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D. R. Adams et al.
LETTER
monitored by evolution of nitrogen gas and by TLC (EtOAc–hex-
anes = 2:1). Note: Compound 9 co-elutes with starting material 6
and can be differentiated by the fact that only 6 is UV active. After
the addition was complete the reaction mixture was allowed to stir
at ca. 5 °C for an additional 20 min prior to slowly warming to r.t.
The reaction mixture at ambient temperature was concentrated to
dryness and reconstituted in EtOAc (15 mL) to produce a white
slurry. The slurry was filtered twice and the filtrate concentrated to
provide a colorless oil (576 mg). The crude oil was chroma-
tographed on silica gel (3:1 to 1:1 hexanes–EtOAc) to yield 155 mg
of diol 9 as a white crystalline solid (40% yield single isomer; 81%
overall yield, combined isomers 9 and 10).
subjected to slow stirring under argon atmosphere. After several
hours the stirring was inhibited by the viscosity of the crude reaction
mixture. The reaction mixture was allowed to stand at r.t. under ar-
gon atmosphere. NMR analysis after 43 h indicated a 1:0.6 ratio of
idesolide to monomer 2. The reaction was allowed to proceed for an
additional 5.5 h before the mixture was diluted with CHCl3 and fil-
tered. The filtrate was concentrated in vacuo to provide 54 mg of a
colorless oil that was stored at –78 °C overnight. Oily white crystals
were observed, and the crude material was triturated with pentanes
(4 × 0.2 mL) and hexanes (6 × 0.2 mL) to provide 25 mg of (–)-
idesolide (1, 57% yield) as white crystalline solid. Rf = 0.48 (hex-
20
anes–EtOAc = 1:1); mp 136–139 °C; [a]D –242.523 (c 1.0,
CHCl3). FT-IR (film): 3365, 3030, 2955, 2848, 1755, 1738, 1439,
1350, 1259, 1124, 975, 802, 751 cm–1. 1H NMR (600 MHz, CDCl3):
d = 6.01 (m, 2 H), 5.61 (dd, J = 1.83, 9.99 Hz, 1 H), 5.49 (dd,
J = 2.52, 10.08 Hz, 1 H), 3.93 (s, 3 H), 3.79 (s, 3 H), 2.41 (m, 2 H),
2.27 (m, 4 H), 2.15 (m, 1 H), 1.85 (m, 1 H). 13C NMR (150 MHz,
CDCl3): d = 173.21, 169.09, 132.47, 130.68, 126.54, 126.17,
110.96, 102.17, 86.44, 76.70, 54.26, 52.78, 31.05, 29.74, 24.40,
22.44. MS (EI+): m/z = 340. HRMS: m/z calcd for C16H20O8: 340.12;
found: 340.11499. Anal Calcd: C, 56.47; H, 5.92. Found: C, 55.27;
H, 5.84.
Compound 9: Rf = 0.50 (EtOAc–hexanes = 2:1); mp 68–71 °C
(EtOAc); [a]D20 –36.083 (c 1.0, CHCl3). FT-IR (film): 3441, 2953,
1735, 1436, 1262, 772 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.68–
1.85 (m, 1 H), 1.86–1.97 (m, 1 H), 2.21–2.32 (m, 2 H), 3.86 (s, 3 H),
4.04 (dd, J = 11.68, 3.77 Hz, 1 H), 5.62 (dt, J = 9.80, 2.07 Hz, 1 H),
6.05 (ddd, J = 9.70, 4.24, 3.01 Hz, 1 H). 13C NMR (75 MHz,
CDCl3): d = 175.77, 132.90, 125.35, 73.82, 70.85, 53.42, 26.47,
24.91. MS (EI+): m/z = 172. HRMS: m/z calcd for C8H12O4: 172.07;
found: 172.07388. Anal Calcd: C, 55.81; H, 7.02. Found: C, 55.68;
H, 7.15.
Compound 10: light brown oil. Rf = 0.39 (EtOAc–hexanes = 2:1);
Methyl (1S)-1-Hydroxy-2-oxocyclohex-3-ene carboxylate (11)
To a solution of diene 6 (65 mg, 0.381 mmol) in toluene (1.5 mL)
was added Grubbs first-generation catalyst (15 mg, 0.019 mmol)
under argon and with stirring. The lightly colored brown/yellow so-
lution quickly turned purple upon addition of catalyst. The reaction
was heated to 111 °C and turned to a clear brown color over several
minutes. The reaction was monitored by TLC analysis and deemed
complete after approximately 17 h. The reaction mixture was con-
centrated to dryness, and the crude black oil (70 mg) was chromato-
graphed on silica gel (hexanes–EtOAc = 2:1 to hexanes–EtOAc =
1:1) to yield 28 mg (43% yield) of enone 11 as a light brown/red oil.
Rf = 0.52 (hexanes–EtOAc = 1:1). FT-IR (film): 3460, 2955, 2938,
1741, 1681, 1436, 1389, 1259, 1220, 1198, 1139, 1114, 1070 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.09 (m, 1 H), 6.17 (d, J = 10.20
Hz, 1 H), 4.24 (OH, s, 1 H), 3.79 (s, 3 H), 2.62 (m, 3 H), 2.10 (m, 1
H). 13C NMR (75 MHz, CDCl3): d = 194.76, 170.68, 152.74,
126.63, 52.98, 32.06, 24.21. MS (EI+): m/z = 170. HRMS: m/z calcd
for C8H10O4: 170.06; found: 170.05791.
20
1
[a]D –21.924 (c 1.0, CHCl3). H NMR (300 MHz, CDCl3): d =
5.85 (md, J = 1.51, 8.61 Hz, 1 H), 5.58 (qd, J = 2.04, 10.19 Hz, 1
H), 4.50 (m, J = 1.81 Hz, 1 H), 2.32 (m, J = 3.42 Hz, 1 H), 2.08 (m,
J = 2.21 Hz, 1 H), 2.05–1.65 (m, 4 H), 1.50–1.35 (m, 1 H). 13C
NMR (75 MHz, CDCl3): d = 176.25, 128.99, 127.93, 74.50, 72.25,
69.03, 53.23, 34.35, 30.32, 24.05, 21.17, 19.86. MS (EI+): m/z =
172. HRMS: m/z calcd for C8H12O4: 172.07; found: 172.07356.
Anal Calcd: C, 55.81; H, 7.02. Found: C, 53.89; H, 7.49.
Methyl (1S)-1-Hydroxy-6-oxocyclohex-2-enecarboxylate (2)
To a solution of diol 9 (409 mg, 2.37 mmol) in DMSO (7.9 mL) was
added 2-iodoxybenzoic acid (1.99 g, 7.12 mmol) in portions over 1
min. The white slurry turned to a light yellow and clear mixture over
several minutes. The reaction was monitored by TLC analysis (hex-
anes–EtOAc = 1:1) and stirred at r.t. for 15.5 h prior to workup. The
reaction mixture appeared as a slightly yellow-white slurry and was
filtered. The filtrate was dropped into a stirring volume of H2O (18
mL) and produced a white precipitate that was stirred at r.t. for 0.5
h prior to filtration. The mother liquor was extracted with Et2O
(10 × 8 mL, 7 × 7 mL, 6 × 4 mL) and EtOAc (2 × 6 mL). The organ-
ic layers were combined and dried over MgSO4, filtered, and con-
centrated to provide an orange oil (585 mg crude). The crude
material was subjected to silica gel chromatography (hexanes–
EtOAc = 2:1) and provided 240 mg (59% yield) of a-hydroxy ke-
tone 2 as a colorless oil that was stored for short periods of time in
Acknowledgment
The authors are grateful to the following agencies for financial sup-
port of this work: Noramco, Inc., Natural Sciences and Engineering
Research Council of Canada (Idea to Innovation and Discovery
Grants); Canada Research Chair Program, Canada Foundation for
Innovation, Research Corporation, TDC Research, Inc., TDC Re-
search Foundation, and Brock University. One of us (C.A.) thanks
the Fonds zur Förderung der wissenschaftlichen Forschung (Austri-
an Science Fund, FWF) for financial support of this work during the
Summer 2010 (Project FWF-P20697-N19). We thank Professor
Shigefumi Kuwahara, Tohoku University, for providing advice, ex-
perimental data, and a sample of (–)-idesolide.
20
the freezer. Rf = 0.58 (hexanes–EtOAc = 1:1); [a]D –239.702 (c
1.0, CHCl3). FT-IR (film): 3468, 2957, 1744, 1725, 1438, 1259,
1138, 1040, 996, 875, 813 cm–1. 1H NMR (300 MHz, CDCl3): d =
2.46–2.71 (m, 3 H), 2.88–2.95 (m, 1 H), 3.72 (s, 3 H), 4.33 (s, 1 H,
OH), 5.72 (dt, J = 1.67, 9.74 Hz, 1 H), 6.06 (dt, J = 3.83, 9.72, 1 H).
13C NMR (75 MHz, CDCl3): d = 205.78, 170.36, 131.88, 127.62,
77.99, 53.46, 35.11, 26.89. MS (EI+): m/z = 170. HRMS: m/z calcd
for C8H10O4: 170.06; found: 170.05791.
References
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Synlett 2011, No. 5, 725–729 © Thieme Stuttgart · New York