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16 A 0.3 M solution of Grignard reagent 4a in THF was prepared as follows: Magnesium
powder (1.04 g, 42.65 mmol) was flame heated, allowed to cool to
r.t., and activated by successively adding a crystal of iodine and
a solution of 1,2-dibromoethane (0.1 mL) in THF (7 mL) under argon.
The mixture was refluxed for 25 min (until bubbling of acetylene
gas ceased), and then cooled to 0 ˚C. A solution
of 3-chloromethylfuran¹5a (497 mg, 4.27 mmol) in
THF (3 mL) was then added at once. Vigorous stirring was continued
for 4 h at -3 to 0 ˚C (salt-water bath).
The mixture was decanted over 15 min without stirring. The resulting
THF solution of 4a (0.3 M) could be kept
for 1-3 h at -3 to 0 ˚C without
any signs of decomposition.
17
Tamura M.
Kochi J.
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1971,
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Baker R.
Ekanayake NJ.
Simon A.
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19
Synthesis of Neotorreyol
(8)
To a stirred solution of acetate 5a (434
mg, 1.33 mmol) in THF (3 mL) was added Li2CuCl4 in
THF (0.1 M, 1.33 mL, 0.133 mmol). After cooling to 0 ˚C,
a freshly prepared solution of Grignard reagent 4a in
THF¹6 (0.3 M, 8.5 mL, 2.55 mmol) was added over
10 min at 0 ˚C. After 10 min the reaction mixture
was allowed to warm to r.t. and stirring continued for 18 h before
quenching with brine (3 mL). The mixture was poured to EtOAc (15
mL), the organic layer was separated, washed with brine (2 × 10
mL), dried over MgSO4, and concentrated under reduced
pressure. The residue was subjected to column chromatography on
silica gel (2% EtOAc in hexanes) to give 361 mg of a mixture consisting
of cross-coupled product 10 and 1,2-di-3-furylethane.
Due to difficulties in separating the Wurtz homocoupling product
at this stage, crude 10 was used as is for
the subsequent reaction; it was dissolved in THF (3 mL) and aq HCl
(1 M, 1.25 mL) was added with stirring at r.t. After 16 h, the mixture
was poured into EtOAc (15 mL), the organic layer was separated,
washed with brine (1 × 10 mL), dried
over MgSO4, and concentrated under reduced pressure. The
product was purified by flash chromatography on silica gel (8% EtOAc
in hexanes) to give neotorreyol (8) as
a colorless oil (227 mg, 73% over 2 steps); R
f
= 0.35
(20% EtOAc-hexanes). IR (NaCl, film): 3341, 2920,
2855, 1501, 1446, 1383, 1164, 1065, 1025, 874, 778 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.34 (s,
1 H), 7.21 (s, 1 H), 6.28 (s, 1 H), 5.37 (t, J = 5.8
Hz, 1 H), 5.17 (t, J = 5.8
Hz, 1 H), 3.99 (s, 2 H), 2.45 (t, J = 7.4
Hz, 2 H), 2.25 (q, J = 7.4
Hz, 2 H), 2.13 (q, J = 7.4
Hz, 2 H), 2.03 (t, J = 7.4
Hz, 2 H), 1.67 (s, 3 H), 1.60 (s, 3 H). ¹³C
NMR (100 MHz, CDCl3): δ = 142.8, 139.1, 135.6,
135.0, 126.2, 125.2, 124.3, 111.3, 69.2, 39.5, 28.6, 26.3, 25.2,
16.3, 13.9. ESI-HRMS: m/z calcd
for C15H22O2: 234.1627; found:
234.1620.
20
Lee TW.
Corey EJ.
J. Am. Chem. Soc.
2001,
123:
1872
21
Data for Acetylene
11
Colorless oil; R
f
= 0.20 (hexanes). IR
(NaCl, film): 3302, 2921, 2855, 1501, 1444, 1384, 1164, 1065, 1025,
874, 779, 634 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.34 (s,
1 H), 7.21 (s, 1 H), 6.28 (s, 1 H), 5.39 (t, J = 5.8
Hz, 1 H), 5.17 (t, J = 5.8
Hz, 1 H), 2.88 (s, 2 H), 2.45 (t, J = 7.4
Hz, 2 H), 2.25 (q, J = 7.4
Hz, 2 H), 2.13 (q, J = 7.4
Hz, 2 H), 2.09 (s, 1 H), 2.03 (t, J = 7.4
Hz, 2 H), 1.69 (s, 3 H), 1.59 (s, 3 H). ¹³C NMR
(100 MHz, CDCl3): δ = 142.8, 139.1,
135.7, 129.6, 126.3, 125.2, 124.2, 111.3, 82.4, 70.3, 39.6, 28.8,
28.7, 26.8, 25.2, 16.3, 16.2. ESI-HRMS: m/z calcd
for C17H22O: 242.1673; found: 242.1671.
22a Bromide 7a (mp 77 ˚C) was prepared
by Vilsmeier bromination of β-tetronic acid (86%,
30 g scale) using the procedure of Jas: Jas G.
Synthesis
1991,
965
22b See also: Boukouvalas J.
Lachance N.
Ouellet M.
Trudeau M.
Tetrahedron
Lett.
1998,
39:
7665
23
Synthesis of Butenolide
12
A vial charged with PdCl2(PPh3)2 (18.0
mg, 0.024 mmol), CuI (3.5 mg, 0.018 mmol), and 7a (50.0
mg, 0.291 mmol) was placed on a vacuum pump for 30 min and then
purged with argon. Degassed 1,4-dioxane (0.5 mL) was added, and the
mixture was stirred for 30 min at r.t. To this mixture was added
(using a cannula) a solution of Hünig’s base (64
mg, 0.485 mmol) and alkyne 11 (58.8 mg,
0.243 mmol) in 1,4-dioxane (0.8 mL, purged with Ar). The mixture
was stirred for 18 h at r.t. and then quenched with brine (2 mL).
EtOAc (5 mL) was added and the aqueous layer was separated and extracted
with EtOAc (2 × 10 mL). The combined
organic layers were dried over MgSO4, concentrated under
reduced pressure, and the residue was subjected to flash chromatog-raphy
on silica gel (15% Et2O in pentane) to give
butenolide 12 as a yellow oil (51.6 mg,
66%); R
f
= 0.23
(10% EtOAc-hexanes). IR (NaCl, film): 2920, 2856,
2225, 1779, 1750, 1611, 1446, 1301, 1145, 1043, 1025, 881, 874,
855, 780 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.34 (s,
1 H), 7.20 (s, 1 H), 6.27 (s, 1 H), 6.12 (s, 1 H), 5.35 (t, J = 5.8 Hz,
1 H), 5.17 (t, J = 5.8
Hz, 1 H), 4.78 (s, 1 H), 3.13 (s, 2 H), 2.45 (t, J = 7.4 Hz,
2 H), 2.25 (q, J = 7.4
Hz, 2 H), 2.13 (q, J = 7.4
Hz, 2 H), 2.02 (t, J = 7.4
Hz, 2 H), 1.70 (s, 3 H), 1.60 (s, 3 H). ¹³C NMR
(100 MHz, CDCl3): δ = 173.8, 148.2,
142.8, 139.1, 135.5, 128.4, 127.5, 125.1, 124.4, 121.9, 111.3, 105.8,
73.4, 73.3, 39.4, 30.2, 28.6, 26.8, 25.2, 16.4, 16.3. ESI-HRMS: m/z calcd for C21H24O3:
324.1742; found: 324.1725.
24
Marsh BJ.
Carbery DR.
J. Org. Chem.
2009,
74:
3186
25
Nicolaou KC.
Peng X.-S.
Sun Y.-P.
Polet D.
Zou B.
Lim CS.
Chen DY.-K.
J.
Am. Chem. Soc.
2009,
131:
10587
26
Synthesis of Furospongolide
(1)
To a solution of butenolide 12 (48.7
mg, 0.1501 mmol) in EtOAc-MeOH (3:2, 1 mL) was added 5% Pd(0)
on BaSO4 (127.8 mg). The reaction mixture was stirred
for 5.25 h under a balloon of hydrogen at r.t., filtered through
a Celite pad, and the filtrate was concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (40% Et2O
in pentane) to furnish furo-spongolide (1,
29.4 mg, 60%). Some of the remaining fractions containing 12 and partially hydrogenated product were
combined, concentrated under reduced pressure, and the residue was
dissolved in EtOAc-MeOH (3:2, 1 mL) and rehydrogenated
using 30.2 mg of 5% Pd(0) on BaSO4 for 30 min
at r.t. The solution was filtered through Celite and silica gel
and concentrated to afford an additional 14.5 mg (29%) of
pure 1, thereby making the total yield
89%; colorless oil, R
f
= 0.23 (30% Et2O-pentane).
IR (NaCl, film): 2929, 2857, 1781, 1749, 1638, 1501, 1446, 1384,
1168, 1130, 1064, 1025, 886, 874, 854, 780 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 7.34 (s,
1 H), 7.21 (s, 1 H), 6.28 (s, 1 H), 5.84 (s, 1 H), 5.16 (t, J = 6.8 Hz,
1 H), 5.11 (t, J = 6.8
Hz, 1 H), 4.73 (s, 1 H), 2.45 (t, J = 7.5
Hz, 2 H), 2.35 (t, J = 7.5
Hz, 2 H), 2.26 (q, J = 7.5
Hz, 2 H), 2.11-1.98 (m, J = 7.5
Hz, 6 H), 1.69 (quin, J = 7.5
Hz, 2 H), 1.60 (s, 6 H). ¹³C NMR (100
MHz, CDCl3): δ = 174.4, 170.7, 142.8,
139.0, 135.8, 133.6, 125.9, 125.1, 124.1, 115.6, 111.3, 73.3, 39.8,
39.1, 28.6, 28.1, 26.7, 25.5, 25.3, 16.3, 16.0. ESI-HRMS: m/z calcd for C21H28O3: 328.2050;
found: 328.2038.
27
Liu Y.
Zhang S.
Abreu PJM.
Nat.
Prod. Rep.
2006,
23:
630
