Synthesis of Cyclobutarenes by Palladium-Catalyzed C(sp~3)-H Bond Arylation: Preparation of Methyl 7- Methylbicyclo[4.2.0]Octa-1,3,5-Triene-7-Carboxylate

摘要

A. Methyl 2-(2-chlorophenyl)-2-methylpropanoate (2). A one-necked 500-mL round-bottomed flask (Note 1), equipped with a Teflon-coated magnetic stirring bar (Note 2), is fitted with a rubber septum and connected to a combined argon/vacuum line and evacuated/back-filled with argon twice. The reaction vessel was charged with lithium bis(trimethylsilyl)amide (135 mL, 135 mmol, 2.5 equiv) (Note 3). The flask is then cooled to 0 °C using an ice-bath. A THF (10 mL) solution (Note 4) of methyl (2-chlorophenyl)acetate (1) (10.2 g, 54.1 mmol, 1 equiv) (Notes 5 and 6) is added dropwise and the mixture is stirred for an additional 30 min. Finally, after dropwise addition of a THF (10 mL) (Note 4) solution of iodomethane (8.4 mL, 135.0 mmol, 2.5 equiv) (Note 7), the reaction is stirred at room temperature for 2 h (Notes 8 and 9). After drop-wise addition of saturated aqueous solution of ammonium chloride (50 mL) (Note 10), the aqueous layer is extracted twice with diethyl ether (2 x 100 mL) (Note 11). The combined organic layers are successively washed with a saturated aqueous solution of sodium thiosulfate (50 mL) (Note 12) and brine (50 mL) (Note 13), dried over anhydrous MgSO4 (5 g) (Note 14), filtered and concentrated under reduced pressure. The residue is purified by a short-path distillation under vacuum (58-61 °C/0.11 mmHg) to afford the pure product 2 (10.7-10.8 g, 93-94%) as a colorless oil (Note 15).