Arylation reactions arylations Mizoroki-Heck reaction

Scheme 1.23. Mechanism of palladium-catalyzed arylation of olefins (Mizoroki-Heck reaction).

Under the same experimental conditions, same alkene, ligand and base, the reactivity order of aryl halides in Mizoroki-Heck reactions is usually Arl > ArBr ArCl, suggesting... 

Scheme 6.1 Example of an intramolecular aryl-aryl Mizoroki-Heck reaction proceeding via a palladacycle.

The insertion of olefins into metal-alkyl linkages is the cornerstone of the preparation of polyolefins and a-olefins, and the insertions of olefins into metal-aryl bonds is one step of a common class of palladium-catalyzed coupling reactions (the Mizoroki-Heck reaction). The insertions of olefins into early-metal-alkyl bonds is part of the so-called Cos-see mechanism of Ziegler-Natta olefin polymerization and of Cramer s mechanism for olefin dimerization. The following sections present examples of these insertion reactions and information on the mechanisms of this type of C-C bond formation. 

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). 

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). 

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...

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... 

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... 

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]. 

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... 

While the PNP dimer was an efficient catalyst for the ort/toalkylation/ Mizoroki-Heck reaction, the practicality of the transformation is lessened by the fact that the PNP dimer is not commercially available, and can be quite difficult to prepare. Thus, Catellani adapted the reaction conditions to include commercially available and air-stable Pd(OAc)2 as the catalyst source [46], Under these conditions, the ortho-u kylation/Mizoroki-I Ieck coupling of aryl iodides containing a pre-existing ortho substituent could be carried out. The reaction required higher temperatures, and the addition of KOAc to promote the carbopalladation of norbomene [47] and encourage the o/t/zo-alkylation pathway vs a direct Mizoroki-Heck coupling. 

It is worth noting that the diastereoselectivity of these direct arylations turned out to be complementary to palladium-catalyzed Mizoroki-Heck reactions (Scheme 25). 

Combination of the oxidative addition of aryl halide with olefin insertion followed by -hydrogen elimination provides a useful olefin arylation process catalyzed by a palladium complex (Mizoroki-Heck reaction) [63-65]. The essential part of the catalytic cycle is shown in Scheme 1.23. 

Attention has been paid to P-C bond cleavage of organophosphorus compounds not only for synthetic application but also for understanding of a deactivation process in Mizoroki-Heck reaction [161], Migita-Kosugi-Stille coupling [162], or hydroformylation [163]. Simultaneous arylation originated from triarylphosphine is sometimes involved (Eq. 3.42). 

A non-covalent immobilization of Heck catalyst on silica (SILP concept) has been realized by Hagiwara et al. [217]. They used a silica surface, supported with Pd(OAc)2 dissolved in [BMIM][PFe]. This catalyst was appUed to the Mizoroki-Heck reaction of aryl halides with acrylate without a ligand in n-dodecane as solvent. It was six times reused and the overall TON reached 68 400 (for more details see Section 5.6). 

In the above example, CO2 is added after the reaction to facilitate only the separation. It can, however, be advantageous to add compressed CO2 during the reaction stage, even if it cannot dissolve the catalyst. Ikariya and co-workers reported an example of enhanced product selectivity in the Mizoroki-Heck reaction of ethylene with aryl halides under C02-liquid biphasic conditions [3]. In such reactions, the initially formed styrene derivatives can react with another aryl halide molecule to form stilbenes and 1,1-diphenylethylenes (Scheme 1). 

The Mizoroki-Heck reaction, a palladium-catalyzed coupling of olefins with aryl or vinyl halides/triflates, is a powerful method for carbon-carbon bond formation. " " High efficiency is usually obtained only by starting from expensive aryl iodide (or bromide) or by using a fairly large amount of catalyst. Improvement of the catalytic activity as well as recovery and recycling of the catalyst is needed. 

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. 

Various cyclic compounds can be prepared by the reaction of ketones with bifunctional aryl halides. The jS-naphthol derivative 52 was obtained by a-arylation of dibenzyl ketone (14) with o-bromobenzaldehyde derivative 51, followed by aldol condensation [38], Also the indole derivative 54 was synthesized by the reaction of cyclohexanone with 2-iodoaniline (53). Formation of 54 may be explained by enamine formation at first, followed by intramolecular Mizoroki-Heck reaction, rather than via a-arylation [39],... 

By the reaction of a,-unsaturated carbonyl compounds with the dibromide 55, cyclization occurs by a-arylation, followed by intramolecular Mizoroki-Heck reaction. For example, reaction of verbenone (61) with 55 using PPh3 generates 62 by y-arylation of 61, and subsequent intramolecular Mizoroki-Heck reaction affords the indane 63. The benzocyclobutane 67 was obtained unexpectedly... 

The palladium-catalysed Mizoroki-Heck reaction is the most efficient route for the vinyla-tion of aryl/vinyl halides or triflates. This reaction, in which a C—C bond is formed, proceeds in the presence of a base (Scheme 1.1) [1, 2], Nonconjugated alkenes are formed in reactions involving cyclic alkenes (Scheme 1.2) [le, 2a,c,e,g] or in intramolecular reactions (Scheme 1.3) [2b,d-g] with creation of stereogenic centres. Asymmetric Mizoroki-Heck reactions may be performed in the presence of a chiral ligand [2], The Mizoroki-Heck reaction has been intensively developed from a synthetic and mechanistic point of view, as expressed by the impressive number of reviews and book chapters [1,2]. 

These pioneering studies by Heck have opened the way to a new reaction later called the Mizoroki-Heck reaction (Scheme 1.1). In 1971, Mizoroki et al. reported preliminary results on the PdCh-catalysed arylation of alkenes by iodobenzene in the presence of potassium acetate as base (Scheme 1.5) [4]. No new contribution to the mechanism was proposed, except that palladium particles, formed in situ in the reaction or deliberately added, were suggested to be the active catalyst [4]. 

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