Introduction
Functionalization of the benzene ring of benzofuran is synthetically challenging because direct electrophilic aromatic substitution (SEAr) is directed to the 2- and 3-positions of the furan ring. The Monomer-Polymer-Monomer (MPM) method overcomes this bias via a concise three-step cycle—cationic polymerization, SEAr on the polymer, and thermal depolymerization—enabling regioselective access to 5-substituted benzofurans with high theoretical atom economy.
Concept of the MPM Strategy
In the MPM approach, benzofuran monomers are first “locked” into solvent-soluble, linear polybenzofuran (PBF) chains by cationic polymerization in hexafluoro-2-propanol (HFIP) using trifluoromethanesulfonic acid (TfOH) as the initiator. This polymeric intermediate uniformly activates the benzene ring for subsequent SEAr reactions.
Graphical Abstract
Polymerization in HFIP
Under optimized conditions (0.2 mol % TfOH in HFIP at 0 °C), benzofuran undergoes rapid cationic polymerization to yield soluble, linear PBF. Real-time UV–vis spectroscopy and TD-DFT studies reveal cationic π- and σ-complex intermediates, and 13C NMR shows two characteristic signals at 83.7 ppm and 49.0 ppm.
Regioselective SEAr on PBF
The soluble PBF intermediate undergoes SEAr with various electrophiles—acylation, halogenation, nitration, etc.—installing substituents para to the alkoxy linkage in each repeat unit with excellent regiocontrol and broad functional-group tolerance.
Thermal Depolymerization
Substituted PBF chains cleanly depolymerize at 320 °C under nitrogen to regenerate 5-substituted benzofuran monomers in high yield, completing the MPM cycle with minimal waste and high selectivity.
References
- R. Hua & L. Lu, “A Monomer-Polymer-Monomer (MPM) Organic Synthesis Strategy: Synthesis and Application of Polybenzofuran for Functionalizing Benzene Ring of Benzofuran,” Asian Journal of Organic Chemistry 2021, 10(8), 2137–2142. https://www.sciencedirect.com/science/article/pii/S2193580722023868
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