Compound 10

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

To a flask charged with propargyl alcohol 9 (230 mg, 0.67 mmol, 1 equiv) was added CuI (128 mg, 0.67 mmol, 1 equiv) in the glovebox. The flask was removed, THF (2.4 mL) was added, and the reaction mixture was cooled to –78 °C. MeMgBr (3.0 M in Et­₂O, 1.1 mL, 3.35 mmol, 5 equiv) was then added dropwise over 5 min and the reaction was stirred for 2 h at room temperature. The reaction was re-cooled to –78 °C and I₂ (850 mg, 3.35 mmol, 5 equiv) was added dropwise over 1 min as a solution in THF (610 µL). The reaction mixture was allowed to warm to room temperature and was stirred for 15 min. Next it was cooled to 0 °C, and then quenched with sat. aq. NH₄Cl (3 mL). The mixture was diluted with sat. aq. Na₂S₂O₃ (7 mL) and EtOAc (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na₂SO₄. Evaporation under reduced pressure afforded the crude product, which was purified by flash chromatography (7:3 Hexanes:EtOAc) to provide hydroxyiodide 10 (266 mg, 82% yield) as an off-white foam. Mp: 59.5–61.2 °C; R_f 0.32 (7:3 Hexanes:EtOAc); ¹H NMR (500 MHz, CDCl₃): δ 8.25 (s, 1H), 8.02 (d, J = 7.8, 1H), 7.49–7.55 (m, 2H), 7.41 (s, 1H), 7.28–7.31 (m, 1H), 5.66 (d, J = 11.5, 1H), 5.63 (d, J = 11.5, 1H), 4.49 (d, J = 4.8, 2 H), 3.31 (s, 3H), 1.75 (s, 3 H); ¹³C NMR (500 MHz, CDCl₃): δ 143.5, 141.5, 140.7, 139.6, 127.1, 124.9, 124.5, 122.1, 120.7, 120.7, 113.1, 110.2, 109.5, 94.5, 74.3, 72.0, 56.3, 17.4; IR (film): 3370, 2925, 1599, 1467, 1447, 1422, 1332, 1242, 1110, 1059, 1026, 1011 cm^–1; HRMS-APCI (m/z) [M]^•+ calcd for C₁₈H₁₇BrINO₂, 484.9482; found, 484.9482.