Synthesis of Diarylmethanes through Palladium-Catalyzed Coupling of Benzylic Phosphates with Arylsilanes

Abstract

An efficient approach to the benzylation of arenes has been developed. The reactions described provide straightforward access to diarylmethanes through Pd-catalyzed coupling of benzylic phosphates with arylsilanes in good to excellent yields. The reaction tolerates a wide range of functionalities such as halide, alkoxyl, and nitro groups.

Key words

palladium - diarylmethane - arene - benzylation - Hiyama cross-coupling

• References and notes


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• 23 Preparation of Benzylic Phosphates; General Procedure: To a flask charged with the requisite benzyl alcohol (20.0 mmol), Et₃N (4.2 mL, 30.0 mmol, 150 mol%), DMAP (244 mg, 2.0 mmol, 10 mol%), and THF (5 mL), was added neat diethyl chlorophosphate (2.9 mL, 20.0 mmol, 100 mol%) over a 30 min period at r.t. The resultant white, heterogeneous mixture was stirred for 16 h then poured into a solution of 1 M KHSO₄ (50 mL). The separated organic phase was then washed with sat. aq NaHCO₃ (30 mL) and brine (30 mL), before it was dried over MgSO₄, filtered, and concentrated to give a crude oil. The crude oil was purified by flash chromatography (petroleum ether–EtOAc, 5:1, v/v) to give the product 1a.
• 24 Hiyama Cross-Coupling; General Procedure: An oven-dried Schlenk tube with Pd(OAc)₂ (5 mol%) and dppp (10 mol%) was evacuated and purged with argon three times. A mixture of TBAF (1 M in THF, 0.36 mL), 2a (0.45 mmol), and benzylic phosphate (1a; 0.30 mmol) was dissolved in freshly distilled 1,4-dioxane (1.0 mL), and added at r.t. The reaction mixture was heated with stirring at 100 °C for 24 h, then cooled to ambient temperature and transferred to a round-bottom flask. Silica gel (2.0 g) was added and the solvent was removed under reduced pressure to afford a free-flowing powder. The powder was then dry-loaded onto a silica gel column and purified by flash chromatography using petroleum as the eluent to give the desired product 3aa. All products were synthesized according to this procedure. Yield: 45 mg (90%); colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.30–7.24 (m, 4 H), 7.20–7.14 (m, 6 H), 3.96 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 141.5, 129.1, 128.7, 126.3, 42.3.