Compound 3x

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Compound data: CIF

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

To silver fluoride (9.5 mg, 0.0750 mmol, 30.0 mol%), (DHQD)₂PHAL (hydroquinidine 1,4-phthalazinediyldiether) (19.5 mg, 0.0250 mmol, 10.0 mol%) and CsF (76.0 mg, 0.500 mmol, 2.00 equiv) in a 20.0 mL dried Schlenk tube were added DBDMH (71.5 mg, 0.250 mmol, 1.00 equiv), CH₃CN (2.00 mL) and DCM (1.00 mL). Trifluoromethyl 4-fluorobenzenesulfonate (130 µL, 0.750 mmol, 3.00 equiv) was added to the reaction and the resulting mixture was stirred for 30 min at 25 ^oC, then cooled to -20 ^oC. (E)-3-phenylallyl acetate (1x) (44.1 mg, 0.250 mmol, 1.00 equiv) in DCM (0.200 mL) was added dropwise and the reaction mixture was stirred at -20 ^oC for further 24 h. The reaction was quenched with saturated aqueous solution of Na₂SO₃ (1.0 mL), then followed by saturated aqueous solution of NH₄Cl (2.0 mL) at -20 ^oC. The aqueous layers were extracted with CH₂Cl₂ (8.0 mL × 3). The combined organic layers were dried over anh. MgSO₄. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica gel, eluting with hexanes/EtOAc 40:1 (v/v), to afford 70.3 mg (2R,3S)-2-bromo-3-phenyl-3-(trifluoromethoxy)propyl acetate (3x) as a white solid (82% yield, d.r. >20:1). R_f = 0.20 (hexanes/EtOAc 20:1 (v/v)). NMR Spectroscopy: ¹H NMR (400 MHz, CDCl₃) δ 7.55 – 7.30 (m, 5H), 5.37 (d, J = 6.5 Hz, 1H), 4.51 (dd, J = 11.6, 5.5 Hz, 1H), 4.44 – 4.31 (m, 2H), 2.10 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 170.3, 135.6, 129.6, 128.7, 127.3, 121.5 (q, J = 257.5 Hz), 79.8, 64.0, 50.5, 20.7. ¹⁹F NMR (376 MHz, CDCl₃) δ -58.08 (s, 3F). Mass Spectrometry: HRMS-EI (m/z): Calcd for C₁₂H₁₁F₃O₃ [M-HBr] 260.0660, Found, 260.0662. 85:15 e.r. HPLC (Daicel OD-3+OD-H chiralpak, i-PrOH/hexane = 2/98, 0.3 mL/min, 220 nm) t₁ = 27.257 min (minor), t₂ =28.399 min (major). [α]_D²⁰= +28.3 (c 0.25, CHCl₃). The absolute configuration of the product 3x was assigned by X-ray crystallography. (page S61)