Palladium catalysts Heck reaction

The term Heck reaction summarizes catalytic C-C-coupling processes, such that a vinylic hydrogen is replaced by a vinyl, aryl, or benzyl group, with the latter being introduced from a halide or related precursor compound (cf. eq. (3)) [9 a, 14-16]. Therefore, the final step of product formation is the elimination of a hydrogen halide, and a base is thus required to bind the acid. The olefinic (vinylic) double bond is retained throughout the Heck reaction. Palladium is practically the only catalyst metal used, in the form of certain Pd and Pd" salts or complexes normally 1-5 mol % of catalyst is administered. 

A Biffis, M Zecca, M Basato. Metallic Palladium in the Heck Reaction Active Catalyst or Convenient Precursor Eur J Inorg Chem 1131-1133,2001. 

Heteroaryl halides (or phenolic triflates) take part in palladium-catalysed couplings with a wide range of organometallic and anionic reagents in contrast to the Heck reaction, the catalyst is often provided as preformed Pd(0), in a complex such as tetrakis(triphenylphosphine)palladium(0), Pd(Ph3P)4. 

Apart from their high catalytic activity in the Heck reaction, palladium pincer-catalyzed C-C cross-coupling reactions are of particular interest from mechanistic points of view. While classical Pd°/Pd cycles and mechanisms in which the palladium center of pincer-type cross-coupling catalysts does not change its oxidation state and has in most cases been excluded to be operative [23], considerable... 

We will begin, as in the Suzuki coupling reaction, with the Pd(0) catalyst. In the Heck reaction, the catalyst forms in the reaction mixture from palladium(II) acetate in the presence of triphenylphosphine. 

Heck olefmation [7] is considered as an exceptionally resourceful process among the palladimn catalyzed reactions and has been successfully employed as a powerful tool in industrial manufacturing of pharmaceuticals. In 1972, [8] Heck employed palladium catalyst in the preparation of stilbene from io-dobeneze and industrial styrene. Over the years, advances were made on Heck reaction in a perspective with ligand systems, providing sterocontrol and practically adaptable route to quaternary carbon centers. The Heck reaction includes palladimn catalyzed coupling of sp hybridized centers, for example. 

Heterogeneous catalyst are also effective for the preparation of polymers by the Heck reaction. Palladium-graphite (Pd-Gr) was used for the synthesis of polycinnamamide from N,N -(3,4-oxydiphenylene)bis(acrylamide) and bis(4-iodophenyl) ether (equation 63). No phosphine or bipyridyl ligand was necessary. The presence of tri-< -tolylphosphine actually inhibited the reaction. The molecular weight Mw increased gradually to approximately 9 x 10 over 20 hours and then remained constant (204). 

The best procedures for 3-vinylation or 3-arylation of the indole ring involve palladium intermediates. Vinylations can be done by Heck reactions starting with 3-halo or 3-sulfonyloxyindoles. Under the standard conditions the active catalyst is a Pd(0) species which reacts with the indole by oxidative addition. A major con.sideration is the stability of the 3-halo or 3-sulfonyloxyindoles and usually an EW substituent is required on nitrogen. The range of alkenes which have been used successfully is quite broad and includes examples with both ER and EW substituents. Examples are given in Table 11.3. An alkene which has received special attention is methyl a-acetamidoacrylate which is useful for introduction of the tryptophan side-chain. This reaction will be discussed further in Chapter 13. 

The original Sonogashira reaction uses copper(l) iodide as a co-catalyst, which converts the alkyne in situ into a copper acetylide. In a subsequent transmeta-lation reaction, the copper is replaced by the palladium complex. The reaction mechanism, with respect to the catalytic cycle, largely corresponds to the Heck reaction.Besides the usual aryl and vinyl halides, i.e. bromides and iodides, trifluoromethanesulfonates (triflates) may be employed. The Sonogashira reaction is well-suited for the synthesis of unsymmetrical bis-2xy ethynes, e.g. 23, which can be prepared as outlined in the following scheme, in a one-pot reaction by applying the so-called sila-Sonogashira reaction ... 

Palladium-catalyzed carbon-carbon bond forming reactions like the Suzuki reac-tion as well as the Heck reaction and the Stille reaction, have in recent years gained increased importance in synthetic organic chemistry. In case of the Suzuki reaction, an organoboron compound—usually a boronic acid—is reacted with an aryl (or alkenyl, or alkynyl) halide in the presence of a palladium catalyst. 

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. 

Palladium(II) complexes provide convenient access into this class of catalysts. Some examples of complexes which have been found to be successful catalysts are shown in Scheme 11. They were able to get reasonable turnover numbers in the Heck reaction of aryl bromides and even aryl chlorides [22,190-195]. Mechanistic studies concentrated on the Heck reaction [195] or separated steps like the oxidative addition and reductive elimination [196-199]. Computational studies by DFT calculations indicated that the mechanism for NHC complexes is most likely the same as that for phosphine ligands [169], but also in this case there is a need for more data before a definitive answer can be given on the mechanism. 

The coupling reaction of aryl-alkenyl halides with alkenes in the presence of a palladium catalyst and a base is known as the Heck coupling (Scheme 9.4).6 Since the early 1980s, this type of coupling reaction has been used for die syndiesis of poly(arylenevinylene) and related polymers by polymerization of AB- or AA/BB-type of monomers (Scheme 9.5).7... 

Palladium metal catalysts supported on organic resins containing tertiary amino, cyano, carboxyl, and pyridyl groups have been recently investigated in some Heck reactions, such as the coupling of iodobenzene with methyl acrylate and methyl vinyl ether (Scheme 11) [31]. 

In 2004, Molander et al. developed another type of chiral sulfur-containing ligands for the intermolecular Heck reaction. Thus, their corresponding novel cyclopropane-based phosphorus/sulfur palladium complexes proved to be active as catalysts for the reaction between phenyltriflate and dihydrofuran, providing at high temperature a mixture of the expected product and its iso-merised analogue (Scheme 7.7). The major isomer C was obtained with a maximum enantioseleetivity of 63% ee. 

To assess the utility of this resin, we chose to employ it in the evaluation of the heterogeneity of a commercial polymer-entrapped Pd(OAc)2 precatalyst, Pd-EnCat, also sold by Reaxa. This precatalyst was designed with the goal of providing a heterogeneous catalyst that would allow simple removal of palladium from reactions (24-26). PVPy and QTU were first used as poisons in the Heck reaction of iodobenzene and n-butyl acrylate in DMF using PdfC as the palladium... 

Palladium-catalyzed carbon-carbon cross-coupling reactions are among the best studied reactions in recent decades since their discovery [102, 127-130], These processes involve molecular Pd complexes, and also palladium salts and ligand-free approaches, where palladium(O) species act as catalytically active species [131-135]. For example, the Heck reaction with aryl iodides or bromides is promoted by a plethora of Pd(II) and Pd(0) sources [128, 130], At least in the case of ligand-free palladium sources, the involvement of soluble Pd NPs as a reservoir for catalytically active species seems very plausible [136-138], Noteworthy, it is generally accepted that the true catalyst in the reactions catalyzed by Pd(0) NPs is probably molecular zerovalent species detached from the NP surface that enter the main catalytic cycle and subsequently agglomerate as N Ps or even as bulk metal. 

Supported ultra small palladium on magnetic nanopartides used as catalysts for Suzuki cross-coupling and Heck reactions. Advanced Synthesis and Catalysis, 349, 1917-1922. 

Supported palladium catalysts for fine chemicals synthesis are generally based on metal particles. Nevertheless, a few examples are reported of the use of supported complexes as catalysts for the Heck reaction (see Chapter 9.6). Nearly all the possible immobilization methods have been tested for this reaction. 

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