Reaction Steps
7-Bromoisoquinoline (40 mg, 0.193 mmol, 3 equiv) was dissolved in THF (1 mL, 0.19 M) and cooled down to −72° C. (dry ice-isopropanol bath), after which n-BuLi (88 μL, 2.3 M, 0.19 mmol, 3 equiv) was added dropwise. After 40 minutes, TMEDA (88 μL, 0.58 mmol, 9 equiv) was added into the solution. After 10 minutes, O-TBS-estrone (25 mg, 0.065 mmol, 1 equiv) in THF (0.3 mL, 0.22 M in THF) was added dropwise into the reaction solution. After 40 minutes, the reaction was quenched by the addition of sat. aq. NaHCO3 (5 mL). The aqueous layer was extracted four times (4×10 mL) with EtOAc, washed with sat. aq. NaCl (20 mL), dried over MgSO4, filtered, and concentrated in vacuo. Flash column chromatography (silica gel, 30% EtOAc:hexanes) afforded isoquinolinol Compound 28 (25 mg, 74%) as a yellow foam: Rf=0.31 (1:1 EtOAc:DCM); [α]D=+16.9° (c 0.54, CH2Cl2); IR (neat) νmax=3210, 1496, 1285, 1251, 837 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.28 (s, 1H), 8.51 (d, J=4.8 Hz, 1H), 7.88 (d, J=7.8 Hz, 2H), 7.79 (d, J=8.9 Hz, 1H), 7.65 (d, J=5.6 Hz, 1H), 6.95 (d, J=8.3 Hz, 1H), 6.55-6.50 (m, 2H), 2.87-2.73 (m, 2H), 2.59 (ddd, J=5.1, 9.8, 14.8 Hz, 1H), 2.25 (ddd, J=4.4, 12.5, 17.1 Hz, 1H), 2.10-2.00 (m, 2H), 1.96-1.91 (m, 1H), 1.79 (td, J=4.0, 11.2 Hz, 1H), 1.75-1.65 (m, 2H), 1.50 (dddd, J=2.2, 10.8, 12.7, 21.6 Hz, 1H), 1.47-1.32 (m, 1H), 1.33-1.22 (m, 2H), 1.15 (s, 3H), 0.95 (s, 9H), 0.57 (td, J=4.1, 12.8 Hz, 1H), 0.16 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 153.2, 152.8, 145.2, 142.9, 137.6, 134.6, 132.8, 130.8, 127.9, 125.9, 125.3, 125.2, 120.0, 119.8, 117.0, 86.1, 48.3, 47.4, 43.3, 39.5, 38.9, 33.7, 29.6, 27.4, 26.1, 25.7, 24.2, 18.1, 14.8; HRMS (ESI-TOF) calcd for C33H43NO2Si [M+H]+: 514.3136; found: 514.3140.
