Heck coupling aryl chlorides, palladium® chloride

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],... 

A series of palladium(O) mono-imidazolylidene complexes have also been prepared and used for the Heck reaction of aryl chlorides in [NBu4]Br.29 The authors report that two of their catalysts, (1,3-dimesi-tylimidazolylidene)(naphthoquinone)palladium(0) and (1,3-dimesitylimida-zolylidene)(benzoquinone)palladium(0) (Fig. 5) remain stable throughout the reaction and will couple even non-activated aryl chlorides in good yields. Clearly, the authors believe that the imidazolylidene complex is responsible for this activity. 

The scope of the Heck and related coupling reactions was substantially broadened by the development, in the last few years, of palladium/ligand combinations which are effective with the cheap and readily available but less reactive aryl chlorides [86, 87] rather than the corresponding bromides or iodides. The process still generates one equivalent of chloride, however. Of interest in this context, therefore, is the report of a halide-free Heck reaction which employs an aromatic carboxylic anhydride as the arylating agent and requires no base or phosphine ligands [89]. 

It was shown that palladacycles 1, prepared from palladium(II) acetate and the tris(a-tolyl)- or trimesitylphosphane, are excellent catalysts for the Heck coupling of triflates and halides (including certain aryl chlorides). In this case, oxidation states -l-U and +IV appear to be involved in the catalytic cycle [16]. 

The use of palladium attached to FibreCat catalysts in simple Heck and Suzuki reactions has already been described (1). This work has now been extended to cover a wider variety of FibreCat systems (Figure 1) in the more difficult Suzuki coupling of aryl chlorides (3,4). (NB FibreCat 1000-Dl, D2 and D3 are experimental samples, whereas 1000-D7, D8 and 1001 are all commercially... 

The aryl palladium complexes that are formed via oxidative coupling of aryl halides with palladium(O) can undergo the Heck reaction.238,239 -p e Heck reaction is the coupling of aryl halides or aryl sulfonate esters with alkenes.340 The reaction proceeds with formation of a palladium species such as 401, with elimination of palladium to give arylated alkene derivatives.241 Aryl halides differ greatly in their reactivity, Arl being the most reactive, followed by aryl bromides. In general, aryl chlorides are very unreactive in the Heck... 

The development of Pd colloids as catalyst for C—C coupling reactions is rather recent [5]. The first example was reported by BeUer et al. in 1996 they used preformed Pd coUoids stabihsed by tetra-octylammonium bromide prepared following the Bonneman procedure in the Heck arylation [6]. The colloidal system was effective for the Heck arylation of styrene or butyl acrylate by activated aryl bromides, but showed only moderate to little activity for deactivated aryl bromides and aryl chlorides. To obtain these results, the authors found that the colloidal pre-catalysts must be added slowly to the reaction mixture to avoid the formation of inactive palladium black at the beginning of the reaction. 

One of the earliest reports on use of a phosphonium salt as an IL in such a process was that of Kaufmann and co-workers (9). In this work, the use of tri-butyl(hexadecyl)phosphonium bromide as a recyclable medium for the palladium-mediated Heck coupling of aryl halides with acrylate esters was reported (9). While these reactions proceeded without the use of an additive ligand, elevated temperatures (100 °C) were required and the process was most efficient only with more activated aryl halides [Eq. (1)]. More recently, the use of trihexyl(tetradecyl)-phosphonium chloride (Cyphos IL 101) has been reported as a useful medium for the Suzuki cross-coupling of aryl halides with boronic acid derivatives [Eq. (2)] [10]. In this process, a soluble palladium precursor such as Pd2(dba)3-CHCl3 was dissolved in the phosphonium salt, forming a dark orange solution. This solution was stable in the absence of oxygen for an extended period of time and could be... 

Another method that is widely used for C-C bond formation is the Heck coupling [3]. The arylation of olefinic double bonds is mostly catalyzed by palladium complexes in homogeneous solution. Important advantages of this reaction are the broad availability of arylbromides and chlorides and the tolerance of the reaction for a wide variety of functional groups. There were also developed heterogeneous Pd/C catalysts which exhibit high activity for the Heck reaction of aryl halides with olefins. The reaction conditions are 80 200 °C, solvents (NMP, DMF, tolueneAvater), base addition is necessary (NaOAc, amines, alkali carbonates). The reaction scheme can be described as follows (Eq. 8-22). 

Nickel halides catalyze the conversion of unreactive aryl chlorides into aryl iodides by Nal in DMF at 140 °C. In the presence of a palladium catalyst and an activated olefin, the aryl iodide is transformed into the Heck coupling product. Nickel(O) complexes are poor catalysts for the coupling step. The halide exchange is thought to be a radical reaction since it is suppressed by the addition of 5% p-dinitrobenzene as radical scavenger. While nickel catalysts do not perform... 

Interestingly, BeUer and Zapf have reported that electron-poor phosphites are useful ligands for the coupling of electron-deficient aryl chlorides. Reetz and co-workers discovered that palladium salts in the presence of tetraphenylphosphonium salts and di-methylglycine constitute a very active and selective catalyst system for the Heck aryla-tion of styrene.f Note that the system is more efficient than the palladacycles for converting nonactivated arylpalladium precursors such as chlorobenzene into products. High yields of coupled products are obtained at 150 °C and only minor amounts of cis-stilbene or 1,1-diphenylethene are encountered (Scheme 42). 

Apart from palladacycles, a number of catalyst systems are currently known that show productivities up to 100,000 for Heck and Suzuki reactions of all kinds of aryl bromides. It is important to note that coupling reactions of electron-deficient aryl bromides (e.g., 4-bromoacetophenone), which are often used in academic laboratories, are not suitable as test reactions to judge the productivity of a new catalyst, because simple palladium salts without any Ugand give turnover numbers up to 100,000 with these substrates. Recently, palladium complexes in combination with sterically congested basic phosphines (e.g., tri-tcrt-butylphosphine), carbenes, and also phosphites led to productive palladium catalysts for the activation of various aryl chlorides. 

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