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P. Srihari et al. / Tetrahedron: Asymmetry 21 (2010) 106–111
4.1.11. tert-(3S,4S,5R)-Butyl-[-(2,2-dimethyl-5-vinyl-
[1,3]dioxolan-4-yl-butoxyl-dimethyl-silane 24
quickly. After 15 min stirring, alcohol 11 (1 g, 5.0 mmol) was added
as a solution in 9 mL CH2Cl2 along with a small amount of DMAP
(15 mg). The cooling bath was removed and stirring was continued
for 6 h. The solution was filtered and the solvent was removed un-
der reduced pressure. The resulting oil purified by column chroma-
tography (2% EtOAc/hexane) to give 25 (1.24 g, 84%) as colorless
To a stirred solution of iodomethyltriphenylphosphine (383 mg,
0.94 mmol) in THF (10 mL) was added n-BuLi (0.29 mL, 1.6 M,
0.47 mmol) dropwise at 0 °C. After 30 min, aldehyde 23 (100 mg,
0.31 mmol) was added and the reaction mixture was allowed to
warm to room temperature over 15 min. The resultant mixture
was quenched with saturated aqueous NH4Cl, diluted with ethyl-
acetate (2 ꢁ 5 mL). The combined organic layer was washed with
water and then brine. The organic layer was dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The residue was
purified by chromatography on silica gel (10% EtOAc/hexane) to
oil; ½a 3D0
¼ þ19:7 (c 1.5, CH2Cl2): IR (neat): mmax 2961, 2933,
ꢂ
2873, 1738, 1642, 1459, 1376, 1246, 1217, 1169, 1100,
1065 cmꢀ1 1H NMR (300 MHz, CDCl3): d 0.91 (t, J = 7.4 Hz, 3H),
;
1.23–1.35 (m, 2H), 1.36 (s, 3H), 1.47 (s, 3H), 1.53–1.75 (m, 4H),
2.07 (q, J = 7.0 Hz, 2H), 2.16–2.33 (m, 2H), 4.17 (t, J = 7.4 Hz, 1H),
4.60 (t, J = 7.4 Hz, 1H), 4.92 (q, J = 7.4 Hz, 1H), 4.95–5.06 (m, 2H),
5.21 (d, J = 10.4 Hz, 1H), 5.32 (d, J = 17.0 Hz, 1H), 5.68–5.87 (m,
2H); 13C NMR (75 MHz, CDCl3): d 14.0, 17.9, 23.9, 25.2, 27.5,
33.0, 33.4, 33.7, 71.5, 78.4, 78.9, 108.7, 115.3, 118.5, 133.2, 137.6,
172.5; MS-ES: m/z 297 (M++1); HRMS (ESI); m/z calcd for
C17H28O4Na 319.1885, found 319.1872.
give compound 24 (78 mg, 70%) as a yellow liquid. ½a D27
¼ ꢀ19:6
ꢂ
(c 12.5, CHCl3); IR (neat): mmax 2956, 2933, 2860, 1465, 1374,
1251, 1078,773 cmꢀ1 1H NMR (300 MHz, CDCl3): d 0.03 (s, 3H),
;
0.05 (s, 3H), 0.87 (s, 9H), 0.90 (t, J = 7.2 Hz, 3H), 1.36 (s, 3H),1.37–
1.46 (m, 2H), 1.47 (s, 3H), 1.54–1.71 (m, 2H), 3.80–3.89 (m, 1H),
4.07 (t, J = 7.0 Hz, 1H), 4.55 (t, J = 7.0, 6.4 Hz, 1H), 5.20 (d,
J = 10.4 Hz, 1H), 5.31 (br d, J = 17.2 Hz, 1H), 5.96 (ddd, J = 17.2,
10.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d ꢀ4.3, ꢀ3.7, 14.3, 16.6,
25.3, 25.9, 27.8, 29.6, 36.0, 70.3, 79.0, 79.6, 108.0, 117.6, 134.9;
MS-ESI: m/z 337 (M++Na); HRMS (ESI): m/z calcd for C17H34O3NaSi:
337.2174, found: 337.2174.
4.1.15. Synthesis of herbarumin-1 1 via 10
A degassed solution of Grubbs’ first generation catalyst (0.055 g,
0.06) in CH2Cl2 (30 mL) was added over 30 min to a refluxing solu-
tion of compound 25 (0.1 g, 0.33) in CH2Cl2 (180 mL) and was stirred
for 8 h at reflux. After the starting material was completely
consumed (judged by TLC), the reaction was stopped and allowed
to cool to room temperature. The solvent was removed under re-
ducedpressureto giveadarkbrowncolored residue. Thecrudeprod-
uct was purified by silica gel column chromatography (7% EtOAc/
hexane) to afford E/Z (4:1) mixture of 10 (0.074 g, 82%) as a colorless
liquid.
4.1.12. (R)-1-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-
yl)butan-1-ol (11) from 24
To a stirred solution of TBS ether 24 (75 mg, 0.23 mmol) in THF
(5 mL) at 0 °C, TBAF (0.47 mL, 0.47 mmol, 1 M solution in THF) was
added dropwise at the same temperature. The mixture was al-
lowed to stir at room temperature over 3 h. The resultant mixture
was quenched with water and diluted with diethyl ether (5 mL).
The organic layer was washed with water and then with brine,
respectively. The combined organic layers was dried over anhy-
drous Na2SO4, and concentrated under reduced pressure. The resi-
due was purified by chromatography on silica gel (15% EtOAc/
hexane) to give compound 11 (42 mg, 90%) as a yellow liquid.
The diastereomeric mixture of compound 10 (70 mg, 0.26 mmol)
and trifluoroacetic acid (0.03 mL) in CH2Cl2 (3 mL) was stirred at
room temperature for 8 h until TLC showed complete consumption
of the starting material. The reaction mixture was concentrated un-
der reduced pressure and the resulting residue was purified by col-
umn chromatography (25% EtOAc/hexane) to obtain Herbarumin-
1 (30 mg, 88%), as a low melting solid along with a mixture of E/Z dia-
stereomers 22.4 mg. ½a D31
ꢂ
¼ þ11:2 (c 0.7, EtOH); Lit.3b
½
a 2D0
ꢂ
¼ þ10:8
4.1.13. Synthesis of compound 11 from 14
(c 0.51, EtOH); IR (neat): mmax = 3451, 2959, 2929, 1730, 1455, 1206,
To a solution of an epoxide 14 (600 mg, 3.5 mmol) in THF (8 mL)
at ꢀ40 °C was added CuI (0.134, 0.7 mmol) and stirred at the same
temperature for 15 min. After this time, the pre cooled ethyl mag-
nesium bromide (10.5 ml of 1 M solution in THF, 10.5 mmol) was
added by a cannula. The resulting mixture was stirred at ꢀ40 °C
for 3 h and the reaction was quenched by the addition of aqueous
NH4Cl solution and warmed to room temperature. The layers were
separated and the aqueous layer was extracted with ethyl acetate
(2 ꢁ 20 mL). The combined organic layer was washed with brine,
dried over anhydrous Na2SO4, and concentrated to provide the
crude product. Silica gel column chromatography (15% EtOAc/hex-
ane) afforded the pure product 11 (649 mg, 92%) as a colorless oil.
1061, 811 cmꢀ1; 1H NMR (300 MHz, CDCl3); d 0.91 (t, J = 7.2 Hz, 3H),
1.20–1.40 (m, 2H), 1.50–1.54 (m, 1H), 1.72 (m, 1H), 1.82–2.00 (m,
4H), 2.16 (br s, 1H), 2.38–2.50 (m, 3H), 3.51 (dd, J = 9.8, 1.9 Hz, 1H),
4.42 (br s, 1H,), 4.94 (dt, J = 9.6, 2.4 Hz, 1H), 5.45–5.57 (m, 1H),5.61
(d, J = 15.9, Hz, 1H,); 13C NMR (75 MHz, CDCl3): d 13.8, 18.0, 24.6,
33.3, 33.7, 34.4, 70.2, 73.3, 73.7, 120.8, 130.6, 176.4; MS-ES: m/z
251 (M++Na); HRMS (ESI) m/z calcd for C12H20O4Na, 251.1259, found
251.1248.
4.1.16. Stagonolide A
To a solution of herbarumin-1 (30 mg, 0.13 mmol) in CH2Cl2
(6.0 mL) was added manganese dioxide (229 mg, 2.6 mmol) at
room temperature. After being stirred at the same temperature
for 20 h, the reaction mixture was filtered through a pad of Celite.
The solvent was concentrated under reduced pressure and the
resulting residue was purified by column chromatography (10%
EtOAc/hexane) to obtain stagonolide A (28.5 mg, 96%, based on
recovery of starting material) as a colorless crystalline solid.
½
a 3D0
ꢂ
¼ þ8:8 (c 1.6, CH2Cl2); lit.3a
½
a 2D0
ꢂ
¼ þ8:8 (c.1.2, CH2Cl2). IR
(neat): mmax 3467, 2983, 2959, 2932, 2873, 1642, 1217, 1065,
872 cmꢀ1 1H NMR (300 MHz, CDCl3): d 0.94 (t, J = 7.2 Hz, 3H),
;
1.37 (m, 1H), 1.37 (s, 3H),1.45 (m, 1H), 1.48 (s, 3H), 1.57 (m, 1H),
1.69 (m, 1H), 1.80 (br s, 1H), 3.67 (dt, J = 2.6, 2.3 Hz, 1H), 3.97
(dd, J = 8.1, 6.4 Hz, 1H), 4.63 (t, J = 7.4 Hz, 1H), 5.31 (d, J = 10.4 Hz,
1H), 5.43 (d, J = 17.2 Hz, 1H), 6.04 (ddd, J = 17.2, 10.4, 7.4 Hz, 1H);
13C NMR (75 MHz, CDCl3): d 14.0, 18.3, 25.3, 27.8, 35.8, 69.7,
78.9, 80.7, 108.6, 118.9, 134.7; MS-ES: m/z 223 (M++Na); HRMS
(ESI): m/z calcd for C11H20O3Na, 223.1305, found 223.1304.
Mp = 71–72 °C. ½a 3D2
ꢂ
¼ ꢀ60 (c 0.2, EtOH); IR (neat):
mmax = 3417,
2960, 2930, 2869, 1727, 1692, 1632, 1438, 1398, 1152, 1075,
824 cmꢀ1 1H NMR (300 MHz, CDCl3); d 0.93 (t, J = 7.3 Hz, 3H),
;
1.24–1.50 (m, 2H), 1.58–1.73 (m, 1H), 1.86–2.03 (m, 3H), 2.05
(m, 1H), 2.13 (dd, J= 14.0, 2.3 Hz, 1H), 2.44 (d, J = 5.7 Hz, 1H),
2.47–2.55 (m, 1H), 4.05 (dd, J = 9.5, 6.2 Hz, 1H), 4.65 (dt, J = 9.6,
2.4 Hz, 1H), 6.24–6.37 (m, 1H), 6.42 (d, J = 16.0, Hz, 1H); 13C NMR
(75 MHz, CDCl3); d 13.7, 18.0, 25.0, 33.5, 34.0, 34.2, 74.5, 76.5,
131.9, 143.1, 174.1, 199.6; MS-ES: m/z 249 (M++Na); HRMS (ESI)
m/z calcd for C12H18O4Na, 249.1102, found 249.1095.
4.1.14. (R)-1-((4R,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-
yl)butyl hept-6-enoate 25
A solution of 5-hexenoic acid (792 mg, 5.5 mmol) in CH2Cl2
(8 mL) was cooled to 0 °C. A sample of DCC (1.34 g, 6.5 mmol)
was added in several portions and a white precipitate formed