, method

 I; Yield obtained: 93% (of theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure-

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

(2-fluoromethyl-4'-chloro- [1,1'-biphenyl] -3-yl) methyl ester; see. Stage D, Method I; Yield: 66% (ie theory)

ES HRMS: m / z found: [M + Na] ⁺ , 550.9418.

C22H ₂ o02F ²³ Na ³⁵ Cl ⁷⁹ Br ₂ calculated: 550.9400. ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.49 (3H, m), 7.43 (2H, m), 7.32 (2H, m), 6.78 (1H, d, J = 8.4 Hz), 5.35 (2H, d , J Hf = 48.0 Hz), 5.34 (2H, m), 1.98 (1H, dd, J = 8.4 and 8.5 Hz), 1.92 (1H, d, J = 8.5 Hz), 1.28 (3H, s), 1.25 ( 3H, s) ppm. -

¹³ C NMR (100 MHz, CDC13) δ: 14.05, 26.72, 27.33, 30.78, 34.74, 62.63, 75.67, 75.99, 76.30, 77.1 1, 78.72, 88.48, 127.44, 128.18, 128.66, 129.45, 129.82, 132.35, 132.82, 136.11, 137.46, 169.11 ppm.

Example 55 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-fluoromethyl-6-fluoro) - [1,1'-biphenyl] -3-yl ) methylester

a) Stufe A (Methode II): 6-Fluor-3-iod-benzoesäuremethylester (bekannt aus WO 2009/058237) b) Stufe E (Methode II): 6-Fluor-2-fluormethyl- [ 1 , Γ -biphenyl] -3 -carbonsäuremethylester

a) Step A (Method II): 6-fluoro-3-iodo-benzoic acid methyl ester (known from WO 2009/058237) b) Step E (Method II): 6-fluoro-2-fluoromethyl- [1, Γ-biphenyl] 3 -carboxylic acid methyl ester

1st step: 6-Fluoro-2-methyl- [1, Γ-biphenyl] -3-carboxylic acid methyl ester:

The preparation is carried out from 6-fluoro-3-iodo-benzoic acid methyl ester and phenylboronic acid (compare Example 35b, step E, method II) in the presence of palladium (II) acetate, triphenylphosphine and potassium phosphate in a reaction in toluene at 70 for 6 hours ° C.

2nd step: 2-bromomethyl-6-fluoro- [1, Γ-biphenyl] -3-carboxylic acid methyl ester:

0.10 g (0.4 mmol) of methyl 4-fluoro-2-methyl- [1,1'-biphenyl] -3-carboxylate were mixed with 0.08 g (0.5 mmol) of N-bromosuccinimide (NBS) and 8 mg (0.05 mmol) of azobisisobutyronitrile (AIBN ) dissolved in 10 mL trifluorotoluene. Subsequently, the reaction mixture was stirred at 100 ° C for 16 hours. After cooling, the entire reaction mixture was filtered over magnesium sulfate and washed with a solution washed from 30% ethyl acetate in 300 mL hexane. The solvent was removed in vacuo and the remaining residue used without further purification for the subsequent reaction. This gives 0.10 g (73% of theory) of 2-bromomethyl-6-fluoro- [l, r-biphenyl] -3-carboxylic acid methyl ester.

3rd step: 6-Fluoro-2-fluoromethyl [1, Γ-biphenyl] -3-carboxylic acid methyl ester: The preparation is carried out from 2-bromomethyl-6-fluoro- [1,1'-biphenyl] -3-carboxylic acid methyl ester (2 Step) and TBAF (1.0 M in THF) (see Example a-2, Step A, Method I) within 4 hours of stirring at room temperature. c) Step B (Method II): (4-Fluoro-2-fluoromethyl [1, 1'-biphenyl] -3-yl) methanol; see. Level B,

 Method I (total yield: 3rd step and c) is 48% d. Theory)

d) Stufe D (Methode II): (lR,3R)-3-(2-Chlor-2-trifluormethenyl)-2,2-dimethyl- cyclopropancarbonsäure-(6-fluor-2-fluormethyl-[l , 1 '-biphenyl] -3- yl)methylester, farbloses Öl; vgl. Stufe D, Methode I; Ausb.: 79 % (d. Theorie) ES HRMS: m/z gefunden: 481.0987.

d) Step D (Method II): (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (6-fluoro-2-fluoromethyl- [1, 1 '-] biphenyl] -3-yl) methyl ester, colorless oil; see. Stage D, Method I; Yield: 79% (of theory) ES HRMS: m / z found: 481.0987.

C23H ₂ o02F ₅ ²³ Na ³⁵ Cl calculated: 481.0970. 1 H NMR (400MHz, CDC1 ₃ ): δ 7.46-7.28 (7H, m), 6.93 (1H, d, J = 9.4Hz), 5.32 (1H, s), 5.25 (2H, s), 5.21 (1H, s ), 2.20 (1H, t, J = 8.9 Hz), 2.04 (1H, d, J = 8.4 Hz), 1.30 (6H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.3, 161.9, 159.4, 139.0, 138.0, 136.6, 136.5, 136.4, 132.6, 130.3, 129.5, 128.9, 128.2, 123.7, 123.5, 122.4, 122.2, 122.1, 1 19.5, 1 16.1, 1 16.0, 1 15.9, 115.8, 83.0, 81.3, 60.5, 33.1, 31.4, 29.3, 28.7, 15.3 ppm. - -

Example 56 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl-4'-trifluoromethyl- [1, Γ -biphenyl] -3-yl) methyl ester

a) Stufe A (Methode I, II): 3-Iod-2-methyl-benzoesäuremethylester (vgl. auch WO 2008/016184)

a) Stage A (Method I, II): methyl 3-iodo-2-methylbenzoate (see also WO 2008/016184)

To a mixture of 4.13 g (3.6 ml, 25.0 mmol) of 3-amino-2-methyl-benzoic acid methyl ester in 25 ml of water was added a solution of 5.0 ml of sulfuric acid and 25.0 ml of water. Thereafter, the reaction mixture was cooled to 0 ° C and treated dropwise with a solution of 1.81 g (26.5 mmol) of sodium nitrite in 25 mL of water. After stirring for 1 h, a solution of 6.23 g (37.5 mmol) of potassium iodide in 25 mL of water was added dropwise. Subsequently, stirring was continued for a further hour at 0 ° C. Then the entire reaction mixture was extracted three times with 50 mL dichloromethane. The combined organic phases were washed with 25 mL saturated sodium thiosulfate solution and dried over magnesium sulfate. Thereafter, the organic phase was separated in vacuo and the remaining crude product purified by flash chromatography (silica gel, eluent: 3-5% ethyl acetate in n-hexane). This gives 6.37 g (92% of theory) of methyl 3-iodo-2-methylbenzoate. b) Step B (Method I): (3-iodo-2-methylphenyl) methanol (see also WO 2008/131368)

To a solution stirred solution of 4.29 g (15.5 mmol) of 3-iodo-2-methyl-benzoic acid methyl ester (step A) in 50 mL toluene at room temperature under a protective gas atmosphere (nitrogen) 7.8 mL (15.5 mmol ) of a 2.0 M solution of lithium borohydride in tetrahydrofuran (THF). Subsequently, the entire reaction mixture was stirred at 100 ° C for 30 minutes. Thereafter, 10 mL of a 1M hydrochloric acid solution was added and the solvents were separated. The remaining residue was dissolved in 50 mL diethyl ether and washed successively with 20 mL saturated sodium thiosulfate solution, 20 mL saturated sodium bicarbonate solution and brine. ₅

The organic phase was dried over sodium sulfate, filtered off and concentrated in vacuo.

This gives 3.62 g (95% of theory) of (3-iodo-2-methylphenyl) methanol as a colorless solid which can be used without further purification for the subsequent reaction. c) Step C (Method I, II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride (see also US 4,342,770)

6.20 g (20.0 mmol) of (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (see also M. Eliott et al., Pesticide Sci., 6, 537 -542, 1975) in 100 ml of dry dichloromethane and under an inert gas atmosphere (nitrogen) were added 2.67 g (21.0 mmol) of oxalyl chloride and a catalytic amount (2 drops) of DMF. After three hours of stirring at room temperature, the solution was removed in vacuo and the crude (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid chloride (yellowish oil). used for the next reaction step (step E). d-1) Step D (Method I): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid

3-iodo-2-methyl-benzyl ester

The (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride obtained in step C was stirred in 40 ml of dichloromethane and 3.16 g (40 mmol) of pyridine were added. Subsequently, the reaction mixture was further stirred for one hour at room temperature and then treated with a solution of 4.49 g (18.1 mmol) of (3-iodo-2-methylphenyl) methanol (step C) in 20 ml of dichloromethane. Thereafter, the reaction mixture was stirred for about 18 hours at room temperature. Subsequently, the solvent and excess pyridine were removed in vacuo. The remaining residue was dissolved in 100 ml of diethyl ether and washed successively with 50 ml of water, 50 ml of saturated sodium hydrogencarbonate solution and saturated brine. The organic phase was dried over sodium sulfate and concentrated after filtration in vacuo. The remaining crude product was purified by flash chromatography (silica gel eluent: 2% ethyl acetate in n-hexane). This gives 9.07 g (95% of theory) of (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 3-iodo-2-methyl-benzyl ester as a colorless oil. - -

ES HRMS: m / z found

Cl ₆ Hi702 ²³ Na ⁷⁹ Br ⁸¹ Br ¹²⁷ I [M + Na] ⁺ Calculated: 550.8517. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.83 (dd, J = 7.9, 1.0 Hz, 1H), 7.31 (dd, J = 7.5, 0.7 Hz, 1H), 6.90 (t, J = 7.7 Hz, 1H) , 6.76 (d, J = 8.5 Hz, 1H), 5.14 (d, J = 4.9 Hz, 2H), 2.47 (s, 3H), 1.97 (t, J = 8.5 Hz, 1H), 1.89 (d, J = 8.5 Hz, 1H), 1.27 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.56, 140.40, 140.05, 135.41, 133.75, 129.90, 127.97, 103.57, 89.95, 65.96, 36.15, 32.17, 28.75, 28.09, 24.96, 15.48 ppm. d-2) Step D (Method I): (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 3-iodo-2-methyl-benzyl ester

The (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid 3-iodo-2-methylbenzyl ester was prepared in an analogous manner from (1R, 3R) -3 - (2-chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid chloride (3-iodo-2-methylphenyl) methanol.

ES HRMS: m / z found: 494.9792. CnHi702F ₃ ²³ Na ³⁵ Cl ¹²⁷ I [M + Na] ⁺ calcd: 494.9812. ¹ H NMR (400 MHz, CDCl 3) δ 7.84 (dd, J = 8.0, 1.1 Hz, 1H), 7.30 (d, J = 7.1 Hz, 1H), 6.94-6.86 (m, 2H), 5.15 (d, J = 6.6 Hz, 2H), 2.46 (s, 3H), 2.18 (t, J = 8.9 Hz, 1H), 2.02 (d, J = 8.4 Hz, 1H), 1.30 (s, 6H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.36, 140.42, 140.14, 135.20, 130.31, 130.27, 129.95, 127.98, 122.46, 122.15, 122.08, 119.45, 103.57, 66.13, 33.19, 31.40, 29.22, 28.75, 24.95, 15.33 ppm , e) Step E (Method I): (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl-4'-trifluoromethyl- [1,1'-biphenyl ] -3-yl) methyl ester

To a solution of 528 mg (1.0 mmol) of (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid 3-iodo-2-methyl-benzyl ester in 20 mL toluene 4.5 mg (0.02 mmol) of palladium (II) acetate, 13.1 mg (0.05 mmol) of triphenylphosphine, 0.85 g (4.0 mmol) of potassium phosphate and 235 mg (1.2 mmol) of 4 -Trifluormethylphenylboronsäure given. Thereafter, the reaction mixture was degassed and stirred at 70 ° C for 6 hours. Subsequently, the resulting reaction mixture became - 7 - pressed through a silica gel loaded filter to remove the palladium catalyst and the inorganic salts. The crude product obtained as a pale yellow oil was purified by flash chromatography (silica gel eluent: 3% ethyl acetate in n-hexane). 386 mg (71% of theory) of (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropane-carboxylic acid (2-methyl-4'-trifluoromethyl) - [l, r-biphenyl] -3-yl) methyl ester as a colorless oil.

ES HRMS: m / z found: 568.9739.

C ₂ 3H ₂ i0 ₂ F ₃ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 568.9738. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.68 (d, J = 8.5 Hz, 2H), 7.46 - 7.37 (m, 3H), 7.29 (t, J = 7.6 Hz, 1H), 7.21 (dd, J = 7.6, 1.5 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 5.20 (s, 2H), 2.21 (s, 3H), 1.99 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.4 Hz, 1H), 1.29 (s, 3H), 1.26 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.73, 145.93, 141.93, 135.15, 134.66, 133.84, 130.43, 130.13, 129.77, 129.45, 129.36, 126.27, 125.49, 89.87, 65.40, 36.14, 32.23, 28.78, 28.07, 16.59, 15.50 ppm.

In an analogous manner, examples 2 to 8 were obtained by means of Suzuki coupling (stage E, method I).

Example 57 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-3'-trifluoromethyl- [1, Γ -biphenyl] -3-yl) methyl ester

Output: 68% (ie theory)

ES HRMS: m / z found: 568.9734. C ₂ 3H ₂ i0 ₂ F ₃ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 568.9738. ¹ H NMR (400 MHz, CDCl 3) δ 7.65-7.47 (m, 4H), 7.39 (dd, J = 7.5, 1.4 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.22 (dd, J = 7.6, 1.5 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 5.20 (s, 2H), 2.21 (s, 3H), 1.99 (t, J = 8.4 Hz, 1H), 1.93 (i.e. , J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.26 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.73, 142.98, 141.82, 135.15, 134.76, 133.86, 133.11, 131.15, 130.84, 130.57, 129.38, 129.02, 126.51, 126.28, 124.17, 89.86, 65.43, 36.14, 32.24, 28.78, 28.06, 16.57, 15.51 ppm. - -

Example 58 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-4'-fluoro- [1,1'-biphenyl] -3-yl) methyl ester

Yield: 88% (i.e., theory) ES HRMS: m / z found: 518.9752.

C22H _{2 2} i0 F ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calculated: 518.9770. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.35 (dd, J = 7.5, 1.6 Hz, 1H), 7.29 - 7.23 (m, 3H), 7.20 (dd, J = 7.6, 1.6 Hz, 1H), 7.10 ( t, J = 8.7 Hz, 2H), 6.80 (d, J = 8.3 Hz, 1H), 5.19 (d, J = 1.4 Hz, 2H), 2.21 (s, 3H), 1.98 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDCl 3) δ 170.75, 163.61, 161.16, 142.32, 138.13, 134.93, 133.88, 131.26, 130.73, 128.90, 126.09, 115.53, 115.31, 89.83, 65.54, 36.12, 32.25, 28.79, 28.04, 16.59, 15.51 ppm.

Example 59 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-4'-trifluoromethoxy- [1, Γ -biphenyl] -3-yl) methyl ester

Ausb.: 55 % (d. Theorie)

Yield: 55% (ie theory)

ES HRMS: m / z found: 584.9678. C23H2i0 ₃ F ₃ Na ^{23 79} Br ⁸¹ Br [M + Na] ⁺ calculated: 584.9687. ¹ H NMR (400 MHz, CDCl 3) δ 7.37 (dd, J = 7.5, 1.4 Hz, 1H), 7.34-2.24 (m, 5H), 7.21 (dd, J = 7.6, 1.5 Hz, 1H), 6.80 (i.e. , J = 8.3 Hz, 1H), 5.19 (d, J = 1.5 Hz, 2H), 2.21 (s, 3H), 1.98 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.5 Hz, 1H ), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDC13) δ 170.74, 148.67, 141.94, 140.90, 135.03, 134.80, 133.85, 131.13, 130.61, 129.11, 126.17, 122.21, 121.01, 89.85, 65.47, 36.13, 32.23, 28.78, 28.06, 16.60, 15.50 ppm. - -

Example 60 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-3'-trifluoromethoxy- [1, Γ -biphenyl] -3-yl) methyl ester

Yield: 75% (of theory) ES HRMS: m / z found: 584.9672.

C ₂ 3H ₂ i0 ₃ F ₃ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 584.9687. ^l H NMR (400 MHz, CDC1 ₃₎ δ 7:44 (t, J = 7.9 Hz, 1H), 7:38 (dd, J = 7.5, 1.5 Hz, 1H), 7:30 to 7:15 (m, 5H), 6.80 (d, J = 8.3 Hz, 1H), 5.19 (d, J = 1.3 Hz, 2H), 2.22 (s, 3H), 1.98 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.5 Hz, 1H) , 1.29 (s, 3H), 1.26 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDCl 3) δ 170.72, 149.42, 144.23, 141.76, 135.13, 134.73, 133.86, 130.49, 129.88, 129.29, 128.19, 126.22, 122.35, 122.21, 119.76, 89.87, 65.43, 36.13, 32.24, 28.77, 28.03, 16.51, 15.50 ppm.

Example 61 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-4'-chloro [1,1'-biphenyl] -3-yl) methyl ester

Output: 80% (ie theory)

ES HRMS: m / z found: 534.9435.

C ₂₂ H ₂ i0 ₂ ²³ Na ³⁵ Cl ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 534.9474.

'H NMR (400 MHz, CDCl3) δ 7.48-7.31 (m, 3H), 7.30-7.16 (m, 4H), 6.80 (d, J = 8.3 Hz, 1H), 5.18 (s, 2H), 2.21 (s , 3H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.4 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.74, 142.10, 140.65, 135.01, 134.78, 133.86, 133.41, 131.10, 130.56, 129.06, 128.72, 126.16, 89.84, 65.49, 36.13, 32.24, 28.78, 28.04, 16.58, 15.51 ppm , - -

Example 62 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl-4'-fluoro- [1, Γ -biphenyl] -3-yl) methylester

Yield: 79% (of theory) ES HRMS: m / z found: 463.1072.

C ₂ 3H ₂ i0 ₂ F ₄ ²³ Na ³⁵ Cl [M + Na] ⁺ Calculated: 463.1064. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.35 (dd, J = 7.3, 1.5 Hz, 1H), 7.23 (tdd, J = 9.3, 7.0, 2.0 Hz, 4H), 7.14-7.06 (m, 2H), 6.96 (dd, J = 9.4, 1.0 Hz, 1H), 5.20 (d, J = 4.2 Hz, 2H), 2.23 - 2.16 (m, 4H), 2.06 (d, J = 11.6 Hz, 1H), 1.32 (s , 3H), 1.30 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDC13) δ 170.56, 163.62, 161.18, 142.37, 138.13, 134.75, 131.25, 130.82, 130.43, 128.96, 126.11, 122.19, 119.49, 115.54, 115.33, 65.73, 33.31, 31.37, 29.18, 28.77, 16:56, 15.36 ppm.

Example 63 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl-4'-ethynyl- [1, Γ -biphenyl] -3-yl) methylester

Ausb.: 22 % (d. Theorie)

Yield: 22% (ie theory)

ES HRMS: m / z found: 469.1173. C25H ₂ 202F ₃ ²³ Calculated Na ³⁵ Cl [M + Na] ⁺ : 469.1158. ¹ H NMR (400 MHz, CDCl 3) δ 7.59-7.52 (m, 2H), 7.35 (dd, J = 7.4, 1.5 Hz, 1H), 7.26 (dq, J = 9.0, 2.4 Hz, 3H), 7.21 (dd , J = 7.6, 1.6 Hz, 1H), 6.95 (dd, J = 9.4, 0.9 Hz, 1H), 5.19 (d, J = 4.3 Hz, 2H), 3.12 (s, 1H), 2.28 - 2.13 (m, 4H), 2.06 (d, J = 8.3Hz, 1H), 1.31 (s, 3H), 1.30 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.55, 142.78, 142.57, 134.81, 134.74, 132.33, 130.58, 130.44, 129.79, 129.12, 126.18, 122.17, 121.15, 1 19.47, 83.89, 77.91, 65.68, 33.29, 31.37, 29.18 , 28.79, 16.58, 15.37 ppm. - -

In an analogous manner, Example 9 was obtained at a reaction time of 12 hours at 70 ° C. by means of the Suzuki coupling (stage E, method I).

Example 64 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-3 ', 4'-difluoro [1,1'-biphenyl] -3 - yl) methylester

Yield: 77% (ie theory)

ES HRMS: m / z found: 536.9667. C ₂₂ H ₂ O ₂ F ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 536.9675. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.37 (dd, J = 7.5, 1.4 Hz, 1H), 7.29 - 7.23 (m, 1H), 7.22 - 7.16 (m, 2H), 7.11 (ddd, J = 11.1 , 7.6, 2.1 Hz, 1H), 7.03 - 6.98 (m, 1H), 6.80 (d, J = 8.4 Hz, 1H), 5.18 (s, 2H), 2.21 (s, 3H), 1.99 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.26 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.72, 161.68, 160.97, 159.57, 156.13, 141.26, 139.10, 135.11, 134.78, 133.84, 130.52, 129.28, 126.21, 125.87, 118.86, 117.28, 89.87, 65.42, 36.14, 32.22, 28.78, 28.07, 16.55,

15.50 ppm. Using 2 mol% [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl ₂ (dppf)) and 4 hours of reaction time at 70 ° C., Suzuki coupling (stage E, method I) was used ) Examples 10 to 12 are obtained.

Example 65 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl-3'-fluoro- [1, Γ -biphenyl] -3-yl) methylester

Yield: 84% (ie theory)

ES HRMS: m / z found: 463.1072.

C ₂ 3H ₂ i0 ₂ F ₄ ²³ Na ³⁵ Cl [M + Na] ⁺ Calculated: 463.1064. - ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.41 - 7.34 (m, 2H), 7.26 (t, J = 7.5 Hz, 1H), 7.22 (dd, J = 7.6, 1.7 Hz, 1H), 7.09 - 7.04 (m, 2H), 7.01 (ddd, J = 9.8, 4.7, 2.6 Hz, 1H), 6.95 (dd, J = 9.4, 0.9 Hz, 1H), 5.20 (d, J = 4.7 Hz, 2H), 2.23 - 2.16 (m, 4H), 2.06 (d, J = 8.4 Hz, 1H), 1.31 (s, 3H), 1.30 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl3) δ 170.54, 164.14, 161.69, 144.43, 142.16, 134.81, 130.56, 130.44, 130.06, 129.18, 126.15, 125.54, 122.17, 119.48, 116.66, 114.37, 114.16, 65.65, 33.29, 31.37, 29.17, 28.78, 16.53, 15.36 ppm.

Example 66 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl-4'-trifluoromethyl- [1, Γ-biphenyl] -3-yl) methylester

Ausb.: 96 % (d. Theorie)

Output: 96% (ie theory)

ES HRMS: m / z calculated: 513.1056. C ₂₄ H ₂ i0 ₂ F ₆ ²³ Na ³⁵ Cl [M + Na] ⁺ Found: 513.1032 ¹ H NMR (400 MHz, CDCl 3) δ 7.68 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 7.9 Hz, 2H), 7.39 (dd, J = 7.6, 1.4 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.21 (dd, J = 7.6, 1.5 Hz, 1H), 6.95 (dd, J = 9.4, 1.0 Hz, 1H), 5.20 (d, J = 3.1 Hz, 2H), 2.23 - 2.16 (m, 4H), 2.06 (d, J = 10.7 Hz, 1H), 1.32 (s, 3H), 1.31 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.52, 145.90, 141.97, 134.96, 134.68, 130.51, 130.36, 130.11, 129.80, 129.40, 126.27, 125.50, 122.42, 122.16, 119.47, 65.56, 33.28, 31.38, 29.17, 28.77, 16.54, 15.36 ppm.

Example 67 (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-4'-chloro [1, Γ -biphenyl] -3-yl) methylester

Output: 95% (ie theory)

ES HRMS: m / z found: 479.0750.

C23H2i0 ₂ F ₃ ²³ Na ³⁵ Cl 2 [M + Na] ⁺ calculated: 479.0768. - ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.44-7.31 (m, 3H), 7.29-7.17 (m, 4H), 6.95 (dd, J = 9.3, 0.9 Hz, 1H), 5.19 (d, J = 3.4 Hz, 2H), 2.26 - 2.14 (m, 4H), 2.06 (d, J = 8.4 Hz, 1H), 1.31 (s, 3H), 1.30 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.55, 142.14, 140.59, 134.81, 133.43, 131.09, 130.67, 130.39, 129.66, 129.11, 128.74, 126.18, 121.98, 119.47, 65.68, 33.29, 31.38, 29.20, 28.79, 16.58, 15.37 ppm. Using 2 mol% [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 6 hours of reaction time at 70 ° C., the reaction was carried out by means of Suzuki coupling (stage E, method I). Example 13 was obtained.

Example 68 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-3'-fluoro- [1,1'-biphenyl] -3-yl) methyl ester

Yield: 54% (ie theory)

ES HRMS: m / z found: 518.9758. C ₂₂ H ₂ i0 ₂ F ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 518.9770. ¹ H NMR (400 MHz, CDCl 3) δ 7.41-7.34 (m, 2H), 7.26 (t, J = 7.6 Hz, 1H), 7.21 (dd, J = 7.6, 1.7 Hz, 1H), 7.09-6.98 (m , 3H), 6.80 (d, J = 8.3 Hz, 1H), 5.19 (d, J = 2.0 Hz, 2H), 2.22 (s, 3H), 1.98 (t, J = 8.4 Hz, 1H), 1.93 (i.e. , J = 8.4 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.74, 164.14, 161.69, 144.40, 142.10, 134.75, 133.87, 130.48, 130.05, 129.14, 126.14, 125.56, 1 16.89, 1 14.14, 99.99, 89.84, 65.48, 36.13, 32.24, 28.79, 28.05, 16.56, 15.51 ppm.

Using 2 mol% [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 7 hours of reaction time at 70 ° C., Suzuki coupling (stage E, method I ) obtained Example 14.

Example 69 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-2'-fluoro- [1,1'-biphenyl] -3-yl) methyl ester -

Yield: 57% (ie theory)

ES HRMS: m / z found: 518.9767.

C ₂₂ H ₂ i0 ₂ F ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 518.9770. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.41-7.32 (m, 2H), 7.30-7.18 (m, 4H), 7.14 (ddd, J = 9.5, 8.2, 1.1 Hz, 1H), 6.81 (d, J = 8.1 Hz, 1H), 5.20 (d, J = 4.8 Hz, 2H), 2.17 (d, J = 1.4 Hz, 3H), 1.97 (t, J = 8.3 Hz, 1H), 1.93 (d, J = 8.4 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.76, 161.26, 158.82, 137.04, 136.06, 134.69, 133.92, 132.03, 130.92, 129.58, 129.40, 126.06, 124.46, 116.03, 115.81, 89.80, 65.44, 36.10, 32.27, 28.77, 28.00, 15.50 ppm. Using 2 mol% [1,1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl2 (dppf)) and 12 hours of reaction time at 70 ° C., Suzuki coupling (stage E, method I ) obtained Example 15.

Example 70 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-2'-trifluoromethoxy- [1, Γ -biphenyl] -3-yl) methyl ester

Yield: 41% (ie theory)

ES HRMS: m / z found: 584.9678.

C ₂ 3H ₂ i0 ₃ F ₃ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 584.9687. ¹ H NMR (400 MHz, CDCl 3) δ 7.44-7.32 (m, 4H), 7.30-2.23 (m, 2H), 7.17 (dd, J = 7.6, 1.3 Hz, 1H), 6.81 (d, J = 8.3 Hz , 1H), 5.19 (dd, J = 11.1, 9.0 Hz, 2H), 2.09 (d, J = 1.8 Hz, 3H), 1.98 (td, J = 8.4, 2.2 Hz, 1H), 1.92 (dd, J = 8.4, 3.0 Hz, 1H), 1.27 (d, J = 7.5 Hz, 3H), 1.25 (d, J = 0.8 Hz, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.77, 146.99, 137.77, 135.62, 135.40, 134.57, 133.91, 132.29, 130.76, 129.27, 127.08, 125.85, 122.05, 121.14, 119.48, 89.74, 65.48, 36.10, 32.28, 28.76, 28.01, 16.21, 15.48 ppm. ₅

Using 2 mol% [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCkCdppf)) and 15 hours of reaction time at 70 ° C., the Suzuki coupling (stage E, method I) gave the examples 16 and 17 received.

Example 71 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl- (2 ', 3'-difluoro) - [1, 1'-biphenyl] - 3 -yl) methyl ester

Yield: 20% (ie theory)

ES HRMS: m / z found: 536.9654.

C ₂₂ H ₂ O ₂ F ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 536.9675. Example 72 (1R, 3R) -3- (2-chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl-2'-fluoro- [1, Γ -biphenyl] -3-yl) methylester

Output: 82% (ie theory)

ES HRMS: m / z found: 463.1084. C23H2i0 ₂ F ₄ ²³ Calculated Na ³⁵ Cl [M + Na] ⁺ : 463.1064. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.40-7.33 (m, 2H), 7.30-7.18 (m, 4H), 7.17-7.11 (m, 1H), 6.96 (dd, J = 9.4, 1.0 Hz, 1H ), 5.21 (d, J = 6.9 Hz, 2H), 2.18 (dd, J = 12.7, 4.9 Hz, 4H), 2.06 (d, J = 1 1.1 Hz, 1H), 1.31 (s, 3H), 1.30 ( s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.57, 161.25, 158.81, 137.08, 136.10, 134.49, 132.01, 131.02, 130.49, 129.62, 129.46, 126.08, 124.48, 122.18, 119.49, 116.04, 115.82, 65.63, 33.32, 31.35, 29.16, 28.77, 16.26, 15.36 ppm.

Using 2 mol% [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 18 hours of reaction time at 70 ° C., the reaction was carried out by means of Suzuki coupling (stage E, method I). Example 18 was obtained. - -

Example 73 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl- (3 ', 4'-difluoro) - [1, 1'-biphenyl] - 3 -yl) methyl ester

Yield: 60% (ie theory)

ES HRMS: m / z found: 536.9665. C ₂₂ H ₂ O ₂ F ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 536.9675. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.39 (dd, J = 7.6, 1.4 Hz, 1H), 7.27 (t, J = 7.7 Hz, 1H), 7.25 - 7.17 (m, 2H), 6.98 - 6.86 ( m, 2H), 6.80 (d, J = 8.2 Hz, 1H), 5.19 (d, J = 2.7 Hz, 2H), 2.15 (d, J = 1.4 Hz, 3H), 1.98 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.4 Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.74, 164.04, 161.69, 161.33, 158.74, 136.10, 134.83, 133.88, 132.58, 131.01, 129.57, 126.15, 125.72, 111.74, 111.53, 104.29, 89.83, 65.37, 36.11, 32.25, 28.77, 28.04, 16.24, 15.49 ppm.

Using 2 mol% [1,1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl ₂ (dppf)) and 20 hours of reaction time at 70 ° C., Suzuki coupling (stage E, Me Method I) Examples 19 and 20 were obtained.

- 7 -

Example 74 (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl- (3 ', 4', 5'-trifluoro) - [1,1 '- biphenyl] -3-yl) methyl ester

Yield: 50% (i.e., theory) ES HRMS: m / z found: 554.9577.

C ₂₂ Hi90 ₂ F ₃ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 554.9581. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.38 (dd, J = 7.6, 1.3 Hz, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.16 (dd, J = 7.7, 1.4 Hz, 1H) , 6.96 - 6.87 (m, 2H), 6.79 (d, J = 8.4 Hz, 1H), 5.18 (s, 2H), 2.21 (s, 3H), 1.99 (t, J = 8.4 Hz, 1H), 1.92 ( d, J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.26 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDCl 3) δ 170.67, 161.20, 158.99, 152.50, 149.91, 140.40, 138.15, 135.32, 134.63, 133.81, 130.26, 129.65, 126.34, 113.88, 89.92, 65.28, 36.16, 32.21, 28.77, 28.08, 16.51, 15.49 ppm.

Example 75 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl- (2 ', 4'-difluoro) - [1,1'-biphenyl ] -3-yl) methyl ester

Ausb.: 98 % (d. Theorie)

Yield: 98% (ie theory)

ES HRMS: m / z found: 481.0993. C23H ₂ o02F ₅ ²³ Na ³⁵ Cl [M + Na] ⁺ calculated: 481.0970.

'H NMR (400 MHz, CDCl3) δ 7.39 (dd, J = 7.6, 1.3 Hz, 1H), 7.31-7.17 (m, 3H), 7.00-6.86 (m, 3H), 5.20 (d, J = 4.7 Hz , 2H), 2.23 - 2.13 (m, 4H), 2.06 (d, J = 8.5 Hz, 1H), 1.31 (s, 3H), 1.30 (s, 3H) ppm. ¹³ C NMR (101 MHz, CDCl 3) δ 170.53, 161.69, 161.20, 158.85, 157.76, 139.96, 136.14, 134.62, 132.50, 131.10, 130.39, 129.63, 126.17, 125.63, 122.17, 1 19.47, 1 1 1.55, 104.30, 65.56 , 33.30, 31.36, 29.16, 28.77, 16.24, 15.35 ppm. - -

Using 2 mol% of [1, 1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCkCdppf)) and 22 hours of reaction time at 70 ° C., the example was obtained by means of Suzuki coupling (stage E, method I) 21 received.

Example 76 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl- (2'-trifluoromethyl) - [1, Γ -biphenyl] -3-yl) methylester

Output: 48% (theory)

ES HRMS: m / z found: 568.9759.

C ₂ 3H ₂ i0 ₂ F ₃ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 568.9738. ^l H NMR (400 MHz, CDC1 ₃₎ δ 7.76 (d, J = 7.6 Hz, 1H), 7:57 (t, J = 7.2 Hz, 1H), 7:49 (t, J = 7.5 Hz, 1H), 7:39 (d , J = 7.3 Hz, 1H), 7.23 (t, J = 7.8 Hz, 2H), 7.14 (d, J = 7.3 Hz, 1H), 6.81 (dd, J = 8.2, 1.7 Hz, 1H), 5.18 (dd , J = 15.2, 4.4 Hz, 2H), 1.99 (d, J = 1.7 Hz, 3H), 1.98 - 1.90 (m, 2H), 1.27 (d, J = 7.2 Hz, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 168.44, 138.69, 137.80, 133.07, 132.06, 131.62, 129.70, 129.46, 127.96, 127.05, 126.82, 125.55, 124.06, 122.93, 120.69, 87.48, 63.12, 33.78, 29.97, 29.94, 26.46, 25.71, 14.26, 13.17 ppm.

Using 2 mol% of [l, l-bis (diphenylphosphino) ferrocenes] dichloropalladium (II) (PdCl 2 (dppf)) and 24 hours of reaction time at 70 ° C., Suzuki coupling (stage E, method I) was used. Examples 22 and 23 are obtained. Example 77 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl- (2 ',

 5'-difluoro) - [1,1'-biphenyl] -3-yl) methyl ester

Yield: 37% (ie theory) - -

ES HRMS: m / z found

C ₂₂ H ₂ O ₂ F ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 536.9675. ¹ H NMR (400 MHz, CDC1 ₃ ) δ 7.41 (dd, J = 7.5, 1.2 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.21 (dd, J = 7.6, 1.3 Hz, 1H) , 7.14 - 7.01 (m, 2H), 6.96 (ddd, J = 8.7, 5.7, 3.1 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 5.19 (d, J = 2.8 Hz, 2H), 2.18 (d, J = 1.2Hz, 3H), 1.98 (t, J = 8.4Hz, 1H), 1.93 (d, J = 8.4Hz, 1H), 1.28 (s, 3H), 1.25 (s, 3H) ppm ,

¹³ C NMR (101 MHz, CDCl 3) δ 170.76, 164.60, 160.05, 157.61, 157.26, 135.94, 134.87, 133.87, 130.69, 129.78, 126.22, 118.42, 118.19, 117.11, 116.85, 116.12, 89.82, 65.33, 36.13, 32.23, 28.78, 28.09, 16.30, 15.49 ppm. Example 78 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (2-methyl-4'-ethynyl- [1, Γ -biphenyl] -3-yl) methyl ester

Yield: 25% (ie theory)

ES HRMS: m / z found: 524.9877. C ₂₄ H ₂₂ 0 ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 524.9864. ¹ H NMR (400 MHz, CDCl 3) δ 7.55 (d, J = 8.2 Hz, 2H), 7.38-7.34 (m, 1H), 7.31-2.24 (m, 3H), 7.21 (dd, J = 7.6, 1.5 Hz , 1H), 6.80 (d, J = 8.3 Hz, 1H), 5.19 (d, J = 1.4 Hz, 2H), 3.12 (s, 1H), 2.21 (s, 3H), 1.98 (t, J = 8.4 Hz , 1H), 1.92 (d, J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.25 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.74, 142.84, 142.53, 135.01, 134.71, 133.87, 132.32, 130.48, 129.80, 129.08, 126.16, 121.14, 89.84, 83.91, 77.88, 65.50, 36.12, 32.25, 28.78, 28.04, 16.59, 15.51 ppm. - -

Example 79 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2-methyl- (3 ',

 5'-difluoro) - [1,1'-biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 3-Iod-2-methyl-benzoesäuremethylester ( b e k a n n t

a) Step A (Method II): 3-iodo-2-methyl-benzoic acid methyl ester (known

 2008/016184); see. Step A, Method I b) Step E (Method II): Methyl 3 ', 5'-difluoro-2-methyl- [1, -biphenyl] -3-carboxylate

To a solution of 552 mg (2.0 mmol) of methyl 3-iodo-2-methylbenzoate in 20 ml of toluene was added 36.6 mg (0.05 mmol) of [1,1-bis (diphenylphosphino) ferrocenes] dichloropalladium (II ) (PdCl2 (dppf)), 1.70 g (8.0 mmol) of potassium phosphate and 488 mg (3.0 mmol) of 3,5-difluorophenylboronic acid. Subsequently, the reaction mixture was degassed and stirred at 100 ° C for 24 hours. Thereafter, the resulting reaction mixture was forced through a silica gel-loaded filter to remove the palladium catalyst and the inorganic salts. The crude product obtained as a pale yellow oil was purified by flash chromatography (silica gel eluent: 3% ethyl acetate in hexane). 500 mg (95% of theory) of methyl 3 ', 5'-difluoro-2-methyl- [1,1'-biphenyl] -3-carboxylate are obtained. c) Step B (Method II): (3 ', 5'-Difluoro-2-methyl- [1, 1'-biphenyl] methanol, see Step B, Method

 I; yield obtained: 88% (of theory) d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (3 ', 5'- difluoro-2-methyl- [l, 1'-biphenyl] -3-yl) methyl ester; see. Level D,

Method I; Output: 95% (ie theory)

ES HRMS: m / z found: 536.9656. C22H ₂ o02F ₂ ²³ Na ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calculated: 536.9675. - ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.38 (dd, J = 7.5, 1.3 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 7.19 (dd, J = 7.6, 1.4 Hz, 1H), 6.86 - 6.77 (m, 4H), 5.18 (s, 2H), 2.22 (s, 3H), 1.99 (t, J = 8.4 Hz, 1H), 1.93 (d, J = 8.5 Hz, 1H), 1.29 (s, 3H), 1.26 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.71, 164.23, 161.76, 145.50, 141.14, 135.19, 134.61, 133.83, 130.20, 129.52, 126.26, 112.71, 102.84, 89.88, 65.35, 36.15, 32.22, 28.78, 28.08, 16.52, 15.50 ppm.

In an analogous manner, examples 25 and 26 were obtained by means of stage D, method II (compare also stage D, method I).

Example 80 (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid [2-methyl-3-one

(Thien-3-yl)] benzyl

a) Stufe A (Methode II): 3-Iod-2-methyl-benzoesäuremethylester (bekannt aus Stufe A, Methode

a) Step A (Method II): Methyl 3-iodo-2-methylbenzoate (known from Step A, Method

 I) b) Step E (Method II): methyl 2-methyl-3-thien-3-yl-benzoate; see. Level E, method

 II; Example 24; Yield obtained: 87% (theory)

c) Stufe B (Methode II): 2-Methyl-3-thien-3-yl)benzylalkohol; vgl. Stufe B, Methode I; erhaltene

c) Step B (Method II): 2-methyl-3-thien-3-yl) benzyl alcohol; see. Stage B, Method I; obtained

 Yield: 98% (theory)

d) Stufe D (Methode II): (lR,3R)-3-(2,2-Dibromethenyl)-2,2-dimethyl-cyclopropancarbonsäure- [2-methyl-3-(thien-3-yl)]benzylester; vgl. Stufe D, Methode I; Ausb.: 92 % (d. Theorie)

d) Step D (Method II): (1R, 3R) -3- (2,2-dibromoethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid [2-methyl-3- (thien-3-yl)] benzyl ester; see. Stage D, Method I; Yield: 92% (ie theory)

ES HRMS: m / z found: 506.9449. - -

C ₂ oH ₂ oO ₂ ²³ NaS ⁷⁹ Br ⁸¹ Br [M + Na] ⁺ calcd: 506.94283. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.37 (dd, J = 4.9, 3.0 Hz, 1H), 7.33 (dd, J = 7.3, 1.3 Hz, 1H), 7.31 - 7.28 (m, 1H), 7.26 - 7.21 (m, 1H), 7.19 (dd, J = 3.0, 1.2Hz, 1H), 7.11 (dd, J = 4.9, 1.2Hz, 1H), 6.80 (d, J = 8.3Hz, 1H), 5.18 (i.e. , J = 3.3 Hz, 2H), 2.28 (s, 3H), 1.98 (t, J = 8.4 Hz, 1H), 1.92 (d, J = 8.4 Hz, 1H), 1.29 (s, 3H), 1.25 (s , 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.76, 142.49, 138.13, 135.35, 134.93, 133.90, 130.77, 129.54, 128.91, 126.08, 125.44, 123.29, 89.81, 65.57, 36.11, 32.26, 28.78, 28.02, 16.66, 15.52 ppm ,

Example 81 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid [2-methyl-3 - (3-thienyl)] benzyl ester

Output: 93% (ie theory)

ES HRMS: m / z found: 451.0715.

C ₂ iH ₂ o0 ₂ F ₃ ²³ NaS ³⁵ Cl [M + Na] ⁺ calcd: 451.0722. ¹ H NMR (400 MHz, CDCl 3) δ 7.37 (dd, J = 4.9, 3.0 Hz, 1H), 7.34-2.28 (m, 2H), 7.23 (t, J = 7.5 Hz, 1H), 7.18 (dd, J = 3.0, 1.3 Hz, 1H), 7.11 (dd, J = 4.9, 1.3 Hz, 1H), 6.95 (dd, J = 9.4, 0.9 Hz, 1H), 5.19 (d, J = 5.9 Hz, 2H), 2.28 (s, 3H), 2.18 (t, J = 8.9 Hz, 1H), 2.05 (d, J = 8.3 Hz, 1H), 1.31 (s, 3H), 1.30 (s, 3H) ppm.

¹³ C NMR (101 MHz, CDCl 3) δ 170.54, 142.44, 138.17, 135.37, 134.75, 130.86, 130.46, 129.51, 128.95, 126.08, 125.46, 123.29, 122.17, 122.02, 119.48, 65.74, 33.31, 31.35, 29.13, 28.78, 16.62, 15.37 ppm. Example 82 (1R, 3R) -3- (2,2-Dibromoethenyl) -2,2-dimethylcyclopropanecarboxylic acid (6-fluoro-2-methyl- [1, Γ -biphenyl] -3-yl) methyl ester

a) Stufe A (Methode II): 6-Fluor-3-iod-2-methyl-benzoesäuremethylester (bekannt aus

a) Step A (Method II): 6-fluoro-3-iodo-2-methyl-benzoic acid methyl ester (known from

WO 2009/058237) b) Step E (Method II): 6-Fluoro-2-methyl- [1, Γ -biphenyl] -3-carboxylic acid methyl ester

The preparation is carried out from methyl 6-fluoro-3-iodo-2-methylbenzoate and phenylboronic acid (compare Example 24b, Step E, Method II) in the presence of palladium (II) acetate, triphenylphosphine and potassium phosphate at 6 hours reaction in toluene at 70 ° C. The 6-fluoro-2-methyl- [l, l '- biphenyl] -3-carboxylic acid methyl ester is obtained in 82% yield. c) Step B (Method II): 6-Fluoro-2-methyl- [1, 1'-biphenyl] methanol; see. Stage B, Method I; yield obtained: 89% (of theory) d) Step D (Method II): (1R, 3R) -3- (2,2-dibromethenyl) -2,2-dimethyl-cyclopropanecarboxylic acid (6-fluoro-2-one) methyl [1,1'-biphenyl] -3-yl) methyl ester; see. Stage D, Method I; Yield: 67% (ie theory)

ES HRMS: m / z found: 516.9787.

C22H2i0 ₂ F ²³ Na ⁷⁹ Br ₂ found: 516.9790. ¹ H NMR (400MHz, CDC1 ₃ ): δ 7.43-7.22 (6H, m), 7.01 (1H, d, J = 10.6Hz), 6.80 (1H, d, J = 8.5Hz), 5.16 (2H, s) , 2.25 (3H, s), 1.97 (1H, t, J = 8.5 Hz), 1.89 (1H, d, J = 8.5 Hz), 1.26 (3H, s), 1.22 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.6, 161.6, 159.2, 141.0, 138.7, 138.6, 138.5, 133.9, 132.4, 129.8, 128.7, 127.5, 120.7, 120.5, 117.5, 117.3, 89.9, 60.5, 36.2, 32.2, 28.8, 28.1, 20.9, 15.5 ppm.

Example 83 (1R, 3R) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (6-fluoro-2-methyl- [1, Γ -biphenyl] -3-yl) methyl ester

Yield: 40% (i.e., theory) ES HRMS: m / z found: 463.1048. C23H2i0 ₂ F ₄ ²³ Calculated Na ³⁵ Cl: 463.1064. - - ^l H NMR (400MHz, CDC1 _3): δ 7:35 to 7:14 (6H, m), 6.93 (1H, d, J = 10.7 Hz), 6.86 (1H, d, J = 9.3 Hz), 5.12 (2H, s), 2.17 (3H, s), 2.10 (1H, t, J = 8.8 Hz), 1.95 (1H, d, J = 8.4 Hz), 1.21 (3H, s), 1.19 (3H, s) ppm.

¹³ C NMR (100 MHz, CDCl 3) δ 170.4, 161.7, 159.2, 141.0, 138.9, 138.6, 132.4, 130.5, 128.6, 128.6, 127.5, 122.3, 122.2, 122.0, 120.4, 120.3, 1 19.5, 117.5, 1 17.3, 60.7, 33.3, 31.4, 29.2, 28.8, 20.8, 15.3 ppm.

- 5 -

Biological examples

Mosquito test [Anopheles funestus FANG (sensitive) and Anopheles funestus FUMOZ-R (resistant)] Solvent 1: acetone

Solvent 2: Dow Corning 556 Silicone Fluid To prepare the active compound preparations according to the invention, the amount of active compound required for the desired concentration (%> m / v) is dissolved in 0.7 ml of solvent 1 and then mixed with 0.7 ml of solvent 2.

Each 1, 4 ml of a drug solution are dropped onto a filter paper and the soaked papers dried overnight. Each 20 non-blood-fed, 3-5 day old female mosquitoes [Anopheles funestus FANG (sensitive) or Anopheles funestus FUMOZ (resistant)] are brought into contact with one of the soaked filter papers for 60 minutes. Subsequently, the mosquitoes are removed from the filter paper and supplied with sugar water.

After 24 hours, the effect is determined in%. 100% means that all mosquitoes have been killed. 0% means that no mosquitoes have been killed.

The determined effect in% is plotted as a function of the active substance concentration and the LC50 is determined from the resulting curves (LC50 = mean lethal concentration.) The mean lethal concentration LC50 is the statistically calculated concentration of a substance that is expected to be 50% of the exposed animals within the study period afterwards leads to death.). The quotient "LC50 (FUMOZ-R) / LC50 (FANG)" represents the resistance ratio RR and is then determined accordingly from the LC50 values.

In this test, z. B. the following compounds of the preparation examples a significantly reduced RR value compared to the standard bifenthrin and thus an improved Resistenzbrechung:

Example 45 (λ, 3A) -3- (2-Chloro-2-trifluoromethenyl) -2,2-dimethylcyclopropanecarboxylic acid (2,6-difluoro-LC50 RR

 3-thien-2-yl) benzyl ester

FANG Concentration 0.54 0.18 0.06 0.02 0.007 0.00074 0.00025 0.017%

 (%)

 Mortality (%) 100 100 99 55 6 5 0

 1 1

FUMOZ Concentration 1, 2 0.6 0.4 0.3 0.2 0.1 0.05 0.025 0.19% R (%)

 Mortality (%) 100 100 99 89 46 4 2 0

Claims

claims 1. Use of the compounds of the formula (I),

wherein a radical of the formula (LI)

 in which is alkyl, alkoxy, haloalkyl, alkylthio, alkylsulfoxyl, alkylsulfonyl, haloalkoxy, haloalkylthio, haloalkylsulfoxyl, haloalkylsulfonyl, alkylamino, dialkylamino, cyano, halogen or hydroxy and p is a number from 0 to 2, optionally substituted hetaryl or one of the leftovers from the series

where the arrow marks the bond to the adjacent ring, Xi, Χι ', Xi "are independently alkyl, haloalkyl, cycloalkyl, halogenocycloalkyl, alkenyl, haloalkenyl, alkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkoxyalkyl, haloalkoxyalkyl, alkylthio, haloalkylthio, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, fluoro, Bromine, chlorine, iodine, nitro, cyano, amino, alkylamino, dialkylamino, R _{2 is} methyl, cyano, halo or haloalkyl and Yi and Y ₂ independently represent halogen or haloalkyl for controlling insecticide-resistant insects. 2. Use of the compounds according to claim 1 for combating pyrethroid-resistant insects. 3. Use of the compounds according to claim 1 or 2, characterized in that the insects from the family of Culicidae, Muscidae or Blattidae originate. 4. Use according to claim 3, characterized in that the insects are of the family Culicidae. 5. Use according to claim 4, characterized in that the insects are selected from the genera Aedes aegypti, Aedes albopictus, Anopheles stephensi, Culex quinque-fasciatus, Anopheles albimanus, Anopheles funestus, Anopheles gambiae, Culex pipiens pallens, Anopheles minimus, Anopheles arabiensis and Anopheles sacharovi. 6. Use according to claim 5, characterized in that the insects are selected from the group of the genera Culex quinquefasciatus and Anopheles gambiae.