Y. Li et al. / Tetrahedron 70 (2014) 7229e7240
7239
The mixture was quenched with a 1:1:1 mixture of saturated
aqueous sodium bicarbonate, 1 M sodium thiosulfate and water
(18 mL) and the biphasic mixture was stirred vigorously for 20 min.
The separated aqueous layer was washed with DCM (2ꢂ10 mL), and
the combined organic layers were then washed with brine (10 mL),
dried over MgSO4 and concentrated to leave the corresponding
aldehyde 45c, which was used immediately without further
purification.
A solution of n-butyl lithium (2.0 mL, 3.74 mmol, 1.85 M in
hexane) was added dropwise to a stirred solution of diisopropyl-
amine (0.54 mL, 3.74 mmol) in THF (7 mL) under argon at ꢀ78 ꢁC,
and the resulting mixture was warmed to room temperature where
it was stirred for 15 min. The mixture was cooled to ꢀ78 ꢁC, and
then a solution of ethyl propiolate (0.36 mL, 3.74 mmol) in THF
(3 mL) was added dropwise over 10 min. The mixture was stirred at
ꢀ78 ꢁC for 1 h, and then a solution of the crude aldehyde 45c in THF
(2 mL) was added over 5 min. The resulting mixture was stirred at
ꢀ78 ꢁC for 6 h, and then quenched with saturated aqueous NH4Cl
(20 mL) and diethyl ether (20 mL). The separated aqueous extract
was washed with diethyl ether (3ꢂ20 mL), and the combined or-
ganic layers were then washed with brine (50 mL), dried over
MgSO4 and concentrated to leave a pale yellow gum. Purification by
column chromatography (2:1 to 1:1, petrol/EtOAc) gave a 3:1
mixture of E- and Z-isomers of the substituted propiolate (205 mg,
43%) as a 1:1 mixture of diastereoisomers; see Supplementary data
for 1H and 13C NMR spectra; HRMS m/z C23H29O8Naþ (MBr79Naþ)
requires 535.0943, found 535.0949.
4.72 (1H, dd, J¼8.0, 6.0, CHOH), 4.23 (2H, q, J¼7.2, OCH2CH3), 3.82(3H,
s, OCH3), 3.15e3.08 (2H, m, CH2), 2.96 (1H, dd, J¼13.5 and 8.0,
CH2CHOH), 2.86 (1H, dd, J¼13.5 and 6.0, CH2CHOH), 2.50e2.42 (2H,
m, CH2),1.99 (3H, br s, CH3),1.30 (3H, t, J¼7.2, OCH2CH3); dC (100 MHz,
CDCl3) 164.2 (CO2CH3),160.0 and 159.9 (C),153.2 (CO2CH2CH3),150.8
(C), 136.2 and 132.0 (CH]CH), 133.9 (C]CH), 118.2 and 105.6 (CH]
CH), 116.7 (]CH), 114.6 (C), 108.8 (CH), 87.4 (C^C), 76.6 (C^C), 62.1
(OCH2CH3), 61.1 (CHOH), 51.4 (OCH3), 40.9 (CH2CHOH), 31.1 and 29.1
(CH2), 27.1 and 26.8 (CH2), 25.6 (CH3), 13.9 (OCH2CH3);
C
20H23BrO6Naþ (MBr79Naþ) requires 461.0575, found 461.0573. Iso-
mer 2: dH (400 MHz, CDCl3) 6.50(1H, s, FurH), 6.26e5.90 (2H, m, CH]
CHBr), 6.15 (1H, br s, ]CH), 4.68 (1H, t, J¼6.5, CHOH), 4.26 (2H, q,
J¼7.1, OCH2CH3), 3.84 (3H, s, OCH3), 3.11 (2H, dt, J¼7.1, 2.1, CH2), 2.65
(2H, d, J¼6.5, CH2CHOH), 2.49e2.41 (2H, m, CH2), 2.07 (3H, s, CH3),
1.33 (3H, t, J¼7.1, OCH2CH3); dC (100 MHz, CDCl3) 164.2 (CO2CH3),
159.7 and 159.6 (C), 153.2 (CO2CH2CH3), 150.9 (C), 136.2 and 132.1
(CH]CH), 133.1 (C]CH), 118.2 and 105.6 (CH]CH), 117.5 (]CH),
114.8 (C), 109.1 (CH), 86.8 (C^C), 77.2 (C^C), 62.2 (OCH2CH3), 60.5
(CHOH), 51.4 (OCH3), 47.8 (CH2CHOH), 31.1 and 29.1 (CH2), 27.1 and
26.8 (CH2), 19.0 (CH3), 13.9 (OCH2CH3); HRMS m/z C20H23BrO6Naþ
(MBr79Naþ) requires 461.0575, found 461.0573.
c) The butenolide stannaneevinyl bromide
Tetrakis(triphenylphosphine)palladium (0) (5 mmol%) was added
to a stirred solution of the above (Z-isomer of the vinyl furan)
substituted propiolate (1 equiv) in degassed DMFat 0 ꢁC. After 10 min
a solution of Bu3SnH (1.1 equiv, 1 M in hexane) was added dropwise
over 10 min and the resulting mixture was stirred at 0 ꢁC for 1 h.
Copper iodide (20 mol % to 100 mol %) and caesium fluoride (0 mol %
to 100 mol %), were added sequentially, and the mixture was then
stirred at room temperature for 12 h. The mixturewas quenched with
saturated aqueous NH4Cl (10 mL) and ethyl acetate (10 mL), and the
separated aqueous layer was then washed with ethyl acetate
(3ꢂ10 mL). The combined organic extracts were washed with brine
(10 mL), then dried over MgSO4 and concentrated to leave a pale
yellow gum. Purification by column chromatography (10:1 to 1:1,
petrol/EtOAc) gave the Z-isomer of the butenolide stannane as the
major product (47e69%): dH (400 MHz, CDCl3) 7.47 (1H, s, CH]CSn),
6.42 (1H, s, FurH), 6.25e5.90 (2H, m, CH]CHBr), 6.12 (1H, br s, ]CH),
5.19 (1H, apt t, J¼7.4, CHOH), 3.84 (3H, s, OCH3), 3.18e3.05 (2H, m,
CH2), 2.89 (1H, dd, J¼13.5 and 7.4, CH2CHO), 2.74 (1H, dd, J¼13.5 and
6.4, CH2CHO), 2.48e2.40 (2H, m, CH2), 1.99 (3H, br s, CH3), 1.58e1.48
(6H, m, CH2),1.38e1.28 (6H, m, CH2),1.12e1.06 (6H, m, CH2), 0.90 (9H,
t, J¼7.3, CH3); dC (100 MHz, CDCl3) 177.5 (CO2CH), 164.9 (CH]CSn),
164.0 (CO2CH3), 159.9 (C), 159.8 (C), 136.1 and 131.9 (CH]CH), 135.6
(C), 133.6 (C), 118.3 and 105.7 (CH]CH), 116.4 (]CH), 114.8 (C), 108.8
(CH), 83.8 (CHO), 51.4 (OCH3), 37.8 (CH2CHO), 31.2 and 29.2 (CH2),
28.9 (3ꢂCH2), 27.2 and 26.9 (CH2), 27.1 (3ꢂCH2), 25.9 (CH3), 13.6
(3ꢂCH2), 9.7 (3ꢂCH3); HRMS m/z C30H45BrO5SnNaþ (MNaþ) requires
707.1370, found 707.1368.
4.11. Synthesis of the butenolide stannaneevinyl bromide
(47)
a) Methyl
2-(4-bromobut-3-en-1-yl)-5-{4-[(tert-butyldiphe-
nylsilyl)oxy]-2-methylbut-1-en-1-yl}furan-3-carboxylate.
The vinyl bromide was elaborated from the 2,3,5-trisubstituted
furan 42 following: i) deprotection of the TBS group (86%); ii) oxi-
dation of the resulting alcohol with DesseMartin periodinane and
finally iii) a Takai reaction (72% over two steps) using the same
reagents and experimental condition that had been used to prepare
44a, 44b and 45, respectively. The vinyl bromide showed: Isomer 1:
dH (400 MHz, CDCl3) 7.78e7.65 (4H, m, Ph), 7.50e7.35 (6H, m, Ph),
6.51 (1H, s, FurCH), 6.30e6.10 (1H, m, ]CH), 6.08 (1H, br s, ]CH),
6.03e5.89 (1H, m, CH]CH), 3.92e3.85 (2H, m, CH2OSi), 3.85 (3H, s,
CO2CH3), 3.17e3.07 (2H, m, CH2), 2.72 (2H, t, J¼6.6, CH2), 2.52e2.40
(2H, m, CH2), 1.90 (1H, br s, CH3), 1.08 (9H, br s, Si(CH3)3); see
Supplementary data for full 13C NMR spectra. Isomer 2: dH
(400 MHz, CDCl3) 7.78e7.65 (4H, m, Ph), 7.50e7.35 (6H, m, Ph), 6.44
(1H, s, FurH), 6.30e6.10 (1H, m, ]CH), 6.06 (1H, br s, ]CH),
6.03e5.89 (1H, m, ]CH), 3.92e3.85 (2H, m, CH2OSi), 3.87 (3H, s,
CO2CH3), 3.17e3.07 (2H, m, CH2), 2.52e2.40 (4H, m, CH2), 1.93 (1H,
br s, CH3), 1.09 (9H, br s, Si(CH3)3); see Supplementary data for full
13C NMR spectra; HRMS m/z C31H37O4BrSiNaþ (MBr79Naþ) requires
603.1542, found 603.1540.
4.12. (4S,9R,10S,14R,16S)-6-Methyl-2,8,11-trioxo-3-
oxatetracyclo[7.6.1.04,16,010 14
, ]hexadeca-1(15),6-diene-10-
b) Methyl 2-(4-bromobut-3-en-1-yl)-5-(7-ethoxy-4-hydroxy-2-
methyl-7-oxohept-1-en-5-yn-1-yl)furan-3-carboxylate.
carboxylate (56a)
Two drops of water were added to a stirred solution of the
vinylbutenolide 38a (10.1 mg, 26.1 mol) in trifluoroacetic acid
The substituted propynoate was prepared from the above silyl
ether/vinyl bromide in three steps: i) deprotection of the silyl ether
group (87%); ii) oxidation or the resulting alcohol to the corre-
sponding aldehyde and iii) reaction of the aldehyde with ethyl pro-
piolate (87% over two steps) using the same reagents and reaction
conditions that were used to prepare 45b, 45c and 46, respectively.
The isomeric propiolates were separated by careful column chro-
matography (2:1, hexanes/EtOAc). Isomer 1: dH (400 MHz, CDCl3)
6.45 (1H, s, FurH), 6.25e5.90 (2H, m, CH]CHBr), 6.12 (1H, br s, ]CH),
m
(2.0 mL) at room temperature. The mixture was stirred at room
temperature for 2 h and then concentrated in vacuo, with azeo-
tropic removal of water using toluene (3ꢂ2 mL). Purification of the
residue by column chromatography on silica (petrol/EtOAc), gave
23
the polycycle 56a (7.1 mg, 82%) as a colourless oil. [
a
]
þ72.5 (c
D
0.235, CHCl3); nmax (CHCl3)/cmꢀ1 1760, 1730, 1667, 1435, 1263, 1239;
dH (500 MHz, CDCl3) 6.87 (1H, app. t, J¼3.6, OC(O)C]CH), 6.13 (1H,
br s, COCH]CCH3), 4.75 (1H, ddd, J¼12.3, 9.5 and 2.9, C(O)CH), 3.80