Solid support catalysts Heck reaction

A further evidence on the acceleration enjoyed by a typical Pd-catalysed reaction, the Heck reaction, in an ionic phase ( V-mcthyl-Y.Y. V.-trioctylammonium chloride or Aliquat 336) is found in a triphasic protocol developed by Tundo and coworkers. 7b.The arylation of electron poor olefins is catalysed by palladium supported on charcoal (Pd/C) and is carried out in the heterogeneous isooctane/Aliquat 336/water system (Figure 27). Under this multiphasic condition, Aliquat 336 forms a third liquid phase between the organic and the aqueous phase that traps the catalyst. The use of phosphines is not necessary. As a matter of fact, Aliquat 336 incorporates the solid-supported catalyst and ensures an efficient mass transfer between the bulk phases resulting in an increase of the reaction rate of an order of magnitude compared to the reaction in the absence of the ionic liquid. A determing role is played by the base while I LN drives the reaction towards the formation of ethyl cinnamate, reaction carried out in the presence of KOH lead to formation of Ullmann dimerisation products. 

There is evidence in some cases that C-C coupling by heterogeneous catalysts also occurs by soluble metal colloids (or smaller species) leached from solid supports, such as silica. In the 1970s, the catalytic activity of palladium black for C-C coupling was already reported by Mizoroki et al. [11,12], Various examples of Heck reactions with heterogeneous catalysts have been reported since then [13]. Therefore, while heterogeneous catalysts are not the main focus of this section, they are addressed where appropriate. 

The application of microwaves in Mizoroki-Heck reactions is well documented. There are several overviews of this topic [12, 200-204]. During the last year, new trends in the Mizoroki-Heck reaction conducted under microwave irradiation are the application of solid-supported catalysts and the combination with other activation methods for example,... 

Applications of Suzuki and Heck cross-coupling reactions were adopted by Gallop and coworkers [131] to prepare diverse biaryl- and styryl-substituted (3-lactams on solid support. The catalyst system, [PdCl2(dppf)]-TEA, was found to be efficient to promote C-C bond formation around a (3-lactam template (Schemes 26 and 27). 

Most recently, the test has been applied to examination of the mechanism of a heterogeneous Heck reaction, promoted by Pd on alumina [25]. In the presence of the solid catalyst, 4-iodobenzamide coupled efficiently with butyl acrylate yielding the cinnamate, and it was suspected that the catalytic agent was a soluble form of palladium released from and then recaptured by the alumina support. To test this, the amide was attached to a commercially available resin with suitable functionality, and the supported amide (15 in Scheme 9.10) was allowed to react with the acrylate and Pd on alumina. The same product, identified after release from the polymer by TFA treatment, was formed, and further experiments were able to narrow down the form of the soluble catalysing palladium species. 

Another particularly attractive substrate class for industrial Heck reactions are the arenediazonium salts, because of to their ready availability from anilines. Matsuda et al. found that for these highly reactive compounds, ligand-free Pd(dba)2 suffices as catalyst [32], Even palladium catalysts on solid supports are highly effective [33], The diazotization of an aniline 25 and its olefination can be performed separately, or in one pot (Scheme 12). 

For each of the immobilized catalysts, the reaction kinetics were slower for each recycle run relative to the fresh catalyst for the Mizoroki-Heck reaction of iodoben-zene with n-butyl acrylate. These resnlts indicated that it was likely some catalyst had deactivated or some palladinm had leached from the snpported catalyst. The use of insoluble supported catalysts allowed for the utilization of fdtration tests to provide additional insight into the catalyst stability. The filtration tests were conducted by filtering off the snpported catalyst and analyzing the remaining solntion for catalytic activity. These filtered solntions continned to show conversion after removal of the solid catalyst, indicating that at least some portion of the reactivity conld be attribnted to active palladinm that had leached from the snpported catalyst. 

Since the renaissance of solid-phase organic chemistry in 1992, carbon-carbon bond formation reactions on solid support have probably been the best studied reactions. Many different facets of the Suzuki, Heck and Stille reactions have been evaluated. The influence of linkers, catalyst, solvents, microwave, polymer-bound aryl halides or polymer-bound arylboronic acids (or stannanes) have been studied in detail. 

Tliere are some excellenl reviews on the use of solid bases in Fine C hemistry 9. 14, 16, 17, 175, 184]. In this section we will comment on some of those base-catalyzed processes. For simplicity purposes, we will not refer to bifunclional catalysis (i.e, metal phase solid base) but only to catalysis by bases. Tlicrefore, for instance, we will not mention on reactions as important as Heck-, Suzuki-, Sonogashira- and Slille-typc ones (248, 249). Similarly, when talking on selective hydrogenation of cilral, wx will not comment on the use of metal-supported catalysts 1250-252], but only on solid bases. 

With the aim of preparing elaborate molecules in the solid phase, chemists are searching for robust and versatile methods to assemble complex carbon frameworks in the insoluble support. One of the predominant sequences for creating carbon-carbon bonds in the solid phase is Pd-catalysed coupling reactions. The Heck reaction, for instance, is a convenient way to diversify activated alkenes (Scheme 5a). This coupling involves an arene with iodide, bromide, triflate or diazonium on one hand, and an alkene (generally electron poor) on the other, in the presence of a catalyst and a base. 

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