Heck reaction active catalysts

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

Influence of Pd dispersion and reduction degree. The catalytic results summarized in Table 1 illustrate that all parameters investigated are of importance for the activity in the Heck reaction. All catalysts show conversions between 45 and 90 % of bromobenzene (after 20 hours) and high selectivities to -stilbene (> 90 %) no dehalogenation of bromobenzene occuned in any experiment (Table 1). 

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. 

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. 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

The Pd-catalysed Heck reaction performed with thiourea as the Ugand exhibit good activities for some catalysts. As for carbene ligands [104], steric hindrance improves catalytic results. Thus, thioureas wearing bulky substituents afford the formation of air- and moisture-stable Pd complexes [105]. For example, the catalyst obtained with 2mol% Pd(dba)2 and Ar,M -dimesitylene-ethylene thiourea (Scheme 24) was still active even after 2 months in an air atmosphere. 

Regarding bis-NHC chelating ligands, several structures that differ in the motifs used for the enlargement of the tether have been proposed as catalysts for the Mizoroki-Heck reaction. They range from non-functionalised aliphatic chains [23-25] to phenyl [26], biphenyl [27], binaphthyls [28] and to chains containing additional coordination positions like ethers [29], amines [30], and pyridines in an evolution towards pincer complexes [31-35], In most cases, the activity of aryl bromides in Mizoroki-Heck transformations was demonstrated to be from moderate to high, while the activation of chlorides was non-existent or poor (Scheme 6.7). 

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. 

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. 

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. 

Figure 23 Preparation and activity in Heck reaction of glass bead/palladium catalysts.

Although only a dozen known metal complexes were tested in this manner, proof of principle was demonstrated. The test revealed Wilkinson s catalyst to be the most active hydrosilylating agent, its use in this type of reaction being known. However, the study also led to the discovery that a palladacycle, [Pd (o-tolyl)2PC6H4 (OAc)]2, which is usually considered to be potent in Heck reactions, is also an excellent hydrosilylation catalyst.37,38 Control experiments showed that the relative order of catalyst activity is the same when conventional substrates are used in place of the dyes (8). 

A silver(i) complex having the heterosubstituted 3-methyl-l-(2-pyridylmethyl)imidazol-2-ylidene ligand, [Ag(carbene)2] [I/Agl2] 37, was reported, which was further reacted to give a series of palladium(n) carbene complexes that were demonstrated to be active catalysts toward Heck, Suzuki, and Sonogashira coupling reactions.87... 

Greater durability of the colloidal Pd/C catalysts was also observed in this case. The catalytic activity was found to have declined much less than a conventionally manufactured Pd/C catalyst after recycling both catalysts 25 times under similar conditions. Obviously, the lipophilic (Oct)4NCl surfactant layer prevents the colloid particles from coagulating and being poisoned in the alkaline aqueous reaction medium. Shape-selective hydrocarbon oxidation catalysts have been described, where active Pt colloid particles are present exclusively in the pores of ultramicroscopic tungsten heteropoly compounds [162], Phosphine-free Suzuki and Heck reactions involving iodo-, bromo-or activated chloroatoms were performed catalytically with ammonium salt- or poly(vinylpyrroli-done)-stabilized palladium or palladium nickel colloids (Equation 3.9) [162, 163],... 

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. 

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