Palladium-Catalyzed Synthesis of Fluorenes by Intramolecular C(sp²)–H Activation at Room Temperature

Abstract

The synthesis of fluorenes by intramolecular Pd-catalyzed C(sp²)–H activation of 2-arylbenzyl chlorides was conducted at room temperature by using commercially available triphenylphosphine and pivalic acid as ligands. The desired reactions proceeded efficiently at room temperature, and various substrates were converted into the corresponding fluorene derivatives in excellent yields.

Key words

palladium catalysis - ligands - C–H activation - fluorenes - cyclization

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• 11 9H-Fluorene (3a); Typical Procedure In advance, Cs₂CO₃ was dried by heating under vacuum for 3 h then stored in a glovebox. A 10-mL Schlenk flask was charged with the dried Cs₂CO₃ (0.16 g, 0.50 mmol) in a glovebox, then taken out of glovebox and dried by heating under a vacuum for at least 5 min. The flask was backfilled with argon and then PdCl₂(PPh₃)₂ (1.4 mg, 0.0020 mmol, 1.0 mol%) and pivalic acid (1c; 20 mg, 0.20 mmol, 1.0 equiv) were added. The flask was then evacuated and backfilled with argon three times. THF (0.50 mL) and 2a (37 μL, 0.20 mmol) were added, and the mixture was stirred at 25 °C for 18 h. The mixture was then analyzed by GC with tetradecane (50 μL) as an internal standard. H₂O (5 mL) and EtOAc (5 mL) were added, and the mixture was extracted with EtOAc (3 × 5 mL). The collected organic layers were combined, washed with brine (5 mL), dried (MgSO₄), and concentrated. The residue was purified by chromatography (silica gel, hexane–acetone) to give a colorless solid; yield: 32.1 mg (96%). ¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 7.8 Hz, 2 H), 7.56 (d, J = 7.3 Hz, 2 H), 7.39 (t, J = 7.3 Hz, 2 H), 7.31 (td, J = 7.4, 1.1 Hz, 2 H), 3.92 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.2, 141.7, 126.7, 126.7, 125.0, 119.8, 36.9. EI-HRMS: m/z: [M – H]⁺ calcd for C₁₃H₉: 165.0704; found: 165.0702.