Compound 5a

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Compound data: HPLC

Compound data: 1H NMR

Compound data: 13C NMR

Compound data: 19F NMR

Compound data: 19F NMR

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

General procedure C: For fluorination products that cannot be separated in chiral HPLC, the aldehyde moiety was transformed into an amide group as following: To a solution of 3 (0.05 mmol) in t-BuOH (0.5 mL) were added a solution of NaClO₂ (13.6 mg, 0.15 mmol), NaH₂PO₄ (41.4 mg, 0.3 mmol) in water (0.5 mL) and 2-methylbut-2-ene (106 uL, 1 mmol). The reaction mixture was stirred for 1 h, and concentrated in vacuo. The crude residue was acidified with 1 N HCl (aq), extracted with DCM. The combined organic layers were dried with Na₂SO₄, filtered and concentrated in vacuo. Without further purification, the corresponding carboxylic acid was used directly in the next step. To a solution of carboxylic acid in DCM (2 mL) was added (COCl)₂ (10 uL) and a drop of DMF at 0 ^oC. The mixture was stirred for 3 h at room temperature, and solvent was removed in vacuo. The residue was redissolved in DCM (2 mL), and 4-bromoaniline, triethylamine were added. The resulting mixture was stirred overnight at room temperature. Upon completion, the solution was washed with 1 N HCl (aq), sat. NaHCO3 (aq), and brine. The combined organic layers were dried with Na₂SO₄, filtered and concentrated in vacuo. The crude residue was purified on silica gel to give 5.5a was prepared from 3a following general procedure C described above (91% ee). The ee value was determined by HPLC analysis on a Chiralcel AS-H column (10% isopropanol in hexanes, 0.8 mL/min) with retention time of 13.6 min (minor) and 15.9 min (major). Absolute stereochemistry was confirmed via X-Ray analysis of the crystal obtained using DCM/pentane as recrystallization solvents. ¹H NMR (600 MHz, CDCl₃): δ 7.84 – 7.78 (m, 3H), 7.65 (br s, 1H), 7.51 (br s, 4H), 6.09 (dq, J = 47.5, 6.2 Hz, 1H), 1.73 (dd, J = 24.2, 6.4 Hz, 3H). ¹³C NMR (150 MHz, CDCl₃): δ 165.37, 144.64 (d, J = 19.7 Hz), 136.30, 134.36 (d, J = 5.0 Hz), 132.24, 131.13 – 130.27 (m), 127.95 (q, J = 3.7 Hz), 127.17 (d, J = 9.8 Hz), 123.64 (q, J = 3.6 Hz), 123.40 (d, J = 272.6 Hz), 121.76, 118.01, 88.24 (d, J = 167.6 Hz), 23.07 (d, J = 24.7 Hz). ¹⁹F NMR (376 MHz, CDCl₃): δ –62.99, –168.50. HRMS (ESI-TOF): m/z calculated for C₁₆H₁₃BrF₄NO⁺ [M+H]⁺ 390.0111, found 390.0111