Reaction Steps
A solution of 34A (170 mg, 0.206 mmol) in acetonitrile (3 mL) and dichloromethane (6 mL) was cooled to 0° C. To this solution, was added phosgene (20% in toluene, 0.112 mL, 0.226 mmol). The mixture was stirred at 0° C. for 5 min, and rt for 1 h. The mixture was bubbled with Ar for 10 min to remove excess phosgene. The resulting solution was added dropwise over 3 h via syringe pump into a solution of TEA (0.287 mL, 2.058 mmol) in CH2Cl2 (260 mL). The solution was stirred for 16 h, and then concentrated and purified by flash chromatography to give a mixture of diastereoisomers (98 mg, 0.115 mmol, 55.9% yield). The diastereomers were separated by a prep chiral HPLC equipped with a OD column to give 34B (38 mg, 0.045 mmol, 38.8% yield). MS (ESI) m/z: 852.3 [M+1]+. 1H NMR (500 MHz, methanol-d4) δ ppm 8.10 (1H, d, J=5.8 Hz), 7.78 (1H, dd, J=7.8, 1.5 Hz), 7.55 (1H, d, J=5.8 Hz), 7.51 (1H, d, J=8.0 Hz), 7.41 (1H, d, J=12.1 Hz), 7.06 (1H, d, J=8.3 Hz), 7.04 (1H, d, J=1.7 Hz), 6.61 (1H, dd, J=12.0, 2.1 Hz), 6.27 (1H, d, J=1.1 Hz), 5.67-5.78 (2H, m), 4.63 (1H, t, J=11.0 Hz), 4.24 (1H, d, J=17.9 Hz), 3.98 (1H, dd, J=10.7, 4.4 Hz), 3.45-3.57 (2H, m), 3.34-3.41 (3H, m), 2.28 (3H, s), 1.38 (3H, d, J=6.9 Hz), 1.35 (3H, d, J=6.9 Hz), 1.33 (3H, d, J=6.9 Hz), 1.28 (18H, s).
