Compound 4c

(R)-2-(1-fluoroethyl)-6-phenoxybenzaldehyde

From: Controlling Pd(iv) reductive elimination pathways enables Pd(ii)-catalysed enantioselective C(sp3)−H fluorination

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Compound data: HPLC

Compound data: 1H NMR

Compound data: 13C NMR

Compound data: 19F NMR

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a solution of 3k (0.1 mmol, 17.0 mg) in DMF (0.5 mL) were added PhOH (0.3 mmol, 28.2 mg) and K2CO3 (0.3 mmol, 41.5 mg). The reaction mixture was stirred for 2 h at 100 oC. Upon completion, the reaction mixture was diluted with ethyl acetate and washed with water and brine. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by preparative TLC to afford 4c (21.7 mg, 89% yield, 95% ee). The ee value was determined by SFC analysis on a Chiralcel OD-3 column (0% isopropanol, 2.0 mL/min) with retention time of 9.656 min (minor) and 11.156 min (major). 1H NMR (600 MHz, CDCl3): 10.62 (s, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.40 (t, J = 7.5 Hz, 2H), 7.19 (t, J = 7.4 Hz, 1H), 7.06 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.3 Hz, 1H), 6.43 (dq, J = 48.9, 6.2 Hz, 1H), 1.64 (dd, J = 24.3, 6.2 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 191.20 (d, J = 4.5 Hz), 161.01 (d, J = 1.6 Hz), 156.32, 146.44 (d, J = 19.6 Hz), 135.46 (d, J = 1.4 Hz), 130.14, 124.42, 122.71 (d, J = 4.1 Hz), 119.69 (d, J = 15.3 Hz), 119.39, 117.53, 88.32 (d, J = 167.3 Hz), 23.43 (d, J = 24.9 Hz). 19F NMR (376 MHz, CDCl3): δ –172.89. HRMS (ESI-TOF): m/z calculated for C15H14FO2+ [M+H]+ 245.0972, found 245.0972.