-EXPERIMENTAL-
[on chemistry] “Because right now, this is a job. If I advance any higher, this would be my career. And if this were my career, I'd have to throw myself in front of a train.” - Jim Halpert
Lactone 59. DDQ (14.0 g, 61.7 mmol, 1.91 equiv) was added to a solution of Michael adduct
58 (23.8 g, 32.3 mmol, 1.00 equiv), CH2Cl2 (200 mL) and H2O (10 mL). The reaction mixture
was vigorously stirred at rt for 1.5 h, then poured into chilled 1 N aqueous NaOH and
extracted with CH2Cl2 (3 x 200 mL). The combined organic extracts were dried over MgSO4,
filtered, and evaporated under reduced pressure to give the crude product. Purification by
flash chromatography (10% EtOAc-hexanes, 30% EtOAc-hexanes, 50% EtOAc-hexanes)
furnished a mixture of alcohol and lactone products. The mixture of crude products was
dissolved in CH2Cl2 (300 mL) and treated with PPTS (2.0 g, 7.96 mmol). After stirring at rt
for 1.5 h, the reaction mixture was poured into chilled 1 N aqueous HCl, and extracted with
CH2Cl2 (3 x 200 mL). The combined organic layers were dried over MgSO4, then
concentrated under reduced pressure to give a residue the crude product. Purification by
flash chromatography (SiO2, 25% EtOAchexanes, 30% EtOAc-hexanes, 50% EtOAc-hexanes)
afforded lactone 59 (16.5 g, 28.2 mmol, 77% yield). 1H NMR (500 MHz, CDCl3): δ 7.98 (d, J
= 8.1, 2H), 7.60 (t, J = 7.0, 4H), 7.54–7.51 (m, 1H), 7.44–7.39 (m, 4H), 7.37–7.32 (m, 4H),
4.53 (t, J = 3.1, 1H), 4.42 (ddd, J = 11.4, 10.7, 5.0, 1H), 4.25–4.20 (m, 1H), 4.19–4.10 (m,
2H), 4.01 (dd, J = 11.7, 4.2, 1H), 3.89 (dd, J = 11.7, 2.8, 1H), 2.62–2.58 (m, 2H), 2.26 (dd,
J = 18.2, 12.2, 1H), 2.07–2.03 (m, 1H), 1.92–1.89 (m, 1H), 1.16 (t, J = 7.1, 3H), 0.97 (s,
9H); 13C NMR (125 MHz, CDCl3): δ 170.9, 170.5, 165.2, 135.6, 135.4, 132.9, 132.5, 131.9,
129.73, 129.69, 128.6, 128.2, 127.60, 127.56, 84.4, 80.5, 67.7, 63.1, 61.6, 39.4, 30.3, 26.5,
24.3, 18.9, 13.9; IR (film): 1749, 1643 cm-1; HRMS-FAB (m/z): [M+ H]+ calcd for
C34H40NO6Si, 586.2625; found, 586.2630; Anal. Calcd for C34H39NO6Si: C,69.71; H 6.71;
N, 2.39; found: C, 69.45; H, 6.62; N, 2.25; [α]26405 +147.4, [α]26435 +122.8, [α]26546
+69.5, [α]26577 +59.8 [α]26D +64.8 (c 0.95, CHCl3).
Glossary
- Flash chromatography – fast form of column chromatography, a way of purifying and separating compounds
