Heck reaction, Mizoroki

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). 

Scheme 6.5 Catalytic cycle for the Mizoroki-Heck reaction...

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). 

Other classes of complexes that have been studied in depth in the Mizoroki-Heck reaction are those having a bidentate ligand containing both a NHC and a phosphine. The development of these structures was encouraged by early theoretical work from Rosch, who calculated that such ligands should be promising catalysts for this... 

As mentioned in the discussion of the reaction mechanism for this transformation, the active species is a dicoordinate Pd(0) complex, and it is unclear whether an associative or a dissociative process is operative for oxidative addition. In this context, different NHC complexes containing only one carbene ligand have been tested in the Mizoroki-Heck reaction. The most successful are those prepared by Beller, which were able to perform the Mizoroki-Heck reaction of non-activated aryl chlorides with moderate to good yields in ionic liquids (Scheme 6.13). The same compounds have also been applied to the Mizoroki-Heck reaction of aryldiazonium... 

Scheme 6.13 Mizoroki-Heck reaction of non-activated aryl chlorides and diazo compounds using Seller s catalytic systems...

For example, the Mizoroki-Heck reaction consists of the reaction of an unsaturated halide with alkenes under basic conditions catalyzed by a Pd source dissolved in... 

Silver salts are also employed to create more effective chiral catalysts by exchange of counter anions. For example, in the Mizoroki-Heck reaction of alkenyl or aryl halides, silver salts are employed to form effective chiral Pd intermediates by abstracting a halide group from the Pd11 precursor species (Scheme 53).227,228... 

Oestreich M (2007) Directed Mizoroki-Heck Reactions. 24 169-192 Ohler E, see Mulzer J (2004) 13 269-366... 

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-... 

In the Mizoroki-Heck reaction aryl bromides and activated aryl chlorides could be employed with moderate turnovers. This holds true for both the complexes of monodentate such as 60 as well as the complexes of chelating ones... 

Application of the complexes 63 in the Mizoroki-Heck reaction did not reveal higher activity than the previously examined palladium(II) complexes. However, in the Suzuki-Miyaura reaction, a drastically increased activity was observed with complex 63. Catalysis starts without a measurable induction period at mild temperatures accompanied by an extraordinarily high turnover frequency (TOF) of 552 [mol product x mol Pd x h ] at the start of the reaction for the coupling of p-chlorotoluene and phenyl boronic acid [Eq. (48)]. ... 

The Mizoroki-Heck reaction in liquid imidazolium salts as the solvent is a special case of an in situ system Under the reaction conditions NHC complexes of palladium are formed as the active catalyst from the solvent and the ligand-free palladium precursor. In general, ionic liquids are novel reaction media for homogeneous catalysis. They allow easy separation of product and catalyst after the reaction. ... 

Scheme 2 Mizoroki-Heck reactions performed in the ionic liquid 4b...

Rahman et al used a novel high throughput reactor to produce substituted acetylene by the Sonogashira reaction and the Mizoroki-Heck reaction in series using the same IL in a one-pot operation. The products were obtained in good yields and the contamination from the previous reaction was not carried forward to the next. 

Mizoroki-Heck reaction, for cross-coupling polymerization,... 

Interestingly, it then took almost 10 years until the chemical community became fully aware of the enormous synthetic utility of this transformation. Since then, the Mizoroki-Heck reaction (or simply Heck reaction) has become one of the most popular C-C bond-forming reactions, accounting for several thousand publications overall. 

Bulky ligands as above have also proved to be effective in other palladium-catalyzed reactions of aryl halides, e.g., amination [16-19], Suzuki-Miyaura reaction [20-22], Mizoroki-Heck reaction [23, 24], Migita-Kosugi-Stille reaction [25], and aryloxylation and alkoxylation [26-28] as well as the reaction with various carbon nucleophiles as described below. The ligands are considered to enhance both the initial oxidative addition of aryl halides and the reductive elimination of products [29, 30]. The effectiveness of the commercially available simple ligand, P(f-Bu)3, was first described for the amination by Nishiyama et al. [16]. 

M. Oestreich (Ed.), The Mizoroki-Heck Reaction, John Wiley Sons, Ltd, Chichester, 2009. 

Alkenyl, Alkynyl, Aryl and Heteroaryl Acids. Treatment of readily accessible (E)- and (Z)-alkyl and aryl substituted vinyl boronates (196) with triethyl phosphite in the presence of lead diacetate results in their stereospecific transformation into (E)- and (Z)-vinylphosphonates (197) (Scheme 53). ° Palladium acetate catalysed Mizoroki-Heck reaction of arylboronic acids (198) with diethyl vinylphosphonates (199) is an effective synthetic approach to... 

Palladium-catalyzed arylation and vinylation of alkene is referred to as the Mizoroki-Heck reaction and is one of the most widely used Pd(0)-catalyzed C-C bond formations in organic synthesis. However, the reaction has not been extensively employed for C-glycosylation [96]. The example shown in O Scheme 67 outlines the reaction of iodopyridine and furanose gly-cal for the synthesis of C-nucleoside [97]. The mechanism began with the oxidative addition of iodopyridine to Pd(0) catalyst, and the resulting organo-palladium species was inserted by... 

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