Reaction Steps
A flame-dried 250-mL round-bottomed flask was charged with diisopropylamine (5.8 mL, 41.3 mmol, 3.5 equiv) and THF (100 mL). The resulting solution was cooled to 0° C. and n-butyllithium (1.65 M in hexanes, 25.0 mL, 41.3 mmol, 3.5 equiv) was added dropwise. The reaction was stirred at 0° C. for 30 min and then cooled to −78° C. A solution of ketone 6 (6.8 g, 11.8 mmol, 1.0 equiv) in THF (25 mL) was added dropwise, and the resulting mixture was stirred for 45 min and warmed to −45° C. Formaldehyde gas (CH2O(g), prepared by heating paraformaldehyde ((CH2O)n, 5.0 g, 166.7 mmol, 14.1 equiv) to 145° C. under a positive pressure of nitrogen) was bubbled through the reaction. The reaction was stirred at −45° C. until full conversion to product was indicated by TLC analysis, typically 1 h. The reaction was quenched by the addition of a saturated NH4Cl(aq.) (30 mL), and the resulting mixture was extracted with Et2O (3×30 mL). The combined organic extracts were dried with magnesium sulfate and concentrated in vacuo. The crude product was purified via flash chromatography (50:50 to 60:40 EtOAc:hexanes) to give alcohol 8 as a clear, viscous oil (4.9 g, 70%). Analytical data: [α]D19+11.2 (c=1.00, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.35-7.26 (m, 10H), 7.21 (t, J=7.0 Hz, 1H), 6.59 (d, J=16.0 Hz, 1H), 6.28 (dd, J=16.0, 9.0, 1H), 5.32 (s, 1H), 5.11 (d, J=12.0 Hz, 1H), 5.02 (d, J=12.0 Hz, 1H), 4.98 (t, J=8.5 Hz, 1H), 4.40 (q, J=6.5 Hz, 1H), 3.85-3.82 (m, 1H), 3.73-3.71 (m, 1H), 2.93 (s, 6H), 2.82-2.70 (m, 2H), 1.23 (d, J=6.5 Hz, 3H), 0.87 (s, 9H), 0.10 (s, 3H), 0.09 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 208.5, 158.7, 155.9, 136.8, 136.6, 132.3, 128.4, 128.3, 128.1, 127.9, 127.5, 127.1, 126.6, 74.2, 71.7, 66.6, 58.1, 55.2, 40.7, 36.6, 25.7, 19.2, 17.8, −3.7, −5.0; LRMS (ESI+) Calcd. for C32H47N3O6Si+H, 598.33. Found, 598.32. IR (thin film, cm−1) 3429, 2954, 1716, 1646, 1507, 1252, 966, 695, 530; TLC (50:50 hexanes:EtOAc): Rf=0.20.
