Total Synthesis of Umuravumbolide and Hyptolide
10 min by addition of satd. NH4Cl. The organic layer was sepa-
rated and the aqueous phase was extracted with EtOAc (3 ϫ
10 mL). The combined organic phase was dried with anhyd
3.82 (s, 3 H), 3.63–3.44 (m, 2 H), 2.02–1.76 (m, 2 H), 1.35–1.23 (m,
7 H), 1.05–1.04 (m, 12 H), 0.97–0.93 (m, 3 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ = 159.0, 141.4, 141.1, 129.4, 129.2, 113.9,
Na2SO4, concentrated, and purified by column chromatography 113.7, 113.7, 73.6, 72.6, 70.9, 66.4, 55.3, 38.0, 37.7, 22.8, 22.6, 17.4,
over silica gel (EtOAc/PE, 40:60) to give pure aminoxy alcohol
(1.5 g, 80%). The aminoxy alcohol (1.5 g, 3.5 mmol) was dissolved
in MeOH (10 mL) , 3% copper sulfate was added and the reaction
mixture was stirred for 12 h. After completion of the reaction
(monitored by TLC) it was quenched by addition of satd. NH4Cl.
The organic layer was separated and the aqueous phase was ex-
tracted with EtOAc (3ϫ 10 mL). The combined organic phase was
dried with anhyd Na2SO4, concentrated, and purified by silica gel
chromatography (EtOAc/PE, 50:50) to give pure diol 20 (0.66 g,
80%) as a colourless liquid. [α]2D5 = +41.86 (c = 0.2, CHCl3). IR
17.2, 14.3 ppm. HRMS (ESI+): m/z calcd. for C26H44O4Si [M +
Na]+ 471.2907; found 471.2907.
(5R,9S,11R,12S)-11-(Benzyloxy)-7,7-diisopropyl-1-(4-methoxyphen-
yl)-12,14,14,15,15-pentamethyl-5,9-divinyl-2,6,8,13-tetraoxa-7,14-
disilahexadecane (4): Compound 4 was prepared from coupling
fragments 6 and 7 by following the procedure described for 3, yield
87%; colourless liquid; [α]2D5 = 26.86 (c = 0.2, CHCl3). IR (CHCl3):
ν
˜
= 2935, 2856, 1713, 1600, 1504, 1265, 1065, 1071, 920,
max
885 cm–1. 1H NMR (CDCl3, 400 MHz): δ = 7.27–7.15 (m, 7 H),
6.82–6.77 (m, 2 H), 5.84–5.62 (m, 2 H), 5.12–4.91 (m. 4 H), 4.48–
4.19 (m, 6 H), 4.03–3.79 (m, 1 H), 3.73 (s, 3 H), 3.66–3.26 (m, 3
H), 1.68–1.66 (m, 4 H), 1.53–1.33 (m, 2 H), 1.07 (d, J = 6.31 Hz,
3 H), 0.95–0.94 (m, 12 H), 0.83 (s, 9 H), –0.02 (s, 6 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ = 159.0, 140.9, 139.3, 139.1, 130.8,
129.1, 128.2, 127.6, 127.3, 127.2, 114.6, 113.7, 81.6, 72.9, 72.7, 71.6,
71.2, 70.6, 55.2, 39.9, 26.0, 25.8, 18.0, 17.4, 17.3, –4.6, –4.7 ppm.
HRMS (ESI+): m/z calcd. for C39H646Si2 [M + Na]+ 707.4139;
found 707.4139.
(CHCl ): νmax = 3412, 3020, 2978, 1652, 1534, 1248, 1237 cm–1. 1H
˜
3
NMR (CDCl3, 400 MHz): δ = 7.31–7.19 (m, 5 H), 4.77–4.41 (m, 2
H), 3.99–3.78 (m, 3 H), 3.56–3.47 (m, 2 H), 3.41–3.29 (m, 1 H),
1.58–1.54 (m, 2 H), 1.10–1.07 (m, 3 H), 0.82–0.81 (m, 9 H), –0.01
(s, 6 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 138.0, 128.5,
127.9, 83.0, 72.4, 70.5, 70.1, 66.8, 33.0, 29.6, 25.8, 18.9, –4.8 ppm.
HRMS (ESI+): m/z calcd. for C19H35O4Si [M + H] 355.2305; found
355.2301.
(2S,3R)-3-(Benzyloxy)-4-[(S)-oxiran-2-yl]butan-2-yloxy(tert-butyl)di-
methylsilane (21): Compound 21 was prepared by following the
(4S,7R)-4-Butyl-2,2-diisopropyl-7-[2-(4-methoxybenzyloxy)ethyl]-
4,7-dihydro-1,3,2-dioxasilepine (22): A solution of 3 (0.1 g,
0.22 mmol) in toluene (50 mL) was degassed for 5 min with argon,
then Grubbs-II catalyst (0.006 g, 0.006 mmol) was added and the
solution was degassed again. The mixture was stirred at 80 °C for
18 h, before the solvent was removed in vacuo and the residue was
purified by flash chromatography (PE/ethyl acetate, 95:5) to give
cyclised product 22 (0.082 g, 88%); [α]2D5 = +3.00 (c = 0.65, CHCl3).
procedure described for 13, yield 90%; colourless liquid; [α]2D5
=
+12.8 (c = 0.5, CHCl ). IR (CHCl ): νmax = 2930, 2856, 1620, 1600,
˜
3
3
1557, 1501, 1310 cm–1. 1H NMR (CDCl3, 400 MHz): δ = 7.30–7.21
(m, 5 H), 4.74–4.45 (m, 2 H), 3.87–3.79 (m, 1 H), 3.51–3.30 (m, 1
H), 3.05–2.95 (m, 1 H), 2.73–2.61 (m, 1 H), 2.44–2.35 (m, 1 H),
1.92–1.37 (m, 2 H), 1.10 (t, J = 6.22 Hz, 3 H), 0.81–0.79 (m, 9 H),
–0.02–0.04 (m, 6 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 138.8,
135.6, 128.3, 127.8, 127.5, 81.7, 73.1, 70.5, 50.1, 47.8, 34.5, 34.0,
25.8, 19.2, –4.4, –4.7 ppm. HRMS (ESI+): m/z calcd. for
C19H33O3Si [M + H] 337.2199; found 337.2196.
IR (CHCl ): ν
= 2929, 2865, 1612, 1513, 1465, 1248, 1092,
˜
3
max
884 cm–1. 1H NMR (CDCl3, 400 MHz): δ = 7.23–7.21 (m, 2 H),
6.91–6.88 (m, 2 H), 5.92–5.45 (m, 2 H), 4.88–4.48 (m, 2 H), 3.79
(s, 3 H), 3.75–3.43 (m, 4 H), 1.40–1.29 (m, 10 H), 1.03 (s, 12 H),
0.89–0.87 (m, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 159.1,
135.5, 134.8, 133.9, 129.32, 113.7, 72.8, 71.0, 67.9, 66.7, 55.3, 38.6,
38.3, 22.6, 22.5, 17.6, 17.2, 14.1 ppm. HRMS (ESI+): m/z calcd.
for C24H41O4Si [M + H]+421.2774; found 421.2775.
(3S,5R,6S)-5-(Benzyloxy)-6-[(tert-butyldimethylsilyl)oxy]hept-1-en-
3-ol (7): Compound 7 was prepared by following the procedure
described for 5, yield 80%; colourless liquid; [α]2D5 = +26.42 (c =
1.1, CHCl ). IR (CHCl ): ν = 3290, 3032, 2430, 1652, 1561,
˜
max
3
3
1504, 1215, 1012, 901, 876 cm–1. 1H NMR (CDCl3, 400 MHz): δ =
7.27–7.16 (m, 5 H), 5.83–5.67 (m, 1 H), 5.21–4.96 (m, 2 H), 4.77–
4.41 (m, 2 H), 4.25–4.18 (m, 1 H), 3.93–3.77 (m, 1 H), 3.56–3.46
(m, 1 H), 1.74–1.59 (m, 2 H), 1.09 (d, J = 6.42 Hz, 3 H), 0.83–0.82
(m, 9 H), –0.01 (s, 6 H) ppm. 13C NMR (CDCl3, 100 MHz): δ =
140.8, 138.2, 128.4, 127.9, 127.7, 114.2, 83.2, 72.5, 71.3, 76.6, 40.1,
37.5, 25.7, 18.9, –4.6, –4.7 ppm. HRMS (ESI+): m/z calcd. for
C20H34O3Si [M + H] 351.2355; found 351.2350.
(4S,7R)-4-{(2R,3S)-2-(Benzyloxy)-3-[(tert-butyldimethylsil-
yl)oxy]butyl}-2,2-diisopropyl-7-{2-[(4-methoxybenzyl)oxy]ethyl}-4,7-
dihydro-1,3,2-dioxasilepine (23): A solution of 4 (0.075 g,
0.109 mmol) in toluene (18 mL) was degassed for 5 min with argon,
then Hoveyda–Grubbs second-generation catalyst (2 mg,
3.28 μmol) was added and the solution was degassed again. The
mixture was stirred at 80 °C for 18 h, before the solvent was re-
moved in vacuo and the residue was purified by flash chromatog-
raphy (PE/ethyl acetate, 90:10) to give cyclised product 23 (0.054 g,
(5R,9S)-7,7-Diisopropyl-1-(4-methoxyphenyl)-5,9-divinyl-2,6,8-
trioxa-7-silatridecane (3): Dichlorodiisopropylsilane (0.085 mL,
0.48 mmol) was added to imidazole (0.089 g, 1.31 mmol) in CH2Cl2
(0.24 mL) at 0 °C. The solution was stirred for 5 min, then frag-
ment 5 (0.05 g, 0.437 mmol) in CH2Cl2 (0.18 mL) was added drop-
wise over 1 h at 0 °C. The mixture was stirred for a further 15 min
at 0 °C, then a solution of fragment 6 (0.097 g, 0.437 mmol) in
CH2Cl2 (0.035 mL) was added at 0 °C. The reaction mixture was
warmed to room temperature and stirred for 14 h, then filtered and
washed with hexane. Concentration in vacuo afforded a crude oil,
which was purified by flash chromatography on silica gel (PE/ethyl
acetate, 95:5) to afford bis-alkoxysilane 3 (0.196 g, 87 %) as a
75%); [α]2D5 = 27.98 (c = 0.8, CHCl ). IR (CHCl ): ν
= 2931,
˜
max
3
3
2901, 2301, 1800, 1654, 1466, 885, 847, 770, 681 cm–1. 1H NMR
(CDCl3, 400 MHz): δ = 7.27–7.18 (m, 7 H), 6.83–6.78 (m, 2 H),
5.60–4.63 (m, 2 H), 4.61–4.36 (m, 4 H), 4.16–3.97 (m, 1 H), 3.87–
3.78 (m, 1 H), 3.73 (s, 3 H), 3.65–3.35 (m, 3 H), 2.36–1.46 (m, 7
H), 1.11 (d, J = 6.19 Hz, 3 H), 0.98–0.94 (m, 12 H), 0.83 (s, 9 H),
–0.01 (s, 6 H) ppm. 13C NMR (CDCl3, 100 MHz): δ = 159.2, 138.7,
129.4, 128.2, 128.0, 127.8, 127.5, 113.7, 80.9, 72.9, 72.7, 71.0, 68.5,
67.9, 64.9, 55.2, 39.1, 39.0, 30.2, 25.8, 18.0, 17.2, 16.9, –4.5,
–4.6 ppm. HRMS (ESI+): m/z calcd. for C37H60O6Si2 [M + H]+
657.4007; found 657.4007.
colourless oil. [α]2D5 = –1.98 (c = 1.3, CHCl ). IR (CHCl ): ν
=
˜
max
2-[(4R,7S)-7-Butyl-2,2-diisopropyl-4,7-dihydro-1,3,2-dioxasilepin-4-
yl]ethanol (24): To a stirring solution of PMB ether 22 (0.070 g,
0.164 mmol) in CH2Cl2/H2O (0.5:0.03) was added DDQ (0.046 g,
0.199 mmol). The resulting mixture was stirred for 10 min at room
3
3
2933, 2867, 1613, 1514, 1464, 1248, 1089, 1039, 920, 885 cm–1. H
NMR (CDCl3, 400 MHz): δ = 7.31–7.24 (m, 2 H), 6.92–6.85 (m, 2
H), 5.95–5.74 (m, 2 H), 5.23–5.01 (m, 4 H), 4.55–4.24 (m, 4 H),
1
Eur. J. Org. Chem. 2013, 4586–4593
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4591