Reaction Steps
3-Pentyl trichloroacetimidate was prepared as follows. Under an atmosphere of nitrogen, a solution of 3-pentanol (8.815 g, 100 mmol) in anhydrous Et2O (14 mL) was added dropwise to NaH (0.4 g, 10 mmol, 60% oil dispersion prewashed with hexane) suspended in Et2O (10 mL). The mixture was stirred for 10 min at room temperature, and added dropwise over a period of 20 min to a cold (−5° C.) solution of trichloroacetonitrile (15 mL, 150 mmol) in Et2O (20 mL) under an atmosphere of nitrogen. The reaction mixture was warmed to room temperature, and stirred for 2 h. After removal of solvent, the residue was triturated with MeOH/hexane (1:19, 10 mL) with vigorous stirring for 1 min to give precipitates, which were filtered off and washed with cold hexane. The filtrate was evaporated under reduced pressure to dryness, giving 3-pentyl trichloroacetimidate (16 g, 70% yield) as light brown oil. TLC (EtOAc/hexane, 1:4) Rf=0.3; 1H NMR (600 MHz, CDCl3) δ 8.17 (1 H, br s, NH), 4.89 (1 H, m, J=6.0 Hz), 1.69 (4 H, qd, J=7.4, 6.0 Hz), 0.94 (6 H, t, J=7.4 Hz); 13C NMR (150 MHz, CDCl3) δ 162.7, 92.2, 81.9, 25.7 (2×), 9.4 (2×); HRMS calcd for C7H13Cl3NO (M++H): 232.0063, found: m/z 232.0067. Under an atmosphere of nitrogen, the freshly prepared 3-pentyl trichloroacetimidate (350 mg, 1.5 mmol) and CF3SO3H (13 μL, 0.15 mmol) were added to a solution of alcohol 10a (321 mg, 1.2 mmol) in CH2Cl2 (15 mL). The reaction mixture was stirred at room temperature for 24 h, during which more imidate and CF3SO3H (350 mg and 13 μL mmol) were added 5 times every 4 h period. The reaction was quenched with aqueous NaHCO3 solution (5%). The aqueous layer was extracted with CH2Cl2 (2×). The combined organic phase was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography (EtOAc/hexane, 3:7) to afford the alkylation product 11a (317 mg, 78% yield). Colorless solid, mp 115-117° C.; TLC (EtOAc/hexane, 1:1) Rf=0.4; [α]D20=−48.9 (c=1.1, CHCl3); IR (neat) 2101, 1712, 1655 cm−1; 1H NMR (600 MHz, CDCl3) δ 6.75 (1 H, s), 5.98 (1 H, d, J=7.4 Hz), 4.53 (1 H, d, J=5.0 Hz), 4.51-4.16 (3 H, m), 3.33-3.28 (2 H, m), 2.82 (1 H, dd, J=17.6, 5.6 Hz), 2.22-2.16 (1 H, m), 2.00 (3 H, s), 1.49-1.45 (4 H, m), 1.25 (3 H, t, J=7.1 Hz), 0.95-0.80 (6 H, m); 13C NMR (150 MHz, CDCl3) δ 171.1, 165.8, 137.9, 128.1, 82.0, 73.4, 61.0, 58.0, 57.2, 30.5, 26.2, 25.6, 23.5, 14.1, 9.5, 9.3; HRMS calcd for C16H27N4O4(M++H): 3390.2032, found: m/z 339.2035.
