Heck olefination, palladium-catalysed

Another methodology that is widely used for C-C bond formation is the Heck coupling (Heck, 1985 T.suji, 1995). The Heck reaction involves the palladium-catalysed arylation of olefinic double bonds (Eqn. (12)) and provides an alternative to Friedel-Crafts reactions for attaching carbon fragments to aromatic rings. 

The palladium-catalysed addition of aryl, vinyl, or substituted vinyl groups to organic halides or triflates, the Heck reaction, is one of the most synthetically useful palladium-catalysed reactions. The method is very efficient, and carries out a transformation that is difficult by more traditional techniques. The mechanism involves the oxidative addition of the halide, insertion of the olefin, and elimination of the product by a p-hydride elimination process. A base then regenerates the palladi-um(0) catalyst. The whole process is a catalytic cycle. 

A further evidence on the acceleration enjoyed by a typical Pd-catalysed reaction, the Heck reaction, in an ionic phase ( V-mcthyl-Y.Y. V.-trioctylammonium chloride or Aliquat 336) is found in a triphasic protocol developed by Tundo and coworkers. 7b.The arylation of electron poor olefins is catalysed by palladium supported on charcoal (Pd/C) and is carried out in the heterogeneous isooctane/Aliquat 336/water system (Figure 27). Under this multiphasic condition, Aliquat 336 forms a third liquid phase between the organic and the aqueous phase that traps the catalyst. The use of phosphines is not necessary. As a matter of fact, Aliquat 336 incorporates the solid-supported catalyst and ensures an efficient mass transfer between the bulk phases resulting in an increase of the reaction rate of an order of magnitude compared to the reaction in the absence of the ionic liquid. A determing role is played by the base while I LN drives the reaction towards the formation of ethyl cinnamate, reaction carried out in the presence of KOH lead to formation of Ullmann dimerisation products. 

The palladium-catalysed arylation of olefins with aryl halides, the Heck reaction, is usually performed in polar solvents such as acetonitrile or dimethyl sulfoxide, in combination with a base and a Pd(ii) pre-catalyst that may or may not be associated with a phosphorus ligand. Given that quaternary ammonium or phosphonium salts are known to increase reaction rates, ILs emerged as promising solvents for this reaction.In the case of imidazolium-based ionic liquids, the solvent, beside providing an unusual coulombic environment. 

A standard Heck reaction, as shown in the example below, involves the palladium-catalysed reaction of a halide with an alkene, most commonly an electron-deficient aUcene such as an acrylate, but other types can also be used. Heck-type cyclisation onto olefins is a useful reaction for ring synthesis. 

The palladium-catalysed Heck reaction of aryl or vinyl halides with olefins has been widely used in synthetic chemistry. The reaction works impressively well with a wide range of electron-deficient and neutral olefins, generally affording (1-arylatcd products. In the case of electron-rich olefins, however, a mixture of regioisomers is usually obtained under standard Heck reaction conditions (Figure 5.1).[1] This... 

Thus, traMi-3-alkyl-6-(phthalimido)cyclopentenes were prepared in excellent to modest yields from the corresponding tran -chloroalkene by the palladium coupling reaction [84d]. Inexpensive and efficient Pd-TMG systems, Pd(OAc)2-TMG or PdC -TMG, have been developed for the Heck reaction of an olefin with an aryl halide, in which TMG (1) acts as a ligand [84e]. In the reaction of iodobenzene with butyl acrylate the turnover numbers were up to 1000000. TMG (1) was used as a base for the palladium catalysed asymmetric Wagner-Meerwein shift of nonchiral vinylcyclopropane and cyclobutane derivatives leading to asymmetric synthesis of cyclobutanones, cyclopentenones, y-butyrolactones and 5-valerolactones [85] (Scheme 4.34). Replacement of TMG (1) with an inorganic bases such as lithium or cesium carbonate resulted in little effect. 

Compared with palladium-catalysed Heck reactions, the studies of nickel-catalysed Heck reactions are far fewer. Theoretical studies show that oxidative addition and olefin insertion occur easier in the nickel system than in the palladium system. On the other hand, p-hydride elimination and catalyst regeneration through HX removal are more difficult in a nickel-based catalytic system." The former characters may make the nickel-catalysed Heck reaction of alkenyl or aryl chloride proceed relatively easily and the latter... 

Heck, R.F. (1979) Palladium catalysed reactions of organic halides with olefins. Acc. Chem Res., 12, 146. 

R. F. Heck, Palladium-Catalysed Reactions of Organic Halides with Olefins , Acc. Chem. Res., 1979,12,146. 

Palladium-catalysed Heck addition of Ar-I to terminal olefins RCH=CH2 has been reported to proceed under ligand-free conditions, with just (AcO)2Pd and AcOAg in AcOH at 110°C, and shown to afford double arylation products RCH=CAr2. Both electron-poor and electron-rich aryl iodides react efficiently. ... 

Here, the term Heck-type reaction is taken to include palladium-catalyzed C-C coupling processes where vinyl or aryl derivatives are functionalized with olefins, alkynes, or organometallic reagents [see Eqs. (1) and (2)] [1]. Aryl and vinyl chlorides are most reluctant to undergo Pd-catalysed activation, as expected from the C-X bond dissociation energies [2]. 

The Mizoroki-Heck reaction [eqn (9.1)] is a valuable synthetic tool for the catalytic formation of a range of aryl-olefins, and other related building blocks, widely used in the pharmaceutical and fine chemicals industries. Many palladium-containing compounds are known to catalyse the reaction to varying extents. Over the past two decades [(NHC)Pd]-based systems have been increasingly employed, and seem to provide some advantages with respect to other catalysts. 

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