Synthesis of Substituted Fluorenes by Cascade Allenylation, Electrocyclization and Intramolecular Friedel–Crafts Reaction of 1,3-Diene-Substituted Propargylic Alcohols

Abstract

A concise, one-step synthesis of substituted fluorenes through TiCl₄-promoted cascade allenylation, electrocyclization and intramolecular Friedel–Crafts reaction of 1,3-diene-substituted propargylic alcohols has been developed. An interesting ­substituent-dependent regioselectivity was observed.

Key words

allenylation - electrocyclization - intramolecular ­reactions - Friedel–Crafts - 1,3-dienes - fluorenes

• References and Notes

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• 9 General procedure for the preparation of propargylic alcohols 1: To a solution of phenylacetylene (0.56 g, 5.5 mmol) in anhydrous THF (15 mL) was added n-BuLi (1.6 M in hexane, 3.44 mL, 5.5 mmol) dropwise at –78 °C, and the reaction mixture was stirred for 0.5 h at that temperature, followed by the addition of a solution of 1,5-diphenylpenta-2,4-dien-1-one (1.17 g, 5 mmol) in THF (10 mL) dropwise. The mixture was allowed to warm to r.t. and stirred for 4 h. The mixture was quenched by addition of sat. NH₄Cl and the aqueous layer was extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layers were washed with brine, dried (Mg₂SO₄), filtered and concentrated in vacuo. The crude product was purified by neutral Al₂O₃ column chromatography (PE–EtOAc) to give 1a as a yellow oil (1.38 g, 82%). ¹H NMR (CDCl₃, 500 MHz): δ = 2.65 (s, 1 H), 6.05–6.10 (m, 1 H), 6.61–6.67 (m, 1 H), 6.77–6.81 (m, 2 H), 7.25–7.39 (m, 11 H), 7.52–7.54 (m, 2 H), 7.71 (s, 1 H), 7.73 (d, J = 1.5 Hz, 1 H); ¹³C NMR (CDCl₃, 125 MHz): δ = 143.5, 137.1, 136.7, 134.2, 131.8, 129.7, 128.7, 128.6, 128.5, 128.4, 128.0, 127.8, 127.7, 126.5, 125.8, 122.4, 90.0, 87.4, 73.2; Anal. Calcd for C₂₅H₂₀O: C, 89.25; H, 5.99. Found: C, 89.21; H, 5.95
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• 11 General procedure for the preparation of fluorenes 2: To a stirred solution of propargylic alcohol (0.50 mmol) in chlorobenzene (1 mL) was added dropwise a solution of TiCl₄ (94.8 mg, 0.50 mmol) in chlorobenzene (1 mL) at 0 °C. The mixture was stirred at r.t. for 8 h, then the reaction mixture was quenched with sat. NaHCO₃ and the aqueous layer was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic extracts were dried over anhydrous Mg₂SO₄, filtered, and concentrated in vacuo. The crude product was purified by thin-layer chromatography on silica gel to afford the desired product 2. 1,9-Diphenyl-9H-fluorene (2a; 93.8 mg, 59%); white solid; mp 131–132 °C; ¹H NMR (CDCl₃, 500 MHz): δ = 5.24 (s, 1 H), 6.58–6.60 (m, 2 H), 6.89–6.94 (m, 3 H), 7.11–7.12 (m, 2 H), 7.18–7.20 (m, 6 H), 7.35–7.37 (m, 1 H), 7.47 (t, J = 7.5 Hz, 1 H), 7.83 (d, J = 7.5 Hz, 2 H); ¹³C NMR (CDCl₃, 125 MHz): δ = 148.8, 145.8, 141.9, 140.8, 140.7, 140.6, 140.5, 128.6, 128.4, 128.1, 127.9, 127.8, 127.5, 127.2, 126.8, 125.9, 125.2, 119.9, 118.8, 54.0; HRMS (EI): m/z calcd for C₂₅H₁₈: 318.1409; found: 318.1374
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