Reaction Mizoroki-Heck arylation

Recently, the present authors have achieved a facile recycling method for both catalyst and reachon medium using F-626 in a Mizoroki-Heck arylation reaction of acrylic acids [11]. The procedure employed a fluorous carbene complex, prepared in situ from a fluorous imidazolium salt, palladium acetate as the catalyst and F-626 as a single reaction medium. When acrylic acid was used as a substrate, separation of the product from the reaction mixture was performed simply by filtration with a small amount of FC-72. The FC-72 solution containing the fluorous Pd-catalyst and F-626 was evaporated and the residue containing the catalyst and F-626 (96% recovery) can be recycled for the next run (Scheme 3.5-6). They tried to reuse the catalyst, and observed no loss of catalytic activity in five re-use cycles. 

An easy recycling method involving both catalyst and reaction medium was achieved in a Mizoroki-Heck arylation reaction of acrylic acid, using a fluorous carbene complex (prepared in situ fl om a fluorous ionic liquid and palladium acetate) as the catalyst and a fluorous ether solvent (F-626) as the reaction medium. Because of the very low solubility of arylated carboxylic acids in F-626, the products precipitated during the course of the reaction. After separation of the products and amine salts by filtration, the filtrate, which contained the fluorous Pd catalyst, could be recycled for several runs (Scheme 13). The Mizoroki-Heck reaction was effectively promoted by a fluorous SCS pincer palladium, which is discussed in Section 3.4.5. 

The Heck reaction (Mizoroki-Heck reaction) is the reaction of an unsaturated halide (or triflate) with an alkene and a strong base and palladium catalyst to form a substituted alkene [41, 42]. The reaction is performed in the presence of an organo-palladium catalyst. The halide or triflate is an aryl, benzyl, or vinyl compound, and the alkene contains at least one proton and is often electron deficient, such as acrylate ester or an acrylonitrile. The catalyst can be tetrakis(triphenylphosphine)palladium... 

Microwave-heated Mizoroki-Heck reactions in water using uitralow palladium catalyst concentrations have been performed by Arvela and Leadbeater. Different catalyst concentrations were investigated using a commercially available lOOOppm palladium solution as the catalyst source (Figure 3.9) [61]. Impressively, useful Mizoroki-Heck arylations were performed with palladium concentrations as low as 500 ppb. 

Hulten er a/. [68] made use of an enol ether and an iodo-substituted precursor to optimize HIV-1 protease inhibitors in a high-yielding manner using an a-selective Mizoroki-Heck arylation and subsequent hydrolysis (Figure 3.16). This class of reactions using ethylene glycol vinyl ether can now be performed in neat water without the use of toxic TlOAc [47]. 

Fukuyama, T., Arai, M., Matsubara, H. and Ryu, I. (2004) Mizoroki-Heck arylation of a,fi-unsaturated acids with a hybrid fluorous ether, F-626 facile filtrative separation of products and efficient recycling of a reaction medium containing a catalyst. J. Org. Chem., 69, 8105-7. 

Aiming to overcome the limitations of the previous protocols, GooKen et al. then extended their own studies using easily available carboxylic esters [29], This indeed paved the way to waste-minimized Mizoroki-Heck reactions, in which any byproduct was efficiently recyclable such that waste formation was limited to carbon monoxide and water (47->48 Scheme 7.10). Subsequently, this technique has proven to be viable for converting various 4-nitrophenyl esters 47 in the presence of a PdCfi-LiCl-isoquinoline catalyst system into styrenes 48. Under Lewis acid catalysis, 4-nitrophenol (49) cleanly reacts with benzoic acid at the same temperature required for the Mizoroki-Heck arylation (49 47), thereby regenerating 4-nitrophenyl ester 47. 

In the quest for additional active catalysts for the Mizoroki-Heck reaction, the advent of N-heterocychc carbene (NHC) ligands was warmly welcomed [32], Transition metal-transition metal-phosphine complexes, and have therefore attracted considerable interest as competitive alternatives in Mizoroki-Heck chemistry, which requires high reaction temperatures. Since the seminal application of NHC ligands in Mizoroki-Heck arylations by Herrmann et al. [33], several research groups have introduced novel palladium catalyst-NHC ligand combinations. These were tested and assessed in standard couplings of simple iodo- or bro-moarenes 60 and activated acceptors such as acrylates 61 or styrene (63) [32], and a selection of impressive examples is summarized in Scheme 7.14. 

The benchmark was set by Herrmarm s carbene complex 65 which, under optimized reaction conditions, showed a respectable TON of 13000. In a similar study by Baker et al., the Mizoroki-Heck arylation of iodobenzene (60b) with 63 in the presence of catalyst 66 bearing a chelating NHC ligand with a cyclophane backbone showed an outstanding TON of 7100000 [34]. In another study, Buchmeiser et al. introduced a new class of NHC based on 1,3-disubstituted tetrahydropyrimi-... 

Dendritic catalysis have been used in various chemical reactions, including the Suzuki-Miyaura reaction, Mizoroki-Heck reaction, hydrogenation reaction, carbonylation and hydroformylation reactions, oxidation reaction, polymerization and oligomerization reactions, arylation reaction, alkylation reaction, and asymmetric synthesis [6]. Recently, dendritic catalysts have been reviewed by Astmc et al. [6], In another review article. Reek et al. reviewed the applications of dendrimers as support for recoverable catalysts and reagents [58]. The authors believed that catalytic performance in these systems depends on used dendritic architecture. 

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...

Related reactions, that have been catalysed by NHC/Pd systems, are the intramolecular Mizoroki-Heck using catalysts formed in situ from imidazolium salts and a Pd(0) source [69], and the arylation of allylic alcohols by a benzothiazole-Pd complex [70,71] (Scheme 6.14). 

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. 

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... 

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

Hiyama and co-workers have reported that the Mizoroki-Heck-type reaction of aryl- and alkenylsilanols is efficiently promoted by a Pd(OAc)2/Cu(OAc)2/LiOAc system (Equation (9)).50 50a in contrast, a dicationic Pd(ll) complex prepared in situ from Pd(dba)2, a diphosphine (dppe or dppben), and Cu(BF4)2 catalyzes 1,4-addition of aryltrialkoxysilanes to a-enones and a-enals in aqueous media (Equation (10)).51 The Pd-catalyzed 1,4-addition of the arylsilanes can be achieved also by using excess amounts of TBAF 3H20, SbCl3, and acetic acid.52... 

A rhodium(l)-catalyzed system in THF is also effective in the Mizoroki-Heck-type reaction of arylsilanediols with acrylates (Scheme 4).53 Interestingly, the use of aqueous THF switches the reaction to 1,4-addition forming /3-arylated esters. The proposed catalytic cycles for these reactions involve 1,4-addition of an arylrhodium species to an acrylate. The change of the reaction pathway is probably because, in aqueous THF, the resultant Rh enolate 6 undergoes protonolysis rather than /3-elimination. Similar Rh-catalyzed 1,4-additions to a,/3-unsaturated carbonyl compounds have been achieved with arylsilicones,54 arylchlorosilanes,55 and aryltrialkoxysilanes.56,57 The use of a cationic Rh-binap complex leads to highly enantioselective 1,4-additions of alkenyl- and arylsilanes.58 583... 

---