The Journal of Organic Chemistry
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1312 (w), 1258 (m), 1200 (m), 1121 (m), 1051 (m), 968 (m), 925
(m), 854 (m) cm−1; 1H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.47
(s, 1H), 7.14 (s, 1H), 5.61−5.28 (m, 6H), 4.08−3.92 (m, 4H), 3.88 (s,
3H), 3.85 (s 3H), 2.49 (t, J = 6.6 Hz, 2H), 2.16−2.02 (m, 2H), 2.0−
1.85 (m, 6H), 1.8−1.55 (m, 6H), 1.35−1.20 (m, 6H); 13C NMR (100
MHz, CDCl3) δ 168.5, 167.2, 150.9, 147.9, 134.8, 131.7, 130.9, 130.5,
129.3, 125.6, 125.3, 124.8, 123.8, 122.7, 120.9, 116.5, 111.6, 86.0, 66.3,
66.2, 52.8, 52.6, 34.9, 34.1, 32.7, 32.6, 29.6, 29.6, 29.2, 29.2, 29.0,
28.9, 26.9, 25.9, 18.1; HRMS (ESI) m/z 531.2958 [calcd for C30H43O8
(M + H) 531.2958].
additional Et3N (169 μL, 1.24 mmol, 0.3 equiv) and TMSCl (163 μL,
1.21 mmol, 0.3 equiv) were added. The reaction mixture was stirred at
0 °C for an additional hour and then diluted sequentially with CH2Cl2
(20 mL), water (5 mL), and saturated aqueous NaHCO3 (5 mL). The
layers were separated, and the aqueous layer was extracted with
CH2Cl2 (2 × 20 mL). The combined organic layers were washed with
brine, dried over Na2SO4, and concentrated in vacuo. Purification via
silica gel chromatography (5−50% EtOAc/hexanes eluent) furnished
TMS-acetal 38α (131 mg, 5.3% yield, eluting first), TMS-acetal 38β
(1012 mg, 40.5% yield, eluting second), and lactols-α/β (650 mg,
29.5% yield, eluting third) as clear oils. 38α: FTIR (thin film/NaCl)
2954 (s), 2929 (s), 2855 (s), 1736 (s), 1725 (s), 1643 (m), 1436 (m),
1355 (m), 1276 (s), 1250 (s), 1208 (s), 1188 (s), 1145 (m), 1083 (s),
Acetates 36α and 36β. To a stirred solution of phenol 35 (3.18 g,
5.99 mmol, 1.0 equiv) at reflux in 1,2-dichloroethane (32 mL) was
added a solution of Pb(OAc)4 (3.99 g, 8.99 mmol, 1.5 equiv) in 1,2-
dichloroethane (40 mL; total concentration of reaction, 0.083 M). The
solution was maintained at reflux for 10 min and then cooled to rt and
concentrated in vacuo. Purification via silica gel chromatography
(short plug ∼4 cm, 25% EtOAc/hexanes eluent) furnished an
inseparable mixture of acetates 36α and 36β (3.31 g, 94% yield) as
a clear oil. Acetate 36β: 1H NMR (500 MHz, CDCl3) δ 5.45−5.38 (m,
4H), 4.00−3.92 (m, 4H), 3.81 (s, 3H), 3.79 (s, 3H), 3.82−3.78 (m,
1H), 3.73 (d, J = 3.6 Hz, 1H), 3.61 (dd, J = 12.4, 2.6 Hz, 1H), 2.15−
1.80 (m, 12H), 1.70−1.55 (m, 9 H), 1.4-.12 (m, 8H); 13C NMR (125
MHz, CDCl3) δ 200.9, 168.5, 166.6, 164.0, 140.7, 131.7, 131.5, 131.1,
131.0, 125.2, 125.1, 125.1, 124.2, 110.4, 110.3, 92.0, 75.1, 66.9, 65.9,
53.9, 53.0, 52.8, 52.7, 45.2, 41.2, 36.1, 35.1, 34.1, 32.6, 29.6, 29.2, 29.2,
28.9, 27.1, 26.0, 21.5, 18.1; HRMS (ESI) m/z 589.3020 [calcd for
C32H45O10 (M + H) 589.3013]. Acetate 36α: FTIR (thin film/NaCl)
2929 (m), 1749 (s), 1725 (s), 1434 (m), 1368 (m), 1283 (s) 1229
cm−1; 1H NMR (500 MHz, CDCl3) δ 5.45−5.35 (m, 4H), 4.67−4.62
(m, 1H), 4.09 (d, J = 3 Hz, 1H), 4.08−3.82 (m, 4H), 3.86 (s, 1H),
3.80 (s, 3H), 3.77 (s, 3H), 3.78−3.74 (m, 1H), 3.63 (d, J = 1.5 Hz,
1H), 2.15−1.8 (m, 10H), 1.85−1.78 (m, 1H), 1.72−1.55 (m, 9H),
1.46−1.24 (m, 8H); 13C NMR (125 MHz, CDCl3) δ 195.9, 170.0,
165.5, 164.7, 139.4, 133.3, 131.5, 131.0, 125.2, 125.1, 124.8, 118.6,
113.6, 110.4, 93.0, 75.9, 69.9, 66.8, 66.2, 53.9, 53.1, 52.9, 52.9, 52.8,
44.2, 39.4, 35.7, 35.4, 34.1, 32.7, 30.8, 29.6, 29.2, 27.2, 15.9, 21.9, 20.7,
18.1, 18.1; HRMS (ESI) m/z 589.3022 [calcd for C32H45O10 (M + H)
589.3013].
Preparation of Silyl Ethers 38α and 38β: Lactols. To a cooled
solution (0 °C) of acetates 36α,β (56.2 mg, 0.106 mmol, 1.0 equiv) in
MeOH (5 mL) was added K2CO3 (29.3 mg, 0.212 mmol, 2.0 equiv). The
reaction mixture was warmed to rt, and stirred for 40 min. The reaction
was then cooled to 0 °C, quenched with 1 N HCl (5 mL), and extracted
with CH2Cl2 (3 × 5 mL). The combined organic layers were washed with
brine (10 mL), dried over Na2SO4, and concentrated in vacuo.
Purification by preparative TLC (33% EtOAc/hexanes eluent) gave
lactol-α (11.2 mg, 19.4% yield, higher band) and lactol-β (33.7 mg, 58.3%
yield, lower band) as clear oils. Lactol-α: FTIR (thin film/NaCl) 3436
(br), 2930 (s), 2856 (m), 1725 (s), 1634 (w), 1435 (m), 1364 (w), 1225
(s), 1172 (m), 1085 (m), 1043 (m), 967 (m), 925 (w), 736 (m) cm−1;
1H NMR (400 MHz, CDCl3) δ 5.41 (m, 4H), 4.4−3.9 (m, 5H), 3.81 (s,
3H), 3.79 (s, 3H), 3.76 (s, 1H), 3.57 (d, J = 1.2 Hz, 1H), 3.37 (d J = 2.9
Hz, 1H), 2.12−1.9 (m, 8H), 1.78−1.55 (m, 10H), 1.35−1.22 (m, 8H);
13C NMR (125 MHz, CDCl3) δ 199.3, 165.2, 165.1, 139.6, 134.8, 131.5,
130.9, 125.3, 125.1, 110.5, 89.6, 77.0, 73.1, 66.7, 66.1, 53.9, 52.9, 43.7,
41.9, 36.2, 35.7, 34.2, 32.7, 30.7, 29.6, 29.2, 27.2, 26.1, 18.1, 18.1; HRMS
(ESI) m/z 547.2906 [calcd for C30H43O9 (M + H) 547.2907]. Lactol-β:
FTIR (thin film/NaCl) 3200 (br), 2928 (s), 2855 (s), 1723 (s), 1699 (s),
1695 (s), 1642 (s), 1435 (s), 1357 (m), 1280 (m), 967 (m), 924 (m)
cm−1; 1H NMR (400 MHz, CDCl3) δ 5.43−5.38 (m, 4H), 3.96 (s, 4H),
3.81 (s, 3H), 3.78 (s, 3H), 3.56 (d, J = 2.5 Hz, 1H), 3.52 (s, 1H), 3.13 (d,
J = 3.2 Hz, 1H), 2.1−1.75 (m, 9H), 1.7−1.55 (m, 8H), 1.42−1.20 (m,
8H); 13C NMR (125 MHz, CDCl3) δ 206.8, 165.5, 165.1, 139.8, 133.3,
131.5, 131.0, 125.1, 125.1, 110.3, 89.9, 74.4, 66.5, 65.8, 53.8, 52.8, 52.8,
45.8, 40.8, 35.9, 39.9, 34.3, 32.6, 29.6, 29.1, 29.1, 27.1, 26.2, 18.1; HRMS
(ESI) m/z 547.2913 [calcd for C30H43O9 (M + H) 547.2907].
1
1045 (m), 847 (s) cm−1; H NMR (400 MHz, CDCl3) δ 5.48−5.35
(m, 4H), 4.00−3.89 (m, 4H), 3.78 (s, 3H), 3.76 (s, 3H), 3.54 (dd, J =
12.1, 2.3 Hz, 1H), 3.47 (d, J = 2.5 Hz, 1H), 3.0 (d, J = 3.4 Hz, 1H),
2.15−1.70 (m, 8H), 1.66−1.52 (m, 10H), 1.41−1.19 (m, 8H). 0.11 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 205.6, 165.9, 165.4, 140.4,
132.6, 131.5, 130.9, 125.0, 110.5, 91.7, 73.4, 66.3, 65.3, 55.3, 52.7, 52.5,
48.7, 41.4, 35.6, 35.0, 34.8, 32.6, 29.6, 29.1, 28.3, 27.1, 26.4, 18.1, 1.44;
HRMS (ESI) m/z 619.3298 [calcd for C33H51O9Si (M + H)
619.3302]. 38β: FTIR (thin film/NaCl) 2954 (s), 2928 (s), 2855
(m), 1755 (s), 1725 (s), 1640 (w), 1436 (m), 1361 (w), 1277 (s),
1249 (s), 1185 (m), 1154 (w) 1082 (m), 1046 (s), 966 (m), 875 (m),
848 (s), 758 (w) cm−1; 1H NMR (500 MHz, CDCl3) δ 5.46−5.37 (m,
4H), 4.07−4.00 (m, 2H), 3.95−3.86 (m, 3H), 3.80 (s, 3H), 3.78 (s,
3H), 3.46 (d, J = 1.5 Hz, 1H), 3.19 (d, J = 2.7 Hz, 1H), 2.12−1.92 (m,
8H), 1.71−1.55 (m, 10H), 1.34−1.20 (m, 8H), 0.12 (s, 9H); 13C
NMR (125 MHz, CDCl3) δ 198.8, 165.6, 165.4, 140.2, 134.1, 131.5,
130.9, 125.2, 125.0, 110.7, 91.4, 72.9, 66.6, 66.2, 54.9, 52.7, 52.6, 45.4,
44.0, 35.8, 35.5, 34.6, 32.7, 31.1, 29.6, 29.2, 27.2, 26.9, 26.0, 18.0, 1.5;
HRMS (ESI) m/z 619.3306 [calcd for C33H51O9Si (M + H)
619.3302].
Preparation of Tertiary Amine 40: Enolate 39. To a solution of
diisopropylamine (537 μL, 4.08 mmol, 2.5 equiv) in THF (5 mL) at
−78 °C was added n-BuLi (1.6 M in hexane: 2.4 mL, 3.84 mmol,
2.4 equiv) dopwise over 5 min. The resultant mixture was stirred at
−20 °C for 5 min, and then cooled to −78 °C. To this mixture was
added methyl-3-(dimethylamino)propionate (515 μL, 3.6 mmol,
2.2 equiv) in THF (2 mL) dropwise over 5 min. The reaction
mixture was stirred at −78 °C for 30 min, 0 °C for 15 min, and rt for
15 min, and then cooled to −78 °C.
Tertiary Amine 40. A solution of TMS-ether ketone 38β (1.01 g,
1.63 mmol, 1.0 equiv) in THF (10 mL) was added dropwise to enolate
39 over 10 min. The temperature was maintained at −78 °C for 1 h, at
which time it was treated with EtOAc (5 mL) and saturated NH4Cl
(3 mL) and then warmed to rt. The layers of the biphasic mixture were
separated, and the aqueous layer was extracted with EtOAc (2 × 10 mL).
The combined organic layers were washed with brine, dried over Na2SO4,
and concentrated in vacuo. Purification via silica gel chromatography (5−
10% MeOH/CH2Cl2 eluent) furnished 40 (1.31 g, 93.5% yield) as a clear
oil. FTIR (thin film/NaCl) 3467 (br), 2951 (s), 2928 (s), 2856 (m),
2772 (w), 1721 (s), 1644 (m), 1436 (m), 1347 (w), 1274 (s), 1249 (s),
1195 (m), 1169 (m), 1087 (m), 1071 (m), 1046 (m), 966 (w), 921 (w),
867 (w), 845 (m) cm−1; 1H NMR (400 MHz, CDCl3) δ 5.44−5.36 (m,
4H), 4.90 (dd, J = 10.6, 5.2 Hz, 1H), 4.00−3.90 (m, 4H), 3.76 (s, 3H),
3.73 (s, 3H), 3.66 (s, 3H). 3.22 (dd, J = 13.0, 8.3 Hz, 1H), 3.01 (d, J = 1.7
Hz, 1H), 2.79−2.69 (m, 2H), 2.67 (d, J = 2.5 Hz, 1H), 2.29−2.20 (m,
2H), 2.20 (s, 6H), 2.10−1.90 (m, 4H), 1.69−1.49 (m, 10H), 1.33−1.18
(m, 8H), 0.20 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 176.1, 166.5,
166.5, 139.7, 136.7, 131.8, 131.5, 124.8, 124.6, 111.5, 99.7, 80.7, 73.8, 66.1,
65.0, 60.1, 52.2, 52.2, 51.8, 50.7, 50.2, 49.1, 46.4, 37.1, 36.3, 34.9, 34.7,
32.7, 29.7, 29.5, 28.6, 27.4, 26.6, 18.1, 2.0; HRMS (ESI) m/z 750.4252
[calcd for C39H63NO11Si (M + H) 750.4249].
Preparation of Lactone 37β: Unsaturated Ester. Before
beginning the reaction, a column of basic alumina was prepared: h =
3 cm, d = 4.5 cm, packed with CH2Cl2 (it is critical that the pad
of alumina be short and thick). To a solution of tertiary amine 40
(767 mg, 1.02 mmol, 1.0 equiv) in CH2Cl2 (5 mL) at −78 °C was added
a solution of m-CPBA (275 mg, 1.53 mmol, 1.5 equiv) in CH2Cl2
Silyl Ethers 38α/38β. To a solution of lactols-α/β (2.1 g, 4.04
mmol, 1.0 equiv) in CH2Cl2 (40 mL) at 0 °C was added Et3N
(676 μL, 4.84 mmol, 1.2 equiv) and TMSCl (651 μL, 4.84 mmol, 1.2
equiv). The reaction mixture was stirred at 0 °C for 5h, at which point
485
dx.doi.org/10.1021/jo302353g | J. Org. Chem. 2013, 78, 477−489