Synthesis
To an oven-dried Schlenk tube were added 2-bromo-4-fluorobenzaldehyde (100.0-204.8 mg, 0.54 mmol), phenylacetylene (110.2 mg, 1.08 mmol), Pd(OAc)2 (4.8 mg, 4 mol%), xantphos (25 mg, 8 mol%), and K3PO4 (458 mg. 2.16 mmol), followed by the addition of anhydrous toluene (1.0 mL). The reaction mixture was stirred at 120 °C for 2-6 h under the protection of N2 atmosphere. The progress of the reaction was monitored by TLC until 2-bromo-4-fluorobenzaldehyde was completely converted to 4-fluoro-2-(phenylalkynyl)benzaldehyde. After completion of the reaction, the mixture was filtered through diatomaceous earth and washed with CH2Cl2. The filtrate was concentrated under reduced pressure and the resulting crude product was purified by silica gel column chromatography (petroleum ether/ethyl acetate as eluent) to give 4-fluoro-2-(phenylalkynyl)benzaldehyde in 72-91% yield, the product being a viscous liquid or semi-solid.
References
[1] Chemistry - A European Journal, 2015, vol. 21, # 41, p. 14401 - 14409
[2] Synthesis (Germany), 2017, vol. 49, # 23, p. 5149 - 5158
[3] Organic and Biomolecular Chemistry, 2012, vol. 10, # 9, p. 1922 - 1930
[4] Chemistry - A European Journal, 2015, vol. 21, # 50, p. 18122 - 18127
[5] Chemical Communications, 2010, vol. 46, # 17, p. 2950 - 2952
