For Heck reaction

Pd-catalysts with heterocyclic ligands as catalysts for Heck reaction 98CSR427. 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

Nanometer size Pd colloids in block copolymer micelles of polystyrene polyvinylpyridine as catalysts have been used is a novel way by Klingelhofer for Heck reaction of C-C coupling of aryl halides with olefins. 

Fluorous-derivatized phosphines have also been used for Heck reactions in scCC>2 together with palladium acetate [7]. The fluorous groups improve the solubility of the catalyst in the SCF compared to nonfluorous ligands. An example of a Heck reaction that uses a fluorous-derivatized phosphine to improve the solubility of a Pd(OAc)2 catalyst is shown in Scheme 10.5. 

As detailed elsewhere, the fluorous palladacycle acetates and hahdes 7 and 8 were synthesized [38,39]. These feature three Rfg ponytails, and were poorly soluble in common organic solvents at room temperature, and insoluble in DMF. However, they were very soluble in DMF at higher temperatures. All were effective catalyst precursors for Heck reactions (100-140 °C), and precipitated (as the halides) upon cooling. However, a number of control experiments established that 7 and 8 served as steady-state sources of colloidal palladium nanoparticles, formed anew with each cycle imtil the palladacycles were exhausted. These, or low-valent Pd(0) species derived therefrom, were the true catalysts. 

Poly-(N,N-dipyrid-2-yl-7-oxanorborn-2-en-5-ylcarbamido PdCl2)-grafted Monolithic Supports for Heck Reactions... 

Palladacycles, such as (80), derived from tri(l-naphthyl)phosphine, proved to be very active catalysts for Heck reactions to produce (81) (ArX = Phi, 4-MeCOC6H4Br,... 

In contrast, ionic liquids have been reported to be suitable solvents for Heck reactions because the products can be readily separated from the ionic liquids containing the homogeneous palladium catalysts. An early test with a palladium complex in ionic liquids showed remarkably improved recyclability of the catalyst (255), but palladium black still formed after several runs with recycled catalyst. 

Figure 6.6 (a) A silica immobilised palladium catalyst for Heck reactions, (b) The same catalyst prepared in... 

Littke, A. F. Fu, G. C. A versatile catalyst for Heck reactions of aryl chlorides and aryl bromides under mild conditions./. Am. Chem. Soc. 2001, 123, 6989-7000. 

Almost simultaneously, several groups developed efficient procedures for Heck reactions of deactivated chloroarenes 22 involving sterically crowded monodentate phosphines as activating ligand on the palladium (Scheme 11) [31]. Littke and Fu employed commercially available P(t-Bu)3, Hartwig P(t-Bu)3 or bis-t-butyl-ferroce-nylphosphine, and Beller di(l-adamantyl)-n-butylphosphine. The use of biscyclo-hexylmethylamine as the base instead of alkali metal carbonates or phosphates significantly extends the scope of the Fu procedure in respect of the olefin partner. 

A general catalytic cycle proposed for Heck reaction is shown in Fig. 7.17. While all the steps in the catalytic cycle have precedents, the proposed reaction mechanism lacks direct evidence. The basic assumption is that under the reaction conditions, the precatalyst is converted to 7.64, a coordinatively unsaturated species with palladium in the zero oxidation state. Oxidative addition of ArX, followed by alkene coordination, leads to the formation of 7.65 and 7.66, respectively. Alkene insertion into the Pd-C bond followed by /3-H abstraction gives 7.67 and 7.68, respectively. Reductive elimination of HX, facilitated by the presence of base B, regenerates 7.64 and completes the catalytic cycle. The C-C coupled product is formed in the 7.67 to 7.68 conversion step. 

Kohler K, Heidenreich RG, Krauter JGE, Pietsch J (2002) Highly active palladium/activated carbon catalysts for Heck reactions correlation of activity, catalyst properties, and Pd leaching. Chem Eur J 8 622-631... 

Some studies have been undertaken with respect to anion effects in imidazolium based ionic liquids. As illustrated above, [C4Ciim]Br may be a superior solvent to [C4Ciim][BF4] for Heck reactions, as highly active carbene intermediates are more likely to arise in the former while with the latter these are either not formed or undergo transformation into a less active species as illustrated in Scheme 6.1.[20]... 

Zhao F, Murakami K, Shirai M, Arai M (2000) Recyclable homogeneous/heterogeneous catalytic systems for heck reaction through reversible transfer of palladium species between solvent and support. J Catal 194 479... 

De Vries AHM, Parlevhet FJ, Schmieder-Van De Vondervoort L, Mommers JHM, Henderickx HJW, Walet MAM, De Vries JG (2002) A practical recycle of a Ugand-free palladium catalyst for Heck reactions. Adv Synth Catal 344 996... 

Halopyridines are typically poor substrates for Heck reactions due to the possibility of pyridyl-bridged palladium dimers preventing additional reactions. Improved reaction conditions, of catalyst and the use of DMA as cosolvent, have allowed greater functional group tolerance [136], This was reduced to practice in the transformation of 388 into 389. 

General procedure for Heck reactions [49] A 50 rtiL pressure tube was charged with Pd-pol (1.98 wt% Pd 0.1 mol%), potassium acetate (12 mmol), iodobenzene 46 (5 mmol), styrene 58 (6 mmol), n-dodecane as an internal standard, and DMF (6 mb). The stirred mixture was heated to 90 °C until completion of the reaction, as monitored by GLC and GC-MS analyses. The catalyst was subsequently recovered by filtration, washed sequentially with acetone, water, further acetone, and diethyl ether, and dried under vacuum. 

The increase of the catalyst turnover numbers is indeed one other major area where further improvements could be expected. Such improvements have recently been achieved for the standard Heck reaction by the use of high pressure conditions [86], the use of preformed palladacycles as catalysts [87], or by using a macrocyclic tetraphole as hgand [88].Dendritic diphosphine-palladium complexes as catalysts for Heck reactions have also been reported to possess superior stabihty compared to the monomeric parent compounds [89]. Transferring such iimovations to the AHR remains an important goal. 

MT Reetz, E Westermann, R Lohmer, G Lohmer. A Highly Active Phosphine-free Catalyst System for Heck Reactions of Aryl Bromides. Tetrahedron Lett 39 8449-8452,1998. 

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