Reaction Steps
Acyl azide 338 (7 mg, 0.0114 mmol) in benzene (1 mL) was stirred at 80° C. for 6 h, after which the solvent was removed and the residue dissolved in THF. In a separate flask, a 0.19 M solution of 1-lithio-phenylacetylene was prepared by deprotonation of phenylacetylene (in THF) with n-BuLi (0.88 equiv.) at −78° C. To this solution (0.2 mL, 0.19 M) in THF was added the isocyanate in THF (0.5 mL) at −78° C. After stirring at −78° C. for 50 min, saturated NH4Cl (3 mL) and water (0.6 mL) were added and the resulting mixture was diluted with Et2O (45 mL), the layers separated, and the organic layer washed with brine, dried over MgSO4, filtered and concentrated. Filtration over silicagel (14% EtOAc in hexanes) provided a crude product (6 mg) which was treated with 370 μL of a solution HF pyridine in THF at RT. After stirring for 48 h at RT, the reaction was quenched with a phosphate buffer (pH 7.0; 10 mL), extracted with EtOAc (3×15 mL), dried over MgSO4 and concentrated. Purification by EC (silicagel, 33% EtOAc in hexanes) gave 2 mg of compound 349 (56%). 349: [α]D=−42 (c 0.1, MeOH); IR 2927, 1652, 1605, 1500, 1451, 1294, 1218, 1123; 1H-NMR (400 MHz, CD3OD) δ 7.58 (2H, app. dt, J=1.6, 6.8 Hz), 7.40-7.52 (3H, m), 7.14 (1H, app.t, J=8.0 Hz), 6.82 (1H, d, J=14.0 Hz), 6.74 (1H, d, J=8.4 Hz), 6.66 (1H, d, J=7.2 Hz), 5.51 (1H, ddd, J=7.6, 7.6, 14.4 Hz), 5.26-5.44 (3H, m), 4.14 (1H, dd, J=3.6, 9.2 Hz), 3.58 (1H, dd, J=8.4, 16.4 Hz), 3.38 (1H, br), 2.36-2.50 (2H, m), 2.29 (1H, br.d, J=14.4 Hz), 1.84-1.94 (1H, m), 1.72-1.84 (3H, m), 0.88 (3H, d, J=6.8 Hz); MS (ES) m/z (%): 460.22 ([M+H]+, 100) HRMS (FAB) Calcd for C28H29NO5Li (MLi+): 466.2206. Found: 466:2204.
