Heck aryl halide activation

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

The Mizoroki-Heck reaction is a metal catalysed transformation that involves the reaction of a non-functionalised olefin with an aryl or alkenyl group to yield a more substituted aUcene [11,12]. The reaction mechanism is described as a sequence of oxidative addition of the catalytic active species to an aryl halide, coordination of the alkene and migratory insertion, P-hydride elimination, and final reductive elimination of the hydride, facilitated by a base, to regenerate the active species and complete the catalytic cycle (Scheme 6.5). 

This method ensures the deposition of very reactive metal nanoparticles that require no activation steps before use. We shall review here the following examples of catalytic reactions that are of interest in line chemical synthesis (a) the hydrogenation of substituted arenes, (b) the selective hydrogenation of a, 3-unsaturated carbonyl compounds, (c) the arylation of alkenes with aryl halides (Heck reaction). The efficiency and selectivity of commercial catalysts and of differently prepared nanosized metal systems will be compared. 

Under all the conditions studied, addition of bare Si02-SH to Heck or Suzuki coupling reactions using a variety of bases, aryl halides and solvents resulted in complete cessation of the catalytic activity (35). These results suggest that catalysis with this precatalyst is also associated with labile palladium species that... 

Ohta s group investigated the heteroaryl Heck reaction of thiophenes and benzothiophenes with aryl halides [127] and chloropyrazines [128]. Addition of the electrophiles invariably took place at C(2) as exemplified by the formation of arylbenzothiophene 156 from the reaction of benzothiophene and p-bromobenzaldehyde [127]. As expected, the heteroaryl Heck reaction of 2-thienylnitrile, an activated thiophene, with iodobenzene afforded the arylation product 157 [129],... 

Palladium chemistry of heterocycles has its idiosyncrasies stemming from their different structural properties from the corresponding carbocyclic aryl compounds. Even activated chloroheterocycles are sufficiently reactive to undergo Pd-catalyzed reactions. As a consequence of a and y activation of heteroaryl halides, Pd-catalyzed chemistry may take place regioselectively at the activated positions, a phenomenon rarely seen in carbocyclic aryl halides. In addition, another salient peculiarity in palladium chemistry of heterocycles is the so-called heteroaryl Heck reaction . For instance, while intermolecular palladium-catalyzed arylations of carbocyclic arenes are rare, palladium-catalyzed arylations of azoles and many other heterocycles readily take place. Therefore, the principal aim of this book is to highlight important palladium-mediated reactions of heterocycles with emphasis on the unique characteristics of individual heterocycles. 

The scope of the multiphasic system was extended to coupling reactions—like the Heck reaction—using a heterogeneous supported catalyst, such as Pd/C. The rationale here lay in the observation that aryl halides were activated in the multiphasic system (as seen for hydrodehalogenation), and that therefore they should also be activated toward C-C coupling reactions. 

The Heck reaction is a C-C coupling reaction where an unsaturated hydrocarbon or arene halide/triflate/sulfonate reacts with an alkene in presence of a base and Pd(0) catalyst so as to form a substituted alkene. Kaufmann et al. showed that the Heck reaction carried out in presence of ILs such as tetra-alkyl ammonium and phosphonium salts without the phosphine ligands, resulted in high yields of product. They attributed the activity to the stabilizing effect of ammonium and phosphonium salts on Pd(0) species. Carmichael et al. used ionic liquids containing either A,A -dialkylimidazolium and A-alkylpyridinium cations with anions such as halide, hexafluorophosphate or tetrafiuoroborate to carry out reactions of aryl halide and benzoic anhydride with ethyl and butyl acrylates in presence of Pd catalyst. An example of iodobenzene reacting with ethyl acrylate to give trans-et vy cinnamate is shown in Scheme 14. 

The Heck reactions depicted so far all involve the coupling of halopyridines and other olefins. The alternate approach, coupling of a vinylpyridine with an aryl halide is also feasible, although less commonly employed. 4-Vinylpyridine was coupled successfully with diethyl 4-bromobenzylphosphonate (7.50.) in the presence of a highly active catalyst system consisting of palladium acetate and tn-o-tolylphosphine to give the desired product in 89% yield, which was used for grafting the pyridine moiety onto metal oxides.70... 

The palladium-catalyzed C-C coupling between aryl halides or vinyl halides and activated alkenes in the presence of a base is referred as the Heck Reaction . Recent developments in the catalysts and reaction conditions have resulted in a much broader range of donors and acceptors being amenable to the Heck Reaction. 

The arylation of activated alkenes with aryl halides in the presence of base was discovered by R. F. Heck in 1971 and is now one of the standard methods for C—C bond formation. The catalysts are mostly palladium or nickel phosphine complexes, which react via a succession of oxidative addition and insertion reactions, as shown in the following simplified cycle ... 

Both complexes were used in the Heck reaction between activated aryl halides (Br, Cl) and styrene. The C,N,C pincer complex was by far more active than the C,C,C counterpart and produced a higher ratio of trani-stilbene with a significantly greater yield... 

The transformation that has come to be known as the Heck reaction is broadly defined as the palladium(O)-mediated coupling of an aryl or vinyl halide or triflate with an alkene. The basic mechanism for the Heck reaction of aryl halides or trifiates (as outlined in more detail in the Key Chemistry), involves initial oxidative addition of the chiral palladium(O) catalyst to afford a a-arylpalladium(II) complex. Coordination of an alkene and subsequent carbon-carbon bond formation by syn insertion provide a a-alkylpalladium(II) intermediate, which readily undergoes P-hydride elimination to release the alkene product. Finally, the hydridopalladium(II) complex has to be converted into the active palladium(O) catalyst to complete the catalytic cycle. 

The influence of high pressure on the Heck reactions of selected alkenyl and aryl halides, respectively, i.e., 1-iodocyclohex-l-ene, iodobenzene, bromobenzene, with methyl acrylate has been investigated and the activation parameters of these reactions determined [142], Two different catalyst cocktails were used in this study, the classical system (Pd(OAc)2, NEtg, PPhg) and the one reported by Herrmann, Beller and others [16] (la). The temperature-dependent and the pressure-dependent rate coefficients both follow the order PhI/Pd(OAc)2 > 1-iodocyclohexene/Pd(OAc)2 > Phl/la > PhBr/la and the activation enthalpies as well as the activation entropies exhibit the trend 1-iodocyclohexene/Pd(OA)2 < Phl/Pd(OAc)2 < Phl/la < PhBr/la. The absolute values of the activation volumes, which were ascertained from the pressure-dependent rate coefficients, increase as follows l-iodocyclohexene/Pd(OAc)2 < PhI/Pd(OAc)2 Phl/la < PhBr/la. Under high pressure, the lifetime of the active palladium catalyst and thereby the turnover numbers are greatly enhanced [88]. 

---