Air-Stable Phophine Oxide Ligand

4,4,5,5-Tetramethyl-1,3,2-dioxaphospholane 2-oxide (1) is an air-stable phosphine oxide ligand, which forms hydrogen-bond-stabilized bidentate complexes with transition metals to enhance cross-coupling reactions. In the Kumada cross-coupling reaction, for example, this ligand can be applied even to reactions with substrates having less reactivity, such as tosylates, especially electron-poor aryl or heteroaromatic tosylates, to give the corresponding coupling products in good yields.

Typical Procedure: Preparation of 4’-methoxy-3-(trifluoromethyl)biphenyl²⁾
A solution of Pd(dba)₂ (2.9 mg, 0.005 mmol, 0.5 mol%) and 1 (1.6 mg, 0.010 mmol, 1.0 mol%) in dry dioxane (4.0 mL) is stirred under N₂ for 5 min at ambient temperature, and then treated with (4-methoxyphenyl)magnesium bromide (0.5 M in THF, 3.0 mL, 1.50 mmol). The resulting mixture is stirred for 5 min at ambient temperature. Thereafter, 3-(trifluoromethyl)phenyl tosylate (317 mg, 1.00 mmol) is added, and the resulting suspension is stirred at 80 °C for 22 h. At ambient temperature, aqueous HCl (2.0 mL, 2.0 N), Et₂O (50 mL), and H₂O (30 mL) are added. The separated aqueous phase is extracted with Et₂O (50 mL x 2 times). The combined organic layers are dried over MgSO₄ and concentrated in vacuo. The remaining residue is purified by column chromatography on silica gel (pentane) to yield 4’-methoxy-3-(trifluoromethyl)biphenyl (237 mg, Y. 94%) as a colorless liquid.