Copper-Catalyzed Electrophilic Chlorocyclization Reaction Using Sodium Chloride as the Source of Electrophilic Chlorine

Abstract

The synthesis of 2,3-disubstituted benzo[ b ]thiophenes with selective placement of a chlorine moiety at the 3 position while maintaining diversity at the 2 position has only been accomplished by a handful of conditions in the past. The development of a greener, less expensive, and simpler method is paramount for the exploration of innovative compounds for application in medicinal and materials chemistry. Herein, the first reported copper-catalyzed electrophilic chlorocyclization method was developed and employed across diverse substrates to generate highly functionalized 2,3-disubstituted benzo[ b ]thiophenes and 2,3,5-trisubstituted thiophenes in very high yields. This method was optimized in both ethanol and acetonitrile in a comparative solvent study. The utility of this method was further expanded beyond chlorocyclization by changing the sodium halide to generate bromo- and iodocyclization products in excellent yields.

Highly Efficient and Selective Electrochemical Synthesis of Substituted Benzothiophenes and Benzofurans in Microcontinuous Flow

“…Until recently, only electrophilic cyclization of the 2-alkynylthioanisoles was used to obtain C-3 halogenated benzothiophenes . Larock and co-workers reported the synthesis of C-3 halogenated benzothiophenes with I 2 and Br 2 as electrophilic reagents (Scheme a). − Kesharwani and co-workers independently reported copper-mediating electrophilic cyclization and using sodium halide as the source of halogen to synthesize the C-3 halogenated benzothiophenes (Scheme b). − However, in those methods, the substrate scope was limited and some environmental unfriendly reagents were used such as poisonous and corrosive iodine and bromine, and transition-metal catalysts, which were hard to remove completely and had limited potential application in the pharmaceutical industry. Consequently, the development of a practical and green alternative protocol to synthesize this class of compounds is still highly desirable.…”

Reductive 3-Silylation of Benzofuran Derivatives via Coupling Reaction with Chlorotrialkylsilane

“…Conventionally, 2-silylation of heteroaromatics can be easily achieved by a reaction with an organometallic reagent followed by the electrophilic attack of chlorotrialkylsilanes (Scheme A) . In comparison with traditional methods, many of the recent synthetic approaches to silylated benzofurans are investigated such as the catalytic direct silylation by C–H activation (Scheme B) and the intramolecular cyclization of alkynylsilanes (Scheme C) . These processes are generally useful and reliable; however, the main products in almost all of the reactions are 2-silylated benzofuran derivatives except for some examples , and the reactions sometimes demand hazardous reactants or the troublesome preparation of starting materials.…”

Platinum Complexes from C–H Activation of Sterically Hindered [C^N] Donor Benzothiophene Imine Ligands: Synthesis and Photophysical Properties

“…Strong field ligands with carbon donors, the rigidity of the conjugated ring system, and the strong spin–orbit coupling of the heavy-metal center are explanations for the favorable photophysical properties of cyclometalated compounds, including long-lived excited triplet states. − Thiophenes are also known for their photophysical properties and are implicated in a variety of applications, including solar cells and photodetectors. − Benzothiophenes are thiophenes with an additional fused aromatic ring. Benzothiophene fragments are known in pharmaceuticals and dyes and thus have been studied. − The additional size and conjugation may enhance the desirable properties of the cyclometalated complexes with benzothiophene-derived ligands. Bismetalated complexes are less studied than their monometalated analogues; − however, perhaps with the additional strong field chelates, C^N ligands may improve the properties of these cyclometaled species .…”