Nucleophilic aromatic palladium catalysis

Biaryl structures are found in a wide range of important compounds, including natural products and organic functional materials [8,80,81]. One of the most common and useful methods for preparing biaryls is the palladium-catalyzed coupling of aryl halides with arylmetals (Scheme 1, mechanism A). On the other hand, aryl halides have been known to couple directly with aromatic compounds as formal nucleophiles under palladium catalysis. While the intramolecular cases are particularly effective, certain functionalized aromatic compounds such as phenols and aromatic carbonyl compounds, as well as... 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

A tandem Suzuki-Miyaura coupling/nucleophilic aromatic substitution to carba-zoles was developed by St. Jean et al. (Scheme 51) [210]. Reaction of A -sulfonyl-protected 2-aminophenylboronates 216 with l-bromo-2-fluorobenzenes 217 under palladium(0)-catalysis provides the Af-sulfonyl-protected carbazoles 218. This annulation is compatible with a variety of electron-withdrawing groups (e.g., aldehydes, esters, and sulfones) and has been applied to an efficient synthesis of glycosinine (147) (four steps, 50% overall yield). 

Nucleophilic aromatic substitution and palladium catalysis compared... 

Direct nucleophilic displacement of halide and sulfonate groups from aromatic rings is difficult, although the reaction can be useful in specific cases. These reactions can occur by either addition-elimination (Section 11.2.2) or elimination-addition (Section 11.2.3). Recently, there has been rapid development of metal ion catalysis, and old methods involving copper salts have been greatly improved. Palladium catalysts for nucleophilic substitutions have been developed and have led to better procedures. These reactions are discussed in Section 11.3. 

The conversion of trifluoromethylphenyl halide 4 is almost quantitative (90-100 %), in heterogeneous (Pd/C), as well as in homogeneous conditions [(Ph3)4Pd, bipyPdCl2, (Ph3P)2PdCl2] (Scheme 2). However, the product of the nucleophilic arylation is formed only in very low yield, in both palladium(O) and palladium(II) catalysis. On the other hand, whatever the complex used, the formation of the reduction product, the trifluoromethylbenzene, is important, even with apparently a moderate yield (which can be explained by a partial loss of trifluoromethylbenzene, a highly volatile product Any other aromatic product apart 6 and 7 cannot be detected in the reaction mixture). 

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