Ligand-free Palladium Catalysts

Scheme 7.7 Homeopathic, phosphine ligand-free palladium catalyst in Mizoroki-Heck reactions.

Apart from the catalytic systems based on Pd/phosphines typically used in Mizoroki-Heck reactions, many other types of new palladium catalysts have been developed over the last decade. Avoiding the use of the phosphine ligands is a great advantage as they usually cannot be recovered and they frequently hamper the isolation and purification of the final product. One viable alternative is the use of ligand-free palladium catalysts usually in the form of Pd(OAc)2. At the high temperatures required for Mizoroki-Heck reactions, most ligand-free palladium complexes are unstable and have a tendency to form soluble Pd(0) nanoparticles [32]. The question arises as to the role played by the Pd nanopartides formed and whether... 

Bhattacharya S, Srivastava A, Sengupta S (2005) Remarkably facile Heck and Suzuki reactions in water using a simple cationic surfactant and ligand-free palladium catalysts. Tetrahedron Lett 46(20) 3557-3560... 

Hallberg et al. have shown that microwaves accelerate palladium-catalyzed reactions (e.g. Suzuki, Heck, Tsuji-Trost, Stille) in solution or with supported polymers [127]. Most recently, Villemin and Caillot have reported that, in the Suzuki reaction, the use of a ligand-free palladium catalyst, palladium acetate, without the use of solvent under microwave irradiation produces good yields of biphenyl products, one of which is shown in Equation 89 [128]. 

The palladium-catalyzed conversion of allylic chlorides into allylboronates has been achieved using ligand-free palladium catalysts (Scheme 6.11) [24]. Developing such procedures was attractive from a practical perspective since there are no added ligands that... 

Palladium-catalyzed carbon-carbon cross-coupling reactions are among the best studied reactions in recent decades since their discovery [102, 127-130], These processes involve molecular Pd complexes, and also palladium salts and ligand-free approaches, where palladium(O) species act as catalytically active species [131-135]. For example, the Heck reaction with aryl iodides or bromides is promoted by a plethora of Pd(II) and Pd(0) sources [128, 130], At least in the case of ligand-free palladium sources, the involvement of soluble Pd NPs as a reservoir for catalytically active species seems very plausible [136-138], Noteworthy, it is generally accepted that the true catalyst in the reactions catalyzed by Pd(0) NPs is probably molecular zerovalent species detached from the NP surface that enter the main catalytic cycle and subsequently agglomerate as N Ps or even as bulk metal. 

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. ... 

A practical ligand-free palladium-catalyzed intramolecular reductive Heck cyclization was developed by Liu et al. <07TL2307>. The authors found that water was an essential component of the reaction mixture. Using a series of aryl halide intermediates this cyclization resulted in the desired 1,2,3,4-tetrahydroisoquinolines in high yields. Cook and co-workers found that InCU was an efficient catalyst for an intramolecular Friedel-Crafts cyclization of Ar-(4-bromobut-2-enyl)-A-(bcnzyl)-4-methylbcnzcncsulfonamidc to form the desired 3-substituted tetrahydroisoquinolines <07OL1311>. 

De Vries and coworkers found another solution based on kinetic considerations of the reactions outUned in Scheme 10.5 The formation and growth of the nanoparticles must be higher order in the palladium concentration, whereas the catalytic cycle is first order or even half order (if the catalyst resting species is dimeric) in palladium. Thus, increasing the substrate catalyst ratio will slow down the former process more than the latter [61]. Indeed this non-obvious solution is the crux to what has been dubbed homeopathic paUadium by Beletskaya [62] and by de Vries [61]. The essence is that the ligand-free paUadium catalyst becomes more active at lower doses. The concept becomes immediately clear upon observation of Fig. 10.11. At 1 mol% of palladium the catalyst almost immediately precipitates as palladium black, leading to low conversions even after prolonged periods. 

Besides the Hartwig-Buchwald reaction, amination can be achieved by a Pd-catalyzed variant of the Ullmann reaction in the presence of copper salts. Though the scope of this reaction is much narrower, it does not require expensive phosphine ligands and thus is more economical. The arylation of diphenylamine with water-insoluble aryl iodides can be achieved in aqueous microemulsions in the presence of phosphine-free palladium catalyst and copper(I) iodide (Scheme 58). 

See for example Alimardanov A, Schmieder-van de Vondervoort L, deVries AHM, de Vries JG. Use of homeopathic ligand-free palladium as catalyst for aryl-aryl coupling reactions. Adv Synth Catal. 2004 346 1812-1817. 

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