Phosphine ligand-free direct arylation

Scheme 21 Ruthenium-catalyzed phosphine ligand-free direct arylation...

More recently, a phosphine ligand-free ruthenium-catalyzed direct arylation with aryl bromides as electrophiles was disclosed. Notably, the use of inexpensive RuCl3(H20)n as catalyst in NMP as solvent allowed for economically attractive C-H bond functionalizations of pyridine, oxazoline and pyrazole derivatives, also with more sterically hindered orfftosubstituted aryl bromides as electrophiles (Scheme 21) [79, 80],... 

However, efforts were also directed to the development of phosphine-free catalysts. For example, the ligand-free Pd(OAc)2 promoted Suzuki reaction in water was reported using microwave heating. In this way, a low palladium loading (0.4 mol.%) was required and the cross coupling proceeded quickly (5-10 min reaction time), using boronic acids and aryl iodides, bromides and chlorides. 

Transition metal catalyzed processes are useful tools for the synthesis of functionalized thiophenes. Thus for instance, a phosphine-free, palladium catalyzed coupling protocol for the synthesis of 2-arylbenzo[d]thiophenes from various 3-substituted benzo[6]thiophenes and aryl bromides or iodides has been reported <04T3221>. Likewise, 2,2 -bithiophenes have been 5,5 -diarylated directly with aryl bromides in the presence of Pd(OAc)2, bulky phosphine ligands and CS2CO3 <04T6757>. A series of electron-deficient and relatively electron-rich benzo[6]thienyl bromides have been shown to participate in palladium catalyzed amination reactions, as exemplified by the interesting conversion of 63 to the tetracyclic system 64 upon reaction with 2-aminopyridine 65 <04EJO3679>. 

Subsequently, it was found that the use of [RhCl(coe)2]2, along with an electron-poor phosphine ligand and CsOPiv as base, allowed for the direct arylation of N—H free pyrroles when employing aryl iodides as electrophiles (Scheme 9.15) [27]. Interestingly, this protocol also proved appHcable to the direct arylation of (aza)indoles. 

The carbonylation of aryl halides with alcohols and amines catalysed by palladium complexes with triphenylphosphine ligand is the convergent and direct route to the synthesis of aromatic esters as well as aromatic amides. Even though these palladium complexes are widely employed as the best catalytic system, those catalysts are difficult to separate and reuse for the reaction without further processing. The major drawbacks are oxidation of triphenylphosphine to phosphine oxide, reduction of palladium complex to metal and termination of the catalytic cycle. The phosphine-free, thermally stable and air resistant catalyst (1) containing a carbon-palladium covalent bond (Figure 12.3) has been found to be a highly selective and efficient catalyst for the carbonylation of aryl iodides.[1]... 

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