Synthesis of Dysiherbaine and Analogues
(115 mL) at 0 °C was added LiBH4 (1.00 g, 46.0 mmol). The
resulting solution was stirred at 0 °C for 10 min before it was
quenched with saturated aqueous potassium sodium tartrate (50
mL). The mixture was stirred at 0 °C for 1 h and extracted with
ethyl acetate (2 × 300 mL). The combined organic layers were
washed with brine (50 mL), dried over Na2SO4, filtered, and
concentrated under reduced pressure. Flash column chromatography
(silica gel, 50% ethyl acetate/hexanes) afforded oxazolidinone 28
(3.16 g, 64%) as a white foam: [R]28D -22.8 (c 0.89, CHCl3); IR
0.04 (s, 6H); 13C NMR (125 MHz, CDCl3) δ (major diastereomer)
158.0, 138.0, 128.4, 128.3, 128.1 (×2), 127.2, 75.7, 74.7, 73.5,
73.4, 72.8, 66.5, 66.0, 60.9, 38.8, 35.7, 25.9 (×3), 18.3, -5.5 (×2);
HRMS (ESI) m/z calcd for C23H36NO6SiINa [(M + Na)+] 600.1254,
found 600.1233.
Bicyclic Ether 31. A solution of TBS ether 30 (41.9 mg, 0.0726
mmol) in pyridine (2 mL) was heated at reflux for 24 h. The
resulting solution was then cooled to room temperature and
concentrated under reduced pressure. The residue was dissolved
in ethyl acetate (20 mL), washed with aqueous 1 M HCl (5 mL),
saturated aqueous NaHCO3 (5 mL), and brine (5 mL), filtered, and
concentrated under reduced pressure. Flash column chromatography
(silica gel, 50% ethyl acetate/hexanes) afforded bicyclic ether 31
(22.9 mg, 70%) along with the C4 diastereomer (3.2 mg, 10%) as
1
(film) 3302, 2917, 2850, 1756, 1384, 1219, 1128, 1090 cm-1; H
NMR (500 MHz, CDCl3) δ 7.35-7.26 (m, 5H), 5.65 (s, 1H), 5.19
(s, 1H), 5.07 (s, 1H), 4.52 (d, J ) 11.5 Hz, 1H), 4.40 (d, J ) 11.5
Hz, 1H), 4.35 (d, J ) 14.5 Hz, 1H), 4.28 (dd, J ) 6.5, 2.0 Hz,
1H), 4.13 (dd, J ) 9.0, 6.0 Hz, 1H), 4.02 (d, J ) 12.0 Hz, 1H),
3.96 (d, J ) 12.0 Hz, 1H), 3.71 (dd, J ) 10.5, 9.0 Hz, 1H), 3.65
(dd, J ) 14.5, 2.5 Hz, 1H), 3.53 (ddd, J ) 10.5, 9.0, 2.5 Hz, 1H),
2.92 (d, J ) 14.5 Hz, 1H), 2.22 (dd, J ) 14.5, 9.0 Hz, 1H); 13C
NMR (125 MHz, CDCl3) δ 158.6, 141.7, 138.3, 128.4 (×2), 127.8
(×2), 127.7, 115.6, 77.1, 74.9, 72.9, 71.9, 66.5, 61.0, 38.4, 34.8;
HRMS (ESI) m/z calcd for C17H20NO4INa [(M + Na)+] 452.0335,
found 452.0307.
a white foam, respectively. 31: [R]28 +11.4 (c 1.49, CHCl3); IR
D
1
(film) 3348, 2928, 2855, 1754, 1470, 1383, 1092 cm-1; H NMR
(500 MHz, CDCl3) δ 7.34-7.26 (m, 5H), 6.36 (s, 1H), 4.63 (d, J
) 12.0 Hz, 1H), 4.59 (d, J ) 12.0 Hz, 1H), 4.56 (dd, J ) 10.0, 1.0
Hz, 1H), 4.52 (dd, J ) 14.0, 7.0 Hz, 1H), 4.29 (dd, J ) 9.0, 5.0
Hz, 1H), 4.09 (dd, J ) 6.0, 5.5 Hz, 1H), 3.98 (d, J ) 14.0 Hz,
1H), 3.51 (d, J ) 10.0 Hz, 1H), 3.42 (d, J ) 10.0 Hz, 1H), 3.90
(d, J ) 10.0 Hz, 1H), 3.88 (d, J ) 10.0 Hz, 1H), 3.36 (dd, J )
14.0, 2.0 Hz, 1H), 2.26 (dd, J ) 13.0, 8.0 Hz, 1H), 2.20 (dd, J )
13.0, 7.0 Hz, 1H), 0.84 (s, 9H), 0.00 (s, 6H); 13C NMR (125 MHz,
CDCl3) δ 158.7, 137.2, 128.5 (×2), 128.1 (×2), 127.9, 85.6, 77.9,
73.9, 73.5, 72.1, 71.2, 67.4, 66.8, 51.4, 36.3, 25.8 (×3), 18.2, -5.6
(×2); HRMS (ESI) m/z calcd for C23H35NO6SiNa [(M + Na)+]
472.2131, found 472.2116. C4 diastereomer: [R]28D -0.45 (c 1.05,
Diol 29. To a solution of OsO4 (1% solution in tert-butanol, 313
µL, 0.0123 mmol), (DHQD)2AQN (21.1 mg, 0.0246 mmol), K2-
CO3 (102 mg, 0.738 mmol), and K2[Fe(CN)6] (243 mg, 0.738
mmol) in water (2.5 mL) at 0 °C were added a solution of
oxazolidinone 28 (106 mg, 0.246 mmol) in tert-butanol (2.5 mL)
and methanesulfonamide (46.8 mg, 0.492 mmol). The resulting
mixture was stirred at room temperature for 17.5 h before it was
quenched with saturated aqueous Na2SO3 (5 mL). The resulting
mixture was stirred at room temperature for an additional 30 min.
The organic layer was separated, and the aqueous layer was
extracted with CH2Cl2 (5 × 10 mL). The combined organic layers
were dried over Na2SO4, filtered, and concentrated under reduced
pressure. Flash column chromatography (silica gel, 3% methanol/
CHCl3) afforded diol 29 (101 mg, 88%) as an inseparable 4.8:1
CHCl3); IR (film) 3280, 2927, 2855, 1757, 1470, 1384, 1093 cm-1
;
1H NMR (500 MHz, CDCl3) δ 7.35-7.26 (m, 5H), 6.00 (s, 1H),
4.51 (d, J ) 12.0 Hz, 1H), 4.51 (d, J ) 14.0 Hz, 1H), 4.48 (d, J )
12.0 Hz, 1H), 4.45 (dd, J ) 14.0, 7.0 Hz, 1H), 4.24 (dd, J ) 9.0,
5.0 Hz, 1H), 4.09 (dd, J ) 5.5, 5.5 Hz, 1H), 3.99 (d, J ) 14.0 Hz,
1H), 3.71 (d, J ) 10.0 Hz, 1H), 3.59 (d, J ) 10.0 Hz, 1H), 3.38
(dd, J ) 14.0, 2.0 Hz, 1H), 3.33 (d, J ) 10.0 Hz, 1H), 3.31 (d, J
) 10.0 Hz, 1H), 2.25 (dd, J ) 13.0, 7.0 Hz, 1H), 2.21 (dd, J )
13.0, 7.0 Hz, 1H), 0.89 (s, 9H), 0.12 (s, 3H), 0.11 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 158.7, 138.1, 128.5 (×2), 127.8 (×2),
127.5, 85.1, 77.7, 73.9, 73.6, 73.5, 71.8, 66.6, 65.4, 51.1, 36.1, 25.9
(×3), 18.5, -5.6 (×2); HRMS (ESI) m/z calcd for C23H35NO6-
SiNa [(M + Na)+] 472.2131, found 472.2115.
mixture of diastereomers as a colorless oil: [R]28 -28.2 (c 0.44,
D
1
CHCl3); IR (film) 3387, 2918, 1752, 1384, 1071 cm-1; H NMR
(500 MHz, CDCl3) δ (major diastereomer) 7.37-7.28 (m, 5H), 5.67
(br s, 1H), 4.61 (d, J ) 11.5 Hz, 1H), 4.45 (d, J ) 11.5 Hz, 1H),
4.31 (d, J ) 14.0 Hz, 1H), 4.24 (dd, J ) 6.5, 2.0 Hz, 1H), 4.06
(dd, J ) 9.5, 6.5 Hz, 1H), 3.67 (dd, J ) 10.0, 9.5 Hz, 1H), 3.59
(dd, J ) 10.0, 1.5 Hz, 1H), 3.55-3.51 (m, 3H), 3.44 (d, J ) 9.5
Hz, 1H), 3.40 (d, J ) 9.5 Hz, 1H), 3.28 (s, 1H), 2.39 (dd, J )
15.0, 1.5 Hz, 1H), 2.32 (dd, J ) 7.0, 7.0 Hz, 1H), 1.57 (dd, J )
15.0, 10.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ (major
diastereomer) 158.5, 137.6, 128.4 (×2), 128.3 (×2), 127.9, 75.7,
74.6, 73.4, 72.7, 65.6, 66.1, 60.5, 43.3, 38.2, 34.6; HRMS (ESI)
m/z calcd for C17H22NO6INa [(M + Na)+] 486.0390, found
486.0390.
N-Methyl Oxazolidinone 32. To a solution of oxazolidinone
31 (68.6 mg, 0.153 mmol) in DMF (1.5 mL) at 0 °C was added
sodium hydride (oil free, 11.0 mg, 0.458 mmol). After being stirred
at 0 °C for 30 min, the reaction mixture was treated with
iodomethane (29 µL, 0.47 mmol). The resulting solution was
allowed to warm to room temperature and stirred for 17 h. Saturated
aqueous NH4Cl (3 mL) was added, and the mixture was extracted
with ethyl acetate (3 × 5 mL). The combined organic layers were
washed with brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure. Flash column chromatography (silica gel,
40% ethyl acetate/hexanes) afforded N-methyl oxazolidinone 32
TBS Ether 30. To a solution of diol 29 (51.6 mg, 0.111 mmol),
triethylamine (52 µL, 0.37 mmol), and DMAP (2.72 mg, 0.0222
mmol) in CH2Cl2 (1.2 mL) at 0 °C was added TBSCl (27.4 mg,
0.133 mmol). The resulting solution was allowed to warm to 35
°C and stirred at the same temperature for 37 h. The mixture was
extracted with ethyl acetate (20 mL), then washed with water (5
mL), aqueous 1 M HCl (5 mL), saturated aqueous NaHCO3 (5 mL),
and brine (5 mL). The organic layer was dried over Na2SO4, filtered,
and concentrated under reduced pressure. Flash column chroma-
tography (silica gel, 40% ethyl acetate/hexanes) afforded TBS ether
30 (54.0 mg, 84%) as an inseparable 4.8:1 mixture of diastereomers,
(61.5 mg, 87%) as a white foam: [R]28 +17.1 (c 1.11, CHCl3);
D
IR (film) 3398, 2927, 2855, 1755, 1432, 1094, 1027 cm-1; 1H NMR
(500 MHz, CDCl3) δ 7.32-7.22 (m, 5H), 4.50 (d, J ) 13.0 Hz,
1H), 4.48 (d, J ) 13.0 Hz, 1H), 4.25 (d, J ) 6.5 Hz, 1H), 4.21 (d,
J ) 13.5 Hz, 1H), 4.12 (d, J ) 5.5, 1H), 3.97 (d, J ) 4.0 Hz, 1H),
3.70 (dd, J ) 6.5, 5.5 Hz, 1H), 3.64 (d, J ) 11.0 Hz, 1H), 3.61 (d,
J ) 11.0 Hz, 1H), 3.58 (d, J ) 10.0 Hz, 1H), 3.53 (dd, J ) 13.5,
1.5 Hz, 1H), 3.45 (d, J ) 10.0 Hz, 1H), 2.91 (s, 3H), 2.35 (dd, J
) 14.0, 5.0 Hz, 1H), 2.07 (d, J ) 14.0 Hz, 1H), 0.85 (s, 9H), 0.01
(s, 6H); 13C NMR (125 MHz, CDCl3) δ 159.4, 138.7, 128.2 (×2),
127.5 (×2), 127.3, 84.3, 76.9, 74.0, 73.6, 73.5, 68.9, 66.8, 64.1,
54.9, 36.5, 30.0, 25.8 (×3), 18.1, -5.5 (×2); HRMS (ESI) m/z
calcd for C24H37NO6SiNa [(M + Na)+] 486.2288, found 486.2268.
Alcohol 33. A suspension of N-methyl oxazolidinone 32 (61.5
mg, 0.133 mmol) and 20% Pd/C (1.5 g) in ethyl acetate (1.3 mL)
was stirred at room temperature under hydrogen atmosphere for 4
h. The mixture was filtered through a pad of Celite, and the filtrate
as a white foam: [R]28 -17.8 (c 1.17, CHCl3); IR (film) 3303,
D
1
2924, 2853, 1755, 1384, 1250, 1089 cm-1; H NMR (500 MHz,
CDCl3) δ (major diastereomer) 7.34-7.25 (m, 5H), 5.59 (br s, 1H),
4.57 (d, J ) 12.0 Hz, 1H), 4.47 (d, J ) 12.0 Hz, 1H), 4.28 (d, J )
15.0 Hz, 1H), 4.23 (dd, J ) 6.5, 2.0 Hz, 1H), 4.08 (dd, J ) 7.0,
7.0 Hz, 1H), 3.68, (d, J ) 15.0 Hz, 1H), 3.68 (dd, J ) 8.0, 7.5 Hz,
1H), 3.55 (dd, J ) 14.0, 2.5 Hz, 1H), 3.54 (s, 2H), 3.45 (d, J ) 9.0
Hz, 1H), 3.36 (d, J ) 9.0 Hz, 1H), 3.08 (s, 1H), 2.37 (dd, J )
15.5, 1.5 Hz, 1H), 1.62 (dd, J ) 15.5, 7.5 Hz, 1H), 0.87 (s, 9H),
J. Org. Chem, Vol. 73, No. 1, 2008 271