Reaction Steps
Oven-dried LiC1 (0.276 g, 6.511 mmol, 7.3 equiv) was vigorously stirred in THF (9.0 mL) until fully dissolved. Trans β-lactam 15 (0.420 g, 0.889 mmol, 1.0 equiv) was added and cooled to 0° C. A solution of MeMgBr (0.98 mL, 0.987 mmol, 1.1 equiv, 1M THF) was added dropwise and stirred at 0° C. for 2 h, at which time the ice-bath was removed and the reaction allowed to slowly warm to room temperature. After stirring for 48 h sat. NHCl(aq) was added to quench the reaction, which was further diluted with EtOAc. The organics were washed with water, followed by brine and dried over Na2SO4. The organics were concentrated in vacuo and purified by flash column chromatography (35% EtOAc/hexanes) to provide the pure ketone 16 (Rf=0.32, 0.135 g, 36% yield) and recovered starting material 15 (Rf=0.16, 0.249 g) representing an 87% yield (based on recovered starting material, brsm). m.p.=52-54° C.; [α]D23=+71.875° (c=0.8, MeOH); 1H NMR (500 MHz, CDCl3): δ 7.31-7.36 (m, 9H); 7.20-7.22 (m, 6H); 5.41 (ddd, J=2.2, 3.5, 10.3 Hz, 1H); 4.03 (d, J=2.1 Hz, 1H); 3.57 (s, 3H); 2.36 (s, 3H); 2.13 (dd, J=10.3, 16.2 Hz, 1H); 1.73 (dd, J=3.5, 16.2 Hz, H); 13C NMR (125 MHz, CDCl3): δ 200.04, 170.45, 163.17, 141.83, 129.82, 128.26, 128.00, 74.54, 66.68, 52.01, 52.01, 37.15, 30.70; IR (thin film): 3059, 2953, 1759, 1714, 1597, 1493, 1444, 1359, 1337, 1177, 1034, 752, 700, 639 cm−1; HRMS for [M+Na]C27H25NO4Na calc'd., 450.16758, found, 450.16980 (Error=4.9322 ppm).
