Study On The Synthesis Of CF₃-containing Benzofurans And Benzothiophenes By Transition Metal-catalyzed Cyclizations

Transition metal-catalyzed coupling reaction has emerged as one of the most powerful methodologies for C-O and C-S bond formation in organic chemistry. It is well known that benzofurans and benzothiophenes are important organic compounds, which widely exist in biologically active molecules and natural products. In consideration of the importance and the practicability of benzofurans and benzothiophenes, chemistry researchers keep on working hard for new synthetic method and have made many progresses. This paper focuses on the development of new methods for the synthesis of CF3-containing benzofurans and benzothiophenes by transition metal-catalyzed coupling reaction, and includes the following four parts.(1) The recent research on the synthesis of benzofurans and benzothiophenes by transition metal-catalyzed reactions has been reviewed.(2) A palladium-catalyzed tandem elimination/annulation of β-chloro-β-(trifluoromethyl)styrenes with 2-halophenols for the synthesis of 3-trifluoromethylbenzofurans was developed. This reaction used low cost olefins as reactant and the post-process was convenient.(3) A copper-catalyzed thiolation annulation of o-halostyrenes with sodium hydrosulfide was developed. This reaction allows to prepare a variety of benzothiophenes in moderate to good yields.(4) An iron-catalyzed tandem annulation of aromatic alkynol and diaryl disulfides for the synthesis of benzothiophenes was developed. This protocol could be applied as a new strategy for constructing benzofuran ring as well as a new synthetic application of trifluoromethyl-containing building blocks. We also developed the ortho C-H activation of diphenyl disulfides.