Palladium-Catalyzed Coupling of Biphenyl-2-yl Trifluoromethanesulfonates with Dibromomethane to Access Fluorenes

Abstract

A facile and efficient method has been developed for the synthesis of fluorenes by Pd-catalyzed C–H alkylation of biphenyl-2-yl trifluoromethanesulfonates. The trifluoromethanesulfonates are more readily available and more environmentally benign than biphenyl iodides, and are advantageous substrates for traceless directing-group-assisted C–H activation. The reaction generates C,C-palladacycles as the key intermediates that form two C(sp²)–C(sp³) bonds through reaction with CH₂Br₂. The reaction tolerates various functional groups, permitting easy access to a range of fluorene derivatives.

Key words

palladium catalysis - fluorenes - C–H bond activation - biphenyl triflates - dibromomethane

Publication History

Received: 16 January 2022

Accepted after revision: 11 February 2022

Accepted Manuscript online:
11 February 2022

Article published online:
10 March 2022

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• 14 Fluorenes 3; General Procedure A 25 mL Schlenk tube equipped with a stirrer bar was charged with the appropriate biphenyl-2-yl triflate 1 (0.2 mmol, 1.0 equiv), CH₂Br₂ (1.4 mmol, 7.0 equiv), Pd(OAc)₂ (0.02 mmol, 0.1 equiv), KHCO₃ (0.4 mmol, 2.0 equiv), KOAc (0.6 mmol, 3.0 equiv), i-PrOH (0.2 mL), and DMF (2.0 mL). The tube was then frozen with liquid N₂ and exchanged with N₂ to remove air. The mixture was then stirred at 60 °C for 12 h until the reaction was complete. The resulting mixture was diluted with EtOAc and washed with sat. aq NaCl (3×). The organic phase was collected and dried (MgSO₄), and the residue was purified by column chromatography (silica gel, petroleum ether/EtOAc). 9H-Fluorene (3a) White solid (80%). ¹H NMR (400 MHz, CDCl₃): δ = 7.81 (d, J = 7.5 Hz, 2 H), 7.56 (d, J = 7.4 Hz, 2 H), 7.39 (t, J = 7.3 Hz, 2 H), 7.32 (td, J = 7.3, 0.9 Hz, 2 H), 3.92 (s, 2 H). ¹³C NMR (101 MHz, CDCl₃): δ = 143.2, 141.7, 126.7, 126.7, 125.0, 119.8, 36.9. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₃H₁₁: 167.0855; found: 167.0865. 2-Methyl-9H-fluorene (3b) White solid (56%). ¹H NMR (400 MHz, CDCl₃): δ = 7.76 (d, J = 7.5 Hz, 1 H), 7.68 (d, J = 7.7 Hz, 1 H), 7.53 (d, J = 7.4 Hz, 1 H), 7.39–7.35 (m, 2 H), 7.31–7.25 (m, 1 H), 7.20 (d, J = 7.7 Hz, 1 H), 3.87 (s, 2 H), 2.44 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 143.5, 143.0, 141.8, 139.0, 136.5, 127.5, 126.6, 126.2, 125.7, 124.9, 119.6, 119.5, 36.8, 21.6. HRMS (ESI-TOF): m/z [M – H]⁺ calcd for C₁₄H₁₁: 179.0855; found: 179.0866. 3-Methyl-9H-fluorene (3c) White solid (70%). ¹H NMR (400 MHz, CDCl₃): δ = 7.78 (d, J = 7.5 Hz, 1 H), 7.62 (s, 1 H), 7.54 (d, J = 7.4 Hz, 1 H), 7.44 (d, J = 7.6 Hz, 1 H), 7.38 (t, J = 7.4 Hz, 1 H), 7.34–7.27 (m, 1 H), 7.14 (d, J = 7.6 Hz, 1 H), 3.87 (s, 2 H), 2.47 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 143.6, 141.8, 141.7, 140.3, 136.3, 127.6, 126.6, 126.5, 125.0, 124.7, 120.4, 119.70, 36.5, 21.5. HRMS (ESI-TOF): m/z [M – H]⁺ calcd for C₁₄H₁₁: 179.0855; found: 179.0873. 4-Methyl-9H-fluorene (3d) White solid (44%). ¹H NMR (400 MHz, CDCl₃): δ = 7.94 (d, J = 7.7 Hz, 1 H), 7.58 (d, J = 7.4 Hz, 1 H), 7.40 (t, J = 7.9 Hz, 2 H), 7.32 (td, J = 7.4, 0.7 Hz, 1 H), 7.22 (t, J = 7.4 Hz, 1 H), 7.16 (d, J = 7.4 Hz, 1 H), 3.92 (s, 2 H), 2.74 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 143.6, 143.6, 142.7, 139.8, 133.0, 129.0, 126.6, 126.4, 126.0, 124.9, 123.1, 122.4, 37.1, 21.1. HRMS (ESI-TOF): m/z [M – H]⁺ calcd for C₁₄H₁₁: 179.0855; found: 179.0880.