Ligandless systems

The use of expensive catalysts, sometimes difficult to prepare and recover, is a concern, especially when working in large scale. Also, as previously mentioned, the very common use of phosphine-based catalysts oftentimes brings along undesired oxidation side-reactions and formation of difficult-to-remove phosphine oxides. To overcome these problems, ligandless systems are of interest for this and other cross-coupling reactions. 

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During the current decade, reactions based on direct C-H functionalisation, and in particular Pd-catalysed direct arylation, have witnessed extraordinary progress. The use of NHC-Pd catalysts (especially well-defined complexes) in these transformations is much less documented than ligandless systems or those using commercially available phosphines in situ. 

An important observation with respect to these catalytic systems is the fact that the presence of quaternary ammonium salts (R N X ) notably enhances their catalytic efficiencies. As mentioned earlier (see Section 3.2.5), in these ligandless systems, complexes such as [(Ar) (Solvent)PdXJ and [Ar(alkene)PdX2] are detected by extended X-ray absorption fine structure (EXAFS). 

The ligandless Beletskaya catalysts, PdCl2(CH3CN)2 used in DMF or acetone with tin-substituted alkynes and sp -hybridized iodides and bromides. This system is very reactive and relatively cheap. The disadvantage is that it decomposes quickly under development of catalyticaUy inactive Pd-black particles [20 c]. 

A similar reaction was reported by Kabalka et al. where ligandless and solvent-free Suzuki couplings were performed with potassium fluoride on alumina. This reaction is very interesting as the catalyst used was palladium powder, the least expensive form of palladium available32. The authors demonstrated the simplicity of the procedure by efficient isolation of the biaryl products via a simple filtration. This could be done as the palladium catalyst remains adsorbed on the alumina surface. A small amount of water in the matrix was beneficial for the outcome of the reactions. Recycling of the catalyst was possible by adding fresh potassium fluoride to the palladium/alumina surface and the catalytic system remained effective at least through six reaction cycles (Scheme 2.6). 

The major improvement compared to the Rh(I) catalysts was the ability of the Cu(I)/RB (OR )2 system to also carboxylate alkenyl-boronic esters in very good yield, under similar conditions. Interestingly, the system functioned better under ligandless conditions, producing the corresponding unsaturated carboxylic acids in good yields. 

The development of catalytic systems using neat water as solvent is of high importance to industrial and environmentally friendly applications. In this respect, water is perhaps the ultimate solvent because of its lack of toxicity and ready availability. Leadbeater has published several papers where the Suzuki-Miyaura reaction has been optimized for aqueous conditions [9,120]. Aryl bromides and iodides were coupled and the corresponding products isolated in good yields with an attractive ligandless protocol. Some reactions gave increased yields with the addition of tetrabutylammonium bromide (TBAB) [121], Recently, an application for a scaled-up Suzuki-Miyaura synthesis in water using an automated batch stop-flow apparatus was also published (Scheme 46) [89]. 

Equations 12.45103 and 12.46104 show two examples of intramolecular Heck olefination. In the first case, under Jeffrey s ligandless conditions, the Pd catalyst also acts to isomerize a C=C bond to give a final product that has the C=N bond in conjugation with the aromatic ring. The second example demonstrates how the Heck reaction can cause alkynes as well as alkenes to undergo 1,2-insertion. The transformation is also a nice application of tandem Pd-catalyzed reactions to create a rather complex ring system. 

Carbonylation of reactive iodides proceeds using PdCl2(PPh3)2 as a standard catalyst under mild conditions in the presence of a base. Several modified catalyst systems have been reported. For example, ligandless Pd charcoal is an active catalyst at 140 °C [1]. Uozumi reported that the amphiphilic phosphine-Pd complex (Pd-PEP) bound to PEG-PS resin is a very active and useful catalyst. Carbonylation... 

Aminations of pyridyl systems, as well as related heteroaromaties (e.g., bromopyrimidines), have been achieved in moderate-to-good 3delds under ligandless conditions using Cu powder in the presence of CsOAc in DMSO. Both iodides and bromides serve equally well both primary and secondary amines can be used and the procedure is insensitive to both air and moisture. 

It is important to note that many coupling reactions can be carried out under so-called ligandless conditions, i.e., even in the total absence of phosphine or carbene ligands. In many of these catalytic systems soluble Pd complexes are generated under the reaction conditions. These catalytic systems, some of which have reportedly been used in industry, are therefore basically homogeneous in nature. 

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