Process for the preparation of an olefin-substituted aromatic or heteroaromatic compound

A process for the synthesis of olefins having aromatic substituents is described in which olefins are reacted with aryl halides in the presence of catalysts consisting of palladium compounds and tetraaryl phosphonium salts.

The present invention relates to a novel process for the synthesis of
 oletins having aromatic substituents using a novel and particularly active
 palladium-containing catalyst system, optionally in the presence of
 selectivity-enhancing additives.
 In industrial chemistry, oletins having aromatic substituents play an
 important role, e.g., as starting materials for polymers, sunscreen agents
 (UV absorbers), fine chemicals and prodrugs.
 A known method for the preparation of such olefins is the so-called Heck
 reaction in which iodo- or bromoaromatics ArX (X=I, Br) and, in rare
 cases, chloroaromatics (X=Cl) are reacted with oletins in the presence of
 stoichiometric amounts of a base and catalytic amounts of a palladium
 compound (F. Heck, "Vinyl Substitutions with organopalladium
 Intermediates" in Comprehensive Organic Syntheses, Vol. 4, Pergamon Press,
 Oxford, 1991, p. 833; R. F. Heck, Palladium Reagents in Organic Syntheses,
 Academic Press, London, 1985; R. F. Heck, Org. React. (N.Y.) 1982, 27,
 345; A. de Meijere, F. E. Meier, Angew. Chem. 1994, 106, 2473; J. Tsuji,
 Palladium Reagents and Catalysts: Innovations in Organic Synthesis, Wiley,
 Chichester, 1995).
 ##STR1##
 However, the Heck reaction has not been used for industrial application to
 date (B. Cornils, W. A. Herrmann, Applied Homogeneous Catalysis with
 Organometallic Compounds, VCH, Weinheim, 1996). This is due to the fact,
 inter alia, that the reactivity of haloaromatics ArX decreases very fast
 in the order ArI&gt;ArBr&gt;ArCl. Thus, in the research field, the
 reactive iodoaromatics are employed usually; for industrial application,
 however, they are much too expensive or difficult to obtain. The common
 catalysts and precatalysts, such as palladiumtetrakis(triphenylphosphane)
 Pd(PPh.sub.3).sub.4 or Pd(OAc).sub.2 in the presence of excess PPh.sub.3,
 give significantly lower yields in the case of bromoaromatics while the
 reactions of the chloroaromatics, which are available in particularly
 large amounts in the industry, proceed with completely unsatisfactory
 yields. As a cause thereof, Heck states the formation of
 tetraarylphosphonium compounds whereby the catalyst is decomposed with the
 precipitation of elemental Pd powder (R. F. Heck, Org. React. (N.Y.) 1982,
 27, 345; C. B. Ziegler, R. F. Heck, J. Org. Chem. 1978, 43, 2941). Indeed,
 catalytic C--C bond formation processes with inert chloroaromatics,
 especially in terms of Heck reactions, are considered a special challenge
 (V. V. Crushin, H. Alper, Chem. Rev. 1994, 94, 1047; B. Cornils, W. A.
 Herrmann, Applied Homogeneous Catalysis with Organometallic Compounds,
 VCH, Weinheim, 1996).
 The Heck reaction of chlorobenzene with styrene to form trans-stilbene
 proceeds to 60% when 1 mole % Pd(OAc).sub.2 is used in the presence of 2
 mole % of the ligand 1,4-bis(diisopropylphosphino)butane (Y. Ben-David, M.
 Portnoy, M. Gozin, D. Milstein, Organometallics 1992, 11, 1995) This is
 among the best results reported in the literature, but it has not been
 transferred to electron-deficient olefins, such as acrylates, since the
 highly nucleophilic phosphane initiates undesired polymerizations. Another
 particular disadvantage is the fact that relatively large amounts of an
 expensive (or difficult-to-obtain) ligand which is sensitive to oxidation
 are required. Further, transfer to other substrates was successful only in
 single cases. Thus, for example, the reaction of styrene with
 4-chlorotoluene proceeds to only 50% (Y. Ben-David, M. Portnoy, M. Gozin,
 D. Milstein, Organometallics 1992, 11, 1995).
 The use of Pd salts, such as Pd(OAc).sub.2, in the presence of excess
 tris(o-tolyl)phosphane P(o-Tol).sub.3 involves an active catalyst system
 with which the Heck reaction of bromoaromatics, especially if activated by
 electron-withdrawing substituents, proceeds with little satisfactory to
 good yields (20-90%) (A. Spencer, J. Organomet. Chem. 1983, 258, 101; J.
 Organomet. Chem. 1984, 270, 115; EP 0078768 A1 and EP 0103544 A1). In
 contrast, activated chloroaromatics react with quite poor yields. At any
 rate, the tact that P(o-Tol).sub.3 is an expensive and difficult-to-obtain
 phosphane is a drawback.
 In more recent works, it is reported that certain pallada-cycles prepared
 from Pd(OAc).sub.2 and P(o-Tol).sub.3 are unusually active catalysts in
 the Heck reaction. Thus, even non-activated bromoaromatics, such as
 bromobenzene or bromoanisole, could be reacted with n-butyl acrylate to
 form the corresponding Heck products (94-96%) (W. A. Herrmann, C.
 Bro.beta.mer, W. Ofele, C.-P. Reisinger, T. Priermeier, M. Beller, H.
 Fischer, Angew. Chem. 1995, 107, 1989; DE 4421730 C1 and EP 0725049 A1).
 However, transfer to chloroaromatics was only partially successful. Only
 activated chloroaromatics, such as 4-chlorobenzaldehyde, could be reacted
 with n-butyl acrylate (81%), and only in the presence of a tenfold excess
 of tetrabutylammonium bromide as an additive. Non-activated
 chloroaromatics, such as chlorobenzene, 4-chloroanisole or chlorotoluene,
 could not be made to react. Another disadvantage of all these reactions is
 the fact that the expensive and difficult-to-obtain tris(o-tolyl)phosphane
 must be employed in the preparation of the catalyst.
 Also, there have been numerous attempts to employ Pd-containing
 heterogeneous catalysts in the Heck reaction. While the results are
 altogether acceptable for the use of iodoaromatics, no generally
 satisfactory solution to the problem exists to date in the case of bromo-
 or chloroaromatics (V. V. Grushin, A. Alper, Chem. Rev. 1994, 94, 1047).
 Thus, for example, moderate yields are obtained in the reaction of
 chlorobenzene with styrene using various supported Pd catalysts, even if a
 tenfold excess of chlorobenzene is used (M. Julia, M. Duteil, C. Grand, E.
 Kuntz, Bull. Soc. Chim. Fr. 1973, 2791; K. Kaneda, M. Higuchi, T. Imanaka,
 J. Mol. Catal. 1990, 63, L33). Undesired side-products include benzene and
 diphenyl.
 Thus, it is clear that there is still an urgent need for simple or readily
 available palladium catalysts for the Heck reaction of chloro- and
 bromoaromatics.
 The present invention provides a solution to the problems described above
 since it has surprisingly been found that compounds of the type of the
 above formula III are readily available using a Heck reaction. As
 catalysts, there are used common palladiumn(II) salts PdXY or their
 CH.sub.3 CN, PhCN or PPh.sub.3 complexes, wherein typically X=Y=Cl, Br, I,
 RCO.sub.2 [R=C.sub.1 -C.sub.22, CF.sub.3, CCl.sub.3, CH.sub.2
 N(CH.sub.3).sub.2, C.sub.6 H.sub.5 ] or RSO.sub.3 (R=C.sub.1 -C.sub.22,
 CF.sub.3, C.sub.4 F.sub.9, CCl.sub.3, C.sub.6 H.sub.5, p--CH.sub.3 C.sub.6
 H.sub.4), or typically X=Cl, Br, I, RCO.sub.2 (R=C.sub.1 -C.sub.22,
 CF.sub.3, CCl.sub.3, CH.sub.2 OCH.sub.3, C.sub.6 H.sub.5), and typically
 Y=C.sub.6 H.sub.5, o--, m--, p--CH.sub.3 C.sub.6 H.sub.4, o-, m-,
 p--Cl--C.sub.6 H.sub.4, o-, m-, p--CHOC.sub.6 H.sub.4, o-, m-,
 p--CN--C.sub.6 H.sub.4, o-, m-, p--NO.sub.2 --C.sub.6 H.sub.4, o-, m-,
 p--PhCO--C.sub.6 H.sub.4, o-, m-, p--F--C.sub.6 H.sub.4, 1-C.sub.10
 H.sub.7 or 2-C.sub.10 H.sub.7, which are mixed with tetraarylphosphonium
 salts Ar.sup.1 Ar.sup.2 Ar.sup.3 Ar.sup.4 P.sup.+ Z.sup.-, wherein
 Ar.sup.1, Ar.sup.2, Ar.sup.3 and Ar.sup.4 represent identical or different
 aryl residues, typically Ar=C.sub.6 H.sub.5, o-, m-, p--CH.sub.3 --C.sub.6
 H.sub.4, o-, m-, p--Cl--C.sub.6 H.sub.4, o-, m-, p--CHO--C.sub.6 H.sub.4,
 o-, m-, p--CN--C.sub.6 H.sub.4, o-, m-, p--NO.sub.2 --C.sub.6 H.sub.4, o-,
 m-, p--PhCO--C.sub.6 H.sub.4, o-, m-, p--F--C.sub.6 H.sub.4, 1-C.sub.10
 H.sub.7 or 2-C.sub.10 H.sub.7, and Z=Cl, Br, RCO.sub.2 (R=C.sub.1
 -C.sub.22, CF.sub.3, CCl.sub.3, C.sub.6 H.sub.5) or RSO.sub.3 (R=C.sub.1
 -C.sub.22, CF.sub.3, C.sub.4 F.sub.9, C.sub.6 H.sub.5, p--CH.sub.3 C.sub.6
 H.sub.4). Preferably, PdCl.sub.2, PdCl.sub.2 (CH.sub.3 CN).sub.2,
 Pd(OAc).sub.2, C.sub.6 H.sub.5 PdCl or C.sub.6 H.sub.5 PdCl.PPh.sub.3 or
 their dimeric or oligomeric forms are used in the presence of
 tetraphenylphosphonium chloride or bromide. The ratio of PdXY to Ar.sup.1
 Ar.sup.2 Ar.sup.3 Ar.sup.4 P.sup.+ Z.sup.- ranges between 1:1 and 1:10, a
 ratio of 1:6 being preferably selected.
 Aprotic dipolar solvents, such as dimethylformamide (DMF) dimethylacetamide
 (DMA), dimethylsulfoxide, propylene carbonate,
 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) or
 1-methyl-2-pyrrolidinone (NMP), preferably DMF or NMP, are used as the
 solvents.
 Metal salts, such as sodium, potassium, cesium, calcium or magnesium salts
 of carboxylic acids, or the corresponding carbonates or bicarbonates, or
 amines, such as triethylamine or trioctylamine, preferably sodium acetate,
 are used as the base. The ratio of base to aryl halide ranges between 1:1
 and 5:1, preferably 1.5:1 to 2:1.
 As selectivity-enhancing additives, there are used nitrogen-containing
 carboxylic acids, such as common .alpha.- or .beta.-amino acids H.sub.2
 N(R)CHCO.sub.2 H or H.sub.2 N(R)CHCH.sub.2 CO.sub.2 H [R=H, CH.sub.3,
 C.sub.6 H.sub.5, CH.sub.2 C.sub.6 H.sub.4, CH(CH.sub.3).sub.2 ], or their
 N-alkylated forms R'NH(R)CHCO.sub.2 H or R'NH(R)CHCH.sub.2 CO.sub.2 H, or
 R'.sub.2 N(R)CHCO.sub.2 H or R'.sub.2 N(R)CHCH.sub.2 CO.sub.2 H
 [R'=CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, C.sub.4 H.sub.9, or
 R'+R'=(CH.sub.2).sub.4 or (CH.sub.2).sub.5 ], or their sodium or potassium
 salts, anthranilic acid or N,N-dimethylanthranilic acid, or
 pyridinecarboxylic acids (or their sodium or potassium salts), such as
 2-pyridinecarboxylic acid, or aromatic nitrogen-containing heterocycles,
 such as pyridine, lutidine, 2,2'-dipyridyl or quinoline. Preferably,
 N,N-dimethylglycine is used. The ratio of additive to palladium ranges
 between 100:1 and 1:1, preferably between 50:1 and 1:1. The use of these
 additives results in a substantial or complete suppression of
 side-reactions with the undesired formation of reduction or coupling
 products, such as benzene or diphenyl (both from PhX), usually occurring
 in the Heck reaction, or undesired double Heck reactions with the olefin.
 Further, the selectivity for the trans-isomer is increased. The
 nitrogen-containing compounds may also be directly employed as an additive
 and at the same time as a base.
 Reaction temperatures of between 60.degree. C. and 180.degree. C. may be
 selected; preferably, the reactions are allowed to proceed between
 100.degree. C. and 150.degree. C.
 As to the aryl component ArX, a wide variety of aryl and heteroaryl
 chlorides, bromides, o-tosylates, o-mesylates or o-triflates may be
 employed, for example, benzene, naphthalene, pyridine or quinoline
 derivatives.
 In the olefin component of the above formula II, R.sup.1, R.sup.2 and
 R.sup.3 are independently hydrogen, alkyl-(C.sub.1 -C.sub.8), phenyl, 1-
 or 2-naphthyl, vinyl, O-alkyl-(C.sub.1 -C.sub.8), O-phenyl, CN, CO.sub.2
 H, CO.sub.2 -alkyl-(C.sub.1 -C.sub.8), CO.sub.2 -phenyl, CONH.sub.2,
 CONH-alkyl-(C.sub.1 -C.sub.5), CON(alkyl).sub.2 -(C.sub.1 -C.sub.5),
 fluoro, chloro, PO(phenyl).sub.2, PO(alkyl).sub.2 -(C.sub.1 -C.sub.5),
 CO-phenyl, CO-alkyl-(C.sub.1 -C.sub.5), NH-alkyl-(C.sub.1 -C.sub.4),
 SO.sub.3 H, PO.sub.2 H, SO.sub.3 -alkyl-(C.sub.1 -C.sub.4) or SO.sub.2
 -alkyl-(C.sub.1 -C.sub.4); further, cyclic derivatives are also possible,
 namely if R.sup.1 +R.sup.2 =(CH.sub.2).sub.n or R.sup.2 +R.sup.3
 =(CH.sub.2).sub.n, wherein n may be from 2 to 16.

EXAMPLES
 The palladium catalysts used may be synthesized separately prior to the
 actual reaction, or generated in situ.
 Example A
 Preparation of (Ph.sub.4 P).sub.2 PdCl.sub.4
 70 mg (0.4 mmol) of PdCl, and 295.9 mg (0.79 mmol) of Ph.sub.4 PCl in 4 ml
 of acetonitrile are heated at 115.degree. C. with stirring for some
 minutes. Upon slowly cooling, 350.4 mg (0.38 mmol) of red-brown needles
 crystallize from the clear red-brown solution. Yield: 95. 7%;
 Empirical formula: C.sub.48 H.sub.40 P.sub.2 Cl.sub.4 Pd, M=927.02 g/mol;
 Elemental analysis: found [%]: 61.64 C, 4.60 H, 6.57 P, 15.83 Cl, 10.84 Pd
 calculated [%]: 62.19 C, 4.35 1H, 6.68 P, 15.30 Cl, 11.48 Pd; .sup.31 P
 NMR: .delta.=23.4 ppm (d.sub.7 -DMF).
 X-ray Crystal Structure Analysis: FIG. 1
 Example B
 Preparation of [PPh.sub.3 PdPh(.mu.-Cl)].sub.2
 112.3 mg (0.50 mmol) of Pd(OAc).sub.2 and 375.3 mg (1.0 mmol) of Ph.sub.4
 PCl are dissolved in 10 ml of acetonitrile to give a red-brown solution
 which is stirred at room temperature for 30 minutes. After the addition of
 0.5 ml of ethanol, the mixture is stirred in a closed vessel at 40.degree.
 C. for 30 minutes. A light-green fine precipitate forms immediately and
 grows upon heating. The precipitate is isolated and dried under vacuum.
 Yield: 95.2 mg (0.099 mmol, 39.6%); Empirical formula: C.sub.48 H.sub.40
 P.sub.2 Cl.sub.2 Pd.sub.2, M=962.54 g/mol; Elemental analysis:
 found [%]: 59.60 C, 4.14 H, 6.77 P, 7.65 Cl, 22.05 Pd calculated [%]: 59.89
 C, 4.19 H, 6.44 P, 7.37 Cl, 22.11 Pd;
 Example C
 [PPh.sub.3 PdPh(.mu.-Cl)].sub.2 +Na dimethylglycinate
 48.3 mg (0.05 mmol) of [PPh.sub.3 PdPh(.mu.-Cl)].sub.2 and 13.0 mg (0.10
 mmol) of Na dimethylglycinate are suspended in 2 ml of DMF. Upon heating
 to 70.degree. C., a clear green solution forms.
 .sup.31 P NMR: .delta.=31.2 ppm (d.sub.7 -DMF).
 Example D
 Preparation of trans-bis (N,N-dimethylglycinato) Pd
 2.0 g (19.4 mmol) of dimethylglycine and 0.58 g (1.97 mmol) of sodium
 tetrachloropalladate are dissolved in 10 ml of water at room temperature.
 To the solution, which is orange in color, is added 0.473 g (8.43 mmol) of
 KOH. After 3 hours of stirring, the light yellow solution is concentrated
 to half its volume at room temperature, upon which yellow crystals
 precipitate. The crystals are recrystallized from hot methanol.
 Yield: 0.403 g (1.2 mmol, 60.9%) Empirical formula: C.sub.8 H.sub.14
 N.sub.4 O.sub.4 Pd, M=336.64 g/mol; Elemental analysis:
 found [%]: 29.10 C, 4.22 H, 16.80 N, 31.3 Pd calculated [%]: 28.54 C, 4.19
 H, 16.64 N, 19.01 0, 31.61 Pd.
 X-ray Crystal Structure Analysis: FIG. 2
 Example E
 (CH.sub.3 CN).sub.2 PdCl.sub.2 +6 Ph.sub.4 PCl+6 dimethylglycine
 25.94 mg (0.1 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2 and 224.89 mg (0.6
 mmol) of Ph.sub.4 PCl are dissolved in 5 ml of DMF together with 61.87 mg
 (0.6 mmol) of dimethylglycine. The clear orange solution is stirred at
 room temperature for 1 hour, the solvent is evaporated and recondensed
 under vacuum, and the residue is dried under high vacuum to leave 304.2 mg
 of an orange-brown solid having a Pd content of 3.32%.
 Example F
 Preparation of the Base Ph.sub.4 POAc
 In a 100 ml round-bottom flask, 0.838 g (2.24 mmol) of phosphonium chloride
 and 0.365 g (2.19 mmol) of silver acetate are dissolved in 20 ml of water.
 After 1 hour, the voluminous AgCl precipitate is filtered off, and the
 water is removed in a rotary evaporator. The crystalline residue is taken
 up in ethanol and filtered over cotton wool. Half of the ethanol is
 removed to form a white crystalline solid.
 Yield: 637.5 mg (1.6 mmol, 73.1%) .sup.1 H NMR (200 MHz, d.sub.7 -DMF):
 .delta.=1.5 (s), 3H, CH.sub.3 --; 7.4-7.9 (m), 20H, phenyl.
 .sup.13 C NMR (50 MHz, d.sub.7 -DMP): .delta.=24.5 (s), CH.sub.3 --; 118.5,
 130.9, 135.2, 135.8 (d) phenyl; 173.0 (s) COO--.
 Examples with Styrene and Br- or Cl-aromatics
 In the following Examples, the reactions were performed in a Schlenk vessel
 with a Young-Hahn seal, unless otherwise stated.
 Example 1
 To a reaction vessel standing on a scale, 5.2 mg (0.02 mmol) of (CH.sub.3
 CN).sub.2 PdCl.sub.2 and 45.1 mg (0.12 mmol) of Ph.sub.4 PCl are added,
 followed by two cycles of evacuation and flushing with argon. Under argon,
 164 mg (2 mmol) of anhydrous sodium acetate, 114.8 mg (1.00 mmol) of
 chlorobenzene and 150.8 mg (1.45 mmol) of styrene are added. After the
 addition of 1 ml of NMP, the vessel is sealed, and the mixture is stirred
 first at 120.degree. C. for 45 minutes and then at 150.degree. C. for 11
 hours.
 After the reaction, the GC standards n-decane and n-hexadecane are added,
 and 3 ml of diethyl ether is added to the mixture. After filtering off the
 solids, the filtrate is examined by gas chromatography: With 78.5%
 conversion of Cl-benzene, an 80% yield of Heck products (86.5%
 trans-stilbene, 0.3% cis-stilbene, and 13.2% 1,1-diphenylethene) is
 obtained.
 Example 2
 A reaction is performed as described in Example 1, except that DMF is used
 as the solvent rather than NMP. Stirring is performed at 150.degree. C.
 for 5.5 hours. With 78.99% conversion of Cl-benzene, a 72.1% yield of Heck
 products (86.1% trans-stilbene, 0.9% cis-stilbene, and 13.0%
 1,1-diphenylethene) is obtained.
 Example 3
 A reaction is performed as described in Example 1, except that DMA is used
 as the solvent rather than NMP. Stirring is performed at 150.degree. C.
 for 8 hours. With 55.2% conversion of Cl-benzene, a 61.2% yield of Heck
 products (83.8% trans-stilbene, 1.1% cis-stilbene, and 15.1%
 1,1-diphenylethene) is obtained.
 Example 4
 A reaction is performed as described in Example 1, except that 10.3 mg
 (0.04 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 59.7 mg (0.16 mmol) of
 Ph.sub.4 PCl, 157.6 mg (1.92 mmol) of anhydrous sodium acetate, 107.1 mg
 (0.95 mmol) of chlorobenzene and 136.2 mg (1.31 mmol) of styrene in 1 ml
 of DMF are reacted. Stirring is performed at 150.degree. C. for 8 hours.
 With 95.6% conversion of Cl-benzene, a 70.4% yield of Heck products (84.9%
 trans-stilbene, 0.7% cis-stilbene, and 14.4% 1,1-diphenylethene) is
 obtained.
 Example 5
 A reaction is performed as described in Example 1, except that 104.2 mg
 (1.00 mmol) of styrene is used, and the reaction mixture is stirred at
 150.degree. C. for 8 hours. With 88.7% conversion of Cl-benzene, a 78%
 yield of Heck products (86.5% trans-stilbene, 0.3% cis-stilbene, 13.2%
 1,1-diphenylethene) is obtained.
 Example 6
 A reaction is performed as described in Example 1, except that 102.8 mg
 (0.99 mmol) of styrene and 164.8 mg (1.46 mmol) of chlorobenzene are used,
 and the reaction mixture is stirred at 150.degree. C. for 5.5 hours. With
 94.6% conversion of Cl-benzene, an 82.1% yield of Heck products (86.7%
 trans-stilbene, 0.9% cis-stilbene, 12.4% 1,1-diphenylethene) is obtained.
 Example 7
 A reaction is performed as described in Example 1, except that 13.9 mg
 (0.02 mmol) of (Ph.sub.3 P).sub.2 PdCl.sub.2 and 29.9 mg (0.08 mmol) of
 ph.sub.4 PCl in 1 ml of DMF is used as the catalyst. Stirring is performed
 at 150.degree. C. for 5.5 hours. With 77.2% conversion of cl-benzene, a
 69.6% yield of Heck products (84.7% trans-stilbene, 0.8% cis-stilbene,
 14.5% 1,1-diphenylethene) is obtained.
 Example 8
 A reaction is performed as described in Example 1, except that 18.5 mg
 (0.02 mmol) of (Ph.sub.4 P).sub.2 PdCl.sub.4 (preparation as in Example A)
 to which 0.08 mmol of Ph.sub.4 PCl has been added is used as the catalyst
 in 1 ml of DMF. Stirring is performed at 120.degree. C. for 0.3 hours and
 at 150.degree. C for 12 hours. With 80% conversion of Cl-benzene, an 85.1%
 yield of Heck products (86.1% trans-stilbene, 0.9% cis-stilbene, 13.0%
 1,1-diphenylethene) is obtained.
 Example 9
 A reaction is performed as described in Example 1, except that 9.6 mg (0.02
 mmol) of [PPh.sub.3 PdPh(.mu.-Cl)].sub.2 (preparation as in Example B) to
 which 44.98 mg (0.121 mmol) of Ph.sub.4 PCl has been added is used as the
 catalyst in 1 ml of NMP. Stirring is performed at 150.degree. C. for 12
 hours. With 86.2% conversion of Cl-benzene, an 86.4% yield of Heck
 products (84.8% trans-stilbene, 0.9% cis-stilbene, 14.4%
 1,1-diphenylethene) is obtained.
 Example 10
 A reaction is performed as described in Example 1, except that 5.6 mg (0.02
 mmol) of Pd(tetramethylethylenediamine)Me.sub.2 and 46.0 mg (0.12 mmol) of
 Ph.sub.4 PCl to which 9.9 mg (0.1 mmol) of dimethylglycine has been added
 is used as the catalyst. Stirring is performed at 150.degree. C. for 12
 hours. With 84.9% conversion of Cl-benzene, an 81.5% yield of Heck
 products (96.8% trans-stilbene, 0.7% cis-stilbene, 2.5%
 1,1-diphenylethene) is obtained.
 Example 11
 A reaction is performed as described in Example 1, except that 18.6 mg
 (0.02 mmol) of Pd(dibenzylideneacetone).sub.2 and 45.0 mg (0.12 mmol) of
 Ph.sub.4 PCl in 1 ml of DMF is used as the catalyst. Stirring is performed
 at 150.degree. C. for 6 hours. With 26.5% conversion of Cl-benzene, a
 34.2% yield of Heck products (84.3% trans-stilbene, 1.4% cis-stilbene,
 14.4% 1,1-diphenylethene) is obtained.
 Example 12
 A reaction is performed as described in Example 1, except that 195.7 mg
 (2.04 mmol) of Na propionate in 1 ml of DMF is used as the base. Stirring
 is performed at 150.degree. C. for 12 hours. With 73% conversion of
 Cl-benzene, a 55.1% yield of Heck products (84.0% trans-stilbene, 1.9%
 cis-stilbene, 14.9% 1,1-diphenylethene) is obtained.
 Example 13
 A reaction is performed as described in Example 12, except that 1 ml of NMP
 is used as the solvent. With 75% conversion of Cl-benzene, a 68.0% yield
 of Heck products (84.2% trans-stilbene, 1.9% cis-stilbene, 14.7%
 1,1-diphenylethene) is obtained.
 Example 14
 A reaction is performed as described in Example 1, except that 144.3 mg
 (1.0 mmol) of Na benzoate in 1 ml of DMF is used as the base. Stirring is
 performed at 150.degree. C. for 5.5 hours. With 52.4% conversion of
 Cl-benzene, a 55.5% yield of Heck products (84.4% trans-stilbene, 1.0%
 cis-stilbene, 14.7% 1,1-diphenylethene) is obtained.
 Example 15
 A reaction is performed as described in Example 14, except that 1 ml of NMP
 is used as the solvent. With 60% conversion of Cl-benzene, a 58.0% yield
 of Heck products (84.2% trans-stilbene, 1.9% cis-stilbene, 14.7%
 1,1-diphenylethene) is obtained.
 Example 16
 A reaction is performed as described in Example 1, except that 311.6 mg
 (2.15 mmol) of Na picolate in 1 ml of DMF is used as the base. Stirring is
 performed at 150.degree. C. for 12 hours. With 26.7% conversion of
 Cl-benzene, a 32.1% yield of Heck products (97-4% trans-stilbene, 1.1%
 cis-stilbene, 1.5% 1,1-diphenylethene) is obtained.
 Example 17
 A reaction is performed as described in Example 16, except that 1 ml of NMP
 is used as the solvent. With 31.59% conversion of Cl-benzene, a 34.0%-
 yield of Heck products (84.2% trans-stilbene, 1.9% cis-stilbene, 14.7%
 1,1-diphenylethene) is obtained.
 Example 18
 A reaction is performed as described in Example 1, except that 12.5 mg
 (0.12 mmol) of dimethylglycine is added to the first two educts as an
 additive. Stirring is performed at 120.degree. C. for 30 minutes and at
 150.degree. C. for 12 hours. With 95.6% conversion of Cl-benzene, a 100%
 yield of Heck products (96.4% trans-stilbene, 0.7% cis-stilbene, 2.9%
 1,1-diphenylethene) is obtained.
 Example 19
 A reaction is performed as described in Example 18, except that 1 ml of DMF
 is used as the solvent. With 95.2% conversion of Cl-benzene, an 83.6%
 yield of Heck products (96.4% trans-stilbene, 0.7% cis-stilbene, 2.9%
 1,1-diphenylethene) is obtained.
 Example 20
 A reaction is performed as described in Example 1, except that 13.9 mg
 (0.02 mmol) of (Ph.sub.3 P).sub.2 PdCl.sub.2 and 29.9 mg (0.08 mmol) of
 Ph.sub.4 PCl in 1 ml of NMP to which 9.9 mg (0.1 mmol) of dimethylglycine
 has been added is used as the catalyst. Stirring is performed at
 150.degree. C. for 12 hours. With 81.4% conversion of Cl-benzene, a 79.6%
 yield of Heck products (96.81% trans-stilbene, 0.71% cis-stilbene, 2.5%
 1,1-diphenylethene) is obtained.
 Example 21
 A reaction is performed as described in Example 1, except that 9.6 mg (0.02
 mmol) of [PPh.sub.3 PdPh(.mu.-Cl)].sub.2 to which 44.98 mg (0.12 mmol) of
 Ph.sub.4 PCl has been added is used as the catalyst in 1 ml of NMP to
 which 9.8 mg (0.1 mmol) of dimethylglycine is added. Stirring is performed
 at 150.degree. C. for 12 hours. With 89.2% conversion of Cl-benzene, an
 87.4% yield of Heck products (99.9% trans-stilbene, 0.9% cis-stilbene,
 2.2% 1,1-diphenylethene) is obtained.
 Example 22
 A reaction is performed as described in Example 1, except that 0.02 mmol of
 the catalyst solution described in Example C to which 44.98 mg (0.12 mmol)
 of Ph.sub.4 PCl has been added is used as the catalyst in 1 ml of NMP.
 Stirring is performed at 150.degree. C. for 12 hours. With 82.4%
 conversion of Cl-benzene, an 83.5% yield of Heck products (96.9%
 trans-stilbene, 0.9% cis-stilbene, 2.2% 1,1-diphenylethene) is obtained.
 Example 23
 A reaction is performed as described in Example 1, except that 6.7 mg (0.02
 mmol) of the catalyst described in Example D to which 45 mg (0.12 mmol) of
 Ph.sub.4 PCl has been added is used as the catalyst in 1 ml of NMP.
 Stirring is performed at 150.degree. C. for 12 hours. With 91.5%
 conversion of Cl-benzene, an 89.7% yield of Heck products (96.7%
 trans-stilbene, 0.9% cis-stilbene, 2.4% 1,1-diphenylethene) is obtained.
 Example 24
 A reaction is performed as described in Example 1, except that 64.1 mg
 (0.02 mmol) of the catalyst described in Example E is used in 1 ml of NMP.
 Stirring is performed at 150.degree. C. for 12 hours. With 98.2%
 conversion of Cl-benzene, a 97.6% yield of Heck products (97.1%
 trans-stilbene, 0.9% cis-stilbene, 2.0% 1,1-diphenylethene) is obtained.
 Example 25
 A reaction is performed as described in Example 1, except that 18.5 mg
 (0.02 mmol) of (Ph.sub.4 P).sub.2 PdCl.sub.4 to which 30.0 mg (0.08 mmol)
 of Ph.sub.4 PCl has been added is used as the catalyst in 1 ml of DMF to
 which 9.6 mg (0.09 mmol) of dimethylglycinie is added. Stirring is
 performed at 120.degree. C. for 0.3 hours and at 150.degree. C. for 12
 hours. With 98% conversion of Cl-benzene, a 97.4% yield of Heck products
 (96.1% trans-stilbene, 0.9% cis-stilbene, 3.0% 1,1-diphenylethene) is
 obtained.
 Example 26
 A reaction is performed as described in Example 1, except that 14.8 mg
 (0.12 mmol) of picolinic acid is used as the additive, and stirring is
 performed only at 150.degree. C. for 12 hours. With 65.6% conversion of
 Cl-benzene, a 70.1% yield of Heck products (96.9% trans-stilbene, 0.9%
 cis-stilbene, 2.2% 1,1-diphenylethene) is obtained.
 Example 27
 A reaction is performed as described in Example 26, except that 1 ml of DMF
 is used as the solvent. With 89.0% conversion of Cl-benzene, an 81% yield
 of Heck products (96.9% trans-stilbene, 0.9% cis-stilbene, 2.2%
 1,1-diphenylethene) is obtained.
 Example 28
 A reaction is performed as described in Example 1, except that 50.3 mg of
 Ph.sub.4 PBr (0.12 mmol) is used instead of Ph.sub.4 PCl, and 1 ml of DMF
 is used as the solvent. With 74.8% conversion of Cl-benzene, a 77.3% yield
 of Heck products (85.9% trans-stilbene, 0.6% cis-stilbene, 13.5%
 1,1-diphenylethene) is obtained.
 Example 29
 A reaction is performed as described in Example 1, except that 47.8 mg
 (0.12 mmol) of Ph.sub.4 POAc is used as the phosphonium salt in 1 ml of
 DMF. Stirring is performed at 150.degree. C. for 12 hours. With 73. 5%
 conversion of Cl-benzene, a 71.9% yield of Heck products (85.7%
 trans-stilbene, 0.9t cis-stilbene, 13.4% 1,1-diphenylethene) is obtained.
 Example 30
 A reaction is performed as described in Example 1, except that 15.7 mg
 (0.12 mmol) of piperidine-2-carboxylic acid is used as the additive. With
 84% conversion of Cl-benzene, an 87% yield of Heck products (96.2%
 trans-stilbene, 0.8% cis-stilbene, 2.97% 1,1-diphenylethene) is obtained.
 Example 31
 A reaction is performed as described in Example 1, except that 14.1 mg
 (0.12 mmol) of proline is used as the additive, and stirring is performed
 only at 150.degree. C. for 12 hours. With 69.4% conversion of Cl-benzene,
 a 71.1% yield of Heck products (94.7% trans-stilbene, 0.1% cis-stilbene,
 4.4% 1,1-diphenylethene) is obtained.
 Example 32
 A reaction is performed as described in Example 31, except that 1 ml of DMF
 is used as the solvent. With 89.6% conversion of Cl-benzene, an 82.6%
 yield of Heck products (92.3% trans-stilbene, 0.8% cis-stilbene, 6.8%
 1,1-diphenylethene) is obtained.
 Example 33
 A reaction is performed as described in Example 1, except that 3.8 mg
 (0.015 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2 and 34.0 mg (0.09 mmol) of
 Ph.sub.4 PCl as the catalyst and 147.1 mg (1.86 mmol) of pyridine as the
 additive are reacted. Stirring is performed at 150.degree. C. for 20
 hours. With 86.4% conversion of Cl-benzene, a 67.9% yield of Heck products
 (91.69 trans-stilbene, o.6% cis-stilbene, 7.8% 1,1-diphenylethene) is
 obtained.
 Example 34
 To a reaction vessel standing on a scale which is sealed with a septum cap,
 5.3 mg (0.02 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 45 mg (0.12 mmol) of
 Ph.sub.4 PCl and 12.4 mg (0.12 mmol) of dimethylglycine are added,
 followed by two cycles of evacuation and flushing with argon. Under argon,
 657.7 mg (8 mmol) of anhydrous sodium acetate and 1 ml of NMP are added.
 452 mg (4.01 mmol) of Cl-benzene and 636 mg (6.11 mmol) of styrene is
 mixed with 1 ml of NMP and added dropwise in 6 portions within 6 hours,
 the first portion being added at room temperature and the others at
 140.degree. C. Stirring is performed at 140.degree. C. for a total of 24
 h. According to the processing described in Example 1 using 10 ml of
 diethyl ether, a 64.2% yield of Heck products (97.4% trans-stilbene, 0.6%
 cis-stilbene, and 2.0%- 1,1-diphenylethene) is obtained with 76.6%
 conversion of Cl-benzene.
 Example 35
 A reaction is performed as described in Example 1, except that 3.9 mg
 (0.015 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 34.9 mg (0.09 mmol) of
 Ph.sub.4 PCl, 520.9 mg (6.35 mmol) of anhydrous sodium acetate, 499.6 mg
 (3.118 mmol) of Br-benzene and 489.3 mg (4.7 mmol) of styrene are reacted
 in 1.5 ml of DMF. Stirring is performed at 130.degree. C. for 5 hours.
 According to the processing described in Example 1, a 74.8% yield of Heck
 products (85.0% trans-stilbene, 0.5% cis-stilbene, and 14.5%
 1,1-diphenylethene) is obtained with 74.6% conversion of Br-benzene.
 Example 36
 A reaction is performed as described in Example 1, except that 503.5 mg
 (3.2 mmol) of p-nitrochlorobenzene and 493.9 mg (4.74 mmol) of styrene are
 reacted in 1.5 ml of DMF. As the catalyst, 3.9 mg (0.015 mmol) of
 (CH.sub.3 CN).sub.2 PdCl.sub.2 and 34.9 mg (0.093 mmol) of Ph.sub.4 PCl is
 used. Stirring is performed at 135.degree. C. for 12 hours. According to
 the processing described in Example 1, a 15.9% yield of Heck products is
 obtained with 68.5% conversion of p-nitrochlorobenzene.
 Example 37
 A reaction is performed as described in Example 1, except that 124.7 mg
 (0.99 mmol) of p-chlorotoluene and 113. 7 mg (1.09 mmol) of styrene are
 reacted in 1 ml of DMP. As the catalyst, 10.4 mg (0.04 mmol) of (CH.sub.3
 CN).sub.2 PdCl.sub.2 and 89.6 mg (0.24 mmol) of Ph.sub.4 PCl is used.
 Stirring is performed at 150.degree. C. for 4.3 hours. According to the
 processing described in Example 1, a 22.9% yield of Heck products is
 obtained with 70.7% conversion of p-chlorotoluene.
 Example 38
 A reaction is performed as described in Example 1, except that 160.1 mg
 (1.036 mmol) of p-chloroacetophenone and 125.8 mg (1.21 mmol) of styrene
 are reacted in 1 ml of NMP. As the catalyst, 5.1 mg (0.02 mmol) of
 (CH.sub.3 CN).sub.2 PdCl.sub.2 and 44.8 mg (0.12 mmol) of Ph.sub.4 PCl is
 used. Stirring is performed at 120.degree. C. for 0.5 hours and at
 150.degree. C. for 12 hours. According to the processing described in
 Example 1, a 48.2% yield of Heck products is obtained with 74.6%
 conversion of p-chloroacetophenone.
 Example 39
 A reaction is performed as described in Example 1, except that 3.9 mg
 (0.015 mmol) of (CH.sub.2 CN).sub.2 PdCl.sub.2, 34.9 mg (0.09 mmol) of
 Ph.sub.4 PCl, 496.0 mg (6.05 mmol) of anhydrous sodium acetate, 638.74 mg
 (3.07 mmol) of 3-bromoquinoline and 427.0 mg (4.1 mmol) of styrene are
 reacted in 1.5 ml of DMF. Stirring is performed at 130.degree. C. for 5
 hours. According to the processing described in Example 1, a 72.5% yield
 of Heck products (85.1% trans-stilbene, 0.8% cis-stilbene, and 14.1%
 1,1-diphenylethene) is obtained with 78.5% conversion of 3-bromoquinoline.
 Examples with Acrylates and Br- or Cl-aromatics
 Example 40
 To a reaction vessel standing on a scale, 5.1 mg (0.02 mmol) of (CH.sub.2
 CN).sub.2 PdCl.sub.2 and 45 mg (0.12 mmol) of Ph.sub.4 PCl are added,
 followed by two cycles of evacuation and flushing with argon. Under argon,
 147.7 mg (1.8 mmol) of anhydrous sodium acetate, 110.4 mg (0.98 mmol) of
 chlorobenzene and 184.2 mg (1.0 mmol) of ethylhexyl acrylate are added.
 After the addition of 1 ml of NMP, the vessel is sealed, and the mixture
 is stirred first at 120.degree. C. for 60 minutes and then at 150.degree.
 C. for 20 hours.
 After the reaction, the GC standards n-decane and n-hexadecane are added,
 and 3 ml of diethyl ether is added to the mixture. After filtering off the
 solids, the filtrate is examined by gas chromatography: With 31.6%
 conversion of Cl-benzene, a 34.6% yield of Heck product is obtained.
 Example 41
 A reaction is performed as described in Example 40, except that 5.0 mg
 (0.019 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 45 mg (0.12 mmol) of
 Ph.sub.4 PCl, 177.2 mg (2.16 mmol) of sodium acetate, 116.4 mg (1.03 mmol)
 of chlorobenzene, 152.9 mg (1.193 mmol) of butyl acrylate and 1 ml of DMF
 are used. Stirring is performed at 160.degree. C. for 5.5 hours. With
 29.5% conversion of Cl-benzene, a 14.8% yield of Heck product is obtained.
 Example 42
 A reaction is performed as described in Example 40, except that 5.3 mg
 (0.02 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 45.2 mg (0.12 mmol) of
 Ph.sub.4 PCl, 185.4 mg (2.26 mmol) of sodium acetate, 120.3 mg (1.07 mmol)
 of chlorobenzene, 189.4 mg (1.48 mmol) of tert-butyl acrylate and 1 ml of
 NMP are used. Stirring is performed at 120.degree. C. for 1 hour and at
 150.degree. C. for 20 hours. With 28.7% conversion of Cl-benzene, a 27.5%
 yield of Heck product is obtained.
 Example 43
 A reaction is performed as described in Example 40, except that 5.1 mg
 (0.02 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 45 mg (0.12 mmol) of
 Ph.sub.4 PCl, 228 mg (2.8 mmol) of sodium acetate, 120.0 mg (1.07 mmol) of
 chlorobenzene, 337.8 mg (1.70 mmol) of ethylhexyl methacrylate and 1 ml of
 DMF are used. With 93% conversion of Cl-benzene, an about 40% yield of
 Heck product is obtained.
 Example 44
 A reaction is performed as described in Example 40, except that 1.3 mg
 (0.005 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 11.9 mg (0.032 mmol) of
 Ph.sub.4 PCl, 1.676 g (20.43 mmol) of sodium acetate, 1.54 g (9.81 mmol)
 of Br-benzene, 1.86 g (14.48 mmol) of butyl acrylate and 5 ml of DMF are
 used. For the processing, 10 ml of diethyl ether is used. With 100%
 conversion of Br-benzene, a 92.3% yield of Heck product is obtained.
 Example 45
 A reaction is performed as described in Example 40, except that 5.4 mg
 (0.02 mmol) of (CH.sub.3 CN).sub.2 PdCl.sub.2, 45 mg (0.12 mmol) of
 Ph.sub.4 PCl, 175 mg (2.13 mmol) of sodium acetate, 196.9 mg (1.05 mmol)
 of p-Br-anisole, 328.9 mg (1.79 mmol) of ethylhexyl acrylate and 1 ml of
 NMP are used. With 100% conversion of p-Br-anisole, a 90% yield of Heck
 product is obtained.
 Examples with Cyclofrexene and Haloaromatics
 Example 46
 A reaction is performed as described in Example 1, except that 162.6 mg
 (1.04 mmol) of bromobenzene and 121.9 mg (1.48 mmol) of cyclohexene are
 reacted with the same catalyst in 1 ml of NMP to which 14.1 mg (0.14 mmol)
 of dimethylglycine is added as the additive. Stirring is performed at
 140.degree. C. for 8 hours. With 38.5% conversion of bromobenzene, a 30.9%
 yield of Heck products (double bond isomer ratio of 48.4:51.6) is
 obtained.
 Example 47
 A reaction is performed as described in Example 1, except that 115.9 mg
 (1.03 mmol) of chlorobenzene and 120.0 mg (1.4 mmol) of cyclohexene are
 reacted with the same catalyst in 1 ml of NMP to which 13.0 mg (0.13 mmol)
 of dimethylglycine is added. Stirring is performed at 150.degree. C. for
 12 hours. With 22.3% conversion of chlorobenzene, a 17.7% yield of Heck
 products (double bond isomer ratio of 28.4:71.6) is obtained.
 Example 48
 A reaction is performed as described in Example 1, except that 212.1 mg
 (1.07 mmol) of bromoacetophenone and 122.7 mg (1.49 mmol) of cyclohexene
 are reacted with the same catalyst in 1 ml of NMP to which 14.7 mg (0.14
 mmol) of dimethylglycine is added. Stirring is performed at 140.degree. C.
 for 8 hours. With about 10% conversion of bromoacetophenone, a 10.3% yield
 of Heck products (double bond isomer ratio of 43.7:56.3) is obtained.
 Example with Ethylene and Haloaromatics
 Example 49
 11.85 g (50 mmol) of 2-bromo-6-methoxynaphthalene is dissolved in 50 ml of
 DMP and transferred to a 100 ml stainless steel autoclave equipped with a
 magnetic stirrer together with 8.2 g (100 mmol) of NaOAc, 260 mg (1 mmol)
 of (CH.sub.3 CN).sub.2 PdCl.sub.2 and 225.1 mg (6 mmol) of Ph.sub.4 PCl.
 Stirring is performed for 14 hours under an ethylene pressure of 20 bar.
 Yield of 2-vinyl-6-methoxynaphthalene: 78%.