Biphenyls and aromatic olefins can be used in a wide variety of ways, as chemical special- ties in the preparation of liquid crystals, as photoinitiators, UV-absorbers, optical brighteners, ligands for catalysts and as starting materials in the preparation of intermediates for agro- chemicals and pharmaceutical products.

A method frequently used for the synthesis of biphenyls is palladium-catalysed cross- coupling (so-called Suzuki coupling), in which iodinated or brominated aromatic compounds or arylsulfonates are reacted with arylboron derivatives in the presence of palladium cata- lysts. This methodology is described, for example, in N. Miyaura et al., Synthetic Communi- cations, 11 (1981), 513; A. Suzuki in Metal-catalyzed Cross-coupling Reactions, Chapter 2, Wiley-VCH, Weinheim 1998, in U. S. Patent Specification and in EP-A-470 795.

A method frequently used for the synthesis of aromatic olefins is the palladium-catalysed coupling reaction, the so-called Heck reaction, in which iodinated or brominated aromatic compounds are reacted with olefins in the presence of palladium catalysts. This methodolo- gy is described, for example, 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. Brise and A. De Meijere in Metal-catalyzed Cross-coupling Reactions, Chapter 3, Wiley-VCH, DE-Weinheim 1998.

Despite their valable broad applicability in synthesis, those methods have disadvantages.

For example, unless one is willing to use amounts of catalyst of more than 1 mol %, only small amounts of product can be prepared on a laboratory scale using the coupling reactions mentioned. In the Suzuki reaction, when using the customary palladium catalysts, e. g.

Pd (PPh3) 4, Pd (OAc) 2 and triphenylphosphine, undesired secondary reactions are observed as a result of aryl transfer from the catalyst to the substrate; D. F. O'Keefe et al. Tetrahedron Lett., 1992,6679. The recovery of the palladium catalyst in the coupling reactions men- tioned is complicated, in that, in order to separate off the palladium residue from the reaction mixture, it is first necessary to convert it into a palladium salt, e. g. palladium chloride or pal- ladium acetate.

The problem underlying the present invention is to find catalysts suitable for coupling reacti- ons of the Suzuki cross-coupling type for biphenyls and for coupling reactions of the Heck coupling type for aromatic olefins, which catalysts may be expected to have improved "turnover numbers" (mol product/mol catalyst) and improved reactivity and selectivity compa- red with the catalysts used in such coupling reactions.

The problem is solved by the present invention, which relates to a process for the preparati- on of biphenyls and aromatic olefins using olefinic palladium complex compounds.

The present invention relates to a process for the preparation of biphenyls of formula wherein A and B are substituents; m and n are integers from zero to five and define the number of substituents on the phenyl radicals D and E; or aromatic olefins of formula wherein C denotes (a) substituent (s), o is an integer from zero to five and defines the num- ber of substituents on the phenyl radical F, and R6, R7 and Re are hydrogen or substituents, in which process a) for the preparation of biphenyls of formula (1) a phenyl derivative of formula wherein A, B, m and n are as defined for formula (1) and X is a leaving group, is subjected to a coupling reaction with an arylboronic acid derivative of formula wherein A, B, m and n are as defined for formula (1) and Y is the group-B (OH) 2 or a mono-or di-ester derivative of-B (OH) 2; and b) for the preparation of aromatic olefins of formula (2) a phenyl derivative of formula wherein C and o are as defined for formula (2) and X is a leaving group, is subjected to a coupling reaction with an olefin of formula wherein R6, R7 and R8 are as defined for formula (2), in each case in the presence of a catalytically effective amount of an olefinic palladium complex compound of formula P-(tert-butyl) 3 (7a) <-Pd \z wherein Z is an anionic ligand selected from the group consisting of Cl, Br~ and 1 ions; and, after either process variant a) or b) has been carried out, the biphenyl of formula (I) or the con- densed aromatic olefin of formula (2) is isolated.

The catalysts used in the process are readily accessible by simple synthesis, for example according to the method of B. Akermark et aL, Organometallics 1987,6,620-628, and exhi- bit substantially improved reactivity and selectivity. The catalysts used in the process are further distinguished by a high degree of stability. Active palladium catalysts having a tert- butyl ligand are normally unstable and have to be generated in situ (G. C. Fu et al Angew.

Chem. J. Org. Chem. 1999,64,10), or have to be synthesised by compli- cated multi-step synthesis (S. L. Buchwald et al J. Am. Chem. Soc. 1998,120,9722).

After the reaction is complete, the dissolved olefinic palladium complex compounds can be decomposed with atmospheric oxygen to form palladium black. This residue can be used again directly for catalyst synthesis without first having to be converted into a palladium salt, e. g. palladium chloride or palladium acetate, according to the method of Y. Inoue et al. Syn- thesis 1984,3,244.

The terms and expressions used in the description of the invention preferably have the follo- wingmeanings: Biphenyls of formula (1) are substituted on the phenyl ring D preferably by from one to five substituents from the group A, which consists of the substituents R, R2, R3, R4 and R5, and are also substituted on the phenyl ring E preferably by from one to five substituents from the group B, which consists of the substituents from the group R6, R7, R8, Rg and R, o.

Suitable substituents are listed in the List of Radical Names according to IUPAC Rules and remain unchanged under the conditions of the coupling reactions. The substituents may be selected as desired.

Suitable substituents A from the group Ri, Rs, Ra, R4 and R5 may be selected, for example, from the group of functional groups or derivatised functional groups consisting of amino, C,-C4alkylamino, di-C1-C4alkylamino, 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 he- terocyclic aryl radicals, or condensed carbocyclic, heterocyclic or carbocyclic-heterocyclic radicals, which may themselves be combined as desired with further such radicals and sub- stituted by the mentioned functional groups or derivatised functional groups.

The mentioned substituents and radicals may also be interrupted by one or more bivalent radicals from the group-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,-Caalkyl)-,-S (=0) 2-N (C1-C4alkyl)-,-(C,-C4alkyl) N-S (=O)-, -(C1-C4alkyl) N-S (=0) 2-, -P (=O)-,-P (=O)-O-,-O-P (=O)- and -O-P(=O)-O-, Two substituents from the group R1, R2, R3, R4 and R5 may also be bivalent, bridge-forming C2-C6alkylene, C4-C8alkyldiylidene or C4-Cealkenytdiylidene groups, preferably butanediylide- ne, especially 2-butenediylidene, which are joined to the phenyl ring D or to heteroaryl sub- stituents A, for example pyridyl, or are condensed to form an aromatic bicyclic system, which may also be substituted by the mentioned functional groups or substituents.

Suitable substituents B from the group R6, R7, R8, Rg and R, o are as defined for R, to R5 and may also be substituted by further substituents. RI, R2, R3, R4 and Rs and R6, R7, R8, Rg and Rlo are each defined independently of the others.

Suitable substituents A from the group Ri, R2, R3, R4 and R5 are especially functional groups from the group consisting of amino, C1-C4alkylamino, for example methyl-or ethyl-amino, di- C1-C4alkylamino, for example dimethyl-or diethyl-amino, hydroxy, oxo, thio,-NO2, carboxy and halogen, or are substituents from the group C,-C2oalkyl, C2-C20alkenyl, C2-C2o-alkynyl, C4-C12cycloalkenyl,C2-C12heterocycloalkyl,carbocyclicC3-C12c ycloalkyl,C7-C12bicycloalkyl, carbocyclicC7-C18aralkylandC2-C16heteroarylalkyl,whichmayC6- C16aryl,C2-C16heteroaryl, themselves be substituted by the mentioned functional groups and interrupted by the men- tioned bivalent radicals.

C,-C20Alkyl is, for example, methyl, ethyl, n-or iso-propyl or n-, sec-or tert-butyl or straight- chain or branched pentyl, hexyl, heptyl, octyl, isooctyl, nonyl, tert-nonyl, decyl, undecyl or dodecyl.

C2-CZOAlkenyl 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-C12Bicycloalkyl 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 hetero atoms 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 tri-cyclic, for example phenyl, naphthyl, indenyl, azulenyl or anthryl.

C2-C, 5Heteroaryl is preferably monocyclic or condensed with a further heterocycle or with an aryl radical, for example phenyl, and preferably contains one or two, and in the case of nitro- gen up to four, hetero atoms from the group O, S and N. Suitable substitu ents are derived from furan, thiophene, pyrrole, pyridine, bipyridine, picolylimine, y-pyran, y-thiopyran, phen- anthroline, pyrimidine, bipyrimidine, pyrazine, indole, coumarone, thionaphthene, carbazole, dibenzofuran, dibenzothiophene, pyrazole, imidazole, benzimidazole, oxazole, thiazole, dit- hiazole, isoxazole, isothiazole, quinoline, isoquinoline, acridine, chromene, phenazine, phenoxazine, phenothiazine, triazine, thianthrene, purine or tetrazole.

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

C2-C,5Heteroarylalkyl preferably consists of the mentioned heterocycles, which substitute, for example, C,-C4alkyl radicals, where possible in the terminal position, but also in the adjacent position (1-position) or in the a-position (2-position), depending upon the length of the car- bon chain.

In an aromatic olefin of formula (2), the index o preferably has the values from one to five.

The phenyl ring F is preferably substituted by from one to five substituents C from the group consisting of the substituents R 1, R2, R3, R4 and R5 as defined above under formula I for A and R, to R5. In the olefinic side chain, R6, R7 and R8 are hydrogen or substituents also as defined above under formula I for A and Ri to Rs. In the phenyl derivative of formula (3a) or (3b) used according to process variant a), X is a leaving group which is eliminated in the coupling reaction, the so-called cross-coupling ac- cording to Suzuki. That type of reaction is illustrated in the following reaction for the prepa- ration of a photoinitiator.

A suitable leaving group X, for example for coupling reactions of the Suzuki type, is known and is, for example, halogen, e. g. chlorine, bromine or iodine, or an organosulfonyl radical, for example mesyl, p-toluenesulfonyl or trifluoromethanesulfonate.

It has been found that when using catalysts of formula (7a) chlorine is suitable as leaving group. Coupling reactions of the Suzuki type otherwise occur with satisfactory yield and high TON only with higher halogens, for example bromine or iodine, as leaving group. The present process is a palladium-catalyst-mediated coupling, according to the Suzuki method, of a substituted aryl chloride deactivated by means of electron-rich or electron-repelling groups.

In a particular process variant, the substituents A (m = 1) or B (n = 1) in a phenyl derivative of formula (3a) or (3b) may also be a further leaving group X having the meanings me n- tioned. The phenyl derivative in question of formula (3a) or (3b) in that case contains two leaving groups X. Such a derivative can be coupled with two equivalents of arylboronic acid derivative of formula (4a) or (4b) so that in the process product obtainable in that manner a phenyl ring E is joined to two phenyl rings D. In an analogous manner, products are obtained in which a phenyl ring D is joined to two phenyl rings E.

In a further process variant, the substituents A and B in phenyl derivatives of formula (3a) or (3b) may also contain further leaving groups X. The phenyl derivative in question (3a, 3b) in that case contains two or more leaving groups X. Such a derivative can be coupled with ap- propriate equivalents of arylboronic acid derivative of formula (4a) or (4b) so that in the process product obtainable in that manner the phenyl rings D or E are addition coupled with further phenyl rings D or E at the substituents A or B. That process variant is illustrated by the following coupling reaction: wherein cat. (above the reaction arrow) denotes the use of the catalyst of formula (7a).

In the arylboronic acid derivatives of formulae (4a) and (4b) used according to process vari- ant a), Y is also a leaving group having the meanings-B (OH) 2 or a mono-or di-ester deriva- tive of-B (OH) 2. Mono-or di-ester derivatives of-B (OH) 2 are, for example, -B (O-C,-C4AIk) 2 or-BOH-C,-C4AIk, wherein C,-C4AIk is preferably methyl or ethyl, or -B (O-Ar) 2 or-BOH-Ar, wherein Ar is preferably aryl.

In the phenyl derivative of formula (5) used according to process variant b), the index o and the substitutents C are as defined for formula (2). A suitable leaving group X, for example for coupling reactions of the Heck type, is known and is, for example, halogen, e. g. bromine or iodine.

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

The process according to the invention is preferably so carried out that the reaction partners of the coupling reaction may be reacted with one another in any desired order. Preferably the phenyl derivatives having the leaving groups X, that is to say compounds of formula (3a) or (3b), or compounds of formula (5), are used as starting material and the arylboronic acid derivatives of formula (4a) or (4b), or the olefin compound of formula (6), are added thereto.

By a cross-coupling reaction, the phenyl rings D and E can be combined with one another using the starting materials of formulae (3a) and (4a) to form the combination D with E, using the starting materials of formulae (3a) and (4b) to form the combination D with D, using the starting materials of formulae (3b) and (4a) to form the combination E with E and using the starting materials of formulae (3b) and (4b) to form the combination E with D.

The expression"catalytic amounts"preferably denotes an amount of from approximately 0.0001 to 5.0 mol %, especially from 0.001 to 1.0 mol %, based on the amount of the substrate used.

The molar ratio of the reaction partners of the coupling reactions of compounds of formula (3a) or (3b) to the arylboronic acid derivative of formula (4a) or (4b), or of compounds of formula (5) to the olefin compound of formula (6), is generally in the range of from 1: 1 to 1: 10, a ratio in the range of from 1: 1 to 1: 2 being preferred. The reaction takes place with cooling up to the boiling temperature of the solvent, especially from room temperature to the boiling temperature of the solvent (reflux conditions). Suitable solvents are customary, espe- cially higher-boiling, solvents, for example non-polar aprotic solvents, e. g. xylene or toluene, or polar aprotic solvents, e. g. dimethylformamide. Working up and isolation of the obtainable reaction product of formula (1) or (2) are effected in a manner known per se using customary purification methods, for example removal of the solvent and subsequent separation me- thods, e. g. fine distillation, recrystallisation, preparative thin-layer chromatography, column chromatography, preparative gas chromatography, etc..

In a particular embodiment of the process a) for the preparation of biphenyls of formula (1) a phenyl derivative of formula (3) is sub- jected to a coupling reaction with an arylboronic acid derivative of formula (4); or b) for the preparation of aromatic olefins of formula (2) a phenyl derivative of formula (5) is subjected to a coupling reaction with an olefin of formula (6) in each case in the presence of an olefinic palladium complex compound (6a), and, after eit- her process variant a) or b) has been carried out, the biphenyl of formula (1) or the conden- sed aromatic olefin of formula (2) is isolated.

The invention relates also to olefinic palladium complex compounds of formula ,) P-(tert-butyl) 3 7a,) \\-Pd, \ Z wherein Z is an anionic ligand selected from the group consisting of Br and 1 ions.

In particular, the invention relates to compounds of formulae P- 3 P-(tert-butyl) 3 <-Pd and (7a"_Pd Br These olefinic palladium complex compounds, which are the subject matter of the invention, and the known palladium complex compounds are prepared in a manner known per se, by reacting a known dimeric allyl-halo-palladium complex with the compound tri-tert- butylphosphine which introduces the ligand L: Pd llx Pd _) > 2 L: P- (tert-butyl) 3CP- (tert-butyl) 3 -bd XI (7b) (7a) That reaction can be carried out analogously 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.

The present invention relates also to the process for the preparation of the novel olefinic palladium complex compounds of formula (7a).

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

The invention relates also to the use of an olefinic palladium complex compound of formula (7a)/P- (tert-bUtyl) 3 (7a) < <-Pd \ Z wherein Z is an anionic ligand selected from the group consisting of Cl, Br'and I'ions; in the catalytic preparation of biphenyls or olefinic aromatic compounds by means of cou- pling reactions.

Preferred subject matter of the invention is the use of olefinic palladium complex compounds of formula (7a) for the catalysis of coupling reactions by means of Suzuki coupling of arom a- tic compounds and Heck coupling of aromatic compounds with olefins.

The following Examples illustrate the invention: Examples A. synthesis Starting materials: The three dimeric starting materials di-µ-chloro(#3-2-allyl)dipalladium(II) (Y. Tatsuno et al. Inorg. Synth. 14,220 (1979), di-µ-bromo(#3-2-allyl)dipalladium(II) (Y. Inoue et al. Synthesis 3,244 (1984) and di-µ-iodo(#3-2-allyl)dipalladium(II) (Y. Inoue et al. Synthe- sis 3,244 (1984) are used according to B. Aakermark etal. Organometallics 6,620 (1987); Y. Hayashi etal. J. Chem. Soc. DaltonTrans 1519 (1989): Representative procedure: Example 1 (K1): µ-chloro(tri-tert-butylphosphino)(#-allyl)pappadium(II) Di-u-chloro (n2-allyl) dipalladium (ll) (500 mg, 1.37 mmol) is dissolve in dry THF (10 ml) at room temperature under argon. A solution of tri-tert-butylphosphine (553 mg, 2.73 mmol) in THF (5 ml) is added at room temperature to the stirred yellow mixture, and the resulting yel- low solution is then stirred for three hours at room temperature. The solution is filtered through silica gel and concentrated, yielding u-chloro (tri-tert-butylphosphino) (n-allyl)- palladium (lI) in the form of a yellow solid.

Yield: 970 mg Elemental analysis for C H32PPdCl: C H P Pd Calculated: 46.89 8.58 7.98 27.49 Found: 46.76 8.37 8.04 27.62 Example 2 (K2): u-bromo (tri-tert-butylphosphino)(#3-allyl)palladium(II) Yellow powder Yield: 95%.

Elemental anaysis for C15H32PPdBr: C H P Pd Calculated: 41.93 7.51 7.21 24.77 Found: 42.05 7.44 7.30 24.39 31PNMR (101 MHz, CDC13) # 84. 21 (s) Example 3 (K3): u-iodo (tri-tert-butylphosphino)(#3-allyl)palladium(II) Yellowish powder Yield: 89%.

Elemental C15H32PPdl:for C H P Pd Calculated: 37.79 6.77 6.50 22.32 Found: 37.93 6.55 6.33 22.19 3'PNMR (101 MHz, CDCI3) 8 65.10 (s) B. Suzuki couplinq Example 4: Aryl chloride + phenylboronic acid usinq catalysts K1-K3: "Cl Pt-Bu3 B (OH) 2 + CI 140°C, xylene, IC1C03 General procedure: µ-Halo(tri-tert-butylphosphino)(#3-allyl)palladium(II) (K1-K3) (e. g. K1 5.4 mg, 0.014 mmol, 0.1 mol %), K2CO3 (3.88 g, 28.05 mmol) and phenylboronic acid (2.57 g, 21.04 mmol) are added to a solution of 3-chloroanisole (2.0 g, 14.03 mmol) in xylene (isomeric mixture, 20 ml), and the reaction mixture is heated at reflux for 60 minutes.

GC analysis: conversion 100%, yield 3-methoxybiphenyl >99% The mixture is subjected to aqueous working up and the solvent is removed by evaporation.

3-Methoxybiphenyl (yield >95%, purity >99% GC) is isolated without purification.

'HNMR identical to the data described (J. Chem. Soc. Perkin Trans. 1,1304 (1972); ibid 1306.

Elemental C13H11O:for C H Calculated: 85.22 6.05 Found: 85.31 6.08 Examples 5 to 30 Table 1 illustrates syntheses according to the methodology of Suzuki coupling (method X1: coupling of aryl bromides; method X2: coupling of aryl chlorides) of aromatic halides with arylboronic acids.

Table 1 Exam-Halide A Boronic acid Product C Catalvst Meth. Time Yield % D) e B K fppml fhj 5 Br 5 Xl 1 >99 0 HO, B (Kl-K3) (K1 K ) BU B1 ° \/\ 5 X1 1 87 B2 i (K1-K3) ex T 03 (K1-K3) 12 96 3 X1 (K1-K3) S. YY'= yvr\, o'X1'2'99 Al 6H B3 C3 (Kl 3 X1 (K1-K3) 8 F F 30 xi 2 >99 8 Ho. e 60 °"B4 3 X1 (K1-K3) Table 1 Exam-Halide A Boronic acid Product C Catalys Meth. Time Yield % B'e B K rppml fh] Cul (K1-K3) A1 OH 85 C5 10 Br 30 Xl 7 90 o Ho. cs (K-K3) A1 OH B6 11 I B °/\/\ 5 X1 2 97 A1 OH B6 1 1 HO vJ loMe >% Me (K1-K3) X1 2 97A1 OH B7 TiYVr'xi'2'97 I cl (kil A1 OH B8 13 4 HOvBJ25Me OçSMe (K 1-K3) X1 16 82 o I Ho. e K1-K3 A1 OH B9 A1 14 e 30 Xl 1 94 , p 6H 0, (Kl-K3) 4 53 A1 B10 C10 15 X1 5 si Y"OHB9 C9 (K1-K3) A1 c"\ (K1-K3) 4 53 -OH 30 si 30 X1 (K1-K3) 5 X1 (K1-K3) 0--' en (K1-K3) 4 53 1 A1 ° 30 X1 (K1-K3) 16 MOO Br MeO 30 xi 1 > 99 HO, (Kl-K3) a a2 OH C12 B1 Table 1 Exam-Halide A Boronic acid Product C Catalvst Meth. Time Yield u pie B fopml fhj 'f7MeO-Br, MeO'30'X1") 93 Ho.B w \/ (K1-K3) A2 OH B2 C13 Cl C13 18 MeO) C, Br Cl meo 30 xi 1 89 / ci/K _K3\ A2 OH B3 C14 B3 19 MeO, Br F MOO 30 Xl 2. 5 91 HO, A2 B4 C1s OH B4 cs 20 Meo B i M 100 X1 16 96 Ho. e w (K1-K3) A2 OH B6 C16 A2 OH B6ei6 Meo Br Meo 30 X1 1 97 HO -a I C17 OMe 22 Meo Br oMe Meo 30 X1 3 70 A2 HO 1O) B8 XOMe (K1-K3) 23 MeOs C, Br HOs gB43 MeO< ? (K1-K3) X1 4 81OH B8 C18 23 Meo w Br w 30 X1 4 81 HO. B (Kl-K3) 8 0 six (K1- 3) A2 OH11 C20 25 loo Xl 1 97 LBr no Lj)-fy-fYc. r HO, B"aCi-ct (Kl-K3) i/OH B3 C21 A3 Table 1 Exam-Halide A Boronic acid Product C Catalyst Meth. Time Yield [% 1 ple B K fopml fhl 26 Br HO, 30 xi 4 88 wno2 HOBJÇ NO2 (K1-K3) 2 >99 A4 OH B1 C22 100 X1 (K1-K3) 27 0\ loo X2 1 >99 I I o i Ho. s -- (K1-K3) I A5 OH B1 28 MeOA CI < MeO 1000 X2 3 94 Ho. e/\/ (K1-K3) A6 OH B1 C12 _ 29 Br HO, 5000 xi 18 84 5000 X 1 18 84 (K1-K3) (isolated) N OH Bl-N \ 0C23 HO. OH K1-K3 isol OH N AU C71 ou C. Heck coupling Example 31: 4-Bromobenzaldehyde (20.4 g, 110 mmol), n-butyl acrylate (19.7 g, 154 mmol), 2, 6-di-tert- butylphenol (10 mg) and sodium acetate (9.9 g, 120 mmol) are mixed with dimethylacetami- de (200 ml) and, after the addition of 4 ppm of lEl-halo (tri-tert-butylphosphino)(#3-allyl)palla- dium (II) (K1-K3), are stirred for 90 minutes at 190°C (oil bath). GC analysis (conversion 100%, yield 4-formylcinnamic acid n-butyl ester 99%).

The mixture is subjected to aqueous working up and extracted with ether, the organic phase is washed several times with water and filtered through silica gel and the solvent is removed by evaporation. 4-Formylcinnamic acid n-butyl ester (purity >99% GC) is obtained, without purification, in a yield of >95%.

Elemental analysis C14H16O3: C H Calculated: 72.39 6.94 Found: 72.46 7.00 Example 32: 4-Chloroacetophenone (3.51 g, 25 mmol), n-butyl acrylate (4.49 g, 35 mmol), 2,6-di-tert- butylphenol (2 mg) and sodium acetate (2.25 g, 27.5 mmol) are mixed with dimethylacetami- de (110 ml) and, after the addition of (1.25 mmol) µ-halo(tri-tert-butylphosphino)(#3- allyl) palladium (II) (K1-K3), are stirred at 190°C (oil bath).

The reaction is terminated after 6 hours.

GC analysis: conversion 60%, yield 4-formylcinnamic acid n-butyl ester 75%.

The mixture is subjected to aqueous working up and extracted with ether, and the organic phase is washed several times with water, filtered through silica gel and concentrated.

Yield: 50% 4-acetylcinnamic acid n-butyl ester.

Elemental analvsis for C1stt 3- C H Calculated: 73.15 7.45 Found: 72.98 7.45