Metal Mizoroki-Heck reaction

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). 

Other successful examples of catalysts containing NHC ligands are found in palladium- and nickel-catalyzed carbon-carbon bond formations. The catalyst development with these metals has focused in particular on Heck-type reactions, especially the Mizoroki-Heck reaction itself [Eq. (42)] and various cross coupling reactions [Eq. (43)], e.g., the Suzuki-Miyaura reaction ([M] = and the Kumada-Corriu reaction ([M] = MgBr). " Related reactions like the Sonogashira coupling [Eq. (44)]326-329 Buchwald-... 

The enantioselective spiro ring construction is an important issue because many natural compounds have chiral spiro centers [103,104]. Pd catalyses of Spiro cyclizations have been reported by asymmetric intramolecular Mizoroki-Heck reactions [105,106]. In spite of a similar potential, transition metal-catalyzed ene-type carbocyclization has never been applied to asymmetric spiro cyclizations [107-110]. 

Base NR 3, MOAc (M = alkaline metal), K3PO4... Scheme 5.7 Mizoroki-Heck reaction. 

Table 5.5 Mizoroki-Heck reactions based on the use of Pd supported on metal oxide catalysts. 

Efforts have been made to explain the high rate acceleration of Mizoroki-Heck reactions in ionic liquids. The formation of the dialkylimidazol-2-ylidene palladium complex under conditions similar to those employed for the Mizoroki-Heck reaction has been studied. The C2-H proton of the imidazolium cation exhibits high acidity and can be deprotonated to form a carbene species, behaving as a good ligand for transition metals. Therefore, in the presence of a palladium salt and a base, [bmim][Br] formed the dimeric carbene complex 89, which further evolved to the monomeric c/x-90 and trans-9Q complexes. Each of these exists as an anti and a syn rotamer owing to the sterically demanding (V-alkyl substituents (Scheme 35 only the anti-90 rotamers are represented). 

The Suzuki-Miyaura cross-coupling reaction is a standard method for carbon-carbon bond formation between an aryl halide or triflate and a boronic acid derivative, catalyzed by a palladium-metal complex. As with the Mizoroki-Heck reaction, this cross-coupling reaction has been developed in ionic liquids in order to recycle and reuse the catalyst. In 2000, the first cross-coupling of a halide derivative with phenylboronic acid in [bmim] [BF4] was described. As expected, the reaction proceeded much faster with bromobenzene and iodobenzene, whereas almost no biphenyl 91 was obtained using the chloride derivative (Scheme 36). The ionic liquid allowed the reactivity to be increased, with a turnover number between 72 and 78. Furthermore, the catalyst could be reused repeatedly without loss of activity, even when the reaction was performed under air. Cross-coupling with chlorobenzene was later achieved - although with only a moderate yield (42%) - using ultrasound activation. 

It is important to stress that, in most other transition-metal-catalysed reactions, the control of catalytic processes is achieved through the choice, refinement and adjustment of stable ancillary ligands remaining in the coordination shell throughout all steps of the catalytic cycle. In those areas, the design of ligands is the essence of the art. The Mizoroki-Heck reaction, on the other hand, is very reluctant towards the control of catalytic activity via ancillary ligands. 

The involvement of very small particles of palladium metal ranging in size from a few to hundreds of nanometres in Mizoroki-Heck reactions, as well as in other palladium-catalysed reactions, is well-known. 

Scenario 4. Nanoparticles are formed during the reaction initiated by soluble palladium precatalysts. Our experience in phosphine-free (mostly aqueous) systems led us at an early stage to hypothesize that these protocols go hand in hand with formation of palladium sols [4, 83]. Since 2000, the observation of palladium sols in Mizoroki-Heck reactions has become ubiquitous. So, if one were to decide to compile a list of references that mention the formation of sols, that list would practically coincide with a list of references which deal with the development of new phosphine-free catalytic systems. In fact, the idea that it is the dispersed palladium metal which catalyses (or, more correctly, serves as precatalyst) the Mizoroki-Heck reaction should be traced back to the seminal pubUcations by Heck in 1972 [2], who clearly attiibuted catalytic activity in a phosphine-free catalytic system to palladium metal formed by reduction of Pd(OAc)2 by the alkene or the amine. This idea fell into oblivion until its rediscovery in the course of a general interest in nanoscale systems in the late 1990s. 

Since then, statements that palladium nanoparticles or sols are true catalysts in a given catalytic system have become not infrequent. Indeed, in many cases it is clearly seen that, after the addition of precatalyst, a brownish-grey colour of palladium sol appears immediately and hansmission electron microscope measurements reveal the nanoparticles of metal. From the discussion of various preformed sols in Mizoroki-Heck reactions (Scenarios 1-3), it becomes evident that palladium nanoparticles display rather hmited activity with respect to scope, TONs and TOF values. On the other hand, in the discussion of various SRPCs, we see many examples of high activity and quite extended scope of substrates reaching to aryl chlorides. 

In a given reacting system, usually not all palladium is engaged in the catalytic process. The amount engaged depends on kinetics and the concentrations of reactants. The excess of palladium exists either in palladium(II) (102) or as palladium(O) (36) both are unstable under the conditions of Mizoroki-Heck reactions and should be protected (Scheme 2.23) palladium(II) (102) is unstable towards reduction if not protected in the form of an SRPC (102 103), palladium(0) (36) is unstable towards clusterization and growth of metal particles (36 —101 —70) and is protected by additives or components of reaction media in the form of anionic complexes 100 [36,84]. If we consider the reversibihty of formation... 

Evidence for the intermediacy of a-arylpalladium acetate complexes c was provided by the isolation of their trinuclear dialkyl sulfide adducts [11]. The two following steps, insertion of the alkene 4 and )8-hydride elimination, correspond to the classical Mizoroki-Heck reaction pathway. The resulting palladium(0) species, which is likely to be stabilized in the form of a hydridopalladium carboxylate e, is then reoxidized by molecular oxygen to the initial palladium(II) acetate (a) under liberation of water. The precise mechanism of this reoxidation is not yet fully understood, but it seems that, at elevated oxygen pressures, it is not rate-determining even in the absence of promoters. Mechanistic studies by Jacobs and coworkers [10] indicate that the beneficial effect of adding transition metal salts, originally intended to facilitate this oxidation step, in fact arises from an acceleration... 

In domino transition-metal-catalysed processes, cross-coupling reactions can also be nsed as the starting transformation. Most often, Suzuki, Stille and Sonogashira reactions are employed in this context. They can be combined with a Mizoroki-Heck reaction and other palladium-catalysed transformations. 

For recent reviews on the Mizoroki-Heck reaction, see (a) Alonso, F., Beletskaya, I.P. and Yus, M. (2005) Non-conventional methodologies for transition-metal catalysed carbon-carbon coupling a critical overview. Parti theHeckie ction.Tetrahedron,61,11771-835 (b) Erase, S. and de Meijere, A. (2004) Cross-couphng of organyl halides with alkenes the Heck reaction, in... 

Mizoroki-Heck Reactions with Metals Other than Palladium... 

Gedanken and coworkers [194] exploited power ultrasound to generate in situ amorphous-carbon-activated palladium metallic clusters that proved to be a catalyst for Mizoroki-Heck reactions (without phosphine ligands) of bromobenzene and styrene (yield to an appreciable extent of 30%). The catalyst is stable in most organic solvents, without showing any palladium powder segregation, even after heating them to 400 °C. 

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