Structural Insights into the TES/TFA Reduction of Differently Substituted Benzofurans: Dihydrobenzofurans or Bibenzyls?

Abstract

Various polysubstituted benzofurans were reduced by using triethylsilane in trifluoracetic acid. 2,3-Dihydrobenzofurans or bibenzyl compounds were obtained in high yields, depending on the nature of the substituents at C2 and on the benzene ring of the core structure. A p-anisole substituent at C2 of benzofurans always led to the corresponding bibenzyls.

Key words

benzofurans - dihydrobenzofurans - bibenzyls - triethylsilane - trifluoroacetic acid - reduction

• References and Notes

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• 18 TFA/TES Reduction: Typical Procedure In a round-bottomed flask under an Ar atmosphere, the appropriate benzofuran substrate (0.5 mmol) was dissolved in TFA (7.5 mL), and TES (6 equiv) was added. The reaction was monitored every hour by GC/MS. When complete, the reaction was quenched with aq NaHCO₃ at 0 °C until the effervescence stopped. The mixture was then extracted with EtOAc (×3), and the extracts were washed with brine, dried (Na₂SO₄), filtered, and concentrated under vacuum. The crude product was analyzed by GC/MS or NMR. Generally, the dihydrobenzofurans had similar R_f values to those of the starting benzofurans, so purification by column chromatography on silica gel was avoided when the reaction showed a low conversion. 2-Hexyl-2,3-dihydro-1-benzofuran (2b) Prepared by reduction of 1b with according to the typical procedure; yield: 60% (NMR). ¹H NMR (500 MHz, CDCl₃); δ = 7.56s (s, 1 H), 7.12 (m, 2 H), 6.81 (m, 1 H), 4.75 (m, 1 H), 3.25 (m, 2 H), 2.85 (m, 2 H), 1.25 (m, 8 H), 0.81 (m, 3 H).