Palladium-catalyzed synthesis benzo thiophenes

Palladium-catalyzed amination of the benzo[h]thiophene nucleus has also been applied to the synthesis of 3-[(4-pyridinyl)amino]benzo[h]thiophenes 295 which are selective serotonin re-uptake inhibitors [187b]. The synthesis of several of the inhibitors is illustrated. 

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>. 

Chloro-2,3-diethyl-2-cyclobutenone (611) undergoes a palladium-catalyzed cross-coupling with 2-(tri- -butyl)stannyl-5-trimethylsilylthiophene (612) to give the intermediate compound (614) (Equation (110)). Without isolation, (614) is converted to the benzothiophene (613) on thermolysis at 100°C followed by acetylation. Although this procedure seems not to be generally applicable to benzo[6]thiophene synthesis, it provides a general synthesis of dibenzothiophenes, and thus a series... 

A facile and selective palladium-catalyzed carbonylative domino synthesis of benzothiophenes was developed by Alper and Zeng in 2011 [273]. 2-Carbon-ylbenzo[Z ] thiophene derivatives were produced from 2-gem-dihalovinylthiophe-nols in 24-73 % yields (Scheme 2.39). This protocol involved an intramolecular C-S coupling/intermolecular carbonylation cascade sequence and allowed for access to various highly functionalized benzo[h]thiophenes. 

In 2004, Lemaire[73] developed a new mechanism for the synthesis of benzo[h]thiophene through palladium-catalyzed C-H arylation of benzothiophene derivatives with aryl iodides. Mori [74] discovered a new catalytic system for the... 

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