DD297637A5 - METHOD OF CROSS-COUPLING WITH METALLIC PALLADIUM CATALYST - Google Patents

Abstract

Compounds of formula I, R1Z (E) mR2Iworin R1, R2, Z, E and m have the meaning given in claim 1 can easily and in high yields by coupling organometallic compounds of formula II, R1ZMetIIwobei R1 and Z have the meaning given, and Met Li, Na, K, ZnX, * * * * HgX or SnX3, wherein each X independently of one another is a radical of the formula R1Z, halogen, alkyl or alkoxy having in each case 1 to 6 C atoms or a cyclopentadienyl radical, X can also be OH, with compounds of the formula * E, R2 and m have the meaning given, and Y is halogen or OSO2CnF2n1, in which n represents an integer value of 1 to 10, with transition metal catalysis optionally in the presence of a metal alcoholate, characterized in that the transition metal catalyst is metallic palladium, optionally applied to a carrier material. {high yields; Coupling; organometallic compound; Transition metal catalysis; metal alcoholate; Palladium; Traegermaterial}

Description

Field of application of the invention

The invention relates to a process for the cross-coupling of organometallic compounds with halogen compounds or perfluoroalkylsulfonates to produce compounds of general formula I,

R ¹ and R ² each independently represent a group of the formula IV,

R- (A'-ZV (A ² ) _P IV

Each R independently of one another is an unsubstituted or substituted by CN or at least one halogen alkyl or alkenyl radical having up to 18 carbon atoms, wherein one or more non-adjacent CH ₂ groups by a radical selected from the group -O -, -S -, - CO -, - O-CO -, - CO-O- and-CsC- may be replaced, one of the radicals R also halogen.-NC.-CFs.-CNoder-OCFa,

A ¹ and A ^{2 are} each independently

a) a 1,4-phenylene radical in which one or two CH groups may be replaced by N,

b) a 1,4-cyclohexylene radical in which one or two non-adjacent CH ₂ groups may be replaced by -O- or -S-,

c) a 1,4-cyclohexenylene, a piperidine-1,4-diyl, a 1,4-bicyclo [2,2,2] -octylene or a naphthalene-2,6-diylrost wherein the radicals a) and b) one or more times may be substituted by halogen atoms, cyano and / or methyl groups,

Each Z ¹ is independently CO-O-O-CO-, -CH ₂ CH ₂ -, -CH (CNhCHj-, -CH ₇ -CH (CNK-CH = CH-, -OCH ₂ -, - CH ₂ O-, -CH = N -, - N = CH-, - NO = N -, - N = NO -, - N = N- or a single bond,

ο and ρ are each independently of one another 0.1 or 2, and the sum of all ο and ρ is 2,3 or 4, Z is a single bond or an unsubstituted or CN or halogen-substituted alkylene group having 1-4 C atoms, E is an unsubstituted or ethylidene group substituted by CN or halogen, and m is O or 1 by reacting organometallic compounds of the formula II,

R'-Z-Met Il

wherein R ¹ and Z have the meaning given, and

Met Li, Na, K, ZnX, B (X) ₂ , Al (X) ₂ , Ti (XIa, Zr (X) ₃ , HgX or SnX ₃ , wherein each X is independently a radical of the formula R'-Z- Is halogen, alkyl or alkoxy having in each case 1 to 6 C atoms or a cyclopentadienyl radical, where in the case of Met = B (X) ₂ ,

X can also be OH, means, with a compound of formula III,

Y- (E) ₀₁ -R ² III

wherein E, R ² and m have the meaning given, and Y is halogen or OSO ₂ -C _n F _2n + 1, wherein η is an integer value of 1 to 10 means by means of metallic, optionally applied to a support material palladium as Transition metal catalyst, optionally in the presence of a metal alkoxide, coupled.

Characteristic of the known chemical solutions

The previously known processes for the preparation of compounds of the formula I all lead to unsatisfactory results. Above all, these are poor yields and z.T. difficult to access starting compounds responsible. For example, the preparation of 1-cyano-2-fluoro-4- (trans-4-heptylcyclohexyl) benzene, a compound of formula I, according to EP-0119756 from the corresponding 1-acetyl compound only with a yield of approx 1% of theory Also, the preparation of 1-fluoro-2- (trans-4-alkylcyclohexyl) compounds according to the method disclosed in US-4405488 requires considerable synthetic effort and provides the desired products only in unsatisfactory yields. The use of polymer-bound Pd (II) -arylphosphine complexes, which are leached only weakly after reduction to the corresponding Pd (0) complexes by the reaction medium, is suitable for Heck coupling (RF Heck, Org. Reactions [NYI 27,345 (1982 Anderson, Hallberg et al [J. Org. Chem. 50, 3891 [1985]) and Teranishi et al. (J. Organomet. Chem., 162, 403 [1978]). Thereafter, aryl iodides can be coupled with styrenes and acrylates in the presence of a supported Pd-phosphine catalyst. Aryl bromides react much worse or not at all with these catalyst systems. Thus, for 80% conversion in the reaction of bromobenzene with methyl acrylate at 100 ° C already 6 days required (J. Org. Chem. 50,3891 [1985] p.3894 et seq.). Bromobenzene gives stilbene only in traces with styrene (J.Organomet.Chem., 162, 403 [1978] p.40), while iodobenzene gives the isomeric stilbenes in 86% within two hours. Although Pd / c is a suitable catalyst for the Heck coupling of iodobenzene, this system is no longer suitable for the use of bromobenzene.

As in both Heck coupling and Kumada / Negishi coupling (e.g., Kumada et al., J. Am. Chem. Soc., 106, 158 [1984]; Negishi, Acc. Chem. Res. 15,340 [1982] , DE 3632410 and DE 3736489; E. Poetsch, Kontakte [Darmstadt] 1988 [2] pages 15-28 and literature cited therein) the oxidative addition product Ar-PdL ₂ -Br (L = ligand), formed from the Pd (O ) Compound PdL ₂ and

In the same vein, bromoborane, which is one of the reactants, was expected by experts to be less suitable for the Kumada / Neghishi coupling of bromobenzenes. Since the Kumada / Neghishi coupling method is carried out under much milder reaction conditions due to the usually relatively unstable metal derivatives used as the Heck coupling, the success of a Kumada / Negishi coupling with aryl iodides and metallic Pd is not expected.

For this reason alone, it is to be understood that since the cross-coupling of β-bromostyrene with methylmagnesium iodide under Pd (O) catalysis with polymer-bound phosphine ligands described in 1978, the het'.irogenetic catalytic cross-coupling of bromobenzene with Chloro-2-methylphenylmagnesiumchlorid has been described (EP-AO 152450).

Object of the invention

The object of the present invention was to find a preparation process for the compounds of the formula I which does not have the described disadvantages of the previous processes or only to a small extent.

Explanation of the essence of the invention Surprisingly, it has been found that organometallic compounds in the presence of metallic optionally on a Support applied palladium are excellent for the preparation of compounds of formula I are suitable. The invention thus provides a process for the preparation of compounds of the formula I in which organometallic Compounds of formula II coupled with Elektropi methods of formula III under transition metal catalysis, characterized

that the transition metal catalyst is metallic, possibly applied to a support material palladium.

Some of the compounds of the formula I are known, but some are new. The new compounds of the formula I are

also the subject of the invention.

The success of such a stereoselective coupling of aliphatic and aromatic metal organyls with aromatic,

heteroaromatic, aliphatic or cycloaliphatic halogen compounds or sulfonates was all the more surprising, as even in previously known C-C coupling reactions with complexed palladium catalysts β-elimination from the coupling position adjacent CH group either in the preparation of the metal organyl or from

Metalorganyl itself occurs as the steric evolution and the yield strongly affecting side reaction. Woiterhin proves the process to be highly chemoselective, so that even electrophilic groups such as esters or nitriles the Course of the reaction can not affect. In addition, this can be obtained after completion of the reaction

metal palladium metal easily separated, so that no polluting substances can get into the wastewater. In addition, the metals can be varied as desired, whereby the chemo-, stereo- and enantioselectivities of the compounds of the formula II can be specifically influenced and adapted to the respective conditions.

The inventive method is based on the readily available, metallatable compounds of formula V.

R- {A'-Z ') o- (A ² ) pZY' V

wherein R, A ¹ , A ² , Z, Z ¹ , ο and ρ have the meaning given for formula I or II and Y 'is chlorine, bromine, iodine, an easily abstractable hydrogen atom or eino vinyl group, easily in means a metal-ethylene group is convertible means. These are converted by known processes into the corresponding organometallic compounds of the formula II. The methods used are expediently adapted to the nature of the functional groups present in the metalatable compounds of the formula IV.

So z. As the zinc derivatives according to "Methods of Organic Chemistry" (Houben-Weyl), Volume XIII / 2 a, "Methods of Preparation and Conversion of Organozinc Compounds", Georg Thieme Verlag, Stuttgart 1973 or gap et a., J. Org. Chem 50,4761 (1985); the boron compounds are e.g. according to H.C. Brown et al. Chem. Soc. 104,4303 (1982) - chiral 2-butyldimethylboronate, Organometallic 4, 1788 (1985) - Boronates and Borinates, Organometallics 2, 1316 (1985); Tetrahedron Letters 29, 2631 (1988); 1983) - boranates and boronic acid The aluminum compounds are described, for example, as described by Negishi et al., J. Am. Chem. Soc., 109, 2393 (1987) or Ohta et al., As Heterocycles, 26, 2449 (1987); Zirconium compounds are prepared, for example, according to Stille, Angew Chem, Int., Ed., Engl., 25, 508 (1986), and the titanium compounds are prepared, for example, according to Reetz, Top. Curr. Chem., 106, 1 (1982).

The reaction of the metalatable compounds of the formula IV (Y '= chlorine, bromine, iodine) is preferably carried out in an inert solvent, for example ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran or dioxane, hydrocarbons such as hexane, cyclohexane, benzene or toluene or mixtures of these solvents metallic lithium, n-butyllithium, tert-butyllithium, lithium naphthalenide, lithium di-tert-butylnaphthalenide or metallic magnesium at temperatures of -100 ⁰ C to +100 ⁰ C, preferably at -78 ⁰ C to +75 "C.

The deprotonation of the metalatable compounds of the formula V (Y '= H) is preferably carried out in inert solvents, for example hydrocarbons such as pentane, hexane, cyclohexane, benzene or toluene, ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, tert-butyl methyl ether or dioxane or mixtures of these solvents by lithium amido such as lithium diisopropylamide, lithium dicyclohexylamide, lithium bis (trimethylsilyl) amide or lithium tetramethylpiperidine at temperatures of -100 ⁰ C to + 100 ⁰ C, preferably at -78 ⁰ C to +75 ⁰ C. Unter In these conditions, the conversion of the metalatable compounds of formula IV to the lithium or halomagnesium organyls (Y '= Li or MgX) is usually complete in about 10 to 60 minutes. By adding metal compounds of the formula VI,

Met-X Vl

wherein X '* represents each independently Cl, Br, R ^6, OR ⁵ or NR, wherein R ⁵ has the meaning given, to the solutions of Halogenmagnesium- or organolithium compounds at temperatures of from -78 ° C to 2O ⁰ C preferably at - 3O ⁰ C to O ⁰ C, the metal organyls are usually obtained after 60 to 180 minutes of reaction time.

The metal compounds of formula VI can be dissolved or added undissolved. As a rule, they are added in dissolved form, preferably in the same medium in which the halomagnesium or lithium organyl is present.

Subsequently, the solution of the organometallic compound of the formula II is added to the coupling component of the formula III and metallic, optionally also applied to a support material palladium, wherein a selective coupling to the compounds of formula I.

Conveniently, the same solvents as those used for the preparation of the organometallic compounds of the formula II above are used at the temperatures indicated. The required reaction times are usually between about 1 and 100 hours.

In a preferred embodiment of the process according to the invention, the compounds of the formula III are added together with the metallic palladium and a metal alcoholate in an inert solvent to the metal organyls of the formula II. Preferred metal alcoholates are, for. As sodium methylate, sodium ethylate, sodium isopropanolate, potassium tert-butoxide.

The starting compounds used are metallable compounds of the formula V and compounds of the formula III. Suitable halogen compounds are all halides which can be converted into a metal organyl in question.

Preferably, the bromides are used, and also the chlorides or iodides.

The following formulas Va to Vk represent a group of very particularly preferred starting compounds, wherein the aromatic groups are also represented by F, Cl, CN or CH ₃ , the cyclohexyl groups also in the 1-position by F, Cl, CF ₃ , CN or C C ₄ alkyl may be substituted:

R'-Br Va

- ^Br Vb

H R * - </ -CN Vc

-CH ₂ CH ₂ Br Vd

Ve

_R i _ / - yr ^ cN

R ^ - <O} -Br

IVh

, CH ₀ -Br

' ^Δ IVi

IVk

R ¹ therein is preferably an alkyl group having 1-18C atoms, wherein also one or two non-adjacent CH ₂ groups may be replaced by -O- and / or -CO- and / or -CO-O-.

In the formulas I, II, III and IV, R ', R ² and R preferably denote straight-chain or branched alkyl having 1-18C atoms, preferably having 2-10C atoms, and accordingly preferably mean ethyl, propyl, butyl, pentyl , Hexyl, heptyl, octyl, nonyl or decyl, and also methyl, undecyl, dodecyl, tridecyl, tetradecyl or pentadecyl. Also preferred are branched radicals such as isopropyl, 2-butyl, isopentyl, 1-methylpentyl, 2-methylpentyl, 1-methylhexyl or 1-methylheptyl. R ¹ or R ² is preferably also ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, nonoxy and decoxy, and also methoxy, undecoxy, dodecoxy, tridecoxy, tetradecoxy or pentadecoxy or isopropoxy, isopentoxy, 2-butoxy or 1-methylpentoxy.

For the coupling with the organometallic compounds of the formula II usable are all compounds of the forms! III. The bromides (Y = Br) are preferably used (moreover the chlorides (Y = Cl) and perfluoroalkanesulfonates (Y = OSO ₂ - (CF ₂ ) _r -CF ₃ ).) Among the perfluoroalkanysulfonates, particular preference is given to trifluoromethane and perfluoroethane For the coupling of titanium organyls with branched aliphatic compounds of the formula III, iodides are particularly suitable

The following formulas HIa to Hl ν represent a group of very particularly preferred starting compounds, where the aromatic groups are also represented by F, Cl, CN or CH ₃ , the cyclohexyl groups also in the 1-position by F, Cl, CF ₃ , CN or C C ₄ alkyl may be substituted:

Br / O) -OCF "» la

Br- <O) ^{-halogen IIIb}

Br- <O> -CN ^IIIc

-0

-r Br- (O> -CN

Br- / O-R ² Br- / O-ZoS-R ²

Br- ( O> - <O> -R

IIIe

IHf IHg

Br- / OV / O VcH ₂ CH ₂ - / O - -

HIH

Br- / VcH = CH- / o V / O Vr ²

0N-CH ₂ CH ₂ - / OV / θΛ -R

Br-R "

, -0-0H =

- / H V

Br-CH ₂ CH ₂

Br- <O> -R

r ^/

Br- / O y -CO ₂ - / oW N -

N Br ^ OV / O Vr ²

iiijIHk

him

HinHIo

Hip

HiQ

HIr

Ills

Br- <O> -CO ₂ - (H) -

hit

Miu

Br-CH ₉ -CO ₉ -R ²

IHV

R ² therein preferably denotes an alkyl group having 1-15 C atoms, in which also one or two non-adjacent CH ₂ groups may be replaced by -O- and / or -CO- and / or -CO-O-.

Suitable metal compounds of the formula VI are in particular the metal halides or metal oxides. In the case of polyvalent metals also the mixed halometal alkoxides.

Particularly preferred metal compounds of the formula VI are those of the subformulae VI to VI

B (OR ⁵ I ₃ Via BCI (OR ⁶ I ₂ VIb BCI ₃ VIc AICI (R ⁵ ) ₂ VId AICI ₃ VIe CITi (OR ⁶ ) ₃ VIf BrTi (OR ⁶ ) ₃ VIg TiCI ₄ VIh CITi (NRl) ₃ VIi CIZr (OR ⁵ I ₃ VIj HgCI ₂ VIK CISnR ⁵ ₃ VII

Preferred metallic catalysts are metallic Pd (Pd (O)), palladium on activated carbon (Pd / C), where a ratio between palladium and activated carbon may be 1 to 99% by weight, preferably 1 to 10% by weight, and palladium on barium sulfate (Pd / BaSO «). The halogen compounds of the formula IV used as starting compounds are known or can be prepared by known methods, for example as described in Houben-Weyl, Methods of Organic Chemistry, Vol. 5/3 and 5/4. Thus, it is possible, for example, to convert alcohols of the formula IV in which X 'is a hydroxyl group with a phosphorus trihalide or with triphenylphosphine / tetrahalomethane into the corresponding halides.

The metal compounds of the formula VI used as transmetalation reagents are known or can be prepared by known methods, for. B. Gmelin manual.

Also known or obtainable by known methods are the compounds of formula III to be used as coupling components.

For example, halides of the formula III in which X is Br or I, nO and Q is an aromatic can be obtained by replacing the diazonium group by Br or I in a corresponding diazonium salt.

Perfluoroalkylsulfonates of the formula III in which X is OSO ₂ - (CF ₂ I ₁ -CF ₃ can be prepared by esterification of corresponding alcohols of the formula III in which X is a hydroxyl group with perfluoroalkanesulfonic acids or their reactive derivatives The corresponding perfluoroalkanesulfonic acids are known.

Particularly suitable as reactive derivatives of said perfluoroalkanesulfonic acids are the acid halides, especially the chlorides and bromides, furthermore the anhydrides, e.g. As well as mixed anhydrides, azides or esters, in particular alkyl esters with 1-4C atoms in the alkyl group.

In the present invention, therefore, a very advantageous process for simple, high-yielding, stereoselective preparation of compounds of the formula I is available.

The compounds of the formula I are suitable for use as liquid-crystalline materials, such as. In DE-3217 597 and DE-2636684, or may be used as intermediates for the preparation of other liquid crystalline compounds.

The following examples are intended to illustrate the invention without limiting it. Fp = melting point; Cp = clearing point; K = crystalline; N = nematic; I = isotropic. Above and below, percentages are by weight.

Usual work-up in the following means: Add with weakly acidic water, extract with toluene, dry the organic phase, evaporate and purify by chromatography and / or crystallization.

example 1

1A 4'-pentylbiphenyl-4-ylboronic acid

A mixture AUS4-bromomagnesium-4'-pentylbiphenyl (made of 150g4-bromo-4'-4'-pentylbiphenyl and 10.8 g of magnesium) and 450 ml tetrahydrofuran is added at -7O ⁰ C was slowly added to a solution of 156g of triisopropylborate in tetrahydrofuran 10OmI , After warming to 20 ⁰ C, the reaction mixture is treated with 650 ml of a 10% hydrochloric acid solution. After separating the aqueous phase, washing with water and drying to obtain the boronic acid, which is further processed unrefined.

1B 4 "-pentyl-4-cyano-p-terphenyl

A mixture of 5.4 g of boronic acid 1A, 3.7 g of 4-bromobenzonitrile, 50 ml of toluene and 4.2 g of sodium carbonate in 15 ml of water

0.65 g Pd / C (10%), stirred for 24 h at room temperature and heated to boiling for 15 minutes. After usual

Workup and chromatographic purification gives 3.0 g of terphenyl, mp 13O ⁰ C, Cp239 ⁰ C. Analogously, 4 "-alkyl-4-cyano-p-terphenyls are obtained Alkyl- / O - - / O - - / θ \ -CN

Alkyl K / N ( ⁰ C) N / l ( ⁰ C)

H ₇ C ₃ Example 2 182 275 4-bromo-4'-pentylbipheny! ι 2A H9C4 154 242 magnesium 2 B 4 "-pentyl-4-cyano-p-terphenyl 4-bromobenzonitrile HuCE 125 228 triisopropylborate Made of: Na ₂ CO ₃ 1.2 g water 2A bis- (4'-pentylbliphenyl-4-yl) -borin-3-acid 0.74 g Pd / C (10%) Made of: 0.42 g 150 g 5 ml 10.8 g 0.07 g 78 g analogously to Example 1 A

analogously to Example 1A

After customary work-up and purification, 0.7 g of the tarphenyl are obtained. Example 3

3A n-butyl boronic acid

Made of:

3.3 ml n-butyllithium (10M solution in hexane)

6.3 g of trimethylborate analogous to Example 1A

3 B 4- (trans-4-propylcyclohexyl) -4'-butylblphenyl Prepared from:

5.0 g 3A0.7 g Pd / C (10%)

18.0 g of 4- (trans-4-propylcyclohexyl) -4-bromobiphenyl analogously to Example 1B.

After customary work-up and chromatographic purification, the product is obtained as a colorless solid. Analogously, 4 '- (4-trans-alkylcyclohexyl) -4-alkylbiphenyls are prepared.

R ¹ R ² XK / N ( ⁰ C) K / L ( ⁰ C)

C ₆ H _n C ₂ H ₆ H 34 164 C ₈ H ₁₃ C ₂ H ₆ H 44 156 C ₆ H ₁₁ C ₂ H ₆ H 14 158 C ₆ H ₁₁ C ₄ H ₉ H 20 170.5 C ₆ H ₁₁ C ₆ Hn H 13 170 C ₆ Hn C ₂ H ₅ F 26 107

Example 4 4A

8.6 g of cis-4- (trans-4'-propylcyclohexyl) -cyclohexylbromide (prepared from the corresponding trans-alcohol with triphenylphosphine / bromine in acetonitrile in a manner known for the bromination of alcohols) are dissolved in a solvent mixture of 50 ml of toluene / tetrahydrofuran ( 4: 1) with 3.4g zinc bromide and 0.42g thinly hammered lithium disks in a cooled ultrasonic bath exposed to the ultrasound until no lithium is visible. The reaction mixture is treated with 1.6 g of palladium / activated carbon (10%) and 6 g of 4-bromo-2-fluorobenzonitrile and stirred for 18 h at room temperature and heated to boiling for 15 minutes. It is then extracted with weakly acidic water and toluene, the organic phase dried over MgSO ₄ and evaporated. The evaporation residue gives after chromatography on silica gel with petroleum ether / diethyl ether 9: 1 and crystallization from ethanol 7.7 g of 4-cyano-3-fluoro-1- (trans-4 '- (trans-4 "-propylcyclohexyl) -cyclohexyl] benzene from Mp 54.3 ⁰ C and Cp 203 ⁰ C.

Analogously, 6.06 g of cis-4- (trans-4'-butylcyclohexyl) cyclohexyl bromide and 5.4 g of 4-trifluoromethanesulfonyloxy-2-fluorobenzonitrile give 2,3g4-cyano-3-fluoro-1- (trans-4 ' - (trans-4 "-butylcyclohexyl) -cyclohexyl | benzene; K / N 67 ⁰ C, N / l 197.4 ⁰ C.

The following compounds can be prepared analogously (the transition temperatures given refer to the crystalline / nematic (K / N) and nematic / isotropic (N / I) transition.

4- [trans-4 '- (trans-4 "-Alkylcyclohexyl) -cyclohexyl] -hatogenbenzole

Alkyl shark K / N ( ⁰ C) N / l ( ⁰ C)

H ₇ C ₃ F 87.9 158.5 H9C4 F 79.5 152.1 H ₁₃ C ₆ Cl 57.8 173.2

4- (trans-4 '- (trans-4 "-Alkylcyclohexyl) -cyclohexyl) -benzolderivate

Alkyl R ⁴ K / N ( ^O C) N / I ( ⁰ C)

H ₇ C ₃ OCH ₃ 7 ^H 15 79.5 211 H ₉ C ₄ OC ₆ H ₁₃ 70.0 186.3 H ₇ C ₃ CH ₃ 64.6 179.8 H ₁ ] C ₆ C ₃ H ₇ 48.6 181.0 H ₇ C ₃ CsH ₁ I <20 172.0 C ₃ H ₇ COCH ₃ 81 116 C ₂ H ₆ CN 76 195 C ₃ H ₇ CN 55 184 C ₆ H]] - / o Vc 200 270 N

4-I trans-4 '- (trans-4 "-Alkylcyclohexyl) -cyclohexyl] -halogenbenzole

Hal

alkyl <

Alkyl Hal R ⁴ K / N (° C) N / I (° C)

H ₇ C ₃ F H 54.5 92.3 H ₉ C ₄ Cl H 28.3 39.8 H ₇ C ₃ F COCH ₃ 88 293 H ₉ C ₄ F CN 67 197.4

(E)

- (O> CN

trans ^ -alkylcyclohexylaryl derivatives x, 4

K / N ( ⁰ C) N / L ( ⁰ C)

106

169

-CN19

21

04

09

- ^> C157,5

85

- ^ O) -Cl58,5

83

<p) - ^) - CN

90

115.5

K / N (° C)

N / ira

- (O) -Cl - (O) -F

77.5 57

119.5

79

CN

Example 5

5A 4-propylphenylboronic acid Prepared from:

7.96 g of 4-bromopropylbenzene 0.98 g of magnesium

 1.15 g of trimethylborate analogous to Example 1A

5B 4- (trans-4-pentylcyclohexyl) -4'-propyl! Phenyl Prepared from:

3.3 g 5A

5.2 g of 4- {trans-4-pentylcyclohexyl) bromobenzene ml of toluene Na ₂ CO ₃ water Pd / C (10%)

96

131

4.2 g

2.5 ml

0.65 g

Analogously to Example 1B, 5.5 g of the biphenyl derivative are obtained as a colorless solid after customary work-up and chromatographic purification.

Example β

β A 4-trifluoromethoxy-4'-propylblphenyl Prepared from:

1.65 g 5 A

2.5 g of 4-trifluoromethoxybromobenzene 25 ml of toluene 15 ml of water 1.1 g of Na ₂ CO ₃ 0.33 g of Pd / C (10% strength) analogously to Example 5B. After customary work-up and chromatographic purification to obtain 1.8 g of trifluoromethoxybiphenyl.

Example 7

7A 4-trifluoromethoxy-4'-bromophenyl

A mixture of 36.4 g of 4-trifluoromethoxy-4'-bromobenzene and 100 ml of tetrahydrofuran is added at -7O ⁰ C first with 92 ml of a 15% solution of n-butyllithium in hexane and then with a mixture of 18.8 g ZnBr ₂ and 100 ml of tetrahydrofuran are added.

This reaction mixture is admixed with 43.4 g of 1-bromo-4-iodobenzene and 8.8 g Pd / C (10%). After stirring for 24 hours, usual work up and chromatographic purification to obtain 23.9 g of trifluoromethoxybiphenyl.

Example 8

8A p-vinylpropylbenzene Made from:

60 g of p-propylbromobenzene

7.3 g magnesium 33.8 g zinc bromide

500 ml of tetrahydrofuran

35 g of bromoethylene

6.4 g Pd / C (10%) 0.16 g sodium methylate

p-Propylphenylzincbromid! prepared over the appropriate Grignard reagent) is at room temperature with a mixture of bromoethylene, Pd / C unr! Sodium methylate reacted. After usual work-up and chromatographic purification, 37.0 g of product 8A are obtained.

Example 9

9A 4- (trans, trans-4'-pentylblcyclohexyl-4-yl) -2-fluorobenzonitrile

Made of:

6.4 g of 4'-pentyl-4-bromobicyclohexane 2.3 g of zinc bromide 0.28 g of lithium 50 ml of THF: toluene = 1: 44.0 g of 4-bromo-2-fluorobenzonitrile

X g Pd catalyst Y g metal alcoholate

After customary work-up and chromatographic purification, the product is obtained in the yields shown in Table I:

Tab.I representation of 9A

example Pd catalyst metal alcoholate yield G G 9a 0,42gPd / C (10%) 0 5.7 9b 0,42gPd / C (10%) 0.02 NaOCH ₃ 8.6 9c 0,42gPd / C (10%) 0.05KOC (CH ₃ ) ₃ 8.8 9d 0.29gPdCl ₂ dppf 0 8.6

= Comparative Example

* dppf = 1,1'-bis (diphenylphosphino) ferrocene

Example 10

10A 4- (trans, trans-4'-pentylbicyclohexyl-4-yl) -1-trifluoromethoxybonzene

Made of:

6.4 g 4-pentyl-4-bromobicyclohexane Boronic acid 2.3 g zinc bromide 4-bromonicotinic 0.28 g lithium H ₂ O 50 ml THF: toluene = 1: 4 Na ₂ CO ₃ 5 g p-trifluoromethoxybromobenzene Pd / C (10%) 0.42 g Pd / C (10%) 0.02 g sodium analogously to Example 4 After usual work-up, 8.9 g of product 10A are obtained. Example 11 11A 4-phenylncanoic acid Made of: 3.7 g 6.1 g 50 ml 9.6 g 1.6g

Analogously to Example 1, 3.5 g of the product are obtained after customary work-up. Analogously, from 2,4-dimethyl-5-methoxy-4-cyano-3-bromopyridine by reaction with pyridin-4-yl-boronic acid and

subsequent acidic hydrolysis of the methoxy group with hydrochloric acid miirinone

H (WJ Thompson, et al., J. Org. Chem. 53 (9), 2052-2055 (1988)).

Claims (1)

Process for the cross-coupling of organometallic compounds with halogen compounds or perfluoroalkylsulfonates to produce compounds of general formula I, R ¹ -Z- (E) _m -R ² I R ¹ and R ² each independently represent a group of the general formula IV, R- (A ¹ -ZV (A ² ) _P IV R each independently of one another an unsubstituted or substituted by CN or at least one halogen alkyl or alkenyl radical having up to 18 carbon atoms, wherein one or more non-adjacent CH ₂ groups by a radical selected from the group-O -, - S -, - CO-, -O-CO -, - CO-O-and-C = C-may be replaced, one of the radicals R is also halogen, -NC, -CF ₃ , -CN or -OCF ₃ , A ¹ and A ^{2 are} each independently a) a 1,4-phenylene radical in which one or two CH groups can be replaced by N, b) a 1,4-cyclohexylene radical wherein one or two non-adjacent CH ₂ groups may be replaced by -O- or-S-, c) a 1,4-cyclohexenylene, a piperidine-1,4-diyl, a 1,4-bicyclo (2,2,2] -octylene or a naphthalene-2,6-diyl radical where the radicals a) and b) one or more times by halogen atoms, cyano and / or Methyl groups can be substituted,
Z ¹ each independently represents-CO-0, -0-CO -, - CH ₂ CH ₂ -, - CH (CN) -CH ₂ -, - CH ₂ -CH (CN) -, -CH = CH -, - OCH ₂ -, - CH ₂ O -, - CH = N -, - N = CH -, - NO = N -, - N = NO -, - NN-or a single bond, ο and ρ are each independently of one another 0.1 or 2, and the sum of allo and ρ is 2,3 or 4, Z is a single bond or an unsubstituted or CN or halogen-substituted alkylene group having 1-4 C atoms, E is an unsubstituted or substituted by CN or halogen ethylidene group, and m is O or 1 mean, by organometallic compounds of general formula II, R ¹ -Z-Met II wherein R ¹ and Z have the meaning given and Met is Li, Na, K, ZnX, MgX, B (X) ₂ , Al (X) ₂ , Ti (X) ₃ , Zr (X) ₃ , HgX or SnX ₃ , wherein X each independently of one another is a radical of the formula R ¹ -Z-, halogen, alkyl or alkoxy having in each case 1 to 6 C atoms or a cyclopentadienyl radical, where in the case Met = B (X) ₂ , X may also be OH, means with a compound of general formula III, Y- (E) _m -R ² III wherein E, R ² and m are as defined, and Y is halogen or OSO ₂ -C _n F _{2n +1 (} wherein η is an integer value of 1 to 10, means coupled under transition metal catalysis, characterized in that the Transition metal catalyst is metallic, possibly applied to a support material palladium.