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Huang C, et al. Sci China Chem January (2011) Vol.54 No.1
room temperature. The resulting mixture was immersed into
an oil-bath (70 °C) and stirred till there was no further in-
creasing of the reaction products. The reaction mixture was
cooled down to room temperature, diluted with EtOAc, fil-
tered through Celite and concentrated to give the crude
products. This crude products were purified by flash chro-
matography on silica gel with EtOAc-Pet (20:80 v/v, 200 mL,
25:75 v/v, 160 mL, 33:67 v/v, 90 mL) as the eluent to give
rac-heliespirone A (46.3 mg, 22%, brsm 31%) as a colorless
oil and rac-heliespirone C (58.5 mg, 27%, brsm 39%) as a
faint yellow oil and recovered compound rac-24a (64.7 mg,
30%).
rac-24b (10.0 mg, 68%) as a yellow oil. TLC (EtOAc:Pet,
1:10 v/v): Rf =0.40; IR (neat): 3394, 2955, 2924, 1647, 1053,
1
971 cm1; H NMR (400 MHz, CDCl3) 6.38 (s, 1H), 5.82
(d, J = 2.2 Hz, 1H), 5.71–5.55 (m, 1H), 5.22 (d, J = 10 Hz,
1 H), 5.15 (d, J = 17.2 Hz, 1 H), 4.17 (d, J = 4.1 Hz, 1H),
3.52 (td, J = 10.1, 1.7 Hz, 1H), 2.06 (dd, J = 14.4, 7.6 Hz,
1H), 1.94–1.79 (m, 4H), 1.49 (s, 3H), 1.39 (s, 3H). 13C
NMR (100 MHz, CDCl3) 186.4, 157.0, 138.7, 138.6, 137.0,
121.3, 119.0, 98.0, 82.7, 80.8, 39.6, 32.9, 29.1, 21.9, 15.5.
Compound 28
A 250 mL round-bottomed flask, equipped with a magnetic
stirrer, was charged with K2CO3 (4.19 g, 30 mmol), K3Fe(CN)6
(9.98 g, 30 mmol), (DHQD)2-PHAL (410.0 mg, 0.5 mmol),
K2OsO4·H2O (37.2 mg, 0.1 mmol), water (50 mL) and tert-
butyl alcohol (50 mL). The resulting mixture was stirred at
room temperature till it produced two clear phases. Methane-
sulfonamide (971.0 mg, 1.0 mmol) was added in one-portion
and the reaction mixture was stirred for additional 1.5 h.
The reaction mixture was cooled to 0 ℃. Compound 27 (1.5
mL, 8.0 mmol) was added at once, and the heterogeneous
slurry was stirred vigorously at 0 °C overnight. Solid so-
dium sulfite (5.63 g) was added at 0 °C and the mixture was
allowed to warm to room temperature and stirred for 90 min.
EtOAc (100 mL) and water (50 mL) were added to the reac-
tion mixture. The organic layer was separated and the
aqueous layer was extracted with EtOAc (60 mL × 3). The
combined organic extracts were dried over anhydrous so-
dium sulfate and concentrated to give the crude product.
This crude product was purified by flash chromatography
on silica gel with EtOAc-Pet (33:67 v/v) as the eluent to
give diol 28 (1.57 g, 98%, over 96% ee) as a colorless oil.
[]D13.0 + 40.0 (c 0.10 in CH2Cl2); IR (neat): 3409, 2237,
rac-Heliespirone A
TLC (EtOAc:Pet, 1:1 v/v): Rf = 0.70; IR (neat): 3454, 2974,
1
2930, 1679, 1621, 1241, 1062 cm1; H NMR (600 MHz,
CDCl3) 6.62 (q, J = 1.4 Hz, 1H), 5.30 (ddd, J = 17.0 Hz,
9.7 Hz, 9.7 Hz, 1H), 5.07 (d, J = 16.9 Hz, 1H), 4.97 (d, J=
10.0 Hz, 1H), 4.04 (dd, J = 10.6 Hz, 5.2 Hz, 1H), 3.25 (A of
AB, d, J = 15.5 Hz, 1H), 2.97 (B of AB, d, J=15.5 Hz, 1H),
2.92 (ddd, J = 12.6 Hz, 9.5 Hz, 6.5 Hz, 1H), 2.15 (ddd, J =
12.6 Hz, 10.9 Hz, 1H), 1.96 (d, J = 1.4 Hz, 3H), 1.98–1.94
(m, 1H), 1.33 (s, 3H), 1.10 (s, 3H). 13C NMR (100 MHz,
CDCl3) 201.4, 195.6, 153.6, 137.1, 135.4, 118.6, 87.6,
86.7, 70.3, 57.1, 51.8, 31.9, 28.4, 25.3, 16.0. HRMS (ES) m/z
calcd for C15H20O4Na [M+Na]+ 287.1259, found 287.1261.
rac-Heliespirone C
TLC (EtOAc:Pet, 1:1 v/v): Rf = 0.58; IR (neat): 3469, 2975,
1
1688, 1622, 1420, 1378, 1250, 1115, 1071 cm1; H NMR
(600 MHz, CDCl3) 6.68 (q, J = 1.4 Hz, 1H), 5.59 (ddd, J=
16.8 Hz, 10.3 Hz, 8.6 Hz, 1H), 5.12 (dd, J = 9.3 Hz, 0.8 Hz,
1H), 5.11 (dd, J = 17.0 Hz, 0.8 Hz, 1H), 3.96 (dd, J = 10.7
Hz, 5.1 Hz, 1H), 3.30–3.26 (m, 1H), 2.95 (A of AB, d, J =
16.1 Hz, 1H), 2.84 (B of AB, d, J = 16.2 Hz, 1H), 2.07–2.03
(m, 1H), 1.99 (d, J=1.4 Hz, 3H), 1.96–1.89 (m, 1H), 1.24 (s,
3H), 1.13 (s, 3H). 13C NMR (100 MHz, CDCl3) 196.9,
196.3, 151.9, 137.1, 134.6, 119.9, 86.9, 86.7, 70.3, 48.9,
47.0, 32.4, 27.6, 24.6, 16.2. HRMS (ES) m/z calcd for
C15H20O4Na [M+Na]+ 287.1259, found 287.1257.
1
1706, 1465, 1370, 1258, 1070, 1033 cm1; H NMR (400
MHz, CDCl3 + D2O) 4.21 (q, J=7.1 Hz, 2H), 3.64 (dd, J=
8.9 Hz, 3.3 Hz, 1H), 2.60 (A of AB, dd, J =17.2 Hz, 3.6Hz,
1H), 2.50 (B of AB, dd, J = 17.2 Hz, 8.8 Hz, 1H), 1.29 (t,
J = 7.1 Hz, 3H), 1.24 (s, 3H), 1.17 (s, 3H). 13C NMR (100
MHz, CDCl3) 154.0, 87.8, 75.7, 74.3, 72.4, 62.1, 26.0,
24.3, 22.6, 14.0. HRMS (ES) m/z calcd for C10H16O4Na
[M+Na]+ 223.0946, found 223.0944. Enantiomeric excess
was determined by HPLC analysis [CHIRALCEL OD-H
column, 10% isopropanol-hexane, 1.0 mL/min, 210 nm,
retention times 7.17 min (S) and 8.14 min (R)].
Compound rac-24b
To a solution of compound rac-8b (16.4 mg, 0.056 mmol)
in MeCN (1.0 mL), CAN aq. (156.5 mg in 0.35 mL water)
was added dropwise at 0 °C and the resultant was stirred for
30 min at 0 °C. The reaction mixture was diluted with
EtOAc (10 mL) and brine (5 mL). The organic layer was
separated and the aqueous layer was extracted with EtOAc
(10 mL × 3). The combined organic extracts were washed
with sat. aq. NaHCO3 (10 mL × 2). The resulting aqueous
layer was extracted with EtOAc (10 mL × 2). The combined
organic extracts were dried over anhydrous sodium sulfate
and concentrated to give the crude product. This crude
product was purified by flash chromatography on silica gel
with EtOAc-Pet (6:94 v/v) as the eluent to give compound
Compound 29
To a solution of compound 28 (373.3 mg, 1.86 mmol) in
ethanol (19 mL), Lindlar’s catalyst (39.7 mg, 1.0 mol%)
and quinoline (0.93 mL, 7.44 mmol) were added. The re-
sulting mixture was stirred at room temperature for 30 min
then exposed to an atom. pressure of hydrogen at the same
temperature. The reaction mixture was stirred for 2.5 h. Af-
ter that time, the mixture was filtered through Celite,
washed with EtOAc and the volatiles were removed under