The Journal of Organic Chemistry
Article
2925, 2855, 1653, 1637, 1466, 1458, 1310, 1252, 1143, 1100, 1026,
137.0, 133.7, 131.3, 128.6, 91.0, 80.0, 68.8, 55.0, 47.1, 37.2, 36.1, 33.3,
32.4, 28.8, 25.8, 18.7, 18.1, 18.1, 17.7, 12.4, −4.4, −4.6 ppm; HRMS
(ES+) calcd for C34H60N3O5SSi2 (M + H) 678.3792, found 678.3777.
1
870, 835 cm−1; H NMR (400 MHz, CDCl3) δ 7.88 (dd, J = 8.0, 1.4
Hz, 2H), 7.69 (t, J = 7.6 Hz, 1H), 7.55 (t, J = 8.0 Hz, 2H), 3.96−4.07
(m, 3H), 3.46 (ddd, J = 17.2, 4.8, 2.4 Hz, 1H), 3.30 (ddd, J = 17.2, 6.8,
2.0 Hz, 1H), 2.89 (m, 1H), 2.68−2.75 (m, 1H), 2.46 (td, J = 14.4, 5.6
Hz, 2H), 2.21 (dd, J = 15.2, 4.8 Hz, 1H), 1.97−2.08 (m, 2H), 1.75−
1.86 (m, 2H), 1.03 (d, J = 6.0 Hz, 3H), 0.95 (s, 9H), 0.87 (s, 9H), 0.21
(s, 3H), 0.18 (s, 3H), 0.04 (s, 3H), 0.03 (s, 3H) ppm; 13C NMR (175
MHz, CDCl3) δ 164.5, 156.6, 137.2, 133.9, 130.0, 129.1, 91.6, 72.3,
62.0, 56.1, 43.7, 37.9, 36.2, 32.7, 31.9, 31.2, 30.3, 28.1, 25.79, 25.74,
22.7, 22.0, 18.0, 17.9, 14.1, 0.01, −4.57, −4.58, −4.7 ppm; HRMS (ES
+) calcd for C31H54NO4SSi2 (M + H) 592.3313, found 592.3316.
Imine 58. To a stirred solution of 57 (890 mg, 1.31 mmol) in THF
(45 mL) was added PPh3 (516 mg, 1.97 mmol), and the reaction
mixture was heated to reflux. After 4 h, the reaction was cooled to rt
and the solvent was removed in vacuo. The concentrated compound
was purified by chromatography over basic alumina, eluting with 0−
20% EtOAc/hexanes, to give imine 58 (790 mg, 1.25 mmol, 95%) as a
23
colorless oil. [α]D = +36.0 (c = 1.0, CHCl3); IR (neat) 2946, 2892,
2865, 1650, 1463, 1447, 1388, 1362, 1305, 1256, 1202, 1143, 1105,
1079, 1022 cm−1; 1H NMR (700 MHz, CHCl3) δ 7.88 (dd, J = 8.8, 2.9
Hz, 2H), 7.68 (dd, J = 7.4, 7.1 Hz, 1H), 7.55 (dd, J = 8.1, 7.4 Hz, 2H),
4.12−4.15 (m, 1H), 4.08 (s, 1H), 4.02 (s, 1H), 3.57 (ddd, J = 17.2, 5.2,
2.7 Hz, 1H), 3.36 (ddd, J = 17.3, 7.0, 2.2 Hz, 1H), 2.90 (qd, J = 14.0,
3.5 Hz, 1H), 2.65 (dddd, J = 12.3, 12.1, 2.3, 2.3 Hz, 1H), 2.50 (dd, J =
3.5, 3.5 Hz, 1H), 2.46 (dd, J = 6.1, 6.1 Hz, 1H), 2.32 (dd, J = 4.8, 14.8
Hz, 1H), 1.98−2.04 (m, 2H), 1.79−1.85 (m, 2H), 1.53 (dddd, J = 5.6,
7.6, 5.6, 7.6 Hz, 1H), 1.03−1.06 (m, 21H), 1.02 (d, J = 6.4 Hz, 3H),
0.94 (s, 3H), 0.20 (s, 3H), 0.18 (s, 9H) ppm; 13C NMR (175 MHz,
CHCl3) δ 164.5, 156.8, 137.3, 133.9, 130.1, 129.1, 91.5, 72.4, 62.0,
56.5, 43.5, 37.8, 36.0, 32.7, 31.2, 28.1, 25.7, 22.0, 18.0, 17.9, 12.2, −4.7,
−4.8 ppm; HRMS (ES+) calcd for C34H60NO4SSi2 (M + H)
634.3782, found 634.3773.
TIPS Ether 57. To a stirred solution of 50 (636 mg, 1.56 mmol) in
CH2Cl2 (7.8 mL) at 0 °C were added Pr2NEt (1.2 g, 1.6 mL, 9.3
i
mmol) and TBSOTf (1.03 g, 0.9 mL, 3.9 mmol) sequentially. After 1
h, the reaction was quenched by sat. aq NaHCO3 (12 mL) and
extracted with CH2Cl2 (3 × 15 mL). The dried extract (MgSO4) was
concentrated in vacuo. An analytical sample of 52 was obtained by
purification by chromatography over silica gel, eluting with 0−15%
20
EtOAc/hexanes: [α]D = +16.7 (c = 1.21, CHCl3); IR (neat) 3406,
2954, 2928, 2858, 2101, 1631, 1446, 1284, 1258, 1142, 1077, 1023,
1
910, 840, 781, 689, 601 cm−1; H NMR (700 MHz, CHCl3) δ 7.92
(dd, J = 8.4, 1.4 Hz, 2H), 7.68 (t, J = 7.7 Hz, 1H), 7.57 (t, J = 14.7 Hz,
2H), 4.27 (s, 1H), 4.15−4.19 (m, 1H), 4.04 (s, 1H), 3.98 (s, 1H), 3.69
(dd, J = 12.6, 4.9 Hz, 1H), 2.87 (dd, J = 13.3, 6.3 Hz, 1H), 2.54 (m,
1H), 2.25−2.32 (m, 2H), 2.10−2.14 (m, 2H), 1.78−1.81 (m, 1H),
1.71 (t, J = 13.3 Hz, 1H), 1.55−1.57 (m, 2H), 0.89 (d, J = 6.3 Hz, 3H),
0.84 (s, 9H), 0.12 (s, 3H), 0.09 (s, 3H) ppm; 13C NMR (175 MHz,
CHCl3) δ 156.2, 138.4, 134.0, 129.7, 129.1, 105.6, 92.3, 75.8, 75.0,
56.4, 42.0, 37.1, 34.2, 34.0, 31.7, 25.7, 22.6, 21.5, 18.0, 0.04, −4.6, −4.8
ppm; HRMS (ES+) calcd for C25H40N3O5SSi (M + H) 522.2458,
found 522.2482.
Tricycle 59. To a sealed tube loaded with imine 58 (251 mg, 0.396
mmol) were added sequentially Zn(OTf)2 (435 mg, 1.19 mmol) and
1,2-dichloroethane (15.8 mL) and heated to 94 °C. After 6 h, the
reaction was cooled to rt. After 10 min, the reaction was quenched by
sat. aq NaHCO3 (10 mL) and extracted with CH2Cl2 (3 × 15 mL).
The dried (MgSO4) extract was concentrated in vacuo and purified by
chromatography over silica gel, eluting with 2−30% EtOAc/hexanes,
20
to give 59 (118 mg, 0.227 mmol, 57%) as a white foam. [α]D
=
The crude TBS-enol ether 52 was dissolved in 1,2-DCE (8.0 mL).
−23.0 (c = 1.0, CHCl3); IR (neat) 2925, 2864, 1711, 1647, 1462,
1296, 1137, 1077 cm−1; 1H NMR (700 MHz, CDCl3) δ 7.94−7.96 (m,
2H), 7.73 (ddt, J = 7.5, 2.2, 1.1 Hz, 1H), 7.60−7.63 (m, 2H), 4.85−
4.90 (m, 1H), 3.36 (dd, J = 14.5, 7.2 Hz, 1H), 3.33 (d, J = 2.5 Hz, 1H),
2.91 (dd, J = 14.5, 9.2 Hz, 1H), 2.71−2.76 (m, 1H), 2.59 (ddd, J =
17.8, 5.7, 1.5 Hz, 1H), 2.49 (dt, J = 15.1, 1.6 Hz, 1H), 2.29 (td, J =
17.9, 1.9 Hz, 1H), 2.23 (dd, J = 18.0, 1.9 Hz, 1H), 2.21 (dd, J = 10.7,
5.3 Hz, 1H), 1.89−1.98 (m, 3H), 1.61 (dd, J = 13.4, 5.4 Hz, 1H), 1.47
(dd, J = 13.9, 5.7 Hz, 1H), 1.06−1.09 (m, 21H), 1.04 (d, J = 6.3 Hz,
3H) ppm; 13C NMR (175 MHz, CDCl3) δ 209.5, 137.8, 134.0, 129.6,
129.1, 71.7, 63.4, 57.8, 50.5, 47.5, 45.3, 43.2, 35.6, 35.5, 35.2, 24.9,
21.7, 18.1, 18.0, 12.3 ppm; HRMS (ES+) calcd for C28H46NO4SSi (M
+ H) 520.2917, found 520.2891.
Hemiketal SI-3. A solution of acetonide 44 (120 mg, 0.284 mmol)
in 60% AcOH (aq) (2.9 mL) was stirred at rt. After 15 h, water (10
mL) was added and the reaction mixture was treated with sat. aq
NaHCO3 (30 mL). The aqueous mixture was extracted with EtOAc (3
× 50 mL), washed with brine (50 mL), dried (MgSO4), and
concentrated in vacuo. The concentrated compound was purified by
i
To the solution were added Pr2NEt (3.1 g, 4.2 mL, 24.1 mmol),
DMAP (193 mg, 1.58 mmol), and TIPSOTf (3.2 g, 2.8 mL, 10.4
mmol) sequentially and heated to 40 °C. After 84 h, the reaction was
cooled to rt, diluted with CH2Cl2 (10 mL), and quenched by sat. aq
NaHCO3 (15 mL), and the aqueous layer was extracted with CH2Cl2
(3 × 20 mL). The dried extract (MgSO4) was concentrated in vacuo
and purified by chromatography over silica gel, eluting with 0−15%
EtOAc/hexanes, to give 57 (890 mg, 1.31 mmol, 85%) as a colorless
20
oil. [α]D = −34.0 (c = 0.5, CHCl3); IR (neat) 2944, 2892, 2866,
2103, 1713, 1627, 1463, 1447, 1386, 1362, 1297, 1255, 1201, 1170,
1
1142, 1081, 1015 cm−1; H NMR (400 MHz, CHCl3) δ 8.05−8.08
(m, 2H), 7.63 (dddd, J = 7.3, 7.4, 1.3, 1.3 Hz, 1H), 7.52 (dd, J = 8.0,
7.4 Hz, 2H), 4.84−4.89 (m, 1H), 4.11 (s, 1H), 3.99 (s, 1H), 3.56 (dd,
J = 2.5, 13.3 Hz, 1H), 3.35 (td, J = 1.3, 14.6 Hz, 1H), 3.13 (dd, J = 2.4,
2.4 Hz, 1H), 3.07 (dd, J = 6.0, 5.7, Hz, 1H), 2.48−2.64 (m, 3H), 2.19−
2.27 (m, 2H), 2.01 (dd, J = 11.7, 14.5, 1H), 1.73−1.87 (m, 2H), 1.07−
1.14 (m, 21H), 0.94 (s, 9H), 0.59 (d, J = 6.7 Hz, 3H), 0.23 (s, 3H),
0.18 (s, 3H) ppm; 13C NMR (100 MHz, CHCl3) δ 206.8, 157.1,
M
J. Org. Chem. XXXX, XXX, XXX−XXX