Heck vinylation reaction

Figure 1 Regioselectivity in Heck vinylation reactions arrows show the site of C-C bond formation...

Another example of a successful transfer of a TPPTS-based catalytic system into water/C02 media is the Heck vinylation reaction [Eq. (8)] [33, 34]. Butyl acrylate and styrene were coupled successfully with iodobenzene using a [Pd(OAc)2]/TPPTS catalyst in situ in the presence of SCCO2 at different pressures. The reaction was carried out at 60 °C for 17 h using triethylamine as a base. With a catalyst/substrate ratio of 1 200, a maximum turnover number of 36 at a moderate CO2 pressure of 8 MPa was reached. With ethylene glycol as polar co-solvent instead of water, turnovers of up to 135 could be obtained. Catalyst recycling was achieved by phase separation after complete decompression of the reaction mixture, yielding similar conversions at least three times. Very little metal leaching into the product phase was observed with palladium contaminations below 0.1 ppm. 

Yang, Y, Zhou, R., Zhao, S. et al. (2003) Silica-supported poly-y-aminopropylsilane Ni, Cu +, Co + complexes efficient catalysts for Heck vinylation reaction. J. Mol. Catal. A, 192, 303-6. 

Bhanage, B.M., Zhao, F.G., Shirai, M. and Aral, M. (1998) Comparison of activity and selectivity of various metal-TPPTS complex catalysts in ethylene glycol-toluene biphasic Heck vinylation reactions of iodobenzene. Tetrahedron Lett., 39,9509-12. 

Alternatively, a catalytic system consisting of the tetrapodal phosphine ligand Tedicyp 66 and the allylpalladium chloride dimer ([PdCl(C3H5)]2) can be used for efficient Heck vinylation reactions (Scheme 48, Table 26) [341]. The crosscoupling of 3,4-dibromothiophene 116 with various alkenes 117 gives rise to the corresponding vinylated products 118 and 119. 

Heck vinylation 22 Heck vs. Diels-Alder 278 Heck-Mizoroki reaction 194 Heterocycles, benzocondensed 246, 249, 252... 

A similar approach was used by the Alcaide group [183] in the synthesis of tricyclic (3-lactams 6/1-391 from 6/1-390 (Scheme 6/1.99). In this domino process the primarily obtained it-allyl-Pd-complex reacts with the N-nucleophile of the urethane moiety to form a C-N-bond and a vinyl halide. The final step is then an intramolecular Heck-type reaction of the vinyl halide with the alkyne moiety and re-... 

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

Bis(pyrazolyl)borate copper complex 47 has been employed as a catalyst in the homogeneous and heterogeneous styrene epoxidation reactions <00JCS(CC)1653>. Pyrazole palladacycles 48 have proven to be stable and efficient catalysts for Heck vinylations of aryl iodides <00JCS(CC)2053>. An asymmetric borane reduction of ketones catalyzed by N-hydroxyalkyl-/-menthopyrazoles has been reported <00JHC983>. 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

In a related approach, Murakami synthesized clavicipitic acid and costaclavine [79], and later extended this chemistry to a synthesis of chanoclavine-I featuring the intramolecular Heck vinylation 240 to 241 [266], The corresponding enone failed to cyclize under these conditions. Noteworthy is that radical cyclizations, which often compete successfully with Heck reactions, were poor in this system. 

Following our first report on the palladium-catalyzed reaction of vinyl triflates with olefins (Heck-type reaction), oxidative insertion of palladium(O) into the carbon-oxygen bond of easily available vinyl triflates ... 

Fig. 21. Heck-type vinylation reaction with PolyHIPE-supported Pd catalyst...

Bienayme and Yezeguelian [63] described a new synthesis of retinal via a Heck vinylation of a C15 tertiary allylic alcohol with a C5 iodoacetal. Thus, the bromo acetal was prepared by a known procedure [64], by a bromination-dehydrobromination reaction sequence (E and Z isomers 40/60). 

When the Heck vinylic arylation reaction is carried out with an olefin which is either a gas or a low boiling liquid, it must be run in a pressure vessel. Depending upon the product desired, the olefin is usually present in an excess concentration in order to insure formation of vinyl substituted products. In the case of the reaction of ethylene with 2 the stoichiometry of the reactants is critical (Fig. 5). If 4-bromobenzocyclobutene 2 is present in higher concentrations than ethylene, a different monomer, l,2-di(4-benzocyclobutenyl)-ethylene 11 is obtained. 

However, it has turned out that there are a few synthetic methods having broad scope, that is, (a) for the synthesis of dioxepins and dithiepins (i) transacetalization of the corresponding diol or dithiol, respectively, with an open chain acetal (ii) treatment of the corresponding diol or dithiol with sodium borohydride and reaction of the resulting dianion with a gem-dihalogen derivative. The latter method is particularly useful for the synthesis of dioxepins and dithiepins unsubstituted in the 2-position (b) for the synthesis of 4,5-dihydro-l,3-dioxepins (i) metal- or base-catalyzed double-bond isomerization and (ii) Heck vinylation or arylation, respectively, for the synthesis of 6-substituted 4,5-dihydro-l,3-dioxepins. 

The Heck-type reaction of vinylic bromides with alkenes in the presence of nucleophiles such as stabilized enolates or secondary amines (morpholine or piperidine) are efficient three-component reactions that were developed in the late 1970s... 

Several other examples of the utility of Pd-mediated reactions in synthesis of aryl and vinyl derivatives of pyrrole and indole were reported. Schmidt and coworkers examined arylation of 1-vinylpyrroles under Heck conditions. Reaction took place at the A-vinyl group. While the parent compound gave a mixture of -and -arylation, 2,3-dialkyl-1-vinylpyrroles preferred -substitution. <95RCB767> Grieb and Ketcha used Suzuki coupling conditions to prepare several 1-... 

The inter- and intramolecular Heck reactions provide other routes to substituted pyridines . Although electron-deficient 2-bromopyridines are resistant to substitution under Heck conditions, the aminopyridine 142 affords a high yield of the adduct 143 (Equation 68) <1998T6311>. The intermolecular Heck reaction of a 3-pyridyltriflate with ethyl acrylate is accelerated by LiCl <1999SL804>. An efficient Heck vinylation of 3-substituted-2-bromo-6-methylpyridines with methyl acrylate has been developed <2005T4569>. 

Bauerle and coworkers [38] suggested and applied Pd-catalyzed cross-coupling reactions of 3 -bromocoumarin derivatives for the generation of coumarin libraries with a highly diverse substitution pattern. In the case of 3-bromocoumarin (18), the reaction conditions for combinatorial Heck vinylations with alkenes 19, Suzu-... 

The Heck-type reaction. The Heck reaction135 (or some modified procedure of it) is certainly one of the most powerful tools used in the preparation of precursors with acetylenic and vinylic subunits. For instance, in the case of precursors 46-49 the synthesis is conveniently achieved by a cross-coupling reaction in the presence of palladium complexes as catalyst. Two pathways are possible, as represented by equations 9 and 10108. 

With a combination of organic halide, alkene or alkyne, and palladium catalyst, the reaction may take a superficially similar, but different pathway other than a Heck-type reaction. In these, the halogen is retained in the products, as an alkyl or vinyl halide. These results occur when the starting organic halide is allyl, a- to a carbonyl or similar group, or attached to a perhalogenated carbon atom. In much of the early work, mixtures with Hecklike elimination products were obtained, due to elimination caused by the presence of amine bases in the reaction mixture (equation 165)323. 

Ruthenium(O) complexes such as Ru(COD)(COT) catalyze the dehydrohalo-genative coupling of vinyl halides with olefins to give substituted conjugated dienes in a Heck-type reaction [11]. Thus, alkenyl halides readily react with activated olefins to produce dienes 16 (Eq. 7). Oxidative addition of vinyl halide, followed by regioselective insertion of an electron-deficient olefin and by -hydrogen elimination leads to the diene. 

Here, the order of coupling can be nicely illustrated upon varying the stoichiometry of the aryl halide and the reaction conditions. The amination proceeds faster and at lower temperatures than the Heck reaction, as shown by symmetrical N,N-diarylation at 60 °C followed by the Heck vinylations of a second aryl halide at 110 °C to give the amino stilbene derivatives 109 (Scheme 38). 

There are scattering examples that neutral organosilanes R-SiMe3 undergo a desilylative coupling reaction with aryl halides in the presence of a palladium catalyst. Hallberg and his co-workers disclosed that trimethyl(vinyl)silane reacts with an arylpalladium(II) complex to afford coupled products accompanied by aryl-substituted alkenylsilanes formed through the Heck type reaction... 

The use of aryl triflates or other sulfonates in the amine arylation reaction is highly desirable from a synthetic standpoint since a large variety of phenols are easily accessed and derivatized. Aryl and vinyl triflates have enjoyed great utility in other Pd-catalyzed transformations such as the Stille [77] and Suzuki [78] couplings, and the Heck [79] reaction. 

Heck s reaction can result in regioisomers, depending on whether the reaction proceeds at the a or (3 carbons in the alkene. A selectivity > 99% to the a-arylation product was achieved in the Heck coupling of 1-bromonaphthalene to butyl vinyl ether in [bmim][BF4], In contrast, the same reaction in toluene, acetonitrile, DMF, or DMSO... 

Ionic liquids can be used as replacements for many volatile conventional solvents in chemical processes see Table A-14 in the Appendix. Because of their extraordinary properties, room temperature ionic liquids have already found application as solvents for many synthetic and catalytic reactions, for example nucleophilic substitution reactions [899], Diels-Alder cycloaddition reactions [900, 901], Friedel-Crafts alkylation and acylation reactions [902, 903], as well as palladium-catalyzed Heck vinylations of haloarenes [904]. They are also solvents of choice for homogeneous transition metal complex catalyzed hydrogenation, isomerization, and hydroformylation [905], as well as dimerization and oligomerization reactions of alkenes [906, 907]. The ions of liquid salts are often poorly coordinating, which prevents deactivation of the catalysts. 

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