2-(Di-tert-butylphosphino)biphenyl → 4,4,6,6-Tetramethyl-2-(o-nitrophenyl)-cyclohex-2-en-1-one

Participants

Reaction Conditions

Reaction Steps

A 250-mL modified Schlenk-type flask was charged with 2-iodo-4,4,6,6-tetramethyl-cyclohex-2-en-1-one (3, 1.06 g, 3.96 mmol, 1 equiv), 2-nitrophenyl boronic acid (661 mg, 3.95 mmol, 1.0 equiv), Pd2(dba)3 (181 mg, 0.198 mmol, 0.05 equiv), 2-(di-t-butylphosphino)-biphenyl (236 mg, 0.791 mmol, 0.20 equiv), and barium hydroxide octahydrate (3.73 g, 11.8 mmol, 3.0 equiv). Tetrahydrofuran (64 mL) and distilled water (13 mL) were added sequentially to the flask, and the resulting red, heterogeneous mixture was heated to 38° C. The progress of the reaction was monitored by thin-layer chromatography (20% ethyl acetate-hexanes, Rf=0.37, 0.61 for product, starting material, respectively; UV, CAM). After 1.5 h, the reaction was allowed to cool to 23° C., then was quenched by the addition of saturated aqueous ammonium chloride solution (30 mL). The layers were separated, and the aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with brine (20 mL), and then were dried over sodium sulfate. Filtration and concentration of the dried organic layers afforded a brown oil which was purified by flash column chromatography (10% ethyl acetate-hexanes), to afford 4,4,6,6-tetramethyl-2-(o-nitrophenyl)-cyclohex-2-en-1-one (4, 755 mg, 70%) as a white solid. 4,4,6,6-Tetramethyl-2-(o-nitrophenyl)-cyclohex-2-en-1-one (4) could be further purified by re-crystallization from hot 10% ethyl acetate-hexanes solution (white crystals, mp 101-102° C.).

Provenance & Evidence