Facile Access to Benzothiophenes through Metal-Free Iodine-­Catalyzed Intermolecular Cyclization of Thiophenols and Alkynes

Abstract

A novel iodine-catalyzed method for the synthesis of benzothiophene derivatives through cascade reactions of substituted thiophenols with alkynes has been demonstrated under metal- and solvent-free conditions. The present protocol uses inexpensive and environmentally friendly molecular iodine as the catalyst, and the corresponding products are obtained in moderate to excellent yields. Such an efficient, economical, and green transformation should provide an attractive approach to various benzothiophenes within organic and medicinal chemistry.

Key words

iodine-catalyzed - metal-free - benzothiophenes - thiophenols - alkynes

• References and Notes


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• 12 Synthesis of Substituted Benzothiophenes; General Procedure: A 25 mL Schlenk tube equipped with a magnetic stirring bar was charged with I₂ (12.7 mg, 0.05 mmol), substituted thiol 1 (0.5 mmol) and alkyne 2 (0.75 mmol). The tube was evacuated twice and backfilled with nitrogen, and DTBP (2.5 mmol) was added into the tube under nitrogen atmosphere. The tube was sealed with a balloon and the mixture was stirred under nitrogen atmosphere at 110 °C for 18 h. Upon completion of the reaction, the resulting solution was cooled to r.t., and the solvent was removed with the aid of a rotary evaporator. The residue was purified by column chromatography on silica gel (PE–EtOAc) to give 3. Methyl 3-Phenylbenzo[b]thiophene-2-carboxylate (3a): Compound 3a was obtained according to the general procedure and purified by column chromatography (PE–EtOAc, 30:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.92 (d, J = 8.0 Hz, 1 H), 7.60 (d, J = 8.0 Hz, 1 H), 7.50–7.57 (m, 4 H), 7.46 (d, J = 8.0 Hz, 2 H), 7.39 (t, J = 8.0 Hz, 1 H), 3.83 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 163.0, 144.3, 140.5, 134.6, 129.7, 128.2, 128.1, 127.8, 127.3, 125.4, 124.9, 122.5, 52.3. MS (ESI): m/z = 268.1 [M + Na]⁺.