Mizoroki-Heck reaction ligands

All of these reactions involve transition metals such as palladium, copper, and ruthenium, usually in complex with certain types of ligands. After we see the practical applications of these reactions for carbon—carbon bond formation, we shall consider some general aspects of transition metal complex structure and representative steps in the mechanisms of transition metal—catalyzed reactions. We shall consider as specific examples the mechanism for a transition metal—catalyzed hydrogenation using a rhodium complex called Wilkinsons catalyst, and the mechanism for the Heck—Mizoroki reaction. 

Other types of ligands have been used. Of note are the benzotriazole ligands developed by Verma et al. [49]. These ligands have been applied in a variety of cross-coupling reactions, including the Heck-Mizoroki reaction (Figure 1.8). 

Figure 1.8 Heck-Mizoroki reactions using the benzotriazole ligand of Verma et al. [49].

As tdready mentioned above, the intermolecular asymmetric catalytic Heck-Mizoroki reaction was first reported by Hayashi [12d,e, 13,15] and since then various groups have made contributions in this area. Of note was the report in 2009 by Guiry s group [57] who achieved enantioselectivities of up to 96% ee, using novel HetPHOX ligands 7a—f for the benchmark reaction with cydohexenyl, phenyl, and 2-naphthyl triflate with 2,3-dihydrofuran (Scheme 1.21). The problem with this reaction is the extensive reaction time (7 days) at the elevated temperature of 80 °C. The kinetic product 8 (or... 

Scheme 1.21 Asymmetric Heck-Mizoroki reactions using HetPHOX ligands as reported by Fitzpartick et al. [57],...

In 2008, Portnoy s group [76] reported the use of bidentate phosphine ligands immobilized to Wang polystyrene beads with polyether dendron spacers, which formed active catalysts for the Heck-Mizoroki reaction when treated with Pd(dba)2 (Figure 1.21). Two series of immobilized palladium catalysts were investigated, one series termed Gn-I was prepared by incubating the... 

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-... 

Pd-complexes have also been impregnated on an amorphous silica support vnth the aid of a solution containing [BM IMjlPFej dissolved in tetrahydrofuran and these systems were applied as highly efficient catalysts for promoting Mizoroki-Heck coupling reactions between various aryl halides and cyclohexyl acrylate in alkanes without the presence of additional ligand (Scheme 5.6-8) [105]. 

Edmondson et al. [138] developed a synthesis of 2,3-disubstituted indoles using an am-ination as the first step (Scheme 8.67). The reaction of 264 and 265 with catalytic amounts of Pd2(dba)3 and the ligand 268 gave compound 267 in high yield. To get to the final indole, a second charge of palladium had to be added after 12 h, otherwise only the amination product was isolated. It can be assumed that in the first step the enaminone 266 is formed, which then cyclizes in a Mizoroki-Heck-type reaction to give 267. In a similar way, reaction of 264 and 269 led to 270 by an acyl migration in the Mizoroki-Heck cyclization product. 

Accordingly, catalytic and stoichiometric amounts of cuprous salts were employed for Mizoroki-Heck-type reactions of various conjugated alkenes [ 19]. Intermolecular catalytic arylations of methyl acrylate (1, not shown) and styrene (2) were accomplished under ligand-free conditions using CuBr (3) or Cul (4) as catalyst in A-methyl-2-pyrrolidinone (NMP) as solvent various aryl iodides could be employed (Scheme 10.2). On the contrary, aryl bromides and chlorides, as well as aliphatic halides, were found to be unsuitable substrates. The reactions employing an alkenyl bromide, methylmethacrolein or methyl methacrylate required stoichiometric amounts of copper salts. 

While this ligand-free copper-catalysed Mizoroki-Heck-type reaction required relatively high temperatures of 150 °C [19], the use of DABCO (9) as ligand allowed for significantly milder reaction conditions [20]. Thereby, satisfying isolated yields were even achieved for orf/jo-substituted electron-rich aryl iodides and alkenyl bromides (Scheme 10.4). However, aryl bromides, particularly electron-rich ones, were converted only sluggishly. 

Scheme 10.4 DABCO (9) as ligand for a copper-catalysed Mizoroki-Heck-type reaction.

Scheme 10.16 Nickel-catalysed Mizoroki-Heck-type reactions with TPPTS (53) as ligand.

Palladium acetate immobilized on reversed-phase amorphous silica gel with the aid of an ionic liquid, [BMIm] PFs, was highly efficient in Mizoroki-Heck type reactions in water under ligand-free conditions. In several runs (up to the sixth reuse) a 95% average yield was obtained with a turnover number (TON, the number of converted substrate molecules per catalytically active centre, mol x mol ) of 1600000 and a turnover frequency (TOP, TON per time unit, mol x mol x h ) of 71000h [34]. 

The group of Tumas published Mizoroki-Heck coupling reactions of iodobenzene (5, X = I) with styrene (4) (or acrylic ester 47) in SCCO2 with a selectivity of 94-99% by using fluorinated ( C02-philic ) ligands like 48 (Scheme 15.10). These results are comparable to those obtained for transformations in toluene as a solvent [106]. Similar data were... 

Scheme 15.10 Mizoroki-Heck coupling reactions in SCCO2 with fluorinated ligands.

Mizoroki-Heck type reaction of aryl pivalates has been reported by Watson s group [Eq. (15)] [64], A bidentate phosphine serves as an effective ligand in this reaction as well. 

Styrenes can be coupled with aryl and heteroaryl iodides in the presence of iron(ll) chloride and potassium iert-butoxide in dimethyl sulfoxide at 60 °C (Scheme 4-230). This Mizoroki-Heck type reaction provides stereoselectively the corresponding ( )-alkenes. Proline and picolinic acid are the most efficient ligands in this system. Aryl bromides may be also introduced in this reaction, however with lower yield. ... 

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... 

Scheme 6.7 Application of bis-NHC chelating ligands in the Mizoroki-Heck reaction...

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... 

Transition metal-catalysed reactions have emerged as powerful tools for carbon-carbon (C-C) bond formation [1], Cross-coupling reactions (Suzuki-Miyaura, Mizoroki-Heck, Stille, etc.) are recognised to be extremely reliable, robust and versatile. However, some other catalysed arylation reactions have been studied and have been reported to be very efficient [2]. In recent years, A -heterocyclic carbenes (NHC) have been extensively studied and their use as ligands for transition-metal catalysis has allowed for the significant improvement of many reactions [3]. This chapter highlights the use of NHC-bearing complexes in those arylation reactions. 

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. ... 

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