Five-membered heterocycles, direct arylations, palladium

Palladium-catalyzed arylations of simple electron-rich five-membered heteroarenes with one heteroatom, such as furans, thiophenes, and pyrroles, with aryl iodides, bromides, or chlorides are among the most frequently studied direct arylation reactions [31, 39, 85]. These reactions usually afforded five-membered heterocycles, which were arylated at the position adjacent to the heteroatom in moderate to good yields. These reactions were mainly accomplished with electrophilic catalysts and proceeded more efficiently using aryl bromides with electron-withdrawing groups. This is in agreement with an electrophilic SEAr-type mechanism relying on a palladium(0)/palladium(ll) manifold [86]. Selected results of catalytic direct arylations of simple electron-rich five-membered heteroarenes (124—126) with aryl iodides, bromides, or chlorides are summarized in Table 9.2. 

Palladium-catalyzed Direct Arylation of Indoles and Thiophenes. Five-membered ring heterocycles possessing only one heteroatom and no Af-oxide function can also be arylated using palladium(II) complexes, a phosphine ligand, and an inorganic base. In one example, a tandem palladium-catalyzed Heck coupling reaction and direct intramolecular C2 arylation reaction on a )V-(2-chlorobenzyl)-5-bromoindole was reported (eq 30). The procedure, which is catalyzed by palladium acetate, uses tn-tert-butylphosphonium tetrafluoroborate as a ligand and ferf-butyl acrylate as the alkene for the Heck reaction (eq 30). ... 

Sultones are the internal esters of hydroxy sulfonic acids and are the sulfur analogs of lactones. Sultones are demanded scaffolds in medicinal chemistry research. Biological studies on sultones are mainly concerned with their toxicological, skin sensitization, and antiviral activities [20]. Sultones are synthetically useful heterocycles which can react with a variety of compounds to introduce the alkylsulfonic acid function and therefore used as sulfoalkylating agents [21]. There have been several new developments for the synthesis of sultones which have also been applied in the total synthesis of natural products. In recent years, the palladium-catalyzed direct arylation of several aromatics via a C-H bond activation using aryl halides has led to successes. An intramolecular version of this reaction has allowed the synthesis of several biaryls via the formation of five- to seven-membered rings. Thus, the sultones should be synthesized by C-H activation via two pathways (Scheme 4.14). 

C-H Activation. Tri-terf-butylphosphine, combined with palladium acetate, acts as an effective catalytic system for the direct Ar-H arylation of heterocycles. This system has been applied for the functionalization of various five- and six-membered ring heterocycles containing one or more heteroatoms. A base (CS2CO3,... 

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