[1,4]-Aza-Brook Rearrangement for Efficient Formation of Benzynes and Their Cycloaddition

Abstract

An efficient benzyne cycloaddition triggered by an aza-Brook rearrangement is reported. In this reaction, 2-(trimethylsilyl)aryl triflates bearing a benzylic secondary amine group at the 3-position undergo base-promoted [1,4]-carbon-to-nitrogen silyl migration (aza-Brook rearrangement) to generate benzyne intermediates, which are then trapped by intermolecular or intramolecular cycloaddition involving 1,3-dienes or 1,3-dipoles. This procedure furnishes various cycloadducts in yields of up to 99%.

Key words

silyl migration - amines - aza-Brook rearrangement - benzyne, cycloaddition

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• 23 General Procedure for Benzyne Cycloadditions with Dienes or 1,3-Dipoles To a solution of silyl triflate (0.20 mmol) and dienes or 1,3-dipoles (1.00 mmol) in anhydrous THF (2 mL) under argon atmosphere at –78 °C was added KHMDS (0.50 M in toluene, 0.44 mL, 0.22 mmol) dropwise. After being stirred for 30 min at –78 °C, sat. NH₄Cl (2 mL) was added, and the reaction mixture was stirred for 10 min at r.t. Then 2 M NaOH (5.0 mL) was added, and the resulting mixture was extracted with EtOAc (10 mL) for three times. The combined organic layers were washed with brine, dried over MgSO₄, filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography using EtOAc–PE as eluent to obtain cycloadducts. This General Experimental Procedure was carried out using 80.6 mg (0.20 mmol) of 5a, 108 μL (1.00 mmol) of 2,5-dimethylfuran. Column chromatography afforded 50.0 mg (90%) of 6a as a pale yellow solid; mp 126–127 °C; R_f  = 0.30 (PE–EtOAc, 10:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.22 (t, 2 H, J = 7.7 Hz), 7.09 (d, 1 H, J = 6.1 Hz), 7.00–6.92 (m, 2 H), 6.83 (d, 1 H, J = 5.3 Hz), 6.77 (t, 2 H, J = 6.7 Hz), 6.66 (d, 2 H, J = 8.0 Hz), 4.45 (d, 1 H, J = 12.3 Hz), 4.20 (d, 1 H, J = 12.3 Hz), 3.92 (br, 1 H), 2.01 (s, 3 H), 1.91 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.0, 150.7, 147.9, 147.2, 147.0, 131.2, 129.5, 126.5, 125.5, 118.2, 118.0, 113.0, 90.1, 88.3, 45.8, 17.4, 15.4. ESI-HRMS: m/z [M + H]⁺ calcd for C₁₉H₂₀NO: 278.1539; found: 278.1539. See the Supporting Information for experimental details and characterization data for all new compounds.
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