Biphenyls and aromatic olefins can have versatile uses as chemical speciaiities for the pre- paration of liquid crystals, as photoinitiators, UV absorbers, fluorescent whitening agents, ligands for catalysts and as starting materials for the preparation of intermediates for agro- chemicals and pharmaceutical products.

A frequently used method for the synthesis of biphenyls is the palladium-catalysed cross- coupling (so-called Suzuki coupling) in which iodine aromatic compounds or bromine aro- matic compounds or arylsulfonates are reacted with arylboron derivatives in the presence of palladium catalysts. This method is described, inter alia, in N. Miyaura et al., Synthetic Communications, 11 (1981), 513 ; A. Suzuki in Metal-catalyzed Cross-coupling Reactions, chapter2, Wiley-VCH, Weinheim 1998, in U. S. patent specification 5, 130, 439 and in EP-A-470 795.

A frequently used method for the synthesis of aromatic olefins is the palladium-catalysed coupling reaction, the so-called Heck reaction, in which iodine aromatic compounds or bromine aromatic compounds are reacted with olefins in the presence of palladium cata- lysts. This method is described, inter alia, in R. F. Heck, acc. Chem. Res. 1979, 12, 146 ; R.

F. Heck, Org. React. 1982, 27,345; and in R. F. Heck, Palladium Reactions in Synthesis, Academic Press, London 1985, S. Brase and A. De Meijere in Metal-catalyzed Cross- coupling Reactions, chapter 3, Wiley-VCH, DE-Weinheim 1998.

In spite of their interesting broad utility, these methods have drawbacks regarding the syn- thesis. For example, if one does not want to use the catalyst in amounts of more than 1 mol %, then only small amounts of product can be produced on a laboratory scale by the cited coupling reactions. In the Suzuki reaction, the use of conventional palladium catalysts, e. g. Pd (PPh3) 4, Pd (OAc) 2 and triphenyl phosphine, results in undesirable side reactions through aryl transference from the catalyst to the substrate; D. F. O'Keefe et al. Tetrahedron Lett., 1992,6679. The recovery of the palladium catalyst is elaborate in the case of the cited coupling reactions, the separation of the palladium residue from the reaction mixture re- quiring first the conversion of that residue into a palladium salt, e. g. palladium chloride or palladium acetate.

It is the object of this invention to find suitable catalysts for coupling reactions of biphenyls of the Suzuki cross-coupling type and of aromatic olefins of the Heck coupling type which pro- mise improved turnover numbers (mol product/mol catalyst) and enhanced reactivity and selectivity over the catalysts used in such coupling reactions.

This object is achieved by the present invention which provides a novel, inventive process for the preparation of biphenyls and aromatic olefins using olefinic palladium complex com- pounds.

This invention relates to a process for the preparation of biphenyls of formula wherein A and B define substituents; m and n define integers from 0 to 5 and the number of substituents at the phenyl radicals D and E; or of aromatic olefins of formula wherein C defines substituents, o defines integers from 0 to 5 as well as the number of sub- stituents at the phenyl radical F, and R6, R7 and R8 are hydrogen or substituents, which pro- cess comprises a) subjecting a phenyl derivative of formula wherein A, B, m and n have the meanings cited for formula i and X is a leaving group, for the preparation of the biphenyls (I) to a coupling reaction with an arylboronic acid deriva- tive of formula wherein A, B, m and n have the meanings cited for formula I and Y is the-B (OH) 2 group or mono-or diester derivatives of-B (OH) 2; and b) subjecting a phenyl derivative of formula wherein C and o have the meanings cited for formula 11 and X is a leaving group, for the preparation of the aromatic olefins (II) to a coupling reaction with an olefin of formula wherein R6, R7 and R8 have the meanings cited for formula 11, each in the presence of a catalytically effective amount of an olefinic palladium complex compound of formula wherein L is a neutral ligand having electron-donor properties, Z is an anionic ligand and D is a substituent, and p is an integer from 0 to 5 and defines the number of substituents at the allyl group; or a') subjecting a phenyl derivative (111 a) or (Illb), wherein A, B, m and n have the meanings cited for formula I and X is chloro, bromo or iodo, for the preparation of the biphenyls (I) to a coupling reaction with an arylboronic acid derivative (IV a) or (IV b), wherein A, B, m and n have the meanings cited for formula I and Y is the-B (OH) 2 group or mono-or di- ester derivatives of-B (OH) 2; or b') subjecting a phenyl derivative (V), wherein C and o have the meanings cited for for- mula 11 and X is bromo or iodo, for the preparation of the aromatic olefins (II) to a coup- ling reaction with an olefin (VI), wherein R6, R7 and R8 have the meanings cited for formula 11, in the presence of a catalytically effective amount of an olefinic, ionic palladium complex compound of formula wherein Z, and Z2 are anionic ligands and K+ is a non-coordinating cation and D and p have the cited meanings, and isolating the biphenyl (I) or the condensed aromatic ole- fin (II) after the completion of the process variants a), b), a') or b').

The catalysts used in this process can be easily obtained by simple synthesis, for example by the method of B. Akermark et al., Organometallics 1987,6,620-628, and have substan- tially improved reactivity and selectivity. After the reaction is complete, the dissolved olefinic palladium complex compounds can be degraded to palladium black using atmospheric oxy- gen. Using the method of Y. Inoue et al. Synthesis 1984,3,244, this residue can be used again directly for the catalyst synthesis without any detour over the conversion into a palla- dium salt, such as palladium chloride or palladium acetate.

The terms and denotations used in this description of the invention preferably have the followingmeanings: Biphenyls (I) are preferably substituted at the phenyl ring D by 1 to 5 substituents from the group A containing the substituents Ri, R2, R3, R4 and R5, and at the phenyl ring E also pre- ferably by 1 to 5 substituents from the group B containing the substituents from the group R6, R7, R8, Rg and Rio. Suitable substituents are listed in the List of Radical Names, which is valid according to IUPAC Rules, and remain unchanged under the conditions of the coupling reactions. Any of the substituents may be selected. Suitable substituents A from the group R"R2, R3, R4 and R5 are selected, for example, from the group consisting of the functional groups or derivatised functional groups consisting of amino, C,-C4alkylamino, C,-C4dialkyl- amino, hydroxy, oxo, thio,-N02, carboxy, carbamoyl, sulfo, sulfamoyl, ammonio, amidino, cyano, formylamino, formamido and halogen, or are saturated or unsaturated aliphatic, cycloaliphatic or heterocycloaliphatic radicals, carbocyclic or heterocyclic aryl radicals, con- densed carbocyclic, heterocyclic or carbocyclic-heterocyclic radicals, which may in turn be combined with any others of these radicals and which may be substituted by the cited func- tional groups or derivatised functional groups.

The cited substituents and radicals can additionally be interrupted by one or more than one bivalent radical selected from the group consisting of-O-,-S-,-C (=O)-O-,-O-C (=O)-, -C (=O)-N (C,-C4alkyl)-,-N (C,-C4alkyl)-C (=O)-,-S (=O)-,-S (=0) 2-,-S (=O)-O-,-S (=0) 2-O-, -O-S (=O)-,-O-S (=0) 2-,-S (=O)-N (C,-C4alkyl)-,-S (=0) 2-N (C,-C4ålkyl)-,-(C,-C4alkyl) N-S (=O)-, -(C,-C4alkyl)(C,-C4alkyl) N-S (=0) 2-,-P (=O)-,-P (=O)-O-,-O-P (=O)-and-O-P (=O)-O-.

Two substituents from the group R"R2, R3, R4 and R5 can also be bivalent, bridge-like C2- C6alkylene, C4-Cealkyldiylidene or C4-C8alkenyldiylidene groups, preferably butanediylidene, more preferably 2-butenediylidene, which are bound to the phenyl ring D or to the heteroaryl substituent A, e. g. pyridyl, or which are condensed to an aromatic bicycle, which can like- wise be substituted by the cited functional groups or substituents.

Suitable substituents B from the group R6, R7, RB, Rg and Riohave the meanings cited for R, to R5 and can also be substituted by further substituents. Ri, Rz, Ra, R4 and Re and R6, R7, R8, Rg and Ro are defined each independently of one another.

Suitable substituents A from the group RI, R2, R3, R4 and R5 are preferably functional groups from the group consisting of amino, C1-C4alkylamino, for example methylamino or ethylami- no, C-C4dialkylamino, for example dimethylamino or diethylamino, hydroxy, oxo, thio,-N02, carboxy and halogen, or are substituents from the group C,-C20alkyl, C2-C2oalkenyl, C2-C2o- alkynyl, C3-C2cycloalkyl, C7-C, 2bicycloalkyl, C4-Cl2cycloalkenyl, C2-C"heterocycloalkyl, car- bocyclic C6-C, 6aryl, C2-C, 5heteroaryl, carbocyclic C7-C, 6aralkyl and C2-C, 5heteroarylalkyl, which can in turn be substituted by the cited functional groups and which can be interrupted by bivalent radicals.

C,-CZOAlkyl is, for example, methyl, ethyl, n-or isopropyl or n-, sec-or tert-butyl and also straight-chain or branched pentyl, hexyl, heptyl, octyl, isooctyl, nonyl, tert-nonyl, decyl, undecyl or dodecyl.

C2-C20Alkenyl is, for example, vinyl, allyl, 2-or 3-butenyl, isobutenyl or n-penta-2,4-dienyl.

C2-C2oAlkynyl is, for example, 1-or 2-propynyl.

C3-C, 2Cycloalkyl is, for example, cyclopropyl, dimethylcyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

C7-C,2Bicycloalkyl is, for example, bornyl or norbornyl.

C4-C, 2Cycloalkenyl is, for example, cyclopentadienyl or cyclohexenyl.

C2-C"Heterocycloalkyl preferably contains 4 or 5 carbon atoms and one or two heteroatoms from the group O, S and N. Examples are the substituents derived from oxirane, azirine, 1,2- oxathiolane, pyrazoline, pyrrolidine, piperidine, piperazine, morpholine, tetrahydrofuran or tetrahydrothiophene.

Carbocyclic C6-C, 6aryl is, for example, mono-, bi-or tricyclic, typically phenyl, naphthyl, indenyl, azulenyl or anthryl.

C2-C, 5Heteroaryl is preferably monocyclic or is condensed with another heterocycle or with an aryl radical, e. g. phenyl, and preferably contains one or two, in the case of nitrogen up to four, heteroatoms selected from the group consisting of O, S and N. Suitable substituents are derived from furan, thiophene, pyrrole, pyridine, bipyridine, picolylimine, y-pyrane, y-thio- pyrane, phenanthroline, pyrimidine, bipyrimidine, pyrazine, indole, coumarone, thionaph- thene, carbazole, dibenzofuran, dibenzothiophene, pyrazole, omidazole, benzimidazole, oxazole, thiazole, dithiazole, isoxazole, isothiazole, quinoline, isoquinoline, acridine, chro- mene, phenazine, phenoxazine, phenothiazine, triazine, thianthrene, purine or tetrazole.

Carbocyclic C7-C, 6aralkyl preferably contains 7 to 12 carbon atoms, for example benzyl, 1- or 2-phenethyl or cinnamyl.

C2-Cl5Heteroarylalkyl preferably consists of the cited heterocycles which substitute e. g. C,- C4alkyl radicals, depending on the length of the carbon chain where possible terminally or else also in adjacent position (1-position) or in a-position (2-position).

In an aromatic olefin of formula 11, the index o preferably means 1 to 5. The phenyl ring F is preferably substituted by 1 to 5 substituents C from the group containing the substituents Ri, R2, R3, R4 and R5which are as defined above under formula I for A and Ri to R5. In the olefi- nic side chains, R6, R7 and R8 are hydrogen or substituents which are also as defined above under formula I for A and R, to R5.

In the phenyl derivative of formula III a or III b used in accordance with process variant a), X is a leaving group which is expelled during the coupling reaction, the so-called Suzuki cross- coupling. This reaction type is illustrated by the following reaction for the preparation of a photoinitiator.

A suitable leaving group X is known e. g. for the coupling reactions of the Suzuki type and is, for example, halogen, e. g. chloro, bromo or iodo, or an organosulfonyl radical, e. g. mesyl, p- toluenesulfonyl or trifluoromethanesulfonate. It has been found that chlorine is suitable as leaving group when the catalysts (VII a) are used. Otherwise, coupling reactions of the Suzuki type proceed with satisfactory yield and TON only when higher halogens, e. g. bromo or iodo, are used as leaving group. The above process is the first palladium catalyst-mediat- ed coupling of a deactivated (by electron-rich or electron-shifting groups), substituted aryl chloride by the Suzuki method.

In a special process variant, the substituents A (m = 1) or B (n = 1) in a phenyl derivative of formula III a or III b can also be an additional leaving group X having the cited meanings.

The phenyl derivative (III a, III b) concerned contains in this case two leaving groups X. It is possible to couple such a derivative with two equivalents of arylboronic acid derivatives of formula IV a or IV b so that a phenyl ring E is combined with two phenyl rings D in the pro- cess product which can be thus obtained. In analogy, products are obtained wherein one phenyl ring D is combined with two phenyl rings E.

In another process variant, it is possible that the substituents A and B in phenyl derivatives of formula III a or III b also contain additional leaving groups X. The phenyl derivative (III a, III b) concerned contains in this case two or more leaving groups X. Such a derivative can be coupled with corresponding equivalent arylboronic acid derivatives of formula IV a or IV b so that the phenyl rings D or E in the process product which can be thus obtained are addi- tionally coupled to the substituents A or B with further phenyl rings D or E. This process variant is illustrated by the following coupling reaction: wherein cat. (above the reactions arrow) signifies the catalyst (VII a).

In the arylboronic acid derivatives of formulae IV a and IV b used in accordance with pro- cess variant a), Y is also a leaving group defined as-B (OH) 2 or mono-or diester derivatives of-B (OH) 2. Mono-or diester derivatives of-B (OH) 2 are, for example, -B (O-C,-C4alk) 2 or-BOH-C1-C4alk, where C,-C4alk is preferably methyl or ethyl,-B (O-Ar) 2 or -BOH-Ar, where Ar is preferably aryl.

In the phenyl derivative (V) used according to process variant b), the index o and the sub- stituents C have the meanings cited for formula 11. A suitable leaving group X is known, for example, for the Heck type coupling reactions and is typically halogen, e. g. bromo or iodo.

In an olefinic palladium complex compound of formula Vil a, L is a neutral ligand having electron-donor properties. Suitable ligands are, for example, phosphine ligands of the ter- tiary phosphine type.

A suitable tertiary phosphine preferably contains 3 to 40, more preferably 3 to 18, carbon atoms and preferably conforms to formula: PR1 R2R3 (Vll I), wherein R', R2 and R3 are each independently of one another C,-C2oalkyl, C4-C, 2cycloalkyl, C2-C"heterocycloalkyl, C6-C, saryl, C7-C, saralkyl or C2-C,5heteroarylalkyl having the mean- ings cited above, which radicals may be substituted by substituents selected from the group consisting of C,-C6alkyl, C,-C6alkoxy, C,-C6haloalkyl, C6-C, saryl,-N02, S03, ammonium and halogen. R'and R2 together can be tetra-or pentamethylene which is unsubstituted or sub- stituted by C,-C6alkyl, C,-C6haloalkyl,-N02 or C-C6alkoxy which are condensed with 1 or 2 bivalent 1,2-phenylene radicals, R3 having the meaning cited above.

Also preferred are sterically exacting radicals R', R2 and R3, for example cyclic or branched, particularly preferably a, a-dibranched and, very particularly preferably a-branched, alkyl groups.

Particularly preferred are those compounds (Vlil), wherein R', R2 and R3 are methyl, ethyl, n-or i-propyl, n-, i-, s-or t-butyl, 1-, 2-or 3-pentyl, 1-, 2-, 3-or 4-hexyl, cyclopentyl, cyclo- hexyl, phenyl, naphthyl or benzyl, for example (i-C3H7) 3P, (C5H9) 3P and (C6H") 3P.

An anionic ligand is, for example, the hydride ion (H-) or a ligand which is derived, for exam- ple, from inorganic or organic acids by the splitting off of protons, e. g. a halide (F-, Cl-, ber and I-) or anions of oxygen acids or derivatives thereof, for example SnCI3~, SnCI5~, BF4-, B (aryl) 4', Pifs, SbF6-or AsF6.

Anions of oxygen acids are, for example, sulfate, phosphate, perchlorate, perbromate, per- iodate, antimonate, arsenate, nitrate, carbonate, the anion of a C,-C8carboxylic acid, for example formiate, acetate, propionate, butyrate, benzoate, phenylacetate, mono-, di-or trichloro-or-fluoroacetate, sulfonates, for example mesylate, ethanesulfonate, propanesul- fonate, n-butanesulfonate, trifluoromethanesulfonate (triflate); benzenesulfonate or p-to- luenesulfonate which are unsubstituted or substituted by C,-C4alkyl, C,-C4alkoxy or halogen, in particular by fluoro, chloro or bromo, for example benzenesulfonate, tosylate, p-methoxy- or p-ethoxybenzenesulfonate, pentafluorobenzenesulfonate or 2,4,6-triisopropylbenzene- sulfonate.

Particularly preferred anionic ligands are H-, F, Cl-, Br, BF4-, PFe", SnCI33, SbF6-, AsF6-, <BR> <BR> CF3SO3-, C6H5-S03-, 4-methyl-C6H5-S03, 3, 5-dimethyl-C6H5-SO3,2,4,6-trimethyl-C6H5-S03 and 4-CF3-C6H5-S03-and also cyclopentadienyl (Cp'). Cl', B, or I-are particularly pre- ferred.

Suitable substituents D remain unchanged under the conditions of the coupling reactions.

Any substituents may be chosen. Suitable substituents D are selected from the group con- sisting of Ri, Rz, R3, R4 and R5. Index p is preferably 1 and 2. Suitable substituents are typi- cally selected from the group consisting of hydroxy, halogen, e. g. chloro, carboxy and esteri- fied carboxy, e. g. methoxy-or ethoxycarbonyl, or are saturated or unsaturated aliphatic, cycloaliphatic or heterocycloaliphatic radicals, carbocyclic or heterocyclic aryl radicals, con- densed carbocylic, heterocyclic or carbocyclic-heterocyclic radicals or suitable combinations of these radicals, which may in turn be substituted by one or more than one substituent from the group consisting of hydroxy, halogen, oxo, esterified carboxy, e. g. ethoxy-or methoxy- carbonyl, and acyl, e. g. acetyl.

Suitable olefinic palladium complex compounds (Vil a) containing substituents at the allyl group are represented by the following structural formulae: wherein X and L have the cited meanings and are preferably tricyclohexylphosphine or tri- isopropylcyclophosphine and halogen, typically chloro, bromo or iodo.

The substituents of the allyl group can also be combined to polynuclear bridged complexes in the sense of the following structure: Preferred olefinic palladium complex compounds (Vil a) are those containing no substituents at the allyl group which is bound to palladium (index p is 0), L is the tricyclohexylphospine or triisopropylcyclophosphine group and X is halogen, typically chloro, bromo or iodo.

In an olefinic ionic palladium complex compound of formula VII b, D and p have the mean- ings cited above for compounds of formula Vil a. The index p is preferably 0. The meanings of the anionic ligands of Z, and Z2 correspond to the meaning of Z. Z, and Z2 are preferably halogen, typically chloro, bromo or iodo. The non-coordinating cation K+ is voluminous and corresponds in size to the palladium complex anion which carries a negative charge be- cause of the presence of the second anionic ligand Z2. A preferred non-coordinating cation K+ is, for example, the tetraphenylphosphonium cation.

The reaction conditions for the coupling reactions are described in the literature and corre- spond to the reaction conditions known for the so-called Suzuki coupling and Heck coupling reactions.

The process of this invention is preferably carried out such that the reactants can be reacted with each other in any order. Preferably, the phenyl derivatives with the leaving groups X, i. e. compounds of formula III a or III b, or compounds V, are placed first in a vessel and then the arylboronic acid derivatives of formula IV a or IV b or the olefin compound (VI) are added.

In the sense of a cross-coupling, the phenyl rings D and E can be combined to the combina- tion D with E by using the starting materials III a and IV a, to the combination D with D by using the starting materials III a and IV b to the combination E with E by using the starting materials III b and IV a, and to the combination E with D by using the starting materials III b and IV b.

The term catalytic amounts preferably means amounts of about 0.0001-5.0 mol%, more preferably of 0.001-1.0 mol%, based on the amount of the substrate used.

The molar ratio of the reactants of the coupling reactions of the compounds of formula III a or III b to the arylboronic acid derivatives of formula IV a or IV b, or of the compounds (V) to the olefin compound (VI), is usually in the range from 1: 1 to 1: 10, the preferred ratio being in the range from 1: 1 to 1: 2. The reaction is carried out at temperatures up to the boiling tem- perature of the solvent, preferably at room temperature up to the boiling temperature of the solvent (reflux conditions). Suitable solvents are customary, preferably higher-boiling, sol- vents, for example non-polar aprotic solvents, e. g. xylene or toluene, or polar aprotic sol- vents, e. g. dimethylformamide. The obtainable reaction product (I) or (II) is worked up and isolated in a manner known per se by conventional purification processes, for example after removal of the solvent and subsequent separation processes, such as precision distillation, recrystallisation, preparative thin-layer chromatography, column chromatography, prepara- tive gas chromatography and the like.

A particular embodiment of the process comprises a) subjecting a phenyl derivative (111) for the preparation of the biphenyls (1) to a coupling reaction with an arylboronic acid derivative (IV); or b) subjecting a phenyl derivative (V) for the preparation of the aromatic olefin (II) to a coup- ling reaction with an olefin (VI), each in the presence of an olefinic palladium complex compound (Vil a), wherein L is a neutral ligand having electron-donor properties, Z is halogen and p is 0, or in the presence of an olefinic ionic palladium complex compound (Vil b), wherein Z, and Z2 are halogen, K' is the tetraphenylphosphonium cation and p is 0 and, after carrying out the process variants a) or b), isolating the biphenyls (I) or the condensed aromatic olefin (II).

In a particularly preferred process variant, each of the coupling reactions are carried out in the presence of an olefinic palladium complex compound (Vil a), wherein L is triisopropyl- phosphine or tricyclohexylphosphine, Z is halogen, typically chloro, bromo or iodo, and p is 0.

This invention also relates to olefinic palladium complex compounds of formula wherein L is a neutral ligand having electron-donor properties, I is iodine and D is substi- tuents, and p is an integer from 0 to 5 and defines the number of the substituents at the allyl group.

A particularly preferred subject matter of this invention are palladium complex compounds of formula wherein i-Pr is isopropyl, Hal is chloro or bromo and D is substituents, and p is an integer from 0 to 5 and defines the number of substituents at the allyl group, and also olefinic com- plex compounds of formula wherein Cy is cyclohexyl, Cl is chloro and D is substituents, and p is an integer from 0 to 5 and defines the number of substituents at the allyl group.

A particularly preferred subject matter of this invention are the compounds of formulae The preparation of such olefinic palladium complex compounds, which are a subject matter of this invention, and of the known palladium complex compounds is carried out in a manner known per se by reacting a known dimeric allyt-halo-palladium complex with a compound introducing the ligand L, for example with triisopropyl-or tricyclohexylphosphine: This reaction can be carried out in analogy to the method according to B. Akermark et al., Organometallics 1987,6,620-628 or Y. Hayashi et al. J. Chem. Soc. Dalton Trans. 1989, 1519.

This invention also relates to the process for the preparation of the novel olefinic palladium complex compounds (Vil a).

The preparation of the dimeric allyl-halo-palladium complexes is known and is described, inter alia, in Y. Tatsuno et al., Inorg. Synth. 1979, 14 220 ; Y. lnoue et al. Synthesis, 1984,3, 244; B. M. Trost et aL J. Amer. Chem. Soc. 1980,102,3572.

Olefinic ionic palladium complex compounds of formula VII b are known. Their preparation is described in R. J. Goodfellow et al., J. Chem. Soc. (A), 1966,784.

The use of olefinic palladium complex compounds of formula VII a and of the olefinic ionic palladium complex compounds of formula Vil b for the catalysis of coupling reactions of aromatic compounds with each other and of aromatic compounds with olefins is, in principe, novel and inventive. Accordingly, the use according to this invention relates both to known and to novel compounds which are covered by formulae Vil a and Vil b.

In another of its aspects, this invention relates to the use of an olefinic palladium complex compound of formula wherein L is a neutral ligand having electron-donor properties, Z is an anionic ligand and D is substituents, and p is an integer from 0 to 5 and defines the number of substituents at the allyl group, and to the use of an olefinic ionic palladium complex compound of formula wherein Z, and Z2 are anionic ligands, K+ is a complex-stabilising cation and D is substi- tuents, and p is an integer from 0 to 5 and defines the number of substituents at the allyl group, for the catalytic preparation of biphenyls or olefinic aromatic compounds by coupling reactions.

A preferred subject matter of this invention is the use of olefinic palladium complex com- pounds of formula VII a and of the olefinic ionic palladium complex compounds of formu- la VII b for the catalysis of coupling reactions in the sense of the Suzuki coupling of aromatic compounds and of the Heck coupling of aromatic compounds with olefins.

The following Examples illustrate the invention: Examples A Suzuki coupling Table 1 illustrates syntheses according to the method of the Suzuki coupling (method X1: coupling of aryl bromides; method X2: coupling of aryl chlorides) of aromatic halides with arylboronic acids.

Table 1: Suzuki coupling of aromatic halides with arylboronic acids No. Halide A Boronic acid B Product C Catalyst K Method Time Yield Ippm][h] [%] \/\ 5 (K1-K14) X1 1 >99 00 HO yo- 1'AtOH A1 pH Ci B1 2 Br 5 (KI-K14) xi 1 87 Ha, u B CI A1 OH B2 C2 CI 3Br ci 0 10 (Kl-K14) xi 1. 6 >99 n") r jj\>- \S- XSCt 0 3 (Kl-K14) Xl 12 96 HO, A1 OH B3 C3 4 Br F 0 30 (Kl-Kl 4) Xl 2 >99 °9,9 HOvBw \J \=/3 (K1-K14) X1 2 60 HO, A1 OH C4 B4 e I No. Halide A Boronic acid B Product C Catalyst K Method Time Yield [Ppm] [h] [%] B CI CI CI 100 (K1-K14) X1 16 66 °tWHOv, B1 <3cl A1 OH g5 C5 B5C5 I:,, Br 1 0 30 (Kl-K14) Xl 7 90 0 HO )) foc Al 6H B6 C6 7(K1-K14)'97 Hui B OYE A1 OH s7 c7 OMe 8Br OMe 0 5 (Kl-K14) xi 1 >99 orme 0 HO, v B A1 OH B8 C8 9Br SMe 0 100 (Kl-Kl 4) Xl 16 82 se B'fla v B A1 OH B9 C9 [I I I I I I I I No. Halide A Boronic acid B Product C Catalyst K Method Time Yield [ppm] [h] [%] 10(K1-K14)'X1'1'94 0 HOBW 5 (Kl-Kl 4) xi 4 53 U OH O I B10 C10 Br<Br OX 100 (K1-K14) X1 1 96 0 » HOsBU \=/\=/% 30 (K1-K14) X1 4 53 u B A1 OH C11 B11 12MeO>Br MeO 30 (K1-K14) X1 1 99 HO A2 OU A2OU B1C12 13 MeO Br MeO 30 (K1-K14) X1 1 93 HO. W I/ B CI A2 oh B2C13 cri I I I I I I No. Halide A Boronic acid B Product C Catalyst K Method Time Yield lPPm] [h] 1%] 14 MeOs Br ~ MeO 30 (K1-K14) X1 1 89 HO. OH B3 C14 A2OH 15MeO + Br ~ MeO 30 (K1-K14) X1 2. 5 91 A2OH BOA B4C15 16MeOBrMeO100 (K1-K14) XI'16'96 HO B A26H B6 C16 17MeO Br MeO 97 (/HO. w/ HO a A2 OH B7 C17 OMe 18 MeOs Br ~ OMe MeO 30 (K1-K14) X1 3 70 Ho. w/\ ! \ A2 OH B8 C18 I i e i No. Halide A Boronic acid B Product C Catalyst K Method Time Yield [ppm] [h] [%] 19 MeO Br 30 (K1-K14) X1 4 81 HO.1! 0 HO B A2OH C19 B10 20MeO Br MeO 1000 X1 1 90 < HOB v < (K1-K14) HA, A2 OH C20 B11 C20 , CI 100 (K1-K14) X1 1 97 |j >Br | HOB4 | < >Cl}HO, B3 ksl ci Oh 0'H B3 A3 C21 22Br 30 (K1-K14) X1 4 88 C NO2 HOvB U NO 100 (K1-K14) X1 2 >99 / NO 2 I A4OH B1 C22 A4 No. Halide A Boronic acid B Product C Catalyst K Method Time Yield Ippm] [h] [%] 23C)/-\/-100 (K1-K11)'X2'99 HO YC-Q ce A5 OH gy 24 Me0 C, Me0 1000 (K1-K11) X2 3 94 " ; r- B A6 OH s1 C12 5000 X1 18 84 (isolated) 25 r , Br H I 1 (K1-K6) Br B'O 01 H BI -N N O A7 O C23 No. Halide A Boronic acid B Product C Catalyst K Method Time Yield Ippm] (h] [%] 26C,, CI, OMe OMe 500 000 X2 3 82 (isolated) HO,(Kl-K6) "B OMe N N 0'H N ou OH B7 N N OH OU C24 All aryl halides A used, with the exception of A6 and A7, and boronic acids B are commer- cially available (for example from Acros, Aldrich, Alfa, Avocado, Fluka, Lancaster or Riedel- de Haen) and can be used without prior purification. The solvents xylene (isomeric mixture, Fluka) and dimethoxyethane (Fluka) are to be dried before use by letting them stand over molecular sieve 4A. K2CO3 and Cs2CO3 are used in dry form, supplie by Fluka. The analyti- cal data of the products C either correspond to the data described in the literature or are provided in: C1 (J. Chem. Soc. Perkin Trans.

C2 (Tetrahedron, 1994,50,8301).

C3 (J. Org. Chem., 1980,45,441).

C4 (Mol. Cryst. Liq. Cryst., 1991,200,109).

C5 (Med. Promst. SSR, 1965, 17, 13; Chem. Abstr. 1963, 59, 12693, Chem. Abstr. 1972, 77,19386).

C6 (Mol. Cryst. Liq. Cryst., 1991,200,109).

C7 (J. Am. Chem. Soc., 1954,76,2357 ; ibid 1954,76,2361; Tetrahedron, 1994,50,8301).

C8 (Tetrahedron, 1985, 41, 5619 ; Mol. Cryst. Liq. Cryst., 1991,200,109 ; J. Org. Chem., 1993,58,5434).

C9 (J. Med. Chem., 1983,26,1196) C10 analytical data: (purity >99% GC); molecular mass C, 8H, 4O: 246.31; calcd. C: 87.78%, H: 5.73%; found C: 87.52%, H: 5.80%.

This compound has already been described, but without indication of analytical data: (Tetrahedron Lett., 1993,34,4019 ; Russ. J. Org. Chem., 1994,30,827).

C11 analytical data: (purity >99% GC); molecular mass C16Hl4O : 222.29; calcd. C: 86.45%, H: 6.35%; found C: 86.31%, H: 6.19%.

C12 (see Example 1.1).

C13 analytical data: (purity >99% GC); molecular mass C, 3H"OCI: 218.68; calcd. C: 71.40%, H: 5.07%; found C: 71.58%, H: 5.05%.

C14 (Bull. Chem. Soc. Jpn., 1963,980; ibid, 1963, 982 ; Biomed. Mass Spectrom., 1977, 310; Can. J. Chem., 1982,60,990).

C15 (Z. Naturforsch. B Anorg. Chem. Org. Chem., 1983,38,226; J. Org. Chem., 1989,54, 4844; Spectrochim. Acta Part A, 1981,37,689).

C16 (Tetrahedron, 1994,50,8301).

C17 (Tetrahedron, 1970,26,4041 ; Phosphorous, SulfurSilicon Relat. Elem., 1994,92,231; Magn. Reson. Chem., 1986,24,81).

C18 (Helv. Chim. Acta, 1988,71,1199).

C19 (J. Chem. Soc. Perkin Trans 1,1973,1451 ; ibid, 1973, 1454).

C20 analytical data: (purity >99% GC); molecular mass C15H, 4O : 246.31; calcd. C: 85.68%, H: found C: 85.74%, H: 6.59%.

C21 (Chem. Ber., 7978,111, 1323; J. Org. Chem., 1984,9,1594).

C22 (Tetrahedron Lett., 1995,36,6567 ; Bull. Chem. Soc. Jpn., 1995,68,1701).

C23 (see Example 2).

C24 (see Example 3).

Example 1 (example of method X1): 1.1 Suzuki coupling of an aryl bromide with a phenylboronic acid using the catalysts K1-K14 (see Table 1, No. 12, method X1): 30 ppm (0.0018 mmol) each of the catalysts K1 to K14 (1.2), 16.3 g of K2CO3 (117.6 mmol) and 10.8 g of phenylboronic acid B1 (88.3 mmol) are added to a solution of 11.0 g of 3-bromoanisol A2 (58.8 xi) in 110 ml of xylene. The reaction mixture is refluxed for 60 minutes. GC analysis (reaction: 100%, yield: 3-methoxybiphenyl C12 >99%). The mixture is worked up in water and the solvent is evaporated. 3-Methoxybiphenyl C12 is isolated without any further purification (yield: >95%, purity: >99% GC).'H-NMR-identical with the described data (J. Chem. Soc. Perkin Trans. 1,1972,1304; ibid. 1306). Molecular mass C13HH"O : 183.23; calcd. C: 85.22%, H: 6.05%; found C: 85.31%, H: 6.08%.

1.2 Il-Halo-phosphine (n3-allyl) palladium (l l) catalysts used.

1.2.1 K 1:-Chloro (tricyclohexylphosphine) (n3-allyl) palladium (ll). The preparation is described in G. M. Direnzo et al. J. Am. Chem. Soc. 1996,118,6225, or H. Lehmkuhl and V. Dimitrov J. Organomet. Chem. 1996, 519, 83).

1.2.2.1 K 2: u-Chioro (triisopropylphosphine) (3-allyl) palladium (II). 23.2 g (63.37 mmol) of di-, u- chloro (n3-2-allyl) dipalladium(II) are dissolve in 500 ml of dry THF at room temperature under argon. 27 ml (140 mmol) of triisopropylphosphine are slowly added to the stirred yellow solution and the resulting lemon yellow solution is then stirred for 3 hours at room temperature. The solution is filtered and concentrated to a volume of about 50 ml. After adding 300 mi of dry hexane, the product precipitates as a yellow solid. The precipitate is collected by filtration and dried in vacuo, giving a yellow powder; yield: 41.8 g (96%).

Molecular mass C12H26PPdCI; 343.17; calcd. C: 42.00%, H: 7.64%, P: 8.97%, Pd: found C: 41.88%; H: 7.68%, P: 8.85%, Pd: 31.29%; 3'P-NMR (101 MHz, CDC13): 8 = 53.36 (s).

1.2.2.2 The preparation of the dimeric di-g-chloro (n3-2-allyl) dipalladium(II) is carried out in accordance with Y. Tatsuno etal., Inorg. Synth. 1979, 14,220.

1.2.3 K 3: ,-Bromo (tricyclohexylphosphine) (3-allyl) palladium (II). The preparation is described in T. Yamamoto et al. Organometallics, 1986,5,1559.

1.2.4.1 K 4: A-Bromo (triisopropylphosphine) (n3-allyl) palladium (II). In analogy to the preparation of K 2 (1.2.2.1), 28.82 g (63.37 mmol) of di-, u-bromo (n3-2-allyl) dipalladium (ll) are reacted with 26.7 ml (140 mmol) of triisopropylphosphine. The precipitate is collected by filtration and dried in vacuo, giving a yellow powder; yield: 40.29 g (82%).

Molecular mass C12H26PPdBr: 387.64; calcd. C: 37.18%, H: 6.76%, P: 7.99%, Pd: 27.45%; found C: 37.25%, H: 6.74%, P: Pd: 27.47%; 31P-NMR (101 MHz, CDCb): 8 = 52.87 (s).

1.2.4.2 The preparation of the dimeric di-R-bromo (n3-2-allyl) dipalladium (ll) is carried out in accordance with Y. lnoue et al. Synthesis, 1984,3,244.

1.2.5.1 K 5: Il-iodo (tricyclohexylphosphine) (n3-allyl) palladium (ll). In analogy to the preparation of K 2 (1.2.2.1), 10.2 g (18.6 mmol) of di-ll-iodo (n3-2-allyl) dipalladium (il) are reacted with 11.5 g (40.9 mmol) of tricyclohexylphosphine. The precipitate is collected by filtration and dried in vacuo, giving a yellow powder; yield: 18.6 g (90%); molecular mass C2'H38PPdl: 554.83; calcd. C: 45.46%, H: 6.90%, P: 5.58%, Pd: 19.18%; found C: 45.53%, H: 6.01%, P: 5.45%; Pd: 19.21%; 31P-NMR (101 MHz, Ceci3): 8 = 40.52 (s).

1.2.5.2 The preparation of di-,-iodo (3-2-allyl) dipalladium (II) is carried out in accordance with Y. Inoue et al. loc. cit.

1.2.6 K 6: A-lodo (tri-isopropylphosphine) (n3-allyl) palladium (ll). In analogy to the preparation of K 2 (1.2.2.1), 15.7 g (28.6 mmol) of di-ll-iodo (n3-2-aliyl) dipalladium (il) are reacted with 12.0 ml (62.9 mmol) of triisopropylphosphine. The precipitate is collected by filtration and dried in vacuo, giving a yellow powder; yield: 17.9 g (72%); molecular mass C12H26PPdl: 434.64; calcd. C: 33.16%, H: 6.03%, P: 7.13%, Pd: 24.48%; found C: 33.15%, H: 6.00%, P: 7.18%, Pd: 24.44%; 31P-NMR (101 MHz, Ceci3); 8 = 52.90 (s).

1.2.7.1 K 7: F-Chloro (tricycloheXylphosphine) (n3-1-phenylpropenyl) palladium (ll). In analogy to the preparation of K 2 (1.2.2.1), 518 mg (1.0 mmol) of di-R-chloro (n3-1-phenylpropenyl) di- palladium (II) are reacted with 617 mg (2.2 mmol) of tricyclohexylphosphine. The precipi- tate is collected by filtration, dried in vacuo, dissolved in dichloromethane and filtered through silica gel. Evaporation of the solvent and drying of the solid in vacuo gives a yellow powder; yield: 734 mg (68%); molecular mass C27H42PPdl: 539.46; calcd. C: 60.12%, H: 7.85%, P: 5.74%, Pd: 19.72%; found C: 60.18%, H: 7.80%, P: 5.65%, Pd: 19.93; 3'P-NMR (101 MHz, CDCb); 8 = 46.05 (s).

1.2.7.2 The preparation of the dimeric di-p-chloro (n3-1-phenylpropenyl) dipalladium (ll) is carried out in accordance with A. Goliaszewski and J. Schwarz Tetrahedron 1985, 41,5779.

1.2.8 K 8: F-Chloro (tricyclohexylphosphine) (3-3-methylbutenyl) palladium (lI). The preparation is described in B. dkermark et al. Organometallics 1987,6,620.

1.2.9.1 K 9 :, u-Chloro (tricyclohexylphosphine) 1 0_113-2-m ethyl e nebicyclo- [3. 1. 1 heptyl) palladium (ll). In analogy to the preparation of K 2 (1.2.2.1), 3.31 g (5.97mmol) of di- tl-chloro (6, 6-dimethyl-2,3,10-#³-2-methylenebicyclo-[3.1.1]heptyl)dipal ladium(II) are reac- ted with 3.68 g (13.13 mmol) of tricyclohexylphosphine, giving an orange, elastic mass; yield: 5.86 g (88%); molecular mass C28H48PPdCl: 557.52; calcd. C: 60.32%, H: 8.68%, P: 5.56%, Pd: 19.09%; found C: 59.99%, H: 8.61%, P: 5.35%, Pd: 19.25%; 3'P-NMR (101 MHz, CDC13); 8 = 25.71 (s).

1.2.9.2 The preparation of the dimeric di-g-chloro 10-r3-2-methylenebicyclo- [3.1.1.] heptyl) dipalladium (II) is carried out in accordance with B. M. Trost et al. J. Amer.

Chem. Soc. 1980,102,3572; ibid. 1978,100,3407.

1.2.10.1 K 10: A-Chloro (tricycloheXylphosphine) (n3-2-chloropropenyl) palladium (ll). In analogy to the preparation of K 2 (1.2.2.1), 8.73 g (20.1 mmol) of di-w-chloro (3-2-chloropropenyl) di- palladium (II) are reacted with 12.39 g (44.2 mmol) of tricyclohexylphosphine. The preci- pitate is collected by filtration and dried in vacuo, giving an orange powder; yield: 17.4 g (87%); molecular mass C2, H37PPdC12: 497.80; calcd. C: 50.67%, H: 7.49%, P: 6.22%, Pd: 21.37%; found C: 50.70%, H: 7.45%, P: 6.14%, Pd: 21.46%; 31P-NMR (101 mHz, CDC13); 8 = 59.13 (s).

1.2.10.2 The preparation of the dimeric di-.-chloro (i3-2-chloropropenyl) dipalladium (II) is carried out in accordance with J.-E. Backvall et al. Organometallics 1997,16,1058.

1.2.11 K 11: g-Trichlorotin (tricyclohexylphosphine) (3-allyl) palladium (II). The preparation is carried out as described in M. Gianotti et al. Inorg. Chimica Acta : g-Chloro (tricyclohexylphosphine) (T, 3-allyl) palladium (II) (324 mg, 0.7 mmol) is dissolve in dry dichloromethane (20 ml) under argon. Tin (II) chloride is added to the stirred yellow solution. The resulting suspension is stirred for another 2 hours at room temperature.

After evaporating the solvent, a faintly yellow powder is obtained, yield: 330 mg (72%).

Molecular mass C2, H38PPdSnCI3: 653.00; calcd. C: 38.63%, H: 5.87%, P: 4.74%, Pd: 16.29%; found C: 38.55%, H: 5.88%, P: 4.61%, Pd: 15.98%; 3'P-NMR (101 mHz, Ceci3); 8 = 41.14 (s).

K12: Dichloro (n3-allyl) (tetraphenylphosphonium) palladate The preparation is described in R. J. Goodfellow et al., J. Chem. Soc. (A), 1966,784.

K13: Dibromo (n3-allyl) (tetraphenylphosphonium) palladate The preparation is described in R. J. Goodfellow et al., J. Chem. Soc. (A), 1966,784.

K14: Diiodo (n3-allyl) (tetraphenyiphosphonium) pailadate The preparation is carried out in analogy to R. J. Goodfellow et al., J. Chem. Soc. (A), 1966,784: 20 ml of H20 are added under argon to 595 mg (1.08 mmol) of di-, u-iodo (n3-2-allyl) di- palladium (ll) and 720 mg (4.34 mmol) of potassium iodide. The stirred suspension is heated for 30 minutes to 60°C. 1.04 g (2.22 mmol) of tetraphenylphosphonium iodide are added to the resulting orange solution which is then cooled to room temperature. The mixture is extracted with dichloromethane (3x10 ml) and the combined extracts are dried with magnesium sulfate. Filtration and removal of the solvent by distillation gives an orange powder, yield: 1.58 g (99%).

Molecular mass C27H25PPdl2: 740.70; calcd. C: 43.78%, H: 3.40%, P: 4.18%, Pd: 14.37%; found C: 43.97%, H: 3.50%, P: 4.31%, Pd: 13.98%; 3'P-NMR (101 mHz, CDCI3); 8 = 23.73 (t).

Example 2 (example of method X11: Synthesis of a photoinitiator by Suzuki coupling using the catalysts K 1-K 6 (see Table 1, No. 24): A solution of 3.18 g (8.83 mmol) of 2-benzyl-1- (4-bromophenyl)-2-dimethylaminobutan-1-one A7 in 300 ml of dimethoxyethane is charged with 0.044 mmol each of the catalysts K 1-K 6 (1.2), 1.0 ml of a 2N aqueous Cs2CO3solution and 1.51 g (12.36 mmol) of phenylboronic acid B1. This reaction mixture is heated for 18 hours under reflux conditions. GC analysis (reac- tion: 100%, yield: 2-benzyl-1-biphenyl-4-yl-2-dimethyiaminobutan-1-one C23 : 85%). The mix- ture is worked up in water and filtered through silica gel; yield: 84%; molecular mass C25H27NO: 357.50; calcd. C: 83.99%, H: 7.61%, N: 3.92%; found C: 84.05%; H: 7.60%, N:3.81%.

Example 3 (example of method X2): Suzuki coupling of an aryl chloride with a phenylboronic acid using the catalysts K1-K11 (see Table 1, No. 24, method X2): A solution of 8.34 g of 3-chloroanisol A6 (58.8 mmol) in 110 ml of xylene is charged with 1000 ppm (0.059 mmol) each of the catalysts K1 to K11 (1.2), 16.3 g of K2CO3 (117.6 mmol) and 10.8 g of phenylboronic acid B1 (88.3 mmol). The reaction mixture is refluxed for 60 mi- nutes. GC analysis (reaction 95%, yield 3-methoxybiphenyl C12 >94%). The mixture is worked up in water and the solvent is evaporated. 3-Methoxybiphenyl C12 (yield: >95%, purity: >99% GC) is isolated without any further purification. 'H-NMR-identical with the de- scribed data (J. Chem. Soc. Perkin Trans. 1,1972,1304; ibid. 1306). Molecular mass C'3H11O: 183.23; calcd. C: 85.22%, H: 6.05%; found C: 85.31%, H: 6.08%.

Example 4 (additional example of method X2): Synthesis of a UV absorber by Suzuki coupling, using the catalysts K 1-K 6 (see Table 1, No. 25): A solution of 220 mg (0.44 mmol) of 2- (4, 6-bis-4-chlorophenyl)- [1,3,5] triazin-2-yl-5-hexyloxy- phenol A7 in 20 mi of dimethoxyethane is charged with 0.0025 mmol each of the catalysts K 1-K 6 (1.2), 0.5 ml of a 2N aqueous Cs2CO3solution and 213 mg (1.4 mmol) of methoxy- phenylboronic acid B7, and the reaction mixture is heated for 3 hours under reflux condi- tions. DC analysis (reaction >95%). The mixture is worked up in water and filtered through silica gel; yield 2- [4, 6-bis- (3'-methoxybiphenyl-4-yl)- [1,3,5] triazin-2-yl]-5-hexytoxyphenol C24: 82%; molecular mass C4iH39N30: 637.79; calcd. C: 77.21%, H: 6.16%, N: 2.20%; found C: 77.15%, H: 6.09%, N: 2.15%.

B Heck couplina<BR> Table 2 illustrates syntheses according to the Heck coupling method<BR> Table 2: Heck coupling of aromatic halides with olefins No. Halide A Olefin D Product C Catalyst K Method Time meia [ppm] [h] [% j 1O-5 (K1-K11) Y 1. 5 >99 où C 5 Al C25 y ^/O O-366000 Y 6 55 oJU-"J-\/" (K1-K11) 0 OBu A5 ! A5C25 0 3 MeO, Br 10000 y 24 90 OBu Me0 OBu (K1-Ki 1) D1 O C26 4 Br OH 10 000 Y 80 (isolated) (Kl-Kl 1) A1 p2 OH C27 p All aryl halides A and olefins D used are commercially available (for example from Acros, Aldrich, Alfa, Avocado, Fluka, Lancaster or Riedel-de Haen) and can be used without any prior purification. The solvent dimethylformamide (Fluka) is to be dried before use by letting it stand over molecular sieve 4A. NaOAc can be obtained and used in dry form from Fluka.

The analytical data of the products C either correspond to the data described in the litera- ture or are provided in: C25 (see Example 4).

C26 (J. Chem. Soc. Perkin Trans. 1,1990,2207).

C27 analytical data: (purity >99% GC); molecular mass C17H, 60: 252.31; calcd. C: 80.93%, H: 6.39%; found C: 80.81%, H: 6.41%.

Example 5 (example of method Y): Heck coupling of aryl bromide with acrylate using the catalysts K 1-K 11: 20.4 g (110 mmol) of 4-bromobenzaldehyde A1,19.7 g (154 mmol) of n-butylacrylate D1, 10 mg (0.05 mmol) of 2,6-di-tert-butylphenol and 9.9 g (120 mmot) of sodium acetate are mixed with 200 ml of dimethylacetamide and, after adding 5 ppm each of the catalysts K 1- K 11 (1.2), are stirred for 90 minutes at 190°C in an oil bath. The mixture is worked up in water and extracted with ether. The organic phases are washed several times with water and are filtered through silica gel. The solvent is evaporated, giving 4-formylcinnamic acid-n- butyl ester C25 (purity >99% GC) without any purification in a yield of >95%. Analytical data identical with the described data (J. Organomet. Chem, 1995,491,1-2, C1; Angew. Chem., 1995,107,1989). Molecular mass C, 4H, 603: 232.28; calcd. C: 72.39%, H: 6.94%; found C: 72.46%, H: 7.00%.