Programmed Synthesis of Tetra-Aryl Thiophenes with Stepwise, Ester-Controlled Regioselectivity

Abstract

Herein, we report a modular synthetic route to access tetra-arylated thiophene compounds with four different substituents with programmed chemical control provided by an ester activating/directing group. This method enables the functionalization of individual positions of thiophene sequentially via regioselective halogenations and cross-coupling reactions. The reaction sequence described provides tetra-arylated thiophenes in higher yields than previous routes and employs practical reaction protocols, simple catalytic systems, and short reaction times.

A Modular and Catalytic Methodology To Access 2,5-Furan-Based Phenylene/Thiophene Oligomers through a One-Pot Decarboxylative Cross-Coupling from 5-Bromofurfural

“…This synthesis entails a mild Suzuki–Miyaura cross-coupling, followed by aldehyde oxidation and a decarboxylative cross-coupling (DCC) to produce the desired oligofurans. Heterocyclic arylation via DCC has been previously reported to access 2,5-diarylated furans, , 2,3,4,5-multiarylated thiophenes, and oligothiophenes . However, no reports have demonstrated the capability to perform one-pot DCC to produce furan oligomers.…”

“…38 Initial optimization began by coupling neutral acid partner 4a with 2,5-dibromothiophene using previously optimized DCC conditions, producing oligomer 5b in fair yields (49%, see Table S9). 41 Although initial results were promising, conditions resembling the DCC reaction of oligothiophenes greatly improved the yield of this transformation (85%). 42 The success of this experiment relates to the use of tris(o-tolyl) phosphine, a sterically hindered ligand, achieving high temperatures quickly via microwave radiation and sonicating the solution under inert argon gas before the addition of the Pd-catalyst (5 mol %).…”

Regiodivergent Synthesis of Brominated Pyridylthiophenes by Overriding the Inherent Substrate Bias

“…Thiophene is traditionally functionalized using electrophilic aromatic substitution, 11 deprotonation, 12 or cross-coupling reactions. 13 C-H activation can also introduce a variety of functional groups. 14 Our research group has focused on applying halogen dance reactions, which involve the migration of a bromo or iodo group on the aromatic ring through successive intermolecular halogen-metal exchanges, 15,16 leading to the synthesis of multiply functionalized thiophenes.…”

“…1 H NMR (400 MHz) and13 C{ 1 H} NMR (100 MHz) spectra were measured on JEOL ECZ400 spectrometer. Chemical shifts for 1 H NMR are reported in parts per million (ppm) downfield from tetramethylsilane with the solvent resonance as the internal standard (CHCl3: δ 7.26 ppm, DMSO-d5: δ 2.50 ppm), and coupling constants are given in hertz (Hz).…”

Metal-Free C–S Bond Formation in Elemental Sulfur and Cyclobutanol Derivatives: The Synthesis of Substituted Thiophenes

“…For instance, articaine is used as a dental anesthetic and suprofen is a well-known nonsteroidal anti-inflammatory drug (Figure ). Thiophenes can serve as useful and valuable building blocks for the assembly of molecular complexity. , Conventional routes for the synthesis of substituted thiophenes involve cyclization of substrates with sulfurating reagents and functionalization of the preconstructed thiophene nucleus . The former method mainly includes two or three starting materials. ,, Despite the versatility and overall efficiency of this transformation, the thiolation of the cyclobutanols with sulfur powder is less explored.…”