Superacid-Mediated Intramolecular Cyclization/Condensation: Facile One-Pot Synthesis of Spirotetracyclic Indanones and ­Indenes

Abstract

A facile, superacid-promoted, domino, one-pot synthesis of novel spirotetracyclic indanones through intramolecular Friedel–Crafts acylation/alkylation of α,β-unsaturated cinnamic acid esters is presented. Interestingly, when the β-aryl group contained electron-withdrawing substituents such as fluoro, chloro, or bromo, the reaction took a different mechanistic path and afforded arylindenes as the end products.

Key words

superacids - Friedel–Craft reaction - spiro compounds - indanones - indenes - domino reactions

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• 22 Spirotetracyclic indanones 9; General Procedure An oven-dried Schlenk tube was charged with the appropriate β-aryl α,β-unsaturated ester 3a–i (0.25 mmol) and DCE (2 mL) under N₂. TfOH (0.1 mL, 1.5 mmol) was then added and the mixture was stirred at 50 °C for 30–36 h until the reaction was complete (TLC). The reaction was quenched with aq. NaHCO₃, and the mixture was extracted with CH₂Cl₂ (3 × 20 mL). The organic layers were combined, washed with sat. brine, dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, PE–EtOAc) to give the appropriate spirotetracyclic indanone 9a–i (76–90%). 6′-Methyl-2′,3′-dihydro-1,1′-spirobi[inden]-3(2H)-one (9b) Brown viscous liquid; yield: 54 mg (87%); TLC: R_f (3b) = 0.50, (9b) = 0.60 (PE–EtOAc, 96:4, UV detection). IR (MIR-ATR): 2922, 2851, 1710, 1601, 1461, 1287, 1236, 816, 763 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.79 (d, J = 7.8 Hz, 1 H, ArH), 7.57 (ddd, J = 7.3, 7.3, and 1.0 Hz, 1 H, ArH), 7.41 (ddd, J = 7.3, 7.3, and 1.0 Hz, 1 H, ArH), 7.27 (d, J = 7.8 Hz, 1 H, ArH), 7.21 (d, J = 7.8 Hz, 1 H, ArH), 7.08 (d, J = 7.8 Hz, 1 H, ArH), 6.57 (s, 1 H, ArH), 3.19–3.00 (m, 2 H, CH₂), 2.94 (d, J = 18.6 Hz, 1 H, CH _aH_b), 2.87 (d, J = 18.6 Hz, 1 H, CH_a H _b), 2.55–2.44 (m, 1 H, CH₂), 2.40–2.30 (m, 1 H, CH₂), 2.22 (s, 3 H, ArCH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 205.9 (s, C=O), 161.6 (s, ArC), 149.0 (s, ArC), 140.2 (s, ArC), 136.9 (d, ArC), 136.0 (s, ArC), 135.4 (d, ArCH), 128.1 (d, ArCH), 127.8 (d, ArCH), 125.1 (d, ArCH), 124.3 (d, ArCH), 123.3 (d, ArCH), 123.0 (d, ArCH), 54.4 [s, C(CH₂)₂], 52.4 (t, CH₂), 42.9 (t, CH₂), 30.8 (t, CH₂), 21.2 (q, ArCH₃). HRMS (APCI+): m/z [M + H]⁺ calcd for C₁₈H₁₇O⁺: 249.1274; found: 249.1279.
• 23 Indenes 10; General Procedure An oven-dried Schlenk tube was charged with the appropriate β-aryl α,β-unsaturated ester 3j–o (0.25 mmol) and DCE (2 mL) under N₂. TfOH (0.1 mL, 1.5 mmol) was then added and the mixture was stirred at 50 °C for 12 h until the reaction was complete (TLC). The reaction was quenched with aq. NaHCO₃ and the mixture was extracted with CH₂Cl₂ (3 × 20 mL). The organic layers were combined, washed with sat. brine, dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, PE–EtOAc) to give the appropriate indene 10j–o (68–78%). 3-(4-Chlorophenyl)-5-methyl-1H-indene (10n) Brown viscous liquid; yield: 47 mg (78%). TLC: R_f (3n) = 0.45, (10n) = 0.60 (PE–EtOAc, 97:3, UV detection). IR (MIR-ATR): 2920, 1726, 1613, 1487, 1393, 1288, 1093, 1014, 885, 803, 731 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.57 (dd, J = 8.3 and 2.0 Hz, 2 H, ArH), 7.47 (dd, J = 8.3 and 2.0 Hz, 3 H, ArH), 7.38 (s, 1 H, ArH), 7.14 (d, J = 8.3 Hz, 1 H, ArH), 6.58 (t, J = 2.0 Hz, 1 H, CH=C), 3.49 (d, J = 2.0 Hz, 2 H, CH₂), 2.45 (s, 3 H, ArCH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 144.0 (s, ArC), 143.7 (s, ArC), 141.7 (s, ArC), 135.8 (d, ArC), 134.6 (s, ArC), 133.3 (s, ArC), 131.7 (d, ArCH), 129.0 (d, 2 C, ArCH), 128.7 (d, 2 C, ArCH), 125.9 (d, ArCH), 123.9 (d, ArCH), 120.7 (d, CH=C), 37.8 (t, CH₂), 21.6 (q, ArCH₃). HRMS (APCI+): m/z [M + H]⁺ calcd for C₁₆H₁₄Cl⁺: 241.0779; found: 241.0787.